Monday, May 08, 2006

Genetic susceptibility to bird flu?

Dr. Robert Webster, one of the most eminent and experienced influenza virologists has been quoted as saying there might be a genetic component in susceptibility to bird flu. His views were echoed by another long time virologist, Hiroshi Kida.
"There has not been a single case of infection involving husband and wife," Kida said told Reuters. Kida is with the department of disease control at Hokkaido University in Japan.

Kida explained that people infected with H5N1 have a carbohydrate receptor on cells lining their throats. The receptor -- called alpha 2,3 -- is predominantly found in birds. Avian influenza viruses like to bind to this class of receptors to replicate and cause disease.

Human influenza viruses, however, prefer to bind to another receptor called alpha 2,6, which is dominant in humans.

"I think people who are infected with avian strains are special. They must have alpha 2,3 receptors," Kida said. (Reuters)
Infectious disease is a product of three interacting components, the host (here, people), the agent (the H5N1 influenza virus) and the environment (conditions of exposure, temperature, etc.). All three take part for influenza, as they do for almost every human disease, including those often thought of as "purely genetic." For example, harm from the inborn error of metabolism, phenylketonuria (PKU) requires a diet containing the amino acid phenylalanine (an "environmental" variable). For this reason, it is wise to be careful when interpreting claims of a genetic component to disease. The environment and how it modifies host defenses are also relevant in most every instance, as are host factors that are not strictly genetic, like occupational history, age and nutritional status.

The appeal of genetics as an explanation in bird flu stems largely from the fact that only a few of those heavily exposed to infected poultry have thus far become infected, giving rise to the question of what is "different" about them. Resort to some inborn defect or susceptibility seems so natural that we often don't think beyond it. If one person smokes half a pack a day and contracts lung cancer while another smokes three packs a day and dies in their nineties of "old age," we naturally think it's "in the genes." Possibly.

But consider this. If I flip a coin and it comes up tails and you flip the same coin, under identical conditions and it comes up heads, we don't say that I have the "tails" gene and you have the "heads" gene. Or if you see a movie and like it and I see the same movie and hate it, we don't say you have the movie-loving gene and I have the movie-hating gene.

Genetic factors are probably at work in virtually every human disease. We are an outbred species and hence vary from each other genetically in ways that might be important for one disease or another. But the situation is almost certainly far more complex. Hunting for a bird flu susceptibility gene isn't likely to get us very far, especially as the virus rapidly changes itself, changing the equation with it.

Kida's claim that no co-habiting unrelated cases have been described shouldn't be taken at face value, either. I don't know if it is true or not, since it is often difficult to be sure of case identities and their circumstances. This has been a disease of young people, so most cases in household clusters have been sibs or related cousins. If true, it as an interesting observation that might provide some ideas for new research. But it shouldn't be seized on as the key factor, any more than the very preliminary data the virus can only find cells to infect deep in the lung is the answer to why the virus so far has had low transmissibility. It might (or might not) be a factor, but we are far from being sure.

We want science to move fast and in the case of flu science it is moving with uncommon rapidity. But it is still a relatively slow process, as much as we wish instant answers.