Research on potential of bird flu virus to spread between humans is finally published

BMJ 2012; 344 doi: (Published 04 May 2012) Cite this as: BMJ 2012;344:e3233
  1. Zosia Kmietowicz
  1. 1London

Controversial research about a strain of avian flu that could potentially spread between humans has been published in Nature. It had been withheld from publication for five months after US advisers said that it posed security risks. A second paper is expected to appear soon in Science.

An editorial in Nature concludes that the lessons for publishers from the months of deliberations and meetings among scientists, security agencies, research journals, ethicists, and others is that “where there is a benefit to public health or science, publish!”1

A report of the research by a team from the University of Wisconsin-Madison was submitted to Nature in August last year, but publication was delayed after the US government’s biosecurity advisers warned that public health could be endangered if the trial’s methods fell into the wrong hands.2 The advisers also recommended delaying publication of a second research paper by a team at Rotterdam’s Erasmus Medical Centre that was submitted to the US journal Science.

However, after a second meeting in March and redrafting of the manuscripts, the National Science Advisory Board for Biosecurity, which provides recommendations on research publication at the request of the US government, voted unanimously that the paper from the Wisconsin-Madison team could be published and voted by 12 to six in favour of publishing the Erasmus Medical Centre’s paper.3 Among the reasons given was the fact that the papers stated the potential benefits of the research to public health.

The researchers from Wisconsin-Madison report that avian H5N1 flu viruses in the wild may be just a small step away from spreading effectively between mammals.4 In a commentary article, experts on flu say that although the illness caused by bird flu is severe, the virus does not pass readily from one person to another.5 There have been only about 600 cases of bird flu in humans since the strain was first identified more than 16 years ago, although half of these people have died. The reason for the low incidence is that the virus sticks to cells deep inside the lungs, which makes it harder to spread through coughs and sneezes.

To find out whether H5N1 can easily evolve to be more infectious, Yoshihiro Kawaoka and his team at Wisconsin-Madison mutated the virus’s haemagglutinin (HA) gene to make it bind more readily to human cells than it does to bird cells. The team then combined this gene with seven others from the H1N1 flu virus, which caused a pandemic in 2009 and which spread much more easily than the bird flu virus.

After acquiring four mutations the researchers found that the hybrid virus could spread between ferrets, the best model for flu transmission in humans. Three of the mutations allowed the HA protein to stick to receptor molecules on mammalian cells, and the fourth stabilised the protein. None of the ferrets died, and they responded to treatment with antivirals and the H5N1 flu vaccine.

The researchers point out that it is not known whether mutated virus will spread as readily between people as it did between ferrets. But the research is important because, they write, the findings “emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolate.” It will also help to “inform the development, production and distribution of effective countermeasures.”

The editorial in Nature says that given the “enormous implications for flu research,” the National Science Advisory Board for Biosecurity’s deliberations over whether to allow publication of the studies “were too limited.” The board is unique, it says, and valuable, but its processes should be reviewed.

Although the World Health Organization will soon publish guidelines on international standards for biosafety, these will not provide a framework for strengthened implementation, and “the absence of such a framework is an urgent concern for all researchers working with dangerous organisms, and for all who fund and publish their work,” says the editorial.


Cite this as: BMJ 2012;344:e3233