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FROM Sciencenews.org <http://sciencenews.org/articles/20050409/bob9.asp>

PART I
CODE OF MANY COLORS:
Can researchers see race
in the genome?
by Christen Brownlee


Historian Frank W. Sweet of the University of Florida in Gainesville recounts the classic rags-to-riches tale of Louetta Chassereau, an early 20th-century socialite. As a baby, Chassereau was adopted from an orphanage by a well-to-do white couple. She later married a wealthy man, and her children attended the best white-only schools.

 However, a dilemma developed when Chassereau’s husband died, leaving everything in his will to his beloved wife. Enraged, her husband’s relatives contested the will. The reason? Although people in her community had always thought of her as white, “Louetta had started life as a Black baby,” says Sweet in a recent essay. Because Chassereau was born of black parents, according to an antimiscegenation law of the time, Chassereau legally could marry only a black man. The white family claimed that she had no right to the fortune.

 Although the courts ruled in Chassereau’s favor in 1940, saying that her life’s path had made her “irrevocably white,” her in-laws remained unconvinced.

 In the past 65 years, defining race hasn’t become less ambiguous. While it’s abundantly clear that race exists from a sociological standpoint—racism wouldn’t take place without it—does that categorization also exist biologically?

 Current genetic research hasn’t yet come up with a black-and-white answer. Nevertheless, understanding the biology underlying perceptions of race could have dramatic implications.

 Racy subject

It’s difficult to get most scientists even to say the word race when referring to people. That’s because in traditional scientific language, races are synonymous with subspecies—organisms in the same species that can interbreed but nevertheless are distinctive genetically.

 Many species split into subspecies after being separated geographically for an extended amount of time. During generations of genetic mixing within but not between the isolated groups, some of each group’s genes develop slightly different versions, or alleles. Scientists often use a rule called Wright’s F statistic to judge whether separate groups are actually subspecies. If 25 percent or more of one group’s alleles are different from another’s, then by F-statistic standards, the two groups are considered subspecies. A difference of 100 percent would separate them into distinct species.

 Subspecies, or races, exist for many animals—for example, the alleles in some populations of grey wolves score up to 70 percent on the F-statistic scale. However, the groups of people considered to be of different races have allelic differences of at most 15 percent, too little to constitute subspecies.

 To the nonscientist, however, race clearly is a meaningful term, says Vivian Ota Wang of the Ethical, Legal, and Social Implications Research Program at the National Human Genome Research Institute (NHGRI) in Bethesda, Md. The concept seems to depend on a collection of physical features, “like a checklist,” she says, “so that people can categorize each other into groups.” Items on the list might include skin tone, hair texture, and the shapes of eyes, noses, or lips.

 Most people don’t carry a conscious perception of the checklist. Wang says that race has a lot in common with Supreme Court Justice Potter Stewart’s famous definition of pornography: We know it when we see it.

 About 100,000 years ago, defining race wasn’t an issue—all early humans lived in Africa and had similar characteristics. That relatively small population of recently evolved humans carried the majority of alleles present in people today.

 But over the next 50,000 years or so, as humans separated into groups, slight differences among populations crept into the genome. First, as waves of emigrants left Africa and spread throughout the world, our ancestors took slightly different groups of alleles with them. Just as each handful of jellybeans scooped out of a jar might have a different mix of flavors, every group of migrant humans carried a slightly different array of alleles.

 Later, when roaming humans settled into permanent residences on different continents, new genetic mutations gradually built up within groups as they adapted to their distinct environments. Because people mated most frequently with others from the same region, each population developed its own set of mutational differences, some influencing survival and some being just genetic quirks.

 Share, share alike

According to Lisa Brooks, a geneticist at the NHGRI, the genetic differences within each population take several forms. Some people have certain segments of DNA wedged within stretches that run without interruption in other people. Conversely, genetic pieces present in many people are missing in others. Also, stretches of DNA can be flipped so that they read backwards, or they might contain small repeated segments, called microsatellites, that vary in number from person to person.

 The genetic variation that most interests Brooks is called a single nucleotide polymorphism, or SNP (pronounced “snip”). It’s a one-letter change in the string of DNA components that go by the letters A, C, G, and T. For example, where one person might have a section that reads TAAACA, another person’s section might read TAAAGA.

 Most SNPs occur in places in the genome that aren’t used for making proteins—the so-called junk DNA. But the few SNPs that land squarely in a gene or in a regulatory region near a gene can alter characteristics influenced by that gene—for example, physical appearance or propensity for disease.

 Sets of adjacent SNP alleles in the same chromosome region are called haplotypes. Through a collaboration called the International HapMap Project, researchers around the world are recording and analyzing the SNPs present in four populations: Utah residents with European ancestry, a Nigerian population called the Yoruba, Han Chinese in Beijing, and Japanese inhabitants of Tokyo.

 Although the study wasn’t designed to probe the genetics of race per se, one of the major findings from HapMap so far, says Brooks, is the enormous similarity between the four groups’ SNP patterns. In an interview, Brooks illustrated her point by drawing on a piece of paper four largely overlapping circles, with only slim slivers of each ring peeking out at the edge.

 RACING IN CIRCLES. Research has shown that the range of DNA variety in populations, represented here by circles of various colors, overlaps by about 85 percent. Only a few of each group’s DNA snippets are unique.

Brooks points to the large area where the circles overlap and explains that about 85 percent of variation is shared by all populations. By default, the genetic variation in the slivers includes the alleles that lead to differences among populations, including those on the typical racial checklist. “Superficial traits, like skin color or hair texture, aren’t typical in their patterns of variation of [most of] the genome,” says Brooks.

 This concept can be hard to grasp for people who believe that racial groups are fundamentally different genetically, says Georgia Dunston of Howard University’s National Human Genome Center in Washington, D.C.

 Dunston studies how the human immune system distinguishes between a person’s tissues and foreign material, such as a splinter, a bacterium, or a transplanted organ. The genes responsible for this recognition are called histocompatibility genes. Having similar histocompatibility genes is a major factor in successful organ transplants.

 In tissue matching, a bastion of genetic differences between people, Dunston finds that race is not the determining factor. “We have this thinking in America that there are some deep differences in biology between whites and blacks, that tissue in whites is more similar to [tissue in] whites than tissue in blacks,” she says. “But when we look at the genetics, because of the tremendous variation in all groups, and especially in the group called ‘black,’ it’s not uncommon at all to find two blacks who could be very different from each other.”

 In some cases, a black organ donor, Dunston adds, can better match a white recipient than a black one.

 What’s the difference?

Nevertheless, no geneticist can overlook the slim fringes on Brooks’ overlapping-circles diagram. According to Brooks, the longer people in a population have mated in close association, and so share the same ancestors and kin, the more similar will be their genes—and all the traits they encode—in that 15 percent of the genome.

 Race and family origin aren’t entirely synonymous in modern times, when people can relocate around the globe. However, many researchers have found that the distribution of certain genetic variations can lump people into ancient ancestral groups uncannily similar to what nonscientists call races.

 For example, Noah Rosenberg of the University of Southern California in Los Angeles and his colleagues published a study in 2002 that analyzed the number and type of microsatellite variations in the DNA of 1,056 people from 52 populations around the world.

 Rosenberg’s team masked any information about the study volunteers’ ancestral backgrounds and then plugged the microsatellite information into a computer program that clusters people by genetic similarities. Six main clusters emerged.

 After restoring individuals’ ancestry data to the files, the researchers found that five of the six microsatellite clusters corresponded with geographic regions: Africa, Eurasia (Europe, the Middle East, central and south Asia), east Asia, Oceania (islands of the central and South Pacific), and the Americas (specifically native Americans). The sixth and smallest cluster linked to an isolated group of mountain-dwelling Pakistanis known as the Kalash.

 The scientists weren’t surprised that people’s genetic mutations usually lump them into continental groups. For much of history, people have been land bound and so have mated mostly with people from the same continent.

 However, Rosenberg says that he was surprised that he and his colleagues found it impossible to predict with certainty which combination of gene variants any specific person in each cluster had. The computer runs couldn’t determine, for example, exact shades of skin color or types of hair texture for individuals.

 “In a lot of classical anthropological views of race, race is thought to be a quality predictive of a large variety of traits about a person. We found that for any given person, it’s not possible to predict accurately which [variant] they have at any particular site in the genome based on their group membership,” Rosenberg says.

 Neil Risch of the Stanford University School of Medicine and his colleagues recently used a similar method to come to a very different conclusion. Using microsatellite information from another study that had looked for a genetic link with hypertension in several U.S. populations, Risch’s team ran data from 3,636 people through a computer program similar to Rosenberg’s. However, instead of searching for clusters based on geography, Risch and colleagues compared clusters from the genetic data with self-described race/ethnicity categories.

 The genetic data sorted into four categories—white, African American, east Asian, and Hispanic—which neatly matched what each person had checked on a form at the beginning of the study. Only five people had results inconsistent with their self-described race/ethnicity, giving an error rate of 0.14 percent, the team reports in the February American Journal of Human Genetics.

 “This shows that people’s self-identified race/ethnicity is a nearly perfect indicator of their genetic background,” says Risch.

 Racism realism

Risch’s results have stirred up controversy among many geneticists. For instance, Mark Shriver of Pennsylvania State University in State College says that Risch’s method “can overcluster people,” making associations between individuals and their race that don’t exist with other types of analyses. Shriver and others haven’t found similar clusters when they applied a different computer program to similar data.

 Shriver also contends that the study’s separation of people into four racial groups shrinks the natural range of genetic variation, making people within each group seem more alike than they really are.

 Rather than there being clear racial lines, says Shriver, “there’s really a continuum of variation across the globe.” If researchers sampled only people in Africa and Sweden, the genetic differences between the two groups would be striking. However, a sampling of people from Africa, Sweden, and everywhere in between would reveal only small differences between each population and its neighbors. “You won’t see a place where you’ll say, ‘There’s the racial divide,’“ says Shriver.

 Nevertheless, Shriver works with a company that uses what variation there is among populations to trace people’s ancestry. The company, DNAPrint Genomics in Sarasota, Fla., starts with DNA from a customer’s inner cheek. After comparing the sample’s genetic markers with those in a data set collected from people around the world, the company estimates what percentage of the person’s ancestry is African, East Asian, European, or Native American.

 The results can be surprising. When Shriver, who considers himself to be white, analyzed his own DNA, he found that it contained the Duffy null allele, found only in descendants of sub-Saharan Africans. “The test estimated that I have 11 percent west African ancestry,” says Shriver.

 In spring 2003, Shriver and his colleagues applied the test to an urgent task—they were instrumental in catching a Louisiana serial killer. After analyzing DNA from semen at the crime scenes, Shriver and his colleagues estimated that the killer was 85 percent African and 15 percent Native American. Officers eventually arrested Derrick Todd Lee, a black man whose DNA matched that left at the scenes. As testament to the uncertainty of eyewitnesses, Lee was convicted although several people had reported seeing a white man at the scene of several of the murders.

 Although an ancestry test had put police on the right track in this case, Shriver expresses concern about the test’s potential for misuse in other social realms. One danger, he notes, is attempting to correlate ancestry with qualities such as intelligence, athletic performance, or musical ability. “It’s hard to know what the right use is. We have to be vigilant,” he says.

 Researchers may never nail down a precise connection between race and genetics, but there’s little chance that the concept of race will ever go away, says Charles Rotimi of Howard University’s genome center. Over the centuries, some people have used race to set discriminatory categories and then give themselves privileges and take privileges from others. People who have been advantaged by racism aren’t likely to give it up, Rotimi says.

 “Look at the Hutus and the Tutsis,” he adds, referring to two Rwandan tribes that have been fighting each other for decades. “You don’t need genetics to be racist.”


References:

Tang, H. . . . and N.J. Risch. 2005. Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies.American Journal of Human Genetics 76(February):268-275. Abstract available at http://www.journals.uchicago.edu/AJHG/journal/
issues/v76n2/41839/brief/41839.abstract.html?
erFrom=-807749556546761969Guest.

Further Readings:

Harder, B. 2005. The race to prescribe. 167(April 16):247-248. Available at http://www.sciencenews.org/articles/20050416/bob8.asp.

Rosenberg, N.A., et al. 2002. Genetic structure of human populations. Science 298(Dec. 20):2381-2385. Available at http://www.sciencemag.org/cgi/content/full/298/5602/2381.

Shriver, M.D., et al. 2004. The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs. Human Genomics 1(May):274-286. Abstract.

Shriver, M.D., and R.A. Kittles. 2004. Genetic ancestry and the search for personalized genetic histories. Nature Reviews Genetics 5(August):611-618. Abstract available at http://dx.doi.org/10.1038/nrg1405.

Sweet, F.W. 2004. The rate of black-to-white "passing." Backintyme. Available at http://www.backintyme.com/Essay040915.htm.

Additional information about DNAPrint genomics can be found at http://www.dnaprint.com/.

 Sources:

Lisa D. Brooks
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076
Mailstop Code 9305
Bethesda, MD 20892-9305

Neil Risch
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

Noah Rosenberg
Program in Molecular and Computational Biology
University of Southern California
1042 W 36th Place
DRB 289
Los Angeles, CA 90089-1113

Charles Rotimi
Howard University
2941 Georgia Avenue, N.W.
Cancer Center Building, Room 614
Washington, DC 20060

Frank W. Sweet
Backintyme
30 Medford Drive
Palm Coast, FL 32137-2504

Mark D. Shriver
Anthropology and Genetics
Penn State University
409 Carpenter Building
University Park, PA 16802

Sarah Tishkoff
Department of Biology
Biology/Psychology Building
University of Maryland, College Park
College Park, MD 20742

Vivian O. Wang
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suter 4076
Mailstop Code 9305
Bethesda, MD 20892-9305

–––––––––––––––––––––––––
From Science News, Vol. 167, No. 15, April 9, 2005, p. 232
–––––––––––––––––––––––––

PART II:

The Race to Prescribe
Drug for African Americans may debut amid debate
by Ben Harder

Most modern medical research into race or ethnicity focuses on the disturbingly long list of health disparities among different groups. For example, compared with whites, blacks are 30 percent more likely to die of heart disease at any given age and 40 percent more likely to die of a stroke. Overall, blacks have an average life expectancy that's 5 years shorter than that of whites.

 Identifying such inequalities is one step toward helping each population get appropriate medical care. Sometimes, that requires making the same tests and treatments available across the board, but it may also mean tailoring medicine to particular groups. For instance, a controversial new drug for heart failure may soon be approved specifically for African American patients. The drug, developed under the trade name BiDil and now being reviewed by the Food and Drug Administration, is likely to become the first therapy that the agency approves specifically for treatment of an ethnic or racial group.

 Many physicians hail BiDil, which is produced by NitroMed in Lexington, Mass. Not only is it a lifesaving medication for a defined population of patients but it also serves as a promising new model for drug development. These proponents argue that research embracing racial differences in biology could lead to safer new treatments.

 Race-based medicine could be a steppingstone to the higher goal of "targeted treatment," says Lawrence Lesko of FDA's Center for Drug Evaluation Research in Rockville, Md. Lesko and other advocates of this approach envision treatment tailored to people according to the results of genetic tests. They say that race-based medicine is just a first step toward discerning people's genetic makeup for the sake of better individual treatments.

 Some researchers and medical-policy analysts, however, are troubled by the implications of practicing medicine according to patients' racial identities. They emphasize the incomplete correlation between genes of medical importance and labels of race or ethnicity (SN: 4/9/05, p. 232: http://www.sciencenews.org/articles/20050409/bob9.asp).

 Cautious voices also warn that the wrong precedent by FDA in its handling of BiDil could contribute to, rather than reduce, health disparities between blacks and whites. Government endorsement of race-based therapies could spare companies the trouble of searching for biological beacons that could guide treatment in all populations, says Phyllis Griffin Epps of the University of Houston's Health Law and Policy Center. "As we move toward individualized medicine, race-based medicine might generate more problems than it solves," she says.

 "There's only one human race," says cardiologist Anne L. Taylor of the University of Minnesota in Minneapolis. "But within that race, there are subpopulations that have small variations. Those variations can have an impact, and we have to explore them."

 Heart of the matter

BiDil is a combination of two drugs that have had a roller coaster history in heart failure therapy. At one time, they were seen as the most promising combination therapy available, but drugs such as ACE inhibitors eclipsed them in the early 1990s.

 But while the newer medicines were more effective than the older compounds in cutting heart failure deaths in whites, the disease remained a stubbornly persistent killer in blacks. Today, among 45- to 64-year-olds, blacks are nearly twice as likely as whites to have heart failure and are 2.5 times as likely to die from it.

 There's evidence that isosorbide nitrate, one of BiDil's ingredients, strengthens the heart by chemically donating nitric oxide to tissues. Nitric oxide widens blood vessels, reduces inflammation, and performs other functions essential to cardiovascular health. Researchers hypothesize that hydralazine, BiDil's other component, relaxes blood vessels while also, as an antioxidant, keeping nitric oxide active.

 Several studies have suggested that active nitric oxide tends to be less abundant in blacks than in whites. That could partially explain why heart failure is a more serious disease among the former group, says Taylor.

 Nearly a decade ago, FDA considered but rejected an application by a small biotech company to market BiDil. The application followed a trial that included patients of various ethnic backgrounds. The drug had showed only an inconsistent beneficial effect.

 In 1999, University of Minnesota researchers reexamined the earlier data. They found that black people with heart failure had tended to benefit from the combination, while most whites hadn't.

 With the support of NitroMed and the Association of Black Cardiologists in Atlanta, Taylor in 2001 launched a trial to test the effectiveness of BiDil specifically in blacks. The researchers asked patients with advanced heart failure to identify their ancestries. Only patients claiming African descent were invited to join the trial.

 The study ultimately included 1,050 patients at 161 sites around the country. All the volunteers were already receiving heart failure drugs. Half of them then got BiDil in addition to their preexisting therapy, while half had a placebo added to their treatment.

 The experimental therapy was a major success. Patients receiving BiDil were 43 percent less likely to die during a year of treatment than were those not getting that medication. The difference was so profound that a group of independent scientists monitoring the study recommended last summer that it be brought to an early end so that volunteers on the placebo could be switched to the potentially lifesaving treatment.

 Taylor and her colleagues ended the study on July 19, 2004, and published their results in the Nov. 11, 2004 New England Journal of Medicine.

 Now, FDA is reviewing their study as part of the evidence that the agency may use to approve the patented combination pill for use in blacks. Given the strength of the study's results, approval is widely expected, if not universally welcomed.

 Many of a kind

While BiDil would be the first drug approved specifically for use in a racially defined subset of people, a patient's racial and ethnic group is already an important consideration for doctors prescribing certain treatments.

 At least 29 medications have varying effects in different racial or ethnic populations, says biologist David B. Goldstein of the University College London. In the November 2004 Nature Genetics, he and his colleague Sarah K. Tate gave a detailed account of these treatments, which range from antipsychotics to cancer-chemotherapy drugs.

 "Many differences in drug response associated with race or ethnicity are due to environmental [factors such as diet] rather than population genetic differences," they say. "In the case of BiDil, it is not currently known whether it works differently in African Americans and European Americans because of genetics, environment, or both."

 Genetic traits do appear to underlie some differences in disease susceptibility and response to therapies. For example, researchers have noted for years that because of differences in enzyme activity, people of Asian descent metabolize cholesterol-lowering statin drugs more slowly than other people do. As a result, some studies suggest, Asians are more susceptible to side effects at a given dose of statins. FDA recently advised physicians not to administer the highest allowed dose of one such drug, rosuvastatin (Crestor), to people of Asian ancestry.

 The biological mechanism remains opaque in other instances where medications have differential effects in various ethnic groups.

 "Our understanding of race and drug response is at best very superficial," says Lesko. Basing medical decisions on a patient's self-reported race, rather than on clinically meaningful genetic traits, he says, is "like telling time with a sundial instead of looking at a Rolex watch." All the same, he and others say, the proverbial sundial is useful when no high-accuracy wristwatch is yet available.

 "Until such time as you can go and directly sample [the relevant genetics of] an individual, the question is going to be, What proxies can you use?" says pediatrician and professor of law Ellen Wright Clayton of Vanderbilt University's Center for Genetics and Health Policy in Nashville. "The big one is going to be race."

 Defining groups by the external cues used to indicate race is far from ideal, Lesko says. "But in the absence of other alternatives, we need some way to group patients," he adds.

 That makes the shortcut of judging patients' races—or asking them to categorize themselves—an appealing alternative for doctors. BiDil is "the first racial drug," says Troy Duster, a sociologist at New York University. "That means there's going to be a second, and a third."

 Push for precision

Scientists have a "critical obligation" to identify the medically essential genetic variations that correlate with racial identity, Clayton says. It's those variations, not the identity, that should ultimately guide treatment, she says.

 In some cases, scientists have already progressed from a racial distinction to a genetic one. Researchers at Vanderbilt and elsewhere noticed several years ago an overall difference between the reactions of groups of white and black patients to the anti-HIV drug efavirenz. That agent was considerably more likely to cause side effects in blacks than in whites. Instead of simply recommending a lower dose of the drug for the black patients, the researchers decided to investigate further.

 David W. Haas of Vanderbilt and his colleagues identified a single genetic site with natural variation in both races. One genetic variant, which is seven times more common in blacks than in whites, slows metabolism of efavirenz. That accounts for the different risks of side effects in the two groups, the scientists reported
(SN: 2/21/04, p. 117: Available to subscribers at www.sciencenews.org/articles/20040221/fob6.asp). An individual's variant at the genetic site is more useful for guiding treatment than is his or her self-reported race, Haas says. However, there's no commercial test currently available for distinguishing those variants.

 Taylor and her colleagues are working to move BiDil treatment from a race-based to a gene-specific approach. They're examining genetic differences in a subset of the BiDil trial's volunteers to look for a deeper biological explanation of how the drug works and for whom it's best.

 Unearthing specific segments of DNA that explain individuals' differences in drug response would be ideal for patients, Clayton says, but economics might be working in just the opposite direction.

 Testing patients' genetic differences is more costly and time-consuming than is interviewing them about their ancestry. Furthermore, Lesko says, there's no point in approving a drug for genetics-based clinical use unless a test for the relevant genetic trait is widely available to doctors.

 FDA has released guidelines on how pharmaceutical companies can develop such diagnostics, and last December, it approved the first commercial screening test for a gene that affects drug metabolism. That test can guide physicians in the dosages that they prescribe for certain antidepressants, antipsychotics, and chemotherapy drugs. However, relatively few drug companies see potential for profit from such products, Lesko says.

 What's more, pharmaceutical firms may find it better for business to delve no deeper than racial differences. Lesko says that information identifying which patients won't benefit from a drug might narrow, rather than expand, the number of people for whom the drug can be recommended.

 On the other hand, he adds, both drug companies and patients would benefit from genetic tests that flag people—of any race—most likely to suffer drug-related side effects. In the case of the HIV drug efavirenz, for example, doses could be adjusted for the whites, as well as for the blacks, who have the genetic trait that's been associated with problems.

 Fewer side effects mean less regulatory hassle for the companies, so the pursuit of drug safety could drive research that pulls back the veil of race, Lesko says.

 Given today's concern over drug safety, that improvement in treatment precision could make a difference in patients' lives and on companies' bottom lines, ultimately advancing the prospect of individualized medicine. One day, people may be treated not by the color of their skin but by the content of their genome.
 References:

2004. FDA clears first of kind genetic lab test. Food and Drug Administration press release. Dec. 23. Available at http://www.fda.gov/bbs/topics/news/2004/new01149.html.

Bloche, M.G. 2004. Race-based therapeutics. New England Journal of Medicine 351(Nov. 11):2035-2037. Extract available at http://content.nejm.org/cgi/content/extract/351/20/2035.

Federico, M.J., R.A. Covar, et al. 2005. Racial differences in T-lymphocyte response to glucocorticoids. Chest 127(February):571-578.

Duster, T. 2005. Race and reification in science. Science 307(Feb. 18):1050-1051.

Goldstein, D.B., and J.N. Hirschhorn. 2004. In genetic control of disease, does 'race' matter? Nature Genetics 36(December):1243-1244.

Haas, D.W., et al. 2004. Pharmacogenetics of efavirenz and central nervous system side effects: An Adult AIDS Clinical Trials Group study. AIDS 18(Dec. 3):2391-2400. Abstract.

Hare, J.M., 2004. Nitroso-redox balance in the cardiovascular system. New England Journal of Medicine 351(Nov. 11):2112-2114. Extract available at http://content.nejm.org/cgi/content/extract/351/20/2112.

Tate, S.K., and D.B. Goldstein, 2004. Will tomorrow’s medicines work for everyone? Nature Genetics 36(November):S34-S42. Available at http://dx.doi.org/10.1038/ng1437.

Taylor, A.L., et al. 2005. Correspondence: Isosorbide dinitrate and hydralazine in blacks with heart failure. New England Journal of Medicine 352(March 10):1041-1043. Extract available at http://content.nejm.org/cgi/content/extract/352/10/1041.

Taylor, A.L., et al. 2004. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. New England Journal of Medicine 351(Nov. 11):2049-2057. Abstract available at http://content.nejm.org/cgi/content/abstract/351/20/2049.


 Further Readings:

Brownlee, C. 2005. Code of many colors. Science News 167(April 9):232-234. Available at http://www.sciencenews.org/articles/20050409/bob9.asp.

Harder, B. 2004. Drug racing: Gene tied to HIV-drug response. Science News 165(Feb. 21):117. Available to subscribers at http://www.sciencenews.org/articles/20040221/fob6.asp.

For information on the African American Heart Failure Trial (A-HeFT), go to http://www.aheft.org.

For further information about the Association of Black Cardiologists, go to http://www.abcardio.org/.

For information about BiDil®, go to http://www.nitromed.com/BiDil.asp.

 Sources:

Ellen W. Clayton
Division of General Pediatrics
Children's Hospital Outpatient Center
Suite 5028, Medical Center East
Nashville, TN 37232-8555

 Ronina A. Covar
Department of Pediatrics
Division of Allergy-Clinical Immunology
National Jewish Medical and Research Center
1400 Jackson Street A303
Denver, CO 80206

Troy Duster
Institute for the History of the Production of Knowledge
New York University
269 Mercer Street
New York, NY 10003-6687

Phyllis Griffin Epps
Health Law and Policy Center
University of Houston Law Center
100 Law Center
Houston, TX 77204

David Goldstein
Department of Biology
Galton Labs
University College London
London WC1E 6BT
United Kingdom

David W. Haas
Vanderbilt University
School of Medicine
21st Avenue South at Garland Avenue
Nashville, TN 37232

Lawrence J. Lesko
Office of Clinical Pharmacology and Biopharmaceutics
Center for Drug Evaluation Research
Food and Drug Administration
Rockville, MD

Anne L. Taylor
Department of Medicine/Cardiology
University of Minnesota Medical School
Minneapolis, MN 55455

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From Science News, Vol. 167, No. 16, April 16, 2005, p. 247
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