Biotechnology: Biotechnology: reading between the reading between the lines of science and safetylines of science and safety

Why has regulation proved to be so difficult?Why has regulation proved to be so difficult?

Jada M. HueberJada M. Hueber

20022002

BiotechnologyBiotechnology: : reading between the reading between the lines of science and safetylines of science and safety

Where did genetic Where did genetic engineering come from?engineering come from?

Where can we find Where can we find genetically modified genetically modified organisms today?organisms today?

What are some reasons for What are some reasons for support / concern?support / concern?

Are genetically modified Are genetically modified organisms regulated by the organisms regulated by the government?government?

Is biotechnology safe?Is biotechnology safe?

Genetic Engineering:Genetic Engineering: backgroundbackground

19661966 Marshall Nirenberg & Har Gobind Khorana finished unraveling the Marshall Nirenberg & Har Gobind Khorana finished unraveling the genetic code. genetic code.

1973 1973 Herbert Boyer & Stanley Cohen performed the first recombinant Herbert Boyer & Stanley Cohen performed the first recombinant DNA cloning experiment using restriction enzymes to insert DNA into a DNA cloning experiment using restriction enzymes to insert DNA into a plasmid and use the transgenic plasmid (a circular bacterial 'chromosome') to plasmid and use the transgenic plasmid (a circular bacterial 'chromosome') to transform bacteria. transform bacteria.

19801980 U.S. Supreme Court rules that living organisms can be patented. U.S. Supreme Court rules that living organisms can be patented. 19831983 First transgenic plant (tobacco). First transgenic plant (tobacco).

1985 1985 First transgenic plant produced-- resistant against a definite insect First transgenic plant produced-- resistant against a definite insect species.species.

1987 1987 A transgenic plant produced resistant to a particular kind of A transgenic plant produced resistant to a particular kind of herbicide.herbicide.

GMO History continued...GMO History continued... 19881988 First transgenic plant producing a pharmaceutical. First transgenic plant producing a pharmaceutical.

19941994 Transgenic tomatoes contain a softening inhibition gene. These Transgenic tomatoes contain a softening inhibition gene. These FlavrSavr tomatoes are sold in stores for a short time before being taken off FlavrSavr tomatoes are sold in stores for a short time before being taken off the market. the market.

1998 1998 AprilApril, a UK supermarket chain bans use of GMOs in its products, a , 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 move which over the following 18 months is followed by the other UK supermarket chains. supermarket chains. MayMay, widespread contamination of the UK canola crop , widespread contamination of the UK canola crop by GM oilseed rape contaminated seed imported from Canada by Advanta.by GM oilseed rape contaminated seed imported from Canada by Advanta.

Some sources cite Gregor Mendel, the Austrian Monk who studied genetics in 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 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 difference between the modern science of biotechnology and plant breeding for desired traits which has been going on for centuries? Keep this question in desired traits which has been going on for centuries? Keep this question in mind...mind...

The Science of Genetic The Science of Genetic EngineeringEngineering

making a modified genemaking a modified gene

Isolate desired gene

(increased shine)

Isolate plasmid DNA

(apple)

Gene inserted into plasmid.

Insert modified plasmid into bacterium for replication.

Grow in culture to replicate.

Making the transgenic cell… ...and Making the transgenic cell… ...and growing GMOs!growing GMOs!

Transfer copies into carrier bacterium.

A. tumefaciens (agrobacterium)

Bacterium inserts DNA into plant cell.

Transgenic cellCell division

Grow cells in culture to form

plantlets.

Transfer to soil…

Transgenic plants with new traits!

Where can I find GMOs?Where can I find GMOs?

All of these brands, and All of these brands, and many more, have been many more, have been identified as using GMOs identified as using GMOs in their ingredients. in their ingredients. Sometimes, as in the case Sometimes, as in the case of Gerber baby foods, the of Gerber baby foods, the product is found to product is found to contain GMOs despite contain GMOs despite company efforts to company efforts to discontinue the use of GM discontinue the use of GM crops.crops. Kellogg’s, Kraft, McDonald’s, Nestle USA, and Quaker Oats all Kellogg’s, Kraft, McDonald’s, Nestle USA, and Quaker Oats all

sell foods with GM ingredients in the U.S. but not in their products sell foods with GM ingredients in the U.S. but not in their products overseas where consumer opposition is strong.overseas where consumer opposition is strong.

The growing popularity of GE cropsThe growing popularity of GE crops

In January, the In January, the International Service International Service for the Acquisition of for the Acquisition of Agri-biotech Agri-biotech Applications (ISAAA) Applications (ISAAA) announced that global announced that global acreage of GE crops acreage of GE crops increased 19% in 2001 increased 19% in 2001 (130 million acres).(130 million acres).

From 1998 to 1999, From 1998 to 1999, global GE crop acreage global GE crop acreage grew 143%.grew 143%.

Who grows GE crops?Who grows GE crops?

Three countries Three countries produce more than produce more than 95% of the GE crops 95% of the GE crops in the world; in the world; Argentina, Canada, Argentina, Canada, and the United and the United States.States.

Only four crops are Only four crops are currently beingcurrently being grown on a large grown on a large scale: canola, corn, scale: canola, corn, cotton, and soybeans.cotton, and soybeans.

What good are GMOs?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.

Imagine food enough to feed the world...

Produce can be designed to be healthier, less fattening, etc...

Photos: www.thebiggestpixel.com/people01.html & www.picturesof.net

Substantial EquivalenceSubstantial Equivalence: a new variety of food : a new variety of food must be as safe as traditionally bred varieties and foods.must be as safe as traditionally bred varieties and foods.

Summary of safety assessment:Summary of safety assessment:

Compositionally equivalent to conventional varietiesCompositionally equivalent to conventional varieties

Nutritionally equivalent and perform comparably to Nutritionally equivalent and perform comparably to conventional varieties in food production and for livestock and conventional varieties in food production and for livestock and poultry feed.poultry feed.

Contains protein that is proven safe for consumption.Contains protein that is proven safe for consumption.

Regulation jurisdiction: the Regulation jurisdiction: the Coordinated Framework systemCoordinated Framework system

A) If the biotech product is aA) If the biotech product is a microbemicrobe, the EPA, the EPA regulates it.regulates it.

B) If the biotech product is aB) If the biotech product is a plant or insectplant or insect, USDA-, USDA-APHIS regulates it.APHIS regulates it.

C) If the biotech product is aC) If the biotech product is a food or medicinefood or medicine, the , the FDA regulates it. FDA regulates it.

D) If theD) If the research was funded by the federal research was funded by the federal governmentgovernment, the National Institutes of Health , the National Institutes of Health (NIH) or USDA regulates the product of the (NIH) or USDA regulates the product of the research.research.

The Four Principles of Regulatory The Four Principles of Regulatory ReviewReview

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

2) for biotechnology products that require review, 2) for biotechnology products that require review, regulatory review should be designed to minimize regulatory review should be designed to minimize regulatory burden while assuring protection of regulatory burden while assuring protection of public health and welfare;public health and welfare;

3) regulatory programs should be designed to 3) regulatory programs should be designed to accommodate the rapid advances in biotechnology; accommodate the rapid advances in biotechnology; andand4) in order to create opportunities for the 4) in order to create opportunities for the application of innovative new biotechnology application of innovative new biotechnology products, all regulation in environmental and products, all regulation in environmental and health areas should use performance standards health areas should use performance standards rather than specific rigid controls or specific rather than specific rigid controls or specific designs for compliance.designs for compliance.

Federal regulators seek to protect human Federal regulators seek to protect human safety, intellectual property rights of safety, intellectual property rights of individuals and corporations, and the individuals and corporations, and the genetic integrity of existing plant and genetic integrity of existing plant and animal species...animal species...

In 1980, the U.S. Supreme Court allows patents of living In 1980, the U.S. Supreme Court allows patents of living organisms because biotechnology procedures had made organisms because biotechnology procedures had made possible a human invention from a naturally-occurring possible a human invention from a naturally-occurring organism.organism.

the conundrumthe conundrum

Genetically modified organisms are “substantially equivalent” to conventional varieties. Therefore, they don’t require labeling.

&

Genetically modified organisms are not “products of nature,” but “human invention.” Therefore, they are able to be patented.

Corporate v. Consumer Demands: Corporate v. Consumer Demands: labelinglabeling

The New York Times reported that a “biotech industry poll” showed that The New York Times reported that a “biotech industry poll” showed that 93%93% of Americans wants genetically engineered foods labeled. of Americans wants genetically engineered foods labeled.

The American Government and the biotech industry are concerned that The American Government and the biotech industry are concerned that labeling will be misleading to consumers, since they claim traditional labeling will be misleading to consumers, since they claim traditional crops and GE crops substantially equivalent.crops and GE crops substantially equivalent.

Consumer Advocates claim that the popularity of GMOs has to do with 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 the fact that consumers are not given the choice, because they are not fully informed about what they are purchasing.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 United States Government Notice: This product contains a genetically engineered material, or was produced with genetically engineered material, or was produced with

genetically engineered material.genetically engineered material.

The biotech industry claims that The biotech industry claims that genetically modified organisms will genetically modified organisms will

be good for the environment. be good for the environment.

So why are environmentalists So why are environmentalists worried?worried?

Environmental issuesEnvironmental issues

““Biotechnology has the potential to create more Biotechnology has the potential to create more and better sources of food, to reduce pesticide and better sources of food, to reduce pesticide use, increase yields, and improve nutrition and use, increase yields, and improve nutrition and quality of life.” quality of life.” Dr. Sally McCammon, USDA Animal and Plant Health Dr. Sally McCammon, USDA Animal and Plant Health Inspection ServiceInspection Service

0

2

4

6

8

10

12

>4 ppb >2 ppb

RR cornwatershedsN=131otherwatershedsN=1,185

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).

““When I started farming 23 years ago we didn’t use the most powerful When I started farming 23 years ago we didn’t use the most powerful chemicals on the market, we didn’t flood the land with fertilizer, and we chemicals on the market, we didn’t flood the land with fertilizer, and we still made a good living...Our gross revenue to expense ratio was 3 to 1. 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 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 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 to expense ratio has dropped to 1.25 to 1, on a good year, just enough to pay the grocery bill.”pay the grocery bill.” Lloyd FearLloyd FearRed River Valley, ManitobaRed River Valley, Manitoba

Growers planting RR crops have three choices regarding weed control:Growers planting RR crops have three choices regarding weed control:

• Apply early to avoid early-season yield losses from fast growing Apply early to avoid early-season yield losses from fast growing grasses, possibly suffering yield losses from late season weeds;grasses, possibly suffering yield losses from late season weeds;

• Delay applications until most weeds have germinated, risking loss of Delay applications until most weeds have germinated, risking loss of yield to early weeds; or,yield to early weeds; or,

• Apply Roundup twice or more, and/or a residual herbicide at planting Apply Roundup twice or more, and/or a residual herbicide at planting or when Roundup is applied.or when Roundup is applied.

In one situation, after the first two applications of Roundup Ultra In one situation, after the first two applications of Roundup Ultra (total of 60 oz/A) weeds had survived. They were eventually (total of 60 oz/A) weeds had survived. They were eventually controlled by a third application of 48 oz/A. Further tests were controlled by a third application of 48 oz/A. Further tests were done involving RR crops and weed management. The effective done involving RR crops and weed management. The effective rates were at or above typical field use rates (32 oz).rates were at or above typical field use rates (32 oz).

““It is not clear which are greater – the successes of modern high-It is not clear which are greater – the successes of modern high-intensity agriculture, or its shortcomings…A greener revolution is intensity agriculture, or its shortcomings…A greener revolution is needed – a revolution that incorporates accumulated knowledge of needed – a revolution that incorporates accumulated knowledge of ecological processes and feedbacks, disease dynamics,ecological processes and feedbacks, disease dynamics,soil processes and microbial ecology” (Tilman 1998).soil processes and microbial ecology” (Tilman 1998).

““Everyone expects that a higher percentage of soybean acres will Everyone expects that a higher percentage of soybean acres will be planted to GMO varieties and that most farmers doing sobe planted to GMO varieties and that most farmers doing so will will need to apply two or three applications of two or more need to apply two or three applications of two or more herbicides.”herbicides.”Charles M. Benbrook, PhD.Charles M. Benbrook, PhD.

= the combined result of = the combined result of survival, reproduction, and dispersal.survival, reproduction, and dispersal.

Without a quantitative estimate of spread, risk analysis is doomed to Without a quantitative estimate of spread, risk analysis is doomed to anecdotal statusanecdotal status

““Virtually all spread models predict that at first the observed rate of Virtually all spread models predict that at first the observed rate of spread will be slow and will gradually accelerate to some asymptotic spread will be slow and will gradually accelerate to some asymptotic maximum rate. Thus, without some form of quantitative analysis, it is maximum rate. Thus, without some form of quantitative analysis, it is not wise to conclude spread will be negligible simply because after one not wise to conclude spread will be negligible simply because after one generation, most genetically engineered organism or genes are generation, most genetically engineered organism or genes are discovered close to their initial point of release” (Kareiva, et al. 1991).discovered close to their initial point of release” (Kareiva, et al. 1991).

Asymptotic Rate of Spread (ARS)-- in units of distance/time, the rate at Asymptotic Rate of Spread (ARS)-- in units of distance/time, the rate at which an gene’s aerial range increases in radius.which an gene’s aerial range increases in radius.

Spatial distribution of genotypesSpatial distribution of genotypes

Disperse pollenDisperse pollen

Mating & seedling Mating & seedling productionproduction

Selection in favor of to Selection in favor of to get next generationget next generation

Gene-Spread model:Gene-Spread model: yellow circles spread and increase in frequency as a yellow circles spread and increase in frequency as a result of dispersal and selection.result of dispersal and selection.

Spread is of particular concern regarding Spread is of particular concern regarding biodiversity and the creation of “superweeds”...biodiversity and the creation of “superweeds”...

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

resistant to the herbicide.resistant to the herbicide. SS

The concern is similar for insects. The concern is similar for insects. Will natural selection lead to a Will natural selection lead to a population of insects unharmed by population of insects unharmed by modern pesticides?modern pesticides?

In the field, nature’s predisposition to In the field, nature’s predisposition to adaptation has made things more complicated.adaptation has made things more complicated.

Initially it was stated that it was extremely unlikely that Initially it was stated that it was extremely unlikely that Roundup resistance would appear in weeds. Shortly after Roundup resistance would appear in weeds. Shortly after these statements were made the first case of Roundup these statements were made the first case of Roundup resistance appeared in Australia...resistance appeared in Australia...

According to Bob Hartzer of Iowa State University:According to Bob Hartzer of Iowa State University:

Herbicide resistance is defined as the inherited ability of a weed Herbicide resistance is defined as the inherited ability of a weed to survive a herbicide dose that kills the wild type of that to survive a herbicide dose that kills the wild type of that species.species. The two important points of this definition are The two important points of this definition are 1) the ability to survive the herbicide is genetic and passed 1) the ability to survive the herbicide is genetic and passed along to progeny, and along to progeny, and 2) the native population is controlled by the herbicide.2) the native population is controlled by the herbicide.

Researchers have documented glyphosate resistance in a Researchers have documented glyphosate resistance in a rye grass species. rye grass species.

Waterhemp was highlighted in the 1998 edition of the Waterhemp was highlighted in the 1998 edition of the Weed Control Manual as the most worrisome “Up and Weed Control Manual as the most worrisome “Up and Coming Weed” nationwide due to the emergence of Coming Weed” nationwide due to the emergence of resistance to triazine and ALS herbicides and its ability to resistance to triazine and ALS herbicides and its ability to withstand Roundup applications.withstand Roundup applications.

The Roundup Ready system cost an amazing $68.77 per acre in The Roundup Ready system cost an amazing $68.77 per acre in 1999. Fifty percent more than the cost of seed+weed management 1999. Fifty percent more than the cost of seed+weed management systems in recent years, largely because farmers had to use more systems in recent years, largely because farmers had to use more chemicals.chemicals.

RRRR

“ “A pest management system that relies predominantly on A pest management system that relies predominantly on one tactic is inherently vulnerable. The more generations one tactic is inherently vulnerable. The more generations of a pest in a season, and the longer the pest is subject to of a pest in a season, and the longer the pest is subject to selection pressure from a single tactic, the greater the selection pressure from a single tactic, the greater the odds the pest will adapt around the tactic and adapt odds the pest will adapt around the tactic and adapt quickly.” quickly.” Charles M. Benbrook, PhD.Charles M. Benbrook, PhD.

When Bt-transgenic crops were introduced, Monsanto admitted that When Bt-transgenic crops were introduced, Monsanto admitted that resistance was a possibility, but unlikely if a 5 percent “buffer zone” of resistance was a possibility, but unlikely if a 5 percent “buffer zone” of traditional plants was planted as well. Then the following discoveries were traditional plants was planted as well. Then the following discoveries were made:made:

Bt Bt endotoxin expression under field conditions is not uniform, providing endotoxin expression under field conditions is not uniform, providing some insects with a chance to avoid plant tissues delivering a lethal dose.some insects with a chance to avoid plant tissues delivering a lethal dose.

Resistance gene to Resistance gene to Bt Bt endotoxin appears to be a dominant trait.endotoxin appears to be a dominant trait.

BtBt-corn can adversely impact populations of key beneficial insects.-corn can adversely impact populations of key beneficial insects.

Resistance to Resistance to Bt Bt is not as rare as previously suspected.is not as rare as previously suspected. Since the release of these studies, Monsanto increased the necessary safe buffer zone to 50 percent.

Antibiotic Gene MarkersAntibiotic 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.

Allergies!?...Allergies!?... NEW

The National Academy of Sciences has said that GM food might The National Academy of Sciences has said that GM food might cause allergic reactions, some serious, even life-threatening.cause allergic reactions, some serious, even life-threatening.

Physicians are not required to report allergic reactions observed in Physicians are not required to report allergic reactions observed in patients, and there is no existing registry to record such data. patients, and there is no existing registry to record such data. Therefore, without data being collected and analyzed, stable Therefore, without data being collected and analyzed, stable conclusions regarding the existence or possibility of new allergens conclusions regarding the existence or possibility of new allergens cannot be made.cannot be made.

Current testing for allergenicity often compares the new protein with Current testing for allergenicity often compares the new protein with known allergens such as wheat, peanuts, milk, eggs, and known allergens such as wheat, peanuts, milk, eggs, and crustaceans.crustaceans.

In 1992, the United Nations met in Rio de Janerio for the In 1992, the United Nations met in Rio de Janerio for the Conference on Environment and Development. The Conference on Environment and Development. The subsequent declaration contained the following statement.subsequent declaration contained the following statement.

Principle 15Principle 15 In order to protect the environment, the In order to protect the environment, the precautionary approach will be widely applied by States precautionary approach will be widely applied by States according to their capabilities. Where there are threats of according to their capabilities. Where there are threats of serious or irreversible damage, lack of full scientific serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.effective measures to prevent environmental degradation.

In short, follow the precautionary principle...In short, follow the precautionary principle...

US and EUUS and EU

U.S. government agencies take a “risk-based” approach to U.S. government agencies take a “risk-based” approach to regulating biotechnology. That is, they focus on the end regulating biotechnology. That is, they focus on the end product, and its risks, instead of the process by which it was product, and its risks, instead of the process by which it was created.created.

In contrast, the EU considers GMOs to be special category of In contrast, the EU considers GMOs to be special category of organism. A quote from the Commission of European organism. A quote from the Commission of European Communities Directive on the Deliberate Release to the Communities Directive on the Deliberate Release to the Environment of Genetically Modified Organisms reads,Environment of Genetically Modified Organisms reads,

““It is evident that a case-by-case examination and an It is evident that a case-by-case examination and an environmental risk assessment is appropriate for the use of environmental risk assessment is appropriate for the use of genetically modified organisms.”genetically modified organisms.”

Why has regulation proved so difficult?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.

• 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.

“I hope I’ve 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 than…rhetorical admonitions that it’s not nice to fool with Mother Nature.” Dr. Donald Kennedy, president of Stanford University; 1992