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Study Guide in GE 6: Science, Technology, and Society Module No. 12

STUDY GUIDE FOR MODULE NO. 12

GENETICALLY MODIFIED ORGANISMS (GMOs) AND GENE

THERAPY
MODULE OVERVIEW

According to Bragdon in the module released by Biodiversity International entitled “Law and policy of
relevance to the management of plant genetic resources”, biotechnology uses biological systems, living
organisms, or derivatives thereof, to make or modify products or processes for specific use. Biotechnology
includes such early practices as selective breeding of farm animals and using microorganisms to make wine
and cheese. Today, biotechnology also encompasses genetic engineering, the direct manipulation of genes
for practical purposes. Genetic engineering has launched a revolution in biotechnology, greatly expanding the
scope of its potential applications. Tools from the DNA toolbox are now applied in ways that affect everything
from agriculture to criminal law to medical research. Modern biotechnology gives scientists molecular tools for
obtaining a better understanding of the structure and function of genes in living organisms. Modern
biotechnology has aimed to develop new precision tools and diagnostics; speed up breeding gains and
efficiency; develop pest- and disease-resistant crops; combat salinity, drought, and problems of agriculture;
enhance the nutritional quality of food; increase crop varieties and choice; reduce input and production costs;
and increase profits.

This module discusses two applications of genetic engineering: genetically modified organisms and
gene therapy. GMOs and gene therapy are both powerful technologies with the potential to improve our lives.
However, it is important to use these technologies responsibly and to carefully consider the potential risks and
benefits.

MODULE LEARNING OUTCOMES

At the end of this Module, you should have:

1. discussed the ethics and implications of GMOs and potential future impacts;
2. described gene therapy and its various forms;
3. explored the opportunities that may be opened by gene therapy in the future; and
4. assessed the potential benefits and detriments to global health of GMOs and gene therapy

GENETICALLY MODIFIED ORGANISMS (GMOs)

A genetically modified organism (GMO) is one that has acquired by artificial means (through
recombinant DNA methods, gene modification, or transgenic technology) one or more genes from another
species or even from another variety of the same species. The majority of the GM organisms that contribute
to our food supply are crop plants. GM crops are widespread in the United States, Argentina, and Brazil;
together these countries account for over 80% of the world’s acreage devoted to such crops.

Most methods for cloning pieces of DNA in the laboratory share certain general features. One
common approach uses bacteria, most often Escherichia coli. E. coli chromosome is a large circular molecule
of DNA. In addition, E. coli and many other bacteria have plasmids, small circular DNA molecules that
replicate separately from the bacterial chromosome. A plasmid has only a small number of genes; these
genes may be useful when the bacterium is in a particular environment but may not be required for survival or
reproduction under most conditions.

To clone pieces of DNA in the laboratory, researchers first obtain a plasmid and insert DNA from
another source (“foreign” DNA) into it. The resulting plasmid is now a recombinant DNA molecule. The
plasmid is then returned to a bacterial cell, producing a recombinant bacterium. This single cell reproduces
through repeated cell divisions to form a clone of cells, a population of genetically identical cells. Because the
dividing bacteria replicate the recombinant plasmid and pass it on to their descendants, the foreign DNA and
any genes it carries are cloned at the same time. The production of multiple copies of a single gene is called
gene cloning.

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Roles of GMOs

Currently, GMOs play many significant roles and have several benefits in different areas. Mainly,
GMOs have seen its most prominent role in agriculture, which resulted in having greater crop yields, having
resistance to pests, diseases, and droughts. Examples include Bt corn, Bt cotton, Bt talong (where corn,
cotton, and eggplants have been modified with gene from Bacillus thuringensis which make them resistant to
certain pests) rainbow papaya (where protein from papaya ringspot virus was introduced to papaya), and
Roundup Ready soybean (where the herbicide glyphosphate was introduced to soybeans to resist certain
herbicides). These GMOs include the additional benefit of reducing pesticide use, maintaining healthy soil,
and sustaining agricultural productivity throughout the year. Developments also led to nutritional
enhancement of crops, such as Golden Rice, where beta-carotene was introduced to rice which fortified it with
vitamin A; shelf-life preservation, such as Arctic apple, which prevents early browning, and Flavr Savr tomato,
which reduces softening; increased growth rate, such as AquAdvantage salmon, where genes was introduced
to Pacific salmon to make them grow faster; and reduced farming waste, such as Enviropig which has less
phosphorus in their waste.

In addition to agriculture, it also has benefits in medicine, biotechnology, and research. Many
medicines and vaccines have been developed more efficiently and cost-effectively with the help of GMOs,
such as the production of vinblastine that is used for cancer treatments such as Hodgkin’s lymphoma using
genetically-modified periwinkle plant; cyclomaltodextrin, which is used as a food flavor enhancer that was
produced by Bacillus modified by Thermoanaerobacter; hepatitis B vaccine from genetically-modified yeast;
and hormones such as human growth hormone and Humulin, a genetically engineered insulin for Type I
diabetes patients. Others have uses in research such as production of fluorescent proteins used in
microscopy by genetically modified bacteria, GMOs used as vectors and model organisms, among others.
They can also be used for bioremediation (e.g., Nicotiana glauca or shruc tobacco, where it was modified with
phytochelatin TaPCSI1 to help it accumulate high levels of zinc, lead, cadmium, nickel, and boron and
produce high biomass.

GMOs have also found some applications in several industries such as flower production (e.g., Blue
Rose, where 31,51-hydroxylase gene was introduced), paper production (e.g., poplar trees, where genes that
code for ferulic acid was inserted to modify lignin structure), and silk production from genetically modified
bacteria.

Potential Risks of GMOs

Many are concerned with the effect of GMOs in human health. Some believe that it might cause
allergic reactions, unintended mutations, resistance to drugs, change in the balance of microorganisms in the
body, or produce unintended toxins. It may also change the nutritive value of food or cause persistence of
genes in GMOs after consumption, which could have negative effects to human health.

There are also legitimate environmental concerns, such as crossbreeding of GMO and non-GMO
organisms which would have unintended negative environmental impacts; disrupting evolutionary processes
such as creation of new pest and weed resistance, new diseases, and new negative interactions between
organisms; and reduction in biodiversity.

Moreover, it has also some perceived social, economic, ethical and cultural issues. Some are
concerned that those which hold information in the creation of GMOs will hold the economic power, which will
control the market and food supply and may cause suffering of small-scale businesses. Reliance on GMOs
may also reduce the use of traditional farming techniques and traditional plant crops, which will have a
negative cultural impact. There are ethical issues regarding GMOs, such as man “playing God” and violation
of nature.

Many of the risks associated with GMOs have been linked to inadequate studies on its long-term
effects. Thus, it is important that their long-term effects are continuously studied.

Initiatives on Safety from GMOs

1. Codex Alimentarius Commission (Codex). This intergovernmental body created by the Food and
Agricultural Organization (FAO) and World Health Organization (WHO), develops the International
Food Code, which gives the standards for the use of GMOs for food. Some of these guidelines

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include standards for food before it is available to the market and its potential effects,labeling of
products, and determining the source of GMO products.

2. Cartagena Protocol on Biosafety. This is an international environmental treaty under the

Convention on Biological Diversity that regulates the safe transboundary movements, handling, and
use of Living Modified Organisms (LMOs). It requires exporters to seek consent from importers
before its first shipment of LMOs. This is to protect biodiversity, determine risks, and give guidance to
countries where LMOs will be transported to.

3. International Trade Agreement on labeling of GM food and food products. Many organizations
and governments have strict guidelines in labeling products that are genetically modified. This is to
ensure that the consumers are informed and can make the proper choice prior to the consumption of
these products, as well as allow governments to impose its rules regarding trade of GMOs. This is
also a way of ensuring danger prevention concerning GMOs.

The Philippines and GMOs

GMO concern in the Philippines started in the 1990s, with the creation of National Committee on
Biosafety of the Philippines through Executive Order No. 430 of 1990. The NBCP developed guidelines on
the planned release of GMOs and potentially harmful exotic species in 1998.

In 2002, the Department of Agriculture (DA) released Administrative Order No. 8, the guideline for the
transportation and release to the environment of GM plants and plant products. This was also the same year
when GMO started and the same year when the Philippines became the first Asian country to approve
cultivation of GMOs (genetically modified corn). From then until today, there are 70 GMO applications
approved by DA, 62 for food feed and processing and 8 for propagation.

In 2004, the Philippines was classified by International Service for acquisition of agro-biotech
applications as one of the 14 biotech-mega countries which grow 50,000 hectares or more GMO crops
annually. In the same year, Senator Juan Flavier authored a bill on labeling of GM food and food products but
it did not pass. In 2012, Representative Teddy Casiño and other congressmen aimed for the same bill.

In 2005, the Negros Organic Island was established through a memorandum of agreement (MOA)
between Negros Occidental and Negros Oriental. This MOA bans the entry of GMOs to their provinces.

In 2010, the Organic Agriculture Act was issued, encouraging organic-agriculture rather than GMO-
related agriculture. Similar to the Negros provinces, Davao City passed the Organic Agriculture Ordinance in
2010, which prevented the field testing of Bt eggplant in UP Mindanao. Eventually, the Bt eggplant field
testing was put to an end through the Supreme Court in December 2015, nullifying Administrative Order No. 8
of DA.

In March 17, 2016, the DA, DENR, DOST, DOH, and DILG passed Joint Department Circular No. 1,
on rules and regulations for the research and development, handling and use, transboundary movement,
release in the environment, and management of GM plants and plant products using modern biotechnology.
This joint circular paves way to issuances for planting and importing GM crops in the country.

GENE THERAPY

Gene therapy is an application of biotechnology that aims to treat diseases through the transfer of
functional genes to cells which contain defective genes which cause diseases. This may also involve the
modification of existing genes that cause genetic disorders. This may cause the treatment of the disease, as
the functional gene may express functional products. Alternatively, gene therapy may also prevent certain
diseases from happening, especially if the germline is treated.

Gene therapy may be traced back in the 1970s, when the possibility of using genes to treat diseases
was first conceived. Clinical trials of gene therapy followed in the 1980s, with success met in the 1990s when
Ashanti de Silva was treated with a heritable disorder called severe combined immunodeficiency (SCID).
Individuals with SCID have no functional immune system and usually die from what would normally be minor
infections. Because of the treatment, da Silva was able to lead a normal life.

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Following the success of de Silva’s treatment, other clinical trials ensued, including those for cancer,
neurodegenerative diseases, cardiovascular disease, and infectious diseases, such as HIV. Over a 10-year
period, from 1990 to 1999, more than 4000 people underwent gene therapy for a variety of genetic disorders.
These trials often failed and thus led to a loss of confidence in gene therapy.

However, in 1999, Jesse Gelsinger died when being treated of a liver condition using gene therapy.
In the aftermath of the tragedy, several government and scientific inquiries were conducted. Investigators
learned that clinical trial scientists had not reported other adverse reactions to gene therapy and that some of
the scientists were affiliated with private companies that could benefit financially from the trials. Jesse’s death
had dealt a severe blow to the struggling field of gene therapy.

Types of Gene Therapy

Gene therapy can be generally classified into two categories based on the type of cell targeted and
how a disease is treated: somatic gene therapy and germline gene therapy. Somatic gene therapy involves
the integration of functional genes into affected body cells (or somatic cells). This means that the effects will
only be experienced by the individual which received the therapy and not by his or her progeny. On the other
hand, germline gene therapy involves the integration of functional genes to sex cells or gametes. This
means that the effects will be experienced by the progeny of those who undergone the therapy. Germline
gene therapy is rife with many issues due to its implications, which could be seen by the end of this module.

Gene therapy can also be classified according to how invasive it is. In vivo gene therapy is a type of
gene therapy involving the direct delivery of the functional genes to the body, usually intravenously. The use
of viral vectors is usually the technique for this therapy. This type of gene therapy usually has minimal
invasiveness since the delivery of the genes are direct and no cell isolation and manipulation is necessary.
However, this may also trigger certain immune responses and the delivery to the target may also pose some
challenges. An example of this is treatment for hemophilia B, where the gene is delivered intravenously to
target the patient’s liver to ensure production of necessary proteins for clotting.

In situ gene therapy necessitates direct delivery of the gene to the target organ or tissue, usually
through injections or some other gene transfer techniques. This is a more localized approach and does not
necessarily need removal or body parts. However, for it to ensure its effectiveness, delivery of the gene to the
target organ or tissue is necessary. A good example of this gene therapy is for treatment of muscular
dystrophy, where the cells are directly injected to the muscle.

When gene therapy is performed by isolating cells from the body, manipulating the genes of these
cells, and reintroducing them back to the body, the technique is ex vivo gene therapy. Generally, the cells
are cultured to ensure that there is sufficient supply of cells to bring back to the body. The beauty of this
technique is that it allows better testing of the cells and that the cells come from the body of the patient,
ensuring less immune response and higher chances of success. However, the technique is also time-
consuming and may cost more. An example of this is the Chimeric Antigen Receptor (CAR) T-cell therapy,
used in treatment for certain cancers such as leukemia and lymphoma.

Gene therapy can also be classified as gene addition or gene editing. Gene addition therapy
involves putting functional cells inside the body to compensate for genes that are missing or mutated. Usually
used for diseases caused by a single gene, gene addition therapy does not entail the replacement of the
faulty gene; it just provides instructions to the body to produce functional genes.

In contrast to this, gene editing therapy involves the correction of the genes of the patient either by
inactivating the gene that causes the disease or inserting a gene that could correct or repair the mutated
gene. This is usually used for diseases caused by multiple genes.

Stem Cell Gene Therapy

Bodies grow and heal thanks to cells that retain the ability to divide, generating both new cells like
themselves and cells that go on to specialize. Stem cells renew tissues so that as the body grows, or loses
cells to apoptosis, injury, and disease, other cells are produced that take their places.

A stem cell divides by mitosis to yield either two daughter cells that are stem cells like itself, or one
that is a stem cell and one that is a partially specialized progenitor cell. The characteristic of self-renewal is

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what makes a stem cell a stem cell—its ability to continue the lineage of cells that can divide to give rise to
another cell like itself. Our more than 260 differentiated cell types develop from lineages of stem and
progenitor cells.

A fertilized ovum is the ultimate stem cell. It is totipotent, which means that it can give rise to every
cell type, including the cells of the membranes that support the embryo. Other stem cells and progenitor cells
are pluripotent: their daughter cells have fewer possible fates. Some are multipotent: Their daughter cells
have only a few developmental “choices.”

As stem cell descendants specialize, they express some genes and ignore others. All cells, however,
synthesize proteins for basic “housekeeping” functions, such as energy acquisition and protein synthesis.

Many, if not all, of the organs in an adult human body have stem or progenitor cells. These cells can
divide when injury or illness occurs and generate new cells to replace damaged ones. Stem cells in adults
may have been set aside in the embryo or fetus in particular organs as repositories of future healing.
Evidence suggests that some stem cells, such as those from bone marrow, can travel to and replace
damaged or dead cells elsewhere in the body, in response to signals that are released in injury or disease.
Because every cell contains all of an individual’s genetic material, any cell type, given appropriate signals, can
in theory become any other. This concept is the basis of much of stem cell technology.

Stem Cell Sources

1. Embryonic stem (ES) cells are not actually cells from an embryo but are created in a laboratory dish
using certain cells from a region of a very early embryo called an inner cell mass (ICM). Some ICM
cells, under certain conditions, become pluripotent and can self-renew—they are stem cells. The ICM
cells used to derive ES cells can come from two sources: “leftover” embryos from fertility clinics that
would otherwise be destroyed, and from nuclear transfer, in which a nucleus from a person’s somatic
cell is transferred to an egg cell that has had its own nucleus removed.

2. Induced pluripotent stem (iPS) cells are somatic cells that are “reprogrammed” to differentiate into
any of several cell types. This change may require a journey back through developmental time to an
ES cell-like state, then to specialize anew as a different, desired cell type. Or, cells can be
reprogrammed directly into another cell type. Deriving iPS cells does not require the use of any cells
from an embryo.

3. Adult or tissue-specific or somatic stem cells are found in the tissues of fetuses, embryos and
children, and not just in adult bodies. Adult stem cells self-renew, but most are multipotent, giving rise
to a few types of specialized daughter cells. Many potentially valuable adult stem cells are routinely
discarded as medical waste.

Stem Cell Applications

1. Drug discovery and development. Stem cell cultures supply the human cells that are affected in a
particular disease, which may be difficult or impossible to culture. Drugs are tested on these cells.
Using stem cells in drug development can minimize the need to experiment on animals and can weed
out drugs with adverse effects before they are tested on people.

2. Observation for the earliest signs of a disease. Diseases may begin long before symptoms appear
in a person. Researchers are now observing the beginnings of hundreds of diseases—and
discovering new ways to treat them.

3. Implants and transplants for treatments. This approach is not new—the oldest such treatment, a
bone marrow transplant, has been around for more than half a century. Many other uses of adult stem
cells, delivered as implants, transplants, or simply infusions into the bloodstream, are being tested.

4. Reprogramming proteins directly into the body to stimulate stem cells in their natural niches.
Once we understand the signals, we might not need the cells. The applications of stem cells seem
limited only by our imaginations.

Gene Therapy Concerns

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Concerns regarding gene therapy can be roughly subdivided into two categories: scientific and
ethical. Scientific concerns mainly delve into questions regarding the feasibility of conducting gene therapy,
the dangers that the said therapy could pose to human health, and the processes involving gene therapy.
Ethical concerns mainly delve into questions on access to the technology, focus on research, privacy, and
usage.

Scientific Concerns

Most concerns on gene therapy have something to do with safety: that is, how dangerous can the
procedure be done and whether it will have some unwanted effects. Issues such as immune system
response on introduced cells, effects on unintended cell targeting, possibility of gene overexpression, effects
of the inserted gene to other cells and processes, possibility of triggering oncogenes which could cause
cancers, and others are legitimate and serious.

Other issues involve the efficacy of the treatment itself. This depends on certain factors such as
correct identification of cells to treat, number of cells to be treated for a noticeable effect, duration of the
functions of the treated cells, control of the transferred gene, number of sequences that is targeted, route of
gene delivery, number of therapeutic genes necessary for the improvement of a condition, nature of the
disease, and many others. These issues stem from the lack of research and the ethical concerns on gene
research that are currently being obeyed by scientists.

Additionally, questions on reversibility and long-term effects are also concerns of the scientific
community. There is a possibility that any adverse effect of the therapy may cause irreversible damage, and
these damages may cause lethal consequences. There is also limited knowledge on the consequences of the
therapy and studies should still be conducted to have better understanding on this issue.

Ethical Concerns

Ethical concerns on gene therapy include very serious questions. One of which is access to
treatment. Gene therapy will understandably be costly. This poses concern on access to treatment by those
who cannot afford it. Selection of whether a certain individual should get treatment may not be driven by
need, but through finances.

Discrimination is another issue that gene therapy may pose. This works on different levels. For
example, some researchers may feel that certain diseases should be studied much further than others,
causing discrimination to other diseases which also need attention. This could also show in our treatment of
those who are different when gene therapy becomes a norm; that is, we may treat others differently due to
them having certain diseases. Some institutions, like insurance companies and employers, may also
discriminate against those who have certain diseases which can or cannot be treated due to gene therapy.
There could be a possibility of mandatory genetic testing in these institutions to determine whether one has a
potential to become ill of a certain genetic disease, which is viewed nowadays as discriminatory.

Privacy is another concern. Since genetic information is personal information, there are questions
regarding the security of this information provided, who holds it, and who can have access to it. This is
especially true nowadays when information is stored electronically. Another concern is the amount of
information one needs to provide to have proper treatment.

Because of lack of understanding of the public regarding gene therapy, this may also cause issues on
informed consent and whether a certain patient truly understands the procedures he or she will undergo. This
is particularly important since our knowledge on the long-term effects of gene therapy is very limited, and this
lack of knowledge may affect the acceptance or rejection of treatment.

Many concerns also delve towards the proper use of germline gene therapy. For example, whether
gene therapy could cause eugenics to proliferate and whether gene therapy could be applied for unfair
enhancement of human traits are valid and legitimate concerns. This could cause an extermination of certain
sectors of society and decline in diversity.

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The progress of gene therapy research is also affected by concerns regarding deaths among
volunteers and entry of the injected gene into the germline. As these are possibilities, this may cause
complications on whether research efforts should be discontinued or not.

Even the most basic questions such as what is considered a disorder that needs to be treated,
whether germline therapy should be practiced, and the line between responsible and irresponsible usage of
gene therapy is very difficult to answer. It is therefore no wonder that gene therapy is still considered a highly
polarizing issue by many.

SUMMARY

 Biotechnology uses biological systems, living organisms, or derivatives thereof, to make or modify
products or processes for specific use.
 Genetic engineering or the direct manipulation of genes for practical use has brought revolution in
biotechnology.
 Genetically modified organism (GMO) is acquired by artificial means (through recombinant DNA
methods, gene modification, or transgenic technology) one or more genes from another species or
even from another variety of the same species.
 Benefits of GMOs are mostly for agriculture and medicine.
 Potential risks of GMOs are of human health, biodiversity, animal welfare and also ethical issues
such as violating the rule of nature.
 Gene therapy is a therapeutic technique that aims to transfer normal genes into a patient’s cells.
 Stem cells renew tissues so that as the body grows, or loses cells to apoptosis, injury, and disease.

REFERENCES

 MacNamara, D., Valverde, V., and Beleno, R. (2018). Science, Technology, and Society. pp. 96-104.
Quezon City: C&E Publishing.
 Serafica, J., et al. (2018) Science, technology and society. pp. 122-132. Quezon City: Rex Bookstore.
 Dubock, A. (2014). The politics of golden rice. GM Crops & Food, 5(3), 210-222.
 Duguet, A. et al. (2013). Ethics in Research with Vulnerable Populations and Emerging Countries:
The Golden Rice Case. Journal of International Law and Commercial Regulations, 38(4), 979-1013
 Silici, Laura. (2014). Agroecology What it is and what it has to offer. IIED Issue Paper.
 MacNamara, D., Valverde, V., and Beleno, R. (2018). Science, Technology, and Society. pp. 109-
114. Quezon City: C&E Publishing.
 Serafica, J., et al. (2018) Science, technology and society. pp. 165-169. Quezon City: Rex Bookstore.

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