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What Really Happened in Malta This September When Contagious Bird Flu Was First Announced

The views expressed are those of the author and are not necessarily those of Scientific American.


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malta ESWI meeting

A view from the ESWI meeting in Malta, where Ron Fouchier first described the contagious H5N1 strain. Katherine Harmon

A controversy over whether the U.S. government should allow details of a deadly new flu strain to be published in scientific journals has recently caught fire in the media. But I first heard the news of the mutated virus months ago in Malta at the European Scientific Working group on Influenza (ESWI) meeting.

The morning was sunny and warm on September 12 in St. Julian’s. Inside the Intercontinental hotel and conference center, young researchers, jaded veteran scientists and jet-lagged policy makers piled their plates with softly scrambled eggs, American-style sausages and an obligatory piece of fruit or two, shoveling in the offerings and mumbling hellos, in the bright, sky-lit hotel restaurant.

Just across the hall, however, in the cannily named Eden Arena, the room was dark, as researchers prepared to mount the stage and explain some of the many ways that humanity might soon be threatened by a truly terrifying flu pandemic.

So maybe it wasn’t quite that dramatic, but perhaps it should have felt more so. Less than an hour later, a suspiciously sniffly Ron Fouchier, a lanky virologist from the Erasmus Medical Center in Rotterdam with a wry smile and reassuringly understated manner, would announce that he and his lab had found a way to make the deadly H5N1 that would likely be just as transmissible from one human to the next as the seasonal flu.

Circulating seasonal strains, such as H3N2, are adept at attaching to the human nasal cavity and trachea, making them easily transferable among people via a sneeze, cough or sigh. But fortunately for us, H5N1, as it has circulated in bird populations, has not yet developed this capability. Fouchier and his team wanted to see if it was possible to give it that power.

So they “mutated the hell out of H5N1,” Fouchier said, towering over the podium at the meeting’s Monday morning plenary session. But as it turns out, they hardly needed to. With just a few genetic substitutions, the virus was able to affix to nose and trachea cells—a development “which seemed to be very bad news,” he said. Fortunately for the lab’s test ferrets, a common animal model for human flu transmission, the flu still didn’t seem to pass airborne from animal to animal.

And that was when “someone finally convinced me to do something really, really stupid,” Fouchier recounted. They put the mutated H5N1 into the nose of one ferret, then took a sample of nasal fluid from that ferret and put it in the nose of another. After 10 ferrets, the virus began spreading from ferret to ferret via the air just about as easily as a seasonal flu virus.

In all that ferret hopping, the virus gained only five new genetic substitutions. And that was also “very bad news,” Fouchier proclaimed, adding an “indeed” for emphasis, just in case the ramifications were lost on any of the hundreds of flu folks in the audience.

At the time, Fouchier declined to specify the exact locations of the mutations but noted that the key substitutions are in the HA and PB2 areas. All of the mutations needed to make the virus an airborne threat have already been detected in the wild, but they have not been found together in a single virus “just yet,” Fouchier noted. The discovery also confirmed that H5N1 would not need to mingle with a mammalian virus before becoming easily transmissible among us.

H5N1 has killed about half of the people who have gotten it (most were likely infected directly from contact with fowl—hence its common nickname, bird flu). For comparison, the 1918 influenza pandemic strain of H1N1 killed between 10 and 20 percent of those who caught it.

“This is a very dangerous virus,” Fouchier said, posing the question so many in the audience had surely been mulling over: “Should these experiments be done?” His answer was cool “yes.” He defends his lab’s work, which was funded by grants from the U.S. government, and he has spent the past weeks reassuring interviewers that the virus is closely controlled. “It’s important that we keep working with these viruses,” he said. And he advocates that the findings have an important power to “send out the message that H5N1 could become airborne,” he said. And that knowledge should spur scientists and policy makers alike to work harder to develop better vaccines and try to eradicate it in the wild.

The virus itself already kills—or necessitates the culling of—millions of chickens in Asia each year, which can be a huge economic hit to local farmers. To say nothing of the danger that each new infection—in human or fowl—ups the odds that these mutations will come together on their own. Knowing which mutations are needed to make H5N1 transmissible among humans could put scientists and those in charge of tracking the virus on closer watch for any of them when they appear in the wild.

At a reception the next evening in Malta, Maria Van Kerkhove, of the Imperial College London’s School of Public Health, told me that from a scientific perspective, she thought this particular recombination has a “low probability” of occurring. But given its exceedingly high mortality rate it’s a “really high-impact thing to prepare against—it’s like preparing against terrorism.”

But that was the end of the terrorism talk—a threat that has repeatedly been raised in arguments against publication of the full findings in Science and Nature (Scientific American is part of Nature Publishing Group). The scientists at the ESWI meeting seemed already in agreement with a concept recently articulated by the film Contagion, released earlier that month. As Laurence Fishburne’s character, an infectious disease expert in the movie says: “Someone doesn’t have to weaponize the bird flu—the birds are already doing that.” Only in the real life case these days, we’re fixated on ferrets. Fluish ferrets—and a switch-by-switch map of the mutated virus—or not, a nefarious influenza plot seems unlikely. Without a vaccine and with such quick and frequent global travel, any group unleashing such a deadly virus would eventually wind up putting half of their own at risk as well.

Katherine Harmon Courage About the Author: Katherine Harmon Courage is a freelance writer and contributing editor for Scientific American. Her book Octopus! The Most Mysterious Creature In the Sea is out now from Penguin/Current. Follow on Twitter @KHCourage.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. treal10 9:29 pm 12/31/2011

    This is an irresponsible and alarmist article that totally misrepresents the significance of the data. Have you done a literature search for publications on this topic or interviewed any flu researchers to get their opinions on this? This type of experiment has been going on for YEARS – that is why we understand what we do about flu transmission and virulence. That is why we have vaccines that have been tested in animals for efficacy before they reach our children and grandparents. The work you were presented with in Malta was funded with NIH dollars, was accepted for presentation at an international conference, and was accepted for publication in a top scientific journal because it is important and is NOT reckless. We have much to learn about avian flu viruses and the likelihood that humans could come up with a more virulent virus than could emerge in nature is miniscule, at best. You have fallen prey to a scientist who is hoping to get some publicity from folks like you who don’t understand the significance (or lack thereof) of some basic science experiments.

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  2. 2. fixerdave 2:16 am 01/1/2012

    “Without a vaccine and with such quick and frequent global travel, any group unleashing such a deadly virus would eventually wind up putting half of their own at risk as well.”

    True, it’s rather useless as a conflict weapon – totally uncontrollable. Yet, it’s not hard to imagine someone unconcerned with such things. The actual mutations are not that hard to create if, and this is a big ‘if’, you’re unconcerned about a clear process or even surviving the results. Basically, just collect and breed together as many strains of flu as possible… until it’s out of control. They’ll do the gene swapping all by themselves.

    Who would do such a crazy thing? Well, a crazy person. You know, someone that thinks there are too many people on this planet and that killing off half of them would save the whales, solve global warming, postpone peak oil, stop the seas from being over-fished… etc, etc, etc,… Honestly, lots of very real problems would be solved rather quickly by rapid depopulation. Yes, you’d have to be a first-class wacko to believe the ends justified the means, but there’s not really a shortage of those types around these days.

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  3. 3. ASHIK 3:43 am 01/1/2012

    U.S government should allow details of a deadly new flu strain to be published in scientific journals.Public gets aware of dangerous possibilities of how infection can spread.

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  4. 4. CRS, DrPH 3:56 pm 01/1/2012

    I disagree with comments by treal10 and fixerDave. As a researcher who has studied bioterrorism since the 1970′s (Soviet Union conflict), the old consensus was that creation of powerful bioweapons with no vaccine was not something that an enemy of the USA would accomplish.

    However, since then, we have seen the rise of a number of groups who demonstrate total disregard for humanity in general and their own populations in particular. Religious cults such as Aum Shinrikyo, governments led by totalitarian regimes and religions that practice suicide attacks all represent grave dangers to the world if they become equipped with weaponized viruses , and providing them with the recipe to re-engineer viruses is dangerous.

    We also cannot discount the possibility of lab accidents or mischief by researchers. Bruce Ivins, a US Army researcher in anthrax, demonstrated the dangers of mixing lab research into bioweapons with mentally unstable personalities.

    The US Government and others were wise to request a block on publication, but I fear that these techniques will become disseminated eventually. I agree with the closing words of the editorial:

    “Whether this experiment is published or not, it is a reminder of the power of biology and its potential. We need new approaches for the rapid development of large quantities of medicines or vaccines to protect us against new emerging viruses. But engineering highly transmissible strains of avian flu is not the way to get us there.”

    Please read this editorial by the Center for Biosecurity of UPMC:
    http://www.upmc-biosecurity.org/website/resources/publications/2011/2011-12-15-editorial-engineering-H5N1

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  5. 5. Interface 9:43 pm 01/1/2012

    We are already promoting weaponization of H5N1 on a massive scale . This is not done by terrorists and not in labs that may be prone to accidents. There are billions of interactions between domesticated infected poultry and mammals (pigs, humans, ferrets, cats – incidentally the ferret population in China is booming). There interactions are man-made because all involved are owned or controlled by humans…

    It’s frightening that just 5 mutations are needed — and it’s even more frightening that there are so many opportunities for this to happen in the farms in developing countries. The least-biosecure lab has far better biosecurity than millions of H5N1-infected poultry farms in developing countries.

    The lack of veterinary standards, veterinarians, and poor animal health in developing countries pose a much greater pandemic risk than bioterrorism. These pathogens should be controlled at their animal source, in livestock. If not, it seems pointless to try to control them in research labs.

    Circulation of H5N1 in poultry and the ensuing pandemic risk are a man-made problem. Reducing this risk deserves much more attention, but it hasn’t even been mentioned in discussions of the present controversy perhaps because developing country poultry farmers are not influential and developing country veterinarians practically do not exist…

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  6. 6. CRS, DrPH 4:21 am 01/2/2012

    Interface, you bring up very valid points on the natural history of all influenza viruses including H5N1! Domestication of fowl and swine, and close contact with human farmers, has long been the “reassortment engine” that has driven new pandemic flu strains. It is a given in the epidemiology community that, eventually, reassortment of H5N1 will happen, and it is just a matter of virulence and timing.

    However, experiments in deliberate reassortment are very dangerous and should not be conducted, even at the highest level of biosecurity. A precedent was set with the archiving and handling of remaining stocks of variola (smallpox) virus, which is very tightly monitored and controlled. There are many who advocate total destruction of this pathogen, but I am not one, as I think it would be a loss to science.

    Enough has been published on the H5N1 reassortment experiments that many will be tempted to recreate these results with the information at hand. It would not take much equipment to do this, and wild H5N1 virus is not difficult to obtain. I’m quite afraid that groups ranging from the criminal to the insane will undertake this work, and there are no limits on their activities.

    I am reminded of the myth of Prometheus….

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  7. 7. CRS, DrPH 5:29 am 01/2/2012

    Speaking of Aum Shinrikyo, this just surfaced in the news:

    http://news.yahoo.com/japan-cult-member-nabbed-17-years-run-030945153.html

    The world has plenty of crazy, murderous groups who would love to unleash a pandemic!

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  8. 8. ttheobald 7:58 am 01/2/2012

    Both sides of the publication issue have valid points, to me. While it is dangerous to publish in freely-available journals (because of the risk of a nihilistic readership), preparedness for what can surely be considered a massive risk is also necessary. As such, the block from publication makes good sense. The information remains available, is given to persons with genuine interest in vaccination, and is kept from all but the most determined hands.

    Those individuals with genuine research interest need to demonstrate a valid reason why they would need to reproduce or obtain a sample of this strain. The only reason I can see from where I sit is work on an immunization, but there may be other reasons.

    T

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  9. 9. Interface 10:23 am 01/2/2012

    CRS says: ” Domestication of fowl and swine, and close contact with human farmers, has long been the “reassortment engine” that has driven new pandemic flu strains. ”

    It would seem to make a lot of sense to modify this “engine” so it does not churn billions of H5n1 viruses. Shouldn’t it be the highest priority for science to thwart the virus at its animal source rather than wait till it transmits among humans? For instance there are no reliable and practical poultry vaccines, though they would be at least 1000 times more cost effective for preventing human illness than a human flu vaccine emerging in limited quantities only after a pandemic is underway….

    The concern about scientific work on H5N1 getting into the wrong hands may be just rearranging deckchairs on the Titanic? The “reassortment engine” made possible by an absence of public veterinary health standards is wholly a man-made creation.

    There is much too little concern about prevention of a pandemic, which is only possible by controlling the virus at its animal (livestock) source.

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  10. 10. CRS, DrPH 3:28 pm 01/2/2012

    Interface, you bring up an excellent point:

    “It would seem to make a lot of sense to modify this “engine” so it does not churn billions of H5n1 viruses. Shouldn’t it be the highest priority for science to thwart the virus at its animal source rather than wait till it transmits among humans? ”

    In fact, modern confinement agriculture in the developed world practices a very high level of biosecurity in their operations to prevent sick workers from infecting swine & poultry and vice-versa. The recent swine H1N1 seems to have originated from a Mexican swine operation near Veracruz, MX (I work with Cargill down there). No matter how good the biosecurity is, viruses seem to find a way.

    Regardless, H5N1 is widely disseminated throughout nature in swans, geese and other migrating birds. History has shown that as waterfowl migrate, they shed the virus in geographic regions & initiate natural reassortment with wild animals. Confined agriculture certainly can facilitate this, but as you point out, there are many preventive steps that should be taken. It all costs money, right?

    Good discussion, thanks!

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  11. 11. sidelight 10:29 pm 01/2/2012

    No need for a deliberate release of the new H5N1. It’s a virus. We’ll see it soon. Anthrax terrorist was a secure, government lab scientist. Time to work on vaccines.

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  12. 12. Interface 1:29 am 01/3/2012

    Contact between wild birds carying H5N1 and humans is extremely rare. Contact between H5N1-infected poultry and humans (and pigs, ferrets, cats) is common in livestock production in developing countries. The probabilities of reassortment are proportional to frquency. Why is nothing being done to fix the “reassortment engine” of livestock production in developing countries?

    There are countries that have not a single veterinarian. Who will diagnose the first H5N1-infected pig there? Seems like we collectively prefer to wait for the human cases….by which time it’s too late (people fly , so containment is impossible whereas pigs and chickens don’t fly). Poor animal health is a threat to the entire world.

    CRS, you’re right it costs money to improve veterinary standards so that poor animal health does not endanger humans. The cost is a fraction of the cost of vaccines for humans and a tiny fraction (on the order of 1/4,000) of the costs of a severe pandemic ($3 trillion). It would be fine not to spend on biosecurity in the ‘reassortment engine’ if science told us that a severe pandemic is a once-in-4,000 years event. If the probability is higher (1/4% per year?, 1/2% per year? 1 % ? 2%?), it will cost many, many times more if veterinary standards are left dismal. It would probably make sense to assemble virologists and insurance experts to sort out where and how much to spend on prevention. The World Organization for Animal Health has assessed the disease control systems in more than 100 countries, so it’s known what should be done.

    The ‘reassortment engine’ of poor countries’ livestock production is as much man-made as labs. It’s not someone else’s problem, unfortunately.

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  13. 13. ttheobald 5:10 am 01/3/2012

    While improvement of animal standards is a laudable goal, I can’t consider it a reasonable one. China is a perfect example of why not – for thousands of years, pigs and ducks/geese have lived side-by-side in village farmers’ lands. While I would welcome preventative measures, I can’t look at human history and assume we’ll realistically see them implemented until after a major disaster.

    Vaccinating livestock costs major money – the research behind it, the delivery of serum, and the application of same. It would have to be done with every animal, which means an endless supply for the billions and billions of farm animals involved, with a constantly-rotating vaccine. That’s just not going to get done.

    Vaccinating the human population in anticipation of, or reaction to, a strain of flu is the only option I can see as being a realistic goal here.

    T

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  14. 14. Interface 1:05 pm 01/3/2012

    Improvement in animal health may be laudable, but it is even more an economic imperative. It’s far cheaper to control a disease in livestock than to deal with the same disease in humans. A 50 cents per chicken vaccine looks expensive to the farmer relative to the price of a chicken. But add this up over all at-risk chickens and the cost is very, very modest compared to the reduced pandemic risk in humans. Imagine, no need to buy $4 billion worth of Tamiflu (nearly all expired?), perhaps just $1 billion would suffice.

    The benefit of an averted severe pandemic is on the order of $30 billion per year (1% probability times $3 trillion cost), every year. Improved animal health is a very good deal, not expensive. May even be laudable, but that’s not the point. We should not maintain a “reassortment engine” that is a net burden to people, not a net benefit.

    Cost of improved animal health is, for instance, in People, Pathogens and Our Planet: http://siteresources.worldbank.org/INTARD/Resources/PPP_Web.pdf

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  15. 15. CRS, DrPH 9:09 am 01/4/2012

    t’bald says: While improvement of animal standards is a laudable goal, I can’t consider it a reasonable one. China is a perfect example of why not – for thousands of years, pigs and ducks/geese have lived side-by-side in village farmers’ lands.
    ——
    Indeed! Historically, a Chinese farmer would have a pig or two, some ducks and chickens, all living in the house with the family! This afforded an easy reassortment pathway for influenza viruses!

    These days, animal husbandry is larger scale, but not much cleaner in PRC. Fecal matter from fowl is commonly used for swine feed to cut costs, giving ample opportunities for virus transmission.

    Widespread vaccination of humans AND animals remains a dream. The USA cannot even reach CDC’s targets, see: http://www.cdc.gov/flu/professionals/vaccination/national-flu-survey.htm

    Many harmful illnesses such as foot & mouth can be vaccinated against, and this is mandated in some countries. However, agriculture is notoriously resistant to implementing changes that reduce risks to human health, and absent very strong regulatory drivers, this will not change.

    Given all of that, I don’t see “wild” influenza reassortment to be any bigger of a risk than in the past. Eventually, it is predicted that H5N1 will break out as a pandemic, and I personally doubt it will be as severe as some claim (1918 Spanish Flu, which killed primarily due to secondary bacterial respiratory infections that we can now treat).

    However, mischievous scientists like Ivins have proven they can unleash real misery, and past governments like the USSR and their bioweapons production demonstrate that these biotechnologies can be corrupted. I agree with many that these experiments (U Wisconsin, etc.) are too dangerous to undertake.

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  16. 16. e-man 10:37 am 01/4/2012

    Vaccination is not a silver bullet against avian influenzas in poultry.

    It has been demonstrated experimentally that vaccination doesn’t completely prevent chickens or ducks from becoming infected by H5N1 influenza viruses, or transmitting them to other birds, it only prevents them from developing systemic disease.

    This is why in pre-H5N1 days the vaccination of poultry flocks against avian influenzas was not recommended by FAO and OIE, and was actively discouraged in most countries around the world.

    Because vaccinated flocks can be infected without exhibiting any marked signs of any outbreak.

    This how we got where we are today with the H5N1 and H9N2 viruses, both of which emerged from China where poultry vaccination is widespread, and poultry vaccine-production and use historically poorly regulated in many areas.

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  17. 17. Interface 8:45 pm 01/25/2012

    Wouldn’t more resources allow scientists and veterinarians develop effective vaccines and implement disease control in poultry and other livestock? Why not try? Costs are very modest relative to the enormous benefits.

    We did send humans to the moon, so we should be able to prevent pandemics by controling pathogens at their livestock source….

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