Facing up to flu

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The potential for mutant-flu research to improve public health any time soon has been exaggerated. Timely production of sufficient vaccine remains the biggest challenge.

Amid the scientific controversy over lab-created strains of the H5N1 avian influenza virus that can skip between mammals, it is easy to lose sight of an important public-health question: what will help the wider world to prepare for a flu pandemic? The question is crucial, because when it comes to setting priorities, the fuss over how to regulate the controversial research must not be allowed to distract from a much bigger concern. The world is ill-prepared for a severe flu pandemic of any type. In particular, it cannot yet produce enough vaccine to protect more than just a small proportion of people.

The problem was demonstrated by the 2009 pandemic of H1N1 flu. Vaccines only became available months after the outbreak began, and after the first wave had peaked in many countries. Health systems were stretched despite the relative mildness of the pandemic. The mutant-flu research does nothing to prevent a repeat of this situation.

Research to create mammalian-transmissible strains is vital basic science that could deepen our understanding of flu viruses, and of what allows a virus to jump from other species and spread easily in humans. These insights may one day produce better ways to tackle a pandemic, including ones we cannot picture today. But scientists need to be more modest and realistic with their claims about the short-term public-health benefits of such research, and provide better explanations that include the caveats.

For example, many commentators say that the biggest public-health benefit promised by the research is in the field of disease surveillance. The experiments reveal one combination of mutations that allowed the H5N1 virus to jump between species and then spread; in theory, animal-health experts can now watch out for these mutations in affected animals such as pigs and birds.

In practice, the immediate benefits are minimal. Surveillance of influenza in animals is slow and patchy at best, and follow-up sequencing of samples more so. And the mutations that we know about are likely to be outnumbered by those about which we are still ignorant.

Consider H5N1 in pigs. There is almost no systematic flu surveillance in the animals (see Nature 459, 894895; 2009). Infections are infrequent, symptoms are mild and the pig industry is concerned that talk of swine flu could unfairly taint the image of pork. As a result, the world's one billion or so pigs have yielded partial DNA sequences of just 24 H5N1 isolates, meaning that were a pandemic H5N1 virus to emerge from pigs, just as H1N1 did in 2009, there would be little or no possibility of detecting it in advance.

That does not mean that the idea of using the mutant-flu research to improve surveillance is without merit; far from it. Further work could yield a more comprehensive bank of mutations, and greater investment could create specialized centres to screen more samples in affected countries, in real time. Improving flu-virus surveillance should be a public-health priority, but international groups and governments have, in the past, been reluctant to fund it adequately. If the world is serious about preparing for a pandemic, this must change. Done properly, surveillance could one day give early warning of an approaching pandemic. What then?

At present, such advance knowledge would make little difference to the world's limited abilities to manufacture and distribute vaccines. Current techniques can produce vaccine only six months after a pandemic emerges. Doing so faster and in much larger quantities is the most urgent public-health priority when it comes to planning for the next pandemic.

The mutant-flu studies contribute little to this goal. They offer no serious immediate application in vaccine research (see page 142). Any benefits to drug development — which are important, but less so than churning out vaccine for a pandemic — are more likely to flow from longer-term basic research. The mutant-flu work could certainly help this research. Yet the work itself carries a risk. An accidental, or intentional, release of the mutant viruses from a lab could spark an H5N1 pandemic that we are currently in no position to mitigate.

The fact that the risks seem to far outweigh the public-health benefits of the research, at least in the short term, means that there is no need to rush headlong into an expansion of the work. Rather, regulators and flu researchers must take whatever time they need to decide the best way for such work to proceed safely.


  1. Report this comment #38469

    Anurag Chaurasia said:

    Good basic research on the hot topic like H5N1 bring the concerned researcher in the lime light immediately while society get benefited in long run along with associated risk factor.

    Anurag chaurasia,ICAR,India,anurag_vns1@yahoo.co.in,anurag@nbaim.org.in,+919452196686(M)

  2. Report this comment #38480

    Giovanni Maga said:

    It is undeniable that understanding the way an avian virus such as H5N1 can adapt to mammals is an essential piece of information, whose impact on our ability to predict and counteract the emergence of a pandemic virus is, however, foreseeable at best in the long run. As a matter of facts, predicting the appearance of a pandemic strain is nowadays nearly impossible, not only because of lack of surveillance (which is a major problem), but most of all because we are basically clueless about which particular combination of gene segments/mutations will enable a virus to efficiently jump among species. A matter further complicated by the high number of H and N subtypes currently present in wild birds flu viruses (for example, human infections by pathogenic avian strains have been reported for at least three H subtypes, H5, H7 and H9). H5N1 is the avian virus showing the highest number of human infections so far, but the fact that upon continuous circulation for almost 15 years the virus is still confined into a dead-end infection in human host, with no sign of adaptation, cast a doubt on its real ability to become pandemic. The major justification for the great attention this virus deserves is the high mortality rate in humans. Of major concern are those reassortants that arise from pigs and more efficiently spill into the human population. A/H1N1v 2009 is a perfect example, but the recent observation of the emergence of H1N2 swine viruses in people in the USA is something one should not underestimate. Hence, currently our best chance to become aware of a new pandemic threat relies in our ability to detect the virus immediately after its "jump" and to quickly respond. Faster vaccine development is the main course of action, but given the difficulty to shorten the time required to produce a safe vaccine, antiviral drugs seem to me the best first-line defense to protect a large number of people in the face of a new pandemic. Unfortunately, anti-flu drug development and stockpiling has been neglected for many years, under the comfortable assumption that our vaccines were good enough to protect us. It's time to wake up.
    Giovanni Maga Phd – Molecular Virology Unit, Institute of Molecular Genetics CNR, Italy

  3. Report this comment #38484

    Viktor Müller said:

    A clear distinction needs to be made between the modified strains created in the two labs. The virus Fouchier et al have created has retained the high virulence of the parental 'bird flu' in the ferret host: there is, therefore, a fair chance that it would also be virulent in humans and could cause a deadly pandemic, should it escape the lab by accident. In contrast, the virus of Kawaoka and colleagues contains only the hemagglutinin gene of the virulent H5N1 avian virus, and did not kill the infected ferrets. The risks of the two strains seem to be quite different. In terms of benefits, it is unclear what further gain could emerge from continued research on the virulent virus created by Fouchier. In contrast, the virus created by Kawaoka might be considered for a possible emergency use as an 'infectious vaccine' should an outbreak of virulent H5N1 occur before we had an efficient means of defence (vaccine or drug) against it. In this case, a systematic worldwide release of the low-virulence strain might be able to generate herd immunity against the H5 antigen and protect against the devastation of the virulent strain. Continued research on the Kawaoke strain (virulence in other animal models, cross-protection afforded against other H5N1 strains) might help us assess the feasibility of this option. More on the modified strains here: http://www.mdpi.com/1999-4915/4/2/276/.

  4. Report this comment #38495

    Jms rndll said:

    And do think you people are scientists, these are some of the scariest comments I have read in my entire life. Why is it, that evolution and NATURAL adaptation seems to only apply to non human animals?

  5. Report this comment #63537

    Davy Jones said:

    Among the many side matters they narrate, the bottom line issues are: a) (The influenza vaccine) ?is about 60-per-cent-effective in protecting against influenza, although in some years, it is far less effective;? and b) ?We get the influenza vaccine every year and encourage others to do so. Despite its shortcomings, it is the only vaccine we have right now.?

    Cook @ site

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