Strained relations: fears of a man-made flu pandemic

The risk of a man-made pandemic has startled virologists and epidemiologists to the extent that two papers on the subject were once deemed too dangerous to publish

Officials pile dead chickens into bags in Hong Kong earlier this year in a mass cull after the deadly H7N9 virus was discovered in poultry imported from mainland China. Photograph: Philippe Lopez/AFP/Getty Images

Officials pile dead chickens into bags in Hong Kong earlier this year in a mass cull after the deadly H7N9 virus was discovered in poultry imported from mainland China. Photograph: Philippe Lopez/AFP/Getty Images

Thu, Jul 24, 2014, 01:00

US virologist Yoshihiro Kawaoka has form when it comes to sparking controversy. Last month, his team at the University of Wisconsin-Madison published a paper that described engineering an entirely new flu virus that causes severe illness when transmitted between ferrets in sneezed, airborne droplets.

Kawaoka is one of a small number of researchers tinkering with the genomes of bird-flu strains to model how they might acquire human pandemic potential. Many fear these hubristic microbiologists might trigger a man-made plague if the synthetic bugs ever escape from their laboratories.

In another project, Kawaoka developed a version of one of the most dangerous influenza viruses yet known. Bird-flu strains contain genes highly similar to the 1918 Spanish flu (which was resurrected from permafrost in 2005), and Kawaoka’s team selected the most similar from eight avian viruses to create a viable 1918-like hybrid.

When inoculated into ferrets, this proved far more virulent than a wild duck virus, but less so than the 1918 virus, which killed one ferret. However, unlike the 1918 virus, it did not transmit between them.

They then spliced in entire 1918 genes, focusing on proteins critical for transmission. Two of three ferrets died, but crucially, they infected other ferrets in neighbouring cages. Through successive mutations, the team selected ever more transmissible strains in a “forced evolution” towards infecting mammalian and human hosts, by adapting the viruses to the lower temperature and pH environment of the human nose and throat.

To flu virologists, this paper delivers a cascade of data on the mechanisms by which avian viruses hop the species barrier. But the risk of a man-made pandemic has startled other virologists and epidemiologists. Simon Wain-Hobson of the Pasteur Institute in Paris chairs the Foundation for Vaccine Research, which has petitioned US president Barack Obama and president of the European Commission Manuel Barroso in a letter signed by 56 microbiologists, including Nobel laureate Richard Roberts. They call for an urgent review of the dangers of such “gain-of-function” research and claim the science is speculative and of little use in producing vaccines or anti-viral drugs.

Meanwhile, the Centers for Disease Control in Atlanta have just closed down their biosafety level-three labs (such as Kawaoka heads at Wisconsin) due to safety breaches there. Eighty-four workers were exposed to live anthrax last month and there was an accidental release in March of an avian flu cross-contaminated with the lethal H5N1 strain. The Atlanta centre’s own 2012 analysis reported 727 US incidents of theft, loss or release of “select agents and toxins” from 2004 to 2010, causing 11 lab-acquired infections.

A May report in PLoS Medicine cited the 1977 pandemic, which many scientists believe escaped a lab, causing “significant mortality” over many years.

Prof Tom Jeffries, a member of Wisconsin’s Institutional Biosafety Committee, has voted against Kawaoka’s work. Nature this month also published correspondence from the US National Institute of Allergy and Infectious Diseases to the committee, insisting Kawaoka’s latest work falls squarely under new “dual-use research of concern” criteria, which necessitates serious “risk mitigation”.

The new dual-use regulations arose after late 2011, when the US National Science Advisory Board for Biosecurity declared a Kawaoka paper (and one by Ron Fouchier in Rotterdam) too dangerous to publish. Both had enhanced the human transmissibility of the deadly H5N1 bird flu, Kawaoka by “reassorting” it with the contagious 2009 swine flu. Fouchier had publicly quipped that his was “probably one of the most dangerous viruses you can make”, alarming anthrax expert Paul Keim, chair of the US advisory board.

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