Matsen, Bedford named Howard Hughes Medical Institute Investigators

Two computational biologists at Fred Hutchinson Cancer Research Center have been named Howard Hughes Medical Institute Investigators, one of the most coveted honors in biomedical research.

Drs. Trevor Bedford and Frederick "Erick" Matsen have each earned acclaim for their roles in the use of genetically based family trees to track the evolution of viruses, most recently that of SARS-CoV-2, the virus responsible for COVID-19. They are among 33 HHMI Investigators whose appointments were announced today.

Bedford became a scientific celebrity for his prescient warnings about the sudden emergence of the novel coronavirus in January 2020, while Matsen is renowned in the field for his mathematical acumen, developing computational tools that allow scientists to track rapid changes in genes sequenced from viral isolates.

“This is a terrific recognition of the remarkable research coming from the Bedford and Matsen labs,” said Fred Hutch President and Director Dr. Thomas J. Lynch Jr., who holds the Raisbeck Endowed Chair. “Most importantly is the endorsement of the impact of that work.”

Matsen: Developing algorithms for data analysis

Matsen’s research involves the development of computer algorithms that can speed up the process of analyzing enormous quantities of biological data. He describes that work as toolmaking and “computational basic research,” the kind that explores what types of algorithms are possible, even if many of them end up as blind alleys. He has been writing algorithms for faster analysis of those branching charts, known as phylogenetic trees, which use genetic sequencing of evolving viruses to trace their emergence and spread.

His specialty is the use of a mathematically rich statistical technique known as “Bayesian inference.” It accounts for uncertainties that are inherent in using gene sequencing data to build these trees, which describe the evolutionary relationship of the sequences. By explicitly accommodating uncertainty, researchers can be more confident in what they can and cannot conclude about the evolutionary history of the virus. His longterm goal is to deliver algorithms that his fellow HHMI investigator Bedford can use to track the global spread and evolution of SARS-CoV-2.

Matsen now contemplates the free-wheeling possibilities of the HHMI award.

“The most important thing is that we can take on hard problems, the kind where maybe I have nothing to show for three or four years, which in the usual grant cycle is a scary place to be in,” he said. “But it is also one that I do think deep advances can come from.”

Although the scientists are contemporaries, Bedford views Matsen as a mentor. Both are faculty members in the Hutch’s Herbold Computational Biology Program, established in 2007 to help merge biological science with mathematics and computer science. They are also good friends, who sometimes hike and snowshoe in the Cascade Mountains together. Matsen, who grew up in Seattle and has been on the Hutch faculty since 2010, knew of Bedford’s rising reputation and helped introduce him to the Hutch when he started looking for a faculty position.

“My greatest dream is to directly advance Trevor’s research with new algorithms,” he said. “Not by taking the existing tools and expanding them, but by re-imagining things from scratch.”

Bedford: Tracing viruses’ emergence and spread

Bedford appreciates HHMI not only for its model of encouraging new ideas, but also for its support of open science, for which he has been an early and vocal advocate. It is the practice of making results of research readily available to the public, without the delays and paywalls that accompany much of the written findings of academic research. HHMI is a founder of eLife, an open science journal dedicated to the rapid dissemination of biological research.

“I’ve been really impressed with eLife as a journal. I like reviewing for them and publishing papers with them,” he said.

Bedford’s deep understanding of phylogenetic trees place him at the center of the world scientific community in the scramble — which continues — to understand SARS-CoV-2. In February of 2020, he used the sparse amount of available genetic data on the new virus to conclude it was already spreading rapidly, and largely unnoticed, in Washington state. His timely warning led to a rapid shutdown of the region, likely saving thousands of lives.

As a result, the mild-mannered Bedford became an early popular superhero of the pandemic. Already accustomed to communicating on Twitter, he quickly gained 330,000 followers. He is regularly quoted in leading newspapers eager for clues about new variants of SARS-CoV-2 and the ever-changing trajectory of the virus throughout the world.

Last year, Fortune named the now 39-year-old associate professor to its list of “40 under 40.” In addition, he and Nextstrain — a website he co-developed that posts the phylogenetic trees of SARS-CoV-2 and other global pathogens — last year received a special Webby Award for helping the world understand this new disease.

It is sobering, Bedford said, to realize that this acclaim and the recent HHMI award came as a result of the pandemic.

“I’m honored. I did not think this would be in the cards for me,” he said. “But it’s kind of a strange thing, bittersweet, for this to be on the back of a global tragedy.”

Although there are no strings attached to his HHMI award, Bedford said he will continue to work in the worldwide struggle against the pandemic.

“COVID will be with us for the next forever,” Bedford said. “It is framing a lot of how I’m approaching research at the moment.”

Because there has been an explosion in the number of genomic sequences of SARS-CoV-2 around the world, Bedford said he is eager to collaborate with Matsen as his friend and colleague develops better computational tools to analyze this flood of information effectively.

“Just four years ago, a large data set for an epidemic might have been 2,000 genomes, like with Ebola in West Africa. As of today, I think we have 3.7 million SARS-CoV-2 genomes. So much of what we are able to do with that is limited by the tools and algorithms we have. They definitely are not keeping up with the deluge of data that now exists,” Bedford said.

With more advanced algorithms, he said he is hoping to be able to merge epidemiological data — tracking cases in world populations — with the evolutionary data from the massive genome sequencing that is now underway.

Bedford also believes that the experience dealing with the COVID-19 surge will inform the ongoing work — from his pre-pandemic life — of tracking various strains of influenza and other pathogens, which is vital for choosing vaccines and strategies against these threats.

Dr. Harmit Malik, a Hutch evolutionary biologist now in his second consecutive term as an HHMI Investigator, was delighted that two more colleagues have joined those ranks.

“Through their work on tracing viral evolution in real time, Trevor and his colleagues have revolutionized the field, so much so that it is hard to imagine what the field looked like in the ‘dark ages’ prior to Nextstrain,” he said. “Erick is such a powerhouse mathematician and thinker that I cannot think of anyone else who could have made so many original contributions to so many diverse fields.

“This award is an acknowledgement of their creativity, and it will free them up to be even more unfettered in their science, which can only bode well for those who are lucky enough to work alongside them,” he said.

Besides Bedford and Matsen, the other current HHMI Investigators at Fred Hutch are Drs. Biggins and Malik, evolutionary biologist Dr. Jesse Bloom, and molecular biologist Dr. Steven Henikoff. Nine other Hutch scientists are former HHMI Investigators, including Hutch President and Director Emeritus Dr. Gary Gilliland from 1996-2009.