Does Race Exist?
If races are defined as genetically discrete groups, no. But
researchers can use some genetic information to group individuals
into clusters with medical relevance
By Michael J. Bamshad and Steve E. Olson
Scientific American
November 17 2003
<http://sciam.com/article.cfm?chanID=sa006&colID=1&articleID=00055DC8-3BAA-1FA8-BBAA83414B7F0000>
Look around on the streets of any major city, and you will see
a sampling of the outward variety of humanity: skin tones ranging
from milk-white to dark brown; hair textures running the gamut
from fine and stick-straight to thick and wiry. People often
use physical characteristics such as these--along with area of
geographic origin and shared culture--to group themselves and
others into "races." But how valid is the concept of race from
a biological standpoint? Do physical features reliably say anything
informative about a person's genetic makeup beyond indicating
that the individual has genes for blue eyes or curly hair?
The problem is hard in part because the implicit definition of
what makes a person a member of a particular race differs from
region to region across the globe. Someone classified as "black"
in the U.S., for instance, might be considered "white" in Brazil
and "colored" (a category distinguished from both "black" and
"white") in South Africa.
Yet common definitions of race do sometimes work well to divide
groups according to genetically determined propensities for certain
diseases. Sickle cell disease is usually found among people of
largely African or Mediterranean descent, for instance, whereas
cystic fibrosis is far more common among those of European ancestry.
In addition, although the results have been controversial, a
handful of studies have suggested that African-Americans are
more likely to respond poorly to some drugs for cardiac disease
than are members of other groups.
Over the past few years, scientists have collected data about
the genetic constitution of populations around the world in an
effort to probe the link between ancestry and patterns of disease.
These data are now providing answers to several highly emotional
and contentious questions: Can genetic information be used to
distinguish human groups having a common heritage and to assign
individuals to particular ones? Do such groups correspond well
to predefined descriptions now widely used to specify race? And,
more practically, does dividing people by familiar racial definitions
or by genetic similarities say anything useful about how members
of those groups experience disease or respond to drug treatment?
Image: NANCY BURSON INDIVIDUALS from different populations are,
on average, just slightly more different from one another than
are individuals from the same population. In general, we would
answer the first question yes, the second no, and offer a qualified
yes to the third. Our answers rest on several generalizations
about race and genetics. Some groups do differ genetically from
others, but how groups are divided depends on which genes are
examined; simplistically put, you might fit into one group based
on your skin-color genes but another based on a different characteristic.
Many studies have demonstrated that roughly 90 percent of human
genetic variation occurs within a population living on a given
continent, whereas about 10 percent of the variation distinguishes
continental populations. In other words, individuals from different
populations are, on average, just slightly more different from
one another than are individuals from the same population. Human
populations are very similar, but they often can be distinguished.
Classifying Humans
As a first step to identifying links between social definitions
of race and genetic heritage, scientists need a way to divide
groups reliably according to their ancestry. Over the past 100,000
years or so, anatomically modern humans have migrated from Africa
to other parts of the world, and members of our species have
increased dramatically in number. This spread has left a distinct
signature in our DNA.
To determine the degree of relatedness among groups, geneticists
rely on tiny variations, or polymorphisms, in the DNA--specifically
in the sequence of base pairs, the building blocks of DNA. Most
of these polymorphisms do not occur within genes, the stretches
of DNA that encode the information for making proteins (the molecules
that constitute much of our bodies and carry out the chemical
reactions of life). Accordingly, these common variations are
neutral, in that they do not directly affect a particular trait.
Some polymorphisms do occur in genes, however; these can contribute
to individual variation in traits and to genetic diseases.
As scientists have sequenced the human genome (the full set of
nuclear DNA), they have also identified millions of polymorphisms.
The distribution of these polymorphisms across populations reflects
the history of those populations and the effects of natural selection.
To distinguish among groups, the ideal genetic polymorphism would
be one that is present in all the members of one group and absent
in the members of all other groups. But the major human groups
have separated from one another too recently and have mixed too
much for such differences to exist.
Polymorphisms that occur at different frequencies around the
world can, however, be used to sort people roughly into groups.
One useful class of polymorphisms consists of the Alus, short
pieces of DNA that are similar in sequence to one another. Alus
replicate occasionally, and the resulting copy splices itself
at random into a new position on the original chromosome or on
another chromosome, usually in a location that has no effect
on the functioning of nearby genes. Each insertion is a unique
event. Once an Alu sequence inserts itself, it can remain in
place for eons, getting passed from one person to his or her
descendants. Therefore, if two people have the same Alu sequence
at the same spot in their genome, they must be descended from
a common ancestor who gave them that specific segment of DNA.
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One of us (Bamshad), working with University of Utah scientists
Lynn B. Jorde, Stephen Wooding and W. Scott Watkins and with
Mark A. Batzer of Louisiana State University, examined 100 different
Alu polymorphisms in 565 people born in sub-Saharan Africa, Asia
and Europe. First we determined the presence or absence of the
100 Alus in each of the 565 people. Next we removed all the identifying
labels (such as place of origin and ethnic group) from the data
and sorted the people into groups using only their genetic information.
Our analysis yielded four different groups. When we added the
labels back to see whether each individual's group assignment
correlated to common, predefined labels for race or ethnicity,
we saw that two of the groups consisted only of individuals from
sub-Saharan Africa, with one of those two made up almost entirely
of Mbuti Pygmies. The other two groups consisted only of individuals
from Europe and East Asia, respectively. We found that we needed
60 Alu polymorphisms to assign individuals to their continent
of origin with 90 percent accuracy. To achieve nearly 100 percent
accuracy, however, we needed to use about 100 Alus.
Other studies have produced comparable results. Noah A. Rosenberg
and Jonathan K. Pritchard, geneticists formerly in the laboratory
of Marcus W. Feldman of Stanford University, assayed approximately
375 polymorphisms called short tandem repeats in more than 1,000
people from 52 ethnic groups in Africa, Asia, Europe and the
Americas. By looking at the varying frequencies of these polymorphisms,
they were able to distinguish five different groups of people
whose ancestors were typically isolated by oceans, deserts or
mountains: sub-Saharan Africans; Europeans and Asians west of
the Himalayas; East Asians; inhabitants of New Guinea and Melanesia;
and Native Americans. They were also able to identify subgroups
within each region that usually corresponded with each member's
self-reported ethnicity.
The results of these studies indicate that genetic analyses can
distinguish groups of people according to their geographic origin.
But caution is warranted. The groups easiest to resolve were
those that were widely separated from one another geographically.
Such samples maximize the genetic variation among groups. When
Bamshad and his co-workers used their 100 Alu polymorphisms to
try to classify a sample of individuals from southern India into
a separate group, the Indians instead had more in common with
either Europeans or Asians. In other words, because India has
been subject to many genetic influences from Europe and Asia,
people on the subcontinent did not group into a unique cluster.
We concluded that many hundreds--or perhaps thousands-- of polymorphisms
might have to be examined to distinguish between groups whose
ancestors have historically interbred with multiple populations.
The Human Race
Given that people can be sorted broadly into groups using genetic
data, do common notions of race correspond to underlying genetic
differences among populations? In some cases they do, but often
they do not. For instance, skin color or facial features--traits
influenced by natural selection--are routinely used to divide
people into races. But groups with similar physical characteristics
as a result of selection can be quite different genetically.
Individuals from sub-Saharan Africa and Australian Aborigines
might have similar skin pigmentation (because of adapting to
strong sun), but genetically they are quite dissimilar.
In contrast, two groups that are genetically similar to each
other might be exposed to different selective forces. In this
case, natural selection can exaggerate some of the differences
between groups, making them appear more dissimilar on the surface
than they are underneath. Because traits such as skin color have
been strongly affected by natural selection, they do not necessarily
reflect the population processes that have shaped the distribution
of neutral polymorphisms such as Alus or short tandem repeats.
Therefore, traits or polymorphisms affected by natural selection
may be poor predictors of group membership and may imply genetic
relatedness where, in fact, little exists.
Another example of how difficult it is to categorize people involves
populations in the U.S. Most people who describe themselves as
African-American have relatively recent ancestors from West Africa,
and West Africans generally have polymorphism frequencies that
can be distinguished from those of Europeans, Asians and Native
Americans. The fraction of gene variations that African- Americans
share with West Africans, however, is far from uniform, because
over the centuries African-Americans have mixed extensively with
groups originating from elsewhere in Africa and beyond.
Over the past several years, Mark D. Shriver of Pennsylvania
State University and Rick A. Kittles of Howard University have
defined a set of polymorphisms that they have used to estimate
the fraction of a person's genes originating from each continental
region. They found that the West African contribution to the
genes of individual African-Americans averages about 80 percent,
although it ranges from 20 to 100 percent. Mixing of groups is
also apparent in many individuals who believe they have only
European ancestors. According to Shriver's analyses, approximately
30 percent of Americans who consider themselves "white" have
less than 90 percent European ancestry. Thus, self-reported ancestry
is not necessarily a good predictor of the genetic composition
of a large number of Americans. Accordingly, common notions of
race do not always reflect a person's genetic background.
Membership Has Its Privileges
Understanding the relation between race and genetic variation
has important practical implications. Several of the polymorphisms
that differ in frequency from group to group have specific effects
on health. The mutations responsible for sickle cell disease
and some cases of cystic fibrosis, for instance, result from
genetic changes that appear to have risen in frequency because
they were protective against diseases prevalent in Africa and
Europe, respectively. People who inherit one copy of the sickle
cell polymorphism show some resistance to malaria; those with
one copy of the cystic fibrosis trait may be less prone to the
dehydration resulting from cholera. The symptoms of these diseases
arise only in the unfortunate individuals who inherit two copies
of the mutations.
Genetic variation also plays a role in individual susceptibility
to one of the worst scourges of our age: AIDS. Some people have
a small deletion in both their copies of a gene that encodes
a particular cell-surface receptor called chemokine receptor
5 (CCR5). As a result, these individuals fail to produce CCR5
receptors on the surface of their cells. Most strains of HIV-1,
the virus that causes AIDS, bind to the CCR5 receptor to gain
entry to cells, so people who lack CCR5 receptors are resistant
to HIV-1 infection. This polymorphism in the CCR5 receptor gene
is found almost exclusively in groups from northeastern Europe.
Several polymorphisms in CCR5 do not prevent infection but instead
influence the rate at which HIV-1 infection leads to AIDS and
death. Some of these polymorphisms have similar effects in different
populations; others only alter the speed of disease progression
in selected groups. One polymorphism, for example, is associated
with delayed disease progression in European-Americans but accelerated
disease in African-Americans. Researchers can only study such
population-specific effects--and use that knowledge to direct
therapy--if they can sort people into groups.
In these examples--and others like them--a polymorphism has a
relatively large effect in a given disease. If genetic screening
were inexpensive and efficient, all individuals could be screened
for all such disease- related gene variants. But genetic testing
remains costly. Perhaps more significantly, genetic screening
raises concerns about privacy and consent: some people might
not want to know about genetic factors that could increase their
risk of developing a particular disease. Until these issues are
resolved further, self-reported ancestry will continue to be
a potentially useful diagnostic tool for physicians.
Ancestry may also be relevant for some diseases that are widespread
in particular populations. Most common diseases, such as hypertension
and diabetes, are the cumulative results of polymorphisms in
several genes, each of which has a small influence on its own.
Recent research suggests that polymorphisms that have a particular
effect in one group may have a different effect in another group.
This kind of complexity would make it much more difficult to
use detected polymorphisms as a guide to therapy. Until further
studies are done on the genetic and environmental contributions
to complex diseases, physicians may have to rely on information
about an individual's ancestry to know how best to treat some
diseases.
Race and Medicine
But the importance of group membership as it relates to health
care has been especially controversial in recent years. Last
January the U.S. Food and Drug Administration issued guidelines
advocating the collection of race and ethnicity data in all clinical
trials. Some investigators contend that the differences between
groups are so small and the historical abuses associated with
categorizing people by race so extreme that group membership
should play little if any role in genetic and medical studies.
They assert that the FDA should abandon its recommendation and
instead ask researchers conducting clinical trials to collect
genomic data on each individual. Others suggest that only by
using group membership, including common definitions of race
based on skin color, can we understand how genetic and environmental
differences among groups contribute to disease. This debate will
be settled only by further research on the validity of race as
a scientific variable.
A set of articles in the March 20 issue of the New England Journal
of Medicine debated both sides of the medical implications of
race. The authors of one article--Richard S. Cooper of the Loyola
Stritch School of Medicine, Jay S. Kaufman of the University
of North Carolina at Chapel Hill and Ryk Ward of the University
of Oxford--argued that race is not an adequate criterion for
physicians to use in choosing a particular drug for a given patient.
They pointed out two findings of racial differences that are
both now considered questionable: that a combination of certain
blood vessel-dilating drugs was more effective in treating heart
failure in people of African ancestry and that specific enzyme
inhibitors (angiotensin converting enzyme, or ACE, inhibitors)
have little efficacy in such individuals. In the second article,
a group led by Neil Risch of Stanford University countered that
racial or ethnic groups can differ from one another genetically
and that the differences can have medical importance. They cited
a study showing that the rate of complications from type 2 diabetes
varies according to race, even after adjusting for such factors
as disparities in education and income.
The intensity of these arguments reflects both scientific and
social factors. Many biomedical studies have not rigorously defined
group membership, relying instead on inferred relationships based
on racial categories. The dispute over the importance of group
membership also illustrates how strongly the perception of race
is shaped by different social and political perspectives.
In cases where membership in a geographically or culturally defined
group has been correlated with health-related genetic traits,
knowing something about an individual's group membership could
be important for a physician. And to the extent that human groups
live in different environments or have different experiences
that affect health, group membership could also reflect nongenetic
factors that are medically relevant.
Regardless of the medical implications of the genetics of race,
the research findings are inherently exciting. For hundreds of
years, people have wondered where various human groups came from
and how those groups are related to one another. They have speculated
about why human populations have different physical appearances
and about whether the biological differences between groups are
more than skin deep. New genetic data and new methods of analysis
are finally allowing us to approach these questions. The result
will be a much deeper understanding of both our biological nature
and our human interconnectedness.
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