Biotech Guide
Uploaded by
englishwomanBiotech Guide
Uploaded by
englishwomanThere are more than 400 biotech drug products and
VACCINES currently in clinical trials targeting more
than 200 diseases, including various cancers, Alzheimers
Guide to
disease, heart disease, diabetes, multiple sclerosis,
Biotechnology
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. 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
2007
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
Putting the Pieces Together: Omics ...............................29
Genomics, proteomics and bioinformatics
What Is Biotechnology?......................................................1
Product Development Applications .................................31
Cells and Biological Molecules...........................................1
Health-Care Applications
34
Diagnostics .......................................................................34
Market Capitalization, 19942005 .....................................3
Therapeutics .....................................................................34
U.S. Industry Statistics: 19942005 ...................................3
Personalized Medicine ......................................................37
New Biotech Drug and Vaccine Approvals/
New Indication Approvals by Year.................................4
Regenerative Medicine .....................................................39
North American Biotech Companies
by State and Province ....................................................4
Plant-Made Pharmaceuticals............................................41
Biotechnology Industry Facts
Total Financing, 19982005 ...............................................5
Biotech Industry Financing, 2005 .....................................5
Time Line
Biotechnology Policy Milestones .....................................16
The Technologies
and Their Applications
Vaccines ............................................................................39
Therapeutic Developement Overview
42
Biotech Drug Development Process ................................44
Approved Biotechnology Drugs
45
Agricultural Production Applications 65
Monoclonal Antibodies .....................................................18
Crop Biotechnology ..........................................................65
Includes production improvement, impact on developing countries, environmental and economic benefits,
and regulations
Cell Culture ......................................................................19
Forest Biotechnology .......................................................69
Recombinant DNA Technology ........................................21
Cloning .............................................................................21
Animal Biotechnology ......................................................70
Includes companion animals, applications for human
medicine, and environmental and conservation efforts
Protein Engineering ........................................................22
Aquaculture ......................................................................76
Biosensors ........................................................................22
Global Area of Transgenic Crops,
1995 to 2005: Industrial and Developing Countries ..78
18
Bioprocessing Technology................................................18
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
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
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
82
Food Biotechnology
87
Improving the Raw Materials ...........................................87
Food Processing................................................................88
Food Safety Testing ..........................................................89
BIO Statement of Ethical Principles 109
Intellectual Property
111
What Is a Patent? ............................................................111
The Purpose of a Patent .................................................111
Patentable Inventions.....................................................112
Patent Requirements ......................................................112
Industrial and Environmental
Applications
90
The Patent Application ...................................................113
Industrial Sustainability...................................................90
Patenting Organisms ......................................................113
Biocatalysts .......................................................................91
Patent Licensing .............................................................114
Biofuel ..............................................................................92
Green Plastics ...................................................................93
Biotechnology Resources
Nanotechnology................................................................93
Periodicals, Headline Services and Web Sites ...............115
Environmental Biotechnology .........................................94
General Science Journals ..............................................116
Industries That Benefit.....................................................95
Biotech Education & Careers .........................................116
Some Industrial Biotech Applications
by Sector ......................................................................95
Selected Recent Reports on Biotechnology ...................116
Glossary
Consumer Products Made
with Industrial Biotechnology
96
Examples of Industrial Enzymes
98
Preparedness for
Pandemics and Biodefense
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
115
119
Biotechnology: A Collection of Technologies
What Is Biotechnology?
reak biotechnology into its roots
and you have
biothe use of biological processes; and
technologyto 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 organismstheir biological moleculesin addition to using whole organisms.
A more appropriate definition in the new sense of the
word is this:
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
natures 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 todays biotechnology.
New Biotechnologythe 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.
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 proteinssuch as human
insulin and other therapiesin cultured cells under
controlled manufacturing conditions. Boyer went on
to co-found Genentech, which today is biotechnologys
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, Alzheimers disease, heart disease, diabetes, multiple sclerosis,
AIDS and arthritis.
2
N
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).
Biotechnology Industry Organization N Guide to Biotechnology
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 biosciencesincluding not just biotechnology
but all life sciences activitiesemployed 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.
Bioethanolmade from crop wastes using biotech
enzymescould 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, BIOs membership consisted of more than 1,100 biotechnology companies,
academic centers, state and local associations and
related enterprises.
Market Capitalization, 19942005*
450
410
400
353.5
336.8
330.8
350
300
250
225
206
200
137.9
150
83
100
52
45
41
1994
1995
50
93
0
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
Year
*Amounts are U.S. dollars in billions.
Sources:
Ernst & Young LLP
BioWorld
U.S. Biotech Industry Statistics: 19942005*
Year
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
Sales
32.1
28.1
28.4
24.3
21.4
19.3
16.1
14.5
13
10.8
9.3
7.7
Revenues
50.7
43.8
39.2
29.6
29.6
26.7
22.3
20.2
17.4
14.6
12.7
11.2
R&D Expense
19.8
19.6
17.9
20.5
15.7
14.2
10.7
10.6
9.0
7.9
7.7
7.0
Net Loss
4.1
6.8
5.4
9.4
4.6
5.6
4.4
4.1
4.5
4.6
4.1
3.6
No. of Public
Companies
329
331
314
318
342
339
300
316
317
294
260
265
1,415
1,346
1,473
1,466
1,457
1,379
1,273
1,311
1,274
1,287
1,308
1,311
No. of Companies
*Amounts are U.S. dollars in billions.
Source:
Ernst & Young LLP, annual biotechnology industry reports, 19952006. 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
40
36
38
37
34
35
Number of Approvals
30
25
25
19
20
5
3
2
0
7
5
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
374
350
300
256
250
200
134
81
100
75
74
68
59
58
56
50
48
47
45
33
25
Connecticut
143
150
Washington
Number of Companies
Source:
Ernst & Young LLP
Biotechnology Industry Organization N Guide to Biotechnology
Regions
Alberta
Florida
Texas
New York
Georgia
Pennsylvania
New Jersey
British Columbia
Maryland
North Carolina
Quebec
Ontario
Massachusetts
0
California
20
10
Source:
BIO
25
15
15
25
Total Financing, 19982005 (in billions of U.S. dollars)
38
40
35
30
25
20
20.8
20.1
2004
2005
16.9
15.1
15
11.8
10.5
10
5.4
5
0
1998
1999
2000
2001
2002
2003
Source:
BioWorld
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.
Potatoes first cultivated for food.
40002000 B.C.
N
Biotechnology first used to leaven bread and ferment
beer, using yeast (Egypt).
Production of cheese and fermentation of wine (Sumeria, China and Egypt).
First antibiotic: moldy soybean curds used to treat
boils (China).
An Arab chieftain first uses artificial insemination to
produce superior horses.
1590
N
Using Darwins theory, plant breeders crossbreed cotton, developing hundreds of varieties with superior
qualities.
Farmers first inoculate fields with nitrogen-fixing
bacteria to improve yields.
William James Beal produces first experimental corn
hybrid in the laboratory.
1877A technique for staining and identifying bacteria is developed by Koch.
1878The first centrifuge is developed by Laval.
1879Fleming discovers chromatin, the rod-like
structures inside the cell nucleus that later came to be
called chromosomes.
Janssen invents the microscope.
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.
1900
N
1830Proteins discovered.
1833First enzyme discovered and isolated.
Biotechnology Industry Organization N Guide to Biotechnology
Drosophila (fruit flies) used in early studies of genes.
1902
18301833
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 waythe laws of heredity.
18701890
1663
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
First insecticide: powdered chrysanthemums (China).
1322
Pasteur proposes microbes cause fermentation.
1859
A.D. 100
N
Schleiden and Schwann propose that all organisms are
composed of cells, and Virchow declares, Every cell
arises from a cell.
1857
Babylonians control date palm breeding by selectively
pollinating female trees with pollen from certain male
trees.
500 B.C.
N
18351855
The term immunology first appears.
1906
N
The term genetics is introduced.
1911
N
The first cancer-causing virus is discovered by Rous.
1930
N
U.S. Congress passes the Plant Patent Act, enabling
the products of plant breeding to be patented.
1914
N
Bacteria are used to treat sewage for the first time in
Manchester, England.
1933
N
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.
1938
N
Penicillin discovered as an antibiotic: Alexander Fleming.
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 plantsknown today as
hybridization.
The term molecular biology is coined.
1941
N
1928
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.
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 bacteriophagea virus that infects bacteria.
Penicillin mass-produced in microbes.
1944
N
DNA is proven to carry genetic informationAvery et al.
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.
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
1946
N
8
N
Discovery that genetic material from different viruses
can be combined to form a new type of virus, an example of genetic recombination.
Recognizing the threat posed by loss of genetic diversity,
the U.S. Congress provides funds for systematic and
extensive plant collection, preservation and introduction.
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.
Discovery of interferons.
First synthetic antibiotic.
1960
N
Exploiting base pairing, hybrid DNA-RNA molecules
are created.
Messenger RNA is discovered.
1961
N
1963
N
1951
Artificial insemination of livestock using frozen semen
is accomplished.
1953
N
The scientific journal Nature publishes James Watson
and Francis Cricks manuscript describing the double
helical structure of DNA, which marks the beginning
of the modern era of genetics.
An enzyme involved in the synthesis of a nucleic acid
is isolated for the first time.
Biotechnology Industry Organization N Guide to Biotechnology
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
1955
New wheat varieties developed by Norman Borlaug
increase yields by 70 percent.
1964
N
USDA registers first biopesticide: Bacillus thuringiensis, or Bt.
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.
First guidelines for recombinant DNA experiments
released: National Institutes of HealthRecombinant
DNA Advisory Committee.
1969
N
An enzyme is synthesized in vitro for the first time.
1970
N
Norman Borlaug receives the Nobel Peace Prize (see
1963).
Discovery of restriction enzymes that cut and splice
genetic material, opening the way for gene cloning.
1971
N
First complete synthesis of a gene.
1977
N
First expression of human gene in bacteria.
Procedures developed for rapidly sequencing long sections of DNA using electrophoresis.
1978
N
High-level structure of virus first identified.
Recombinant human insulin first produced.
North Carolina scientists show it is possible to introduce specific mutations at specific sites in a DNA
molecule.
1972
N
The DNA composition of humans is discovered to be
99 percent similar to that of chimpanzees and gorillas.
Initial work with embryo transfer.
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.
1979
N
ALSO IN THE 1970s
N
First commercial company founded to develop genetically engineered products.
Discovery of polymerases.
Techniques for rapid sequencing of nucleotides perfected.
Gene targeting.
RNA splicing.
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.
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.
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 interferoninto a
bacterium.
Nobel Prize in Chemistry awarded for creation
of the first recombinant molecule: Berg, Gilbert,
Sanger.
1976
N
The tools of recombinant DNA are first applied to a
human inherited disorder.
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.
Human growth hormone first synthesized.
Guide to Biotechnology N Biotechnology Industry Organization
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.
1984
N
The DNA fingerprinting technique is developed.
The entire genome of the human immunodeficiency
virus is cloned and sequenced.
1985
N
Genetic markers found for kidney disease and cystic
fibrosis.
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.
1981
10
Scientists at Ohio University produce the first transgenic animals by transferring genes from other animals into mice.
Chinese scientist becomes the first to clone a fisha
golden carp.
1982
N
Applied Biosystems, Inc., introduces the first commercial gas phase protein sequencer, dramatically reducing
the amount of protein sample needed for sequencing.
First recombinant DNA vaccine for livestock developed.
First biotech drug approved by FDA: human insulin
produced in genetically modified bacteria.
First recombinant vaccine for humans: hepatitis B.
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 CaliforniaBerkeley 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 cropgene-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 genetic transformation of a plant cell: petunia.
1983
N
1986
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.
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.
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 animala transgenic
mouse.
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.
1989
N
First approval for field test of modified cotton: insectprotected (Bt) cotton.
Plant Genome Project begins.
The first experimental gene therapy treatment is performed successfully on a 4-year-old girl suffering from
an immune disorder.
The first transgenic dairy cowused to produce human milk proteins for infant formulais 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.
ALSO IN THE 1980s
N
Studies of DNA used to determine evolutionary history.
Recombinant DNA animal vaccine approved for use in
Europe.
1992
Use of microbes in oil spill cleanup: bioremediation
technology.
Ribozymes and retinoblastomas identified.
American and British scientists unveil a technique for
testing embryos in vitro for genetic abnormalities such
as cystic fibrosis and hemophilia.
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.
The Human Genome Projectan international effort
to map all the genes in the human bodyis launched.
1993
N
Merging two smaller trade associations creates the
Biotechnology Industry Organization (BIO).
FDA approves bovine somatotropin (BST) for increased
milk production in dairy cows.
Guide to Biotechnology N Biotechnology Industry Organization
11
1994
N
First FDA approval for a whole food produced
through biotechnology: FLAVRSAVR tomato.
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.
1995
N
The first baboon-to-human bone marrow transplant is
performed on an AIDS patient.
The first full gene sequence of a living organism other
than a virus is completed, for the bacterium Hemophilus influenzae.
12
Gene therapy, immune system modulation and recombinantly produced antibodies enter the clinic in the
war against cancer.
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.
ALSO IN THE 1990s
N
First conviction using genetic fingerprinting in the U.K.
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.
1996
N
The discovery of a gene associated with Parkinsons
disease provides an important new avenue of research
into the cause and potential treatment of the debilitating neurological ailment.
2000
N
First complete map of a plant genome developed: Arabidopsis thaliana.
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.
Biotech crops grown commercially on nearly 5 million
acres worldwide: Argentina, Australia, Canada, China,
Mexico and the United States.
First biotech crop field-tested in Kenya: virus-resistant
sweet potato.
Rough draft of the human genome sequence is announced.
A group of Oregon researchers claims to have cloned
two Rhesus monkeys.
2001
1997
N
First animal cloned from an adult cell: a sheep named
Dolly in Scotland.
First weed- and insect-resistant biotech crops commercialized: Roundup Ready soybeans and Bollgard
insect-protected cotton.
First complete map of the genome of a food plant
completed: rice.
Researchers with Chinas 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-
1998
N
University of Hawaii scientists clone three generations
of mice from nuclei of adult ovarian cumulus cells.
Human embryonic stem cell lines are established.
Scientists at Japans Kinki University clone eight identical calves using cells taken from a single adult cow.
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.
International consortia sequence the genomes of the
parasite that causes malaria and the species of mosquito that transmits the parasite.
2003
N
Researchers find a vulnerability gene for depression
and make strides in detecting genetic links to schizophrenia and bipolar disorder.
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.
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.
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.
Researchers announce successful results for a vaccine
against cervical cancer, the first demonstration of a
preventative vaccine for a type of cancer.
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.
Chinas State Food and Drug Administration grants
the worlds 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.
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.
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.
Guide to Biotechnology N Biotechnology Industry Organization
13
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.
2004
N
The FDA approves the first anti-angiogenic drug for
cancer, AVASTIN (bevacizumab).
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.
14
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 chimpanzeehumanitys 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 19181919.
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 Units 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 agricultures
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.
2005
N
Researchers at the University of Georgia successfully
produce a cow cloned from the cells of a carcass.
FDA for the first time approves a drug for a specific
race. The drug, NitroMeds BiDil, treats congestive
Biotechnology Industry Organization N Guide to Biotechnology
Global biotech crop acreage reaches 222 million acres.
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.
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.
In his State of the Union address, President Bush
expresses support for bioethanol made from agricultural wastes. Doesnt 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
USDAs 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 productsincluding 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
Guide to Biotechnology N Biotechnology Industry Organization
15
Biotechnology Policy Milestones
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 recipientssuch as universities and small businessesown federally funded
inventions.
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
16
Leading biologists call for a voluntary moratorium on
recombinant DNA experiments while safety standards
are set.
1975
N
The U.S. Patent and Trademark Office grants Harvard University a patent for a mouse used for cancer
research (the OncoMouse).
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.
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.
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
The NIH adopts guidelines for federally funded recombinant DNA research, with oversight provided by the
Recombinant DNA Advisory Committee.
1993
N
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.
The Patent and Trademark Act Amendments of
1980commonly known as the Bayh-Dole Actlay
Biotechnology Industry Organization N Guide to Biotechnology
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
President Nixon calls for a War on Cancer and signs
the National Cancer Act into law, stimulating new
research.
1974
N
The National Institute of Health is created (later to be
pluralized as National Institutes of Health).
1971
N
1983
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.
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
17
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.
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.
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
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.
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.
18
A form of bioprocessing, microbial fermentation, has
been used for thousands of yearsunwittinglyto
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.
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.)
Biotechnology Industry Organization N Guide to Biotechnology
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
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.
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.
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.
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
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.
Tositumomab (Bexxar) is a conjugate of a monoclonal antibody against CD20 and the radioactive isotope
iodine-131. It has been approved to treat lymphoma.
the rest of a human antibody molecule, thus replacing its
own hypervariable regions. Zenapax, Vitaxin, Mylotarg,
Herceptin, and Xolair are examples.
Trastuzumab (Herceptin) binds to HER2, a receptor for epidermal growth factor found on some breast
cancers and lymphomas.
Cell Culture
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).
ANGIOGENESIS INHIBITOR
N
Bevacizumab (Avastin) blocks the vascular endothelial growth factor (VEGF) receptor and has been
approved for the treatment of colorectal cancer.
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-
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
19
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.
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
supplementand may one day replaceanimal 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.
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 embryosspecifically 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.
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.
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 cellsa
significant advance because of the risk of viruses and
other macromolecules in the mouse cells being transmitted to the human cells.
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.
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 cells genetic material
with the patients 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.
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 foods 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
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.
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 natures 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 Mendels laws of heredity. In 1953, James
Watson and Francis Crick deduced DNAs 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
Cloning
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.
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.
produce new medicines and safer vaccines.
ANIMAL CLONING
treat some genetic diseases.
enhance biocontrol agents in agriculture.
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
21
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.
22
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
mothers 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.
Protein Engineering
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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
Biosensors
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 transducera 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.
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
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.
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. Nanotechnologythe study, manipulation and manufacture of
ultra-small structures and machines made of as few as
one moleculewas 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 engineeringcell 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, DNAs 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.
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 DNAs 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
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.
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
23
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
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.
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 dowhich 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
cells job. In addition, a cells protein profile varies with
its health, age, and current and past environmental
conditions.
Protein microarrays will be used to
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.
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
study the relationship between protein structure and
function.
Whole-cell microarrays circumvent the problem of protein stability in protein microarrays and permit a more
accurate analysis of protein interactions within a cell.
assess differential protein expression in order to identify new drug leads.
SMALL-MOLECULE MICROARRAYS
evaluate binding interactions between proteins and
other molecules.
Biotechnology Industry Organization N Guide to Biotechnology
Small-molecule microarrays allow pharmaceutical
companies to screen ten of thousands of potential drug
candidates simultaneously.
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.
Research Applications Of
Biotechnology
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.
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 differentiationgroups
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.
A delicate balance exists between factors that
stimulate cell division and those that inhibit it. Any
disruption of this balance leads to uncontrolled cell
proliferationcanceror 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 proliferationcanceror cell death.
Studying cells in culture has led to a radical revision
of our view of cell death. Formerly we assumed all cells
Guide to Biotechnology N Biotechnology Industry Organization
25
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
26
After animal cells differentiate into tissues and organs,
some tissues retain a group of undifferentiated cells to
replace that tissues 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.
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 plasticitycells 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
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 cells 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 cells identity
and take it back to its embryonic state of complete
plasticity? Before Dollys 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 cells identity and
take it back to its embryonic state of complete plasticity?
Before Dollys birth, we did not know we could ask that
question, much less answer it.
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
identityadult sheep mammary gland cell nucleuswas
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 abovegrowth, proliferation,
differentiation, apoptosisand 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
genomethe total genetic material in an organismis
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 organisms 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.
pieces of DNA (or, more often, its close relative, RNA)
that prevent production of the protein encoded in the
blocked DNA.
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.
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.
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.
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
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 biotechs 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
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 Alzheimers 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.
Putting the Pieces Together:
Omics
iotechs 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 levelthe
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.
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-
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
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.
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
29
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.
30
The fruit fly (Drosophila melanogaster) has proven to be
an invaluable model in the study of inherited genes. The
humble flys 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.
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 proteins 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 organisms 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.
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.
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
Biotechnology Industry Organization N Guide to Biotechnology
When the Human Genome Project began, the first task
researchers took on was developing the necessary tools
for completing the projects goals and objectives. Proteomics researchers likewise are developing tools to address many proteomics objectives, such as
N
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 processsuch as disease
development, the steps in the infection process or
the biochemical response of a crop plant to insect
feedingby measuring waxing and waning protein
production.
discovering how a protein interacts with other proteins within the cell and from outside the cell.
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.
One of the most formidable challenges facing researchers
today remains in informatics: how to make sense of the
massive amount of data provided by biotechnologys 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-
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.
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
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
31
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 genes function or the protein it encodes.
For example, new product discoveries based solely on DNA
sequence data acquired through structural genomics include
32
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.
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
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 errorhence 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 errorhence 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 bulls-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,
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
medicines 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
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.
34
A familiar example of biotechnologys 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 patients 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.
Biotechnology Industry Organization N Guide to Biotechnology
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
Alzheimers Disease, and Parkinsons Diseaseailments
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 patients 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.
Therapeutics
iotechnology will make possible improved versions
of todays 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 bodys 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-
logical substances also rely on natures 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.
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 dont
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
factor VIIIa protein involved in the blood-clotting
process, lacked by some hemophiliacs.
insulina 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 patients body with
an accurate instruction manuala 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.
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 Huntingtons 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
For example, the cytokine branch, which stimulates
other immune system branches, includes the interleukins, interferons and colony-stimulating factorsall 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.
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 Parkinsons 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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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.
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.
Organs and cells from other speciespigs and other animalsmay be promising sources of donor organs and therapeutic cells. This concept is called xenotransplantation.
Organs and cells from other speciespigs and
other animalsmay be promising sources of donor
organs and therapeutic cells. This concept is called
xenotransplantation.
The most significant obstacle to xenotransplantation is
the immune systems 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.
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
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.
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 medicinealso called targeted therapyis beginning to have
a powerful impact on research and treatment, especially
in cancer.
This concept of personalized medicinealso called
targeted therapyis 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.
New tests have been launched recently that identify patients likely to respond to Iressa, Tarceva, Gleevec and
Guide to Biotechnology N Biotechnology Industry Organization
37
Campath, and patients developing resistance to Gleevec.
Tests are available to choose the correct dosage of a
powerful chemotherapy drug for pediatric leukemiathe
tests have saved lives by preventing overdose fatalities.
One of the most exciting new tests is Genomic Healths
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 products 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 productsboth
medicines and testsare 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.
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 Affymetrixs
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 bodys ability
to metabolize some commonly prescribed drugs including antidepressants, anti-psychotics, beta-blockers, and
some chemotherapy drugs.
Biotechnology Industry Organization N Guide to Biotechnology
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, its 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 patientsa 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 drugs target,
epidermal growth factor receptor.
Genetic variationsmutations that affect drug receptors, pathways and metabolizing enzymesare 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 patientsirrespective
of racelikely 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.
Regenerative Medicine
iotechnology permits the use of the human bodys
natural capacity to repair and maintain itself. The
bodys 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 tubes 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 patients 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 Alzheimers Disease.
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
39
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.
Various researchers are developing vaccines against
diseases such as diabetes, chronic inflammatory
disease, Alzheimers 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 theres 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.
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.
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).
Biotechnology is also broadening the vaccine concept
beyond protection against infectious organisms. Various
Researchers are also developing skin patch vaccines for
tetanus, anthrax, influenza and E. coli.
Using these techniques of biotechnology, scientists have
developed antigen-only vaccines against life-threatening
diseases such as hepatitis B and meningitis.
40
researchers are developing vaccines against diseases such
as diabetes, chronic inflammatory disease, Alzheimers
Disease and cancer.
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 pharmaceuticalssuch 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 USDAs 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, Alzheimers disease,
kidney disease, Crohns 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-Hodgkins 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.
Field trials with protein-producing plants are providing
the essential building blocks for innovative treatments
for diseases such as cancer, HIV, heart disease, diabetes,
Alzheimers disease, kidney disease, Crohns disease,
cystic fibrosis, multiple sclerosis, spinal cord injuries,
hepatitis C, chronic obstructive pulmonary disease,
obesity and arthritis.
Guide to Biotechnology N Biotechnology Industry Organization
41
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.
and, if a product is approved, post-marketing studies and
surveillance.
ANIMAL TESTING
BIOLOGICS & DRUGS
Many biotech products are biologics, meaning they are
derived from living sources such as cells. Biologics are
complex mixtures whose active ingredientsusually
proteinsare 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.
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.
42
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 FDAs Center for Drug
Evaluation and Research (CDER, usually pronounced
cedar). Vaccines, blood products, and cell and gene
therapies are regulated by the FDAs 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
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.
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 BIOs 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 drugs 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 randomizedthat is, randomly assignedto
one or the other arm.
lessmeaning 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 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.
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.
Other key terms for clinical trials:
PHASE II
Investigatorsthe doctors or other healthcare professionals conducting a trial.
Institutional review boardslocal oversight groups at
hospitals, universities and other healthcare facilities
that ensure trials are conducted ethically and as safely
as possible.
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 conditionsfor example,
testing a cancer drug in a variety of cancersin order to
define the best patient population(s) for Phase III trials.
Endpointsa clinical trials outcome measures (such
as tumor shrinkage, viral clearance, or survival).
PHASE III
Indicationthe 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).
Clinical trials must be sufficiently poweredthat is, must
enroll enough patients with appropriately selected endpointsto 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 trials 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
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 products structure,
manufacturing, lab testing and clinical trials.
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
43
application receipt. For a standard review product, the
agencys 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.
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.
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.
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.
Advisory committee recommendations are non-binding,
however. The final regulatory decision rests with the agency.
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.
POST-APPROVAL
Every approved drug comes with an official product
label, in a standardized format, whose contents are
44
Biotech Drug Development Process
Discovery
(210 years)
Preclinical Testing
(Lab and animal testing)
Phase I
(2030 healthy volunteers used to check
for safety and dosage)
Phase II
(100300 patient volunteers used to check
for efficacy and side effects)
Phase III
(1,0005,000 patient volunteers used to
monitor reactions to long-term drug use)
FDA Review & Approval
Postmarketing
Testing
0
10
Year
Source:
Ernst & Young LLP
Biotechnology Industry Organization N Guide to Biotechnology
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.
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Abelcet
(liposomal formulation of
anphotericin B)
Enzon
Treatment of invasive fungal infections in
patients who are refractory to or intolerant of
conventional amphotericin B
Nov 1995
Abraxane
(paclitaxel, first-in-class
protein bound particle)
American Pharmaceutical
Partners Inc.
Treats breast cancer after failure of combination
therapy for metastatic disease or relapse within six
months of adjuvant chemotherapy
Jan 2005
Abreva
(docosanol)
AVANIR Pharmaceuticals and
GlaxoSmithKline, Inc.
Topical treatment of recurrent cold sores (herpes
simplex infection)
Jul 2000
Actimmune
(interferon gamma-1b)
InterMune
Pharmaceuticals, Inc.
Treatment of chronic granulomatous disease;
treatment of severe, malignant osteopetrosis
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)
Nov 1987
Jun 1990
Jun 1996
Sep 2001
AcuTect
Berlex Laboratories
(technetium Tc-99 apcitide)
Imaging agent for deep-vein thrombosis
Sept 1998
Adacel
(tetanus toxoid, reduced
diphtheria toxoid and
acellular pertussis vaccine,
absorbed)
Aventis Pasteur Limited
Booster immunization against tetanus, diphtheria
and pertussis as a single dose in individuals 11
through 64 years of age
Jun 2005
Adagen
(adenosine deaminase)
Enzon, Inc.
Treatment of severe combined immunodeficiency
disease (SCID)
Mar 1990
ADVATE
(recombinant clotting
factor)
Baxter Healthcare Corp.
Hemophilia A
Jul 2003
Agenerase
(amprenavir)
Vertex Pharmaceuticals and
GlaxoSmithKline
HIV
Apr 1999
Albutein
(human albumin)
Alpha Therapeutic Corp.
Treatment of hypovolmeic shock; an adjunct in
hemodialysis; used in cardiopulmonary bypass
procedures
Jan 1986
Aldurazyme
(laronidase)
BioMarin Pharmaceutical Inc. and
Genzyme
Mucopolysaccharidosis-1
Apr 2003
Alferon N
(interferon alfa-N3, human
leukocyte derived)
Interferon Sciences, Inc.
Treatment of genital warts
Oct 1989
Aloxi
(palonosetron HCl)
MGI Pharma Inc. and Helsinn
Healthcare SA
Prevention of acute nausea and vomiting in
chemotherapy
Jul 2003
Guide to Biotechnology N Biotechnology Industry Organization
45
46
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Alphanate
(human antihemophilic
factor)
Alpha Therapeutic Corp.
Treatment of hemophilia A or acquired factor VIII
deficiency
Feb 1997
AlphaNine SD
(virus-filtered human
coagulation factor IX)
Alpha Therapeutic Corp.
Prevention and control of bleeding in patients with
factor IX deficiency due to hemophilia B
Jul 1996
AmBisome
(liposomal
amphotericin B)
Gilead Sciences, Inc., and Fujisawa
Healthcare
Treatment of fungal infections in patients with
depressed immune function and with fever of
unknown origin; treatment of cryptococcal
meningitis in HIV-infected patients
Aug 1997
Jun 2000
AMEVIVE
(alefacept)
Biogen Idec
Moderate to severe chronic plaque psoriasis
Jan 2003
AMPHOTEC
(lipid-based colloidal
dispersion of
amphotericin B)
InterMune
Pharmaceuticals, Inc.
Second-line treatment of invasive aspergillosis
infections
Nov 1996
AndroGel
(testosterone)
Unimed Pharmaceuticals,
Inc. (subsidiary of Solvay
Pharmaceuticals )
Testosterone-replacement therapy in males with
testosterone deficiency
Feb 2000
Angiomax
(bivalirudin)
The Medicines Company
Anticoagulant in conjunction with aspirin
in patients with unstable angina undergoing
percutaneous transluminal coronary angioplasty;
patients undergoing percutaneous intervention
Dec 2000
Jun 2005
Apligraf
(living human skin
substitute, from
collagen, fibroblasts and
keratinocytes)
Organogenesis, Inc., and Novartis
Pharmaceuticals Corp.
Treatment of venous leg ulcers; treatment of
diabetic foot ulcers
May 1998
Jun 2000
Aranesp
(darbepoetin alfa)
Amgen
Anemia associated with chronic renal failure;
chemotherapy-induced anemia in patients with
non-myeloid malignancies
Sep 2001
Jul 2002
Argatroban
Texas Biotechnology Corp. and
GlaxoSmithKline
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
Jun 2000
Apr 2002
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
Allergan, Inc.
Oct 2002
Biotechnology Industry Organization N Guide to Biotechnology
Topical treatment of facial fine wrinkling, mottled
hypo- and hyperpigmentation, and benign facial
lentigines
Jul 2006
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Avastin
(bevacizumab)
Genentech
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
Feb 2004
Jun 2006
Oct 2006
AVINZA
(extended-release
morphine sulfate)
Ligand Pharmaceuticals and Elan
Corp., plc
Once-daily treatment of moderate to severe pain
in patients who require continuous opioid therapy
for an extended period of time
Mar 2002
AVONEX
(interferon beta 1-alpha)
Biogen Idec
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
May 1996
Feb 2003
BeneFix
(coagulation factor IX)
Wyeth
Treatment of hemophilia B
Feb 1997
Betaseron
(interferon beta 1-B)
Berlex Laboratories (subsidiary
of Schering-Plough) and Chiron
Corp.
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
BEXXAR
(tositumomab and
tositumomab I-131)
Corixa Corp. and
GlaxoSmithKline
CD20-positive, follicular non-Hodgkins lymphoma
refractory to rituximab; CD20-positive relapsed
or refractory, low grade, follicular or transformed
non-Hodgkins lymphoma
Jun 2003
Jan 2005
BiDil
(isosorbide dinitrate and
hydralazine)
NitroMed Inc.
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
Jun 2005
Bioclate
(antihemophilic factor)
Aventis Behring
Treatment of hemophilia A for the prevention and
control of hemorrhagic episodes; perioperative
management of patients with hemophilia A
Dec 1993
BioTropin
(human growth hormone)
Biotech General
Treatment of human growth hormone deficiency
in children
May 1995
Boostrix
(tetanus toxoid, reduced
diphtheria toxoid and
acellular pertussis vaccine,
absorbed)
GlaxoSmithKline
Booster immunization against tetanus, diphtheria
and pertussis as a single dose in adolescents 10-18
years of age
May 2005
BOTOX COSMETIC
(botulinum toxin type A)
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
Dec 1989
Dec 2000
Apr 2002
Jul 2004
Treatment for Type II diabetes
Apr 2005
Byetta
Amylin Pharmaceuticals
(exenatide injection, first-inclass incretin mimetic)
Guide to Biotechnology N Biotechnology Industry Organization
47
48
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Campath
(alemtuzumab)
Millennium Pharmaceuticals, Inc.,
and Berlex Laboratories, Inc.
B-cell chronic lymphocytic leukemia in patients
who have been treated with alkylating agents and
who have failed fludarabine therapy
May 2001
Oct 2004
Captique
Injectable Gel
(non-animal stabilized
hyaluronic acid)
Genzyme Corp. and Inamed
Corp.
Facial wrinkle correction
Nov 2004
Carticel
(autologous cultured
chondrocytes)
Genzyme
Reconstruction of damaged knee cartilage
Aug 1997
CEA-Scan
(acritumomab; technetium99 labeled)
Immunomedics, Inc.
Imaging agent for metastatic colorectal cancer
Jun 1996
Ceredase
(alglucerase; modified
form of betaglucocerebrosidase)
Genzyme
Treatment of type 1 Gauchers disease
Apr 1991
Cerezyme
(imiglucerase; recombinant
form of betaglucocerebrosidase)
Genzyme
Treatment of type 1 Gauchers disease
May 1994
Cialis
(tadalafil)
Lilly ICOS LLC (joint venture of
Eli Lilly and Co. and ICOS Corp.)
Erectile dysfunction
Nov 2003
CLOLAR
(clofarabine)
Genzyme
Refractory or relapsed acute lymphoblastic
leukemia in children
Dec 2004
CNJ-016,Vaccinia Globulin
Intravenous
(purified antibody for
specific vaccinia)
Cangene Corp.
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
Codeprex
Extended-Release
Suspension CIII
(codeine polistirex/
chlorpheniramine
polistirex)
UCB
Cough relief; 12-hour dosing
Jun 2004
Comvax
(Haemophilus B conjugate
[meningococcal
conjugate] and hepatitis B
[recombinant] vaccine)
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
CosmoDerm/
CosmoPlast
(dermal fillers containing
human-based collagen)
Advanced Tissue Sciences Inc. and Wrinkles
Inamed Corp.
Biotechnology Industry Organization N Guide to Biotechnology
Mar 2003
PRODUCT
COMPANY
APPLICATION (USE)
APPROVAL
DATE (FDA)
CroFab
(crotalidae polyvalent
immune Fab, ovine)
Protherics, plc, and Savage
Laboratories (unit of Altana, Inc.)
Rattlesnake antivenom
Oct 2000
Cubicin
(daptomycin)
Cubist Pharmaceuticals Inc.
Complicated skin and skin structure infections
caused by susceptible strains of bacteria; S. aureus
bacteremia and endocarditis
Sep 2003
May 2006
CytoGam
(CMV immune
globulin IV)
MedImmune, Inc.
Prevention of cytomegalovirus (CMV) in kidney
transplant patients; prevention of CMV disease
associated with kidney, lung, liver, pancreas and
heart transplants
Dec 1998
Apr 1990
DACOGEN
(decitabine for injection)
MGI Pharma and SuperGen
Myelodysplastic syndromes
May 2006
DaunoXome
(liposomal form of the
chemotherapeutic agent
daunorubicin)
Gilead Sciences
First-line treatment for HIV-related Kaposis
sarcoma
Apr 1996
Depocyt
(sustained-release
formulation of cytarabine)
SkyePharma
and Enzon
Treatment of lymphomatous meningitis
Apr 1999
DepoDur
(morphine sulfate;
extended-release liposome
injection)
Endo Pharmaceuticals, Inc., and
SkyePharma plc
Pain following major surgery
May 2004
Dermagraft
(human-based, tissueengineered living dermal
substitute)
Advanced Tissue Sciences, Inc.,
and Smith & Nephew, plc
Diabetic foot ulcers
Sep 2001
DigiFab
(digoxin immune fab
[ovine])
Protherics, plc
Digoxin toxicity
Sep 2001
Doxil
Alza (subsidiary of
(liposomal formulation of
Johnson & Johnson)
doxorubicin hydrochloride)
Second-line therapy for Kaposis sarcoma in AIDS
patients; metastatic carcinoma of the ovary in
patients with disease that is refractory to both
paclitaxel- and platinum-based chemotherapy
regimens
Nov 1995
Jun 1999
ELAPRASE
(idursulfase)
Shire plc
Hunter syndrome (mucopolysaccharidosis II)
Jul 2006
Elestat
(epinastine)
Inspire Pharmaceuticals Inc.,
Allergan Inc. and Boehringer
Ingelheim
Prevention of itching associated with allergic
conjunctivitis
Oct 2003
Eligard
(slow-release formulation
of leuprolide acetate)
Atrix Laboratories and SanofiSynthelabo
Advanced prostate cancer; six-month sustained
release formulation
Jan 2002
(additional formulation
cleared in Jul 2002)
Dec 2004
Elitek
(rasburicase)
Sanofi-Synthelabo
Management of plasma uric acid levels in pediatric
chemotherapy patients
Jul 2002
Emtriva
(emtricitabine)
Gilead Sciences
HIV infection in adults
Jul 2003
Guide to Biotechnology N Biotechnology Industry Organization
49
50
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Enbrel
(etanercept)
Amgen and Wyeth
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
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)
GlaxoSmithKline
Hepatitis B vaccine; adults with chronic hepatitis C
infection
Sep 1989
Aug 1998
Epogen
(epoietin alfa)
Amgen
Treatment of anemia associated with chronic renal
failure and anemia in Retrovir-treated HIV-infected
patients; pediatric use
Jun 1989
Jul 1999
Erbitux
(cetuximab)
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
Feb 2004
Mar 2006
ESTRASORB
(estradiol)
Novavax Inc. and King
Pharmaceuticals
Moderate to severe vasomotor symptoms in
menopausal women
Oct 2003
Evoclin Foam
(formerly Actiza)
(clindamycin)
Connetics Corp.
Acne vulgaris
Oct 2004
Exjade
Novartis AG
(deferasirox, once-daily oral
iron chelator)
Chronic iron overload due to blood transfusions in Nov 2005
adults and children age 2 or older
Fabrazyme
(agalsidase beta)
Genzyme
Fabrys disease
Apr 2003
FACTIVE
(gemifloxacin)
Oscient Pharmaceuticals
Mild to moderate community-acquired pneumonia
and acute bacterial exacerbation of chronic
bronchitis; community-acquired pneumonia due to
multidrug-resistant Streptococcus pneumoniae
Apr 2003
Jul 2003
FENTORA
(fentanyl buccal tablet)
Cephalon
Management of breakthrough pain in cancer
patients already receiving opioid therapy
Sep 2006
Fertinex
(urofollitropin)
Serono S.A.
Treatment of female infertility to stimulate ovulation
in women with ovulatory disorders and in women
undergoing assisted reproductive technologies
Aug 1996
FluMist
(influenza virus vaccine;
live, intranasal)
MedImmune Inc.
Prevention of flu
Jun 2003
Biotechnology Industry Organization N Guide to Biotechnology
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Fluarix
(influenza virus vaccine)
GlaxoSmithKline Biologicals
For active immunization of adults 18 years and
older against influenza disease caused by influenza
virus types A and B
Aug 2005
Focalin
(dexmethylphenidate
hydrochloride)
Celgene Corp. and Novartis
Pharmaceuticals Corp.
Attention deficit hyperactivity disorder
Nov 2001
Follistim
(follitropin beta)
Organon (unit of Akzo Nobel)
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
Sep 1997
Feb 2002
FortaFlex
(bioengineered collagen
matrix)
Organogenesis, Inc., and Biomet,
Inc.
Rotator cuff repair
Apr 2002
FORTEO
(teriparatide)
Eli Lilly and Company
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
FORTICALNasalSpray Unigene Laboratories Inc.
(calcitonin salmon)
FOSRENOL
Shire Pharmaceuticals Group
(lanthanum carbonate)
Nasal Spray treats postmenopausal osteoporosis in Aug 2005
women with low bone mass
Reduction of blood phosphate levels in patients
undergoing kidney dialysis
Oct 2004
Frova
(frovatriptan succinate)
Vernalis Group, plc, and Elan
Corp., plc
Migraine
Nov 2001
FUZEON
(enfuvirtide)
Trimeris Inc. and Roche
HIV-1 infection; product granted traditional
approval
Mar 2003
Oct 2004
GAMMAGARD
(Immune Globulin
Intravenous [Human]
Solution)
Baxter HealthCare Corp.
Treatment of primary immunodeficiency disorders
associated with defects in humoral immunity
May 2005
Ganite
(gallium nitrate)
Genta Inc.
Cancer-related hypercalcemia resistant to
hydration
Sep 2003
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 peridontal bone defects and
associated gingival recession
Nov 2005
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
Aug 1995
Nov 1997
Jul 2001
Geref
(semorelin acetate)
Treatment of growth hormone deficiency in
children with growth failure
Oct 1997
Serono S.A.
Guide to Biotechnology N Biotechnology Industry Organization
51
52
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Gleevec
(imatinib mesylate)
Novartis Pharmaceuticals Corp.
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
Gliadel Wafer
(polifeprosan 20 with
carmustine implant)
Guilford Pharmaceuticals, Inc.
Newly diagnosed patients with high-grade
malignant glioma as an adjunct to surgery and
radiation
Feb 2003
GlucaGen
(glucagon)
Novo Nordisk
Treatment of severe hypoglycemic reactions in
insulin-treated diabetics, and for diagnostic use
Jun 1998
Gonal-F
(follitropin alfa)
Serono S.A.
Treatment of infertility in women not due to
primary ovarian failure; treatment of infertility in
men and women
Sep 1998
Jun 2000
Hectorol Capsules
(doxercalciferol)
Bone Care International, Inc.
Secondary hyperparathyroidism patients
undergoing chronic renal dialysis; additional
indication of secondary hyperparathyroidism that
develops in earlier stages of chronic kidney disease
prior to dialysis
Jun 1999
Apr 2004
Helixate
(antihemophilic factor)
Aventis Behring
Factor VIII for treatment of hemophilia A; secondgeneration factor VIII formulated with sucrose for
treatment of hemophilia A
Feb 1994
Jun 2000
Hepsera
(adefovir dipivoxil)
Gilead Sciences, Inc.
Chronic hepatitis B
Sep 2002
Herceptin
(trastuzumab)
Genentech, Inc.
Treatment of patients with metastatic breast
cancer whose tumors overexpress the HER2
protein
Sep 1998
Hextend
(hetastarch)
BioTime, Inc.
Plasma volume expander for treatment of
hypovolemia during surgery
Mar 1999
Humalog
(insulin)
Eli Lilly and Company
Treatment of diabetes
Jun 1996
Humate-P
(antihemophilic factor/
von Willebrand factor
complexhuman)
Aventis Behring
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
Apr 1999
Humatrope
(somatotropin)
Eli Lilly and Company
Treatment of growth hormone deficiency in
children; somatotropin deficiency syndrome in
adults; long-term treatment of children of short
stature (unknown cause)
Aug 1996
Mar 1997
Jul 2003
HUMIRA
(adalimumab)
Cambridge Antibody Technology
and Abbott Laboratories
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
Dec 2002
Jul 2004
Oct 2005
Jul 2006
Biotechnology Industry Organization N Guide to Biotechnology
PRODUCT
COMPANY
APPLICATION (USE)
APPROVAL
DATE (FDA)
Humulin
(human insulin)
Eli Lilly and Company
Treatment of diabetes
Oct 1982
Hylaform
(Hylan-B gel)
Genzyme and Inamed
Correction of moderate to severe facial wrinkles
and folds
Apr 2004
Hylaform Plus
(Hylan-B gel; large-particle
size hyaluronic acid-based
dermal filler)
Genzyme and Inamed
Correction of moderate to severe facial wrinkles
and folds
Oct 2004
Hylenex
(recombinant human
hyaluronidase)
Halozyme Therapeutics Inc.
Adjuvant agent to increase the absorption and
dispersion of other injected drugs
Dec 2005
Imagent
(perflexane lipid
microspheres)
Alliance Pharmaceutical Corp.,
Imaging agent for use in echocardiography
Cardinal Health, Inc., and InChord
Communications, Inc.
Jun 2002
Increlex
(mecasermin)
Tercica Inc. and Genentech Inc.
Long-term treatment for growth failure in children
with severe primary IGF-1 deficiency
Aug 2005
Infergen
(interferon alfacon-1)
InterMune Pharmaceuticals, Inc.,
and Amgen
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
Oct 1997
Dec 1999
INFUSE
Bone Graft/LT-CAGE
(device utilizing
recombinant human bone
morphogenetic protein
[rhBMP-2])
Wyeth and Medtronic Sofamor
Danek
For use in spinal fusion surgery to treat certain
types of spinal degenerative disease; acute, open
tibia shaft fractures in adults
Jul 2002
Apr 2004
INTEGRA
Dermal Regeneration
Template (bilayer
membrane system for skin
replacement)
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
Integrilin
(eptifibatide for injection)
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
May 1998
Jun 2001
Intron A
(alpha-interferon)
Schering-Plough Corp.
Treatment of hairy cell leukemia; genital warts;
AIDS-related Kaposis 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
Jun 1986
Jun 1988
Nov 1988
Feb 1991
Jul 1992
Dec 1995
Mar 1997
Nov 1997
Aug 1998
IPLEX
(mecasermin rinfabate
[rDNA origin])
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
Dec 2005
ISTOLOL
(timolol)
ISTA Pharmaceuticals and Senju
Pharmaceutical Co.
Glaucoma
Jun 2004
53
Guide to Biotechnology N Biotechnology Industry Organization
54
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Kepivance
(palifermin)
Amgen
Severe oral mucositis in cancer patients with
hematologic blood cancers undergoing high-dose
chemotherapy, with or without radiation, followed
by a bone marrow transplant
Dec 2004
Kineret
(anakinra)
Amgen
Moderately to severely active rheumatoid arthritis
in adult patients who have failed disease-modifying
antirheumatic drugs
Nov 2001
KogenateFS
(antihemophilic factor)
Bayer Corp.
Factor VIII for treatment of hemophilia A; secondgeneration factor VIII formulated with sucrose for
treatment of hemophilia A
Sep 1989
Jun 2000
Lantus
(insulin glargine)
Sanofi Aventis
Biosynthetic basal insulin for adult and pediatric
patients with type 2 diabetes
Apr 2000
Leukine
(granulocyte macrophage
colony-stimulating factor)/
Leukine Liquid
Berlex Laboratories
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
Mar 1991
Sep 1995
Nov 1995
Dec 1995
Nov 1996
Leustatin
(cladribine or 2-CDA)
Ortho Biotech, Inc. (subsidiary of
Johnson & Johnson)
First-line treatment of hairy cell leukemia
Mar 1993
Levemir
(insulin detemir [rDNA
origin] injection)
Novo Nordisk
Treatment of diabetes mellitus (Type I and Type II);
for use in children
Jun 2005
Oct 2005
Lexiva
(fosamprenavir)
Vertex Pharmaceuticals Inc. and
GlaxoSmithKline
HIV infection
Oct 2003
LUCENTIS
(ranibizumab injection)
Genentech
Wet age-related macular degeneration
Jun 2006
LUNESTA
(formerly Estorra)
(eszopiclone)
Sepracor, Inc.
Insomnia
Dec 2004
Luveris
(lutropin alfa for injection)
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
Oct 2004
Luxiq
(betamethasone)
Connetics Corp.
Relief of inflammatory and pruritic manifestations
of corticosteroid-responsive dermatoses of the
scalp
Feb 1999
LYMErix
(recombinant OspA
lipoprotein)
SmithKline Beecham Biologicals
(subsidiary of GlaxoSmithKline)
Prevention of Lyme disease
Dec 1998
Macugen
(pegaptanib sodium
injection)
Eyetech Pharmaceuticals, Inc. and
Pfizer
Neovascular (wet) age-related macular
degeneration
Dec 2004
Biotechnology Industry Organization N Guide to Biotechnology
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Menactra
(Meningococcal
Polysaccharide
[Serogroups A, C,Y and
W-135] Diphtheria Toxoid
Conjugate Vaccine)
Sanofi Pasteur
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.
Jan 2005
Metadate CD
(bi-phasic release
formulation of
methylphenidate)
UCB
Attention deficit hyperactivity disorder
Apr 2001
Metvixia
(developed under trade
name Metvix)
(methyl aminoleyulinate)
PhotoCure ASA and Galderma
SA
Photodynamic treatment of actinic keratosis
Jul 2004
Mitozytrex
(MitoExtra proprietary
version of mitomycin)
SuperGen, Inc.
Disseminated adenocarcinoma of the stomach or
pancreas
Nov 2002
Mylotarg
(gemtuzumab ozogamicin)
UCB and Wyeth
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
May 2000
Myobloc
(botulinum toxin
type B)
Elan Corp.
Treatment of cervical dystonia
Dec 2000
Myozyme
(alglucosidase alfa)
Genzyme
Pompe disease
Apr 2006
Naglazyme
(galsulfase)
BioMarin Pharmaceuticals
Enzyme replacement therapy for
mucopolysaccharidosis VI (MPS VI)
May 2005
Nabi-HB
(hepatitis B immune
globulinhuman)
Nabi Pharmaceuticals
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
Mar 1999
NAMENDA
(memantine)
Neurobiological Technologies Inc.
and Forest Laboratories
Moderate to severe Alzheimers disease
Oct 2003
Natrecor
(nesiritide)
Scios (unit of Johnson & Johnson)
Acutely decompensated congestive heart failure
with shortness of breath at rest or with minimal
activity
Aug 2001
Neulasta
(pegfilgrastim)
Amgen
Reduction of incidence of infection as manifested
by febrile neutropenia in non-myeloid cancer
patients receiving certain chemotherapies
Jan 2002
Neumega
(oprelvekin)
Wyeth
Prevention of severe chemotherapy-induced
thrombocytopenia in cancer patients
Nov 1997
Neupogen
(filgrastim)
Amgen
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
Feb 1991
Jun 1994
Dec 1994
Dec 1995
Apr 1998
Guide to Biotechnology N Biotechnology Industry Organization
55
56
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
NeutroSpec
(formerly LeuTech)
(technetium [99m Tc]
fanolesomab)
Palatin Technologies and
Mallinckrodt Imaging (Tyco
Healthcare)
Diagnosis of appendicitis in patients with equivocal
signs
Jul 2004
Nexavar
(sorafenib, tablets)
Onyx Pharmaceuticals Inc. and
Bayer Pharmaceuticals Inc.
For patients with advanced renal cell carcinoma
Dec 2005
Norditropin
(somatropin)
Novo Nordisk
Treatment of growth hormone deficiency in
children
May 1995
Novantrone
(mitoxantrone)
Amgen
Treatment of acute nonlymphocytic leukemia;
hormone refractory prostate cancer; secondary
progressive multiple sclerosis
Dec 1987
Nov 1996
Feb 2000
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)
Novo Nordisk
Treatment of diabetes
Oct 1982
Jun 1991
(Novolin L, R and
70/30)
Jul 1991
(Novolin N)
NovoLog
(insulin aspart)
Novo Nordisk
Insulin analog for adults with diabetes mellitus; for
pump therapy in diabetes
May 2000
Dec 2001
NovoSeven
(coagulation factor VIIa)
Novo Nordisk
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
Mar 1999
Jul 2005
Nuflexxa
(1% sodium hyaluronate)
Savient Pharmaceuticals, Inc.
Pain associated with osteoarthritis of the knee in
patients who have failed to respond adequately
to conservative non-pharmacologic therapy and
simple analgesics
Dec 2004
Nutropin/
Nutropin AQ
(somatropin)
Genentech, Inc.
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
Nov 1993
Jan 1994
Jan 1996
Dec 1996
Dec 1999
Jul 2005
Nutropin Depot
(sustained-release
formulation of somatropin)
Alkermes, Inc., and Genentech,
Inc.
Growth hormone deficiency
Dec 1999
OLUX Foam
(clobetasol proprionate)
Connetics Corp.
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
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Oncaspar
(PEG-L-asparaginase)
Enzon, Inc., and Sanofi Aventis
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
Feb 1994
Jul 2006
Ontak
(denileukin diftitox)
Ligand Pharmaceuticals, Inc.
Treatment of patients with persistent or recurrent
cutaneous T-cell lymphoma whose malignant cells
express the CD25 component of the interleukin-2
receptor
Feb 1999
Oracea
(capsule formulation
of doxycycline)
CollaGenex Pharmaceuticals
Rosacea
May 2006
Orapred ODT
(prednisolone sodium
phosphate tablets)
BioMarin Pharmaceutical and
Alliant Pharmaceuticals
Inflammation and asthma indications
Aug 2006
OrCel
(composite cultured skin;
bi-layered cellular matrix)
Ortec International, Inc.
For patients with recessive dystrophic epidemolysis Feb 2001
bullosa undergoing hand reconstruction surgery;
Aug 2001
treatment of donor site wounds in burn victims
Orencia
(abatacept, fully human
soluable fusion protein)
Bristol-Myers Squibb Company
Reducing signs and symptoms of rheumatoid
arthritis
Dec 2005
Orfadin
(nitisinone)
Swedish Orphan International AB
and Rare Disease Therapeutics,
Inc.
Hereditary tyrosinemia type 1
Jan 2002
Orthoclone OKT3
(muromomab-CD3)
Ortho Biotech, Inc.
Reversal of acute kidney transplant rejection
(subsidiary of Johnson & Johnson)
Jun 1986
Orthovisc
(high-molecular-weight
hyaluronan)
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
Feb 2004
Ovidrel
(human chorionic
gonadotropin)
Serono S.A.
Treatment of infertility in women
Sep 2000
Pacis
(live attenuated Bacillus
Calmette-Guerin)
Shire BioChem, Inc., (subsidiary
of Shire Pharmaceuticals Group,
plc) and UroCor, Inc.
Bladder cancer immunotherapy
Mar 2000
Panretin
(alitretinoin)
Ligand Pharmaceuticals, Inc.
The topical treatment of cutaneous lesions of
patients with AIDS-related Kaposis sarcoma
Feb 1999
Pediarix
(diphtheria and tetanus
toxoids and acellular
pertussis adsorbed,
hepatitis B [recombinant]
and inactivated polio-virus
vaccine combined)
GlaxoSmithKline
Prevention of diphtheria, tetanus, pertussis,
hepatitis B and polio
Dec 2002
Pegasys
(peginterferon alfa-2a)
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
57
58
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
PEG-Intron
(pegylated version of
interferon alfa-2b)
Enzon, Inc., and Schering-Plough
Corp.
Monotherapy for chronic hepatitis C; combination
therapy with Rebetol for treatment of hepatitis C
in patients with compensated liver disease
PHOTOFRIN PDT
(porfimer sodium)
Ligand Pharmaceuticals, Inc.
Palliative treatment of totally and partially
Nov 1995
obstructing cancers of esophagus; ablation of high- Aug 2003
grade dysplasia in Barretts esophagus patients who
do not undergo esophagectomy
Plenaxis
(abarelix)
Praecis Pharmaceuticals Inc.
Palliative treatment of men with advanced
symptomatic prostate cancer under certain
conditions
Nov 2003
Prandin
(repaglinide)
Novo Nordisk
Type 2 diabetes
Dec 1997
Prevnar
(pneumococcal 7valent conjugate vaccine
[diphtheria CRM-197
protein])
Wyeth
Vaccine for infants and toddlers, 1215 months,
to prevent invasive pneumococcal disease;
immunization of infants and toddlers against otitis
media caused by vaccine serotypes
Feb 2000
Oct 2002
PRIALT
(ziconotide intrathecal
infusion)
Elan Corp. plc
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
Dec 2004
Procrit
(epoietin alfa)
Ortho Biotech, Inc. (subsidiary of
Johnson & Johnson)
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
Dec 1990
Apr 1993
Dec 1996
Proleukin, IL-2
(aldesleukin)
Chiron Corp.
Treatment of kidney carcinoma; treatment of
metastatic melanoma
May 1992
Jan 1998
ProQuad
(measles, mumps, rubella
and varicella virus vaccine
live)
Merck & Co. Inc.
Measles, mumps, rubella, and varicella in children 12 Sep 2005
months to 12 years
ProstaScint
(indium In 111 capromab
pendetide)
Cytogen Corp.
Imaging agent for newly diagnosed patients with
biopsy-proven prostate cancer
Oct 1996
Protropin
(somatrem)
Genentech, Inc.
Treatment of growth hormone deficiency in
children
Oct 1985
PROVIGIL
Tablets (modafinil)
Cephalon, Inc.
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
Dec 1998
Jan 2004
Pulmozyme
(dornase alfa)
Genentech, Inc.
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
Dec 1993
Dec 1996
Mar 1998
Quadramet
(samarium SM-153
lexidronam)
Berlex Laboratories (subsidiary
of Schering-Plough) and Cytogen
Corp.
Pain relief in patients with osteoblastic metastatic
bone lesions that enhance on radionuclide bone
scan
Mar 1997
RAPTIVA
(efalizumab)
Xoma Ltd. and Genentech
Chronic moderate to severe psoriasis
Oct 2003
Biotechnology Industry Organization N Guide to Biotechnology
Jan 2001
Aug 2001
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Rebetron
(combination of ribavirin
and alpha interferon)
Schering-Plough Corp.
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
Jun 1998
Dec 1998
Rebif
(interferon beta 1-a)
Serono S.A., and
Pfizer, Inc.
Relapsing forms of multiple sclerosis
Mar 2002
Recombinate rAHF/
(antihemophilic factor)
Baxter Healthcare Corp.
Blood-clotting factor VIII for the treatment of
hemophilia A
Feb 1992
Recombivax HB/
Recombivax HB
Dialysis Formulation
(hepatitis B vaccine)
Merck & Company, Inc.
Vaccination against hepatitis B; hepatitis B vaccine
Jul 1986
for adolescents and high-risk infants; adults; dialysis; Jan 1987
pediatrics
Jan 1989
Jun 1993
ReFacto
(antihemophilic factor)
Wyeth
Control and prevention of hemophilia A and short- Mar 2000
term prophylaxis to reduce bleeding episodes
Refludan
(lepirudin)
Berlex Laboratories (subsidiary
of Schering-Plough)
For anticoagulation in patients with heparin-induced
thrombocytopenia and associated thromboembolic
disease in order to prevent further thromboembolic
complications
Mar 1998
Regranex Gel
(gel becaplermin)
Ortho-McNeil (subsidiary of
Johnson & Johnson) and Chiron
Corp.
Platelet-derived growth factor treatment of
diabetic foot ulcers
Dec 1997
Remicade
(infliximab)
Centocor, Inc. (subsidiary of
Johnson & Johnson)
Short-term management of moderately to severely
active Crohns 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 Crohns 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 Crohns 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
Crohns disease; inhibiting progression of structural
damage and improving physical function in patients
with psoriatic arthritis; chronic severe plaque
psoriasis in adults
Aug 1998
Nov 1999
Feb 2002
Jun 2002
Apr 2003
Sep 2004
May 2005
Sep 2005
May 2006
Aug 2006
Sep 2006
Remodulin
(treprostinil sodium)
United Therapeutics Corp.
Treatment of pulmonary arterial hypertension
in patients with NYHA Class II-IV symptoms to
diminish symptoms associated with exercise
May 2002
Guide to Biotechnology N Biotechnology Industry Organization
59
60
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Renagel Capsules
(sevelamer hydrochloride)
Genzyme
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 products phosphorous and calciumphosphorous control are consistent with the
National Kidney Foundations aggressive guidelines
Nov 1998
Jul 2000
Mar 2004
ReoPro
(abciximab)
Centocor, Inc. (subsidiary of
Johnson & Johnson) and Eli Lilly
and Company
Reduction of acute blood clotrelated
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
Dec 1994
Dec 1997
RespiGam
(immune globulin enriched
in antibodies against
respiratory syncytial virus
[RSV])
MedImmune, Inc.
Prevention of respiratory syncytial virus in infants
under 2 with bronchopulmonary dysplasia or
history of prematurity
Jan 1996
RESTASIS
(cyclosporine ophthalmic
emulsion)
Allergan, Inc.
Chronic dry eye disease in patients whose tear
production is presumed to be suppressed due to
ocular inflammation
Dec 2002
Retavase
(reteplase)
Centocor, Inc. (subsidiary of
Johnson & Johnson)
Management of acute myocardial infarction in
adults
Oct 1996
Revlimid
(lenalidomide)
Celgene Corp.
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
RISPERDAL
CONSTA
(long-acting formulation of
risperidone)
Alkermes Inc. and Johnson &
Johnson
Schizophrenia
Oct 2003
Rituxan
(rituximab)
Biogen Idec and Genentech, Inc.
Treatment of relapsed or refractory, lowgrade or follicular, CD20-positive B-cell nonHodgkins 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-Hodgkins
lymphoma in combination with anthracyclinebased chemotherapy regimens; first-line treatment
of previously untreated patients with follicular
CD20+, B-cell non-Hodgkins 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
COMPANY
APPLICATION (USE)
APPROVAL
DATE (FDA)
Roferon-A
(interferon alfa-2a)
Hoffmann-La Roche, Inc.
Treatment of hairy cell leukemia; AIDS-related
Kaposis sarcoma; chronic phase Philadelphia
chromosomepositive chronic myelogenous
leukemia; hepatitis C
Jun 1986
Nov 1988
Oct 1995
Nov 1995
Saizen
(human growth hormone)
Serono S.A.
Treatment of growth hormone deficiency in children;
replacement of endogenous growth hormone in
adults with growth hormone deficiency
Oct 1996
Aug 2004
SANCTURA
(trospium chloride)
Indevus Pharmaceuticals, Inc., and
Odyssey Pharmaceuticals, Inc.,
(subsidiary of PLIVA)
Overactive bladder with symptoms of urge urinary
incontinence, urgency and urinary frequency
May 2004
Sarafem
(fluoxetine hydrochloride)
Indevus Pharmaceuticals, Inc., and
Eli Lilly and Company
Treatment of premenstrual dysphoric disorder
Jul 2000
SecreFlo
Repligen Corp.
(synthetic porcine secretin)
Pancreatic assessment; aid in location
and cannulation of pancreatic ducts in
patients undergoing endoscopic retrograde
cholangiopancreatography
Apr 2002
Nov 2002
Sensipar
(cinacalcet HC1)
NPS Pharmaceuticals and Amgen,
Inc.
Secondary hyperthyroidism in chronic kidney
disease patients on dialysis; elevated calcium levels
in patients with parathyroid carcinoma
Mar 2004
Simulect
(basiliximab)
Novartis Pharmaceutical Corp.
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
May 1998
Mar 2001
SOMAVERT
(pegvisomant)
Nektar Therapeutics and Pfizer
Acromegaly
Mar 2003
Symlin
(pramlintide acetate
injection)
Amylin Pharmaceuticals Inc.
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
Mar 2005
SYNAGIS
(palivizumab)
MedImmune, Inc.
FDA cleared addition of new safety and efficacy data Jun 1998
supporting the drugs use in young children with
hemodynamically significant congenital heart disease
Tamiflu
(oseltamivir phosphate)
Gilead Sciences, Inc., and
Hoffmann-La Roche, Inc.
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
Oct 1999
Nov 2000
Dec 2000
Tarceva
(erlotinib)
OSI Pharmaceuticals, Inc. and
Genentech
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
Nov 2004
Nov 2005
Targretin
(bexarotene)/
Targretin Gel
(bexarotene)
Ligand Pharmaceuticals, Inc.
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
Dec 1999
Jun 2000
(Targretin Gel
Formulation)
Improving luminal diameter in native coronary
arteries for treatment of de novo lesions
Mar 2004
Taxus Express2
Angiotech Pharmaceuticals, Inc.,
(paclitaxel-eluting coronary and Boston Scientific Corp.
stent)
Guide to Biotechnology N Biotechnology Industry Organization
61
62
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
Thymoglobulin
(antithymocyte globulin;
rabbit)
Genzyme
Treatment of acute rejection of kidney transplant
in conjunction with immunosuppression
Dec 1998
Thyrogen
(thyrotropin alfa)
Genzyme
Adjunctive diagnostic tool for serum thyroglobulin
(Tg) testing with or without radioiodine imaging in
the follow-up of patients with thyroid cancer
Dec 1998
TNKase
(tenecteplase)
Genentech, Inc.
Treatment of acute myocardial infarction
Jun 2000
Tracleer
(bosentan)
Actelion Ltd.
Pulmonary arterial hypertension with WHO Class
III or IV symptoms
Nov 2001
Trisenox
(arsenic trioxide)
Cell Therapeutics, Inc.
Treatment of acute promyelocytic leukemia
Sep 2000
Truvada
Gilead Sciences
(emtricitabine and tenofovir
disoproxil fumarate)
HIV (as part of combination therapy)
Aug 2004
Twinrix
(hepatitis A inactivated and
hepatitis B [recombinant]
vaccine)
SmithKline Beecham Biologicals
(unit of GlaxoSmithKline)
Immunization against hepatitis A and B viruses
May 2001
Tygacil
(tigecycline injection)
Wyeth
Treatment of complicated skin structure infections
and complicated intra-abdominal infections
Dec 2005
TYSABRI
(formerly ANTEGREN)
(natalizumab)
Biogen Idec and Elan Corp.
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
Nov 2004
Jun 2006
Vectibix
(panitumumab)
Amgen
Metastatic colorectal cancer
Sep 2006
VELCADE
(bortezomib)
Millennium Pharmaceuticals Inc.
Relapsed and refractory multiple myeloma;
treatment of multiple myeloma in patients who
have received at least one prior therapy
May 2003
Mar 2005
Velosulin BR
(insulin; buffered
formulation)
Novo Nordisk
Diabetes
Jul 1999
Venoglobulin-S
(human immune globulin
intravenous 5% and 10%
solutions)
Alpha Therapeutic Corp.
Treatment of primary immunodeficiencies;
idiopathic thrombocytopenic purpura; Kawasaki
disease
Nov 1991
Jan 1995
Ventavis Inhalation
Solution
(iloprost)
CoTherix Inc. and Schering AG
Pulmonary arterial hypertension in patients with
NYHA Class III or IV symptoms
Dec 2004
Vidaza
(azacitidine)
Pharmion Corp.
Myelodysplastic syndromes (all five subtypes)
May 2004
Biotechnology Industry Organization N Guide to Biotechnology
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
VIGIV,Vaccinia Immune
Globulin Intravenous
(intravenous immune
globulin)
DynPort Vaccine
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.
Viracept
(nelfinavir)
Agouron Pharmceuticals Inc.
(subsidiary of Pfizer)
HIV
Mar 1997
Viread
(tenofovir disoproxil
fumarate)
Gilead Sciences
For use in combination with other antiretroviral
agents for treatment of HIV-1 infection
Oct 2001
VISTIDE
(cidofovir injection)
Gilead Sciences Inc.
Treatment of cytomegalovirus retinitis in AIDS
patients
Jun 1996
Visudyne
(verteporfin for injection)
QLT, Inc., and CIBA Vision
Treatment of wet form of age-related macular
degeneration; predominantly classic subfoveal
choroidal neovascularization due to pathologic
myopia (severe nearsightedness)
Apr 2000
Aug 2001
Vitrase
ISTA Pharmaceuticals Ltd.
(hyaluronidase for injection;
lyophilized, ovine)
Spreading agent to facilitate dispersion and
absorption of other drugs; FDA approved singleuse vial
May 2004
Dec 2004
Vitravene
(fomivirsen)
Treatment of cytomegalovirus retinitis in patients
with AIDS
Aug 1998
Vivitrol
Alkermes and Cephalon
(naltrexone for extended
release injectible suspension)
Monthly injection to treat alcohol dependence
Apr 2006
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
May 2000
Wellferon
(interferon alfa-n1,
lymphoblastoid)
GlaxoSmithKline
Treatment of chronic hepatitis C in patients 18 years
of age or older without decompensated liver disease
Mar 1999
WinRho SDF
(Rho[D] immune globulin)
Nabi Biopharmaceuticals
Prevention of Rh isoimmunization in pregnant
women and the treatment of thrombocytopenic
purpura
Mar 1995
XIFAXAN
(rifaximin)
Salix Pharmaceuticals Ltd.
Travelers diarrhea caused by noninvasive strains of
E. coli in patients 12 years of age and older
May 2004
Xigris
(drotrecogin alfa)
Eli Lilly and Company
Severe, life-threatening sepsis
Nov 2001
Xolair
(omalizumab)
Genentech, Tanox Inc. and
Novartis Pharmaceuticals
Moderate to severe persistent asthma in adults
and adolescents
Jun 2003
Xyrem
(sodium oxybate)
Orphan Medical, Inc.
Cataplexy associated with narcolepsy
Jul 2002
Zavesca
(miglustat)
UCB and Actelion Ltd.
Mild to moderate Type 1 Gauchers disease in
patients for whom enzyme replacement therapy is
not an option
Aug 2003
Isis Pharmaceuticals, Inc., and
CIBA Vision
Guide to Biotechnology N Biotechnology Industry Organization
63
64
APPROVAL
DATE (FDA)
PRODUCT
COMPANY
APPLICATION (USE)
ZEGERID
(omeprazole powder for
oral suspension)
Santarus
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
Zenapax
(daclizumab)
Hoffmann-La Roche, Inc., and
Protein Design Labs
Humanized monoclonal antibody for prevention of
kidney transplant rejection
Dec 1997
Zevalin
(ibritumomab tiuxetan)
IDEC Pharmaceuticals Corp.
Relapsed or refractory low-grade, follicular, or
transformed B-cell non-Hodgkins lymphoma
Feb 2002
Zonegran
(zonisamide)
Elan Corp
Adjunctive therapy in treatment of partial seizures
in adults with epilepsy
Mar 2000
Zorbtive
(human growth hormone)
Serono S.A.
Short bowel syndrome (product previously
approved under the trade name Serostim for
AIDS wasting)
Aug 1996
Dec 2003
Zylet
(loteprednol etabonate
and tobramycin ophthalmic
suspension)
Pharmos Corp. and Bausch &
Lomb
Steroid-responsive inflammatory ocular conditions
for which a corticosteroid is indicated and where
superficial bacterial ocular infection or a risk of
infection exists
Dec 2004
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. Societys demand
for resources provided by plants and animals will increase
as the worlds 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.
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 years 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 todays 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.
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.
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
65
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.
66
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 Japans
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
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.
tions in Brazil, Thailand and Venezuela and provided
their scientists with training in transgenic techniques.
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.
For many farmers in developing countries, especially
those in sub-Saharan Africa, the Green Revolution never
materialized because its agricultural practices required
upfront investmentsirrigation systems, machinery, fuel,
chemical fertilizers and pesticidesbeyond the financial
reach of small-scale farmers.
Todays biological agricultural revolution is knowledge
intensive, not capital intensive, because its technological
advances are incorporated into the crop seed.
Todays 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 biotechnologys 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
Cornell University donated transgenic technology for
controlling the papaya ring spot virus to research institu-
Japans 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 Indonesias 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.
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
67
improve existing exports and create new ones, leading to a
more diversified economy and increased independence.
tolerant crops decrease soil erosion by permitting farmers
to use conservation tillage.
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 applicabilityor lack of itof 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:
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.
The Malacca government in Malaysia formed a unit in
the Chief Ministers 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.
68
N
Pakistans Ministry of Science and Technology prepared a biotechnology action plan and funded a threeyear program to promote biotechnology research and
development.
Ugandas National Council of Science and Technology established its first commercial agricultural biotechnology
lab to produce disease-free coffee and banana plantlets.
Egypts 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.
According to the National Center for Food and Agricultural Policys (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 cropscanola, 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
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.
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-
Biotechnology Industry Organization N Guide to Biotechnology
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.
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.
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 foods 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.
Forest Biotechnology
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 trees amount
of cellulose, the raw material for papermaking, and to
decrease the amount of lignin, a tough molecule that
must be removed in papermaking.
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
69
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
70
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.
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
Improved animal health.
Enhancements to animal products.
Environmental and conservation benefits.
Advances in human health.
Animal biotechnology includes all animalslivestock,
poultry, fish, insects, companion animals and laboratory
animalsand 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 functionseverything 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
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 commonplaceproviding farmers, ranchers and pet enthusiasts powerful tools for
breeding the best animals.
Cloning does not change an animals genetic makeup: it is
simply another form of sophisticated assisted reproduction.
Cloning allows livestock breeders to create an exact genetic
copy of an existing animalessentially 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.
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 productivitya 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.
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
Increased nutritional value.
Quality assurance.
Higher efficiency production.
Stronger disease resistance.
Improved animal welfareless 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.
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
industrys 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.
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.
Whats 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
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.
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 Administrations 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
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
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.
Genetic analysis of animal pathogens is leading to
an improved understanding of the factors that cause
disease and how best to control them.
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.
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:
Genetic mapping and the development of DNA markers are being used to identify genes in chickens that
have developed a resistance to Mareks 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.
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 meats 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.
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.
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
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 1950s. Livestock
cloning is newest tool in the ART toolbox.
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 speciesbut 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
73
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.
Genetic technologies are finding a place in the
beef industry.
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
traitfor 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.
D. ADDITIONAL HEALTH APPLICATIONS OF
BIOTECHNOLOGY IN ANIMAL AGRICULTURE
The biotechnology industry has proposed additional
unique solutions for animal health and food safety.
N
74
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.
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
A study published in 2005 by the University of Connecticut and Japans 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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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 sheeps
summer diet.
Scientists are working to develop biotech shrimp that
lack the protein responsible for 80 percent of shrimp
allergies.
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.
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.
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.
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.
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 worlds smallest
wild sheep. There are thought to be fewer than 1,000
adult mouflons in Sardinia, Corsica and Cyprus.
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.
In January 2001, the worlds 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.
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.
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.
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.
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
75
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
76
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
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 Pompes disease
in their milk. Pompes 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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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.
COMPANION ANIMALS
Approximately 164 million dogs and cats are companion
animals in the United States (in more than 60 percent of
all American households). Americas 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
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.
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
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.
Guide to Biotechnology N Biotechnology Industry Organization
77
Industrial and Developing Countries
(million acres)
Global Area of Transgenic Crops, 1995 to 2005:
Industrial and Developing Countries (million acres)
140
120
100
Developing
60
Industrial
80
B
J
J
B
1995
1996
J
B
1997
1998
B
1999
B
2000
Year
20
40
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
2004
2005
+/-
% Change
117.6
59
123.1
55
+5.5
+4.7
Argentina
40
20
42.2
19
2.2
5.5
Brazil
12.3
23.2
10.4
10.9
88.6
Canada
13.3
14.3
6.4
9.1
8.2
3.7
-.9
-9.9
4.5
2.0
4.5
--
1.4
USA
China
Paraguay
--
--
India
1.2
3.2
South Africa
1.2
1.2
7.5
0
0
167
<1
Uruguay
.74
<1
.74
<1
Australia
.5
<1
.74
<1
Mexico
.24
<1
.25
<1
<.1
Romania
.24
<1
.25
<1
<.1
Philippines
.24
<1
.25
<1
<.1
Spain
.24
<1
.25
<1
<.1
Colombia
.12
<1
<.25
<1
<.1
<.25
<1
<.1
<.25
<1
<.1
<.25
<1
<.1
<.25
<1
<.1
Iran
Honduras
-<.12
Portugal
--
Germany
<.12
-<1
-<1
.24
France
--
--
<.25
<1
<.1
Czech Republic
--
--
<.25
<1
<.1
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
48
Global Area of Transgenic Crops in 2004 and 2005 by Crop
(million acres)
2004
Soybean
120
2005
+/-
% Change
+60
134.4
60
14.4
12
Maize
47.7
+23
52.3
24
4.6
9.6
Cotton
22.2
+11
24.2
11
9.0
Canola
10.6
+6
11.4
0.8
7.5
200.5
100
222.3
100
21.8
Total
11
Source:
Clive James, 2005
Global Area of Transgenic Crops, 1996 to 2005, by Crop
(million acres)
140
120
(million acres)
100
Soybean
Corn
Cotton
80
B
B
B
Canola
60
40
20
0
H
B
FJ
1996
B
J
H
F
H
F
1997
1998
H
F
H
F
1999
2000
J
H
F
2001
H
H
H
F
H
F
2002
2003
2004
2005
Year
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
79
Global Area of Transgenic Crops in 2004 and 2005 by Trait
(million acres)
2004
2005
+/-
144.5
72
157.3
71
12.5
Insect resistance (Bt)
38.5
19
40
18
1.5
Bt/Herbicide tolerance
16.8
24.9
11
8.1
49
100
222.2
100
22.1
11
Herbicide tolerance
Total
200
% Change
9
Source:
Clive James, 2005
Global Area of Transgenic Crops, 1995 to 2005, by Trait
(million acres)
160
140
80
(million acres)
120
100
Herbicide Tolerance
Insect resistance (Bt)
Bt/Herbicide tolerance (stacked)
B
B
B
Virus resistance/Other
80
B
60
B
40
20
0
H
FJ
B
1995
F
JBH
1996
B
J
F
H
H
F
H
F
1997
1998
1999
Source:
Clive James, 19972005
Biotechnology Industry Organization N Guide to Biotechnology
J
H
2000
Year
J
H
J
H
F
F
2001
J
H
F
2002
F
2003
F
2004
2005
Transgenic Crop Area as % of Global Area of Principal Crops
(million acres)
Crop
Global area
Transgenic crop area
224.8
134.9
60
86.5
24.2
28
Canola
64.2
11.5
18
Maize
363.1
50.8
14
Total
738.6
221.4
30
Soybean
Cotton
Transgenic area as % of global area
Source:
Clive James, 2005
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.
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).
82
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
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
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 Monsantos
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 12 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.
Bollgard II Insect-Protected Cotton (Developed by Monsanto) Bollgard II is Monsantos 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.
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. Hansens) 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.
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 nations cows. The FDA approved it in 1993.
ChyMax (fermentation-derived) (Developed by Pfizer,
marketed by Chr. Hansens) 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
83
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
84
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.
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
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 plants 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
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.
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 todays 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.
85
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 BASFs Amflora potato, which provides
pure amylopectin starch directly from the potato tuber.
Guide to Biotechnology N Biotechnology Industry Organization
RICE
MISCELLANEOUS
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.
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
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.
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
86
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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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. Todays 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.
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.
Another nutritional concern related to edible oils is the
negative health effects produced when vegetable oils are
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
87
88
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.
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.
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.
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.
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 12
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
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.
Food Processing
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.
TABLE 1
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.
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
89
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 biotechnologys third waveindustrial 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
90
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.
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.
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.
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.
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 endeavoragriculture. A final
advantage of using plant biomass as feedstock is that as
our crop of feedstock grows, it consumes CO2one of the
greenhouse gases.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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.
Unlike many chemical reactions that require very high
temperatures and pressures, reactions using biological
molecules work best under conditions that are compatible with lifethat 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.
Biocatalysts
ndustrial biotechnology companies develop new
enzymes, biocatalysts, to be used in manufacturing
processes of other industries. Enzymes are proteins
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.
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-
Guide to Biotechnology N Biotechnology Industry Organization
91
ture or pressure found in some industrial manufacturing
processeshence 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.
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.
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 Bushs 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 todays 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.
Biofuel
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.
A 2004 Natural Resources Defense Council report
projects biofuels could add $5 billion to farmer profits
by 2025.
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
Also in 2004, the Ag Energy Working Group of the Energy Future Coalition published a report showing how
Americas 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.
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 worlds 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 worlds
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 selectinputs, manufacturing process or final productbiotechnology 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.
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
93
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 wont need living expression systems for largescale production. It is not difficult to imagine completely new, commercially attractive polymers being
developed using recombinant DNA technology.
94
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.
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
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 organismanimals,
plants, bacteria and so forthingests 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.
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-
SOME INDUSTRIAL BIOTECH
APPLICATIONS BY SECTORS
N
Biological fuel cells
Pulp and paper bleaching
Fine and bulk chemicals
Biopulping (paper industry)
Chiral compound synthesis
Specialty textile treatment
Synthetic fibers for clothing
Pharmaceuticals
Food flavoring compounds
Biobased plastics
Bioethanol for
transportation
Metal refining
Vitamin production
Oil and gas desuphurization
Leather degreasing
Biohydrogen
Electroplating/metal
cleaning
Nutritional oils
Biopolymers for plastic
packaging
Coal bed methane water
treatment
Chem/bio warfare agent
decontamination
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.
Metal ore heap leaching
Biopolymers for automobile
parts
Enzyme food processing
aids
Rayon and other synthetic
fibers
Sweetener production
(high-fructose corn syrup)
Oil well drill hole
completion (non-toxic cake
breakers)
95
Road surface treatment for
dust control
Textile dewatering
Vegetable oil degumming
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
Consumer Goods Made With Industrial Biotech
CONSUMER
PRODUCT
OLD PROCESS
NEW INDUSTRIAL BIOTECH ENABLING
BIOTECHPROCESS TECHNOLOGY
CONSUMER
BENEFIT
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
Microorganisms genetically
enhanced to produce baking
enzymes (directed evolution
and recombinant DNA)
Detergent
Phosphates added as
brightening and cleaning
agents
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
Elimination of water
pollution from phosphates
N Brighter, cleaner clothes
with lower-temperature
wash water
N Energy savings
High-quality bread
Longer shelf life
N No potassium bromate
N
Polyester Bedding
Polyester* produced
chemically from
petroleum feedstock
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
Vitamin B2
Toxic chemicals, such as
aniline, used in a ninestep chemical synthesis
process
One-step fermentation
process uses vegetable oil
as a feedstock
Genetically enhanced microbe
developed to produce vitamin
B2 (directed evolution)
Biologically produced
without chemicals
N Greatly reduces
hazardous waste
generation and disposal
Stonewashed Jeans
Open-pit mining of
pumice; fabric washed
with crushed pumice
stone and/or acid
Fabric washed with
biotechnology enzyme
(cellulase) to fade and
soften jeans or khakis
Textile enzymes produced
by genetically enhanced
microbe (extremophiles and
recombinant DNA)
Paper Bleaching
Wood chips boiled in a
harsh chemical solution
to yield pulp for paper
making
Enzymes selectively
degrade lignin and break
down wood cell walls
during pulping
Wood-bleaching enzymes
produced by genetically
enhanced microbes
(recombinant DNA)
Ethanol Fuel
Food and feed grains
fermented into ethanol
(a technology that is
thousands of years old)
Cellulase enzyme
technology allows
conversion of crop
residues (stems, leaves,
straw, and hulls) to sugars
that are then converted
to ethanol
Genetically enhanced
organism developed to
produce enzymes that
convert agricultural wastes
into fermentable sugars
(directed evolution, gene
shuffling)
96
*any synthetic fiber
Biotechnology Industry Organization N Guide to Biotechnology
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
Less mining
Softer fabric
N Reduced energy
consumption
N Lower cost
N
Reduces use of chlorine
bleach and reduces toxic
dioxin in the environment
N Cost savings due to lower
energy and chemical costs
Renewable feedstock
Reduces greenhouse gas
emissions
N Increases domestic energy
production
N Is more energy efficient to
produce than old process
N
CONSUMER
PRODUCT
OLD PROCESS
NEW INDUSTRIAL BIOTECH ENABLING
BIOTECHPROCESS TECHNOLOGY
CONSUMER
BENEFIT
Antibiotics
Chlorinated solvents and
hazardous chemicals used
to produce antibiotics
through chemical
synthesis
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)
65% reduction in energy
consumption
N Overall cost savings
Contact Lens
Solution
Surfactants and/or saline
solutions (do not remove
protein deposits) used to
clean lenses
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
97
Guide to Biotechnology N Biotechnology Industry Organization
Examples of Industrial Enzymes
ENZYMES
SOURCE OR TYPE
APPLICATIONS
Laundry and dishwashing detergents,
industrial pipe/tank cleaners, textiles, pulp and
paper, fermentation ethanol
Carbohydrases
Alpha-amylase
Bacterial A-amylase (e.g., Bacillus subtilis),
Fungal A-amylase (e.g., Aspergillus niger),
Alkaline A-amylase
Textiles, starch syrups, laundry and
dishwashing detergents, paper desizing,
fermentation ethanol, animal feed
B-amylase
From a strain of Bacillus
Brewing, maltose syrup
Cellulase
B-Glucanase
Dishwashing detergents, animal feed, textiles,
bioenergy production
exo-B-1,4-glucanase, endo-B-1,4-glucanase
B-Glucosidase
Dextranase
Brewing industry
Transforms isoflavone phytoestrogens in
soymilk
Made by various microorganisms (e.g.,
Leuconostoc mesenteriodes)
Hydrolyzes the polysaccharide dextran
Dextrinase (almost identical to
A-glucosidase)
Cleaves dextrin into two molecules of
glucose
A-Galactosidase (melibiase)
Could increase yield of sucrose; potential use
in the beet sugar industry
98
Glucoamylase
Aspergillus niger, Rhizopus, Endomyces
Manufacture of dextrose syrup and highfructose syrup
Hemmicellulase/Pentosanase/Xylanase
Thermomyces lanuginosus, Penicillium
simplicissimum
Baking, fruit juice manufacture, wood pulp
processing
Invertase
Lactase
Manufacture of invert syrup from cane or
beet sugar (use is minor)
Kluyveromyces lactis, Asperigillus oryzae, Bacillus
Eliminates lactose from dairy foods
Naringinase
Debitter citrus peel
Pectinase
Fruit processing
Pullulanase
Klebsiella aerogenes, Bacillus acidipullulyticus,
Bacillus subtilis
Antistaling agent in baked goods
Brewing, baking goods, protein processing,
distilled spirits, laundry and dishwashing
detergents, lens cleaners, leather and fur,
chemicals
Proteases
Acid proteinase
Endothia parasitica, Rhizopus, Aspergillus niger,
A. oryzae
Baking, improves dough handling
Alkaline protease
Bacillus subtilis, Bacillus licheniformis
Detergents, leather and fur
Bromelain
Pineapple stem
Food industry
Pepsin
Porcine or bovine stomach
Cheese production
Lactococcus lactis
Food and animal feed
Peptidases
Aminopeptidase
Biotechnology Industry Organization N Guide to Biotechnology
ENZYMES
SOURCE OR TYPE
APPLICATIONS
Subtilisin
Bacillus subtilis var. Carlsberg, Bacillus
lichenformis
Chiral resolution of chemical compounds or
pharmaceuticals
Lipases and Esterases
Phospholidases, pregastric esterases,
phosphatases
Cleaners, leather and fur, dairy, chemicals
Aminoacylase
Porcine kidney, Aspergillus melleus
Optical resolution of amino acids
Glutaminase
Bacillus, Aspergillus
Conversion of glutamine to glutamate
Lysozyme
Chicken egg white, Saccharomyces cerevisiae,
Pichia pastoris
Antibacterial (germicidal in dairy industry)
Penicillin acylase
Bacillus megaterium, Escherichia coli
Chemical synthesis
Endo-peptidase
Isomerase
Converts glucose syrup to high-fructose
syrup in food industry
Oxireductases
Chemicals, detergent bleaches, pulp bleaching
Alcohol dehydrogenase
Saccharomyces cerevisiae,Thermoanarobium brockii Chiral synthesis of chemicals
Amino acid oxidase
Porcine kidney, snake venom
Chiral resolution of racemic amino acid
mixtures
Catalase
Aspergillus niger
desugaring of eggs
Chloroperoxidase
Algae, bacteria, fungi, mammalian tissues
Steroid synthesis
Peroxidase
Horseradish
Laundry and wood pulp bleaches
Lyases
Acetolactate decarboxylase
Brewing industry
Aspartic B-decarboxylase
Manufacture of L-alanine from L-aspartic acid
Histidase
Achromobacter liquidum
Cosmetics
Transferases
Cyclodextrin glycosyltransferase
Manufacture of cyclodextrins from starch
Sources:
Diversa & Novo Nordisk
Guide to Biotechnology N Biotechnology Industry Organization
99
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.
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.
100
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.
A Strategic Asset
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
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 soldiers 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.
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.
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 organisms survival or
replication. Projects are under way targeting both.
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 organisms 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.
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.
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.
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.
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
101
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.
102
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.
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
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.
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 fathers DNA is contained in the
childs 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 childs are ignored in the analysis. To establish
paternity, the remaining DNA fragments in the childs
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 womans
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.
DNA typing recently helped scientists solve the mystery of the Mexican group of Pacific loggerhead turtles.
Guide to Biotechnology N Biotechnology Industry Organization
103
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.
104
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 works 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.
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, BIOs 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.
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
105
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 cellsthe egg and spermthat pass on genetic
composition.
106
MEDICAL PRIVACY AND GENETIC
DISCRIMINATION
BIO recognizes the need for confidentiality of all individually identifiable medical information. We support national
policylegislation or regulationsto protect the confidentiality of all personal medical information, including
data derived from genetic tests. The industry believes that
an individuals 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, BIOs board of directors called for
strong controls on the use of all confidential medical
information, including genetic information. At BIOs
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
This option could be jeopardized if genetic information
were used to discriminate.
STEM CELLS
Researchers can now separate early, undifferentiated
stem cells from blastocyststhe 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.
BIO is opposed to human reproductive cloningusing
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 womans 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, Parkinsons, Alzheimers 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 reprogramminghow 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 academys 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.
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
107
with regulatory requirements for testing, while maintaining the scientific integrity of the research.
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.
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.
108
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
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
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.
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-
malsthose with genes from another species, usually
humansto 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.
110
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
worlds 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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
Intellectual Property
iotechnology is an industry of ideas and invention.
That makes intellectual propertytypically in
the form of patentsthe most important asset at
most biotech companies. These companies are often small
firmsmost biotechs have 50 or fewer employeesdeveloping products that can take upwards of 10 years and
hundreds of millions of dollars in investment to bring to
the marketplace.
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.)
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
manincluding modified cells and other biological
materialsmay be patented.
TYPES OF PATENTS
What Is a Patent?
patent is an agreement between the government and
an inventor whereby, in exchange for the inventors
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
Once a patent has expired, anyone may make, use, offer
for sale, sell or import the invention without permission
of the patentee.
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:
Congress shall have powerto 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
111
has two basic purposes: to promote the advancement of
technology and to protect the inventor.
Other types of inventions or discoveries cannot be patented; these include naturally occurring organisms, laws of
nature, natural or physical phenomena, and abstract ideas.
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.
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.
112
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.
Thats why societies that protect inventors with patents are
the worlds most advanced, scientifically and technologically.
Patentable Inventions
nder U.S. law, various types of invention can be patented. These are:
A processfor 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 machinefor example, a flat-screen high-definition
television set or an X-ray machine.
An article of manufacturefor example, a silicon
computer chip or a specially molded piece of plastic
for an automobile bumper.
A composition of matterfor 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.
Biotechnology Industry Organization N Guide to Biotechnology
BIOTECHNOLOGY PATENTS
Biotechnology inventions generally fall into one of two
classes:
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.
Patent Requirements
o obtain a patent on a new invention, an inventor
must show that these three criteria are met:
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 cant meet this requirement.
2. The invention is useful. The inventor must show that
the invention has a real-world use. It isnt 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.
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.
113
2. A drawing illustrating the invention, if such a drawing
is necessary for understanding the invention.
living organisms was re-examined, and confirmed.
A landmark case involved Ananda Chakrabartys
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 Chakrabartys 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.
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).
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
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
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
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
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
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.
Biotechnology Resources
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:
N
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].
Periodicals, Headline Services
and Web Sites
FROM BIO
BIO.org. BIOs 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.
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 industrys work
in global health. All resources are available at www.
bvgh.org.
BioCentury. BioCenturys 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. BioWorlds 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.
Science.bio.org. Each business morning, BIO shares links
to all of the days significant biotech science stories,
including both mainstream press and journal articles.
FierceBiotech. This business-focused summary of the days
biotech news highlights is delivered via e-mail. Learn
more or sign up at www.fiercebiotech.org.
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.
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.
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 Organizations
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.
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.
Guide to Biotechnology N Biotechnology Industry Organization
115
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.
116
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 Institutes 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.
General Science Journals
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
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.
Selected Recent Reports on
Biotechnology
GENERAL & HEALTHCARE
Beyond Borders: Global Biotechnology Report 2006.
Ernst & Youngs 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.
Biotech 2006Life 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.
BioWorlds annual report aggregates the biotech
industrys financial, partnering and drug approval
information for 2005, with analysis explaining what
it all means. See www.bioworld.com for purchase
information.
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 Nations 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 Developments
annual report offers a brief synopsis of the years major
regulatory and R&D issues. Available for downloading
at csdd.tufts.edu. Published 2006.
Parexels 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.
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
117
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.
118
GM crops: the global socio-economic and
environmental impactthe 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
biotecha 29 percent increase over 2004 production.
Available for downloading at www.ncfap.org. Published
November 2006.
INDUSTRIAL & ENVIRONMENTAL
25 by 25: Agricultures Role in Ensuring U.S. Energy
Independence. This report by the Ag Energy Working
Biotechnology Industry Organization N Guide to Biotechnology
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
Americas 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 Americas
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.
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.
Alzheimers disease A disease characterized by, among
other things, progressive loss of memory. The
development of Alzheimers 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.
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
Alzheimers 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.
Amplification The process of increasing the number of
copies of a particular gene or chromosomal sequence.
Autosome Any chromosome other than a sex
chromosome.
Anaerobic Growing in the absence of oxygen.
Avirulent Unable to cause disease.
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.
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
119
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.
120
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.
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.
Biochemical The product of a chemical reaction in a
living organism.
Biomaterials Biological molecules, such as proteins
and complex sugars, used to make medical devices,
including structural elements used in reconstructive
surgery.
Biochip An electronic device that uses organic molecules
to form a semiconductor.
Bioprocess A process in which living cells, or components
thereof, are used to produce a desired product.
Bioconversion Chemical restructuring of raw materials
by using a biocatalyst.
Bioreactor Vessel used for bioprocessing.
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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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.
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.
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 fromand are genetically
identical toa 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.
Guide to Biotechnology N Biotechnology Industry Organization
121
Co-factor A nonprotein substance required for certain
enzymes to function. Co-factors can be co-enzymes or
metallic ions.
Culture medium Any nutrient system for the artificial
cultivation of bacteria or other cells; usually a complex
mixture of organic and inorganic materials.
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.
Cyto- Referring to cell.
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.
122
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
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 PCRthe polymerase chain
reaction.
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.
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 cells
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.
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.
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.
Endostatin An endogenous protein that blocks the
proliferation of blood vessels.
Guide to Biotechnology N Biotechnology Industry Organization
123
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.
G
Gel electrophoresis A process for separating molecules
by forcing them to migrate through a gel under the
influence of an electric field.
124
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.
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 individuals genetic
material. Genetic testing can be used to gather
information on an individuals 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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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).
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.
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
125
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.
126
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
bodys 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.
Biotechnology Industry Organization N Guide to Biotechnology
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.
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 bodys 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.
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.
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.
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.
Macrophage colony stimulating factor (M-CSF) A
natural hormone that stimulates the production
of white blood cells, particularly monocytes (the
precursors of macrophages).
Mutagen A substance that induces mutations.
Medium A substance containing nutrients needed for cell
growth.
Mutation A change in the genetic material of a cell.
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.
Mutant A cell that manifests new characteristics due to a
change in its DNA.
Myeloma A type of cancer cell (plasma cell) that is used in
monoclonal antibody technology to form hybridomas.
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
127
128
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.
Pathogen Disease-causing organism.
Noncoding DNA DNA that does not encode any product
(RNA or protein). The majority of the DNA in plants
and animals is noncoding.
Peptide Two or more amino acids joined by a linkage
called a peptide bond.
Passive immunity Immunity acquired from receiving
preformed antibodies.
Nuclease An enzyme that, by cleaving chemical bonds,
breaks down nucleic acids into their constituent
nucleotides.
Personalized medicine The use of individual molecular
(often genetic) information to prevent disease, choose
medicines and make other critical decisions about
health.
Nucleic acids Large molecules, generally found in the
cells nucleus and/or cytoplasm, that are made up of
nucleotides. The two most common nucleic acids are
DNA and RNA.
Phagocyte A type of white blood cell that can ingest
invading microorganisms and other foreign material.
See also Macrophage.
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 RNAs sugar is ribose. The sequence of the bases
within the nucleic acid determines the sequence of
amino acids in a protein. See also Base.
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.
Nucleus The structure within eukaryotic cells that
contains chromosomal DNA.
Pharmacogenetics The study of inherited differences
(variation) in drug metabolism and response. See also
pharmacogenomics.
Phenotype Observable characteristics resulting from
interaction between an organisms genetic makeup
and the environment. Compare Genotype.
Oligonucleotide A polymer consisting of a small number
(about two to 10) of nucleotides.
Oncogene Gene thought to be capable of producing
cancer.
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.
Oncogenic Cancer causing.
Plasma The fluid (noncellular) fraction of blood.
Oncology Study of cancer.
Plasmapheresis A technique used to separate useful
factors from blood.
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
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.
Fully differentiated cells from many plants are
totipotent.
Pure culture In vitro growth of only one type of
microorganism.
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.
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.
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).
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.
Prokaryote An organism (e.g., bacterium, virus,
cyanobacterium) whose DNA is not enclosed within a
nuclear membrane. Compare Eukaryote.
Recombinant DNA (rDNA) The DNA formed by
combining segments of DNA from two different
sources.
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.
Regeneration Laboratory technique for forming a new
plant from a clump of plant cells.
Prophage Phage nucleic acid that is incorporated into the
hosts chromosome but does not cause cell lysis.
Replication Reproduction or duplication, as of an exact
copy of a strand of DNA.
Protein A molecule composed of amino acids. There
are many types of proteins, all carrying out different
functions essential for cell growth.
Replicon A segment of DNA (e.g., chromosome or
plasmid) that can replicate independently.
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 proteins specific function but
also how it interacts with other proteins.
Regulatory gene A gene that acts to control the proteinsynthesizing activity of other genes.
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.
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
129
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 DNAs 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.
130
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
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
patients 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.
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 bodys 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 bodys 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 hosts 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 cells
reproductive machinery.
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
131
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.
132
Biotechnology Industry Organization N Guide to Biotechnology
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
You might also like
- Introduction: Understanding Biotechnology: Title: The Evolution and Impact of BiotechnologyNo ratings yetIntroduction: Understanding Biotechnology: Title: The Evolution and Impact of Biotechnology5 pages
- Exploring The Current State of The Biotech Industry - Innovations, Challenges, and Future ProspectsNo ratings yetExploring The Current State of The Biotech Industry - Innovations, Challenges, and Future Prospects3 pages
- Policy Brief: Modern Biotechnology and The OECDNo ratings yetPolicy Brief: Modern Biotechnology and The OECD8 pages
- Lesson 1.1 Introduction To BiotechnologyNo ratings yetLesson 1.1 Introduction To Biotechnology2 pages
- Managing Innovations in Biotechnology: Uropean Project Semester 2006No ratings yetManaging Innovations in Biotechnology: Uropean Project Semester 200677 pages
- Biotechnology Business Possibilities and ProspectsNo ratings yetBiotechnology Business Possibilities and Prospects106 pages
- Biotechnology and Biological Preparations758578294No ratings yetBiotechnology and Biological Preparations75857829424 pages
- Biotechnology For Human Welfare: Naiyyum Choudhury Professor, BRAC University & Secretary, BASNo ratings yetBiotechnology For Human Welfare: Naiyyum Choudhury Professor, BRAC University & Secretary, BAS82 pages
- Biotech Developments & Future Impact: Peter Brenders, President & Ceo, Biotecanada Capdm, May 10, 2006No ratings yetBiotech Developments & Future Impact: Peter Brenders, President & Ceo, Biotecanada Capdm, May 10, 200636 pages
- Medical Law and Technological Advances: Innovation and Technology in Global Medical Law: Global Medical Law: Fundamentals, Responsibility, and InnovationFrom EverandMedical Law and Technological Advances: Innovation and Technology in Global Medical Law: Global Medical Law: Fundamentals, Responsibility, and InnovationNo ratings yet
- Medical Ethics and Bioethics: Global Perspectives and Challenges: Global Medical Law: Fundamentals, Responsibility, and InnovationFrom EverandMedical Ethics and Bioethics: Global Perspectives and Challenges: Global Medical Law: Fundamentals, Responsibility, and InnovationNo ratings yet
- Cleanroom Technology: Fundamentals of Design, Testing and OperationFrom EverandCleanroom Technology: Fundamentals of Design, Testing and Operation3.5/5 (2)
- Professional insect rearing: Strategical points and management methodFrom EverandProfessional insect rearing: Strategical points and management methodNo ratings yet
- Entrepreneurs have the DACMAR Advantage: 6-steps for successful biotech start-upsFrom EverandEntrepreneurs have the DACMAR Advantage: 6-steps for successful biotech start-upsNo ratings yet
- EPA 608 Study Guide Complete Exam Preparation and Review for HVAC Technicians, Including Practice Questions and Essential TipsFrom EverandEPA 608 Study Guide Complete Exam Preparation and Review for HVAC Technicians, Including Practice Questions and Essential TipsNo ratings yet
- Guidelines for Combustible Dust Hazard AnalysisFrom EverandGuidelines for Combustible Dust Hazard AnalysisNo ratings yet
- Advanced Distillation Technologies: Design, Control and ApplicationsFrom EverandAdvanced Distillation Technologies: Design, Control and ApplicationsNo ratings yet
