GENETIC ENGEENERING AND GENE THERAPY

@james
Lesson Objectives:

At the end of this module, the students are expected to:

1. identity issues on genetically modified organisms (GMOs);

2. discuss different implications and impact of GMOs;

3. create a reflection paper on the impact of GMOs in the Global and Philippine context;

4. pre-design and suggest their own hypothetical GMO product that has significant societal contributions
and guided and anchored with scientific concepts;

5. describe gene therapy and its various forms; and,

6. assess the issues on potential benefits and detriments of Gene Therapy to global health.

• Ms. Ellasus volunteered for demo-testing in her field. Bt Corn yielded 7.2 tons per acre as compared to
a regular yield of 4.2 tons per hectare. No insecticide spraying was needed. This is one of the success
stories of genetically modified organisms (GMOs) (Ongkiko, 2016).

• Genetic engineering has been with the human society since selective breeding was introduced to
humankind and when animals were domesticated. Yet, the process of genetic alterations is all but
natural.

• It was in 1951 that the term genetic engineering was coined by Jack Williamson, author of the science
fiction novel Dragon's Island (Stableford 2004). This was years before actual research findings on the
DNA's role in heredity and its structure, the double-helix of Watson and Crick, were published.

• Through continuous search for development, genetic engineering no longer stayed in science fiction
novel. It became a reality in science laboratories. The general process of genetic engineering is the
deliberate manipulation of the organism's genes, where it may involve transfer of genes from another
organism.

To date, there are ongoing researches on GMOs such as using genetically modified male mosquitoes as
pest control over female mosquito caries of Zika virus.

• However, despite the many possibilities of creating solutions for problems and opening doors for
innovations, genetic engineering faces much opposition. Opponents raise ethical, social, and
environmental issues related to genetic engineering and its GMOs

• This module will present the existence of genetic engineering, specifically GMOs in the different areas
of life, the impact to humankind, and the controversies that surround them.
@elaine
Genetically Modified Organism

• Genetically modified organism (GMO) is the term used for an organism created through genetic
engineering. The World Health Organization (WHO, 2014) defines GMO as an "organism, either plant,
animal, or microorganism, in which the genetic material (DNA) has been altered in a way that does not
occur naturally by mating or natural recombination."

• The development of GMOs was perceived to help in the advancement of technology for the benefit of
humans in different industries like agriculture and medicine. GMOs in Food and Agricultural Industries
The Center for Ecogenetics and Environmental Health (CEEH, 2013) identified the following roles of
GMOs in the food and agricultural industries:

1. Pest resistance - genetically modified plants to resist certain pests.

● An example is Bt Corn. The DNA (genome) of the Bt Com has been modified with the gene of
Bacillus thuringiensis, a soil bacterium that produces proteins which is toxic to corn borers (worms).
https://www.permaculturenews.org/2012/08/14/bt-toxicity-confirmed-flawed-studies-exposed/

2. Virus resistance - genetically modified plants to resist certain viruses.

● An example is GM papaya or rainbow papaya. The papaya ringspot virus (PRSV) is known to be
detrimental to papaya plants. The protein of PRSV was introduced to the papaya plant through plant
tissue which turned out to be resistant to the virus itself. The effect was like the vaccine of humans have
against measles or influenza virus

3. Herbicide tolerance - genetically modified plants to tolerate herbicide.

● An example is Roundup Ready soybean. Glyphosate or Glufosynate, an herbicide for weeds,

was introduced to soybeans making it tolerant to the herbicide itself. Farmers then can spray the
herbicide killing the weeds but not the soybeans.

4. Fortification - genetically modified plants fortified with certain minerals.

● An example is Golden Rice. Betacarotene, a precursor of vitamin A, was introduced through

biosynthesis genes to the rice, making the rice grains fortified with vitamin A.

5. Cosmetic preservation - genetically modified plants resist natural discoloration.

● An example is Arctic Apple. The apple variety was genetically modified to suppress the
browning of apple due to superficial damage.

Central dogma of molecular biology, and gene silencing.

A. DNA encodes the information for the cell. When a gene is activated the information is copied to RNA,
an unstable intermediate that then is deciphered by the cell to make a protein, in this case the PPO
enzyme.

B. Scientists can add a genetically engineered copy of a gene in the backwards orientation. When copied
to RNA, the strand effectively cancels out the expression of the native gene.

C. Other times a gene can be turned on to a high level, and that causes the native gene (and the added
gene) to be shut down and RNA intermediates removed. That's what happens in the Arctic Apple.
6. Increase growth rate - a genetically modified organism that has higher yield in growth than normal
species.

● An example is AquAdvantage salmon. A gene from an ocean pout, an eel-like fish was
introduced to Pacific Chinook salmon. making the salmon grow faster than its normal rate.

@ capoy
GMOs in Non-Food Crops and Microorganisms

Genetically modified organisms (GMOs) in non-food crops and some microorganisms involve the
following:

1. Flower production - GMOs in flower production are seen in modified color and extended vase life of
flowers.

Examples are Blue Roses. The so-called "blue" roses, which are in reality, lime or purple, contained
cyanidin 3,5-diglucoside, together with large amounts of flavonols. (Elomaa & Holton, 1994).

2. Pharmaceutical productions modified plants to produce pharmaceutical products.

Examples are periwinkle plants. Bacterial genes were added to the periwinkle plant to enhance the
production of vinblastine, an alkaloid usually added to drugs for cancer treatments like Hodgkin's
lymphoma

3. Bioremediation - use of modified plants that can assist in the bioremediation of polluted sites.

An example is shrub tobacco. Nicotiana glauca, or shrub tobacco genetically modified with phytochelatin
TapCSII, is used for bioremediation. It shows high level accumulation of zinc, lead, cadmium, nickel, and
boron and produces high biomass.

4. Drug production - use of modified microorganisms that can be used in medicines.

Another example is Artemisinin. Artemisinic acid is a compound used for antimalarial drug extracted
from sweet wordwood plant. Through genetic engineering, it can be synthetically produced by yeast and
bacteria with sweet wordwood plant gene (Zimmer, 2006).

5. GMOs in the medical field - genetic engineering is playing a significant role from diagnosis to
treatment of human-dreaded diseases. It helps in the production of drugs, gene therapy, and laboratory
researches.

One classic example is Humulin, the genetically engineered insulin used by Type 1 diabetes patients who
are insulindependent.

In the past, insulin is extracted from the pancreases of pigs and cows that have caused allergic reactions
to some diabetics using it.

IN 1978, researchers from the City of Hope National Medical Center and Genentech Biotechnology
Company were able to produce human insulin. The gene for insulin was inserted to bacterial DNA that
was able to produce almost exactly the same human insulin. This was a breakthrough in the mass
production of human insulin. In 1996. modified human insulin was approved, called the Humalog.

@ Flordeline
Benefits of GMOs

Studies show some of the potential benefits of GMOs:

● Higher efficiency in farming - with the use of pesticide resistant/herbicide-tolerant GMO crops, there
will be less use for herbicides/pesticides, and lower cost for labor and cultivation.

● Increase in harvest - GMO crops resistant to pests and diseases means increase in potential growth
and harvest.

● Control in fertility - controlling the purity of the hybrid seeds (GMO seeds) ensures higher yields.

● Increase in food processing - altered characteristics of GMO crops help ease food processing.

● Improvement of desirable characteristics - GMOs offer longer shelf life, enhanced color and taste,
enhanced production or reduction of enzymes, and other modified characteristics of plants, animals,
and microorganisms

● Nutritional and pharmaceutical enhancement - GMO crops like maize fortified with lysite and Golden
Rice fortified with Vitamin A and iron. There are now edible vaccines for viral and diarrheal diseases.

● Reduce the use of fertilizer and pesticide.

Potential Risks of GMOs

Opponents of GMOs have the following major concerns:

1. Since genetic engineering is still a young branch of science, there are inadequate studies on the
effects of GMOs to humans and the environment.

2. Genetic engineering promotes mutation in organisms which the long-term effect is still unknown.

3. Human consumption of GMOs might have the following effects:

● More allergic reactions - GMO food may trigger more allergic reactions, more so create new ones as
side effect of the gene alteration.

● Gene mutation - GMO food may develop abnormalities and mutation, more than the desired product
of the gene alteration.

● Antibiotic resistance - GMO food contains antibiotic resistant genes: this may cause disease-causing
bacteria likely to be more antibiotic-resistant too. Increasing the possibility or widespread of the
disease.

● Nutritional value - GMO food may have change in their nutritional value

Potential Environmental Risks caused by GMOs Karki (2006) summarized the perceived potential
environmental risks caused by GMOs. The identified major risks are the following:

1. Risk in gene flow - there is a potential risk of the modified gene to be transferred from the GMO crop
to its wild relative or organism in the soil and human intestine (when ingested). For example, a decaying
GMO plant could possibly transfer the modified genes to the bacteria and fungi in the soil. Bacteria and
fungi are capable of using a genetic material from their surroundings. There are no studies yet on the
effects of the absorbed modified gene to the other organisms

2. Emergence of new forms of resistance and secondary pests and weed problems - GMO crops resistant
to certain pesticides may trigger new form of pest resistance while GMO herbicide- tolerant crops may
lead to the over use of the herbicides which may trigger new form of weed resistance.

3. Recombination of Virus and Bacteria to Produce New Pathogens - the modified gene can be
transferred and integrated in the viral or bacterial genes which may lead to viral or bacterial gene
modification or mutation. This living modified virus and bacteria may then cause new disease that may
affect other organisms including human beings.

@ liwanag
Other direct and indirect environmental risks caused by GMOS (Molfino & Zucco, 2008):

1. Direct environmental risks are:

● introduction of the GMOs in the natural environment may cause disruption of the natural
communities through competition or interference;
● the possibility of unexpected behavior of the GMOs in the environment if it escapes its intended use
and may post threats or become pest;

● may cause harmful effects to ecosystem processes if GMOs interfere with the natural biochemical
cycles; and

● the persistence of GMO genes after its harvest which may cause negative impacts to the consumer of
GMO products.

2. Indirect environmental risks are:

● alteration of agricultural practices like managing negative impacts of GMOs to the environment such
as evolution of insects, pests, and weeds that became resistant to GMO crops;

● may have impacts to biodiversity caused by the alteration in agricultural practices; and

● may have varied environmental impacts due to GMOs interaction and release in the natural
environment.

Potential Human Health Risks caused by GMOs

• A major concern in the use and consumption of GMOs is its effect on human beings, primarily on
human health. Some potential human health risks are identified (Akhter, 2001), such as:

o consumption of GMO may have adverse effects since it is not naturally or organically produced;

o consumption of GMOs may alter the balance of existing microorganism in the human digestive system;

o production of toxins may be detrimental to human health; and

o production of allergens may have adverse effects on humans.

• Worldwide, there are many groups that campaign against GMO food consumption. They encourage
people to boycott GMO products and to be vigilant in checking if the food they buy his GMO ingredients.

• In the Philippines, the Supreme Court has ruled against the use of Bt eggplant, another genetically
modified crop (Ongkiko, 2016).

• The primary issue on GMOs presented in public debates unnatural production or what is termed to be
a violation of nature. The creation of new organisms, like GMOs posts moral issues on defiance to
natural laws. Another concern is the potential risks to the environment and human health, to which so
much is unknown yet.

@LUNA
Biosafety on GMOs
 • There are initiatives for the protection of the general human population regarding the issues and
concerns about GMOs. International organizations developed principles and treaties that somehow
ensure biosafety on GMOs. Some of these initiatives are as follows

● The Codex Alimentarius Commission (Codex). The Food and Agricultural Organization (FAO) together
with the World Health Organization (WHO) created The Codex Alimentarius Commission (Codex).

○ Codex is an intergovernmental body that develops the Codex Alimentarius, know us the International
Food Code.

○ Codex is responsible for the development of standards, codes of practices, guidelines, and
recommendations on food safety. With the pressing issues and concerns on GMOs, in 2003, Codex has
developed principles for the human health risk analysis of genetically modified (GM) food products.

○ The principles include pre-market assessments of GM food products and its evaluation of direct and
indirect effects.

○ However, the Codex principles has no binding effect on national legislation but through the sanitary
and phytosanitary measures of the World Trade Organization, national legislators are encouraged to
complement their national standards with the Codex Principles (WHO, 2014).

● Cartagena Protocol on Biosafety. Established in 2003. Cartagena Protocol is an international

environmental treaty that regulates the transboundary movements of Living Modified Organisms
(IMOs). The Cartagena Protocol requires exporters to seek consent from the importers before its first
shipment of LMOS (WHO, 2014).

● International Trade Agreement on labeling of GM food and food products. The agreement requires
exporters of GM food and food products to label their products and give rights to importing parties to
reject or accept the GM products. The premise of this policy is that consumers have the right to know
and the freedom to choose GM or non-GM products (Whitman, 2000).

● The World Health Organization (WHO, 2014) claims that all GM products that are available in the
international market have passed safety assessment by national authorities. The safety assessments
basically look at the environmental and health risk factors and food safety usually follows the Codex
Food Code.
@DELA CRUZ
GENE THERAPY

• Medical science has detected many human diseases related to defective genes. These types of
diseases are not curable by conventional methods like taking readily available medicines. Gene therapy
is a potential method to either treat or cure genetic-related human illnesses.

• In 2015, a team of researchers at the Harvard Medical School and the Boston Children’s Hospital
stated that they were able to restore basic hearing in genetically deaf mice using gene therapy. The
Boston Children’s Hospital research team also reported that they have restored a higher level of
hearing-down to 25 decibels which is actually equivalent to a whisper. They used an improved gene
therapy vector developed at the Massachusetts Eye and Ear that was identified as “Anc80” which
enables the transfer of genes to the inaccessible outer hair cells when introduced into the cochlea
(Fliesler, 2017).

• Human gene therapy was actually first realized in 1971 when the first recombinant DNA experiments
were planned. It can be simply viewed as insertion foreign DNA into a patient’s tissue that hope to
successfully eradicate the targeted disease. It was actually inspired by the success of recombinant DNA
technology which occurred over the last 20 years. Without a doubt, gene therapy is the most promising
yet possibly unfavorable medical field being studied.

The Basic Process

There are several approaches to gene therapy. These are the following (Fliesler, 2017):

● Replacement of mutated gene that causes disease with a healthy copy of the gene.

● Inactivation of a mutated gene that is functioning improperly.

● Introducing a new gene into the body to help fight disease.

In general, a gene cannot be directly inserted into a human gene or cell. A gene is inserted into another
gene using a carrier or vector. At present, the most common type vector are viruses that have been
genetically changed to carry normal human DNA. Viruses have evolved a way of encapsulating and
transporting their genes to human cells in a pathogenic manner (Science Daily, 2017).

Two Types of Gene Therapy

The idea of gene therapy is based on correcting a disease at its root fixing the abnormal genes that
appear to lead to certain diseases. There as essentially two forms of gene therapy.

1. Somatic gene therapy. It involves the manipulation of genes in cells that will be helpful to patient but
not inherited to the next generation (Nimsergern, 1988)

2. Germ-line gene therapy. It involves the genetic modification of germ cells or the origin cells that will
pass the change on to the next generation (Your Genome, 2017)
In the given diagram, (1) germ-line gene therapy, the gene therapy or gene editing is introduced at the
embryonic stage. Thus, all cells contain the gene(s) that need(s) to be repaired. Since the entire genome
(total of all genes of an individual) of the patient is edited, these genes can be passed on to the next
generation. (2) In somatic gene therapy, certain organ of the body has only received the edited gene,
thus the edited gene will not be passed on to the next generation

@ROMELYN
Stem Cell Gene Therapy and Stem Cell Therapy

• Stem cells are mother cells that have the potential to become any type of cell in the body. • One of the
main characteristics of stem cells is their ability to selfrenew or multiply while maintaining the potential
to develop into other types of cells.

• Stem cells can become cells of the blood, heart, bones, skin, muscle, brain, among others.

• There are different sources of stem cells and they have different capacities to develop into multiple
types of cells.

• Stem cells are derived from different sources. Two of which are embryonic and somatic stem cells. o
The embryonic stem cells are derived from a four-or five-day-old human embryo that is in the blastocyst
phase of development. The embryos are usually extras that have been created in IVF (in vitro
fertilization) clinics where several eggs are fertilized in a test tube then implanted into a woman (Crosta,
2013).
o The somatic stem cells are cells that exist throughout the body after embryonic development and are
found inside of different types of tissue.

▪ These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels,
skeletal muscles, skin and the liver.

▪ They remain in a nondividing state for years until activated by disease or tissue injury.

▪ These stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types
from the originating organ or even regenerate the entire original organ.

▪ It is generally thought that adult or somatic stem cells are limited in their ability to differentiate based
on their tissue of origin, but there is some evidence to suggest that they can differentiate to become
other cell types (Crosta, 2013).

The Bioethics of Gene Therapy

There are ethical issues involved in gene therapy. Some of the inquiries cited are (Genetics Home
Reference, 2017):

1. How can “good” and “bad” uses of gene therapy be distinguished?

2. Who decides which traits are normal and which constitute a disability or disorder?

3. Will the high costs of gene therapy make it available only to the wealthy?

4. Could the widespread use of gene therapy make society less accepting of people who are different?

5. Should people be allowed to use gene therapy to enhance basic human traits such as height,
intelligence, or athletic ability

Another controversy that involves the germline therapy is genetic modification of germ cells that will
pass the change on the next generation. There are a lot of questions on the effects of the gene
alteration to the unborn child and the next generation, since the alteration can be passed on. In the
United States, the government does not fund researches on human germline gene therapy.