The Economist, Vol. 356, 16 September 2000, pp. 87-88
A meeting in London has destroyed the idea that AIDS was the accidental result of a polio-vaccination campaign conducted in the 1950s. But the disease's origins are still mysterious
IT IS a long way from the Wistar Institute in Philadelphia to the Royal Society in London. But the participants in a meeting at the society earlier this week, innocently entitled "Origins of AIDS and the HIV epidemic", might have been forgiven for thinking that they could hear sighs of relief from the other side of the Atlantic ocean. For the real purpose of the meeting was to debate the accusation that some of the Wistar's researchers may have been inadvertently responsible for the global AIDS epidemic-and by the end of the meeting that notion had more or less been laid to rest.
In the late 1950s a group at the Wistar, led by a virologist called Hilary Koprowski, created an oral polio vaccine called CHAT. The hypothesis was that some batches of CHAT were accidentally contaminated with the virus that became HIV-1, the strain responsible for most cases of AIDS. These batches, so the theory went, were given to several thousand people in what was then the Belgian Congo and its associated UN Trust Territories (now, respectively, the Democratic Republic of the Congo, and the states of Rwanda and Burundi). With such a start in life, an enterprising virus could hardly fail to become epidemic. And so, according to the theory, it did.
Although he did not invent it, this theory's most vocal proponent is a writer named Edward Hooper. He outlined his reasons for believing it in a book called "The River", which was published almost exactly a year ago. He noted that the earliest known sample of HIV-1 was collected in 1959 from a Congolese man (administration of the vaccine began in 1957). He suggested that early cases of the disease, or of infection with the virus, were closely correlated with places where vaccine trials had been carried out. He wondered if Dr Koprowski's connections with a chimpanzee-research station at a place in the Congo called Lindi had led him to mix a few chimpanzee kidneys with the monkey kidneys that were used to grow the polio virus needed to make CHAT. (HIV-1 appears to be a chimpanzee virus that has leapt the "species barrier" to man.) And he suggested that the institute make available for study the small number of samples of CHAT that remained in its freezers to see if there was any trace of either HIV-1 or chimpanzee DNA in any of them.
It duly did so, and the results of the analyses were announced at the meeting. All seven remaining samples were investigated by three separate and independent laboratories. All were pronounced as clean as a whistle. And in a conference that bubbled with barely suppressed vitriol, most of the other speakers undermined Mr Hooper's ideas so badly that by the end his edifice was barely standing.
Some of the most convincing evidence came from analyses of the virus's evolutionary history. These are done by looking at differences between the genetic material of the seven or eight main subtypes of HIV-1 and asking how long those differences took to arise. Although this is a theoretical process, the reliability of a given method can be checked by asking it to "hindcast" the age of viral samples taken from people in the past, and the reliability of the whole idea can be checked by seeing if the results from the different methods agree.
The CHAT theory obviously relies on AIDS happening after the introduction of the vaccine. But two of the speakers, Bette Korber from the Los Alamos National Laboratory in New Mexico and Anne-Mieke Vandamme, of the University of Leuven in Belgium, employing three different methods of calculation between them, showed that the most recent common ancestor of the existing subtypes probably existed in the 1920S or 1930s. That complicates the CHAT theory enormously, for it would mean that the vaccine must have introduced all the subtypes separately-each, presumably, from the kidneys of a different chimpanzee that was infected with the relevant virus.
The correlation between vaccination sites and early records of HIV-1 was also called into question. On the face of it, that correlation seems close. According to Mr Hooper, 64% of the early instances of AIDS were at or near places where CHAT was tried out. But a closer analysis by Stanley Plotkin, one of Dr Koprowski's original collaborators, who now advises Aventis, a Franco-German drug firm, suggested that this correlation is in fact spurious.
First, both the vaccination campaigns and the sites of origin of the samples and medical records that show early HIV-1 infections are concentrated in places which it is easy to get to. That, alone, might be enough to explain the coincidence. But in addition, many of the samples and records come from big cities. To vaccinate a few hundred people in a village and find a disease there a decade later is one thing. To do the same in a city is another. The chance that those who were vaccinated are those who succumbed is far lower. And on top of that there are both vaccination sites with no early HIV-1 record, and records that are hundreds of kilometres from a vaccination site.
Another damning observation was made by a speaker called John Beale. He examined the way CHAT was made, and estimated how many HIV particles would get through each stage of the process, if any were present in the first place. His conclusion was that one particle might survive for every 10,000 billion that started. Even the body of a person with full-blown AIDS contains only a few hundred million HIV particles. A mere kidney would have far fewer.
The crux of Mr Hooper's argument, however, was that Dr Koprowski did, indeed, use chimpanzee kidneys to make some of his vaccine. Dr Koprowski, who was one of the speakers, denied it. So did Dr Plotkin and Paul Osterrieth, another collaborator on the CHAT work. Dr Koprowski explained that his connection with the laboratory in Lindi was because he was testing CHAT on chimps prior to unleashing it on people. He was not collecting kidneys.
Mr Hooper fought back, with reports of interviews with people who had worked in Lindi and at another laboratory connected with Dr Koprowski in Bujumbura in Burundi. They recalled kidneys being removed from chimpanzees in these places, and then shipped out. But there is no evidence that such kidneys were used to make CHAT.
The CHAT theory of AIDS, in other words, has sunk. Or if it has not (the clinching evidence would have to be a human HIV-1 sample from before 1957), it is holed below the waterline and is going down fast. But disproving it does not bring researchers any closer to working out what really happened, and Mr Hooper, though he has turned out to be wrong on the specifics, has raised a general point that needs answering-because for AIDS to emerge at the time it did was a very peculiar thing.
One peculiarity is that people have shared Africa with chimpanzees for as long as mankind has existed. So why should it take until the early decades of the 20th century for the virus to cross from one to the other? Another is that, although HIV-1 (or, more strictly, HIV-1 group M) is the main cause of AIDS, it is not the only one. A smaller epidemic caused by HIV-2, a virus that comes originally from a monkey called the sooty mangabey, is raging in West Africa. And two other versions of HIV-1, known as groups N and O, are so different from group m that they must have separate origins in the chimpanzee population. That one AIDs-causing virus should have leapt into the human population at the moment it did is odd enough. That four should do so at more or less the same time stretches coincidence to breaking point. It seems far more likely that some human agency was involved in the transfer. But what was it?
One theory is that population growth is to blame. This was outlined by Albert Osterhaus, of Erasmus University in Rotterdam. More people means more and bigger cities. And urban folk have more opportunities for promiscuity than rural ones-or at least more potential partners to choose from. In the past, HIV might have passed naturally from a chimp to a man in the forest on many occasions (the so-called "cut hunter" theory, which hypothesises a bloody encounter of one sort or another between the two species) but been unable to sustain itself for lack of subsequent hosts. Population growth could have put paid to that constraint and allowed the virus to spread.
Another consequence of population growth is a demand for new farm land. In Africa, this means cutting down forests, which would increase the amount of contact between man and chimp. Rather than cut hunters, you would end up with cut farmers.
Both of these ideas emphasise changes in human exposure to animal viruses. But there is another possibility: that the animal viruses themselves were somehow changed by human intervention.
Preston Marx, of Tulane University in Louisiana, made a suggestion about what might have happened. He observed how the price of syringes dropped after their invention, reaching a point between the first and second world wars when they were cheap enough to be deployed widely, but expensive enough to require re-use. He also noted that when monkey viruses similar to HIV are moved experimentally from one species to another, and then moved from animal to animal in the second species, their virulence increases significantly.
Careless re-use of syringes, he suggests, could have had the same effect in people -- transferring a benign chimp virus from a cut hunter or farmer to another host, where it became nastier, and then to another where it become nastier still. Once nasty enough, this virus would start spreading by more conventional means. Such a process could work in parallel for different viruses in different places, explaining the existence of four different types Of mDS virus.
This idea is, of course, as speculative as Mr Hooper's, and it could end up being shot down in flames as easily. But then again, it might be right. If it were, it would be one of the saddest examples of the law of unintended consequences in history.