Heterodox Views In The Academy Could Save Lives
The left won't stop trying to debunk the lab leak hypothesis, and it's not going to help us prepare for the future
Former CDC director Robert Redfield has been appearing recently on conservative talk shows and testified before Congress that there was a deliberate effort among scientists in the gain-of-function (GOF) virology community to direct attention away from the likelihood that the novel coronavirus of 2019 came from a lab. The left-wing media is downplaying it, while the right-wing media is elevating the story. Whenever a hypothesis is this partisan, it should raise all of our alarm bells.
According to Redfield, the researchers’ feared that their "critical" gain-of-function research program would be in jeopardy if public opinion were to sway against them, and that this would lead to increased regulations and restrictions on their programs.
This is not the first time unfamiliar sciencey-sounding things have freaked out the public. It’s also not the first time the experts have tried to tell everyone it’s going to be just fine. We should learn from these mistakes.
Can GOF predict evolution’s “forced moves”?
Starting in the early 2000s, after the first SARS epidemic, there was a growing consensus among scientists that coronaviruses were a candidate for a global pandemic. A highly cited 2007 review article by Vincent Cheng and colleagues at the University of Hong Kong was among the first to formally call out this risk. The painful irony is that gain-of-function studies became one of the ways to study coronaviruses to try to get ahead of possible pandemics, to develop prevention strategies based on adaptations viruses may someday acquire.
One of the main techniques used in GOF research is “passaging,” though it is not unique to GOF. Passaging – isolating an infectious agent from a sick individual and giving it to a healthy one – is a microbiology technique that was pioneered by Louis Pasteur in the 1850s to study bacteria. It was adapted to virology after the discovery of viruses in the early 20th century. Passaging is one of the few ways by which infectious disease researchers can demonstrate causality. If you isolate a suspected infectious agent from a sick individual and give it to a healthy one, and it causes the same symptoms, you have a good case that the agent caused the infection.
As it turns out, serial passaging (through multiple individuals over time) exposes pathogens to selection pressures which prefer particular mutants over others and amplify those traits in the population. So in that sense, it can be used to simulate transmission and viral evolution in the lab. Gain-of-function research can take advantage of this feature of passaging to give viruses new abilities useful to humans (the ability to kill cancer cells, adapt human viruses to animal models to make studying them safer, carry gene products to treat genetic diseases), and new abilities that are not so useful, such as the ability to jump from animals to humans or transmit through the air. Gain-of-function research has given us a great deal of insight into how viral evolution and transmission works and was involved in developing flu vaccines.
But it may have also caused the COVID-19 pandemic, a very reasonable hypothesis which has, for political reasons, been labeled a conspiracy theory. Redfield’s interviews have brought this issue back to the surface of public discourse.
To be clear, I am not part of the GOF community. My background is in food safety. The only viral cell culture system I’ve ever used was mouse norovirus. I am not qualified to give a comprehensive overview of all the safer GOF methods and alternatives. I’ve linked references so you can see them for yourself. My interest in this topic is more philosophical, because I like to read about evolution and philosophy of science. I am usually on the lookout for ways in which I and others misunderstand things we shouldn’t. As such, I am doubtful that gain-of-function experiments can accurately predict viral adaptation well enough to make it worth the risk. I am not alone, although this appears to be a minority viewpoint among experts.
One of the most prominent GOF critics is Marc Lipsitch, a Harvard epidemiologist. Alarmingly, he published a paper in PloS Medicine way back in 2014 explaining that GOF research has the potential to cause a global pandemic. In 2018, he criticized the influenza vaccine research for using GOF techniques. He and another author, David Relman, both claim that there was no rigorous attempt made by GOF researchers to show that modifying live viruses offered unique benefits over safer alternatives.
He was also suspicious, as I am, that GOF results aren’t very generalizable. Natural selection in the wild and artificial selection in the lab, let alone artificial selection in two different labs, does not produce the same outcome. We do not really know if artificially fast forwarding evolution to anticipate future viruses will accurately predict real future viruses because we cannot know all of the factors which influence selection.
Philosopher Daniel Dennet, author of Darwin’s Dangerous Idea (1995), would call any supposed “inevitable” outcome of evolution a “forced move,” which may be familiar to those who play chess. It is a move you have to make given the positions of the other pieces on the board, to avoid losing. My reading of the facts is that it sounds like GOF proponents think they can predict evolution’s forced moves, but I don’t think they can. Simply showing that something is possible doesn’t mean it will happen.
Of course, plenty of scientific work doesn’t have to have a direct practical application to be valuable, because of the basic science questions it answers. But, if that work has the very real risk of sparking a global pandemic, and we have at least one data point now demonstrating that it can, why bother, especially if there are alternatives?
I fear that the politicization of the COVID-19 pandemic is likely to make open conversations about GOF even more difficult, even among researchers themselves. I’m not surprised that criticizing GOF is a minority viewpoint. Is it political? I can’t tell. Are these critics right? If politics muddies the waters, then we can’t know that either.
It is not really up for debate anymore that academia leans left on the political spectrum. A hypothesis favored by one side of the aisle will not be properly challenged if there are few members of the scientific community who either occupy the other side or are willing to fearlessly and honestly engage with opposing viewpoints.
When a hypothesis is partisan, we can’t have open conversations
Unfortunately, because the origin of SARS-CoV-2 is so radioactively partisan, one side is now even more heavily motivated to protect GOF research because of its connection to another hypothesis with the stain of conservatism on it – the lab leak hypothesis.
Back in 2020, a widely-circulated paper explained that there was no evidence of commercial kits in the clinical isolates. But, you don't need a commercial kit to modify RNA. Today, op-eds are still arguing that the lab leak hypothesis isn’t consistent with how viral evolution and transmission work. According to a piece on Real Clear Science,
“It’s not something that can happen accidentally, because the genetics of transmission are so subtle and complex — the result of numerous specific tiny adaptations.”
She claims the virus needed time to circulate, to be acted upon by natural selection, to eventually evolve its transmissibility from human to human because such a thing is not possible to engineer in one shot, and engineered viruses so far have not shown an ability to spread. But, we do not know if it did or did not have that time because we still don’t really know how long it circulated in the population before the first case was identified.
This is also an argument from incredulity, similar to how creationists say that evolution couldn’t be the explanation for diversity because of how complex life is. In fact, evolution is exactly how mind-bogglingly complex things can happen, more or less “by accident.” And we can’t predict that any particular adaptation must or cannot happen. We can only demonstrate that it can happen.
To me, all hypotheses are fair game. Maybe SARS-CoV-2 really did jump species and develop the ability to transmit by air naturally. But, the lab leak hypothesis became labeled a conservative conspiracy theory, and once something becomes associated with conservatives, it becomes a taboo among academics to discuss seriously. Instead, it becomes a target for “debunking” which does little but generate talking points and reassure people who already agree. Yet that is what most of the pro-natural-origin articles amount to, and a lab leak is not that unreasonable a possibility.
A conspiracy theory is, after all, a hypothesis. It may enter crazy territory when its proponents do not offer a way to falsify it and then extrapolate unfounded conclusions. There are certainly lab leak proponents who take it in this direction. But there is nothing wrong with asking a question if you do it scientifically.
We CAN Handle the Truth
The GOF scientists who were motivated to cover up the lab leak hypothesis and shield it from proper inquiry did have one valid fear: that if the public knew this was a risk, they would never trust science again. They were right. But lying by omission to avoid causing panic backfired quite badly, as it did with the communication about masks. If we were to have another pandemic, it wouldn't matter if the CDC had their budget tripled. None of their messaging would be effective. Politicize science at our peril, indeed.
Redfield's interviews have also reignited the anti-vaccine movement, which is an unwarranted logical leap. Conservative media personalities have been spreading this sentiment, rightfully upset about Redfield’s claims, but also tacking on vaccine fears and mask rejection, which are separate science questions. Like two genes on the same chromosome, opinions within ideologies also travel together as they propagate. Team Natural Origin is also Team Vaccine, and Team Lab Leak is also Team Anti-Vax. But it doesn’t have to be so.
The virus could have come from a lab and been covered up, and a safe and effective vaccine could still have been developed. Still, it’s hard not to sympathize with the anti-vaccine crowd. If the CDC, NIH, our elected officials, and the media were not truthful about COVID, what else were they omitting? Were they creating a crisis, exploiting one, or both?
If public health officials had shown willingness to talk openly about ALL of the questions, without hand-waving, dodging, and paternalism, it would have helped us come together and prepare. Now, all emergency warnings will be seen as command-and-control plots rather than true concern for public safety. And we’ll never know if they are or not. Talking across ideological boundaries will be harder now than ever. I fear we will not be any better prepared for the next crisis than we were for COVID-19.
This is a well written and important piece. I agree with the author that both the lab leak and natural origin hypotheses should be open for exploration. Sadly, the damage to science has been done...and the GOF function research community and most scientists frankly deserve the bulk of the blame for the public's rightful distrust of science. The reality is that GOF research that was being funded by NIH at the Wuhan lab of virology had been made illegal by the US Congress. Elected officials, not the scientific community, had the final word on whether such research should be allowed. The arrogant scientific community broke the law. It does not matter at that point whether the virus arose from a lab leak. The scientific community demonstrated that it cannot be trusted with the resources to conduct such research. The massive defunding science is now facing is the least of what should occur. Frankly...many in the GOF research community should be under arrest and facing prison time for taking risks that public officials had denied them the right to engage in. The scientific community will not hope to regain any credibility until it demands these scientists pay the price for their arrogance.
I am the author of this post and I want to issue some corrections, as the blog owner doesn't seem to want to take the piece down.
First of all, I want to emphasize that I do not consider "just asking questions" to be a valid rhetorical device to shoe-horn bad thinking into academia. I do believe conspiracy theories to be hypotheses, but not all of them are good, and most people who peddle them do not treat them as hypotheses at all. Including some people reading this blog. I included this statement to attempt to make this clear ----- "It may enter crazy territory when its proponents do not offer a way to falsify it and then extrapolate unfounded conclusions. There are certainly lab leak proponents who take it in this direction. But there is nothing wrong with asking a question if you do it scientifically." --- However I realize the ease at which readers can dismiss this sentence as being about other people, and not them. It is not and never has been my intention to promote conspiracy thinking and I am horrified at the possibility that it may have been interpreted this way. In my attempt to be balanced, I failed.
Second of all, The WiV laboratory on the hotseat was not doing simulated evolution. They were genetically modifying virus particles. I failed to make this clear because I was editing for length and by mistake a false connection between WiV and passaging/simulated evolution resulted. Furthermore, my reason for explaining passaging was to give some clarity to the misunderstanding if it's gain-of-function, then it's bad, but there are lots of types of GOF and not all of them are risky. In the literature, the "risky" type of GOF is the type that generates "PPPs" or Potential Pandemic Pathogens. This is what Marc Lipsitch opposes. His perspective on this makes sense to me as someone who reads a lot about the philosophy of science behind evolution. But Lipsitch disagreeing with GOF doesn't mean he supports lab leak. Another accidental conflation I didn't intend to make.
Furthermore, after exchanges behind the scenes with another HxSTEM reader, who should be submitting a piece to follow up this one soon, I realized that I am not actually qualified to assess the two perspectives on the lab leak hypothesis. This paper (https://www.cell.com/cell/fulltext/S0092-8674(24)00901-2) seems rigorous and traces a common ancestor of the pandemic virus and a virus found at the Wuhan market to be the same, along with evidence that various mammal species were shedding viruses at that time in the location where the bulk of initial cases were. This does provide very good support for a natural origin. However, Matt Ridley shares his rejected COVID-19 origin paper on his substack which can be found here: https://rationaloptimistsociety.substack.com/i/164035356/the-preponderance-of-evidence-suggests-that-the-covid-pandemic-began-as-a-result-of-a-research-accident. In this paper, he explains why he still believes the lab leak hypothesis. I am not qualified to assess either of these papers to determine which is making the better case. You are welcomed to read both of them as well as the many hundreds of other papers on this topic and decide for yourself.
You may find, though, that in doing that you're just as in over your head as I was in trying to weigh in on this issue. I do not belong in this discussion, and I apologize for having accidentally strengthened the anti-science movement. I will say that I think there's not much I can do to stop the anti-science movement as a whole because it likely started long before I was ever born and reached the point of no return before I ever finished college.
One of my own career goals was to try to bridge the gap between the right and the left on science issues and help people understand that you don't have to sign on to an entire ideology just because you agree with one part of it, a thing I see a lot of people doing regardless of education level. HxSTEM's mission is one that I support, but all too often these groups claiming to want to "think for themselves" just become a reservoir for populist paranoia and oversimplification of key issues. Academia leans left, and this means anyone who doubts any part of the progressive left-leaning worldview is suddenly a conservative and ends up over here.
I had intended to write another post about the mRNA vaccine, which I support, and which breaks from the usual cluster of viewpoints, which I thought I was clear about in my last few paragraphs but it seems I wasn't. But I have decided not to weigh in anymore on this topic at all. Thanks for reading, and I am sorry for making things worse.