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March 30, 2020 – As doctors around the country scramble to diagnose cases of COVID-19, scientists at the University of California, Berkeley’s Innovative Genomics Institute (IGI) are creating from scratch a diagnostic lab with the capability to process more than 1,000 patient samples per day.
This pop-up laboratory, the effort of a unique volunteer team of academic and corporate partners, will provide desperately needed testing capacity in the Bay Area for those with COVID-19 symptoms and also help public health officials assess how widespread the epidemic is.
“The UC Berkeley team is racing to address this critical public health situation by establishing a testing lab that will be immediately impactful in our community, while also generating data that contributes to understanding the spread of the SARS-CoV-2 virus,” said Jennifer Doudna, professor of molecular and cell biology and of chemistry and IGI executive director. SARS-CoV-2 is the coronavirus that causes COVID-19.
Thanks to the emergency modification of state and federal regulations and California’s declared state of emergency, the IGI was able to partner with clinicians at University Health Services, UC Berkeley’s student health center, and both local and national companies to bring in the robotic and analytical equipment needed, establish a safe and robust pipeline for clinical sample intake and processing, obtain the required regulatory approvals and train a crew of highly skilled scientists accustomed to conducting fundamental research to analyze patient swabs with a quick-turnaround goal of less than 24 hours.
The scientists — more than 50 volunteers from UC Berkeley, UC San Francisco and local data management companies — plan to test their first actual viral samples early this week and aim for certification under the Clinical Laboratory Improvement Amendments (CLIA) program by next week.
While the testing lab will focus initially on samples from students and other members of the UC Berkeley community, the team is already coordinating with medical centers around the East Bay to eventually offer rapid turnaround to also meet their diagnostic needs.
“We mobilized a team of talented academic scientists, partnered with experts from companies and pulled together, in a matter of a few days, a group that is operating like a biotech company. It is really a remarkable story,” said Doudna, who is also a Howard Hughes Medical Institute investigator.
The lab will run testing based on a process approved by the Food and Drug Administration, but with higher throughput than many commercial labs, some of which still must run samples manually, one at a time. The high-throughput machines, some sourced from campus research labs, can test more than 300 samples at once and provide the diagnostic result in less than four hours from receipt of patient swabs. Using robotics and a streamlined process, the IGI pop-up lab will soon perform 1,000 tests daily, with the ability to ramp up to 3,000 tests per day if necessary.
“We are implementing an existing test in a way that leverages robotics and rapid turnaround times so that we can deliver results quickly to medical centers around the East Bay and provide a critical service to our community in this time of need,” Doudna said.
“This is just an amazing opportunity,” said Guy Nicolette, UC Berkeley’s assistant vice chancellor for University Health Services. “I am amazed at how quickly Berkeley was able to mobilize and to take advantage of the newer rules in order to innovate more quickly. The lab side of things has been so reliant on human manual work that this would be a game changer in a lot of ways.”
Given limitations on the number of test kits available in California and evolving guidelines on who should be tested, medical staff at UHS’s Tang Center have to date sent out only a couple of dozen swabs from students for testing by local commercial labs. One was returned as positive for the SARS-CoV-2 virus that causes COVID-19. But according to Nicolette, turnaround in the Bay Area has varied widely and can exceed a week, leaving symptomatic patients and clinicians unsure of their status, often creating anxiety.
He is optimistic that the on-campus diagnostic lab will allow much wider testing that will provide a better picture of how prevalent the virus is, given that many people suffer mild or no symptoms, yet can be contagious. Large-scale testing has been key to the ability of other countries to control the spread of disease by identifying infected individuals, he said.
“There are other aspects of broader testing that would be so clinically powerful,” he said. “We could make better decisions about health, about work, about possibly how long we need to continue to socially distance, based on what we find.”
The power of automation and robotics
The IGI’s scientific director for technology and translation, Fyodor Urnov, played a major role in mobilizing resources — equipment, people and money — after a March 13 meeting of 59 people within the institute. The basic technique needed to test for a virus — isolating RNA from a sample and amplifying it using the polymerase chain reaction (PCR) — is routine in dozens of labs at most universities. The key, Urnov said, was to quickly figure out how to scale and automate the process for clinical use.
UC Berkeley labs possessing high-throughput PCR machines donated their equipment to the cause, while IGI established robotic sample handling as well as secure data management.
“We threw our R&D (research and development) mindset into understanding how we can scale it up and accelerate it, because we understood this fundamental need of the medical community,” said Urnov, a professor of molecular and cell biology who spent 15 years in the biotech industry before coming to UC Berkeley. “Who we are as scientists really connected to an unmet need.”
Clinical testing of patient samples is highly regulated, requiring CLIA certification not only of lab scientists, but of the actual laboratory space, equipment and quality control procedures. While the Tang Center has two CLIA-certified lab scientists, the center does not have a Biosafety Level 2 (BSL2) lab required for testing viruses like SARS-CoV-2.
Thanks to the new regulations, however, the Tang Center’s certification is being extended to the BSL2 lab in the IGI, and the scientists who volunteered to do the testing are now taking an accelerated training program to be able to operate the equipment 24/7, if necessary.
Aside from fast turnaround, Urnov said, the main focus is accuracy, something that dogged the Centers for Disease Control and Prevention’s original test kits and delayed widespread testing for a critical month at the beginning of the epidemic in the United States.
“We have controls for our controls,” he said. ”A lot of work has gone into ensuring that we are accurate when we tell clinicians whether their patient is positive or negative.”
As Urnov and his team ramp up diagnostics, other researchers at UC Berkeley have broken into about a dozen “rapid research response teams” to focus on other COVID-related research projects, including possible improved diagnostics, new drugs to treat the infection and ways to deliver drugs to patients.
“We are talking about a group of more than 100 people who are actively participating in research projects, including people from UCSF, Stanford and the Gladstone Institutes,” Doudna said. “These longer-term projects address the ongoing need to understand this family of viruses and to prepare for future outbreaks now.”