Monday, May 29, 2006

Orent gets it (mostly) right

I've been tough on journalist Wendy Orent here because I thought her widely read op-ed pieces on bird flu were wrong-headed, inaccurate and unhelpful in getting people ready for a possible pandemic. Yesterday she had another op-ed in the LA Times and I'm glad to say it's on the right track. Not that I agree with everything she says, but it's informative and helpful to readers who want to understand some of the controversies. Here's the lede:
There's a lot of bird flu virus out there. Despite encouraging news from Vietnam and Thailand, neither of which has reported any bird or human cases of the lethal H5N1 strain this year, the situation in Indonesia continues to worsen. Eight members of a family contracted the disease, and seven of them died this month. The timing suggests person-to-person transmission. Although not the first instance of such transmission, it's the single largest cluster that has been seen, according to virologist Earl Brown of the University of Ottawa. Indonesia appears to lack the resources to combat the disease.

The virus is also active in Egypt and has spread to Israel, Jordan and the territories where Palestinians live. Africa has a wide belt of infection. With the disease spread over so much of the world, more people in contact with sick birds means more opportunities for humans to catch the virus. This appears how human influenza pandemics have begun — through human contact with sick birds.

But 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. (LA Times)
The rest is a discussion of what she and others think this talk of mutation means. I might disagree in details, but essentially I agree we don't know much about what it would take. Most scientists don't believe a chicken virus turns into an easily transmissible human virus in one step (although it's possible). But Orent goes further. Her view is that natural selection is the key to the virus's evolution and it can't happen suddenly, requiring instead a period of adaption in mammalian and probably human hosts.

This isn't an unreasonable point of view, and this adaptation might be occurring now in Indonesia and elsewhere. But I think it's wrong to believe it is the only point of view. Here are a couple of other possibilities.

Whatever genetic changes are needed for transmissibility in humans may be traveling along with some that are useful for the virus in birds. Selection pressure doesn't explain everything, as we see in the sudden emergence of amantadine resistance in virtually all flu virus in the US. Amantadine is not used much in the US, so this isn't selection. Most likely it is a "hitchiker" effect with the amino acid change conferring amantadine resistance linked with another genetic feature that conveys some selective advantage (a point made by bioinformatician EC Holmes). Here's another possibility. It takes multiple genetic switches to be flipped to produce enhanced transmissibility in humans (let's say ten) but eight or nine are already flipped, leaving only one or two to go. Since we are largely ignorant of what it takes, we are also ignorant about how many switches are flipped already. Here's yet another point. Genetic changes that enhance transmissibility don't have to confer selective advantages or be linked to them. Without such an advantage the virus will eventually be replaced by another, more fit one, but the transient period could be very nasty. None of this is not a repudiation of Darwinism. It is consistent with the current neo-Darwinian synthesis ushered in by Sewall Wright, Ernst Mayr and others in the 1930s and 1040s.

So it's good to see Ms. Orent on board. A flu-denier has now become a useful source of information. I hope she's right about her viral evolution scenario. But the distinct possibility she isn't is good enough reason to prepare.