Disease research I seem to recall...
Remus Shepherd
in the late 1990s. If I remember correctly, scientists in Australia were
trying to make calicivirus more deadly to rabbits. In so doing, they added
a protein to the virus coat that made it effectively invisible to immune
cells, boosting its lethality to near 100%. Problem was, the 'cloak' protein
worked on all immune systems, including human, and it was a simple addition
that could be added on to any virus. What they had discovered was a way to
make any virus into an unstoppable plague.
I remember reading about this research, but since then I haven't heard
anything about it. Nor can I find anything about it now. That leads me to
two possibilities: Either my memory is false and I imagined this research,
or it was real but was swiftly suppressed and has now fallen down the memory
hole.
Does anyone remember this research, or can anyone find evidence of it,
anywhere?
... ...
Remus Shepherd <re...@panix.com>
Journal: http://www.livejournal.com/users/remus_shepherd/
care...@gmail.com
Science 17 September 1999:
Vol. 285. no. 5435, p. 1842
DOI: 10.1126/science.285.5435.1842
Prev | Table of Contents | Next
News Focus
BIOLOGICAL CONTROL:
Australian Biocontrol Beats Rabbits, But Not Rules
Elizabeth Finkel*
MELBOURNE--In 1859, Thomas Austin, one of Victoria's landed gentry,
introduced a few European rabbits onto his estate for sport--and
Australians have been cursing him ever since. To stop millions of
foliage-eating rabbits from turning huge tracts into desert, Australia
has become the only nation to successfully use a biocontrol agent on a
vertebrate. Officials released the myxomatosis virus in the 1950s, and
then, as that virus's potency waned, followed it with the European
rabbit calicivirus disease (RCD) in 1995. The new virus appears to be
a stunning success: Rabbit numbers are way down and once barren
deserts are blooming (Science, 10 January 1997, p. 154). Yet for
biocontrol officials, the calicivirus experience has been a major
embarrassment, a sobering lesson in the unpredictability of biocontrol
agents.
The problem is that RCD escaped into the wild while it was still being
tested on an island off the Australian coast. The Commonwealth
Scientific and Industrial Research Organisation (CSIRO) had already
determined that the virus would not harm humans or Australia's unique
native mammals. But before the CSIRO could complete field tests on how
well the virus spread, flying insects are thought to have picked it up
from two infected rabbits and carried it to the mainland. The escape
left the CSIRO legally vulnerable and has eroded public trust in
biocontrol. "We have a track record of an escape," says Bob Seamark,
director of another biocontrol institute, the Pest Animal Control
Cooperative Research Center in Canberra. "This is a problem for us,"
one that may come back to haunt Seamark's agency in a few years when
it attempts to release a next-generation biocontrol agent, a myxoma
virus that carries an antifertility gene.
Officials had planned to seek public approval for the release--after
they finished field trials--as part of an act protecting CSIRO legally
should anything go wrong. But because the escape happened before the
public consultation was finished, CSIRO now faces a lawsuit from those
in the wild rabbit trade, including the makers of Australia's famous
icon, the rabbit-pelt Akubra hat.
The lesson, biocontrol researchers say, is that biocontrol agents are
so likely to escape that agencies should seek public approval before
starting field trials. "The question is at what point should the
public be responsible for [permitting] the release," says Niall Byrne,
a former PR officer for the Australian Animal Health Laboratories in
Geelong, which did the testing. If CSIRO had gotten approval before
the field trial, then RCD might be considered a complete success.
Indeed, Australia's farmers already count it as such. In the arid
zones that make up two-thirds of the country, where rabbits have been
most voracious, farmers are reporting near-total eradication and
saving an estimated $3 million to $4 million per year in rabbit
control. CSIRO ecologist Brian Cooke's studies show that the virus is
retaining its punch, unlike the myxomatosis virus, whose effectiveness
dropped from 99% to 70% after 4 years. "This is no flash in the
pan,"he says. And for the first time since the 1800s, there are signs
of regeneration in Australia's fragile ecosystems. The vast Nullarbor
plain that stretches across the southern coast is coming alive with
knee-high acacia seedlings next to big old trees that predate the
rabbits; similar scenes of young and old cypress pines can be seen in
northern Victoria.
Next time, biocontrol officials say, they'll be as smart about
politics as they were about the science. "We got a lot of
understanding from the process going wrong," says CSIRO scientist Lyn
Hinds. "It wasn't the steps we took but the order we took them in."
Elizabeth Finkel writes from Melbourne, Australia.
1. Media releases, Australia and New Zealand Rabbit
Calicivirus Disease Programn. Canberra. South Australia.
23 October and 29 October 1995.
2. ''Rabbit calicivirus disease and public health'' (Australia
and New Zealand Rabbit Calicivirus Disease
Program. Canberra. South Australia. 1 March 1996).
3. W. Xu. Rev. Sci. Tecl. O.I.E. (Off. Int. Epizoot.) 10.
393 (1991).
4. D. A. Gregg and C. House. Vet. Rec. 125. 603
(1989).
5. S. Bennett. A'ustralia and New Zealand Rabbit Calicivirus
Disease Program-Update'' (Canberra,
South Australia. 16 April 1996), p. 3: F. A. Leighton.
M. Artois. L. Cappucci. D. Gavier-Widen. J. P.
Norisse. J. Wildl. Dis. 31. 541 (1995): C. M. Simon et
al.. Recueil Med. Vet. 170, 841 (1994).
6. A. W. Smith and P. M. Boyt. J. Zoo Wildl. Med. 21. 3
(1990): E. T. Clayson et al.. Am. Trop. Med. H,yg. 53.
228 (1995).
7. D. 0. Matson et al.. Arch). Virol.. in press.
Science 5 July 1996:
Vol. 273. no. 5271, pp. 15 - 18
DOI: 10.1126/science.273.5271.15b
Prev | Table of Contents | Next
Letters
Release of RHD Virus in Australia
Letters from:
David O. Matson
Alvin W. Smith
The defenders of the rabbit hemorrhagic disease (RHD) virus release
program (Dan Drollette, News & Comment, 12 Apr., p. 191; ScienceScope,
19 April, p. 341) appear to have confused the concepts of "host
switching" and "host range" (1). Alvin Smith and I have raised the
concern that the host range of this agent, first described in 1984, is
not known. Our concern has been that widespread release of this virus
to a continent apparently lacking experience with it would reveal
unfortunate new information about the host range of the agent. While
it is possible that the RHD virus might switch hosts, suddenly
developing an ability to replicate in another species, we agree that
this would be unlikely, although the possibility is enhanced by the
ecological conditions in Australia.
The question of host range, while generally applicable, has particular
relevance because of our knowledge of caliciviruses as a family. Some
caliciviruses, although within a genome group different from that of
the rabbit calicivirus, are known to have a broad host range (2, 3).
Because it took 50 years to learn what is now known about the host
range of some calicivirus strains, it is reasonable to believe that
the host range for the RHD virus, described in 1984, is not yet known.
The possibility that the RHD virus might find a host among the large
number of previously unchallenged species in Australia seems
reasonable.
Scientists from the Commonwealth Scientific and Industrial Research
Organization (CSIRO) have addressed this concern by conducting
challenge experiments in 28 species of animals. These experiments have
not been published.
Smith is described as an isolated critic. However, he has isolated
more species of caliciviruses than anyone else, from approximately 30
species of animals (2). His work led to the hypothesis that the
vesicular exanthem of swine virus (a calicivirus) outbreaks in pigs in
the southwest United States from the 1930s to the 1950s were related
to San Miguel sea lion caliciviruses. This hypothesis was
substantiated by his own work and recently proved independently by
others (4).
The plans for studying the RHD viral agent in Australia clearly
failed. Release of a lethal agent into the wild without knowledge of
its route of transmission was a mistake. On the other hand, Brian Cook
of CSIRO makes a valid point, quoted in Drollette's article, that the
Australians face a difficult challenge, namely, weighing the potential
"risk of a virus which might cross over into another species against
the inevitability of losing more of our native speices." This is an
appropriate concern and certainly justifies the efforts toward
studying the RHD virus as a potential biological control agent.
However, approval of the RHD virus program after an accidental release
would set a poor precedent for future studies of biologic control.
David O. Matson
Center for Pediatric Research,
Eastern Virginia Medical School, and
Children's Hospital of The King's Daughters,
855 West Brambleton Avenue,
Norfolk, VA 23510, USA
References and Notes
1. For example, see B. J. Coman, "Environmental impact associated
with the proposed use of rabbit calicivirus disease for integrated
rabbit control in Australia. February 1996." This is an environmental
impact statement prepared for the Australia and New Zealand Rabbit
Calicivirus Program.
2. A. W. Smith and P. M. Boyt, J. Zoo. Wildl. Med. 21, 3 (1990).
3. T. Berke et al., 35th Interscience Conference on Antimicrobial
Agents and Chemotherapy, San Francisco, CA, October 1995.
4. J. D. Neill, R. F. Meyer, B. S. Seal, Virology 69, 4484 (1995).
If the escaped RHD virus can be declared an official "biological
agent" by the Australian government, that would remove liability, but
to receive such "approval" the virus must be shown to be species-
specific, infecting only the European domestic rabbit Oryctolagus
cuniculus (1).
CSIRO scientists, ostensibly investigating host range, gave 30 species
of domestic, wild, and laboratory animals a low virus count (1000
rabbit lethal dose50) so as not to "force a response," according to
Harvey Westbury, senior veterinary virologist of the Australian Animal
Health Laboratory (quoted in Drollette's article). But this dosage is
below the immunogenic and infectivity threshold in 28 of the 30
species tested (four animals per test)--only about 1/30,000 of the
dose a predator would receive eating a single infected rabbit liver.
To test human susceptibility, Australian authorities examined serum
samples from only six people (all were laboratory workers and were
antibody-negative) and did not examine high-risk individuals such as
ranchers, biologists, and hunters who handle infected rabbits. One
laboratory worker tested during an RHD outbreak in Mexico was positive
for the RHD antibody (2).
Sudden appearance (3) and high mortality (95%) indicate that that RHD
almost certainly did not originate in rabbits and is not species-
specific. The cause of death (disseminated intravascular blood clots
with fibrin-depleted blood oozing from orifices and into tissues) is
not described for any other calicivirus. The likelihood of this
"hemorrhagic" factor emerging in other species infected with
caliciviruses is unknown. The mechanisms of virus movements across
land and ocean channels are unknown.
Rabbit calicivirus has yet to be grown in cell culture. Therefore,
vaccines and some diagnostic reagents are ground-up livers from
diseased rabbits. Koch's postulates are unfulfilled, and,
consequently, there is confusion about etiology (3, 4).
Adequate surveys to determine disease or infection in nonrabbit
species that have been exposed naturally have not been carried out.
Serologic testing of extremely small numbers of nonrabbit species,
exposed experimentally and naturally, has yielded antibodies [in the
mouse, kiwi, dog, fox, and human (5)], yet without proof (mice
excepted), Australian officials have stated that infection did not
occur. Despite much evidence suggesting otherwise (6), Australian
government agencies declared RHD to be species-specific for rabbits
and not infectious to other animals or humans. [Four of the five known
calicivirus groups cause disease in humans (7)]. These same agencies
have notified the Australian people that it would be safe for them to
eat rabbits exposed to RHD and to feed these rabbits to their pets
(1).
I discussed these critical factors with Drollette, but he did not
mention them in his article. These factors were considered by the
recently elected Australian government in rethinking the official
position on the targeted March-April 1996 release of this new
hemorrhagic disease virus. Additional studies have been ordered before
reconsideration of RHD virus as a "biological agent" and a sanctioning
of its deliberate spread. If these studies are carried out to truly
test the host specificity and zoonotic potential of this new and
deadly virus, then scientific credibility could be restored.
Alvin W. Smith
Laboratory for Calcivirus Studies,
College of Veterinary Medicine,
Oregon State University,
Corvallis, OR 97331, USA
E-mail: smi...@comail.orst.edu
References
1. Media releases, Australia and New Zealand Rabbit Calicivirus
Disease Program, Canberra, South Australia, 23 October and 29 October
1995.
2. "Rabbit calicivirus disease and public health" (Australia and
New Zealand Rabbit Calicivirus Disease Program, Canberra, South
Australia, 1 March 1996).
3. W. Xu, Rev. Sci. Tech. O.I.E. (Off. Int. Epizoot.) 10, 393
(1991).
4. D. A. Gregg and C. House, Vet. Rec. 125, 603 (1989).
5. S. Bennett, "Australia and New Zealand Rabbit Calicivirus
Disease Program--Update" (Canberra, South Australia, 16 April 1996),
p. 3; F. A. Leighton, M. Artois, L. Cappucci, D. Gavier-Widen, J. P.
Norisse, J. Wildl. Dis. 31, 541 (1995); C. M. Simon et al., Recueil
Med. Vet. 170, 841 (1994).
6. A. W. Smith and P. M. Boyt, J. Zoo Wildl. Med. 21, 3 (1990); E.
T. Clayson et al., Am. Trop. Med. Hyg. 53, 228 (1995).
7. D. O. Matson et al., Arch. Virol., in press.
Remus Shepherd
> Science 17 September 1999:
> Vol. 285. no. 5435, p. 1842
> DOI: 10.1126/science.285.5435.1842
> Prev | Table of Contents | Next
> News Focus
> BIOLOGICAL CONTROL:
> Australian Biocontrol Beats Rabbits, But Not Rules
> Elizabeth Finkel*
Thank you! That's almost what I'm looking for. It describes the
accidental outbreak, but not the science behind why the modified virus
is such a danger.
Derek Lyons
>care...@gmail.com <care...@gmail.com> wrote:
>> Science 17 September 1999:
>> Vol. 285. no. 5435, p. 1842
>> DOI: 10.1126/science.285.5435.1842
>
>> Prev | Table of Contents | Next
>> News Focus
>> BIOLOGICAL CONTROL:
>> Australian Biocontrol Beats Rabbits, But Not Rules
>> Elizabeth Finkel*
>
> Thank you! That's almost what I'm looking for. It describes the
>accidental outbreak, but not the science behind why the modified virus
>is such a danger.
That would be because it utterly and completly fails to even mention a
modified virus. I suspect your memory is faulty, though your bias
remains healthy.
D.
--
Touch-twice life. Eat. Drink. Laugh.
http://derekl1963.livejournal.com/
-Resolved: To be more temperate in my postings.
Oct 5th, 2004 JDL
Remus Shepherd
> Remus Shepherd <re...@panix.com> wrote:
> > Thank you! That's almost what I'm looking for. It describes the
> >accidental outbreak, but not the science behind why the modified virus
> >is such a danger.
> That would be because it utterly and completly fails to even mention a
> modified virus. I suspect your memory is faulty, though your bias
> remains healthy.
Well, that's what I was trying to prove: Whether or not my memory was
faulty. If this is the news article I remember, then my memory failed.
Not quite sure this is it, however -- I don't recall an outbreak, only a
laboratory experiment.
Carey
> Derek Lyons <fair...@gmail.com> wrote:
>> Remus Shepherd <re...@panix.com> wrote:
>>> Thank you! That's almost what I'm looking for. It describes the
>>> accidental outbreak, but not the science behind why the modified virus
>>> is such a danger.
>
>> That would be because it utterly and completly fails to even mention a
>> modified virus. I suspect your memory is faulty, though your bias
>> remains healthy.
>
> Well, that's what I was trying to prove: Whether or not my memory was
> faulty. If this is the news article I remember, then my memory failed.
> Not quite sure this is it, however -- I don't recall an outbreak, only a
> laboratory experiment.
>
You are probably conflating the calicivirus project with a separate and
more recent one having to do with modified mousepox viruses:
Science 26 January 2001:
Vol. 291. no. 5504, p. 585
DOI: 10.1126/science.291.5504.585
AUSTRALIA:
Engineered Mouse Virus Spurs Bioweapon Fears
Elizabeth Finkel
MELBOURNE, AUSTRALIA--The surprising virulence of a virus genetically
altered to reduce rodent infestations in Australia has raised alarm over
whether such research could be hijacked to produce biological weapons.
In an unusual twist, those sounding the alarm are not environmental
activists but the scientists themselves. Despite their warning, released
with the research results this month in an electronic version of the
Journal of Virology, it's not clear whether the unexpected result, which
turned a vector into a potent killer, could be duplicated in viruses
that affect humans. But scientists say it should serve as a warning to
the community to be more aware of the potentially harmful consequences
of their work.
The goal of the research was certainly benign. The scientists were
attempting to sterilize rodents by using a virus to trigger an antibody
attack against mouse egg proteins. But when the researchers attempted to
beef up this virus by incorporating the immune system hormone
interleukin-4 (IL-4) into its genetic payload, the virus turned into a
killer, wiping out all the animals. Even vaccination offered little
protection.
The potency of this modified virus startled officials at the
Co-operative Research Center (CRC) for the Biological Control of Pest
Animals in Canberra, whose scientists had teamed up with the John Curtin
School of Medical Research at the Australian National University in
Canberra. So on 16 January the CRC issued a press release timed to
accompany the article that pleaded for stronger measures to combat the
threat of biowarfare arising from such good intentions. Not
surprisingly, the press release triggered sensational warnings in the
Australian media and elsewhere.
"This is the public's worst fears about GMOs [genetically modified
organisms] come true," says CRC director Bob Seamark, who led the
research. Adds Annabelle Duncan, a former deputy head of the United
Nations team of inspectors in Iraq and now chief of molecular science at
the Commonwealth Scientific and Industrial Research Organization
(CSIRO), "This shows that something we had thought was hard--increasing
the pathogenicity of a virus--is easy."
The focus of all this attention is a mousepox virus that had been
engineered to carry the mouse egg shell protein ZP3, or zona pellucida
3, as a mouse contraceptive. The foreign protein triggers an antibody
response that within several months destroyed eggs in female mice, at
least in one laboratory strain of mice. But when Seamark's group tried
the technique on a second strain of mice, known as Black 6, it was
ineffective.
To boost the antibody response, Seamark called on the immunological
expertise of Ian Ramshaw's group at the Australian National University.
In previous work, they had shown that adding IL-4 to the genetic payload
of the vaccinia virus increased the antibody-producing response in mice
and toned down the effectiveness of virus-clearing killer T cells.
Hoping to take advantage of this shift, Seamark's team inserted the IL-4
gene into the mousepox virus. They expected only to strengthen the
antibody response in the resistant Black 6 strain, but instead the virus
overwhelmed the mice, proliferating out of control and destroying their
livers. Even mice that had been vaccinated against the virus fared
poorly, with half dying immediately and the remainder developing a
chronic abscess at the site of infection. "This was a shock to us," says
Seamark, who worries about the close relationship between mousepox and
smallpox, once a scourge to humans. "We [also] had shown that a commonly
used technology could overwhelm resistance and render vaccination useless."
The team spent the next 18 months confirming the data and debating
whether to go public with them. In the end, disclosure won out over
concerns about educating future bioterrorists and alarming the public.
"We need the public to trust us if we are going to seek their approval
to release pest-control viruses down the track," says Seamark, the
driving force behind a consensus conference on GMOs held 2 years ago in
Canberra (Science, 5 March 1999, p. 1427). But any intentional release,
he hastens to add, won't involve viruses carrying the IL-4 gene. "These
are confined to the high-security lab," he says.
Such fears may be overrated, says Ron Jackson, the CRC virologist who
carried out much of the work. Jackson suspects that the findings may be
peculiar to the mousepox virus, which naturally carries other proteins,
such as interferon g binding protein, that weaken the antiviral
response. He notes that the result did not occur with the vaccinia virus
in Ramshaw's lab.
At the same time, he and other scientists point out that many viruses
employ immune system modifiers as part of their arsenal, including the
human Epstein-Barr virus and primate cytomegaloviruses. "I wouldn't say
that mousepox is an exception," says immunologist Chris Burrell of the
University of Adelaide in South Australia. "The more we look, the more
we find viruses that carry these types of genes."
The implications of this finding are of intense interest to
organizations such as the Federation of American Scientists, which has
formed a working group to develop a protocol that would add verification
powers to the currently toothless international convention on biological
weapons. "Until now, we considered genetically engineered organisms
little threat compared to the naturally occurring ones," says
microbiologist Mark Wheelis of the University of California, Davis, a
member of the working group. "But with genomics and proteomics, we're
going to see a lot more of this sort of thing."
Remus Shepherd
> > Well, that's what I was trying to prove: Whether or not my memory was
> > faulty. If this is the news article I remember, then my memory failed.
> > Not quite sure this is it, however -- I don't recall an outbreak, only a
> > laboratory experiment.
> You are probably conflating the calicivirus project with a separate and
> more recent one having to do with modified mousepox viruses:
> Science 26 January 2001:
> Vol. 291. no. 5504, p. 585
> DOI: 10.1126/science.291.5504.585
> AUSTRALIA:
> Engineered Mouse Virus Spurs Bioweapon Fears
Thank you! That's it, that's dead on target. It also explains why I
couldn't find any references to it; I was stuck on thinking it was
calicivirus. At least I got the continent right.
So the research wasn't suppressed, it's just laying out there available
to anyone. I would expect to hear more people talking about it. Maybe
it's because the lethality-boosting technique might be specific to smallpox
type viruses, and people are scared enough of smallpox already.
As a bogeyman for a sci-fi tale, though, this is exactly what I needed.
Thanks again!
Greg Goss
>Remus Shepherd <re...@panix.com> wrote:
>
>>care...@gmail.com <care...@gmail.com> wrote:
>>> Science 17 September 1999:
>>> Vol. 285. no. 5435, p. 1842
>>> DOI: 10.1126/science.285.5435.1842
>>
>>> Prev | Table of Contents | Next
>>> News Focus
>>> BIOLOGICAL CONTROL:
>>> Australian Biocontrol Beats Rabbits, But Not Rules
>>> Elizabeth Finkel*
>>
>> Thank you! That's almost what I'm looking for. It describes the
>>accidental outbreak, but not the science behind why the modified virus
>>is such a danger.
>
>That would be because it utterly and completly fails to even mention a
>modified virus. I suspect your memory is faulty, though your bias
>remains healthy.
I remember the story, too. A modified virus of some kind with pretty
close to total lethality in its target animal. Much more lethality
than the researchers were expecting. But I don't remember enough to
be useful to google it. Just enough to act as a second vague voice
plaintively asking "Does someone else remember this?"
--
Tomorrow is today already.
Greg Goss, 1989-01-27
Thomas Womack
Greg Goss <go...@gossg.org> wrote:
>I remember the story, too. A modified virus of some kind with pretty
>close to total lethality in its target animal. Much more lethality
>than the researchers were expecting. But I don't remember enough to
>be useful to google it. Just enough to act as a second vague voice
>plaintively asking "Does someone else remember this?"
http://online.sfsu.edu/~rone/GEessays/BioterrorMousepox.htm
(added an interleukin-4 gene to mousepox, with the result that the
virus produced IL4 in quantities enough to screw up the host's immune
system entirely)
Tom