There are more than 400 biotech drug products and vaccines currently in clinical

trials targeting more than 200 diseases, including various cancers, Alzheimer’s
disease, heart disease, diabetes, multiple sclerosis, AIDS and arthritis. •
Biotechnology is responsible for hundreds of medical diagnostic tests that keep
other conditions early enough to be successfully

Guide to

the blood supply safe from the AIDS virus and detect

Biotechnology
2007

treated. Home pregnancy tests are also biotechnology diagnostic products. •

Consumers are enjoying biotechnology foods such as papaya, soybeans and corn. The
tools of biotechnology allow plant breeders to select single genes that produce
desired traits and move them from one plant to another. • environmental
biotechnology products make it possible to clean up hazardous waste more
efficiently by harnessing pollution-eating microbes without the use of caustic
chemicals. • industrial biotechnology applications have led to cleaner processes
that produce less waste and use less energy and water in such industrial sectors
as chemicals, pulp and paper, textiles, food, energy, and metals and minerals. For
example, most laundry detergents produced in the United States contain
biotechnology-based enzymes. • Food & agriculture applications are lifting yields
and creating hardier crops. • Forensic medicine, as well
The Guide to Biotechnology is compiled by the Biotechnology Industry Organization
(BIO) Debbie Strickland, BIO, Director of Marketing, Editor Contributors Deb
Carstoiu, BIO, Director of State Media Relations and Advocacy Elinor Van Dyck,
Blue House Publishing, Art Director Barbara Glenn, BIO, Managing Director of
Animal Bitoechnology Crispin Littlehales, Writer/Editor Adrienne Massey, Ph.D.,
Writer/Editor
Contents
Biotechnology: A Collection of Technologies 1
Putting the Pieces Together: ‘Omics’ ...............................29 Genomics,
proteomics and bioinformatics Product Development
Applications .................................31 What Is
Biotechnology?......................................................1 Cells and
Biological Molecules...........................................1

Health-Care Applications Biotechnology Industry Facts 2

Market Capitalization, 1994–2005 .....................................3 U.S.
Industry Statistics: 1994–2005 ...................................3 New Biotech
Drug and Vaccine Approvals/ New Indication Approvals by
Year.................................4 North American Biotech Companies by State
and Province ....................................................4 Total
Financing, 1998–2005 ...............................................5 Biotech
Industry Financing, 2005 .....................................5

34

Diagnostics ......................................................................
.34
Therapeutics .....................................................................
34 Personalized Medicine ......................................................37
Regenerative Medicine .....................................................39
Vaccines .........................................................................
...39 Plant-Made Pharmaceuticals............................................41

Therapeutic Developement Overview

42

Biotech Drug Development Process ................................44

Time Line

Biotechnology Policy Milestones .....................................16

Approved Biotechnology Drugs

45

The Technologies and Their Applications

Agricultural Production Applications 65 18

Crop Biotechnology ..........................................................65
Includes production improvement, impact on developing countries, environmental and
economic benefits, and regulations Forest
Biotechnology .......................................................69 Animal
Biotechnology ......................................................70 Includes
companion animals, applications for human medicine, and environmental and
conservation efforts
Aquaculture ......................................................................
76 Global Area of Transgenic Crops, 1995 to 2005: Industrial and Developing
Countries ..78 Global Area of Transgenic Crops in 2004 and 2005 by
Country ..................................................................78
Global Area of Transgenic Crops in 2004 and 2005 by
Crop ...............................................................79 Global Area
of Transgenic Crops, 1996 to 2005, by
Crop ........................................................................79
Global Area of Transgenic Crops in 2004 and 2005 by
Trait ...............................................................80

Bioprocessing Technology................................................18
Monoclonal Antibodies .....................................................18 Cell
Culture ......................................................................19
Recombinant DNA Technology ........................................21
Cloning ..........................................................................
...21 Protein
Engineering ........................................................22
Biosensors .......................................................................
.22 Nanobiotechnology...........................................................23
Microarrays ......................................................................
.23

Biotechnology Tools in Research and Development

25

Research Applications ......................................................25

Includes stem cell technology, cloning, microarray technology, antisense and RNA
interference, and gene knockouts

Guide to Biotechnology n Biotechnology Industry Organization

Global Area of Transgenic Crops, 1995 to 2005, by
Trait ........................................................................80
Transgenic Crop Area as Percentage of Global Area of Principal
Crops ....................................81 Global Status of Biotech Crops in
2005 ...........................81

Other Uses

102

DNA Fingerprinting........................................................102

Ethics

104

BIO
Activities ..................................................................104
Ethical
Issues ..................................................................105

Agricultural Biotech Products on the Market Food Biotechnology

82 87

BIO Statement of Ethical Principles 109 Intellectual Property 111

Improving the Raw Materials ...........................................87 Food

Processing................................................................88 Food
Safety Testing ..........................................................89

What Is a Patent? ............................................................111

The Purpose of a Patent .................................................111
Patentable Inventions.....................................................112
Patent Requirements ......................................................112 The
Patent Application ...................................................113
Patenting Organisms ......................................................113
Patent Licensing .............................................................114

Industrial and Environmental Applications

90

Industrial Sustainability...................................................90
Biocatalysts .....................................................................
..91
Biofuel ..........................................................................
....92 Green
Plastics ...................................................................93
Nanotechnology................................................................93
Environmental Biotechnology .........................................94 Industries
That Benefit.....................................................95 Some
Industrial Biotech Applications by
Sector ......................................................................95

Biotechnology Resources

115
Periodicals, Headline Services and Web Sites ...............115 General Science
Journals ..............................................116 Biotech Education &
Careers .........................................116 Selected Recent Reports on
Biotechnology ...................116

Glossary Consumer Products Made with Industrial Biotechnology Examples of

Industrial Enzymes Preparedness for Pandemics and Biodefense 96 98

119

100

Policy............................................................................
...100 A Strategic
Asset .............................................................100 Vaccines,
monoclonal antibodies, DNA- or RNA-based therapeutics, and detection and diagnosis
Other Approaches ...........................................................101
Biotechnology Industry Organization n Guide to Biotechnology
Biotechnology: A Collection of Technologies
What Is Biotechnology?

reak biotechnology into its roots and you have

bio—the use of biological processes; and technology—to solve problems or make

useful products. Using biological processes is hardly a noteworthy event. We began
growing crops and raising animals 10,000 years ago to provide a stable supply of
food and clothing. We have used the biological processes of microorganisms for
6,000 years to make useful food products, such as bread and cheese, and to
preserve dairy products. Why is biotechnology suddenly receiving so much
attention? During the 1960s and ’70s our understanding of biology reached a point
where we could begin to use the smallest parts of organisms—their biological
molecules—in addition to using whole organisms. A more appropriate definition in
the new sense of the word is this: “New” Biotechnology—the use of cellular and
biomolecular processes to solve problems or make useful products. We can get a
better handle on the meaning of the word biotechnology by simply changing the
singular noun to its plural form, biotechnologies. Biotechnology is a collection
of technologies that capitalize on the attributes of cells, such as their
manufacturing capabilities, and put biological molecules, such as DNA and
proteins, to work for us.

All cells have the same basic design, are made of the same construction materials
and operate using essentially the same processes. DNA (deoxyribonucleic acid), the
genetic material of almost all living things, directs cell construction and
operation, while proteins do all the work. Because DNA contains the information
for making proteins, it directs cell processes by determining which proteins are
produced and when. All cells speak the same genetic language. The DNA information
manual of one cell can be read and implemented by cells from other living things.
Because a genetic instruction to make a certain protein is understood by many
different types of cells, technologies based on cells and biological molecules
give us great flexibility in using nature’s diversity. In addition, cells and
biological molecules are extraordinarily specific in their interactions. As a
result, biotechnology products can often solve specific problems, generate gentler
or fewer side effects and have fewer unintended consequences. Specific, precise,
predictable. Those are the words that best describe today’s biotechnology.

Cells and Biological Molecules

ells are the basic building blocks of all living things. The simplest living
things, such as yeast, consist of a single, self-sufficient cell. Complex
creatures more familiar to us, such as plants, animals and humans, are made of
many different cell types, each of which performs a very specific task. In spite
of the extraordinary diversity of cell types in living things, what is most
striking is their remarkable similarity. This unity of life at the cellular level
provides the foundation for biotechnology.

Guide to Biotechnology n Biotechnology Industry Organization

Biotechnology Industry Facts
n

The biotechnology industry originated in the 1970s, based largely on a new

recombinant DNA technique whose details were published in 1973 by Stanley Cohen of
Stanford University and Herbert Boyer of the University of California, San
Francisco. Recombinant DNA is a method of making proteins—such as human insulin
and other therapies—in cultured cells under controlled manufacturing conditions.
Boyer went on to co-found Genentech, which today is biotechnology’s largest
company by market capitalization. Biotechnology has created more than 200 new
therapies and vaccines, including products to treat cancer, diabetes, HIV/AIDS and
autoimmune disorders. There are more than 400 biotech drug products and vaccines
currently in clinical trials targeting more than 200 diseases, including various
cancers, Alzheimer’s disease, heart disease, diabetes, multiple sclerosis, AIDS
and arthritis. Biotechnology is responsible for hundreds of medical diagnostic
tests that keep the blood supply safe from the AIDS virus and detect other
conditions early enough to be successfully treated. Home pregnancy tests are also
biotechnology diagnostic products. Consumers are enjoying biotechnology foods such
as papaya, soybeans and corn. Biopesticides and other agricultural products also
are being used to improve our food supply and to reduce our dependence on
conventional chemical pesticides. Environmental biotechnology products make it
possible to clean up hazardous waste more efficiently by harnessing pollution-
eating microbes without the use of caustic chemicals. Industrial biotechnology
applications have led to cleaner processes that produce less waste and use less
energy and water in such industrial sectors as chemicals, pulp and paper,
textiles, food, energy, and metals and minerals. For example, most laundry
detergents produced in the United States contain biotechnology-based enzymes. DNA
fingerprinting, a biotech process, has dramatically improved criminal
investigation and forensic medicine, as well as afforded significant advances in
anthropology and wildlife management. The biotech industry is regulated by the
U.S. Food and Drug Administration (FDA), the Environmental Protection Agency (EPA)
and the Department of Agriculture (USDA).

As of Dec. 31, 2005, there were 1,415 biotechnology companies in the United
States, of which 329 were publicly held. Market capitalization, the total value of
publicly traded biotech companies (U.S.) at market prices, was $410 billion as of
Dec. 31, 2005. The biotechnology industry has mushroomed since 1992, with U.S.
health-care biotech revenues increasing from $8 billion in 1992 to $50.7 billion
in 2005. Biotechnology is one of the most research-intensive industries in the
world. The U.S. biotech industry spent $19.8 billion on research and development
in 2005. The top five biotech companies invested an average of $130,000 per
employee in R&D in 2005. In 1982, recombinant human insulin became the first
biotech therapy to earn FDA approval. The product was developed by Genentech and
Eli Lilly and Co. Corporate partnering has been critical to biotech success. In
2005, biotech companies signed 564 new agreements with pharmaceutical firms and
354 with fellow biotechs, according to BioWorld. Most biotechnology companies are
young companies developing their first products and depend on investor capital for
survival. Biotechnology attracted more than $20 billion in financing in 2005 and
has raised more than $100 billion since 2000. The biosciences—including not just
biotechnology but all life sciences activities—employed 1.2 million people in the
United States in 2004 and generated an additional 5.8 million related jobs. The
average annual wage of U.S. bioscience workers was $65,775 in 2004, more than
$26,000 greater than the average private sector annual wage. Bioethanol—made from
crop wastes using biotech enzymes—could meet a quarter of U.S. energy needs by
2025. The Biotechnology Industry Organization (BIO) was founded in 1993 to
represent biotechnology companies at the local, state, federal and international
levels. As of December 2006, BIO’s membership consisted of more than 1,100
biotechnology companies, academic centers, state and local associations and
related enterprises.

2
n

Biotechnology Industry Organization n Guide to Biotechnology

Market Capitalization, 1994–2005*
450 400 353.5 350 300 250 200 150 100 50 0 1994 1995 1996 1997 1998 1999 Year
*Amounts are U.S. dollars in billions. Sources: Ernst & Young LLP BioWorld 2000
2001 2002 2003 2004 2005 45 41 52 83 93 137.9 225 330.8 336.8 410

206

U.S. Biotech Industry Statistics: 1994–2005*

Year Sales Revenues R&D Expense Net Loss No. of Public Companies No. of Companies
2005 32.1 50.7 19.8 4.1 329 1,415 2004 28.1 43.8 19.6 6.8 331 1,346 2003 28.4 39.2
17.9 5.4 314 1,473 2002 24.3 29.6 20.5 9.4 318 1,466 2001 21.4 29.6 15.7 4.6 342
1,457 2000 19.3 26.7 14.2 5.6 339 1,379 1999 16.1 22.3 10.7 4.4 300 1,273 1998
14.5 20.2 10.6 4.1 316 1,311 1997 13 17.4 9.0 4.5 317 1,274 1996 10.8 14.6 7.9 4.6
294 1,287 1995 9.3 12.7 7.7 4.1 260 1,308 1994 7.7 11.2 7.0 3.6 265 1,311

*Amounts are U.S. dollars in billions. Source: Ernst & Young LLP, annual
biotechnology industry reports, 1995–2006. Financial data based primarily on
fiscal-year financial statements of publicly traded companies.

Guide to Biotechnology n Biotechnology Industry Organization

New Biotech Drug and Vaccine Approvals/ New Indication Approvals by Year
40 36 35 30 Number of Approvals 25 20 15 10 5 0 5 2 0 0 3 1 3 6 5 9 7 4 7 15 25 25
20 25 34 40 37 38

19

Source: BIO

1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997
1998 1999 2000 2001 2002 2003 2004 2005 Year

North American Biotech Companies by State and Province

400 350 300 Number of Companies 256 250 200 150 100 50 0 North Carolina New York
Quebec Texas Massachusetts Pennsylvania British Columbia Connecticut Washington
Ontario Maryland Georgia New Jersey California Alberta Florida 143 134 81 75 74
374

68

59

58

56

48

47

45

33

25

Source: Ernst & Young LLP Biotechnology Industry Organization n Guide to

Biotechnology

Regions
Total Financing, 1998–2005 (in billions of U.S. dollars)
40 35 30 25 20.8 20 15.1 15 10 5.4 5 0 1998 Source: BioWorld 1999 2000 2001 2002
2003 2004 2005 11.8 10.5 16.9 20.1 38

Biotech Industry Financing, 2005

Total: $20,114.9 Million (all figures in millions)

Public offerings: $5,579.6 (27.7%) Venture funding: $4,808.9 (23.9%) Other

financings of public companies: $9,726.4 (48.4%)

Source: BioWorld

Guide to Biotechnology n Biotechnology Industry Organization

Time Line
8000 B.C. n Humans domesticate crops and livestock.
n

Potatoes first cultivated for food.

1835–1855 n Schleiden and Schwann propose that all organisms are composed of
cells, and Virchow declares, “Every cell arises from a cell.” 1857 n Pasteur
proposes microbes cause fermentation. 1859 n Charles Darwin publishes the theory
of evolution by natural selection. The concept of carefully selecting parents and
culling the variable progeny greatly influences plant and animal breeders in the
late 1800s despite their ignorance of genetics. 1865 n Science of genetics begins:
Austrian monk Gregor Mendel studies garden peas and discovers that genetic traits
are passed from parents to offspring in a predictable way—the laws of heredity.
1870–1890 n Using Darwin’s theory, plant breeders crossbreed cotton, developing
hundreds of varieties with superior qualities.
n

4000–2000 B.C. n Biotechnology first used to leaven bread and ferment beer, using
yeast (Egypt).
n

Production of cheese and fermentation of wine (Sumeria, China and Egypt).

Babylonians control date palm breeding by selectively pollinating female trees
with pollen from certain male trees.

500 B.C. n First antibiotic: moldy soybean curds used to treat boils (China). A.D.
100 n First insecticide: powdered chrysanthemums (China).

1322 n An Arab chieftain first uses artificial insemination to produce superior

horses. 1590 n Janssen invents the microscope. 1663 n Hooke discovers existence of
the cell. 1675 n Leeuwenhoek discovers bacteria. 1761 n Koelreuter reports
successful crossbreeding of crop plants in different species. 1797 n Jenner
inoculates a child with a viral vaccine to protect him from smallpox. 1830–1833 n
1830—Proteins discovered.
n

Farmers first inoculate fields with nitrogen-fixing bacteria to improve yields.

William James Beal produces first experimental corn hybrid in the laboratory. 1877
—A technique for staining and identifying bacteria is developed by Koch. 1878—The
first centrifuge is developed by Laval. 1879—Fleming discovers chromatin, the rod-
like structures inside the cell nucleus that later came to be called chromosomes.

n n

1900 n Drosophila (fruit flies) used in early studies of genes. 1902 n The term
immunology first appears. 1906 n The term genetics is introduced.

1833—First enzyme discovered and isolated.

Biotechnology Industry Organization n Guide to Biotechnology
1911 n The first cancer-causing virus is discovered by Rous. 1914 n Bacteria are
used to treat sewage for the first time in Manchester, England. 1915 n Phages, or
bacterial viruses, are discovered. 1919 n First use of the word biotechnology in
print. 1920 n The human growth hormone is discovered by Evans and Long. 1928 n
Penicillin discovered as an antibiotic: Alexander Fleming.
n

1930 n U.S. Congress passes the Plant Patent Act, enabling the products of plant
breeding to be patented. 1933 n Hybrid corn, developed by Henry Wallace in the
1920s, is commercialized. Growing hybrid corn eliminates the option of saving
seeds. The remarkable yields outweigh the increased costs of annual seed
purchases, and by 1945, hybrid corn accounts for 78 percent of U.S.-grown corn.
1938 n The term molecular biology is coined. 1941 n The term genetic engineering
is first used, by Danish microbiologist A. Jost in a lecture on reproduction in
yeast at the technical institute in Lwow, Poland. 1942 n The electron microscope
is used to identify and characterize a bacteriophage—a virus that infects
bacteria.
n

A small-scale test of formulated Bacillus thuringiensis (Bt) for corn borer

control begins in Europe. Commercial production of this biopesticide begins in
France in 1938. Karpechenko crosses radishes and cabbages, creating fertile
offspring between plants in different genera. Laibach first uses embryo rescue to
obtain hybrids from wide crosses in crop plants—known today as hybridization.

Penicillin mass-produced in microbes.

1944 n DNA is proven to carry genetic information—Avery et al.

n

Waksman isolates streptomycin, an effective antibiotic for tuberculosis.

Guide to Biotechnology n Biotechnology Industry Organization

1956 n Kornberg discovers the enzyme DNA polymerase I, leading to an understanding
of how DNA is replicated. 1958 n Sickle cell anemia is shown to occur due to a
change of a single amino acid.
n

DNA is made in a test tube for the first time.

1959 n Systemic fungicides are developed. The steps in protein biosynthesis are
delineated. ALSO IN THE 1950s n Discovery of interferons. 1946 n Discovery that
genetic material from different viruses can be combined to form a new type of
virus, an example of genetic recombination.
n n

First synthetic antibiotic.

Recognizing the threat posed by loss of genetic diversity, the U.S. Congress
provides funds for systematic and extensive plant collection, preservation and
introduction.

1960 n Exploiting base pairing, hybrid DNA-RNA molecules are created.

n

Messenger RNA is discovered.

1947 n McClintock discovers transposable elements, or “jumping genes,” in corn.

1949 n Pauling shows that sickle cell anemia is a “molecular disease” resulting
from a mutation in the protein molecule hemoglobin. 1951 n Artificial insemination
of livestock using frozen semen is accomplished. 1953 n The scientific journal
Nature publishes James Watson and Francis Crick’s manuscript describing the double
helical structure of DNA, which marks the beginning of the modern era of genetics.
1955 n An enzyme involved in the synthesis of a nucleic acid is isolated for the
first time.
Biotechnology Industry Organization n Guide to Biotechnology

1961 n USDA registers first biopesticide: Bacillus thuringiensis, or Bt. 1963 n

New wheat varieties developed by Norman Borlaug increase yields by 70 percent.
1964 n The International Rice Research Institute in the Philippines starts the
Green Revolution with new strains of rice that double the yield of previous
strains if given sufficient fertilizer. 1965 n Harris and Watkins successfully
fuse mouse and human cells. 1966 n The genetic code is cracked, demonstrating that
a sequence of three nucleotide bases (a codon) determines each of 20 amino acids.
(Two more amino acids have since been discovered.)
1967 n The first automatic protein sequencer is perfected. 1969 n An enzyme is
synthesized in vitro for the first time. 1970 n Norman Borlaug receives the Nobel
Peace Prize (see 1963).
n

First guidelines for recombinant DNA experiments released: National Institutes of

Health–Recombinant DNA Advisory Committee.

1977 n First expression of human gene in bacteria.

n

Procedures developed for rapidly sequencing long sections of DNA using

electrophoresis.

Discovery of restriction enzymes that cut and splice genetic material, opening the
way for gene cloning.

1978 n High-level structure of virus first identified.

n n

1971 n First complete synthesis of a gene. 1972 n The DNA composition of humans is
discovered to be 99 percent similar to that of chimpanzees and gorillas.
n

Recombinant human insulin first produced. North Carolina scientists show it is

possible to introduce specific mutations at specific sites in a DNA molecule.

Initial work with embryo transfer.

1979 n Human growth hormone first synthesized. ALSO IN THE 1970s n First
commercial company founded to develop genetically engineered products.
n n

1973 n Stanley Cohen and Herbert Boyer perfect techniques to cut and paste DNA
(using restriction enzymes and ligases) and reproduce the new DNA in bacteria.
1974 n The National Institutes of Health forms a Recombinant DNA Advisory
Committee to oversee recombinant genetic research. 1975 n Government first urged
to develop guidelines for regulating experiments in recombinant DNA: Asilomar
Conference, California.
n

Discovery of polymerases. Techniques for rapid sequencing of nucleotides

perfected. Gene targeting. RNA splicing.

n n

The first monoclonal antibodies are produced.

1980 n The U.S. Supreme Court, in the landmark case Diamond v. Chakrabarty,
approves the principle of patenting organisms, which allows the Exxon oil company
to patent an oil-eating microorganism.
n

1976 n The tools of recombinant DNA are first applied to a human inherited
disorder.
n

The U.S. patent for gene cloning is awarded to Cohen and Boyer. The first gene-
synthesizing machines are developed. Researchers successfully introduce a human
gene— one that codes for the protein interferon—into a bacterium. Nobel Prize in
Chemistry awarded for creation of the first recombinant molecule: Berg, Gilbert,
Sanger.

n n

Molecular hybridization is used for the prenatal diagnosis of alpha thalassemia.

Yeast genes are expressed in E. coli bacteria. The sequence of DNA base pairs for
a specific gene is determined.

n n

Guide to Biotechnology n Biotechnology Industry Organization

n

The first genetic markers for specific inherited diseases are found. First whole
plant grown from biotechnology: petunia. First proof that modified plants pass
their new traits to offspring: petunia.

n n

1984 n The DNA fingerprinting technique is developed.

n

The entire genome of the human immunodeficiency virus is cloned and sequenced.

1985 n Genetic markers found for kidney disease and cystic fibrosis.
n

Genetic fingerprinting entered as evidence in a courtroom. Transgenic plants

resistant to insects, viruses and bacteria are field-tested for the first time.
The NIH approves guidelines for performing genetherapy experiments in humans.

10

1981 n Scientists at Ohio University produce the first transgenic animals by

transferring genes from other animals into mice.
n

Chinese scientist becomes the first to clone a fish—a golden carp.

1986 n First recombinant vaccine for humans: hepatitis B.

n

1982 n Applied Biosystems, Inc., introduces the first commercial gas phase protein
sequencer, dramatically reducing the amount of protein sample needed for
sequencing.
n n

First anticancer drug produced through biotech: interferon. The U.S. government
publishes the Coordinated Framework for Regulation of Biotechnology, establishing
more stringent regulations for rDNA organisms than for those produced with
traditional genetic modification techniques. A University of California–Berkeley
chemist describes how to combine antibodies and enzymes (abzymes) to create
pharmaceuticals. The first field tests of transgenic plants (tobacco) are
conducted. The Environmental Protection Agency approves the release of the first
transgenic crop—gene-altered tobacco plants. The Organization of Economic
Cooperation and Development (OECD) Group of National Experts on Safety in
Biotechnology states: “Genetic changes from rDNA techniques will often have
inherently greater predictability

First recombinant DNA vaccine for livestock developed. First biotech drug approved
by FDA: human insulin produced in genetically modified bacteria. First genetic
transformation of a plant cell: petunia.
n
n

1983 n The polymerase chain reaction (PCR) technique is conceived. PCR, which uses
heat and enzymes to make unlimited copies of genes and gene fragments, later
becomes a major tool in biotech research and product development worldwide.
n

The first genetic transformation of plant cells by TI plasmids is performed. The

first artificial chromosome is synthesized.

Biotechnology Industry Organization n Guide to Biotechnology

compared to traditional techniques” and “risks associated with rDNA organisms may
be assessed in generally the same way as those associated with non-rDNA
organisms.”
1987 n First approval for field test of modified food plants: virus-resistant
tomatoes.
n

Frostban, a genetically altered bacterium that inhibits frost formation on crop

plants, is field-tested on strawberry and potato plants in California, the first
authorized outdoor tests of a recombinant bacterium.

1988 n Harvard molecular geneticists are awarded the first U.S. patent for a
genetically altered animal—a transgenic mouse.
n

A patent for a process to make bleach-resistant protease enzymes to use in

detergents is awarded. Congress funds the Human Genome Project, a massive effort
to map and sequence the human genetic code as well as the genomes of other
species.
n

The first experimental gene therapy treatment is performed successfully on a 4-

year-old girl suffering from an immune disorder. The first transgenic dairy cow—
used to produce human milk proteins for infant formula—is created. First insect-
protected corn: Bt corn. First food product of biotechnology approved in U.K.:
modified yeast. First field test of a genetically modified vertebrate: trout.

11

1989 n First approval for field test of modified cotton: insectprotected (Bt)
cotton.
n

n n

Plant Genome Project begins.

ALSO IN THE 1980s n Studies of DNA used to determine evolutionary history.

n

Recombinant DNA animal vaccine approved for use in Europe. Use of microbes in oil
spill cleanup: bioremediation technology. Ribozymes and retinoblastomas
identified.

1992 n American and British scientists unveil a technique for testing embryos in
vitro for genetic abnormalities such as cystic fibrosis and hemophilia.
n

n
The FDA declares that transgenic foods are “not inherently dangerous” and do not
require special regulation.

1990 n Chy-Max™, an artificially produced form of the chymosin enzyme for cheese-
making, is introduced. It is the first product of recombinant DNA technology in
the U.S. food supply.
n

1993 n Merging two smaller trade associations creates the Biotechnology Industry
Organization (BIO).
n

The Human Genome Project—an international effort to map all the genes in the human
body—is launched.

FDA approves bovine somatotropin (BST) for increased milk production in dairy
cows.

Guide to Biotechnology n Biotechnology Industry Organization

1994 n First FDA approval for a whole food produced through biotechnology:
FLAVRSAVR™ tomato.
n n

The first complete animal genome, for the C. elegans worm, is sequenced. A rough
draft of the human genome map is produced, showing the locations of thousands of
genes. Five Southeast Asian countries form a consortium to develop disease-
resistant papayas.

The first breast cancer gene is discovered. Approval of recombinant version of

human DNase, which breaks down protein accumulation in the lungs of CF patients.
BST commercialized as POSILAC® bovine somatotropin.
n

ALSO IN THE 1990s n First conviction using genetic fingerprinting in the U.K.
n

1995 n The first baboon-to-human bone marrow transplant is performed on an AIDS

patient.
n

Discovery that hereditary colon cancer is caused by defective DNA repair gene.
Recombinant rabies vaccine tested in raccoons. Biotechnology-based biopesticide
approved for sale in the United States. Patents issued for mice with specific
transplanted genes. First European patent on a transgenic animal issued for
transgenic mouse sensitive to carcinogens.

n n

The first full gene sequence of a living organism other than a virus is completed,
for the bacterium Hemophilus influenzae. Gene therapy, immune system modulation
and recombinantly produced antibodies enter the clinic in the war against cancer.

12

1996 n The discovery of a gene associated with Parkinson’s disease provides an

important new avenue of research into the cause and potential treatment of the
debilitating neurological ailment. 1997 n First animal cloned from an adult cell:
a sheep named Dolly in Scotland.
n

2000 n First complete map of a plant genome developed: Arabidopsis thaliana.

n

Biotech crops grown on 108.9 million acres in 13 countries. “Golden rice”

announcement allows the technology to be available to developing countries in
hopes of improving the health of undernourished people and preventing some forms
of blindness. First biotech crop field-tested in Kenya: virus-resistant sweet
potato. Rough draft of the human genome sequence is announced.

First weed- and insect-resistant biotech crops commercialized: Roundup Ready®

soybeans and Bollgard® insect-protected cotton. Biotech crops grown commercially
on nearly 5 million acres worldwide: Argentina, Australia, Canada, China, Mexico
and the United States. A group of Oregon researchers claims to have cloned two
Rhesus monkeys.

1998 n University of Hawaii scientists clone three generations of mice from nuclei
of adult ovarian cumulus cells.
n n

2001 n First complete map of the genome of a food plant completed: rice.
n

Human embryonic stem cell lines are established. Scientists at Japan’s Kinki
University clone eight identical calves using cells taken from a single adult cow.
n

Researchers with China’s National Hybrid Rice Research Center report developing a
“super rice” that could produce double the yield of normal rice. Complete DNA
sequencing of the agriculturally important bacteria Sinorhizobium meliloti, a
nitro-

Biotechnology Industry Organization n Guide to Biotechnology

gen-fixing species, and Agrobacterium tumefaciens, a plant pest.
n

A single gene from Arabidopsis inserted into tomato plants to create the first
crop able to grow in salty water and soil.

2002 n The first draft of a functional map of the yeast proteome, an entire
network of protein complexes and their interactions, is completed. A map of the
yeast genome was published in 1996.
n

International consortia sequence the genomes of the parasite that causes malaria
and the species of mosquito that transmits the parasite. The draft version of the
complete map of the human genome is published, and the first part of the Human
Genome Project comes to an end ahead of schedule and under budget. Scientists make
great progress in elucidating the factors that control the differentiation of stem
cells, identifying over 200 genes that are involved in the process. Biotech crops
grown on 145 million acres in 16 countries, a 12 percent increase in acreage. More
than onequarter (27 percent) of the global acreage was grown in nine developing
countries. Researchers announce successful results for a vaccine against cervical
cancer, the first demonstration of a preventative vaccine for a type of cancer.
Scientists complete the draft sequence of the most important pathogen of rice, a
fungus that destroys enough rice to feed 60 million people annually. By combining
an understanding of the genomes of the fungus and rice, scientists can elucidate
the molecular basis of the interactions between the plant and pathogen. Scientists
are forced to rethink their view of RNA when they discover how important small
pieces of RNA are in controlling many cell functions. Japanese pufferfish genome
is sequenced. The pufferfish sequence is the smallest known genome of any
vertebrate. Scientists at Stony Brook University in New York assemble a synthetic
virus, polio, using genome sequence information. The project raises ethical and
security questions.

2003 n Researchers find a vulnerability gene for depression and make strides in
detecting genetic links to schizophrenia and bipolar disorder.
n

GloFish®, the first biotech pet, hits the North American market. Specially bred to
detect water pollutants, the fish glows red under black light thanks to the
addition of a natural fluorescence gene. Worldwide biotech crop acreage rises 15
percent to hit 167.2 million acres in 18 countries. Brazil and the Philippines
grow biotech crops for the first time in 2003. Also, Indonesia allows consumption
of imported biotech foods, and China and Uganda accept biotech crop imports. The
U.K. approves its first commercial biotech crop in eight years. The crop is a
biotech herbicide-resistant corn used for cattle feed. The U.S. Environmental
Protection Agency approves the first transgenic rootworm-resistant corn, which may
save farmers $1 billion annually in crop losses and pesticide use. An endangered
species (the banteng) is cloned for the first time. 2003 also brought several
other cloning firsts, including mules, horses and deer. Dolly, the cloned sheep
that made headlines in 1997, is euthanized after developing progressive lung
disease. Dolly was the first successful clone of an adult mammal. Japanese
researchers develop a biotech coffee bean that is naturally decaffeinated. China’s
State Food and Drug Administration grants the world’s first regulatory approval of
a gene therapy product, Gendicine, developed by Shenzhen SiBiono GenTech. The
product delivers the p53 gene as a therapy for squamous cell head and neck cancer.
Guide to Biotechnology n Biotechnology Industry Organization

13

n
2004 n The FDA approves the first anti-angiogenic drug for cancer, AVASTIN®
(bevacizumab).
n

heart failure in self-identified black patients. The company hopes a genetic test
can be developed to identify patients likely to benefit, regardless of race.
n

The FDA clears a DNA microarray test system, the AmpliChip® Cytochrome P450
Genotyping Test, to aid in selecting medications for a wide variety of common
conditions. An RNA-interference product for age-related “wet” macular degeneration
becomes the first RNAi product to enter a clinical trial. The United Nations Food
and Agriculture Organization endorses biotech crops and states that biotechnology
is a complementary tool to traditional farming methods that can help poor farmers
and consumers in developing nations. The National Academy of Sciences’ Institute
of Medicine finds biotech crops do not pose any more health risks than do crops
created by other techniques, and that food safety evaluations should be based on
the resulting food product, not the technique used to create it. FDA finds biotech
wheat safe after a food safety review. Monsanto introduces low-linolenic soybeans
(produced through conventional breeding methods) that will reduce or eliminate
trans fatty acids in processed soybean oil. Chicken genome sequenced by the
Chicken Genome Sequencing Consortium. First cloned pet, a kitten, is delivered to
its owner. Laboratory rat genome is sequenced. Researchers complete the sequence
of the chimpanzee—humanity’s closest primate relative. The Canadian biotech
company Iogen achieves the first commercial production and delivery of bioethanol,
producing the fuel with biotech enzymes and wheat straw. California voters pass
Proposition 71, which supports embryonic stem cell research with $3 billion in
funding over 10 years.

The Energy Policy Act is passed and signed into law, authorizing numerous
incentives for bioethanol development. The National Institutes of Health in
December launches a pilot project to determine the feasibility of The Cancer
Genome Atlas. The ultimate goal would be a complete map of the genomic changes
involved in all types of human cancer. Using new genome sequence information,
scientists at the Centers for Disease Control & Prevention partially synthesize
the flu virus that killed at least 20 million people worldwide in 1918–1919.
Scientists at Harvard University report success in converting skin cells into
embryonic stem cells through fusion with existing embryonic stem cells. USDA,
Monsanto and Genaissance Pharmaceuticals announce a joint soybean genome project.
The British government approves the Equine Fertility Unit’s research in using
nuclear transfer in horse cloning. On May 7, the one billionth acre of biotech
seed is planted. The World Health Organization (WHO) issues the report Modern Food
Biotechnology, Human Health and Development, which states biotech foods can
contribute to enhancing human health and development. According to the report,
biotech foods can increase crop yield, food quality, and the diversity of foods
which can be grown in a given area. They lead to better health and nutrition and
thereby help raise health and living standards. The British research firm PG
Economics Ltd. finds that the global use of biotech crops has added $27 billion to
farm income, and greatly reduced agriculture’s negative impacts on the
environment. The National Science Foundation, USDA, and the Department of Energy
award $32 million to a team of university and private laboratory researchers to
sequence the corn genome. A consortium of scientists led by the National Human
Genome Research Institute publishes the dog genome, which belongs to a 12-year-old
boxer.

n
n

14

n n

n n n

2005 n Researchers at the University of Georgia successfully produce a cow cloned

from the cells of a carcass.
n

FDA for the first time approves a drug for a specific race. The drug, NitroMed’s
BiDil®, treats congestive

Biotechnology Industry Organization n Guide to Biotechnology

n

Global biotech crop acreage reaches 222 million acres.

2006 n A team of researchers headed by the University of Illinois receives a $10

million federal grant to complete the sequence of the swine genome. The project is
expected to be completed within two years.
n

the roundworm Caenorhabditis elegans. The biotech pigs were cloned, and six of the
10 clones produced increased levels of omega-3 fatty acids, which are believed to
ward off heart disease.
n

In his State of the Union address, President Bush expresses support for bioethanol
made from agricultural wastes. “Doesn’t it make sense,” he asked, “to determine
whether or not we can use these raw materials to make something out of nothing so
that we continue the advance of ethanol and so the market for ethanol expands
throughout the United States?” The National Institutes of Health begins a 10-year,
10,000-patient study using a genetic test that predicts breast-cancer recurrence
and guides treatment. Patients whose cancer is deemed unlikely to recur will be
spared chemotherapy. The genetic test, Oncotype DX™ was developed by the biotech
company Genomic Health and is already commercially available. In January, the
American Dietetic Association (ADA) publishes a reaffirmed statement of support on
agricultural and food biotechnology. The ADA states that agricultural
biotechnology techniques can enhance the quality, safety, nutritional value, and
variety of food available for human consumption while increasing the efficiency of
food production, food processing, food distribution, and environmental and waste
management. Dow AgroSciences announces it has received the first regulatory
approval for a plant-made vaccine from USDA’s Center for Veterinary Biologics. The
vaccine protects poultry from Newcastle disease, and is the first plant-made
vaccine to be approved. Renessen LLC, a joint venture of Monsanto and Cargill,
receives approval from USDA to begin selling the first crop improved through
biotechnology with added benefits for use in animal feed. The product, Mavera™
High Value Corn with Lysine, has been improved to grow with increased levels of
lysine, an amino acid that is essential for animal diets, especially those of
swine and poultry. USDA awards $5 million to a consortium of public wheat breeders
and 18 universities for wheat genome research. Researchers develop biotech pigs
that produce high levels of omega-3 fatty acids. The biotech pigs were developed
by inserting the “fat-1” gene that comes from

The World Trade Organization issues a confidential final ruling on the

U.S./Canada/Argentine challenge against the European Union (EU) on approval of new
biotech crops. According to news reports, the ruling concludes that the EU
breached its trade commitments with respect to 21 agricultural biotechnology
products—including types of oilseed, rape, maize and cotton. The French
agriculture ministry authorizes 17 new field tests for biotech corn and tobacco
crops.

Sources: Access Excellence Biotech 90: Into the Next Decade, G. Steven Burrill
with the Ernst & Young High Technology Group Biotechnology Industry Organization
Genentech, Inc. Genetic Engineering News International Food Information Council
ISB News Report International Service for the Acquisition of Agri-Biotech
Applications Texas Society for Biomedical Research Science Science News The
Scientist

15

Guide to Biotechnology n Biotechnology Industry Organization

Biotechnology Policy Milestones
1902 n The Biologics Control Act passes to ensure purity and safety of serums,
vaccines and similar products. 1906 n The Food and Drugs Act is signed into law,
prohibiting interstate commerce in misbranded and adulterated food, drinks and
drugs. (Note: For a detailed FDA timeline, visit
http://www.fda.gov/opacom/backgrounders/miles.html.) 1930 n The National Institute
of Health is created (later to be pluralized as National Institutes of Health).
1971 n President Nixon calls for a War on Cancer and signs the National Cancer Act
into law, stimulating new research. 1974 n Leading biologists call for a voluntary
moratorium on recombinant DNA experiments while safety standards are set. 1975 n
Some 150 scientists, attorneys, government officials and journalists meet at the
Asilomar Conference Center near Monterey, Calif., to discuss recombinant DNA
research and develop strict safety protocols. 1976 n The NIH adopts guidelines for
federally funded recombinant DNA research, with oversight provided by the
Recombinant DNA Advisory Committee. 1980 n The Supreme Court decides in Diamond
vs. Chakrabarty that anything made by “the hand of man,” including biotechnology-
modified organisms, is patentable. The decision helps open the floodgates to a
wave of investment that includes the first biotech IPOs.
n

the ground rules for technology transfer from academia to industry. The act
creates a uniform patent policy among federal agencies that fund research and
specifies that federal grant recipients—such as universities and small businesses—
own federally funded inventions.
1983 n The Orphan Drug Act is signed into law, creating new incentives to conduct
R&D on therapies for rare diseases. More than 250 orphan drugs have reached the
U.S. market in the years since. 1988 n The U.S. Patent and Trademark Office grants
Harvard University a patent for a mouse used for cancer research (the OncoMouse®).
n

16

The United States launches the Human Genome Project when Congress appropriates
funds for the Department of Energy and the National Institutes of Health to
support research to determine the structure of complex genomes.

1992 n The FDA clears the way for agricultural biotechnology products with a
safety assessment and guidance to industry.
n

The Prescription Drug User Fee Act is signed into law, instituting fees for drug
approval applicants that provide the FDA with resources to review products faster.
The successful program is reauthorized in 1997 and 2002 and is up for
reauthorization again in 2007.

1993 n The Biotechnology Industry Organization (BIO) is created out of the merger
of two predecessor organizations, the Industrial Biotechnology Association and the
Association of Biotechnology Companies. (A history of BIO is posted on bio.org in
the “About BIO” section.) 1997 n The Food and Drug Administration Modernization
Act (FDAMA) is signed into law, codifying administrative changes begun in 1995 and
introducing new reforms. Provisions include criteria for fast-track drug
development, easier patient access to experimental drugs and medical devices, and
an online database of clinical trials.

The Patent and Trademark Act Amendments of 1980—commonly known as the Bayh-Dole
Act—lay

Biotechnology Industry Organization n Guide to Biotechnology

1998 n Congress undertakes a doubling of the National Institutes of Health budget
in five years, raising it to $27 billion by 2003. 2000 n The Biomass Research and
Development Act is signed into law to promote conversion of biomass into biobased
industrial products. 2001 n President Bush announces that federal funding will be
made available to support research using embryonic stem cell lines created as of
Aug. 9, 2001. 2002 n The Farm Security and Rural Investment Act includes biotech
measures such as significantly increased funding for research and risk assessment
and new programs for promoting biotechnology in developing countries. 2003 n The
Medicare Modernization Act becomes law, providing prescription drug coverage for
senior citizens and the disabled beginning Jan. 1, 2006. 2004 n The FDA publishes
a white paper outlining the Critical Path Initiative, which seeks to expedite drug
development by promoting the use of technologies such as computer-based predictive
models, biomarkers, imaging technologies and improved clinical trial design.
n

17

The Project BioShield Act is signed into law, providing $5.6 billion over 10 years
for the federal government to procure diagnostics, therapies and vaccines to
protect Americans from chemical, nuclear and biological warfare agents.

2005 n The Energy Policy Act of 2005 passes, authorizing $3.6 billion in funding
for bioenergy and biobased products.
n

Pandemic legislation signed into law provides $3.8 billion for preparedness,
including $3 billion for medical countermeasures. The legislation also includes
liability protection for manufacturers of these products.

Guide to Biotechnology n Biotechnology Industry Organization

The Technologies and Their Applications

H
T

ere are a few of the new biotechnologies that use cells and biological molecules
and examples of their applications in medicine, agriculture, food processing,
industrial manufacturing and environmental management.

The specificity of antibodies also makes them powerful diagnostic tools. They can
locate substances that occur in minuscule amounts and measure them with great
accuracy. For example, we use monoclonal antibodies to
n n n n

locate environmental pollutants. detect harmful miroorganisms in food. distinguish

cancer cells from normal cells. diagnose infectious diseases in humans, animals
and plants more quickly and more accurately than ever before.

Bioprocessing Technology
he oldest of the biotechnologies, bioprocessing technology, uses living cells or
the molecular components of their manufacturing machinery to produce desired
products. The living cells most commonly used are one-celled microorganisms, such
as yeast and bacteria; the biomolecular components we use most often are enzymes,
which are proteins that catalyze biochemical reactions. A form of bioprocessing,
microbial fermentation, has been used for thousands of years—unwittingly—to brew
beer, make wine, leaven bread and pickle foods. In the mid-1800s, when we
discovered microorganisms and realized their biochemical machinery was responsible
for these useful products, we greatly extended our use of microbial fermentation.
We now rely on the remarkably diverse manufacturing capability of naturally
occurring microorganisms to provide us with products such as antibiotics, birth
control pills, amino acids, vitamins, industrial solvents, pigments, pesticides
and food-processing aids. Today, we are using recombinant DNA technology, coupled
with microbial fermentation, to manufacture a wide range of biobased products
including human insulin, the hepatitis B vaccine, the calf enzyme used in
cheesemaking, biodegradable plastics, and laundry detergent enzymes. Bioprocessing
technology also encompasses tissue engineering and manufacturing as well as
biopharmaceutical formulation and delivery.

In addition to their value as detection devices, monoclonal antibodies (MAbs) can

provide us with highly specific therapeutic compounds. Monoclonal antibodies
joined to a toxin can selectively deliver chemotherapy to a cancer cell while
avoiding healthy cells. We are developing monoclonal antibodies to treat organ-
transplant rejection and autoimmune diseases by targeting them specifically to the
type of immune system cell responsible for these attacks, leaving intact the other
branches of the immune system.
MAbs FOR IMMUNE-RELATED CONDITIONS n Muromomab-CD3 (OKT3) is used to prevent acute
rejection of organ transplants. A modified version of OKT3 shows promise in
inhibiting the autoimmune destruction of beta cells in Type 1 diabetes mellitus.
n

18

Infliximab (Remicade®) binds to tumor necrosis factor-alpha and has shown promise
against some inflammatory diseases such as rheumatoid arthritis. Omalizumab
(Xolair®) binds to IgE and prevents it from binging to mast cells. The drug is
used against allergic asthma. Daclizumab (Zenapax®) binds to part of the IL-2
receptor and is used to prevent acute rejection of transplanted kidneys. The drug
also shows promise against T-cell lymphoma.
n

Monoclonal Antibodies

onoclonal antibody technology uses immune-system cells that make proteins called
antibodies. We have all experienced the extraordinary specificity of antibodies:
Those that attack a flu virus one winter do nothing to protect us from a slightly
different flu virus the next year. (Specificity refers to the fact that biological
molecules are designed so that they bind to only one molecule.)

MAbs USED TO KILL OR INHIBIT CANCER CELLS n Rituximab (Rituxan®) binds to the CD20
molecule that is found on most B-cells and is used to treat B-cell lymphomas
n

Ibritumomab tiuxetan (Zevalin®) is used against the CD20 molecule on B-cells (and
lymphomas) conjugated to either of two radioactive isotopes in conjunction with
Rituxan.

Biotechnology Industry Organization n Guide to Biotechnology

n

Tositumomab (Bexxar®) is a conjugate of a monoclonal antibody against CD20 and the

radioactive isotope iodine-131. It has been approved to treat lymphoma.
Trastuzumab (Herceptin®) binds to HER2, a receptor for epidermal growth factor
found on some breast cancers and lymphomas. Cetuximab (Erbitux®) blocks HER1,
another epidermal growth factor receptor, and has been approved to treat
colorectal cancer. Gemtuzumab ozogamicin (Mylotarg®) is a conjugate of a
monoclonal antibody that binds to CD33, a cellsurface molecule expressed by the
cancerous cells in acute myelogenous leukemia, and calicheamicin, a complex
oligosaccharide that makes double-stranded breaks in DNA. The drug is the first
immunotoxin that shows promise in the fight against cancer. Alemtuzumab (Campath®)
binds to CD52, a molecule found on white blood cells, and has produced complete
remission of chronic lymphocytic leukemia (for 18 months and counting).

the rest of a human antibody molecule, thus replacing its own hypervariable
regions. Zenapax®, Vitaxin, Mylotarg®, Herceptin®, and Xolair® are examples.

Cell Culture

ell culture technology is the growing of cells outside of living organisms.

PLANT CELL CULTURE An essential step in creating transgenic crops, plant cell
culture also provides us with an environmentally sound and economically feasible
option for obtaining naturally occurring products with therapeutic value, such as
the chemotherapeutic agent paclitaxel, a compound found in yew trees and marketed
under the name Taxol®. Plant cell culture is also an important source of compounds
used as flavors, colors and aromas by the food-processing industry. INSECT CELL
CULTURE Insect cell culture can broaden our use of biological control agents that
kill insect pests without harming beneficial insects or having pesticides
accumulate in the environment. Even though we have recognized the environmen-

19

ANGIOGENESIS INHIBITOR n Bevacizumab (Avastin®) blocks the vascular endothelial

growth factor (VEGF) receptor and has been approved for the treatment of
colorectal cancer. OTHER n Abciximab (ReoPro®) inhibits the clumping of platelets
by binding the receptors on their surface that normally are linked by fibrinogen.
This therapy is helpful in preventing the re-clogging of the coronary arteries in
patients who have undergone angioplasty.

Monoclonal antibodies can be created in mice, but mouse antibodies are “seen” by
the human immune system and often the human patient mounts an immune response,
which not only eliminates the therapeutic MAb administered, but also causes damage
to the kidneys. To reduce the problem of human anti-mouse antibodies (HAMA),
scientists use chimeric, or humanized, antibodies. To form a chimeric antibody,
one must combine the antigenbinding parts (variable regions) of the mouse antibody
with the effector parts (constant regions) of a human antibody. Infliximab,
rituximab and abciximab are examples. To create human antibodies, one combines
only the amino acids responsible for making the antigen binding site (the
hypervariable regions) of a mouse antibody and

Guide to Biotechnology n Biotechnology Industry Organization

tal advantages of biological control for many decades, manufacturing biological
control products in marketable amounts has been impossible. Insect cell culture
removes these manufacturing constraints. In addition, like plant cell culture,
insect cell culture is being investigated as a production method of therapeutic
proteins. Insect cell culture is also being investigated for the production of VLP
(viruslike particle) vaccines against infectious diseases such as SARS and
influenza, which could lower costs and eliminate the safety concerns associated
with the traditional eggbased process. A patient specific cancer vaccine that
utilizes insect cell culture has reached Phase III clinical trials.
MAMMALIAN CELL CULTURE Livestock breeding has used mammalian cell culture as an
essential tool for decades. Eggs and sperm, taken from genetically superior bulls
and cows, are united in the lab, and the resulting embryos are grown in culture
before being implanted in surrogate cows. A similar form of mammalian cell culture
has also been an essential component of the human in vitro fertilization process.

Researchers also are working on ways to harvest stem cells from placentas and from
fat. Some are looking at cellular reprogramming as a way to get specialized body
cells, like skin cells, to revert to a primordial state so that they can be coaxed
into various types of tissues. Embryonic stem cells are also under study as
potential therapies. As the name suggests, embryonic stem cells are derived from
embryos—specifically those that develop from eggs that have been fertilized in
vitro (in an in vitro fertilization clinic) and then donated by consent for
research purposes. The embryos are typically four or five days old and are each a
hollow microscopic ball of cells called the blastocyst. The potential value of
stem cell therapy and tissue engineering can best be realized if the therapeutic
stem cells and the tissues derived from them are genetically identical to the
patient receiving them. Human embryonic stem cells are isolated by transferring
the inner cell mass into a nutrient rich culture medium. There the human stem
cells proliferate. Over the course of several days, the cells of the inner cell
mass divide and spread all over the dish. Researchers then must remove the growing
cells and divide them into fresh culture dishes. This process of replating the
cells, called subculturing, is repeated many times over many months. Each cycle of
subculturing cells is called a passage. Embryonic stem cells that have
proliferated in cell culture for six or more months without differentiating (i.e.,
remain pluripotent) and appear genetically normal are referred to as an embryonic
stem cell line. The inner surface of the culture dish may be coated with mouse
embryonic skin cells that have been engineered not to divide. This is called the
“feeder layer.” It provides a sticky surface to which the human embryonic cells
attach. Recently scientists have been figuring out ways to grow embryonic stem
cells without using mouse feeder cells—a significant advance because of the risk
of viruses and other macromolecules in the mouse cells being transmitted to the
human cells. The potential value of stem cell therapy and tissue engineering can
best be realized if the therapeutic stem cells and the tissues derived from them
are genetically identical to the patient receiving them. Therefore, unless the
patient is the source of the stem cells, the stem cells need to be “customized” by
replacing the stem cell’s genetic material with the patient’s before cueing the
stem cells to differentiate into a specific cell type. To date, this genetic
material replacement and reprogramming can be done effectively only with embryonic
stem cells.

20

Our use of mammalian cell culture now extends well beyond the brief maintenance of
cells in culture for reproductive purposes. Mammalian cell culture can supplement—
and may one day replace—animal testing to assess the safety and efficacy of
medicines. Like plant cell culture and insect cell culture, we are relying on the
manufacturing capacity of mammalian cells to synthesize therapeutic compounds, in
particular, certain mammalian proteins too complex to be manufactured by
genetically modified microorganisms. For example, monoclonal antibodies are
produced through mammalian cell culture. Scientists are also investigating the use
of mammalian cell culture as a production technology for vaccines. In 2005, the
Department of Health and Human Services awarded a $97 million contract to Sanofi
Pasteur to develop mammalian cell culturing techniques to speed the production
process for new influenza vaccines and thereby enhance pandemic preparedness.
Therapies based on cultured adult stem cells, which are found in certain tissues
like the bone marrow and brain, are on the horizon as well. Researchers have found
that adult stem cells can be used by the body to replenish tissues. Adult
hematopoietic stem cells already are being transplanted into bone marrow to
stimulate the generation of the various types of blood cells necessary to
rejuvenate an immune system. These stem cells can be harvested in large quantities
from umbilical cord blood, but they are difficult to isolate and purify.
Biotechnology Industry Organization n Guide to Biotechnology
Recombinant DNA Technology

increase agricultural yields and decrease production costs. decrease allergy-

producing characteristics of some foods. improve food’s nutritional value. develop
biodegradable plastics. decrease water and air pollution. slow food spoilage.
control viral diseases. inhibit inflammation.

ecombinant DNA technology is viewed by many as the cornerstone of biotechnology.

The term recombinant DNA literally means the joining or recombining of two pieces
of DNA from two different species. Humans began to preferentially combine the
genetic material of domesticated plants and animals thousands of years ago by
selecting which individuals would reproduce. By breeding individuals with valuable
genetic traits while excluding others from reproduction, we changed the genetic
makeup of the plants and animals we domesticated. Now, in addition to using
selective breeding to combine valuable genetic material from different organisms,
we combine genes at the molecular level using the more precise techniques of
recombinant DNA technology. Genetic modification through selective breeding and
recombinant DNA techniques fundamentally resemble each other, but there are
important differences:
n

n n n n n n

Cloning

Genetic modification using recombinant DNA techniques allows us to move single

genes whose functions we know from one organism to any other. In selective
breeding, large sets of genes of unknown function are transferred between related
organisms.

loning technology allows us to generate a population of genetically identical

molecules, cells, plants or animals. Because cloning technology can be used to
produce molecules, cells, plants and some animals, its applications are
extraordinarily broad. Any legislative or regulatory action directed at “cloning”
must take great care in defining the term precisely so that the intended
activities and products are covered while others are not inadvertently captured.
MOLECULAR OR GENE CLONING Molecular or gene cloning, the process of creating
genetically identical DNA molecules, provides the foundation of the molecular
biology revolution and is a fundamental and essential tool of biotechnology
research, development and commercialization. Virtually all applications in
biotechnology, from drug discovery and development to the production of transgenic
crops, depend on gene cloning.

21

By making our manipulations more precise and our outcomes more certain, we
decrease the risk of producing organisms with unexpected traits and avoid the
time-consuming, trial-and-error approach of selective breeding. By increasing the
breadth of species from which we can obtain useful genes, we can access all of
nature’s genetic diversity. Techniques for making selective breeding more
predictable and precise have been evolving over the years. In the early 1900s,
Hugo DeVries, Karl Correns and Eric Tshermark rediscovered Mendel’s laws of
heredity. In 1953, James Watson and Francis Crick deduced DNA’s structure from
experimental clues and model building. In 1972, Paul Berg and colleagues created
the first recombinant DNA molecules, using restriction enzymes. Ten years later,
the first recombinant DNA-based drug (recombinant human insulin) was introduced to
the market. By 2000 the human genome had been sequenced and today we use
recombinant DNA techniques, in conjunction with molecular cloning to
n n n

Virtually all applications in biotechnology, from drug discovery and development

to the production of transgenic crops, depend on gene cloning. The research
findings made possible through molecular cloning include identifying, localizing
and characterizing genes; creating genetic maps and sequencing entire genomes;
associating genes with traits and determining the molecular basis of the trait.
For a full discussion, see page 27.
ANIMAL CLONING Animal cloning has helped us to rapidly incorporate improvements
into livestock herds for more than two decades and has been an important tool for
scientific researchers
Guide to Biotechnology n Biotechnology Industry Organization

produce new medicines and safer vaccines. treat some genetic diseases. enhance
biocontrol agents in agriculture.
since the 1950s. Although the 1997 debut of Dolly, the cloned sheep, brought
animal cloning into the public consciousness, the production of an animal clone
was not a new development. Dolly was considered a scientific breakthrough not
because she was a clone, but because the source of the genetic material that was
used to produce Dolly was an adult cell, not an embryonic one. Recombinant DNA
technologies, in conjunction with animal cloning, are providing us with excellent
animal models for studying genetic diseases, aging and cancer and, in the future,
will help us discover drugs and evaluate other forms of therapy, such as gene and
cell therapy. Animal cloning also provides zoo researchers with a tool for helping
to save endangered species. There are two different ways to make an exact genetic
copy of an organism such as a sheep or a laboratory mouse. Artificial embryo
twinning (AET) is the old-fashioned way to clone. AET mimics the natural process
of creating identical twins, only in a Petri dish rather than the mother’s womb.
Researchers manually separate a very early embryo into individual cells and then
allow each cell to divide and develop on its own. The resulting embryos are placed
into a surrogate mother, where they are carried to term and delivered. Since all
the embryos come from the same zygote, they are genetically identical. Somatic
cell nuclear transfer (SCNT) involves the isolation of a somatic (body) cell,
which is any cell other then those used for reproduction (sperm and egg, known as
the germ cells). In mammals, every somatic cell has two complete sets of
chromosomes, whereas the germ cells have only one complete set. To make Dolly,
scientists transferred the nucleus of a somatic cell taken from an adult female
sheep and transferred it to an egg cell from which the nucleus had been removed.
After some chemical manipulation, the egg cell, with the new nucleus, behaved like
a freshly fertilized zygote. It developed into an embryo, which was implanted into
a surrogate mother and carried to term.

The most pervasive uses of protein engineering to date are applications that alter
the catalytic properties of enzymes to develop ecologically sustainable industrial
processes. Enzymes are environmentally superior to most other catalysts used in
industrial manufacturing because, as biocatalysts, they dissolve in water and work
best at neutral pH and comparatively low temperatures. In addition, because
biocatalysts are more specific than chemical catalysts, they also produce fewer
unwanted byproducts. The chemical, textile, pharmaceutical, pulp and paper, food
and feed, and energy industries are all benefiting from cleaner, more energy-
efficient production made possible by incorporating biocatalysts into their
production processes. The characteristics that make biocatalysts environmentally
advantageous may, however, limit their usefulness in certain industrial processes.
For example, most enzymes fall apart at high temperatures. Scientists are
circumventing these limitations by using protein engineering to increase enzyme
stability under harsh manufacturing conditions. In addition to industrial
applications, medical researchers have used protein engineering to design novel
proteins that can bind to and deactivate viruses and tumor-causing genes; create
especially effective vaccines; and study the membrane receptor proteins that are
so often the targets of pharmaceutical compounds. Food scientists are using
protein engineering to improve the functionality of plant storage proteins and
develop new proteins as gelling agents. In addition, new proteins are being
developed to respond to chemical and biological attacks. For example, hydrolases
detoxify a variety of nerve agents as well as commonly used pesticides. Enzymes
are safe to produce, store and use, making them an effective and sustainable
approach to toxic materials decontamination.

22

Biosensors

Protein Engineering
P

rotein engineering technology is used, often in conjunction with recombinant DNA

techniques, to improve existing proteins, such as enzymes, antibodies and cell
receptors, and to create proteins not found in nature. These proteins may be used
in drug development, food processing and industrial manufacturing.

iosensor technology couples our knowledge of biology with advances in

microelectronics. A biosensor is composed of a biological component, such as a
cell, enzyme or antibody, linked to a tiny transducer—a device powered by one
system that then supplies power (usually in another form) to a second system.
Biosensors are detecting devices that rely on the specificity of cells and
molecules to identify and measure substances at extremely low concentrations.

Biotechnology Industry Organization n Guide to Biotechnology

When the substance of interest binds with the biological component, the transducer
produces an electrical or optical signal proportional to the concentration of the
substance. Biosensors can, for example,
n

Most appropriately, DNA, the information storage molecule, may serve as the basis
of the next generation of computers. DNA has been used not only to build
nanostructures but also as an essential component of nanomachines. Most
appropriately, DNA, the information storage molecule, may serve as the basis of
the next generation of computers. As microprocessors and microcircuits shrink to
nanoprocessors and nanocircuits, DNA molecules mounted onto silicon chips may
replace microchips with electron flow-channels etched in silicon. Such biochips
are DNA-based processors that use DNA’s extraordinary information storage
capacity. Conceptually, they are very different from the DNA chips discussed
below. Biochips exploit the properties of DNA to solve computational problems; in
essence, they use DNA to do math. Scientists have shown that 1,000 DNA molecules
can solve in four months computational problems that would require a century for a
computer to solve. Other biological molecules are assisting in our continual quest
to store and transmit more information in smaller places. For example, some
researchers are using light-absorbing molecules, such as those found in our
retinas, to increase the storage capacity of CDs a thousand-fold. Some
applications of nanobiotechnology include
n n

measure the nutritional value, freshness and safety of food. provide emergency
room physicians with bedside measures of vital blood components. locate and
measure environmental pollutants. detect and quantify explosives, toxins and
biowarfare agents.

n n

Nanobiotechnology

anotechnology, which came into its own in 2000 with the birth of the National
Nanotechnology Initiative, is the next stop in the miniaturization path that gave
us microelectronics, microchips and microcircuits. The word nanotechnology derives
from nanometer, which is one-thousandth of a micrometer (micron), or the
approximate size of a single molecule. Nanotechnology—the study, manipulation and
manufacture of ultra-small structures and machines made of as few as one molecule—
was made possible by the development of microscopic tools for imaging and
manipulating single molecules and measuring the electromagnetic forces between
them. Nanobiotechnology joins the breakthroughs in nanotechnology to those in
molecular biology. Molecular biologists help nanotechnologists understand and
access the nanostructures and nanomachines designed by 4 billion years of
evolutionary engineering—cell machinery and biological molecules. Exploiting the
extraordinary properties of biological molecules and cell processes,
nanotechnologists can accomplish many goals that are difficult or impossible to
achieve by other means. For example, rather than build silicon scaffolding for
nanostructures, DNA’s ladder structure provides nanotechnologists with a natural
framework for assembling nanostructures and its highly specific bonding properties
bring atoms together in a predictable pattern to create a nanostructure.
Nanotechnologists also rely on the self-assembling properties of biological
molecules to create nanostructures, such as lipids that spontaneously form liquid
crystals.
23

increasing the speed and power of disease diagnostics. creating bio-nanostructures

for getting functional molecules into cells. improving the specificity and timing
of drug delivery. miniaturizing biosensors by integrating the biological and
electronic components into a single, minute component. encouraging the development
of green manufacturing practices.

n n

Microarrays

icroarray technology is transforming laboratory research because it allows us to

analyze tens of thousands of samples simultaneously. Researchers currently use
microarray technology to study gene structure and function. Thousands of DNA or
protein molecules are arrayed on glass slides to create

Guide to Biotechnology n Biotechnology Industry Organization

DNA chips and protein chips, respectively. Recent developments in microarray
technology use customized beads in place of glass slides.
DNA MICROARRAYS DNA microarrays are used to
n n n

detect mutations in disease-related genes. monitor gene activity. diagnose

infectious diseases and identify the best antibiotic treatment. identify genes
important to crop productivity. improve screening for microbes used in
bioremediation.

n n

DNA-based arrays will be essential for converting the raw genetic data provided by
the Human Genome Project and other genome projects into useful products. Gene
sequence and mapping data mean little until we determine what those genes do—which
is where protein arrays come in.

24

PROTEIN MICROARRAYS While going from DNA arrays to protein arrays is a logical
step, it is by no means simple to accomplish. The structures and functions of
proteins are much more complicated than that of DNA, and proteins are less stable
than DNA. Each cell type contains thousands of different proteins, some of which
are unique to that cell’s job. In addition, a cell’s protein profile varies with
its health, age, and current and past environmental conditions.

The fundamental principle underlying microarray technology has inspired

researchers to create many types of microarrays to answer scientific questions and
discover new products.
TISSUE MICROARRAYS Tissue microarrays, which allow the analysis of thousands of
tissue samples on a single glass slide, are being used to detect protein profiles
in healthy and diseased tissues and validate potential drug targets. Brain tissue
samples arrayed on slides with electrodes allow researchers to measure the
electrical activity of nerve cells exposed to certain drugs. WHOLE-CELL
MICROARRAYS Whole-cell microarrays circumvent the problem of protein stability in
protein microarrays and permit a more accurate analysis of protein interactions
within a cell. SMALL-MOLECULE MICROARRAYS Small-molecule microarrays allow
pharmaceutical companies to screen ten of thousands of potential drug candidates
simultaneously.

Protein microarrays will be used to

n n

discover protein biomarkers that indicate disease stages. assess potential

efficacy and toxicity of drugs before clinical trials. measure differential
protein production across cell types and developmental stages, and in both healthy
and diseased states. study the relationship between protein structure and
function. assess differential protein expression in order to identify new drug
leads. evaluate binding interactions between proteins and other molecules.

n
Biotechnology Industry Organization n Guide to Biotechnology
Biotech Tools in Research and Development

he previous section describes the fundamental scientific and technological

advances which together constitute biotechnology. Here we describe some of the
many tangible rewards afforded by biotech. Both academic and industrial scientists
have come to depend on various biotechnologies to study the workings of biological
systems in remarkably precise detail. These biotech research tools have allowed
them to answer longstanding scientific questions and have changed the questions
they ask, the problems they tackle and the methods they use to get answers. Using
the wealth of information this research provides, companies then rely on
biotechnology tools and techniques throughout product development and
commercialization.

UNDERSTANDING CELL PROCESSES Researchers are making considerable progress in

charting the path of a cell from a single, fertilized egg to a whole organism, a
feat that has eluded them for decades. The development of a multicelled organism
from a single cell involves cell proliferation and cell differentiation—groups of
cells becoming specialized, or differentiated, to perform specific tasks. Cell
differentiation is the process of turning off certain genes within a group of
cells while turning on others. Scientists are optimistic about elucidating the
many steps in the differentiation pathway and identifying the external and
internal factors regulating the process. The breakthroughs that gave birth to this
optimism are the development of a protocol for maintaining human stem cells in
culture and the birth of the cloned sheep Dolly.

Research Applications Of Biotechnology

A delicate balance exists between factors that stimulate cell division and those
that inhibit it. Any disruption of this balance leads to uncontrolled cell
proliferation—cancer—or cell death. For decades we have known the basic
requirements for keeping small numbers of plant and animal cells in culture for
many decades. We maintained these cultures primarily to collect products that
cells produce naturally. For example, plant cell culture gives us flavors, colors,
thickeners and emulsifiers for food processing. Researchers now are keeping cells
in culture to investigate the molecular basis of many cell processes, especially
cell growth, proliferation, differentiation and death. All cells progress through
essentially the same cycle: They increase in size up to a certain point, the
genetic material replicates, and the cell divides in two. Understanding what
controls the cell cycle is essential to understanding the cause of many human and
animal diseases, the basis of increasing crop plant yields, and a means for
quickly increasing the cells used to manufacture products as diverse as fermented
foods and medicines. Improvements in cell culture technology have allowed us to
better understand the molecular basis of the cell cycle. The rigorously controlled
sequence of steps in the cell cycle depends on both genetic and nutritional
factors. A delicate balance exists between factors that stimulate cell division
and those that inhibit it. Any disruption of this balance leads to uncontrolled
cell proliferation—cancer—or cell death. Studying cells in culture has led to a
radical revision of our view of cell death. Formerly we assumed all cells

esearchers use biotechnology to gain insight into the precise details of cell
processes: the specific tasks assigned to various cell types; the mechanics of
cell division; the flow of materials in and out of cells; the path by which an
undifferentiated cell becomes specialized; and the methods cells use to
communicate with each other, coordinate their activities and respond to
environmental changes. Researchers dissect these processes into the smallest
possible bits of useful information. This requires identifying the molecular
players involved in each facet of the process, elucidating the nature of their
interactions and discovering the molecular control mechanisms that govern these
interactions. Once they have teased apart details of the process, they must then
reassemble the pieces in a way that provides insight into the inner workings of
cells and, ultimately, of whole organisms. Interestingly, the tools of
biotechnology have also become important research tools in many branches of
science other than cell and molecular biology, such as chemistry, engineering,
materials science, ecology, evolution and computer science. The biotech-driven
discoveries in these fields help the biotech industry and others discover and
develop products, as well as help industries improve their performance in areas
such as environmental stewardship and workplace safety.

25

Guide to Biotechnology n Biotechnology Industry Organization

died through an unorganized, passive mechanism as cell parts and processes
gradually deteriorated. Now we know that much cell death is a highly organized,
well-planned sequence of events programmed into the genome. Prolonged cell stress
and other factors trigger programmed cell death, or apoptosis, in which the cell
dismantles itself in an orderly way, breaks down its genome and sends a signal to
the immune system to dispatch white blood cells that will remove it. Programmed
cell death eliminates cells with damaged DNA, removes immune system cells that
attack healthy cells and shapes tissue formation during development. A better
understanding of cell death can also help us figure out why only some cells with
environmentally damaged DNA turn cancerous; what breaks down in autoimmune
diseases; and how to create better tissues for replacement therapies.
STEM CELL TECHNOLOGY After animal cells differentiate into tissues and organs,
some tissues retain a group of undifferentiated cells to replace that tissue’s
damaged cells or replenish its supply of certain cells, such as red and white
blood cells. When needed, these adult stem cells (ASCs) divide in two. One cell
differentiates into the cell type the tissue needs for replenishment or
replacement, and the other remains undifferentiated.

into an ESC with the right combination of factors? Why do stem cells retain the
potential to replicate indefinitely? Is the factor that allows continual
proliferation of ESCs the same factor that causes uncontrolled proliferation of
cancer cells? If so, will transplanted ESCs cause cancer? The answers to these
questions and many more will determine the limits of the therapeutic potential of
ESCs and ASCs. Only when we understand the precise mix of factors controlling
proliferation and development will we be able to reprogram cells for therapeutic
purposes. Using stem cell cultures, researchers have begun to elaborate the
intricate and unique combination of environmental factors, molecular signals and
internal genetic programming that decides a cell’s fate. Israeli scientists
directed ESCs down specific developmental pathways by providing different growth
factors. Others discovered that nerve stem cells require a dose of vitamin A to
trigger differentiation into one specific type of nerve cell, but not another.
What factors wipe out a differentiated cell’s identity and take it back to its
embryonic state of complete plasticity? Before Dolly’s birth, we did not know we
could ask that question, much less answer it. Another type of ASC, mesenchymal
stem cells, can differentiate into at least three different cell types (fat cells,
bone cells and cartilage cells) when cultured cells are given the proper mix of
nutrients and growth factors. However, the stem cells must be touching each other
to become fat cells; if the cell density is too high, they will not differentiate
into bone cells even when provided the appropriate nutrients and chemical signals.
Researchers have recently demonstrated that some types of mesenchymal stem cells
might have even more developmental flexibility in vivo. When injected into mouse
embryos, these cells differentiate into most of the cell types found in mice. In
2005, researchers at Johns Hopkins University began what is believed to be the
first clinical trial in the United States of adult mesenchymal stem cells to
repair muscle damaged by heart attack. Another approach to developing therapies
based on cells takes a different tack. Rather than determining the molecular
events that turn a stem cell into a specific cell type, scientists are studying
the de-differentiation process. What factors wipe out a differentiated cell’s
identity and take it back to its embryonic state of complete plasticity? Before
Dolly’s birth, we did not know we could ask that question, much less answer it.

26

Embryonic stem cells (ESCs) have much greater plasticity than ASCs because they
can differentiate into any cell type. Mouse embryonic stem cells were discovered
and cultured in the late 1950s. The ESCs came from 12-dayold mouse embryo cells
that were destined to become egg or sperm (germ cells) when the mouse matured. In
1981, researchers found another source of mouse ESCs with total developmental
plasticity—cells taken from a 4-dayold mouse embryo. In the late 1990s researchers
found that human ESCs could be derived from the same two sources in humans:
primordial germ cells and the inner cell mass of 5-day-old embryos. Scientists
also have been able to isolate pluripotent stem cells from human placentas donated
following normal, full-term pregnancies. Under certain culture conditions, these
cells were transformed into cartilagelike and fat-like tissue. Maintaining
cultures of ESCs and ASCs can provide answers to critical questions about cell
differentiation: What factors determine the ultimate fate of unspecialized stem
cells? How plastic are adult stem cells? Could we convert an ASC
Biotechnology Industry Organization n Guide to Biotechnology
Scientists had assumed a specialized animal cell could not revert to the
unspecialized status it relinquished in the first few days after the fertilized
egg began to divide. (Interestingly, specialized plant cells retain the potential
to de-specialize.) They assumed a gene turned off during the differentiation
process could not simply be activated. The birth of Dolly proved that assumption
was incorrect. In a procedure known as somatic cell nuclear transfer, a nucleus
from a fully differentiated body (somatic) cell was placed in an egg, and its
identity—adult sheep mammary gland cell nucleus—was erased. That egg developed
into Dolly. The birth of Dolly showed that the genetic programming of a nucleus
from a specialized somatic cell can be erased and reprogrammed, in vitro, by
placing it in an egg cell. The egg develops into a 5- or 6-day-old embryo that is
genetically identical to the animal that provided the nucleus, and cells taken
from the embryo can develop into any cell type found in the animal. Because we
have learned how to generate ESCs containing undifferentiated genetic material
from adult cells for some animals, it is likely we could develop techniques for
using human patients’ own genetic material to develop replacement cells and
tissues. Others have found that differentiated blood cells, when starved, revert
to a stem cell-like condition. With the proper coaxing, scientists converted those
cells into nerve and liver cells and even into blood vessels, which consist of two
cell types with very different functions: muscle cells for contraction and cells
lining the inner surface for movement of substances into and out of the blood. In
addition, scientists have established conditions for de-differentiating a highly
specialized type of nerve cell into a type of neural stem cell, which were then
reprogrammed into many other types of cells found in the nervous system. In 2005,
Harvard University scientists succeeded in creating cells similar to ESCs by
fusing a human skin cell with an ESC. The resulting hybrid cell was de-
differentiated and ESC-like. Continued progress in this area of de-differentiation
and re-differentiation could some day obviate the need for ESCs in research.
UNDERSTANDING GENE FUNCTION The cell processes described above—growth,
proliferation, differentiation, apoptosis—and many more are carried out and
controlled by proteins. Proteins are the molecular players that regulate and drive
each minute step of the overall process.

Understanding the details of cell processes in health and disease means

understanding proteins. Because genes contain the information for making proteins,
understanding proteins means understanding gene function. The tools of
biotechnology give scientists myriad opportunities to study gene function. Here
are only a few of the ways biotechnology allows investigators to probe the genetic
basis of cell functions. Molecular Cloning If scientists voted for the most
essential biotechnology research tool, molecular cloning would likely win. If
scientists voted for the most essential biotechnology research tool, molecular
cloning would likely win. Either directly or indirectly, molecular cloning has
been the primary driving force of the biotechnology revolution and has made
remarkable discoveries routine. The research findings made possible through
molecular cloning include identifying, localizing and characterizing genes;
creating genetic maps and sequencing entire genomes; associating genes with traits
and determining the molecular basis of the trait. Molecular cloning involves
inserting a new piece of DNA into a cell in such a way that it can be maintained,
replicated and studied. To maintain the new DNA fragment, scientists insert it
into a circular piece of DNA called a plasmid that protects the new fragment from
the DNAdegrading enzymes found in all cells. Because a piece of DNA is inserted,
or recombined with, plasmid DNA, molecular cloning is a type of recombinant DNA
technology. The new DNA, now part of a recombinant molecule, replicates every time
the cell divides. In molecular cloning, the word clone can refer to the new piece
of DNA, the plasmid containing the new DNA and the collection of cells or
organisms, such as bacteria, containing the new piece of DNA. Because cell
division increases, or “amplifies,” the amount of available DNA, molecular cloning
provides researchers with an unlimited amount of a specific piece of genetic
material to manipulate and study. In addition to generating many copies of
identical bits of genetic material, molecular cloning also enables scientists to
divide genomes into manageable sizes. Even the simplest genome—the total genetic
material in an organism—is too cumbersome for investigations of single genes. To
create packages of genetic material of sizes that are more amenable to studies
such as gene sequencing and mapping, scientists divide genomes into thousands of
pieces and insert each piece into different cells. This collection of cells
containing an organism’s entire genome is known as a
Guide to Biotechnology n Biotechnology Industry Organization

27
DNA library. Because identifying and mapping genes relies on DNA libraries created
with molecular cloning, “to clone” can also mean to identify and map a gene. One
of the primary applications of molecular cloning is to identify the protein
product of a particular gene and to associate that protein with the appearance of
a certain trait. While this is useful for answering certain questions, genes do
not act in isolation of one another. To truly understand gene function, we need to
monitor the activity of many genes simultaneously. Microarray technology provides
this capability. Microarray Technology Researchers can now gain a richer
appreciation of gene function because microarray technology allows them to monitor
the expression of hundreds or thousands of genes at one time. Recently, a 12,000-
gene microarray allowed researchers to identify the 200 or so genes that, based on
their gene expression profiles, distinguish stem cells from differentiated cells.

pieces of DNA (or, more often, its close relative, RNA) that prevent production of
the protein encoded in the blocked DNA. A related, but mechanistically different
method of silencing genes is known as RNA interference (RNAi). Antisense
technology works by using a single strand of DNA or RNA to physically block
protein production from the RNA template. In RNA interference, adding small,
double-stranded pieces of RNA to a cell triggers a process that ends with the
enzymatic degradation of the RNA template. RNA interference, which was discovered
serendipitously in plants in the 1990s, appears to be a natural mechanism that
virtually all organisms use to defend their genomes from invasion by viruses. RNAi
therapies are now in clinical testing. Precisely blocking the functions of single
genes to assess gene function can provide important insights into cell processes.
Precisely blocking the functions of single genes to assess gene function can
provide important insights into cell processes. Most cell processes are structured
as pathways that consist of small biochemical steps. Sometimes the pathway
resembles a chain reaction and consists of a complex cascade of events caused by
one protein causing changes in another protein. At other times, the pathway is a
sequence of enzyme-catalyzed reactions in which each enzyme (protein) changes a
molecule slightly and then hands it off to the next enzyme. The physical
manifestation of a certain trait or disease is the culmination of many or all of
these steps. Gene Knockouts One of biotech’s most powerful research tools for
elucidating gene function is targeted mutations, or gene knockouts. By deleting or
disrupting specific genes in cells, we gain valuable information about the role a
given gene plays in the expression of a certain protein. When gene-knockout
technology is combined with our ability to derive genetically identical animals
from cultured cells, we can determine how the absence of this protein affects the
whole organism. Scientists have created a wide variety of genetically identical
colonies of mice with very specific genes knocked out to study the processes of
gene regulation, DNA repair and tumor development. For years scientists have used
animal models of disease to understand the pathophysiology of disease in humans.
Our research capabilities in disease pathology broadened greatly

28

Monitoring simultaneous changes in gene function will shed light on many basic
biological functions. For example, scientists are using microarrays to observe the
changes in gene activity that occur as normal cells turn cancerous and begin to
proliferate. In addition to providing information on possible causes of cancer,
this type of information can shed light on the genes that let a cell know that it
is time to divide. Microarrays that display various tissue types allow us to
determine the different genes that are active in different tissues. Simply being
able to link an active gene to a tissue type can clue researchers in on its
function. For example, a plant gene active in leaves but not roots or seeds may be
involved in photosynthesis. Different environmental conditions also affect gene
expression. Researchers subject plants to stresses such as cold and drought, and
then they use microarray technology to identify the genes that respond by
initiating protein production. Researchers are also comparing gene activities of
microbes that live in environments contaminated with pollutants to that of others
that live in pristine environments to identify genes that break down environmental
contaminants. Antisense and RNA Interference Another approach to understanding the
relationship of genes, proteins and traits involves blocking gene expression and
measuring resulting biochemical or visible changes. Scientists use antisense
technology to block genes selectively. Antisense molecules are small
Biotechnology Industry Organization n Guide to Biotechnology
as we coincidentally learned more about the genetic causes of diseases, developed
methods of knocking out specific genes, and learned how to maintain cultures of
embryonic stem cells. Using this suite of technologies, researchers have created
animal disease models for Alzheimer’s disease, aging, cancer, diabetes, obesity,
cardiovascular disease and autoimmune diseases. Using nuclear transfer and
embryonic stem cell culture, we should be able to develop animal disease models
for many more species.

gram are structural genomics research on a grand scale. In addition to genome

mapping and sequencing, the objective of structural genomics research is gene
discovery, localization and characterization. Private and public structural
genomics projects have generated genome maps and complete DNA sequences for many
organisms, including crop plants and their pathogens, disease-causing bacteria and
viruses, yeast that are essential to the food processing and brewing industries,
nitrogen-fixing bacteria, the malaria parasite and the mosquito that transmits it,
and the microbes we use to produce a wide variety of industrial products. In
addition, in the spring of 2003, the Human Genome Project was completed (“rough
drafts” were completed in 2000). Because all living organisms share a common
heritage and can translate genetic information from many other organisms into
biological function, the different genome projects inform each other, and any gene
discovered through these projects could have wide applicability in many industrial
sectors. Knowing the complete or partial DNA sequences of certain genes or markers
can provide researchers with useful information, even if the precise details of
gene function remain unknown. For example, sequence data alone can
n

Putting the Pieces Together: ‘Omics’

iotech’s powerful research tools have set the fast pace for basic scientific
discovery. They have enabled researchers to tease apart cellular and genetic
processes so thoroughly that we are beginning to understand biological systems at
their most fundamental level—the molecular level. But biological organisms do not
operate as molecular bits and pieces. The only way to truly understand organisms
is to reassemble these bits and pieces into systems and networks that interact
with each other. This need to assemble separate findings into a complete picture
has given birth to a rash of “omics”: genomics, proteomics, metabolomics,
immunomics, and transcriptomics. These research avenues attempt to integrate
information into whole systems rather than focus on the individual components in
isolation from each other. The biotechnologies are important tools in these
endeavors, but the information technologies are also essential for integrating
molecular data into a coherent whole. The fields of research described below
bridge scientific discoveries in cellular and molecular biology with their
commercial applications.
GENOMICS Genomics is the scientific study of the genome and the role genes play,
individually and collectively, in determining structure, directing growth and
development, and controlling biological functions. It consists of two branches:
structural genomics and functional genomics.

29

help plant breeders follow specific traits in a breeding program and test for
inheritance without having to rear the plants to reproductive maturity. be used to
isolate specific recombinant molecules or microbes with unique biochemistry.
identify the genes involved in complex traits that are controlled by many genes
and those that have an environmental component. detect microbial contaminants in
cell cultures.
n

Structural Genomics The field of structural genomics includes the construction and
comparison of various types of genome maps and large-scale DNA sequencing. The
Human Genome Project and the less well-publicized Plant Genome Research Pro-

Functional Genomics While sequencing entire genomes, discovering genes and mapping
them are truly remarkable achievements, they represent only the first milestone in
the genomics revolution. Gene sequence and mapping data mean little until we
determine what those genes do, how they are regulated, and how the activity of one
affects others. This field of study, known as functional genomics, enables
researchers to navigate the complex structure of the human genome and to make
sense of its content. Studies show that mammalian genomes have roughly the same
number of genes and, in some cases, species less complex than mammals have a
higher number of genes.
Guide to Biotechnology n Biotechnology Industry Organization
It is not, however, the number of genes that is important to our understanding of
the various species, but, rather the compositional, functional, chemical and
structural differences that dictate differentiation. Evolutionary analysis is
emerging as a critical tool for elucidating the function and interactions of genes
within a genome. Molecular evolutionists use comparative genomics techniques and
biofinormatics technologies to analyze the number of changes that DNA sequences
undergo through the course of evolution. Using this data, researchers can
recognize functionally important regions within genes and even construct a
molecular timescale of species evolution. The fruit fly (Drosophila melanogaster)
has proven to be an invaluable model in the study of inherited genes. The humble
fly’s desirable attributes include hardiness, availability and short generation
time. As a result, a wealth of research and data produced from the study of the
fruit fly are publicly available. Researchers at the Center for Evolutionary
Functional Genomics at the Arizona Biodesign Institute in Arizona have developed
“FlyExpress,” a web-based informatics tool that uses advanced image processing and
database techniques. Using this system, researchers can rapidly analyze gene
expression patterns in embryonic image data.
PROTEOMICS Each cell produces thousands of proteins, each with a specific
function. This collection of proteins in a cell is known as its proteome, and
proteomics is the study of the structure, function, location and interaction of
proteins within and between cells. The Human Proteome Organization estimates that
since a human gene is able to code for potentially thousands of proteins,
researchers could ultimately establish the genesis of at least one million
proteins in the human proteome.

subunits (nucleotides). Proteins, which consist of a chain of up to 22 randomly

repeating subunits (amino acids), wind into complicated, intricate shapes, and
those shapes are essential to each protein’s function. We know that the sequence
of amino acids affects the shape a protein assumes, but we are not clear on the
rules that govern the folding process. Therefore, using the amino acid sequence to
predict protein shape and, through this, protein functionality is beyond our
current capabilities. There are thousands of proteins that differ greatly from one
another, even within the same individual, but DNA molecules are remarkably
similar. In addition, unlike the unvarying genome, an organism’s proteome is so
dynamic that an almost infinite variety of protein combinations exists. The genome
is largely constant, irrespective of cell type and age, but the proteome varies
from one cell type to the next, from one year to the next, and even from moment to
moment. The cellular proteome changes in response to other cells in the body and
external environmental conditions. A single gene can code for different versions
of a protein, each with a different function. The genome is largely constant,
irrespective of cell type and age, but the proteome varies from one cell type to
the next, from one year to the next, and even from moment to moment. When the
Human Genome Project began, the first task researchers took on was developing the
necessary tools for completing the project’s goals and objectives. Proteomics
researchers likewise are developing tools to address many proteomics objectives,
such as
n

30

cataloging all of the proteins produced by different cell types. determining how
age, environmental conditions and disease affect the proteins a cell produces.
discovering the functions of these proteins. charting the progression of a process
—such as disease development, the steps in the infection process or the
biochemical response of a crop plant to insect feeding—by measuring waxing and
waning protein production. discovering how a protein interacts with other proteins
within the cell and from outside the cell.
n

Genes exert their effects through proteins; gene expression is protein production.
Ultimately, we must combine structural genomics, functional genomics and
proteomics to fully comprehend the relationship between genes, protein production
and traits. And yet, proteomics presents researchers with challenges more numerous
and more difficult than those encountered in genomics research. The structure of a
protein molecule is much more complicated than the DNA molecule, which is a linear
molecule composed of only four randomly repeating

n n

Biotechnology Industry Organization n Guide to Biotechnology

BIOINFORMATICS TECHNOLOGY Biotechnology as we know it today would be impossible
without computers and the Internet. The common language of computers allows
researchers all over the world to contribute and access biological data; the
universal language of life enables collaborations among scientists studying any
plant, animal or microbe.

tial component of every step in product research, development and

commercialization.
SYNTHETIC BIOLOGY Now that scientists have broken genomes apart, can they put them
together? Synthetic biology, sometimes described as the inverse of systems
biology, seeks to do just that and assemble genomes and whole organisms. In 2002,
researchers at Stony Brook University synthesized the polio virus. Three years
later, the 1918 pandemic flu virus was synthesized at the Armed Forces Institute
of Pathology.

One of the most formidable challenges facing researchers today remains in

informatics: how to make sense of the massive amount of data provided by
biotechnology’s powerful research tools and techniques. The primary problems are
how to collect, store and retrieve information; manage data so that access is
unhindered by location or compatibility; provide an integrated form of data
analysis; and develop methods for visually representing molecular and cellular
data. Bioinformatics technology uses computational tools provided by the
information technology revolution, such as statistical software, graphics
simulation, algorithms and database management, for consistently organizing,
accessing, processing and integrating data from different sources. Bioinformatics
consists, in general, of two branches. The first concerns data gathering, storing,
accessing and visualization; the second branch focuses more on data integration,
analysis and modeling and is often referred to as computational biology. Systems
biology is the branch of biology that attempts to use biological data to create
predictive models of cell processes, biochemical pathways and, ultimately, whole
organisms. Systems biology is the branch of biology that attempts to use
biological data to create predictive models of cell processes, biochemical
pathways and, ultimately, whole organisms. Systems biologists develop a series of
mathematical models of processes and pathways to elucidate the full complexity of
the interactions that occur in biological systems. Only with iterative
biosimulations generated by computers will we be able to develop a complete
picture of the system we are studying. As an indicator of how essential computers
have become to biotechnology labs, the phrase in silico has joined in vivo and in
vitro as a descriptor of experimental conditions. Over time, biotechnology
products will be increasingly focused on systems and pathways, not single
molecules or single genes. Bioinformatics technology will be an essen-

On a more positive note, synthetic biologists also are seeking to build organisms
that can create energy and medicines. A project to develop a bacterial strain that
can produce a malaria drug precursor attracted more than $40 million in funding
from the Gates Foundation.

Product Development Applications

31

ust understanding biological systems in health and disease is not enough.

Companies must turn the information gleaned from basic research, genomics and
proteomics into useful products. The tools and techniques of biotechnology are
helpful not only in product discovery but also are useful throughout the
development process.
PRODUCT DISCOvERY A fundamental challenge facing many sectors of the biotechnology
industry is how to improve the rate of product discovery. Many believe that
current technology can vastly reduce the time it takes to discover a drug. What is
more, biotechnology is creating the tools to pinpoint the winning compounds far
earlier in the process.

For example, because we had long known the amino acid sequences of insulin and
growth hormone, we began commercial production of recombinant versions relatively
soon after we first used recombinant DNA technology to genetically change
microbes. Discovering endogenous proteins that stimulate the immune system and red
blood cell production led rapidly to their use as therapeutics. Other basic
research has led to new prod-

Guide to Biotechnology n Biotechnology Industry Organization

ucts such as enzymes for food processing or industrial manufacturing and microbes
with novel biochemistry for breaking down or synthesizing molecules. In addition,
knowing only portions of the DNA sequence of certain genes can provide useful
products, even without knowing about the gene’s function or the protein it
encodes. For example, new product discoveries based solely on DNA sequence data
acquired through structural genomics include
n n

intervention. Often, the biotechnology-derived therapeutic compound will not be a

gene, protein or any type of biological molecule, but the therapeutic target will
always be a gene or protein. Having structure and function information about the
genes and their protein products involved in diseases makes finding useful
molecules more rational than trial and error—hence the phrase rational drug
design. Having structure and function information about the genes and their
protein products involved in diseases makes finding useful molecules more rational
than trial and error—hence the phrase rational drug design. Having the complete
roster of the molecular players also gives us multiple targets to monitor,
modulate or block; every step in a complex sequential process is a possible point
of intervention. Knowing the molecular player associated with each step also
allows us to focus strategically on the malfunctioning points in a pathway to
correct the problem. As a result, we can target products to problems more
accurately. For example, we have elaborated the cascade of events that typifies
programmed cell death (apoptosis), and we now know chemotherapy and radiation
induce apoptosis. Therefore, tumors that resist chemotherapy and radiation
treatments have changes in their apoptosis mechanism. Targeting the molecules
involved in apoptosis should lead to new therapies for resistant tumors. Using our
knowledge of genomics and proteomics, we can identify not only the molecular
target, but also the location of its bull’s-eye, which is usually one or a few
locations within a protein molecule. The new field of chemical genomics allows us
to identify small inorganic molecules that bind to those sites. These small
molecules can be drawn from a collection of molecules built painstakingly by
chemists over decades, or they might be the products of a relatively new
technology that uses robotics to generate millions of chemical compounds in
parallel processes, combinatorial chemistry.
PRODUCT DEvELOPMENT Genomics, proteomics, microarray technology, cell culture,
monoclonal antibody technology and protein engineering are just a few of the
biotechnologies that are being brought to bear at various stages of product
development. Understanding the molecular basis of a process will provide measures
of product efficacy that can be assayed in cells, which can save companies time
and money and lead to better products. For example,

diagnostic tests for plant, animal and human diseases. tests to identify the
presence of genetically modified food products. antisense molecules to block gene
expression. tests to identify genetic susceptibilities to certain diseases.
diagnostics for microbial contaminants in food products or donated blood. tests
for drug-resistant mutants of HIV and other pathogens. gene-based therapeutics,
such as DNA vaccines and gene therapies.

n n

32

n
In general, however, the information accumulating from studies of structural and
functional genomics, proteomics and basic biology bolsters new product discovery
by helping us understand the basic biology of the process we want to control or
change. Understanding the process leads to new and better products, and sometimes
provides new uses for old products. For example, understanding the molecular basis
of high blood cholesterol and diabetes, as well as the molecular mechanism of
action of the statins, leads many researchers to believe that the statins, which
were designed to reduce cholesterol levels, might also help people with diabetes.
The benefits of understanding to new product discovery apply to all industrial
sectors that use biotechnology: pharmaceuticals, diagnostics, agriculture, food
processing, forestry and industrial manufacturing. Medical applications of
biotechnology illustrate how understanding molecular details encourages product
discovery. New Targets The deconstruction of disease pathways and processes into
their molecular and genetic components illuminates the exact point in the process
that is malfunctioning and, therefore, the point in need of therapeutic
Biotechnology Industry Organization n Guide to Biotechnology
agricultural biotechnology companies developing insectresistant plants can measure
the amount of protective protein that a plant cell produces and avoid having to
raise plants to maturity. Pharmaceutical companies can use cell culture and
microarray technology to test the safety and efficacy of drugs and observe adverse
side effects early in the drug development process. In addition, by genetically
modifying animals to produce the therapeutic protein target or developing
transgenic animal models of human diseases that closely resemble the
pathophysiology of human diseases, the results from clinical trials should be more
applicable to human systems. As a result, companies can identify safe and
effective product candidates much earlier in the product development process. The
biotechnologies can also improve profitability by shortening the product
development process because a single technology might be used at many steps in the
process. For example, a small piece of DNA that the research lab uses to locate a
gene in the genome of a plant pathogen may eventually become a component of a
diagnostic test for that pathogen. A monoclonal antibody developed to identify
therapeutic leads might be used to recover and purify that therapeutic compound
during scale-up. Targeted Products We have already described the value detailed
information about cell differentiation holds for advances in tissue engineering
and regenerative medicine. Without this information, regenerative medicine would
have little future. Similar scenarios apply to all cell processes. For example,
because we now understand the cell cycle and apoptosis, we are better able to
develop products to treat diseases rooted in these processes. All cancers stem
from uncontrolled cell multiplication and autoimmune diseases from a failure of
apoptosis. Drugs for controlling these problems can be targeted to any of the
molecules or cell structures involved in these cell processes. Functional genomics
has provided information on the molecular changes that occur in precancerous
cells. Knowing this, we can develop detection tests for molecular markers that
indicate the onset of cancer before visible cell changes or symptoms appear. Many
chemotherapeutic agents target proteins active during cell division, making no
distinction between healthy cells that divide frequently (such as those that
produce hair or blood cells) and cancerous cells. To protect those healthy cells,
some companies are developing medicines that would stop the cell cycle of healthy
cells before delivering a dose of a chemotherapeutic agent.

33
Products Tailored to Individuals We are entering the age of personalized medicine
in which genetic differences among patients are acknowledged and used to design
more effective treatments. A medicine’s effectiveness and safety often varies from
one person to the next. Using data acquired in functional genomics, we will be
able to identify genetic differences that predispose patients to adverse reactions
to certain drugs or make them good subjects for other drugs. This tailoring of
therapeutics to the genetic makeup of the patient is known as pharmacogenomics.
Just as people do not respond to a drug the same way, not all stages or types of a
disease are the same. Medicines targeted to earlier stages of a disease will not
affect a disease that has moved beyond that stage. Some disease processes leave
molecular footprints as they go from one stage to the next. Knowing the molecular
details allows physicians to diagnose how far the disease has progressed and
design an appropriate therapy. Some diseases also vary in aggressiveness. For
example, some forms of breast cancer are more aggressive than others and require
different therapeutic approaches. By identifying the unique molecular markers or
different types of cancer, we help physicians choose the correct treatment.
Guide to Biotechnology n Biotechnology Industry Organization
Health-Care Applications

B
W

iotechnology tools and techniques open new research avenues for discovering how
healthy bodies work and what goes wrong when problems arise. Knowing the molecular
basis of health and disease leads to improved methods for treating and preventing
diseases. In human health care, biotechnology products include quicker and more
accurate diagnostic tests, therapies with fewer side effects and new and safer
vaccines.

Diagnostics
e can now detect many diseases and medical conditions more quickly and with
greater accuracy because of new, biotechnology-based diagnostic tools. A familiar
example of these benefits is the new generation of home pregnancy tests that
provide more accurate results much earlier than previous tests. Tests for strep
throat and many other infectious diseases provide results in minutes, enabling
treatment to begin immediately, in contrast to the two- or three-day delay of
previous tests.

The wealth of genomics information now available will greatly assist doctors in
early diagnosis of hereditary diseases, such as type I diabetes, cystic fibrosis,
early-onset Alzheimer’s Disease, and Parkinson’s Disease—ailments that previously
were detectable only after clinical symptoms appeared. Genetic tests will also
identify patients with a predisposition to diseases, such as various cancers,
osteoporosis, emphysema, type II diabetes and asthma, giving patients an
opportunity to prevent the disease by avoiding triggers such as diet, smoking and
other environmental factors. Biotechnology-based diagnostic tests are not only
altering disease diagnosis but also improving the way health care is provided.
Many tests are portable, so physicians conduct the tests, interpret results and
decide on treatment literally at the patient’s bedside. In addition, because many
of these diagnostic tests are based on color changes similar to a home pregnancy
test, the results can be interpreted without technically trained personnel,
expensive lab equipment or costly facilities, making them more available to poorer
communities and people in developing countries. Physicians will someday be able to
immediately profile an infection being treated and, based on the results, choose
the most effective antibiotics. But the human health benefits of biotechnology
detection methodologies go beyond disease diagnosis. For example, biotechnology
detection tests screen donated blood for the pathogens that cause AIDS and
hepatitis.

34

A familiar example of biotechnology’s benefits is the new generation of home

pregnancy tests that provide more accurate results much earlier than previous
tests. Biotechnology also has created a wave of new genetic tests. Today there are
almost 1,000 such tests, according to genetests.org. Many of those tests are for
genetic diseases, while others test predisposition to disease. Emerging
applications include tests to predict response to medicines and assist with
nutritional planning. Biotechnology has lowered the costs of diagnostics in many
cases. A blood test developed through biotechnology measures low-density
lipoprotein (“bad” cholesterol) in one test, without fasting. We now use
biotechnology-based tests to diagnose certain cancers, such as prostate and
ovarian cancer, by taking a blood sample, eliminating the need for invasive and
costly surgery. In addition to diagnostics that are cheaper, more accurate and
quicker than previous tests, biotechnology is allowing us to diagnose diseases
earlier in the disease process, which greatly improves a patient’s prognosis.
Proteomics researchers are discovering molecular markers that indicate incipient
diseases before visible cell changes or disease symptoms appear. Soon physicians
will have access to tests for detecting these biomarkers before the disease
begins.

Therapeutics

iotechnology will make possible improved versions of today’s therapeutic regimes

as well as innovative treatments that would not be possible without these new
techniques. Biotechnology therapeutics approved by the U.S. Food and Drug
Administration (FDA) to date are used to treat many diseases, including leukemia
and other cancers, anemia, cystic fibrosis, growth deficiency, rheumatoid
arthritis, hemophilia, hepatitis, genital warts, and transplant rejection. The
therapies discussed below share a common foundation. All make use of biological
substances and processes designed by nature. Some use the human body’s own tools
for fighting infections and correcting problems. Others are natural products of
plants and animals. The large-scale manufacturing processes for producing
therapeutic bio-

Biotechnology Industry Organization n Guide to Biotechnology

logical substances also rely on nature’s molecular production mechanisms. Here are
just a few examples of the types of therapeutic advances biotechnology now makes
feasible.
USING NATURAL PRODUCTS AS THERAPEUTICS Many living organisms produce compounds
that have therapeutic value for us. For example, many antibiotics are produced by
naturally occurring microbes, and a number of medicines on the market, such as
digitalis, are made by plants. Plant cell culture, recombinant DNA technology and
cellular cloning now provide us with new ways to tap into natural diversity.

insulin—a protein hormone that regulates blood glucose levels. Diabetes results
from an inadequate supply of insulin.

USING GENES TO TREAT DISEASES Gene therapy presents an opportunity using DNA, or
related molecules such as RNA, to treat diseases. For example, rather than giving
daily injections of missing proteins, physicians could supply the patient’s body
with an accurate instruction manual—a nondefective gene— correcting the genetic
defect so the body itself makes the proteins. Other genetic diseases could be
treated by using small pieces of RNA to block mutated genes.

As a result, we are investigating many plants and animals as sources of new

medicines. Ticks and bat saliva could provide anticoagulants, and poison-arrow
frogs might be a source of new painkillers. A fungus produces a novel, antioxidant
enzyme that is a particularly efficient at mopping up free radicals known to
encourage tumor growth. Byetta™ (exenatide), an incretin mimetic, was chemically
copied from the venom of the gila monster and approved in early 2005 for the
treatment of diabetes. PRIALT® (ziconotide), a recently approved drug for pain
relief, is a synthetic version of the toxin from a South Pacific marine snail. The
ocean presents a particularly rich habitat for potential new medicines. Marine
biotechnologists have discovered organisms containing compounds that could heal
wounds, destroy tumors, prevent inflammation, relieve pain and kill
microorganisms. Shells from marine crustaceans, such as shrimp and crabs, are made
of chitin, a carbohydrate that is proving to be an effective drug-delivery
vehicle. Marine biotechnologists have discovered organisms containing compounds
that could heal wounds, destroy tumors, prevent inflammation, relieve pain and
kill microorganisms.
REPLACING MISSING PROTEINS Some diseases are caused when defective genes don’t
produce the proteins (or enough of the proteins) the body requires. Today we are
using recombinant DNA and cell culture to produce the missing proteins.
Replacement protein therapies include
n

Only certain genetic diseases are amenable to correction via replacement gene
therapy. These are diseases caused by the lack of a protein, such as hemophilia
and severe combined immunodeficiency disease (SCID), commonly known as the “bubble
boy disease.” Some children with SCID are being treated with gene therapy and
enjoying relatively normal lives, although the therapy has also been linked to
leukemia. Hereditary disorders that can be traced to the production of a defective
protein, such as Huntington’s disease, may be best treated with RNA that
interferes with protein production. Medical researchers also have discovered that
gene therapy can treat diseases other than hereditary genetic disorders. They have
used briefly introduced genes, or transient gene therapy, as therapeutics for a
variety of cancers, autoimmune disease, chronic heart failure, disorders of the
nervous system and AIDS. In late 2003, China licensed for marketing the first
commercial gene therapy product, Gendicine, which delivers the P53 tumor
suppressor gene. The product treats squamous cell carcinoma of the head and neck,
a particularly lethal form of cancer. Clinical trial results were impressive:
Sixty-four percent of patients who received the gene therapy drug, in weekly
injections for two months, showed a complete regression and 32 percent attained
partial regression. With the addition of chemotherapy and radiation, results were
improved greatly, with no relapses after three years.
CELL TRANSPLANTS Approximately 18 people die each day waiting for organs to become
available for transplantation in the United States. To circumvent this problem,
scientists are investigating ways to use cell culture to increase the number of
patients who might benefit from one organ donor. Liver cells grown in culture and
implanted into patients kept them alive until
Guide to Biotechnology n Biotechnology Industry Organization

35

factor VIII—a protein involved in the blood-clotting process, lacked by some

hemophiliacs.
For example, the cytokine branch, which stimulates other immune system branches,
includes the interleukins, interferons and colony-stimulating factors—all of which
are proteins. Because of biotechnology, these proteins can now be produced in
sufficient quantities to be marketed as therapeutics. Small doses of interleukin-2
have been effective in treating various cancers and AIDS, while interleukin-12 has
shown promise in treating infectious diseases such as malaria and tuberculosis.
Researchers can also increase the number of a specific type of cell, with a highly
specific function, from the cellular branch of the immune system. Under certain
conditions, the immune system may not produce enough of the cell type a patient
needs. Cell culture and natural growth factors that stimulate cell division allow
researchers to provide or help the body create the needed cell type. Cancer
vaccines that help the immune system find and kill tumors have also shown
therapeutic potential. Unlike other vaccines, cancer vaccines are given after the
patient has the disease, so they are not preventative. They work by intensifying
the reactions between the immune system and tumor. Despite many years of research,
cancer vaccines have not yet emerged as a viable strategy to fight cancer.
Nonetheless, researchers are optimistic that this kind of approach to battling
cancer would be a major improvement over the therapies used today.
SUPPRESSING THE IMMUNE SYSTEM In organ-transplant rejections and autoimmune
diseases, suppressing our immune system is in our best interest. Currently we are
using monoclonal antibodies to suppress, very selectively, the type of cell in the
immune system responsible for organ-transplant rejection and autoimmune diseases,
such as rheumatoid arthritis and multiple sclerosis. Patients given a
biotechnology-based therapeutic often show significantly less transplant rejection
than those given cyclosporin, a medicine that suppresses all immune function and
leaves organ-transplant patients vulnerable to infection.

36

a liver became available. In one study of patients with type 1 diabetes,

researchers implanted insulin-producing cells from organ donors into the subjects’
livers. Eighty percent of the patients required no insulin injections one year
after receiving pancreatic cells; after two years, 71 percent had no need for
insulin injections. In another study, skeletal muscle cells from the subject
repaired damage to cardiac muscle caused by a heart attack. Drugs for suppressing
the immune response must be given if the transplanted cells are from someone other
than the patient. Researchers are devising new ways to keep the immune system from
attacking the transplanted cells. One method being used is cell encapsulation,
which allows cells to secrete hormones or provide a specific metabolic function
without being recognized by the immune system. As such, they can be implanted
without rejection. Other researchers are genetically engineering cells to express
a naturally occurring protein that selectively disables immune system cells that
bind to it. Other conditions that could potentially be treated with cell
transplants are cirrhosis, epilepsy and Parkinson’s Disease.
STIMULATING THE IMMUNE SYSTEM The immune system is made up of different branches,
each containing different types of “soldiers” that interact with each other in
complex, multifaceted ways.

Inflammation, another potentially destructive immune system response, can cause

diseases, such as ulcerative colitis. Two cytokines, interleukin-1 and tumor
necrosis factor, stimulate the inflammatory response, so a number of biotechnology
companies are investigating therapeutic compounds that block the actions or
decrease production of these cytokines.

Biotechnology Industry Organization n Guide to Biotechnology

XENOTRANSPLANTATION Organ transplantation provides an especially effective
treatment for severe, life-threatening diseases of the heart, kidney and other
organs. According to the United Network of Organ Sharing (UNOS), in the United
States more than 92,000 people were on organ waiting lists as of May 19, 2006.

in burn victims. Gauze-like mats made of long threads of fibrinogen, the protein
that triggers blood clotting, can be used to stop bleeding in emergency
situations. Adhesive proteins from living organisms are replacing sutures and
staples for closing wounds. They set quickly, produce strong bonds, and are
absorbed.

Organs and cells from other species—pigs and other animals—may be promising
sources of donor organs and therapeutic cells. This concept is called
xenotransplantation. Organs and cells from other species—pigs and other animals—
may be promising sources of donor organs and therapeutic cells. This concept is
called xenotransplantation. The most significant obstacle to xenotransplantation
is the immune system’s self-protective response. When nonhuman tissue is
introduced into the body, the body cuts off blood flow to the donated organ. The
most promising method for overcoming this rejection may be various types of
genetic modification. One approach deletes the pig gene for the enzyme that is the
main cause of rejection; another adds human genetic material to disguise the pig
cells as human cells. The potential spread of infectious disease from other
species to humans through xenotransplantation needs close attention. However, a
1999 study of 160 people who had received pig cells as part of treatments showed
no signs of ill health related to this exposure. In addition, scientists have
succeeded at deleting the gene that triggers immune activity from a type of pig
that cannot be infected with the virus that causes the most concern.
USING BIOPOLYMERS AS MEDICAL DEvICES Nature has also provided us with biological
molecules that can serve as useful medical devices or provide novel methods for
drug delivery. Because they are more compatible with our tissues and our bodies
absorb them when their job is done, they are superior to most man-made medical
devices or delivery mechanisms.

Personalized Medicine
In the future, our individual genetic information will be used to prevent disease,
choose medicines and make other critical decisions about health. This is
personalized medicine, and it could revolutionize healthcare, making it safer,
more cost-effective and, most importantly, more clinically effective.
Pharmacogenomics is a key term, referring to the use of information about the
genome to develop drugs. Pharmacogenetics is also used to describe the study of
the ways genomic variations affect drug responses. The variations affecting
treatment response may involve a single gene (and the protein it encodes) or
multiple genes/proteins. For example, some painkillers work only when body
proteins convert them from an inactive form to an active one. How well these
proteins do their jobs varies considerably between people. As another example,
tiny genetic differences can change how statin drugs work to lower blood
cholesterol levels. Biotechnology researchers are interested in the use of gene-
based tests to match patients with optimal drugs and drug dosages. This concept of
personalized medicine—also called targeted therapy—is beginning to have a powerful
impact on research and treatment, especially in cancer. This concept of
personalized medicine—also called targeted therapy—is beginning to have a powerful
impact on research and treatment, especially in cancer.
CANCER The biotech breast cancer drug Herceptin® is an example of a
pharmacogenomic drug. Initially approved in 1998, Herceptin® targets and blocks
the HER2 protein receptor, which is overexpressed in some aggressive cases of
breast cancer. A test can identify which patients are overexpressing the receptor
and can benefit from the drug.
37

For example, hyaluronate, a carbohydrate produced by a number of organisms, is an

elastic, water-soluble biomolecule that is being used to prevent postsurgical
scarring in cataract surgery, alleviate pain and improve joint mobility in
patients with osteoarthritis and inhibit adherence of platelets and cells to
medical devices, such as stents and catheters. A gel made of a polymer found in
the matrix connecting our cells promotes healing

New tests have been launched recently that identify patients likely to respond to
Iressa®, Tarceva®, Gleevec® and
Guide to Biotechnology n Biotechnology Industry Organization
Campath®, and patients developing resistance to Gleevec®. Tests are available to
choose the correct dosage of a powerful chemotherapy drug for pediatric leukemia—
the tests have saved lives by preventing overdose fatalities. One of the most
exciting new tests is Genomic Health’s Oncotype DX™, which examines expression of
21 genes to quantify risk of breast cancer recurrence and predict the likelihood
that chemotherapy will benefit the patient. Impressed with the product’s results
in recent studies, the NIH in May 2006 launched a large new study called TAILORx
(Trial Assigning Individualized Options for Treatment [Rx]) that will utilize
Oncotype DX™ to predict recurrence and assign treatment to more than 10,000 women
at 900 sites in the United States and Canada. Many more pharmacogenomic cancer
products—both medicines and tests—are in development. In fact, oncology may be
entering an era when cancer treatment will be determined as much or more by
genetic signature than by location in the body.

AmpliChip® was the first DNA microarray test to be cleared by the FDA. A
microarray is similar to a computer microchip, but instead of tiny circuits, the
chip contains tiny pieces of DNA, called probes.
RACE- AND GENDER-BASED MEDICINE In 2005, the FDA for the first time approved a
drug for use in a specific race: BiDil®, a life-saving drug for heart failure in
black patients. In the 1990s, the drug had failed to beat placebo in a broad
population but showed promise in African Americans. Further testing confirmed
those results.

Although BiDil® thus far is the only drug to win a race-based approval, it’s far
from unique in its differential effects across populations. Many drugs, including
common blood-pressure medicines and antidepressants, exhibit significant racially
correlated safety and efficacy differences. For example, in a large study of one
of the most common blood pressure medications, Cozaar®, researchers found a
reduced effect in black patients—a fact that has been added to the prescribing
information for the drug. Interferon, likewise, appears to be less effective in
blacks with hepatitis than non-Hispanic white patients (19 percent vs. 52 percent
response rate), according to a recent study in the New England Journal of
Medicine. One such study found Japanese cancer patients are three times more
likely to respond to Iressa®, apparently because of a mutation in a gene for the
drug’s target, epidermal growth factor receptor. Genetic variations—mutations that
affect drug receptors, pathways and metabolizing enzymes—are thought to underlie
most of the racial, ethnic and geographic differences in drug response, making the
field ripe for biotech-style personalized medicine. NitroMed, for example, is
collecting genetic material with the hope of developing a test to identify all
patients—irrespective of race—likely to respond to BiDil®. Some companies are
exploring the concept of genderbased medicine to take into account the differences
in male and female response to medicine. Some companies are exploring the concept
of gender-based medicine to take into account the differences in male and female
response to medicine. Aspirin, for example, prevents heart attacks in men but not
in women. At least one biotech company is developing a lung cancer drug that shows
greater promise in women.

38

The idea is simple, but the project is monumental, given the variety of genetic
tools cancer cells use to grow, spread and resist treatment. The National
Institutes of Health in December 2005 announced it was taking on this challenge
through The Cancer Genome Atlas. The project aims to map all gene variations
linked to some 250 forms of cancer, not only the variations that help cause
cancer, but also those that spur growth, metastasis and therapeutic resistance.
OTHER APPLICATIONS In December 2004, the FDA approved Roche and Affymetrix’s
AmpliChip® CYP450 Genotyping Test, a blood test that allows physicians to consider
unique genetic information from patients in selecting medications and doses of
medications for a wide variety of common conditions such as cardiac disease,
psychiatric disease, and cancer.

The test analyzes one of the genes from the family of cytochrome P450 genes, which
are active in the liver to break down certain drugs and other compounds.
Variations in this gene can cause a patient to metabolize certain drugs more
quickly or more slowly than average, or, in some cases, not at all. The specific
enzyme from this family that is analyzed by this test, called cytochrome P4502D6,
plays an important role in the body’s ability to metabolize some commonly
prescribed drugs including antidepressants, anti-psychotics, beta-blockers, and
some chemotherapy drugs.
Biotechnology Industry Organization n Guide to Biotechnology
Regenerative Medicine

iotechnology permits the use of the human body’s natural capacity to repair and
maintain itself. The body’s toolbox for self-repair and maintenance includes many
different proteins and various populations of stem cells that have the capacity to
cure diseases, repair injuries and reverse age-related wear and tear.
TISSUE ENGINEERING Tissue engineering combines advances in cell biology and
materials science, allowing us to create semi-synthetic tissues and organs in the
lab. These tissues consist of biocompatible scaffolding material, which eventually
degrades and is absorbed, plus living cells grown using cell culture techniques.
Ultimately the goal is to create whole organs consisting of different tissue types
to replace diseased or injured organs.

The most basic forms of tissue engineering use natural biological materials, such
as collagen, for scaffolding. For example, two-layer skin is made by infiltrating
a collagen gel with connective tissue cells, then creating the outer skin with a
layer of tougher protective cells. In other methods, rigid scaffolding, made of a
synthetic polymer, is shaped and then placed in the body where new tissue is
needed. Other synthetic polymers, made from natural compounds, create flexible
scaffolding more appropriate for soft-tissue structures, like blood vessels and
bladders. When the scaffolding is placed in the body, adjacent cells invade it. At
other times, the biodegradable implant is seeded with cells grown in the
laboratory prior to implantation. Simple tissues, such as skin and cartilage, were
the first to be engineered successfully. Recently, however, physicians have
achieved remarkable results with a biohybrid kidney that maintains patients with
acute renal failure until the injured kidney repairs itself. A group of patients
with only a 10 to 20 percent probability of survival regained normal kidney
function and left the hospital in good health because the hybrid kidney prevented
the events that typically follow kidney failure: infection, sepsis and multi-organ
failure. The hybrid kidney is made of hollow tubes seeded with kidney stem cells
that proliferate until they line the tube’s inner wall. These cells develop into
the type of kidney cell that releases hormones and is involved with filtration and
transportation. In addition to carrying out these expected metabolic functions,
the cells in the hybrid kidney also responded to signals produced by the patient’s
other organs and tissues.

The human body produces an array of small proteins known as growth factors that
promote cell growth, stimulate cell division and, in some cases, guide cell
differentiation. These natural regenerative proteins can be used to help wounds
heal, regenerate injured tissue and advance the development of tissue engineering
described in earlier sections. As proteins, they are prime candidates for
largescale production by transgenic organisms, which would enable their use as
therapeutic agents. Some of the most common growth factors are epidermal growth
factor, which stimulates skin cell division and could be used to encourage wound
healing; erythropoietin, which stimulates the formation of red blood cells and was
one of the first biotechnology products; fibroblast growth factor, which
stimulates cell growth and has been effective in healing burns, ulcers and bone
and growing new blood vessels in patients with blocked coronary arteries;
transforming growth factor-beta, which helps fetal cells differentiate into
different tissue types and triggers the formation of new tissue in adults; and
nerve growth factors, which encourage nerve cells to grow, repair damage and could
be used in patients with head and spinal cord injuries or degenerative diseases
such as Alzheimer’s Disease.

39
Vaccines

accines help the body recognize and fight infectious diseases. Conventional
vaccines use weakened or killed forms of a virus or bacteria to stimulate the
immune system to create the antibodies that will provide resistance to the
disease. Usually only one or a few proteins on the surface of the bacteria or
virus, called antigens, trigger the production of antibodies. Biotechnology is
helping us improve existing vaccines and create new vac-

Guide to Biotechnology n Biotechnology Industry Organization

cines against infectious agents, such as the viruses that cause cervical cancer
and genital herpes.
BIOTECHNOLOGY vACCINE PRODUCTION Most of the new vaccines consist only of the
antigen, not the actual microbe. The vaccine is made by inserting the gene that
produces the antigen into a manufacturing cell, such as yeast. During the
manufacturing process, which is similar to brewing beer, each yeast cell makes a
perfect copy of itself and the antigen gene. The antigen is later purified from
the yeast cell culture. By isolating antigens and producing them in the
laboratory, it is possible to make vaccines that cannot transmit the virus or
bacterium itself. This method also increases the amount of vaccine that can be
manufactured because biotechnology vaccines can be made without using live
animals.

researchers are developing vaccines against diseases such as diabetes, chronic

inflammatory disease, Alzheimer’s Disease and cancer. Various researchers are
developing vaccines against diseases such as diabetes, chronic inflammatory
disease, Alzheimer’s Disease and cancer.
vACCINE DELIvERY SYSTEMS Whether the vaccine is a live virus, coat protein or a
piece of DNA, vaccine production requires elaborate and costly facilities and
procedures. And then there’s the issue of injections, which can sometimes be
painful and which many patients dislike. Industrial and academic researchers are
using biotechnology to circumvent both of these problems with edible vaccines
manufactured by plants and animals.

Using these techniques of biotechnology, scientists have developed antigen-only

vaccines against life-threatening diseases such as hepatitis B and meningitis.

40

Recently researchers have discovered that injecting small pieces of DNA from
microbes is sufficient for triggering antibody production. Such DNA vaccines could
provide immunization against microbes for which we currently have no vaccines.
Biotechnology is also broadening the vaccine concept beyond protection against
infectious organisms. Various

Genetically modified goats have produced a possible malaria vaccine in their milk.
Academic researchers have obtained positive results using human volunteers who
consumed hepatitis vaccines in bananas, and E. coli and cholera vaccines in
potatoes. In addition, because these vaccines are genetically incorporated into
food plants and need no refrigeration, sterilization equipment or needles, they
may prove particularly useful in developing countries (see also “Plant-Made
Pharmaceuticals”). Researchers are also developing skin patch vaccines for
tetanus, anthrax, influenza and E. coli.

Biotechnology Industry Organization n Guide to Biotechnology

Plant-Made Pharmaceuticals

he flexibility provided by biotechnology presents many opportunities for using

plants in new ways. Advances in biotechnology have made it possible to genetically
enhance plants to produce therapeutic proteins essential for the production of a
wide range of pharmaceuticals—such as monoclonal antibodies, enzymes and blood
proteins. Plant-made pharmaceutical production is regulated under stringent
requirements of the U.S. Department of Agriculture (USDA) and the Food and Drug
Administration (FDA). The primary agency that regulates and monitors this
technology is USDA’s Animal and Plant Health Inspection Service (APHIS). APHIS
requires companies to obtain permits for field trials for therapeutic protein
production. The agency announced new permit conditions in March 2003. Prior to
issuing a test permit, APHIS reviews all plans for seed production, timing of
pollination, harvest, crop destruction, shipment, confinement, and the storage and
use of equipment. Permits are issued for the importation, interstate movement and
field testing of the plants. Field sites are inspected at least five times in a
single growing season by APHIS or state officials, with those inspections
corresponding to critical times in production, such as preplanting site location
evaluation, planting, midseason, harvesting and postharvesting. In 2004, 16
federal permits for growing plant-made pharmaceuticals were issued in 18 states
governing 24 field sites for a total of 277 acres. Therapeutic proteins produced
by transgenic plants to date include antibodies, antigens, growth factors,
hormones, enzymes, blood proteins and collagen. These proteins have been grown in
field trials in a wide variety of plants, including alfalfa, corn, duckweed,
potatoes, rice, safflower, soybeans and tobacco. Field trials with protein-
producing plants are providing the essential building blocks for innovative
treatments for diseases such as cancer, HIV, heart disease, diabetes, Alzheimer’s
disease, kidney disease, Crohn’s disease, cystic fibrosis, multiple sclerosis,
spinal cord injuries, hepatitis C, chronic obstructive pulmonary disease, obesity
and arthritis. Field trials with protein-producing plants are providing the
essential building blocks for innovative treatments for diseases such as cancer,
HIV, heart disease, diabetes, Alzheimer’s disease, kidney disease, Crohn’s
disease, cystic fibrosis, multiple sclerosis, spinal cord injuries, hepatitis C,
chronic obstructive pulmonary disease, obesity and arthritis.

In addition, scientists have made excellent progress in using plants as vaccine-

manufacturing and delivery systems. They have used tobacco, potatoes, tomatoes and
bananas to produce experimental vaccines against infectious diseases, including
cholera, a number of microbes that cause food poisoning and diarrhea (e.g., E.
coli and the Norwalk virus), hepatitis B and the bacterium that causes dental
cavities. A cancer “vaccine” (which is therapeutic and not preventative) to non-
Hodgkin’s lymphoma has also been produced in plants. Since most proteins cannot be
chemically synthesized, there are very few options for protein production for
pharmaceutical purposes: mammalian and microbial cell cultures and plants. More
than $500 million and five years are required to build a facility for mammalian
cell cultures. Using plants to produce therapeutic proteins lowers facility and
production costs associated with plant-made pharmaceuticals. One of the companies
developing plant-produced antibodies estimates that this production method is 25
to 100 times less expensive than cell-fermentation methods. Standard fermentation
methods can produce 5 to 10 kilograms of a therapeutic antibody per year, while
this company reports that it can produce 10,000 kilograms of monoclonal antibodies
per year. Using plants as factories to produce therapeutic proteins also enables
researchers to develop novel and complex molecular forms that could not normally
be grown in mammalian cell cultures. Because protein-producing plants require
relatively little capital investment, and the costs of production and maintenance
are minimal, they may provide the only economically viable option for independent
production of therapeutic proteins in underdeveloped countries.

41

Guide to Biotechnology n Biotechnology Industry Organization

Therapeutic Development Overview
I
n the United States, the Food & Drug Administration regulates the development,
manufacturing and marketing of most biotechnology therapeutics used in healthcare.
BIOLOGICS & DRUGS Many biotech products are biologics, meaning they are derived
from living sources such as cells. Biologics are complex mixtures whose active
ingredients—usually proteins—are hundreds of times larger than the compounds found
in most pills. These products usually must be injected or infused directly into
the bloodstream to be effective.

and, if a product is approved, post-marketing studies and surveillance.

ANIMAL TESTING Once a potential drug has been identified, animal testing is
usually the first step, typically in two or more species, since drug effects vary
across species. Many of these studies are ADME (absorption, distribution,
metabolism and excretion) and toxicity studies. They document absorption of the
drug, how the body breaks it down chemically, the toxicity and activity of the
breakdown products (called metabolites), and the speed at which the drug and its
metabolites are cleared from the body.

Biologics include blood and blood-derived products and vaccines, as well as

biotechnology-based recombinant proteins and monoclonal antibodies. Most biologics
are regulated by the FDA under the Public Health Service Act and require approval
of a biologic license application (BLA) prior to marketing. Through the late-
1990s, biotechnology was closely associated with recombinant and antibody-based
biologics, but increasingly biotech companies are using genetic and other
biological discoveries to develop so-called small-molecule drugs. These are the
chemically simple compounds that are so familiar on pharmacy shelves. They are
often formulated as pills (although small-molecule products may also be injected
or infused) and most are easily duplicated by generic manufacturers through well-
understood chemical processes. The FDA regulates small-molecule drugs under the
Food, Drug and Cosmetic (FD&C) Act. Approval of a new drug application (NDA) is
required before they can be marketed. (Note: A few biologics, notably insulin and
growth hormone, are regulated under the FD&C Act as well.) Although drugs and
biologics are subject to different laws and regulations, drugs and most
therapeutic biologics both fall under the purview of the FDA’s Center for Drug
Evaluation and Research (CDER, usually pronounced “cedar”). Vaccines, blood
products, and cell and gene therapies are regulated by the FDA’s Center for
Biologics Evaluation and Research (CBER, usually pronounced “seeber”).
PRODUCT DEvELOPMENT It typically takes 10 to 15 years and an average of more than
$800 million (including the cost of failures) to develop a new therapy. The
process is rigorous and conducted in multiple stages, beginning with lab and
animal testing, followed by clinical trials in humans, regulatory review
Biotechnology Industry Organization n Guide to Biotechnology

42

Scientists also use animal models of particular diseases to test for efficacy
signals that can guide further refinement of a drug or clinical testing. Although
animal efficacy results are important to drug development, they may be used to
support FDA approval for human use only for biodefense products. Biodefense
products can be tested for safety in humans, but not for efficacy, because it
would be unethical to expose volunteers to chemical warfare agents, anthrax and
the like in order to test whether a medicine or vaccine works. Scientists hope
someday to supplement or replace some animal testing with advanced technologies
such as computer models of human biological pathways. But some animal testing is
likely to remain necessary for maximizing safety before products are tested in
humans. BIO members abide by BIO’s Ethical Principles for the Care and Use of
Animals in Biotechnology Research (see page 109).
CLINICAL TRIALS A drug that passes animal safety studies may move into human
testing following the submission of an investigational new drug (IND) application
to the FDA. Most studies, or trials, of new products may begin 30 days after the
agency receives the IND.

Almost every new drug goes through multiple clinical trials, beginning with early
studies (Phase I) in small groups of patients to test safety. Larger mid-stage
trials (Phase II) examine safety and obtain preliminary efficacy data. The final
stage of pre-market testing (Phase III) seeks to gather convincing efficacy data
in the specific patient population the drug’s developer hopes to treat. The
design, or protocol, of clinical trials varies tremendously, depending on the
nature of the product, the patient population, and efficacy of existing
treatments.
Some drugs, for very rare and devastating diseases, have been approved after
studies in only a handful of patients; others, often products for milder
conditions and/or for which therapies are already available, must be tested in
thousands of patients to win approval. In many trials (especially those for
diseases lacking effective existing treatment), one group of patients (or arm of
the study) receives the drug being tested, while another group (the control group)
receives a placebo that looks just like the drug and is administered the same way.
Patients are randomized—that is, randomly assigned—to one or the other arm. A
trial in which the healthcare provider knows whether the patient is receiving the
placebo or active drug, but the patient does not, is a single-blind trial. One in
which neither the patient nor the healthcare provider knows whether the drug or
placebo is being administered is called double-blind. Especially for trials
measuring efficacy, double-blinded, randomized trials are considered the gold
standard. Other key terms for clinical trials:
n

less—meaning there is no more than a 5 percent probability the outcome resulted

from chance.
PHASE I Usually, the first study a drug or biologic enters is a Phase I trial
enrolling a small number (fewer than 100) of healthy volunteers to test safety and
obtain data on dosing, metabolism and excretion. Some Phase I trials are conducted
in patients with a condition the drug might someday treat. Interesting signs of
efficacy may be noted at this stage, but have little or no statistical weight.

A new type of early human testing, called Phase 0, or microdosing, is popular with
some who hope to lower preclinical development time and cost. Conducted under an
exploratory investigational new drug application, these tests may involve fewer
than 10 patients who receive less than 1 percent of a standard drug dose. Using
cutting edge technologies such as accelerated mass spectrometry, Phase 0 studies
seek to characterize drug metabolism and toxicity.
PHASE II In Phase II, testing expands to include (usually) 100 to 300 participants
who have a disease or condition the product may treat. Additional safety data are
gathered, along with evidence of efficacy. Researchers may conduct Phase II trials
of a drug in several related conditions—for example, testing a cancer drug in a
variety of cancers—in order to define the best patient population(s) for Phase III
trials. PHASE III Phase III brings one or more even larger trials (often about
1,000 to 5,000 patients) in the specific patient population for which the drug
developer hopes to win FDA approval. Phase III trials test efficacy and monitor
for side effects, and multiple Phase III trials in one or more indications may be
conducted for a single product. APPROvAL PROCESS If a therapy succeeds in clinical
trials, the next step is applying for approval with the FDA by filing either a new
drug application (NDA) or biologics license application (BLA). These applications
can run hundreds of thousands of pages and include details on the product’s
structure, manufacturing, lab testing and clinical trials.

43

Investigators—the doctors or other healthcare professionals conducting a trial.

Institutional review boards—local oversight groups at hospitals, universities and
other healthcare facilities that ensure trials are conducted ethically and as
safely as possible. Endpoints—a clinical trial’s outcome measures (such as tumor
shrinkage, viral clearance, or survival). Indication—the specific condition a drug
aims to treat; an indication may be broad (for example, Type II diabetes) or it
may be narrow (for example, insulin-dependent Type II diabetes).

n
n

Clinical trials must be sufficiently powered—that is, must enroll enough patients
with appropriately selected endpoints—to deliver meaningful conclusions. Once data
from a well-designed trial are recorded and analyzed, researchers convey how
confident they are that their conclusions are meaningful through a statistic
called the p-value. This is a calculated measure of the likelihood that a trial’s
conclusion resulted from chance. For example a p-value of 0.01 means there is a 1
percent likelihood the outcome resulted from chance. For a clinical trial to be
counted as a success, it must typically meet its endpoints with a p-value of 0.05
or

As part of the Prescription Drug User Fee Act, the FDA has a goal of acting on a
priority review products (those addressing unmet medical needs) by six months
after the
Guide to Biotechnology n Biotechnology Industry Organization
application receipt. For a standard review product, the agency’s goal is a 10-
month review. The term PDUFA date is the date by which the FDA must act to meet
this goal for a particular product. In weighing an NDA or BLA, particularly for a
novel product, the FDA may seek the guidance of one of its independent advisory
committees. Each committee has 10-15 members and includes experts and
representatives of the public. The committees host public meetings, often
attracting media coverage, at which the pros and cons of the products in question
are presented and debated, culminating with a recommendation either for or against
approval. Advisory committee recommendations are non-binding, however. The final
regulatory decision rests with the agency.
POST-APPROvAL Every approved drug comes with an official product label, in a
standardized format, whose contents are

developed by the FDA and the company marketing the drug. The label contents
include the approved indication, as well as a description of the drug, its side
effects, dosage, clinical trial summaries and other information useful to
physicians. Although doctors may prescribe a therapy “off-label” for indications
not expressly approved by the FDA, manufacturers are prohibited from marketing
off-label indications, and insurance does not always cover such uses. The story
does not end with approval and labeling. Companies often conduct additional Phase
II and III trials in other indications and may apply for approval through a
supplemental NDA or BLA. If approved, the new indication is added to the product
label. Companies also conduct Phase IV trials to refine knowledge about the drug.
In addition, drug makers are required by law to report adverse events to the FDA,
and they are subject to ongoing manufacturing and marketing rules.

44

Biotech Drug Development Process

Discovery (2–10 years) Preclinical Testing (Lab and animal testing) Phase I (20–30
healthy volunteers used to check for safety and dosage) Phase II (100–300 patient
volunteers used to check for efficacy and side effects) Phase III (1,000–5,000
patient volunteers used to monitor reactions to long-term drug use) FDA Review &
Approval

Postmarketing Testing 0 Source: Ernst & Young LLP Biotechnology Industry

Organization n Guide to Biotechnology 2 4 6 8 Year 10 12 14 16
Approved Biotechnology Drugs
(Bold text indicates recombinant and monoclonal antibody products.)
Note: This list includes biologics developed by biotechnology companies and
pharmaceutical companies, as well as small-molecule products developed by
biotechnology companies, and other selected small-molecule or tissue-engineered
products. This list covers approvals and new indications from 1982 through 2005.
Selected 2006 approvals (through Oct. 31) are also included. Please check bio.org
in early 2007 for a complete list of 2006 approvals.

PRODUCT
Abelcet® (liposomal formulation of anphotericin B) Abraxane™ (paclitaxel, first-
in-class protein bound particle) Abreva™ (docosanol) Actimmune® (interferon gamma-
1b)

COMPANY
Enzon

APPLICATION (USE)
Treatment of invasive fungal infections in patients who are refractory to or
intolerant of conventional amphotericin B Treats breast cancer after failure of
combination therapy for metastatic disease or relapse within six months of
adjuvant chemotherapy Topical treatment of recurrent cold sores (herpes simplex
infection) Treatment of chronic granulomatous disease; treatment of severe,
malignant osteopetrosis

APPROvAL DATE (FDA)

Nov 1995

American Pharmaceutical Partners Inc. AVANIR Pharmaceuticals and GlaxoSmithKline,

Inc. InterMune Pharmaceuticals, Inc.

Jan 2005

Jul 2000

Dec 1990 Feb 2000

Activase®/Cathflo® Activase® (alteplase; tissue plasminogen activator)

Genentech, Inc.

Treatment of acute myocardial infarction; acute massive pulmonary embolism; acute

ischemic stroke within first three hours of symptom onset; dissolution of clots in
central venous access devices (Cathflo® Activase®) Imaging agent for deep-vein
thrombosis Booster immunization against tetanus, diphtheria and pertussis as a
single dose in individuals 11 through 64 years of age

Nov 1987 Jun 1990 Jun 1996 Sep 2001 Sept 1998 Jun 2005

45

AcuTect™ Berlex Laboratories (technetium Tc-99 apcitide) Adacel™ (tetanus toxoid,

reduced diphtheria toxoid and acellular pertussis vaccine, absorbed) Adagen®
(adenosine deaminase) ADvATE (recombinant clotting factor) Agenerase® (amprenavir)
Albutein® (human albumin) Aldurazyme® (laronidase) Alferon N® (interferon alfa-N3,
human leukocyte derived) Aloxi (palonosetron HCl) Aventis Pasteur Limited

Enzon, Inc. Baxter Healthcare Corp.

Treatment of severe combined immunodeficiency disease (SCID) Hemophilia A

Mar 1990 Jul 2003

Vertex Pharmaceuticals and GlaxoSmithKline Alpha Therapeutic Corp.

HIV

Apr 1999

Treatment of hypovolmeic shock; an adjunct in hemodialysis; used in

cardiopulmonary bypass procedures Mucopolysaccharidosis-1 Treatment of genital
warts

Jan 1986

BioMarin Pharmaceutical Inc. and Genzyme Interferon Sciences, Inc.

Apr 2003 Oct 1989

MGI Pharma Inc. and Helsinn Healthcare SA

Prevention of acute nausea and vomiting in chemotherapy

Jul 2003

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Alphanate® (human antihemophilic factor) AlphaNine® SD (virus-filtered human
coagulation factor IX) AmBisome® (liposomal amphotericin B) AMEvIvE® (alefacept)
AMPHOTEC® (lipid-based colloidal dispersion of amphotericin B) AndroGel™
(testosterone) Angiomax® (bivalirudin)

COMPANY
Alpha Therapeutic Corp.

APPLICATION (USE)
Treatment of hemophilia A or acquired factor VIII deficiency Prevention and
control of bleeding in patients with factor IX deficiency due to hemophilia B
Treatment of fungal infections in patients with depressed immune function and with
fever of unknown origin; treatment of cryptococcal meningitis in HIV-infected
patients Moderate to severe chronic plaque psoriasis Second-line treatment of
invasive aspergillosis infections

APPROvAL DATE (FDA)

Feb 1997

Alpha Therapeutic Corp.

Jul 1996

Gilead Sciences, Inc., and Fujisawa Healthcare

Aug 1997 Jun 2000

Biogen Idec InterMune Pharmaceuticals, Inc.

Jan 2003 Nov 1996

Unimed Pharmaceuticals, Inc. (subsidiary of Solvay Pharmaceuticals ) The Medicines

Company

Testosterone-replacement therapy in males with testosterone deficiency

Anticoagulant in conjunction with aspirin in patients with unstable angina
undergoing percutaneous transluminal coronary angioplasty; patients undergoing
percutaneous intervention Treatment of venous leg ulcers; treatment of diabetic
foot ulcers

Feb 2000

Dec 2000 Jun 2005

46

Apligraf® (living human skin substitute, from collagen, fibroblasts and

keratinocytes) Aranesp™ (darbepoetin alfa) Argatroban

Organogenesis, Inc., and Novartis Pharmaceuticals Corp.

May 1998 Jun 2000

Amgen

Anemia associated with chronic renal failure; chemotherapy-induced anemia in

patients with non-myeloid malignancies Anticoagulant for prophylaxis or treatment
of thrombosis in patients with heparin-induced thrombocytopenia; anticoagulant for
use in patients with or at risk of heparin-induced thrombocytopenia undergoing
percutaneous coronary interventions

Sep 2001 Jul 2002 Jun 2000 Apr 2002

Texas Biotechnology Corp. and GlaxoSmithKline

Arranon® (nelarabine injection)

GlaxoSmithKline

ATRIPLA™ (efavirenz 600 mg, emtricitabine 200 mg, tenofovir disoproxil fumarate
300 mg) AVAGE™ (tazarotene; also marketed as Tazorac®)

A chemotherapy agent for the treatment of patients with T-cell acute lymphoblastic
leukemia (T-ALL) and T-cell lymphoblastic lymphoma (TLBL) whose disease has not
responded to or has relapsed following treatment with at least two chemotherapy
regimens Gilead Sciences and Bristol-Myers Triple-combination treatment for HIV
infection in Squibb Co. adults

Oct 2005

Jul 2006

Allergan, Inc.

Topical treatment of facial fine wrinkling, mottled hypo- and hyperpigmentation,

and benign facial lentigines

Oct 2002

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Avastin™ (bevacizumab)

COMPANY
Genentech

APPLICATION (USE)
First-line treatment, in combination with 5fluorouracil, of metastatic colorectal
cancer; second-line treatment of metastatic colorectal cancer with 5-fluorouracil-
based chemotherapy; use in combination with carboplatin and paclitaxel
chemotherapy for first-line treatment of patients with unresectable, locally
advanced, recurrent or metastatic non-squamous, non-small-cell lung cancer Once-
daily treatment of moderate to severe pain in patients who require continuous
opioid therapy for an extended period of time Treatment of relapsing-remitting
forms of multiple sclerosis; treatment after initial multiple sclerosis attack if
a brain MRI scan shows abnormalities characteristic of the disease Treatment of
hemophilia B

APPROvAL DATE (FDA)

Feb 2004 Jun 2006 Oct 2006

AVINZA™ (extended-release morphine sulfate) AvONEX® (interferon beta 1-alpha)

Ligand Pharmaceuticals and Elan Corp., plc Biogen Idec

Mar 2002

May 1996 Feb 2003

BeneFix™ (coagulation factor IX) Betaseron® (interferon beta 1-B)

Wyeth Berlex Laboratories (subsidiary of Schering-Plough) and Chiron Corp.

Feb 1997

Treatment of relapsing-remitting multiple sclerosis; Aug 1993 new labeling

includes data from studies in patients Mar 2003 with secondary progressive
multiple sclerosis, and the indications section reflects Betaseron is indicated
for treatment of relapsing forms of MS to reduce the frequency of clinical
exacerbations CD20-positive, follicular non-Hodgkin’s lymphoma refractory to
rituximab; CD20-positive relapsed or refractory, low grade, follicular or
transformed non-Hodgkin’s lymphoma Fixed-dose combination of hydralazine
hydrochloride and isosorbide dinitrate for heart failure in self-identified black
patients; first drug approved for a specific racial group Treatment of hemophilia
A for the prevention and control of hemorrhagic episodes; perioperative management
of patients with hemophilia A Treatment of human growth hormone deficiency in
children Booster immunization against tetanus, diphtheria and pertussis as a
single dose in adolescents 10-18 years of age Jun 2003 Jan 2005

BEXXAR® (tositumomab and tositumomab I-131) BiDil® (isosorbide dinitrate and

hydralazine) Bioclate™ (antihemophilic factor) BioTropin™ (human growth hormone)
Boostrix® (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis
vaccine, absorbed) BOTOX® COSMETIC (botulinum toxin type A)

Corixa Corp. and GlaxoSmithKline

47
NitroMed Inc.

Jun 2005

Aventis Behring

Dec 1993

Biotech General GlaxoSmithKline

May 1995 May 2005

Allergan, Inc.

Cervical dystonia in adults; treatment of strabismus and blepharospasm associated

with dystonia; temporary improvement in appearance of moderate to severe glabellar
lines (frown lines) in adults 65 or younger; primary axillary hyperhidrosis
inadequately managed with topical agents Treatment for Type II diabetes

Dec 1989 Dec 2000 Apr 2002 Jul 2004

Byetta® Amylin Pharmaceuticals (exenatide injection, first-inclass incretin

mimetic)

Apr 2005

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Campath® (alemtuzumab) Captique™ Injectable Gel (non-animal stabilized hyaluronic
acid) Carticel™ (autologous cultured chondrocytes) CEA-Scan® (acritumomab;
technetium99 labeled) Ceredase® (alglucerase; modified form of
betaglucocerebrosidase) Cerezyme® (imiglucerase; recombinant form of
betaglucocerebrosidase) Cialis® (tadalafil)

COMPANY
Millennium Pharmaceuticals, Inc., and Berlex Laboratories, Inc. Genzyme Corp. and
Inamed Corp.

APPLICATION (USE)
B-cell chronic lymphocytic leukemia in patients who have been treated with
alkylating agents and who have failed fludarabine therapy Facial wrinkle
correction

APPROvAL DATE (FDA)

May 2001 Oct 2004 Nov 2004

Genzyme

Reconstruction of damaged knee cartilage

Aug 1997

Immunomedics, Inc.

Imaging agent for metastatic colorectal cancer

Jun 1996

Genzyme

Treatment of type 1 Gaucher’s disease

Apr 1991

Genzyme

Treatment of type 1 Gaucher’s disease

May 1994

Lilly ICOS LLC (joint venture of Eli Lilly and Co. and ICOS Corp.) Genzyme Cangene
Corp.

Erectile dysfunction Refractory or relapsed acute lymphoblastic leukemia in

children

Nov 2003 Dec 2004

48

CLOLAR™ (clofarabine) CNJ-016,Vaccinia Globulin Intravenous (purified antibody for

specific vaccinia)

Treatment and/or modification of the following May 2005 conditions, which are
complications resulting from smallpox vaccination: eczema vaccinatum, progressive
vaccinia; severe generalized vaccinia; vaccinia infections in individuals who have
skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or in
individuals who have eczematous skin lesions because of either the activity or
extensiveness of such lesions; aberrant infections induced by vaccinia virus that
include its accidental implantation in eyes (except in cases of isolated
keratitis), mouth or other areas where vaccinia infection would constitute a
special hazard Cough relief; 12-hour dosing Jun 2004

Codeprex™ Extended-Release Suspension CIII (codeine polistirex/ chlorpheniramine

polistirex) Comvax™ (Haemophilus B conjugate [meningococcal conjugate] and
hepatitis B [recombinant] vaccine) CosmoDerm™/ CosmoPlast™ (dermal fillers
containing human-based collagen)

UCB

Merck & Co., Inc.

Vaccination against Haemophilus influenzae type B and against all known subtypes
of hepatitis B in infants born to HbsAg-negative mothers

Oct 1996

Advanced Tissue Sciences Inc. and Wrinkles Inamed Corp.

Mar 2003

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
CroFab™ (crotalidae polyvalent immune Fab, ovine) Cubicin™ (daptomycin)

COMPANY
Protherics, plc, and Savage Laboratories (unit of Altana, Inc.) Cubist
Pharmaceuticals Inc.

APPLICATION (USE)
Rattlesnake antivenom

APPROvAL DATE (FDA)

Oct 2000

Complicated skin and skin structure infections caused by susceptible strains of

bacteria; S. aureus bacteremia and endocarditis Prevention of cytomegalovirus
(CMV) in kidney transplant patients; prevention of CMV disease associated with
kidney, lung, liver, pancreas and heart transplants Myelodysplastic syndromes
First-line treatment for HIV-related Kaposi’s sarcoma

Sep 2003 May 2006

CytoGam® (CMV immune globulin IV) DACOGEN™ (decitabine for injection) DaunoXome®
(liposomal form of the chemotherapeutic agent daunorubicin) Depocyt™ (sustained-
release formulation of cytarabine) DepoDur® (morphine sulfate; extended-release
liposome injection) Dermagraft® (human-based, tissueengineered living dermal
substitute) DigiFab™ (digoxin immune fab [ovine])

MedImmune, Inc.

Dec 1998 Apr 1990

MGI Pharma and SuperGen Gilead Sciences

May 2006 Apr 1996

SkyePharma and Enzon Endo Pharmaceuticals, Inc., and SkyePharma plc

Treatment of lymphomatous meningitis

Apr 1999

Pain following major surgery

May 2004

Advanced Tissue Sciences, Inc., and Smith & Nephew, plc

Diabetic foot ulcers

Sep 2001

49

Protherics, plc

Digoxin toxicity

Sep 2001
Doxil® Alza (subsidiary of (liposomal formulation of Johnson & Johnson)
doxorubicin hydrochloride)

Second-line therapy for Kaposi’s sarcoma in AIDS patients; metastatic carcinoma of

the ovary in patients with disease that is refractory to both paclitaxel- and
platinum-based chemotherapy regimens Hunter syndrome (mucopolysaccharidosis II)
Prevention of itching associated with allergic conjunctivitis Advanced prostate
cancer; six-month sustained release formulation

Nov 1995 Jun 1999

ELAPRASE™ (idursulfase) Elestat™ (epinastine) Eligard™ (slow-release formulation

of leuprolide acetate) Elitek® (rasburicase) Emtriva™ (emtricitabine)

Shire plc Inspire Pharmaceuticals Inc., Allergan Inc. and Boehringer Ingelheim
Atrix Laboratories and SanofiSynthelabo

Jul 2006 Oct 2003

Jan 2002 (additional formulation cleared in Jul 2002) Dec 2004 Jul 2002 Jul 2003

Sanofi-Synthelabo Gilead Sciences

Management of plasma uric acid levels in pediatric chemotherapy patients HIV

infection in adults

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Enbrel® (etanercept)

COMPANY
Amgen and Wyeth

APPLICATION (USE)
Treatment of moderate to severely active rheumatoid arthritis in patients who have
had an inadequate response to one or more diseasemodifying antirheumatic drugs;
treatment of polyarticular course juvenile rheumatoid arthritis; treatment as a
first-line therapy for moderate to severe active rheumatoid arthritis; reduction
of signs and symptoms of active arthritis in patients with psoriatic arthritis;
anklyosing spondylitis; improvement of physical function in patients with
moderately to severely active rheumatoid arthritis; expanded psoriatic arthritis
label claiming blockage of progression of structural damage; new indication for
the treatment of adults with chronic moderate to severe plaque psoriasis who are
candidates for systemic therapy or phototherapy; FDA approved new labeling
allowing an indication of induction of major clinical response in patients with
rheumatoid arthritis; improving physical function in patients with psoriatic
arthritis Hepatitis B vaccine; adults with chronic hepatitis C infection Treatment
of anemia associated with chronic renal failure and anemia in Retrovir-treated
HIV-infected patients; pediatric use

APPROvAL DATE (FDA)

Nov 1998 May 1999 Jun 2000 Jan 2002 Jul 2003 Jul 2003 Aug 2003 Apr 2004 Sep 2004
Jun 2005

Engerix-B® (hepatitis B vaccine) Epogen® (epoietin alfa) Erbitux™ (cetuximab)

GlaxoSmithKline Amgen

Sep 1989 Aug 1998 Jun 1989 Jul 1999 Feb 2004 Mar 2006

50

ImClone Systems Inc. and Bristol- Patients with metastatic colorectal cancer who
are Myers Squibb refractory to or intolerant of irinotecan; use with radiation
therapy for treating advanced squamous cell carcinoma of the head and neck, and as
a single agent in advanced disease not responsive to platinum-based treatment
Novavax Inc. and King Pharmaceuticals Connetics Corp. Moderate to severe vasomotor
symptoms in menopausal women Acne vulgaris

ESTRASORB™ (estradiol) Evoclin™ Foam (formerly Actiza™) (clindamycin)

Oct 2003 Oct 2004

Exjade® Novartis AG (deferasirox, once-daily oral iron chelator) Fabrazyme®

(agalsidase beta) FACTIVE® (gemifloxacin) Genzyme Oscient Pharmaceuticals

Chronic iron overload due to blood transfusions in Nov 2005 adults and children
age 2 or older Fabry’s disease Mild to moderate community-acquired pneumonia and
acute bacterial exacerbation of chronic bronchitis; community-acquired pneumonia
due to multidrug-resistant Streptococcus pneumoniae Management of breakthrough
pain in cancer patients already receiving opioid therapy Treatment of female
infertility to stimulate ovulation in women with ovulatory disorders and in women
undergoing assisted reproductive technologies Prevention of flu Apr 2003 Apr 2003
Jul 2003
FENTORA™ (fentanyl buccal tablet) Fertinex™ (urofollitropin) FluMist™ (influenza
virus vaccine; live, intranasal)

Cephalon Serono S.A.

Sep 2006 Aug 1996

MedImmune Inc.

Jun 2003

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Fluarix™ (influenza virus vaccine) Focalin™ (dexmethylphenidate hydrochloride)
Follistim™ (follitropin beta)

COMPANY
GlaxoSmithKline Biologicals

APPLICATION (USE)
For active immunization of adults 18 years and older against influenza disease
caused by influenza virus types A and B Attention deficit hyperactivity disorder

APPROvAL DATE (FDA)

Aug 2005

Celgene Corp. and Novartis Pharmaceuticals Corp. Organon (unit of Akzo Nobel)

Nov 2001

Recombinant follicle-stimulating hormone for treatment of infertility; induction

of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism
in whom the cause of infertility is not due to primary testicular failure Rotator
cuff repair

Sep 1997 Feb 2002

FortaFlex™ (bioengineered collagen matrix) FORTEO® (teriparatide)

Organogenesis, Inc., and Biomet, Inc. Eli Lilly and Company

Apr 2002

Treatment of osteoporosis in postmenopausal women at high risk of fracture, and to

increase bone mass in men with primary or hypogonadal osteoporosis who are at high
risk of fracture

Nov 2002

FORTICAL®NasalSpray Unigene Laboratories Inc. (calcitonin salmon) FOSRENOL® Shire

Pharmaceuticals Group (lanthanum carbonate) Frova™ (frovatriptan succinate)
FUZEON™ (enfuvirtide) GAMMAGARD® (Immune Globulin Intravenous [Human] Solution)
Ganite™ (gallium nitrate) Vernalis Group, plc, and Elan Corp., plc Trimeris Inc.
and Roche Baxter HealthCare Corp.

Nasal Spray treats postmenopausal osteoporosis in Aug 2005 women with low bone
mass Reduction of blood phosphate levels in patients undergoing kidney dialysis
Migraine HIV-1 infection; product granted traditional approval Treatment of
primary immunodeficiency disorders associated with defects in humoral immunity Oct
2004 Nov 2001 Mar 2003 Oct 2004 May 2005

51

Genta Inc.

Cancer-related hypercalcemia resistant to hydration Treatment of peridontal bone

defects and associated gingival recession

Sep 2003 Nov 2005

GEM 21S® BioMimetic Therapeutics Inc. (purified recombinant growth factor,
recombinant human platelet derived growth factor (rhPDGFBB), and a synthetic
calcium phosphate matrix, betatricalcium phosphate) Pfizer GenoTropin® (human
somatropin)

Treatment of growth hormone deficiency in children; growth hormone deficiency in

adults; long-term treatment of growth failure in children born small for
gestational age who fail to catch up by age 2 Treatment of growth hormone
deficiency in children with growth failure

Aug 1995 Nov 1997 Jul 2001

Geref® (semorelin acetate)

Serono S.A.

Oct 1997

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Gleevec™ (imatinib mesylate)

COMPANY
Novartis Pharmaceuticals Corp.

APPLICATION (USE)

APPROvAL DATE (FDA)

Chronic myeloid leukemia in blast crisis, accelerated May 2001 phase, or in

chronic phase after failure of Feb 2002 interferon-alpha therapy; treatment of Kit
(CD117) Dec 2002 positive unresectable and/or metastatic malignant
gastrointestinal tumors; first-line treatment of adult patients with newly
diagnosed Philadelphia chromosome-positive chronic myeloid leukemia Newly
diagnosed patients with high-grade malignant glioma as an adjunct to surgery and
radiation Treatment of severe hypoglycemic reactions in insulin-treated diabetics,
and for diagnostic use Treatment of infertility in women not due to primary
ovarian failure; treatment of infertility in men and women Secondary
hyperparathyroidism patients undergoing chronic renal dialysis; additional
indication of secondary hyperparathyroidism that develops in earlier stages of
chronic kidney disease prior to dialysis Factor VIII for treatment of hemophilia
A; secondgeneration factor VIII formulated with sucrose for treatment of
hemophilia A Chronic hepatitis B Treatment of patients with metastatic breast
cancer whose tumors overexpress the HER2 protein Plasma volume expander for
treatment of hypovolemia during surgery Treatment of diabetes Treatment and
prevention of bleeding episodes in hemophilia A adult patients; spontaneous and
trauma-induced bleeding episodes in severe von Willebrand disease in adult and
pediatric patients, and in mild and moderate von Willebrand disease where use of
desmopressin is known or suspected to be inadequate Treatment of growth hormone
deficiency in children; somatotropin deficiency syndrome in adults; long-term
treatment of children of short stature (unknown cause) Patients with moderately to
severely active rheumatoid arthritis who have had insufficient response to one or
more traditional disease modifying antirheumatic drugs; expanded indication to
include improvement in physical function for adult patients with moderately to
severely active RA; reducing signs and symptoms of active arthritis in patients
with psoriatic arthritis; reducing signs and symptoms of active ankylosing
spondylitis Feb 2003

Gliadel Wafer (polifeprosan 20 with carmustine implant) GlucaGen® (glucagon)

Gonal-F® (follitropin alfa) Hectorol® Capsules (doxercalciferol)

Guilford Pharmaceuticals, Inc.

Novo Nordisk Serono S.A.

Jun 1998 Sep 1998 Jun 2000 Jun 1999 Apr 2004

Bone Care International, Inc.

Helixate® (antihemophilic factor) Hepsera™ (adefovir dipivoxil) Herceptin®

(trastuzumab) Hextend® (hetastarch) Humalog® (insulin) Humate-P® (antihemophilic
factor/ von Willebrand factor complex–human)

Aventis Behring

Feb 1994 Jun 2000 Sep 2002 Sep 1998

52

Gilead Sciences, Inc. Genentech, Inc.

BioTime, Inc. Eli Lilly and Company Aventis Behring

Mar 1999 Jun 1996 Apr 1999

Humatrope® (somatotropin)

Eli Lilly and Company

Aug 1996 Mar 1997 Jul 2003 Dec 2002 Jul 2004 Oct 2005 Jul 2006

HUMIRA™ (adalimumab)

Cambridge Antibody Technology and Abbott Laboratories

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Humulin® (human insulin) Hylaform® (Hylan-B gel) Hylaform® Plus (Hylan-B gel;
large-particle size hyaluronic acid-based dermal filler) Hylenex™ (recombinant
human hyaluronidase) Imagent® (perflexane lipid microspheres) Increlex™
(mecasermin) Infergen® (interferon alfacon-1)

COMPANY
Eli Lilly and Company Genzyme and Inamed Genzyme and Inamed

APPLICATION (USE)
Treatment of diabetes Correction of moderate to severe facial wrinkles and folds
Correction of moderate to severe facial wrinkles and folds

APPROvAL DATE (FDA)

Oct 1982 Apr 2004 Oct 2004

Halozyme Therapeutics Inc.

Adjuvant agent to increase the absorption and dispersion of other injected drugs

Dec 2005

Alliance Pharmaceutical Corp., Imaging agent for use in echocardiography Cardinal

Health, Inc., and InChord Communications, Inc. Tercica Inc. and Genentech Inc.
InterMune Pharmaceuticals, Inc., and Amgen Long-term treatment for growth failure
in children with severe primary IGF-1 deficiency Treatment of hepatitis C (HCV) in
patients 18 years or older with compensated liver disease who have anti-HCV serum
antibodies and/or the presence of HCV RNA; subsequent treatment of HCV-infected
patients who have tolerated an initial course of interferon therapy For use in
spinal fusion surgery to treat certain types of spinal degenerative disease;
acute, open tibia shaft fractures in adults

Jun 2002

Aug 2005 Oct 1997 Dec 1999

INFUSE™ Bone Graft/LT-CAGE™ (device utilizing recombinant human bone morphogenetic

protein [rhBMP-2]) INTEGRA® Dermal Regeneration Template (bilayer membrane system
for skin replacement) Integrilin™ (eptifibatide for injection)

Wyeth and Medtronic Sofamor Danek

Jul 2002 Apr 2004

53

Integra LifeSciences Holding Corp. and Ethicon, Inc. (a unit of Johnson & Johnson)

Treatment of full-thickness and deep partialthickness burns; repair of scar

contractures

Mar 1996 Apr 2002

Millennium Pharmaceuticals and Schering-Plough Corp.

Acute coronary syndrome, including both patients managed medically and those
undergoing percutaneous coronary intervention; revised prescribing information
with new dosing regimen for patients undergoing intracoronary stenting Treatment
of hairy cell leukemia; genital warts; AIDS-related Kaposi’s sarcoma; non-A, non-B
hepatitis; hepatitis B; chronic malignant melanoma; extended therapy for chronic
viral hepatitis C; treatment for follicular lymphoma in conjunction with
chemotherapy; treatment of hepatitis B in pediatric patients

May 1998 Jun 2001

Intron A® (alpha-interferon)

Schering-Plough Corp.

Jun 1986 Jun 1988 Nov 1988 Feb 1991 Jul 1992 Dec 1995 Mar 1997 Nov 1997 Aug 1998
Dec 2005

IPLEX™ (mecasermin rinfabate [rDNA origin]) ISTOLOL™ (timolol)

Insmed Inc.

Treatment of growth failure in children with severe primary IGF-1 deficiency

(primary IGF) or with growth hormone (GH) gene deletion who have developed
neutralizing antibodies to GH Glaucoma

ISTA Pharmaceuticals and Senju Pharmaceutical Co.

Jun 2004

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Kepivance (palifermin)

COMPANY
Amgen

APPLICATION (USE)
Severe oral mucositis in cancer patients with hematologic blood cancers undergoing
high-dose chemotherapy, with or without radiation, followed by a bone marrow
transplant Moderately to severely active rheumatoid arthritis in adult patients
who have failed disease-modifying antirheumatic drugs Factor VIII for treatment of
hemophilia A; secondgeneration factor VIII formulated with sucrose for treatment
of hemophilia A Biosynthetic basal insulin for adult and pediatric patients with
type 2 diabetes Treatment of autologous bone marrow transplantation; treatment of
white blood cell toxicities following induction chemotherapy in older patients
with acute myelogenous leukemia; for use following allogenic bone marrow
transplantation from HLA-matched related donors; for use mobilizing peripheral
blood progenitor cells and for use after PBPC transplantation; (Leukine Liquid)
ready-to-use formulation in a multidose vial First-line treatment of hairy cell
leukemia Treatment of diabetes mellitus (Type I and Type II); for use in children
HIV infection Wet age-related macular degeneration Insomnia

APPROvAL DATE (FDA)

Dec 2004

Kineret™ (anakinra) Kogenate®FS (antihemophilic factor) Lantus® (insulin glargine)

Leukine® (granulocyte macrophage colony-stimulating factor)/ Leukine® Liquid

Amgen

Nov 2001

Bayer Corp.

Sep 1989 Jun 2000 Apr 2000 Mar 1991 Sep 1995 Nov 1995 Dec 1995 Nov 1996

Sanofi Aventis Berlex Laboratories

Leustatin™ (cladribine or 2-CDA)

Ortho Biotech, Inc. (subsidiary of Johnson & Johnson) Novo Nordisk

Mar 1993 Jun 2005 Oct 2005 Oct 2003 Jun 2006 Dec 2004

54

Levemir® (insulin detemir [rDNA origin] injection) Lexiva™ (fosamprenavir)

LUCENTIS™ (ranibizumab injection) LUNESTA™ (formerly Estorra) (eszopiclone)
Luveris® (lutropin alfa for injection)

Vertex Pharmaceuticals Inc. and GlaxoSmithKline Genentech Sepracor, Inc.

Serono

For concomitant use with Gonal-f® (follitropin alfa for injection) for stimulation
of follicular development in infertile hypogonadotropic hypogonadal women with
profound luteinizing hormone deficiency Relief of inflammatory and pruritic
manifestations of corticosteroid-responsive dermatoses of the scalp Prevention of
Lyme disease

Oct 2004

Luxiq™ (betamethasone) LYMErix™ (recombinant OspA lipoprotein) Macugen®

(pegaptanib sodium injection)

Connetics Corp.

Feb 1999

SmithKline Beecham Biologicals (subsidiary of GlaxoSmithKline) Eyetech

Pharmaceuticals, Inc. and Pfizer

Dec 1998

Neovascular (wet) age-related macular degeneration

Dec 2004

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Menactra™ (Meningococcal Polysaccharide [Serogroups A, C,Y and W-135] Diphtheria
Toxoid Conjugate Vaccine) Metadate® CD (bi-phasic release formulation of
methylphenidate) Metvixia (developed under trade name Metvix®) (methyl
aminoleyulinate) Mitozytrex (MitoExtra™ proprietary version of mitomycin)
Mylotarg™ (gemtuzumab ozogamicin)

COMPANY
Sanofi Pasteur

APPLICATION (USE)
For active immunization of adolescents and adults 11-55 years of age for the
prevention of invasive meningococcal disease caused by Neisseria meningitidis
serogroups A, C,Y and W-135.

APPROvAL DATE (FDA)

Jan 2005

UCB

Attention deficit hyperactivity disorder

Apr 2001

PhotoCure ASA and Galderma SA

Photodynamic treatment of actinic keratosis

Jul 2004

SuperGen, Inc.

Disseminated adenocarcinoma of the stomach or pancreas Human antibody linked to

calicheamicin (chemotherapeutic) for treatment of CD33 positive acute myeloid
leukemia in patients 60 and older in first relapse who are not considered
candidates for cytotoxic chemotherapy Treatment of cervical dystonia

Nov 2002

UCB and Wyeth

May 2000

Myobloc™ (botulinum toxin type B) Myozyme® (alglucosidase alfa) Naglazyme™

(galsulfase) Nabi-HB™ (hepatitis B immune globulin–human)

Elan Corp.

Dec 2000

Genzyme BioMarin Pharmaceuticals Nabi Pharmaceuticals

Pompe disease Enzyme replacement therapy for mucopolysaccharidosis VI (MPS VI)

Treatment of acute exposure to HbsAg, perinatal exposure of infants born to HbsAg-
positive mothers, sexual exposure to HbsAg-positive persons and household exposure
of infants to persons with acute hepatitis B Moderate to severe Alzheimer’s
disease Acutely decompensated congestive heart failure with shortness of breath at
rest or with minimal activity Reduction of incidence of infection as manifested by
febrile neutropenia in non-myeloid cancer patients receiving certain
chemotherapies Prevention of severe chemotherapy-induced thrombocytopenia in
cancer patients Treatment of chemotherapy-induced neutropenia; bone marrow
transplant accompanied by neutropenia; severe chronic neutropenia; autologous bone
marrow transplant engraftment or failure; mobilization of autologous PBPCs after
chemotherapy

Apr 2006 May 2005 Mar 1999

55

NAMENDA™ (memantine) Natrecor® (nesiritide) Neulasta™ (pegfilgrastim) Neumega®

(oprelvekin) Neupogen® (filgrastim)

Neurobiological Technologies Inc. and Forest Laboratories Scios (unit of Johnson &
Johnson)

Oct 2003 Aug 2001

Amgen

Jan 2002

Wyeth Amgen

Nov 1997 Feb 1991 Jun 1994 Dec 1994 Dec 1995 Apr 1998

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
NeutroSpec™ (formerly LeuTech®) (technetium [99m Tc] fanolesomab) Nexavar®
(sorafenib, tablets) Norditropin® (somatropin) Novantrone® (mitoxantrone) Novolin®
(insulin); Novolin L® (insulin; zinc suspension); Novolin R® (insulin, regular);
Novolin® 70/30 (70% insulin isophane suspension and 30% regular insulin); Novolin
N® (insulin; isophane suspension)

COMPANY
Palatin Technologies and Mallinckrodt Imaging (Tyco Healthcare) Onyx
Pharmaceuticals Inc. and Bayer Pharmaceuticals Inc. Novo Nordisk Amgen

APPLICATION (USE)
Diagnosis of appendicitis in patients with equivocal signs

APPROvAL DATE (FDA)

Jul 2004

For patients with advanced renal cell carcinoma Treatment of growth hormone
deficiency in children Treatment of acute nonlymphocytic leukemia; hormone
refractory prostate cancer; secondary progressive multiple sclerosis Treatment of
diabetes

Dec 2005 May 1995 Dec 1987 Nov 1996 Feb 2000 Oct 1982 Jun 1991 (Novolin® L, R and
70/30) Jul 1991 (Novolin® N)

Novo Nordisk

56

NovoLog® (insulin aspart) NovoSeven® (coagulation factor VIIa)

Novo Nordisk Novo Nordisk

Insulin analog for adults with diabetes mellitus; for pump therapy in diabetes
Treatment of bleeding episodes in hemophilia A or B patients with inhibitors to
factor VIII or factor IX; bleeding episodes in patients with factor VII deficiency
Pain associated with osteoarthritis of the knee in patients who have failed to
respond adequately to conservative non-pharmacologic therapy and simple analgesics
Treatment of growth hormone deficiency in children; growth hormone deficiency in
adults; growth failure associated with chronic renal insufficiency prior to kidney
transplantation; short stature associated with Turner Syndrome; to improve spine
bone mineral density observed in childhood-onset adult growth hormonedeficient
patients and to increase serum alkaline phosphatase; long-term treatment of
idiopathic short stature Growth hormone deficiency

May 2000 Dec 2001 Mar 1999 Jul 2005

Nuflexxa™ (1% sodium hyaluronate)

Savient Pharmaceuticals, Inc.

Dec 2004

Nutropin®/ Nutropin AQ® (somatropin)

Genentech, Inc.

Nov 1993 Jan 1994 Jan 1996 Dec 1996 Dec 1999 Jul 2005
Nutropin Depot™ (sustained-release formulation of somatropin) OLUX® Foam
(clobetasol proprionate)

Alkermes, Inc., and Genentech, Inc. Connetics Corp.

Dec 1999

Short-term topical treatment of moderate to severe dermatoses of the scalp; short-

term topical treatment of mild to moderate plaque-type psoriasis of non-scalp
regions excluding the face and intertriginous areas

May 2000 Dec 2002

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Oncaspar® (PEG-L-asparaginase)

COMPANY
Enzon, Inc., and Sanofi Aventis

APPLICATION (USE)
Treatment of acute lymphoblastic leukemia in patients who are hypersensitive to
native forms of L-asparaginase; use as part of first-line treatment regimen in
acute lymphoblastic leukemia Treatment of patients with persistent or recurrent
cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the
interleukin-2 receptor Rosacea

APPROvAL DATE (FDA)

Feb 1994 Jul 2006

Ontak® (denileukin diftitox)

Ligand Pharmaceuticals, Inc.

Feb 1999

Oracea™ (capsule formulation of doxycycline) Orapred ODT™ (prednisolone sodium

phosphate tablets) OrCel™ (composite cultured skin; bi-layered cellular matrix)
Orencia™ (abatacept, fully human soluable fusion protein) Orfadin® (nitisinone)
Orthoclone OKT3® (muromomab-CD3) Orthovisc® (high-molecular-weight hyaluronan)
Ovidrel® (human chorionic gonadotropin) Pacis® (live attenuated Bacillus Calmette-
Guerin) Panretin® (alitretinoin) Pediarix™ (diphtheria and tetanus toxoids and
acellular pertussis adsorbed, hepatitis B [recombinant] and inactivated polio-
virus vaccine combined) Pegasys® (peginterferon alfa-2a)

CollaGenex Pharmaceuticals

May 2006

BioMarin Pharmaceutical and Alliant Pharmaceuticals Ortec International, Inc.

Inflammation and asthma indications

Aug 2006

For patients with recessive dystrophic epidemolysis Feb 2001 bullosa undergoing
hand reconstruction surgery; Aug 2001 treatment of donor site wounds in burn
victims Reducing signs and symptoms of rheumatoid arthritis Hereditary tyrosinemia
type 1 Dec 2005

Bristol-Myers Squibb Company

Swedish Orphan International AB and Rare Disease Therapeutics, Inc.

Jan 2002

Ortho Biotech, Inc. Reversal of acute kidney transplant rejection (subsidiary of

Johnson & Johnson) Anika Therapeutics, Inc., and Ortho Biotech Products LP Pain
associated with osteoarthritis of the knee in patients who have failed to respond
adequately to conservative non-pharmacologic therapy and simple analgesics
Treatment of infertility in women
Jun 1986 Feb 2004

57

Serono S.A.

Sep 2000

Shire BioChem, Inc., (subsidiary of Shire Pharmaceuticals Group, plc) and UroCor,
Inc. Ligand Pharmaceuticals, Inc. GlaxoSmithKline

Bladder cancer immunotherapy

Mar 2000

The topical treatment of cutaneous lesions of patients with AIDS-related Kaposi’s

sarcoma Prevention of diphtheria, tetanus, pertussis, hepatitis B and polio

Feb 1999 Dec 2002

Roche and Nektar Therapeutics, Inc.

Chronic hepatitis C patients with compensated liver disease who have not been
previously treated with alpha interferon; combination therapy with Ribavirin in
patients with chronic hepatitis C who have compensated liver disease and have not
been previously treated with alpha interferon; use in combination with Ribavirin
to treat chronic hepatitis C in patients with HIV

Oct 2002 Dec 2002 Feb 2005

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
PEG-Intron™ (pegylated version of interferon alfa-2b) PHOTOFRIN® PDT (porfimer
sodium)

COMPANY
Enzon, Inc., and Schering-Plough Corp. Ligand Pharmaceuticals, Inc.

APPLICATION (USE)
Monotherapy for chronic hepatitis C; combination therapy with Rebetol for
treatment of hepatitis C in patients with compensated liver disease

APPROvAL DATE (FDA)

Jan 2001 Aug 2001

Palliative treatment of totally and partially Nov 1995 obstructing cancers of

esophagus; ablation of high- Aug 2003 grade dysplasia in Barrett’s esophagus
patients who do not undergo esophagectomy Palliative treatment of men with
advanced symptomatic prostate cancer under certain conditions Type 2 diabetes
Vaccine for infants and toddlers, 12–15 months, to prevent invasive pneumococcal
disease; immunization of infants and toddlers against otitis media caused by
vaccine serotypes Management of severe chronic pain in patients for whom
intrathecal therapy is warranted and who are intolerant of or refractory to other
treatment, such as systemic analgesics, adjunctive therapies or IT morphine
Treatment of anemia in AZT-treated HIVinfected patients; anemia in cancer patients
on chemotherapy; for use in anemic patients scheduled to undergo elective
noncardiac, nonvascular surgery Treatment of kidney carcinoma; treatment of
metastatic melanoma Nov 2003

Plenaxis™ (abarelix) Prandin™ (repaglinide) Prevnar® (pneumococcal 7valent

conjugate vaccine [diphtheria CRM-197 protein]) PRIALT® (ziconotide intrathecal
infusion)

Praecis Pharmaceuticals Inc.

Novo Nordisk Wyeth

Dec 1997 Feb 2000 Oct 2002

Elan Corp. plc

Dec 2004

58

Procrit® (epoietin alfa)

Ortho Biotech, Inc. (subsidiary of Johnson & Johnson)

Dec 1990 Apr 1993 Dec 1996

Proleukin, IL-2® (aldesleukin) ProQuad® (measles, mumps, rubella and varicella

virus vaccine live) ProstaScint® (indium In 111 capromab pendetide) Protropin®
(somatrem) PROVIGIL® Tablets (modafinil)

Chiron Corp. Merck & Co. Inc.

May 1992 Jan 1998

Measles, mumps, rubella, and varicella in children 12 Sep 2005 months to 12 years

Cytogen Corp.

Imaging agent for newly diagnosed patients with biopsy-proven prostate cancer
Treatment of growth hormone deficiency in children To improve wakefulness in
patients with excessive daytime sleepiness associated with narcolepsy; excessive
sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift-
work sleep disorder Treatment of mild to moderate cystic fibrosis; advanced cystic
fibrosis; pediatric use in infants 3 months to 2 years and children 2 to 4 years
old Pain relief in patients with osteoblastic metastatic bone lesions that enhance
on radionuclide bone scan Chronic moderate to severe psoriasis

Oct 1996

Genentech, Inc. Cephalon, Inc.

Oct 1985 Dec 1998 Jan 2004

Pulmozyme® (dornase alfa) Quadramet (samarium SM-153 lexidronam) RAPTIvA™

(efalizumab)

Genentech, Inc.

Dec 1993 Dec 1996 Mar 1998 Mar 1997

Berlex Laboratories (subsidiary of Schering-Plough) and Cytogen Corp. Xoma Ltd.

and Genentech

Oct 2003

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Rebetron™ (combination of ribavirin and alpha interferon)

COMPANY
Schering-Plough Corp.

APPLICATION (USE)
Combination therapy for treatment of chronic hepatitis C in patients with
compensated liver disease who have relapsed following alpha-interferon treatment;
treatment of chronic hepatitis C in patients with compensated liver disease
previously untreated with alpha interferon therapy Relapsing forms of multiple
sclerosis Blood-clotting factor VIII for the treatment of hemophilia A

APPROvAL DATE (FDA)

Jun 1998 Dec 1998

Rebif® (interferon beta 1-a) Recombinate® rAHF/ (antihemophilic factor) Recombivax

HB®/ Recombivax HB Dialysis Formulation (hepatitis B vaccine) ReFacto®
(antihemophilic factor) Refludan® (lepirudin)

Serono S.A., and Pfizer, Inc. Baxter Healthcare Corp. Merck & Company, Inc.

Mar 2002 Feb 1992

Vaccination against hepatitis B; hepatitis B vaccine Jul 1986 for adolescents and
high-risk infants; adults; dialysis; Jan 1987 pediatrics Jan 1989 Jun 1993 Control
and prevention of hemophilia A and short- Mar 2000 term prophylaxis to reduce
bleeding episodes For anticoagulation in patients with heparin-induced
thrombocytopenia and associated thromboembolic disease in order to prevent further
thromboembolic complications Platelet-derived growth factor treatment of diabetic
foot ulcers Mar 1998

Wyeth Berlex Laboratories (subsidiary of Schering-Plough)

Regranex® Gel (gel becaplermin)

Ortho-McNeil (subsidiary of Johnson & Johnson) and Chiron Corp. Centocor, Inc.
(subsidiary of Johnson & Johnson)

Dec 1997

Remicade® (infliximab)

Short-term management of moderately to severely active Crohn’s disease including

those patients with fistulae; treatment of patients with rheumatoid arthritis who
have had inadequate response to methotrexate alone; improving physical function in
patients with moderately to severely active rheumatoid arthritis who have had an
inadequate response to methotrexate; reducing signs and symptoms, and inducing and
maintaining clinical remission in patients with moderately to severely active
Crohn’s disease who have had an inadequate response to conventional therapy;
reduction of draining enterocutaneous and rectovaginal fistulae and for
maintaining fistula closure in patients with fistulizing Crohn’s disease; FDA
approved expanded label for Remicade in combination with methotrexate as first-
line regimen in patients with moderate to severe rheumatoid arthritis; reducing
the signs and symptoms of psoriatic arthritis; expanded label to treat ulcerative
colitis; pediatric Crohn’s disease; inhibiting progression of structural damage
and improving physical function in patients with psoriatic arthritis; chronic
severe plaque psoriasis in adults Treatment of pulmonary arterial hypertension in
patients with NYHA Class II-IV symptoms to diminish symptoms associated with
exercise

Aug 1998 Nov 1999 Feb 2002 Jun 2002 Apr 2003 Sep 2004 May 2005 Sep 2005 May 2006
Aug 2006 Sep 2006

59

Remodulin™ (treprostinil sodium)

United Therapeutics Corp.

May 2002

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Renagel® Capsules (sevelamer hydrochloride)

COMPANY
Genzyme

APPLICATION (USE)
Reduction of serum phosphorus in patients with end-stage renal disease (ESRD);
reduction of serum phosphorus in hemodialysis patients with endstage renal
disease; FDA approved new labeling showing the product’s phosphorous and
calciumphosphorous control are consistent with the National Kidney Foundation’s
aggressive guidelines Reduction of acute blood clot–related complications for
high-risk angioplasty patients; reduction of acute blood clot complications for
all patients undergoing any coronary intervention; treatment of unstable angina
not responding to conventional medical therapy when percutaneous coronary
intervention is planned within 24 hours Prevention of respiratory syncytial virus
in infants under 2 with bronchopulmonary dysplasia or history of prematurity

APPROvAL DATE (FDA)

Nov 1998 Jul 2000 Mar 2004

ReoPro™ (abciximab)

Centocor, Inc. (subsidiary of Johnson & Johnson) and Eli Lilly and Company

Dec 1994 Dec 1997

RespiGam® (immune globulin enriched in antibodies against respiratory syncytial

virus [RSV]) RESTASIS™ (cyclosporine ophthalmic emulsion) Retavase™ (reteplase)

MedImmune, Inc.

Jan 1996

Allergan, Inc.

Chronic dry eye disease in patients whose tear production is presumed to be

suppressed due to ocular inflammation Management of acute myocardial infarction in
adults

Dec 2002

Centocor, Inc. (subsidiary of Johnson & Johnson) Celgene Corp.

Oct 1996

60

Revlimid® (lenalidomide)

For the treatment of patients with transfusionDec 2005 dependent anemia due to
low- or intermediate-1- Jun 2006 risk myelodysplastic syndromes (MDS) associated
with deletion 5q cytogenetic abnormality with or without additional cytogenetic
abnormalities; combination use with dexmethasone for treatment of multiple myeloma
patients who have received at least one prior therapy Schizophrenia Oct 2003

RISPERDAL® CONSTA™ (long-acting formulation of risperidone) Rituxan™ (rituximab)

Alkermes Inc. and Johnson & Johnson

Biogen Idec and Genentech, Inc.

Treatment of relapsed or refractory, lowgrade or follicular, CD20-positive B-cell

nonHodgkin’s lymphoma; use with methrotrexate to reduce signs and symptoms of
moderately to severely active rheumatoid arthritis who have inadequately responded
to tumor necrosis factor (TNF) antagonist therapies; first-line treatment of
diffuse large B-cell, CD20+, non-Hodgkin’s lymphoma in combination with
anthracyclinebased chemotherapy regimens; first-line treatment of previously
untreated patients with follicular CD20+, B-cell non-Hodgkin’s lymphoma in
combination with CVP (cyclophosphamide, vincristine and prednisolone); low-grade
CD20+, B-cell NHL in patients with stable disease or who achieve a partial or
complete response following first-line treatment with CVP therapy

Nov 1997 Feb 2006 Feb 2006 Sep 2006 Sep 2006

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
Roferon-A® (interferon alfa-2a)

COMPANY
Hoffmann-La Roche, Inc.

APPLICATION (USE)
Treatment of hairy cell leukemia; AIDS-related Kaposi’s sarcoma; chronic phase
Philadelphia chromosome–positive chronic myelogenous leukemia; hepatitis C
Treatment of growth hormone deficiency in children; replacement of endogenous
growth hormone in adults with growth hormone deficiency Overactive bladder with
symptoms of urge urinary incontinence, urgency and urinary frequency Treatment of
premenstrual dysphoric disorder Pancreatic assessment; aid in location and
cannulation of pancreatic ducts in patients undergoing endoscopic retrograde
cholangiopancreatography Secondary hyperthyroidism in chronic kidney disease
patients on dialysis; elevated calcium levels in patients with parathyroid
carcinoma Prevention of acute rejection episodes in kidney transplant recipients;
prevention of rejection in combination with triple immunosuppressive therapy in
renal transplant; use in pediatric renal transplant; and use of IV bolus injection
Acromegaly Used in conjunction with insulin at mealtime to treat Type I and Type
II diabetes in patients who have failed to achieve desired glucose control despite
optimal insulin therapy

APPROvAL DATE (FDA)

Jun 1986 Nov 1988 Oct 1995 Nov 1995 Oct 1996 Aug 2004 May 2004

Saizen® (human growth hormone) SANCTURA™ (trospium chloride) Sarafem™ (fluoxetine

hydrochloride)

Serono S.A.

Indevus Pharmaceuticals, Inc., and Odyssey Pharmaceuticals, Inc., (subsidiary of

PLIVA) Indevus Pharmaceuticals, Inc., and Eli Lilly and Company

Jul 2000 Apr 2002 Nov 2002

SecreFlo™ Repligen Corp. (synthetic porcine secretin)

Sensipar™ (cinacalcet HC1) Simulect® (basiliximab)

NPS Pharmaceuticals and Amgen, Inc. Novartis Pharmaceutical Corp.

Mar 2004

May 1998 Mar 2001

SOMAvERT® (pegvisomant) Symlin® (pramlintide acetate injection) SYNAGIS™

(palivizumab) Tamiflu™ (oseltamivir phosphate)

Nektar Therapeutics and Pfizer Amylin Pharmaceuticals Inc.

Mar 2003 Mar 2005

61

MedImmune, Inc.

FDA cleared addition of new safety and efficacy data Jun 1998 supporting the
drug’s use in young children with hemodynamically significant congenital heart
disease Treatment of most common strains of influenza in adults; prevention of
influenza in adolescents and adults; treatment of acute influenza in children 1
year and older Locally advanced or metastatic non-small-cell lung cancer after
failure of at least one prior chemotherapy regimen; for use in combination with
gemcitabine chemotherapy in patients with pancreatic cancer who have not received
previous chemotherapy Treatment of cutaneous manifestations of cutaneous T-cell
lymphoma in patients who are refractory to at least one prior systemic therapy;
topical treatment of cutaneous lesions in patients with early-stage cutaneous T-
cell lymphoma Improving luminal diameter in native coronary arteries for treatment
of de novo lesions Oct 1999 Nov 2000 Dec 2000 Nov 2004 Nov 2005

Gilead Sciences, Inc., and Hoffmann-La Roche, Inc.

Tarceva™ (erlotinib)

OSI Pharmaceuticals, Inc. and Genentech

Targretin® (bexarotene)/ Targretin Gel® (bexarotene)

Ligand Pharmaceuticals, Inc.

Dec 1999 Jun 2000 (Targretin Gel® Formulation) Mar 2004

Taxus™ Express2™ Angiotech Pharmaceuticals, Inc., (paclitaxel-eluting coronary and

Boston Scientific Corp. stent)

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
Thymoglobulin (antithymocyte globulin; rabbit) Thyrogen® (thyrotropin alfa)
TNKase™ (tenecteplase) Tracleer™ (bosentan) Trisenox™ (arsenic trioxide)

COMPANY
Genzyme

APPLICATION (USE)
Treatment of acute rejection of kidney transplant in conjunction with
immunosuppression Adjunctive diagnostic tool for serum thyroglobulin (Tg) testing
with or without radioiodine imaging in the follow-up of patients with thyroid
cancer Treatment of acute myocardial infarction Pulmonary arterial hypertension
with WHO Class III or IV symptoms Treatment of acute promyelocytic leukemia HIV
(as part of combination therapy)

APPROvAL DATE (FDA)

Dec 1998

Genzyme

Dec 1998

Genentech, Inc. Actelion Ltd. Cell Therapeutics, Inc.

Jun 2000 Nov 2001 Sep 2000 Aug 2004

Truvada™ Gilead Sciences (emtricitabine and tenofovir disoproxil fumarate)

Twinrix® (hepatitis A inactivated and hepatitis B [recombinant] vaccine) Tygacil®
(tigecycline injection) TYSABRI® (formerly ANTEGREN®) (natalizumab) SmithKline
Beecham Biologicals (unit of GlaxoSmithKline)

Immunization against hepatitis A and B viruses

May 2001

Wyeth Biogen Idec and Elan Corp.

Treatment of complicated skin structure infections and complicated intra-abdominal

infections Reduction of clinical relapse frequency in relapsing forms of multiple
sclerosis; supplemental BLA approved, allowing market reintroduction (following
withdrawal in 2005) as monotherapy for relapsing MS Metastatic colorectal cancer
Relapsed and refractory multiple myeloma; treatment of multiple myeloma in
patients who have received at least one prior therapy Diabetes

Dec 2005 Nov 2004 Jun 2006

62

vectibix™ (panitumumab) VELCADE™ (bortezomib) velosulin® BR (insulin; buffered

formulation) Venoglobulin-S® (human immune globulin intravenous 5% and 10%
solutions) Ventavis™ Inhalation Solution (iloprost) Vidaza™ (azacitidine)

Amgen Millennium Pharmaceuticals Inc.

Sep 2006 May 2003 Mar 2005 Jul 1999

Novo Nordisk
Alpha Therapeutic Corp.

Treatment of primary immunodeficiencies; idiopathic thrombocytopenic purpura;

Kawasaki disease Pulmonary arterial hypertension in patients with NYHA Class III
or IV symptoms Myelodysplastic syndromes (all five subtypes)

Nov 1991 Jan 1995

CoTherix Inc. and Schering AG

Dec 2004

Pharmion Corp.

May 2004

Biotechnology Industry Organization n Guide to Biotechnology

PRODUCT
VIGIV,Vaccinia Immune Globulin Intravenous (intravenous immune globulin)

COMPANY
DynPort Vaccine

APPLICATION (USE)

APPROvAL DATE (FDA)

For the treatment and modifications of aberrant Feb 2005 infections induced by
vaccinia virus that include its accidential implantation in eyes (except in cases
of isolated keratitis), mouth, or other areas where vaccinia infection would
constitute a special hazard; eczema vaccinatum; progressive vaccinia; severe
generalized vaccinia, and vaccinia infections in individuals who have skin
conditions such as burns, impetigo, varicella-zoster, or poision ivy; or in
individuals who have eczematous skin lesions because of either the activity or
extensiveness of such lesions. HIV For use in combination with other
antiretroviral agents for treatment of HIV-1 infection Treatment of
cytomegalovirus retinitis in AIDS patients Treatment of wet form of age-related
macular degeneration; predominantly classic subfoveal choroidal neovascularization
due to pathologic myopia (severe nearsightedness) Spreading agent to facilitate
dispersion and absorption of other drugs; FDA approved singleuse vial Treatment of
cytomegalovirus retinitis in patients with AIDS Monthly injection to treat alcohol
dependence Mar 1997 Oct 2001

Viracept® (nelfinavir) Viread™ (tenofovir disoproxil fumarate) VISTIDE® (cidofovir

injection) Visudyne™ (verteporfin for injection)

Agouron Pharmceuticals Inc. (subsidiary of Pfizer) Gilead Sciences

Gilead Sciences Inc. QLT, Inc., and CIBA Vision

Jun 1996 Apr 2000 Aug 2001

Vitrase® ISTA Pharmaceuticals Ltd. (hyaluronidase for injection; lyophilized,

ovine) Vitravene™ (fomivirsen) Isis Pharmaceuticals, Inc., and CIBA Vision

May 2004 Dec 2004 Aug 1998 Apr 2006

63

Vivitrol® Alkermes and Cephalon (naltrexone for extended release injectible

suspension) WelChol™ (colesevelam) Genyzme

Reduction of elevated low-density lipoprotein (LDL) cholesterol alone or in

combination with HMG-CoA reductase inhibitor (statin) in patients with
hypercholesterolemia Treatment of chronic hepatitis C in patients 18 years of age
or older without decompensated liver disease Prevention of Rh isoimmunization in
pregnant women and the treatment of thrombocytopenic purpura Travelers’ diarrhea
caused by noninvasive strains of E. coli in patients 12 years of age and older
Severe, life-threatening sepsis Moderate to severe persistent asthma in adults and
adolescents Cataplexy associated with narcolepsy Mild to moderate Type 1 Gaucher’s
disease in patients for whom enzyme replacement therapy is not an option

May 2000

Wellferon® (interferon alfa-n1, lymphoblastoid) WinRho SDF® (Rho[D] immune

globulin) XIFAXAN™ (rifaximin) Xigris™ (drotrecogin alfa) Xolair® (omalizumab)
Xyrem® (sodium oxybate) Zavesca® (miglustat)

GlaxoSmithKline

Mar 1999

Nabi Biopharmaceuticals

Mar 1995

Salix Pharmaceuticals Ltd. Eli Lilly and Company Genentech, Tanox Inc. and
Novartis Pharmaceuticals Orphan Medical, Inc. UCB and Actelion Ltd.

May 2004 Nov 2001 Jun 2003 Jul 2002 Aug 2003

Guide to Biotechnology n Biotechnology Industry Organization

PRODUCT
ZEGERID™ (omeprazole powder for oral suspension)

COMPANY
Santarus

APPLICATION (USE)

APPROvAL DATE (FDA)

20 mg dose approved for short-term treatment Jun 2004 of active duodenal ulcer,
for heartburn and other Dec 2004 symptoms associated with gastro-esophageal reflux
Feb 2006 disease (GERD), for the short-term treatment of erosive esophagitis that
has been diagnosed by endoscopy, and for the maintenance of healing of erosive
esophagitis; 40 mg formulation subsequently approved for reduction of risk of
upper gastrointestinal bleeding in critically ill patients and the short-term
treatment of benign gastric ulcers; heartburn and other symptoms associated with
gastroesophageal reflux disease, as well as for esophagitis and ulcer indications
Humanized monoclonal antibody for prevention of kidney transplant rejection
Relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s
lymphoma Adjunctive therapy in treatment of partial seizures in adults with
epilepsy Short bowel syndrome (product previously approved under the trade name
Serostim® for AIDS wasting) Steroid-responsive inflammatory ocular conditions for
which a corticosteroid is indicated and where superficial bacterial ocular
infection or a risk of infection exists Dec 1997 Feb 2002 Mar 2000 Aug 1996 Dec
2003 Dec 2004

Zenapax® (daclizumab) Zevalin™ (ibritumomab tiuxetan) Zonegran™ (zonisamide)

Zorbtive™ (human growth hormone) Zylet™ (loteprednol etabonate and tobramycin
ophthalmic suspension)

Hoffmann-La Roche, Inc., and Protein Design Labs IDEC Pharmaceuticals Corp. Elan
Corp Serono S.A.

Pharmos Corp. and Bausch & Lomb

64

Biotechnology Industry Organization n Guide to Biotechnology

Agricultural Production Applications

umans have always relied on plants and animals for food, shelter, clothing and
fuel, and for thousands of years farmers have been changing them to better meet
our evolving needs. Society’s demand for resources provided by plants and animals
will increase as the world’s population grows. The global population, which
numbered approximately 1.6 billion in 1900, has surged to more than 6 billion and
is expected to reach 10 billion by 2030. The United Nations Food and Agriculture
Organization estimates world food production will have to double on existing
farmland if it is to keep pace with the anticipated population growth.
Biotechnology can help meet the ever-increasing need by increasing yields,
decreasing crop inputs such as water and fertilizer, and providing pest control
methods that are more compatible with the environment. Biotechnology can help meet
the ever-increasing need by increasing yields, decreasing crop inputs such as
water and fertilizer, and providing pest control methods that are more compatible
with the environment.

The tools of biotechnology allow plant breeders to select single genes that
produce desired traits and move them from one plant to another. The process is far
more precise and selective than traditional breeding in which thousands of genes
of unknown function are moved into our crops. Biotechnology also removes the
technical obstacles to moving genetic traits between plants and other organisms.
This opens up a world of genetic traits to benefit food production. We can, for
example, take a bacterium gene that yields a protein toxic to a disease-causing
fungus and transfer it to a plant. The plant then produces the protein and is
protected from the disease without the help of externally applied fungicides.
IMPROvING CROP PRODUCTION The crop production and protection traits agricultural
scientists are incorporating with biotechnology are the same traits they have
incorporated through decades of crossbreeding and other genetic modification
techniques: increased yields; resistance to diseases caused by bacteria, fungi and
viruses; the ability to withstand harsh environmental conditions such as freezes
and droughts; and resistance to pests such as insects, weeds and nematodes.

65

Crop Biotechnology

armers and plant breeders have relied for centuries on crossbreeding,

hybridization and other genetic modification techniques to improve the yield and
quality of food and fiber crops and to provide crops with built-in protection
against insect pests, disease-causing organisms and harsh environmental
conditions. Stone Age farmers selected plants with the best characteristics and
saved their seeds for the next year’s crops. By selectively sowing seeds from
plants with preferred characteristics, the earliest agriculturists performed
genetic modification to convert wild plants into domesticated crops long before
the science of genetics was understood. As our knowledge of plant genetics
improved, we purposefully crossbred plants with desirable traits (or lacking
undesirable characteristics) to produce offspring that combine the best traits of
both parents. In today’s world, virtually every crop plant grown commercially for
food or fiber is a product of crossbreeding, hybridization or both. Unfortunately,
these processes are often costly, time consuming, inefficient and subject to
significant practical limitations. For example, producing corn with higher yields
or natural resistance to certain insects takes dozens of generations of
traditional crossbreeding, if it is possible at all.
Natural Protection for Plants Just as biotechnology allows us to make better use
of the natural therapeutic compounds our bodies produce, it also provides us with
more opportunities to partner with nature in plant agriculture. Through science,
we have discovered that plants, like animals, have built-in defense systems
against insects and diseases, and we are searching for environmentally benign
chemicals that trigger these natural defense mechanisms so plants can better
protect themselves. Biotechnology will also open up new avenues for working with
nature by providing new biopesticides, such as microorganisms and fatty acid
compounds, that are toxic to targeted crop pests but do not harm humans, animals,
fish, birds or beneficial insects. Because biopesticides act in unique ways, they
can control pest populations that have developed resistance to conventional
pesticides. A biopesticide farmers (including organic farmers) have used since the
1930s is the microorganism Bacillus thuringiensis, or Bt, which occurs naturally
in soil. Several of the proteins the Bt bacterium produces are lethal to certain
insects, such as the European corn borer, a prevalent pest that costs the United
States $1.2 billion in crop damage each year. Bt bacteria used as a biopestiGuide
to Biotechnology n Biotechnology Industry Organization
cidal spray can eliminate target insects without relying on chemically based
pesticides. Using the flexibility provided by biotechnology, we can transplant the
genetic information that makes the Bt bacterium lethal to certain insects (but not
to humans, animals or other insects) into plants on which that insect feeds. The
plant that once was a food source for the insect now kills it, lessening the need
to spray crops with chemical pesticides to control infestations. The plant that
once was a food source for the insect now kills it, lessening the need to spray
crops with chemical pesticides to control infestations. Herbicide Tolerance Good
planting conditions for crops will also sustain weeds that can reduce crop
productivity as they compete for the same nutrients the desired plant needs. To
prevent this, herbicides are sprayed over crops to eliminate the undesirable
weeds. Often, herbicides must be applied several times during the growing cycle,
at great expense to the farmer and possible harm to the environment. Using
biotechnology, it is possible to make crop plants tolerant of specific herbicides.
When the herbicide is sprayed, it will kill the weeds but have no effect on the
crop plants. This lets farmers reduce the number of times herbicides have to be
applied and reduces the cost of producing crops and damage to the environment.
Resistance to Environmental Stresses In addition to the biological challenges to
plant growth and development just described, crop plants must contend with abiotic
stresses nature dispenses regularly: drought, cold, heat and soils that are too
acidic or salty to support plant growth. While plant breeders have successfully
incorporated genetic resistance to biotic stresses into many crop plants through
crossbreeding, their success at creating crops resistant to abiotic stresses has
been more limited, largely because few crops have close relatives with genes for
resistance to these stresses. The crossbreeding limitation posed by reproductive
compatibility does not impede crop biotechnology; genes found in any organism can
be used to improve crop production. As a result, scientists are making great
strides in developing crops that can tolerate difficult growing conditions. For
example, researchers have genetically modified tomato and canola plants that
tolerate salt levels 300 percent greater than nongenetically modified varieties.
Other researchers have identiBiotechnology Industry Organization n Guide to
Biotechnology

fied many genes involved in cold, heat and drought tolerance found naturally in
some plants and bacteria. Scientists in Mexico have produced maize and papaya that
are tolerant to the high levels of aluminum that significantly impede crop plant
productivity in many developing countries. Increasing Yields In addition to
increasing crop productivity by using built-in protection against diseases, pests,
environmental stresses and weeds to minimize losses, scientists use biotechnology
to improve crop yields directly. Researchers at Japan’s National Institute of
Agrobiological Resources added maize photosynthesis genes to rice to increase its
efficiency at converting sunlight to plant starch and increased yields by 30
percent. Other scientists are altering plant metabolism by blocking gene action in
order to shunt nutrients to certain plant parts. Yields increase as starch
accumulates in potato tubers and not leaves, or as oil-seed crops, such as canola,
allocate most fatty acids to the seeds. Biotechnology also allows scientists to
develop crops that are better at accessing the micronutrients they need. Mexican
scientists have genetically modified plants to secrete citric acid, a naturally
occurring compound, from their roots. In response to the slight increase in
acidity, minerals bound to soil particles, such as calcium, phosphorous and
potassium, are released and made available to the plant. Nitrogen is the critical
limiting element for plant growth and, step-by-step, researchers from many
scientific disciplines are teasing apart the details of the symbiotic relationship
that allows nitrogen-fixing bacteria to capture atmospheric nitrogen and provide
it to the plants that harbor them in root nodules.
n

66
Plant geneticists in Hungary and England have identified the plant gene and
protein that enable the plant to establish a relationship with nitrogen-fixing
bacteria in the surrounding soil. Microbial geneticists at the University of
Queensland have identified the bacterial gene that stimulates root nodule
formation. Collaboration among molecular biologists in the European Union, United
States and Canada yielded the complete genome sequence of one of the nitrogen-
fixing bacteria species. Protein chemists have documented the precise structure of
the bacterial enzyme that converts atmospheric nitrogen into a form the plant can
use.

n
CROP BIOTECHNOLOGY IN DEvELOPING COUNTRIES Today, 70 percent of the people on the
planet grow what they eat, and, despite the remarkable successes of the Green
Revolution in the 1960s, millions of them suffer from hunger and malnutrition.
Continuing population growth, urbanization, poverty, inadequate food distribution
systems and high food costs impede universal access to the higher yields provided
by technological advances in agriculture. In addition, the crops genetically
improved by plant breeders who enabled the Green Revolution were large-volume
commodity crops, not crops grown solely by small-scale subsistence farmers.

tions in Brazil, Thailand and Venezuela and provided their scientists with
training in transgenic techniques.
n

Japan’s International Cooperation Agency built tissue culture facilities at an

Indonesian research institution so that scientists there could develop disease-
free potato materials for planting. The Indonesian researchers are also working
with scientists at Michigan State University to develop insect-resistant potatoes
and sweet potatoes. An Australian agricultural research center collaborated with
Indonesian researchers on studies of nitrogen fixation and development of disease-
resistant peanuts. Seiberdorf Laboratories (Austria) worked with the Kenyan
Agricultural Research Institute to transfer technology for cassava mutagenesis and
breeding. Monsanto has donated virus resistance technologies to Kenya for sweet
potatoes, Mexico for potatoes and Southeast Asia for papaya and technology for
pro-vitamin A production in oilseed crops to India. Pioneer Hi-Bred and the
Egyptian Agricultural Genetic Engineering Research Institute (AGERI) collaborated
to discover potentially novel strains of Bt in Egypt. Pioneer trained AGERI
scientists in methods for characterizing Bt strains and transgenic techniques.
Patents are owned by AGERI and licensed to Pioneer. AstraZeneca trained scientists
from Indonesia’s Central Research Institute for Food Crops in the use of
proprietary technologies for creating insect-resistant maize. The Malaysian palm
oil research institute has collaborated with Unilever and universities in England,
the United States and the Netherlands on research to change the nutritional value
of palm oil and find new uses for it, such as lubricants, fuels, a vitamin E
precursor, natural polyester and biodegradable plastics.

For many farmers in developing countries, especially those in sub-Saharan Africa,

the Green Revolution never materialized because its agricultural practices
required upfront investments—irrigation systems, machinery, fuel, chemical
fertilizers and pesticides—beyond the financial reach of small-scale farmers.
Today’s biological agricultural revolution is knowledge intensive, not capital
intensive, because its technological advances are incorporated into the crop seed.
Today’s biological agricultural revolution is knowledge intensive, not capital
intensive, because its technological advances are incorporated into the crop seed.
As a result, small-scale farmers with limited resources should benefit. In
addition, because of the remarkable flexibility provided by crop biotechnology,
crop improvement through genetic modification need no longer be restricted to the
large-volume commodity crops that provide a return on industrial R&D investments.
A beneficial gene that is incorporated into maize or rice can also be provided to
crops grown by subsistence farmers in developing countries because the requirement
for plant reproductive compatibility can be circumvented. Realizing
biotechnology’s extraordinary capacity for improving the health, economies and
living conditions of people in developing countries, many universities, research
institutions, government agencies and companies in the industrialized world have
developed relationships for transferring various biotechnologies to developing
countries. The nature of the relationship varies, depending on the needs and
resources of the partners involved. For example:
n

67

Cornell University donated transgenic technology for controlling the papaya ring
spot virus to research institu-

While technology transfer has been and, no doubt, will continue to be an essential
mechanism for sharing the benefits of crop biotechnology, many developing
countries are taking the next step: investing resources to build their own
capacity for biotechnology research, development and commercialization. The
leaders in these countries recognize the potential of crop biotechnology to
provide agricultural self-sufficiency, preserve their natural resources, lower
food prices for consumers and provide income to their small farmers. Even more
important, they understand that biotechnology has the potential to

Guide to Biotechnology n Biotechnology Industry Organization

improve existing exports and create new ones, leading to a more diversified
economy and increased independence. But they also know that many of their
agricultural problems are unique and can best be solved by local scientists who
are familiar with the intricacies of the problems, local traditions, and
applicability—or lack of it—of technologies that were developed to solve
agricultural problems in industrialized countries. To move their countries
forward, they are investing human and financial resources in developing local
strength in crop biotechnology. For example:
n

tolerant crops decrease soil erosion by permitting farmers to use conservation

tillage. Because farmers in many countries have grown biotech crops for years,
data are now available for assessing the magnitude of the environmental and
economic benefits provided by biotechnology. In the past few years, a number of
independent researchers have produced reports documenting these benefits.
According to the National Center for Food and Agricultural Policy’s (NCFAP) 2004
report, in 2003 the 11 biotech crop varieties adopted by U.S. growers increased
crop yields by 5.3 billion pounds, saved growers $1.5 billion by lowering
production costs, and reduced pesticide use by 46.4 million pounds. Based on
increased yields and reduced production costs, growers realized a net economic
impact or savings of $1.9 billion. Three new traits for corn and cotton were
introduced in 2003, and the NCFAP study takes into account six biotech crops—
canola, corn, cotton, papaya, soybean and squash. In its report “Conservation
Tillage and Plant Biotechnology,” the Conservation Tillage Information Center
(CTIC) at Purdue University attributes the recent improvements in tillage
reduction to the increased use of the herbicidetolerant varieties produced through
biotechnology. CTIC concludes that the increase in conservation tillage associated
with herbicide-tolerant crops decreases soil erosion by 1 billion tons of soil
material per year, saves $3.5 billion per year in sedimentations costs and
decreases fuel use by 3.9 gallons per acre. According to the International Service
for the Acquisition of Agri-Biotech Applications, a single biotech crop, Bt
cotton, has led to the following environmental and economic benefits for farmers
in developing countries:
n

The Malacca government in Malaysia formed a unit in the Chief Minister’s Office to
promote research and development in biotechnology and established the Sarawak
Biodiversity Center to ensure sustainable use of genetic resources and to build a
strong database for bioresources. Taiwan opened an extension of the Hsinchu
industrial park devoted exclusively to biotechnology. Companies in the park will
have access to $850 million in government research and development funds and $4
billion in state and private venture capital, plus a wide range of support
services including marketing and global patent applications. Pakistan’s Ministry
of Science and Technology prepared a biotechnology action plan and funded a
threeyear program to promote biotechnology research and development. Uganda’s
National Council of Science and Technology established its first commercial
agricultural biotechnology lab to produce disease-free coffee and banana
plantlets. Egypt’s government, a longtime supporter of agricultural biotechnology,
released a report encouraging farmers to plant genetically modified crops to
benefit from reduced pesticide applications, lower production costs, higher yields
and increased income.

68
n

n
n

ENvIRONMENTAL AND ECONOMIC BENEFITS Beyond agricultural benefits, products of crop

biotechnology offer many environmental and economic benefits. As described above,
biotech crops allow us to increase crop yields by providing natural mechanisms of
pest control in place of chemical pesticides. These increased yields can occur
without clearing additional land, which is especially important in developing
countries. In addition, because biotechnology provides pest-specific control,
beneficial insects that assist in pest control will not be affected, facilitating
the use of integrated pest management. Herbicide-

From 1999 to 2000 in China, insecticide usage decreased by 67 percent and yields
increased by 10 percent, leading to income gains of $500 per hectare. Extensive
field trials in India from 1998 to 2001 demonstrated a 50 percent reduction in
insecticide spraying and a 40 percent increase in yields, which equals an increase
in income from $75 to $200 per hectare.

Small farmers in South Africa gained through a 25 percent yield increase and
decreased number of insecticide sprays from 11 to four, reducing pesticide costs
by $45 per acre. The higher cost of Bt seed (up to $15 per hectare for small
farmers) resulted in an average economic advantage of $35 per hectare.

Biotechnology Industry Organization n Guide to Biotechnology

REGULATION OF CROP BIOTECHNOLOGY Since combining specific genes from donor and
host plants does not alter the basic nature of the host plant, the result of
genetic modification is predictable and can be carefully controlled. As with any
new variety of food, the developers test extensively for safety, quality and other
factors.

Forest Biotechnology

U.S. regulatory policy for biotechnology products was established in 1986 with the
publication by the White House Office of Science and Technology Policy of the
“Coordinated Framework.” This framework builds on the work of international expert
bodies (such as the Organization for Economic Cooperation and Development [OECD]
and the U.S. National Academy of Sciences). The responsibilities of regulatory
agencies are clarified, linked to the laws they administer and coordinated with
other agencies that have potentially overlapping responsibilities. The U.S. Food
and Drug Administration (FDA) approves the safety of all foods and new food
ingredients. In addition, all producers are required to ensure the safety and
quality of anything they introduce into the food supply. The FDA requires strict
premarket testing and regulatory oversight of genetic modifications that
significantly alter the nutritional value of the host food, use genetic material
from outside the traditional food supply or use known allergens. The FDA also
requires labeling of any food product produced through biotechnology that
significantly alters the host food’s nutritional value or uses material from a
known allergen. For example, any product that uses a gene from a peanut, which is
a potential allergen, would be subject to testing and labeling requirements. The
FDA also has the authority to order unsafe products off the market. The USDA and
the U.S. Environmental Protection Agency (EPA) impose safety requirements and/or
performance standards on the development of pesticides, herbicides and genetically
enhanced test crops. The USDA regulates to ensure that crop varieties improved
through biotechnology are safe for the agricultural environment. Rigorous
assessments are conducted concerning the derivation of the new varieties and their
performance under contained and controlled field trials. The EPA also coordinates
with the USDA and FDA, using its own statutes to regulate the growing of plants
with pest-protection characteristics. The EPA sets allowable food residue
tolerance levels for any novel compounds that might be used.

hroughout the world, wood provides us with fuel, construction materials and paper,
and its supplies are dwindling rapidly. Wood products are currently a $400 billion
global industry, employing 3 million people. Demand for wood products is expected
to increase, even as major economies, such as Europe and Japan, are unable to grow
enough trees to meet their current demand.
INCREASING PRODUCTIvITY We are using biotechnology to create disease- and insect-
resistant trees and to increase their growth rates.

We are using biotechnology to create disease- and insectresistant trees and to

increase their growth rates. Scientists are also learning how to use biotechnology
to improve the efficiency with which trees convert solar energy into plant
material and to shunt more of that energy into wood production and less into
pollen, flowers or seeds. All of these methods of increasing productivity should
decrease the pressure on natural forests. However, developing trees through the
use of biotechnology is a lengthy undertaking because trees take a long time to
grow. So, researchers are looking to other methods for increasing productivity.
For example, they are using a biotechnology process in a fungus to fight diseases
that infect trees and are working on improving the microorganisms that live on
tree roots and provide trees with nutrients, much as nitrogen-fixing bacteria
increase the nutrients available to soybeans and alfalfa. In addition,
biopesticides have also been used extensively to control forest pests, and we
expect progress in insect cell culture to boost the number of biocontrol agents
available for forest insect control.
ENvIRONMENTAL BENEFITS Perhaps a more important economic role for biotechnology in
this industry will be found in its changing the way we convert trees to useful
products. Extensive research is being conducted to increase a tree’s amount of
cellulose, the raw material for papermaking, and to decrease the amount of lignin,
a tough molecule that must be removed in papermaking.

69

Traditionally, removing lignin from trees has required harsh chemicals and high
energy costs, so changing the cellulose:lignin ratio genetically has important
environmental implications, as does increasing the growth rate

Guide to Biotechnology n Biotechnology Industry Organization

of trees. Because trees absorb carbon dioxide, any advance that allows us to
increase tree yields without cutting down forest could have significant positive
effects on global warming. Other environmental benefits that biotechnology is
providing to the forestry industry include enzymes for
n n

pretreating and softening wood chips prior to pulping. removing pine pitch from
pulp to improve the efficiency of paper-making. enzymatically bleaching pulp
rather than using chlorine. de-inking of recycled paper. using wood-processing
wastes for energy production and as raw materials for manufacturing high-value
organic compounds. remediating soils contaminated with wood preservatives and coal
tar.

The diagnostic tools developed through the use of genomics are improving
management practices, animal health and food quality. Traditionally, decisions
regarding breeding or feedlot selection were made by human observation. But
genomic-based diagnostic and selection tools replace “eyeballing” with scientific
precision and efficiency, leading to more consistent and cost-effective results.
Benefits of DNA-based Products 1. Disease surveillance and food safety: Using DNA
to trace meat and animals through the food chain. 2. Enhanced breeding and
selection: Developing animals with desirable traits such as greater muscle mass or
milk or egg production. 3. Improved animal production efficiency: Creating
management systems based on genetic potential. 4. Enhanced end product quality and
consistency: Certifying branded meat (such as Angus beef) to meet consumer demand.
Genomic technology extends beyond the farm. The major pet registries use
diagnostic tests to verify parentage. Research is under way to develop tests that
can identify breeds in both purebred and mixed-breed animals and to identify
genetic predisposition to disease.
B. ANIMAL CLONING Livestock cloning is the most recent evolution of selective
assisted breeding in the ancient practice of animal husbandry. Arab sheikhs first
used artificial insemination (AI) in horses as early as the 14th century. In the
last 50 years, techniques such as embryo transfer, in vitro fertilization, embryo
splitting, and blastomere transfer have become commonplace—providing farmers,
ranchers and pet enthusiasts powerful tools for breeding the best animals.

n n

70

Animal Biotechnology
I. WHAT IS ANIMAL BIOTECHNOLOGY? Animals are helping to advance biotechnology, and
biotechnology is improving animal health in return. Combining animals and
biotechnology can lead to progress in four areas:
n n n n

Improved animal health. Enhancements to animal products. Environmental and

conservation benefits. Advances in human health.

Animal biotechnology includes all animals—livestock, poultry, fish, insects,

companion animals and laboratory animals—and covers three primary technologies:
genomics, cloning and transgenics.
A. ANIMAL GENOMICS Having access to the genome of a livestock species makes it
possible to identify individual genes and proteins that can control a host of
commercially and economically crucial functions—everything from muscle growth and
tenderness to disease resistance and reproduction. Even subtle differences in the
genetic makeup of an individual animal can greatly affect its value for breeding,
feedlot or branding purposes.
Biotechnology Industry Organization n Guide to Biotechnology

Cloning does not change an animal’s genetic makeup: it is simply another form of
sophisticated assisted reproduction. Cloning allows livestock breeders to create
an exact genetic copy of an existing animal—essentially an identical twin.
Livestock Cloning Benefits Cloning animals is a reliable way of maintaining
highquality livestock to meet our nutritional needs. Identifying and reproducing
superior livestock genetics ensures herds are maintained at the highest quality
possible.
Animal cloning offers benefits to consumers, farmers and endangered species:
n

Cloning accelerates the birth of the best possible stock and provides farmers with
certainty of the genetic makeup of a particular animal. Cloning reproduces the
strongest, healthiest animals, thus optimizing animal well-being and minimizing
the need for veterinary intervention. Cloning can be used to protect endangered
species. For example, in China, panda cells are kept on reserve as insurance
against extinction.

Transgenic technology can also be used to mitigate environmental impacts of

livestock production. The EnviroPig™, for example, dramatically lowers levels of
phosphorus pollution. Such applications underscore the industry’s commitment to
environmental protection.
D. TRANSGENIC ANIMALS FOR ADVANCING HUMAN HEALTH For decades, animals have been
used to produce human pharmaceuticals. Horses, pigs, rabbits and other species
have been enlisted to produce such products as anti-venoms, biologics to prevent
organ transplant rejection and the blood thinner heparin. Biotechnology now allows
us to modify genes in these animals so that the drug proteins are more compatible
with human biochemistry.

C. TRANSGENIC ANIMALS A transgenic animal is one that has had genetic material
from another species added to its DNA. This breakthrough technology allows
scientists to precisely transfer beneficial genes from one species to another.
Transgenic technology can improve the nutritional value of animal products through
enhanced genes. In addition, the technology promises improved animal welfare and
productivity—a critical capability in meeting the food demands of a growing global
population. Transgenic animals currently under development include pigs, cattle,
fish and poultry, each of which will be thoroughly reviewed by the appropriate
federal agencies before entering the marketplace.

Animal production also offers the most efficient, practical way to produce certain
drugs that are difficult to make in sufficient quantities using other methods. For
example, animals can make human antibodies to deadly infectious diseases if they
are modified with human immune genes. Transgenic technology can also be used to
make animal organs more compatible for transplant into humans, a process called
xenotransplantation. Heart valves from pigs are already used to replace damaged
valves in human hearts. If xenotransplantation could be perfected with the help of
transgenics, hundreds of thousands of lives could be saved each year. Animal
Welfare & the Environment Biotechnology animals and their products are extremely
valuable, often fragile, and animal welfare is a priority for everyone working
with these animals. Animal-made pharmaceuticals, for example, cannot be produced
in sick animals and so every effort must be made to ensure animal welfare. Most of
these technologies are being developed in domesticated animal species. Since these
animals live on farms and do not mate with wildlife, the risk to the environment
is miniscule. Moreover, the transgenic animals used to produce pharmaceuticals are
expressly excluded from use in the food supply. What’s Next? Biotechnology is
providing the tools to make all these benefits an everyday reality for consumers.
In addition to food applications, scientists are attempting to modify animals to
produce therapeutic proteins to use in treating cancer, heart attacks, hemophilia,
and rheumatoid
Guide to Biotechnology n Biotechnology Industry Organization

71
Benefits of Transgenic Animals Transgenic animals offer a plethora of benefits
that will improve consumer health and nutrition, as well as animal welfare and
productivity:
n n n n n

Increased nutritional value. Quality assurance. Higher efficiency production.

Stronger disease resistance. Improved animal welfare—less disease and longer
lifespan.

Animal Welfare & the Environment By making animal welfare a priority, transgenic
technology (as well as other animal biotechnology) offers tremendous potential
benefits for animals. Specifically, it can help cut animal mortality and disease,
as well as reduce or eliminate painful standard agricultural practices like
castration and de-horning.
arthritis, among other diseases. Some are researching the possibility of using
these animals to grow transplant organs that can be used when other options have
been exhausted. The largest impediment to successfully implementing these
technologies is the absence of a clear regulatory pathway leading to
commercialization. Another important challenge is educating the public, scientific
and regulatory communities about the safety, effectiveness and benefits of these
products.
II. HOW ARE PRODUCTS OF ANIMAL BIOTECHNOLOGY REGULATED? Animal biotechnology is
making incredible progress. If proven safe for animals, humans and the
environment, it holds vast promise for improving our quality of life. Use of
animal genomics, an extension of traditional animal breeding, is accepted as safe
and is largely unregulated. However, scientists and industry leaders are awaiting
final publication of a federal regulatory framework for cloning and transgenic
animals.

III. USING BIOTECHNOLOGY TO IMPROvE ANIMAL HEALTH Healthy animals provide healthy
foods. As of July 2003, there were 105 animal biotech products, including
bacterins and killed virus vaccines, used in agricultural and companion animals.
The animal health industry invests more than $400 million a year in research and
development.

Biotechnology provides new tools for improving animal health and increasing
livestock and poultry productivity. These improvements come from: 1. An enhanced
ability to detect, treat and prevent diseases and other problems. 2. Better feed
derived from transgenic crops designed to meet the dietary needs of different farm
animals. 3. Improved livestock productivity through improved animal breeding and
disease resistance.
A. ENHANCING DETECTION, TREATMENT AND PREVENTION OF ANIMAL DISEASES The animal
health industry has developed many effective treatments that can prevent and treat
dangerous livestock and poultry diseases. Quick diagnosis and treatment, coupled
with strong preventative measures, help lower production costs and improve overall
animal well-being. Additionally, healthier farm animals result in safer foods for
consumers.
n

72

Three government agencies regulate the animal health industry:

n

The U.S. Department of Agriculture regulates veterinary biologics, vaccines and

diagnostic test kits. The Food and Drug Administration reviews and approves new
pharmaceuticals and feed additives. And the Environmental Protection Agency
regulates pesticides and topical products that kill fleas and other parasites.

The Office of Science and Technology Policy is reviewing the regulatory processes
for the products of animal biotechnology, seeking coordination among the federal
agencies for a science-based, streamlined approach. Little published regulatory
guidance exists for many of the biotechnology products being developed. In 2003,
the U.S. Food and Drug Administration’s Center for Veterinary Medicine published
the draft executive summary of a food safety risk assessment regarding cloning of
farm livestock and their offspring, including the safety of food products for
human consumption. The FDA concluded that meat and milk from animal clones and
their offspring were safe to eat. Next steps include finalizing the risk
assessment and proposing a risk management process. Additionally, studies
conducted by the National Academy of Sciences (NAS) and other new research have
determined that cloned animals and their products are safe for human consumption.
Biotechnology Industry Organization n Guide to Biotechnology

Biotechnology allows farmers to quickly diagnose the following infectious diseases

through DNA and antibody-based tests: brucellosis, pseudorabis, scours, foot-and-
mouth disease, bluetongue, avian leucosis, mad cow disease and trichinosis.
Farmers may soon be able to manage several farm animal diseases through
biotechnology based pharmaceuticals, including foot-and-mouth disease, classical
swine fever and bovine spongiform encephalopathy. New biological vaccines protect
farm animals from a wider range of diseases, including foot-and-mouth disease,
scours, brucellosis, shipping fever, lung infections affecting pigs (pleuro-
pneumonia, pneumonic pasteurellosis, enzootic pneumonia), hemorrhagic septicemia,
fowl cholera, Newcastle disease of poultry, rabies, and infections that affect
cultivated fish. Molecular-based typing of pathogens, such as genetic
fingerprinting, allows for the monitoring of the spread of disease within and
between herds and can identify the source of an outbreak.

n
n

Genetic analysis of animal pathogens is leading to an improved understanding of

the factors that cause disease and how best to control them.

B. BETTER FEED FOR ANIMALS FROM TRANSGENIC CROPS Crops improved through
biotechnology may provide nutritionally enhanced feed for farm animals. Improved
feeds will raise animal size, productivity and growth rates. Biotech versions of
several animal-feed crops are under study:
n

adhesion deficiency, which causes repeated bacterial infections, stunted growth

and death within the first year of life. Other DNA tests can identify a hereditary
condition that produces anemia and retards growth in Japanese black cattle.
n

Genetic mapping and the development of DNA markers are being used to identify
genes in chickens that have developed a resistance to Marek’s disease, a
virusinduced disease similar to cancer. USDA biotech researchers announced a
breakthrough using transgenic technology that will help cows resist mastitis, a
bacterial infection of milk glands that causes inflammation, swelling and lower
milk production. Mastitis results in losses of up to $2 billion annually for U.S.
dairy farmers. Experimental cattle resistant to bovine spongiform encephalopathy
are being produced using biotechnology techniques such as knock-out technology and
cloning. Researchers in Britain are developing chickens using transgenic
technology that are resistant to avian influenza. If the birds are approved by
regulators, it would take only four to five years to breed enough to replace the
entire world population of chickens. Assisted reproductive technologies (ART).
Livestock producers are always interested in improving the productivity of
agricultural animals and have used assisted reproductive technologies since the
first use of artificial insemination in the 1950’s. Livestock cloning is newest
tool in the ART toolbox.

These products are designed to improve the quality of protein, oils or energy
availability in the final animal food product. One crop is designed to improve
shelf life of beef by improving the antioxidant properties of the meat’s fats.
Through biotechnology, increased digestibility of the low-quality roughages will
allow crops to be more useful in feeding livestock. Scientists are working on new
crops to develop feed with edible vaccines for farm animals. In the near future,
pigs could be fed transgenic alfalfa that would stimulate immunity to a serious
intestinal virus.

73

C. IMPROVED LIVESTOCK PRODUCTIVITY THROUGH IMPROVED ANIMAL BREEDING AND DISEASE

RESISTANCE Improved animal breeding. Biotechnology plays a growing role in farm
animal breeding programs. The goal of livestock producers is to select the best
animals for their breeding programs to obtain the same output (milk, eggs, meat,
wool) with less input (food), or increased output with the same input. Improving
animal health as well as increasing muscle mass and decreasing fat in cattle and
pigs have long been goals of livestock breeders.

With genetic mapping techniques, animals that are naturally disease-resistant can
be identified and used for breeding programs, resulting in naturally healthier
offspring. Conversely, animals with genetic weaknesses and defective genes can be
identified and removed from breeding programs. Examples of this work include the
following:
n

New DNA tests can identify pigs with the genetic condition porcine stress
syndrome, which causes tremors and death under stressful conditions. Inherited
weaknesses of cattle can be identified with DNA tests, which are currently being
used in national breeding herds in Japan. Tests can identify leukocyte

Using biotechnology to increase the productivity of livestock is a variation of

selective breeding. We select the best individual animals that possess desirable
traits; then, instead of breeding the animals, we collect eggs and sperm and allow
fertilization to occur in a laboratory dish. This in vitro fertilization is
followed by embryo culture, a form of mammalian cell culture in which the
fertilized egg develops into an embryo. When the embryo is a few days old, it is
taken from the laboratory dish and implanted into a female of the same species—but
not necessarily of the same breed. This is known as embryo transfer. Sometimes,
the embryo, which is a clump of cells at this stage in development, is divided
into several parts, and each cell cluster is implanted. This is a form of cloning
that has been used for a few decades to improve the genetic makeup of the herd
more quickly than by simply relying on a single female that produces one calf per
year.
Guide to Biotechnology n Biotechnology Industry Organization

n
The industry that is commercially cloning farm livestock also uses somatic cell
nuclear transfer. Animals that have been cloned for show ring purposes include
cattle, pigs, sheep and horses.
D. ADDITIONAL HEALTH APPLICATIONS OF BIOTECHNOLOGY IN ANIMAL AGRICULTURE The
biotechnology industry has proposed additional unique solutions for animal health
and food safety.
n

Genetic technologies are finding a place in the beef industry.

n

DNA sequencing of individual animals could serve as the ultimate animal

identification, allowing for tracking of meat from farm to table. A biotech
vaccine for Newcastle disease in chickens was approved by the USDA. This vaccine
is a plantmade pharmaceutical developed to improve animal health. A cattle vaccine
produced in plants could reduce Escherichia coli 0157:H7 shedding in feedlot
cattle, a further assist toward improved food safety on the farm.
n n

In 2003, the first validated SNP beef cattle genome was created. SNP (single
nucleotide polymorphism) technology is being used to identify clusters of genes
that contribute to a trait—for example, leaner beef cattle. Then, through
conventional breeding, lines of cattle are being developed that express the
increased muscling. A DNA test has been approved to verify Angus beef.

74

Worldwide, research teams are working to sequence the genomes of a wide variety of
animals. In October 2004, the Bovine Genome Sequencing Project announced it had
successfully sequenced the cow genome. In December 2004, the Chicken Genome
Sequencing Consortium announced it had sequenced the chicken genome. In late 2005,
a new Consortium for Swine Genome Sequencing was launched.

Iv. ENHANCING ANIMAL PRODUCTS Biotechnology can dramatically improve animal

products that humans consume and use. Some of these improvements result from
vaccines, medicines and diagnostic tests that make animals healthier. However,
biotechnology has also made great strides in enhancing animal products at a
cellular level through genomics, cloning and transgenic technologies. Recent
breakthroughs include the following:
n

Biotech cows can now produce “designer milks” with increased levels of protein
that can improve the diet of children or affect production of cheese and yogurt.
Scientists are now working to remove from milk the proteins that cause lactose
intolerance. It is estimated that 90 percent of the Asian population is lactose
intolerant. Australian scientists have increased wool production by feeding sheep
biotech lupin, a mainstay of sheep’s summer diet. Scientists are working to
develop biotech shrimp that lack the protein responsible for 80 percent of shrimp
allergies.
n

A study published in 2005 by the University of Connecticut and Japan’s Kagoshima

Prefectural Cattle Breeding Development Institute found meat and milk products
from cloned cattle are safe for consumption. The results parallel those of two
National Academy of Sciences reports in 2002 and 2004. Researchers can produce
biotech cows, pigs and lamb with reduced fat and increased lean muscle. Recent
research showed that pigs could be produced with higher heart healthy omega-3
fatty acids, using transgenic technology. Genetic mapping projects allow farmers
to identify highly productive animals for breeding programs. Genomics technology
is being applied to improving the conventional breeding of superior animals in
order to produce desirable traits.

v. ENvIRONMENTAL AND CONSERvATION EFFORTS THROUGH ANIMAL BIOTECHNOLOGY A.

ENVIRONMENTAL IMPACTS Livestock producers are challenged with disposing of more
than 160 million metric tons of manure annually. Animal manure, especially that of
swine and poultry, is high in nitrogen and phosphorus, which can contribute to
surface and groundwater pollution.
n

Several crops improved with biotechnology may offer animal feed that decreases
phosphorus and nitrogen excretion, total manure excretion and offensive odors.

Biotechnology Industry Organization n Guide to Biotechnology

n

Further, the EnviroPig is a biotech pig that is environmentally friendly. This pig
has a gene added to enhance salivary phytase, thereby improving phosphorus
digestibility and retention of phosphorus, with reduced excretion of phosphorus in
the manure of the animal. The goal is to lower the chance of manure contributing
to groundwater contamination in areas that surround livestock farms.

Researchers at the San Diego Zoo also employ other biotech and reproductive
technologies in their conservation efforts. In 1975, they created the Frozen Zoo,
a genetic bank that currently houses frozen cells from more than 7,000 endangered
or threatened mammals, birds and reptiles. Other animal conservation
organizations, including the Zoological Society of London and the Cincinnati Zoo,
have created genetic databases to store cryogenically frozen samples of DNA,
gametes and cell tissues for later use. Recently, Chinese scientists announced
that they are close to cloning the Giant Panda using trans-species cloning
technology. The Giant Panda is a highly endangered species. Furthermore, in 2005,
an endangered species of Mongolian gazelle was cloned for the first time. The year
also marked several other animal cloning firsts, including water buffalo and an
Arab endurance champion horse. Early in 2006, the first commercially cloned horses
were born; champion cutting horses were cloned and healthy foals have been born.
Biotechnology techniques for working with endangered species have not been limited
to cloning. Some researchers are using genetic samples to study the distribution
of species and track the relationships between different groups of animals. These
studies may help to prevent excessive interbreeding among small groups of animals.
Genetic studies also can help produce a healthier population of endangered species
through increased genetic diversity. Conservationists studying the endangered
Florida panther realized that, as the population shrank, inbreeding became more
common. Through genetic testing, researchers found that the panthers were closely
related to Texas cougars and had previously interbred. By introducing some cougars
in the Florida panther breeding pool, scientists increased the genetic diversity
of the species, resulting in a healthier panther population.
vI. ANIMAL BIOTECHNOLOGY TO ENHANCE HUMAN HEALTH Transgenic animal-made antibodies
can be produced from animals that have had human antibody genes transferred to
them. These animals can then be vaccinated against human diseases and antibodies
can be collected from their blood and used for treating diseases in humans.

B. ENDANGERED SPECIES CONSERVATION Biotechnology is providing new approaches for

saving endangered species. Reproductive and cloning technologies, as well as
medicines and vaccines developed for use in livestock and poultry, can also help
save endangered mammals and birds.

Borrowing biotechnology techniques used by livestock breeders, veterinarians at

the Omaha zoo recently used hormonal injections, artificial insemination, embryo
culture and embryo transfer to produce three Bengal tiger cubs. A Siberian tigress
served as the surrogate mother for these embryos. Worldwide, researchers have used
cloning technologies to conserve endangered species. In September 2001,
researchers at the University of Teramo, Italy, created a clone of the European
mouflon, the world’s smallest wild sheep. There are thought to be fewer than 1,000
adult mouflons in Sardinia, Corsica and Cyprus. In January 2001, the world’s first
cloned endangered species, an ox-like guar, was born in the United States, though
it succumbed to a common dysentery infection. There are estimated to be fewer than
36,000 guars in India and Southeast Asia due to human development of their natural
habitat. Researchers also have worked to clone the argali, the largest wild sheep,
but have been unable to produce live offspring. In December 2003, the first cloned
whitetail deer was reported in the United States. Though not an endangered
species, researchers believe the successful clone will provide valuable insight
into cloning other wild animals, including endangered species. In April 2003, the
San Diego Zoo reported the birth of a cloned banteng, a wild cow native to the
island of Java. Since January 2004, the banteng has been on public view at the San
Diego Zoo; it is the first cloned species to be on display to the public at any
zoo.

75

Animals are often used as models for research as many of the technologies
developed for animals can be trans-

Guide to Biotechnology n Biotechnology Industry Organization

ferred to humans. Some of the work being done with animals that will advance human
health:
A. XENOTRANSPLANTATION Extensive research has been done on the potential for using
biotech animals as blood or organ donors for humans. The primary barriers to
successful xenotransplantation include the immune reactions of the recipient to
the graft, the possibility that animal tissues or organs might not function well
in a human recipient, and the possibility that the xenotransplant might carry
infection. Biotechnology has been used to address the problem of immunorejection,
and biotech pigs have been developed with organs that may resist rapid rejection
by the human immune system. B. “PHARM” ANIMALS Researchers are developing
transgenic animals, including cows, goats and sheep, that produce milk containing
therapeutic proteins. These proteins may be used to nourish premature infants or
to treat emphysema, cystic fibrosis, burns, gastrointestinal infections and
immunodeficiency diseases such as AIDS. Some interesting ongoing projects include:
n

Aquaculture
Aquaculture is the growth of aquatic organisms in a controlled environment. The
increased public demand for seafood, combined with the relatively small supply of
aquaculture products provided by U.S. companies, has encouraged scientists and
industry to study ways that marine biotechnology can increase the production of
marine food products. By using biotechnology techniques, including molecular and
recombinant technology, aquaculture scientists study the growth and development of
fish and other aquatic organisms to understand the biological basis of traits such
as growth rate, disease resistance or resistance to destructive environmental
conditions. Researchers are using marine biotechnology to identify and combine
valuable traits in parental fish and shellfish to increase productivity and
improve product quality. The traits scientists and companies are investigating for
possible incorporation into several marine organisms include increased production
of natural fish growth factors and the natural defense compounds marine organisms
use to fight microbial infections. Biotechnology is also improving productivity
through the development of feed additives, vaccines and other pharmaceutical
agents.
A. BIOTECH SALMON As of September 2006, eight states have passed legislation or
have regulations banning various uses of transgenic fish, including Maryland,
California, Oregon, and Washington. In 2005, Alaska passed legislation requiring
labeling of food from transgenic fish. However, no transgenic fish are approved in
the United States, nor in the world, for human consumption at this time.

76

The first drug product for humans produced by a transgenic animal was recently
(July 2006) approved by the European Commission. This protein is human anti-
thrombin, a naturally occurring plasma protein that has both anti-coagulant and
anti-inflammatory properties. The protein is produced by transgenic goats whose
milk contains human anti-thrombin. In 2005 in Argentina, cows were improved with
biotechnology to produce human growth hormone. Scientists estimate that just 15 of
these Jersey cows could produce enough human growth hormone to meet the current
world demand. Dutch researchers are working with biotech rabbits that secrete a
potential drug for Pompe’s disease in their milk. Pompe’s disease is an extremely
rare genetic disorder that can result in crippled muscles, breathing problems and
sometimes death. Scientists are working with biotech goats that produce an
experimental anticancer medication. Biotech cows can now produce the human milk
protein lactoferrin, which is an antibacterial protein that can be used to treat
immunosupressed patients or incorporated into infant formula.

n
n

Some of the biotech improvements being made with fish include:

n

Some biotech salmon reach maturity quickly and do not hibernate, which enables
year-round availability of salmon. Researchers are trying to develop fish that are
more resistant to disease, tolerant of low oxygen levels in the water and tolerant
to freezing temperatures. Some species of fish naturally produce a protein that
allows them to survive in the Arctic. This “anti-freeze” gene has been
transplanted to other species of fish so they can survive in very cold waters.

Biotechnology Industry Organization n Guide to Biotechnology

COMPANION ANIMALS Approximately 164 million dogs and cats are companion animals in
the United States (in more than 60 percent of all American households). America’s
emotional attachment to its pets is evidenced by the estimated $38.4 billion spent
on U.S. pets in 2006. To help companion animals live longer and healthier lives,
pet owners spent more than $7 billion on veterinary care and healthcare products
in 2000 (the most recent year for which a statistic is available).

The animal health industry has developed products that contribute to the well-
being of companion animals. Pets benefit from preventive medicines and disease
treatments that have been improved through biotechnology. Animal vaccines are
critical to preventing diseases such as rabies, distemper, feline leukemia and
hepatitis. In addition, researchers have developed biotechnologybased products to
treat heartworm, arthritis, parasites, allergies, dental problems, heart disease,
kidney failure, separation anxiety, cognitive dysfunction syndrome and other
problems. Recent biotechnology-driven developments in companion animal health care
include the following:
n

Other antibody technology is being used to develop diagnostics for feline

infectious peritonitis and feline immunodeficiency virus.

Other recent biotechnology driven developments in companion animals are listed

below:
n n

An allergen-free cat is being developed. The first biotech animal to be sold to

the public reached the market in January 2004; GloFish are biotech ornamental fish
that contain a gene from a sea anemone. Under black light, the GloFish fluoresce
in a brilliant red color. The U.S. Food and Drug Administration conducted a
complete scientific and technical review of the biotech fish, including assessing
target animal safety, human safety and environmental safety, and found them safe
and environmentally harmless.

77

Immunologists have developed a vaccine for feline immunodeficiency virus (FIV), an

organism carried by as many as 25 percent of cats. In addition to saving cats’
lives, the research for creating the FIV vaccine provides many clues in the
development of an HIV/AIDS vaccine. Gene therapy has restored the vision of dogs
afflicted by Leber congenital amaurosis, an untreatable condition that causes
almost complete blindness. Currently researchers are successfully testing gene
therapy for melanoma, canine lymphoma and bone cancer. Canine lymphoma accounts
for 20 percent of all canine tumors and usually kills within a month of diagnosis.
Gene therapy treatment may prolong life by a year. A rabies vaccine has been
widely used with wild raccoon populations to limit transmission to companion
animals. In the United States, an estimated 40,000 people undergo treatment for
rabies annually at an average cost of $1,650. Projects for mapping the genetic
code of fleas may someday result in products that rid dogs and cats of the insect.
Monoclonal antibody technology is being used to develop treatments for canine
lymphoma.

n
n

Guide to Biotechnology n Biotechnology Industry Organization

Global Area of Transgenic Crops, 1995 to 2005: Industrial and Developing Countries
(million acres)
Industrial and Developing Countries (million acres) 140 120 100 80 60 40 20 0

J B J
Developing Industrial

J J J J

J B B

B J
1995

J B
1996

J B
1997

B
1998

B
1999

B
2000 Year

2001

2002

2003

2004

2005

Source: Clive James, Global Status of Commercialized Transgenic Crops: 2005, ISAAA
Briefs No. 34-2005. Ithaca, N.Y. International Service for the Acquisition of
Agri-biotech Applications, 2005

Global Area of Transgenic Crops in 2004 and 2005 by Country (million acres)
78
USA Argentina Brazil Canada China Paraguay India South Africa Uruguay Australia
Mexico Romania Philippines Spain Colombia Iran Honduras Portugal Germany France
Czech Republic 2004 117.6 40 12.3 13.3 9.1 -1.2 1.2 .74 .5 .24 .24 .24 .24 .12
-<.12 -<.12 --1 1 <1 <1 <1 <1 <1 <1 <1 -<1 -<1 --% 59 20 6 6 5 -2005 123.1 42.2
23.2 14.3 8.2 4.5 3.2 1.2 .74 .74 .25 .25 .25 .25 <.25 <.25 <.25 <.25 <.25 <.25
<.25 % 55 19 10.4 6.4 3.7 2.0 1.4 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 +/+5.5
2.2 10.9 1 -.9 4.5 2 0 0 .24 <.1 <.1 <.1 <.1 <.1 <.1 <.1 <.1 <.1 <.1 <.1 48 167 %
Change +4.7 5.5 88.6 7.5 -9.9 --

Source: Clive James, Global Status of Commercialized Transgenic Crops: 2005, ISAAA
Briefs No. 34-2005. Ithaca, N.Y. International Service for the Acquisition of
Agri-biotech Applications, 2005 Biotechnology Industry Organization n Guide to
Biotechnology
Global Area of Transgenic Crops in 2004 and 2005 by Crop (million acres)
2004 Soybean Maize Cotton Canola Total Source: Clive James, 2005 120 47.7 22.2
10.6 200.5 % +60 +23 +11 +6 100 2005 134.4 52.3 24.2 11.4 222.3 % 60 24 11 5 100
+/14.4 4.6 2 0.8 21.8 % Change 12 9.6 9.0 7.5 11

Global Area of Transgenic Crops, 1996 to 2005, by Crop (million acres)

140 120 100 (million acres) 80 60 40 20 0

B B J H F
Soybean Corn Cotton Canola

B B B B B B J H F
1999

79

J J H F
2000 Year

H B J F
1996

B J H F
1997

J H F
1998

J H F
2001

J H F
2002

J H F
2003

H H F
2004

F
2005

Source: Clive James, Global Status of Commercialized Transgenic Crops: 2005, ISAAA
Briefs No. 34-2005. Ithaca, N.Y. International Service for the Acquisition of
Agri-biotech Applications, 2005

Guide to Biotechnology n Biotechnology Industry Organization

Global Area of Transgenic Crops in 2004 and 2005 by Trait (million acres)
2004 Herbicide tolerance Insect resistance (Bt) Bt/Herbicide tolerance Total
Source: Clive James, 2005 144.5 38.5 16.8 200 % 72 19 9 100 2005 157.3 40 24.9
222.2 % 71 18 11 100 +/12.5 1.5 8.1 22.1 % Change 9 9 49 11

Global Area of Transgenic Crops, 1995 to 2005, by Trait (million acres)

160 140

B B J
Herbicide Tolerance Insect resistance (Bt) Bt/Herbicide tolerance (stacked) Virus
resistance/Other

B B B B B B B

80
120 100 80 60 40 20 0

H F

(million acres)

H F J B
1995

F JH B
1996

B J F H
1997

J H F
1998

J H F
1999

J H

J H F
2001

J H F
2002

J H F
2003

J H F
2004

J H F
2005

2000 Year

Source: Clive James, 1997–2005

Biotechnology Industry Organization n Guide to Biotechnology
Transgenic Crop Area as % of Global Area of Principal Crops (million acres)
Crop Soybean Cotton Canola Maize Total Source: Clive James, 2005 Global area 224.8
86.5 64.2 363.1 738.6 Transgenic crop area 134.9 24.2 11.5 50.8 221.4 Transgenic
area as % of global area 60 28 18 14 30

81

Source: Council for Biotechnology Information

Guide to Biotechnology n Biotechnology Industry Organization

Agricultural Biotech Products on the Market
CANOLA LibertyLink® Canola (Developed by Bayer CropScience) Introduced in 1995,
LibertyLink® Canola allows growers a wide application window to apply Liberty®
herbicide over-the-top during the growing season. This results in effective weed
control while maintaining excellent crop performance and yield.

cutworm, fall armyworm, sugarcane borer, southern corn stalk borer and lesser corn
stalk borer. All Herculex I hybrids also contain LibertyLink®, making them
tolerant to over the top applications of Liberty® herbicide, and some are
available stacked with Roundup Ready Corn 2. Herculex® RW Rootworm Protection and
Herculex® XTRA Insect Protection Corn (Developed by Dow AgroSciences and Pioneer
Hi-Bred International, Inc.) Corn hybrids containing Herculex RW rootworm
protection provide below ground in-plant corn rootworm protection against western,
northern, and Mexican corn rootworm. Corn hybrids containing the Herculex XTRA
insect protection, a combined trait product of both Herculex I and Herculex RW,
provide the broadest spectrum above and below ground in-plant insect protection
available on the corn market. All Herculex RW and Herculex XTRA hybrids also
contain LibertyLink®, making them tolerant to over the top applications of
Liberty® herbicide, and some are available stacked with Roundup Ready Corn 2.
LibertyLink® Corn (Developed by Bayer CropScience) Introduced in 1997 in the
United States and 1998 in Canada, LibertyLink® Corn allows growers a wide
application window to apply Liberty® herbicide over-the-top during the growing
season. Liberty® herbicide kills over 100 grass and broadleaf weeds fast, without
crop injury. NK Knockout™ Corn, NK YieldGard™ Hybrid Corn (developed by Syngenta
Seeds) Syngenta Seeds has produced several corn varieties that have been modified
to provide natural protection against certain pests NK® brand YieldGard® (Bt 11)
Corn (Developed by Syngenta Seeds) Syngenta Seeds has been producing and selling
several corn hybrids since 1997 that have been modified to provide built-in
protection against certain insect pests. (YieldGard® is a registered trademark of
the Monsanto Company.) Roundup Ready® Corn (Developed by Monsanto) Approved in
1997, Roundup® Ready Corn allows over-the-top applications of Roundup® herbicide
during the growing season for superior weed control. YieldGard® Corn Borer
(Developed by Monsanto Company) Introduced in 1997 in the United States,
YieldGard® Corn Borer hybrids offer season-long, whole-plant protection from the
European corn borer and also controls the Southwestern corn borer. YieldGard®
Rootworm-Protected Corn (Developed by Monsanto) YieldGard® corn carries built-in
protection against

InVigor® Hybrid Canola (Developed by Bayer CropScience) InVigor hybrid canola are
high-yielding hybrid canola varieties that are also tolerant to Liberty®
herbicide. InVigor hybrid seed was first sold in Canada in 1996 and in the United
States in 2000. Cooking oils from NEXERA™ Canola Seed (Developed by Dow
AgroSciences, Canada) This new oil, made from NEXERA™ canola seed, has a unique
combination of high oleic (>70 percent) and low linolenic (<3 percent) fatty
acids. These oils also have less than 1 percent trans fats and when used as part
of a healthy meal can deliver a label claim of trans fat-free (<.5 gram per 100-
gram serving).

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Roundup Ready® Canola (Developed by Monsanto) Roundup Ready canola allows growers
to apply Roundup® herbicide over-the-top of the crop during the growing season,
for superior weed control with enhanced crop safety.
CORN NutriDense® Corn (Developed by BASF). This nutritionally enhanced corn
contains a stacked set of output traits designed to enhance animal feed
performance. Traits include higher concentrations of amino acids, oil and certain
minerals.
Rogers® brand Attribute® Bt Sweet Corn (Developed by Syngenta Seeds) Attribute™
insect-protected sweet corn varieties from Syngenta provide a high level of built-
in protection against European corn borer and corn earworm, protecting crops from
ear damage and yield loss. Glyphosate-Tolerant Corn (Developed by Syngenta)
Developed from a plant-derived glyphosate-resistant gene that is evenly expressed
throughout the plant, corn hybrids with Agrisure™ GT Advantage gives farmers
another tool for managing weed pests. Herculex™ I Insect Protection (Developed by
Dow AgroSciences and Pioneer Hi-Bred International, Inc.) These corn hybrids
provide the broadest spectrum above-ground in-plant insect protection currently
available, including first- and second-generation European corn borer,
southwestern corn borer, black cutworm, western bean

Biotechnology Industry Organization n Guide to Biotechnology

corn rootworm. Current products include YieldGard® Rootworm stacked with Roundup
Ready® technology. YieldGard® Plus Corn (Developed by Monsanto) YieldGard® Plus
corn is the first stack of two insect-protection traits in a single seed,
combining the built-in protection against European corn Borer and corn rootworm.
YieldGard® Plus with Roundup Ready® Corn (Developed by Monsanto) YieldGard® Plus
with Roundup Ready® corn is the first seed to contain three separate biotech
traits, with insect protection against European corn borer and corn rootworm and
tolerance to over-the-top applications of Roundup® herbicide.
CARNATIONS Moondust Carnation (Introduced in 1996 by Florigene [Formerly Calgene
Pacific]) The first mauve carnation followed by Moonshadow (1998), a violet
carnation. Carnations are among the species that account for 75 percent of
worldwide flower sales. Conventional breeding failed to produce these flowers with
hues in the mauve-blue-violet range because of a genetic gap; they lack the
ability to produce the blue pigment, delphinidin. Florigene also has an active
research and development program to extend the vase life of flowers. COTTON
Bollgard® Insect-Protected Cotton (Developed by Monsanto) Introduced in 1996,
cotton with Monsanto’s Bollgard gene is protected against cotton bollworms, pink
bollworms and tobacco budworms. Bollgard cotton is a great example of how
biotechnology can reduce the amount of pesticide applications on a specific crop.
According to the technology provider, growers using Bollgard technology sprayed an
average of 2 1⁄2 less applications per acre than conventional cotton growers. This
data is further underscored by EPA research. In just one year, 1999, EPA estimated
that growers who planted Bollgard cotton reduced their insecticide application by
1.6 million pounds.

LibertyLink® Cotton (Developed by Bayer CropScience) LibertyLink® cotton allows

growers a wide application window to apply Liberty® herbicide overthe-top during
the growing season. Liberty® herbicide controls over 100 grass and broadleaf
weeds, with no crop injury. LibertyLink® cotton is offered in top FiberMax®
varieties. Roundup Ready® Cotton (Developed by Monsanto) Approved in 1996, Roundup
Ready® cotton tolerates both over-the-top and postdirected applications of
Roundup® herbicide. Roundup Ready cotton provides growers with an excellent
resource for practicing conservation tillage in their fields. Roundup-Ready® Flex
Cotton (Developed by Monsanto) Next Generation Roundup Ready® cotton is expected
to provide growers with an expanded window of application of Roundup® herbicide.
At this time, Monsanto expects that Roundup-Ready® Flex cotton will be in the
marketplace in 2006. WideStrike™ Insect-Protected Cotton (Developed by Dow
AgroSciences) This new trait provides a broader spectrum of insect protection than
other products currently on the market. This trait protects season long against a
broad range of damaging lepidopteran pests, including cotton bollworm, pink
bollworm, tobacco budworm, armyworms, and loopers.
MILK PRODUCTION Chymogen® (Developed by Genencor International and Marketed by
Chr. Hansen’s) Chymogen is the biotechnology-produced version of an enzyme
(chymosin) found in calves that makes milk curdle to produce cheese. Because it is
produced through biotechnology, it is purer, is more plentiful and eliminates
variability in the quality and availability of the enzyme in calves’ stomachs. It
is used in approximately 60 percent of all hard-cheese products made today.

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Bollgard® II Insect-Protected Cotton (Developed by Monsanto) Bollgard II is

Monsanto’s second generation of insectprotected cotton technology. This new cotton
technology is designed to offer new benefits to cotton growers, including a
broader spectrum of control of damaging insects and better defense against the
development of resistance in target insects. Research indicates that Bollgard II
will provide greater control of cotton bollworm, beet and fall armyworm, and
soybean loopers compared with Bollgard.
Posilac® Bovine Somatotropin (BST) (Developed by Monsanto) BST is a naturally
occurring protein hormone in cows that induces them to produce milk. BST improves
milk production by as much as 10 to 15 percent and is now used by farmers whose
herds represent over 30 percent of the nation’s cows. The FDA approved it in 1993.
ChyMax® (fermentation-derived) (Developed by Pfizer, marketed by Chr. Hansen’s)
ChyMax® is another version of chymosin, an enzyme that causes milk to coagulate.
It is an advanced fermentation ingredient that is of higher purity, quality and
activity than natural rennet.
Guide to Biotechnology n Biotechnology Industry Organization
PAPAYA Rainbow and SunUp (Developed by Cornell Research Foundation and the Papaya
Administrative Committee) Rainbow, a yellow-fleshed hybrid between a conventional
papaya and a genetically enhanced one; and SunUp, a redfleshed transgenic papaya,
have been enhanced to resist papaya ringspot virus (PRSV), the deadly disease
which almost eliminated the papaya industry in Hawaii during the 1990s. PEANUTS
Flavr Runner Naturally Stable Peanut (Developed by Mycogen) Peanuts with modified
fatty acid profile to produce nuts high in oleic acid. The benefit to the industry
is longer shelf life for nuts, candy and peanut butter. RAPESEED Laurical®
(Developed by Calgene, LLC) A less expensive source of high-quality raw materials
for soaps, detergents and cocoa butter replacement fats. Rapeseed plants with more
than 45 percent laurate in oil have been produced. SOYBEANS Roundup Ready®
Soybeans (Developed by Monsanto) Introduced in 1996, Roundup Ready® Soybeans allow
growers to apply Roundup® herbicide over-the-top during growing season. The result
is dependable, superior weed control with no effect on crop performance or yield.
SUNFLOWERS Natreon™ Naturally Stable Sunflower cooking oils (Developed by Mycogen)
Sunflowers with modified fatty acid profile to produce sunflower oil that contains
virtually no trans-fatty acids. These naturally stable characteristics make this
oil very attractive for nutritional drinks, release oils, baking or frying snack
foods and other uses. MISCELLANEOUS Messenger® (Developed by EDEN Bioscience) This
is the first of a series of products based on naturally occurring harpin protein
technology. Approved by the EPA in April 2000, Messenger stimulates growth and
defense pathways inherent within each plant without altering the plant’s DNA.
Messenger treatments promote healthier plants and increased yields, as well as
increased disease resistance and deterrence of insects such as nematodes.
Messenger is a labeled product,
Biotechnology Industry Organization n Guide to Biotechnology

currently being sold in cotton, citrus, apples, strawberries, rice, tomatoes,

peppers, cucurbit vegetables, cane berries, grass seed, potatoes and many other
crops.

In Development
ALFALFA Roundup Ready® Alfalfa (Developed with Monsanto technology) Allows over-
the-top applications of Roundup® herbicide during the growing season for superior
weed control. APPLES Bt Insect-Protected Apple (Developed with Monsanto
technology) These apples will contain built-in insect protection against codling
moth. BANANAS Disease-Resistant Bananas (Developed by DNA Plant Technology
Corporation) These bananas will be resistant to the fungal disease black sigatoka.
CANOLA Disease-Resistant Canola (Developed by DuPont) Canola that can resist
yield-robbing diseases such as Sclerotina. CORN Improved Drought Response Corn
(Developed by DuPont) Hybrid corn that can mine the existing moisture in the soil
more efficiently or survive drought periods and still produce high yields.

84

Increased-Energy-Availability Corn (Developed by DuPont) Corn that livestock can

more readily digest and more efficiently use nutrients in the grain. Nutritionally
Enhanced Corn (Developed by Dow AgroSciences) Corn hybrids that are “nutritionally
enhanced” will provide higher energy and more abundant nutrients for a better-
balanced ration formulation for livestock. Second-Generation YieldGard® Corn Borer
(Developed by Monsanto) The second-generation corn borer protected product in the
YieldGard family is expected to provide an even broader spectrum of insect control
than today’s YieldGard. In addition to the control of the European and
southwestern corn borer, field trials indicate it will provide enhanced control of
the corn earworm, fall armyworm and black cutworm. The next-generation corn-borer
protected corn will contain a new gene with a unique mode of action compared
with YieldGard® Corn Borer or other products on the market, thus providing a
defense against insect resistance and ensuring that insect-protected products will
remain effective and continue to deliver benefits for many years to come. Corn
Amylase for Enhanced Ethanol Production (Developed by Syngenta) Amylase breaks
starch down to sugar and including amylase expression in processor corn has the
potential to reduce the costs of ethanol production up to 10 percent. Glyphosate-
Tolerant Corn (Developed by Syngenta) Developed from a plant-derived glyphosate-
resistant gene that is evenly expressed throughout the plant, this new corn hybrid
will give farmers another tool for managing weed pests. Insect-Resistant Corn
(Developed by Syngenta) Secondgeneration Bt control for both European corn borer
and corn rootworm stacked to provide growers broader insect management controls.
Insect-Resistant and Glyphosate Tolerance Corn (Developed by Syngenta) Glyphosate
tolerance stacked together or separately with second generation Bt control for
both European corn borer and corn rootworm to provide growers further options and
flexibility to achieve desired effects.
COTTON Vegetative Insecticidal Protein Cotton (Developed by Syngenta) This second-
generation insect control has a broader spectrum and a novel mode of action. VIP
Cotton will provide growers an alternative to existing Bt producers and will
improve grower flexibility in managing insect resistance. LETTUCE Roundup® Ready
Lettuce (Developed with Monsanto technology) Allows over-the-top applications of
Roundup® herbicide during the growing season for superior weed control. POTATOES
Amflora Potatoes (Developed by BASF) Potatoes with genetically enhanced starches
offer considerable benefits as raw materials in many industries. Paper, textile
and adhesives industries for example will soon be able to take advantage of BASF’s
Amflora potato, which provides pure amylopectin starch directly from the potato
tuber.
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85
RICE LibertyLink® Rice (Developed by Bayer CropScience) Bayer CropScience is
obtaining appropriate regulatory clearances in key countries. When LibertyLink®
Rice is used together with Liberty® herbicide, it will allow farmers greater weed
control flexibility and may promote water conservation. SOYBEANS LibertyLink®
Soybeans (Developed by Bayer CropScience) Bayer CropScience is obtaining
appropriate regulatory clearances in key countries. When used together with
glufosinate ammonium herbicide (Liberty®, Ignite® 280), it will allow farmers
greater weed control flexibility and important weed resistance management
strategies.

MISCELLANEOUS AquaAdvantage® Salmon, Tilapia, Trout and Flounder (Developed by

Aqua Bounty Farms) The AquaAdvantage® salmon have the capability of growing from
egg to market size (6 to 10 lb.) in one to one-and-a-half years. Conventional
fish-breeding techniques require two to three years to bring a fish to market.
This new salmon could make fish farming more environmentally sustainable, decrease
over-fishing of wild salmon and lower consumer costs. Aqua Bounty expects to
introduce the AquaAdvantage® salmon within two to three years to a public for whom
salmon is an increasingly popular food.

Soybeans with Improved Protein Functionality (Developed by Dupont) Food soy

ingredient that does a better job of improving quality and consistency of food
products.
STRAWBERRIES Strawberry (Developed by DNA Plant Technology Corporation) The
company is adding genes to confer resistance to glyphosate herbicide and fungal
diseases. SUGAR BEETS Roundup Ready® Sugar Beets (Developed by Monsanto) Roundup
Ready® sugar beets are tolerant of Roundup® herbicide and provide growers with a
new weed-control option while the crop is growing. TURF GRASS Roundup Ready®
Creeping Bentgrass (Developed with Monsanto technology) Allows over-the-top
applications of Roundup® herbicide to control Poa Annua, Poa Trivialis and other
weeds of turf on golf course fairways and greens allowing more flexible weed
control and reduced turf management inputs.

Genetically Modified Fruits and Vegetables with Longer Postharvest Shelf Life
(Developed by Agritope, Inc., a wholly owned subsidiary of Epitope, Inc.) Using
ethylene-control technology, Agritope, Inc., has created delayed-ripening, longer-
lasting tomatoes and raspberries. Phytase for Animal Feed (Developed by Syngenta
and Zymetrics) The phytase enzyme releases phosphorousbased nutrients in animal
feed in a form that can be easily digested by single-stomach animals such as pigs,
chickens and turkeys. A phytase supplement can enhance the nutritional value of
the feed and reduce phosphorus levels in animal manure, which can help improve
environmental quality. The new microbial (Zymetrics) and corn phytase (Syngenta)
supplements are designed with enhanced thermostability, which provides livestock
producers more options in developing feed rations.

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Biotechnology Industry Organization n Guide to Biotechnology

Food Biotechnology

e have used biotechnology to manufacture food products for more than 8,000 years.
Bread, alcoholic beverages, vinegar, cheese and yogurt, and many other foods owe
their existence to enzymes found in various microorganisms. Today’s biotechnology
will continue to affect the food industry by providing new products, lowering
costs and improving the microbial processes on which food producers have long
relied. Many of these impacts will improve the quality, nutritional value and
safety of the crop plants and animal products that are the basis of the food
industry. In addition, biotechnology offers many ways to improve the processing of
those raw materials into final products: natural flavors and colors; new
production aids, such as enzymes and emulsifiers; improved starter cultures; more
waste treatment options; “greener” manufacturing processes; more options for
assessing food safety during the process; and even biodegradable plastic wrap that
kills bacteria.

hydrogenated to increase their heat stability for cooking or to solidify oils used
in making margarine. The hydrogenation process results in the formation of trans-
fatty acids. Biotechnology companies have given soybean oil these same properties,
not through hydrogenation, but by using biotechnology to increase the amount of
the naturally occurring fatty acid, stearic acid. Animal scientists are also using
biotechnology to create healthier meat products, such as beef with lower fat
content and pigs with a higher meat-to-fat ratio. Other health and nutritional
benefits of crops improved through biotechnology include increased nutritional
value of crops, especially those that are food staples in developing countries.
Scientists at Nehru University in New Delhi used a gene found in the South
American plant amaranth to increase the protein content of potatoes by 30 percent.
These transgenic potatoes also contain large amounts of essential amino acids not
found in unmodified potatoes. Other examples include golden rice and canola oil,
both of which are high in vitamin A. The golden rice developers further improved
rice with two other genes that increase the amount and digestibility of iron.
Biotechnology also promises to improve the health benefits of functional foods.
Functional foods are foods containing significant levels of biologically active
components that impart health benefits beyond our basic needs for sufficient
calories, essential amino acids, vitamins and minerals. Familiar examples of
functional foods include compounds in garlic and onions that lower cholesterol and
improve the immune response; antioxidants found in green tea; and the
glucosinolates in broccoli and cabbage that stimulate anticancer enzymes. We are
using biotechnology to increase the production of these compounds in functional
foods. For example, researchers at Purdue University and the U.S. Department of
Agriculture, created a tomato variety that contains three times as much of the
antioxidant lycopene as the unmodified variety. Lycopene consumption is associated
with a lower risk of prostate and breast cancer and decreased blood levels of “bad
cholesterol.” Other USDA researchers are using biotechnology to increase the
amount of ellagic acid, a cancer protective agent, in strawberries.
PRODUCT QUALITY We are also using biotechnology to change the characteristics of
the raw material inputs so that they are more attractive to consumers and more
amenable to processing.
Guide to Biotechnology n Biotechnology Industry Organization

Improving the Raw Materials

he first generation of transgenic crops primarily benefited farmers. Although

there are consumer benefits in growing these crops, the benefits are largely
invisible to consumers. For example, studies have shown that because insect-
resistant corn (Bt corn) sustains relatively little insect damage, fungi and molds
cannot infect those plants as easily as non-insect-resistant crops. Therefore, the
level of toxins, such as aflatoxin, produced by these pathogens, some of which are
fatal to livestock, is much lower in Bt corn than non-Bt corn. The benefits of the
next wave of biotechnology crops will be more obvious to consumers. Some of those
benefits will involve improvements in food quality and safety, while others will
provide consumers with foods designed specifically to be healthier and more
nutritious.
HEALTH AND NUTRITIONAL BENEFITS A variety of healthier cooking oils derived from
biotechnology are already on the market. Using biotechnology, plant scientists
have decreased the total amount of saturated fatty acids in certain vegetable
oils. They have also increased the conversion of linoleic acid to the fatty acid
found mainly in fish that is associated with lowering cholesterol levels.

87

Another nutritional concern related to edible oils is the negative health effects
produced when vegetable oils are
Biotechnology researchers are increasing the shelf life of fresh fruits and
vegetables; improving the crispness of carrots, peppers and celery; creating
seedless varieties of grapes and melons; extending the seasonal geographic
availability of tomatoes, strawberries and raspberries; improving the flavor of
tomatoes, lettuce, peppers, peas and potatoes; and creating caffeine-free coffee
and tea. Japanese scientists have now identified the enzyme that produces the
chemical that makes us cry when we slice an onion. Knowing the identity of the
enzyme is the first step in finding a way to block the gene to create “tearless”
onions. Much of the work on improving how well crops endure food processing
involves changing the ratio of water to starch. Potatoes with higher starch
content are healthier because they absorb less oil when they are fried, for
example. Another important benefit is that starchier potatoes require less energy
to process and therefore cost less to handle. Many tomato processors now use
tomatoes derived from a biotechnology technique, somaclonal variant selection. The
new tomatoes, used in soup, ketchup and tomato paste, contain 30 percent less
water and are processed with greater efficiency. A 1⁄2 percent increase in the
solid content is worth $35 million to the U.S. processed-tomato industry. Another
food processing sector that will benefit economically from better quality raw
materials is the dairy products industry. Scientists in New Zealand have now used
biotechnology to increase the amount of the protein casein, which is essential to
cheese making, in milk by 13 percent. Biotechnology also allows the economically
viable production of valuable, naturally occurring compounds that cannot be
manufactured by other means. For example, commercial-scale production of the
natural and highly marketable sweetener known as fructans has long eluded food-
processing engineers. Fructans, which are short chains of the sugar molecule
fructose, taste like sugar but have no calories. Scientists found a gene that
converts 90 percent of the sugar found in beets to fructans. Because 40 percent of
the transgenic beet dry weight is fructans, this crop can serve as a manufacturing
facility for fructans.
SAFETY OF THE RAW MATERIALS The most significant food-safety issue food producers
face is microbial contamination, which can occur at any point from farm to table.
Any biotechnology product that decreases microbes found on animal products and
crop plants will significantly improve the safety of raw materials entering the
food supply. Improved food safety through decreased microbial contamination begins
on
Biotechnology Industry Organization n Guide to Biotechnology

the farm. Transgenic disease-resistant and insect-resistant crops have less

microbial contamination. New biotechnology diagnostics, similar to those described
in the chapter on medical applications of biotechnology, detect microbial diseases
earlier and more accurately, so farmers can identify and remove diseased plants
and animals before others become contaminated. Biotechnology is improving the
safety of raw materials by helping food scientists discover the exact identity of
the allergenic protein in foods such as peanuts, soybeans and milk, so they can
then remove them. Although 95 percent of food allergies can be traced to a group
of eight foods, in most cases we do not know which of the thousands of proteins in
a food triggered the reaction. With biotechnology techniques, we are making great
progress in identifying these allergens. More importantly, scientists have
succeeded in using biotechnology to block or remove allergenicity genes in
peanuts, soybeans and shrimp. Finally, biotechnology is helping us improve the
safety of raw agricultural products by decreasing the amount of natural plant
toxins found in foods such as potato and cassava.

88

Food Processing

M
icroorganisms have been essential to the food-processing industry for decades.
They play a role in the production of the fermented foods listed in Table 1. They
also serve as a rich source of food additives, enzymes and other substances used
in food processing.
IMPROvING FOOD FERMENTORS Because of the importance of fermented foods to so many
cultures, scientists are conducting a lot of work to improve the microorganisms
that carry out food fermentations. The bacterium responsible for many of our
fermented dairy products, such as cheese and yogurt, is susceptible to infection
by a virus that causes substantial economic losses to the food industry. Through
recombinant technology, researchers have made some strains of this bacterium and
other important fermentors resistant to viral infection.

We have known for years that some bacteria used in food fermentation produce
compounds that kill other, contaminating bacteria that cause food poisoning and
food spoilage. Using biotechnology we are equipping many of our microbial
fermentors with this self-defense mechanism to decrease microbial contamination of
fermented foods.
FOOD ADDITIvES AND PROCESSING AIDS Microorganisms have been essential to the food
industry not only for their importance as fermentors, but also because they are
the source of many of the additives and processing aids used in food processing.
Biotechnology advances will enhance their value to the food industry even further.

Food additives are substances used to increase nutritional value, retard spoilage,
change consistency and enhance flavor. The compounds food processors use as food
additives are substances nature has provided and are usually of plant or microbial
origin, such as xanthan gum and guar gum, which are produced by microbes. Many of
the amino acid supplements, flavors, flavor enhancers and vitamins added to
breakfast cereals are produced by microbial fermentation. Through biotechnology,
food processors will be able to produce many compounds that could serve as food
additives but that now are in scant supply or that are found in microorganisms or
plants difficult to maintain in fermentation systems. Food processors use plant
starch as a thickener and fat substitute in low-fat products. Currently, the
starch is extracted from plants and modified using chemicals or energy-consuming
mechanical processes. Scientists are using biotechnology to change the starch in
crop plants so that it no longer requires special handling before it can be used.
Enzymes produced by microbial fermentation play essential roles as processing aids
in the food industry. The first commercial food product produced by biotechnology
was an enzyme used in cheese making. Prior to biotech techniques, this enzyme had
to be extracted from the stomach of calves, lambs and baby goats, but it is now
produced by microorganisms that were given the gene for this enzyme.

The production of high-fructose corn syrup from cornstarch requires three enzymes,
and those same enzymes are important in making baked goods and beer. Other enzymes
are essential to the production of fruit juices, candies with soft centers, and
cheeses. The food industry uses more than 55 different enzyme products in food
processing. This number will increase as we discover how to capitalize on the
extraordinary diversity of the microbial world and obtain new enzymes that will
prove important in food processing.

Food Safety Testing

n addition to the many ways biotechnology is helping us enhance the safety of the
food supply, biotechnology is providing us with many tools to detect
microorganisms and the toxins they produce. Monoclonal antibody tests, biosensors,
polymerase chain reaction (PCR) methods and DNA probes are being developed that
will be used to determine the presence of harmful bacteria that cause food
poisoning and food spoilage, such as Listeria and Clostridium botulinum. We can
now distinguish E. coli 0157:H7, the strain of E. coli responsible for several
deaths in recent years, from the many other harmless E. coli strains. These tests
are portable, quicker and more sensitive to low levels of microbial contamination
than previous tests because of the increased specificity of molecular technique.
For example, the new diagnostic tests for Salmonella yield results in 36 hours,
compared with the three or four days the older detection methods required.
Biotechnology-based diagnostics have also been developed that allow us to detect
toxins, such as aflatoxin, produced by fungi and molds that grow on crops, and to
determine whether food products have inadvertently been contaminated with peanuts,
a potent allergen.

89

TABLE 1
Microbial fermentation is essential to the production of these fermented foods
beer bologna bread/baked goods buttermilk cheeses cider cocoa coffee cottage
cheese distilled liquors kefir miso olives pickles salami sauerkraut sour cream
soy sauce tamari tea tempeh tofu vinegar wine yogurt

Guide to Biotechnology n Biotechnology Industry Organization

Industrial and Environmental Applications

he contributions that biotechnology has made to health care and agriculture have
received much attention from the press and the public, but now society is
beginning to see the benefits of biotechnology’s “third wave”—industrial and
environmental biotech. This third wave of biotechnology is already successfully
competing with traditional manufacturing processes and has shown promise for
achieving industrial sustainability. To industry, sustainable development means
continuous innovation, improvement and use of “clean” technologies to make
fundamental changes in pollution levels and resource consumption. An industrially
sustainable process should, in principle, be characterized by
n n n

Industrial Sustainability

ccording to the Organization for Economic Cooperation and Development (OECD),

industrial sustainability is the continuous innovation, improvement and use of
clean technology to reduce pollution levels and consumption of resources. Modern
biotechnology provides avenues for achieving these goals. In recent years, policy-
makers, corporate executives, private citizens and environmentalists have become
more concerned about sustainable development. In response to that concern, many
leading industrial companies are doing more than meeting their legal minimums.
Many are developing policies and implementation plans for sustainability that
include guidelines for environmental health and safety as well as product
stewardship. The key words to achieving sustainability are “clean” and
“efficient.” Any change in production processes, practices or products that makes
production cleaner and more efficient per unit of production or consumption is a
move toward sustainability. In practical terms, industrial sustainability means
employing technologies and know-how to lessen material and energy inputs, maximize
renewable resources and biodegradable substances as inputs, minimize the
generation of pollutants or harmful waste during product manufacture and use, and
produce recyclable or biodegradable products.
MATERIAL AND ENERGY INPUTS Manufacturing processes have long relied on petroleum,
a nonrenewable resource that generates pollution and solid waste, as a source of
material and energy. Biotechnology provides ways to produce cleaner products and
processes by reducing the use of petroleum inputs. Industrial biotechnology
instead uses natural sugars as feedstocks.

reduction or elimination of toxic waste. lower greenhouse gases. low consumption

of energy and nonrenewable raw materials (and high use of carbohydrate feedstocks,
such as sugars and starch). lower manufacturing cost.

90

Living systems manage their chemistry more efficiently than man-made chemical
plants, and the wastes that are generated are recyclable or biodegradable.
Biocatalysts, and particularly enzyme-based processes, operate at lower
temperatures and produce less toxic waste, fewer byproducts and less emissions
than conventional chemical processes. They may also use less purified raw
materials (selectivity). Use of biotechnology can also reduce energy required for
industrial processes. Finally, just as biotechnology is providing us with new
tools for diagnosing health problems and detecting harmful contaminants in food,
it is yielding new methods of monitoring environmental conditions and detecting
pollutants. Biotechnology in industry employs the techniques of modern molecular
biology to reduce the environmental impact of manufacturing. Industrial
biotechnology also works to make manufacturing processes more efficient for
industries such as textiles, paper and pulp, and specialty chemicals. Some
observers predict biotechnology will transform the industrial manufacturing sector
in much the same way that it has changed the pharmaceutical, agricultural and food
sectors. Industrial biotechnology will be a key to achieving industrial and
environmental sustainability.

Through biotechnology, the use of renewable, biomassbased feedstocks will

increase. Bio-feedstocks offer two environmental advantages over petroleum-based
production: Production will be cleaner, in most cases, and less waste will be
generated. When the biomass source is agricultural refuse, our gains double: We
will enjoy all the advantages of bio-feedstocks while reducing wastes generated
from another human endeavor—agriculture. A final advantage of using plant biomass
as feedstock is that as our crop of feedstock grows, it consumes CO2—one of the
greenhouse gases.

Biotechnology Industry Organization n Guide to Biotechnology

Today at least 5 billion kilograms of commodity chemicals are produced annually in
the United States using plant biomass as the primary feedstock. Biotechnology will
also have an impact on two sources of energy: fossil fuels and new biomass-based
fuels. Innovations wrought by biotechnology can help remove the sulfur from fossil
fuels, significantly decreasing their polluting power. Using biomass for energy
has the same environmental advantages as using biomass feedstocks, so government
labs have devoted significant resources to research on recombinant technology and
bioprocess engineering to improve the economic feasibility of biomass-derived
energy.
INDUSTRIAL MANUFACTURING PROCESSES In addition to working toward sustainability by
using biomass-based material and energy inputs, biotechnology offers us many
options for minimizing the environmental impact of manufacturing processes by
decreasing energy use and replacing harsh chemicals with biodegradable molecules
produced by living things.

produced by all living organisms. In humans, enzymes help digest food, turn the
information in DNA into proteins, and perform other complex functions. Enzymes are
characterized according to the compounds they act upon. Some of the most common
enzymes are proteases, which break down protein; cellulases, which break down
cellulose; lipases, which act on fatty acids and oils; and amylases, which break
starch down into simple sugars. Industrial biotechnology companies look for
biocatalysts with industrial value in the natural environment; improve the
biocatalysts to meet very specific needs, using the techniques described below;
and manufacture them in commercial quantities using fermentation systems similar
to those that produce human therapeutic proteins or bulk yeast for the brewing and
baking industries. In some cases, genetically altered microbes (bacteria, yeast,
etc.) carry out the fermentation. In other cases, either naturally occurring
microbes or microbes genetically modified with other techniques are the production
organism.
DISCOvERING NOvEL BIOCATALYSTS Companies involved in industrial biotechnology
constantly strive to discover and develop high-value enzymes or other bioactive
compounds that will improve current manufacturing processes.

Unlike many chemical reactions that require very high temperatures and pressures,
reactions using biological molecules work best under conditions that are
compatible with life—that is, temperatures under 100° F, atmospheric pressure and
water-based solutions. Therefore, manufacturing processes that use biological
molecules can lower the amount of energy needed to drive reactions. Manufacturing
processes that use biodegradable molecules as biocatalysts, solvents or
surfactants are also less polluting. Microbial fermentation systems have provided
us with some very important industrial solvents, such as ethanol and acetic acid,
for decades. Many surfactants used in chemical manufacturing processes are
biological molecules that microorganisms produce naturally, such as emulsan and
sophorolipids. Marine biotechnologists have recently discovered a surfactant
produced by marine microorganisms that may replace chemical solvents. However, the
biological products that offer us the greatest potential for decreasing the
environmental impact of industrial manufacturing processes are the biocatalysts,
which are living organisms or simply their enzymes.

91

Chemical processes, including paper manufacturing, textile processing and

specialty chemical synthesis, sometimes require very high or very low temperatures
or very acidic or alkaline conditions. Incorporating biocatalysts into
manufacturing processes carried out under extreme conditions requires finding
organisms that can survive there. The best place to begin the search for such an
organism is in natural environments that mimic the extreme manufacturing
conditions, and the best organisms to look for in those environments are
microorganisms. Since the dawn of life, microbes have adapted to every imaginable
environment. No matter how harsh the environment, some microbe has found a way to
make a living there. Life in unusual habitats makes for unique biocatalysts, and
the great majority of that biochemical potential remains untapped. Fewer than 1
percent of the microorganisms in the world have been cultured and characterized.
Through bioprospecting, scientists are discovering novel biocatalysts that will
function optimally at the relatively extreme levels of acidity, salinity, tempera-

Biocatalysts

ndustrial biotechnology companies develop new enzymes, biocatalysts, to be used in

manufacturing processes of other industries. Enzymes are proteins

Guide to Biotechnology n Biotechnology Industry Organization

ture or pressure found in some industrial manufacturing processes—hence the name
extremophiles. Information from genomic studies of microbes is helping researchers
capitalize on the wealth of genetic diversity in microbial populations.
Researchers use DNA probes to fish, on a molecular level, for genes that express
enzymes with specific biocatalytic capabilities. Once snared, such enzymes can be
identified and characterized for their ability to function in industrial
processes, and if necessary, they can be improved with biotechnology techniques.
IMPROvING EXISTING BIOCATALYSTS To improve the productivity-to-cost ratio,
scientists are modifying genes to increase enzyme productivity in microorganisms
currently used in enzyme production. They also give new manufacturing capabilities
to these microbial workhorses by genetically altering them to make enzymes that
come from microbes that are too expensive or too finicky to cultivate in the lab.

straw, according to Burrill & Co. Another 50 billion could be made using such raw
materials as wood-product manufacturing residues, municipal solid waste and garden
waste. Ethanol from dedicated energy crops, like switchgrass, could add even more.
President Bush’s initiative followed passage of the 2005 Energy Policy Act,
landmark legislation for industrial biotech, which authorized over $3 billion in
funding for biofuels and biobased products and established a national renewable
fuels standard. The bill established a goal of displacing 30 percent of today’s
gasoline consumption with ethanol or other biofuels by 2030. A recent Natural
Resources Defense Council report suggests that that potential could be even
higher. Other recent developments in biomass energy include:
n

The Department of Energy announced plans to issue up to $160 million in

competitively awarded grants for construction of pioneer biorefineries. A growing
number of states have implemented their own renewable fuels requirements. Many are
also providing incentives for biorefinery construction. A 2006 report from the
Worldwatch Institute found that “development of biofuels and bio-based co-products
has the potential to increase energy security for many nations; to create new
economic opportunities for people in rural, agricultural areas the world over; to
protect and enhance the environment on local, regional, and global scales; and to
provide new and improved products to millions of consumers.” A 2005 joint report
from the Departments of Energy and Agriculture found that more than 1 billion tons
of biomass are available in the US to produce biofuels and bioproducts, enough to
meet over half of US demand for transportation and chemicals. A 2004 Natural
Resources Defense Council report projects biofuels could add $5 billion to farmer
profits by 2025. Also in 2004, the Ag Energy Working Group of the Energy Future
Coalition published a report showing how America’s farmers can contribute 25
percent of the total energy consumed in the United States by 2025, without
affecting food and feed production. A growing number of states have implemented
their own renewable fuels requirements. Many are also providing incentives for
biorefinery construction.

92

The biotechnology techniques of protein engineering and directed protein evolution

maximize the effectiveness and efficiency of enzymes. They have been used to
modify the specificity of enzymes, improve catalytic properties or broaden the
conditions under which enzymes can function so that they are more compatible with
existing industrial processes.

Biofuel
I

In his January 2006 State of the Union address, President Bush declared: “America
is addicted to oil, which is often imported from unstable parts of the world. The
best way to break this addiction is through technology.” One of his key
technological solutions was “research in cutting-edge methods of producing
ethanol, not just from corn, but from wood chips and stalks, or switch grass.” He
announced a national goal to make this new kind of ethanol practical and
competitive within six years, pledging $150 million in FY 2007 for biomass
research, development and demonstration. Advances in industrial biotechnology and
development of new integrated “biorefineries” are at the heart of ethanol
production from all sources. April 2004 saw the first commercial production of
ethanol from cellulose, made from wheat straw using biotech enzymes. Some 10 to 15
billion gallons of ethanol could be produced each year from corn stalks and husks
and wheat

Biotechnology Industry Organization n Guide to Biotechnology

Green Plastics

Nanotechnology

iotechnology also offers us the prospect of replacing petroleum-derived polymers

with biological polymers derived from grain or agricultural biomass. In 2001, the
world’s first biorefinery opened in Blair, Nebraska, to convert sugars from field
corn into polylactic acid (PLA)—a compostable biopolymer that can be used to
produce packaging materials, clothing and bedding products. Price and performance
are competitive with pretroleum-based plastics and polyesters. Several national
retailers, including Whole Foods and Wal-Mart, are now using PLA packaging. At the
2006 BIO International Convention in Chicago, professional models in PLA designer
gowns put industrial biotech center stage in the world’s first biotech fashion
show. Also in 2001, DuPont, and its development partners Genencor and Tate & Lyle,
created the high-performance polymer Sorona from the bioprocessing of corn sugar
at a biorefinery in Decatur, Illinois. Production of bio-PDO, the renewable raw
material for Sorona, is expected to begin in 2006 at a new DuPont/Tate & Lyle
biorefinery in Loudon, Tennessee. Production sold out months before the plant was
completed. Early in 2006, agri-food giant Archer Daniels Midland signed an
agreement with Metabolix, a small industrial biotech company based in Cambridge,
Massachusetts, to produce polyhydroxyalkanoates (PHAs), a versatile family of
biobased polymers, at a biorefinery in Clinton, Iowa. Industrial scientists have
also genetically modified both plants and microbes to produce polyhydroxybutyrate,
a feedstock for producing biodegradable plastics. Finally, biotechnology provides
us with the opportunity to produce abundant amounts of natural protein polymers,
such as spider silk and adhesives from barnacles, through microbial fermentation.
In place of petroleum-based chemicals to create plastics and polyesters,
biotechnology uses sugar from plant material. Almost all the giant chemical
companies are building partnerships with biotech companies to develop enzymes that
can break down plant sugars. In summary, no matter what stage of industrial
production you select—inputs, manufacturing process or final product—biotechnology
provides tools, techniques and knowhow to move beyond regulatory compliance to
proactive pollution prevention and resource conservation strategies that are the
hallmarks of industrial sustainability.

emember the movie Fantastic Voyage, in which technology existed to shrink a full-
size submarine and its human passengers to microscopic size? Today, industrial
biotech companies are embarking on their own fantastic voyage into the
submicroscopic worlds of biotechnology and nanotechnology. There, they are
exploiting the physio-chemical activities of cells to accomplish tasks at nano
(10-9 meters) scale. Some are taking genomics and proteomics one step further and
exploring how to apply this knowledge gained in the organic world to the inorganic
world of carbon and silicon. For example, Genencor International and Dow-Corning
have partnered to combine their respective expertise in protein-engineered systems
and silicon. Their strategic alliance seeks to apply the biotech business model to
a third outlet of creativity where products can be developed for other companies
based on specific needs. Such convergence of biotech and nanotech promises to
yield many exciting and diverse materials and products. In the area of photonics
lies the potential for developing new micro-optical switches and optical micro-
processing platforms. In the field of catalysis, the use of inorganic carbon or
silicon substrates embedded with biocatalysts has high commercial potential.
BUILDING NANOSTRUCTURES One of the more exciting research-stage nano-biotech
applications uses knowledge about protein engineering to “build” pre-engineered
nanostructures for specific tasks. For instance, we know that certain genes in
aquatic microorganisms code for proteins that govern the construction of inorganic
exoskeletons. In theory, it should be possible to elucidate these gene functions
and re-engineer them to code for nanostructures that could be commercially
important, such as specific silicon chips or micro-transistors.

93

Researchers at the University of Illinois recently discovered a first-of-its-kind

carbon-silicon compound in freshwater diatoms. This discovery promises to open the
door to understanding the molecular process of biosilicification, or the ways
plants and animals build natural structures. This understanding may lead to
applications ranging from low-cost synthesis of advanced biomaterials to new
treatments for osteoporosis. NASA and some companies are also looking at bioactive
ceramics found to have unanticipated bio-adhesive properties. These
Guide to Biotechnology n Biotechnology Industry Organization
properties could provide new ways to purify water since bacteria and viruses
adhere to these ceramic fibers. Protein polymer structures are another area ripe
for research and development. Industrial biotech companies have years of
experience with genetic platform technologies that can be applied to repeating
amino acid sequences. These five to six repeat segments can govern the physical
structure of a host of biopolymers. New technology allows spider silk to be
produced in goats, but in the future it may be possible for scientists to build
polymers in the lab that are even stronger and that won’t need living expression
systems for largescale production. It is not difficult to imagine completely new,
commercially attractive polymers being developed using recombinant DNA technology.
Carbon nanotube technology is another exciting area of research and development in
the nanoworld. Their great tensile strength makes nanotubes perfect for use in new
high-tech composites, for switching in computers, and for the storage of hydrogen
energy for transportation or power-generation applications. Carbon nanotubes can
be coated with reaction-specific biocatalysts and other proteins for specialized
applications. Biotechnology may hold the key to making carbon nanotubes even more
economically attractive. Looking further into the future, we may see the use of
DNA fragments for electronic switching come into play, along with the materials
just discussed. The number of possible new nano-bio combinations is amazingly
large. What does the future market for nanotech look like? The National Science
Foundation estimates that by 2015 the market for nanotech products could exceed $1
trillion. Industrial biotechnology is poised to merge its applications with carbon
and silicon, a merger that could catapult industrial biotech companies from
nanospace into financial hyperspace.

grading wastes, such as polychlorinated biphenyls (PCBs), to harmless compounds.

Marine biotechnologists are studying ways that estuarine bacteria can detoxify
materials such as chemical sea brines that cause environmental problems in many
industries. Environmental biotechnology can more efficiently clean up many
hazardous wastes than conventional methods and greatly reduce our dependence for
waste cleanup on methods such as incineration or hazardous waste dump sites.
HOW DOES IT WORK? Using biotechnology to treat pollution problems is not a new
idea. Communities have depended on complex populations of naturally occurring
microbes for sewage treatment for over a century. Every living organism—animals,
plants, bacteria and so forth—ingests nutrients to live and produces a waste
byproduct as a result. Different organisms need different types of nutrients.
Certain bacteria thrive on the chemical components of waste products. Some
microorganisms, for example, feed on toxic materials such as methylene chloride,
detergents and creosote.

94

Environmental engineers use bioremediation in two basic ways. They introduce

nutrients to stimulate the activity of bacteria already present in the soil at a
hazardous waste site, or they add new bacteria to the soil. The bacteria then
“eat” the hazardous waste at the site and turn it into harmless byproducts. After
the bacteria consume the waste materials, they die off or return to their normal
population levels in the environment. The vast majority of bioremediation
applications use naturally occurring microorganisms to identify and filter
manufacturing waste before it is introduced into the environment or to clean up
existing pollution problems. Some more advanced systems using genetically modified
microorganisms are being tested in waste treatment and pollution control to remove
difficult-to-degrade materials. In some cases, the byproducts of the pollution-
fighting microorganisms are themselves useful. Methane, for example, can be
derived from a form of bacteria that degrades sulfur liquor, a waste product of
paper manufacturing.
ENvIRONMENTAL MONITORING The techniques of biotechnology are providing us with
novel methods for diagnosing environmental problems and assessing normal
environmental conditions so that we can be better-informed environmental stewards.
Companies have developed methods for detecting harmful organic pollutants in the
soil using mono-

Environmental Biotechnology

nvironmental biotechnology is the use of living organisms for a wide variety of

applications in hazardous waste treatment and pollution control. For example, a
fungus is being used to clean up a noxious substance discharged by the paper-
making industry. Other naturally occurring microbes that live on toxic waste dumps
are deBiotechnology Industry Organization n Guide to Biotechnology
SOME INDUSTRIAL BIOTECH APPLICATIONS BY SECTORS
n n n n n n n n

The paper industry: improving manufacturing processes, including the use of

enzymes to lower toxic byproducts from pulp processes. The textiles industry:
lessening toxic byproducts of fabric dying and finishing processes. Fabric
detergents are becoming more effective with the addition of enzymes to their
active ingredients. The food industry: improving baking processes, fermentation-
derived preservatives and analysis techniques for food safety. The livestock
industry: adding enzymes to increase nutrient uptake and decrease phosphate
byproducts. The energy industry: using enzymes to manufacture cleaner biofuels
from agricultural wastes.

Biological fuel cells Fine and bulk chemicals Chiral compound synthesis Synthetic
fibers for clothing Pharmaceuticals Food flavoring compounds Biobased plastics
Biopolymers for automobile parts Bioethanol for transportation Nutritional oils
Oil and gas desuphurization Leather degreasing Biohydrogen Biopolymers for plastic
packaging Coal bed methane water treatment Chem/bio warfare agent decontamination

n n n n

Pulp and paper bleaching Biopulping (paper industry) Specialty textile treatment
Enzyme food processing aids Metal ore heap leaching Electroplating/metal cleaning
Rayon and other synthetic fibers Metal refining Vitamin production Sweetener
production (high-fructose corn syrup) Oil well drill hole completion (non-toxic
cake breakers) Road surface treatment for dust control Textile dewatering
Vegetable oil degumming

n n

n n n

n n n n n

95

n n
n

clonal antibodies and the polymerase chain reaction, while scientists in

government labs have produced antibody-based biosensors that detect explosives at
old munitions sites. Not only are these methods cheaper and faster than laboratory
methods that require large and expensive instruments, but they are also portable.
Rather than gathering soil samples and sending them to a laboratory for analysis,
scientists can measure the level of contamination on site and know the results
immediately.

Industries That Benefit

n

The chemical industry: using biocatalysts to produce novel compounds, reduce waste
byproducts and improve chemical purity. The plastics industry: decreasing the use
of petroleum for plastic production by making “green plastics” from renewable
crops such as corn or soybeans.
Guide to Biotechnology n Biotechnology Industry Organization

n
Consumer Goods Made With Industrial Biotech
CONSUMER PRODUCT
Detergent

OLD PROCESS
Phosphates added as brightening and cleaning agents

NEW INDUSTRIAL BIOTECH ENABLING BIOTECHPROCESS TECHNOLOGY

Addition of biotechnology enzymes as brightening and cleaning agents: n Proteases
remove protein stains n Lipases remove grease stains n Amylases remove starch
stains Genetically enhanced microbes or fungi engineered to make enzymes

CONSUMER BENEFIT
Elimination of water pollution from phosphates n Brighter, cleaner clothes with
lower-temperature wash water n Energy savings
n

Bread

Potassium bromate, a Addition of biotechnology suspected cancer-causing enzymes

to: agent at certain levels, n enhance rising added as a preservative n strengthen
dough and a dough strengthening n prolong freshness agent Polyester* produced
chemically from petroleum feedstock

Microorganisms genetically enhanced to produce baking enzymes (directed evolution

and recombinant DNA)

High-quality bread Longer shelf life n No potassium bromate

n n

Polyester Bedding

96
Vitamin B2 Toxic chemicals, such as aniline, used in a ninestep chemical synthesis
process Open-pit mining of pumice; fabric washed with crushed pumice stone and/or
acid Wood chips boiled in a harsh chemical solution to yield pulp for paper making
Food and feed grains fermented into ethanol (a technology that is thousands of
years old)

Biotech polyester (PLA) Existing bacillus microbe produced from corn sugar used to
ferment corn sugar feedstock to lactic acid; lactic acid converted to a
biodegradable polymer by heating; polymer made into plastic products and polyester
One-step fermentation process uses vegetable oil as a feedstock Genetically
enhanced microbe developed to produce vitamin B2 (directed evolution)

PLA polyester does not harbor body odor like other fibers n Biodegradable n Not
made from petroleum n Does not give off toxic smoke if burned
n

Biologically produced without chemicals n Greatly reduces hazardous waste

generation and disposal
n

Stonewashed Jeans

Fabric washed with biotechnology enzyme (cellulase) to fade and soften jeans or
khakis Enzymes selectively degrade lignin and break down wood cell walls during
pulping Cellulase enzyme technology allows conversion of crop residues (stems,
leaves, straw, and hulls) to sugars that are then converted to ethanol

Textile enzymes produced by genetically enhanced microbe (extremophiles and

recombinant DNA) Wood-bleaching enzymes produced by genetically enhanced microbes
(recombinant DNA) Genetically enhanced organism developed to produce enzymes that
convert agricultural wastes into fermentable sugars (directed evolution, gene
shuffling)

Less mining Softer fabric n Reduced energy consumption n Lower cost

n n

Paper Bleaching

Reduces use of chlorine bleach and reduces toxic dioxin in the environment n Cost
savings due to lower energy and chemical costs
n

Ethanol Fuel

Renewable feedstock Reduces greenhouse gas emissions n Increases domestic energy

production n Is more energy efficient to produce than old process
n n

*any synthetic fiber

Biotechnology Industry Organization n Guide to Biotechnology

CONSUMER PRODUCT
Antibiotics

OLD PROCESS
Chlorinated solvents and hazardous chemicals used to produce antibiotics through
chemical synthesis Surfactants and/or saline solutions (do not remove protein
deposits) used to clean lenses

NEW INDUSTRIAL BIOTECH ENABLING BIOTECHPROCESS TECHNOLOGY

One-step biological process uses direct fermentation to produce antibiotic
intermediate Genetically enhanced organism developed to produce the key
intermediate of certain antibiotics (recombinant DNA)

CONSUMER BENEFIT
65% reduction in energy consumption n Overall cost savings
n

Contact Lens Solution

Protease enzymes remove Genetically enhanced protein deposits from the microbes
engineered to make contact lens protease enzymes (directed evolution)

More effective contact lens cleaning n Less eye irritation

n

97

Guide to Biotechnology n Biotechnology Industry Organization

Examples of Industrial Enzymes
ENZYMES
Carbohydrases

SOURCE OR TYPE

APPLICATIONS
Laundry and dishwashing detergents, industrial pipe/tank cleaners, textiles, pulp
and paper, fermentation ethanol

Alpha-amylase

Bacterial a-amylase (e.g., Bacillus subtilis), Fungal a-amylase (e.g., Aspergillus

niger), Alkaline a-amylase From a strain of Bacillus

Textiles, starch syrups, laundry and dishwashing detergents, paper desizing,

fermentation ethanol, animal feed Brewing, maltose syrup Dishwashing detergents,
animal feed, textiles, bioenergy production

b-amylase Cellulase b-Glucanase b-Glucosidase Dextranase Dextrinase (almost

identical to a-glucosidase) a-Galactosidase (melibiase)

exo-b-1,4-glucanase, endo-b-1,4-glucanase

Brewing industry Transforms isoflavone phytoestrogens in soymilk

Made by various microorganisms (e.g., Leuconostoc mesenteriodes)

Hydrolyzes the polysaccharide dextran Cleaves dextrin into two molecules of

glucose Could increase yield of sucrose; potential use in the beet sugar industry

98
Glucoamylase Hemmicellulase/Pentosanase/Xylanase Invertase Lactase Naringinase
Pectinase Pullulanase Proteases Klebsiella aerogenes, Bacillus acidipullulyticus,
Bacillus subtilis Kluyveromyces lactis, Asperigillus oryzae, Bacillus Aspergillus
niger, Rhizopus, Endomyces Thermomyces lanuginosus, Penicillium simplicissimum

Manufacture of dextrose syrup and highfructose syrup Baking, fruit juice

manufacture, wood pulp processing Manufacture of invert syrup from cane or beet
sugar (use is minor) Eliminates lactose from dairy foods Debitter citrus peel
Fruit processing Antistaling agent in baked goods Brewing, baking goods, protein
processing, distilled spirits, laundry and dishwashing detergents, lens cleaners,
leather and fur, chemicals

Acid proteinase Alkaline protease Bromelain Pepsin Peptidases Aminopeptidase

Endothia parasitica, Rhizopus, Aspergillus niger, A. oryzae Bacillus subtilis,

Bacillus licheniformis Pineapple stem Porcine or bovine stomach

Baking, improves dough handling Detergents, leather and fur Food industry Cheese
production

Lactococcus lactis

Food and animal feed

Biotechnology Industry Organization n Guide to Biotechnology

ENZYMES
Endo-peptidase Subtilisin Lipases and Esterases Aminoacylase Glutaminase Lysozyme
Penicillin acylase Isomerase Oxireductases Alcohol dehydrogenase Amino acid
oxidase Catalase Chloroperoxidase Peroxidase Lyases Acetolactate decarboxylase
Aspartic b-decarboxylase Histidase Transferases Cyclodextrin glycosyltransferase
Sources: Diversa & Novo Nordisk

SOURCE OR TYPE

APPLICATIONS

Bacillus subtilis var. Carlsberg, Bacillus lichenformis Phospholidases, pregastric

esterases, phosphatases Porcine kidney, Aspergillus melleus Bacillus, Aspergillus
Chicken egg white, Saccharomyces cerevisiae, Pichia pastoris Bacillus megaterium,
Escherichia coli

Chiral resolution of chemical compounds or pharmaceuticals Cleaners, leather and

fur, dairy, chemicals Optical resolution of amino acids Conversion of glutamine to
glutamate Antibacterial (germicidal in dairy industry) Chemical synthesis Converts
glucose syrup to high-fructose syrup in food industry Chemicals, detergent
bleaches, pulp bleaching

Saccharomyces cerevisiae,Thermoanarobium brockii Chiral synthesis of chemicals

Porcine kidney, snake venom Aspergillus niger Algae, bacteria, fungi, mammalian
tissues Horseradish Chiral resolution of racemic amino acid mixtures desugaring of
eggs Steroid synthesis Laundry and wood pulp bleaches

Brewing industry Manufacture of L-alanine from L-aspartic acid Achromobacter

liquidum Cosmetics

99

Manufacture of cyclodextrins from starch

Guide to Biotechnology n Biotechnology Industry Organization

Preparedness for Pandemics and Biodefense

n the wake of the September 11 terrorist attacks, BIO surveyed the industry and
found that many biotech companies were already working on defense projects or
developing technologies useful for both conventional health care and for defense
against biological, chemical and radiological/nuclear agents. Biotechnology
companies are also developing novel approaches to prepare for a pandemic,
including the development of new vaccines, antivirals and diagnostic and detection
tools.

our nation for man-made and natural emergencies. In addition, drug-delivery

technology can make urgently needed medications easier to administer on the
battlefield or during a civilian crisis. Medications could even be stored in a
soldier’s backpack.
vACCINES AGAINST WEAPONIZED PATHOGENS Vaccines of varying efficacy and convenience
exist for anthrax, smallpox, plague and tularemia, and vaccines are in development
for other infectious agents that may be used in biological assaults.

Policy

IO has a long-standing policy of opposing the use of biotechnology to develop

weapons of any sort that contain pathogens or toxins aimed at killing or injuring
humans, crops or livestock. Appropriate uses of biotechnology include products and
services to inoculate citizens against infectious agents that may be used in an
attack, to detect biological, chemical or radiological/nuclear attacks, and to
diagnose and treat those who may have been exposed to such attacks.

The major challenges in vaccine technology are to develop vaccines against a

variety of infectious agents (including new strains), to shorten the time needed
to establish immunity (some vaccines require multiple boosters to be effective),
to be able to produce them in large quantities, improve ease of administration,
and make them even safer. Biotechnology companies are working to solve these
problems with new vaccines based on improved delivery technologies and discoveries
made through genetic research. Examples: Researchers are exploring new vaccine
technologies, including vector technology to induce rapid protection. Applications
include a third-generation anthrax vaccine. This strategy has the flexibility to
address a number of different bioterrorism agents and may elicit a long-lasting
immune response after a single oral dose. By manipulating an immunotoxin-hybrid
molecule used to kill tumor cells in lymphoma patients, researchers have created a
vaccine that has been shown to protect mice against ricin, an extremely potent
toxin, without significant side effects. Agricultural biotechnology researchers
are working on fruits and vegetables genetically modified to contain vaccines.
Such foods could protect large populations in a very short period of time.
MONOCLONAL ANTIBODIES Monoclonal antibodies can be used like antibiotics or
antivirals, as a way to treat viral and bacterial infections; they can also be
used to detect the presence of infectious agents or to clear bacterial toxins from
the bloodstream. And, like vaccines, they can confer immunity against biological
agents.

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A Strategic Asset

M
any U.S. biotechnology companies are actively developing medical countermeasure
technologies. Some companies are working on defense-specific technologies under
contracts with the federal government. Many more are working on technologies that
can be used for conventional health care, pandemics and biological defense, such
as antivirals, antibiotics, and diagnostic tools. Recognizing the important value
that the biotechnology industry has in developing bioterror countermeasures,
President Bush announced in January 2003 the Project BioShield initiative, which
would fund new programs at the National Institutes of Health designed to spur
countermeasure development. The Project Bioshield Act was signed into law in July
2004 and authorizes $5.6 billion in procurement funding for medical
countermeasures against chemical, biological, radiological or nuclear attacks.
Similarly, the President approved $3.3 billion in FY 2006 and an additional $2.3
billion in FY 2007 for the Department of Health and Human Services for development
and procurement of medical countermeasures against a potential influenza pandemic.
Biotechnology companies have products and platforms, including vaccines,
therapeutics and diagnostics, that can be enlisted to prepare
Biotechnology Industry Organization n Guide to Biotechnology

Example: An antibody combination that attaches to anthrax toxin and clears it from
the body is under study. The technol-
ogy could be applied to other biowarfare threats, such as dengue fever, Ebola and
Marburg viruses, and plague.
DNA- OR RNA-BASED THERAPEUTICS Researchers are applying genomics and proteomics
technologies to discover weaknesses in viruses and bacteria that can be targeted
with a new generation of antibiotics and antivirals. Such weaknesses include
proteins or segments of RNA essential to an infectious organism’s survival or
replication. Projects are under way targeting both.

sis and allow it to be performed anywhere, without the need to ship samples to
labs. Portable biosensors have been developed to detect the exact DNA sequences of
pathogens in the atmosphere. Such rapid-detection systems provide the precious
time necessary for evacuation, vaccination or other prophylactic measures
necessary to save lives.

RNAi, or RNA interference, is another exciting technology. RNAi technologies aim

to “silence” targeted genes to prevent the manufacture of disease-causing
proteins. RNAi could apply to a number of infectious diseases related to national
preparedness. In a similar vein, the Defense Advanced Research Projects Agency
(DARPA) has funded projects that entail rapid DNA analysis, followed by the rapid
synthesis of drugs that can bind, or disable, segments of DNA crucial to an
infectious organism’s survival. Researchers have completed genome sequences for
numerous infectious agents, including the bacteria that cause malaria, stomach
ulcers and food poisoning, as well as organisms responsible for hospital-acquired
infections, cholera, pneumonia and chlamydia, and for potential biowarfare agents,
such as the organism responsible for bubonic plague (Yersinia pestis).
BATTLEFIELD EPIDEMICS Under battlefield conditions, soldiers are vulnerable to
naturally occurring infections such as influenza. The biotechnology industry is
addressing such illnesses with vaccines (including some under development that
could be taken orally), antivirals and antibiotics. DETECTION AND DIAGNOSIS As we
saw in the anthrax scare of 2001, we need to be able to rapidly determine whether
a person has been exposed to an infectious agent, and we also need capabilities
for detecting these agents in the environment. Some devices have been developed
already for these purposes, and others are in the pipeline.

Other Approaches
Remediation technologies Specialized industrial enzymes can be sprayed over
contaminated areas, rendering infectious agents harmless. Barrier strategies These
strategies center on the creation of molecular barriers to infection. One company,
for example, is developing molecules that adhere to entry sites on mucosal
membranes to prevent the absorption of viruses and bacteria into the bloodstream.
Nonbiological attacks and emergencies Although the spotlight is on bioterrorism,
the biotechnology industry is developing products that may have utility in
treating injuries and illness resulting from conventional attacks as well.
Artificial skin products, for example, were deployed to treat burn victims of the
September 11 attacks. Other biotechnology products with potential applications in
an emergency include blood products (such as blood replacement and purification
products now in development) and surgical products.

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Example: Portable detectors. DARPA provided funding for a portable detection

device that can analyze DNA from a sample to detect the presence of a preselected
infectious agent in 30 minutes. Such devices speed diagnoGuide to Biotechnology n
Biotechnology Industry Organization
Other Uses
DNA Fingerprinting

NA fingerprinting, which is also known as DNA typing, is a DNA-based

identification system that relies on genetic differences among individuals or
organisms. Every living thing (except identical twins, triplets, and so on) is
genetically unique. DNA typing techniques focus on the smallest possible genetic
differences that can occur: differences in the sequence of the four building
blocks of DNA. These building block molecules, or nucleotides, are commonly
designated A, T, C and G. Some uses of DNA typing compare the nucleotide sequence
of two individuals to see how similar they are. At other times, the scientist is
interested in assessing sequence similarity between a DNA sample and the known
sequence of a reference sample. DNA typing has become one of the most powerful and
widely known applications of biotechnology today. It is used for any task where
minute differences in DNA matter, such as determining the compatibility of tissue
types in organ transplants, detecting the presence of a specific microorganism,
tracking desirable genes in plant breeding, establishing paternity, identifying
individual remains, and directing captive breeding programs in zoos.
DNA TYPING TECHNIQUES Scientists have developed two main techniques to look
directly at minute differences in genes. Each technique has advantages and
disadvantages, and both are used in basic and applied research, by clinicians,
public health officials, forensic scientists and commercial labs. The technique of
choice depends upon the question being asked, amount of DNA available, capability
to minimize contamination, cost and urgency. Sometimes both techniques are used in
combination.

makes thousands of copies of a specific DNA sequence in a matter of hours. PCR,

like restriction analysis, allows us to compare two DNA samples to see if they
come from the same individual, but it also allows us to detect the presence or
absence of particular bits of DNA in a sample. Used in this way, PCR can quickly
and accurately diagnose infections such as HIV and chlamydia and detect genes that
may predispose an individual to many forms of cancer and cystic fibrosis, or help
protect an individual from HIV-AIDS. To successfully identify minute differences
in DNA molecules, scientists must focus DNA-typing techniques on regions of the
DNA molecule that are highly variable between two individuals. This is one of the
reasons they often use DNA from mitochondria instead of nuclear DNA, which does
not tend to vary as much from one individual to the next. Another reason for using
mitochondrial DNA is its unique inheritance pattern; virtually all is inherited
from the female parent.
FORENSIC USES In criminal investigations, DNA from samples of hair, bodily fluids
or skin at a crime scene are compared with those obtained from suspected
perpetrators. DNA typing was first used in Great Britain for law enforcement
purposes in the mid-1980s and was first employed in the United States in 1987.
Today, the Federal Bureau of Investigation performs most DNA typing for local and
state law enforcement agencies, and private biotechnology companies also perform
DNA fingerprinting tests.

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One technique, known as restriction analysis, uses naturally occurring enzymes

that cut DNA at very precise locations. Because of differences in the sequence of
nucelotides, the enzymes cut DNA samples from different individuals in different
places. The cut fragments of DNA are different sizes and compose a DNA pattern, or
“fingerprint,” unique to each individual. Comparing the different-sized DNA
fragments of two samples provides very strong evidence about whether or not the
two samples came from a single source or individual. Another DNA typing technique,
the polymerase chain reaction (PCR), makes use of the process by which cells
duplicate their DNA before they divide into two cells. PCR
Biotechnology Industry Organization n Guide to Biotechnology

DNA typing has reaped positive return in many states, where the genetic records of
prisoners were matched with samples recovered from murders and sexual assaults.
DNA typing has exonerated innocent individuals for crimes they were convicted of
before DNA fingerprinting became available. The widespread acceptance of DNA
typing by court systems around the country has led many states to pass laws
requiring people convicted of sex offenses and other crimes to be DNA typed and
included in statewide offender databases. Law enforcement officials hope to
someday integrate the FBI and various state DNA offender records into a single
national database that would allow for the rapid comparison and matching of known
offenders with genetic material recovered from crime scenes. DNA typing is also
used to identify the remains of unknown individuals, as in the recent
identification of the Unknown Soldier, or to identify the bodies of people slain
in political upheavals. American soldiers now deposit samples in a DNA data bank
as a backup for the metal dog tags they wear in combat.
PATERNITY Paternity determination is possible with DNA typing because half of the
father’s DNA is contained in the child’s genetic material. Using restriction
analysis, DNA fingerprints of the mother, child and alleged father are compared.
The DNA fragments from the mother that match the child’s are ignored in the
analysis. To establish paternity, the remaining DNA fragments in the child’s DNA
fingerprint, which have been inherited from the biological father, are then
compared to the DNA sequences of the alleged father. ANTHROPOLOGY Scientists are
using DNA typing to help piece together the thousands of fragments gathered from
the Dead Sea Scrolls. With DNA typing they can separate scrolls written on
sheepskin from those on goatskin. From this, scientists are reconstructing the
pieces as they were originally assembled.

DNA typing can determine the degree of relatedness among human fossils from
different geographic locations and geologic eras. The results shed light on the
history of human evolution. Scientists used DNA fingerprinting to identify the
remains of Czar Nicholas Romanov II of Russia and his family, executed by the
Bolsheviks in 1918. They compared DNA from bones with DNA from blood samples of
living descendants of Nicholas II, including Prince Philip of Great Britain. The
results of DNA typing disproved one woman’s claim that she was the Russian Grand
Duchess Anastasia and had survived the Romanov massacre.
WILDLIFE MANAGEMENT The more we understand about the genetic makeup of natural
populations, the better our conservation and management plans will be. Scientists
use DNA typing to measure the amount of genetic variation between different
populations of a species, determine the geographic distributions of species, help
preserve endangered or threatened species, and determine the genetic resilience of
wild populations of endangered species. For example, we now know that cheetahs are
at risk of extinction largely because there is virtually no genetic variation in
the species.

Pacific loggerheads nest in Japan and Australia, not in Mexico, yet very young
loggerheads are often found off the Mexican coast. Biologists assumed the young
loggerheads could not have swum the 10,000 miles from Japan to Mexico, and even
farther from Australia, so the origin of the Mexican loggerheads was a mystery.
Using DNA typing, however, biologists established that the young loggerheads in
Mexico are, in fact, born in Australia or Japan, are carried to Mexico by ocean
currents, and then swim back to Australia or Japan when they are ready to breed.
DNA fingerprinting has also been used to monitor illegal trade in protected
species. For example, scientists determined that fish products on sale in Japan
included whale meat that had been illegally imported, as well as other species
that had been hunted illegally. Similar studies conducted on ivory uncovered
elephant poaching in countries where it is illegal. Finally, some countries,
including the United States, are using DNA typing to prevent the importation of
caviar from endangered sturgeon species.

103

DNA typing recently helped scientists solve the mystery of the Mexican group of
Pacific loggerhead turtles.
Guide to Biotechnology n Biotechnology Industry Organization
Ethics

iotechnology was born under unique social and political circumstances,

establishing a precedent that shaped the development of the industry and continues
to influence its character even today. In 1973, a few days after Drs. Herbert
Boyer and Stanley Cohen described their successful attempt to recombine DNA from
one organism with that of another, a group of scientists responsible for some of
the seminal breakthroughs in molecular biology sent a letter to the National
Academy of Sciences (NAS) and the widely read journal Science, calling for a self-
imposed moratorium on certain scientific experiments using recombinant DNA
technology. The scientists temporarily halted their research and publicly asked
others to do the same. Even though they had a clear view of their work’s
extraordinary potential for good and no evidence of any harm, they were uncertain
of the risks some types of experiments posed. They suggested that an international
group of scientists from various disciplines meet, share up-to-date information
and decide how the global scientific community should proceed. International
scientists in this exceptionally competitive field complied with this request to
halt certain research. A few months after the request for a self-imposed
moratorium, the scientists sent a second letter, endorsed by the NAS, to the
National Institutes of Health (NIH), asking it to establish an advisory committee
for evaluating the risks of recombinant DNA, develop procedures to minimize those
risks and devise guidelines for research using recombinant DNA. In response to the
request, the NIH formed the Recombinant DNA Advisory Committee (RAC), which
received its official charter in October 1974. In February 1975, 150 scientists
from 13 countries, along with attorneys, government officials and 16 members of
the press, met at the Asilomar Conference Center to discuss recombinant DNA work,
consider whether to lift the voluntary moratorium and, if so, establish strict
conditions under which the research could proceed safely. The conference attendees
replaced the moratorium with a complicated set of rules for conducting certain
kinds of laboratory work with recombinant DNA, but disallowed other experiments
until more was known. The final report of the Asilomar Conference was submitted to
the NAS in April 1975, and a conference summary was published in Science and the
academy Proceedings on June 6, 1975. At no other time has the international
scientific community voluntarily ceased the pursuit of knowledge before any
problems occurred, imposed regulations on itself and been so open with the public.
Biotechnology Industry Organization n Guide to Biotechnology

The NIH-RAC met for the first time hours after the Asilomar conference ended. The
committee adopted the conference consensus as interim rules for federally
supported laboratories in the United States. It spent the next year developing an
initial set of guidelines for recombinant dna molecule research. After public
review of the draft guidelines, the RAC published the final version in July 1976.
Comparable organizations in other countries promulgated similar guidelines
overseeing laboratory research with recombinant DNA. BIO member companies have
voluntarily adhered to these guidelines since their inception. Over the next few
years, the RAC revised the guidelines in the face of accumulating data that
supported the safety of recombinant DNA laboratory research. Oversight policies of
laboratory research in many other countries relaxed as well. During the early
1980s, as the biotechnology industry moved from basic research into product
development, the RAC assumed the responsibility of formulating safety standards
for industrial manufacturing using recombinant organisms and reviewed proposals
voluntarily submitted by companies such as Genentech and Eli Lilly. As data
supporting the safety of recombinant DNA research and product development grew,
and biotechnology products moved toward commercialization under the regulatory
oversight of the Food and Drug Administration, Environmental Protection Agency and
U.S. Department of Agriculture, the RAC began to focus more on social and ethical
issues, precipitated primarily by the use of recombinant DNA in humans for
therapeutic purposes. Thus, from its inception, the biotech industry has supported
public discussion and appropriate regulation of its work. BIO values the important
role the academic scientific community and the RAC have played in the early stages
of recombinant DNA research, biotechnology manufacturing and human gene transfer
trials. Their approach, supported voluntarily by private and public researchers,
ensured the thoughtful, responsible and very public introduction of and discussion
about this new technology.

104

BIO Activities

IO is committed to the socially responsible use of biotechnology to save or

improve lives, improve the quality and abundance of food, and protect our
environment. Our board of directors has adopted a Statement of Ethical Principles,
and we continue to refine a compre-
hensive vision of ways to ensure biotechnology is used for the betterment of
humankind and not abused. As our companies develop technologies that promise to
benefit humankind, these technologies also may bring ethical questions. To help us
examine bioethics issues as they arise, BIO several years ago formed a committee
on bioethics. In June 2006, BIO’s Board of Directors approved the establishment of
a Board standing committee on bioethics to enable industry executives to
participate in policy, strategy and planning discussions regarding bioethics
issues that confront all sectors of the industry: human health, food and
agriculture, and industrial and environmental biotechnology. We actively encourage
discussion of ethical and social implications of scientific developments in
biotechnology. In response to a call from U.S. Supreme Court Justice Stephen
Breyer and others for an ongoing conversation about the societal impacts of legal
and judicial decisions, BIO and Ernst & Young initiated the Biojudiciary Project.
The 501(c)(3) organization aims to develop informative, objective educational
materials and programs to help judges, law clerks and attorneys learn more about
biotechnology. Biotechnology has extraordinary potential to improve the health and
well-being of people in the developing world, but significant impediments exist to
the development and dissemination of diagnostics, therapeutics and vaccines for
the infectious diseases prevalent in developing countries. To explore the
obstacles and devise mechanisms for circumventing them, BIO and the Bill and
Melinda Gates Foundation joined forces in 2004 to establish BIO Ventures for
Global Health, a new non-profit organization. BVGH works with companies, donors
and investors to bring new vaccines, therapies, diagnostics and delivery tools to
market in developing nations. To further encourage public discussion of the
ethical and social aspects of biotechnology, BIO initiated dialogue with leaders
of major religious traditions and denominations. We also have met with members of
the public who describe themselves as deeply religious. These activities led to
the signing of a memorandum of understanding between BIO and the National Council
of Churches in 2003. BIO and the biotechnology industry respect the power of the
technology we are developing, and we accept the need

for appropriate regulation. We work with state, federal and international

regulatory bodies to shape the development of regulatory policies that foster
safe, effective and beneficial products. We must continue to address ethical
questions that arise as science progresses. While biotechnology can greatly
improve the quality of life, we recognize that this new technology should be
approached with an appropriate mixture of enthusiasm, caution and humility.

Ethical Issues

wide variety of social and ethical issues are associated with biotechnology
research, product development and commercialization. Below, we discuss some of
these issues. For additional information on these and topics not discussed here,
please visit our Web site at www.bio.org.
GENE THERAPY Gene therapy is subject to greater oversight than virtually all other
therapeutic technologies. The NIH guidelines require federally funded institutions
and their collaborators to submit detailed information about proposed and ongoing
clinical trials of gene therapy products. Much of this information must be
disclosed to the public. The FDA, which has statutory authority to regulate gene
therapy products including clinical trials, collects detailed information about
investigational products and clinical trials, reviews adverse event reports, and
requires annual reports of all ongoing trials. The combined activities and
responsibilities of the FDA, through its statutory role as the regulator of drug
development, and the NIH/Recombinant DNA Advisory Committee (RAC), as the forum
for public discussion, have served to protect patients while ensuring that
important research moves ahead.
105

The field of gene therapy continues to focus on patients with severe and life-
threatening diseases who usually have few treatment options or who have failed all
available therapies. Thousands of patients have now received somatic cell
(nonreproductive cell) gene therapies targeted at life-threatening genetic
diseases, cancer and AIDS. Since the first clinical trial, started in 1990, more
sponsors and academic researchers have moved into the area of gene therapy and are
conducting human clinical trials, but the research pace has remained slow and
deliberate. Even after a decade of research and clinical testing, many of the gene
therapy clinical trials active today are in early-phase studGuide to Biotechnology
n Biotechnology Industry Organization
ies (Phase I/II) that evaluate the safety of the gene therapy vector (the agent
used to carry new DNA into a cell). Gene therapies continue to be in early stages
of development because researchers are methodically exploring options for routes
of administration, dosing regimes, patient populations, indications, combination
therapies and novel vectors. BIO believes that both the FDA and the NIH/RAC play
important roles in the oversight process. BIO recommends that any system of
oversight for gene therapy provide the agencies with safety data while ensuring
patient confidentiality and protection of trade secrets. BIO is always ready to
work with the NIH/RAC and the FDA to develop a system that protects patients
without hurting the integrity of the product development process.
GERM-LINE GENE THERAPY MORATORIUM For more than a decade, the academic and
industrial research communities have observed a voluntary moratorium on gene
therapy procedures that would affect the germ-line cells—the egg and sperm—that
pass on genetic composition.

This option could be jeopardized if genetic information were used to discriminate.

STEM CELLS Researchers can now separate early, undifferentiated stem cells from
blastocysts—the 5-day-old ball of cells that eventually develops into an embryo.
Such embryonic stem cells can differentiate into any cell type found in the human
body, and they also have the capacity to reproduce themselves. The ability to
maintain stem cell lines in culture and direct their development into specific
cell types holds the potential to save many lives by controlling cancer, re-
establishing function in stroke victims, curing diabetes, regenerating damaged
spinal cord or brain tissue and successfully treating many diseases associated
with aging.

These undifferentiated cells lines are also powerful research tools. By studying
these cells, we will begin to understand the mechanisms that guide cell
differentiation and de-differentiation. Scientists have also learned that
undifferentiated cells from other tissue (for example, “adult” stem cells) have
value. BIO supports research on these cells. However, according to the NIH and the
NAS, only the embryonic stem cell can be turned into any cell type. On August 9,
2001, President Bush announced federal funding would be allowed for research on
embryonic stem cell lines that were derived from blastocysts prior to 9:00 p.m.
that day. Fewer cell lines than anticipated are available for federal funding. A
stem-cell bill calling for the relaxation of the restrictions passed the House in
2005 and the Senate in 2006. President Bush vetoed the legislation, however, and
the House failed to override the veto, leaving the 2001 restrictions in place. In
the meantime, privately funded research has advanced and use of stem cells in
human clinical trials may start soon.
CLONING Cloning is a generic term for the replication in a laboratory of genes,
cells or organisms from a single original entity. As a result of this process,
exact genetic copies of the original gene, cell or organism can be produced.

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MEDICAL PRIvACY AND GENETIC DISCRIMINATION BIO recognizes the need for
confidentiality of all individually identifiable medical information. We support
national policy—legislation or regulations—to protect the confidentiality of all
personal medical information, including data derived from genetic tests. The
industry believes that an individual’s medical information must be respected,
treated confidentially and safeguarded from discriminatory misuse. This protection
must be balanced, however, with the need to continue valuable medical research
into new diagnostic tests, therapies and cures. BIO believes that protecting
patient privacy and promoting medical research are mutually attainable goals.

In September 1996, BIO’s board of directors called for strong controls on the use
of all confidential medical information, including genetic information. At BIO’s
urging, 11 national biotechnology industry groups from around the world have also
endorsed the call for strong protections against the misuse of personal medical
information. BIO supports legislation that prohibits insurers from denying
individuals insurance based on their genetic information. People should have the
option of using diagnostic or predictive tests that can help them recognize early
warning signs of disease and seek proper treatment.
Biotechnology Industry Organization n Guide to Biotechnology

BIO is opposed to human reproductive cloning—using cloning technology to create a

human being. BIO was one of the first national organizations to offer public
support for voluntary moratorium on research into cloning a whole human being.
Human reproductive cloning would
involve taking the nucleus of a somatic cell (a body cell that is neither an egg
nor a sperm) of a person and inserting it into an unfertilized egg from which the
nucleus has been removed. The egg containing the somatic cell nucleus is then
implanted into a woman’s uterus. In theory, this would lead to the development of
a human being after a gestation period. Reproductive cloning is too dangerous and
raises far too many ethical and social questions to be undertaken. There are grave
moral, ethical and safety concerns surrounding this issue. Another type of cloning
involves somatic cell nuclear transfer to an egg, as described above. However, as
the egg divides, the undifferentiated cells are kept in culture and never
implanted. A few days after cell division begins, stem cells are separated from
the rest of the cells. The stem cells continue to divide, creating a cell line
that is genetically identical to the somatic cell from which the nucleus was
removed. Undifferentiated cells that are genetically identical to the patient have
remarkable therapeutic potential. Given the proper environments, these cells could
develop into new tissues that could replace diseased tissues and cure diseases
such as diabetes, Parkinson’s, Alzheimer’s and various types of cancer and heart
disease. This avenue of study could produce replacement skin, cartilage and bone
tissue for burn victims and nerve tissue for those with spinal cord or brain
injuries. Research is also going on regarding the environmental cues, genes and
structures that direct cell differentiation into whole organs composed of
different tissue types. This application of cloning technology is often referred
to as therapeutic cloning, or somatic cell nuclear transfer (SCNT). One reason for
doing SCNT is to understand the process of reprogramming—how the egg cell takes
genetic material from a fully differentiated cell and turns it back into an
undifferentiated cell. Once that process is understood, egg cells would not be
needed and this process could be replicated in a lab. Because of the remarkable
potential of cellular cloning to cure diseases and restore function to diseased
tissues, in 2002 the National Academy of Sciences released a report supporting the
use of cloning for therapeutic purposes, but opposing its use for reproductive
cloning. BIO agrees with academy’s conclusions and positions.
FOOD AND AGRICULTURE Agriculture is fundamental to the economies and environments
of the entire world. Agricultural biotechnology is

used to modify plants and animals to meet consumer demand for more healthful,
nutritious foods, and to produce foods in more environmentally sustainable ways.
Crops and animals are also being modified to provide new, more plentiful and safer
sources of medicine to treat human diseases. BIO is dedicated to open discussion
with consumers, farmers, legislators and opinion leaders regarding ethical issues
in the use of agricultural biotechnology. BIO member companies affirm and uphold
the sciencebased regulation and government oversight of agricultural biotechnology
by the Food and Drug Administration, the U.S. Department of Agriculture and the
Environmental Protection Agency. This oversight ensures the safety and quality of
the food supply and has established effective performance standards for developing
safe techniques to reduce agricultural losses to plant disease, insect pests and
weeds. We believe the public should fully participate in the introduction of these
new products both through an open, accessible and accountable regulatory system
and through exercise of free market choice via market mechanisms. We encourage
increased awareness and understanding of how agricultural biotechnology is being
applied and its impact on farming practices, the environment and biological
diversity.
USE OF ANIMALS IN RESEARCH Research involving animals has been critical to
understanding the fundamental processes of human biology that are so integral to
modern medicine. Biotechnology companies have depended on this research to develop
more than 200 drugs and vaccines approved by the U.S. Food and Drug
Administration, helping 800 million people worldwide and preventing incalculable
human suffering.

107
BIO members are compelled by ethical and legal concerns to evaluate the safety and
efficacy of potential medicines and food products before they are given to humans
and animals; the use of animals in research is a requirement for many such
products. The appropriate and responsible use of animals is therefore an
indispensable part of biomedical and agricultural research. BIO members are
committed to act ethically and to apply high standards of care when using animals
in scientific procedures. BIO members are committed to reducing the number of
animals used for research when it is possible to develop, validate and use
alternative methodologies consistent
Guide to Biotechnology n Biotechnology Industry Organization
with regulatory requirements for testing, while maintaining the scientific
integrity of the research. BIO affirms and upholds the science-based regulation
and oversight of animal research by the U.S. government agencies. Furthermore, BIO
members abide by the regulatory requirements of all other countries in which they
conduct animal research. In addition, many BIO members welcome external unbiased
agencies, such as the Association for Assessment and Accreditation of Laboratory
Animal Care, to evaluate their facilities, provide feedback on programs, and
accredit their work. In addition to human therapeutics, animal research has also
been critical to the development of biotechnologyderived veterinary biologics and
vaccines approved by the USDA to improve the health of livestock, poultry and
companion animals. Genomics, transgenics, and cloning technologies provide new
approaches for advancing the quality and efficiency of the production of meat,
milk, and eggs and reducing the environmental impact of agriculture. These
technologies are also being used to help preserve endangered species. The ability
to conduct humane and responsible animalbased research must be preserved to help
conquer disease, alleviate suffering, and improve quality of life. BIO believes
that such use is a privilege, imposing a responsibility to provide proper care and
humane treatment in accordance with the following principles:
n

Sciences, National Research Council (The Guide for the Care and Use of Laboratory
Animals, 7th ed.,1996) and the Federation of Animal Science Societies (The Guide
for the Care and Use of Agricultural Animals in Agricultural Research and
Teaching, 1999). Animals must be properly housed, fed and kept in surroundings
appropriate to their species. BIO is committed to the minimization of discomfort,
distress, and pain consistent with sound scientific practices. Investigators and
personnel shall be appropriately qualified for and experienced in conducting
procedures on animals and in the husbandry and handling of the species being
studied.
n

108

Regulatory Oversight. Animal biotechnology research (including products from

transgenic animals) is subject to science-based regulatory oversight by the U.S.
Food and Drug Administration (FDA), the U.S. Department of Agriculture (USDA), the
U.S. Environmental Protection Agency (EPA), the National Institutes of Health
(NIH), the Centers for Disease Control and Prevention (CDC), the U.S. Fish and
Wildlife Service (FWS) and other local agencies. BIO will actively work with these
agencies to ensure high standards of care and use for all animals involved in
biotechnology research. Increased Public Awareness. BIO encourages increased
public awareness and understanding by raising awareness of how biotechnology
research involving animals is being applied in human health, animal health,
agricultural, industrial and environmental areas. Open Discussion of Ethical
Considerations. BIO seeks to actively and thoroughly study the ethical
considerations involved in the use of animals in biotechnology, and to openly
discuss these issues with ethicists, consumers, medical professionals, farmers,
legislators, scientists, opinion leaders, and other interested groups.

Humane Treatment of Animals. BIO members are committed to improving the quality of
human and animal life with biotechnology, while taking responsibility for
respecting the animals that support their research and for treating those animals
humanely. Judicious Use of Animals. BIO is committed to the judicious use of
animals in biotechnology research for experimental purposes. Alternative
methodologies that reduce the number of animals used for research, replace animal
experiments with non-animal methods when possible, and refine the use of animals
in research (such as using cell and tissue cultures and computer modeling in early
screening of the toxic potential of a substance) should be used whenever possible.
Biotechnology offers great promise for further reducing use of animals in
research. High Standards of Care. High standards of care should be maintained for
animals used in biotechnology research as published by the Institute for
Laboratory Animal Research, Commission on Life

Biotechnology Industry Organization n Guide to Biotechnology

BIO Statement of Ethical Principles
We respect the power of biotechnology and apply it for the benefit of humankind.
We will pursue applications of biotechnology that promise to save lives or improve
the quality of life. We will avoid applications of our technology that do not
respect human rights or carry risks that outweigh the potential benefits. We
listen carefully to those who are concerned about the implications of
biotechnology and respond to their concerns. The resolution of bioethical issues
requires broad public discourse. We acknowledge our responsibility to consider the
interests and ideas of all segments of society and to be sensitive to cultural and
religious differences. We will seek dialogue with patients, ethicists, religious
leaders, health-care providers, environmentalists, consumers, legislators and
other groups who share an interest in bioethical issues. We help educate the
public about biotechnology, its benefits and implications. For informed debate to
occur, the public and our elected representatives need greater knowledge and a
better understanding about biotechnology and its applications. BIO and its members
pledge to advance public awareness and understanding. We place our highest
priority on health, safety and environmental protection in the use of our
products. In the United States, biotech products are extensively regulated by
federal agencies such as the Food and Drug Administration, the Environmental
Protection Agency and the Department of Agriculture. Our industry supports
science-based regulation by government agencies to safeguard health, ensure safety
and protect the environment. We support strong protection of the confidentiality
of medical information, including genetic information. Individually identifiable
medical information must be treated confidentially and safeguarded from misuse. We
oppose the use of medical information to promote intolerance, to discriminate
against or to stigmatize people. We respect the animals involved in our research
and treat them humanely. Laboratory animals are essential to research on new
therapies and cures. We test new treatments on laboratory animals to assess
product safety before administering them to humans. We develop transgenic ani-

mals—those with genes from another species, usually humans—to test treatments for
life-threatening diseases. We also develop transgenic sheep, goats and cattle by
inserting a gene that allows them to produce human pharmaceuticals in their milk.
We breed animals that may provide tissues and organs for transplantation to
humans. We will follow rigorously all government regulations and professional
standards in the United States, such as the Animal Welfare Act and the federal
guidelines for animal care and use promulgated by the National Institutes of
Health. We are sensitive to and considerate of the ethical and social issues
regarding genetic research. We will not, for example, treat genetic disorders by
altering the genes of human sperm or eggs until the medical, ethical and social
issues that will arise from this kind of therapy have been more broadly discussed
and clarified. Also, we support continuation of the voluntary moratorium on the
potential cloning of entire human beings, with the understanding that research
should continue on the cloning of genes and cells to benefit humankind. We adhere
to strict informed-consent procedures. For clinical research conducted in the
United States, the National Institutes of Health and the Food and Drug
Administration require informed consent from all participants and approval by a
national or local review board. We adhere to these requirements in our medical
research, except in situations in which obtaining consent is not necessary (e.g.,
research on anonymous information) or not possible (e.g., emergency care of
unconscious patients).
Guide to Biotechnology n Biotechnology Industry Organization

109
We develop environmental biotechnology to clean up hazardous waste more
efficiently with less disruption to the environment and to prevent pollution by
treating waste before it is released. Many environmental engineering firms,
industry and governments are using biotechnology to harness the power of naturally
occurring organisms to degrade contaminants at hazardous waste sites. We will
strive to optimize the costefficiencies and environmental advantages associated
with using biotechnology while protecting human health and the environment. We
also will continue to develop and implement more environmentally safe and cost-
effective means of treating hazardous waste streams in industrial processes. We
oppose the use of biotechnology to develop weapons. We support the Biological
Weapons Convention, a treaty signed by the United States and many other nations
banning development and use of biological weapons. We will not undertake any
research intended for use in developing, testing or producing such weapons.

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We will abide by the ethical standards of the American Medical Association and,
where appropriate, other healthcare professional societies to ensure that our
products are appropriately prescribed, dispensed and used. These ethical standards
are designed to ensure that health-care professionals do not receive monetary or
other compensation that might adversely affect how they care for their patients.
We develop our agricultural products to enhance the world’s food supply and to
promote sustainable agriculture with attendant environmental benefits. There are
significant advantages to increasing the yield of crops. Farmers must produce
increasing amounts of food per acre to feed a growing global population. We will
strive to make this possible while reducing the amount of external supplements
(fertilizers, pesticides, etc.) necessary. We will develop our products with an
eye toward good stewardship of our agricultural and environmental resources and
the sustainability of such development. With regard to the development of new
agriculture crops, we pledge to abide by established standards of environmental
safety at home and abroad.

We continue to support the conservation of biological diversity. The genetic

variation of animals, plants and other organisms is a valuable natural resource.
The environment is constantly changing, and without an adequate store of genetic
diversity, organisms will not be able to adapt. Genetic diversity decreases every
time a species, breed or crop variety becomes extinct. Working with governments
and other organizations, we will help to catalog and conserve these precious
resources.

Biotechnology Industry Organization n Guide to Biotechnology

Intellectual Property

iotechnology is an industry of ideas and invention. That makes intellectual

property—typically in the form of patents—the most important asset at most biotech
companies. These companies are often small firms—most biotechs have 50 or fewer
employees—developing products that can take upwards of 10 years and hundreds of
millions of dollars in investment to bring to the marketplace. In fact, biotech
historians credit the resolution of a patent case in 1980 with lifting the
industry off the ground. In that case, Diamond v. Charkrabarty, the court held
that anything touched by the hand of man—including modified cells and other
biological materials—may be patented.

10 years of patent protection left. (The Hatch-Waxman Act partially offsets the
time lost in development of drugs, but the period of “effective patent protection”
is still much shorter than for other products.) Once a patent has expired, anyone
may make, use, offer for sale, sell or import the invention without permission of
the patentee.
TYPES OF PATENTS Three types of patents exist: utility, design and plant patents.
Utility patents are granted to those who invent or discover new and useful
machines or processes, while design patents are issued to inventors of new,
original and ornamental design for an article of manufacture. Plant patents are
given to those who invent or discover, then asexually reproduce a new plant type.
PATENT PROTECTION IN THE CONSTITUTION A patent grants exclusive rights to
inventors for limited periods. The first law providing exclusive rights to the
makers of inventions for limited time periods seems to have been in Italy in the
15th century. Even before the signing of the Federal Constitution of the United
States, most states had their own patent laws. The U.S. Constitution entrusted
Congress to provide protection for inventions. The basis for the federal patent
and copyright systems is found in the Constitution of the United States, Article
1, Section 8, Clause 8, which states:

What Is a Patent?

patent is an agreement between the government and an inventor whereby, in exchange

for the inventor’s complete disclosure of the invention, the government gives the
inventor the right to exclude others from making, using, selling or importing the
invention for a limited time. Note that the property right provided in a patent is
quite different from what we typically think of when we own property. What is
granted is not the right to make, use, offer for sale, sell or import, but the
right to stop others from making, using, offering for sale, selling or importing
the invention. The United States Patent & Trademark Office (PTO) evaluates patent
applications and issues patents. Patents usually last 20 years from the date on
which the patent application is filed (not when it is issued). Thus, the
enforceable term of a patent is between 17 and 20 years; exactly how much shorter
depends on how long it is under PTO review. The PTO provides a three-year period
for the agency to issue a patent. Anything beyond three years will be added to the
end of the patent term. For example, if an application is examined in the PTO for
four years before it is issued, the enforceable patent term will be 18 years. In
highly regulated industries such as biotechnology, the “effective” period of
patent protection may be much less than 17-20 years. Why? As an example, consider
a drug whose patent is issued during Phase I trials. Before it can enter the
market, the drug still has to undergo at least two more rounds of clinical testing
and an evaluation period at the FDA, all of which may take five to 10 years. By
the time the drug reaches patients, it may have less than
111

Congress shall have power…to promote the Progress of Science and useful Arts by
securing for limited Times to Authors and Inventors the exclusive Right to their
respective Writings and Discoveries. Congress has enacted various laws relating to
patents. The first U.S. patent law was enacted in 1790. Today, in the United
States, patents are granted by the U.S. Patent and Trademark Office (PTO) and are
effective only within the United States and its territories. The term of a new
patent is 20 years from the date on which the application for the patent was filed
in the United States or, in certain cases, from the date an earlier, related
application was filed.

The Purpose of a Patent

he rationale for a patent system is to provide an advantage to society as a whole

by rewarding the development of new inventions. Thus, the patent system
Guide to Biotechnology n Biotechnology Industry Organization
has two basic purposes: to promote the advancement of technology and to protect
the inventor.
PROMOTING TECHNOLOGICAL ADvANCEMENT The patent system provides a process for the
disclosure of valuable information that can stimulate research across the globe.
To obtain a patent, an inventor must “teach” the public how to make and use the
invention in the best way the inventor knows. Thus, the patent system rewards only
those inventors who are willing to share their inventions with the whole world.

Other types of inventions or discoveries cannot be patented; these include

naturally occurring organisms, laws of nature, natural or physical phenomena, and
abstract ideas.
BIOTECHNOLOGY PATENTS Biotechnology inventions generally fall into one of two
classes:

Moreover, the information disclosed in a patent application is usually available

to the public long before a patent issues. If a patent application is filed
internationally or (from 2000 onwards) in the United States, it is published 18
months after its initial filing. The exception to this rule is that an applicant
who has filed only in the U.S. and not abroad may request that the U.S.
application not be published. If however, the applicant files in a foreign
country, then the U.S. patent application will be published.

1. New compositions of matter related to newly discovered isolated genes or

proteins or to pharmaceutical inventions based on those genes or proteins. One
cannot patent a naturally occurring gene or protein as it exists in the body, but
one can patent a gene or protein that has been isolated from the body and is
useful in that form as a pharmaceutical drug, screening assay or other
application. 2. Methods of treating patients with a given disease through the use
of a particular gene or protein. Even if someone has a patent on a gene or
protein, a second inventor can obtain a patent on a new use of that gene or
protein, if the second inventor discovers a new use for the substance.

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Once published, a patent application and all its information are available to
anyone. Thus, the patent system greatly stimulates the flow of scientific and
technological knowledge. That’s why societies that protect inventors with patents
are the world’s most advanced, scientifically and technologically.

Patent Requirements

Patentable Inventions

o obtain a patent on a new invention, an inventor must show that these three
criteria are met:

U
n n

nder U.S. law, various types of invention can be patented. These are:

A process—for example, a process of making a chemical by combining chemical X with

chemical Y, or a method of treating a cancer patient by administering a specific
drug. A machine—for example, a flat-screen high-definition television set or an X-
ray machine. An article of manufacture—for example, a silicon computer chip or a
specially molded piece of plastic for an automobile bumper. A composition of
matter—for example, a new pharmaceutical drug or a new plastic for use in kitchen
counters. Any new and useful improvement to an invention that falls under any of
these categories.

1. The invention is novel and nonobvious: that is, the invention is really new.
The invention must not have been described or discovered by another before the
inventor filed a patent application. The invention must also not be obvious from
the prior work of others. In patenting a gene or a protein, the requirement for
novelty and nonobviousness usually means that the inventor must know the chemical
structure of the new gene or protein. If that structure already is known, the
inventor can’t meet this requirement. 2. The invention is useful. The inventor
must show that the invention has a real-world use. It isn’t enough just to find a
new gene or protein. The inventor must specify what the uses are; for example,
whether the gene or protein is useful as a drug for disease X or as a target for
disease Y or as a diagnostic marker for disease Z. 3. The application describes
the invention in sufficient detail to allow the public to make and use the
invention.

Biotechnology Industry Organization n Guide to Biotechnology

The inventor must teach or “enable” other persons that are skilled in the
technological area of the invention to use the invention described by the
inventor. In addition to the above criteria, a description of the material or tool
for which a patent is sought cannot have been published in print, either in the
United States or abroad. Also, if the invention has been on sale or in use in the
U.S. for a year before the application is filed, a patent will not be awarded to
the invention.

The Patent Application

o obtain a patent, the inventor is required to submit a patent application to each

country in which he or she desires to obtain patent protection. In the United
States, a complete patent application must contain the following components: 1. A
written English language document (called the specification) that clearly
describes and explains the invention. Attached to the specification must be at
least one “claim” that sets forth the desired legal parameters of the claimed
invention. 2. A drawing illustrating the invention, if such a drawing is necessary
for understanding the invention. 3. An oath or declaration by the inventor(s)
claiming inventorship. 4. A filing fee (about $400–$800, or more, depending on the
patent application). living organisms was re-examined, and confirmed. A landmark
case involved Ananda Chakrabarty’s invention of a new bacterium genetically
engineered to degrade crude oil. In 1980, the Supreme Court clearly stated that
new microorganisms not found in nature, such as Chakrabarty’s bacterium, were
patentable. Chakrabarty received a patent in 1981 (U.S. Pat. No. 4,259,444). In
the Chakrabarty decision, the Supreme Court stated that “anything under the sun
that is made by the hand of man” is patentable subject matter. Therefore, if a
product of nature is new, useful and nonobvious, it can be patented if it has been
fashioned by humans.
n

113

Patenting Organisms

ome living things can be patented, but not all. Like any invention, a living thing
must be “new” in order to be patented. More importantly, living organisms under
consideration for patenting cannot be those that occur or exist in nature. Thus,
one cannot obtain a patent on just any living creature, such as a mouse, because
mice have been around for a long time. If someone makes a kind of mouse that never
existed before, however, then that kind of mouse might be patented. Here are a few
examples of patentable organisms:
n

Plants: In 1930, the U.S. Congress passed the Plant Patent Act, which specifically
provided patent protection for newly invented plants that are asexually
reproduced. In 1970, Congress provided similar protection for newly invented
sexually reproduced plants. Animals: In the 1980s, the question of whether
multicellular animals could be patented was examined. The key case involved a new
kind of “polyploid” oyster that had an extra set of chromosomes. This new, sterile
Guide to Biotechnology n Biotechnology Industry Organization

Microbes: As long ago as 1873, Louis Pasteur received a U.S. patent for yeast
“free from organic germs or disease.” With the growth of genetic engineering in
the late 1970s, the patentability of
n
oyster was edible all year round because it did not devote body weight to
reproduction during the breeding season. The PTO found that such organisms were in
fact new and therefore eligible for patenting. It found this particular type of
oyster to be obvious, however, and thus did not allow a patent for it.
Nonetheless, the polyploid oyster paved the way for the patenting of other
nonnaturally occurring animals. In 1988, Philip Leder and Timothy Stewart were
granted a patent on transgenic nonhuman mammals (U.S. Pat. No. 4,736,866) that
covered the so-called Harvard mouse, which was genetically engineered to be a
model for the study of cancer.
n

ers. If the two patent owners want to sell the protein for the new use, they would
need to grant a license to each other. Such licenses are often called cross-
licenses. In rapidly developing fields of technology, cross-licenses are very
common. If a third party does use a patented invention without a license, the
patent owner can seek legal remedies for infringement. Such remedies can include
damages and an injunction against the infringer to prevent future use.

114

Natural Compounds: Natural compounds, such as a human protein or the chemical that
gives strawberries their distinctive flavor, are not themselves living, but occur
in nature. Thus, they are new and can be patented only if they are somehow removed
from nature. Therefore, a compound that is purified away from a strawberry, or a
protein that is purified away from the human body can be patented in its purified
state. Such a patent would not cover the strawberry or the person. The U.S. PTO
does not allow anyone to patent a human being under any circumstances.

Patent Licensing

patent license is a contract between the owner of a patent and an independent

party who wishes to make, use or sell the invention claimed in the patent. Such a
contract is in essence a promise by the patent owner that the owner will not sue
the independent party, called the licensee, for patent infringement, provided that
he or she complies with the terms of the contract. Typically, the licensee agrees
to pay the patent owner a percentage of the revenue the licensee receives from
sale of the invention and/or other license fees. Many inventions require
significant capital investment before they can be used commercially. By licensing
a patented invention to a third party, a patent owner who may not have the
resources to fully develop an invention can work with a third party to
commercialize it. In some cases, a license from more than one person may be
necessary to use an invention effectively. For example, one party could obtain a
patent on a new protein, while a second party obtains a patent on a new use of
that same protein. In order to sell that protein for the new use, a third party
would require a license from both patent ownBiotechnology Industry Organization n
Guide to Biotechnology
Biotechnology Resources

B
n n n

IO has compiled a list of publications, Web sites, e-mail services and other
resources that we believe are especially useful in learning about biotechnology
and monitoring progress. A few notes about the list: It includes both free sources
and those that charge fees. Most items on the list are non-BIO resources. BIO
staff are not responsible for and cannot assist with access to non-BIO resources.
Biotechnology is a fluid industry. When using any biotech resource (including this
book), it is a good idea to note the publication date and check other sources for
the most complete and current information. This list is not intended to be
comprehensive, but if we have omitted a useful resource, please let us know by e-
mailing [email protected].

OTHER SOURCES BIO Ventures for Global Health. The BVGH Web site includes an
interactive pipeline database on diseases affecting developing countries, as well
as news, features and policy reports on the biotechnology industry’s work in
global health. All resources are available at www. bvgh.org.

BioCentury. BioCentury’s weekly flagship publication features analysis and news

summaries on the biotech industry. BioCentury also provides a daily news summary,
published each weekday evening. Subscription information and full product listings
are available at www.biocentury.com. BioSpace. BioSpace tracks a wide range of
biotechnology company, clinical and financial news and data, and offers e-mail
headline services. Explore offerings at www.biospace.com. Biotechnology
Healthcare. This monthly magazine delivers selected industry news and includes
features on science, product development, financial issues, and reimbursement.
Subscription information and selected articles are available at www.
biotechnologyhealthcare.com. BioWorld. BioWorld’s offerings include a daily
biotech newspaper, as well as weekly publications on financial and international
news. Subscription information and full product listings are available at
www.bioworld.com. FierceBiotech. This business-focused summary of the day’s
biotech news highlights is delivered via e-mail. Learn more or sign up at
www.fiercebiotech.org. Genetic Engineering News. This tabloid-sized trade magazine
is published twice monthly and includes news and features on the industry. GEN is
free to qualified industry subscribers. Apply for a subscription at www.
genengnews.com. Health Affairs. Published every other month, this is one of the
definitive sources for healthcare data and analysis, with articles on issues of
access, reimbursement, innovation and quality. Visit www.healthaffairs.org for
subscription information. Industrial Biotechnology. This quarterly journal covers
industrial and environmental biotechnology applications in chemicals, energy, and
manufacturing. Subscription information is available at www. liebertpub.com.

Periodicals, Headline Services and Web Sites

FROM BIO BIO.org. BIO’s award-winning Web site offers a wealth of information on
biotechnology applications as well as archives of speeches, policy papers, special
reports and comments on issues of interest to the biotech community.

115

Science.bio.org. Each business morning, BIO shares links to all of the day’s
significant biotech science stories, including both mainstream press and journal
articles. BIO SmartBrief. This popular e-mail service provides headlines and brief
summaries of all the important biotech news of the day, from sources around the
world. Visit www.smartbrief.com/bio/ to sign up. Food & Ag Weekly News. This e-
mail publication covers BIO activities, policy news and mainstream news coverage
of agricultural biotechnology. It is available only to BIO members. For
information on joining BIO, visit www.bio.org/join. BIO News. The Biotechnology
Industry Organization’s members-only magazine covers BIO activities as well as
selected biotechnology financial, legislative and regulatory news. Information on
joining BIO is available at www.bio.org/join.

Guide to Biotechnology n Biotechnology Industry Organization

In Vivo. Windhover Information publishes this monthly magazine of commentary and
analysis on biotechnology, pharmaceuticals and other industries. The emphasis is
on business strategies and industry trends. Windhover offers a suite of additional
publications and data as well. Visit www.windhover. com for subscription
information. Nature Biotechnology. This specialty publication from the Nature
Publishing Group is published monthly and includes news, features and journal
articles. Subscription information is available on www. nature.com. Signals
Magazine. Recombinant Capital publishes this online magazine of biotech industry
trends and analysis. The magazine and archives are free, with no registration
required. Visit www.signalsmag.com. Tufts CSDD Impact Report. The Tufts Center for
the Study of Drug Development publishes a singletopic report every other month
covering original research on product development issues affecting pharmaceutical
and biotech companies. For a list of topics covered and subscription information,
visit csdd.tufts.edu. Why Biotech. Operated by the Council for Biotechnology
Information, this media- and consumer-friendly Web site includes feature stories,
links to reports, and extensive data on agricultural biotechnology. Access is
free, with no registration required. Visit www. whybiotech.com. Your World. The
Biotechnology Institute’s magazine is published twice a year and targets grades 7
through 12. Each issue combines in-depth features on a single topic with
supplemental educational activities and materials. See www.biotechinstitute.org
for a list of topics covered, subscription information, and free pdf downloads of
every issue.

Biotech Education & Careers

ote: Many job-listing Web sites and services cover the biotech industry. Below are
resources that offer added content of interest. Biotechnology Institute. The
Biotechnology Institute focuses on K-12 biotechnology education, offering teacher-
student resources and programs. Publications include Genome: The Secret of How
Life Works, Your World magazine, and Shoestring Biotechnology, a laboratory guide
for teachers with a shoestring budget. BioView. BioView has compiled a list of
schools offering specialized biotechnology degree and certificate programs. Visit
bioview.com/education.html for the list. Sciencecareers. Science magazine has
compiled extensive career resources and articles for science students and job
seekers at sciencecareers.sciencemag.org.

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Selected Recent Reports on Biotechnology

GENERAL & HEALTHCARE Beyond Borders: Global Biotechnology Report 2006. Ernst &
Young’s annual survey of the biotechnology industry tracks company data and
industry trends, compares U.S. biotech performance to that of the rest of the
world, and ranks top U.S. and Canadian biotech regions. Published April 2006. See
www.ey.com for contact information.

General Science Journals

Biotech 2006—Life Sciences: A Changing Prescription. Each year, the life sciences
merchant bank Burrill & Co. publishes a detailed report on the biotech industry,
describing new developments in healthcare, agriculture and industrial
applications, as well as providing an overview of biotech business activities. See
www.burrillandco.com for purchase information. Published April 2006. BioWorld
State of the Industry Report, 2006. BioWorld’s annual report aggregates the
biotech industry’s financial, partnering and drug approval information for 2005,
with analysis explaining what it all means. See www.bioworld.com for purchase
information.
T

he following science journals, while not biotech-exclusive, provide extensive

biotechnology coverage: Nature, Science, Scientific American, The New Scientist,
and The Scientist. Nature and Science are often are first to publish important
breakthroughs, such as the human genome sequence.

Biotechnology Industry Organization n Guide to Biotechnology

Genomics and Global Health. This report from the University of Toronto explores
how genomics and related technologies can help achieve the United Nations
Millennium Development Goals in global health. The report follows up on the
recommendations of Top 10 Biotechnologies for Improving Health in Developing
Countries. Both reports can be downloaded through www.bvgh.org. Published in
September 2002 (Top 10) and October 2004 (Genomics and Global Health). Growing the
Nation’s Biotech Sector: State Bioscience Initiatives 2006. This report from BIO
and the Battelle Memorial Institute presents updated data, examines growth trends
and identifies cities with the largest and most concentrated employment in several
bioscience subsectors. The report also identifies key trends in state and regional
initiatives to support the biosicences. Available for downloading on www.bio.
org/local/battelle2006/. Published April 2006. Innovation or Stagnation: Challenge
and Opportunity on the Critical Path to New Medical Products. This report from FDA
explains why drug development is so slow and offers ideas for accelerating the
process. This landmark report initiated the Critical Path Initiative. Available
for downloading at www.fda.gov/oc/ initiatives/criticalpath/. Published March
2004. Medical Biotechnology: Achievements, Prospects and Perceptions. Published by
the United Nations Institute for Advanced Studies, this book examines the drivers
of medical and pharmaceutical biotechnology development in the United States,
Europe and Japan and provides case studies for several developing countries.
Available for purchase through www.ias. unu.edu. Published September 2005. OECD
Biotech Statistics 2006. This publication of the Organization of Economic
Cooperation and Development includes data for 23 OECD countries and two observer
countries, plus China (Shanghai), and takes a major step forward in improving the
comparability of biotechnology indicators among countries. Available for
downloading on www.oecd.org. Published May 2006. Outlook 2006. The Tufts Center
for Drug Development’s annual report offers a brief synopsis of the year’s major
regulatory and R&D issues. Available for downloading at csdd.tufts.edu. Published
2006. Parexel’s Bio/Pharmaceutical R&D Statistical Sourcebook 2006/2007. This book
contains

studies, analysis, articles and extensive data sets on R&D/regulatory activity and
spending across the pharmaceutical and biotech sectors. See www.parexel. com for
purchase information. Personalized Medicine: The Emerging Pharmacogenomics
Revolution. PriceWaterhouseCoopers explains how personalized medicine can remake
the pharmaceutical industry and the challenges to realizing that vision. Available
for downloading on www.pwc.com. Published February 2005. Personalized Medicine:
Hopes and Realities. This Royal Society report provides a thorough overview of
scientific, development and clinical issues in personalized medicine. Available
for downloading at www.royalsoc.ac.uk (select Adobe Acrobat Reader to open).
Published September 2005. A Survey of the Use of Biotechnology in U.S. Industry.
In 2003, the U.S. Commerce Department published data from the most comprehensive
survey ever conducted of companies using biotechnology. The book includes data on
jobs, financial performance and technological applications, and is available for
downloading at www.technology.gov/reports. Published October 2003.
MARKET REPORTS A number of publishers, consultants and analysts publish detailed
reports on specialized biotechnology sectors (anything from microarrays to
diabetes drugs). Sites offering such reports for sale include www.datamonitor.com,
www. marketresearch.com, www.visiongainintelligence.com,
www.researchandmarkets.com, www.thefreedoniagroup. com and www.frost.com.
AGRICULTURE Biotechnology-Derived Crops Planted in 2004— Impacts on U.S.
Agriculture. This report from the National Center for Food and Agricultural Policy
explores the impact of six biotech crops on U.S. farmers’ yields and incomes. The
report includes data for individual states. Published December 2005.

117

Brief 34: Global Status of Commercialized Biotech/ GM Crops: 2005. Each year, the
International Service for the Acquisition of Agri-Biotech Applications publishes a
global survey of biotech crops plantings. Data are provided by crop and by

Guide to Biotechnology n Biotechnology Industry Organization

country. Available for downloading at www.isaaa. org. Published January 2006. The
Economic Status and Performance of Plant Biotechnology in 2003: Adoption, Research
and Development in the United States. This study explores the economic impact of
agricultural biotechnology and includes data from companies, states and academic
institutions. The author, C. Ford Runge, Ph.D., is the director of the Center for
International Food and Agricultural Policy at the University of Minnesota.
Available for downloading on www.whybiotech.com. Published December 2003. The
Global Diffusion of Plant Biotechnology: International Adoption and Research in
2004. This study of plant biotech R&D and adoption offers both a comprehensive
overview and individual country profiles from around the world. Available for
downloading on www.whybiotech.com. Published December 2004.

Group of the Energy Future Coalition shows how farmers can contribute 25 percent
of U.S. total energy consumption. Available at www.bio.org/ind/25x25.pdf.
Published August 2004. Achieving Sustainable Production of Agricultural Biomass
for Biorefinery Feedstock. This BIO report details how American farmers can feed
the growing biofuel industry by harnessing cellulosic biomass. It also proposes
guidelines and incentives to encourage farmers to produce sufficient raw materials
for the growing biorefinery and biofuels industry in a sustainable way. Available
at bio.org/ind. Published November 2006. Growing Energy: How Biofuels Can Help End
America’s Oil Dependence. This Natural Resources Defense Council report describes
how biofuels can cut U.S. dependence on foreign oil while lifting farm profits by
2025 if action is taken now. The NRDC published a follow-up issue paper, Bringing
Biofuels to the Pump: An Aggressive Plan for Ending America’s Oil Dependence. Both
are available for downloading at www.nrdc.org. Published December 2004, July 2005.
Industrial and Environmental Biotechnology: Current Achievements, Prospects and
Perceptions. This report by the United Nations Institute of Advanced Studies
provides an overview of I&E biotechnology. Available for downloading on
www.ias.unu.edu. Published September 2005. New Biotech Tools for a Cleaner
Environment: Industrial Biotechnology for Pollution Prevention, Resource
Conservation and Cost Reduction. Produced by BIO, this report applies case-study
data from the Organization for Economic Cooperation and Development to whole
industries, describing the potential for biotech processes to cut raw material
consumption and pollution. Available for downloading on www.bio.org/ind/.
Published June 2004. Policy Recommendations and Report of the Bioenergy and
Agriculture Working Group. This report, by a working group of the Energy Future
Coalition, recommends that government take aggressive steps to shift to renewable,
agriculture-based fuels, such as bioethanol. Available for downloading on www.bio.
org/ind/. Published June 2003.

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GM crops: the global socio-economic and environmental impact—the first nine years,
1996-2004. This report from the U.K. firm PG Economics provides cumulative data on
the positive environmental and income impact of biotech crops. It is available for
downloading at www.pgeconomics. co.uk. Published October 2005. Modern Food
Biotechnology, Human Health and Development: An Evidence-Based Study. This World
Health Organization report describes health and quality-of-life benefits that
biotech foods can deliver. Available for downloading at www.who. int/foodsafety.
Published 2005. Quantification of the Impacts on U.S. Agriculture of Biotechnology
Derived Crops Planted in 2005. This study from the National Center for Food and
Agricultural Policy suggests biotech is helping meet increased demand for corn to
manufacture ethanol. According to the author, U.S. farmers produced an additional
7.6 billion pounds of corn thanks to biotech—a 29 percent increase over 2004
production. Available for downloading at www.ncfap.org. Published November 2006.
INDUSTRIAL & ENvIRONMENTAL 25 by 25: Agriculture’s Role in Ensuring U.S. Energy
Independence. This report by the Ag Energy Working
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Glossary
A
Acclimatization Adaptation of an organism to a new environment. Action letter An
official FDA communication that informs an NDA or BLA sponsor of a decision by the
agency. An approval letter allows commercial marketing of the product. Active
immunity A type of acquired immunity whereby resistance to a disease is built up
by either having the disease or receiving a vaccine to it. Adjuvant Insoluble
material that increases the formation and persistence of antibodies when injected
with an antigen. Aerobic Needing oxygen for growth. Agrobacterium tumefaciens A
common soil bacterium used as a vector to create transgenic plants. Allele Any of
several alternative forms of a gene. Allogenic Of the same species, but with a
different genotype. Also allogeneic. Alzheimer’s disease A disease characterized
by, among other things, progressive loss of memory. The development of Alzheimer’s
disease is thought to be associated, in part, with possessing certain alleles of
the gene that encodes apolipoprotein E. Amino acids Building blocks of proteins.
There are 20 common amino acids: alanine, arginine, aspargine, aspartic acid,
cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine,
lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan,
tyrosine and valine. Two more amino acids have been discovered in microbes:
selenocysteine and pyrrolysine. Amplification The process of increasing the number
of copies of a particular gene or chromosomal sequence. Anaerobic Growing in the
absence of oxygen. Antibiotic Chemical substance formed as a metabolic byproduct
in bacteria or fungi and used to treat bacterial infections. Antibiotics can be
produced naturally, using microorganisms, or synthetically. Antibody Protein
produced by humans and higher animals in response to the presence of a specific
antigen. Anticodon Triplet of nucleotide bases (codon) in transfer RNA that pairs
with (is complementary to) a triplet in messenger RNA. For example, if the codon
is UCG, the anticodon is AGC. See also Base; Base pair; Complementarity. Antigen A
substance that, when introduced into the body, induces an immune response by a
specific antibody. Antigenic determinant See Hapten. Antihemophilic factors A
family of whole-blood proteins that initiate blood clotting. Some of these
proteins, such as factor VIII, can be used to treat hemophilia. See also Factor
VIII; Kidney plasminogen activator. Antisense A piece of DNA producing a mirror
image (“antisense”) messenger RNA that is opposite in sequence to one directing
protein synthesis. Antisense technology is used to selectively turn off production
of certain proteins. Antiserum Blood serum containing specific antibodies against
an antigen. Antisera are used to confer passive immunity to many diseases.
Apolipoprotein E (Apo E) Certain alleles of the gene that encodes the protein
apolipoprotein E have been associated with the development of heart disease and
Alzheimer’s disease. Assay Technique for measuring a biological response.
Attenuated Weakened; with reference to vaccines, made from pathogenic organisms
that have been treated so as to render them avirulent. Autoimmune disease A
disease in which the body produces antibodies against its own tissues.
Autoimmunity A condition in which the body mounts an immune response against one
of its own organs or tissues. Autosome Any chromosome other than a sex chromosome.
Avirulent Unable to cause disease.

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B
Bacillus subtilis A bacterium commonly used as a host in recombinant DNA
experiments. Important because of its ability to secrete proteins.
Guide to Biotechnology n Biotechnology Industry Organization
Bacillus thuringiensis (Bt) Naturally occurring soil bacterium that generates a
protein toxic to a variety of lepidoptera, such as corn borers, but is harmless to
people and animals. Bacteriophage Virus that lives in and kills bacteria. Also
called phage. Bacterium Any of a large group of microscopic organisms with a very
simple cell structure. Some manufacture their own food, some live as parasites on
other organisms, and some live on decaying matter. Base A key component of DNA and
RNA molecules. Four different bases are found in DNA: adenine (A), cytosine (C),
guanine (G) and thymine (T). In RNA, uracil (U) substitutes for thymine. Also
known as nitrogenous bases. A base, a phosphate molecule and a sugar joined
together constitute a nucleotide. Base pair Two nucleotide bases on different
strands of the nucleic acid molecule that bond together. The bases can pair in
only one way: adenine with thymine (DNA), or uracil (RNA) and guanine with
cytosine. Bioassay Determination of the effectiveness of a compound by measuring
its effect on animals, tissues or organisms in comparison with a standard
preparation. Bioaugmentation Increasing the activity of bacteria that break down
pollutants by adding more of their kind. A technique used in bioremediation.
Biocatalyst In bioprocessing, an enzyme that activates or speeds up a biochemical
reaction. Biochemical The product of a chemical reaction in a living organism.
Biochip An electronic device that uses organic molecules to form a semiconductor.
Bioconversion Chemical restructuring of raw materials by using a biocatalyst.
Biodegradable Capable of being reduced to water and carbon dioxide by the action
of microorganisms. Bioenrichment A bioremediation strategy that involves adding
nutrients or oxygen, thereby bolstering the activity of microbes as they break
down pollutants.

Bioinformatics The science of informatics as applied to biological research.

Informatics is the management and analysis of data using advanced computing
techniques. Bioinformatics is particularly important as an adjunct to genomics
research, because of the large amount of complex data this research generates.
Biolistic device A device that shoots microscopic DNAcoated particles into target
cells. Biological oxygen demand (BOD) The amount of oxygen used for growth by
organisms in water that contains organic matter. Biologic A therapeutic or
prophylactic derived from a living source (human, animal or unicellular). Most
biologics are complex mixtures that are not easily identified or characterized,
and many are manufactured using biotechnology. Biological products often represent
the cutting-edge of biomedical research and are sometimes the most effective way
to prevent or treat a disease. Biologic response modifier A substance that alters
the growth or functioning of a cell. Includes hormones and compounds that affect
the nervous and immune systems. Biomass The totality of biological matter in a
given area. As commonly used in biotechnology, refers to the use of cellulose, a
renewable resource, for the production of chemicals that can be used to generate
energy or as alternative feedstocks for the chemical industry to reduce dependence
on nonrenewable fossil fuels. Biomaterials Biological molecules, such as proteins
and complex sugars, used to make medical devices, including structural elements
used in reconstructive surgery. Bioprocess A process in which living cells, or
components thereof, are used to produce a desired product. Bioreactor Vessel used
for bioprocessing. Bioremediation The use of microorganisms to remedy
environmental problems, rendering hazardous wastes nonhazardous. Biosynthesis
Production of a chemical by a living organism. Biotechnology The use of biological
processes to solve problems or make useful products.

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Biotransformation The use of enzymes in chemical synthesis to produce chemical
compounds of a desired stereochemistry. Blastocyst (Blastula) The 4- to 5-day-old
ball of undifferentiated cells from which a prospective embryo develops. In
mammals it consists of two distinct parts: the inner cell mass and the
trophoblast. B lymphocytes (B-cells) A class of lymphocytes, released from the
bone marrow, that produce antibodies. Bovine somatotropin (BST) A hormone secreted
by the bovine pituitary gland. It is used to increase milk production by improving
the feed efficiency in dairy cattle milk. Also called bovine growth hormone. BRCA1
and BRCA2 (BReast CAncer genes 1 and 2) Two genes that normally help to restrain
cell growth, but which can contain certain genetic mutations associated with the
development of breast and ovarian cancer. Note, however, that inherited BRCA1 and
BRCA2 mutations are thought to account for less than 10 percent of all breast and
ovarian cancers. Recent evidence suggests that somatic cell genetic mutations
(i.e., noninherited genetic mutations) in these two genes may also play a role in
the development of cancer.

Cell line Cells that grow and replicate continuously outside the living organism.
Cell-mediated immunity Acquired immunity in which T lymphocytes play a predominant
role. Development of the thymus in early life is critical to the proper
development and functioning of cell-mediated immunity. Chemical genomics Using
structural and functional genomic information about biological molecules,
especially proteins, to identify useful small molecules and alter their structure
to improve their efficacy. Chimera The individual (animal or lower organism)
produced by grafting an embryonic part of one individual onto an embryo of either
the same or a different species. Chromosomes Threadlike components in the cell
that contain DNA and proteins. Genes are carried on the chromosomes. Clinical
studies Human studies that are designed to measure the efficacy of a new drug or
biologic. Clinical studies routinely involve the use of a control group of
patients that is given an inactive substance (placebo) that looks like the test
product. Clone A term that is applied to genes, cells or entire organisms that are
derived from—and are genetically identical to—a single common ancestor gene, cell
or organism, respectively. Cloning of genes and cells to create many copies in the
laboratory is a common procedure essential for biomedical research. Note that
several processes commonly described as cell “cloning” give rise to cells that are
almost but not completely genetically identical to the ancestor cell. Cloning of
organisms from embryonic cells occurs naturally in nature (e.g., identical twins).
Researchers have achieved laboratory cloning using genetic material from adult
animals of several species, including mice, pigs and sheep. Codon A sequence of
three nucleotide bases that specifies an amino acid or represents a signal to stop
or start a function. Co-enzyme An organic compound that is necessary for the
functioning of an enzyme. Co-enzymes are smaller than the enzymes themselves and
sometimes separable from them.

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C
Callus A cluster of undifferentiated plant cells that can, in some species, be
induced to form the whole plant. Carbohydrate A type of biological molecule
composed of simple sugars such as glucose. Common examples include starch and
cellulose. Carcinogen Cancer-causing agent. Catalyst An agent (such as an enzyme
or a metallic complex) that facilitates a reaction but is not itself changed
during the reaction. Cell The smallest structural unit of a living organism that
can grow and reproduce independently. Cell culture Growth of cells under
laboratory conditions. Cell differentiation The process by which descendants of a
common parental cell achieve specialized structure and function Cell fusion See
Fusion.

Guide to Biotechnology n Biotechnology Industry Organization

Co-factor A nonprotein substance required for certain enzymes to function. Co-
factors can be co-enzymes or metallic ions. Colony-stimulating factors (CSFs) A
group of lymphokines that induce the maturation and proliferation of white blood
cells from the primitive cell types present in bone marrow. Combinatorial
chemistry A product discovery technique that uses robotics and parallel synthesis
to generate and screen quickly as many as several million molecules with similar
structure in order to find chemical molecules with desired properties. Co-
metabolism A microbe oxidizing not only its main energy source but also another
organic compound. Complementarity The relationship of the nucleotide bases on two
different strands of DNA or RNA. When the bases are paired properly (adenine with
thymine [DNA] or uracil [RNA]; guanine with cytosine), the strands are
complementary.

Culture medium Any nutrient system for the artificial cultivation of bacteria or
other cells; usually a complex mixture of organic and inorganic materials. Cyto-
Referring to cell. Cytogenetics Study of the cell and its heredity-related
components, especially chromosomes. Cytoplasm Cellular material that is within the
cell membrane and surrounds the nucleus. Cytotoxic Able to cause cell death.

D
Deoxyribonucleic acid (DNA) The molecule that carries the genetic information for
most living systems. The DNA molecule consists of four bases (adenine, cytosine,
guanine and thymine) and a sugar-phosphate backbone, arranged in two connected
strands to form a double helix. See also Complementary DNA; Double helix;
Recombinant DNA. Differentiation The process of biochemical and structural changes
by which cells become specialized in form and function. Diploid A cell with two
complete sets of chromosomes. Compare Haploid. DNA See Deoxyribonucleic acid. DNA
chip A small piece of glass or silicon that has small pieces of DNA arrayed on its
surface. DNA fingerprinting The use of restriction enzymes to measure the genetic
variation of individuals. This technology is often used as a forensic tool to
detect differences or similarities in blood and tissue samples at crime scenes.
DNA hybridization The formation of a double-stranded nucleic acid molecule from
two separate strands. The term also applies to a molecular technique that uses one
nucleic acid strand to locate another. DNA library A collection of cloned DNA
fragments that collectively represent the genome of an organism. DNA polymerase An
enzyme that replicates DNA. DNA polymerase is the basis of PCR—the polymerase
chain reaction.

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Complementary DNA (cDNA) DNA synthesized from a messenger RNA rather than from a
DNA template. This type of DNA is used for cloning or as a DNA probe for locating
specific genes in DNA hybridization studies. Computational biology A subdiscipline
within bioinformatics concerned with computation-based research devoted to
understanding basic biological processes. Conjugation Sexual reproduction of
bacterial cells in which there is a one-way exchange of genetic material between
the cells in contact. Crossing over Exchange of genes between two paired
chromosomes. Cross-licensing Legal, contractual procedure in which two or more
firms with competing, similar technologies and possible conflicting patent claims
strike a deal to reduce the need for legal actions to clarify who is to profit
from applications of the technology. Culture As a noun, cultivation of living
organisms in prepared medium; as a verb, to grow in prepared medium.

Biotechnology Industry Organization n Guide to Biotechnology

DNA probe A small piece of nucleic acid that has been labeled with a radioactive
isotope, dye or enzyme and is used to locate a particular nucleotide sequence or
gene on a DNA molecule. DNA repair enzymes Proteins that recognize and repair
certain abnormalities in DNA. DNA sequence The order of nucleotide bases in the
DNA molecule. DNA vaccines Pieces of foreign DNA that are injected into an
organism to trigger an immune response. Double helix A term often used to describe
the configuration of the DNA molecule. The helix consists of two spiraling strands
of nucleotides (a sugar, phosphate and base) joined crosswise by specific pairing
of the bases. See also Deoxyribonucleic acid; Base; Base pair. Diagnostic A
product used for the diagnosis of disease or medical condition. Both monoclonal
antibodies and DNA probes are useful diagnostic products. Drug delivery The
process by which a formulated drug is administered to the patient. Traditional
routes have been oral or intravenous perfusion. New methods deliver through the
skin with a transdermal patch or across the nasal membrane with an aerosol spray.

Enzyme A protein catalyst that facilitates specific chemical or metabolic

reactions necessary for cell growth and reproduction. Erythropoietin (EPO) A
protein that boosts production of red blood cells. It is clinically useful in
treating certain types of anemia. Escherichia coli (E. coli) A bacterium that
inhabits the intestinal tract of most vertebrates. Much of the work using
recombinant DNA techniques has been carried out with this organism because it has
been genetically well characterized. Eukaryote A cell or organism containing a
true nucleus, with a well-defined membrane surrounding the nucleus. All organisms
except bacteria, viruses and cyanobacteria are eukaryotic. Compare Prokaryote.
Exon In eukaryotic cells, that part of the gene that is transcribed into messenger
RNA and encodes a protein. See also Intron; Splicing. Expression In genetics,
manifestation of a characteristic that is specified by a gene. With hereditary
disease, for example, a person can carry the gene for the disease but not actually
have the disease. In this case, the gene is present but not expressed. In
industrial biotechnology, the term is often used to mean the production of a
protein by a gene that has been inserted into a new host organism. Extremophiles
Microorganisms that live at extreme levels of pH, temperature, pressure and
salinity.

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E
Electrophoresis A technique for separating different types of molecules based on
their patterns of movement in an electrical field. Electroporation The creation of
reversible small holes in a cell wall or membrane through which foreign DNA can
pass. This DNA can then integrate into the cell’s genome. Enzyme-linked
immunosorbent assay (ELISA) A technique for detecting specific proteins by using
antibodies linked to enzymes. Embryonic stem cells Cells that can give rise to any
type of differentiated cell. They can be derived from two sources: the inner cell
mass from a blastocyst or the primordial germ cells (eggs and sperm) of an older
embryo. Endostatin An endogenous protein that blocks the proliferation of blood
vessels.

F
Factor VIII A large, complex protein that aids in blood clotting and is used to
treat hemophilia. See also Antihemophilic factors. Feedstock The raw material used
for chemical or biological processes. Fermentation The process of growing
microorganisms for the production of various chemical or pharmaceutical compounds.
Microbes are normally incubated under specific conditions in the presence of
nutrients in large tanks called fermentors.

Guide to Biotechnology n Biotechnology Industry Organization

Functional foods Foods containing compounds with beneficial health effects beyond
those provided by the basic nutrients, minerals and vitamins. Also called
nutraceuticals. Functional genomics A field of research that aims to understand
what each gene does, how it is regulated and how it interacts with other genes.
Fusion Joining of the membrane of two cells, thus creating a daughter cell that
contains some of the same properties from each parent cells. Used in making
hybridomas.

Genetic code The code by which genetic information in DNA is translated into
biological function. A set of three nucleotides (codons), the building blocks of
DNA, signifies one amino acid, the building blocks of proteins. Genetic
modification A number of techniques, such as selective breeding, mutagenesis,
transposon insertions and recombinant DNA technology, that are used to alter the
genetic material of cells in order to make them capable of producing new
substances, performing new functions or blocking the production of substances.
Genetic predisposition Susceptibility to disease that is related to a genetic
predisposition mutation, which may or may not result in actual development of the
disease. Genetic screening The use of a specific biological test to screen for
inherited diseases or medical conditions. Testing can be conducted prenatally to
check for metabolic defects and congenital disorders in the developing fetus as
well as postnatally to screen for carriers of heritable diseases. Genetic testing
The analysis of an individual’s genetic material. Genetic testing can be used to
gather information on an individual’s genetic predisposition to a particular
health condition, or to confirm a diagnosis of genetic disease. Genome The total
hereditary material of a cell, comprising the entire chromosomal set found in each
nucleus of a given species. Genomics The study of genes and their function. Recent
advances in genomics are bringing about a revolution in our understanding of the
molecular mechanisms of disease, including the complex interplay of genetic and
environmental factors. Genomics is also stimulating the discovery of breakthrough
health-care products by revealing thousands of new biological targets for the
development of drugs and by giving scientists innovative ways to design new drugs,
vaccines and DNA diagnostics. Genomic-based therapeutics may include “traditional”
small chemical drugs, as well as protein drugs and gene therapy. Genotype Genetic
makeup of an individual or group. Compare Phenotype. Germ cell Reproductive cell
(sperm or egg). Also called gamete or sex cell.

G
Gel electrophoresis A process for separating molecules by forcing them to migrate
through a gel under the influence of an electric field. Gene A segment of
chromosome. Some genes direct the syntheses of proteins, while others have
regulatory functions. See also Operator gene; Structural gene; Suppressor gene.
Gene amplification The increase, within a cell, of the number of copies of a given
gene. Gene knockout The replacement of a normal gene with a mutated form of the
gene by using homologous recombination. Used to study gene function. Gene machine
A computerized device for synthesizing genes by combing nucleotides (bases) in the
proper order. Gene mapping Determination of the relative locations of genes on a
chromosome. Gene sequencing Determination of the sequence of nucleotide bases in a
strand of DNA. See also Sequencing. Gene therapy The replacement of a defective
gene in an organism suffering from a genetic disease. Recombinant DNA techniques
are used to isolate the functioning gene and insert it into cells. More than 300
single-gene genetic disorders have been identified in humans. A significant
percentage of these may be amenable to gene therapy.

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Germplasm The total genetic variability, represented by germ cells or seeds,
available to a particular population of organisms. Glycoprotein A protein
conjugated with a carbohydrate group. Granulocyte One of three types of white
blood cells. Granulocytes digest bacteria and other parasites. Granulocyte-
macrophage colony stimulating factor (GMCSF) A natural hormone that stimulates
white blood cell production, particularly that of granulocytes and monocytes (the
precursors of macrophages). Growth factors Naturally occurring proteins that
stimulate the growth and reproduction of specific cell types. Growth factors are
essential to regenerative medicine and tissue engineering. Growth hormone A
protein produced by the pituitary gland that is involved in cell growth. Human
growth hormone is used clinically to treat dwarfism. Various animal growth
hormones can be used to improve milk production as well as produce a leaner
variety of meat.

Homologous Corresponding or alike in structure, position or origin. Hormone A

chemical or protein that acts as a messenger or stimulatory signal, relaying
instructions to stop or start certain physiological activities. Hormones are
synthesized in one type of cell and then released to direct the function of other
cell types. Host A cell or organism used for growth of a virus, plasmid or other
form of foreign DNA, or for the production of cloned substances. Host-vector
system Combination of DNA-receiving cells (host) and DNA-transporting substance
(vector) used for introducing foreign DNA into a cell. Human Genome Project An
international research effort aimed at discovering the full sequence of bases in
the human genome. Led in the United States by the National Institutes of Health
and the Department of Energy. Human immunodeficiency virus (HIV) The virus that
causes acquired immune deficiency syndrome (AIDS). Hybridization Production of
offspring, or hybrids, from genetically dissimilar parents. The process can be
used to produce hybrid plants (by crossbreeding two different varieties) or
hybridomas (hybrid cells formed by fusing two unlike cells, used in producing
monoclonal antibodies). See DNA hybridization. Hybridoma The cell produced by
fusing two cells of different origin. In monoclonal antibody technology,
hybridomas are formed by fusing an immortal cell (one that divides continuously)
and an antibody-producing cell. See also Monoclonal antibody; Myeloma.

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H
Haploid A cell with half the usual number of chromosomes, or only one chromosome
set. Sex cells are haploid. Compare Diploid. Hapten The portion of an antigen that
determines its immunological specificity. When coupled to a large protein, a
hapten stimulates the formation of antibodies to the two-molecule complex. Also
called antigenic determinant. Hemagglutination Clumping (agglutination) of red
blood cells. Heredity Transfer of genetic information from parent cells to
progeny. Histocompatibility Immunologic similarity of tissues such that grafting
can be done without tissue rejection. Histocompatibility antigen An antigen that
causes the rejection of grafted material from an animal different in genotype from
the host animal. Homeobox Family of genes that regulate activities of other genes
(turns genes on and off).

I
Immune response The response of the immune system to challenge by a foreign
antigen. Immune serum Blood serum containing antibodies. Immune system The
combination of cells, biological substances (such as antibodies) and cellular
activities that work together to provide resistance to disease. Immunity
Nonsusceptibility to a disease or to the toxic effects of antigenic material. See
also Active immunity; Cell-mediated immunity; Natural active immunity; Natural
passive immunity; Passive immunity.
Guide to Biotechnology n Biotechnology Industry Organization
Immunoassay Technique for identifying substances based on the use of antibodies.
Immunodiagnostic The use of specific antibodies to measure a substance. This tool
is useful in diagnosing infectious diseases and the presence of foreign substances
in a variety of human and animal fluids (blood, urine, etc.). The approach is
currently being investigated as a way of locating tumor cells in the body.
Immunofluorescence Technique for identifying antigenic material that uses an
antibody labeled with fluorescent material. Specific binding of the antibody and
antigen can be seen under a microscope by applying ultraviolet light rays and
noting the visible light that is produced. Immunogen Any substance that can elicit
an immune response. Immunoglobulin General name for proteins that function as
antibodies. These proteins differ somewhat in structure and are grouped into five
categories on the basis of these differences; immunoglobulin G (IgG), IgM, IgA,
IgE and IgD. Immunology Study of all phenomena related to the body’s response to
antigenic challenge (i.e., immunity, sensitivity and allergy). Immunomodulators A
diverse class of proteins that boost the immune system. Many are cell growth
factors that accelerate the production of specific cells that are important in
mounting an immune response in the body. These proteins are being investigated for
use in possible treatments for cancer. Immunotoxins Specific monoclonal antibodies
that have a protein toxin molecule attached. The monoclonal antibody is targeted
against a tumor cell, and the toxin is designed to kill that cell when the
antibody binds to it. Inducer A molecule or substance that increases the rate of
enzyme synthesis, usually by blocking the action of the corresponding repressor.
In situ In its original or natural place or position. Interferon A class of
lymphokine proteins important in the immune response. There are three major types
of interferon: alpha (leukocyte), beta (fibroblast) and gamma (immune).
Interferons inhibit viral infections and may have anticancer properties.

Interleukin A type of lymphokine that regulates the growth and development of

white blood cells. Twelve interleukins (IL-1 through IL-12) have been identified
to date. Intron In eukaryotic cells, a sequence of DNA that is contained in the
gene but does not encode for protein. The presence of introns “splits” the coding
region of the gene into segments called exons. See also Exon; Splicing.
Investigational New Drug Application (IND) An application to begin studies of a
new drug or biologic on humans. The IND gives the plan for the study and contains
formulation, manufacturing and animal test result information. In vitro Literally,
“in glass.” Performed in a test tube or other laboratory apparatus. In vivo In a
living organism. Islet cells Pancreatic cells that are the source of insulin and
two other hormones involved in regulating glucose metabolism and absorption.
Isoenzyme One of the several forms that a given enzyme can take. The forms may
differ in certain physical properties, but function similarly as biocatalysts.
Isogenic Of the same genotype.

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K
Kidney plasminogen activator A precursor to the enzyme urokinase, which has blood-
clotting properties.

L
Leukocyte A colorless cell in the blood, lymph and tissues that is an important
component of the body’s immune system. Also called white blood cell. Library A set
of cloned DNA fragments that taken collectively contain the entire genome of an
organism. Also called a DNA library. Ligase An enzyme used to join DNA or RNA
segments together. Linkage The tendency for certain genes to be inherited together
due to their physical proximity on the chromosome.

Biotechnology Industry Organization n Guide to Biotechnology

Linker A fragment of DNA with a restriction site that can be used to join DNA
strands. Lipoproteins A class of serum proteins that transport lipids and
cholesterol in the bloodstream. Abnormalities in lipoprotein metabolism have been
implicated in certain heart diseases. Lymphocyte A type of leukocyte found in
lymphatic tissue in the blood, lymph nodes and organs. Lymphocytes are
continuously made in the bone marrow and mature into antibody-forming cells. See
also B lymphocytes; T lymphocytes. Lymphokine A class of soluble proteins produced
by white blood cells that play a role, as yet not fully understood, in the immune
response. See also Interferon; Interleukin. Lymphoma Form of cancer that affects
the lymph tissue.

Microbial herbicides and pesticides Microorganisms that are toxic to specific

plants or insects. Because of their narrow host range and limited toxicity, these
microorganisms may be preferable to their chemical counterparts for certain pest-
control applications. Microbiology Study of living organisms that can be seen only
under a microscope. Microinjection The injection of DNA using a very fine needle
into a cell. Microorganism Any organism that can be seen only with the aid of a
microscope. Also called microbe. Mitosis Process of cell reproduction whereby the
daughter cells are identical in chromosome number to the parent cells. Compare
Meiosis. Molecular genetics Study of how genes function to control cellular
activities. Monoclonal antibody (MAb) Highly specific, purified antibody that is
derived from only one clone of cells and recognizes only one antigen. See also
Hybridoma; Myeloma. Monocytes One of three types of white blood cells. Monocytes
are precursors to macrophages. Multigenic Of hereditary characteristics, one that
is specified by several genes. Mutagen A substance that induces mutations. Mutant
A cell that manifests new characteristics due to a change in its DNA. Mutation A
change in the genetic material of a cell. Myeloma A type of cancer cell (plasma
cell) that is used in monoclonal antibody technology to form hybridomas.

M
Macrophage A type of white blood cell produced in blood vessels and loose
connective tissues that can ingest dead tissues and cells and is involved in
producing interleukin-1. When exposed to the lymphokine macrophage-activating
factor, macrophages also kill tumor cells. See also Phagocyte. Macrophage colony
stimulating factor (M-CSF) A natural hormone that stimulates the production of
white blood cells, particularly monocytes (the precursors of macrophages). Medium
A substance containing nutrients needed for cell growth. Meiosis Process of cell
reproduction whereby the daughter cells have half the chromosome number of the
parent cells. Sex cells are formed by meiosis. Compare Mitosis. Messenger RNA
(mRNA) Nucleic acid that carries instructions to a ribosome for the synthesis of a
particular protein. Metabolism All biochemical activities carried out by an
organism to maintain life.

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N
Natural active immunity Immunity that is established after the occurrence of a
disease. Natural killer (NK) cell A type of leukocyte that attacks cancerous or
virus-infected cells without previous exposure to the antigen. NK cell activity is
stimulated by interferon. Natural passive immunity Immunity conferred by the
mother on the fetus or newborn.
Guide to Biotechnology n Biotechnology Industry Organization
Nitrogen fixation A biological process (usually associated with plants) whereby
certain bacteria convert nitrogen in the air to ammonia, thus forming a nutrient
essential for plant growth. Nitrogenous base See Base. Noncoding DNA DNA that does
not encode any product (RNA or protein). The majority of the DNA in plants and
animals is noncoding. Nuclease An enzyme that, by cleaving chemical bonds, breaks
down nucleic acids into their constituent nucleotides. Nucleic acids Large
molecules, generally found in the cell’s nucleus and/or cytoplasm, that are made
up of nucleotides. The two most common nucleic acids are DNA and RNA. Nucleotides
The building blocks of nucleic acids. Each nucleotide is composed of sugar,
phosphate and one of four nitrogen bases. The sugar in DNA is deoxyribose and
RNA’s sugar is ribose. The sequence of the bases within the nucleic acid
determines the sequence of amino acids in a protein. See also Base. Nucleus The
structure within eukaryotic cells that contains chromosomal DNA.

P
Passive immunity Immunity acquired from receiving preformed antibodies. Pathogen
Disease-causing organism. Peptide Two or more amino acids joined by a linkage
called a peptide bond. Personalized medicine The use of individual molecular
(often genetic) information to prevent disease, choose medicines and make other
critical decisions about health. Phagocyte A type of white blood cell that can
ingest invading microorganisms and other foreign material. See also Macrophage.
Pharmacogenomics The science that examines the inherited variations in genes that
dictate drug response and explores the ways these variations can be used to
predict whether a patient will have a good response to a drug, a bad response to a
drug, or no response at all. See also pharmacogenetics. Pharmacogenetics The study
of inherited differences (variation) in drug metabolism and response. See also
pharmacogenomics. Phenotype Observable characteristics resulting from interaction
between an organism’s genetic makeup and the environment. Compare Genotype.
Photosynthesis Conversion by plants of light energy into chemical energy, which is
then used to support the plants’ biological processes. Phytoremediation The use of
plants to clean up pollution. Plasma The fluid (noncellular) fraction of blood.
Plasmapheresis A technique used to separate useful factors from blood. Plasmid A
small circular form of DNA that carries certain genes and is capable of
replicating independently in a host cell. Pluripotent cells Having the capacity to
become any kind of cell or tissue in the body. Embryonic stem cells and cells of
the inner cell mass are pluripotent. Adult stem cells are multipotent. The
mammalian embryo (blastocyst trophoblast plus inner cell mass) is totipotent
because it can become an entire organism.

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O
Oligonucleotide A polymer consisting of a small number (about two to 10) of
nucleotides. Oncogene Gene thought to be capable of producing cancer. Oncogenic
Cancer causing. Oncology Study of cancer. Operator gene A region of the
chromosome, adjacent to the operon, where a repressor protein binds to prevent
transcription of the operon. Operon Sequence of genes responsible for synthesizing
the enzymes needed for biosynthesis of a molecule. An operon is controlled by an
operator gene and a repressor gene. Organic compound A compound containing carbon.

Biotechnology Industry Organization n Guide to Biotechnology

Fully differentiated cells from many plants are totipotent. Polyclonal Derived
from different types of cells. Polymer A long molecule of repeated subunits.
Polymerase General term for enzymes that carry out the synthesis of nucleic acids.
Polymerase chain reaction (PCR) A technique to amplify a target DNA sequence of
nucleotides by several hundred thousandfold. Polypeptide Long chain of amino acids
joined by peptide bonds. Preclinical studies Studies that test a drug on animals
and in other nonhuman test systems. Safety information from such studies is used
to support an investigational new drug application (IND). Prokaryote An organism
(e.g., bacterium, virus, cyanobacterium) whose DNA is not enclosed within a
nuclear membrane. Compare Eukaryote. Promoter A DNA sequence that is located in
front of a gene and controls gene expression. Promoters are required for binding
of RNA polymerase to initiate transcription. Prophage Phage nucleic acid that is
incorporated into the host’s chromosome but does not cause cell lysis. Protein A
molecule composed of amino acids. There are many types of proteins, all carrying
out different functions essential for cell growth.

Pure culture In vitro growth of only one type of microorganism.

R
Radioimmunoassay (RIA) A test combining radioisotopes and immunology to detect
trace substances. Such tests are useful for studying antibody interactions with
cell receptors, and can be developed into clinical diagnostics. Rational drug
design Using the known three-dimensional structure of a molecule, usually a
protein, to design a drug molecule that will bind to it. Usually viewed as an
alternative to drug discovery through screening many molecules for biological
activity. Reagent Substance used in a chemical reaction. Recombinant DNA (rDNA)
The DNA formed by combining segments of DNA from two different sources.
Regeneration Laboratory technique for forming a new plant from a clump of plant
cells. Regulatory gene A gene that acts to control the proteinsynthesizing
activity of other genes. Replication Reproduction or duplication, as of an exact
copy of a strand of DNA. Replicon A segment of DNA (e.g., chromosome or plasmid)
that can replicate independently. Repressor A protein that binds to an operator
adjacent to a structural gene, inhibiting transcription of that gene. Restriction
enzyme An enzyme that breaks DNA in highly specific locations, creating gaps into
which new genes can be inserted. Restriction fragment length polymorphism (RFLP)
The variation in the length of DNA fragments produced by a restriction
endonuclease that cuts at a polymorphic locus. This is a key tool in DNA
fingerprinting and is based on the presence of different alleles in an individual.
RFLP mapping is also used in plant breeding to see if a key trait such as disease
resistance is inherited.

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Protein A protein produced by the bacterium Staphylococcus aureus that

specifically binds antibodies. It is useful in the purification of monoclonal
antibodies.
Proteomics Each cell produces thousands of proteins, each with a specific
function. This collection of proteins in a cell is known as the proteome, and,
unlike the genome, which is constant irrespective of cell type, the proteome
varies from one cell type to the next. The science of proteomics attempts to
identify the protein profile of each cell type, assess protein differences between
healthy and diseased cells, and uncover not only each protein’s specific function
but also how it interacts with other proteins. Protoplast The cellular material
that remains after the cell wall has been removed from plant and fungal cells.

Guide to Biotechnology n Biotechnology Industry Organization

Reticuloendothelial system The system of macrophages, which serves as an important
defense system against disease. Retrovirus A virus that contains the enzyme
reverse transcriptase. This enzyme converts the viral RNA into DNA, which can
combine with the DNA of the host cell and produce more viral particles. Rheology
Study of the flow of matter such as fermentation liquids. Rhizobium A class of
microorganisms that converts atmospheric nitrogen into a form that plants can
utilize for growth. Species of this microorganism grow symbiotically on the roots
of certain legumes, such as peas, beans and alfalfa. Ribonucleic acid (RNA) A
molecule similar to DNA that delivers DNA’s genetic message to the cytoplasm of a
cell where proteins are made. Ribosome A cellular component, containing protein
and RNA, that is involved in protein synthesis.

Somatic cell gene therapy Somatic cell gene therapy involves the insertion of
genes into cells for therapeutic purposes; for example, to induce the treated
cells to produce a protein that the body is missing. It does not affect genetic
makeup of a patient’s offspring and generally does not change all, or even most,
cells in the recipient. Somatic cell gene therapy is only one way of applying the
science of genomics to improve health care. Somatic cell nuclear transfer The
transfer of a nucleus from a fully differentiated cell into an egg that has had
its nucleus removed. Splicing The removal of introns and joining of exons to form
a continuous coding sequence in RNA. Stop codon One of three codons in messenger
RNA that signal the end of the amino acid chain in protein synthesis. Structural
gene A gene that codes for a protein, such as an enzyme. Substrate Material acted
on by an enzyme. Suicide gene A gene that codes for an antibiotic that can kill
the host bacterial cell. It is genetically modified into the bacterium along with
a molecular switch that is controlled by a nutrient in the environment. When the
nutrient disappears, the suicide gene is switched on and the bacterium dies.
Suppressor gene A gene that can reverse the effect of a mutation in other genes.
Systems biology A hypothesis-driven field of research that creates predictive
mathematical models of complex biological processes or organ systems.

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RNA interference A natural process used by organisms to block protein production.

S
Scale-up Transition from small-scale production to production of large industrial
quantities. Selective medium Nutrient material constituted such that it will
support the growth of specific organisms while inhibiting the growth of others.
Sepsis The presence in the blood or other tissues of pathogenic microorganisms or
their toxins; the condition associated with such presence. Sequencing Decoding a
strand of DNA or gene into the specific order of its nucleotides: adenine,
cytosine, guanine and thymine. This analysis can be done manually or with
automated equipment. Sequencing a gene requires analyzing an average of 40,000
nucleotides. Serology Study of blood serum and reactions between the antibodies
and antigens therein. Single-cell protein Cells or protein extracts from
microorganisms, grown in large quantities for use as protein supplements. Somatic
cells Cells other than sex or germ cells.
Biotechnology Industry Organization n Guide to Biotechnology

T
Technology transfer The process of transferring discoveries made by basic research
institutions, such as universities and government laboratories, to the commercial
sector for development into useful products and services. Template A molecule that
serves as the pattern for synthesizing another molecule. Terminator Sequence of
DNA bases that tells the RNA polymerase to stop synthesizing RNA.
Tertiary structure The total three-dimensional shape of a protein that is
essential to protein function. Therapeutics Compounds that are used to treat
specific diseases or medical conditions. Thymus A lymphoid organ in the lower
neck, the proper functioning of which in early life is necessary for development
of the immune system. Tissue culture In vitro growth in nutrient medium of cells
isolated from tissue. Tissue plasminogen activator (tPA) A protein produced in
small amounts in the body that aids in dissolving blood clots. T lymphocytes (T-
cells) White blood cells that are produced in the bone marrow but mature in the
thymus. They are important in the body’s defense against certain bacteria and
fungi, help B lymphocytes make antibodies and help in the recognition and
rejection of foreign tissues. T lymphocytes may also be important in the body’s
defense against cancers. Toxin A poisonous substance produced by certain
microorganisms or plants. Transcription Synthesis of messenger (or any other) RNA
on a DNA template. Transdifferentiation The process whereby a specialized cell de-
differentiates and re-differentiates into a different cell type; or the process
whereby an adult stem cell from a specific tissue type becomes a cell type from a
very different tissue (for example a nerve stem cell differentiates into a kidney
cell). Transduction Transfer of genetic material from one cell to another by means
of a virus or phage vector. Transfection Infection of a cell with nucleic acid
from a virus, resulting in replication of the complete virus. Transfer RNA (tRNA)
RNA molecules that carry amino acids to sites on ribosomes where proteins are
synthesized. Transformation Change in the genetic structure of an organism by the
incorporation of foreign DNA. Transgenic organism An organism formed by the
insertion of foreign genetic material into the germ line cells of organisms.
Recombinant DNA techniques are commonly used to produce transgenic organisms.

Translation Process by which the information on a messenger RNA molecule is used

to direct the synthesis of a protein. Transposon A segment of DNA that can move
around and be inserted at several sites in bacterial DNA or in a phage, thus
alerting the host’s DNA. Tumor necrosis factors (TNFs) Rare proteins of the immune
system that appear to destroy some types of tumor cells without affecting healthy
cells.

V
Vaccine A preparation that contains an antigen, consisting of whole disease-
causing organisms (killed or weakened) or parts of such organisms, that is used to
confer immunity against the disease that the organisms cause. Vaccine preparations
can be natural, synthetic or derived by recombinant DNA technology. Vector The
agent (e.g., plasmid or virus) used to carry new DNA into a cell. Virion An
elementary viral particle consisting of genetic material and a protein covering.
Virology Study of viruses. Virulence Ability to infect or cause disease. Virus A
submicroscopic organism that contains genetic information but cannot reproduce
itself. To replicate, it must invade another cell and use parts of that cell’s
reproductive machinery.

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W
White blood cells Leukocytes. Wild type The form of an organism that occurs most
frequently in nature.

X
X-ray crystallography An essential technique for determining the three-dimensional
structure of biological molecules. This information aids in the discovery of
products that will interact with the biological molecule.

Guide to Biotechnology n Biotechnology Industry Organization

Xenobiotics Synthetic chemicals believed to be resistant to environmental
degradation. A branch of biotechnology called bioremediation is seeking to develop
biological methods to degrade such compounds. Xenotransplantation The
transplantation of living organs, cells or tissues from animals into humans.

Y
Yeast A general term for single-celled fungi that reproduce by budding. Some
yeasts can ferment carbohydrates (starches and sugars) and thus are important in
brewing and baking.

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Notes
Notes
Biotechnology Industry Organization 1225 Eye Street, NW Suite 400 Washington, DC
20005 202-962-9200 (phone) 202-962-9201 (fax) www.bio.org