Since it emerged in Hong Kong in 1997, H5N1 influenza has killed millions of chickens, mostly in Asia. People are rarely infected, but when that happens they are likely to die. Since 2003 there have been 602 human cases and 355 deaths.
In the lab, Kawaoka started with an H5N1 strain that had killed several people in Vietnam in 2004. He isolated the gene for “hemagglutinin,” which is most responsible for contagiousness. He put into it two mutations that allow the flu virus to attach more easily to cells in a person’s throat.
He then combined that doctored gene with the “normal” genes from the strain of H1N1 flue that caused the human flu pandemic in 2009. Two more mutations in hemagglutinin appeared during lab experiments and after ferrets — which stand in for people in flu studies — were infected with the virus.
Together, the four mutations made the engineered virus transmissible through the air, although it didn’t kill the ferrets who caught it, or even make them very sick. Whether “wild” bird flu virus containing them would be both contagious and deadly isn’t known.
However, the experiment has given scientists an idea of what mutations to look out for — which was the purpose of the research from the beginning.
One of the mutations is already widespread in H5N1 strains circulating in the Middle East. Some of those strains also carry a mutation in a different gene that makes growth in human cells easier.
“These viruses may be several steps closer to those capable of efficient transmission in humans and are of concern,” Kawaoka and his colleagues wrote in their Nature article.
A second paper, by Dutch scientist Ron A. M. Fouchier, that made a more contagious bird flu virus using other methods, is awaiting publication at the journal Science.
The National Science Advisory Board for Biosecurity, a panel of independent experts that advises the federal government, in December asked the two journals to hold off publishing the papers while researchers and governments thought about how to handle this kind of research. In late March the board looked at the experiments more closely and said it no longer opposed publication.