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.

Scientists restart bioweapons research, with NIH's blessing

For more than a decade now, two scientists–one in the U.S. and one in the Netherlands–have been trying to create a deadly human pathogen from avian influenza. That's right: they are trying to turn "bird flu," which does not normally infect people, into a human flu.

Not surprisingly, many scientists are vehemently opposed to this. In mid-2014, a group of them formed the Cambridge Working Group and issued a statement warning of the dangers of this research. The statement was signed by hundreds of scientists at virtually every major U.S. and European university. (Full disclosure: I am one of the signatories.)

In response to these and other concerns, in October 2014 the U.S. government called for a "pause" in this dangerous research. NIH Director Francis Collins said that his agency would study the risks and benefits before proceeding further.

Well, four years later, the risks and benefits haven't changed, but the NIH has (quietly) just allowed the research to start again, as we learned last week in an exclusive report from Science's Jocelyn Kaiser.

I can't allow this to go unchallenged. This research is so potentially harmful, and offers such little benefit to society, that I fear that NIH is endangering the trust that Congress places in it. And don't misinterpret me: I'm a huge supporter of NIH, and I've argued before that it's one of the best investments the American public can make. But they got this one really, really wrong.

For those who might not know, the 1918 influenza pandemic, which killed between 50 and 100 million people worldwide (3% of the entire world population at the time), was caused by a strain of avian influenza that made the jump into humans. The 1918 flu was so deadly that it "killed more American soldiers and sailors during World War I than did enemy weapons."

Not surprisingly, then, when other scientists (including me) learned about the efforts to turn bird flu into a human flu, we asked: why the heck would anyone do that? The answers were and still are unsatisfactory: claims such as "we'll learn more about the pandemic potential of the flu" and "we'll be better prepared for an avian flu pandemic if one occurs." These are hand-waving arguments that may sound reasonable, but they promise only vague benefits while ignoring the dangers of this research. If the research succeeds, and one of the newly-designed, highly virulent flu strains escapes, the damage could be horrific.

One of the deadliest strains of avian flu circulating today is H5N1. This strain has occasionally jumped from birds to humans, with a mortality rate approaching 50%, far more deadly than any human flu. Fortunately, the virus has never gained the ability to be transmitted directly between humans.

That is, it didn't have this ability until two scientists, Ron Fouchier in the Netherlands and Yoshihiro Kawaoka at the University of Wisconsin, engineered it to gain this ability. (Actually, their work showed that the virus could be transmitted between ferrets, not humans, for the obvious reason that you can't ethically test this on humans.)

Well, Fouchier and Kawaoka are back at it again. NIH actually lifted the "pause" in December 2017, and invited scientists to submit proposal for this type of research. Fouchier confidently stated at the time that all he had to do was "find and replace" a few terms in his previous proposal and it would likely sail through peer review. It appears he was correct, although according to the Science article, his study has been approved but not yet actually funded. Kawaoka's project is already under way, as anyone can learn by checking the NIH grants database.

And by the way: why the heck is a U.S. funding agency supporting research in the Netherlands anyway? If Fouchier's work is so great (and it isn't), let the Netherlands fund it.

I've said it before, more than once: engineering the flu to be more virulent is a terrible idea. It appears the review process at NIH simply failed, as multiple scientists stated to Vox last week. This research has the potential to cause millions of deaths.

Fouchier, Kawaoka, and their defenders (usually other flu scientists who also benefit from the same funding) like to claim that their project to engineer a deadlier bird flu will somehow help prevent a future pandemic. This argument is, frankly, nonsense: influenza mutates while circulating among millions of birds, and no one has any idea how to predict or control that process. (I should mention that I know a little bit about the flu, having published multiple papers on it, including this paper in Nature and this paper on H5N1 avian flu.)

Fouchier and Kawaoka have also argued that we can use their work to create stockpiles of vaccines in advance. Yeah, right. We don't even stockpile vaccines for the normal seasonal flu, because it mutates too fast, so we have to produce new vaccines each year. And the notion that anyone can predict a future pandemic strain so precisely that we could design a vaccine based on their prediction is laughable.

I can't quite fathom why NIH seems to be so enraptured with the work of these two labs that, rather than simply deny them funding, it has ignored the warnings of hundreds of scientists and now risks creating a new influenza pandemic. Much as I hate to say this, maybe it's time for Congress to intervene.