|September 11, 2003
Stephen M. Apatow
Founder, Director of Research & Development
Humanitarian Resource Institute
Humanitarian University Consortium Graduate Studies
Center for Medicine, Veterinary Medicine & Law
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.
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.  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. 
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).
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.
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.
Scientist issue: 30 AUGUST 2003
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.
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.
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
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.
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."
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.
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.
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
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."
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.
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
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."
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.
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