The resumption of experiments to enhance the transmission capabilities of H5N1 bird flu (influenza) viruses has renewed controversy within the scientific community over this research area (1). Critics have called into question both the fundamental scientific merits of the work as well as raising concerns the artificially augmented viruses might escape the laboratory and create a pandemic. Explaining it contains “proprietary and grant competition information” (1) a risk-benefit review of the situation conducted by the government will not be made public, irritating some of those questioning the value and advisability of this research. Notwithstanding concerns about divulging confidential information and given that some methods and results have already been published in the open literature, it is hard to believe a suitably redacted account of the testimony, evidence and discussions leading to the final go-ahead decision cannot be assembled. This leaves the public with no visibility into an important decision-making process allegedly made in the greater public interest.
Chance and Necessity
It is sometimes necessary to work with exceptionally dangerous pathogenic agents. Well-trained personnel in appropriately constructed facilities adhering to carefully designed operational protocols can perform such efforts with a high degree of safety. However, when it comes to conducting experiments designed to increase the transmission risk of a potentially pandemic pathogen (PPP) like avian influenza H5N1 where the consequences of error could be catastrophic, will high-containment facilities operated under the most stringent rules ensure safe containment?
Shortly after a research moratorium had been lifted (1), heightened concerns following publicized accidents at high bio-containment labs forced another general suspension of gain-of-function experiments with avian influenza and other dangerous viruses. Pathogen escapes from laboratory control that produced disease outbreaks are documented in the public record (2) and safety lapses at high-containment facilities continue to be reported (3). Attempts have been made to quantify the public health risk posed by research with PPPs such as H5N1 bird flu viruses (4). Noting the expanding number of laboratories now attempting to create airborne route-transmissible highly pathogenic avian influenza viruses, one author concludes the current risk of an accidental pandemic is now about equally likely as a natural event (4). It is impossible to gauge whether a human pandemic caused by an escaped engineered bird flu virus would produce an elevated death rate (4), but the realization such a tragic event could be so likely to occur is shocking.
Half a Job?
Making certain all laboratories performing PPP research have adequate resources, proactive plans in place to mitigate mishaps and well-trained staff are essential, but may be addressing only the most tractable part of a far larger, more problematic and steadily expanding biosecurity problem. In addition to rigorous oversight of trained professional scientists and their facilities, it is essential to account for the possibility a PPP such as H5N1 bird flu artificially selected to be airborne transmissible between humans may be deliberately released (5). Unfortunately, the diverse roster of actors who conceivably might hatch such plots ranges from a single, demented person to entire nation-states. Along with the limited factual information available on such actors, risk estimates of the threats posed by nefarious actions more precise than assertions ‘it could happen’ are guesswork (5).
The authorities are divided over the interpretations of objective evidence for prior deliberate releases of pathogenic agents. There is no question that the Amerithrax event of 2001 was an attack with a biological agent, but even with an intense forensic effort and solid corroborating physical evidence, figuring out who launched it was mired in egregious error and controversy (6).
Based on genetic sequence analyses, a consensus has been reached the 1977 Russian influenza pandemic was not a natural event (7). This strange situation has figured prominently in the debate over whether or not to permit experiments to create H5N1 bird flu viruses that might be capable of efficient airborne transmission between humans. Noting that the 1977 H1N1 influenza pandemic was more likely to have come about due to vaccine development or vaccine trials than a laboratory error, some scientists argue this possibility should temper concerns over accidental release of augmented influenza viruses from a secure research facility (7). As no objective evidence exists either way, how reassuring that line of reasoning is depends on what one wishes to believe constitutes the true account of events explaining the sudden 1977 Russian flu virus emergence. However, the vaccine hypothesis leaves a few more open questions to explore.
Why That Vaccine?
Influenza vaccine production and testing procedures do seem intrinsically more likely to cause an accidental release of virus than research lab work. However, it is important to keep in mind a vaccine production mishap scenario still fits well with the deliberate use concerns posed by Inglesby and Relman (5). The release during production/testing operations hypothesis leads to questions about exactly who, and for what purpose, was going to the trouble and expense to manufacture vaccine for a flu virus that had not circulated for over 20 years and therefore had no conceivable clinical utility. Whatever their true purpose and origins, the events of 1977-78 demonstrate it is possible to launch an influenza pandemic that would be highly effective against a select immunologically naïve population such as persons of prime military service age.
Too Much Information
Inglesby and Relman (5) point out that technology widely available today makes publishing complete genetic sequences of agents like lab-created influenza almost equivalent to distributing the virus itself. Researchers would not provide such potentially dangerous viruses to persons without an appropriate need to acquire them and a demonstrated capacity to work with them safely. Unfortunately, refusing sample requests may no longer present an insurmountable barrier for persons denied access by professional scientists. Some experiments creating H5N1 influenza viruses with possible person-to-person airborne transmission capability have been published in full (4). That means persons who would like to have such a virus and finding themselves stymied by professional scientists could make use of the published genetic sequence blueprints to build their own.
Smallpox is extinct and the virus responsible for the original SARS outbreak seems to be as well. However, PPP viruses like influenza H5N1 are still in circulation in some parts of the world which elevates the potential threat for possible illegitimate acquisition and malevolent use. Persons without a technical capacity to synthesize a virus genome in vitro might be able to acquire samples and emulate published methods to gin up viruses that have potential for airborne spread between humans or create other types of mayhem. Knowing with certainty that others before them have succeeded could be a vital bit of information – and motivation – to press forward with their own plans.
Decisions regarding the information about influenza research appropriate for release have led us to astonishing contradictions and an alarming predicament. When it comes to the possible risks posed by PPP research, the authorities have dutifully restricted information that would enable the public to make informed decisions about the research priorities of professional scientists. At the same time, they have allowed the essential knowledge required to create and re-create potentially deadly pandemic forms of influenza viruses to be actively disseminated to the entire world through open publication in the scientific literature. There is no telling who might end up making use of that information.
(1) Jocelyn Kaiser. EXCLUSIVE: Controversial Experiments That Could Make Bird Flu More Risky Poised to Resume. Science, 8 February 2019. https://www.sciencemag.org/news/2019/02/exclusive-controversial-experiments-make-bird-flu-more-risky-poised-resume
(2) Martin Furmanski. Laboratory Escapes and Self-Fulfilling Prophecy Epidemics. Center for Arms Control and Nonproliferation. https://armscontrolcenter.org/wp-content/uploads/2016/02/Escaped-Viruses-final-2-17-14-copy.pdf
(3) Denise Grady. Deadly Germ Research is Shut Down at Army Lab Over Safety Concerns. The New York Times, 5 August 2019. https://www.nytimes.com/2019/08/05/health/germs-fort-detrick-biohazard.html
(4) Lynn C. Klotz. Is There a Role for the Biological Weapons Convention in Oversight of Lab-Created Potential Pandemic Pathogens? Bulletin of the Atomic Scientists, 27 August 2019. bit.ly/327nis6
(5) Thomas V. Inglesby and David A. Relman. How Likely is it that Biological Agents Will Be Used Deliberately to Cause Widespread Harm? EMBO Reports 17(2):127-130. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290809/
(6) Scott Shane. F.B.I., Laying Out Evidence, Closes Anthrax Case. The New York Times, 19 February 2010. https://www.nytimes.com/2010/02/20/us/20anthrax.html
(7) Michelle Rozo and Gigi K. Gronvall. The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate. mBio 6(4): e01013-15. https://mbio.asm.org/content/mbio/6/4/e01013-15.full.pdf