Biotechnology: reading between the lines of science and safety Why has regulation proved to be so difficult?

1
Biotechnology reading between the lines of
science and safetyWhy has regulation proved to
be so difficult?

• Jada M. Hueber
• 2002

2
Biotechnology reading between the lines of
science and safety

• Where did genetic engineering come from?
• Where can we find genetically modified organisms
  today?
• What are some reasons for support / concern?
• Are genetically modified organisms regulated by
  the government?
• Is biotechnology safe?

3
Genetic Engineering background

• 1966 Marshall Nirenberg Har Gobind Khorana
  finished unraveling the genetic code.
• 1973 Herbert Boyer Stanley Cohen performed
  the first recombinant DNA cloning experiment
  using restriction enzymes to insert DNA into a
  plasmid and use the transgenic plasmid (a
  circular bacterial 'chromosome') to transform
  bacteria.
• 1980 U.S. Supreme Court rules that living
  organisms can be patented.
• 1983 First transgenic plant (tobacco).
• 1985 First transgenic plant produced--
  resistant against a definite insect species.
• 1987 A transgenic plant produced resistant to
  a particular kind of herbicide.

4
GMO History continued...

• 1988 First transgenic plant producing a
  pharmaceutical.
• 1994 Transgenic tomatoes contain a softening
  inhibition gene. These FlavrSavr tomatoes are
  sold in stores for a short time before being
  taken off the market.
• 1998 April, a UK supermarket chain bans use
  of GMOs in its products, a move which over the
  following 18 months is followed by the other UK
  supermarket chains. May, widespread contamination
  of the UK canola crop by GM oilseed rape
  contaminated seed imported from Canada by
  Advanta.
• Some sources cite Gregor Mendel, the Austrian
  Monk who studied genetics in pea plants, as the
  first genetic engineer. This brings to question,
  what is the difference between the modern science
  of biotechnology and plant breeding for desired
  traits which has been going on for centuries?
  Keep this question in mind...

5
The Science of Genetic Engineeringmaking a
modified gene
Isolate desired gene (increased shine)

Isolate plasmid DNA (apple)
Gene inserted into plasmid.
Grow in culture to replicate.
Insert modified plasmid into bacterium for
replication.
6
Making the transgenic cell ...and growing
GMOs!
Bacterium inserts DNA into plant cell.
Transfer copies into carrier bacterium.
A. tumefaciens (agrobacterium)
Grow cells in culture to form plantlets.
Transgenic cell
Cell division
Transgenic plants with new traits!
Transfer to soil
7
Where can I find GMOs?

• All of these brands, and many more, have been
  identified as using GMOs in their ingredients.
  Sometimes, as in the case of Gerber baby foods,
  the product is found to contain GMOs despite
  company efforts to discontinue the use of GM
  crops.

Kelloggs, Kraft, McDonalds, Nestle USA, and
Quaker Oats all sell foods with GM ingredients in
the U.S. but not in their products overseas where
consumer opposition is strong.
8
The growing popularity of GE crops

• In January, the International Service for the
  Acquisition of Agri-biotech Applications (ISAAA)
  announced that global acreage of GE crops
  increased 19 in 2001 (130 million acres).
• From 1998 to 1999, global GE crop acreage grew
  143.

9
Who grows GE crops?

• Three countries produce more than 95 of the GE
  crops in the world Argentina, Canada, and the
  United States.
• Only four crops are currently being grown on a
  large scale canola, corn, cotton, and soybeans.

10
What good are GMOs?
Imagine medicinal fruits that help prevent
illness...
Golden Rice is engineered to contain
beta-carotene, a vital nutrient that can prevent
blindness in malnourished children.
Crops can defend themselves against pests and
viruses, decreasing the amount of chemicals used
by farmers.
Crops can be engineered to thrive in previously
inhospitable soils, giving farmers in developing
nations a livelihood.
Produce can be designed to be healthier, less
fattening, etc...
Imagine food enough to feed the world...
Photos www.thebiggestpixel.com/people01.html
www.picturesof.net
11
Substantial Equivalence a new variety of food
must be as safe as traditionally bred varieties
and foods.

• Summary of safety assessment
• Compositionally equivalent to conventional
  varieties
• Nutritionally equivalent and perform comparably
  to conventional varieties in food production and
  for livestock and poultry feed.
• Contains protein that is proven safe for
  consumption.

12
Regulation jurisdiction the Coordinated
Framework system

• A) If the biotech product is a microbe, the EPA
  regulates it.
• B) If the biotech product is a plant or insect,
  USDA-APHIS regulates it.
• C) If the biotech product is a food or medicine,
  the FDA regulates it.
• D) If the research was funded by the federal
  government, the National Institutes of Health
  (NIH) or USDA regulates the product of the
  research.

13
The Four Principles of Regulatory Review

• 1) federal government regulatory oversight should
  focus on the characteristics and risks of the
  biotechnology product and not the process by
  which it is created

2) for biotechnology products that require
review, regulatory review should be designed to
minimize regulatory burden while assuring
protection of public health and welfare
3) regulatory programs should be designed to
accommodate the rapid advances in biotechnology
and
4) in order to create opportunities for the
application of innovative new biotechnology
products, all regulation in environmental and
health areas should use performance standards
rather than specific rigid controls or specific
designs for compliance.
14
Federal regulators seek to protect human safety,
intellectual property rights of individuals and
corporations, and the genetic integrity of
existing plant and animal species...
In 1980, the U.S. Supreme Court allows patents of
living organisms because biotechnology procedures
had made possible a human invention from a
naturally-occurring organism.
the conundrum
Genetically modified organisms are substantially
equivalent to conventional varieties. Therefore,
they dont require labeling.
Genetically modified organisms are not products
of nature, but human invention. Therefore,
they are able to be patented.

15
Corporate v. Consumer Demands labeling
The New York Times reported that a biotech
industry poll showed that 93 of Americans wants
genetically engineered foods labeled.
The American Government and the biotech industry
are concerned that labeling will be misleading to
consumers, since they claim traditional crops and
GE crops substantially equivalent. Consumer
Advocates claim that the popularity of GMOs has
to do with the fact that consumers are not given
the choice, because they are not fully informed
about what they are purchasing.
H.R. 3377 Genetically Engineered Food Right to
Know Act label United States Government Notice
This product contains a genetically engineered
material, or was produced with genetically
engineered material.
16
Environmental issues

• The biotech industry claims that genetically
  modified organisms will be good for the
  environment.
• So why are environmentalists worried?

17
Biotechnology has the potential to create more
and better sources of food, to reduce pesticide
use, increase yields, and improve nutrition and
quality of life. Dr. Sally McCammon, USDA
Animal and Plant Health Inspection Service
Studies reported by the Monsanto Corporation
suggest that crops engineered to be
herbicide-tolerant reduce the use of agricultural
chemicals, and therefore, contamination of the
environment. This practice of choosing the best
combination of tools to control crop pests is
called Integrated Pest Management (IPM).
Percent of samples
Total major corn herbicide concentration
18
When I started farming 23 years ago we didnt
use the most powerful chemicals on the market, we
didnt flood the land with fertilizer, and we
still made a good living...Our gross revenue to
expense ratio was 3 to 1. Today, we are on the
cutting edge, using GMOs, changing crop varieties
almost yearly, using chemicals as if we farmed in
Europe, and our revenue to expense ratio has
dropped to 1.25 to 1, on a good year, just enough
to pay the grocery bill. Lloyd FearRed River
Valley, Manitoba

• Growers planting RR crops have three choices
  regarding weed control
• Apply early to avoid early-season yield losses
  from fast growing grasses, possibly suffering
  yield losses from late season weeds
• Delay applications until most weeds have
  germinated, risking loss of yield to early weeds
  or,
• Apply Roundup twice or more, and/or a residual
  herbicide at planting or when Roundup is applied.

19
It is not clear which are greater the
successes of modern high-intensity agriculture,
or its shortcomingsA greener revolution is
needed a revolution that incorporates
accumulated knowledge of ecological processes and
feedbacks, disease dynamics, soil processes and
microbial ecology (Tilman 1998).
In one situation, after the first two
applications of Roundup Ultra (total of 60 oz/A)
weeds had survived. They were eventually
controlled by a third application of 48 oz/A.
Further tests were done involving RR crops and
weed management. The effective rates were at or
above typical field use rates (32 oz).
Everyone expects that a higher percentage of
soybean acres will be planted to GMO varieties
and that most farmers doing so will need to apply
two or three applications of two or more
herbicides. Charles M. Benbrook, PhD.
20
the combined result of
survival, reproduction, and dispersal.
Spread
Without a quantitative estimate of spread, risk
analysis is doomed to anecdotal status
Asymptotic Rate of Spread (ARS)-- in units of
distance/time, the rate at which an genes aerial
range increases in radius.
Virtually all spread models predict that at
first the observed rate of spread will be slow
and will gradually accelerate to some asymptotic
maximum rate. Thus, without some form of
quantitative analysis, it is not wise to conclude
spread will be negligible simply because after
one generation, most genetically engineered
organism or genes are discovered close to their
initial point of release (Kareiva, et al. 1991).
21
Gene-Spread model yellow circles spread and
increase in frequency as a result of dispersal
and selection.
Spatial distribution of genotypes
Disperse pollen
Mating seedling production
Selection in favor of to get next generation
22
Spread is of particular concern regarding
biodiversity and the creation of superweeds...

• Superweeds develop if herbicide-tolerant modified
  crops cross-breed with weedy relatives. The
  resulting plants would be resistant to the
  herbicide.

S
The concern is similar for insects. Will natural
selection lead to a population of insects
unharmed by modern pesticides?
In the field, natures predisposition to
adaptation has made things more complicated.
23
Initially it was stated that it was extremely
unlikely that Roundup resistance would appear in
weeds. Shortly after these statements were made
the first case of Roundup resistance appeared in
Australia...
According to Bob Hartzer of Iowa State
University Herbicide resistance is defined as
the inherited ability of a weed to survive a
herbicide dose that kills the wild type of that
species. The two important points of this
definition are 1) the ability to survive the
herbicide is genetic and passed along to progeny,
and 2) the native population is controlled by
the herbicide.
24
RR

• Researchers have documented glyphosate resistance
  in a rye grass species.
• Waterhemp was highlighted in the 1998 edition of
  the Weed Control Manual as the most worrisome Up
  and Coming Weed nationwide due to the emergence
  of resistance to triazine and ALS herbicides and
  its ability to withstand Roundup applications.

The Roundup Ready system cost an amazing 68.77
per acre in 1999. Fifty percent more than the
cost of seedweed management systems in recent
years, largely because farmers had to use more
chemicals.
25
A pest management system that relies
predominantly on one tactic is inherently
vulnerable. The more generations of a pest in a
season, and the longer the pest is subject to
selection pressure from a single tactic, the
greater the odds the pest will adapt around the
tactic and adapt quickly.
Charles M. Benbrook, PhD.

• When Bt-transgenic crops were introduced,
  Monsanto admitted that resistance was a
  possibility, but unlikely if a 5 percent buffer
  zone of traditional plants was planted as well.
  Then the following discoveries were made
• Bt endotoxin expression under field conditions
  is not uniform, providing some insects with a
  chance to avoid plant tissues delivering a lethal
  dose.
• Resistance gene to Bt endotoxin appears to be a
  dominant trait.
• Bt-corn can adversely impact populations of key
  beneficial insects.
• Resistance to Bt is not as rare as previously
  suspected.

Since the release of these studies, Monsanto
increased the necessary safe buffer zone to 50
percent.
26
Antibiotic Gene Markers

• AGM are used to identify transferred cells
  within the DNA, but many worry that the genes
  could inadvertently be transferred to humans,
  decreasing the effectiveness of some antibiotics.
• Scientific studies show that this is an
  unlikely, but possible scenario, so...
• The genes chosen confer resistance to a narrow
  range of specific antibiotics no longer
  considered important for medical treatment.
  And...
• The FDA has suggested that biotech companies find
  alternatives to antibiotic resistance genes.

27
Allergies!?...
NEW
tissues
The National Academy of Sciences has said that GM
food might cause allergic reactions, some
serious, even life-threatening.
Physicians are not required to report allergic
reactions observed in patients, and there is no
existing registry to record such data. Therefore,
without data being collected and analyzed, stable
conclusions regarding the existence or
possibility of new allergens cannot be made.
Current testing for allergenicity often compares
the new protein with known allergens such as
wheat, peanuts, milk, eggs, and crustaceans.
28
In 1992, the United Nations met in Rio de Janerio
for the Conference on Environment and
Development. The subsequent declaration contained
the following statement.
Principle 15 In order to protect the environment,
the precautionary approach will be widely applied
by States according to their capabilities. Where
there are threats of serious or irreversible
damage, lack of full scientific certainty shall
not be used as a reason for postponing
cost-effective measures to prevent environmental
degradation.
In short, follow the precautionary principle...
29
US and EU
U.S. government agencies take a risk-based
approach to regulating biotechnology. That is,
they focus on the end product, and its risks,
instead of the process by which it was created.
In contrast, the EU considers GMOs to be special
category of organism. A quote from the Commission
of European Communities Directive on the
Deliberate Release to the Environment of
Genetically Modified Organisms reads, It is
evident that a case-by-case examination and an
environmental risk assessment is appropriate for
the use of genetically modified organisms.
30
Why has regulation proved so difficult?

• The process of policy cannot keep up with the
  pace of science.
• The pro-business approach of U.S. regulatory
  agencies often conflicts with consumer
  sentiments.
• I have studied the linkages between technology,
  policy, economics and the environment during most
  of my career. It is clear to me that the role of
  traditional farm policy is greatly diminished,
  that the private sector now largely controls the
  selection of technologies that are reaching
  farmers, and that the discipline of the open
  market is being undermined by industry
  consolidation.
• 
  Charles M. Benbrook, PhD.

31

• Disregard for the precautionary principle by
  corporations, scientists, and regulators.
• A national myopia that trades possible
  ecological problems for quick business profits.

The science of biotechnology holds great
possibilities that should be explored for the
future. It should also be recognized, however,
that biotechnology is an area of science not
fully experienced by nature. Any science
concerning the release of human invention into
the environment, especially if intended for
consumption, should be put to the most rigorous
testing.
32
I hope Ive persuaded you that this particular
challenge is complex, tricky, difficult, and that
solving it will require much more than
straightforward risk assessment or cost benefit
analysis, and certainly more thanrhetorical
admonitions that its not nice to fool with
Mother Nature. Dr. Donald Kennedy, president of
Stanford University 1992