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University of Nebraska Medical Center

How a rural school teacher became a top COVID sleuth

Nature A self-taught Indiana man is among a cadre of community scientists who scour the SARS-CoV-2 genome for problematic mutations.

In late January, a team of scientists reported an ominous discovery: the widely used COVID-19 drug molnupiravir might be spurring the evolution of SARS-CoV-2 variants1. Four of the authors work at prominent UK universities. But one has neither attended graduate school nor stepped foot in a research laboratory.

The outlier is Ryan Hisner, a school science teacher from rural Monroe, Indiana. He has attracted the attention of prominent virologists from all over the world for his uncanny ability to detect unusual mutations to the SARS-CoV-2 genome — mutations that might be a harbinger of the next variant to sweep the world.

Hisner is just one of a motley crew of self-taught ‘community scientists’ from around the globe who spend hours poring through genetic sequences to track SARS-CoV-2’s evolution. Among the ranks include science enthusiasts such as Hisner, retired researchers and anonymous sleuths who go only by their online usernames. Most do this work for no pay.

They might be amateurs, but their work is indispensable, says Jesse Bloom, an evolutionary virologist at Fred Hutchinson Cancer Center in Seattle, Washington. SARS-CoV-2 spawns variants at an exceptionally fast pace, leaving scientists such as Bloom scrambling to keep up while managing their research programmes. Hisner’s Twitter profile, which has now garnered more than 13,000 followers, is one of Bloom’s first stops to stay up to speed on the latest mutations and publications, he says.

“Ryan has an almost encyclopaedic knowledge of the virus,” Bloom says. “It’s refreshing to see someone who is so up to speed on the literature — more so than any other ‘professional’ I’ve ever met.”

Not only does SARS-CoV-2 mutate quickly, but there is also an “unprecedented flood of data” because tens of thousands of viral genetic sequences are added to online repositories every day, says Angie Hinrichs, a bioinformatician at the University of California, Santa Cruz. Trained public-health officials monitor these uploads, but “it really helps to have more eyes”, says Hinrichs, who keeps track of changes to the virus by plotting new genetic information on a phylogenetic tree that now has more than 15 million sequences.

Tom Peacock, a virologist at Imperial College London who co-authored the molnupiravir study, which has not yet been peer reviewed, says that without Hisner and other community scientists, new SARS-CoV-2 mutations “would go under the radar for a little longer. Even a couple days’ advance notice can be really helpful for updating vaccines if need be.”

Biology by the book

After COVID-19’s onset in 2020, Hisner’s students would ask him questions about the pandemic that stumped him. To find answers and to track the latest research, Hisner started following scientists on Twitter. To his surprise, scientists often answered his questions, although his account had few followers.

When it became evident in mid-2021 that SARS-CoV-2 variants would pose a threat to efforts to control viral spread, Hisner became curious about how mutations were helping the virus to evade immunity. His curiosity landed him in small group chats in which scientists discussed the technical minutiae of emerging SARS-CoV-2 mutations. Hisner realized he had large gaps in his knowledge of basic biology, so he sought textbook recommendations from the group members.

After a year of lurking in these group chats and reading textbooks, Hisner spent at least 5 hours each day during his summer vacation in 2022 learning how to download coronavirus sequences from online databases and compare them with millions of others using phylogenetic software. Soon he started to contribute to Pango, a group that tracks and names SARS-CoV-2 lineages.

Sequence spotter

Bioinformatician Áine O’Toole at the University of Edinburgh, UK, helped to create Pango, which initially included about a dozen scientists. But it soon became clear that there were far too many samples for the original Pango members to track them all, Hinrichs says. In early 2021, O’Toole spread the word about an online site where users can submit proposals for new lineages, which opened this process to the world. Today, most lineage proposals come from community scientists, Hinrichs says.

O’Toole says she never expected to see such public support for Pango when the project launched. “I can’t believe there’s still so much energy and interest at this stage of the pandemic” from community scientists, she says.

Hisner first proposed a new SARS-CoV-2 lineage in June 2022. He has since made more than 100 more proposals, making up about 7% of all submissions. Even during the school year, he has continued to devote an hour every morning and a couple more in the evening to variant-hunting.

He’s become a specialist in identifying variants from chronic infections — rare cases where someone doesn’t clear the virus within a few weeks, offering the virus ample opportunity to mutate and adapt to human hosts. “Almost every major variant, except a few of the recent ones, originated in a chronic infection,” Hisner says. “That’s really under-recognized, so I’m trying to draw attention to that by documenting these lineages.”

Going pro

Although Hisner is not compensated for his work, his labour has paid dividends: Darren Martin, a bioinformatician at the University of Cape Town in South Africa, reached out through Twitter to offer Hisner the opportunity to do research and obtain a graduate degree. “That’s my unusual path to graduate school, thanks to Twitter,” says Hisner.

For now, Hisner, who is quicker to rattle off the latest spike protein mutations he’s spotted than to talk about his future ambitions, plans to complete his graduate work remotely and continue teaching. But he’s open to the idea of pursuing a doctorate after he finishes his master’s work.

Peacock says it’s been refreshing to have community scientists help with surveillance. “People in academia get jaded, so it’s nice to work with someone so enthusiastic” like Hisner, he says.

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