We warned about dangerous gain-of-function work years ago.

NIH ignored us.

I’ve been re-reading some things that I and others wrote about the dangers of creating deadly new viruses in the lab, “super bugs” as some have called them. Today I’m sharing some of my earlier commentary along with a fresh perspective, in light of the pandemic that the world suffered starting in 2020.

Here’s what I wrote in late 2017.

Some scientists really want to earn their "mad scientist" label. Ever since Mary Shelley's Frankenstein, novelists and screenwriters have shown us the dangers of letting mad scientists pursue their dreams without any controls. Of course, those stories are fiction.

In the microbial world, though, technology has caught up with fiction. Scientists today can create viruses from scratch, as they first did with the polio virus, back in 2002. Using the tools of modern genomics, virologists and microbiologists can make pathogens much, much more deadly. But would anyone really want to do this? The answer, we now know, is yes.

A few years ago, some virologists in the Netherlands and the U.S. had the oh-so-clever idea of modifying a bird flu virus to make it more deadly to humans. What would it take, they wondered, to turn the bird flu into a human flu? They decided to give it a try, and they announced their plans to the world. Then, just a few months later, they published results (in the journal Nature), showing that they had succeeded, using a bird flu called H7N9.

That wasn't even their first try. Only a year earlier, they did the same thing using a different bird flu virus (H5N1). Both of these bird flu strains have killed people, but the wild-type version of the virus rarely infects humans. The scientists running these experiments aimed to create a strain that could get into humans much more easily.

Why did they do this? Are they truly just mad scientists? Well, not really. The answer is in the links I shared above: these experiments were published in Nature, one of the world’s most prestigious scientific journals, and they were written up in high-profile venues such as The New York Times. And if that weren’t enough, these experiments gained enough acclaim within the virology community that the work was funded (after peer review) by the U.S. National Institutes of Health.

Many scientists, though, were mortified. Way back in 2014, 18 leading microbiologists and infectious disease experts, including Nobel laureate Sir Richard Roberts, formed the Cambridge Working Group to oppose efforts to create super-viruses in the lab. Hundreds of other scientists (including me) joined the group as charter members.

In response to the concerns raised by these scientists, in 2014 NIH announced a moratorium on these so-called "gain of function" (GOF) experiments, at least in the U.S. The NIH convened an expert panel, the NSABB, who commissioned a 1,000-page report and then issued their own report, which was released in May of 2016.

The NSABB panel defined "research of concern" thusly:

"...research that could generate a pathogen that is: 1) highly transmissible and likely capable of wide and uncontrollable spread in human populations; and 2) highly virulent and likely to cause significant morbidity and/or mortality in humans."

This does not sound like a good idea! So what did the NSABB recommend? Well, this:

"Research proposals involving GOF research of concern ... should receive an additional, multidisciplinary review, prior to determining whether they are acceptable for funding."

Weak tea at best. “Additional review”? How about banning such work entirely? At the time, I imagined mad scientists rubbing their hands together in glee.

And then, in late 2017, NIH announced it woud end the moratorium on gain-of-function research. They made this announcement just a week before Christmas, when many people are probably not paying attention. Coincidence? Perhaps. In his statement announcing the end of the moratorium, former NIH Director Francis Collins wrote:

"I am confident that the thoughtful review process ... will help to facilitate the safe, secure, and responsible conduct of this type of research in a manner that maximizes the benefits to public health."

Dr. Collins still seems to think he did nothing wrong, based on his interview just last week with Andrew Sullivan.

Many scientists were warning, thoughout the 2010’s, that gain-of-function research was highly risky and carried few if any benefits, Harvard's Marc Lipsitch, one of the leaders of the Cambridge Working Group, commented that "we don't need to do these dangerous experiments. Indeed there are many ways that can (and have) been used to answer the public health question with greater generality, little to no safety risk, and much lower cost."

Here was my take back in 2017 on this blog:

Let's weigh the pluses and minuses of gain-of-function (GoF) research on pathogenic viruses, shall we?
Pluses:

• Creating novel pathogens might lead to insights in the basic biology of viruses and bacteria.

• Creating hard-to-kill pathogens might help us develop better anti-virals and anti-bacterials, although more effective strategies already exist.

Minuses:

• The viruses could accidentally escape, and millions of people could die.

• The viruses could get into the wrong hands, and millions of people could die.

We all know what happened just 2 years later: COVID-19.

Did COVID-19 start out in the labs at the Wuhan Institute of Virology in Wuhan, China? Maybe: this is still a subject of fierce debate.

But one thing is pretty certain: if the U.S. had simply maintained its ban on this dangerous work, and refused to fund it – and if journals such as Nature would also refuse to publish it – then China would never have even started doing gain-of-function research. China was following the lead of the U.S., which made GoF fashionable.

Even today, virologists continue to insist that GoF work has all sorts of ridiculously implausible benefits, including “faster computers.” No, I’m not making that up; see Table 2 of this opinion piece from some of the world’s leading virologists.)

And one final note: the main benefit that its proponents claim for GoF research has always been this: it will help us prevent the next pandemic. How did that work out?