This letter was prepared in response to the Australian Biological Control Authority's "request for comment" regarding the issue of declaring the Rabbit Hemorrhagic Disease (RHD) agent, also called Rabbit Caliciviral Disease (RCD) agent, a biological agent. The public comment period closed 10 January 1996.

30 December 1995

To: Biological Control Authority
GPO Box 858
Canberra ACT 2601

Copies to:

Dear Concerned Parties:

The purpose of this letter is to express our concern about the use of caliciviruses in rabbit eradication efforts. I am Alvin W. Smith, DVM, PhD, Professor of Veterinary Medicine at Oregon State University. I have headed Calicivirus study laboratories in the United States since 1972 and have been so engaged at the Laboratory for Calicivirus Studies at Oregon State University since 1980. My colleague is David O. Matson, MD, PhD, Associate Professor at the Center for Pediatric Research in Norfolk, Virginia. He and I have collaborated on Calicivirus research for many years. He is also the most knowledgeable individual in the United States on Caliciviruses which cause disease in humans and on the overall molecular biology of Caliciviruses.

I first learned of the Rabbit Calicivirus plague in Australian rabbits through an Associated Press release printed on 28 November and was chagrined to learn of the several years' effort leading to this event in the absence of a full scientific forum. Unfortunately, newspapers and Internet communications have been substituted for scientific publications. This has impeded scientific discourse that normally would have led to a proper evaluation of the use of Caliciviruses as biological vectors. The news release from Oregon State University (copy enclosed) has generated a great deal of antagonism from CSIRO, some of which has deteriorated to personal attacks presumably in an attempt to discredit the information provided. The scientific basis for our concerns has not been addressed.

Our concern is that the rabbit Calicivirus may jump species barriers. There is considerable scientific evidence to support this concern. We do not understand why that evidence has not been addressed by the research administrators in Australia who are charged with approving this vector system to control unwanted rabbit populations. CSIRO has partially acknowledged this evidence in its own public statements which warned people to protect pet rabbits from exposure to insects and birds that might be contaminated with the rabbit Calicivirus.

We believe an international panel of Calicivirus researchers should be convened to examine all aspects of Calicivirus spread and disease in both humans and other target, nontarget and reservoir species. While it might first appear that Australia would be a proper setting for such a panel meeting, the content of the discourse to which we have been exposed in the public arena in Australia, suggests that perhaps New Zealand or the United States would be a better venue.

We would suggest that any action toward approving the caliciviral agent as a vector for rabbits be delayed until a full unbiased and scientific evaluation has been completed including definitive answers to the following questions and issues.

1. What about safety? What is the potential for infection or disease in non-target species? CSIRO experiments using 28 species suggests that infection or disease did not readily occur or was not detected in those species under the conditions of the experimental exposure using the available tools for recovering virus and detecting antibody conversion. These experiments say nothing about future exposure of these same species nor hundreds of others including humans that could be exposed to literally thousands of calicivirus variants that will be generated as billions of calicivirus replicates are generated in millions of infected, dead, and dying rabbits.

2. What about human safety factors and what is the potential for human infection? Four of the five calicivirus genetic groups already are known to infect humans.

3. How good are the laboratory tests for detecting rabbit calicivirus infection? Do assays detect type specific antibodies to rabbit calicivirus and to the variants of rabbit calicivirus that occur during the normal replicative cycle of this agent? Other caliciviruses have been studied for decades yet these tests are still not definitive in all circumstances. Their weaknesses primarily involve specificity and sensitivity where variants are to be compared or low copy numbers of a specific virus type may need to be detected. RT-PCR and other current diagnostic and research tools are helpful but have well recognized limitations.

4. What about the specific virulence factor that kills the rabbits, that is the alteration of the blood clotting mechanism? What is the precise mechanism? What are the genetic markers in the virus for this trait and can this trait be passed between species as the virus adapts to new species? Caliciviruses have been repeatedly isolated from 3 species of seals born prematurely which exhibited what has been termed "perinatal hemorrhagic syndrome" and from stillborn piglets with "purpura hemorrhagia". Although the causal relationships between the caliciviruses and the blood disease conditions are not known, this evidence suggests that caliciviruses causing hemorrhage can move between species and retain certain critical virulence properties in different species. Many similar examples for other virulence traits among calicivirus strains that cross species are known. Alterations of blood clotting mechanisms are just one example.

5. What has surveillance revealed about the prevalence of caliciviral infections that may already be established in Australian animals and people? Has there been wide scale testing? What assays were used? How good are the assays? How might the findings of antibodies against multiple calicivirus types and variants confound surveillance for rabbit calicivirus infection in all populations at risk now that the rabbit calicivirus has been released?

6. What is the original source of rabbit caliciviruses? Almost certainly it jumped species to become a killer virus of rabbits. If not, there must be a switching mechanism for this virus that changed it from a simple infection of rabbits to a deadly killer agent. Is this mechanism understood? Understanding the origins of rabbit calicivirus should provide persuasive arguments for suggesting that the calicivirus is capable of jumping species. Additional powerful arguments involve the known interspecies movements of the San Miguel/Vesicular Exanthema Caliciviruses, the feline Calicivirus, the Hepatitis E Calicivirus of humans, and the Norwalk-like group of human caliciviruses. Should we simply assume that the rabbit calicivirus group is the only calicivirus group that does not adapt between species when it took 40+ years to recognize cross species movements of calicivirus strains belonging to the other genogroups?

7. What will be the United States and other governments policies toward Australian agricultural products now that this Foreign Animal Disease agent is widespread on your continent? We believe an open forum is the best way to gain consensus on this and other scientific issues. With respect to the scientific community the plans to release rabbit calicivirus have been conducted as a closed shop operation. It is our opinion that this has brought some measure of discredit to all scientists. We want to reverse that perception.

With Highest Regard,


Alvin W. Smith, DVM, PhD
Professor and Head,
Laboratory for Calicivirus Studies
Oregon State University

David O. Matson, MD, PhD
Associate Professor,
Center for Pediatric Research
Eastern Virginia Medical School

Enclosures:

List of people and agencies faxed copies of the above letter on January 3, 1996.

AUSTRALIA:
The Honorable Paul Keating, Prime Minister
fax 61-6-273-4100

The Honorable Bob Collins, Senator
fax 61-6-273-4120

The Honorable Peter Cook, CSIRO Minister for Science
fax 61-6-273-4104

The Biological Control Authority, Canberra
fax 61-6-272-5596

Wilson deSilva, The Sunday Age
fax 61-6-593-9400

Dr. Harvey Westbury and Keith Murray, CSIRO AAHL
fax 61-5-227-5555

Mrs. Marguerite Wegner
fax 61-9-354-2985

Tim Childs, Humane Society International
fax 02-9973-1729


NEW ZEALAND:
The Right Honorable James Bolger, Prime Minister
fax 64-4-473-7045

The Honorable John Falloon, Minister of Agriculture and Fisheries
fax 64-4-471-1765

The Honorable Philip Burdon, Minister of Trade Negotiations
fax 64-3-343-0785

Dr. J. Morgan Williams, New Zealand National RCD Coordinator
fax 64-4-471-1765

Dr. Neil Cherry, Regional Councillor
fax 64-3-343-3693


UNITED STATES:
Chris Lidgate, Willamette Week
fax 503-243-1115

Dr. David Matson
fax 804-668-6476

Anyone seeking additional information regarding RHD/RCD disease in Australia may wish to contact Mrs. Wegner who has been actively involved in the rabbit calicivirus debate and has said she can provide additional information.

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