Contact: Stephen M. Apatow
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The topic of genetically modified organisms (GMOs) has once again entered into widespread discussion as per the release of the following article "Designer Diseases" published in the New Scientist, 27 August 2003. Concerns relate to (1) the genetic modification of a virus designed for release, replication and spread as a form of pest control, (2) the inability to control the spread of the agent once released into wildlife, (3) the capacity for mutation, recombination and potential to jump species, and (4) the potential for accidental or deliberate spread/transport to other countries.

Serious concerns relating to this field of research entered the international spotlight in January, 2001, when Australian scientists developing a contraceptive vaccine for controlling field mice populations sought to enhance the vaccines effectiveness by inserting the gene for the immune regulatory protein interleukin-4 (IL-4) into mousepox, which was being used as a carrier virus.  IL-4 is a substance that is normally produced in mice, but insertion of the IL-4 gene into the mousepox genome unexpectedly transformed the normally benign virus into a virulent strain that shut down the immune system and killed all the animals in the experiment.  In addition to rendering mousepox lethal in mice genetically resistant to the virus, the inserted gene made the mousepox vaccine ineffective - the recombinant virus killed even those mice that had previously been vaccinated. [1]  Since human beings possess the interleukin-4 gene, it is possible that inserting this gene into a poxvirus that infects humans, such as smallpox or monkeypox, could create a lethal strain that would be resistant to the existing smallpox vaccine. [2]

In response to the threats presented, the international community is seeking guidance by the World Organization for Animal Health (OIE), Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO).

References:

[1] R.J.Jackson et al. (2001), "Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Supresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox," Journal of Virology, 75 (2001), pp. 1025-10.
[2] Tucker, Regulating Scientific Research of Potential Relevance to Biological Warfare, Monterey Institute of International Studies - After 9/11: Preventing Mass-Destruction Terrorism and Weapons Proliferation, Center for Nonproliferation Studies, Occasional Paper No.8, May 2002, p. 24.

http://www.eurekalert.org/pub_releases/2003-08/ns-dd082703.php

New Scientist issue: 30 AUGUST 2003

Designer diseases

EVERY few years, a plague of European house mice infests one of Australia's grain regions. Roads turn into fur carpets of squashed mice. Millions of dollars' worth of grain is eaten or spoiled. Homes and buildings are damaged. The only defence is poison, a slow painful death for the mice, and for any other animals that can get at the bait.

How much better it would be to have a kinder, gentler form of pest control, one that renders female mice infertile, preventing plagues before they start and leaving native wildlife untouched.

And that is just what the Pest Animal Control-Cooperative Research Centre (PAC-CRC) in Canberra hopes it has created. Its agent could be undergoing contained field trials in Australia within two years, and be commercially available within five.

But there's a catch. The agent in question is a genetically modified virus designed to replicate and spread. It is a new, man-made disease, one of several being developed (see "On the drawing board", opposite). Once released, they will be as hard to control as any other wildlife disease. Like natural diseases, they could be accidentally or deliberately taken to other countries. They could mutate or recombine with other viruses. They could jump species. The consequences could be disastrous.

The European house mouse may be an exotic pest in Australia, for instance, but in many countries it is a native animal and a key part of the food chain. Nor is the mouse virus the only "disseminating" or transmissible genetically modified organism with the potential to spark international conflict. A team in New Zealand is modifying a parasitic nematode to sterilise brushtail possums a devastating pest in New Zealand but a protected species in Australia. "Once you've let it go, you can't get it back," admits Warwick Grant, head of the team at AgResearch in Upper Hutt. "Biological control has a chequered history. The stakes are pretty high and you don't want to get it wrong."

Meanwhile, on a small island in Spain, a transmissible GMO with quite a different purpose has already been tested. It is a living vaccine that protects rabbits from myxomatosis and calicivirus. These diseases have decimated Spanish rabbit populations,  causing consternation among hunters as well as affecting predators such as the threatened Iberian lynx and the Spanish imperial eagle. Australian farmers, by contrast, were only too happy when calicivirus escaped from a research station on Wardang  Island in 1995. For them, the arrival of the Spanish virus would be a disaster, allowing rabbit populations to boom.  If the potential for international conflict is obvious, the means of preventing it is not. None of the researchers contacted by New  Scientist knew who to consult in countries that might be adversely affected by the transmissible GMOs they are developing,  what they would do if a country objected to the GMO, and what international laws govern the release of such organisms.

The confusion is understandable. Within the European Union, the European Agency for the Evaluation of Medicinal Products must approve the commercial use of the Spanish GMO rabbit vaccine- and it is unlikely to do so given the current European distaste for GMOs, according to team member Juan B‡rcena of the Centre for Animal Health Research (CISA) in Madrid.

Around the world, various organisations have put out recommendations on the use of GMOs in general, but only one, the World Organisation for Animal Health (OIE), is anywhere close to exerting control over transmissible GMOs. Earlier this year, a report from its Working Group on Wildlife Diseases again raised concerns about these organisms. The OIE has yet to establish an official position on the issue, but if it does, member countries would likely take notice. But for now, PAC-CRC teams in Australia only need permission from the Office of the Gene Technology Regulator to release a GMO. The OGTR considers a GMO's potential impact on the environment and can consult internationally. But it is not clear whether the OGTR has the power or the will to refuse to allow a transmissible GMO to be released in Australia because of its potential impact in another country. The head of the OGTR, Sue Meek, declined to be interviewed.

"The public is not even aware of these developments," says Robert Henzell of the Animal and Plant Control Commission in Adelaide, South Australia. He thinks that transmissible GMOs could be useful in places like Australia, with its vast tracts of   sparsely populated land. But the job of pest control must be done safely, Henzell says. "We want to talk about these things before they are let go, rather than pick up the pieces later."

Tony Peacock, head of the PAC-CRC, argues that Australia's island status and its distance from other countries, allied with quarantine procedures, would be enough to stop a GMO from leaving its shores. But those barriers were not enough to stop people illegally taking calicivirus from Australia to New Zealand in 1997. Peacock also says that the consequences, should the mouse GMO escape, would not necessarily be disastrous, because the speed it spreads depends on the density of the mouse population. "The GMO is designed to avoid plaguing, not to wipe out a population," he says.

But that is not good enough for Henzell, who is organising a symposium on transmissible GMOs in New Zealand later this year.  One topic up for discussion there is the development of safety measures that would help stop such organisms straying. One tactic would be to engineer a GMO to die out after few generations. But this runs counter to the whole idea of transmissible GMOs, which is that by being self-sustaining they avoid the huge expense of methods like laying bait.

Another option, says Henzell, would be to engineer an organism so that it is activated only in the presence of a specific chemical, such as something found only in the diet of animals in the country where it is intended to work. Alternatively, a second transmissible GMO that protects animals from the first could be developed for use in non-target countries. "We ought to at least consider these things and ask whether they are possible," says Henzell. "But there's been nothing done so far."

And the potential for transmissible GMOs to spread to other countries is just one of the safety issues. What if the mouse virus- a modified mouse cytomegalovirus- jumps species and starts infecting one of Australia's own endangered rodents, or even people?  "You can't assume that the modified virus will act like the parental strain," warns Adrian Gibbs, an expert on viral evolution   formerly at the Australian National University in Canberra.

So far PAC-CRC has shown only that the mouse GMO does not infect rats, and that three species of native rodents are  immune to the unmodified virus. It is gearing up to conduct safety experiments that will test the virus's ability to infect a wide range of species, including some rare mouse species in the US. The ultimate experiment will be releasing the virus. If it turns out that PAC-CRC has got it wrong, there may be little anyone can do about it.

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