Going Apeshit, The Ugly
The most depressing part
The final part of this series will be less a technical analysis and more a meditation on circumstances surrounding the science about the origin of HIV. We’re going to look at just how plausible it really was for pandemic HIV-1 to have started from an ambitious vaccine trial, and try to frame Worobey et al.’s contribution to this science in this historical context.
I don’t think it’s pretty.
Meandering down the Congo
A key part of the logic underlying Worobey et al. was described in Part II of this series.
Chimpanzees living near Koprowski’s lab in Kisangani were more likely to be captured by humans in Kisangani than chimpanzees further away from Kisangani.
How plausible is it that this premise is incorrect and the chimpanzees at the Lindi camp came from down the river in the west? I dug into Peter Forbath’s 1977 book The River Congo to investigate this question. The book is basically a history of Europeans greedily and futilely trying to plunder Africa’s wealth navigate the river and often being met with disaster. Forbath opens with a detailed description going down the navigable portions of the river.
We are here at the beginning of the longest navigable stretch of the Congo, a 1000-mile journey around the river’s great bend and back across the equator to Kinshasa (formerly Leopoldville), the capital of Zaire.
…
The journey [from Kisangani to Kinshasa] that took Stanley seven weeks now takes about seven days.
…
… at every village we pass the Lokele are expecting us and come out in their canoes loaded with goods to trade with the boat’s passengers. They are quite relentless in this trade; throughout the journey, the riverboat is never without at least a dozen and often as many as a hundred dugout canoes tied up alongside, and what the Lokele bring aboard for sale or barter reflects the changing nature of the lands we pass through. First there are manioc and sugar cane, then bananas and avocados … then smoked eels and fresh-killed monkeys, then smoked monkeys, live forest pigs …
So it’s definitely possible to send live animals up and down the river, trade is ubiquitous, and everything is on the menu.
The European misadventures into the mouth of the Congo were entirely premised on the idea that freight travel in a waterway is hundreds of time more efficient than travel across normal land per unit weight or per mile traveled. Once stuff is loaded onto a boat, you only have to steer the boat. Compared to travel in the dense rainforest near Kisangani where Michael Worobey claims Koprowski’s chimpanzees came from, water travel may be literally millions of times more efficient. Forbath notes that in the mid-20th century, it only takes a week or so to go 1000 miles down the river, and potentially a bit more going up it. This is not a long time.
Forbath does not give exact dates for this travel, and he does not mention seeing trade in chimpanzees, but this was potentially after the CITES treaty in 1973 which brought the unregulated trade of such animals to an end. Before independence in the DRC in 1960, trade in such animals was likely “the wild west”, to borrow a phrase.
In an obscene bout of irony, Worobey’s zoonosis thesis here is that the chimpanzees Koprowski’s lab used would have had to be local to Kisangani. A developed colonial animal trade could not possibly have resulted in chimpanzees moving 1000 miles up the river because that was for scientific research and not for monkey soup or whatever. In his reckoning, this of course is the same type of wild animal trade that definitely, dispositively, brought SARS-COV-2 1000 miles from Yunnan to a market in Wuhan.
Donnez-moi une break.
The Nifty Fifties
The twentieth century was a golden age in our combat against the Red Queen, infectious diseases that had destabilized societies since the beginning of urban life. In his brilliant book Plagues and Peoples, William McNeill concludes the final chapter pointing out that just during the first half of the 20th century large-scale, effective mitigation measures were deployed against enemies as diverse as diphtheria, yellow fever, plague, influenza, TB, typhoid, and syphilis. The 1950s was a transition time into the back half of the century where smallpox was finally driven extinct and most relevant to this poast, polio was dealt a mortal wound. I’d be remiss if I didn’t mention in the closing pages of this 1976 book McNeill states
A … possibility is that biological research aimed at discovering effective ways of paralyzing enemy populations by disseminating lethal disease organisms among them might succeed in unleashing epidemiological disaster on part—or perhaps on all of the world.
This is the ugly part. What were the western medical researchers who studied infectious diseases in the 1950s up to? What norms did they adhere to? What experimental lines did they consider worth crossing?
The Whitecoats
Starting in 1955, two years before Koprowski’s trials began, the US military gave drafted conscientious objectors the opportunity to be infected with biowarfare agents rather than face deployment overseas. This, of course, was done at Fort Detrick, not some remote military outpost. This was actually one of the better episodes of the 1950s, compared to the many, many experiments performed on actual prisoners that also took place during this period.
Willowbrook
Beginning in 1956, just one year before Koprowski’s oral vaccine trials, Saul Krugman intentionally fed retarded children at Willowbrook school a processed form of feces. But not just any feces; it was from others infected with viral hepatitis. Consent forms were easier to obtain or ignore or accidentally lose when the subjects were retarded. The idea was to confirm the avenue by which hepatitis spread. Eventually, this knowledge fueled a new vaccine campaign against viral hepatitis. In his book In the Name of Science, Andrew Goliszek notes Willowbrook was only the most famous example of experimentation on retarded children. Also in 1956, investigators at the Walter E. Fernald school also performed dangerous irradiation experiments on children with little upside.
Sea spray
One of the craziest stories I had never heard of before reading Raina MacIntyre’s book Dark Winter was Operation Sea Spray, in the fall of 1950. Apparently without informing anyone, the military sprayed a massive amount of serratia all over the Bay Area. From what I can parse, this was meant to be a proxy for an Anthrax attack, and they wanted to figure out what the potential geographical dispersion of such a bioattack would be. MacIntyre also notes that similar insane experiments were conducted in the UK during the 1950s and 1960s.
Such experimentation was widely deemed acceptable in the United States. Now, many experiments are overseen by IRBs, but those did not exist, and scientists largely worked by norms and self-regulation. The examples above were the rule, not the exception by the lights of the time. They only sound wayward to modern ears.
What do all of these 1950s episodes have in common? Well, they were all grossly unethical by modern standards. They all involved only US citizens on US soil. While some were secret, all were sanctioned by actual institutions or research programs. Most importantly, all of them were non-competitive, basic scientific experimentation. No one was necessarily on the road to fortune or fame from this work.
Compare this to Koprowski’s CHAT trials in the DRC. His trials were meant to test an experimental vaccine on colonially-compliant, third world subjects, half a world away from any real western oversight. Moreover, Koprowski had competitors who were also attempting large scale vaccination against polio. Sabin and Salk were both racing Koprowski during the 1950s to develop and test polio vaccines. Salk ended up a household name and a modern day medical saint, whereas Koprowski is a sketchy historical footnote.
The very fact that Koprowski and Paul Osterrieth set up a lab in Kisangani should be a red flag to any thinking person. Rules could be bent, corners could be cut, speed could be prioritized, because even the lax ethical and procedural standards of the time in the US weren’t unbuttoned enough to win a competition to vaccinate against polio first. We see modern day analogs of this, with the Viral Hemorrhagic Fever Consortium setting up shop in Sierra Leone, and scientists going to sociopathic lengths to ensure priority.
So given this 1950s background and their decampment to Central Africa, when Koprowski or Plotkin or Osterrieth state that they would never have produced vaccines in Kisangani or used chimpanzee tissue for culture if monkeys were not available, I don’t believe them. These scientists were products of both their time and circumstances, and neither should incline people to give them the benefit of the doubt.
With no other information, the idea that scientists created a calamitous plague by accident in Central Africa by reckless usage of animals is not some lunatic theory but a very plausible one requiring careful forensic investigation. Worobey et al.’s contribution does not meet that standard.
Horizontal gene transfer
Phylogenetics is everywhere is virology! Every paper has some version of a phylogenetic tree. Entire literatures are stacked on top on inference using BEAST and mrbayes and IQ-tree. We’re told where viruses originate, how they originate, when they originate, how they evolve, all on the basis of sequence-based phylogenetic analyses. Some of these accepted phylogenies seem implausible or at least confused, but still it goes on. Pronouncements are made, knowledge is accumulated, H-indices go up, and Eddie Holmes wins awards.
Amid all this, one puzzle here is the virological fascination with recombination, a type of horizontal gene transfer. In its most basic form, this can happen when two sort-of-related viruses infected the same cell at once and swap genetic material. Consider Worobey’s figure I reproduced in Part I.
Notice how it’s purely vertical descent. The branches don’t ever intersect or cross. You can quibble about it, but the basic rule in phylogenetic analysis is vertical gene transfer, and at best the exception is horizontal gene transfer. There are even fairly sophisticated ways to detect recombination in sequence data (sliding window based strategies or studying tree concordance on separate genes). Virologists seem quick to use recombination to explain anomaly, but they also tend to treat phylogenetic models assuming vertical gene transfer as gospel, vessels of real-world knowledge. See the contradiction?
Retroviruses like HIV-1 are apparently among those most likely to undergo recombination. The Nef gene that Worobey examines in the refutation paper is one of the fastest evolving regions of nucleic acid known to science. Are those facts linked? Should we surmise HIV recombination is happening all the time or shouldn’t we?
If your workhorse method of producing knowledge about evolution (phylogenetics) generally assumes that your workhorse method for explaining unexplained viral evolution (recombination) doesn’t happen, you should be a bit more modest about your conclusions.
Coda
The major high-level issue with Worobey et al. is its essential glibness.
This paper is under the Nature header “brief communications”. It’s less than 900 words. Its opening sentence looks like this.
So you initially cite five previous publications, which apparently prove the thing you want to prove, and you want to be the sixth publication people cite, phrasing your title to be the capstone “refutation”, after which you produce a tenuous and underwhelming argument for a deus ex machina style origin of the most insidious plague in recorded history.
Just during the year Worobey et al. was published, 2004, 1.6 million people died of AIDS; many of these victims lived in hopelessly impoverished parts of the world, others were concentrated among a perennially despised minority in rich parts of the world. Andrew Sullivan’s recent harrowing conversation with Anderson Cooper about the AIDs plague among gay men is part of what initially inspired me to write up the research for this series.
Don’t worry twinks and bears of the world who survived this, Michael Worobey rolled into Africa and super-duper proved this wasn’t a man-made disaster. Look at his single 1200bp vRNA scrap! Your loved ones can rest in peace.
Say what you want about Hooper and The River, and many have, but it is a dogged and exhaustive investigation of this subject. It’s a multidisciplinary endeavor with first-hand interviews, primary documentation, geographic and epidemiological analysis. It takes minute or two for my browser to load, and its notes alone run almost 150 pages. Anything else would simply be phoning it in more for millions of HIV’s victims, and Worobey is scientifically phoning it in here.