Before the coronavirus pandemic, University of Alaska professors Devin Drown and Eric Bortz were studying African Swine Fever, a threat to the global supply of pork.
Lisa Smith was researching HIV’s effects on the brain. And Will George was studying coronaviruses in Alaska bats.
Now, all four are part of Alaska’s quickly intensifying hunt for new, more contagious variants of the coronavirus — the painstaking process of sequencing that state officials say is essential to keeping the virus in check.
Alaska already sequences a large proportion of its positive coronavirus tests compared to other states. But officials say they’re aiming to do even better, particularly after they ran into problems with a faulty sequencing machine a few weeks ago that delayed detection of Alaska’s first case of a more-contagious strain of the coronavirus originally found in Britain.
Now, the state health department has pulled together a group of researchers from Alaska’s public health labs and its university system in hopes of speeding up the process and expanding it dramatically.
Officials want to be sequencing some 20% of Alaska’s positives within a few weeks. That rate would far exceed the level of surveillance even by world leaders like Britain, which has analyzed some 6% of its cases.
“Among the state health departments, Alaska is definitely one of the leaders of the pack,” said Dr. Jay Butler, a former Alaska chief medical officer who’s now deputy director for infectious diseases at the CDC.
Alaska has several advantages over other states in its push to boost its sequencing infrastructure, Butler said in an interview. It has a centralized public health infrastructure in Gov. Mike Dunleavy’s administration; it also has a relatively small population, making it easier to sequence a larger proportion of its positive tests.
Then, Butler added, there’s the potential for “cross-fertilization” between the state’s public health efforts and Alaska’s university system.
A complex process
Butler’s agency has issued sharp warnings about the new coronavirus strains, which arise from naturally-occurring mutations in its genetic code.
One of the strains known as B.1.1.7, originally found in Britain, could be 50% more contagious, and the CDC projects that it will be responsible for most new cases of COVID-19 in the U.S. by March. Another variant originally found in South Africa is also more contagious and, scientists say, appears to be able to evade at least one vaccine.
The state has found just one case of these variants so far, in a traveler infected with the B.1.1.7 strain who officials say followed isolation guidelines and likely did not spread it to others. But those officials also say they expect more cases soon, given the strains’ rapid spread outside Alaska.
“Alaska is doing very well, compared to other states. But it’s very important that we don’t let our guard down, especially as we start to see these new variants emerge,” Dr. Joe McLaughlin, the state epidemiologist, said at a news conference last week.
Sequencing individual strains is more complicated than testing for the existence of the coronavirus itself. The process requires researchers to document each individual piece of the virus’ genetic code, which contains some 30,000 pieces.
First, Alaskans must be identified as carrying the virus through a standard COVID-19 test, with positive tests shipped to the state virology lab in Fairbanks on dry ice.
Not every positive sample can be sequenced, though. Certain types of tests use up the entire sample to identify a person as positive for COVID-19, leaving none left to sequence. Others are processed at out-of-state labs.
“Sequencing has become more of a detective game, where I have to search out specimens and figure out where they are in the world, and how to get them back to the lab,” said Jayme Parker, a top state lab official.
The state is trying to sequence positive tests from across Alaska, which Parker said is aimed at providing a representative view of the different strains of virus spreading in different areas. The state also wants to sequence COVID-19 cases from travelers, and a new Anchorage commercial lab, Beechtree Molecular, is providing the state with samples collected at Alaska’s major airports.
Other samples prioritized for sequencing are COVID-19 cases from coronavirus outbreaks or clusters and those in vaccinated people, Parker said.
Experts say sequencing capacity is critical in allowing the state to track variants as they enter Alaska. But they also note that the technology can be used to retroactively trace how the coronavirus is spreading around the state.
In Britain, scientists used sequencing to trace a cluster of cases of the same strain to a dialysis clinic. And university researchers in Alaska have analyzed sequencing data to examine whether the state’s COVID-19 surges stemmed from homegrown strains of the virus, or ones brought from Outside.
‘The run is failing’
Lisa Smith, the former HIV researcher, was finishing her doctorate at University of Alaska Fairbanks at the start of the pandemic when she got pulled into working at the virology lab. She’s now leading the state’s sequencing program.
Scientists at the virology lab have been sequencing strains of the coronavirus for much of the past year. But the rise of the new, more contagious variants has made the work more urgent, and an incident in December prompted state officials to make a new push to expand their sequencing bandwidth.
That month, workers at the Fairbanks lab were trying to sequence about 300 samples that they suspected could be the B.1.1.7 strain.
But as they prepared to sequence one of their last batches, they encountered a cascade of failures, including a broken machine. Ultimately, one of the samples popped up as a hit for B.1.1.7 — but by that point, it was weeks after the swab was collected.
University researchers could have picked up the slack while the state’s machine was offline. But the state didn’t have a formal system to transfer the specimens, Parker said.
“People were saying, ‘The run is failing,’ and I kept seeing these emails,” Parker said. “I started looking at what we were really dealing with and felt like this was the moment I needed to get everyone together and make sure that we have a consolidated plan.”
Now, the state’s public health labs have formed what Parker calls a sequencing “consortium” with university labs in Fairbanks and Anchorage run by the two professors, Drown and Bortz.
Rather than sequencing solely at the Fairbanks virology lab, the state aims to expand its bandwidth by also sending samples to Drown’s lab at University of Alaska Fairbanks, and to Anchorage’s state-run public health lab.
The state will look to Bortz’s lab, at University of Alaska Anchorage, when it needs sequencing results urgently, since scientists there use a different machine that can handle fewer samples but generates data more quickly.
Once the system is in place within a few weeks, Parker said she expects to be able to sequence more than 300 samples weekly, up from the roughly 100 that are being processed now — though she added that it could be difficult to secure that many positive samples.
“I want to get decent visibility on what’s circulating,” Parker said. “I don’t want to over-sequence, to the point where we’re just sequencing the same viruses over and over again.”
“We were ready”
On Monday, Bortz’s lab at UAA was bustling with students, some of whom have shifted their work to COVID-19 in the past year.
Among the researchers was George, who was previously studying bat coronaviruses.
On Monday, he was manipulating samples of SARS-CoV-2, the virus that causes COVID-19, to test a new protocol for identifying concerning strains. The idea is to sequence specific areas of the virus’ genetic code, rather than the whole thing, George said.
If the protocol works, it could allow for quicker detection of the strains, along with analysis of lower-quality samples that otherwise wouldn’t be adequate for sequencing.
While it was hard to interest friends in harmless bat coronaviruses, it’s been exhilarating to shift his focus to a global public health crisis, George said.
“It’s kind of cool to see things come to life, and to see people actually care about your research,” he said.
In addition to studying new sequencing protocols, the university researchers also want to develop methods that would allow the work to be done in remote locations, like rural villages or hub communities. That could speed up the identification of coronavirus strains, since currently samples have to be shipped to the virology lab in Fairbanks before they can be sequenced.
Drown, the Fairbanks professor, argues that the university labs’ contributions to coronavirus sequencing underscores the value of investing in academic research in the state — even as Alaska lawmakers have sharply reduced the university system’s budget in recent years.
“Being able to transfer our skills quickly to this pandemic is what the university is for,” he said. “We were ready to do it.”