A few weeks into California’s stay-at-home order in March of last year, Sri Kosuri started thinking. Coronavirus testing was already looking like a mess. He knew that if we were to get the upper hand on the virus, testing needed to be cheap and widespread. Kosuri, a biologist who co-founded the Emeryville-based firm Octant, which uses DNA sequencing to search for new drug targets, wondered if his own technology could detect the virus. So he and a handful of his colleagues went back into the lab and got an answer: Not only could their platform detect the virus, but it could also do so cheaply, and it could process lots of samples at once.
Initially, Kosuri wasn’t sure what to do with that. The testing logjams were a massive, widespread issue, a puzzle that a large logistics company or the federal government should more easily solve than a 12-person biotech startup in California. “It just seemed like someone else was going to solve the problem,” Kosuri says.
But when it became clear there was no coordinated solution coming down from on high, Octant changed its tune. Its coronavirus detection platform, which Octant made open-source, has since been used by UCLA and other institutions. At the end of last year, the company announced it was partnering with the Boston-based Ginkgo Bioworks to open a 22,000-square-foot testing facility in Emeryville.
Octant isn’t alone. The Bay Area — full of world-class brainpower and the nimble, disruptive mindset that comes with startup culture — is home to hundreds of biotech companies. The pandemic has been both an opportunity and a challenge for these firms, a lengthy scramble to rethink existing tools and research, to level up ideas and bring them to the world at scale. As a result of long days in the lab and unexpected collaborations, the region is producing some of the most promising and innovative tools in the ongoing, patchwork fight against COVID-19.
Staying a step ahead of nature
The biotech community’s waking hours are spent thinking about solutions to our most pressing health problems, so it was clear when the virus arrived that companies were poised to make major contributions. It was just a question of how quickly they could offer improvements — and how to sustain them. “This is a marathon,” says Angela Bitting, senior vice president of corporate affairs at the South San Francisco company Twist Bioscience. “It’s a marathon with a lot of sprints interwoven.”
Twist, among other things, makes synthetic RNA, which can be used as a control to verify that a genetic test — like many common COVID tests — is running accurately. In March 2020, the company introduced synthetic controls for COVID tests, and then set about figuring out how else they could contribute. They’ve since rolled out gene panels that help researchers identify and analyze not just the coronavirus, but also a multitude of other viruses — a capability the current pandemic has proved is critical. And they’ve had to stay on top of virus mutations, adjusting their synthetic controls as necessary to make sure they can verify the accuracy of tests as the virus evolves.
“Nature has given us COVID and Zika and the Spanish flu and you name it,” says Bitting. “We need to … make sure that we are staying ahead of that and have tools in place.”
Getting in the game
For Berkeley Lights in Emeryville, the race began while the virus was still largely confined to China. Berkeley Lights focuses on optofluidics, using light to move individual cells in microfluidic chips. This allows them to identify molecules that may be helpful against various diseases — like antibodies that can block the coronavirus protein from binding with its receptor in humans.
In very early February, eight mice in China were infected with the virus, then escorted by police more than 1,200 miles across the country to a lab where the global biosciences company GenScript — using Berkeley Lights’ technology — was able to identify possible antibodies. Once the mice arrived, the process took 24 hours. Traditional methods of antibody screening can take months.
“When COVID-19 became more prevalent, we shifted our priority to help our customers who were actively involved in finding a cure,” notes Anupam Singhal, a senior product manager at Berkeley Lights. The company’s technology has since been used to identify hundreds of potential antibodies.
Because collaborators and suppliers in China are common in the biotech world, companies had an early glimpse of what the entire world would soon look like — but also the chance to act in unexpected ways.
“We were hearing horror stories” more than a year ago, says Rohan Dixit, the founder and CEO of San Francisco’s Lief Therapeutics. His company offers a wearable patch that monitors heart rate variability as a biofeedback tool. Under the FDA’s emergency guidance for mental health during the pandemic, Lief’s patch is being used to treat anxiety disorders that have arrived hand in hand with our current reality.
Early in the pandemic, Dixit was on the phone with a friend who began to cry. A nurse at UCSF, she was scared about going into work; there wasn’t enough protective gear to keep everyone safe. “I had never expected the United States health care system and the people who work every day in it to be experiencing that,” Dixit says. “I just assumed that we would have supply chains that would be there and that would work.”
So in addition to their work on Lief, Dixit and his co-workers began reaching out to their network of suppliers in China, who then connected them with manufacturers who helped locate masks. In April and May, he and his colleagues sent 50,000 medical-grade masks to health care organizations around the country. “We’d work all day on mental health tools and Lief,” recalls Dixit, “and we’d work all night when China was awake on trying to find the right masks. ”
“Tons and tons of late nights,” echoes Trevor Martin of Mammoth Biosciences. Mammoth, which Martin co-founded with, among others, UC Berkeley’s Nobel Prize–winning Jennifer Doudna, is using the gene-editing tool CRISPR to test for the coronavirus. Mammoth’s approach, which uses CRISPR technology to detect and amplify the viral genetic sequence in a patient sample, provides the same accuracy as other nucleic acid tests — the gold standard in testing — but more quickly and with less manpower, says Martin. Diagnosing viruses using CRISPR is a new frontier for a relatively new technology, and COVID has been an important test case. “It’s exciting to bring a technology out of the lab,” he says. “We want to have an impact.”
The future, and the lessons we can learn from the pandemic, are on Martin’s mind. “What if you just stockpiled millions of these decentralized tests that you could easily reprogram in less than a few weeks to go after any new emerging disease? How do you think about surveillance long term?” he poses.
Early on in the pandemic, when he was trying to ensure his COVID test worked, Octant’s Kosuri was on the hunt for a qPCR machine to detect DNA, so he could validate his results against a more traditional testing method. The machines were in short supply, but he finally tracked one down at a local vegan materials company, whose scientists used it in the molecular analysis of new fabrics. It wasn’t how the head of the company thought his equipment would be used, but when Kosuri got in touch, he was more than happy to lend it to the fight. “Everyone was energized to try and help,” says Kosuri.
The local biotech community’s response to the virus has been characterized by a spirit of collaboration and innovation, and researchers hope to apply that ethos to future challenges. “Diseases are a global issue, and therefore we must think globally,” says Berkeley Lights’ Singhal. “It’s our responsibility to work together to fight them.”