GAIN OF FUNCTION RESEARCH
From chapter 11 of Films from the Future: The technology and Morality of Science Fiction Movies. This section draws lightly the 2016 movie Inferno, which is referenced in places. Even though the chapter was written in early 2018, nearly two years before the emergence of COVID, it feels quaintly naive given everything that’s happened with the current pandemic. But as questions are asked about the origins of SARS-CoV-2, gain of function research is back in the headlines, and here, the chapter is as relevant as ever.
Weaponizing the Genome
In 2012, two groups of scientists published parallel papers in the prestigious journals Science and Nature that described, in some detail, how to genetically engineer an avian influenza virus. What made the papers stand out was that these scientists succeeded in making the virus more infectious, and as a result, far deadlier. The research sparked an intense debate around the ethics of such studies, and it led to questions about the wisdom of scientists publishing details of how to make pathogens harmful in a way that could enable others to replicate their work.
The teams of scientists, led by virologists Ron Fouchier and Yoshihiro Kawaoka, were interested in the likelihood of a highly pathogenic flu virus mutating into something that would present a potentially catastrophic pandemic threat to humans. The unmodified virus, referred to by the code H5N1, is known to cause sickness and death in humans, but it isn’t that easy to transmit from person to person. Thankfully, the virus isn’t readily transmitted by coughs and sneezes, and this in turn limits its spread quite considerably. But this doesn’t mean that the virus couldn’t naturally mutate to the point where it could successfully be transmitted by air. If this were to occur (and it’s certainly plausible), we could be facing a flu pandemic of astronomical proportions.
To get a sense of just how serious such a pandemic could be, we simply need to look back to 1918, when the so-called “Spanish flu” swept the world. The outbreak of Spanish flu in the early 1900s is estimated to have killed around fifty million people, or around 3 percent of the world’s population at the time. If an equally virulent infectious disease were unleashed on the world today, this would be equivalent to over 200 million deaths, a mind-numbing number of people. However, the relative death toll would likely be far higher today, as modern global transport systems and the high numbers of people living close to each other in urban areas would likely substantially increase infection rates.
It’s this sort of scenario that keeps virologists and infectious-disease epidemiologists awake at night, and for good reason. It’s highly likely that, one day, we’ll be facing a pandemic of this magnitude. Viruses mutate and adapt, and the ones that thrive are often those that can multiply and spread fast. Here, we know that there are combinations of properties that make viruses especially deadly, including human pathogenicity, lack of natural resistance in people, and airborne transmission. There are plenty of viruses that have one, or possibly two, of these features, yet there are relatively few that combine all three. But because of the way that evolution and biology work, it’s only a matter of time before some lucky virus hits the jackpot, much as we saw back in 1918.
Because of this, it makes sense to do everything we can to be prepared for the inevitable, including working out which viruses are likely to mutate into deadly threats (and how) so we can get our defenses in order before this happens. And this is what drove Fouchier, Kawaoka, and their teams to start experimenting on H5N1.
H5N1 is a virus that is deadly to humans, but it has yet to evolve into a form that is readily transmitted by air. What interested Fouchier and Kawaoka was how likely it was that such a mutation would appear, and what we could do to combat the evolved virus if and when this occurs. To begin to answer this question, they and their teams of scientists intentionally engineered a deadly new version of H5N1 in the lab, so they could study it. And this is where the ethical questions began to get tricky.
This type of study is referred to as “gain-of-function” research, as it increases the functionality and potential deadliness of the virus. Maybe not surprisingly, quite a few people were unhappy with what was being done. Questions were asked, for instance, about what would happen if the new virus was accidentally released. This was not an idle question, as it turns out, given a series of incidents where infectious agents ended up being poorly managed in labs. But it was the decision to publicly publish the recipe for this gain-of-function research that really got people worried.
Both Science and Nature ended up publishing the research and the methods, but only after an intense international debate about the wisdom of doing so. However, the decision was, and remains, controversial. Proponents of the research argue that we need to be ready for highly pathogenic and transmissible strains of flu before they inevitably arise, and this means having the ability to develop a stockpile of vaccines. This in turn depends on having a sample of the virus to be protected against. But this type of research makes many scientists uneasy, especially given the challenges of preventing inadvertent releases.
Concerns like this prompted a group of scientists to release a Consensus Statement on the Creation of Potential Pathogens in 2014, calling for greater responsibility in making such research decisions. These largely focused on the unintended consequences of well- meaning research. But there was also a deeper-seated fear here: What if someone took this research and intentionally weaponized
a pathogen?
This was one of the issues considered by the US National Science Advisory Board for Biosecurity as it debated drafts of the H5N1 gain-of-function papers in 2011. In a statement released on December 20, 2011, the NSABB proposed that that the papers should not be published in their current form, recommending “the manuscripts not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm.” However, this caused something of a furor at the time among scientists. The NSABB is an advisory body in the US and has no real teeth, yet its recommendations drew accusations of “censorship” in a scientific community that deeply values academic freedom.
The NSABB eventually capitulated, and supported the publication of both papers as they finally appeared in 2012—including the embedded “how-to” instructions for creating a virulent virus. But the question of intentionally harmful use remained. And it’s concerns like this that underpin the plot in Inferno.
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Fouchier, Kawaoka, and their teams showed that it is, in principle, possible to take a potentially dangerous virus and engineer it into something even more deadly. To the NSABB and others, this raised a clear national security issue: What if an enemy nation or a terrorist group used the research to create a weaponized virus? Echoes of this discussion stretched back to the 2001 anthrax attacks in the US, where the idea of “weaponizing” a pathogenic organism became part of our common language. Since then, discussions over whether and how biological agents may be weaponized have become increasingly common.
Intuitively, genetically engineering a virus to weaponize it feels like it should be a serious threat. It’s easy to imagine the mayhem a terrorist group could create by unleashing an enhanced form of smallpox, Ebola, or even the flu. Thankfully, most biosecurity experts believe that the risks are low here. Despite these imagined scenarios, it takes substantial expertise and specialized facilities to engineer a weaponized pathogen, and even then, it’s unclear that the current state of science is good enough to create an effective weapon of terror.
More than this, though, most experts agree that there are far easier and cheaper ways of creating terror, or taking out enemy forces, than using advanced biology. And because of this, it’s hard to find compelling reasons why an organization would weaponize a pathogen, rather than using far easier and cheaper ways of causing harm. Why spend millions of dollars and years of research on something that may not work, when you can do more damage with less effort using a cell phone and home-made explosives, or even a rental truck? The economics of weaponized viruses simply don’t work outside of science fiction thrillers and blockbuster movies. At least, not in a conventional sense.
And this is where Inferno gets interesting, as Zobrist is not a terrorist in the conventional sense. Zobrist’s aim is not to bring about change through terror, but to be the agent of change. And his mechanism of choice is a gain-of-function genetically engineered virus. Unlike the potential use of genetically modified pathogens by terrorists, or even nation-states, the economics of Zobrist’s decision actually make some sense, warped as they are. In his mind, he envisions a cataclysmic future for humanity, brought about through out- of-control overpopulation. and he sees it as a moral imperative to use his expertise and wealth to help avoid it, albeit by rather drastic means.
As this is movie make-believe, the technology Zobrist ends up developing is rather implausible. But it’s not that far-fetched. Certainly, we know from the work of Fouchier, Kawaoka, and others that it is possible to engineer viruses to be more deadly than their naturally-occurring counterparts. And we’re not that far from hypothetically being able to precisely design a virus with a specific set of characteristics, an ability that will only accelerate as we increasingly use cyber-based technologies and artificial-intelligence-based methods in genetic design. Because of these converging trends in capabilities, when you strip away the hyperbolic narrative and cliffhanger scenarios from Inferno, there’s a kernel of plausibility buried in the movie that should probably worry us, especially in a world where powerful individuals are able to translate their moral certitude into decisive action.
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