There is likely to be widespread agreement with much of the FDA’s rationale for approving BiDil (a combination of hydralazine hydrochloride and isosorbide dinitrate; H-I) as a treatment for heart failure. In particular, most would agree that the evidence of effectiveness provided by the African American Heart Failure Trial (A-HeFT) is compelling. Likewise, few health scientists would believe that it is either necessary or responsible to withhold therapies such as BiDil from those who might benefit until there is a full understanding of how they work. And although there is substantial concern that biomedical differences between racial groups are routinely misinterpreted as evidence of innate genetic differences (hence Jonathan Kahn’s call for all such claims to be supported by genetic evidence), most would concede that using race as a “descriptive” variable can help identify differences in health and access/response to treatment that might warrant further investigation or intervention.

The goal of this paper is to present a succinct overview, from a clinician’s perspective, of the importance and implications of research on heart failure in African Americans. It first gives a brief outline of the rationale and results of the African-American Heart Failure Trial (A-HeFT), which showed evidence for the effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine (ISDN/Hyd), marketed as BiDil (NitroMed Inc.), in this population. Finally, it underscores the necessity of treating African Americans with evidence-based medicine given that humanistic physicians and other clinicians strive to provide holistic treatment to their patients.

Most researchers and clinicians recognize the difficulty with utilizing race as a category for inclusion in trials. While race lacks any true biologic definition, it is potentially beneficial as a consideration in clinical studies, based on prior evidence of certain potential differences across self-identified racial/ethnic groups in morbidity and mortality and responses to medicine. Even though use of race as a classification is a problematic distinction, it should not be ignored. If clinical trials demonstrate significant improvement with targeted treatment in African Americans, clinicians should not withhold life-saving drugs that result from such studies.

In a recent discussion about how scientific knowledge might potentially change our understanding of the nature and extent of human genetic, cultural, or biological variation, the sociologist David Skinner identified two competing visions of the future: one that was decidedly dystopian, which conjured up a “re-racialized” future, and an opposing utopian future in which the potential for racialized thinking might be finally overcome. We can situate the ongoing debates about the congestive heart failure drug BiDil, approved by the Food and Drug Administration (FDA) for use only by African Americans, in relation to these differing future prospects.

When the FDA announced its approval of BiDil in June 2005, it located the drug, and perhaps the future of pharmaceutical development, within a particular vision of the future, heralding BiDil as “representing a step toward the promise of personalized medicine.” The discourse of “personalized medicine” can be characterized as part of a utopian future, one in which clinicians will be able to make increasingly individualized decisions based on each patient’s genetic makeup so that the drugs they take will be those that work best for them.

In 2000, researchers from the Human Genome Project (HGP) proclaimed that the initial sequencing of the human genome definitively proved, among other things, that there was no genetic basis for race. The genetic fact that most humans were 99.9% the same at the level of their DNA was widely heralded and circulated in the English-speaking press, especially in the United States. This pronouncement seemed proof that long-term antiracist efforts to de-biologize race were legitimized by scientific findings. Yet, despite the seemingly widespread acceptance of the social construction of race, post-HGP genetic science has seen a substantial shift toward the use of race variables in genetic research and, according to a number of prominent scholars, is re-invoking the specter of earlier forms of racial science in some rather discomfiting ways. During the past seven years, the main thrust of human genetic research, especially in the realm of biomedicine, has shifted from a concern with the 99.9% of the shared genome — what is thought to make humans alike — towards an explicit focus on the 0.1% that constitutes human genetic variation. Here I briefly explore some of the potential implications of the conceptualization and practice of early 21st century genetic variation research, especially as it relates to questions of race.

The presence of the Tuskegee Syphilis Study was palpable at the June 16, 2005, Food and Drug Administration’s (FDA) Advisory Committee meeting on BiDil, a heart medication from the pharmaceutical company NitroMed that sought approval as the first race-specific drug. So ubiquitous is the restless and unsettled spirit of Tuskegee that it continues to hover over the African American public and the biomedical research/health care provider communities more than three and a half decades after the actual study “died.” No one invoked the word “Tuskegee” in that dimly lit meeting room as BiDil gained the Advisory Committee’s approval. Yet its power was exerted even when it was not named. The FDA Committee’s chairman, Cleveland Clinic cardiology chief Steven Nissen, acknowledged this after the committee met: “We were putting [Tuskegee]…to rest.”

The popular press plays an important role in science communication, both reflecting and shaping public attitudes about particular issues and technologies. It is a key source of health information and can help to frame public debates about science and health care controversies. Given this powerful role, there has long been a concern that media representations of genetics are overly simplistic and inappropriately deterministic in tone. If true, media representations may hurt collective deliberations about science issues and misinform the public regarding the relevance of genetics in a variety of contexts — including the relevance of genetics and biology to the existing social categories of “race.”

Race is becoming an increasingly common lens through which biomedical researchers are studying the relevance of genes to group predispositions that may affect disease susceptibility and drug response. These investigations contravene decades of research in the natural and social sciences demonstrating that social categories of race have little genetic significance. Nevertheless, a resounding debate has ensued over the utility of race in biomedical research — particularly as new drugs claiming to serve particular racial populations enter the marketplace. Now that the Food and Drug Administration (FDA) has approved BiDil as the first race-specific treatment despite conflicting evidence and unsettled debates, is there a way for federal regulators to promote research that may address minority health concerns without giving undue credence to the dangerous idea that social understandings of race are genetically relevant? It may be useful for the FDA to turn to an area with experience negotiating such dilemmas — constitutional law — and its approach — strict scrutiny — to help guide when and under which circumstances government should give effect to racial categories in biomedicine.

Reflecting on the tension of which he was aware between the imperial West and the still-mysterious East, Victorian writer Rudyard Kipling (1865-1936) penned the above phrase to express the incommensurable situation wherein the Westerner never understands the Asian, as the latter’s culture differs too greatly from his own. However, aware that East and West nevertheless cannot remain separated forever, the author ends the poem with an eventual encounter between the two.

Over 100 years have passed since this poem was written, yet the ambivalent encounter between East and West that it depicts still exists and is currently playing out within the field of pharmaceuticals. On one side of the divide are the many people in the industry who want to standardize global acceptance of drugs; on the other are the local authorities who want to maintain the overruling legal need not to compromise on health care at a national level. In this sense, the divergence and unity that Kipling captures is what this paper aims to discuss as it addresses how race is debated at the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

The BiDil controversy in America coincides with a renewed interest in the linkages between race and therapeutics, whether in the medical history of the United States itself, or in the colonial world. During the colonial era in South Asia, many anthropological and medical researchers conducted research which compared the European and “colonial” body, contrasting everything from blood composition to brain weight between the races of the Indian Empire. This, as Mark Harrison has shown, was fundamentally a phenomenon of the 19th century, arguing that “[i]t was only after 1800 that racial identities came to be fixed and that India was viewed with terror, as a reservoir of filth and disease.” Racist attitudes in British Indian colonial medicine are not hard to discover. They underpinned, for instance, campaigns to improve the appallingly high maternal and infant mortality rates in which the blame was placed squarely upon the women and the indigenous midwives who delivered them rather than the poverty in which they lived. As such, Peers Dimmock, a professor of gynecology and obstetrics at the Calcutta Medical School, opened his address to the First Indian Medical Congress in 1894 with a diatribe against “the unclean and repulsive traditionary [sic] methods of the native midwives.”

During World War II, scientists funded by the United States government conducted mustard gas experiments on 60,000 American soldiers as part of military preparation for potential chemical warfare. One aspect of the chemical warfare research program on mustard gas involved race-based human experimentation. In at least nine research projects conducted during the 1940s, scientists investigated how so-called racial differences affected the impact of mustard gas exposure on the bodies of soldiers. Building on cultural beliefs about “race,” these studies occurred on military bases and universities, which became places for racialized human experimentation.

The BiDil affair brought once again to the fore questions of race and medicine. As discussed in other essays in this collection, the emergence of BiDil as the first medication approved and marketed for treating specific racial groups raises important questions for medicine and society: How are race and ethnicity framing our understanding of health and illness? Should treatment decisions be based on the race and ethnicity of patients? Should we encourage the development of race-specific medical treatments in order to reduce health disparities? Or is this approach dangerous, and can it lead to unwanted consequences including racial stigmatization? These questions are not new, and since the introduction of race as a scientific construct in the late-19th century, race has played an important part in the history of medicine, most notoriously during World War II and the Holocaust. Yet the identification of race medicine with Nazi science tends to obscure the vast use of race as a medical construct by a wide range of medical scientists and practitioners across the political spectrum. In many instances, racial minorities were preoccupied with race medicine in order to promote the health of their own communities. One such group was that of Jewish physicians.

If we want to understand the allure of pharmaceuticals, we need to look beyond both medical efficacy and profit motives. The success (or failure) of a drug depends not only on these, but also on how it mobilizes prior conceptions of identity. The extent to which a drug is taken — or talked about — is related to commodity properties that exceed the physiological and the economic. In implicit contrast to the discussions of BiDil elsewhere in this collection, I explore how the links between race and pharmaceuticals can be both unstable and generative even when the drug in question is old and generic. By attending closely to an encounter around generic thiazide outside of a medical or marketing context, I show that although pharmaceuticals can seem to rely on scientific data and marketing for their power, they are, in fact, also subject to claims on many more registers that cannot quite subsume or refute each other.

Public discourse on race-specific medicine typically erects a wall between the scientific use of race as a biological category and the ideological battle over race as a social identity. Scientists often address the potential for these therapeutics to reinforce a damaging understanding of “race” with precautions for using them rather than questioning their very development. For example, Esteban Gonzalez Burchard, an associate professor of medicine and biopharmaceutical sciences at the University of California, San Francisco, states, “We do see racial differences between populations and shouldn’t just close our eyes. Unfortunately, race is a politically charged topic, and there will be evildoers. But the fear should not outweigh the benefit of looking.” Although it is recognized that ideology influences the social meaning of race, it is usually assumed that there is a separate, prior scientific understanding of race that is not contaminated by politics.

There are two critical steps in determining whether a medical experiment involving human subjects can be conducted in an ethical manner: assessing risks and potential benefits and obtaining potential subjects’ informed consent. Although an extensive literature on both of these aspects exists, virtually nothing has been written about human experimentation for which the objective is not to prevent, cure, or mitigate a disease or condition, but to enhance human capabilities. One exception is a 2004 article by Rebecca Dresser on preimplantation genetic modification — one of the most controversial enhancement technologies — in which she states, “Under existing research ethics principles, it would be unethical for investigators to perform modifications exposing embryos expected to develop into healthy children to significant risk in exchange for a possible physical or mental enhancement.” But Dresser does not explain why such an experiment would be unethical under existing principles, and her conclusion is not self-evident.

Research drawn from data contained in medical records is a common and immensely important means of scientific investigation in epidemiology and health services research. It provides valuable knowledge regarding risk factors for disease, the safety of pharmaceuticals and medical procedures, and the quality of medical care. Electronic information technology has greatly enhanced the capability of conducting research using medical records, but it has also generated increasing concern about invasions of privacy. Both practical and scientific considerations militate against soliciting consent for population-based observational research. Retrospective review of existing medical records, especially with large samples, poses insuperable barriers to locating human subjects in order to obtain their informed consent. When efforts are made to obtain informed consent for prospective research drawn from disease and treatment registries, mounting evidence has accumulated that substantial selection biases are introduced into the data, as those who consent are not necessarily representative of the population of relevant patients.

Many activities concerning the unknown involve the potential for risk, and clinical research is no exception. Some research participants experience correlative benefit; others do not. When the participants are adults, as in Phase I trials with healthy volunteers, we rely on a highly individualistic decision-making process based on autonomous choice. This assumes that the ability to make voluntary, competent, informed choices, evaluating the risks and benefits from a personal perspective, offers the best protection for research participants. Rightly or wrongly, we depend heavily on informed consent for protection. We have further refined our post-Nuremberg ethical principles by requiring that safety and toxicity of drugs and devices be first assessed on the least vulnerable. In addition, we assume Institutional Review Boards (IRBs) will screen out protocols involving an inappropriate level of risk.

Twenty-four U.S. states have enacted HIV exposure laws that prohibit HIV-positive persons from engaging in sexual activities with partners to whom they have not disclosed their HIV-status. From a public health perspective, HIV serostatus exposure laws can be viewed as structural interventions that seek to limit the spread of HIV by acting at the policy level. A central premise of these laws is that informed partners are more likely to protect themselves by declining sex, by substituting less risky activities for higher-risk ones, or by using condoms, than are uninformed partners. However, the effectiveness of these laws at preventing HIV transmission is not known.

There is little standardization among existing HIV exposure laws, which vary substantially with respect to the sexual activities that are prohibited without prior serostatus disclosure. Among the strictest laws are those in Arkansas, Michigan, New Jersey, and Ohio which mandate disclosure prior to almost any type of sexual contact.