A Typology of the Effects of (Trans)Gene Flow on the Conservation and Sustainable Use of Genetic Resources

[Full report is available at: ftp://ftp.fao.org/ag/cgrfa/bsp/bsp35e.pdf]

Executive Summary

At its Ninth Session, the Commission on Genetic Resources for Food and Agriculture “recognized the need to go ahead with the Draft Code of Conduct on Biotechnology as it relates to Genetic Resources for Food and Agriculture, with the aim to maximize the positive effects of biotechnologies and minimize any potential negative effects or risks (…)”. At its Tenth Session, when considering the Document, Progress on the Draft Code of Conduct on Biotechnology as it Relates to Genetic Resources for Food and Agriculture: policy issues, gaps and duplications, Members of the Commission identified amongst others the field of “GMO gene flow and the question of liability” as one of the most appropriate for further work and decided that it should be taken into consideration when designing the Commission’s Multi-Year Programme of Work.

This background study paper gives an overview of current research regarding the full range of possible effects of transgene flow on human health, the environment, the various stakeholders in the food and feed production chain and on the in situ and ex situ conservation of plant genetic resources for food and agriculture. The study further describes responses that governments and/or stakeholders have made, or which could be envisioned, in order to address some or all of these effects.

This background study paper considers transgene flow according to the effects it may have, as the basis for an objective evaluation of transgene flow and possible ways to deal with it. Chapters II-IV constitute the evaluation of transgene flow and Chapters V-VI are discussions on management and further scientific and policy work that might deal with this flow. In Chapter II, gene flow and transgene flow are placed into a scientific context. This is followed by a typology of transgene flow according to its different effects as biological, social and legal in Chapters III-IV. Chapter V considers transgene containment options. Finally, Chapter VI highlights various priority areas for policy, including technical and regulatory policy.

Gene flow – What is it?
Gene flow is a serious issue in the assessment and management of risks created by genetically modified organisms (GMOs) and the transgenes their genomes carry. There is consensus in the scientific community that genes flow whether they are transgenes produced by recombinant DNA techniques, or genes that arose without human intervention or management. Nevertheless, the flow of transgenes from plants derived from recombinant DNA techniques (GM plants) has specific or special impacts on biology, ecology, agriculture, society and culture.

Transgenes flow with normal reproductive processes; this is called vertical gene transfer.
Transgenes also may be transferred by infectious processes using microbial vectors such as viruses; this is called horizontal gene transfer. Transgenes also move when a plant carrying a transgene moves to a new environment, via seeds or propagules.

Gene flow is often discussed in terms of limiting reproductive barriers. The barriers include special and temporal proximity conducive to mating, and floral and mating system compatibility to achieve mating. Plants have two types of mating systems, asexual and sexual. Asexual reproduction does not require them to produce or receive pollen. Sexually reproducing plants may be primarily self pollinating or outcrossing. The former use their own pollen or pollen from extremely close neighbors and the latter preferentially use pollen from other populations. In addition, some plants attract animal pollinators while others rely on the wind to move pollen. Likewise, some plants have well-developed animal networks for distributing their seeds and others disperse seeds using physical vectors such as the wind or waterways. All crop plants have highly specialized animal vectors in the form of humans for distributing their seeds or other reproductive parts.

In biology, barriers are almost always incomplete or spatially and/or temporally variable. Corn seed is transported in viable form from the United States across the Pacific Ocean to New Zealand, where it is now routinely grown and harvested even though it is neither native nor apparently capable of surviving without human assistance. Fertility, as a measure of overall sexual compatibility, can be lost, developed and improved depending on a host of factors both genetic and environmental. Therefore, plants that may normally fall outside of the necessary proximities and compatibilities are not definitively denied access to genes, but they may receive them less frequently (Jenczewski et al., 2003).

Reproductive and physical barriers have their limits when it comes to containing genes and plants. Gene flow is a powerful force for genetic change. Modern commercial agriculture and field trials accentuate the natural power of gene flow because of the enormous scales upon which they are conducted and the constant re-introduction of transgenes and transgenic plants through trade.

“Classical theory of evolution points out that gene flow is capable of counteracting other
evolutionary forces like mutation, drift and selection. In modern industrial agriculture a stand of maize could contain a million plants, and under these conditions gene flow from transgenic maize to local landraces is expected to be very high. Under these conditions, the rate of incorporation of foreign alleles after hybridization is likely to be orders of magnitude higher than typical mutation rates” (p. 154-155 Serratos-Hernández et al., 2004).
Optimistically, a combination of biological and/or socially constructed barriers may inhibit
transgene flow and thus permit a sustainable state of co-existence between GM and non-GM plants.

However, the scale of agriculture, particularly with certain transgenic crops, and the scale at which flow can occur, is sometimes enough to overcome large quantitative barriers to gene flow. The limits of reproductive barriers and the scale of the application are critical knowledge for estimating the likelihood that barriers will remain effective.

Possible effects of transgene flow on agriculture, biological diversity and human health
To be considered in this typology, the effect of transgene flow had to be judged to be either unique or specific and not a general effect attributed to GM plants. This focus is consistent with the label “transcendent risks”, those that derive from the use of GM plants (Adi, 2006). Every attempt has been made to stay within those criteria. Of course, the perceived border between a general effect of GM plants and one specific to transgene flow may differ between individuals.

The consequences of transgene flow are difficult to generalize. This is because of the variety of transgenes being developed, plants being made transgenic, environments in which GM plants are being introduced, legal systems operating worldwide, and stakeholder motivations. The only generalization that is possible is that transgene flow offers no intended benefits. Gene flow may not always be harmful, but it is highly unlikely to offer a fortuitous or designed advantage for those in the biotechnology industry, farmers that adopt GM crops, farmers that choose not to, those who value the present biodiversity of plants and wildlife, or those who monitor GM presence for safety or regulatory reasons. Gene flow potentially undermines the revenue of developers when those who do not buy transgenic seed nevertheless benefit from its agronomic properties. Simultaneously the industry may have increased costs from protecting their intellectual property, or exposure to additional liabilities. Farmers who do or do not adopt GM crops gain nothing from the flow of transgenes to wild relatives or to neighbors’ farms. They may even incur liabilities if transgenes do flow. Non-GM farmers also risk losing differentiated market certifications.

Presently, there is too much variability in how gene flow studies have been designed and conducted to permit a ubiquitous power of prediction on the pathways, rates and effects of transgene flow in any particular environment in which a particular crop is growing in a given year. For example, while many studies have been conducted on pollen flow using different configurations of plots and other variables, their use in risk assessment is limited by:
local variation in environmental conditions including wind currents, pollinator behavior and
the difficulty of extrapolating results from small-scale, short-term trials to the parameters of general release;
different criteria for estimating gene flow; and
limitations in identifying effects on wild relatives.

However, two consensus opinions have formed. The first is that transgene flow is a highly likely event. The second is that each assessment requires a case-specific study.

There is less agreement on the likelihood of gene introgression (Hails and Morley, 2005).
Introgression requires additional events to maintain an exotic gene and cause it to enter a pathway where it continues to increase in frequency in either a self-sustaining (e.g., wild) population or within a seed production system. However, once a gene has made the transition from occasional flow to environmentally- (including human)-supported maintenance, the frequency at which it is found in unintended genomes is expected to rapidly increase.AgricultureTransgenes that confer an advantage upon a plant are generally expected to introgress in plants growing in environments that reward the trait. Selective advantages can make the plant more competitive or fecund in its current environment, or adapt it to a new environment. An example of the former is a transgene that makes a weed pest-resistant and thus more competitive with crops. An example of the latter is a gene that
adapts the plant to more arid conditions and thus allows the plant to colonize new environments.

What remains unanswered is how to predict in what environments and in what genomes a
transgene, or even a component of a transgene (such as an exotic promoter, intron or selectable marker), might confer a selective advantage. Some genes that are deleterious to one organism can be of use to others; this may only be discovered long after the genes have introgressed.

Whereas conferring a selective advantage significantly increases the probability of flow, it is not absolutely essential. Transgenes may flow because they are physically linked to other genes that confer advantages or by drift. That is, they may increase or persist due to random events. Finally, and importantly for commercialized transgenes, their repeated introduction on large scales can simply sustain them in the wild.

The effects on agriculture could include development of new weeds, loss of genetic resources, loss of valuable agronomic and commercial options and unanticipated or unintended effects on agronomic traits.

Weeds are already a large burden on agriculture, so any transgene flow that augmented this burden would be significant. Wild plants could be converted into more effective weeds by the flow of transgenes from GM crops when those new genes make the wild plant more effective at growing where it is not desired. Similarly, GM crops can become weeds by flow of genes to them from wild plants, particularly if those genes restore the GM crops’ characteristics that reduce their dependency on humans. GM crops can also become weeds when they cannot be eradicated at will from agricultural land, perhaps because they have accumulated multiple herbicide tolerances, or frequent introductions of the same species of plant into the environment contributes to the invasiveness of the species in an environment in which the species previously did not grow (Novak, 2007).

Crop diversity
Considerable effort is devoted worldwide to maintaining a diversity of genetic resources for crop improvement. What genes will be beneficial in the future cannot with accuracy be predicted now.

So both in situ and ex situ collections of wild relatives of present day crops, as well as different cultivars of crops, are secured and managed. The purity of accessions is specifically threatened by unintended gene flow.

Gene flow creates potential heterogeneity of traits. This heterogeneity may compromise
management strategies such as the use of refuges surrounding pest-resistant plants. For traits such as pesticides, heterogeneity may promote the evolution of resistance among damaging insect pests.

Wild biodiversity
The effects on wild biodiversity could be a reduction in the number of species on local and global scales. In plants, some existing genes might be replaced by transgenes, or unmodified plants might be replaced by transgenic plants. Both outcomes can cause sweeps of the gene pool and lower its diversity.

Animal biodiversity may be affected by the expression of compounds in plants that have a direct toxicity, allergenicity or anti-nutrient quality in consuming herbivores, or indirectly as they move up the food chain. Diversity may also be affected by the secondary loss of food sources due to the elimination of particular kinds of insects or other animals. Neither of the above effects is special to transgene flow. However, the animals that are affected may be different from those expected due to the movement of the transgene into different populations of plants or the plants into new environments.

Human and animal health
Crops that are being modified to serve as “biofactories” for the production of pharmaceutical
products (PMPs: plant-made pharmaceuticals) and industrial chemicals (PMIPs: plant-made
industrial products), or altered nutritional value, pose special risks to human and animal health.

Such crops may be considered non-food, because they have no history of safe use or because they are expected to be unsuitable as human food. They may also be considered non-food/non-feed, if their use is to be further restricted.

Those risks may carry over to plants that unintentionally receive those transgenes through gene flow. For example, a gene for the production of a vaccine protein may be expressed in a non-GM crop through gene flow, with the same spectrum of concerns surrounding the inclusion of either the original or the hybrid crop entering the human food supply. Alternatively, novel hazards might arise from transgene flow. The expression of a protein in one food crop may be significantly different from its expression in another. This was illustrated using the example of a protein from beans with a history of safe use as human food being a potential allergen when produced in peas (Prescott et al., 2005).

Possible legal and economic effects of transgene flow
A quantitatively new level of legal exposure for “biotech” seed producers and farmers that produce plants and plant products has been created by a combination of new international legal frameworks and the inherent biological capacity of crop plants to mix at all levels of their lifecycles (from pollen movement to co-mingling of seed in silos). As transgenes are the basis of international agreements such as the Cartagena Protocol on Biosafety, their presence and not just their impact is the level at which they have legal consequences. This creates new challenges for countries that enter into international trade of organisms that are meant to be free of transgenes.

National laws and international agreements allow for transgenes and transgenic crops to be
protected as intellectual property (IP) (Rosendal et al., 2006, Tvedt, 2005). IP is an especially potent issue for farmers who do not wish to use transgenic crops or transgenes. “The point is illustrated through the example of property rights in agricultural biotechnology, and specifically Monsanto Canada Inc v. Schmeiser. In that case, the Canadian Patent Act was interpreted to bestow expansive IP protection for a molecularly engineered gene, effectively nullifying the farmer’s classic property rights in his plants and seeds” (p. 6 DeBeer, 2005).
In addition, many states are bound through international agreements on plant genetic resources and IP, such as the International Treaty for Plant Genetic Resources for Food and Agriculture (ITPGFRA, Correa, 2006), the UPOV Conventions of 1978 and 1991 (UPOV, Sechley and Schroeder, 2002) and TRIPS, for Trade Related Aspects of Intellectual Property Rights Agreement (Sechley and Schroeder, 2002).

Those who grow transgenic crops either on purpose or by accident could become exposed to legal actions or market rejections. Those growing crops with transgenes may be prosecuted or sued if they fail to properly acknowledge the seed producer’s IP. Liability extends to damages to property, human health, the environment or loss of earnings. This is particularly poignant in light of recent market rejections of some GM crops based on perceptions of an inability to segregate GM and non-GM material.

Long-term effects of transgene spread in the context of internationally enforced IP laws could
threaten different agri-ecosystems. These form the basis of traditional and subsistence farming systems which often include reliance on seed saving and sharing.

Managing transgene flow
Some effects of transgene flow have already been realized, such as multi-herbicide tolerant canola in Canada, recurrent discoveries of illegal GM corn in New Zealand, and trade disruptions from mixing regulated GM crops (e.g., Starlink corn) with unregulated crops. Other effects are hypothetical, but plausible. This leaves us with the question of whether some effects, should they arise at all, can be managed to acceptable levels. Using existing transgenic crops as examples, transgene flow may be managed in some environments to a level that meets quantitative safety, legal and cultural requirements. The flow of transgenes can be restricted using physical and/or biological containment strategies, with transgene-based containment a possible future option.

Abstinence from the release of transgenes outside of contained laboratories, is another option. It appears at this time that no single containment strategy, other than abstinence, can be considered foolproof, and possibly no combination of methods from all strategies would prevent occasional escapes (Committee on the Biological Confinement of Genetically Engineered Organisms, 2004).

Thus, the reasons for containing a transgene(s) in question will dictate whether containment is an appropriate means to meet ecological and social goals. For example, relying on containment to prevent a particular outcome may not be appropriate when a GM crop contains a transgene that would result in unacceptable human health or environmental outcomes if it were to transfer to wild relatives.

Managing transgene flow is considered by some to be the same challenge as managing the flow of any exotic or other gene that is considered to be a threat to human health, the environment or IP. In terms of the physical and biological strategies for managing gene flow, this view is probably correct. In terms of the types of harms that might result from the failure of management, however, this view is not generally agreed. In part, it cannot be true for some genes, such as those that produce potent human pharmaceutical agents, dsRNA with the ability to silence human genes, or allergens the genes for which would not be present in the twelve plants that supply 95% of cropbased foods for humans (Adi, 2006). Such genes may never have been part of their genomes or if they had been, would long ago have been eliminated by human selection against such plants.

Uncertainties in gene flow
Uncertainties in gene flow remain concentrated in these areas:
what will be the harms or benefits that transgene flow may create?
can management reduce the frequency or impact of any potential harms that may result from transgene flow to acceptable levels for the most dangerous commercialized or field tested transgenes?
what are the cumulative effects of transgene flow on species, crops, conservation areas, and soci-cultural frameworks?
what are the consequences of transgene flow when considered in the context of liability laws, international trade and market expectations, intellectual property (IP) rights and
differentiated market certification programs?

Future research priorities should focus on key scientific uncertainties about the impacts of transgene flow. These include identifying the characteristics of transgenes that may contribute to their introgression via fitness-enhancing effects and in introgression pathways that do not depend on the immediate selective value of the transgene to plants. This will require a combination of evolutionary and population genetics and researchers with expertise in global genetic change. It is worth stressing the point that introgression is not necessary for some hypothetical harms to derive from transgene flow. Even local, single flow events could cause harm. For example, the escape into another crop of a transgene that makes a human allergen, or the escape of a transgene that makes seeds sterile into an endangered wild relative. Therefore, the focus should remain on the potential for transgene flow for some transgenes, not just the effects of introgression.

Complex and unanticipated effects of gene stacking should be explored. Most importantly, the potentially destructive effects of transgene flow from PMPs and PMIPs on human health and biodiversity require discussion of policies or invention of containment options that will prevent transgene flow.

Future policy priorities should focus on creating a more uniform and constructive approach to
distributing the benefits of biotechnology without imposing penalties on those farmers and
consumers who chose not to use the products of biotechnology. In particular, changes should be encouraged where necessary to legal systems that place responsibility for containing GM crops on those who sell them and their products.


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