Race Is Seen as Real Guide to Track Roots of Disease
New York Times
July 30, 2002
By NICHOLAS WADE
Challenging the widely held view that race is a
"biologically meaningless" concept, a leading population
geneticist says that race is helpful for understanding
ethnic differences in disease and response to drugs.
The geneticist, Dr. Neil Risch of Stanford University, says
that genetic differences have arisen among people living on
different continents and that race, referring to
geographically based ancestry, is a valid way of
categorizing these differences.
Dr. Risch's position was prompted by an editorial last year
in The New England Journal of Medicine asserting that "
`race' is biologically meaningless," and one in Nature
Genetics warning of the "confusion and potential harmful
effects of using `race' as a variable in medical research."
Dr. Risch's assertion, in a paper in the online journal
Genome Biology, comes as researchers and physicians are
trying to interpret the DNA data streaming from the Human
Genome Project and to make sense of the fact that the
pattern of data differs among ethnic groups.
All humans have the bulk of their genetic heritage in
common and possess the same set of genes. But because of
mutations, or changes in DNA, each gene comes in several
slightly different versions, and some of them are more
common in one ethnic group than another. These genetic
differences often have medical significance, since some
occur among genes that affect susceptibility to disease and
the response to drugs.
It has long been known that some diseases are not evenly
distributed. For example, a mutation that causes
hemochromatosis, a disorder of iron metabolism, is rare or
absent among Indians and Chinese but occurs in 7.5 percent
of Swedes. A common mutation that causes sickle cell anemia is prevalent
among Africans and is thought to have
originated among Bantu-speakers before the Bantu expansion 2,000 years
Lactose intolerance, the loss of the ability to digest
lactose after weaning, is the default condition of
humankind but among Northern Europeans the ability is often
retained into adulthood. The reason is a mutation that may
have been favored among early cattle farmers.
The apparent correlation between race, genetic data and
disease has prompted at least two schools of thought among
biomedical researchers. One holds that race is so poorly
defined that it is not a reliable biological concept and
should be banished, if possible, from scientific vocabulary. This is the
view espoused by The New England Journal of Medicine.
Many population geneticists, on the other hand, say it is
essential to take race and ethnicity into account to
understand each group's specific pattern of disease and to
ensure that everyone shares equally in the expected
benefits of genomic medicine.
Meanwhile a proposal for avoiding racial labels, at least
for drug trials, has recently been made by Dr. David
Goldstein, a population geneticist at University College,
London. He has suggested that patients be assigned to
different genetic groups by analyzing their DNA. The
process gives much the same result as asking people to
identify their ethnicity, but yields a more accurate division in terms
of how people respond to drugs, Dr. Goldstein says. He adds that the expense
of the genetic testing will be affordable in drug trials.
In asserting that race is a valid concept for medical
research, Dr. Risch has plunged into an arena where many
fear to tread. He also takes issue with Dr. Goldstein's
race-sidestepping proposal, saying it will lead to
Race, as Dr. Risch describes it, has arisen because of the
numerous small genetic differences that have developed in
populations around the world. Many studies, Dr. Risch
writes, have shown that these differences cluster into five
major groups, which are simply the world's major
When modern humans spread out of Africa and across the
globe, these early populations bred for many generations in
substantial isolation from one another, allowing genetic
differences to build up between groups. These five
geographically isolated groups, in Dr. Risch's description,
are sub-Saharan Africans; Caucasians, including people from
Europe, the Indian subcontinent and the Middle East;
Asians, including people from China, Japan, the Philippines
and Siberia; Pacific Islanders; and Native Americans.
There are also many peoples who are genetic admixtures of
the major groups. Somalis and Ethiopians, on the boundary
between Caucasians and Africans, are an admixture of the
two, Dr. Risch said, as are African-Americans.
Dr. Risch calculates on the basis of existing surveys that
testing a person's DNA at 100 random sites along the
genome, or at 30 specially chosen ones, would be sufficient
to distinguish the major racial groups. It would require
tests at some 50 specially chosen sites to distinguish
people from different ethnic groups within a race, he said.
The ancestral human population would have contained within
it many genetic differences and alternative gene forms
inherited from the predecessor species. This shared pool of
differences still accounts for 85 percent to 90 percent of
those seen in the global human population, according to
many measures. The differences between ethnic groups
account for the other 10 percent to 15 percent. This
well-known analysis, however, is based on commonly
occurring versions of genes, and rare versions of genes,
when measured, may show a greater tendency to be specific
to different populations, Dr. Risch said.
Dr. Risch believes that race, when self-defined by
continent of ancestry, is a true reflection of these
genetic differences, including those important for
understanding disease. "There is great validity in racial/
ethnic self-categorizations, both from the research and
public policy points of view," he says.
Editors of both the journals criticized by Dr. Risch
expressed respect for his views. Dr. Robert Schwartz, the
deputy editor of The New England Journal of Medicine and
the author of its editorial, said Dr. Risch's article was
"a serious piece of work and merits a lot of thought."
Dr. Bette Phimister, editor of Nature Genetics, said that
"Risch's point that there is a high and useful degree of
correlation between ethnicity/race and genetic structure,
is well taken, and one with which we agree."
Both editors also expressed support for the proposal
advanced by Dr. Goldstein, that of bypassing race by going
directly to the genetic markers in each patient that might
correlate with drug response or disease.
Dr. Goldstein, too, said he agreed with Dr. Risch that "the
geographic patterning of genetic variation is real and has
medical implications and one does need to take account of
"Neil is arguing against some people in the medical
community who say racial labels have nothing to do with
drug response, and he is right," he said.
But Dr. Goldstein says he believes the genetic variation
can be studied directly, without invoking race. In an
article last year in Nature Genetics, he and colleagues
analyzed genetic markers in people from eight ethnic
groups. When the people were regrouped according to their
genetic markers, that proved a better guide to drug
response than did their ethnic group, Dr. Goldstein
But Dr. Risch said it was unsatisfactory to sidestep race,
because it might lead researchers to ignore the many other
factors besides genetics that are associated with race. Dr.
Goldstein's genetic marker system, which divides people
into almost exactly the same categories as does
geographically based race, would compel a researcher to
think the only differences between two groups were genetic.
If the two groups were Caucasian-Americans and
African-Americans, say, the researcher might be blinded to
other explanations, like a difference in access to medical
Dr. Goldstein said that to understand the geographical
pattern of human genetic variation, "you want the best
representation you can find, and it is a technical question
as to whether explicit genetic representation or racial
labels are better."
"That's an argument we will have in the scientific
literature, and Neil will lose," Dr. Goldstein continued.
Race and ethnicity have become important considerations for
biologists hunting for the variant genes the predispose
people to common diseases. Failure to take ethnicity into
account can confound a study, particularly if the disease
in question is more common in one ethnic group than
Scientists often hunt for genes in laboratory animals by
mutating them with radiation or chemicals. No one would
think of inducing informative sets of mutations in people,
but nature has already performed the experiment by shaping
the human population into groups with differing
susceptibilities to disease. This genetic differentiation
among races is one that some gene hunters would like to
Dr. Stephen O'Brien, a geneticist at the National Cancer
Institute, said that the conclusion that race was not a
valid concept "comes from honest and brilliant people who
are not population geneticists."
"That doesn't mean they are insincere," Dr. O'Brien said.
"It's just that they haven't really looked at it. What is
happening here is that Neil and his colleagues have decided
the pendulum of political correctness has taken the field
in a direction that will hurt epidemiological assessment of
disease in the very minorities the defenders of political
correctness wish to protect."
Others play down the medical usefulness of racial
differences. "We can't wish away these boundaries," said
Dr. Aravinda Chakravarti, a population geneticist at Johns
Hopkins. "But I'm not convinced that knowing these
boundaries is necessarily useful for genetic research."
Dr. Risch concludes his review by noting that every race
and ethnic group within a race has its own set of diseases
and clinical priorities, which a new arsenal of genetic
tools is poised to address. "We need to value our diversity
rather than fear it," he writes. "Ignoring our differences,
even if with the best of intentions, will ultimately lead
to the disservice of those who are in the minority."