Not long after SARS-CoV-2 was first identified in December 2019 as the cause of an alarming cluster of severe pneumonia cases in central China, the U.S. Centers for Disease Control and Prevention correctly advised that the virus should be isolated and studied only in laboratories with advanced containment capabilities, meaning those with a biosafety level (BSL) of 3 or higher.
Things have changed radically since then. In huge swaths of the country, Americans are being instructed to shelter in place under the assumption that any human contact carries a high risk of transmitting the virus.
This is why the CDC’s current guidance that the SARS-CoV-2 virus be cultured only in BSL-3 facilities no longer makes sense, given that it is already spreading in our communities. A trip to the grocery store now poses a much greater risk of SARS-CoV-2 infection than conducting vaccine research at a well-managed BSL-2 facility, where virus-handling occurs in a negative-pressure HEPA-filtered biosafety cabinet using a full complement of personal protective equipment. While the precautions in a BSL-2 facility aren’t, by definition, as extensive as BSL-3 precautions, BSL-2 facilities still use highly effective, institutionally engrained, federally regulated safeguards to avoid laboratory-acquired infections or accidental release of a pathogen into the environment.
The advantage is that BSL-2 research and manufacturing capacity is available in abundance compared to BSL-3 and BSL-4 facilities.
Despite the best initial intentions, we are now at a point where the BSL-3 restrictions are counterproductive, presenting a meaningful hurdle to Covid-19 research. If the general population operates under the expectation that the virus is already omnipresent, we need to unshackle the best and brightest research institutions — including those without BSL-3 facilities — to find new solutions for stopping the pandemic.
The way to do that is to reduce limitations on which labs can culture SARS-CoV-2, which means allowing BSL-2 labs to do this. Culturing the virus and conducting animal testing are essential initial steps on the path to human clinical trials for many promising drug, vaccine, and diagnostic candidates.
My firm, Adjuvant Capital, is witnessing firsthand the extent to which the BSL-3 restriction is impeding research on promising Covid-19 solutions. Three of our portfolio companies are working around the clock on Covid-19 interventions, but all have been stymied by access to BSL-3 labs in recent weeks. The cost and availability of these labs have been the single biggest bottleneck in researching and testing critical vaccine and diagnostic technologies. While the more than 200 BSL-3 labs may seem sufficient on paper, the actual number of suites that can be rented by third-party researchers is extremely limited. Not surprisingly, these suites are in high demand and thus very difficult to access.
The U.S. National Institute of Allergy and Infectious Diseases (NIAID) recognizes this issue, noting that many “U.S. institutions and companies with infectious disease research programs have BSL-3 laboratory suites required to perform their research. Most such laboratories, however, are small, dedicated to particular uses, or in need of modernization.” Complicating matters further, there is no reliable directory of BSL-3 facilities, let alone resources to quickly screen near-term availability and cost for third-party use.
Perhaps Silicon Valley will take notice of this opportunity for innovation in the future, but right now most researchers rely on old-fashioned professional networks and trial-and-error outreach to find the resources they need.
BSL-3 access isn’t the only headwind to innovation under current biocontainment guidelines. As Melanie Ott, a virologist at the Gladstone Institutes in San Francisco, noted in a recent STAT Q&A, research in BSL-3 labs is also more cumbersome. “Everything takes double the time in a laboratory like this. And every time you go in there, you have to write a protocol and get it approved.”
The simple solution to this bottleneck is for the CDC to immediately issue new guidance allowing workers to culture SARS-CoV-2 virus in BSL-2 facilities. Doing that would dramatically expand access to the lab space necessary for developing vaccine candidates and conducting animal testing and lower the barrier to entry for doing so. That would open the floodgates of innovation.
Adjuvant has been tracking Covid-19 solutions from the earliest days of the outbreak. In our view, there are three fundamental ways to blunt the damage of pandemics like SARS-CoV-2:
- Preparedness and containment: that ship has sailed
- Brute force: social distancing/shelter in place, at enormous cost to the global economy
- Innovation: diagnostics, treatments, and vaccines, to control the disease
Brute force, our current best hope, will help prevent a public health calamity and save many lives, but comes with enormous and sustained damage to the economy for as long as it is maintained. Innovation is our only hope if we want to neutralize this threat and avoid a protracted economic disaster.
The U.S. needs to remove impediments to innovation and make vaccine research as easy as possible until the community spread of SARS-CoV-2 has been suppressed. Reducing unnecessary restrictions on handling a virus that is already widely circulating is an immediate, free, high-impact way to unleash America’s innovators to tackle this challenge. Reducing the biosafety level for working with SARS-CoV-2 should not be a controversial decision in light of the current crisis.
The benefit of reducing biosafety thresholds should always be carefully balanced against the safety of the researchers and the surrounding communities. But given the magnitude of the current Covid-19 crisis and the prevalence of SARS-CoV-2 in our communities, I suspect that lab leaders and technicians at all BSL levels are likely eager to contribute to the solution — if permitted to do so.
Glenn Rockman is the founder and managing partner of Adjuvant Capital. Several companies in the Adjuvant investment portfolio could benefit from implementing the primary recommendation in this article.