Scientists have re-created the deadly 1918 flu virus and used it to infect animals. WTF?

With all the controversy about gain-of-function research and all the concerns about how dangerous it is, you might think that scientists have stopped doing that kind of work.

Well, no.

In the latest news, a team of scientists in Canada and the U.S. report that they have re-created the 1918 influenza virus and used it to infect macaques. Let’s be clear here: the 1918 flu vanished from the Earth, long ago. It’s simply not a threat, or it least it wasn’t, until someone figured out a way to bring it back.

Why would anyone do this? I’ll get to that, but first a little background.

The 1918 flu pandemic was the worst plague since the Black Death, which occured in the mid-14th century. During World War I, a new flu virus swept the planet, killing upwards of 50 million people. It probably infected a third of the entire world population at the time.

Since Covid-19 appeared, the 1918 flu pandemic has been cited often (sometimes called the Spanish flu), usually to compare or constrast it with Covid-19. Sure, Covid is bad, but at least it’s not as bad as what the world experienced in 1918.

About 20 years ago, a small team of researchers led by Jeffery Taubenberger and Ann Reid figured out how to sequence the genome of the 1918 flu. In a series of papers spread over six years, they described how they recovered pieces of the flu virus from human samples that had been frozen for nearly 100 years, including corpses buried in the permafrost of Siberia and Alaska. In 2005, they reported the complete sequence in the journal Nature. Their main discovery was that the 1918 flu had originally been a bird flu, which jumped into humans sometime before 1918. Taubenberger and others, including Adolfo Garcia-Sastre at Mt. Sinai School of Medicine, also re-constructed the virus and tested it on mice, that same year. Not surprisingly, the mice died.

It didn’t take long before gain-of-function researchers said “hey, why don’t we reconstruct the flu virus and see what happens in primates?” The tools of modern genetics make it possible to reconstruct a virus from scratch, using just the sequence.

In 2007, only two years after the 1918 flu sequence was completely decoded, influenza researcher Yoshihiro Kawaoka at the University of Tokyo and the University of Wisconsin described, in a paper in Nature, how he and his colleagues used the sequence to create live, infectious 1918 flu viruses. To demonstrate that these really were flu viruses, they infected 7 macaques with them. Not surprisingly, the macaques got severely ill, and the scientists eventually euthanized all of them.

(Insiders may recognize Kawaoka’s name: he and Dutch scientist Ron Fouchier are widely known for their gain-of-function research that aimed to give deadly bird flu the ability to infect mammals. I’ve called them out on this in the past, and I’ve openly asked why NIH was funding this work.)

In the new paper, a team of researchers at the Public Health Agency of Canada, the University of Manitoba, and Oregon Health & Science University re-created the 1918 flu virus again, and infected 15 macaques. This time they used more realistic doses, and the macaques didn’t get so sick, suffering only “mild” or “moderate” disease. Maybe macaques “are not ideal for the development and testing of novel pandemic influenza-specific vaccines and therapies,” they concluded.

So let’s review: flu scientists have been using the sequence of a long-vanished, extremely deadly virus to reconstitute the virus and infect animals, and then observe how sick they get. (Kawaoka did it a second time, in a study published in 2019.)

Why do they do it? All of the papers give essentially the same reason: these experiments, they say, will help us develop animal models in which we can test vaccines. These same justifications have been used for decades, but flu vaccines haven’t improved one whit, as far as I can tell.

But hold on a minute! Even if you accept their argument that infecting macaques and other animals with influenza virus will help develop better vaccines, why use the 1918 influenza virus at all?

They don’t answer that question, because there really is no good answer. The fact is that the experiments will be more relevant if they use currently circulating flu strains–because those are the strains that we need vaccines against.

I imagine that the scientists doing this work truly believe the arguments they make, about how their work will help design better vaccines and therapies. But they’ve been making similar arguments for decades, and it just hasn’t played out that way.

The 1918 flu disappeared long ago, and there’s no way it could possibly re-appear naturally. There’s only one way that the 1918 flu becomes a threat to human health again: through a lab leak. Re-creating the virus in a lab makes that possible.

We’re still trying to figure out if Covid-19 had a natural origin or whether it started as a lab leak. Even if it turns out to have a natural source, the intense discussions about the lab leak hypothesis have been useful, because they made it clear that lab leaks happen, and that they should be considered a genuine risk.

In recognition of this risk, scientists and non-scientists alike have called for a worldwide ban on gain-of-function research. That hasn’t happened yet, although NIH has issued a carefully worded statement about the kinds of work that it supports.

Most of the recent controversy over gain-of-function research has focused on research that makes viruses more deadly. I hope it’s clear that re-creating a deadly virus from scratch is another form of gain-of-function research, one that carries equally great risks with little or no potential benefit. We should put a halt to both types of work.

There’s an easy way to eliminate the risk that a lab leak might release the 1918 influenza virus into the human population: stop re-creating the virus. The 1918 flu disappeared from the natural world long ago–or to be more precise, it evolved into a much, much milder form of influenza. The deadly form that was recently re-created in several labs does not exist in nature today. Let’s keep it that way.

Should the government allow scientists to create new super-viruses?

Let's suppose a bunch of scientists proposed to take one of the most infectious human viruses—influenza, say—and turn it into a super-bug. Is this a good idea?

Or to put it another way: should scientists be artificially mutating viruses so that they have the potential to become a worldwide pandemic?

Right about now you might be asking: is anyone actually doing this, and if so, what on earth are they thinking?

And yet, several of the world's most prominent influenza researchers have been engaged in exactly this enterprise for several years now. They call their work "gain of function" experiments, because they manipulating viruses to give them new (and very dangerous) functions.

I wrote about this last year, after a group led by Ron Fouchier at Erasmus Medical Center in the Netherlands and Yoshihiro Kawaoka of the University of Wisconsin announced, in a letter to Nature, that they were going to create a new strain of H7N9 influenza virus that had the potential to turn into a human pandemic. Sure enough, just a few months later, Fouchier published results showing they had done just that, although they reported that their newly engineered strain had only "limited" transmissibility between ferrets (the animal they used for all their experiments).

Fouchier and Kawaoka had already done the same thing with the deadly H5N1 "bird flu" virus, causing a huge outcry among scientists and the public. As reported in Science magazine almost three years ago, Fouchier admitted that his artificially mutated H5N1 was "probably one of the most dangerous viruses you can make."

And yet he did it anyway—and then did it again, with H7N9.

Many other scientists were and are extremely concerned about these experiments, which some of us consider dangerous and irresponsible. This past July, a large group of scientists known as the Cambridge Working Group (of which I am a member) released a statement calling for a hiatus, saying:

"Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches."

Just two days ago, the U.S. government responded, announcing that it was going to take a serious look at whether creating these superbugs is a good idea. The Office of Science and Technology Policy (OSTP) is creating two committees to "assess the potential risks and benefits" of these experiments, particularly those involving the influenza, SARS, and MERS viruses.

Until the committees come up with recommendations, the government is halting any new funding for these experiments and asking for a voluntary "pause" on existing work.

Not surprisingly, Fouchier and his colleagues have argued that their work has benefits; that it has "contributed to our understanding of host adaptation by influenza viruses, the development of vaccines and therapeutics, and improved surveillance." Yet these arguments are tenuous at best. Fouchier and company have failed to show that the mutations they found in ferret experiments are likely to occur in the natural course of human outbreaks, which means that using their viruses for vaccine development would be a huge mistake.

And to claim that creating super-viruses in the lab will lead to "improved surveillance" is, frankly, laughable. Surveillance means getting out in the field and collecting samples from sick people. Gain-of-function laboratory experiments have basically nothing to do with surveillance.

Harvard's Marc Lipitsch has been one of the prominent voices arguing against this line of research, writing just last week that the scientific benefits of these experiments are very limited, for reasons detailed in his article. Lipitsch is also one of the founding members of the Cambridge Working Group.

According to the announcement from The White House, the first committee to evaluate the merit of these experiments will meet in just a few days, on 22 October. Meetings will continue throughout the winter, with recommendations expected sometime in the spring of 2015.

We have enough problems with influenza, and now with Ebola too, without scientists creating incredibly deadly new viruses that might accidentally escape their labs. Let's hope that the OSTP does the right thing and shuts down these experiments permanently.