Discussion of Klaus Ammann's paper, 28th October 1997

An example of a non-transgenic plant causing a nuisance is provided by Zentaria pstove of the variety Wallaciaca which is a very rare endemic species from the driest of the prairies at Wallace in southern Canada. It caused one of the worst invasions in Switzerland. Through the Commonwealth Institute insects were introduced to control the plant in a project led by Prof. Heinz Mùller of Fribourg University. They succeeded, but there is always a risk with biological control like any other. Host specificity in a new environment is not known, not even for viruses. It was difficult at first to pin the species down.

Even Williamson, an expert on invasive plants, cannot give a straightforward definition of weediness. Weediness is seen differently depending on who is involved. Agronomists define a weed as a plant that is unwelcome in their fields. But is this valid. Should a certain weed presence be allowed, albeit at risk of slight lowering of yield, to gain the benefits of supporting natural insect populations? There is evidence that if monocultures are not pursued so rigidly, natural insect predation on pests is enhanced. As yet unfinished experiments in wheat fields with strips of weeds hosting a rich insect biodiversity seem to point support this.

Genetic engineering too has a very great potential for attaining a more ecologically sound agriculture. For instance, it could be used to transfer genes from traditional though disused cultivars into the varieties used today. Classic breeding has led to the problem of incorporation of fewer beneficial genes in crops because selection tended to be based solely on yield. Crossing experiments force you to lose precious genes. This can be overcome by genetic engineering.

Even so we cannot simply use transgenes without testing them, for instance the viral genes we insert in potato. In such a case people are tending simply to put the new transgenic into immediate use. But it may be better first to take the transgenic through a breeding programme to see how this new information is responded to by nature, how it is moulded to suit nature. It is not strictly true that transgenic crops are rushed onto the market, the development rarely if at all takes less than 10 to 12 years. After introducing the transgene it is a very long process to reach a marketable crop. This has been seriously underestimated.

Only with the advent of molecular genetics did people realise how precious the genetic heritage is. Kew Gardens got a £40m grant to establish a world gene bank to store hundreds of thousands of seed varieties. Of course this isnot done for conservation purposes - that would only be by planting and growing - but for the genes themselves. One example in Switzerland of loss of a genome is the Fribourg cow. It was just thrown away by traditional breeders after it was bred for hundreds of years. People would not let this happen nowadays.

The precision of transgenesis allows us for the first time to delineate the true risks, because all these transgenes are markers. That gives us the precision. Developments in genetic engineering have led to a sort of backlash on classical breeding in the sense that it now receives risk assessment scrutiny in a way that it never did before. However, that classical methods could bring about the danger of an invasive species should not be used as a cheap excuse for not maintaining vigilance over genetic engineering.

With the knowledge of the genomes and the mapping that is being done we shall see more biotechnology done by the molecular approach, for instance by taking distantly related species and accelerating the back-crossing process to get a new trait free of the other interference which would preclude a commercially viable crop. However, while there are no regulatory requirements regarding the gene content of food, the position remains unclear for both old and new methods. The ampicillin gene issue in Novartis' Bt-maize (containing the gene for Bacillus thuringiensis toxin) is a red herring, however, because experts agree that the gene cannot be transposed because the transposon is missing. Nevertheless, even if transposition is not possible, transfer is possible, for instance to gut microorganisms of animals of humans. Also DNA has proved to be relatively stable for months if not years in certain soil microenvironments, such as in clay particles. It has been shown recently in Germany that bacteria can pick up recombinant DNA from plants. Against this has to be borne in mind that the ampicillin resistance gene originates from the wild, it is in nature, even in the human gut. The addition of the gene via a transgenic organism may therefore not have any great impact on a natural bacterial population. When huge amounts of such transgenes are released into the environment then perhaps it will have serious implications for our use of antibiotics in medicine, especially as the antibiotic and its structural relatives are still in use. We should be wary of using the natural presence of antibiotic resistance as a cheap excuse for not doing risk assessment. For example, the relatively recent work on transfers of resistance is confined to E. coli. Other species may pose a greater threat but the work has not been done.

Professor Guenther Stozky was here at a meeting on genetic engineering and has since become concerned that his work is being misused by one of the opponents of genetic engineering. He is indeed concerned about the environmental risks of recombinant DNA releases, but his is a long term concern. So far his experiments are confined purely to artificial soils and he is aware of their limitations. As they stand they do not yet to point to the need to put a stop to release of genetically manipulated organisms in the wild. Efforts are under way to involve him in a Monsanto-Novartis research framework for long term monitoring of transgenics.

The quantitative aspect does indeed need to be put in perspective. The relative contribution of the transgenic to antibiotic resistance gene transfers in nature may be of the order of one to a thousand. Another factor which puts recombinant DNA technology into the shadows in this respect is the use of antibiotics in animal feeds. However, the limitations of research done so far do not rule out a significant effect from transgenics too.

Perhaps psychologically it is a mistake to use the ampicillin gene as a marker. With the soya bean, Monsanto has been lucky to lose the ampicillin marker in a way that at first was not understood. However, markers other than antibiotic genes can be used. Marker genes for transgenesis of wheat are now available and work on wheat is in progress. The early breeders tackled wheat as if they were playing blind man's buff.

The fact that Novartis is commercialising a product with the ampicillin gene marker illustrates another aspect of concern about genetic engineering and that is the economic aspect, the seeming need to rush something through without retracing one's steps and trying to improve the product before going onto the market. This is the really worrying aspect, that industry just does not have the time or money to do the job properly. Against this it should be noted that the people who assessed the safety of the product are independent scientists sitting on government regulatory committees. But things have moved on. In France, for instance, if you want to do even a small scale field test you have to show that the only genes present are the ones expressing the traits of final interest. A construct containing the Bt resistance gene, the kanamycin resistance gene and the ampicillin resistance gene with no attempt to prune down the inserted genes to the bare minimum would be a non starter as a project now.

The issue of maintaining species separation, for instance in the light of the claimed potential for transfer of transgenes, needs to be seen against the daily ingestion of approximately 15 grams of foreign genes measured as DNA. There has been no concern in the past - why now? We have hitherto maintained our species identity. One answer is that what have been traditionally regarded as species boundaries are transgressed by modern recombinant DNA technology. This needs long term monitoring, for instance through the project supported by the European Science Foundation.

We tend to focus on the risks of genetic engineering without realising that the term 'human genes' is meaningless. 99.4% of our genes are the same as those of chimpanzee. If we drink a beer we are 30% 'cannibals' because the yeast has that content of human genes. This is the last part of the shock of Darwinism which has not hit us yet. We like to think we own our genes as human beings. But the greater part of the genome is widely dispersed throughout the living world as a common heritage of all living beings. In our minds we are stillsomehow stuck as creationists rather than evolutionists.

As 75-80% of the population, at least European polls, does not want transgenic crops on the supermarket shelves, it would be interesting to hear what non-molecular biologists think about the problem. It would not be appropriate simply to dismiss them as creationists. The experts have the task of enhancing cultural knowledge and the shock of the advent of genetic engineering will hopefully create more real knowledge about its inventions.

There is a difference between whether we eat recombinant genes or normal ones. The normal ones may indeed be combined with promoters yet the organism which consumes them is already adapted to dealing with them. The eukaryote cannot normally transcribe a prokaryote's gene. But in recombinant DNA technology the normal arrangement is broken down. The foreign gene is deliberately made transcribable by the foreign recipient organism. If, for instance, a plant containing a transgene equipped with a microbial promoter decomposes in the soil, the probability of getting a transformation in the soil microflora is higher than with normal plant genes. The recombinant gene is something different. Against this there needs to be borne in mind the natural plant genes which can express in microorganisms, for instance in mitochondria and plastids. Higher plants are like a symbiosis of cellular organelles of apparently ancient prokaryotic origin. This allows the exploitation of maternal lines of inheritance in genetic engineering via the plastid genes.

Whilst the laboratory tests may be extremely thorough, what is to be watched more carefully in the future is the effect of mass releases of combinations of transgenes.

We need to keep in mind the distinction between risk assessment research and risk assessment evaluation. With the latter there is clearly scope for differences of opinion. What is worrying the opponents of the technology might be illustrated by the example of how patients often first present their problems to their family doctors. What the patient describes as the main worry often turns out on further investigation to be a manifestation of another deeper concern or problem. In the case of the 'no-goers', those against gene technology, they may be grasping at improbable alleged risks as arguments to support their position. The problem which may really concern them is not, for example, that an ampicillin resistance gene might run amok and thus render all our antibiotics absolutely useless, but is something far more deep rooted and of broader significance. It may be something to do with the social order which allows large companies, for instance, to steamroller policies that undoubtedly change our culture into communities which feel powerless to resist them. It is a David-Goliath syndrome. Such a feeling of powerlessness may stem from the fact that social structures for publicly debating the new technology were never there at the outset. We are already so far into the implementation of the technology in the economic sphere of the social order, for instance we are already focusing on patenting of life issues and the fine detail of a European directive for this, that people are wondering: where was the original debate that belongs first and foremost in the cultural and rights/legal spheres?

Switzerland on a world scale is in the lead in molecular genetics research, but when it comes to commercialising the results of its basic science it is way behind. For example, it sold the plans for the P60, a billion dollar engine project, for $150,000. Another example: the Federal School of Technology, Zurich leads in software design, but where are the Swiss computer companies? The same sort of thing applies with the transgenics. The Swiss public has not had the opportunity to debate the technology at the outset, over 15 years ago, as happened in the USA. This leads to public worries about it, to resentment against the USA, which is perceived to be imposing their products on the country, for instance the Monsanto Roundup-ready soya bean. Only in July 1995 Monsanto realised that it had to go through separate regulatory processes in Switzerland because it is not part of the European Community. That sort of thing is creating the pressure on the public and the resulting atmosphere of distrust.

Whilst there may have been some public debate in the USA the impression gained in Europe is that it was not very heated. Indeed, one might have the impression it never fully engaged the public's attention there. Americans have quite a different fundamental attitude towards technological progress.

In concluding the morning discussion, one speaker pointed out that arguing whether an ampicillin resistance gene is or is not a risk is not getting to the heart of the matter. They experienced the discussion environment of the meeting as quite exceptional and suggested that the scientists present could be entirely open about what it is about the technology that really does scare them. The fear of genetic engineering in humans was put forward as the most serious fear in people's minds.