The second of two controversial papers on the bird flu (avian influenza A/H5N1 virus) was published Friday, June 22 in Science. The first was published on May 22 in Nature. What was controversial wasn't the findings but whether the studies should be made public at all, or even if the work should have done in the first place. Although both papers finally got the go ahead for publication, does the published work warrant all the concern?
Both studies focused on understanding how much change would be required in the bird flu to enable it to transmit from human to human through aerosol infection? This is the core of the concern. Right now, humans only catch the current bird flu strains from direct contact with infected birds. It seems important to understand better how the virus could change and become more more infective to humans. However, the same information could also be turned around and used by neferious groups to make a more infectious version of the bird flu virus. How much of a concern is this?
Why doesn't the bird flu infect humans?
Cell surfaces have receptors that activate in response to different molecules and enable cells to react to their environment. Some receptors trigger a response from the cells to engulf particles when activated.
A virus has to get inside a cell to reproduce. On influenza viruses, one of the proteins on the coat around the virus core, hemagglutinin, displays a type of sugar that sticks to and activates a certain type of cell receptor. The cell then engulfs the virus bringing it inside. The specific variant of hemagglutinin on the bird flu is H5.
There is a little difference in structure between the bird cell and human cell hemagglutinin receptors. This difference make difficult for bird flu H5 to infect human cells, so humans are only infected when directly exposed to very high concentrations of the bird flu. However, bird viruses with other variations of H5 have been able to infect human cells. Many of the standard seasonal flu strains originated in birds, then jumped to humans after some mutations.
How Many Changes for the Bird Flu to Become a Human Flu?
The studies looked at the amount of mutations needed for the bird flu H5 protein to easily infect mammals. They used ferrets which display a lot of the same flu symptoms as humans. The two studies took slightly different approaches.
The first study by a group at the University of Wisconsin used a random mutation approach and found multiple combinations of mutations that conferred particular traits which make the virus more suitable for mammalian transmission and infection.
The second study from a group at Erasmus University in the Netherlands used a more engineered approach, and introduced 3 mutations that were known to make the H5 protein stick better to the receptors on human cells, then tested to see what other mutations were needed to make the strain more infective. The result from this study was that 2 additional mutations (5 total) were enough to make a virus more infectious to mammals and increase its capacity for airborne infectivity—4 mutations of the H5 gene and one in another gene.
Should This Information be Published?
Both studies provide important information about flu virus biology, and how the virus could change into a more infectious and deadly variant. While this work could conceivably be used to design more pathogenic version of bird flu, many scientific studies provide general and specific information on how to make a whole host of more dangerous biologics and chemicals.
The real significance of the work is that it provides useful data about how viruses work and what makes them pathogenic. Frankly, it is not possible to predict the cause of the next dangerous viral outbreak. To play a guessing game whether the next outbreak will be the bird flu or SARS, or some other virus is foolish. You have better odds winning a million in Las Vegas this weekend.
What is practical to defend against the next outbreak is to gain a more complete and thorough understanding of viral biology and pathogenicity. This will enable us to respond smarter and faster to the next outbreak. While we won't know how or where a new serious viral outbreak will occur, it is an almost certain bet that it will occur and we need to be ready when it does. We need the type of data from these studies and many others to be ready.
