How likely is it that a widespread avian influenza virus could evolve into a deadly new pandemic form of human flu? And does open scientific inquiry into the answer to that question potentially make it easier for someone to unleash an infectious bioengineered plague on the world? Both those sets of worries collided in the wake of discoveries about the H5N1 avian influenza (bird flu) virus that were published in 2012. See also: Avian influenza (bird flu)

In recent years, many epidemiologists have expressed concern about the potential for the world to be struck by another highly lethal influenza outbreak like the Spanish flu pandemic of 1918. Medical records suggest that the Spanish flu, often called the most devastating outbreak of infectious disease in history, killed at least 20 million people around the world and possibly tens of millions more. Most of its victims were young adults, in contrast to most strains of flu, which primarily kill the elderly and young children. Studies have confirmed that the Spanish flu virus, designated H1N1 influenza, had until a relatively short time before caused disease only in birds, but had then mutated into a new form that could infect humans. Part of the reason why H1N1 was so deadly in humans was that the “unfamiliarity” of the previously avian virus triggered systemic inflammatory response syndrome (SIRS)— a massive overreaction by the patient’s immune system, also called a cytokine storm, that destroyed the lungs. See also: Cytokine; H1N1 influenza; Influenza; Pandemic of 1918

Epidemiologists therefore watch outbreaks of avian flu extremely carefully, especially ones that involve a virus called H5N1, which has many features like those of H1N1 and is seen as a leading candidate to become the cause of a future pandemic. Nevertheless, scientists were generally able to reassure the public that it is usually hard for viruses to migrate from one host species to another and that their transmissibility and deadliness normally diminish in the process. (Some humans, mostly ones living and working on farms, have been infected with H5N1 by contact with birds. In cases of this human H5N1 disease, the mortality rates may have run as high as 60%. Evidence of person-to-person transmission has been lacking, however, and that is the crucial requirement for a pandemic to occur.)

Those consolations rang hollow after announcements by two teams of scientists working independently on H5N1 in 2011, both of which found that the virus might be able to hop from birds to mammals with ominous, surprising ease. Groups led by Ron Fouchier at the Erasmus Medical Center in the Netherlands and by Yoshihiro Kawaoka at the University of Wisconsin-Madison artificially infected laboratory ferrets with H5N1. Within few viral generations, they were able to select for a strain of virus that was transmissible between ferrets through the air. This altered strain differed from the standard form of the virus in only nine mutations. Just nine mutations—an unexpectedly small number—differentiated the highly transmissible strain from the standard form of the virus.

One implication of these results, which experts recognized immediately when the results were announced at a conference, was that the emergence of a severe human disease from avian H5N1 might occur faster than previously believed. Another was that military forces or terrorists might exploit knowledge of the techniques used by the Dutch and Wisconsin groups to create a lethal bioengineered flu virus as a weapon.

The U.S. National Science Advisory Board for Biosecurity (NSABB) therefore urged in late 2011 that flu researchers and scientific journals observe a voluntary moratorium on releasing all the details of how the experiments were performed. Many scientists objected that the benefit to medical research that could come from the free release of the information outweighed the actual risk that it could be put to malicious ends. In January 2012, an international group of 40 scientists nonetheless announced they would observe the voluntary moratorium suggested by the NSABB.

Fouchier, Kawaoka, their colleagues, and the journals agreed to withhold the results for some time, pending review. Eventually, experts concluded that the deadliness of the mutant H5N1 diminished sharply enough in the process of becoming air-transmissible that the work did not pose an immediate threat. Papers from both groups were published in June, one in the journal Science, one in Nature. The NSABB was inspired by these results to revise U.S. federal policies and place more curbs on basic research with clear relevance to potential biological weapons.

In January 2013, in a statement published online jointly by Science and Nature, the same international group of influenza researchers announced that they were ending the moratorium and that experimental study of H5N1 would recommence. A moratorium remained in effect for research in the United States and for laboratories receiving U.S. funding, however, and it currently remains to be seen when that will change.