BIOLOGY AND RACE: A CLEARER LINK

NEW GENETIC RESEARCH ESTABLISHES FIRMER BASIS FOR CONNECTION

(second part of fourth page feature on the human genome)

Thursday, May 8, 2003

Research of immediate clinical importance seems to raise fewer hackles than the theoretical consideration of race and biology.

Among the members of the panel on the ethical, social and policy implications of studies of human genetic variation at the annual meeting of the American Association for the Advancement of Science was Scott Weiss, professor of medicine at Harvard Medical School, who specializes in asthma. He spoke about "pharmacogenetics," the study of how genes influence an individual's response to drug treatments,.

Asthma is a common, chronic disease of immense importance; 17 million people have it, 12 million of them under 18. It's the most common cause of hospital admissions and of time lost from school, and it's 80 percent more common than it was 15 years ago. A study released last month determined that more than a quarter of children in Harlem have asthma, twice the level researchers expected to find.

Like other common, chronic diseases, Weiss said, asthma's cause is unknown, but it is apparently influenced both by environmental factors -- parents' smoking, for example -- and by genetic factors, possibly involving more than 160 separate genes.

The goal of Weiss' research team was to identify a specific gene or genes that affect how well individuals respond to the inhaled steroids often used to treat asthma. That's important, because one class of commonly used drugs, glucocorticoids, can have severe side effects, including cataracts, loss of bone minerals and in the case of children, reduced height. If doctors could know in advance who was unlikely to benefit from the drugs, they could avoid at least unnecessary side effects.

First the researchers chose a set of 14 genes that were likely to be influential, based on what's known about their function. Each of them occurs in several variants, called alleles, and as with most of the genes that have been studied, all the variants occur in different ethnic populations but not equally often. And variations in drug response also occur in different ethnic populations, but not equally often; If in a given clinical trial, one gene variant matches up statistically with a response variant, it's an indication that they may be related physiologically as well.

In the first clinical trial the researchers studied, which included 470 adults, almost all Caucasian, with moderate to severe asthma, they found five possible gene candidates. Next they looked at a clinical trial on a very different population, 1,041 children, 25 percent African-American or Hispanic, with relatively mild asthma cases. One of the five possibles checked out in that group too, suggesting the result might be broadly generalizable.

The experiment proves the concept works, Weiss said, but he's concerned about equity and access. Most asthma trials are very small, "and finding any effect is difficult, let alone one specific to an ethnic group," he said.

Research that leads obviously and immediately to better medical treatment is easier to defend -- or perhaps more accurately put, harder to attack for political reasons -- than research whose applications are less direct and which might be more vulnerable to being abused. But without the knowledge gained from basic research, applied research is less likely to succeed.