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.

Research on artificially engineered flu strains expected to kill 2000 people per year

2,000 deaths expected for each year of research on how to turn avian flu into a more deadly virus. 

That’s the estimate in a new analysis by Harvard University’s Marc Lipsitch, professor and director of the Center for Communicable Disease Dynamics in the Harvard School of Public Health.

I heard Lipsitch present his results at an invitation-only hearing held at the National Academy of Sciences on December 15. The purpose of the two-day meeting, which was organized by the National Science Advisory Board for Biosecurity (NSABB), was to discuss the risks and benefits of “gain of function” research on viruses, especially the influenza virus.

What is gain-of-function (GOF) research? In this context, GOF means experiments designed to give a pathogen new powers, such as the ability to infect new species, or to jump from person to person more easily. Scientists have already conducted GOF experiments on the flu virus, and now they are considering other viruses including SARS and MERS.

What prompted the NSABB hearing was the series of experiments by researchers in the U.S. and the Netherlands designed to transform avian influenza (or “bird flu”) into a human-transmissible virus. These novel, lab-created flu strains have the potential to cause a worldwide pandemic. When virologists Ron Fouchier and Yoshi Kawaoka first published their experiments two years ago, the public, the press, and many members of the scientific community (including me; see here and here) expressed serious alarm. After a brief hiatus, though, the experiments continued. 

In mid-October, the U.S. government announced a “pause” in gain-of-function experiments, which has Fouchier, Kawaoka, and their colleagues very upset.

At the NSABB meeting in December, the vast majority of panelists were influenza researchers defending GOF research, arguing that it could lead to valuable insights about the flu. As a group, they seem to have convinced themselves that everything is fine, and they want to tell the rest of us that there’s nothing to worry about. Prof. Lipsitch (and a couple of other speakers) stood out as a voice of reason. He was one of the very few scientists who took a hard look at the risks and also pointed out alternative, low-risk methods for answering the same scientific questions.

Lipsitch conducted a careful risk analysis (something apparently not even considered by Fouchier and Kawaoka) looking at the chances of a virus escaping a lab, of such a virus causing further infections, the likely number of fatalities, and more. It turns out that the scientific community has excellent data quantifying all the key variables involved, as Lipsitch documented. He and his colleague Tom Inglesby just published these figures, with supporting data, in the journal mBio.

Using conservative estimates, many of them provided by influenza researchers themselves, Lipsitch calculated that for each year of gain-of-function research on pandemic viruses, we can expect at least 2,000 fatalities worldwide. And that’s only the low end: at the other extreme, this estimate rises to 1.4 million fatalities per year.

Lipsitch also described many other ways to study and defeat influenza, all of them with little or no risk, which he’s published in the journal PLoS Medicine. His point is that even if we accept the supposed benefits of GOF research, there are far less risky ways to obtain those same benefits.

One of the most ironic–or outrageous–claims of the pro-GOF scientists is that these experiments will help us predict future pandemic flu strains, and even help us design a vaccine in advance of outbreaks. The irony is that this year, the seasonal flu vaccine is a poor match to the strains that are circulating. This vaccine was chosen only 9 months ago, based on extensive surveillance of circulating flu strains, demonstrating how difficult it is to predict even the regular seasonal flu. As a result, we’re having a very bad flu season this year (aside: it's still worth getting the flu vaccine).

During the discussion at the NSABB meeting, an audience members observed that the claims of Fouchier, Kawaoka, and other pro-GOF scientists is hubris. She pointed out that not only are they claiming that they can predict future outbreaks–which no one has ever done accurately–but that we should invest billions of dollars stockpiling specially-designed vaccines based on their predictions. (This was indeed suggested by one of the presenters.) 

2000 deaths per year. And that’s only the direct risk: what about the risk from publishing these experiments? What happens when we provide instructions on how to build deadly biowarfare agents to anyone with an internet connection? Indeed, “gain of function” research on pandemic pathogens is really biowarfare research, which supposedly ended after the Cold War.

I’m a huge supporter of biomedical research and of NIH in general. NIH research has yielded tremendous benefits to the public health, as I’ve written before. We don’t need to overreact by cutting medical research in general, but we can make the “pause” in gain-of-function research permanent. There are far better things to do with our research funds. If you want to register your concerns, write to the NSABB at nsabb@od.nih.gov and tell them to recommend a permanent halt to gain-of-function research on pathogenic viruses.

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.

Scientists are creating a dangerous flu strain, just to prove they can

In an outrageous display of chutzpah, a group of flu researchers led by Ron Fouchier of Erasmus Medical Center in the Netherlands announced today, in a letter to the journal Nature, that they were planning to engineer the new H7N9 avian flu strain to give it new, possibly much more deadly capabilities.  Fouchier is the same scientist who, two years ago, adapted the highly pathogenic H5N1 flu strain so that it could be passed from human to human, which it cannot do in its natural form.  The resulting outcry delayed publication of his paper, but it eventually did appear.

Now they want to do the same thing, and much more, with the new H7N9 influenza virus, which has killed 43 people in China to date, and which epidemiologists are tracking with great concern.

They should track Fouchier and his lab instead.

Wait a second, protests Fouchier.  He promises that

"All experiments proposed by influenza investigators are subject to review by institutional biosafety committees. The committees include experts in the fields of infectious disease, immunology, biosafety, molecular biology and public health; also, members of the public represent views from outside the research community."

Sorry, but I'm not reassured.  Fouchier's group wants to do this research because it's all they know how to do - and, I suspect, because they enjoy the publicity.  Despite their claims that the research is vital to our understanding of the flu, none of their past work, including their work on H5N1, has changed our ability to respond to a pandemic.  As flu expert Michael Osterholm said in a report by the Associated Press:

"H5N1 surveillance is as haphazard today as it was two years ago. Should we do the work if it's not actually going to make a difference?"

Precisely.  Fouchier and his colleagues can't do surveillance, nor do they work on vaccine development.  They have laboratories where they can engineer the flu virus to make new strains, so that's what they want to do. Two years after their controversial H5N1 experiments, they haven't contributed to any improvement in our ability to control a pandemic, nor have they shown how to develop a better flu vaccine.  The benefits of creating a deadly new H7N9 virus are marginal, at best.

What about the risk? As reported in the Daily Mail, Fouchier and his colleague Yoshihiro Kawaoka themselves said

"H7N9's pandemic risk would rise 'exponentially' if it gained the ability to spread more easily among people."

Really?  And from this they conclude that it's a good idea to engineer a virus that can do exactly that - spread more easily among people? Are we supposed to take this risk because of some theoretical benefit from a vague "better understanding" of how mutations in the virus change its pathogenicity?

Although Fouchier is in Rotterdam, the NIH funds part of his work through the National Institute of Allergies and Infectious Diseases (NIAID).  Dr. Anthony Fauci, the head of NIAID, offered the reassurance that a special panel will review this H7N9 project, and

"If the risk is felt to be too high by this outside review, they will recommend it won't be done and we won't fund it."

Despite this additional oversight, I remain skeptical. These special panels tend to include other scientists who are very sympathetic with the work they're reviewing, as was demonstrated two years ago when the H5N1 work was published despite the grave concerns expressed by many outside the field.  I predict they will approve Fouchier and Kawaoka's experiments.

Here's a thought: put me on the panel: I've published multiple research papers on the influenza virus (including this paper in Nature and this paper on H5N1 avian flu), so I think it's fair to say I'm qualified.  But somehow I doubt they will do that.

Is the government hiding something about the next flu pandemic?

Remember the flu pandemic? The one that swept the world just two years ago? You might be forgiven if this has slipped your mind - after all, it doesn't seem like such a big deal now. That's because we got lucky: despite many dire warnings about the danger of another 1918 "Spanish flu", when the 2009 pandemic arrived, it was far milder than previous pandemics. Hundreds of millions of people got the flu in 2009, but for most of them, it wasn't so bad. In fact, the new flu is less severe the old flu - the strain that was circulating before the new pandemic hit.

Now we have two flus circulating: the "old" H3N2, and the 2009 pandemic flu, called H1N1. (And the vaccine protects against both of them, so get your flu shot! Your friends, neighbors, and co-workers will all benefit.)

We really dodged a bullet in 2009. Despite our best efforts, it took 7 months (April to November) before a new vaccine was ready. Before we realized how mild it was, people were desperately snapping up stores of Tamiflu, an anti-viral medicine that only barely helps to treat the flu. If it had been like 1918, Tamiflu wouldn't have helped much, and tens of millions would have died.

The 2009 pandemic originated in pig farms in Mexico. We don't know precisely where it made the first leap into humans, but it appears that two different strains joined together in a pig somewhere to create the new H1N1. The flu has a nasty habit of jumping the species barrier, hopping to humans from both pigs and chickens.

So now that we know all this, next time will be different, right? The world's influenza scientists are monitoring pigs and chickens closely now, keeping a close eye on any new flu strains. Right? RIGHT???

Er, no. Not exactly. For one thing, surveillance in pigs appears to be nonexistent. I checked to see how many flu sequences from pigs in Mexican have been desposited in the public archive at GenBank since 2009 (using this terrific database). The result? One, in 2009. Nothing from 2010 or 2011. Hello, is anyone awake at the CDC and the WHO?

This despite the fact that scientists have serious concerns that the deadly H5N1 avian flu (the "bird flu") could combine its genes with H1N1 and create a really nasty new flu strain. And scientists have long had concerns that pigs could be the mixing vessels for new flu outbreaks - exactly what happened in 2009.

But wait… maybe they are monitoring the flu, but they're just not telling us. That would feed into all the fringe government conspiracy groups that claimed the 2009 pandemic was an intentionally engineered government-funded enterprise (see this BMJ article for more). I don't believe any of those conspiracy theories - most of them are just nuts - but read on.

Sharing data about flu viruses has been a touchy subject with the WHO and the CDC for years. As reported by the University of Minnesota's CIDRAP,

"In late 2006, virus sharing became an international flash point when Indonesia broke a long tradition of free international sharing of flu virus specimens by withholding its H5N1 virus samples as a protest against the high cost of commercial vaccines derived from such samples. The controversy has drawn attention to the problem of equitably distributing vaccines in the event of a pandemic."

A few months ago, the WHO finally agreed on a new set of principles on data sharing, which states that

"The WHO GISRS laboratories [which includes the CDC] will submit genetic sequences data to GISAID and Genbank or similar databases in a timely manner."

Excellent! If they do it.

As every biomedical scientist knows, GenBank is a free, public database of genetic sequence data that contains millions of sequences, from humans, bacteria, viruses, you name it. But GISAID is another database, in Switzerland - one that I initially supported - just for flu data. The original mission of GISAID was that data deposited there would go to GenBank as well, with little or no delay. But in a classic bait-and-switch move, the GISAID board changed that policy after the database was up and running, and now they can sit on data as long as they want.

OK, you say, but it's a private database, so they can do what they want. True enough. But here's the surprising bit: the CDC deposits most of its flu sequences ONLY in GISAID, where they can milk them for scientific results for years without sharing them with others. As one of GISAID's original supporters, I have an account there, and here's what I found.

So far, the CDC has deposited sequences from 6,801 flu isolates in GISAID, of which only a tiny handful are in GenBank. 3201 of these originated in the U.S., so there can't be any foreign government insisting that they be kept secret. These provide critical data that could help scientists predict what is coming in the next flu season. But you can't get these sequences without a GISAID account. And even if you have a GISAID account, as I do, you have to agree not to release the data as a condition of getting a look.

So why does the CDC deposit sequences in GISAID? I think it's precisely because of the restrictions. CDC's scientists don't want others to look at "their" data, because they're afraid someone else might discover something important and publish it before them.

The CDC, of course, is part of the U.S. government, and all its work is funded by the public. But it seems that the CDC flu scientists have forgotten their public health mission - or at least, they appear to be more concerned about their own careers (and the papers they might publish) than about making sure the world is ready for the next pandemic.

And by the way, even these sequences don't seem to include anything from pigs in Mexico. Hello, CDC? You are looking at swine flu now, aren't you?

Perhaps I'm being a bit harsh. I love the CDC: they do a terrific job most of the time, providing vital services to protect the public from infectious diseases. But their internal scientists sometimes seem to operate within a cocoon, and I'm afraid that's happening here. This culture of secrecy has got to stop, and I suspect that will only happen under pressure from the outside. The CDC Director, Thomas Frieden, needs to tell his flu people to start sharing what they know with the rest of the world. And they can start by putting their data in GenBank.

Oscillo – what? Homeopathic flu “cures” and dead ducks

Oscillococcinum sounds like medicine. And if you saw this package in a store next to all the other cold and flu remedies, you might be tempted to give it a try. It looks just like a box of anthistamines or other real medicines. With flu season coming soon, you might want to look at this box more closely before you buy it.

You can buy oscillococinum at Walgreen’s, Target, Amazon.com, and many other places. At Walgreen’s, one of the largest pharmacy chains in the U.S., it’s listed under “Cough and Cold” where it sells for $9.99 (a savings of $4.50!) for 6 doses.

It sounds like medicine, but it’s not. The front of the box says (in small print) that it’s “homeopathic medicine,” which isn’t medicine at all. In fact, it’s nothing more than a sugar pill, which is why the product can advertise that it has “no side effects” and “no drug interactions.”

But in much larger print, the package says “Flu-like Symptoms”, followed by a list of symptoms: “Feeling run-down, hadaches, body aches, chills, fever.” Anyone might be fooled into thinking this product is supposed to treat these conditions. If you go to the manufacturer’s (Boiron) website, they make the explicit claim that it “Temporarily relieves flu-like symptoms such as feeling run down, headache, body aches, chills and fever.” The Walgreen’s website says the same thing.

What’s in Oscillococcinum, and how can its producer get away with these claims?

Oscillo contains “Anas barbariae hepatis et cordis extractum 200CK.” Don’t be fooled by the Latin – it just means extract from the heart and liver of a duck. Yes, they kill ducks to make this stuff. The manufacturer then dilutes it to 200C, which in homeopath-speak means that 1 gram of extract is diluted to one part in 10⁴⁰⁰. Yes, that’s 10 raised to the power 400. Wow! The entire known universe has far fewer than 10⁴⁰⁰ molecules. If you filled the entire solar system with water, and mixed in one molecule of duck liver, it would be much more concentrated than this stuff. Oscillo is so diluted that there is essentially zero chance that even a single molecule of the original extract is in the product. The package does say that sugar is added to the pills, and that’s all they are: sugar pills.

The idea that infinitely diluted substances can cure disease is a type of magical thinking, and it’s at the heart of homeopathy, whose proponents believe that the more dilute something is, the more powerful its effects. This bit of nonsense goes against basic principles of chemistry and physics, but no matter: homeopaths continue to insist on it.

And I shouldn’t forget to mention that there’s not a whit of evidence that extracts made from the heart and liver of a duck can cure the flu. Nope, not a chance.

The French-based manufacturer, Boiron, and the U.S. stores selling Oscillo can get away with this because it’s not a drug at all – it’s a supplement. Supplements are basically unregulated in the U.S., thanks to laws passed decades ago, some of them specifically designed to protect homeopaths. As long as you don’t claim that your product can treat a specific illness, you can sell it.

The box itself doesn’t say that Oscillococcinum cures the flu, but the product’s manufacturers have been making this claim on their website. Some of them have stepped over the line: the FDA sent a warning letter to one homeopathic marketer this past summer telling them that Oscillo “has not been approved or otherwise authorized by FDA for use in the diagnosis, mitigation, prevention, treatment , or cure of the H1N1 Flu Virus” and requesting that they “immediately cease marketing unapproved or unauthorized products for the diagnosis, mitigation, prevention, treatment, or cure of the H1N1 Flu Virus.”

Unfortunately, the FDA only steps in when the claims get particularly outrageous, or when (as here) they involve a high-profile disease such as avian flu. The purveyors of Oscillo can simply modify their packaging (and websites) slightly and go right ahead misleading the public.

So if you want to waste $10 on 6 sugar pills, go ahead. But at least try find a product that doesn’t require dead ducks.

Further reading: see Orac’s recent post on this same topic here.

Flu vaccine shortage

This is just a brief post to point out a news article on the wires today (from Agence France-Presse) quoting me at some length about the shortage of H1N1 (swine) flu vaccine in the U.S. The article discusses why the egg-based vaccine production method, which is woefully obsolete, needs to be replaced if we're to avoid such shortages. I also made a point about how risky it is for us (as a society) to be relying on chicken eggs for a virus that could wipe out chicken flocks. See the article at Yahoo news, here, or at the Daily Telegraph in the UK, here.