Mad scientists? Or, is there any justification for trying to recreate a deadly virus?

by Matthew Cobb

I saw this article by the excellent Ian Sample on The Guardian website last night, and was simply appalled. A group of US and Japanese scientists, led by Yoshihiro Kawaoka of the School of Veterinary Medicine at University of Wisconsin-Madison decided to try and recreate the Spanish Flu virus which killed millions of people after WW1. The abstract of their paper, ‘Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential’, published in Cell Host & Microbe, starts off well:

Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918- like pandemic viruses may emerge in the future.

In other words, as everyone knows, we are in danger of another flu pandemic that could kill millions of people. The abstract continues:

To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited pathogenicity in mice and ferrets higher than that in an authentic avian influenza virus.

Yes, that’s right. To see whether a virus with characteristics like the 1918 virus would be dangerous, they created it! And you know what? It was dangerous.

The Discussion of the article concludes with a justification of their study:

To prepare for such a scenario [a new pandemic – MC], it is important to understand the molecular mechanisms of pathogenicity and transmissibility of avian influenza viruses. Such information provides support for pandemic preparedness activities (vaccines and antivirals are effective control measures), demonstrates the value of continued surveillance of avian influenza viruses, and emphasizes the need for evaluation and integration of improved risk assessment measures.

I am really not convinced by this, and I am amazed that the paper includes not a word about the apparent ethical/biosecurity issues. People have been arguing about whether to destroy the last remaining samples of smallpox, but we know how to cure that, and it is nowhere near as infectious as the 1918 flu virus. This seems to me to be a colossal and dangerous mistake. Nothing that I have read in the paper convinces me that the insight they have gained is worth the risk of the damn thing getting out.

Lord May, former President of the Royal Society, is quoted in The Guardian article:

“The work they are doing is absolutely crazy. The whole thing is exceedingly dangerous. Yes, there is a danger, but it’s not arising form the viruses out there in the animals, it’s arising from the labs of grossly ambitious people.”

Marc Lipsitch, professor of epidemiology at Harvard School of Public Health, said:

“I am worried that this signals a growing trend to make transmissible novel viruses willy-nilly, without strong public health rationale. This is a risky activity, even in the safest labs. Scientists should not take such risks without strong evidence that the work could save lives, which this paper does not provide,” he added.

Kawaoka defended his work from criticism, referring to some of his previous work:

“There were discussions on the usefulness of stockpiling H5N1 [bird flu] vaccines until our H5N1 papers were published. Similarly, this paper strongly supports stockpiling anti-influenza drugs. If this is not a ‘lifesaving benefit’, what is?” he said.

NIH, who funded the research, said this:

Carole Heilman, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases (Niaid) in the US, said: “This study was conducted as part of a research project on understanding the molecular mechanisms of virulence of the 1918 influenza virus. NIH peer review determined that the research was scientifically meritorious. It was also determined that the information gained had the potential to help public health agencies in their assessment of circulating and newly emerging strains. In addition, NIH determined that all the research was being done under appropriate biosafety conditions and with appropriate risk mitigation measures.”

I’m afraid I’m with Simon Wain-Hobson, a virologist at the Pasteur Institute in Pari:

“It’s madness, folly. It shows profound lack of respect for the collective decision-making process we’ve always shown in fighting infections. If society, the intelligent layperson, understood what was going on, they would say ‘What the F are you doing?'”

What do readers think? Am I over-reacting? I’d be especially interested in anyone with insight into this field – is this information of any conceivable use in the fight against the next flu pandemic? Best of all would be if the authors, or anyone else involved in the reviewing the paper or the original research application, chipped in below the line to convince me and, I suspect, many readers, that this is not some colossal, hubristic mistake.

You can download the article for free, it appears, here.

64 Comments

  1. GBJames
    Posted June 12, 2014 at 12:10 pm | Permalink

    My 2 cents: Very unwise. I don’t understand the point of creating horror-show viruses on purpose. Nor do I understand the point in keeping smallpox around just in case we figure out something to do with it someday.

    On a planet in the middle of another great mass extinction, adding more potential catastrophes doesn’t make much sense to me. Aren’t there extant avian flu viruses that merit the study?

    • Spirula
      Posted June 12, 2014 at 12:48 pm | Permalink

      I did research with a virologist and asked her about this very question. Her response was that although there have been no new cases since the early 70’s, both the US CDC and the Russian equavilent have high security labs where smallpox virus is maintained. Clearly, both thought the other might use it as a biological weapon. Also, it is not known for certain that no other secret cultures exist. It also provides both countries with the ability to rapidly produce a vaccine should the virus be released.
      Doesn’t make me feel any better about it, but the rational isn’t all that unreasonable.

      • JBlilie
        Posted June 12, 2014 at 1:17 pm | Permalink

        The vaccine is developed from cow pox. You don’t need smallpox virus to do it.

        • Spirula
          Posted June 12, 2014 at 4:51 pm | Permalink

          Thanks. I did not know that. Maybe she was referring to a weaponized version and you would need the “original” to detect the difference. It was a conversation I had over 3 decades ago so I may have forgotten some of the details.

      • gravelinspector-Aidan
        Posted June 12, 2014 at 3:26 pm | Permalink

        Also, it is not known for certain that no other secret cultures exist.

        It doesn’t need to be a “secret” culture ; there’s the potential for preservation of the organisms in the bodies of high-Arctic explorers etc buried in permafrost. Whether it’s a real case, I don’t know but the potential is there.

  2. AndrewD
    Posted June 12, 2014 at 12:13 pm | Permalink

    mike the mad biologist’s take on this is here
    http://mikethemadbiologist.com/2014/06/12/what-recreating-the-spanish-flu-really-risks/

    • Posted June 12, 2014 at 12:33 pm | Permalink

      There are two comments about the bad thing created in the lab at the bottom of mike’s take.

      Person 1): I wonder when the US Army will weaponize this?

      Person 2): Yesterday. But don’t worry, you can trust them.

    • infiniteimprobabilit
      Posted June 12, 2014 at 11:59 pm | Permalink

      I love Mike’s by-line:
      “Helping idiots who desperately need my assistance by calling them fucking morons since 2004.”

  3. gluonspring
    Posted June 12, 2014 at 12:18 pm | Permalink

    Correct me if I am wrong, but my impression of how the author claims this will contribute to saving lives is to scare public health officials into stockpiling anti-viral drugs. Seems like a good film outlining what we already know and suspect about the emergence of new viruses could do that.

    I don’t see anything in this that suggests that they have learned anything useful about actually fighting new deadly strains. The supposed benefit seems purely to be that it will light a fire under public health officials to, you know, do what they probably should be doing anyway.

    • gluonspring
      Posted June 12, 2014 at 12:34 pm | Permalink

      The mechanism that confers droplet transmission might be useful to understand. Especially if there were some way to neutralize this effect, perhaps through vaccine design or other agents that can have the same effect as these antibodies:

      http://www.jci.org/articles/view/69377

      However, these and other authors have already looked into this before this paper:

      http://www.ncbi.nlm.nih.gov/pubmed/22722205
      http://www.pnas.org/content/early/2011/08/05/1111000108

      So I’m really not clear on what this paper adds other than to emphasize that only a few amino acid changes from existing pools could generate a new strain like this. The main practical benefit of that knowledge seems to be to spur (scare) public health officials into taking action that, in my view, they should already be taking.

      • Todd Steinlage
        Posted June 12, 2014 at 8:23 pm | Permalink

        Isn’t it beneficial for epidemiological modeling? Sequencing is often done during epidemics to see what strains are circulating. This information may be useful.

        Research often repeats older research, sometimes with the same results, sometimes with different or more refined results. I’m not overly worried about it, but I work with plant viruses 🙂

        • Posted June 13, 2014 at 9:27 am | Permalink

          But surely plant viruses are almost as bad: we depend on agriculture, forests, etc.

      • Sergio Graziosi
        Posted June 13, 2014 at 2:05 am | Permalink

        The main practical benefit of that knowledge seems to be to spur (scare) public health officials into taking action that, in my view, they should already be taking.

        Talking about questionable public health practices, I fear your view has been shaped by profit-led decisions on data (non)disclosure. If you are thinking that “taking action” means stockpiling Neuraminidase inhibitors (Tamiflu et al.), we now know that the public was misled by omission.

        See the latest update of the relevant Cochrane review, the BBC coverage (presents both views), and this Guardian article by Goldacre (clearly committed to one side).
        [Side note: if you find the above appalling (as I do), you may want to have a look at the All Trials campaign]

        For the current matter, I’m very close to the fence: you can’t predict how useful understanding new things might be, making it impossible to balance risk and benefits a priori. As a consequence, allowing this sort of high-risk research is always going to be controversial, but we can’t just say: the benefits so far have been too little to justify the risk. This may change in an instant if a breakthrough is made. Hence, we need a better a priori criteria to make a decision, but unfortunately I can’t formulate one that convinces me. As a result, I’d be inclined to take the majority stance and say that this study should not have been funded, but also admit that I can’t be sure.
        The other more disturbing idea is that the study was funded because it was (correctly) hoped that it would be possible to use it to scare people and governments into spending millions to stockpile drugs that won’t help. If in doubt, follow the money :-/

  4. lamacher
    Posted June 12, 2014 at 12:36 pm | Permalink

    This is a blunder of the highest order, worthy of Inspector Clouseau. They should be ashamed of this hubris.

  5. Posted June 12, 2014 at 12:46 pm | Permalink

    My grandfather survived the 1918 influenza, so I hope I inherited some of his genes that did the job. But I think it is unlikely that the bird flu influenza virus would mutate exactly back to the deadly 1918 strain, so preparing vaccines for the 1918 strain might be a useless exercise. But you might need it if adding this strain back to this world, this seems to me not responsible at all. But I’m not a virologist…

    • gravelinspector-Aidan
      Posted June 12, 2014 at 3:29 pm | Permalink

      I think you’ll find that the genes that give your immune system it’s priming are comprehensively re-shuffeld each generation so you’d only get a quarter of your grandparent’s resistance genes.
      Which may help. Or may not.

      • Posted June 12, 2014 at 4:21 pm | Permalink

        Not quite right. At MOST you would expect to get 1/4 of the genes responsible for grandpa’s survival. But, that assumes there is some sort of gene for that. Which we quite frankly don’t know. Hence why this research could be helpful. But in reality it is extremely unlikely to be a single gene but rather a cluster of genes along with developmental aspects unique to gramps that led to him being able to survive infection. The likelihood that this will be passed on to even the F1 generation is extremely low. The only case in which it would work is if the virus was thwarted because a specific cell surface marker or specific immune cell variant allowed specific resistance against the specific lethality of that specific virus. In which case the 1/4 chance idea works… ASSUMING that the new virus in question also has that Achilles heel. In other words, possible but not very likely at all.

  6. Gregory Kusnick
    Posted June 12, 2014 at 12:47 pm | Permalink

    I’m far from an expert on this, but it seems to me that the claim being made is that it’s only a matter of time before the natural reshuffling of avian flu genes effectively resurrects the 1918 virus anyway, or something very much like it.

    If the counterclaim is that we needn’t worry about that because we already have adequate tools for controlling such outbreaks, then where’s the danger in artificially re-creating it?

    On the other hand if what makes it dangerous is that we can’t control it, then surely there’s some value in learning how to control it before the next naturally occurring flu pandemic (which seems to be what this work aims to do).

    Or is the argument that the next natural pandemic will likely have entirely novel “molecular mechanisms of pathogenicity and transmissibility” so that nothing we might learn from the re-created virus will be of any practical use? If so, on what basis do we think that?

    Note that I’m not advocating one position or the other here, just trying to clarify the issues, because (to me at least) it’s not obviously a no-brainer either way.

    • Vicki
      Posted June 12, 2014 at 6:08 pm | Permalink

      I think the counterclaim is that the re-emergence of such a virus us not inevitable, and that it does happen, in however many months, years, or decades before it happened by chance, we might develop better mechanisms for controlling flu outbreaks than we have today.

      Also, if someone told me that I have the choice of developing cancer next week or the same cancer twenty years from now, I’d take twenty years from now even if I knew that there would be no progress in cancer treatment between now and then, because I would want those twenty years.

      Even if there’s no progress in antiviral drugs, vaccines, or other infection control measures between now and when such a virus reemerges on its own, billions of people get to live however many years longer before possibly catching that flu.

      The argument here seems to be “if we recreate this nasty virus in the lab, it will spark development of vaccines and antivirals, which didn’t happen because of the 2009 H5N1 outbreak, and won’t happen because of any other argument or incentive.”

      • Gregory Kusnick
        Posted June 12, 2014 at 6:47 pm | Permalink

        Perhaps I’m misunderstanding you, but you seem to be arguing that billions of people will die early deaths because of this research. That seems rather unlikely.

        There’s a risk that some unknown number of people may die if the reconstructed virus escapes from the lab and sparks an outbreak. I don’t know how to quantify that risk, and it’s not clear to me that anybody else does either. So I don’t think we can say with any confidence that billions of lives will be saved by prohibiting such research.

  7. Moarscienceplz
    Posted June 12, 2014 at 12:48 pm | Permalink

    With 40% of my fellow Americans sure that the Earth is less than 10 ky old, and the high number of anti-vaccine people, I am more scared of the hoi polloi being given yet more veto power over scientific research than I am about 1 or 2 more pandemics being added to the ones we naturally can expect.

    • Todd Steinlage
      Posted June 12, 2014 at 8:31 pm | Permalink

      Absolutely agree. The lay public has shown again and again that they do not care and do not understand. Science is not a popularity contest. I don’t want to be seen as an elitist, but frankly many people are motivated by media “personalities” like Alex Jones or others who don’t know what the fuck they’re talking about.

  8. eric
    Posted June 12, 2014 at 12:49 pm | Permalink

    Kinda in the middle. On one hand, I’d rather not second-guess the microbiologists and virologists in the NSF that gave this the green light. Palin did that, and I don’t want to be her. Also, I think the risk of holding it in a lab could be made acceptably low – after all, 40 years of smallpox storage, no slip-ups. Whether they did make it acceptably low is a different argument. The devil is in the research method details, but I’m not going to say offhand that no possible safety procedures would make it worth the risk.

    OTOH, I don’t see how this will accomplish the goal they set for themselves. They say that the spanish flu differs by only a few amino acids from current bird flus. Well okay, but knowing evolution, I would think that any new flu would also differ from both versions by a few amino acids. So your spanish flu understanding is not going to be any better at predicting the new virus’ effects than the data you could have collected from current disease types. So what did you gain by swapping one genetically distant cousin for another, more dangerous, equally genetically distant cousin?

    • Ben Sheldon
      Posted June 12, 2014 at 1:47 pm | Permalink

      Not quite “40 years of smallpox storage, no slip-ups” – this case from 1978 in the UK resulted in the death of Janet Parker, and the suicide of the Head of the Microbiology Dept at the University of Birmingham:

      http://en.wikipedia.org/wiki/Janet_Parker

    • gravelinspector-Aidan
      Posted June 12, 2014 at 3:32 pm | Permalink

      after all, 40 years of smallpox storage, no slip-ups.

      Several slip ups. In particular, Birmingham in IIRC 1977, which killed one person and scared the living excrement out of my home town.

  9. Posted June 12, 2014 at 12:58 pm | Permalink

    Although the researchers may be trying to do something ‘sensational’, I for one can see that there is some value in developing this virus, under super-duper tightly controlled multiply redundant safety conditions. Since the damn thing could re-form naturally, I would be in favor in taking preparative steps that could help us detect the strain in the field, and to test the effectiveness of vaccines.

    • GBJames
      Posted June 12, 2014 at 1:06 pm | Permalink

      “…the damn thing could re-form naturally…”

      This is the part that I’m not convinced of. It seems like one of those logically possible but astronomically improbably things that cause people to focus on the wrong risks.

      • Michael
        Posted June 12, 2014 at 1:28 pm | Permalink

        When one considers the virus load of a single infected animal is probably in the billions, and the number of animals infected could be millions, it’s possible that “astronomically improbably things” may happen faster then we might expect.

        This is my biggest concern when it comes to GMO’s, that shuffling genes between plants, mammals, insects and fungus could make it even easier for a virus to change to something much more deadly, allowing a plant virus to jump to mammals, or insects…

        I haven’t been able to find any information concerning this and it’s probability.

        • Posted June 12, 2014 at 3:23 pm | Permalink

          Well… if you Google for info about GMO’s you will get a lot of hits from anti-GMO sites. I have examined these as time allows, and I can report that all I have seen is a lot of hype and hysteria and pseudoscience. Twisting of facts, and imagining the worst of all possible worlds from something less likely than what good ‘ol evolution can create on its own.
          My position on GMO’s is to keep an eye on them, but to worry more about things like asteroids and F5 tornadoes.

          • Michael
            Posted June 12, 2014 at 10:03 pm | Permalink

            I agree there is a lot of anti GMO nonsense on the internet. But that doesn’t mean there has been much research done on trans-genetic GMO organisms and the possibility of a dangerous pathogen created.

            It may very well be an extremely low probability event, but these types of viruses would be extremely dangerous. New crossover viruses tend to be high mortality.

        • Todd Steinlage
          Posted June 12, 2014 at 8:44 pm | Permalink

          There is a concept relating to the diversity of viral populations, called a quasi-species cloud. Awesome name. It represents the diversity possible after numerous cycles of replication. Since RNA viruses have high mutation rates, they can generate new strains fairly quickly (of course other constraints limit their viability).

          • Posted June 13, 2014 at 5:31 am | Permalink

            Sure, a copy of virus DNA put into transgenic plants or animals could mutate into something novel, but my view is ‘so what’? The odds of a problem are overwhelmingly diminished compared to what native viruses can dish out.
            As I understand it, the viruses used are engineered with extra DNA baggage. They have a big foreign gene or two put into them. This is the DNA researchers wanted to go into the GMO in the first place. They have other genetic modifications that help researchers cut the DNA with enzymes. B/c of the extra DNA, the modified virus DNA is very crippled.
            Plants and animals are loaded with native virus DNA inserts. Its the the native viruses that can (and have) evolved into new pathogens.

            • Michael
              Posted June 13, 2014 at 9:21 am | Permalink

              Perhaps I did not make myself clear. I’m not concerned about viruses used in GMO work. Not at all.

              I’m talking about natural viruses infecting trans genetic organisms possibly allowing the viruses to cross species.

              The more genetic material that is transferred into another species, the higher the possibility of a natural virus crossing species. If the amount is extremely small, then its highly unlikely.

              On the other hand, a pig with human blood gene(s) or another with human transplant-able organs has a higher possibility of getting infected with a natural virus, and that virus mutating to allow infection in humans.

              An animal raised for human blood and organs would be kept in reasonably sterile environments, but this is an example.

              Pigs are already a vector for human viruses. Pigs can get some bird flu and humans can get pig flu. It is thought that a pig flu virus mixed with a bird virus in swine, which created a new deadlier strain of flu which crossed to humans.

              I don’t believe the amount of material transferred in most GMO work would make any difference, but they have worked on pigs and sheep to make human blood, human transplant organs and cows making human milk.

              The industry is in it’s infancy, an industry that I think it holds a lot of promise. But I think it needs to be watched too. Too many high value industries have captured their regulators.

  10. Michael
    Posted June 12, 2014 at 1:15 pm | Permalink

    The possibility of a world wide pandemic has scared me ever since I first read Stephen King’s novel The Stand. Although that was fiction, (with a fair amount of superstition and religion) the Spanish Flu was not, and it killed over a 100 million people, most of which were healthy men and women in the prime of their lives.

    Unfortunately it’s worse then just some scientists creating viruses in the lab. Growing viruses isn’t hard and if you don’t really care too much about safety, it doesn’t cost a lot of money.

    It’s always been within the ability of even the poorest country to create biological weapons. Now it’s within the grasp of middle income individuals.

    As laboratory equipment prices fall neighborhood laboratories are beginning to spring up in larger cities. Sort of like a co-op woodworking shop, except the focus is on biotechnology. They have boards that oversee what is being done to prevent mad scientist scenarios, but as used equipment prices fall, the cost to equip a home lab plummets.

    The major factor restraining crazy people from making their own killer pandemic will be skill and knowledge. It will always be easier to grab a gun and shoot up a school or business then it will be to spend months, perhaps years collecting viruses, screening and propagating for maximum lethality combined with maximum transmission.

    Eventually it may be possible to create full DNA sequences to order with a DNA synthesis machine, which are already in use in some labs. They allow a gene to be created from scratch without having to have the entire lethal pathogen around. Eventually they might even allow the creation of entire bacteria or virus, made to order via a downloaded DNA sequence over the internet, cut and pasted with some other sequence then printed like a 3D printer.

    What scares me is it’s not a question of if it will happen, but when the next pandemic will occur, and that there are people who would help it along if they could.

    So load up on duct tape, face mask filters, plastic sheeting and hand sanitizer. Sooner or later we’re going to get hit with a pandemic. What we don’t know is just how bad it’s going to be.

    • mecwordpress
      Posted June 12, 2014 at 1:43 pm | Permalink

      I understand what you’re saying and I think given the chance it if is possible to weaponize something, someone will try. My only comment is that for tactical use biological weapons are extremely poor weapons. There is no way for those who deploy it to prevent the weapon from attacking them. In fact, it is very likely to. Missles, bombs, bullets, even chemicals, don’t spread or bounce back. Apart from mistakes that result in “friendly fire”* incidents those kinds of weapons are relatively safe for the attacker to use. Not so with biological weapons. As weapons of terror they may be useful so there may be strategic reasons to make them.

      *The mother of all oxymorons.

      • Draken
        Posted June 12, 2014 at 2:28 pm | Permalink

        But we’ve seen plenty of scenarios where religiously motivated or downright insane people don’t give a rat’s fluffy bum about their own life. And that makes them really scary.

      • Todd Steinlage
        Posted June 12, 2014 at 8:52 pm | Permalink

        I’ve heard that weaponizing many biologicals is difficult. For example, anthrax was milled into a very fine powder to make it carry on air currents and deposit deep in lungs. At least as of 10 years ago, that was difficult for many state actors to do (not sure why). Also, depending on the agent, many are negatively impacted by UV radiation or heat. Maybe more useful for causing fear than strategic purposes.

    • Michael
      Posted June 12, 2014 at 10:13 pm | Permalink

      I should point out, when I say sooner or later a pandemic will occur, I believe it most likely to be a naturally occurring one. It’s almost inevitable. Viruses are the most numerous life form on the face of the planet.

      When I say crazy people, I mean those who don’t care if the weapon they create backfires on them. How many spree killers go out knowing they aren’t going to come back? How many take out their wives and children first or parents first?

      Lets face it, many people who use violence in the middle east or other places must know their actions will cause repercussions. One killing often begets more killing, just like gang killings in LA. That’s why the killing goes on even after centuries have passed.

      Most of these people can’t even really be called crazy. They are simply irrational humans.

  11. JBlilie
    Posted June 12, 2014 at 1:20 pm | Permalink

    Seems like a very bad idea to me.

  12. Damien
    Posted June 12, 2014 at 1:21 pm | Permalink

    It’s spelled PariS!!!!!!!!!!!!!

    Oh, and is Pr Coyne over reacting? No idea, not my trade, but the fact that other biologists find it crazy suggest that it might be.

  13. Kyle Penderman
    Posted June 12, 2014 at 1:46 pm | Permalink

    Don’t tell me some terrorists groups are not already considering ways to acquire it.

    All you need is one sympathizer in the lab, or a breach in security. Anyone see 12 Monkeys?

  14. Hempenstein
    Posted June 12, 2014 at 1:49 pm | Permalink

    I know enough virologists and enough people on regulatory committees to be confident that a group @ U Wisconsin Madison is not a dangerous bunch of crackpots running wild.

    That said, by the time I might fully digest this paper, the show will have moved on, so here are a couple things I spotted from a quick skim of the paper.

    End pg 699:

    Because all of the viruses tested in this study possess the NA gene from either the 1918 virusor the 1918-like avian virus, these viruses should be highly susceptible to oseltamivir, so appropriate control measures would be available to combat the 1918-like avian virus used in this study.

    (Thus, if something like 1918 broke out, with biomolecular details similar to 1918, we have drugs now that can be expected to be efficacious in such situations.)

    And then, pg 701, end first column, start second:

    Taken together, our results reveal the global distribution of avian influenza virus genes encoding proteins that differ from the 1918 virus proteins by only a few amino acids and the existence of avian influenza viruses possessing human-type amino acid residues (i.e., PB2 E627K, HA E190D, and HA G225D). Considering the fact that many of these avian influenza viruses were isolated in recent years (i.e., from 1990 to 2011), our study demonstrates the continued circulation of avian influenza viruses that possess 1918 virus-like proteins and may acquire 1918 virus-like properties.

    (Very similar stuff is out there now.)

    • Posted June 12, 2014 at 2:52 pm | Permalink

      If we’re pinning our faith on oseltamivir (aka tamiflu) then we really are in the brown stuff. Recall this is the flu/antiviral drug the UK and US Govt have stockpiled at a cost of over US $ 2 Bn without their being any properly convincing evidence that it really does anything against the ‘flu. While the ‘Zombie 1918’ strain might be expected to be more sensitive to the drug than current ‘epidemic ‘flu strains, due to having the more susceptible form of Neuraminidase, I wouldn’t want to be basing my safety calculations on a drug that marginal.

  15. R. Dale Caldwell
    Posted June 12, 2014 at 2:13 pm | Permalink

    Where are the univesities’ research watchdog committees? NIH may have thoght it to be “meretorious” but I think it foolhardy and dangerous.

  16. Gaius Brutus
    Posted June 12, 2014 at 2:29 pm | Permalink

    Everybody writes about the risk of an accident.
    Nobody seems to remember the pious Christian Anthrax scientist.

  17. Ken Pidcock
    Posted June 12, 2014 at 3:09 pm | Permalink

    I’m not qualified to comment on the value, or lack thereof, of this particular endeavor, but I would push back against the notion that the emergence of a virulent influenza pandemic is just a matter of time and chance. Emergence is an evolutionary process, not just the existence of a particular genotype. It may well be that the strain in question could not reproduce successfully in current populations. For one thing, any action to impede transmission will have the effect of selecting against virulence, and there are more such actions available to us than there were in 1918.

  18. Posted June 12, 2014 at 3:11 pm | Permalink

    I am a medical doctor but infectious disease is not my specialty. That said, I think that this could actually be a reasonable move. We still do not really understand the mechanisms behind why the 1918 pandemic was so deadly. And we have evidence that in the H1N1 pandemic people who survived the 1918 pandemic fared better from cross immunity. And other evidence that cross antigenicity can actually make a less lethal flu more lethal for a person infected. But in any event there is significant remaining questions as to why flu in general and that flu in particular was so deadly, with evidence of multiple reasons but also conflicting evidence. Finding out mechanisms of lethality plus infectivity could provide some novel ideas for how to treat, prevent, and decrease the lethality of the INEVITABLE flu pandemic.

    That said, I don’t know where the balance lay. It is not like it is a guarantee that this research will yield anything useful, nor that if it does it will actually be all the helpful. And obviously the disastrous problems that could arise from it are, well, disastrous. One would need to assume that very high level safety precautions are taken and so far we have every reason to believe that they would be (the CDC and multiple labs around the world have safely stored vastly deadlier viruses for decades. One could argue that it could be stolen, weaponized, whatever. But the problem I see with that line of reasoning is that stealing would be a Mission Impossible style movie thing which is highly unlikely (nuclear bombs would be an easier target and better for terrorists trying to do serious damage; just remember how little of a deal the anthrax scare was a decade ago). As for the rest… well, the technology is there. Weaponization isn’t going to come from public work. It will come from black site research that will happen regardless of whatever legitimate research is going on.

    • Hempenstein
      Posted June 12, 2014 at 7:06 pm | Permalink

      I have a memory (which may be wrong!) of seeing speculations re. the severity of the 1918 flu as based largely on the large numbers of exhausted people (WWI soldiers) housed in cramped quarters, which gave rise to its rapid spread, in turn facilitating its spread into the civilian population due to the presence of a vastly increased viral load. The suggestion that accompanied that notion was that if it came along now + with better therapeutics available, it wouldn’t cause nearly the epidemic it did in 1918. No idea where such views are now, but this study may help support/discount such viewpoints.

    • conservationtrust
      Posted June 17, 2014 at 6:33 am | Permalink

      Actually, we DO understand why the 1918 influenza virus was so deadly: see both “Flu” by Gina Kolata and the new “The Viral Storm” by Nathan Wolfe. I totally concur with your statement about novel ideas resulting from understanding the mechanisms of lethality plus infectivity to prevent and decrease the next flu pandemic – and research like the article in question is part of that.

  19. gluonspring
    Posted June 12, 2014 at 4:08 pm | Permalink

    What I glean from these comments and others on other sites is that evaluating the merits and risks of this kind of research is difficult. I think what it highlights is the need for a special kind of review for proposals such as this. Perhaps the NIH already does that, but if the review process is just the usual grant approval process, well, I don’t think that’s adequate here.

    The normal grant approval process involves mostly people in the same or very similar field to those proposing the grant. Obviously that’s who will understand the proposal best, and will understand best what may be learned from it, but I’m not sure they are the best ones to evaluate the risks. Specialists tend to have a myopic and inflated view of the utility of what they are doing and may tend to view these proposals with a more bland attitude (hey, that’s cool!) than would a less invested party (holy crap!). I think there are some kinds of research that should have some independent risk or ethics review that involves people from outside the specialty. Someone to ask challenging questions such as “What if someone in the lab is disgruntled?”. Again, maybe that happens now. Surely pathogen research has a different approval process than other research? If not, it probably should.

    • Posted June 12, 2014 at 4:22 pm | Permalink

      “What I glean from these comments and others on other sites is that evaluating the merits and risks of this kind of research is difficult.”

      BINGO!

  20. madscientist
    Posted June 12, 2014 at 5:05 pm | Permalink

    Unfortunately I don’t know any virologists. On the conceptual side I think there may be great opportunities to learn things by playing with these viruses. I think the hysteria about people working with them is due to uninformed fear rather than relevant facts. For all we know, exposing the modern population to that exact same pathogen may not have the devastating effect which it had 100 years ago.

    Could a future pandemic be prevented by studying these viruses? Of course – and of course not, but you’ll never know if you don’t try. Remaining ignorant will gain nothing.

    • John Scanlon, FCD
      Posted June 13, 2014 at 3:39 am | Permalink

      “I think the hysteria about people working with them is due to uninformed fear rather than relevant facts.”

      When Bobby May says it’s a stupid idea, I’m tempted to get off the fence on his side. Argument from authority, I know, but… suppose you were a physicist, and heard an opinion about a physics question (not in your specialty) by Dirac or Feynman, would that be an influence? Besides, he was at uni with my parents.

      But if it were anybody else, I’d probably call it hysteria. 🙂

  21. Posted June 12, 2014 at 7:11 pm | Permalink

    Someone ask ERV. Remember ERV? Isn’t she a virologist or something similar?

    • Posted June 12, 2014 at 9:20 pm | Permalink

      Abbie Smith, yes. And I agree with her. Ignorance is definitely not bliss, where it concerns these bugs – and another pandemic (not necessarily of the exactly the same type) IS only matter of time, esp. given the ridiculous population levels we have now over those of 1918. Similarly, smallpox just might save our butts someday.

  22. John J. Fitzgerald
    Posted June 12, 2014 at 9:25 pm | Permalink

    Jerry,

    Thank you for blowing the whistle on this asshole! (Pardon the vulgarity!)

    We do not need a repeat of the 1918 influenza disaster!

    Onward!

    John J. Fitzgerald

    • Dominic
      Posted June 13, 2014 at 5:04 am | Permalink

      Matthew…!

  23. Dominic
    Posted June 13, 2014 at 5:08 am | Permalink

    I think that if we CAN do it we probably will.

    If it were not for unethical experimentation there are many advances that would never have happened, inoculation being one! For those of you who read Norwegian –
    http://www.forskning.no/artikler/2014/juni/393612

    • bobsgutarshop
      Posted June 13, 2014 at 6:35 am | Permalink

      Damn! . . . I’m learning Norwegian NEXT week.

  24. marvol19
    Posted June 13, 2014 at 8:54 am | Permalink

    This reminds me of the anecdote I read long ago about a man who gets caught trying to take a bomb onto an airplane in his hand luggage.

    When asked why he did this, he explains that this is to improve safety. He’s read that the risk of a plane carrying a bomb is 1 in 1 million, so the risk of a plane carrying two bombs is only 1 in 1 trillion. As he is not planning to set off his bomb, he has just reduced the risk of the plane being blown up by one million!

  25. Posted June 17, 2014 at 4:03 am | Permalink

    As a (trainee) geneticist, I can see why there would be merits to doing this kind of work.

    By re-creating genes/proteins in modern viruses with similar sequence/structure to the 1918 pandemic virus, we have a chance of understanding what made the latter virus so successful at invading host cells, replicating therein, and infecting new hosts. This is what the authors argue, and the people who support their work: that this kind of research is crucial at understanding what made the 1918 pandemic flu virus different from other flu viruses, to help us avoid similar pandemics in the future. To look at how the sequence of the 1918 virus differs from less pathogenic strains, and how this affects the resultant structure of its proteins, and how these interact with host cells, holds the key to understanding the biology and function of the pandemic flu virus — and therefore also to how to prevent infection in the future.

    As a (wannabe) philosopher of science, I am however finding it harder to justify this kind of work.

    As the matter stands, virologists have been working on trying understand the molecular mechanisms of flu viruses for decades, without any truly breakthrough discoveries having resulted (as so often is the case in science). We understand the flu virus in detail, but not sufficiently to be of any direct use to us. Without virologists understanding the average flu virus well enough to prevent epidemics of annual, benign strains, how can we expect them to gain any effective understanding of more pathogenic strains? It is important to understand the basics before you move on to more complicated things, and failure to do so seems, to me, like mis-guided sensationalism without any genuine purpose.

  26. conservationtrust
    Posted June 17, 2014 at 6:20 am | Permalink

    Jerry, I’m an RN, retired PNP, former Army nurse, and Local Health Officer. And I totally support the research done by this study! I recommend to you two excellent books,”Flu” by Gina Kolata, subtitled “The Story of the Great Influenza Pandemic of 1918 and the Virus that Caused It” and “The Viral Storm” by Nathan Wolfe, subtitled “The Dawn of a New Pandemic Age”. This is not an idle academic exercise: in our age of swift intercontinental travel, when folks can spread illness before they even know they are sick, understanding how these organisms work enables us to rapidly react and counteract when they appear. Think the current MERS virus from Saudi Arabia, and how quickly it was contained. As Nathan Wolfe puts it: “We live in a world fraught with risk from new pandemics. Fortunately, we also now live in an era with the tools to build a global immune system. This huge but simple idea is that we should and can be doing a much better job to predict and prevent pandemics.” You have to understand your enemy if you want to successfully defeat him.


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