Distal truths
"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.
Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.
These two publications from the earliest months of the COVID-19 pandemic came under intense scrutiny including the US Congress. One is a commentary, the other a statement. Neither provided any new data. A remarkable analysis of the dark side of the proximal origins paper has been made by Gilles Demaneuf. USRTK did an excellent job too.
While virologists the world over embraced a natural origin for the COVID-19 coronavirus, nobody has commented on the strength of the virology, or lack of it, in these two publications. This essay seeks to see how the virology stood up then and six years later. Let’s go proximal first.
Our comparison… identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies and biochemical experiments, SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2. Strictly speaking, structural and biochemical traits are not genome features. Next, for something to be optimal implies a comparison to numerous experiments involving multiple strains. There was so little data back then it was not possible to use the word optimal.
With hindsight, we have learnt that binding of the Spike protein to the ACE2 receptor molecule changed with the emergence of each new variant. It was increased for the first variant, alpha and seesawed through to Omicron BA 3. The binding of the prototype, delta and Omicron BA 3 Spike proteins for ACE2 is indistinguishable yet the disease profiles of all three variants were different. The tightness of the binding of Spike for ACE2 is subordinated to the optimization of the virus.
The coronavirus’s journey from the prototype to alpha, beta, gamma, delta variants and onwards to omicron can be taken as prima face evidence that the initial virus wasn’t optimized for humans from the evolutionary perspective. This is a good moment to remind folks of Theodosius Dobzhansky’s famous remark: Nothing in biology makes sense except in the light of evolution.
So how do we handle the remark that the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation. The affinity of some bat coronaviruses for ACE2 is high by general standards in virology but not enough to raise eyebrows. It no doubt arose in bats through natural selection. The key question is how quickly some bat coronaviruses can adapt to the human ACE2 molecule? With hindsight the answer is pretty quickly. All this is uncoupled to purposeful manipulation. As it is, the latter sentence is logically disconnected from the former. A linguistic UFO no doubt.
Next and (ii) the spike protein of SARSCoV-2 has a functional polybasic (furin) cleavage site at the S1–S2 boundary. Much e-ink has been spilt about the furin cleavage site. Two points. First, back then there was but one bat coronaviruses akin to the COVID-19 virus. Who could have foreseen that among the next 20 bat coronaviruses, there wouldn’t be one with such a feature? Indeed, it is likely that SARS-CoV-2-like viruses with partial or full polybasic cleavage sites will be discovered in other species wrote the proximal authors indicating they were banking on it. Yet even today nobody has found such a feature. The rub is that bat coronaviruses in Southern China, northern Vietnam and Laos have been inexplicably under sampled. After six years On reading would have expected thousands of SARS2 like bat genomes to have been generated (Cancel Virology). There must be a reason for it. The logical conclusion is that some people don’t want more SARS2 like bat coronavirus genomes to become public.
Second, the impact of a furin cleavage site depends on the viral strain. Years ago, it was shown that the introduction of a furin cleavage site into a H6N1 bird flu virus increased pathogenesis. By contrast, for chicken H5N1, H5N2 and H7N7 viruses it did not. The virulence is based on additional pathogenic determinants. Thus, finding a furin cleavage site was suggestive of a contributor to virulence, but was hard to interpret in early 2020. We know today that it is important.
In the section Theories of SARS-CoV-2 origins they serve up their conclusions - It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus - before stating the competing hypotheses, although the UFO provided an inkling this would happen. Anyway, they served a great double whammy. Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV- 2 is not derived from any previously used virus backbone. Emphasis added.
First, who mentioned genetic manipulation? Ron Fouchier used naturally arising mutations to adapt H5N1 bird flu virus to aerosol transmission to ferrets. Second, what if the virus backbone used was that of an unpublished virus, then what? Readers will know that researchers amass tons of data in the years prior to getting their work published, so this is a distinct possibility. The fact is that back in early 2020, the genetic data irrefutably did not show anything about the origins of the virus apart from the fact that it originally came from bats. To affirm otherwise was and is science fiction.
In the next two sections they discuss their pet hypotheses and make some unsubstantiated remarks on which we’ll pass. The following section starts with We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2. By now they’re in wrapping up mode even though in theory, it is possible that SARS-CoV-2 acquired RBD [receptor binding domain] mutations during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV. Yet rather than leave it open, they provide arguments to suggest that key features of the Spike protein arose naturally none of which are definitive. They simply declare their bias.
Under Conclusions we read that a Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. Prevent? You mean it will help us stop spillover infections? Until we have at least a hundred, and preferably many more, bat like SARS2 viruses and know their penchant for the human ACE2 protein, this is more science fiction. Not having this data is slowing down virology.
Although the evidence shows that SARSCoV-2 is not a purposefully manipulated virus is trundled out without reason. It was not possible to say anything without access to lab notebooks or the WIV coronavirus database that was taken down in September 2019. Traits, smoking guns for some, but invoking the high burden of scientific proof, the jury is out. What is highly abnormal, so much so that the word suspicious is in order, is the astounding dearth of SARS2-like bat coronaviruses genomes published to date.
Moving on, the second publication is a Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19. That’s good of you, and yes, we felt their pain too. But why speak out? The rapid, open, and transparent sharing of data on this outbreak is now being threatened by rumours and misinformation around its origins. We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin. Apart from what has been revealed by USRTK on the dark side to this paper and the numerous conflicts of interest, three remarks.
• Since when are scientists bothered by conspiracy theories? OK Steve Bannon was one of the first peddlers, but he was never a virologist and could easily have screwed things up, if not invented them. Why are you even listening to him?
• And while you’re apparently bothered by conspiracy theories do you really think a statement in The Lancet will shut them down? No, they will feed on your intervention. Naïve to say the least.
• The important words, indeed, the raison d’être from the authors’ perspective is does not have a natural origin. Yet back in February and March 2020 when this text was written there were no data either way to conclude. This was an unsubstantiated assertion, and yet The Lancet nodded it on. Scientific conclusions are based on data and discussion just in case that needs reminding.
Scientists from multiple countries have published and analysed genomes of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and they overwhelmingly conclude that this coronavirus originated in wildlife… On reading read a couple of the papers cited to support this adamant conclusion. Unfortunately, they said nothing of the sort at which point dizziness set in. Fortunately, a cup of coffee righted things.
Conspiracy theories do nothing but create fear, rumours, and prejudice that jeopardise our global collaboration in the fight against this virus. We support the call from the Director-General of WHO to promote scientific evidence and unity over misinformation and conjecture. Again, do you really think you can counter conspiracy theorists this way?
Note the self-righteous and melodramatic We want you, the science and health professionals of China, to know that we stand with you in your fight against this virus… Stand with our colleagues on the frontline! We speak in one voice.
Rhetoric apart, what are you doing peddling untruths about COVID origins? As scientists you knew back then there was insufficient data to support any hypothesis. Sure, you had a preference but coupling your prejudices to support for Chinese health care professionals who were battling this bastard of a virus, working phenomenally long hours, some paying with their lives, was and remains obscene. The Chinese medics deserved better.
Both publications, they cannot be called scientific papers, had the goal of trashing the lab leak hypothesis out of hand. We’ve seen this before. Nine years earlier an Op Ed in the Washington Post entitled A flu virus risk worth taking by Drs. Fauci, Nabel and Collins from the NIH shut down discussion on dangerous gain of function flu research (Chilled Virology). No virologist dared speak out against dangerous GOF research or COVID origins.
The NIH was omnipresent and complicit in both stories. Scientific knowledge is made by those at the coal face, not the administrators. Shutting down discussion is a professional failure.
If ever a disaster were to happen, then virology and the scientific establishment would take an awful hammering. Who was responsible, who would be scapegoated? The rapid response was to deny, deflect, double down and trash critics even though the work was indistinguishable from the immoral development of biological weapons of mass destruction - the hand of Sapiens (Biosomething).
And while the scientific jury is out on COVID-19 this is mainly because too many people, for example many of these authors, are not cooperating instead of helping all of us learn from the past. Hmm, there was a phrase somewhere… now where was it? Ah yes, in a publication entitled The proximal origin of SARS-CoV-2.
In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter.
Conclusions
The monumental error of these authors along with those of the Op Ed in the Washington Post was to have believed they could decide science by decree. It is earned by hard work, checking, challenging, repeating, the forging of a consensus and ultimately transformation into knowledge.
For DGOF research on viruses and COVID origins fears of a cock up and shouldering responsibility by those on the Olympian mountaintops were and still are enough to explain everything.
The publications need to be retracted as does the Op Ed. As to content, it’s life, Jim, but not as we know it.
Aside 1
The journal editors have been refractory to retracting these publications. The argument goes something like as there was no original data, at worst the authors were wrong in some of their analyses. After all, nobody’s perfect. Plus, it is up to the authors to initiate the retraction process. This a weak defense that shouldn’t count in science where being clear and precise is essential. The journals could at least have flagged them as wanting, biased and unhelpful not to mention acknowledging their dark sides.
That said, they are excellent examples of what not to do.
The journal editors, like so many scientists are unaware of their responsibilities as outlined by fifth principle on oversight in the 2005 InterAcademy Panel statement on biosecurity. Scientists with responsibility for oversight of research or for evaluation of projects or publications should promote adherence to these principles by those under their control, supervision or evaluation and act as role models in this regard. Emphasis added.
Sadly, it’s unlikely to change any time soon. Like bioethicists. Apparently, role models are a thing of the past, for suckers. Go tell that to the Chinese doctors who gave everything in early 2020 while others spun words. Or emergency staff today.
Aside 2
Colonel (Ret.) Robert Redfield, MD and former Director of the CDC at the beginning of the COVID pandemic was interviewed recently. Redfield has a top secret security clearance and says all the evidence pointing to a lab accident has not yet been declassified. And yet the Lancet and Nature Medicine publications were so adamant... Embarrassments don’t stop. Of course, we’ve seen this before from others over COVID origins (Being sure without data).
Aside 3
In a recent interview, the new NIH Director Jay Bhattacharya, said that My view is it’s pretty close to certain. [that the pandemic was the result of a lab accident that happened in Wuhan, China] But again, scientists disagree with me on this.
Aside 4
It seems the earliest recorded hand of Sapiens goes back to an outline made some 67,800 years ago in a cave in Indonesia.
As always, thank you for your pertinent analysis! Sorry I take the liberty to comment and suggest something that I sincerely hope you may find interesting. I recently published several unappreciated and unrecognized features overlapping the FCS that could play a critical role in a lab context (ongoing or past scenarios) Please see here: https://www.mdpi.com/2075-1729/16/2/199# (just published). If it's too long, would you consider the final figure for a summary, please? I would love to hear what you think. Thank you!