The Mysterious Case of the COVID-19 Lab Leak Theory – Community News

The Mysterious Case of the COVID-19 Lab Leak Theory

There are twelve hundred different mutations between the genomes of RaTG13 and SARS-CoV-2 – scattered variations demonstrating the messiness of evolution. The number and distribution of these mutations are too great for RaTG13 to be the direct precursor of SARS-CoV-2; they separated from a common ancestor at least twenty years ago. But its genetic proximity means “we must search for the ancestors of” SARS-CoV-2 in sites where relatives like RaTG13 are found,” Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center, told me in September. “At this time, the close relatives of SARSCoV-2 is known to have existed in two locations: bat caves in Yunnan and in the Wuhan Institute of Virology.”

Geography aside, the nature of the experiments undertaken by the WIV and its partners has given rise to concern. In 2015, Shi co-authored a groundbreaking study, in Nature, with Ralph Baric, a coronavirus expert at the University of North Carolina. Using groundbreaking genetic technology, Baric explored which viral structures might give a coronavirus the ability to infect humans. The work involved synthesizing what is known as a chimeric virus, named after the mythical beast whose parts come from various animals; in this case a modified clone of SARS was combined with a spike protein from one of the bat coronaviruses that Shi had discovered in Yunnan.

Their research took place at a time that was fraught for virologists. Four years earlier, a Dutch scientist named Ron Fouchier decided to see if he could make the deadly bird flu virus H5N1 more transmissible. After failing to genetically re-engineer the virus, Fouchier turned to a classic method: He repeatedly passed the virus through live ferrets, forcing the virus to evolve into its new host. After ten laps, the virus was in the air. He had created a pathogen in his lab that was ready for a pandemic.

The experiment, which formed a type of study known as “gain-of-function,” raised alarm. There were high-level meetings, op-eds and reports declaring such work much more risky than valuable. In 2014, President Barack Obama ordered a pause in research on job growth related to flu, SARS, and MERSuntil a new regulatory process could be created. However, Baric was in the middle of his chimeric virus experiment. He petitioned the NIH Board of Biosafety, which granted him and other researchers an exemption from the hiatus.

When Baric tested the chimeric virus in a culture of human airway cells, its spike protein was found to be able to bind to the cell receptor. ACE2, suggesting the virus was now ready to jump of sorts. It caused disease in live mice. Given this unexpected outcome, Baric concluded, “scientific review panels may consider similar studies building chimeric viruses from circulating strains too risky to pursue.”

That didn’t happen. Baric’s experiments, which the NIH found to be no gain-of-function, continued at the University of North Carolina. Shi’s lab developed its own platform for making chimeric viruses. She crossed another bat coronavirus from Yunnan called WIV1 – with clones of several novel spike proteins, and tested the creation in humanized mice. The viruses multiplied rapidly. One made the mice emaciated, a sign of serious pathogenesis. What made this work particularly risky was that: WIV1 was already known to be potentially dangerous to humans. Baric himself had made this clear in a 2016 study titled “SARS-Like WIV1-CoV Poised for Human Emergence”.

Some of these experiments at the WIV were funded by the US government, according to Shi’s published papers, as well as NIH-funded grant applications and progress reports obtained by the Intercept. In 2014, the NIH awarded a New York-based nonprofit called the EcoHealth Alliance a five-year grant of $3.7 million, a portion of which — about $600,000 — went to WIV Fauci, and the NIH claimed that The WIV’s work, like Baric’s, did not qualify as gain-of-function research, and thus did not conflict with the Obama-era pause. (The Trump administration lifted the hiatus in 2017 after three years of multi-agency workshops and deliberations resulted in a new regulatory process.) “Don’t mislead people by saying we haven’t taken this seriously for years,” Fauci told me, his voice rises. “By our definition, it was not a gain-of-function, period. If you don’t like the definition, let’s change the definition.”

In recent months, natural-origin skeptics have pointed to the fact that Shi conducted her chimeric virus experiments in a biosafety level 2 lab, which, compared to biosafety level 3, does not require the same precautions, such as full PPE, medical supervision for researchers, mandatory biosafety cabinets, controlled airflow and two sets of self-closing, lockable doors. (Shi conducted live animal experiments in a BSL-3 lab in a separate facility.) Because they were working with new bat viruses rather than viruses known to infect humans directly, the low biosecurity setting was in line with Chinese laws. . But Susan Weiss, a coronavirus expert at the University of Pennsylvania medical school who co-authored a recent paper outlining evidence for natural origin with Andersen and others, was surprised when I told her she had worked in BSL-2. . “That’s not a good idea,” she said.

Yet none of Shi’s documented work on chimeric viruses resulted in the creation of SARS-CoV-2. (“If you are trying to say that that particular experiment could have led to… SARS-CoV-2, that’s completely impossible,” Fauci said.) The chimeric viruses that the WIV has developed are far from SARS-CoV-2 on the coronavirus family tree. According to Shi, the WIV isolated and cultured only three new coronaviruses in their nineteen thousand samples. What this chapter of her work demonstrates, however, is a high level of risk tolerance. “They were essentially playing Russian roulette with the virus that the world expert says is ready for human emergence,” said David Relman, a microbiologist at Stanford. “It’s the willingness to manipulate them without worry.”

In January, the World Health Organization sent a team of international scientists to Wuhan to complete the first phase of a search for SARS-The origin of CoV-2. The group’s report, published in March, ranked a zoonotic spillover — from a bat, via an intermediate, to a human — as the most likely route of origin. They ruled that a lab incident was “extremely unlikely” and devoted only three of the more than 100 pages in the primary report to the theory. As Andersen often says when examining the evidence, “Anything is possible, but I’m interested in what is plausible.”

First, a natural origin has historical precedence. SARS defected from bats to civets at an urban market in November 2002. MERS, which emerged in Saudi Arabia in 2012, went from bats to camels to humans. The civet was identified as the most likely source of SARS within four months of the outbreak; camels were identified within nine months of MERS. But still, SARSThe CoV-2 intermediate — one of the only things that could definitively prove at this point that it didn’t come from the Wuhan labs — has not been found. Such a discovery is also becoming less likely. As members of the WHO mission wrote in an August letter to: Nature“The window is quickly closing on the biological feasibility of performing the critical trace-back of humans and animals inside and outside China.”

A member of the WHO team was Peter Daszak, the president of the EcoHealth Alliance, which is committed to reducing the rise of infectious diseases. Since the first SARS outbreak, he has been one of the WIV’s closest partners, facilitating NIH subcontracts and working extensively with Shi and her team in the field. He has steadfastly vouched for Shi, leading the charge of calling any suggestion of a lab accident a conspiracy theory. “The problem with this lab release hypothesis,” he told me, “is that it depends on one crucial thing: that the virus was in the lab before it came out. But I know that virus wasn’t in the lab. .”

Daszak, a widely publicized disease ecologist, also knows that the diversity of viruses in nature is almost limitless. Recently, he and other EcoHealth scientists built a model to analyze how often coronaviruses can spread from bats to humans in southern China and Southeast Asia. They covered the habitats of all twenty-three bat species known to harbor one SARS-related coronaviruses with maps of human populations. Based on bat-human contact and antibody data, they estimate that about 400,000 people could be infected with… SARS-related coronaviruses per year. “People are exposed to it every year,” Daszak told me. “Maybe they don’t know. They can even get sick and die.”

In other words, spillovers are much more common than anyone realizes. Humans are exposed to bats when they take shelter in caves, harvest bat guano – the world’s best fertilizer – and hunt, slaughter and eat bats, which is a well-documented practice in several parts of the region. “These small villages are on the edge of disappearing forests,” Kendra Phelps, a bat biologist with the EcoHealth Alliance and a co-author of the recent study, told me. “In that forest there are densely packed wildlife, which are super stressed by things like advancing palm oil and rice monocultures.” Stressed animals (just like us) are more likely to get sick and spread the virus.