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.
I’m not sure why anyone would consider doing work with SARS-CoV-2 at BSL2. If anything, we should consider working with this virus and ALL novel isolates at BSL-4. SARS 1.0 and MERS transmit person-to-person and have threatened global pandemics. SARS 2.0 has caused a global pandemic equivalent to 1918 influenza with unprecedented impacts on the global economy. I’m sure there are many more isolates in bats, pangolins, etc. that could jump into the human population and cause similar morbidity/mortality and social destabilization. I’m an arbovirologist and we routinely work at BSL3 while isolating unknown viruses from the field, and these are blood-borne pathogens with no history of person-to-person transmission. We should treat SARS-like coronaviruses like highly pathogenic avian influenza viruses and work with them at BSL-4. We should set this precedent now or else researchers around the world will start amplifying these types of viruses under relaxed conditions and eventually a laboratory-acquired infection will occur. It only takes one. One laboratory-acquired infection with this type of virus can lead to a global pandemic. Is it worth it? I don’t think so.
BSL-3 is entirely appropriate for growing, manipulating, and/or concentrating SARs-CoV-2, given that we do not know the infectious dose and whether the mode of transmission includes aerosols. Many infections are asymptomatic but still spreadable without symptoms. There is no approved treatment or vaccine at the current time. Making a mistake in the risk assessment at this point could be a real disaster.
The author states as fact: ” 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.” But this is not correct, the assumption is not that there is a HIGH risk, just that this is a risk and social distancing is a way or reducing that risk which will result in a decrease in the number of cases. The prevalence of a disease is not the basis for Risk Group classification, RG is based on the risk that the pathogen poses. Using the author’s criteria that if the organism is prevalent in society it can be worked with at a lower safety level, then in African countries during an Ebola outbreak Ebola, RG-4 virus, could be worked at BSL-2. Utter nonsense. So to is his premise. The major difference between a lab and going to a grocery store or hugging a person is that in the lab the SARS-CoV-2 would be grown up in large amounts, high concentrations which increases risk of exposure to the lab personnel. The lab personnel would then bring that home exposing many more. How many more deaths does the author wish to have? And no, working at BSL-3 does not take twice as long. I am a retired biological safety officer with 35 years of experience.
I totally disagree . The current risk group assignments are properly set and containment resuction spells potential disaster. Right or wrong, look at the finger pointing at China regards to the Wuhan facility.
The author states “The advantage is that BSL-2 research and manufacturing capacity…..” as an impediment to speeding up a cure. Why grow a RG-3 organism in a bioreactor, to generate inactivated vaccine? A vaccine can be made using much safer recombinant technology at BSL-2LS or even BSL-1LS. And provides a purer antigen.
If you have a fantastic candidate, propose it to DARPA. If they agree, I’m certain you move up the list for BSL-3 testing space.
I suggest you vet your portfolio pitches through a qualified biosafety professional before waste peoples money.
The author’s ignorance is pretty clear and his intentions are thinly veiled, its obviously all about the $$ for him, not public safety or the safety of the researchers & integrity of the data. He clearly doesn’t understand risk grouping, why risk groups exist and why oversight of overzealousness in the lab could be a good thing. I would bett $$ that this article is in direct response to him failing to identify BSL-3 requirements as a risk to his p
There will be no “convincing” CDC to relax its recommendation that SARS CoV2 CULTURE should be conducted at BSL3. In the first place, the WHO- designated risk group for the virus is Risk Group 3 (infectious by airborne sources, causes serious or lethal human disease, no vaccine or accepted treatment currently available–pushing the envelope toward Risk Group 4), and it would fly in the face of all that is accepted in biological safety to allow the culture of an RG3 viral agent at BSL2. Further, CDC, like all organizations concerned with health and safety, bases its recommendations on risk assessment, as must any laboratory management protocol, and the risk to the research community is quite different than the risk to the wider public if viral culture is being conducted in less than appropriate facilities. On the other hand, since SARS CoV2 is so contagious and infectious, an inadvertently infected researcher would “vector” the virus right out of the lab and into the public. Besides the obvious risks to public health, such an event, even if just once and very isolated, would without question result in mounds of legislation directed at BSL2 laboratories. CDC recommends BSL3 containment for very good reason–be glad there has been no serious discussion of adding SARS CoV2 to the list of Select Agents.
CDC is not really the one to convince. The American Biosafety Association (ABSA) has even more stringent recommendations, and most academic institutions are following those out of an abundance of precaution…and with the liability argument (if most others follow ABSA, we must too). We should ask the American Society for Microbiology’s Council on Microbial Sciences to study the issue and provide a risk-benefit analysis.
Comments are closed.