The NSABB speaks on influenza H5N1

31 January 2012

The National Science Advisory Board for Biosecurity (NSABB) has published “Adaptations of Avian Flu Virus Are a Cause for Concern”, an explanation of their recommendations with respect to influenza H5N1 research (versions at Science and Nature). It starts with the statement that advances in technology now allow manipulation of microbial genomes in ways that could be misused, leading to global harm. They define dual-use research as “research that could be used for good or bad purposes”.

The authors begin their discussion of influenza H5N1 with the usual incorrect statement about the lethality of the virus:

Highly pathogenic avian influenza A/H5N1 infection of humans has been a serious public health concern since its identification in 1997 in Asia. This virus rarely infects humans, but when it does, it causes severe disease with case fatality rates of 59%.

The reference for this information is a WHO summary of confirmed human cases of H5N1. Both WHO and NSABB ignore the serological evidence for many mild or inapparent H5N1 infections. Omitting these data leads to an overestimation of the virulence of the virus, which has apparently played a large role in the NSABB’s decision.

Next, they engage in extensive speculation:

If influenza A/H5N1 virus acquired the capacity for human-to-human spread and retained its current virulence, we could face an epidemic of substantial proportions.

The virus has been circulating since the 1990s and has not acquired the capacity for human to human spread. This doesn’t mean it never will, but the possibility seems remote. The statement ‘retaining its current virulence’ of course refers to the erroneous 59% case fatality rate. What if the fatality rate is 0.1%, like seasonal influenza?

In discussing influenza H5N1 transmission in ferrets, the NSABB notes the value of the research:

The research teams that performed this work did so in a well-intended effort to discover evolutionary routes by which avian influenza A/H5N1 viruses might adapt to humans. Such knowledge may be valuable for improving the public health response to a looming natural threat.

Many have written that the research should never have been done, and that there are no benefits for human health (New York Times, Tom Inglesby, DA Henderson). Clearly the NSABB believes otherwise.

Next the NSABB describes their consideration of risk assessment of the H5N1 ferret studies. Their conclusion:

We found the potential risk of public harm to be of unusually high magnitude. Because the NSABB found that there was significant potential for harm in fully publishing these results and that the harm exceeded the benefits of publication, we therefore recommended that the work not be fully communicated in an open forum.

But there is no description of how they reached this conclusion. What data did they consider when making this decision? What were the benefits and the potential harms, and how did they weigh them? Apparently we must take the word of the panel that they reached the right decision, even though we cannot know what information they used. To convey their decision in this manner is unacceptable and sends the message that the committee did not consider specific data during their deliberations.

They conclude:

The life sciences have reached a crossroads. The direction we choose and the process by which we arrive at this decision must be undertaken as a community and not relegated to small segments of government, the scientific community, or society.

This is precisely why the decision to redact publication should not have been made by the NSABB or any small group of individuals. I agree that this is an ‘Asilomar moment’, a time when scientists must meet to decide what types of microbial research should be regulated. This should be a discussion among a large group of scientists, not bioterrorism policy analysts.

I understand the need to regulate certain types of experiments on microbes. But when I balance the benefits and risks of the H5N1 ferret transmission experiments, it does not make sense to stamp them as dual use and restrict publication of the results. Let publication proceed and then decide how to decide on how to move forward.

  • Drosha

    I’m a bit disturbed that there are so many big name scientists in that commentary (such as Lynn Enquist).  It’s also amazing that they compared this situation to the development of nuclear bomb. Procedures for building a nuclear bomb were unknown at the time while the production of the specific virus that was made in this study can easily be accomplished by using the limited information given to the public.  I also think that even though an asilomar type meeting may be helpful in this case, the parallels with that time are very limited. At that time most of the concerns were about containment of the newly created recombinants, not bioterror usage or publishing information. If the containment were the issue here the local scientific boards could decide the containment level (as they do currently).

  • MWo

    I really can’t take the NSABB seriously any more.  I, as an European, see a bunch of frightended advisors that take incorrect facts to legitimate censorship of scientific data in order to prevent terrorism in the US.
    It’s hard to imagine that these people are respected scientists.

    They state that H5N1 is around in Eurasia for a long time now. So the Europeans should be even more terrified? But they are not; I admit they were a bit at the first outbreaks and there was no epidemic.

    Well, in my opinion it’s an US-feeling-secure thing and I will probably never understand the concerns. At least none of the given points justify censorship.

  • http://twitter.com/cggbamford Connor Bamford

    I love that they began with the comment about how current technology allows for the manipulation of microbial genomes that couldn’t be done before despite Fouchier’s work showing that nothing beats good old fashioned passaging of virus to get what you want.

  • Rishat

    У меня супер иммунитет к гриппу.7 лет не болел гриппом

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  • Elizabeth Hart

    This is a very important issue, discussion on which should
    not be reserved to ‘experts’ with possible conflicts of interest.  The rest of us have a say in this too.

     

    In this regard, I have forwarded an Open Letter, from a
    ‘layperson’s’ perspective to the National Science Advisory Board for
    Biosecurity re the political and ethical implications of lethal virus
    development.

     

    My letter has been acknowledged by the acting chair of the
    NSABB, Paul Keim, and Michael Osterholm, a NSABB member.  I have been advised my letter will be
    considered by the Board.

     

    My open letter raises questions about the legitimacy of the US sponsoring
    lethal virus development – does this contravene the Biological Weapons
    Convention?

     

    Bearing in mind the questionable effectiveness of flu vaccines,
    I also suggest it is time to investigate the ‘influenza industry’, particularly
    the relationships between vaccine manufacturers and governments and other
    public bodies.

     

    The Open Letter can be addressed via this link:  http://bit.ly/AfyAtQ

     

    Elizabeth Hart

  • gsgs

    yes, this should be openly discussed in an internet forum.
    They should present the data, how much the disclosure would
    help potential terrorists and how big the danger is even without the disclosure.
    And how much useful(?) science would be hindered by the secrecy.
    With probability estimates from Fouchier and Kawaoka, please !

    Unless this very discussion might give valuable hints to terrorists
    itself …

    But then, again, they should demonstrate and discuss why it might.

  • Dorian McILROY

    My russian is incredibly rusty, but if I understood correctly, you think you have a super anti-flu immunity, since you haven’t had the flu for 7 years. Am I right?

  • Lance

    Your letter contained as much space dedicated to an anti-vaccine rant, as it did to contributing anything of significance to the debate on H5N1 transmission research. It contains a number of inaccuracies. Just a few examples: the amount of money made by vaccines is small compared with many other drugs. Flu vaccination isn’t of “questionable” benefit – it just isn’t perfect, preventing a little over half of the infections (but possibly also reducing severity). That is better than nothing.

    Regarding this paper: Bodewes R et al. Annual Vaccination against Influenza Virus Hampers Development of Virus-Specific CD8+ T Cell Immunity in Children. Journal of Virology. 2011 Nov;85(22):11995-2000. Epub 2011 Aug 31

    This has been misunderstood by you and others who have quoted it complaining that it argues against flu vaccination. As CD8+ T cells and protection from viral infection is my area of expertise I shall spend a little more time on this.

    1) This paper does not show flu vaccination is ineffective – rather the opposite. The most likely reason why the children given regular flu vaccines didn’t have very strong CD8+ T cell responses is because they had vaccine induced antibodies which prevented infection reducing the need to mount T cell responses. Yippee.

    2) The two groups in the paper are very different making a comparison between them unwise. For example the annually vaccinated group had cystic fibrosis, would have been chronically medicated and may have had very different immune responses. The presence of antibodies to other vaccines given earlier in life (when people with CF are more healthy) and the T cell positive control do not establish immunological equivalence. The response to Staph enterotoxin B (which is like using a hand grenade to kill an ant), for example, is pathologic, not protective.

    3) What has been measured is a surrogate, immunological endpoint. Although interferon gamma responses correlate with protection in many systems and infections, this is not universal and it can be detrimental in some cases. Indeed, if there are conserved T cell epitopes in flu viruses, and pretty much all of us have had flu at some point, then why can flu continue to spread through the human population every year? These responses are unlikely to be completely protective. There may well be viruses that have variable capsids/envelopes but conserved T cell epitopes that ARE protective – it’s just that you haven’t heard of them because we haven’t discovered them because they don’t spread through populations causing disease because immunity is so effective. As Vincent says, we are living in world awash with viruses.

    I believe this paper was discussed on TWiV recently.

  • Elizabeth Hart

    Lance,
    thank you for your interpretation of the Bodewes et al paper.  I’ll look forward to seeing this paper
    being considered in future reviews.

    Flu vaccination of children is
    a controversial topic in Australia.  As reported in The Australian
    newspaper today (16 Feb 2012), CSL’s Fluvax product remains banned for children
    younger than five, having triggered febrile convulsions in one in 100 children
    in 2010.  A toddler, Saba
    Button, suffered brain damage after the shot, and according to her mother,
    Kirsten Button, “she doesn’t talk, she doesn’t walk, she doesn’t eat and she
    can’t see properly”.

    Ms Button said her child had
    been in perfect health before the flu shot, but 16 hours later was on life
    support, with brain injury and organ damage.

    In regard to healthy people
    being pressured to have medical interventions, I refer you to David Sackett’s
    commentary titled “The arrogance of preventive medicine” in which he says: “But
    surely the fundamental promise we make when we actively solicit individuals and
    exhort them to accept preventive interventions must be that, on average, they
    will be the better for it.  Accordingly, the presumption that justifies the aggressive assertiveness with which we go after the
    unsuspecting healthy must be based on the highest level of randomized evidence
    that our preventive manoeuvre will, in fact, do more good than harm. Without
    evidence from positive randomized trials (and, better still, systematic reviews
    of randomized trials) we cannot justify soliciting the well to accept any
    personal health intervention. There are simply too many examples of the
    disastrous inadequacy of lesser evidence as a basis for individual
    interventions among the well: supplemental oxygen for healthy premies (causing
    retrolental fibroplasia), healthy babies sleeping face down (causing SIDS),
    thymic irradiation in healthy children, and the list goes on.”  CMAJ August 20, 2002 vol.
    167 no.
    4 http://www.cmaj.ca/content/167/4/363.full 

    As you acknowledge Lance, flu
    vaccination isn’t perfect, and the results of industry-funded vaccination trials
    need to be subject to much more intensive scrutiny.

    One-off
    vaccinations for childhood diseases such as measles, mumps and rubella, which
    are likely to provide lifetime immunity, seem to be appropriate based on
    current knowledge.  But I am
    not at all comfortable with having a flu vaccination of questionable benefit
    every year, we have no idea of the long-term consequences of vaccination
    throughout life. I resent the insidious way that healthy people are being
    pressured to have this regular medical intervention by governments and other
    ‘authorities’.

    Many millions of people have
    gone through their lives without flu vaccination, and I wonder what is driving
    this fear-mongering about influenza in recent years.  Philip Alcabes, author of “Dread: How
    Fear and Fantasy have Fueled Epidemics”, sums up the situation succinctly: “We
    are supposed to be prepared for a pandemic of some kind of influenza, because
    the flu watchers, the people who make a living studying the virus and who need
    to attract continued grant funding to keep studying it, must persuade the
    funding agencies of the urgency of fighting a coming plague.  There is no particular reason to think
    that there will be another epidemic of flu to equal the 1918 outbreak, and no
    reason to think that if any flu strain does manage to go global it will be any
    worse than the garden-variety strains that come round every winter”.

    As for your comment, Lance,
    that “the amount of money made by vaccines is small compared with many other
    drugs”, I disagree.  For
    example, consider the international multi-million dollar racket of companion
    animal vaccination, where already immune dogs are regularly and needlessly
    revaccinated every year or every three years with core modified live virus
    (MLV) vaccines for parvovirus, distemper virus and adenovirus, (and highly
    immunogenic rabies vaccines in the US).  Questionable
    non-core vaccines for diseases such as bordetella bronchiseptica are also
    pushed every year.  Is
    this about an effective vaccination program for serious diseases, or a
    money-making racket pushing unnecessary vaccines every year?  I
    suggest the latter and I also suggest there are parallels with human vaccination
    that bear further investigation.  (Ref: Australian Campaign for
    Ethical and Evidence-based Vaccination of Companion Animals: http://bit.ly/yj8g5o )

  • Jillbellamy9

     Coming from the military side of things I should think the ‘issue’ is not, as stipulated, that would
    be bio-terrorists would be able to reverse engineer this–but rather
    one related to biological warfare laboratories where such a publication
    could contribute to refining existing techniques in rogue state military
    laboratories.

  • Lance Turtle

    Elizabeth,

    When you say you hope this paper will be included in future reviews, what do you mean exactly? I hope you don’t mean reviews of safety and efficacy – as these questions were not addressed in the paper.

    As far as preventive medicine is concerned – I think that in healthy adults there is indeed little to do. Annual flu vaccination is not recommended where I live (UK) for healthy adults under 65 unless you are pregnant. However I felt the tone of your letter was much more doubtful about flu vaccination than this. During a pandemic vaccination has a rather different role to play in limiting economic impact for example.

    Your example of animal vaccination for the profit seeking behaviour of the vaccine industry is poor (yes of course I know vaccine are sold for profit) – animal farming is ruthless in the pursuit of profit and there’s no way these vaccines would be used if they were not cost effective and didn’t ultimately result in greater yield. Most pet vaccines are just not tested enough and yes I am sure this is about profit but this has little to do with human health (apart from possibly rabies) so I don’t see how that is relevant to the discussion. And the money is still very small compared with drugs for high blood pressure, cholesterol, antidepressants etc.