{"id":4415,"date":"2013-01-24T15:20:41","date_gmt":"2013-01-24T20:20:41","guid":{"rendered":"https:\/\/blogs.nature.com\/spoonful\/?p=4415"},"modified":"2013-01-25T10:13:25","modified_gmt":"2013-01-25T15:13:25","slug":"a-long-pause","status":"publish","type":"post","link":"https:\/\/blogs.nature.com\/spoonful\/2013\/01\/a-long-pause.html","title":{"rendered":"EDITORIAL: A long pause"},"content":{"rendered":"

A version of this editorial appears in the\u00a0February 2013 issue\u00a0of <\/em>Nature Medicine.<\/em><\/p>\n

Last January, scientists voluntarily imposed a pause on research that could lead to the generation of highly\u00a0pathogenic avian influenza viruses with increased transmissibility to mammals. Now, new restrictions currently\u00a0under debate further risk stalling progress in avian flu research.
\n<\/strong><\/em><\/p>\n

****<\/p>\n

In late 2011, a firestorm erupted around two papers under peer\u00a0review on highly pathogenic avian influenza (HPAI) H5N1\u00a0viruses<\/a>. Both identified mutations that would permit airborne\u00a0transmission of the viruses to ferrets. Although the viruses were not\u00a0highly pathogenic in the ferrets, the papers sparked concerns<\/a> that the\u00a0mutant H5N1 viruses might have pandemic potential.<\/p>\n

The concerns are not unwarranted given the history of H5N1 infections.\u00a0The case fatality rate due to H5N1 in humans exceeds 50%, yet\u00a0only 610 infections have been recorded since 2003, in part because of\u00a0its low capacity for human-to-human transmission. However, there\u00a0is fear that avian influenza could acquire the mutations necessary\u00a0to rapidly transmit among humans, similar to seasonal influenza.\u00a0Therefore, a better understanding of the mutations necessary to\u00a0facilitate transmission of H5N1 in mammals and their effects on the\u00a0fitness of the virus is considered by many to be crucial in developing\u00a0countermeasures in the event of an avian flu pandemic.<\/p>\n

Not everyone agrees on the utility\u2014or ethicality\u2014of this type of\u00a0research, which led to the research embargo and delayed publication\u00a0of both papers. (They were ultimately published in May and June of\u00a02012 in Nature<\/a><\/em> and Science<\/a><\/em>, respectively.) The research pause was\u00a0intended to allow researchers to communicate the rationale and the\u00a0safety measures in place for undertaking experiments with H5N1 and\u00a0to allow governments to consider whether new policies are necessary\u00a0for funding such research. Yet the original 60-day moratorium, which\u00a0was only lifted in January 2013, albeit not in the US, lasted more than\u00a0a year, and the US Department of Health and Human Services (HHS)<\/a>\u00a0has recently recommended new regulations that would restrict all\u00a0research using highly pathogenic H5N1 viruses, regulations that could\u00a0hamper efforts aimed at protecting humans.<\/p>\n

Due to its potential effects on animal health and safety, HPAI is classified\u00a0as a US Department of Agriculture (USDA)<\/a> select agent. Low pathogenicity\u00a0strains are excluded from this designation. Since October,\u00a0HHS has sought public comment on whether to make HPAI H5N1\u00a0viruses a tier 1 HHS select agent, a designation currently restricted\u00a0to a handful of agents (including the Ebola and smallpox viruses and\u00a0Bacillus anthracis) that are considered to present \u201cthe greatest risk of\u00a0deliberate misuse with the most significant potential for mass casualties\u00a0or devastating effects to the economy, critical infrastructure, or public\u00a0confidence\u201d<\/a>.<\/p>\n

The new designation might require that H5N1 research in the US\u00a0be done in a biosafety level 4 (BSL-4) laboratory, rather than in an\u00a0enhanced BSL-3 facility where it is currently performed, as well as\u00a0more background screening of personnel and enhanced security measures. Canada has ruled that research on mammalian transmissible H5N1 viruses must be done in a BSL-4 lab, whereas The Netherlands has determined that enhanced BSL-3 containment measures suffice. Additional review measures have also been proposed for US National Institutes of Health<\/a> grants involving studies that would increase mammalian transmissibility of H5N1, and they would entail an extra review step by the HHS if the studies met certain criteria. These regulatory efforts aim to prevent the accidental or intentional release of avian flu, but the unintended consequences are clear: researchers in the US would have less access to facilities in which to carry out H5N1 studies, restricted funding of some studies, lengthy review processes and more obstacles to international collaboration. As the US is the major funder of H5N1 studies, these impediments will have a crippling effect on H5N1 research.<\/p>\n

Academics have weighed in on both sides<\/a> of the argument. The\u00a0Infectious Diseases Society of America<\/a> concurs that H5N1 should be\u00a0an HHS select agent because of its potential risks to human health and\u00a0concerns surrounding the development of mammalian-transmissible\u00a0strains. In contrast, the American Society for Microbiology<\/a> does not\u00a0support the change, given that circulating H5N1 strains are poorly\u00a0transmissible among humans and that the USDA select-agent designation\u00a0sufficiently addresses the biosafety and biosecurity needs.\u00a0Sanofi Pasteur<\/a>, Novartis Vaccines<\/a> and\u00a0MedImmune<\/a>, in turn, have\u00a0requested that attenuated H5N1 strains and low-pathogenicity avian\u00a0influenza viruses be exempt from the HHS select-agent list, as their\u00a0inclusion could hamper vaccine development. In 2012, these vaccine\u00a0manufacturers were awarded contracts by the HHS valued at up to\u00a0$22 billion to develop medical countermeasures against H5N1. How\u00a0global pandemic preparedness might be affected by the proposed\u00a0changes is unclear.<\/p>\n

What is clear is that avian flu research has been set back, and further\u00a0deliberation and a more restrictive funding and regulatory environment\u00a0will exacerbate matters. In our view, the only way to guard\u00a0against a biomedical disaster is through more research and greater\u00a0knowledge\u2014not by making certain types of research nonpermissible\u00a0or unattainable. In June 2012, Science<\/em> published<\/a>\u00a0a follow-up paper\u00a0by the two labs at the heart of the debate, in which surveillance data\u00a0showed that only three additional mutations would be required to\u00a0convert some circulating strains of HPAI H5N1 into highly transmissible\u00a0forms, based on the mutations identified in the original two\u00a0publications. The findings underline the importance of continued\u00a0research on mammalian-transmissible H5N1 viruses. What we don\u2019t\u00a0know can hurt us. Shouldn\u2019t that be the lesson learned?<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

A version of this editorial appears in the\u00a0February 2013 print issue\u00a0of Nature Medicine.  Read more<\/a> Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":249,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[136,17,135],"tags":[187,186,182],"class_list":["post-4415","post","type-post","status-publish","format-standard","hentry","category-infectious-diseases","category-swine-flu","category-virology","tag-bird-flu","tag-h5n1","tag-influenza"],"_links":{"self":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts\/4415","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/users\/249"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/comments?post=4415"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts\/4415\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/media?parent=4415"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/categories?post=4415"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/tags?post=4415"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}