Personalized and Racialized Medicine Are Not The Same
Drs. Joseph L. Graves Jr. and Michael R. Rose
Diverse Online, 06/14/2006
On May 31, 2006, Diverse Online published a story titled "Racial Pill Maker's
Sales Drop in Wider-than-expected Loss" about lackluster sales of the drug
BiDil. The article claimed that BiDil, the heart-failure drug approved only
for Black patients, is expected to usher in the era of personalized medicine.
The article also implies that racial and personalized medicine are equivalent.
However, they are not the same concepts, and continued confusion on this issue
distracts us from the task of adequately addressing health disparities.
First, humans do not have biological races. Physical traits don't partition
individuals or populations into groups that match our social categories.
Examining protein variation does not result in racial groupings either. Large-
scale studies of human DNA variants reveal population subdivision (FST) values
that range between 0.05 and 0.15 across the entire genome. These are values
far below what biologists consider the threshold for establishing racial
differentiation (FST = 0.250.)
The only approach that sometimes partitions individuals into groups similar to
lay conceptions of race is non-coding DNA. This happens when you use a large
number of genetic markers and is similar to forensic DNA typing in that these
markers are powerful clues to ancestry. Coding portions of DNA, however,
doesn't strongly identify racial groups. This is crucial since the coding
portions produce the cellular proteins that predispose us to disease and give
us the ability to metabolize particular drugs. For example, a 14,400
nucleotide sequence of the gene angiotensinogen (AGT) obtained from 368
individuals of African, European and East Asian origin, did not show "racial"
clustering.2 Another study examined Histocompatibility Locus A and sequenced
individuals from the Republic of Macedonia and Greece. The Macedonians were
more similar to an "older" set of Mediterranean populations and the Greeks
were closer to Ethiopians and Sub-Saharan Africans.3
Finally, another recent study of self-reported race and genetic admixture in
Cleveland, Ohio, showed that while 93 percent of those who self-identified
as "White" had predominantly European genetic backgrounds, only 4 percent of
those self-identified as "Black" had predominantly African genetic
backgrounds4. These results illustrate the problem with "racial profiling" in
medicine. For example, a physician could not use "self-described" race to
prescribe drugs for African-American patients in Cleveland because any
particular African-American individual might have European genes controlling
the metabolic pathways the race-specific drug was supposed to impact.
Similarly, doctors prescribing European race-specific drugs to Greeks might be
better off prescribing them African drugs.
This is the real meaning of the idea of "personalized" medicine; specific
genotypes interacting with particular environments determine customized
treatment. Thus a person with a particular set of physical characteristics
will not necessarily adhere to a particular medical profile. The early results
with BiDil did not indicate ineffectiveness on persons of European descent,
rather the results showed greater statistical significance in self-described
African-Americans. Dr. Jay Cohn, the originator of BiDil, stated that he
prescribes the drug to "White" patients who don't respond well to other
drugs5. This is hardly a case for racial medicine. The data on medically
important genetic variation uncovered thus far do not support racial
medicine6.
In the absence of strong scientific evidence supporting racialized medicine,
why is this notion so popular? The motivation for racializing BiDil is more
economic than scientific. NitroMed (the company that markets BiDil) holds the
rights to a race-specific patent. This patent gives them control over BiDil's
profits until 2020. The non-race-specific patent held by NitroMed expires in
20077.
There are a number of reasons we should be concerned about this state of
affairs. First, doctors might be reluctant to prescribe BiDil to those who do
not describe themselves as African-Americans. It is also possible that
clinical trials for non-African-Americans may be delayed until after the
expiration of the race-specific patent in 2020. Second, doctors may come to
assume that BiDil will be the preferred treatment for all African-Americans,
thus vitiating the idea of "personalized" medicine. A third concern is that
such treatments may divert our attention from pursuing research on other
aspects of health disparity.
BiDil is a combination of a nitric oxide donor and an anti-oxidant, which also
acts as a vasodilator. Anti-oxidants protect cells against oxidative damage
resulting from normal cellular respiration and poisons that accumulate over
time. Therefore, higher levels of oxidative harm would occur in individuals
differentially exposed to damaging chemicals. Also, oxidative damage can be
heightened by periods of prolonged stress8. The differential impact of BiDil
could be explained by the fact that African-Americans and European Americans
live in different environments in the United States. Indeed the available
evidence suggests that the longevity differences between these two groups
results more from environmental rather than genetic influences9.
These environmental factors result from the social dominance that persons of
European descent enjoy over persons of African descent in the United States.
This is precisely why biomedical research must come to grips with and
understand the differences between the biological and socially defined meaning
of race. For example, there are a series of studies that document the
relationship of stress to lowered health outcomes10. Indeed, at least one
study has actually experimentally documented a mechanism by which emotional
stress leads to cellular damage11. Thus, we should always expect that
populations who are socially subordinated will have poorer health outcomes.
This raises the question of how best to approach health disparities. Should we
seek medical treatments that are "racially" defined as a capitulation to
injustice? If so, then shouldn't we seek class- or sexual-orientation-based
medicines as well? Or would we be better off addressing the underlying causes
of injustice? Does one approach vitiate the other? These are hard questions.
However, they cannot be adequately addressed so long as we continue to
confuse "racial" with "personal."
Dr. Joseph L. Graves, Jr. is dean of university students and a professor of
biological sciences at North Carolina A&T State University.
Dr. Michael R. Rose is director of the University of California Network for
Experimental Research on Evolution and professor of biological sciences at the
University of California, Irvine.
References
1. Graves, J.L., The Race Myth: Why We Pretend Race Exists in America, (New
York: Dutton), 2005.
2. Jorde, L. and Wooding, S., Genetic Variation, classification, and race, in
Genetics for the Human Race, Nature Genetics Supplement, Volume 36, Number 11,
November 2004, pp. s28- s33.
3. Arnaiz-Villena, A. et al., HLA genes in Macedonians and the sub-Saharan
origin of the Greeks, Tissue Antigens 21:118 - 127, 2001.
4. Sinha, M., Larkin, E.K., Elston, R.C., and Redline, S., Self-reported Race
and Genetic Admixture, N. Eng. J. Med: 354(4): 421.
5. Gellene, D., Heart Pill Intended Only for Blacks Sparks Debate, L.A. Times,
June 16, 2005.
6. Tate, S and Goldstein, B., Will tomorrow's medicines work for everyone?,
Nature Genetics supplement, Volume 36, Number 11, November 2004, pp. s34 - s42.
7. Kahn, J., From Disparity to Difference: How Race-Specific Medicines May
Undermine Policies to Address Inequalities in Health Care, Southern California
Interdisciplinary Law Journal Vol. 15:105, 2006.
8. Taylor, A. et al., Combination of isosorbide dinitrate and hydralazine in
Blacks with Heart Failure, The New England Journal of Medicine, (2004),
351:20, pp. 2049-57;
9. Lee, J. et al., Genetic Influences on Life Span and Survival Among Elderly
African Americans, Caribbean Hispanics, and Caucasians, American Journal of
Medical Genetics, 128A:159-164, 2004.
10. Navarro, V., Race or class versus Race and Class: Mortality differentials
in the United States, Lancet 336 no. 8725: 1238-1240, 1990; Kawachi, I.,
Daniels, N., and Robinson, D., Health disparities by race and class: Why both
matter, Health Affairs. Chevy Chase: Mar/Apr 2005. Vol. 24, Issue 2, pp. 343 -
353.
11. Epel, E.S. et al., Accelerated telomere shortening in response to life
stress, Proceedings of the National Academy of Sciences, 2004; 101(49): 17312-
15.