ANNEX D (AEBC/02/17)

Genetic Modification – is it different?

Sue Mayer

Discussion paper for the AEBC, December 2002

 

This paper is prompted by the discussions in the liability sub-group (and which have been evident in other AEBC fora such as the animals sub-group) about whether GM systems are ‘different’ than other ways of producing new forms of plants, animals or other organisms.  In ‘Crops on Trial’ we identified different perspectives on this issue. One view is that GM is an extension of conventional breeding practices and the outcomes (be they benefits or risks) could be arise from different techniques of crop or animal production. Therefore, GM should not be ‘discriminated’ against or ‘picked out’ for special demands in terms of liability or other regulation. In fact, it is argued, if the same outcomes can be achieved through different methodologies, it is not sensible to concentrate on the technique of production.

 

However, there is another strand of thought that argues that for a whole host of reasons – technical, social, cultural and economic – GM is different and demands particular attention. There are technical differences of substance but these have to be appreciated inside a wider recognition of the forces shaping the application and use of the technology.  And, importantly, that these wider issues shape the nature, scale and likelihood of different impacts. From this perspective, certain regulatory responses are required.

1.      GM and the new biotechnologies are presented as ‘special’ and to be promoted.

On important factor influencing the view that GM is different is the way it has been, and still is, presented in official, scientific and industrial circles as having far reaching potential. This potential, it is said, includes making industry more competitive, transforming agricultural production and, even, addressing world hunger. The special ability that GM brings to transform plants in new ways, with promised advantages for industry, farmers, consumers and the environment has driven policy in both the UK and Europe since the middle of the 1980s[1]. Under successive European Framework research programs, genetic modification has been given special status and support. Putting into place a supportive regime (balanced by regulation to address the risks) has been a key objective of the EU in relation to biotechnology. In 1994, the Agricultural and Food Research Council became the Biotechnology and Biological Science Research Council. The large majority of public funding for research on GM crops and foods has been on science to facilitate their development rather than research into their impacts[2]. Clearly, in science policy and elsewhere, GM has been singled out for special treatment and promotion in ways that other techniques have not. This difference for GM and other genetic technologies, that it can be a very profitable enterprise that will underpin industry, has not been argued for other methods of plant or animals breeding.

 

In fact, at all levels in science and in science and technology policy, GM is treated differently. It appears that the anxiety to downplay difference only emerges when citizens request choice, raise questions and ask for a voice in decision making.  Whilst this quite clear identification of the technology for special status because of potential benefits identified by bureaucrats, industry and politicians these have been contested by the public. The PABE research[3] has shown that the public does not accept benefits to the biotechnology industry and farmers, that may arise from currently available GM crops, as social benefits.

2.      GM can change organisms in ways not possible by other techniques

There are also specific differences about GM and GMOs from a technical and scientific perspective which demand special attention, especially when our knowledge is limited. Examples of how GM raises new questions include:

 

·         Entirely new compounds can be produced in plants and other organisms – following on from herbicide tolerance and insect resistance, come GM plants producing drugs – vaccines, antibodies and therapeutic/diagnostic proteins. It is not conceivable that the complex production and assembly techniques achieved through genetic modification could have arisen through random chemical or radiation mutagenesis, however hard and long you tried. In the USA, four proteins for use in research and diagnostics are being produced commercially in GM maize by the company, Prodigene - avidin[4], β-glucuronidase[5], aprotinin[6] and trypsin[7]. These are biologically active compounds where the environmental consequences of their presence in plants is largely unresearched although avidin, for example, is known to have insecticidal qualities. No gene containment measures are used and movement into food is possible over time if area of use extends and controls fail. The National Academy of Sciences in the USA has criticised their controls[8]. Very recently (November 12^th 2002) the US FDA ordered the destruction of soybeans grown on fields previously used by Prodigene because they were contaminated with residues of GM maize used for the production of a (commercially confidential) therapeutic or diagnostic protein[9].

 

This novelty is not restricted to plants. Viruses have small genomes and genetic modification presents some limited opportunities to increase the capacity of viruses to produce new products, something which could not be achieved by other means. For example, plant viruses have been modified to produce proteins that may be useful as vaccines[10]^{,[11],[12],[13]}. The GM viruses are then used to infect plants where virus replication of the virus and its vaccine protein takes place – the vaccine is then harvested from the plant. Using viruses in this way by adding to their genomes is something which we have no experience to draw upon to evaluate.

 

·         Completely novel mechanisms for agronomic properties can be achieved – whilst it can be argued that conventional breeding and mutagenesis can achieve herbicide tolerance and disease resistance, GM brings in whole new mechanisms to do this and other things, often through the introduction of genes from different kingdoms. In relation to viral disease resistance, this has been achieved through the introduction of genes from viruses which confer resistance through unknown mechanisms, Professors Alan Gray and Ian Cooper have observed[14]:

‘When the transgenes derive from viruses, they are substantially different from current ‘natural’ resistance/tolerance traits in terms of context and ubiquity. Their presence introduces a substantially new dimension into the dynamics of plant/virus coevolution, even though virus-derived nucleic acids are normal constituents of natural plant populations where they undoubtedly contribute to the evolution of viruses, Hitherto, virus evolution has been affected by multiple infections constrained, at least in part, by the serendipitous behaviour of vectors. There is a risk that the spread of virus-derived transgenes will eliminate this element of chance as the presence of viral nucleic acid becomes uncoupled from vector behaviour”.

 

Other mechanisms to produce viral resistance in plants include the use of human viral defense mechanism where a gene coding for a protein triggered by interferon in mammals is introduced into the plant[15]. Very recently, it has been proposed to use a faulty human gene implicated in hereditary colon cancer in humans as a way of ‘improving’ current processes of mutation induction in animals, plants, human cells and microorganisms[16]. The faulty gene leads to normal gene repair mechanisms not working properly and makes cells become ‘hypermutable’ – they are likely to mutate very easily, especially when exposed to chemicals or radiation, but even when they are not.  This can be used to generate a whole array of different mutant cells, plants and animals. The plant kingdom does not appear to have this gene repair mechanism at all, let alone a defective version.

 

Moving mechanisms from one kingdom to another is not possible through other techniques and raises complex questions about potential impact, particularly if they become widespread in usage. There is no evolutionary precedence for such organisms. There are no data upon which to base an assumption that they will behave in a similar way to changes induced by other methods – they may or may not. There is very little data which compares phenotypes achieved by different methods. However, the advent of genetic modification heralds the introduction of completely new mechanisms of disease control, insect resistance and herbicide tolerance not only into crop species but most likely, over time, into related wild species.

 

·         GM allows the same genes and constructs to be used across all species – the development of GM has led to the same genetic constructs are being used across a variety of different crop species and across several continents. GM insect resistant cotton based on the Bt Cry1A gene is being used in North America, Africa, Australia and Asia.  There is Roundup Ready soybean, cotton, maize and oilseed rape in commercial use. Roundup Ready potatoes and wheat are expected shortly among many others. This raises whole new questions for genetic vulnerability. But it is the prevailing economic incentives and intellectual property arrangements that encourage the use of the same genes and techniques in as many varieties of the same crop and in as many different crops as possible[17] and, thereby, intensify this risk. It is not possible through conventional breeding or mutagenesis to impose this form of genetic uniformity across species and continents. There are real issues for food security should, for example, there be rapid emergence of insect and weed resistance.

 

·         Novel pleiotrophic effects may arise – GM, like chemical and radiation induced mutagenesis, can cause unintended changes to the genome. Genes may be disrupted and normal function affected. However, in contrast to mutagenesis, where changes are made to the existing genome, genetic modification may (usually does) involve the addition of genes. A particular additional issue for genetic modification is that many copies may be integrated, additional fragments inserted, gene sequences rearranged and deleted[18]^,[19],[20] – which may result in lack of operation of the genes, instability or interference with other gene function.  In farm animals, it is quite clear that GM brings a raft of completely novel potential impacts, completely outside any experiences with conventional breeding.

 

As a recent paper noted[21]:

            ‘It is incorrect to assume that the current methods of genetic engineering used to express single trangenes in plants are completely targeted and will have no, or minimal, effects on unrelated biochemical pathways in untransformed plants’.

 

This paper was reporting on unintended and unforseen changes in GM insect resistant potatoes based on introduced lectin genes. Levels of glycoalkaloids (chemicals naturally present in potatoes and thought to be associated with a natural insect resistance mechanism) were reduced in the GM plants compared to controls. The effect was considered to be attributable to ‘target gene insertion, marker gene insertion, chromosomal re-arrangements, altered gene expression and/or tissue culture’. GM was found to increase changes seen in tissue culture alone.

 

·         Knowledge of gene function is limited and prediction difficult – the argument is sometimes made that because GM involves the use of genes with well known function making it less ‘risky’ than other techniques. However, our knowledge of genetics is limited and findings from studies such as the human genome project have shown that there are far fewer genes in higher organisms than was predicted – 30-40,000 in man rather than the 120-140,000 originally thought[22]. This means that genes or parts of genes may be involved in different functions, depending on how they are read and which other genes are involved. This undermines the assumption that adding a gene with one known function means that this is the only way it will behave in practice[23]. Indeed, the detailed functioning of DNA is not well understood. The introduction of a gene into two different cells can result in different outcomes and the overall pattern of gene expression can be altered by the introduction of a single gene making the prediction of outcomes extremely difficult if not impossible[24]. Scientific theories and understanding of the ways in which genes work is constantly developing, giving new insights on the complexity of gene function[25].

3.      GM has led to monopolisation of genes and genetic technologies

The advent of GM and associated technologies has driven changes in the accepted rules of intellectual property rights and what is termed discovery and invention. The biotechnology industry has insisted on having intellectual property protection for genes, and the cells, plants and animals made using genetic techniques. A new Directive was introduced in Europe in 1998 which facilitated the patenting of living organisms. Pressure is being exerted on developing countries to bring their intellectual property protection for plants and animals in line with that in the developed world through the TRIPs agreement.

 

Patents on genes, cells, plants and animals and the techniques used in their production have been granted is leading to the monopolisation of certain species by private interests. This can lead to the virtual monopoly control of future modification of crops. One example is cotton where Monsanto has patents on the genes for tolerance to glyphosate and for Bt insect resistance and, on acquiring the company Agracetus in 1997, Monsanto gained access to its patent portfolio which included US 5,159,135, which has exceptionally broad scope, covering all GM cotton.  Monsanto has also made 90% of the patent applications for cotton genes[26]. Other companies are using IPRs to gain control on other staple crops. This situation raises important questions for the control of GM science and for food security.

 

Two recent UK reports have now questioned whether allowing patents on genes is in the public interest because innovation may be stifled not encouraged[27] and recommending that developing countries do not allow patents on genes, plants and animals in order to protect their food security[28].

4.      GM has intensified concentration of the seed market

The advent of genetic modification and the potential to alter organisms more rapidly and in ways not achievable through conventional breeding, attracted the agro-chemical industry to invest in GM crops.  Through a series of acquisitions of seed companies and mergers between agrochemical companies, there has been a consolidation of the seed market. In the US, concentration of the seed market and of transgenic crop research is at levels where antitrust action could be considered[29].  Ten seed companies now own one third of the world’s commercial seed market. The Commission on Intellectual Property Rights recorded in its report (p65) that:

“…in Brazil, following the introduction of plant variety protection in 1997 (but presumably also related to the expected permission to grow GM crops) Monsanto increased its share of the maize seed market from 0% to 60% between 1997 and 1999. It acquired three locally based firms (including Cargill as the result of an international deal), while Dow and Agrevo (now Aventis) also increased their market share by acquisition. Only one Brazillian-owned firm remained with a 5% market share. This trend appears widespread in developing countries”.

 

This consolidation of seed markets, facilitated by GM technology and favourable intellectual property arrangements, poses real dangers for food security if seed becomes too expensive for poorer farmers and no alternative exists.  These kinds of consequences are related to GM, not other plant breeding techniques. It is sometimes argued that these changes would have arisen anyway, and are not associated with the genetic modification technique. To some extent this will be true, but the way in which GM and large corporate interests intersect and drive each other can be seen in the statement by the Chairman of Syngenta’s Board in their latest (2002) Annual Report:

‘Industry consolidation in pursuit of economies of scale will continue. Research in biotechnology, with seeds as the key platform for delivering biotech traits, offers opportunities for higher-value, higher-quality outputs and increased returns in future…Finally, consolidation at the dealer and distributor level will continue’.

 

As the Food Ethics Council argued it in its recent report, ‘TRIPS with everything’, the technology allows patentable products to be produced which influences the market structure[30].

5.      GM has driven the privatisation of biological research

The advent of genetic modification coincided with a political change in science policy and funding. The drive towards wealth generation as fundamental aim of science funding, rather than, say, knowledge acquisition, has forced the biological sciences to focus on those areas where commercial applications are more likely. This has led to genetic technologies being favoured over other areas of science.

 

This privatisation of scientific knowledge in the biological sciences is not restricted to genetic technologies, but because of the emphasis that has been placed on this area of R&D, has shaped the trajectory of genetic science. It has determined what questions have been asked and those that have remained unanswered.  In this way, GM is being introduced under a different approach than for plant or animal breeding in the past, where the enterprise was centred in the public sector.  This affects the purposes to which GM is put and, therefore, the consequences will be different too.

6.      GM alters accepted notions of species barriers

The movement of genes between unrelated species challenges accepted social and cultural (and scientific) meanings of species. As such, it raises questions about our sense of order in the natural (non-human) world. Moving genes between kingdoms will, as out-crossing takes place between GM and wild species, raise questions for conservation and the value that is being placed on conserving genetically distinct populations and sub-species of organisms. Not only will there be movement from domesticated species to wild populations, but genes from unrelated kingdoms may enter certain populations and pose challenges for species preservation.

 

Like the contamination of Antarctica and its ecosystems with persistent chemicals, the movement of genes will be unseen, but humans’ actions will have irreversibly have altered the evolutionary divergence between species in fundamental and possibly dramatic ways. This basic intrusion of human activity into the genetic make-up of other species, raises ethical and cultural concerns. Whether we want to take this step or not under the present or different conditions is an important question and marks GM as a watershed.

 

CONCLUSIONS – WHAT GM AS DIFFERENT MEANS FOR REGULATION

 

It is this whole collection of issues, not necessarily one single point that marks GM as different from this perspective. If you accept the above areas do define GM as ‘different’, what does this mean for public policy and regulation from this perspective?

 

Firstly, there appears to be powerful interests pushing the technology, gaining financial investment and intellectual property rules that support a certain industrial model which is consolidated and global. This brings with it certain hazards, including that the risks may not be evaluated fairly, or the research to do so will not be supported. It also raises questions about food security particularly for the developing world. From a perspective of GMOs as different, there needs to be some balance introduced into this – other agricultural strategies should be supported, not just biotechnology exclusively (or largely); intellectual property laws need to take account of the developing world as well as the developed world; and the global nature of the industry and risks has to be reflected in regulatory mechanisms.

 

Secondly, because current risk assessments tend to be narrowly focussed, from a widely drawn perspective of GMOs as different, this does not capture the potential problems adequately. This is particularly true because of the far-reaching changes that GM can introduce, the possibility that impacts may not be reversible, the likelihood of surprises given our current state of knowledge and the types of GMOs being produced because of a privately driven research agenda. Therefore, the framing of assessments should include comparative evaluations (other options), the question of need and socio-economic criteria. Because of past institutional denial of scientific uncertainty and the potential for surprises, there should be greater exploration of their implications through sensitivity analysis and other techniques. Monitoring, through labelling and traceability is one important dimension of a precautionary approach to GMOs that comes from this perspective.

 

Thirdly, and perhaps most importantly, there is an underlying dispute about the benefits of GM, for the current generation of products at least. A lack of acceptance that the benefits will be ‘social’, drives three clear regulatory demands:

·         One, that there be labelling and choice.

·         Two, that non-GM options must be available and given social support. 

·         Three, that liability (or clear responsibility) for any economic harm to non-GM farmers and for damage to the environment and human health should not fall on society or individuals but lie with the industry.

 

This perspective does not other deny that other interventions may not have the same or more/less serious impacts, just that GM has a particular case to answer which its context can be argued to make things more pressing than for other approaches.