29 Jan 2001

Witness Statement for New Zealand Royal Commission on Genetic Engineering

Dr. Mae-Wan Ho

I am a university-based scientist who got involved in the genetic engineering debate because I was dismayed as to how little scientific information was getting through to our policymakers and to the public. There was much propaganda about the potential benefits, but almost nothing on the hazards, and the scientific evidence simply did not support the claims that the technology is precise or safe.

For the past six and a half years, I have had to follow developments in genetic engineering science much more carefully and extensively than many of the practitioners. It gives me no pleasure to find that all my initial suspicions regarding the dangers of genetic engineering are being confirmed. My detailed witness brief for this Royal Commission was prepared last October, but significant new reports and revelations have appeared since.

The top news item in the Jan. 13 issue of the New Scientist [1] was on a deadly virus created accidentally by researchers in Canberra Australia, who were trying to genetic engineer a contraceptive vaccine for mice. They spliced a gene for the protein interleukin-4 into the vaccine, made from the relatively harmless mousepox virus, which was used as a vehicle to carry egg proteins into the mice. The hope was that interleukin-4 would boost the immune system to make more antibodies against the mouse egg, thereby killing it. When the researchers injected this vaccine into mice, all the mice died. In fact, this synthetic virus was so lethal that it also killed half of all the mice that have been vaccinated against mousepox.

Mousepox virus is related to the human smallpox virus. These findings raise the spectre of biological warfare, and also showed how futile it is to make vaccines against viruses, which are notoriously mutable and unpredictable. But the far greater danger lies in the unintentional creation of deadly pathogens in the course of apparently innocent genetic engineering experiments. That may already have been going on over the past 25 years of increasing commercial exploitation of genetic engineering in both agriculture and medicine. I must stress that genetic engineering uses the same tools and makes similar constructs, whether in agriculture or in medicine; and therefore carries the same risks.

The accompanying New Scientist editorial [2] remarked that five years ago, when biomedical researchers were asked if genetic engineering could create "a virus or bacteria more virulent than nature’s worst", they replied it would be "difficult if not impossible". Some of us have been warning of ‘accidents’ such as this for at least the past six years. I co-authored a detailed review with six colleagues on the evidence suggesting links between genetic engineering and the recent resurgence of drug and antibiotic resistant infectious diseases, which was published in 1998 [3]. We were by no means the first to raise this issue. Scientists who pioneered genetic engineering declared a moratorium in Asilomar in the mid 1970s precisely because they were concerned about this dire possibility.

Unfortunately, overwhelming pressures for commercial exploitation cut the moratorium short. The scientists set up guidelines, based largely on assumptions, all of which have fallen by the wayside as the result of new scientific findings. Instead of tightening the guidelines, our regulators have relaxed them as commercial pressures built up [4].

It does not take a great feat of imagination to see why genetic engineering will accelerate the generation of new viruses and bacteria. I shall explain.

The basic tools of genetic engineering are bacteria, viruses and other genetic parasites that cause diseases and spread drug and antibiotic resistance. All that fall into the hands of genetic engineers are exploited. Genes from dangerous agents, including antibiotic resistance genes, are profusely mixed and matched, or recombined. As every geneticist should know, such recombination of genetic material is one of the main routes to creating new pathogenic strains of bacteria and viruses. The more you recombine, the more chances you get.

Naturally occurring bacteria and genetic parasites are host-specific and respect species barriers, so that the horizontal exchange of genetic material to the genome of unrelated species is kept to a minimum. (Horizontal gene transfer is distinct from the vertical gene transfer that occurs in ordinary reproduction, which results from mating within a species or between closely related species, when genetic material is passed from parent to offspring.) The overwhelming preoccupation of genetic engineering over the past 25 years is to create so-called genetically modified organisms, or GMOs. This involves breaking down species barriers so that genetic material can readily be transferred between species that would never interbreed in nature. In order to do that, they have had to make artificial, genetically modified genetic material, or GM constructs.

Naturally existing genetic material is limited in their ability to successfully cross species barriers. When such genetic material is taken into a cell, it is most likely to be digested to provide energy and building blocks for the cell. In the unlikely event that the genetic material gets into the genome of the cell, other mechanisms can still put it out of action and get rid of it. GM constructs, however, are designed to cross species barriers and to invade genomes. In other words, GM constructs are more likely to transfer horizontally.

Horizontal gene transfer will increase the opportunity for genetic recombination. The GM constructs are already of mixed origins, with base sequences similar to the genetic material of many pathogenic bacteria and viruses. That, again, as every geneticist should know, will greatly increase the probability for genetic recombination, and with a wide assortment of bacteria and viruses.

There is yet another way in which GM constructs will be more likely to recombine. GM constructs are well known to be structurally unstable, as are the GM lines obtained. Structural instability compromises agronomic performance, and raises serious safety concerns, especially with regard to horizontal gene transfer and recombination. I have highlighted this problem for many years, which is well known to practitioners. But they have only just acknowledged this in public.

The latest annual report from the John Innes Center, JIC, a major player in agricultural biotechnology in the UK contains a brief summary of research on GM barley lines [5], showing that they became unstable and variable in later generations of field trials. The researchers concluded, "The results show that transgenic lines need to be examined over a number of generations under field conditions to obtain the necessary data on transgenic stability and agronomic performance", and also call for "detailed molecular and genetic analysis". Both of these I have been demanding for years along with other scientists.

All genes need a special signal to turn on, known as a ‘promoter’. One promoter that is used in practically all GM crops already commercially grown or undergoing field trials is from the cauliflower mosaic virus, the CaMV 35S promoter for short. GM constructs containing this promoter are extra unstable because the promoter has a ‘recombination hotspot’ ie, a weak spot that it is prone to break and recombine with other genetic material, and it does not require similarity in base sequence.

This CaMV promoter is also known to work for genes all across the living world: in plants, bacteria, fungi, and, as we discovered recently in the literature more than 10 years old, also in frog eggs and human cells. It is able to substitute, in part or in whole, for the promoter of many other viruses. Viruses are not only everywhere in the environment, they also lie dormant in the genomes of all organisms, bacteria, plants and animals without exception. And there is evidence that such dormant viruses can be reactivated as a result of genetic recombination. One of the major problems with so-called gene therapy is that viral vectors, which have been disabled so they cannot replicate, often give rise to replicating viruses in cell lines used to package the vectors for efficient delivery into patients [4].

When my colleagues and I pointed out the dangers of the CaMV 35S promoter in the scientific journals [6-9], we were reviled and attacked. Our fiercest critic was leader of a research group in the JIC that had discovered the recombination hotspot. Now, two years later, the same group admits the need to avoid recombination hotspots such as that in the CaMV 35S promoter as well as the ‘origin of replication’ in the plasmid serving as vehicle for the GM construct, which is also often integrated ‘accidentally’ into GM crops [10].

The point I am making is that genetic engineering has unleashed an uncontrollable, self-amplifying process of horizontal gene transfer and recombination that can sweep across the whole of the living world, with potentially explosive consequences in terms of creating viruses and bacteria more virulent than nature’s worst.

I don’t have time to tell you about the terminator genes in the next generation of GM crops, which have been field tested since the early 1990s [11], and several have been approved in the US. One of the genes codes for a universal poison that kills all cells in which it is expressed. The other codes for an enzyme that can scramble up the genome by breaking and rejoining the genetic material at inappropriate places, with lethal consequences.

The terms of the genetic engineering debate have shifted. It is no longer a moratorium that is needed. GM crops are unsafe and unsustainable as well as immoral. We must abandon GM crops right now, along with intensive corporate agriculture. People all over the world are sending strong messages to their governments. They are overwhelmingly rejecting GM and opting for organic produce. The successes of organic, sustainable agricultural practices and technologies have been documented in study after study. At least 3% of the arable land in Africa, Asia and Latin America are already farmed in this way [12], with impressive gains in crop yield as well as social, economic and health benefits. Similar findings are reported for the United States [13].

Organic sustainable agriculture is also important for alleviating, if not reversing global warming. Not only does it significantly reduce the consumption of fossil fuel, it increases organic matter in the soil, in the form of both carbon and nitrogen.

The choice is clear, and we must make it now, while it is still not too late.

1. "Disaster in the making: An engineered mouse virus leaves us one step away from the ultimate bioweapon" New Scientist 13 Jan. 2001, 4-5.
2. "The genie is out, Biotech has just sprung a nasty surprise. Next time, it could be catastrophic" New Scientist Editorial 13 Jan. 2001, 3.
3. Ho MW, Traavik T, Olsvik R, Tappeser B, Howard V, von Weizsacker C and McGavin G. Gene Technology and Gene Ecology of Infectious Diseases. Microbial Ecology in Health and Disease 1998: 10: 33-59.
4. Ho MW, Ryan A, Cummins J and Traavik T. Slipping through the regulatory net. ‘Naked’ and ‘free’ nucleic acids. Submitted for publication.
5. Harwood WA, Hardon J, Ross SM, Fish L, Smith J and Snape JW. Analysis of transgenic barley in a small scale field trial. John Innes Centre & Sainsbury Laboratory Annual Report 1999/2000, p. 29.
6. Ho MW, Ryan A and Cummins J. Cauliflower mosaic viral promoter – a recipe for Disaster? Microbial Ecology in Health and Disease 1999: 11: 194-197.
7. Cummins J, Ho MW and Ryan A. Hazards of CaMV Promoter? Nature Biotechnology 2000: 18: 363.
8. Ho MW, Ryan A and Cummins J. Hazards of transgenic plants with the cauliflower mosaic viral promoter. Microbial Ecology in Health and Disease 2000: 12: 6-11.
9. Ho MW, Ryan A and Cummins J. CaMV 35S promoter fragmentation hotspot confirmed and it is active in animals. Microbial Ecology in Health and Disease 2000: 13:
10. Christou P, Kohli A, Stoger E, Twyman RM, Agrawal P, Gu X. Xiong J, Wegel E, Keen D, Tuck H, Wright M, Abranches R and Shaw P. Transgenic plants: a tool for fundamental genomics research. John Innes Centre & Sainsbury Laboratory Annual Report 1999/2000, p. 30.
11. Ho MW, Cummins J and Bartlett J. Killing fields near you, terminator crops at large. ISIS Report, January 2001
12. "Against the grain: Could we feed the world without causing further environmental damage?" Jules Pretty The Guardian, Tuesday January 16 2001.
13. The Rodale Institute Farming Systems Trial: The first 15 years. Rodale Institute, 1999, Kutztown, PA, USA, Tel (USA) 610 683 1400 www.rodaleinstitute.org
    

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