CONTROVERSIAL BIRD FLU VIRUS STUDY PUBLISHED: The first of two highly debated studies, revealing mutations that…

CONTROVERSIAL BIRD FLU VIRUS STUDY PUBLISHED: The first of two highly debated studies, revealing mutations that could make bird flu pandemic in humans, was just openly published amid fears of spawning bioterrorism.

Here are the facts: H5N1 bird flu virus has circulated in poultry for more than 16 years, only rarely infecting humans. But humans lack immunity to H5N1 and infections are unusually severe, raising fears of a pandemic.

Why is this work necessary and important? We don’t know if airborne H5N1 can be transmitted between humans. We don’t know what mutations may arise in the rapidly evolving virus that could make it transmissible. If we knew this, we could (1) monitor circulating or newly emerging variants for their pandemic potential, (2) focus eradication efforts on viruses that already have acquired subsets of molecular changes critical for transmission in mammals, and (3) stockpile antiviral compounds in regions where such viruses circulate, and initiate vaccine generation and large-scale production before a pandemic.

How was this study done? The research focused on the viral hemagglutininprotein, HA, because it has a major role in determining host range of influenza A viruses. (For example, HA variants from human isolates prefer to bind to sialic acid coats of human cells whereas avian versions will bind well to avian cells). The researchers used a human virus with the avian HA and generated 2million random mutations. They infected ferrets, which are a good model for virology. The best adapted mutants spread to a nearby cage and infected healthy ferrets (none died).

What did they find? The HA protein has a round “head” sitting atop a long “tail” (right image). The mutations shown in red help the viral protein bind the human receptor better (a fragment is shown in orange). The surprise was a 4th mutation in the tail that helps the viral protein do a better job in fusing the virus with the human cell membrane.

What next? So the proverbial cat’s out of the bag. Not so much brouhaha this time around. Since the study was done in ferrets, it’s not known whether they would transmit as well in humans, and how harmful they would be.

Read more:

Open Access Original Paper:

Also, Tommy Leung ‘s ScienceSunday post:

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35 Responses to CONTROVERSIAL BIRD FLU VIRUS STUDY PUBLISHED: The first of two highly debated studies, revealing mutations that…

  1. Rajini Rao says:

    Don’t worry, it has turmeric….that cures everything 😉

  2. Rajini Rao says:

    Perhaps the heavy metal is bringing out doom and despair in my posts, Mahesh Sreekandath ? 🙂

  3. Rajini (Rajini Rao),

    H(appiness) ~ (R(eality) – E(xpectations))


    Clifton R. Farmer (Randy)

  4. Rajini Rao says:

    That’s a good equation to study, Clifton Farmer 🙂

  5. I am glad it was published. The situation reminds of the ethical questions of software vulnerability disclosure except with much higher stakes. I think it is always better to know.

  6. Rajini Rao says:

    I agree Dániel Darabos . Plenty of sensitive information has been published in the past. There are so many natural pathogens and toxins, not including any genetically engineered ones. It’s interesting that you bring up the excellent analogy with software vulnerabilities..never thought of that.

  7. Jim Carver says:

    The real risk here is not publishing. People always are worried about the evil demon and what they could do. No one has ever figured out what someone might do yet, that’s why it’s always a surprise.

    The risk of someone not getting this research and making strides in this field is far too great to try and sequester information. Which never works anyway, btw. that’s me 2$

  8. Chad Haney says:

    The not publishing part, reminds me of the Baxter Healthcare’s Hemassist failed clinical trial. There were several preclinical studies showing that it didn’t really work. That was work done with the same product made by the Army. Baxter claimed it was not the same formulation and proceeded with the clinical trial. Several patients died, prompting Baxter to halt the trial prematurely. I suspect that some of the people doing research with Baxter did not publish the negative results prominently enough.

  9. Rajini Rao says:

    Chad Haney , have you seen this?

    The paper that you link to concludes, “The study also criticizes the lack of timely data put forth by the companies and the lack of published studies. Both Hemopure and Polyheme published studies only several years after the completion of their trials. Additionally, unpublished studies render a thorough IRB review of trials difficult. Natanson et al. argue for the timely and complete disclosure of data to the scientific community to avoid exposing the public to unnecessary risks.”

  10. Chad Haney says:

    Rajini Rao you’ve mentioned jnrbm before but I haven’t looked at it. I left the blood substitute field and learned medical imaging because of the state of research for blood substitutes.

  11. Rajini Rao says:

    Why is it so hard to make a blood substitute? Isn’t it mostly saline? What am I missing?

  12. Chad Haney says:

    Blood substitute is a convenient name, just like artificial blood. The research is really about hemoglobin based oxygen carriers or HBOC. People tried perfluorocarbons but it’s not allosteric like Hb. So you need a lot of oxygen which can be a fire hazard and it causes other issues. Some of the surfactants cause allergies in some people. So the field’s focus is on Hb. Free Hb falls apart and clogs up the kidneys. So Baxter and others tried to cross link Hb to keep it as a tetramer. It turns out that that is not enough. So people, like me, tried polymerizing Hb. I left the field before finding out if any of the large molecular weight formulations had other problems. I suspect there are still other issues since nothing is on the market yet. Oh, and NIH and DoD basically stopped funding research in this area.

  13. Rajini Rao says:

    Oh I see, thanks. Interesting problem. It’s more about protein engineering of Hb to make it both efficient and stable as well as nontoxic. The little red cell does a good job of that.

  14. Chad Haney says:

    The RBC could be fodder for the intelligent design folks. Well except for sickle cell. I’ve said in other threads when conservatives say that private industry can do better than government funded research such as NIH, NSF, or NASA. Look at Baxter, they are a huge company that dumped millions into to blood substitute research. What happened? People died in clinical trials and we still don’t have a product. The other startups have either failed or have stalled. The difference is private industry has to answer to shareholders and they don’t have to know why or how something works. They just have to find something that works. Academic research aims to find out why and how something works so that we can do it better in the future. So yea, without government funding, we haven’t been able to do better than RBCs.

  15. Rajini Rao says:

    Bravo, well said Chad Haney . One can also point to the abrupt cancellation of the first ever stem cell trial by Geron due to, “current environment of capital scarcity and uncertain economic conditions”. I guess that creative spark and curiousity of finding out if it works isn’t enough to keep shareholders happy.

  16. Chad Haney says:

    Rajini Rao sorry I got on my soap box a bit there on your post. Carry on folks H5N1, bird flu, viruses. Talk among yourselves.

  17. Deeksha Tare says:

    Bioterrorism or no bioterrorism, anything, just about anything can happen with viruses!!

    You never know, it might get mutated all of a sudden and wreak havoc.

    Such kind of studies help us understand and get into the shoes of the virus. It’s secret of causing disease and it’s survival instinct (and the killing instinct! ) which enables it to survive, come what may… Even if it has to cross the species barrier, spread to the other end of the world or change its very own face!

  18. Rajini Rao says:

    Reminds me of the scenes from the movie Contagion, Feisal Kamil. Did you guys see it? My lab went as a fun field trip and I even did a review on it for G+ 🙂

  19. Deeksha Tare says:

    Yup! I have seen contagion 🙂

    Similar is the movie ‘Outbreak’. But believe me it’s much more gory!!

  20. Chad Haney says:

    I didn’t see either of those. I recall the trailer for Outbreak looked pretty pathetic, science-wise. Isn’t that usually the case anyway? I think there was a good YouTube video about why it’s bad to go to the movies with an engineer. Item #1, explosions in space; no oxygen = no fire.

  21. Deeksha Tare says:

    Chad Haney , the virus in Outbreak bears close resemblance to Ebola virus. As we all know, the Deadliest and the most feared BSL 4 agent (loosely based on Richard Preston’s Hot Zone I guess.) But there’s too much blood!! Not meant for the faint hearted! And thinking that something like that has happened in the past for real gives me goosebumps!

  22. Deeksha Tare says:

    Yes indeed Feisal Kamil People get hemorrhages, get sick like hell, the virus spreads like wildfire! Except the puke factor, the scientific part is quite interesting. That in the case of a BSL 4 agent outbreak, how you go about it (and also how NOT!) The ways and real applications of biocontainment, the biosafety measures et al!

    We have seen these movies like we’d read our textbooks! Surreal stuff.

  23. Deeksha Tare says:

    Thanks for sharing the links Chad Haney

    Contagion mostly deals with the social, emotional, political and scientific repercussions of an outbreak. Plus the awesome role played by epidemiologists.

  24. Chad Haney says:

    I deal with very mild biohazards, like adenovirus and HSV, so I don’t know if the 48 hr time frame to spread to the whole US is Hollywood BS. Simple geography would suggest that mountains and deserts would be spared.

  25. Deeksha Tare says:

    Feisal Kamil , yet to read that one, seems interesting though 🙂

    Chad Haney but we can’t ignore the ‘people’ who carry the virus in themselves going across mountains and deserts and everywhere. Highly transmissible viruses which get transmitted via the aerosol route thus can travel across quite easily. The disease symptoms though might appear after 48 hrs depending upon the incubation period.

  26. Rajini Rao says:

    I’m away at a conference Feisal Kamil or would post links! If you search with my name and Contagion you’ll find the COOLEST movie ad ever!

  27. Chad Haney says:

    Probably this:

    Fungus Amongus! Bacteria R Beautiful!

    There’s more than one hit from:

    contagion movie inurl:114601143134471609087

  28. I support this publication!

  29. Rajini Rao says:

    Gerd Moe-Behrens , so do I! Interesting that there is not so much public attention now that the data are out? Only a few months back, G+ was flooded with indignant reshares with people asking how scientists could be so stupid as to play with fire 🙂 Oh, how fickle is our attention span!

  30. Rajini Rao Agree, some public discussions have a strange dynamic. For me personally, this discussion was not so much about my desire to get the data. This field is outside my personal research interest. It was about censorship and freedom of science. I personally believe in open and free access to all scientific data. censorship do not stop evil doers. For them we might need a bio defense system. Actually I am coauthoring at the moment a review about safety and security in SynBio. We have a lot of options for engineering safety. see e.g.: Synthetic constructs in/for the environment: Managing the interplay between natural and engineered Biology byMarkus Schmidt a, Víctor de Lorenzo

  31. Rajini Rao says:

    I find the protein structural information fascinating, Gerd Moe-Behrens , but otherwise I’m a virology noob. Looking forward to your review. Synthetic biology is a brave new frontier indeed! Just returned from a meeting with the Biophysical Society where we decided to add Synthetic Biology as a new topic for abstract submissions 🙂

  32. Rajini Rao says:

    He’s starting early on a disreputable career of threadjacking.

  33. Rajini Rao says:

    Mahesh Sreekandath can bring death and destruction to any post, no need for bird flu. Gnotic Pasta , no reaction from kid behind me..hmm. OTOH, I’m quite enjoying it. What is happening?

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