REPORT ON RACE AND GENETIC DETERMINISM
 

Brief on Race and Genetic Determinism
Race Bibliography

The (recent) completion of the Human Genome Project has led many in the scientific community to speculate that we are quickly approaching a time when medicines will be “tailored” to the unique genetic characteristics of each individual. Yet, the time needed to develop the technologies for such treatments, and the associated costs, may keep them from being used in the near future. In the meantime, a push to address health disparities, treat disease, and evaluate disease-risk, has led to a re-invigoration of categories that had, until recently, been considered outside the realm of human biology. Yet, the use of race in biomedical research has been defended by some biologists as appropriate for assessing individuals’ disease risk and other factors associated with health.

The re-invigoration of the use of race as a category has also led to the development of the first race-based drug, BiDil, which became available on the US market in 2005 [1]. Prescribed as a treatment for heart failure in African-Americans, BiDil has won the support of many scientists and physicians and even professional groups such as the Association of Black Cardiologists [2]. It has been called the first tailored treatment—one that may address differences in disease-risk for a particular group. Yet whether the drug is effective in treating heart failure only in African-Americans remains unclear.

The U.S. Food and Drug Administration’s approval of BiDil has resulted in a range of reactions from science and advocacy groups nationwide. A 2005 op-ed piece for the New York Times [], written by British biologist Armand Marie Leroi, indicates how some scientists regard the issue of race and biology. In his essay, Leroi argues that collections of outward features such as hair color, skin color, and nose shape are characteristics that reflect important natural divisions between groups. Other scientists maintain that humans cannot be classified into discrete categories such as those described in Leroi’s essay—that a long history of migration and mating between groups, among other factors, has prevented this. These debates highlight the problems inherent in discussing a term that has many definitions yet no parameters. In the early 1970’s, Richard Lewontin, a Harvard geneticist, revealed that the vast majority of human genetic variation occurs within, rather than between, groups []. His work and that of others have led to a general consensus among biologists that race is not a scientific concept but a social one and that efforts to include it as a meaningful category in science can be misleading.

Yet, there is a growing investment in genetic research in pharmaceutical and other biomedical treatments for medical conditions. Efforts to locate the genetic basis of disease are aimed, ostensibly, at improving health outcomes; advocates state that investigations which use race as a variable will result in improved treatments for disadvantaged groups. But race is an ill-defined variable. The use of race does not provide a rigorous scientific basis from which to gain information about a person’s biology. Findings from numerous studies suggest that, while in some cases a person’s race may provide information about the probability that they may be at risk for developing some diseases, it can also mask the probability of their risk for developing others []. The human species is 99.9 percent the same genetically. The remaining 0.1% of variation accounts both for differences that are visible, such as eye and hair color, and those that are not seen, such as disease-risk. Yet these unseen differences are not consistently represented by an individual’s racial designation. Additionally, though a handful of diseases have been shown to occur more often in some groups than in others, these conditions are not isolated to those groups. This makes it very difficult to make accurate calculations based on an individual’s inclusion in a specific group.

Meanwhile, a range of new genetic technologies has added a somewhat complicated feature to concepts of biology, race, and human rights.  Recently, an industry has emerged whose products may confuse notions of race with biology. The number of companies offering “personal genetic history” analysis has grown over the past decade, reflecting an ongoing public interest in both family and ethnic origins. Many of these companies previously specialized in genealogical research but have expanded the range of their services to encompass the analysis of DNA to trace human lineages back to a geographical region of origin. Much as the 1980’s TV series chronicle “Roots [],” on ABCoffered an historical identity to the African-American community, personal genetic history analysis has been framed as a way for individuals to find their own specific biological “roots.” Press attention has been devoted to the robust response this new technology has elicited from the public. Many human-interest stories have focused on individuals who have purchased ancestry information as a way of drawing a connection to the possible ethnic identities of their ancestors. High-profile public figures, such as talk show host Oprah Winfrey, have used the technology. Winfrey’s recent announcement, on her show, that she is descended from a well-known tribe in Africa [] touched on how these tests are often perceived by consumers as providing a connection to ethnic identity.

Some of these companies have made efforts to underscore that they are not conducting “race” tests. Yet the marketing strategies they employ send an implicit message. An example is illustrated by the DNA Print Genomics web page [], dedicated to ancestry testing products. On this page, the photos of four individuals appear prominently. Though the photos are not labeled, the physical appearance of each individual fits some of the classically defined descriptions of race made by anthropologists. The text on the web page suggests that the groupings reflect descent from particular geographical regions such as East Asia, Europe, Africa, and the Americas, and the presence of the photos suggests that physical appearance can reflect this descent.  But appearance is often how individuals are racially classified as well. This could lead consumers to confuse notions of race with ancestry —and to assume that personal genetic history analysis tests for race. Consumers may take away from such advertisements the idea that race is “coded” into human genes.

Speculations about race and biology have a long history. And though more sophisticated terminology regarding genetics and human ancestry dominates in contemporary academic papers, popular press articles continue to reflect perspectives about race and biology that were popular at the turn of the century. A review of the history of race and science reveals how outdated ideas about race continue to influence contemporary lay understanding.

A Short History of Race and Science

Throughout the world, and depending upon the time, notions of race have varied widely. Race has been used as a way of defining human differences at least as far back as ancient Egypt. In the Book of Gates, a detailed text of the afterlife, Egyptians, Nubians, Asiatics, and Libyans were described as distinct peoples []. Whether an individual was designated black, white, yellow, red, or of any other racial/ethnic group, depended upon the cultural context. For instance, the “one drop of blood” rule, employed in the southern part of the United States during the eighteenth and nineteenth centuries, stated that an individual with any non-white ancestry was “black.” The rule was based on the belief that the races had different kinds of blood as well as corresponding social and intellectual capacities []. At different points in history, individuals with ancestry from regions of Africa, the Middle East, or India, among others, have been considered “black,” and “white” by different societies.

In scientific discourse, race first appeared as a category during the eighteenth century [] when folk notions of blood were transformed into scientific ideas. At that time, anthropologists developed these notions into categories for dividing up the species. Different theorists identified anywhere from three to thirty groupings but the most commonly accepted number of categories was five: Negroid, Caucasoid, Mongoloid, Capoid, and Australoid []. Criteria were based primarily on living in certain regions of the world and on physical features, such as hair texture, skin color, and face shape. Today, these categories still tend to capture concepts of race, but definitions have been broadened to include religious, cultural, historical, and socio-economic status as well. Thus, the parameters constructed to define race remain fluid and inconsistent despite their translation into biological classifications a few hundred years ago. 

During the eighteenth, nineteenth and part of the twentieth centuries, race was thought to represent deeper biological realities that were believed to affect characteristics like morality or intelligence. Johann Blumenbach, a German biologist and social philosopher, was one of the first to connect the subjects of race and biology. His literary piece that detailed an analysis of human skulls, On theNatural Varieties of Mankind, was published in 1795 []Claiming that a skull found in the Caucasus Mountains was a beautiful and ultimately superior form compared to skulls of the “diverging” races, he laid the groundwork for future claims of white biological superiority. His racial designations were widely adopted and reflected, to some extent, peoples’ geographic region of origin, but were largely based on the skin colors “white, yellow, black, red, and brown.” The facial characteristics of these human hierarchies were often interpreted in highly subjective terms. For instance, the sallow color and folds of skin around the eyes of the then-termed “yellow” Mongolians were interpreted as a sign of craftiness. In contrast, the high forehead of a Caucasian was seen as setting “whites” at the farthest remove from lower animals, particularly apes.

Some historians have argued that science was being used as a vehicle to substantiate socially constructed racial hierarchies. Tying race to biology served to further strengthen the idea that some groups were superior to others. A notable declaration of this type was made by [prominent political figure and founding father] Thomas Jefferson. In what can be assumed as an effort to justify the practice of slavery in the new democracy, Jefferson wrote extensively of the “suspicions” that Blacks were inferior to Whites. Jefferson owned many slaves who worked on his plantation in Virginia. Without the availability of the free labor, he, like many wealthy white landowners, would have struggled to retain his economic and socially powerful position as a leader of the new nation. Jefferson addresses the question of the emancipation of African slaves in his piece, On Slavery []: “ ... It will probably be asked, Why not retain and incorporate the blacks into the state, and thus save the expense of supplying, by importation of white settlers, the vacancies they will leave…[they are] in reason much inferior, as I think one could scarcely be found capable of tracing and comprehending the investigations of Euclid; and that in imagination they are dull, tasteless, and anomalous…” Jefferson’s sentiments in this passage reflect the political climate of that time as it related to the emancipation of slaves (this reflects how the use of concepts about biology and race affected large-scale social policies as late as the eighteenth century).

Perspectives such as this carried through the Darwinian revolution of the mid-nineteenth century when social philosophers such as Herbert Spencer re-cast the theory of evolution to explain the social hierarchy of races as an outgrowth of natural selection. A contemporary of Darwin’s, Spencer introduced the concept “survival of the fittest” which advocated against social reform movements that aimed to improve the circumstances of individuals at the bottom of the social hierarchy, often non-Whites and the poor []. The social hierarchies of the day were rationalized as a result of inborn “natural” divisions between the races that had evolved over time. These racial hierarchies became reified into concepts which early researchers utilized as a foundation in their study of the human species. Termed “eugenics” by Francis Galton, this new strain of thought placed emphasis on heredity as a path to the further improvement of the human species []. These ideas were celebrated at the time and came to pervade both the scientific and political landscape during the early part of the twentieth century. Social policies, based on this new  “science” of heredity, were enacted in an effort to perfect human populations through controlled breeding practices. Some of these involved tighter immigration policies and segregated schooling. Others were more extreme—involuntary sterilization of members of particular racial groups, the mentally ill, criminals, etc. Eugenics policies were carried out during the pre-World War II-era in parts of Scandinavia and the United States, but perhaps the best known of these practices was the genocide of the Jewish population by the German Nazis during the war. Despite efforts by groups of scientists and progressive social philosophers, large-scale efforts to discredit eugenics and the “science” of racial hierarchies were not taken seriously until after the discovery of the Jewish holocaust [].

In opposition to eugenics, a counter-movement was forming and slowly gaining popularity among groups of scientists, anthropologists, philosophers, and social theorists throughout the world. The gathering of representatives from over fifty countries to discuss the effects of eugenics at the Universal Races Congress in 1911 [ ], held in London, represented one of the earliest collective efforts to discredit the “race as biology” perspective. W.E.B. Du Bois, on behalf of the then nascent National Association for the Advancement of Colored People (NAACP) was elected co-secretary of the American delegation. It was here that a large body of research on race from the social sciences was presented in an effort to promote an alternative way to think about race and the results of worldwide colonialism. One of the many results of this first congress was a declaration proclaiming the equality of all peoples of the world regarding human endowments. This statement represented a direct opposition to the tenets of race science, and, though this viewpoint did not gain acceptance quickly, it began to have an effect around mid- century.

 

Perspectives on Human Genetic Diversity Emerge

Beginning in the 1960’s and 1970’s, research on disease-risk and work in the field of population genetics fundamentally changed the way scientists viewed the variation of human traits both within and between groups. Since that time, numerous studies have supported the finding by Lewontin that the vast proportion of variations occurs within any given local group []. Additionally, concepts about race-specific diseases began to shift. Research on sickle-cell anemia, a disease thought to affect only African populations, was found to occur in significant proportions of Mediterranean, Middle Eastern, and Indian populations as well. This was linked to the discovery that the geographic specificity with which the corresponding gene variation occurs is related to malaria resistance, not to race []—individuals who inherit only one allele for the trait benefit from a greater resistance to malaria, whereas those who inherit both alleles come to be afflicted with the illness. Prior to these discoveries it was thought that sickle cell anemia was linked to skin color—and therefore suggested obvious parallels with racial designations. This example illustrates how complex human traits vary not from racial group to racial group. Rather, they vary across populations because different selective pressures arise in particular regions of the world.

Findings such as these have resulted in scientists moving away from the idea that race has a biological basis. Still, some researchers believe that racial designations can be of use and have crafted explanations of how human genetic variation can be represented in “racial” terms []. By demonstrating that small markers on portions of DNA cluster in ways that can be shown to vary between the classically defined racial groups, these scientists maintain that race can be found in an individual’s genetic structure. Using short sections of non-functional DNA, known as microsatellites, scientists can cluster populations along continental lines of descent. The variations that occur on these sections represent a tiny portion of an individual’s genome and are chosen because they contain the most information regarding group differences. These do not inform our knowledge about large trait differences, but sometimes can be used to represent a handful of characteristics such as skin color or hair texture []. The focus on these variations has been defended based on their purported usefulness in calculating disease-risk. But this focus provides an unstable foundation from which to calculate such risks. Using the sickle-cell trait as an example, knowledge of African, Mediterranean, and/or Indian ancestry may prompt an individual to get tested for the disease despite the fact that there is no causal connection between the genes linked to this disorder and the small variations that delineate continental ancestry. Focusing on these small variations can mislead both patients and doctors.

Increased immigration and the effects of globalization have greatly encouraged mating between groups. It is possible that as populations throughout the world become even more mixed, concepts of “race” will change accordingly. In terms of health care and disease-risk, modern ancestry testing has sought to provide avenues for assessing mixed populations through admixture analysis, the breaking down of an individual’s genetic lineage based on multiple geographic regions of origin. Though these are not “race” tests, their use has been interpreted as a search for racial mixture. These tests are not exact, but provide estimates that are based on probabilities. It is not clear how admixture analysis can accurately inform research on health risks.

Available evidence suggests that a combination of socioeconomic, environmental, and biological factors that include differences in access to health care, the effects of discrimination, and inherited risk factors contribute heavily to health disparities between racial groups. A balanced perspective regarding how these interact with one another is important in understanding the basis of these disparities. Additionally, distinguishing the difference between race and ancestry is imperative for designing an appropriate approach to preventing and treating disease for all groups. 

 

Race, Ancestry, and Health Disparities

Different racial/ethnic groups demonstrate different risks for developing, and recovering from, certain diseases. For example, White women have an overall higher rate of breast cancer than women of other groups. However, as discussed in the following paragraphs, studies show that the reasons for this do not lie in specific genetic mutations, common to White women. Though, in this case, data suggests a connection between disease-risk, mortality rates, and “race,” the underlying causes for the difference between groups is not related to genetics. Rather, social and environmental factors that are related to a person’s “race” play a major role in these differences. 

However, the ancestry of an individual (as represented by the biogeographical region(s) of origin of his or her ancestors) may affect her or his risk for developing a small number of diseases due to geographically specific selective pressures that have caused mutations over time. It is important to distinguish how a person’s “race” versus their ancestry affects the probability that they will develop certain diseases. The discrepancy between reported or observed race and a person’s ancestry can result in a loss of information important in assessing disease risk. For instance, a person who appears to be of European descent may be classified as “White” based on appearance. However, if this same person has West African ancestry that he or she is not aware of, an increased risk for a disease associated with descent from that region, such as sickle-cell anemia, may not be taken into account by their doctor, resulting in their not being screened for the disease. The assumption that a person’s race, which is often identified by appearance, can inform his or her disease-risk can result in errors such as this. While accurate information about a person’s ancestry may aid physicians in assessing those at risk for a small number of conditions, information about race will not. Often, health disparities between groups do not result from differences related to ancestry, but from differences in treatment, access to healthcare, socioeconomic status, and other environmental factors.

A recent study published in the New England Journal of Medicine [] showed that despite major legislative efforts, disparities in medical treatment based on race continue in the United States. In the last decade, greater attention has been focused on narrowing the gap between groups in terms of healthcare treatment and outcomes. During this time, thirty- four states have established offices of minority health and in 1993, The National Institutes of Health began to require that minority patients be adequately represented in clinical studies.

The 2005 study, “Racial Trends in the Use of Major Procedures Among the Elderly,” focused on the use of high-cost surgical proceduresthat could not be attributed to patients’ clinical characteristics. A.K. Jha led a team that reviewed the Medicare enrollee census for every year from 1992 through 2001. Their sample included 29 million enrollees for each of the years. The use of nine major procedures was reviewed. Despite efforts to improve healthcare for all groups, the data indicated that racial/ethnic differences in the use of procedures did not narrow significantly between 1992 and 2001. The outcomes of legislative efforts suggest that they have not been successful in narrowing disparities between racial/ethnic groups in terms of use of these procedures. In an interview for National Public Radio [], Jha stated that even when access to health care is controlled for, Black patients consistently receive different treatment than White patients: “We’re not talking about small differences; we’re talking about substantial differences that have a very profound impact on whether people live or die, what quality of life they have. And in the year 2005 [these inequities] really should not be something we should be willing to live with.” Appearance serves as a proxy for different treatment by physicians, the study showed.

Research on breast cancer has revealed differences in age of onset of the disease between African American and White groups of women []. Although overall rates of breast cancer are higher in White women, new incidences are rising in African Americans, particularly for those under the age of 50; for women under 35, African Americans are 1.5 times as likely to develop the disease. Additionally, while mortality rates for White women diagnosed with breast cancer have been declining for the past twenty years, this has not been the case for African American women.  A study conducted by Lisa Newman et al., published in a 2002 issue of Cancer [], found that race was an independent predictor of breast cancer mortality—African American women have a 20% higher likelihood of dying than white women following diagnosis. Why do these disparities exist? A broad review of recent research points to several factors. First, differences in treatment may affect overall chances of recovery. A recent visit by a health professional to a “major hospital in middle America” documented in the Breast Cancer Action Newsletter [] found that the treatment of breast cancer in African American women differed from what a typically health-insured woman in the United States could expect when getting screened for the disease. Among other problems, there was a noted lag time in the processing of mammogram results (up to four months, rather than a few days) and biopsies. This may have resulted in higher mortality rates []. Second, there appear to be differences in risk factors for the disease between the two groups. On average, African American women tend to suffer higher rates of other illnesses in addition to breast cancer. Combined with the tendency to get diagnosed during more advanced stages of the disease—and with more aggressive tumors—results in an increased mortality risk when compared to Whites. There may be a genetic contribution to these differences in pathology but little is known regarding how specific genes or markers contribute to the illness. Due to the distribution of income by race, African American women are more likely to live in areas contaminated by pollutants that may affect the onset and course of the disease.

A recent paper published in the American Psychologist by Shields, et al. [] on the use of race variables in genetic studies of complex traits, focused on smoking research as a case study. The authors conducted a broad, trans-disciplinary review of the history of racial categories in medicine, current research practices, and arguments for and against using race variables in genetic analysis. They found that in the context of genetic research, differences in patterns of variation were often being framed in racial or ethnic terms. This was occurring without adequate attention to measures known to affect health such as socioeconomic and other environmental factors, despite the known fact that “identified polymorphisms account for only a small portion of individual variation in disease known to have a genetic component.” All of this has led to a debate within the healthcare field regarding the importance of race/ethnicity as a variable in research on health disparities.

Highlighting the fact that the smoking prevalence among African-Americans and Whites in the United States is similar, the authors underscore important differences regarding age of onset, number of daily cigarettes, and relative success in quitting the habit between the groups. For example, studies show that 37% of African Americans report success with quitting smoking, while 51% of Whites do. The figure for African Americans may be lower due to how socioeconomic status may have confounded many studies’ reported quit rates. Nevertheless, this group has higher mortality rates for diseases associated with the long-term effects of smoking such as lung cancer.

In their review of several studies, the authors found that those who conducted the research tended to rely on participants self-reporting their race/ethnicity rather than asking them about ancestry. Their review found that of thirty-four studies conducted on smoking or nicotine through June 2003 that utilized race/ethnicity as a variable, only six were explicit in describing how race was defined within the specific study. Within those six studies, the authors found that terms like “White” were defined differently.

When race/ethnicity is used as a variable, the accuracy of an individual’s genetic diversity is not always accounted for. This can be seen in the results of a 2003 study by Shriver, et al. [] who looked at self-reported race/ethnicity in a Washington, D.C. sample of participants who identified as African American. Utilizing 31 genetic markers, the data showed that approximately 22% had predominant European or Native American genetic contributions and a lower African one.

The above research on health disparities between racial groups highlights several public health issues. Jha’s study demonstrates that, regardless of the clinical characteristics of a disease, discrimination exists within the medical community towards members of minority groups. When decisions about important surgical procedures, and other medical decisions, are at stake, discrimination can profoundly affect mortality rates and skew data regarding the origins of such disparities.  Second, when researchers and other medical professionals treat race/ethnicity as a category of biology, the accuracy of data remains questionable. The study by Shields, et al. demonstrates that caution is warranted when attributing a genetic perspective to race variables. Third, despite recent policy efforts to decrease between-group disparities, inequities in access to healthcare, screening for illness, and treatment continue. Yet, there has been a general increase in genetic research aimed at finding solutions to these problems. One outcome of this has been an increased investment in research into the development of race-based drugs to target the symptoms of illnesses. The development and F.D.A. approval of the first race-based drug, BiDil, has accelerated these efforts.    

 

Race and Pharmaceuticals: The Case of BiDil

A recent article in an October 11, 2005 web-exclusive of the journal Health Affairs [] described the origins of race-based pharmaceuticals. In their review of the approval process for the heart-failure medication, BiDil, authors Pamela Sankar and Jonathan Kahn underscored how the approval process for the drug shaped its later being cast as a medication for a specific race. The review begins with several drug trials, conducted by the Veteran’s Administration in the 1980’s. The Vasodilator Heart Failure (V-HeFT) Trial I and Trial II were conducted in an effort to find appropriate drug treatments for heart failure. Findings from the first trial indicated that a combination of two generic vasodilators, hydralazine and isosorbide dinitrate (H/I) showed promise in treating the condition. The Second Trial focused on ACE Inhibitors and also showed promise—ACE Inhibitors went on to become the first line treatment for heart failure through the next two decades. Unfortunately, this line of medications did not work effectively for all patients. Therefore an effort was made to bring the H/I combination to the market.

Jay Cohn, the lead research scientist for both studies, attempted to patent the H/I combination treatment in one pill, despite evidence from the trial that suggested the combination of the two generics worked no better than using each one separately. Cohn began several studies to prepare a patent application to present to the U.S. Food and Drug Administration for approval.

In 1997, the Food and Drug Administration rejected Cohn’s application, based on the availability of the generic forms of H/I. Two years later, an analysis of the V-HeFT trials by scientists at the University of Minnesota found that African American individuals in the study responded more positively to the H/I combination. It was following this analysis that speculation about the race-specific use of H/I began. Cohn and another scientist, Peter Carson, worked to determine if a new application might be approved if the H/I combination was shown to be an effective treatment for heart failure patients who were African American.

The two published a paper in 1999 that re-analyzed the data from V-HeFT I based on the small sample of forty-nine African American subjects who were placed on H/I, and data from this re-analysis helped Cohn to re-license the intellectual property rights of H/I to the Massachusetts pharmaceutical company NitroMed. The following year the two scientists re-applied for a patent based on the race-specific application of H/I with the market name BiDil.

The FDA indicated that the data looked promising, and encouraged the two to conduct a new trial on African-American subjects. Cohn, Carson, and NitroMed moved forward with A-HeFT, the African American Heart Failure Trial, utilizing 1,000 African-American subjects suffering from advanced heart failure. The method used to identify the race of the study sample was a self-identification survey. Notably, those not claiming African American as their race were not included in the study.

The trial began in 2003 and was slated to continue through 2005. The study was halted, however, in 2004, when the study’s Data Safety Monitoring Board declared that the positive results of using BiDil were substantial enough that continuing the placebo group would be unethical. Preliminary data showed that the use of the drug resulted in a 43% reduction in the rate of death from any cause and a 33% percent reduction in first hospitalization from heart failure. Shortly thereafter, NitroMed submitted a revised application to the FDA which approved BiDil as a race-specific treatment for heart failure, the first of its kind in history. The marketing rights from this patent continue through the year 2020.

Though BiDil is a treatment that will clearly benefit patients, especially those who do not respond to ACE inhibitors, the costs associated with the use of BiDil, and other concerns associated with the testing process and its approval should not be ignored. Consumers can expect to spend a lot more for the drug. Even after adjusting for dosage amounts, there is a vast difference in price between the generic isosorbide and hydralazine pills (at around $0.25 cents per pill), and the cost of one BiDil (about $1.80 per pill). The average recommended dosage for BiDil is six pills per day, bringing the daily cost to $10.80. In contrast, ACE inhibitors cost relatively little, even the non-generic forms of the drugs commonly prescribed to heart failure patients. A survey of three of these, Vasotec, its generic Enalapril, and Captopen revealed an average daily cost of $1.60, $0.57, and $3.62 respectively []. What prevents doctors from prescribing to patients the much cheaper, generic forms of H/I instead of BiDil? By testing doses that were unavailable commercially, Nitromed effectively eliminated sales competition with manufacturers of the generic versions of H/I.

Additionally, it is not clear whether BiDil is a treatment that works only, or even better, for African Americans. Sankar and Kahn report, “The study of racially differential response to hydralazine/isosorbide dinitrate by Carson and colleagues was based on…[an] analysis of 15-year old data derived primarily from V-HeFT I which enrolled [a small sample size] of 180 African-American subjects.” Other studies have found no such disparities in response to heart failure medications. Derek Exner and colleagues published a study on differential response to ACE inhibitors that showed no difference in mortality rates between blacks and whites [].

Participants from other racial groups were not included in the A-HeFT study. How do we know that BiDil would not be a suitable treatment for Hispanics, Whites, or members of other “racial” groups? Biologist David Goldstein of the University College, London, and his colleague Sarah Tate state in the November 2004 issue of Nature Genetics: "Many differences in drug response associated with race or ethnicity are due to environmental factors [such as diet] rather than population genetic differences…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 [].”

Within the African American population, there exists tremendous variability for characteristics such as disease-risk and mortality rates. New York University professor Troy Duster, explains in his essay, “Race and Reification in Science [],” that in heart failure patients, Americans of African descent show much higher rates of hypertension than Americans of European descent, but darker skinned blacks show higher rates of hypertension than lighter skinned blacks. It is not currently known what the reasons for these differences are or if drug treatments such as BiDil are more or less effective because of this.

What are the implications of the approval and use of BiDil for the future of pharmaceutical research? Duster argues that institutions, such as the FDA, should exercise caution in approving drugs like BiDil. He suggests that regulations be instituted that require companies to conduct research aimed at locating markers that have an “actual functional association” to drugs. This way, patients may be tested for the markers regardless of their race or ancestry, thereby avoiding pitfalls associated with the use of either. Without this type of regulatory action, Duster warns, the use of race threatens to cloud associations between illness and biology.

 

Personal Genetic Histories

The public use of “personal genetic history” (PGH) testing has exploded over the past few years. A quick search on the internet produces a list of companies with names like Ancestry By DNA [], AfricanAncestry.com [], and Family Tree DNA [], which offer services to assist individuals in tracing their “bloodlines” back to a geographic region of origin through the analysis of genetic material. For all its simplicity, a cheek swab is purported to provide many with answers to questions about family history that seemed previously unknowable. 

Many individuals have reported that PGH results offer a connection to racial and ethnic identity that is deeply meaningful for them []. The popularity of these tests underscores the degree to which people associate their identity with their biology. The New York Times ran an article recently entitled, “Blacks Pin Hope on DNA to fill Slavery’s Gaps in Family Trees,” published in the Science section which demonstrated just this. A woman who was interviewed reported that her test showed that her African roots were quite old. Being of light skin color, she had been viewed by members of her community as having lower status, but the test, she said, “showed underneath I’m deepest Africa [].” Though no test can reveal  a person’s racial/ethnic background, consumers may attribute such meanings as inherent within their results.

Consumers may be easily confused both by the different testing options available and the relative accuracy of the results. Though each of the available methods attempts to determine a person’s ancestry by region, they often achieve different results. The first type, lineage-based tests, have been used by evolutionary biologists to trace human origins back to Africa. Going back far enough, DNA from all types of human genomes traces our origins back to that continent. After a sample is extracted and sequenced, it is compared to samples from a database of haplotypes (sets of markers that have been associated with one another because they tend to cluster). The presence of these haplotypes has been attributed to specific geographic regions. Estimates of descent are based on the presence (or absence) of particular haplotypes within a sample [].

The accuracy of matches depends on the database with which the samples are compared. An average database carries haplotypes that range in number from a few thousand to tens of thousands. The majority of these databases are private, and companies tend not to share information with one another. The larger and more varied the samples from each population, the more accurate the matches will be. But these matches are still based on probabilities, not absolutes. Regardless of the size of the database, the more common haplotypes include regions that are quite large and overlap. The results of these overlaps lead to inconsistent and vague estimates of geographical region that consumers are often unaware of. A second issue of concern is that these tests produce estimates that are focused on a single lineage, and therefore ignore other genetic contributors to a person’s DNA (and the vast majority of their ancestors). It should be made explicit that maternal and paternal lineages together do not represent the total genetic diversity represented in an individual’s genome. A customer may be misled into thinking that these test results represent his or her entire genetic history.

The second type of PGH tests for biogeographical ancestry by the use of Ancestry Informative Markers” (AIMs). This small number of markers differs in frequency across population groups, ranging from local to larger continental clusters. A person’s genetic history is estimated by searching his or her DNA for these markers and calculating percentages of ancestry based on their presence and frequency against the known percentages in ancestral populations.  The use of AIMs has also become increasingly widespread in the field of criminology in recent years. AIMs have been seen as useful to criminal investigations, based on their contribution to the understanding of admixture mapping (or how an individual’s genome is made up of differing proportions of markers representing various regions). These calculations are statistically based. However, relative to lineage-based tests, knowledge of how the markers are distributed geographically is less specific. Many potential ancestral patterns could be consistent with one result. For example, M. Shriver and R. Kittles state in their paper “Genetic Ancestry and the Search for Personalized Genetic Histories,” that “a person might show 75% West African and 25% Western European ancestry in a BGA estimate because three grandparents are from West Africa and one is from Western Europe or because all four grandparents are of East African Ancestry.”

What do Personal Genetic Histories tell us about race? Some would say nothing at all. Only 0.1% of the human genome provides information that can give us answers to the story of human migration. And though this information has been helpful in tracing our common origins back to Africa, it has also revealed the seemingly countless movements our species has made everywhere else on the planet. This does not translate into the biology of a “racial/ethnic” identity, however. Unfortunately, it seems unlikely that companies will convey this source of uncertainty to their customers. Yet, a standardized code of conduct should be established for the industry for ethical reasons, especially as the use of these technologies increase, as they have in the criminal justice system. 

Race and the DNA technology of the Criminal Justice System

There has been a major push in the United States to expand the size and use of DNA databases for the purposes of “catching criminals” based on biological evidence left at crime scenes []. This push led the U.S. Attorney General, in 2002, to order the Federal Bureau of Investigation to expand federal databases from 1.5 million to 50 million profiles. Reasons for this updating strategy are numerous but can be distilled into three different categories. First, the DNA from these databases can be used in post-conviction cases (often ones where convictions occurred prior to the development of this technology) to determine whether there has been a wrongful conviction. Second, prior to trial, DNA collected from accused or suspected individuals can be used to match that from crime scenes. Lastly, having DNA samples from previously incarcerated individuals allows law enforcement agents to link future crimes to those guilty of recidivism [].

Why would it be a problem to use DNA evidence to “catch criminals?” There are several problems with the current way that DNA from the accused and forensic DNA from a crime scene are matched that should give us pause when considering the relative accuracy of readings. First, the science is based on samples from a population that is composed mostly of incarcerated individuals. The sets of DNA markers frequently used for matching are derived from these samples. Certain ethnic or racial groups are over-represented in these databases, as they are in the criminal justice system in general. Already, there exists a systematic bias, by race, of a full range of criminal behaviors associated with these groups that has led to the widespread use of the term “racial profiling.”

Have certain racial or ethnic groups always been over-represented within the criminal justice system? In 1933, the prison population was 77% White, which was close to representative of the U.S. population at the time. Beginning then, and increasing dramatically during the 1980’s, the majority of the prison population slowly represented ethnic minorities so that, by 1989, there were seven times as many Black individuals than Whites in the prison system.  This turn-over in demographics occurred for many reasons, but the dramatic over-representation of Blacks in the 1980’s can be attributed to one sweeping social policy of the Reagan Administration known as the “War on Drugs.” During this time, law enforcement officials were trained and encouraged to stop likely drug offenders based on a system that targeted young, minority, males as the most likely to offend. Though, at the time, Blacks accounted for only 15-20% of the country’s drug users, they were suddenly making up half to two-thirds of arrests for drug offenses in urban areas. Thus, the “War on Drugs” had a profound effect on the racial/ethnic makeup of most U.S. prisons [].

Fast-forwarding to today, the term “racial profiling” has come under much scrutiny from both the public and public officials. Several studies by state governments have revealed the extent to which racial biases have disproportionately singled out members of minority groups by law enforcement officials. Despite this awareness, a new type of racial profiling could well occur with the use of forensic DNA. A new terminology known as “ethnic estimation based upon allele frequency variation,” describes a technique used by forensic scientists who find that the utility of population markers helps to narrow lists of suspects. These “ethnic estimations” are based on variable markers at several locations on the DNA (termed “loci”). This is based on the theory that, in a given population, such as the Chinese, a certain marker will occur with greater frequency than it does within another population, such as the Danish. These are proportional estimates only, as these markers are not restricted to individuals of particular races/ethnicities. By choosing markers that have a very high frequency for certain populations, scientists attempt to narrow the likely racial profile of a given suspect. They might do this by choosing several sets of markers in order to get a reading with higher accuracy. However, no matter how many sets of markers are used, there is no way to ensure 100% accuracy. Still, many argue that proportional differences can be of practical significance to criminologists in narrowing down a group of suspects. Yet this method could also result in overlooking a suspect who should be considered, or charging and convicting one who shouldn’t be, simply because they have a less typical DNA profile when compared to other members of their racial/ethnic group.

Another problem, associated with the use of ethnically affiliated DNA markers, lies in the danger of their being associated with undesirable behavioral characteristics. Not much is known about the genetic basis of behavioral characteristics, yet theories abound regarding the origins of the “criminal personality.” Personality features such as aggressiveness or low inhibition, that are thought of as inherent to criminal types, may come to be associated with particular markers—and particular populations. And since the majority of samples that make up U.S. databases are from minority populations, the risk of associating these traits with particular racial or ethnic groups seems high. 



Conclusion

The human species consists of many “fluid bio-cultural units.” In the time we have spent criss-crossing the planet, we have created thousands of diverse cultures, each of which has adapted to, and changed with, different environmental conditions over periods of time. The effects of countless migrations due to famines, wars, weather patterns, the search for economic stability, and other motivators, has engendered a long history of mating between groups. The more recent effects of world travel, web communication and a global economy have only added to this.  As a result, within the “human race,” there are no sub-species that can be ranked into taxonomies according to differences in traits and abilities. As a whole, we are far more alike than different.

Yet, as can be seen in debates around Affirmative Action, and more recently, immigration, race has been perceived as a category that keeps some people “out” while ensuring that others stay “in.” The U.S. Immigration Act of 1924 provided 86% of quotas to the entry of “White,” Northern and Western European immigrants, leaving a much smaller percentage to immigrants from other parts of the world. Today, the situation has not changed much; the view of America as a ‘country of immigrants’ has caused a contentious debate in response to a large influx of immigrants of color. In the spring of 2006, debates around the “problem of immigration” as members of Congress and the media have referred to it, highlight a topic that has brought race back into the forefront of socio-political debate.

The search for human identity has led many to seek answers to social issues such as this one within the realm of biology. The reverse is also true—as the focus on “racial” genes in biomedical research makes clear: we seek answers to the biological in the social. But it is a major mistake to confuse the two. Race is a social category that continues to be misapplied in scientific endeavors. What few clues ancestry categories may be able to give us regarding the origins and incidence of disease often succeed only in masking other important sources of these disorders. Research on health disparities demonstrates that an excessive focus on genetic research into the origins of illness in specific populations often bypasses opportunities to develop appropriate preventive measures for those very populations as well as for others. It also threatens to justify the misplaced concept that race is biological. 

 

References

 “FDA approves BiDil Heart Failure Drug for Black Patients.” Retrieved on March 7, 2006 from: http://www.fda.gov/bbs/topics/NEWS/2005/NEW01190.html

 “FDA Approval Of BiDil brings new hope to black heart failure patients: ABC-Sponsored Heart Failure Trial Leads to First Treatment Specifically for Blacks.” Retrieved on March 7, 2006 from: http://www.abcardio.org/press.htm  

 Leroi, A. M. 2005. A Family Tree in Every Gene. The New York Times. March 14.

 Lewontin, Richard C. 1982. Human diversity. New York, NY: W.H. Freeman & Company.

 Lewontin, R. C.  2005. "The fallacy of racial medicine: confusions about human races." Social Science Research Council: http://raceandgenomics.ssrc.org/ (accessed October 4, 2005).

 Bogle, Donald. 1988. Roots and Roots: The Next Generations: blacks in American film and television: an encyclopedia. New York, NY: Garland.

 “African American Lives” premiered on PBS on February 1 and 8, 2006. Information regarding this program is available at: http://www.pbs.org/wnet/aalives/

 http://www.ancestrybydna.com

  Hornung, Erik. 1999. Ancient Egyption books of the afterlife. New York, NY: Cornell University Press.

 Wright, L. 1994. One drop of blood. The New Yorker. July 24.

Banton, M. P. 1977.The idea of race. London, U.K: Tavistock.

 Cavalli-Sforza, L. L.; P. Menozzi; and A. Piazza. 1994. The history and geography of human genes. Princeton, NJ: Princeton University Press.

Blumenbach, Johann. 1795. On the natural varieties of mankind. Gottingae: Apud Vandenhoek et Rvprecht.

 Jefferson, Thomas.  1781. Notes on the state of Virginia. Boston, MA.

 Spencer, Herbert. 1864-67. The principles of biologyvolumes 1 &2. London, U.K: Williams & Norgate.

 Galton, Francis.  1904. Eugenics: its definition, scope, and aims. The American Journal Of Sociology. 10(1).

 From “Race – The Power of an Illusion: Go Deeper: Race Timeline,” Retrieved March 9, 2006, from: http://www.pbs.org/race/000_About/002_04-background-02-12.htm

 Guterl, M. P. 1999. The new race consciousness: race, nation, and empire in American culture, 1910-1925. Journal of World History, Vol. 10.2, pp. 307-52.

 Marks, J. 2005. The realities of races. Social Science Research Council: http://raceandgenomics.ssrc.org/ (accessed October 4, 2005).

 From “Race – The Power of an Illusion.” Retrieved March 9, 2006, from: http://www.pbs.org/race/000_About/002_04-background-02-12.htm

 Yang, N.; H. Li; L. Criswell; P. Gregersen; M. Alarcon-Riquelme; R. Kittles; R. Shigeta; G. Silva; P. Patel; J. Belmont; and M. Seldin. 2005. Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine. Human Genetics. 10.1007/s00439-005-0012-1. Published online: September 29.

 Lewontin, R.C.  2005. The fallacy of racial medicine: confusions about human races. Social Science Research Council: http://raceandgenomics.ssrc.org/ (accessed October 4, 2005). 

 Jha, A. K.; E. S. Fisher; Z. Li; J Orav; and A. M. Epstein. 2005.  Racial trends in the use of major procedures among the elderly. New England Journal of Medicine. 353(7).

 Ashish K. Jha, interview by Terence Smith for National Public Radio, August 18, 2005. transcript, http://www.pbs.org/newshour/bb/health/july-dec05/unequal_8-18.html

 Polite, B. and O. Olopade. 2005. Breast cancer and race. Perspectives in Biology and Medicine. 48 (supplement): S166-S175.

 Newman, L., et. al. 2002. African American ethnicity, socioeconomic status, and breast cancer survival.  Cancer. 94: 2844-2854.

 Sprague Zones, J.  2005/2006. Struggling to Survive: African American Women and Breast Cancer. Breast Cancer Action Newletter. 89.

 Galst, L. 2001. Does breast cancer discriminate? MAMM. 4(1): 35-41.

 Shields, A.; M. Fortun; E. Hammonds; P. King; C. Lerman; R. Rapp; and P. Sullivan. 2005. The use of race variables in genetic studies of complex traits and the goal of reducing health disparities: a trans-disciplinary perspective. American Psychologist, 60(1): 77-103.

 Shriver, M.; E. Parra; S. Dios; C. Bonila; H. Norton; C. Jovel; et al. 2003. Skin pigmentation, bioeographical ancestry and admixture mapping. Human Genetics. 112: 87-399.

 Sankar, P. and J. Kahn. 2005. BiDil: race medicine or race marketing? Health Affairshttp://content.healthaffairs.org/cgi/content/full/hlthaff.w5.455/DC1 (Published:11 October 2005).

 Commercial pricing for Vasotec, Enalapril, and Captoten retrieved on March 9, 2006 from: http://www.destinationrx.com/prescriptions/refine.asp?BrandName=Vasotec;
http://www.qualitygenerics.com/enalapril.shtml;
http://www.lowcostgenericdrugs.com/index.php?p=drug&drugBrandId=510

 Exner D. V., et al. 2001. Lesser response to angiotensin-converting-enzyme inhibitor therapy in Black as compared with White patients with left ventricular dysfunction. New England Journal of Medicine. 344(18): 1351–1357

Goldstein, D. B. and S. K. Tate. 2004. Will tomorrow’s medicines work for everyone? Nature Genetics. 36(11): S34-S42.

 Duster, T.  2005. Race and reification in science. Science. 307(5712).

 http://www.ancestrybydna.com

 http://www.africanancestry.com

 http://www.familytreedna.com

 Kalb, C. 2006. In Our Blood. Newsweek. CXLVII(6): 47-55.

 Harmon, A. 2005. Blacks Pin Hope on DNA to Fill Slavery’s Gaps in Family Trees. New York Times, July 25, New York Edition.

 Shriver, M. and R. Kittles. 2004. Genetic ancestry and the search for personalized genetic histories. Nature. 5:  611- 618.

 Stevens, A. P. 2001. Arresting Crime: Expanding the scope of DNA databases in America. Texas Law Review. 24; Puri, A.M. 2001. An international DNA database: balancing hope, privacy, and scientific error. Boston College International and ComparativeLaw Review. 24.

Duster, T.  2004. Selective Arrests, an Ever-Expanding DNA Forensic Database, and the Specter of an Early-Twenty-First Century Equivalent of Phrenology. In DNA and the Criminal Justice System: The Technology of Justice. Lazer, D. (Ed.) Cambridge, MA: Massachusetts Institute of Technology. 315-334.

Ibid.

 
 
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