Wound Healing
"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 discussing risky research in virology that were originally published on the Biosafety Now website.
We will republish these essays on our Substack every Friday, so the full archive will become available under the “On Reading” tab at the top of our Substack homepage.
On reading Self-inflicted wounds, by Holden Thorp, Editor-in-chief. Science. 2021; 374:793
This is about the perception the rest of the world has of scientists. There’s such a desire out there to learn more about science, what’s coming down the road, how scientists come up with endless discoveries from galactic clusters down to picometer vibrations.
Science can also strike deep at home when Mum is diagnosed with breast cancer, or the baby with a rare congenital disease. Or when we had to flash a COVID vaccination QR code before eating in a restaurant.
Science is hellishly complex. It’s just not possible to get everything right first-time round. Indeed, it is often the failed experiments that leads to the good one.
We get to the ‘truth’ by iterative experimentation and reasoning generating results that are reproducible and stand the test of time. That is what counts. Yet today, perhaps infected by social media habits there is too much shooting from the hip. This is also partly due to the not being able to separate your hypotheses from the emerging data as well as saying too much. Science needs time, thought and quiet. And if your pet hypothesis doesn’t make the grade it hurts. So, it’s about handling hurt and hubris, something most readers know something about.
Importantly, science is not democratic. If two researchers have different positions or opinions concerning a phenomenon, they do experiments and over time one of them is right and the other not. Sometimes reality holds part of each of their positions. But both can’t be totally right. And if you do the experiment that shows the other to be wrong, then (s)he is well and truly wrong. Maintaining the erroneous position becomes silly or a character defect. As we know, the earth isn’t flat.
So, with the controversy in virology that started in 2011, both sides could’t be right. Either you could predict a future pandemic with precision and with it the strain, or else you can’t. The fact that most virologists are, sort of, in favor of DURC (ex-GOF) research is not the point (Deconstructing the portrait, Going places, Chilled virology). Those in favor cannot prove their case because infecting an individual is ethically unacceptable. Game over.
Back to Thorp. Missteps by researchers and funding agencies around the origins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have provided fodder for conspiracy theorists, and caveats. Missteps, how come? Virology has been in the public’s mind since AIDS burst upon the scene in the 1980s, boosted by SARS1, a 2009 flu pandemic, Chikungunya, Zika, Ebola several times, MERS and more. That’s more than 40 years of limelight. Why is learning so hard in the upper echelons of virology and funders? It makes no sense.
And then comes the first slip. None of these miscues say anything substantive about the science and the conclusion that the virus is almost certainly of zoonotic origin… These lines were written in November 2021. Today the lab leak is credible. Sources? Drs. Fauci and Collins. That doesn’t make it right, and in the absence of data (Specialist Opinion) coming off the fence like this isn’t timely. This shows that almost certainly, almost certainly was an opinion, not a statement of fact.
The editorial is written after DRASTIC went public with the DARPA project that mapped out making bat coronaviruses more dangerous for humans, notably by inserting some proteolytic cleavage sites into SARS like coronaviruses. Such a site in SARS-CoV-2 (cleaved by furin) enables the virus to efficiently infect human cells. How the furin cleavage site wound up in the virus is a focus of debate over the origins of the pandemic. Never mind that the experiments, which hardly posed a threat… Second slip. There is a literature showing that adding a furin cleavage site to some coronaviruses makes them more dangerous. Furthermore, deletion of the furin site in the SARS-CoV-2 Spike protein attenuates disease in hamsters and transgenic mice.
This latter paper in Nature was published in January 2021 and significantly precedes Thorp’s pen. The throwaway comment - which hardly posed a threat – deflects from the importance of this blueprint for a DURC engineered human coronavirus.
Thorp notes that the experiments in the DARPA project experiments were not conducted. Third slip. Every scientist knows that if your research proposal is refused you rewrite/repackage it and sent it elsewhere. What does he know? Surely nothing more than what is in the public domain, this being a euphemism for saying such work was not conducted with DARPA funds. Which we knew.
Anyway, The researchers failed to get ahead of the story. They should have known that the proposal would arouse interest, especially because the collaborators included scientists at the Wuhan Institute of Virology and US scientists. Again, after of 40 years of being in public view, why were the virologists of all people so unsavvy? The revelation of the DARPA proposal caused bedlam because is showed that US and Chinese (WIV) scientists were contemplating more DURC (ex-GOF) research on bat coronaviruses. This editorial emerged when the Delta variant was still wreaking havoc. No finer backdrop was necessary.
Scientists have consistently put forward a picture of themselves as highly objective automatons governed solely by their data, when in reality, science is a messy, human process subject to all features of human frailty. Maybe you expected scientists with their PhDs, logic and laws would do a better job than the rest. That is flattering but any scientist who has been around a bit knows full well that their colleagues are full of foibles and that the highly objective automaton is science fiction. Well, perhaps with the exception of Dr. Spock.
Yet this is a contrived argument. After all, Jack Lemon got it right years ago with his unforgettable ‘Nobody’s perfect’. And Bill Shakespeare before him with more eloquence. Move on.
The sentence Scientists are expected to balance this reality with the fact that their every word and action, when it comes to the pandemic, is under intense scrutiny is close to casting scientists as victims of intense scrutiny. The lay public just wants to know a little more about what they know. That’s not a big or unreasonable ask these days.
The editorial closes with It may seem unfair that scientists are being held to such a high standard. But that is where we find ourselves right now. So, let’s strive to be much more thoughtful, because ineptness can cut deep and damaging wounds. Let’s look at these three sentences.
Science holds itself to a high standard because you can’t invent a smartphone with beliefs. Findings must be reproducible. Things work or they don’t. Words have meaning. There is no room for sloppiness, dross gets sidelined. Every time. Note, this happens even though nobody’s perfect. This is the huge advantage of doing experiments and following scientific method. And it’s been this way for a while.
We find ourselves right now simply because this is the nature of the mission. You can’t blink or bluff your way out.
Virology is hurting due to the ineptness of the science establishment over the handling of the adapting animal viruses to efficient human transmission and the COVID origins debates. An establishment that is top down and not good at sharing knowledge, not good at pedagogy despite the thirst for, and interest from the public. These deep wounds need healing. Start by trusting the public with a little more of the truth.
Aside
Dr. Thorp is a chemist by training and so it’s possible he could miss some of the finer points that are obvious to a virologist. If the tables were reversed, On Reading could well come a cropper. A subsequent Science editorial by Thorp entitled Correction is Courageous is courageous and welcome. It concerns the peer review process. There are things that needed to be said while it mentions the difficulties scientists have in admitting errors which they would like to brush under the carpet. It’s the side of scientific endeavor that gives no pleasure, but which is unavoidable. Let’s hope others pick this up. On reading will cover a number of his recent editorials for he is clearly bothered by the fragility of public trust in science.
Thorp may say that "correction is courageous" but his AAAS journals have eliminated the form of paper (Technical Comment) by which journals traditionally corrected plain errors post-publication. This indefensible policy decision was made pre-Covid. It indicates a general indifference to helping readers find the truth. That doesn't seem to be part of the AAAS business model.
Although the decision predated Covid, it has proved convenient in protecting the two key zoonosis papers (Worobey et al. and Pekar et al.) from the withering criticism they deserve. The Pekar et al. paper in particular has been shown to have multiple mathematical errors whose correction reverses its conclusion. Science belatedly published a correction of only a fraction of these errors. For the rest of the corrections one must turn to the independent pubpeer post-publication discussion site. Discussions of the serious problems with the Worobey paper may be found in papers in the J. Royal Statistical Society, Series A.