LAST month researchers from the University of Texas and the University of Mississippi Medical Centre published a paper in the New England Journal of Medicine. They had studied three versions (or alleles, as they are known) of a gene called PCSK9. This gene helps clear the blood of low-density lipoprotein (LDL), one of the chemical packages used to transport cholesterol around the body. Raised levels of LDL are associated with heart disease. The effect of all three types of PCSK9 studied by Jonathan Cohen and his colleagues was to lower the LDL in a person's bloodstream by between 15% and 28%, and coronary heart disease by between 47% and 88%, compared with people with more common alleles of the gene.

Such studies happen all the time and are normally unremarkable. But this was part of a growing trend to study individuals from different racial groups and to analyse the data separately for each group. The researchers asked the people who took part in the study which race they thought they belonged to and this extra information allowed them to uncover more detail about the risk that PCSK9 poses to everyone.

Yet race and biology are uncomfortable bedfellows. Any suggestion of systematic biological differences between groups of people from different parts of the world—beyond the superficially obvious ones of skin colour and anatomy—is almost certain to raise hackles. There are good reasons for this. The eugenics movement of the late 19th century soon turned racist and that sorry story culminated with the doctrine of racial hygiene and the death camps of Nazi Germany. Yet decades ago, Luca Luigi Cavalli-Sforza of Stanford University showed that the frequencies of different alleles of genes for several blood and immune-system proteins vary geographically. It is now starting to be accepted that these sorts of variation can matter for health. If so, searching for genetic variations in different racial groups is not only acceptable, but also obligatory.

In Dr Cohen's work, the race question proved decisive. Of the 3,363 volunteers who described themselves as “black”, 0.8% carried an allele of PCSK9 called version 142X and 1.8% carried one called version 679X. Among 9,524 self-described “white” volunteers, a mere 0.02% carried version 142X and 0.04% carried version 679X. By contrast, 3.2% of white people carried the third allele under study, version 46L, while only 0.7% of black participants did. The researchers found that these relatively rare alleles correlated with low LDL, and did so in both blacks and whites, allowing them to conclude that it was the gene change that was crucial. If the team had ignored race and simply compared those who had heart disease with those who did not, and asked which alleles were linked to the risk, they would probably have missed the clinical significance of the alleles. This is because they would have appeared so infrequently—in less than 0.3% of the whole study population for version 142X—that their effects would have been swamped. That is even truer for less populous racial groups; indeed, the smaller the group, the less likely researchers are to find important but rare alleles unless they can break the population down. Ignoring race altogether would be to the detriment of medical knowledge about the very people who might benefit.

It is this—the question of who gains—which is allowing the otherwise taboo subject of racial genetics to be broached. If it is minority groups (or, at least, groups that are minorities in America, where most of this work is being done) who are likely to reap the rewards, then the objections are likely to be muted. But they have certainly not gone away.

Race to the finish

For example, according to Richard Cooper, a professor of medicine at Loyola University in Chicago, talking about black people having a gene that predisposes them to some disorder or another “feeds a social process” that is deeply negative. As he observes, black Americans suffer more from high blood pressure than white Americans. “We don't know why, but everyone says it is genetic. But if you look around the world, by far the highest hypertension rates are in Poland, Finland and Russia. Much higher than black Americans. The average difference in blood pressure between blacks and whites is about 4mm of mercury, the difference between whites in the US and Russia is about 20mm. No one has ever said that these white people are genetically predisposed to hypertension: it must be their diet. But when they talk about blacks, it has to be genetics. That, in a nutshell, is the whole problem with this whole way of thinking.”

There is much truth in this criticism. But sometimes you find the opposite: racial differences seem to amplify observable genetic ones. One example cited by Neil Risch, the director of the Centre for Human Genetics at the University of California, San Francisco, concerns ApoE, another gene involved in LDL metabolism. One particular allele of this gene, ApoE4, is associated with an increased risk of Alzheimer's disease.

ApoE4 is relatively common in most racial groups. About 9% of Japanese Americans have it, 14% of white Americans and 19% of black Americans. But the impact of ApoE4 differs significantly between these groups. Individuals of Japanese descent who have two copies of ApoE4 (one from each parent) have a 33-fold increased risk of contracting Alzheimer's disease compared with those who have other versions of ApoE. Those of European descent have a 15-fold increased risk. Blacks, by contrast, have a mere six-fold increase in their risk. “Whether it is due to differences in genetic background or environment, who knows? But if you ignore race, you would never know,” says Dr Risch. Moreover, if the American population was sampled for ApoE4 and Alzheimer's risk without regard for ethnicity, the risk would resemble that of whites, because their numbers would overwhelm the data from the other racial groups. As Dr Risch says, “I think these categories are useful as long as they are predictive. That doesn't prove that the difference is genetic.”

In the genes

In some cases, though, the difference clearly is genetic. A gene called UGT1A1 controls the metabolism of a colon-cancer drug called irinotecan. Approximately 20% of African-Americans, 15% of whites and 1% of Asians have two copies of a non-functional version of this gene called *28. Because individuals lacking functional UGT1A1 are at risk for serious complications if given the standard dose of irinotecan, genetic testing of patients before starting irinotecan therapy has become normal. Yet, while only 1% of Asians have two copies of the *28 allele, which is detected by the genetic test, 2.5% of Asians have another non-functional version called *6 which is not detected by the standard test. Indeed, it does not occur in blacks or whites. Thus, testing Asians for the *28 allele does not provide them with the same quality of care as it does for African-Americans or whites. “Identical treatment is not,” as Dr Risch puts it, “equal treatment.”

On the other hand, focusing too closely on race may not be the right answer either, as the tale of a drug called BiDil illustrates. The drug was originally tested some 20 years ago for its ability to reduce heart failure in high-risk patients. Overall, it had limited effect. In recent years, however, researchers noticed that the few blacks in the study tended to have a better response than the majority white population did. Thus, Nitromed, the company that now owns the drug, designed a clinical trial that compared BiDil plus standard therapies to standard therapies alone, but only in African-American patients. The drug worked, reducing deaths from heart attacks by 43%, and the Food and Drug Administration approved BiDil for use in black Americans, making it the first racially-targeted drug. The flaw, as critics point out, is that the drug was not tested in other racial groups, so there is no strong evidence that it worked better in black Americans than in any other group—nor is there any reason, genetic or environmental, why it should.

This sort of work raises another question, with its own set of sensitivities: how, scientifically, do you define someone's race? In studies such as Dr Cohen's this question is fudged, because people defined themselves. That is a reasonable starting point. But America's population is descended mainly from immigrants and those ancestors have been meeting and mating for centuries. Few native-born Americans trace all of their ancestors back to the same part of the world, so how closely are genes affecting disease linked to genes affecting racial self-identification?

Perhaps the last word should go to Francis Collins, who led America's contribution to the Human Genome Project, and thus helped to open the debate. “The downside of using race, whether in research or in the practice of medicine,” he says, “is that we are reifying it as if it has more biological significance than it deserves. Race is an imperfect surrogate for the causative information we seek. To the extent that we continue to use it, we are suggesting to the rest of the world that it is very reliable and that racial categories have more biological meaning than they do. We may even appear to suggest something that I know is not true: that there are bright lines between populations and that races are biologically distinct.”

Eventually, the technology developed to carry out the Human Genome Project, and the science it has made possible, will make the whole question redundant. It will be possible to look at the genes of each person as an individual. But until that time race, used sceptically, does have value. And unlike previous attempts at racial science, this one could actually do people some good.