Article by Wendy Orent, in LA Times, includes:

… the factors that set off a pandemic remain unknown. No one has ever tracked the evolution of a new pandemic. All we have seen — in 1918, 1957 and 1968 — is the aftermath of that evolution. Still, we are told that all it would take for H5N1 to become a pandemic would be for the virus to mutate so it could spread in a sustained way from person to person. This is known as "mutation to transmissibility." … The H5N1 virus faces several barriers in jumping to and transmitting among humans. The most important is its ability to replicate in and adapt to human tissues, specifically the upper respiratory tract (not in deep lung tissue, where it now seems to grow). In the windpipe, the virus would be more likely to spread in a cough or sneeze, infecting other humans. …

[Earl] Brown recognizes what seems to elude most people who worry about pandemic outbreaks: What's necessary to produce a human-adapted virus is humans — a series of person-to-person infections. Without that chain of transmission, any human adaptation of H5N1 is difficult to imagine. … interact with other viral genes in a human host to improve its ability to infect the host. This is an adaptive process — and it is true whether the new virus arises directly through mutation or even through recombination with a common flu strain. H5N1 is beautifully, tragically adapted to chickens and has proved a monstrous predator. It evolved this way by preying on chickens packed into huge commercial chicken farms in Asia. The bird flu virus is still at the starting gate when it comes to humans. But should any strain of H5N1 manage to survive many sequential transmissions, Darwin's charioteer may drive off. The best transmitters will be favored by selection, as evolutionary biologist Paul W. Ewald of the University of Louisville contends. The process will continue, human by human, until a fully human-adapted, explosive strain emerges. …

At the beginning, viral adaptation to a host is slow. A disease just beginning to transmit is controllable. Surveillance, flexibility, willingness to impose or undergo quarantines, along with international cooperation, will be necessary to stop pandemic flu — or any other disease moving from animals to humans — before Darwin's driver gets ahead of us and nothing can be done.

What Darwin has to say about bird flu Can the disease mutate into a widespread threat to humans? Possibly, but it won't happen overnight.

I emailed Wendy to check whether this rather ominous last sentence (and "explosive strain") meant some change in her thinking re not being possible right now to evolve a virulent flu.

Her reply:

No, I haven't changed my position. A pandemic (without WWI etc. conditions) would NOT be a lethal pandemic – just an ordinary one, like 57 or 68. And quarantine would work in the early stages, as the virus adapts. An explosive strain merely means a highly transmissible strain, not a lethal strain. I am afraid many people may understand this the way you did. It's actually the same argument I've been making for years – just another piece of it. It would be awful if people think I've changed my position, under pressure maybe. Not at all. I haven't changed a bit – I just wanted to show why the phrase "mutate to transmissibility" is essentially meaningless, and that the evolution of any pandemic would have to come through natural selection. That's how it happened in the past; that's how it could happen in the future.