Here is a copy of letter I sent to Michael Catton after he sought my advice concerning release of RHDV in Australia. Listed below are a few personal comments relating to introduction of RHDV for biological control.

1. I am not aware of any incident where a human has sustained a significant exposure to RHDV. In the light of the lack of information, I believe that we should test for antibodies to RHDV in persons who have had contact with infected animals either in the laboratory or the field. It is known for instance that San Miguel Sealion Virus can infect laboratory workers and one can certainly find antibodies to feline calicivirus in humans, suggesting that animal caliciviruses have the potential to infect humans. There is also a calicivirus which was isolated from Herpes like legions in pigmy chimpanzees and another which has caused encephalitis in monkeys that fall within the VESV, SMSLV, genetic cluster. It is probable that viruses that can infect primates would be transmissible to man. I have since learnt that the Australians have screened several hundred people who were likely to have been in contact with RHDV and found no evidence of specific antibodies against RHDV.

2. There is plenty of evidence that viruses related to VESV/SMSLV and FCV can infect different species. Al Smith has summarised the evidence that VESV/SMSLV can infect many species ranging from fish to primates and possibly man. Smith A W. and Boyt P M. (1990) Caliciviruses of Ocean origin. Journal of Zoo and Wildlife Medicine 21: 3-23. Feline calicivirus strains infect many members of the felidae and also dogs.

3. As you must be aware RHDV and EBHSV are genetically closely related and probably had a common ancestor but hares and rabbits are quite distinct groups of animals again suggesting the potential for caliciviruses to cross species barriers as a result of mutation. At the recent European Symposium in Reading on Caliciviruses, 15-17th September 1996, evidence was presented that the inner shell of these two viruses are antigenetically very similar and that the differences relate to the outer domains, which suggests that they had a common ancestor. It was also suggested that RHDV has only become virulent in the last 150 years. Dr Al Smith provided convincing evidence that avirulent forms of VESV/SMSLV can become highly virulent after only one passage through a different species.

4. It is known from recent studies, mainly on human caliciviruses that there are numerous genetic variants indicating the potential for rapid mutation. I believe that if RHDV is released into the immense rabbit population of Australia it will almost certainly undergo mutation many times resulting in more virulent or avirulant forms. A situation which is already known to exist, as a result of attempts to produce effective RHDV vaccines. If the avirulent forms become prevalent then the goal of reducing the rabbit population will not be achieved. On the other hand, it may result in a variant that will enable it to cross species barriers.

5. I think there will be extreme opposition from animal rights activists about using RHDV for biological control, particulary in the light of the particulary unpleasant symptoms, haemorrhaging of the blood vessels in the lung, followed by clotting which lead to death.

6. There is a strong evidence that RHDV can cross physical barriers both from your experience in Australia and from reports in the UK, (Chasey D 1994 Possible Origin of rabbit haemorrhagic disease in the United Kingdom).Their mechanism of transfer has been suggested to be aerosols, insects or birds which clearly do not respect national boundaries, therefore one has to take into consideration that although rabbits are pests in Australia that they are of considerable economic value in many other regions of the world as a source of meat and wool.

7. At the recent meeting it was suggested by the Australians that the vector for RHDV is the bush fly but I believe this is only part of the story judging by the speed at which the virus has moved in Australia, over 20 Km/day and sometimes much further. How did the virus spread from Wardang Island if they say there were no birds!! and they treated the entire test site with insecticides? (It is difficult to believe this statement).

8. We were told by the Australians that the majority of animal challenges were conducted by administering the virus intramuscularly. This is not the natural mode of transmission of caliciviruses; studies should be conducted by administering virus by the naso-oral route. I gather from their experiments that Kiwis showed a seroresponse that may be related to the load of virus administered resulting in a hyperimmune response rather than being indicative of infection, but it clearly requires further investigation.

9. There are a number of avian candidate caliciviruses affecting chickens, pheasants, turkeys, guinea fowl and goldfinches. As far as I am aware no studies have been conducted to determine if they are related to RHDV and at present there is no genomic information to ascertain whether they fall with in the same calicivirus group as RHDV and EBHSV. Are they related? What if migratory birds can carry these viruses? Can caliciviruses recombine to result in a new virus? No one knows where the reservoir for these infections is.

10. The papers presented at the Reading Conference confirmed my belief that we are still at a very early stage of the learning curve, regarding the Caliciviridae and reiterated the need for extreme caution before releasing any virus into a virgin population. One only has to consult the history books to see the damage that has resulted by adopting such a policy.