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Here's Why Biolabs Could Spark Next Outbreak: Top Molecular Biologist

Richard H. Ebright, a professor of chemistry and chemical biology at the Waksman Institute of Microbiology at Rutgers University, discusses the COVID crisis and lax laboratory regulations -- and how to fix them.
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About 44 years ago a curious H1N1 influenza epidemic began in China and the area of the former Soviet Union. Dubbed the “Russian flu,” the respiratory virus was in some ways like the opposite of the current COVID-19 pandemic. It was mostly mild – less deadly than even the typical winter influenza – and it, bizarrely, spared older people. In fact, it mostly struck people age 26 and younger.

Perhaps most odd, the strain of the virus spreading was not at all new.

It appeared, in fact, old -- decades old -- and it closely matched an H1N1 influenza strain of the 1950s that had since seemed to have disappeared.

Fast forward to 2019 to an outbreak of brucellosis in China. Thousands were sickened by the bacterial infection, just before the COVID-19 pandemic erupted and dominated the news.

As different as these two incidents appear, there’s one striking similarity: Neither is believed to have been caused by nature. The Chinese outbreak was traced to a vaccine facility accident, in which waste gas containing bacteria aerosols was released, according to news reports. The 1977 “Russian” flu epidemic is largely believed to have come from a lab, too, though the matter is still of some controversy.

To be clear, nature is the source of the overwhelming majority of disease outbreaks. But the incidents show that work with biological agents can result in outbreaks, too, if a chain of mishaps leads to disaster.

“Laboratory work with a highly transmissible pathogen can trigger a pandemic,” says Richard H. Ebright, a professor of chemistry and chemical biology at the Waksman Institute of Microbiology at the Rutgers University. “What’s most concerning is laboratory work that deliberately seeks to increase a pathogen's transmissibility, through the aerosol routes. This is work that is being performed in the U.S. and elsewhere.”

This might seem like science fiction, but it’s not. 

Aside from a small group of scientists, activists, policy makers and health officials, most people have little idea of research that goes on both near and far from where they live. Viruses and bacteria that would otherwise never be found naturally in, say, Boston or Galveston, Texas, or even Wuhan, China, often do exist in academic laboratories in the U.S., China, Europe, Japan and elsewhere.

Some of these viruses are only really a risk to those handling them, while others could harm nearby people or even populations if they were somehow released, by accident or malice. Some of these labs are even carrying out experiments – so-called “gain of function experiments” – that could make germs that now pose little risk to humans into highly efficient ones that could rapidly sicken millions, says Ebright. U.S. funding for the research was ostensibly put on hold in 2014 but in 2017 was again allowed to proceed.

Pathogens that pose the most risk to people are typically studied in what are called biosafety level 4 labs – those with scientists wearing virtual spacesuits. But other potentially harmful bugs are in far more lax labs. Prior to the SAR-CoV-2 pandemic, for example, the vast majority of bat SARS-related coronaviruses were studied in only biosafety level 2 labs, says Ebright. These are about as secure as the typical dentist's office.

And accidents happen with alarming frequency. A lab worker may get bitten by a mouse infected with SARS-CoV-2, a researcher may get pricked with a needle tainted with Ebola, or a worker might become ill with SARS. Each year, at the most secure lab facilities in the U.S. alone, some of the most dangerous pathogens and toxins go missing and many more are inadvertently released. In just the year 2019, U.S. federal agencies received 219 reports of release and 13 reports of loss of agents on the biological select agents and toxins list of pathogens and toxins. This list, known as BSAT for short, includes Ebola, the original SARS virus, Lassa fever virus and strains of the bacterium that can cause anthrax disease.

“That gives a window into how frequently these (types of accidents) are in the U.S., in the most highly regulated, the most highly monitored – maybe the only regulated and only monitored – components of pathogen research in the U.S.,” says Ebright.

While none of the reported accidents in the U.S. in 2019 resulted any risk to anyone outside the labs and no one died, there have been lab-related illnesses and deaths of researchers in the past here and abroad. And, as the disasters with the Russian flu and the Chinese bacterial outbreak show, accidents can have real consequences if protocol and luck fail to stop them.

“There are regulations with force of law for biosecurity – for example protections against deliberate release or theft – but those cover only the small subset of bioweapons-relevant pathogens and toxins on the select (BSAT) agents list,” says Ebright. “There is a policy for risk-benefits assessment for a subset of gain-of-function research of concern … but it covers only a small set of activities and, more importantly, it exists only on paper and not in practice.”

Ebright has been for much of the past year among a loose group of scientists demanding that the probe into the current SARS-CoV-2 outbreak take into account the possibility of a laboratory or field research mishap -- an idea rejected by some other prominent scientists. If it were the cause, he says, it would not necessarily singularly point the finger at China, but at a global cadre of funding and collaborating nations, such as the U.S. and France. It would also highlight the need for better regulation, tighter policy and greater awareness of what goes on labs in the U.S. and abroad.

Here, as part of an occasional series on ways to prevent the next pandemic, we discuss the COVID-19 crisis, the dangers of current research, and how America can lead the way to safety – if it has the will to do so.

The following interview was conducted by phone early last week with several follow-up emails throughout the weekend. It has been edited for clarity and brevity.

TheStreet: I asked you in February of 2020 about whether you thought it was possible this COVID-19 pandemic was all started by lab accident or through nature – through close contact with a wild animal – and basically you said that either was possible. Has your view changed at all since then?

Ebright: Not at all. The striking thing is how little has changed – you contacted me in the first or second week of February 2020 – and there really are almost no new developments.

The one set of new developments concerns the location and the circumstances under which the published virus with the sequence closest to SARS-CoV-2 was originally isolated. We’re talking about RaTG13, which, if you remember from our discussions over a year ago, was the virus with the genome sequence 96.2% identical to SARS-CoV-2. In March to May of 2020 it became clear that RaTG13 had been sampled in a mine in Yunnan Province, China, in which the year before multiple miners had contracted and died from SARS-like pneumonia. Partial sequences of the virus had been previously published by the Wuhan Institute of Virology lab. The description of the origin of the virus in the Wuhan lab’s January paper reporting its sequence, had material omissions and material misstatements....

That set of facts only became available starting in March of 2020 ... But everything else already was in place by the second week of February 2020. So, it’s quite remarkable to see how the narrative has changed, despite the underlying facts, which were essentially unchanged.

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And, if you remember, I said the facts were consistent with two possible origins: A natural-spillover origin, in which an infected animal contacts a member of the general public, or a research-related origin, in which an infected animal or an infectious sample contacts a researcher doing field collection or laboratory work. That … is still true today. There is no scientific or secure data that would allow you to choose between those two possibilities. There definitely is no secure or scientific data that rules out either.

TheStreet: Just to be clear, it still doesn’t seem plausible or likely that it was some sort of genetically engineered virus….

Ebright: Already by the third week of January 2020, it was clear to anyone looking at the sequence of the virus genome that the sequence showed no signatures of purposeful human manipulation. But any informed person also understood that there are ways to enhance pandemic potential that do not leave signatures, and that the sequence of the virus genome did not allow a definitive conclusion as to whether the virus was genetically modified. That remains true to this day.

TheStreet: Now, carrying this back to the U.S. Should we be concerned about the dramatic increase in capacity at high level biolabs – biosafety level 4 labs – here since the terror attacks of 2001?

Ebright: Definitely discussion needs to turn to biosafety and biosecurity, and the essentially complete absence of biosafety regulations in the U.S. and elsewhere. Biosafety level 4 laboratories, ironically, are not the main flash point and needn’t be the main flash point. The work in Wuhan, that potentially could be linked to the origin of COVID, all was performed at biosafety levels less than biosafety level 4. So the Wuhan Institute of Virology operated a biosafety level 4 facility, but almost all the work on bat SARS-related coronaviruses, was performed at biosafety level 2.

There is an urgent need for public and policy makers to acquaint themselves with how inadequate biosafety and biosecurity standards are, and how even more inadequate ... basically biosafety and biosecurity regulation is, and not just in China, but worldwide. Those standards that allowed bat SARS-related coronaviruses to be studied at biosafety level 2. Exactly the same biosafety level assignments were in place in the U.S. and the European Union.

TheStreet: So, is the risk here that of accidents or is its improper designation of what pathogen should be studied at what safety level or both?

Ebright: Just for some context here: The biosafety level assignments are just recommendations. They do not have the force of law in any country – not in the U.S., EU, or China. So, the assignments are recommendations and the assignments tend to be shockingly lax.

Although SARS-CoV-2 is now assigned to biosafety level 3, prior to 2020, no bat SARS-related coronavirus – except for the original SARS coronavirus and the MERS coronavirus – was assigned as biosafety level 3. All were assigned as biosafety level 2. Remember, that’s just a guideline. Biosafety level 2 is the level that every U.S. dental office operates at and which most U.S. physician's offices operate at. It means there’s a lock on the door, there’s a screen on the window, there are white laboratory coats, and there’s a device to sterilize infectious waste. That was not a biosafety standard that could be used safely for a virus with the transmission properties of SARS-CoV-2. But that’s the level that was used for both the bat SARS-related coronavirus surveillance projects in Wuhan and the bat SARS-related gain of function projects in Wuhan.

So, if at any point they encountered a virus that had the transmission properties of SARS-CoV-2 or very much like that, the probability of an infection of a lab worker would have been high. Biosafety level 2 is not suitable for a pathogen that is transmitted through an aerosol route or through respiratory droplets. Biosafety level 3 is better, but there will be accidents. Biosafety level 4 is more suitable still, but it is so restrictive of operations that few want to work at that level.

TheStreet: Because you have to wear the “space suits”…

Ebright: That’s the one where people have to have an independent air supply and the space suits…

TheStreet: Well, everything is a risk vs. benefit, right?

Ebright: The crucial part is that that risk benefit assessment doesn’t occur. It doesn’t occur in the U.S., in the EU, or in China. When research is proposed for funding, national-level risk-benefit assessment is not part of the standard review process. The only circumstance in which national-level risk-benefit is required is for the very small subset of research that both, one, involves a potential pandemic pathogen and, two, can be reasonably anticipated to increase transmissibility or pathogenicity. For that small subset of activities, U.S. government policy since 2017 has included a requirement to perform risk-benefit assessment. Unfortunately, that requirement almost never has been followed, because funding agencies have concluded that it’s easier simply to ignore the policy. Only two projects, out of the dozens of projects that were covered by the policy, received national-level risk-benefit assessment since the policy went into effect in 2017. The Wuhan project, which clearly was covered by the policy, never underwent a national-level risk-benefit assessment

TheStreet: How can this risk be minimized?

Ebright: It’s very simple. It requires engagement by the public and by policy makers. This has not occurred in the past, but now, in the wake of the COVID-19 pandemic, is much more likely occur, because now, people understand what a pandemic means for their families and their livelihoods. We have a massive vulnerability to future pandemic emergence coming from the lax biosafety and biosecurity risk assessment standards that are in place. We need to address that. I think now there will be engagement from the public and policymakers that could make that happen.

Most scientists who are even aware of the discussion are doing the work and want to continue doing the work. So, self-regulation is self-defeating. But now this is a discussion that has broadened beyond the scientists doing the work.

TheStreet: What specifically can the U.S. do to address the global problem of lax regulation around this research?

Ebright: The U.S. really set the theme for this.... The gain-of-function research has at all times been funded primarily by the U.S. – not just of the gain-of-function research in the U.S., but the gain-of-function research in almost all other countries, just like the Wuhan research. ... So, if the U.S. stopped funding high-risk, low benefit research, that would have immense impact. That’s because U.S. activities have been driving international activities over the last two decades.

TheStreet: So we can lead by funding, as well as by example....

Ebright: Exactly. When we introduce proper oversight of safety, security and proper risk assessment, and when we stop performing high risk, low benefit research, or perform it only with the most extreme risk mitigation protocols in place, we will be setting an example. 

This story has been updated. The line "In March of 2020 ... it became clear that RaTG13 had been sampled in a mine in Yunnan Province..." has been updated to read from "March to May 2020." In addition, some parts of the second-to-last answer were removed per request of Ebright, because they lacked context.