A small percentage of sufferers get progressive nerve damage, and in the very long term it can cause cancers such as leukaemia and lymphoma. A closely related virus, HTLV-2, infects intravenous drug users in America and the Caribbean, which is also associated with nerve damage.
I listened attentively as Essex moved deeper into the heart of the preliminary investigation of the AIDS pandemic.
‘So we were studying HTLV from the standpoint of immune suppression and then, with Gallo, we put forward the hypothesis that retroviruses should be considered as a possible cause of AIDS. It was at that time too, let’s say ’82 – after the clinical syndrome of human AIDS had been announced, and before any human viruses had been claimed for discovery – that the head of the New England Primate Centre, a guy named Ron Hunt, called me. He said that he had seen immunosuppression similar to human AIDS, and to the immunosuppression we had described in cats, in his monkey colony at the Harvard-associated facility about 50km away from the medical campus. He asked me if I would come out and talk to them and make some suggestions about how they might find the cause. I went out there and had discussions with Ron, and with Norman Letvin and two or three others, and I made the suggestion that we look at blood and tissue samples. We found that there was a virus in the animals that had developed lymphoma, and in the ones that were housed with those that developed lymphoma, even though they might not have lymphoma. We showed that it was a retrovirus on serology and by electron microscopy.’
I should explain that the afflicted monkeys were not African monkeys – they were Asian macaques. I asked him if the antibodies they were finding in the macaques in the monkey colony suggested that they were infected not with the human virus, HTLV-1, but with a related retrovirus.
‘Right. It showed that a lot of the monkeys that had lymphoma – and some of the ones that did not have lymphoma but were in the same facility, and were immunosuppressed – had a virus that was cross-reactive with, and morphologically similar to, HTLV-1 in Japanese people. Then, when [HIV-1] the actual cause of AIDS was discovered,5 we already had samples of the causative virus [of the monkey immunosuppression] in our laboratory, and we then asked ourselves whether or not the sick monkeys had a virus exactly like [HIV-1] – and whether or not it clustered with the development of immunodeficiency.
‘I collaborated with Ron Desrosiers and Norm Letvin, with the work in my own laboratory coordinated by Phyllis Kanki, who was a doctoral student of mine at that time. We found that the monkeys that had the AIDS-like immunosuppression, and some of the ones with lymphoma too, were infected with a new virus, which we initially called STLV-III. Later, of course, it was called SIV.’6
SIV is the simian immunodeficiency virus, and its discovery would play a major role in our understanding of the origins of AIDS. But there was an additional, important extrapolation that came from its study. At this time nobody knew where AIDS had come from, geographically or virologically.
‘As soon as we realised there were viruses related to HIV and HTLV in monkeys, it seemed likely these viruses must be coming from Africa, and perhaps the common link with the human AIDS virus would be African. A year or two earlier, Belgian and Dutch researchers published work on the clinical recognition of AIDS in African people. So we said, “Gee, maybe we should look at people in Africa who are high risk for this sort of infection – like female prostitutes and male patients attending STD clinics, and perhaps infectious disease patients – and see if they have a virus that fits somewhere within the spectrum between the monkey viruses and the human viruses.” So we looked at blood samples from these high-risk people and found some cross-reactive antibodies and subsequently we also found actual virus.’
Which virus was he now speaking about?
‘People were clearly infected with a virus very closely related to the monkey virus, in fact virtually indistinguishable from it. And this new virus was clearly related to HIV-1 – but it was also clearly distinguishable from HIV-1.’
Like HIV-1, this second human retrovirus would subsequently be isolated by Luc Montagnier at the Pasteur Institute, and identified as the second human immunodeficiency virus, or HIV-2. But what now interested me was the very close evolutionary link between HIV-2 and the virus Essex’s group had earlier discovered, the simian immunodeficiency virus, SIV.
‘What has been shown since then is that the monkeys in West Africa have a range of SIV viruses. Some of these viruses, from monkeys in exactly the endemic area we were studying, and from mangabeys in particular, have a simian immunodeficiency virus that is indistinguishable from the HIV-2 in people in that area. Yet there are HIV-2 viruses infecting people two or three countries away, like Ghana, that are distinguishable from the HIV-2 infecting people in Senegal, which is 80km away – even though the viruses in people and monkeys in each country are not distinguishable from each other.’
I sat back to reflect on what Essex was telling me. The simian immunodeficiency virus and the human immunodeficiency virus, HIV-2, are actually one and the same virus. In his words: ‘It’s just that you call it one thing if it’s in people and another thing if it’s in mangabey monkeys.’ But there was a further, crucial, implication of what he had discovered. We believe that HIV-1, the main virus of AIDS, was transferred to people from a specific group of chimpanzees. We also know that, in chimpanzees, HIV-1 grows freely and reproduces in their internal organs and tissues, but it causes no evidence of disease. And like HIV-1 in chimpanzees, SIV produces no evidence of disease in mangabey monkeys, even though the virus also multiples freely in the monkeys’ tissues. Yet it seems altogether likely that, on first contact between the viruses and these animal hosts, the viral behaviour is likely to have been very aggressive. If we need any confirmation, we only need recall what happened when the SIV-carrying African mangabeys were housed in the same facility as the Asian macaques at the facility near Harvard. No more is it surprising that when chimpanzees, carrying an SIV virus closely related to what we now recognise as HIV-1, came into contact with people, the forerunner of HIV-1 hopped species to cause the aggressively fatal AIDS in humans.
I posed some relevant questions:
‘Let us say that a particular virus has been infecting an animal for a very long time and the animal and virus have reached the stage where they are coexisting without the virus causing serious disease in the animal. Now say another species of animal – a similar species – comes into contact with the host. It seems likely that the virus will cross species in a very vicious manner – it may prove to be highly lethal. Is it possible that what we are seeing here is an evolutionary mechanism? I also ask myself this: What if this is a symbiotic pattern of evolution, a symbiotic relationship between virus and host? In these circumstances, what might the host animal be getting out of it? And what occurs to me is that one of the things it could be getting out of it is the advantage that if a rival, for food or whatever, comes into its ecological niche, the virus jumps species and wipes out the rival.’
‘Yes, I think that’s a very logical hypothesis. You know the system that most shaped my own thoughts on that and made me write some of the things I did, such as the Scientific American article in which I compound the monkey virus behaviour in the different species with Frank Fenner’s discussion of the myxomatosis epidemic in Australia. And the bottom line of that is that when Europeans brought captive rabbits into Australia for the first time, the rabbits escaped into the wild. And because there were no foxes or natural enemies to control the rabbit populations, they multiplied in numbers and started destroying the crops. So the people there decided they needed to kill off the rabbits. They brought in a myxomatosis virus that those rabbits had not seen before. The myxomatosis virus they brought in killed right away – because it spread very well – some 99.8% of the rabbits. But then two things happened. Number one – within four years, the resistant minority grew so you had a different population of disease-resistant rabbits. Now, even if you brought in a virulent strain it didn’t kill them. And number two – the myxomatosis virus that remained [as a persistent infection in the rabbits] was less virulent, so I think there is crystal-clear
