Genetically Engineered Transmissible Influenza A/H5N1: A Call for Laboratory Safety and Security

The current discussions surrounding 2 independent studies that succeeded in identifying the genetic changes needed for the influenza A/H5N1 virus to be efficiently transmitted between ferrets, a surrogate for human-to-human transmission, highlight significant challenges and raise fundamental questions about research that both benefits humankind but also has the potential for nefarious applications. Both studies were funded by the National Institute of Allergy and Infectious Diseases, with one conducted at the University of Wisconsin–Madison and the other done at Erasmus Medical Center in Rotterdam, the Netherlands. Some preliminary results were shared with the influenza community previously; however, it was only when the lead investigators of these studies attempted to publish their findings in the scientific literature that serious concern surfaced.

The National Science Advisory Board for Biosecurity (NSABB), a formal group established to advise the Department of Health and Human Services and other federal agencies on biosecurity issues, reviewed the studies and recommended that the detailed procedures used in their conduct be excluded from the final publications. It suggested that some process be developed that would allow only those professionals with a bona fide need to know to be granted access to the detailed protocols used. Such a response by peers is virtually unheard of in public health and indeed goes against the openness and transparency upon which scientific progress has traditionally been made. It further raises uncomfortable questions about how such a strategy would be implemented both nationally and internationally, and with whom will the censorship authority be vested to decide what is and is not safe to publish. These discussions are far from over. ¹

The importance of laboratory biosafety and biosecurity preparation and training within the many newly constructed biocontainment laboratories around the world has been relegated to fine print in public discussions, which are currently dominated by research and publication oversight issues. It is in these labs where investigators may rightfully expect to build upon these intriguing findings by either replicating the experiments or obtaining the adapted viruses to further relevant investigations of their own design. Both teams conducting the original experiments used biological safety level 3 (BSL-3) facilities enhanced with additional safety precautions to reduce the risk of aerosol transmission. A debate is currently under way as to whether this level of containment is adequate given the approximately 60% mortality rate seen among infected humans since 2003 when the current sustained transmission of H5N1 avian influenza began. ² A strain of influenza that was efficiently transmitted among humans while causing this level of mortality would result in a global catastrophe unlike anything in recorded history. Given the rapidity with which the novel strain of influenza A/H1N1 virus spread in 2009, it is clear that we cannot rely solely on public health interventions to prevent or control a pandemic of influenza when virtually no one has preexisting immunity and the virus is efficiently spread from person to person. Thus, it is clear that preventing the accidental release of the adapted influenza A/H5N1 virus is of paramount importance.

The obvious way to eliminate the risk would be to not conduct the research. This may yet be the outcome; however, it is hard to envision this being the case. As Michael Osterholm said during a recent interview on this subject, “You can't un-ring a bell.” ³ More likely, some level of research will continue involving these newly created viruses with the work being undertaken at BSL-3 or BSL-4 biocontainment.

The risk of pandemic influenza represents a global threat; as the NSABB concluded early on, the global scientific community has a right to demand a say in what work is to be done and by whom. Importantly, those many countries that have invested in the construction of their own biocontainment laboratories may insist on playing a direct role in future investigations.

The National Research Council recently released a report, Biosecurity Challenges of the Global Expansion of High Containment Biological Laboratories, ⁴ which may serve to help inform future discussions on how best to proceed with this and similar difficult situations involving especially dangerous pathogens, public health, and scientific investigations. The report is based on discussions involving expert representatives from 32 countries who gathered in Istanbul, Turkey, in July 2011. Included were laboratory directors, scientists, engineers, and representatives of government and nongovernment organizations active in scientific investigations, public health, surveillance, biosafety, and biosecurity. Past and present challenges were discussed, and it quickly became clear that considerable variation exists in the physical structure and operational standards of containment laboratories around the world.

Biocontainment laboratories are extremely costly to maintain and operate, require an especially high standard of biosafety from their staff, and represent unique biosecurity challenges. Newly formed groups like the International Federation of Biosafety Associations (www.internationalbiosafety.org) and the National Biocontainment Training Center (www.utmb.edu/nbtc/) are making strides in building a culture of safety and security as a foundation for biocontainment laboratory operations, but there is much yet to be done.

Not unexpectedly, there is an inconsistent regulatory environment among countries relevant to their biocontainment facilities. The balance between potential regulatory costs that may decrease efficiency, increase expenses, and lead to loss of scientists to more permissive fields versus the regulatory benefits of potentially reduced laboratory-associated infections, increased safety and security, and decreased risk to surrounding communities is addressed differently around the world. Challenges in the transport of samples and specimens were also of concern. The unique challenges associated with BSL-4 laboratories where the most dangerous pathogens known are handled were addressed, including the impact of the select agent rules on international collaborations and scientific exchanges. Four overarching discussion topics dominated: personnel reliability; the critical needs for training; community relations and the perceived risks of biocontainment laboratories to the surrounding community; and a discussion of the needs, if any, for additional BSL-4 facilities around the world.

As the scientific community works through the difficult issues raised by the creation of an avian influenza virus that is potentially efficiently transmissible among humans, there is an overarching need to ensure that personnel working in biocontainment facilities around the world, and especially those considering work on this most dangerous pathogen, are well trained and that their facilities are adequately prepared and resourced in terms of safety and security. The risks are simply too great to do anything less.