http://www.washingtonpost.com/ac2/wp-dyn/A60970-2001Sep8?language=printer
Sunday, September 9, 2001; Page B01
Science and politics do not mix very
well, particularly when it comes to such hot-button issues as diversity.
That's certainly the case with the stem cell debate. Although this effect
is surely unintended, if federally funded research is limited to the 64
stem cell lines approved by the Bush administration, potential cures could
end upbeing most useful toa narrow sliver of the world's population: whites
of mostly European ancestry and some Asians. Much of the rest of the world
will find that some promising therapies developed from these lines do not
work very well.
The problem lies in the lack of genetic
and "racial" diversity of the 64 lines. Most of them were harvested from
embryos at U.S., Swedish and Israeli fertility clinics, where patients
are overwhelmingly white. Based on discussions with most of the 10 laboratories
with approved cell lines, we have concluded that as many as 49 of the lines
are from white couples. As Alan Robins, chief science officer for one of
the labs, BresaGen Inc. in Athens, Ga., told us, "Although we do not know
for certain the racial background of our donors, it is reasonable to assume
they are from white couples." About 15 of the lines, harvested at clinics
in Singapore and India, are of South and East Asian parentage, we believe,
based on those discussions. Even if all of these stem cell lines are shown
to be viable for research, that's a very narrow segment of the world's
population and a tiny fraction of what is necessary to ensure genetic diversity
in therapies eventually developed from the cells.
And that's a problem because, as
with whole organ transplants, therapies and tissues derived from stem cells
will likely share the body's tendency to reject as foreign those that come
from different populations. Patients with stem cell transplants will have
to take drugs that suppress the immune system -- drugs that can cause substantial
problems themselves. A menu of far more than 64 lines of embryonic stem
cellswould be necessary to accommodate the vast immunological variety of
human beings.
Scientists have alluded to the problem,
but only indirectly. Harold Varmus, former director of the National Institutes
of Health and now head of Memorial Sloan-Kettering Cancer Center in New
York, and noted Harvard molecular and cellular biologist Douglas Melton
warned in a recent Wall Street Journal commentary that "Even 100 good lines
will likely be inadequate to treat our genetically diverse population without
encountering immune rejection." But while they addressed the theoretical
issue of genetic diversity, Varmus and Melton avoided the practical issue
of its implications. A non-scientist would hardly have understood that
adding hundreds more cell lines would not necessarily result in that much
more genetic diversity. To ensure that, researchers need embryos from a
wide range of populations and ethnic groups.
Although genetic diversity does not
equate with ethnic and racial diversity, they are not unrelated. "If research
is limited primarily to the announced stem cell lines," says Arizona State
evolutionary biologist Joseph Graves Jr., "then you may develop drugs for,
say, Alzheimer's or Parkinson's that work best only in those populations.
There are many genetic variants that are only found in certain Asian populations
[or] only found in sub-populations in Africa [or] only found in certain
European populations."
What does that mean? After all, the
fact that medically significant differences exist between populations would
seem to conflict with a spate of declarations in recent months proclaiming
that "humans are 99.9 percent the same" and "race is biologically meaningless."
The paradox revolves around a common misunderstanding about the notion
of "race" -- in particular, the popular notion thatraces are discrete groups,
each with distinct genetic profiles.
In fact, modern humans are made up
of overlapping, soft-edged genetic clusters. Although humans share most
of their estimated 40,000 genes, there are as many as 500,000 gene components,
or single nucleotide polymorphisms, many of which are more common among
people from one geographical region than from another.
This is not a "black" and "white"
issue. Genetic factors help explain the prevalence of any number of population-specific
diseases and physiological responses to drugs. These differences are rooted
in the different variations of genes, known as alleles. Some populations
have a higher frequency of a specific allele. That has huge medical consequences.
Tay-Sachs is a neurological disease more common among European Jews and
their descendants. Northern Europeans are more susceptible to cystic fibrosis.
A specific allele is a potent risk factor of Alzheimer's in whites but
not for most blacks. Different ethnic and racial populations metabolize
common drugs such as codeine, beta-blockers and antidepressants differently.
African, Mediterranean and some Asian populations are far more likely than
whites to develop a toxic reaction from Primaquine, a drug used to treat
malaria and pneumonia. Genetic variants are associated with Type 1 diabetes,
asthma and thrombophilia, a bleeding disorder -- as well as with sensitivity
to certain foods.These are all "racial" differences of a kind, although
the interaction of genes and environmental factors is extremely complex.
The potential consequences of ignoring
population factors were underscored last Monday with the announcement by
researchers at the University of Wisconsin that they had turned human embryonic
stem cells into blood cells needed for bone marrow transplants for patients
with leukemia or other cancers.
However, not all populations would
benefit equally from such research. Bone marrow transplant registries,
like the newly released stem cell registry, are drawn primarily from white
populations. But people with lots of sub-Saharan African ancestry show
greater variety than Europeans in their HLA, the complex of genes that
effect whether the body rejects a tissue or organ. The combination of these
factors means that white Americans are five times more likely than blacks
to get a bone marrow match from an unrelated donor.
It is well documented that populations
in Africa, where modern humans likely originated, are the most genetically
diverse in the world. A stem cell policy that does not guarantee a significant
percentage of cell lines from various African sub-populations will limit
human biodiversity -- and could limit the effectiveness of drug therapies
on those and other populations not adequately represented in the current
cell lines.
Health and Human Services Secretary
Tommy Thompson offered assurances last Wednesday that "the private sector
will fill any voids if there are any voids" in the quality and diversity
of the stem cell lines. But researchers are extremely doubtful, as are
we, that this will happen. Because minority populations would be generally
less able to afford expensive therapies tailored to their genetic profiles,
private companies would have little economic incentive to spend the kind
of money necessary to ensure therapies would work in genetically distinct
sub-populations, including those of African ancestry.
"The fact that monolithic racial
categories do not show up in the genotype does not mean there are no group
differences between pockets of populations," states Graves, who is African
American. "There are some group differences. We see it in diseases. But
that's a long way from reconstructing century-old racial science."
Misinformation about racial differences
and justifiable concerns about resurrecting "race science" has so far hampered
an open discussion on these critical issues. We found that many scientists
are afraid to discuss the link between stem cells and race in an already
politicized issue.
"We need to look at the causes of
differences in diseases between the various races," warns geneticist Claude
Bouchard, director of the Pennington Biomedical Research Center at Louisiana
State University. "Only by confronting these enormous issues head-on, and
not by circumventing them in the guise of political correctness, do we
stand a chance to evaluate the discriminating agendas and devise appropriate
interventions."
How did we get into thisquandary
and what can be done about it? Much of the responsibility falls on the
shoulders of scientists who haveinsisted that there are no patterned genetic
differences among various populations. In May, a firestorm ensued after
the New England Journal of Medicine published a paper seeking to explain
why blacks with high blood pressure and other cardiovascular conditions
do not fare as well as whites when given the same medications, in part
because of genetically based sensitivities to certain drugs.
J. Craig Venter, a geneticist and
entrepreneur whose company, Celera Genomics, has played a key role in mapping
the human genome, sharply criticized race-based research, although he did
not challenge the science. "It is disturbing to see reputable scientists
and physicians even categorizing things in terms of race," he told the
New York Times. (Intriguingly, Celera's research is based on the DNA from
only five people, an absurdly small fraction of the world's genetic variability.)
Certainly, classic notions of race
based on skin color can be scientifically simplistic. But past mistakes
should not be invoked to censor research and harm potential patients.
In the case of ovarian cancer, for
example, Jewish women of East European ancestry are as much as 40 times
more likely to contract the disease than other women because of their increased
likelihood of having the gene BRCA1. Could such a dramatic pattern exist
for the effectiveness of drugs that might be developed from a limited number
of cell lines? Scientists do not know yet, but some critical differences
are certain to emerge.
Stem cell researchers are discussing
among themselves establishing international cell banks or launching a long-shot
effort to genetically engineer "universal donor cells" stripped of rejection
problems, but those efforts would require government funding, from the
United States and other wealthy nations.
Barring that, it's important to keep
in mind that while polemical demands to exclude population-based differences
as a factor in biomedical research may play to understandable concerns
about past misuse of race in science, they do so at a high price: They
perpetuate the historical tendency to exploit simplistic notions of race
in the name of science and medicine. Ironically, in leaving race out of
the current stem cell debate, history may be repeating itself.
Jon Entine is the author of "Taboo:
Why Black Athletes Dominate Sports and Why We're Afraid to Talk About It"
(Public Affairs). Sally Satel is a psychiatrist, a fellow at the American
Enterprise Institute and the author of "PC, M.D.: How Political Correctness
Is Corrupting Medicine" (Basic Books).
© 2001 The Washington Post Company
By Jon Entine and Sally Satel