Virus hunter: how the renowned virologist who calls himself “the Forrest Gump of COVID” works

As soon as Edward Holmes saw the dark eyes of raccoon dogs looking at him through the bars of the iron cage, he knew he had to capture the moment. It was October 2014. Holmes, a biologist at the University of Sydney, had traveled to China to study hundreds of animal species for new types of viruses.

On a visit to Wuhan, a shopping mall of 11 million people, scientists from the city's Center for Disease Control and Prevention took him to the Huanan Wholesale Seafood Market. In one stall after another in the stuffy space, he saw live wild animals (snakes, badgers, muskrats, birds) being sold for food. But it was the raccoon dogs that made him take out his cell phone to capture reality.

As one of the world's experts on virus evolution, Holmes had an intimate understanding of how viruses can jump from one species to another, sometimes with deadly consequences. The 2002 SARS outbreak was caused by a bat coronavirus in China that infected some type of wild mammal before infecting humans. Among the main suspects, there is an intermediate animal: the raccoon dog.

“You couldn't get a better textbook example about the onset of a disease about to occur,” Holmes, 57, said in an interview. The Englishman did his best not to attract attention when he took a picture of raccoon dogs, which look like long-legged raccoons but are more closely related to foxes. He then took a few more pictures of other animals in their own cages. When a salesman started beating one of the creatures, he put his phone in his pocket and ran away. Or at least this is what a profile of the specialist published by The New York Times as part of its special Profiles in Science assures.

The photos faded from his mind until the last day of 2019. While surfing Twitter from home in Sydney, she learned of an alarming outbreak in Wuhan: SARS-like pneumonia with early cases linked to the Huanan market. “Raccoon dogs,” he thought.

“It was a pandemic waiting to happen, and then it happened,” he said. From that day on, he was drawn into a whirlwind of discoveries and controversies related to the origins of the virus, which made him feel like “the Forrest Gump of coronavirus,” he joked.

He and a Chinese colleague were the first to share the genome of the new coronavirus with the world. He then discovered crucial clues as to how the pathogen probably evolved from bat coronavirus.

And in the controversial geopolitical debate over whether the virus could have leaked from a laboratory in Wuhan, Holmes has become one of the strongest proponents of an opposite theory: that the virus spilled from a wild animal. With colleagues in the United States, he recently published tempting clues that raccoon dogs kept in the same iron cage he photographed in 2014 could have triggered the pandemic.

The specialist's COVID-19 research has earned him international acclaim, including Australia's most important science award. But he has also received claims that his investigation had been overseen by the Chinese military, along with a flood of attacks on social media and even death threats. Despite everything, Holmes has continued to publish a torrent of studies on the coronavirus. His longtime colleagues attribute his constant production in unstable times to an exceptional ability to form great scientific teams and a willingness to immerse themselves in controversial debates.

“He's the right kind of person with the right kind of mindset, because he can be open-minded, involved and think, and not be defensive,” said Pardis Sabeti, a geneticist at MIT's Broad Institute and Harvard. Meanwhile, American researcher, cardiologist and geneticist Eric Topol, current editor-in-chief of Medscape, noted on his Twitter account against Holmes: “He calls himself 'the Forrest Gump of coronavirus', and it's anything but that.”

Hunting for viruses

Holmes studied the evolution of apes and humans, and then turned to viruses. For three decades, working in Edinburgh, Oxford, Pennsylvania and, finally, Sydney, Holmes has published more than 600 articles on the evolution of viruses, including HIV, influenza and Ebola.

When he was invited to the University of Sydney in 2012, he took the opportunity to approach Asia, where he feared that wildlife trade could trigger a new pandemic. “He goes where the fire is,” said Andrew Read, an evolutionary biologist at Pennsylvania State University, who was working with him at the time.

While preparing for the move, Holmes received an unexpected email from a Chinese virologist named Yong-Zhen Zhang, asking him if he would like to study viruses with him in China. Their collaboration quickly expanded to a radical search for new viruses in hundreds of animal species. They studied the spiders torn from the walls of the huts and the fish taken from the South China Sea.

Finally, they found more than 2000 species of viruses new to science, with many surprises among them. Scientists used to think that influenza viruses mainly infected birds, for example, that they could then transmit them to mammals like us. But Holmes and Zhang discovered that fish and frogs also get the flu. “That was quite revealing,” said Andrew Rambaut, an evolutionary biologist at the University of Edinburgh who did not participate in the surveys. “The diversity of viruses that exist is enormous.”

On one of their reconnaissance trips in 2014, the two experts partnered with scientists from the Wuhan Center for Disease Control and Prevention to study animals in the surrounding Hubei province. CDC scientists took them to the Huanan market to see a worrying case of wildlife trade. After the visit, Holmes hoped that he and his colleagues could use the genetic sequencing techniques they had developed for their animal surveys to look for viruses in animals on the market. But his colleagues were more interested in looking for viruses in sick people.

So it was that together with Zhang he began working with doctors at Wuhan Central Hospital, looking for viral RNA in samples of lung fluid from people with pneumonia. Because of this collaboration, he was appointed visiting professor at the Chinese Center for Disease Control and Prevention from 2014 to 2020. Last month, Holmes and his colleagues published their first report on the project, based on samples from 408 patients collected in 2016 and 2017. It turned out that many were sick with more than one virus, and some were also infected with bacteria or fungi. The researchers even saw evidence of a hidden outbreak: six patients were infected with genetically identical enteroviruses. Researchers also continued to study the virosphere, examining soil, sediments and animal feces from all over China. But at the end of December 2019, that work stopped.

The arrival of COVID-19

When Dr. Zhang heard about new pneumonia in Wuhan, he asked his colleagues at Wuhan Central Hospital to send him lung fluid from a patient. He arrived on January 3rd and used the techniques he and Holmes had perfected to search for viruses. Two days later, his team had assembled the genome of a new coronavirus, SARS-CoV-2. Other scientific teams in China had also sequenced the virus. But none of them made it public, because the Chinese government had banned scientists from publishing information about it.

Zhang and Holmes began writing an article about the genome, which would later appear in the journal Nature. Zhang mocked the ban and uploaded the virus genome to a public database hosted by the National Institutes of Health of the United States, but it required a lengthy review so it took days without the information being published online. Holmes urged his collaborator to find another way to share the genome with the world. “It seemed like it had to happen,” he said.

On January 10, they agreed to share it in a forum for virologists and Holmes put it online. That decision was a turning point, according to Jason McLellan, a structural biologist at the University of Texas at Austin, who worked on the mRNA technology that drives the Moderna vaccine. Only with that genetic sequence could researchers start working on tests, drugs and vaccines. Until then, according to McLellan, scientists like him were like runners in their starting blocks, waiting for the starting gun. “It skyrocketed the moment Edward and Yong-Zhen published the genome sequence,” he remarked. “Immediately, Twitter was filled with excitement, emails were exchanged and the race began.”

But according to Chinese media reports, Zhang paid a price for challenging his country's information ban. The day after the genome sequencing was put in place, his laboratory at the Shanghai Public Health Clinical Center was ordered to be shut down in order to “rectify” it. Later, Zhang insisted to a Nature reporter that the move was not a punishment and that his laboratory later reopened. Email requests to the expert to comment on The New York Times story went unanswered. And Holmes declined to comment on Dr. Zhang's current situation.

After sequencing the coronavirus genome, Holmes was perplexed to see some fragments of genetic material that appeared to have been placed there by genetic engineering. In a conference call on February 1, 2020, the scientist shared his concerns with other virus experts, including Dr. Francis Collins, director of the NIH, and Anthony S. Fauci, the leading expert on infectious diseases in the US. Other scientists explained in the call that these characteristics of the genome could easily have occurred through the natural evolution of viruses.

Soon after, Holmes helped researchers at the University of Hong Kong analyze a coronavirus, found in a pangolin , that was closely related to SARS-CoV-2. The virus was especially similar in its surface protein, called pico, which the virus uses to enter cells. Finding such a different biological signature in a wild animal virus strengthened the expert's confidence that SARS-CoV-2 was not the product of genetic engineering. “Suddenly, what seems strange is clearly natural,” he stressed.

Holmes and his colleagues set out some of these findings in a letter published in March 2020. That same month, he published some of his photos of caged animals in the Huanan market in a comment he wrote with Dr. Zhang, suggesting that it could have been the site of an animal spill. But the idea that the virus had been designed in a laboratory continued to gain traction, and the virologist was attacked by his work with Chinese scientists.

In May 2020, The Daily Telegraph, an Australian newspaper, linked it to the Chinese military with an article titled “How the Red Army oversaw coronavirus research.” The paper based its claim on the fact that two scientists involved in the study of pangolin had secondary affiliations with a Chinese military laboratory. Holmes, who said he never met the scientists, noted that they had helped sequence RNA from pangolin tissue.

The University of Sydney responded on behalf of the specialist with a statement: “We strongly defend the right of our researchers to collaborate with scientists around the world in accordance with all relevant Australian government laws and guidelines”. The university noted that the expert's research was funded entirely by Australian grants.

At the end of 2020, the World Health Organization organized an expert group trip to China to investigate the origin of the new coronavirus. Holmes sent them his 2014 market photos, but they never made it to the WHO report. “Some members of the Chinese delegation suggested that I could have made those images,” Holmes warned (Peter Daszak, president of the EcoHealth Alliance and one of the researchers in the WHO report, corroborated this account: Chinese researchers said the photos “were not verifiable and could have been falsified,” said Daszak).

Prevention of future spills

In reports released last month, Holmes and more than 30 collaborators analyzed the first cases of COVID-19, found that they were clustered on the market, and examined mutations in the first coronavirus samples. Chris Newman, a wildlife biologist at Oxford University and co-author of one of the studies, said that his Chinese colleagues saw several wild mammals for sale at the Huanan market in late 2019. Any of them could have been responsible for the pandemic, according to the expert. “Raccoon dogs can't be tested yet, but they are certainly suspicious,” he said.

Some critics have questioned how certain Dr. Holmes and his colleagues can be that an animal from Huanan was the culprit. Although many of the first cases of the new coronavirus were linked to the market, it is possible that other cases of pneumonia have not yet been recognized as early cases of COVID-19. “We still know very little about the first cases, and there are probably additional cases that we don't know about, to draw final conclusions,” explained Filippa Lentzos, a biosafety expert at King's College London. “I remain open to both natural indirect effects and research-related origins.”

Another problem: if infected animals really started the pandemic, they will never be found. In January 2020, when researchers from the Chinese CDC arrived on the market to investigate, all the animals were gone. But Holmes argues that there is more than enough evidence that animal markets could cause another pandemic. Last month, he and his Chinese colleagues published a study of 18 species of animals that are often sold in markets, sourced in the wild or on breeding farms. “They were absolutely full of viruses,” he said.

More than 100 viruses that infect vertebrates came to light, including several potential human pathogens. And some of these viruses had recently jumped the species barrier: the bird flu that infects badgers, the canine coronaviruses that infect raccoon dogs. Some of the animals were also ill with human viruses.

The easiest way to reduce the likelihood of future pandemics, he argued, is to conduct studies like this at the interface between humans and life wild. His own experience in discovering new viruses has convinced him that there is no point in trying to catalog all potential threats in wildlife. “You could never test every virus that exists and then determine which of them can infect humans. I don't think that's feasible,” he said.

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