My students are learning about gain-of-function research — what should I tell them about COVID?

For over a year now there have been conspiracy theories swirling around that COVID was designed and engineered in a Chinese lab, that the research has its origins in the US, and even in some cases that Anthony Fauci–Director of the US National Institute of Allergy and Infectious Diseases–is the evil mastermind behind all of this!

Despite their contorted implausibilities, these theories have persisted in the face of evidence to the contrary. And in recent weeks they have been given a boost as a new wave over concerns around “gain-of -unction research” have hit the headlines.

The timing here is especially relevant to me as I co-teach an undergraduate class on socially responsible and ethical innovation, and next week we’ll be grappling with precisely the type of research that some fear led to the coronavirus pandemic.

This should be a gift–a real-life social challenge playing out around the consequences of advanced research, just as we cover it in class. And yet, the interweaving of conspiracy theories, political power plays and fake news around COVID make navigating this tricky, to say the least.

Gain-Of-Function Research

Gain-of-function research takes a biological organism and genetically engineers it to behave differently. There are many reasons why scientists might do this, but one of the more controversial ones–and the one that tends to attract the most attention–is to genetically engineer pathogen to be more virulent.

On the face of it, this would seem like a really bad idea. But it turns out that there are plenty of good reasons to increase the ability of pathogens to cause harm–and one of the more compelling ones is to ensure that we have the means to combat them if such changes occur naturally.

The importance and the ethics of this type of research came to a head in 2012 as two groups of scientists attempted to publish, in some detail, how to genetically engineer an avian influenza virus. What made this research stand out was that the scientists had succeeded in making the H5N1 virus more infectious, and as a result, far deadlier, and they wanted to let others know how to do this.

Their intentions were laudable (and supported by the US National Institutes of Health)–they feared that it was only a matter of time before H5N1 mutated into an even more deadly virus, and they wanted to ensure that we had every means possible to combat this eventuality before it occurred. But the research was so controversial that it sparked an international debate around funding for and publication of gain-of-function research.

Those two papers were eventually published–one in the journal Nature, and the other in Science. And gain-of-function research continues to be seen as a necessary, although high-risk, way to prepare for future pandemics.  Yet it also remains controversial and misunderstood, and this has fueled accusations that COVID is a result of gain-of-function research gone wrong.

A Conspiratorial Quagmire

For most experts studying the COVID pandemic, the most plausible source of the virus quickly emerged in early 2020 as being likely due to cross-species transmission–most likely originating with bats. However, rumors quickly began spreading that there was a more sinister source–a release from a Chinese lab that had intentionally been working on a highly virulent, and possibly genetically engineered, virus.

As John Bodner, Wendy Welch, and their co-authors write in the (highly recommended) book Covid-19 Conspiracy Theories:

“Despite the clear scientific consensus, several competing conspiracy theories emerged to suggest some element of human intent and agency for the outbreak. The first cluster of CTs [conspiracy theories] have survived the longest, all focused on the level 4 microbiology laboratory in Wuhan. The Wuhan lab conspiracy theories began churning across the Internet once people learned of the lab’s existence. They appeared in online communities, alternative news media, and Fox News; they also came from the mouths of various European and North American politicians. Several variations developed, some of which worked together; others contradicted their sister narratives. Keep in mind the point made earlier: narratives that cannot logically be simultaneously true may still be held as equally true (or equally plausible) if they focus on the same villain.

“In the first version of the story, the lab accidentally released the virus through unsafe practices. After an April 14 article in the Washington Post reported that American officials inspecting the lab had warned of problems with safety and procedures (Rogan, 2020), this CT gained additional traction. However, conspiracy theories about the lab as Ground Zero long predate Rogan’s report.”

Bodner, Welch, and their co-authors go on to explore the social and political drivers behind the “accidental release” conspiracy theory, and more insidious theories around bioweapons research being carried out in the Wuhan lab. As they show, these were conspiracy theories that were fueled by paranoia, deep-rooted (of not evidence-grounded) beliefs, and cynical opportunism, and were fed by politicians who saw them as playing to their base–irrespective of the evidence.

Over the past year, these conspiracy theories haven’t gone away, but they have by and large been peripheral to mainstream responses to COVID. Yet in recent weeks they have blown up, and in quite unexpected ways.

Scientists Join The Fray

On May 14, 2021, a group of eighteen scientists published a letter in the journal Science calling for further investigations into the possibility of COVID being released from a lab in Wuhan.  These are respectable scientists and not the types of people prone to promoting conspiracy theories. And yet in their opinion “Theories of accidental release from a lab and zoonotic spillover both remain viable.”

The May 14 letter in Science didn’t go into details as to how a laboratory accident may have led to the release of a virus that was markedly different from what might be expected from naturally occurring interspecies jumps. Yet the doubts it raised were sufficient to bolster conspiracy theories around gain-of-function research leading to the release (accidental or otherwise) of a genetically enhanced virus.

Writing in the journal Nature, Amy Maxmen raised misgivings around the impact, if not the intent, of the letter in Science. Quoting virologist Angela Rasmussen, she notes that “[E]ven if the letter in Science was well intentioned, its authors should have thought more about how it would feed into the divisive political environment surrounding this issue”.

Part of the challenge is that the letter played into narratives being pushed by some right wing politicians in the US, as well as by conspiracy theorists, and as a consequence it further muddied the water around evidence underlying the emergence and spread of the virus. It also revealed how divisive these issues have become, even within some sectors of the scientific community.

Here, Maxmen’s Nature article notes:

“some aggressive proponents of the lab-leak hypothesis interpreted the letter as supporting their ideas. For instance, a neuroscientist belonging to a group that claims to independently investigate COVID-19 tweeted that the letter is a diluted version of ideas his group posted online last year. The same week, on Twitter, the neuroscientist also lashed out at Rasmussen, who has tried to explain studies suggesting a natural origin of SARS-CoV-2 to the public. He called her fat, and then posted a derogatory comment about her sexual anatomy. Rasmussen says, ‘This debate has moved so far from the evidence that I don’t know if we can dial it back.’”

Such scientist-on-scientist ad hominem attacks are symptomatic of just how messy and unscientific the “debate” over the potential lab origins of the coronavirus have become. And they underline the social and political mines that litter what should be a landscape that is dominated by evidence and public interest, not dogma and self-interest.

And yet, conspiracy theorists and politicians alike know that loud voices often prevail in decision making, irrespective of the rationality or opportunity costs involved. And apparently responding (at least in part) to these loud voices, on May 26, 2021, President Biden “asked the Intelligence Community to redouble their efforts to collect and analyze information that could bring us closer to a definitive conclusion” on whether the coronavirus “emerged from human contact with an infected animal or from a laboratory accident”.

This dictate doesn’t say anything about the nature of any laboratory accident that might have occurred. Yet the inference is clear that, if the pandemic is the result of a laboratory accident, there must have been something going on that led to researchers working with a virus that was more deadly than anything present in the environment. And that, in turn, implies gain-of-function research.

Enter Gain-Of-Function Research

This connection between the White House charge and gain-of-function research will not be lost on some US politicians. On May 11, 2021, senator Paul Rand (R) questioned Anthony Fauci directly about U.S. support for gain-of-function research in Wuhan:

“Juicing up super viruses is not new. Scientists in the U.S. have long known how to mutate animal viruses to infect humans. For years, Dr. Ralph Baric, a virologist in the U.S., has been collaborating with Dr. Shi Zhengli of the Wuhan Virology Institute, sharing his discoveries about how to create super viruses. This gain-of-function research has been funded by the NIH. … Dr. Fauci, do you still support funding of the NIH funding of the lab in Wuhan?” (from Washington Post, May 18, 2021)

Fauci replied:

“Senator Paul, with all due respect, you are entirely and completely incorrect that the NIH has not never and does not now fund gain-of-function research in the Wuhan Institute of Virology.”

Despite Fauci’s statement, it is precisely allegations like this that are fueling conspiracy theories around the origins of COVID. and they are now beginning to drive policy decisions.

One of the more immediate consequences of these concerns, for instance, has been a recent Senate vote to defund Wuhan animal lab and ‘gain-of-function’ experiments in China–an amendment to the Endless Frontiers Act addressing research funding in the US that was sponsored by, among others, senator Rand Paul. It’s an amendment that probably won’t have many immediate consequences to federally-funded research (although the geopolitical  fallout could be serious). But it does signal the possibility of future actions preventing US-based research in this area, which could stifle efforts to avoid future pandemics.

So What Should I Tell My Students?

Gain-of-function research is ethically complex. This is a field of research that intentionally creates dangerous pathogens in order to prevent harm, but in the process raises substantial concerns around possible risks versus potential benefits. From both a scientific and a social perspective there are no clear-cut answers to what is right and wrong here, and as a result, this is an area that demands informed discussion and socially responsive decision-making.

This is why we discuss gain-of-function research in class. This is an area of study that lies at the nexus of what we can do and what we should do as researchers, and either pursuing it or not pursuing it comes with profound risks.  As a result, there are many nuances around its responsible use that go far beyond the science alone.

And yet, within the current politically charged landscape around gain-of-function research, nuanced, considered and socially responsible debate is becoming increasingly hard to have. Politicians, far-right activists, anti-vaccination campaigners, and others, are cynically twisting evidence and co-opting conspiracy theories to serve their own ends. And as a result, conversations around gain-of-function research are now less about social responsibility and more about personal agenda-pushing. In other words, gain-of-function research has become politicized in the worst possible way.

The social ramifications of this could be profound. The further we move away from informed discourse that is predicated on public good, and toward uninformed co-option of speculative ideas and unfounded conspiracies, the harder it gets to make evidence-informed decisions, to remove prejudice and bias from policies and actions, and to build the kinds of global partnerships and collaborations that we desperately need if we’re to build a more just, equitable and vibrant future.

We also open ourselves up to manipulation by others, both personally and collectively, if we start to take conspiracy theories seriously. When we abandon evidence and reason in favor of narrow-minded validation and influence, it’s easy to stoke the fires of misinformation–something that domestic and international adversaries know all too well as they promote the spread of fake news.

Maybe this is where the focus of our discussions should be in class–not so much on the ethics and responsibility that come with powerful science (important as these are), but on the dangers of abandoning any pretense of following science in the pursuit of power and personal gain.

Of course, just to make things muddier still, there’s a small but plausible chance that COVID does have its roots in gain-of-function research. If it does, we have a profound responsibility as a global society to understand what went wrong, and how to prevent this happening in the future–not through finger-pointing, but through working together on socially responsible research and innovation. But if this does turn out to be the case–and I cannot stress enough that this is an extremely low probability scenario–one of our biggest challenges will be having the collective maturity to resist politicizing this further, or using it as fuel for yet another generation of conspiracy theories.

And perhaps this is the biggest takeaway here–not turning this into a science-versus conspiracy debate, or a politically charged melée, but asking how we can learn from what we discover to build a better future for everyone, not just those who look and think like us.

Andrew Maynard
Director, ASU Future of Being Human initiative
Substack: The Future of Being Human