Controversial new research suggests SARS-CoV-2 bears signs of genetic engineering

The claim has yet to be peer-reviewed writes The Economist

Oct 22nd 2022

Astring of about 30,000 genetic letters were all that it took to start the nightmare of covid-19, the death toll from which is likely to be more than 20m. Exactly how this story began has been hotly contested. Many think that covid-19’s emergence was a zoonosis—a spillover, as so many new pathogens are, from wild animals, for it resembles a group of coronaviruses found in bats. Others have pointed to the enthusiastic coronavirus engineering going on in laboratories around the world, but particularly in Wuhan—the Chinese city where the virus was first identified. In February 2021 a team of scientists assembled by the World Health Organisation (who) to visit Wuhan said a laboratory leak was extremely unlikely. However, this conclusion was subsequently challenged by the who’s boss, who said ruling out this theory was premature.

Two recent publications appear to have bolstered the case for a natural origin connected to a “wet market” in Wuhan. These markets sell live animals, often housed in poor conditions, and are known to be sites where new pathogens jump from animal to human. Early cases of covid-19 clustered around this market. But critics counter that there are so many missing data about the epidemic’s initial days that this portrait may be inaccurate.

The opposing idea of a leak from a laboratory is not implausible. The accidental escape of viruses from labs is more common than many people realise. The flu epidemic of 1977 is thought to have started this way. But an escaped virus does not imply an engineered virus. Virology labs are also full of the unengineered sort.

Research such as that done in Wuhan offers a number of ways for a virus to leak out. A researcher on a field trip could have picked it up in the wild and then returned to Wuhan, and so spread it to others there. Or someone might have been infected with a wild-collected virus in the laboratory itself. But some argue that sars-cov-2 could have been assembled in a laboratory from other viruses that were already to hand, and then leaked out.

Into this fray comes an analysis from an unlikely source. Alex Washburne is a mathematical biologist who runs Selva, a small startup in microbiome science based in New York. He is an outsider, although he has worked in the past on virological modelling as a researcher at Montana State University. For this study, Dr Washburne collaborated with two other scientists. One is Antonius VanDongen, an associate professor of pharmacology at Duke University, in North Carolina. The other, Valentin Bruttel, is a molecular immunologist at the University of Würzburg, Germany. Dr Washburne and Dr VanDongen have been active proponents of an investigation into the lab-leak theory.

The trio base their claim on a novel method of detecting plausibly lab-engineered viruses. Their analysis, published on October 20th on bioRxiv, a preprint server, suggests sars-cov-2 has some genomic features that they say would appear if the virus had been stitched together by some form of genetic engineering. By examining how many of these putative stitching sites sars-cov-2 has, and how relatively short these pieces are, they attempt to assess how much the virus resembles others found in nature.

They start from the presumption that creating a genome as long as that of sars-cov-2 would mean combining shorter fragments of existing viruses together. For a coronavirus genome assembly they say an ideal arrangement would be to use between five and eight fragments, all under 8,000 letters long. Such fragments are created using restriction enzymes. These are molecular scissors which cut genomic material at particular sequences of genetic letters. If a genome does not have such restriction sites in opportune places, researchers typically create new ones of their own.

They argue that the distribution of restriction sites for two popular restriction enzymes—BsaI and BsmBI—are “anomalous” in the sars-cov-2 genome. And the length of the longest fragment is far shorter than would be expected. They determined this by taking 70 disparate coronavirus genomes (not including sars-cov-2) and cutting them into pieces with 214 commonly used restriction enzymes. From the resulting collection, they were able to work out the expected lengths of fragments when coronaviruses are cut into varying numbers of pieces.

The paper, which as a preprint has received no formal peer review, and which has not been accepted for publication in a journal, will be picked apart in the coming days—as well it should be, for this is the way that science works. Early reactions, though, have been deeply divided. Francois Balloux, a professor of computational systems biology at University College London, said he found the results intriguing. “Contrary to many of my colleagues, I couldn’t identify any fatal flaw in the reasoning and methodology. The distribution of BsaI/BsmBI restriction sites in sars-cov-2 is atypical”. Dr Balloux said these needed to be assessed in good faith. But Edward Holmes, an evolutionary biologist and virologist at the University of Sydney, said that every one of the features identified by the paper was natural and already found in other bat viruses. If someone were engineering a virus they would undoubtedly introduce some new ones. He added, “there are a whole range of technical reasons why this is complete nonsense.”

Sylvestre Marillonnet, an expert in synthetic biology at the Leibniz Institute for Plant Biochemistry, in Germany, agreed that the number and distribution of these restriction sites did not look quite random, and that the number of silent mutations found in these sites did suggest that sars-cov-2 might have been engineered. (Silent mutations are a result of engineers wanting to make changes in a sequence of genetic material without making changes to the proteins encoded by that sequence.) But Dr Marillonnet also said that there are arguments against this hypothesis. One of them is the tiny length of one of the six fragments, something that “does not seem logical to me”.

The other point Dr Marillonnet makes is that it is not necessary for the restriction sites to have been present in the final sequence. “Why would people introduce and leave sites in the genome when it is not needed?” he wondered. Previous arguments in support of the possibility of a lab leak have stressed that a manipulated virus would not need to have any such tell-tales. However, Justin Kinney, a professor at Cold Spring Harbor Laboratory, in New York, said that researchers have created coronaviruses before and left such sites in the genome. He said the genetic signature indicates a virus ready for further experiments and said it needed to be taken seriously, but warned the paper needed rigorous peer review.

Erik van Nimwegen, from the University of Basel, says there are only small scraps of information and it is “hard to pull anything definitive out of that”. He adds, “one cannot really exclude at all that such a constellation of sites may have occurred by chance”. The authors of the paper concede this is the case. Kristian Andersen, a professor of immunology and microbiology, at the Scripps Research Institute in La Jolla, California, described the pattern, on Twitter, as “random noise”.

Any conclusion that sars-cov-2 was engineered will be hotly contested. China denies the virus came from a Chinese lab, and has asked for investigations into whether it may have originated in America. Dr Washburne and his colleagues say their predictions are testable. If a progenitor genome to sars-cov-2 is found in the wild with restriction sites that are the same, or intermediate, it would raise the chances that this pattern evolved by chance.

Any widely supported conclusion that the virus was genetically engineered would have profound ramifications, both political and scientific. It would put in a new light the behaviour of the Chinese government in the early days of the outbreak, particularly its reluctance to share epidemiological data from those days. It would also raise questions about what was known, when, and by whom about the presumably accidental escape of an engineered virus. For now, this is a first draft of science, and needs to be treated as such. But the scrutineers are already at work.

If the Wuhan lab-leak hypothesis is true, expect a political earthquake

 Thomas Frank in The Guardian

‘My own complacency on the matter was dynamited by the lab-leak essay that ran in the Bulletin of the Atomic Scientists earlier this month.’ Photograph: Thomas Peter/Reuters
 

There was a time when the Covid pandemic seemed to confirm so many of our assumptions. It cast down the people we regarded as villains. It raised up those we thought were heroes. It prospered people who could shift easily to working from home even as it problematized the lives of those Trump voters living in the old economy.

Like all plagues, Covid often felt like the hand of God on earth, scourging the people for their sins against higher learning and visibly sorting the righteous from the unmasked wicked. “Respect science,” admonished our yard signs. And lo!, Covid came and forced us to do so, elevating our scientists to the highest seats of social authority, from where they banned assembly, commerce, and all the rest.

We cast blame so innocently in those days. We scolded at will. We knew who was right and we shook our heads to behold those in the wrong playing in their swimming pools and on the beach. It made perfect sense to us that Donald Trump, a politician we despised, could not grasp the situation, that he suggested people inject bleach, and that he was personally responsible for more than one super-spreading event. Reality itself punished leaders like him who refused to bow to expertise. The prestige news media even figured out a way to blame the worst death tolls on a system of organized ignorance they called “populism.”

But these days the consensus doesn’t consense quite as well as it used to. Now the media is filled with disturbing stories suggesting that Covid might have come — not from “populism” at all, but from a laboratory screw-up in Wuhan, China. You can feel the moral convulsions beginning as the question sets in: What if science itself is in some way culpable for all this?

*

I am no expert on epidemics. Like everyone else I know, I spent the pandemic doing as I was told. A few months ago I even tried to talk a Fox News viewer out of believing in the lab-leak theory of Covid’s origins. The reason I did that is because the newspapers I read and the TV shows I watched had assured me on many occasions that the lab-leak theory wasn’t true, that it was a racist conspiracy theory, that only deluded Trumpists believed it, that it got infinite pants-on-fire ratings from the fact-checkers, and because (despite all my cynicism) I am the sort who has always trusted the mainstream news media.

My own complacency on the matter was dynamited by the lab-leak essay that ran in the Bulletin of the Atomic Scientists earlier this month; a few weeks later everyone from Doctor Fauci to President Biden is acknowledging that the lab-accident hypothesis might have some merit. We don’t know the real answer yet, and we probably will never know, but this is the moment to anticipate what such a finding might ultimately mean. What if this crazy story turns out to be true?

The answer is that this is the kind of thing that could obliterate the faith of millions. The last global disaster, the financial crisis of 2008, smashed people’s trust in the institutions of capitalism, in the myths of free trade and the New Economy, and eventually in the elites who ran both American political parties. 

In the years since (and for complicated reasons), liberal leaders have labored to remake themselves into defenders of professional rectitude and established legitimacy in nearly every field. In reaction to the fool Trump, liberalism made a sort of cult out of science, expertise, the university system, executive-branch “norms,” the “intelligence community,” the State Department, NGOs, the legacy news media, and the hierarchy of credentialed achievement in general.

Now here we are in the waning days of Disastrous Global Crisis #2. Covid is of course worse by many orders of magnitude than the mortgage meltdown — it has killed millions and ruined lives and disrupted the world economy far more extensively. Should it turn out that scientists and experts and NGOs, etc. are villains rather than heroes of this story, we may very well see the expert-worshiping values of modern liberalism go up in a fireball of public anger.

Consider the details of the story as we have learned them in the last few weeks:

• Lab leaks happen. They aren’t the result of conspiracies: “a lab accident is an accident,” as Nathan Robinson points out; they happen all the time, in this country and in others, and people die from them.

• There is evidence that the lab in question, which studies bat coronaviruses, may have been conducting what is called “gain of function” research, a dangerous innovation in which diseases are deliberately made more virulent. By the way, right-wingers didn’t dream up “gain of function”: all the cool virologists have been doing it (in this country and in others) even as the squares have been warning against it for years.

• There are strong hints that some of the bat-virus research at the Wuhan lab was funded in part by the American national-medical establishment — which is to say, the lab-leak hypothesis doesn’t implicate China alone.

• There seem to have been astonishing conflicts of interest among the people assigned to get to the bottom of it all, and (as we know from Enron and the housing bubble) conflicts of interest are always what trip up the well-credentialed professionals whom liberals insist we must all heed, honor, and obey.

• The news media, in its zealous policing of the boundaries of the permissible, insisted that Russiagate was ever so true but that the lab-leak hypothesis was false false false, and woe unto anyone who dared disagree. Reporters gulped down whatever line was most flattering to the experts they were quoting and then insisted that it was 100% right and absolutely incontrovertible — that anything else was only unhinged Trumpist folly, that democracy dies when unbelievers get to speak, and so on.

• The social media monopolies actually censored posts about the lab-leak hypothesis. Of course they did! Because we’re at war with misinformation, you know, and people need to be brought back to the true and correct faith — as agreed upon by experts.

*

“Let us pray, now, for science,” intoned a New York Times columnist back at the beginning of the Covid pandemic. The title of his article laid down the foundational faith of Trump-era liberalism: “Coronavirus is What You Get When You Ignore Science.”

Ten months later, at the end of a scary article about the history of “gain of function” research and its possible role in the still ongoing Covid pandemic, Nicholson Baker wrote as follows: “This may be the great scientific meta-experiment of the 21st century. Could a world full of scientists do all kinds of reckless recombinant things with viral diseases for many years and successfully avoid a serious outbreak? The hypothesis was that, yes, it was doable. The risk was worth taking. There would be no pandemic.”

Except there was. If it does indeed turn out that the lab-leak hypothesis is the right explanation for how it began — that the common people of the world have been forced into a real-life lab experiment, at tremendous cost — there is a moral earthquake on the way.

Because if the hypothesis is right, it will soon start to dawn on people that our mistake was not insufficient reverence for scientists, or inadequate respect for expertise, or not enough censorship on Facebook. It was a failure to think critically about all of the above, to understand that there is no such thing as absolute expertise. Think of all the disasters of recent years: economic neoliberalism, destructive trade policies, the Iraq War, the housing bubble, banks that are “too big to fail,” mortgage-backed securities, the Hillary Clinton campaign of 2016 — all of these disasters brought to you by the total, self-assured unanimity of the highly educated people who are supposed to know what they’re doing, plus the total complacency of the highly educated people who are supposed to be supervising them.

Then again, maybe I am wrong to roll out all this speculation. Maybe the lab-leak hypothesis will be convincingly disproven. I certainly hope it is.

But even if it inches closer to being confirmed, we can guess what the next turn of the narrative will be. It was a “perfect storm,” the experts will say. Who coulda known? And besides (they will say), the origins of the pandemic don’t matter any more. Go back to sleep.