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The scientists who say the lab-leak hypothesis for SARS-CoV-2 shouldn’t be ruled out

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David Relman


It could have been career suicide for scientists to voice suspicions about a possible lab leak, says Metzl, especially when there was already a long history of viral disease outbreaks spilling over from nature. Alina Chan, a postdoctoral fellow specializing in gene therapy and cell engineering at the Broad Institute in Cambridge, Massachusetts, echoes that view. Chan says the risk of challenging the orthodoxy that SARS-CoV-2 has natural origins—an entirely plausible hypothesis, she maintains—is greatest for established scientists in infectious disease with supervisory roles and staffs to support. She herself has spent much of the last year calling for more scrutiny of a potential lab leak, claiming that as a postdoc, she has less to lose.

The vitriol also obscures a broader imperative, Relman says, which is that uncovering the virus’s origins is crucial to stopping the next pandemic. Threats from both lab accidents and natural spillovers are growing simultaneously as humans move steadily into wild places and new biosafety labs grow in number around the world. “This is why the origins question is so important,” Relman says.

“We need a much better sense about where to place our resources and effort,” he adds. And if a lab release for SARS-CoV-2 looks plausible, Relman says, “then it absolutely deserves a whole lot more attention.”


If SARS-CoV-2 did spill over into humans from the wild, how and where did that happen? A year into the pandemic, these remain open questions. Scientists still speculate about whether the virus passed directly into humans from infected bats (known reservoirs for hundreds of different coronaviruses) or through an intermediary animal species. The Huanan Seafood Wholesale Market in Wuhan was initially thought to be the originating site of a potential spillover, since that’s where the first cluster of covid-19—the disease caused by the virus—was detected. But newer evidence suggests that animal or human infections may have been circulating elsewhere for months beforehand, and the focus has since broadened to other markets in the city, wildlife farms in southern China, and other possible scenarios, such as consuming virally contaminated frozen meat originating in other provinces.

Importantly, the virus’s immediate ancestors have yet to be identified. The closest known relative, a coronavirus dubbed RaTG13, is genetically 96% similar to SARS-CoV-2.

A lab-escaped virus, meanwhile, would have been introduced to the world by a researcher or technician who became infected with it. These sorts of lab leaks have happened before, and were implicated in several cases of community transmission during SARS outbreaks in the early 2000s. In 2017, the Wuhan Institute of Virology became the first lab in mainland China to receive a Biosafety Level 4 (BSL-4) designation, the highest security status for a research space. But the institute also has a history of questionable safety practices. The lab’s scientists reported a lack of appropriately trained technicians and investigators at the facility, prompting US diplomatic scientists who visited in 2017 and 2018 to alert the State Department. At the same time, many scientists have pointed out, particularly in the aftermath of a recent, and for some, contentious, examination of the lab-leak hypothesis in New York magazine, that coronaviruses have typically been handled at BSL-2 or BSL-3—lower security levels.

Such caveats aside, a prevailing theory among lab-leak proponents has been that SARS-CoV-2 was not simply brought into the Wuhan lab but was somehow engineered there, given that many of its scientists routinely perform genetic research on coronaviruses and may also have “collaborated on publications and secret projects with China’s military,” according to a US State Department fact sheet released during the last week of the Trump administration. On March 9, a Washington Post columnist, citing an unnamed State Department official, suggested that the Biden administration—while stopping well short of endorsing any particular theory regarding the origin of the virus—did not dispute many of the points made in that fact sheet.

Still, skeptics who doubt the lab-leak hypothesis say SARS-CoV-2 doesn’t look anything like an engineered virus. Instead of appearing in discrete chunks, as would be expected with a genetically engineered microbe, the differences with RaTg13 are distributed randomly throughout the viral genome. In an email to Undark, University of Chicago emeritus virology professor Bernard Roizman wrote that “we are many, many years away from a complete understanding of viral gene functions and regulation—the key elements critical for construction of lethal viruses.”

The virus does have an inexplicable feature: a so-called “furin cleavage site” in the spike protein that helps SARS-CoV-2 pry its way into human cells. While such sites are present in some coronaviruses, they haven’t been found in any of SARS-CoV-2’s closest known relatives. “We don’t know where the furin site came from,” says Susan Weiss, a microbiologist who co-directs the Penn Center for Research on Coronaviruses and Other Emerging Pathogens at the University of Pennsylvania’s Perelman School of Medicine. “It’s a mystery.” Although Weiss says SARS-CoV-2 is unlikely to have been engineered, she adds that the possibility that it escaped from a lab can’t be ruled out.

Stanford microbiologist David Relman believes the lab-leak hypothesis was never given a fair hearing.

ALBERTO E. RODRIGUEZ/GETTY IMAGES

Relman says it’s also possible that scientists working with undisclosed and even more closely related coronaviruses—perhaps one with a furin cleavage site and another with the SARS-CoV-2 gene backbone—may have been tempted to create a recombinant virus so they could study its properties. Indeed, researchers at the Wuhan Institute of Virology initially failed to disclose that eight other SARS-like coronaviruses had been detected in samples collected from the same mine cave where RaTG13 was found. Workers who cleaned bat feces in that cave, located in Yunnan Province near the border with Laos, went on to develop severe respiratory disease, and one of them died.

Petrovsky leans towards another potential scenario, namely that SARS-CoV-2 might be evolved from coronaviruses that snuck into lab cultures. Related viruses in the same culture, he explains, such as one optimized for human ACE2 binding and another not, can swap genetic material to create new strains. “We’ve had this sort of thing happen in our own lab,” he says. “One day, you’re culturing flu, and then one day you sequence it, and you go, ‘Holy shit, where did this other virus come from in our culture?’ Viruses are evolving the whole time, and it’s easy for a virus to get into your culture without you knowing it.” Petrovsky and several coauthors speculated in a paper published as a non-peer-reviewed preprint in May of last year as to whether the virus was “completely natural” or whether it originated with “a recombination event that occurred inadvertently or intentionally in a laboratory handling coronaviruses.” The team wasn’t “saying this is a lab virus,” Petrovsky emphasizes, but rather “just presenting our data.”

But in late April 2020, as Petrovsky’s group was thinking about where to publish their work, “Trump blurted out” that he had reason to believe the virus came out of a Chinese lab, Petrovsky says. And at that point, he adds, much of “the left-wing media” decided “they were going to paint the whole lab thing as a conspiracy theory to bring down Trump.” When Petrovsky approached administrators of the preprint server bioRxiv, the paper was refused. BioRxiv staff replied that it would be more appropriately distributed after peer review, “which stunned us,” Petrovksy says. “We thought the whole point of preprint was to get important information out quickly.”

The paper was subsequently posted on a different preprint server called arXiv.org, based out of Cornell University. Soon reporters came calling, but most were from right-wing news outlets representing what Petrovsky calls “the Murdoch press.” Petrovsky says he had to work at stopping some tendentious reporters from distorting his paper’s findings to shape a narrative that SARS-CoV-2 had unequivocally been manufactured. And at the same time, he says, other media tried “to make a mockery of the whole possibility of the lab thing.”



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The hunter-gatherer groups at the heart of a microbiome gold rush

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The hunter-gatherer groups at the heart of a microbiome gold rush


The first step to finding out is to catalogue what microbes we might have lost. To get as close to ancient microbiomes as possible, microbiologists have begun studying multiple Indigenous groups. Two have received the most attention: the Yanomami of the Amazon rainforest and the Hadza, in northern Tanzania. 

Researchers have made some startling discoveries already. A study by Sonnenburg and his colleagues, published in July, found that the gut microbiomes of the Hadza appear to include bugs that aren’t seen elsewhere—around 20% of the microbe genomes identified had not been recorded in a global catalogue of over 200,000 such genomes. The researchers found 8.4 million protein families in the guts of the 167 Hadza people they studied. Over half of them had not previously been identified in the human gut.

Plenty of other studies published in the last decade or so have helped build a picture of how the diets and lifestyles of hunter-gatherer societies influence the microbiome, and scientists have speculated on what this means for those living in more industrialized societies. But these revelations have come at a price.

A changing way of life

The Hadza people hunt wild animals and forage for fruit and honey. “We still live the ancient way of life, with arrows and old knives,” says Mangola, who works with the Olanakwe Community Fund to support education and economic projects for the Hadza. Hunters seek out food in the bush, which might include baboons, vervet monkeys, guinea fowl, kudu, porcupines, or dik-dik. Gatherers collect fruits, vegetables, and honey.

Mangola, who has met with multiple scientists over the years and participated in many research projects, has witnessed firsthand the impact of such research on his community. Much of it has been positive. But not all researchers act thoughtfully and ethically, he says, and some have exploited or harmed the community.

One enduring problem, says Mangola, is that scientists have tended to come and study the Hadza without properly explaining their research or their results. They arrive from Europe or the US, accompanied by guides, and collect feces, blood, hair, and other biological samples. Often, the people giving up these samples don’t know what they will be used for, says Mangola. Scientists get their results and publish them without returning to share them. “You tell the world [what you’ve discovered]—why can’t you come back to Tanzania to tell the Hadza?” asks Mangola. “It would bring meaning and excitement to the community,” he says.

Some scientists have talked about the Hadza as if they were living fossils, says Alyssa Crittenden, a nutritional anthropologist and biologist at the University of Nevada in Las Vegas, who has been studying and working with the Hadza for the last two decades.

The Hadza have been described as being “locked in time,” she adds, but characterizations like that don’t reflect reality. She has made many trips to Tanzania and seen for herself how life has changed. Tourists flock to the region. Roads have been built. Charities have helped the Hadza secure land rights. Mangola went abroad for his education: he has a law degree and a master’s from the Indigenous Peoples Law and Policy program at the University of Arizona.

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan


Over the last couple of decades, scientists have come to realize just how important the microbes that crawl all over us are to our health. But some believe our microbiomes are in crisis—casualties of an increasingly sanitized way of life. Disturbances in the collections of microbes we host have been associated with a whole host of diseases, ranging from arthritis to Alzheimer’s.

Some might not be completely gone, though. Scientists believe many might still be hiding inside the intestines of people who don’t live in the polluted, processed environment that most of the rest of us share. They’ve been studying the feces of people like the Yanomami, an Indigenous group in the Amazon, who appear to still have some of the microbes that other people have lost. 

But there is a major catch: we don’t know whether those in hunter-gatherer societies really do have “healthier” microbiomes—and if they do, whether the benefits could be shared with others. At the same time, members of the communities being studied are concerned about the risk of what’s called biopiracy—taking natural resources from poorer countries for the benefit of wealthier ones. Read the full story.

—Jessica Hamzelou

Eric Schmidt has a 6-point plan for fighting election misinformation

—by Eric Schmidt, formerly the CEO of Google, and current cofounder of philanthropic initiative Schmidt Futures

The coming year will be one of seismic political shifts. Over 4 billion people will head to the polls in countries including the United States, Taiwan, India, and Indonesia, making 2024 the biggest election year in history.

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Navigating a shifting customer-engagement landscape with generative AI

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Navigating a shifting customer-engagement landscape with generative AI


A strategic imperative

Generative AI’s ability to harness customer data in a highly sophisticated manner means enterprises are accelerating plans to invest in and leverage the technology’s capabilities. In a study titled “The Future of Enterprise Data & AI,” Corinium Intelligence and WNS Triange surveyed 100 global C-suite leaders and decision-makers specializing in AI, analytics, and data. Seventy-six percent of the respondents said that their organizations are already using or planning to use generative AI.

According to McKinsey, while generative AI will affect most business functions, “four of them will likely account for 75% of the total annual value it can deliver.” Among these are marketing and sales and customer operations. Yet, despite the technology’s benefits, many leaders are unsure about the right approach to take and mindful of the risks associated with large investments.

Mapping out a generative AI pathway

One of the first challenges organizations need to overcome is senior leadership alignment. “You need the necessary strategy; you need the ability to have the necessary buy-in of people,” says Ayer. “You need to make sure that you’ve got the right use case and business case for each one of them.” In other words, a clearly defined roadmap and precise business objectives are as crucial as understanding whether a process is amenable to the use of generative AI.

The implementation of a generative AI strategy can take time. According to Ayer, business leaders should maintain a realistic perspective on the duration required for formulating a strategy, conduct necessary training across various teams and functions, and identify the areas of value addition. And for any generative AI deployment to work seamlessly, the right data ecosystems must be in place.

Ayer cites WNS Triange’s collaboration with an insurer to create a claims process by leveraging generative AI. Thanks to the new technology, the insurer can immediately assess the severity of a vehicle’s damage from an accident and make a claims recommendation based on the unstructured data provided by the client. “Because this can be immediately assessed by a surveyor and they can reach a recommendation quickly, this instantly improves the insurer’s ability to satisfy their policyholders and reduce the claims processing time,” Ayer explains.

All that, however, would not be possible without data on past claims history, repair costs, transaction data, and other necessary data sets to extract clear value from generative AI analysis. “Be very clear about data sufficiency. Don’t jump into a program where eventually you realize you don’t have the necessary data,” Ayer says.

The benefits of third-party experience

Enterprises are increasingly aware that they must embrace generative AI, but knowing where to begin is another thing. “You start off wanting to make sure you don’t repeat mistakes other people have made,” says Ayer. An external provider can help organizations avoid those mistakes and leverage best practices and frameworks for testing and defining explainability and benchmarks for return on investment (ROI).

Using pre-built solutions by external partners can expedite time to market and increase a generative AI program’s value. These solutions can harness pre-built industry-specific generative AI platforms to accelerate deployment. “Generative AI programs can be extremely complicated,” Ayer points out. “There are a lot of infrastructure requirements, touch points with customers, and internal regulations. Organizations will also have to consider using pre-built solutions to accelerate speed to value. Third-party service providers bring the expertise of having an integrated approach to all these elements.”

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