Deadly “paleoviruses”: a bioweapon Pandora's box?
Authors: Jean-Nicolas Tournier, Daniel Garin
Journal: The Lancet Infectious Diseases (2006)

We would like to comment on a recent study reporting the recreation of the 1918 influenza "paleovirus".1Tumpey TM Basler CF Aguilar PV et al.Characterization of the reconstructed 1918 Spanish influenza pandemic virus.Science. 2005; 310: 77-80Crossref PubMed Scopus (1056) Google Scholar Beyond this scientific tour de force, these experiments raise huge ethical concerns.2van Aken J Risks of resurrecting 1918 flu virus outweigh benefits.Nature. 2006; 439: 266Crossref PubMed Scopus (4) Google Scholar The medical justifications for such an exercise are open to debate. First, it is not certain that a better understanding of the virus' pathogenesis in a mouse model would be helpful for treating influenza infections in human beings. Second, the predicted efficacy of neuraminidase inhibitors and immunogenicity of H1N1-derived vaccines have already been demonstrated in recombinant influenza A viruses bearing the appropriate H1 and N1 genes.3Tumpey TM Garcia-Sastre A Mikulasova A et al.Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus.Proc Natl Acad Sci USA. 2002; 99: 13849-13854Crossref PubMed Scopus (113) Google Scholar, 4Tumpey TM Garcia-Sastre A Taubenberger JK Palese P Swayne DE Basler CF Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus.Proc Natl Acad Sci USA. 2004; 101: 3166-3171Crossref PubMed Scopus (171) Google Scholar Third, to have a pandemic flu vaccine available on the market in the shortest possible time, the European Agency for the Evaluation of Medicinal Products encourages manufacturers to work on a core dossier using a mock-up strain.5European Agency for the Evaluation of Medicinal ProductsCommittee for Proprietary Medicinal ProductsGuideline on dossier structure and content for pandemic influenza vaccine marketing authorization application.http://www.emea.eu.int/pdfs/human/vwp/471703en.pdfGoogle Scholar However, because of the danger that the virulent 1918 flu strain presents, the strain will never be distributed worldwide for such a purpose. By contrast, the risks of such an exercise are real. First, it is astonishing that this virus has been manipulated in a biosafety level (BSL) 3 laboratory and not at a higher level of containment. Severe acute respiratory syndrome virus escapes from BSL3 labs were reported.6Anon The 1918 flu virus is resurrected.Nature. 2005; 437: 794-795Crossref PubMed Scopus (33) Google Scholar In addition, the H2N2 1957 pandemic strain was accidentally sent to 3700 reference laboratories in 2005.7Nelson R Influenza A H2N2 saga remains unexplained.Lancet Infect Dis. 2005; 5: 332Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar The 1918 flu virus poses a high risk of life-threatening disease, with high spreading aerosol transmission and without enough therapeutic stocks of antivirals available for mass treatment, and thus should have been classified as a BSL4 agent, and even contained in a special high security facility—as in the case of variola virus8Leduc JW Jahrling PB Strengthening national preparedness for smallpox: an update.Emerg Infect Dis. 2001; 7: 155-157Crossref PubMed Scopus (53) Google Scholar—until its expected destruction. Furthermore, the reconstruction of the 1918 pandemic flu virus could be viewed as research with potential for dual use (ie, for civil and military gains) and could even be interpreted as an intentional reinforcement of a highly pathogenic virus, which is forbidden by the Biological Weapons Convention that was agreed in 1972.9United NationsConvention on the prohibition of the development, production and stockpiling of bacteriological (biological) and toxin weapons and on their destruction.http://disarmament.un.org/wmd/bwc/BWCtext.htmGoogle Scholar In addition, the complete publication of the influenza paleovirus genome paves the way for the replication of the work and could be hijacked by rogue states or terrorist organisations to produce biological weapons. It is not the first time that controversy has followed potentially harmful experiments with viruses. Unsuccessful Russian attempts to dig up live variola virus from cadavers buried in the Siberian permafrost were reported.10Enserink M Stone R Public health. Dead virus walking.Science. 2002; 295: 2001-2005Crossref PubMed Scopus (19) Google Scholar After, the publication of data describing the increased pathogenicity of ectromelia virus expressing interleukin 4,11Jackson RJ Ramsay AJ Christensen CD Beaton S Hall DF Ramshaw IA Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox.J Virol. 2001; 75: 1205-1210Crossref PubMed Scopus (471) Google Scholar genetic engineering of interleukin 4-expressing vaccinia or cowpox viruses to check the efficiency of smallpox vaccines was forbidden by French ethical committees. For transparency, and to prevent any suspicion of state interests in dual-use research activities, responsible scientists should now submit to, and comply with, ethical evaluation of their projects at a supranational level for compliance with arms control laws, using either existing international organisations—eg, WHO, the UN—or non-governmental international scientific societies—eg, the Nobel institution.