The UK Royal Society Report on GM animals is supposed to consider scientific evidence. Instead, it takes a permissive, verging on partisan stance. It dismisses all evidence of hazards and argues for more public funds to support research repugnant to the vast majority of civil society, and not in the public interest. Dr. Mae-Wan Ho takes the Report apart.
"Medical research needs more GM animals", the Royal Society says [1]. "Genetically modified animals are essential for medical research and will also play a crucial role in the battle against diseases such as foot and mouth". These sweeping claims come from a Report produced by a working group chaired by highly respected animal behaviourist, Professor Patrick Bateson, Vice-President of the Royal Society. Bateson offended the pro fox-hunt lobby a few years back by stating what most people would think obvious: that the hunted animals do suffer. So, when Prof. Bateson comes out in support of GM animals, one sits up and listens.
The Report claims to be "primarily about the scientific issues". While it does not totally ignore the moral aspects or the wider issues, it is "the importance of informing such debate with sound scientific evidence" that the Society wishes to stress. But it is precisely on sound scientific evidence that the Report falls down so badly. For the most part, it reads like an apology, and worse, a soft sell for practically all the uses and abuses of GM animal technology.
The tone of the Report is set right at the beginning. The legal definition of a genetically modified organism, according to the Internationl Biosafety Protocol negotiated in Montreal Jan. 2000, is "an organism whose genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination of genes". The definition is the result of at least 6 years' deliberation and debate among the top international scientific and legal experts, and hence not to be treated lightly. But the Royal Society opines, "even though this definition seeks to draw a sharp distinction between artificial and natural processes, mutation of specific genes occurs spontaneously under natural conditions." (p.3)
The attempt to blur the distinction between GM and non GM continues two pages on: "Three common mutagenic techniques may be used to produce random genetic changes: exposure to radiation, chemicals or viruses." Nowhere is the reader told that viral transformation is one of the main techniques for making GM animals. In fact, the Report is very short on details as to how animals are genetically modified with viral and other vectors, and on the GM constructs delivered into animals. Nor does it make clear that there are major problems and serious safety concerns inherent to GM technology, for animals as for plants.
The Report hardly refers to problems such as the uncontrollable randomness of GM inserts, the instability of GM constructs and gene transfer vectors and the instability of transgenic lines, all of which make quality control of GMOs and their products well nigh impossible. Also dismissed and underplayed are the dangers of horizontal gene transfer and recombination in creating new viruses and in causing harmful mutations and cancers by random insertion into the genome of cells. Instead, it conveys the impression that GM animal technology is well tried and reliable. "The first GM animal, a mouse, was made in the early 1980s and this technology has been successfully applied to most animals, including cattle, pigs and sheep, poultry, fish and also Drosophila and other insects." (p.6) Only in the final paragraph of this Section is there any mention of the "relative inefficiency of the techniques" and "high death rates of fetuses during development".
Professor Bateson, interviewed in TheGuardian, said that there are already herds of GM animals producing pharmaceutical proteins. For years, I have challenged the biotech companies and other scientists to produce molecular data documenting the genetic stability of transgenic lines, and no one has come up with any. Belgian government scientists have now taken this seriously, and have analysed Monsanto's GM Roundup Ready soya (see "Scrambled genome of RR soya", this issue). They found the GM construct scrambled up, the plant genome at the site of insertion also scrambled up, and a large fragment of unknown origin has got in as well. All this is very different from the original data submitted by Monsanto. They suggested, without evidence, that all the scrambling had occurred on insertion, in which case, Monsanto must have got it wrong. If not, then there must have been scrambling since.
In his interview, Bateson also dismissed the dangers of horizontal gene transfer on grounds that it is a natural process. Indeed it is, but the constructs used in genetic modification technology are anything but natural. They are optimised for horizontal gene transfer: they are made by combining sequences from widely diverse sources of bacteria, viruses, plasmids and transposons and hence possess homologies to all those agents found in the environment. Homology increases the frequency of recombination up 10 million times or more (see "More Horizontal Gene Transfer Happens", this issue). GM constructs are new combinations of genes, almost none of which has previously existed in billions of years of evolution. The transfer of GM constructs, whether horizontal or vertical, cannot therefore, be considered natural. And, on account of the predominantly bacterial and viral origins of the genetic material in GM constructs, they have the potential to generate new bacterial and viral pathogens by recombination.
The Report states, "Despite the daily consumption of non-GM DNA from food in the diet, no evidence exists for the transfer of intact animal genes into humans from the food chain." One reason for this lack of evidence is that no one has investigated the fate of DNA in human beings. Researchers have found that when mice were fed viral and plasmid DNA large gene-size fragments passed out in the faeces. Fragments were found incorporated into blood cells, liver and spleen cells, and even cells of the foetus and the newborn. These results are well known in the GM debate [2], but the Society's Report did not cite them. "GM DNA is no more or no less a hazard to humans than any other form of dietary DNA and the probability of functional gene transfer to humans via the food from a GM animal is remote." (p.20). Is this 'sound science'? Does the Society not know that GM DNA is specifically designed to jump into genomes and to cross species barriers? That we don't need a functional gene transfer to wreak havoc in the cell's genome? A small motif in a promoter sequence may be all that is needed to dramatically alter the expression of host genes.
The Royal Society has not taken all evidence into account. A national enquiry into human gene therapy was sparked off in the United States by the death of a healthy teenager in a clinical trial in 1999. A report released recently by the National Institutes of Health documents the overwhelming failures as well as the dangers from the vectors used. These gene transfer vectors are very similar to those used in GM animals, and one main problem identified is the generation of new viruses by recombination. Another problem is cancer due to uncontrollable random gene insertion into the genome (See "Gene therapy oversold by scientists who disregard risks", this issue).
The Report goes through the list of applications, both actual and potential in some detail. By far the biggest use of GM animals is in medical research, "to create models of human disease and help elucidate disease pathways and allow assessment of new therapies." However, too many models do not give the same disease symptoms as in human beings. "While most mammals may share similar biochemical pathways, it is clear that many physiological processes are different. Thus, it is unlikely and indeed unrealistic to expect every animal model to capture completely all aspects of a human disease." Is that a reason for not using GM animals then? Not at all, according to the Royal Society, even bad models reveal previously unknown pathways.
According to Craig Venter, there are some 30 000 genes in the human genome. This gives at least 60 000 transgenic mice lines, one for 'knock-out' and the other one for 'knock-in', and that's not counting lines containing one of the hundreds of possible variants for every gene, and lines containing multiple gene variants to investigate gene interactions. In order to investigate the effect of different genetic backgrounds, transgenic mice lines containing the same human gene variants have to be created in different inbred mice. The possibilities are mind-boggling. Transgenic mice alone could proliferate until they take over entire animal facilities, and whole Departments not doing transgenic research would have to be closed down to make room for more. If you think I am exaggerating, the Society reports that the use of animals in biomedical research was down 1% from 1998 figures, but GM animals were up 14%, most of them transgenic mice. And it will continue to rise, the Society says, "as the benefits from genetic modification research cannot be realised unless genetic modification research grows." This is the abysmal science of the lack of imagination, let alone the lack of consideration of animal welfare.
Another use of GM animals is as bio-reactors, to produce "substances of benefit to humans" in their milk or other tissues. The Society is coy about the 'other tissues', which happens to be blood, urine and semen. Can this be acceptable in terms of animal welfare? The Society thinks so. Many proteins, such as blood-clotting factors and antibodies, can be formed only in the cells of complex animals. Would cell culture not do? No, proteins such as human albumin, are required on a scale that would not be feasible with cell cultures, and extracting material from human tissues is fraught with danger because of possible contamination with viruses. But the danger of viral contamination is equally great, if not greater, with animals. Benign viruses belonging to one species often become virulent in another. Similarly, endogenous viruses, dormant in their host species, often become infectious in other species, a phenomenon known as xenotropism, a danger already widely recognized in xenotransplantation. The Society is in favour of xeno-transplantation too, despite the fact that many scientists are calling for a ban for fear of viral pandemics [3].
The Society lists many potential benefits of GM animals in agriculture: disease resistance and "desirable alterations in growth rates or feed conversion efficiency, make leaner meat, and enhance anti-microbial properties of milk for newborn animals". Especially good for the Third World, but further research is needed. And it must involve public/private partnership to overcome restrictions of "patent and licensing agreements". "GM insects that carry human disease [sic]", "so that they are incapable of transmitting the disease"? Here, at least the Society has finally taken on board transgenic instability and the dangers of using broad host-range transposons as vectors. But it is still happy for further research and releases to go ahead.
It is only when it comes to GM fish that the Society holds back. Its sister organisation, the Royal Society of Canada, has concluded in their report that "if GM fish escaped, the consequences for wild stocks and the environment would be uncertain. The effectiveness of attempting to render GM fish sterile is also uncertain." Therefore, RS Canada recommended a moratorium on rearing GM fish in marine pens and suggested that approval for commercial production should be conditional on rearing in land-locked facilities. The Royal Society of London endorses all those recommendations, thank goodness.
After weighing up the potential benefits and costs, taking into account animal welfare and safety, "The Royal Society believes that some concerns about animal welfare and food safety aspects of food animal biotechnology are justified." More information and more research, especially on animal welfare are needed. Although, it sees "no qualitative distinction", in terms of welfare, "between genetic modification using modern genetic modification technology and modification produced by artificial selection, chemicals or radiation. Indeed, the targeted character of modern genetic technology may provide fewer welfare problems than the older techniques."
The Society concludes, on practically no evidence whatsoever, that "the development of GM animals has been hugely beneficial in many areas, not least into research on the causes and possible treatments of disease. It also has the potential to bring about other benefits, but serious concerns remain about welfare and health and safety issues that need to be addressed if these are to be realised."
But what the Report really wants to achieve is this: "Continued research on the welfare and uses of GM animals, funded in part from public sources, and with the results made openly available, is essential if these uncertainties are to be properly addressed and the risks understood."
In plain language, the Royal Society is going along with the corporate agenda for practically all the uses and abuses of GM animal. It is condoning the secrecy with which GM animal research, as indeed all GM research is conducted by the industry. It is condoning the privatisation of life and knowledge, and worse, using that as an excuse for squandering yet more public money to support research repugnant to the vast majority of civil society and not in the public interest. The Royal Society may be an independent organisation but it is acting more like a spokesperson for the industry [4].
Animal research in the destructive, mechanistic tradition has long outlived its usefulness [5] (see also "Animal Experiments Worse Than Useless" this issue). The Royal Society ought to be taking the lead in promoting novel, noninvasive, nondestructive techniques that are more humane and more informative as well [6].