A New HIV-1 Sample from 1966

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Just this evening I received a heads-up from an American professor about an on-line article announcing a new piece of work by Michael Worobey, a key member of the "bushmeat school". This is a group of scientists who believe that the "AIDS virus", pandemic HIV-1, transferred to humans a hundred or so years ago, when a human was infected with the nearest ancestral virus to HIV-1 (the simian immunodeficiency virus, or SIV, of the common chimpanzee) in south-eastern Cameroon.

The article reveals that Worobey has spent some years investigating boxes containing 1,652 human tissue samples obtained from patients in KInshasa, Democratic Republic of Congo or DRC (formerly Leopoldville, Belgian Congo), between 1959 and 1967. From a formalin-fixed paraffin block of a piece of lymph node, biopsied from a 38-year-old man in 1966, his team was able to obtain a nearly complete genome of HIV-1. This is the earliest full-length genome of HIV-1 by some ten years. When sequenced, it proved to be from the pandemic strain of HIV-1 (Group M) and from "a sister lineage of subtype C", the HIV-1 strain which, in the last forty years, has come to predominate in the southern countries of Africa. as well as in India.

Surprisingly, Worobey's article does not mention that this is the third earliest sample of pandemic HIV-1 to be discovered in the world, and that all three of these early samples came from the same city. The earliest came from a blood sample taken from an unidentified male in Leopoldville in 1959 (and appeared to be from HIV-1 subtype B or D). The second earliest was obtained from the lymph node of a 60-year-old woman who was biopsied in Leopoldville in 1960, and appeared to be from subtype A.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682493/pdf/nihms-480602.pdf

The next earliest world sample of HIV-1 after 1966 dates from 1976, and also comes from the DRC, from a village called Yambuku, hundreds of miles east of Kinshasa.

As background to his latest discovery Michael Worobey is interviewed in an on-line article by Helen Branswell, on the STAT web-site [see link below]. He says that "having genetic data from the 1960s shows that the circulating viruses were then already extremely genetically diverse - meaning they'd been transmitting among humans for a while. 'The only way that that can happen is if there were several decades of evolution prior to the 1960s', he said."

https://www.statnews.com/2019/07/16/hiv-genetic-code-extracted-evidence-virus-emergence/

So Worobey believes that the key crossover from chimpanzee to human occurred several decades before 1966. In fact, he places the Most Recent Common Ancestor (MRCA) of all HIV-1 Group M strains at a date between 1896 and 1905, although he fails to propose a mean date (which would presumably be either 1900 or 1901). This is some years earlier than other estimates made by molecular biologists from the bushmeat school, which have varied from 1908 to 1932.

Although these calculations are based on the premise that HIV-1 evolution has occurred at a constant rate (using the model of a "molecular clock"), his article makes several references to problems with this sort of phylogenetic dating. For instance, at one point he writes that: "rates of molecular evolution appear to vary according to the time frame considered, so rates estimated over a recent time frame can not necessaily be extrapolated to a deeper time frame". At another point he admits that "molecular clock dating theory has difficulties accommodating the rate differences...observed in simian immunodeficiency viruses". Perhaps this is why the phylogenetic dating of immunodeficiency viruses such as HIV-1 has started to employ a new concept referred to as a "relaxed clock", in which constant rates of evolution no longer apply.

Worobey writes that the actual crossover of the virus from chimp to human must have occurred in or before his mooted date of 1896 to 1905. He also asserts that the crossover occurred in south-eastern Cameroon, where a chimp SIV has been found that (so far, at least) is closer than any other chimp SIV to pandemic HIV-1 in humans.

He fails, however, to acknowledge that there is no empirical evidence of HIV-1 existing before 1959, and that all of his dating calculations are theoretical.

I believe that MIchael Worobey is wrong, and that this is not "the only way" that the three earliest samples of HIV-1 (representing three different subtypes of the virus) could have been obtained from a single city, Leopoldville/Kinshasa, within the space of seven years: 1959 to 1966.

Another way this could have happened is if a viral soup of different variants of chimp SIV had been transferred to humans during a short space of time in Leopoldville itself, for instance in an iatrogenic (physician-caused) accident. There is documentary evidence that different batches of an oral polio vaccine (OPV) called CHAT were given to 75,000 children in Leopoldville in the years 1958-1960. As I have reported elsewhere on this site, there is strong evidence indicating that batches of this particular vaccine were prepared locally in cells of the common chimpanzee. This was a unique event, for no other polio vaccine, as far as we know, was ever made from chimpanzee cells. Different batches of this vaccine were also administered to many thousands of others in the Belgian Congo, including adults, prior to 1958.

This could be how different variants of chimpanzee SIVs, including recombinants, arrived nearly simultaneously in humans. The former head of the Los Alamos HIV Database, Gerry Myers, has referred to this as a "punctuated event". From the perspective of the molecular biologists, it would not be possible to distinguish between a single cross-species transfer event fifty or sixty years earlier (in 1900-1901), and a punctuated event involving several persons in the recent past (for instance in 1957-1958).

Worobey's new article is titled: "A near-full-length HIV-1 genome from 1966 recovered from formalin-fixed paraffin-embedded tissue", and a preprint PDF can be found at:

https://www.biorxiv.org/content/biorxiv/early/2019/07/01/687863.full.pdf

After receiving the heads-up about Worobey's new article, I emailed the professor who had alerted me to it, as follows:

"Many thanks for the heads-up: I hadn't previously seen it. And I haven't yet had the chance to do more than skim through the article or the preprint PDF. This is certainly the product of a lot of hard work. A 1966 sample from Kinshasa, eh? Worobey concludes that this reinforces his argument that the MRCA of pandemic Group M existed 'around 1920 in central Africa', and that the key viral crossover from chimps to humans occurred then or before then. I believe, however, that he continues to ignore a potential alternative interpretation: that this is suggestive not of a single transfer, but of a multiple iatrogenic transfer in the late 1950s in the Belgian Congo, very possibly in Leopoldville/Kinshasa itself."

Within ten minutes, the professor replied: "Yes, I tend to agree with you: in vitro or in vivo viral sex, as the case may be..." He meant that this man's HIV-1 infection could have been the result of being exposed to immunodeficiency viruses which had recombined in vitro (in the polio vaccine) or in vivo (in the body of a person who then infected him, for instance sexually). I very much agree with this reading.

Worobey and his fellow scientists from the bushmeat school would have us believe that they have solved the puzzle of the origin of AIDS, and that the pandemic began when chimp SIV transferred to a human, perhaps a hunter of bushmeat, in around 1900 in southern Cameroon.

What their latest work underlines, however, is that a different explanation (one involving a multiple crossover via a vaccine made in chimp cells) is equally valid, if not more valid.

In fact, the evidence for the OPV theory continues to grow. Why would so many different early variants of HIV-1 turn up in just one single city, Leopoldville/Kinshasa, if the epidemic had arisen at least fifty years earlier and hundreds of miles away in Cameroon? Would not the most parsimonious explanation be that the outbreak was linked to an event that had happened in Leopoldville itself, just a short time before 1959?

The debate continues.

Ed Hooper, July 16th, 2019.