In early 2011, two groups were investigating how flu viruses specific to birds could possibly cross over and create pandemics in humans: one led by
Yoshihiro Kawaoka at the
University of Wisconsin–Madison in Madison, Wisconsin, and another led by
Ron Fouchier at
Erasmus University Medical Center in the Netherlands.
[24][25] Both groups had both
serially passaged H5N1 avian influenza in ferrets, manually taking the virus from one ferret to another, until it was capable of spreading via
respiratory droplets. The normally bird-specific virus, through replication over time in the ferrets' lungs, had adopted several amino acid changes that enabled it to replicate in the mammalian lungs, which are notably colder than those found in birds.
[26][27] This small change also allowed the virus to transmit via droplets in the air made when the ferrets' coughed or sneezed.
[24]
Proponents of the Kawaoka and Fouchier experiments cited several benefits: these answered the question of how a virus like H5N1 could possibly become airborne in humans, allowed other researchers to develop vaccines and therapeutics which specifically targeted these amino acid changes,
[28][29][30] and also demonstrated that there was a linkage between transmissibility in avian viruses and lethality: while the virus had become more transmissible, it had also become significantly less deadly.
[25][31][32] Various critics of the research (including members of Congress) responded to the publications with alarm. Others called the experiments an "engineered doomsday."
[33] Questions were raised by other scientists including Marc Lipsitch of the
T. H. Chan School of Public Health at
Harvard University about the relative risks and benefits of this research.
[34]
At an international technical consultation convened by the WHO it was concluded that this work was an important contribution to public health surveillance of H5N1 viruses and to a better understanding of the properties of these viruses, but that broader global discussions were needed. The European Academies of Science Advisory Council (EASAC) concluded that all required laws, rules, regulations, and codes of conduct are in place in several EU countries to continue this type of work responsibly. In the US, where regulations were previously less strict than in the EU, a new governmental policy and review mechanism was launched for "Potential Pandemic Pathogen Care and Oversight" (P3CO).
In May 2013, a group led by
Hualan Chen, director of
China's
National Avian Influenza Reference Laboratory, published several experiments they had conducted at the
BSL3+ laboratory of the
Harbin Veterinary Research Institute, investigating what would happen if a 2009 H1N1 circulating in humans infected the same cell as an avian influenza H5N1.
[35] Importantly, the experiments had been conducted before a research pause on H5N1 experiments had been agreed upon by the greater virologist community.
[36][37] They used these experiments to determine that certain genes, if reassorted in such a dual-infection scenario in the wild, would allow transmission of the H5N1 virus more easily in mammals (notably guinea pigs as a
model organism for rodent species), proving that certain agricultural scenarios carry the risk of allowing H5N1 to cross over into mammals. As in the Fouchier and Kawaoka experiments above, the viruses in this study were also significantly less lethal after the modification.
[37][38]
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