When chemist Carolyn Bertozzi came to Stanford in 2015, she needed to construct a specialized research space to carry out her work with the bacteria that causes tuberculosis. Because it is both infectious and airborne, it requires what is known as biosafety level 3, or BSL3, containment.

A portion of a lab was converted into Biosafety level 3 space in 2016. The contained area is safe for working with airborne pathogens such as the tuberculosis bacteria or SARS-CoV-2, the virus that causes COVID-19. (Image credit: Meridee Mannino)

Then the COVID-19 pandemic hit, and suddenly her cramped, four-person space became a hot commodity. In response, Bertozzi and a team of researchers are looking to expand the existing facility in the Keck Science Building to accommodate researchers who are pivoting to help fight COVID-19. The construction should take about six months.

“Not only is there an explosive interest in this virus but we need BSL3 space to manage patient testing and move toward ways to treat and monitor patients,” said Bertozzi, who is also the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences. “It is a bottleneck in our ability to understand what makes this virus tick, diagnose people and understand why some people have a more critical response to an infection.”

Testing patient samples for infection can happen outside a BSL3 facility, as can any research that doesn’t involve growing and manipulating live virus. But researchers hoping to develop and test therapies or vaccines need to be able to determine how those treatments affect the virus’ ability to infect cells, and they need to be able to do it within an environment that protects them from infection and contains the virus within the laboratory facility.

“A lot of people are wanting to study COVID-19 and we’re spinning up that capacity as fast as we can,” said Kathryn Moler, Vice Provost and Dean of Research. She said the shared research spaces and structures already in place to support collaboration on campus have been critical to that effort. “The BSL3 facility is a perfect example of how shared spaces can support faculty coming together around a common problem.”

Bertozzi, who is also co-director of Stanford ChEM-H, said the expansion is not only necessary to respond to the COVID-19 pandemic now, it will continue to be needed for tackling new infections as they arise.

“Stanford is a world-class biomedical research institution with both adult and children’s hospitals and we need to be positioned to take a leadership role in tackling urgent emerging problems,” she said. “To do that, we need to have this capacity ready to go.”

Pivoting to COVID-19

Catherine Blish, associate professor of medicine, had been using Bertozzi’s BSL3 space for her own tuberculosis research, but has quickly pivoted her lab to begin studying SARS-CoV-2 (the virus that causes COVID-19).

Blish said training new people to work in a BSL3 environment can take months, but in the interim, she has lab members who can take advantage of what space is available and begin training others. She added that another challenge is scheduling time in the small room.

“We will do everything we can to maximize that space, and we can do a lot of important work, but it’s inadequate for the scope of the work we want and need to do,” Blish said.

Blish is involved in testing whether existing antiviral drugs are effective in treating COVID-19 and is studying SARS-CoV-2 in cells in a lab dish to understand how the virus attaches to cells, invades, divides and ultimately breaks them open and escapes to invade other cells.

“The important thing to understand is that there remains a lot of uncertainty,” Blish said. And until researchers understand the biology of this virus they can’t develop and ultimately test new therapies. Nor can they know whether reports of existing drugs being effective against COVID-19 are true.

“I would caution people against jumping to conclusions about existing drugs without thoroughly evaluating the data,” Blish said.

Emerging infections

The current BSL3 space is part of the Innovative Medicines Accelerator (IMA), which arose out of the Long-Range Vision to speed the pace of new therapeutics. Chaitan Khosla, who leads the IMA and is the Baker Family Co-Director of Stanford ChEM-H, said expanding the space is “arguably the most critical research need for combating this insidious virus.”

The IMA is currently being incubated within Stanford ChEM-H, which supports research at the intersection of medicine, chemistry and engineering targeted at human health. The BSL3 facility is key for the two main priorities of the IMA: prototyping new drugs, like the ones to combat COVID-19, and groundbreaking experimental studies in human biology. In the case of COVID-19, that could mean studying the immune response of people who have COVID-19 in order to understand – and ultimately interrupt – the disease progression.

Kathryn Nobrega, director of research safety within Stanford’s Environmental, Health and Safety department, added that the diverse teams across campus coming together to study COVID-19 include people who may be new to the BSL3 environment, and who need additional training and support.

“As the Stanford community is pivoting toward more COVID-19 research, everyone has something they can bring to the table,” Nobrega said. “Like many problems that Stanford is used to solving, the interdisciplinary approach is critical.”

To better coordinate the efforts, Stanford has formed a review panel to evaluate and prioritize proposals for COVID-19 research, and to ensure appropriate safety precautions both for the scientists and the public. Nobrega said the review panel is considering dozens of new projects tackling COVID-19, and some of those can be done in collaboration with new COVID-19 research in the existing facility before the BSL3 lab expansion is completed.

“This is a fast-moving train,” Nobrega said. For now, that train will help Stanford researchers tackle COVID-19, but it will also set them up to be responsive to future urgent needs.