Putting GMOs in Perspective by Levone


									“Tinkering with Nature: Food and Medicine in the Genomic Age”
May 30, 2002

Part I: Putting GMOs in Perspective
James N. Siedow, Ph.D.

Part II: Gene Therapy: The Science and the Ethics
Michael Yudell, MPH, M.Phil.

Part I: Putting GMOs in Perspective
James N. Siedow, Ph.D.
Vice Provost for Research
Professor of Biology
Developmental, Cell and Molecular Biology Group
Duke University

The “Green Revolution” has come about in large part because of our understanding of
• Genetic modification of plants began in the 1700s and 1800s, when farmers figured out that
   they could cross plants. “Non-natural” genetic manipulation occurred long before the
   development of genetic engineering techniques, and almost all the food we eat has been
   genetically modified from the original wild type plant in some way.
• Because of large-scale understanding of the principles of genetics in the early 1900s,
   systemic hybrid breeding began to take place to exploit naturally occurring mutations.
• In the 1940s, inducing genetic mutations through radiation or chemical treatments began.
• In the last 20 years, recombinant DNA technology developed to the point that production of
   genetically modified organisms (GMOs) became possible. The term is used to apply to
   organisms — plant or animal — that are manipulated using genetic engineering techniques.
• In 1906, Luther Burbank said that we have now advanced our knowledge of genetics to the
   point where we can manipulate life in a way never intended by nature. This statement could
   appear in any current article about GMOs.

Improving on nature — selecting genes that code for desirable traits in plants.
• The most common GM crops currently being planted include genes that provides insect
   resistance and those providing resistance to certain herbicides (usually Round-Up).
• These are known as input traits; they benefit the farmer (who uses less pesticide or
• Output traits (which are more important to the consumer) currently in development include
  delayed ripening and healthy oil composition.
• A number of genetically engineered traits are in the pipeline, including resistance to a
  number of herbicides.

Short history of GM crops:
• The first genetically enhanced plants were introduced in 1996.
•   With an exponential increase in the amount of GM crops being planted, much more is now
    known about them and whether genetic manipulation actually accomplishes what is intended.
•   Since the introduction of GM crops, pesticide use has dropped significantly, particularly on
    GM insect-resistant cotton (reducing pesticide usage by millions of pounds). Since pesticide
    use can lead to groundwater contamination, this is a real benefit (before GM cotton, about 40
    percent of all pesticides used in the U.S. were applied to cotton plants).
•   Anecdotal evidence indicates an increase in insect diversity because of decreased pesticide
•   Herbicide levels in the soil have decreased somewhat following introduction of GM
    herbicide-resistant crops. But the real benefits occur because the herbicide the plants are
    resistant to — Round-Up — breaks down quickly into innocuous compounds and is
    replacing much longer-lived herbicides (some of which are considered groundwater
    pollutants by the EPA).
•   The reduced number of pesticide applications means that there’s less tillage, so top soil is
    better preserved.

Objections to GM crops:
• GM crops can cross-pollinate with wild crops
• GM crops that enter the food supply may cause allergic reactions or even be toxic to some.
• GM crops may be toxic to other organisms in the environment (e.g., the Monarch butterfly)
• GM crops may lead to the development of “super weeds”

Testing of GM crops
• Some argue: “These plants have been tested to death.”
• Three federal agencies oversee various aspects of the testing of GM crops [see “Food Safety:
   A Team Approach” http://www.cfsan.fda.gov/~lrd/foodteam.html].
• There were perhaps 10,000 field trials before GM crops were released in 1996.
• Most tests are performed to assure that plants are stable.
• Testing to demonstrate that the crops don’t contain any unexpected compounds that might
   prove to be toxic probably goes beyond what’s necessary (naturally occurring crops do not
   undergo such scrutiny).
• A recent report by the General Accounting Office (GAO) said that the current screening is
   adequate, but in light of public concern, additional steps are recommended. The GAO report
   noted that the current GM crops are totally safe.

Concerns about cross-pollination between GM and conventional crops or with wild-type
• This is not a new problem — this has occurred for thousands of years
• For the three most popular GM crops — corn, soybeans, and corm — there is no wild
    relative in the U.S.

Concerns about allergens and toxins in GM crops:
• Any new food can be allergenic or toxic to some people (example: kiwi fruit).
• Because GM crops undergo extensive testing before they reach market, they are unlikely to
  be allergenic or toxic. But, of course, the chances are greater with GM crops compared to
  conventional crops.
•   The StarLink corn issue: marketing the corn as cattle feed, when the chance of getting into
    the food supply was significant, “was a tremendously stupid business decision for that
•   Genetic modification also may produce foods that are less allergenic or toxic; right now,
    scientists are working on a variety of wheat that can be eaten by those with a wheat allergy.

Food labeling issues:
• About two-thirds of all processed foods contain GMOs (mostly because of soybeans)
• FDA policy: encourage voluntary labeling by manufacturers
• FDA regulations state that food labeling is mandatory when there’s an issue of health and
• The European Union banned GMO-containing foods four years ago and is demanding
   labeling of U.S GMO-containing food exports.2

For more information:
American Society of Plant Biologists—Statement on Genetic Modification of Plants Using
Biotechnology http://www.aspb.org/publicaffairs/aspb_statement_on_genetic_modifi.cfm (Dr.
Seidow is chair of the ASPB public affairs committee)

“Frankenfood’ Frenzy” (Reason Online): http://reason.com/bi/bi-gmf.shtml. Has numerous links
to sites for and against GMOs.

Pew Initiative on Food and Biotechnology: http://pewagbiotech.org/ . News and information on
agricultural biotechnology and genetically modified food from an independent and objective
source for the public, media and policymakers.

  StarLink is a corn variety that has been genetically modified to contain an insecticidal protein derived from a
naturally occurring bacterium (Bacillus thuringiensis, or Bt.) The Environmental Protection Agency (EPA)
approved the gene-spliced variety of yellow corn in 1998 for use only as animal feed and set a zero-tolerance level
for its use in human food based on the fact that this particular Bt protein — Cry9C — does not break down easily in
the human digestive system, is heat resistant, and could prove allergenic. StarLink corn was detected in taco shells in
mid-September 2000. The discovery resulted in the recall of numerous food products. More information can be
found at: http://www.ncseonline.org/nle/crsreports/agriculture/ag-101.cfm.
  With war looming in Iraq, the Bush administration decided on February 4, 2003, against antagonizing its European
allies and has postponed filing a case against the European Union for its ban on genetically modified food. Robert B.
Zoellick, the United States trade representative, had warned that the administration would decide by early February
whether to sue the Europeans for what he called their "immoral" opposition to genetically modified food that was
leading to starvation in the developing world. Zoellick said that he believed genetically modified food could help
alleviate hunger worldwide and that he wanted the European opposition to be confronted and unfounded fears erased
so that developing nations would accept food from genetically modified crops. Experts agree that the United States
could win a case at the World Trade Organization and force a lifting of the four-year old ban. The ultimate
resolution of this case, however, will rest on labeling not food aid and promises to pit European ideas of food
regulation against American notions about free trade. Many European consumers are demanding labels that identify
which foods have been genetically modified, while the American agricultural industry is just as strongly opposed to
labeling, saying it gives the food a negative connotation.
“Risks and Benefits of Genetically Modified Food.” Univ. of Washington forum exploring the
controversy surrounding GM food. http://scope.educ.washington.edu/gmfood/

Pure Food Partners: http://www.purefoodpartners.org/ . Includes links to N.C. Citizens for Safe
Foods and The Campaign to Label Genetically Engineered Foods.

Part II: Gene Therapy: The Science and the Ethics
Michael Yudell, MPH, M.Phil.
Graduate Research Fellow
Molecular Laboratories
American Museum of Natural History

Some facts about genomes, a.k.a. the “language of God” (President Bill Clinton), “the book
of life,” “the body’s instruction manual.”
• Humans and mice have 90 percent of their genes in common; humans and fruit flies, 36
     percent, humans and zebra fish, 85 percent.
• There are 3.2 billion units of DNA in each human cell.
• An unraveled piece of human DNA would be 6 feet long.
• The first draft of the Human Genome Project was completed in June 2000.
     (http://www.ornl.gov/hgmis/medicine/genetherapy.html for information on the project and
     excellent links)

What do Americans know about genes? Some survey results*:
• 50 percent know that DNA is made up of genes.
• 29 percent have heard of the Human Genome Project.
• 60 percent know what genetically modified (GM) foods are.
• 70 percent think they haven’t eaten GM foods (in fact, almost all of us have — by consuming
  corn and soybean products, the majority which are genetically modified).

*Date of poll unknown.

Gene therapy:
• Somatic cell gene therapy delivers into an organism’s cells one or more genes that are
  missing or malfunctioning. This type of gene therapy has been accomplished in animal
  models and is under investigation in humans.
• Germline therapy — when germ cells are altered with the goal of passing those changes
  along to offspring. (see http://research.mednet.ucla.edu/pmts/Germline/questions/qlist.htm
  for more information). This has not been accomplished in humans.
• The most commonly used method for delivering genes into cells is to use a viral vector. The
  foreign gene is spliced into the viral genome; the viruses infect the cells and insert their
  modified genome into the host’s DNA.
• Problems with using viral vectors include toxicity, immune and inflammatory responses, to
  the virus, as well as difficulty in controlling exactly where the new gene is inserted.
• Researchers are exploring novel methods for delivering genes, since the use of viral vectors
  is fraught with problems and potential dangers.
Gene therapy clinical trials:
• The first gene therapy clinical trial in the U.S. (in 1990) aimed to treat adenosine deaminase
  (ADA) deficiency, a rare disease caused by a single gene mutation that results in a severe
  immunodeficiency. The immune status of the two children who underwent treatment
  improved after they received the gene therapy; however, it worked for only a few months and
  had to be repeated several times over the next two to three years. Some of the re-engineered
  cells still exist and are producing ADA, but the children still require supplemental ADA.
• Clinical gene therapy trials involving numerous types of cancer, immunodeficiencies, blood
  disorders, and other diseases, are overseen by the National Institutes of Health’s Office of
  Biotechnology Activities (NIH OBA): http://www4.od.nih.gov/oba/rac/trialqueryform.asp.
• The death of 18-year-old Jesse Gelsinger in 1999 tragically illustrates dangers of gene
  therapy. He suffered from ornithine transcarbamylase (OTC) deficiency, a rare metabolic
  disorder involving the liver, but it was controlled with a low-protein diet and drugs.
  Gelsinger was given the experimental treatment (an OTC gene carried by an adenovirus
  vector) even though his blood ammonia levels — a measure of liver failure — were higher
  than the highest allowable level deemed safe for the experiment. Moreover, that highest
  allowable level had previously been raised by the researchers without the knowledge or
  permission of the FDA.
• An ongoing trial in France using retrovirally transformed hematopoietic stem cells to treat
  four children with severe combined immunodeficiency disease appears to be successful.3

Ethical issues surrounding gene therapy:
• The primary aim of gene therapy is to treat diseases. Should it be used to enhance our genetic
   makeup — make us taller, faster, smarter?
• The line between gene therapy and genetic enhancement is a bit blurry.
• The Gelsinger case spotlights several medical and ethical issues:
           o what constitutes appropriate informed consent
           o how does the profit motive affect researchers and institutions
           o what assurances do we have that researchers follow approved protocols — strict
               government oversight of research protocols is important to patient safety

For more information:
American Society of Gene Therapy — Statement on Adverse Events in French Trial:
http://www.asgt.org/press_releases/01132003.html .

Society, Religion and Technology Project — Ethics of Gene Therapy.

Access Excellence — Issues and Bioethics. http://www.accessexcellence.org/AB/IE/#Anchor-
Gene-35326 .

 On 1/14/03, the Food and Drug Administration (FDA) issued a clinical hold for clinical trials using such stem cells
after two of 10 infants in the French trial developed T-cell leukemia (for statements from the FDA and the NIH:
http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html and http://www4.od.nih.gov/oba/RAC/X-

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