Perspectives: Personalized and Racialized Medicine Are Not The Same

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.



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