First of all, I would like to commend the authors (Amit Chitnis, Diana Rawls and Jim Moore) for their scholarly and intelligent contribution to the HIV and AIDS origins debate.
I need to state from the outset that although the scenarios they offer to explain the origins of the HIV-1-related and HIV-2-related AIDS epidemics are possible, I personally do not find them persuasive. None the less, I believe that their contribution is important, not least because the authors have introduced a much-needed note of caution and balance into a debate which was otherwise beginning to seem somewhat shrill, partly because of comments made by those who, rightly or wrongly, feel impugned by the hypothesis of iatrogenic origin proposed in "The River".
First, let me address the paper itself, and then let me turn to Jim Moore's comments on same. My responses will also include occasional references to the phone and e-mail dialogue that has taken place between Jim Moore and myself over the past few days.
Many scientists in the AIDS field felt, from the outset, that the Gao and Hahn paper went a couple of steps too far, and that although the Ptt SIV was clearly the direct ancestor of the minor HIV-1 variant, Group N, and possibly the ancestor of Group O, that it was unlikely to be the ancestor of Group M, the major HIV-1 variant responsible for the AIDS pandemic (see "The River", pages 837-840). Gao and Hahn's conclusions were based on a comparison of SIVs from Pan troglodytes troglodytes (the central chimpanzee) with a single SIV isolate from an eastern chimp, or Pan troglodytes schweinfurthi (Pts), of unknown provenance. Essentially because the latter isolate was more distant from HIV-1 Group M than the former group of isolates (and because the putative phylogenetic trees of primates and primate viruses appeared to match), it was concluded that all HIV-1 Group M viruses had evolved from the SIV of Ptt.
A recent paper reporting new Ptt SIVs written by Corbet et al. [J. Virol., 2000, 74(1), 529-534] emphasises the fragility of that conclusion, pointing out that: "Studies of wild-born chimpanzees are too limited to exclude, however, the presence of HIV-1 M- or O-related viruses in animals of other geographic regions, or in sub-species distinct from P.t.troglodytes."
This detail alone demonstrates that the Chitnis paper may be based on false assumptions, and that the historical background presented therein, though intriguing, may be irrelevant to the onset of the HIV-1 Group M AIDS pandemic.
Chitnis, Rawls and Moore draw attention to the poorly-conducted campaigns of vaccination, without adequate sterilization between inoculations, that were staged in French Equatorial Africa (AEF), in the present-day Central African Republic, in the years up to 1919.
The authors specify two distinct types of campaign, directed against sleeping sickness and smallpox. In fact, the sleeping sickness campaigns conducted by Dr Jamot, as noted in the Chitnis chronology, continued until 1935. It seems that during the twenties they were staged elsewhere in AEF, notably in the area nowadays called northern Cameroon, (Chitnis et al., ref. 8, pp 129-130, reference kindly supplied by Jim Moore), and in the thirties, on a more limited scale, in French West Africa (AOF) [River, pp. 681-683].
As far as I know, however, these campaigns were mostly conducted in the savannah regions which are the natural habitat of the tsetse fly, and they do not correlate very well with the range of the chimpanzee, which, with a few exceptions (eg southern Senegal), tends to consist of rain forest. There is, of course, some overlap at the forest fringes, but it seems worth pointing out that one would expect relatively few chimp hunters to have been reached by these campaigns.
In any case, these sleeping sickness campaigns seem to provide a theoretical opportunity for only one further passage of a foreign pathogen (such as SIV) from arm to arm, rather than of serial passaging. A similar objection might be raised against the "bum-punching" campaigns against yaws which were staged by the British authorities in present-day Nigeria during the thirties and forties [River, 681].
Of far more interest, however, are the smallpox campaigns conducted in the
years up to 1912, before dried vacine was developed in 1914. The Chitnis
sources suggest that serial arm-to-arm vaccination may have been used to
"transport" the smallpox agent from the west central African coastline as
far inland as the present-day Central African Republic, and it seems
reasonable to speculate, as does Jim Moore [personal communication], that
material from smallpox pustules may have been injected first into one group
of porters, and then, when their pustules formed, into a second group - and
Here we do have the theroretical possibility of serial passage of a foreign pathogen (such as an SIV reently acquired from a chimp) - although the numbers involved, as Moore concedes, must have been really quite small.
Also interesting is Chitnis et al.'s account of the civil and sexual turmoil that obtained between 1880 and 1910 in what is now Guinea Conakry, in AOF.
However, these historical episodes seem to me to support my hypothesis of origin better than that of Chitnis et al.
[For the record, my central hypothesis is that certain batches of CHAT, an experimental oral polio vaccine (OPV) developed by Dr Hilary Koprowski in Philadelphia in the fifties, may have been prepared in a substrate of chimpanzee kidneys, and that an SIV latently present in some of those kidneys may have infected a proportion of the million persons given those vaccines in central Africa between 1957 and 1960, thus sparking the AIDS pandemic of today. I also point out that similar vaccination campaigns, involving vaccine made from the kidneys of local primates, were conducted in AEF and AOF during the fifties, and that these could be related to the minor outbreaks of AIDS.]
The central reason for my scepticism is that if the events cited by Chitnis et al., involving mass-inoculations (including, in some instances, serial inoculations) and unregulated sexual activity, did indeed provide the "rapid passage" opportunities that they believe may have sparked the HIV-1 and HIV-2 epidemics, why did we have such lengthy time-gaps (of approximately 60 and 70 years, respectively) before the outbreaks of HIV-1-related and HIV-2-related AIDS were recognised? (I shall return to this important question of AIDS recognition, below.)
To me it seems that these historical events only support the hypothesis that HIV-1 was not present in AEF, and that HIV-2 was not present in AOF, in the second decade of the twentieth century - in other words, that the crucial SIV transfers from non-human primates to humans had not yet occurred.
Most particularly, these events fail to tie in convincingly with the apparent initial epicenters of the two major AIDS epidemics: sited in present-day Democratic Republic of Congo (DRC, the former Belgian Congo) for HIV-1 Group M, and in Guinea-Bissau (former Portuguese Guinea) for HIV-2.
The Chitnis paper also fails to explain why 82% of all (46) serologically confirmed African HIV-1 infections through 1980, and 64% of all (28) medically plausible and serologically confirmed African HIV-1-related AIDS cases through 1980 for which we can identify a "town of origin", come from the very towns and villages in the DRC, Burundi and Rwanda where CHAT was administered between 1957 and 1960. Are we to simply ascribe these rather remarkable correlations to coincidence?
(With respect to this, Jim Moore has mentioned to me the possibility of sampling bias - and has suggested that the real correlations may be with hospitals and health centres which were used as bases for CHAT vaccination in the fifties, but which were also later the places where blood samples would have been taken, or to which early patients with AIDS would have tended to gravitate. I do not find this scenario at all persuasive. There were over a hundred hospitals, including mission hospitals, in the former Belgian territories of central Africa, but the first recorded instances of HIV and AIDS did not appear just anywhere; they appeared almost exclusively at, or near, CHAT vaccination venues. The negative correlations further support this. CHAT was not, it seems, fed at all in the central area of the Congo, including the whole of one wealthy and populous province, Kasai. And in contrast to other parts of the DRC, do we not see any early instances of HIV or AIDS from that area. [River, pp 740-748]
Furthermore, Chitnis et al. offer no explanation for the patchwork pattern of HIV-2 infection right across rural and urban regions of Guinea-Bissau - a pattern suggestive to me of a more recent multiple transfer of simian viruses, such as that which might result from a vaccination campaign (possibly through injection) conducted during the fifties or sixties. It is worth emphasising [River, 339 and 638-639] that the earliest-reported centres of high HIV-2-prevalence in Guinea-Bissau correlate exclusively with areas which were occupied by the Portuguese side (rather than the Guinea-Bissan liberation forces under Amilcar Cabral) during the 1963-74 civil war. It is also worth noting that during the sixties the Portuguese (rather belatedly) mounted a "hearts and minds" campaign to deliver health care to Guinea-Bissans, and that these initiatives apparently included mass-vaccinations carried out by military doctors. One of those who had been vaccinated in Caio, which would appear to be the most HIV-2-infected village in the world, told me that participation had not been voluntary. It therefore becomes important to determine which vaccines were involved, and how they were prepared.
Now to the question of timing. In their concluding paragraph, Chitnis et al. point out that their interpretation "is consistent with recent and ongoing genetic analyses" conducted by, among others, Bette Korber. Her key paper on dating the AIDS epidemic, which appears to be based on theoretical calculations of mutation rates, has attracted much advance attention, even though it has not yet been published. However, other interpretations of the data should still be considered.
I shall only note that Dr Korber was initially quoted in the "Philadelphia Inquirer" as saying that her findings would show that there was "no way" that the CHAT trials of the fifties could have triggered the AIDS pandemic, but that some weeks after I had questioned her about this by e-mail, she told me that a note had been published in the Inquirer, to the effect that she had been quoted out of context. Dr Korber, who is clearly a conscientious scientist, has also informed me that her work tries to produce a "timing estimate", and that it does not (ie cannot) disprove the OPV/AIDS hypothesis.
It is also worth pointing out that, as Dr Korber has herself acknowledged in a previous paper [Science, 1998, 280, 1868-1871], theoretical tools like the "molecular clock" do not make allowances for recombination, which is increasingly recognised as a major factor in HIV evolution. Neither do they allow for the possibility of multiple and almost simultaneous transfers of several different chimp SIV variants to humans, which is what I propose happened via the various CHAT feedings conducted in central Africa between 1957 and 1960, thus giving birth to the different HIV-1 Group M subtypes, A to J, that we see today.
To summarise: if SIV-infected chimp kidneys were used to make CHAT (as I believe they were), then it is entirely plausible to propose that different chimp SIV variants would have been transferred to humans in the different vaccination campaigns. And if this multiple transfer scenario is correct, then clearly the whole process of attempting to date the epidemic on the basis of a single transfer of chimp SIV to humans is invalidated.
Early in his comments, Moore turns to the key issue of detection: if AIDS had existed in Africa in Year X, would it have been recognised? He uses the example of Rwanda in the years up to 1986 to propose that HIV can be present at a relatively high level in a community, although its presence may go unrecognised by doctors on the ground. He correctly points out that HIV-prevalence in Rwanda in 1986 was recorded as being 17.8% in urban locales and 1.3% in rural communities, and I can support his argument further by confirming that here, as in Zambia, the presence of AIDS was only recognised in 1983 [Jean Sonnet, personal papers, and River, p. 93]. This means that in 1986, when 95% of Rwandans lived in rural locales, 1.65% of the population was HIV-1-positive. Although we do not know the doubling rates which applied at that time, I would propose that in 1983, when AIDS was first recognised there, 1% of Rwandans (or 50,000 people, as Moore states) may have been infected.
Yet it is rather misleading to suggest that there is no evidence of AIDS-like diseases occurring among Rwandans in the years preceding 1983. As I have reported in The River [pp 764-765], extremely high levels of tuberculosis (16 of 21 tested) were detected in Rwandese refugee children who fled Rwanda for the Congo in the early sixties. Furthermore, three unusual cases of fatal generalised herpes were detected in the mid-sixties in Rwandese and Burundian infants whose parents had fled or migrated to Uganda. Three other unusual deaths in Ugandan pathology records involved Rwandese and Burundian adults - who are very likely to have only recently fled, or migrated from, areas where CHAT had been administered a few years earlier. All the conditions cited above involved typical AIDS indicator diseases. In chapter 9 of The River, I have demonstrated that there are many factors other than HIV infection which can cause immunosuppression (and spark AIDS-like indicator diseases), but it is undeniable that these early Rwandese and Burundian cases may - repeat may - have been caused by HIV infection.
Furthermore, I have previously proposed that many of those who were vaccinated with CHAT may have become, effectively, silent carriers of the contaminating chimp virus, and that it may have been largely their secondary or tertiary contacts, who were exposed to a single- or double-passage human-adapted virus, who became vulnerable to acquiring frank disease, or AIDS. [For the scientific evidence supporting this hypothesis, see The River, pp 751-753.] According to this scenario, one would expect to see a small number of adult deaths in the years following the vaccinations in the late fifties (for only about 10% of the million known doses of CHAT fed in Africa were given to adults or adolescents), followed by a growing number of infections in the sixties, but more importantly in the seventies, when those who were vaccinated as infants or children progressed to sexual maturity, and began to spread their viral infections - mainly to sexual contacts. (Those who were infants at the time of the vaccination campaigns would be particularly vulnerable to viral infections because infants, especially those aged between about two and five months, have lost maternal antibodies, but have not yet acquired antibodies of their own. Furthermore, at least in Leopoldville - later Kinshasa - infants were given fifteen times the normal dose of CHAT vaccine, in a bid to ensure effective immunisation against polio.)
And this, indeed, is what we do see. Apart from the Rwandese and Burundian cases of immunosuppression cited above, I have identified other possible AIDS candidates among fatal cases of Klebsiella studied in Stanleyville/Kisangani in the late fifties, soon after vaccination began there. The earliest plausible secondary (or tertiary) infection that we can detect (circa 1973 in Kinshasa) involves an infant who may have been born to a vaccinated parent, or to one who had acquired infection sexually from a former vaccinee. The earliest plausible secondary case in Rwanda (1977) involves a woman with classic AIDS symptoms who gave birth to three sons, all of whom had symptoms of immunosuppression. All four of them, like the father, tested HIV-positive, but only the father remained symptom-free seven years later. [River, pp 91, 350-351 and 746-747.]
What I am suggesting, then, is that the reason why AIDS was first recognised in central Africa only in 1983 was that HIV only began seeding itself seriously in that area in the mid-to-late seventies, when young CHAT vaccinees achieved adulthood, and began transmitting their infections to others. The gap, if gap there be, would seem to be covered by the normal latency period of AIDS.
Certainly there may, in addition, have been previous AIDS cases in these regions which were "missed" by the medics. For instance, when AIDS was first recognised in Congo and Rwanda in 1983, it was as a result of doctors who had flown in from Europe and America, and who were familiar with the concept of AIDS from gay and intravenous patients in their hospitals at home. By contrast, African doctors had little context into which to fit the new and diversely-presenting cases of immunodeficiency, less ready access to medical journals, and less of a tradition of reporting unusual cases in those journals.
Another factor that could have significantly affected the reporting of unusual diseases in the Congo, Rwanda and Burundi during the sixties and seventies was that these three nations were blighted by extensive and ongoing civil war and civil unrest (often foreign-inspired) from the time of independence onwards. Medical and publishing services effectively broke down in this locale for much of this period.
But in this respect, I would like to distinguish between what I am proposing for the Congo and Rwanda and what I believe Jim Moore's group is postulating for French Equatorial Africa (AEF). To postulate the under-reporting of AIDS during a 15 to 20 year period of massive post-colonial unrest in central Africa is one thing. But to argue that there might have been a "latent" period of some sixty years (for HIV-1) and seventy years (for HIV-2), during which HIV and AIDS were present in humans in AEF and AOF, but went unrecognised, is quite another.
In short, Moore's group have proposed possible mechanisms which could result in occasional chimp SIV infections in humans, and in the onward spread of those infections between humans. To my mind, however, they have not managed to provide a scenario which can persuasively explain the evolution of pathogenic HIV-1 and HIV-2, and the birth of the related AIDS epidemics, so many years later.
(For instance, what in practical terms could have happened to the postulated HIV-1/(Ptt)chimp SIV infections in humans between the 1910s and the 1970s? It seems to me that the only plausible explanation, given the Moore scenario, would have to be that the infection remained sequestered inside an isolated village in west central Africa, and that one infectee left that village - say in the 1950s - to go to the Belgian Congo or somewhere else in central Africa, where he/she infected others and sparked the epidemic. Presumably the infectees in the original village would have to die out, before they had the chance to infect anyone else locally, or else the epidemic there would still be continuing, but at a level of low transmission and low pathogenicity. It is this strange concept - of a village so truly isolated from neighbouring villages that a new infection would not escape from former to latter, that gives me pause. Furthermore, given that we have four outbreaks of AIDS, do we not now need four isolated villages?)
Another factor here is that for most of that sixty to seventy year period, Africa's hospitals were manned by colonial doctors who were conscientious about visiting up-country districts to check on health status, and who maintained a tradition of reporting unusual cases, especially in the (often surprisingly professional) colonial medical journals of the day.
My own perusals of such journals have not encouraged the belief that there were occasional cases of AIDS occurring in Africa in the first half of the twentieth century. Indeed, only a single potential case of AIDS springs to mind (a case of TB and disseminated candidiasis from the Gold Coast - now Ghana - in 1924), about which there is too little information to allow a meaningful diagnosis.
However, this is a useful and valid line of enquiry, and (like Jim Moore) I would be fascinated to see the findings of other researchers on this topic.
A few other points in response to Jim Moore's preamble:
Jim Moore points out that he has only just realised "the nature of the controversy into which we [he and his colleagues] have wandered" by publishing their paper. I fully accept this, and his assurance that his group had no intention of siding with one school against another in the origins of AIDS debate.
None the less, since his paper relates directly to the geography proposed by Beatrice Hahn and the timing proposed by Bette Korber, it will inevitably be used as supporting documentation by detractors of the OPV/AIDS theory. I accept this also.
However, one point is crucial here. As Moore puts it: "Hooper convinces me that the OPV scenario could have happened". I too accept that his scenarios of origin could have happened. At present, we both favour our own scenarios, though that is largely because Moore and his colleagues place more faith than I in the findings of Beatrice Hahn's group on the geographical source of Group M, and the soon-to-be-published conclusions of geneticists who are trying to calculate the dates when HIV might first have arrived in humans. I believe that these issues are still far from proven.
However, there is a great deal of common ground. In particular, we both agree that more sampling of the higher apes is needed, to find the species or sub-species that is host to the SIV that is very close to HIV-1 Group M. If that ancestral host is found to be Pan troglodytes schweinfurthi or Pan paniscus, then Jim Moore (as he readily agrees) will have to have a major rethink. If it is found to be Pan troglodytes troglodytes, or Gorilla gorilla, then it is I who will have to reappraise things.
The debate is still very much open. And it is only by experimentation, discussion and dialogue - of the type which Moore's team clearly favour - that we can hope to move it forward.
Lastly, I'd like to thank Jim Moore for agreeing to post this response on his website.
Ed Hooper, Somerset, UK. January 24, 2000.
Only balanced testing of predictions generated by the different scenarios will [hopefully] be able to distinguish which unlikely history is the correct one.