Before the coronavirus pandemic, University of Alaska professors Devin Drown and Eric Bortz were studying African Swine Fever, which threatens the global pork supply. Lisa Smith was researching HIV’s effects on the brain. 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 the virus’ genes, which state officials say is essential to keep the virus in check.
Alaska already sequences a large proportion of its positive coronavirus tests compared to other states. But officials said they’re aiming to do even better — particularly after a faulty sequencing machine delayed detection of Alaska’s first case of a more contagious COVID-19 strain located first in Britain.
Now, the state health department has pulled together a group of researchers from Alaska’s public health labs and university system in hopes of speeding up and dramatically expanding the sequencing process.
Within a few weeks, Officials want to be testing around 20% of Alaska’s positives cases, a rate far exceeding the level of surveillance even by world leaders such as Britain, which has analyzed about 6% of 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 sequencing infrastructure, Butler said in an interview. It has a centralized public health infrastructure in Gov. Mike Dunleavy’s administration and it 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 response 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.
The strain known as B.1.1.7, originally found in Britain, could be 50% more contagious. The CDC projects 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 appears to be able to evade at least one vaccine, scientists say.
The state has found just one case of the variants so far: A traveler infected with the B.1.1.7 strain who followed isolation guidelines and likely did not spread it to others, officials said. But those officials also said 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,” state epidemiologist Dr. Joe McLaughlin 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 map each individual piece of the virus’ genetic code, which contains some 30,000 pieces.
First, a person has to register positive on a standard COVID-19 test before their samples are packed in dry ice and shipped to the state virology lab in Fairbanks.
Not every sample can be sequenced, however. Certain types of tests use up the entire sample to identify positive COVID-19 cases, 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 for a representative view of distinct strains spreading in different areas, Parker said. The state also wants to sequence COVID-19 cases from travelers. 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 for tracking variants as they enter Alaska. But they also note that the technology can be used to retroactively trace how the coronavirus spreads 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 stem from homegrown strains of the virus, or ones brought from Outside.
“The run is failing”
At the beginning of the pandemic, Lisa Smith, the former HIV researcher, was finishing her doctorate at University of Alaska Fairbanks 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 COVID-19 for much of 2020. But the rise of new, more contagious variants has made the work more urgent, and an incident in December prompted a new push to expand their sequencing bandwidth.
That month, workers at the Fairbanks lab were aiming to sequence about 300 samples they suspected could be strain B.1.1.7.
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 at that point, the swab was already weeks old.
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 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 professors Drown and Bortz running university labs in Fairbanks and Anchorage.
Rather than sequencing solely in the Fairbanks virology lab, the state aims to expand bandwidth by 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 — scientists there use a different machine that can handle fewer samples, but generate data faster.
In a few weeks, once the system is in place, Parker said she expects to sequence more than 300 samples a week, up from the roughly 100 that are being processed now. Though it could be difficult to secure that many positive samples, she added.
“I want to get decent visibility on what’s circulating. 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 UAA lab was bustling with students, some of whom have shifted their work to COVID-19 over the past year.
Among the researchers was George, who was already studying bat coronaviruses before COVID-19 hit.
On Monday, he was manipulating samples of SARS-CoV-2, the virus that causes COVID-19, testing a new way to identify concerning strains. The idea is to sequence specific areas of the virus’ genetic code, rather than the whole thing, George said.
If the new protocol works, it could allow for quicker detection of variants. It could also cope with lower-quality samples that couldn’t be use for sequencing before.
While it was hard to interest friends in harmless bat coronaviruses, George said it’s been exhilarating to shift his focus to a global public health crisis.
“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, university researchers also want to develop methods allowing work to be done in remote locations, such as rural villages or hub communities. That could speed up the identification of coronavirus strains: Currently, samples have to be shipped to the virology lab in Fairbanks before they can be sequenced.
Drown, the Fairbanks professor, argues the universities’ labs’ contributions to coronavirus sequencing underscores the value of investing in academic research in Alaska — even as state lawmakers have slashed the university system’s budget in recent years. He also stressed the importance of grant funding from the National Institutes of Health, through a program called Alaska INBRE.
“Being able to transfer our skills quickly to this pandemic is what the university is for,” Drown said. “We were ready to do it.”