[Paleopsych] SW: Race vs. Genes as Risk Factors in Health

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Public Health: Race vs. Genes as Risk Factors in Health
http://scienceweek.com/2005/sw051007-4.htm

    The following points are made by Mike Bamshad (J. Am. Med. Assoc. 2005
    294:937):
    1) An important goal of 21st-century medicine is to predict an
    individual's medical future -- that is, to identify the set of risk
    factors for disease and predictors of treatment response that
    influence a person's health, with the goal of more effectively
    treating and preventing disease. Throughout much of the world, race --
    using its historical meaning as a descriptor of Africans, Asians,
    Europeans, Native Americans, and Pacific Islanders -- is often
    considered one key determinant of health.[1,2]
    2) Race might influence an individual's health in several ways. It
    might covary with different environmental or genetic factors that
    underlie risk, different interactions between genetic and
    environmental factors, or different combinations thereof. Many
    environmental factors that influence health are known, but most of the
    genetic factors, much less interactions between the two, remain to be
    discovered. Nevertheless, there is widespread speculation that genetic
    factors influencing health differ among racial groups because many
    health-related traits vary among racial groups.[3] This speculation
    has revived a long-standing debate in medical and scientific
    communities about the validity and necessity of using race to make
    inferences about an individual's genetic ancestry, some scientists
    embracing this idea and others dismissing it.[4,5]
    3) In this debate, one issue that is commonly confused is the
    difference between race and ancestry. Ancestry refers to objective
    genetic relationships between individuals and among populations,
    whereas race has always been a somewhat arbitrary definition of
    population boundaries. For example, while an individual might have
    ancestors from Europe, Africa, and North America, he or she still
    might be categorized as an African American. Therefore, race captures
    some biological information about ancestry, but it is not equivalent
    to ancestry.
    4) Yet clinicians often want to know whether it is valid and reliable
    to use race as a proxy to infer an individual's genetic risk for
    disease and treatment response. Whether race matters is, however,
    complicated because it depends on the relationship between the genetic
    risk factor, ancestry, and race. For example, beta-blockers and
    angiotensin-converting enzyme (ACE) inhibitors for hypertension
    treatment may not work as well, on average, in African Americans
    compared with European Americans, but both types of drugs appear to
    work perfectly well in a large fraction of African Americans and
    poorly in some European Americans.
    5) The observation might be explained by a hypothetical genetic
    predictor of positive response to ACE inhibitors that is common in
    European Americans but that is also present in some African Americans
    because of admixture and absent in some European Americans. In such a
    case, the best predictor of treatment response might be the presence
    of the variant (ie, direct testing); the next best might be an
    accurate estimator of genetic ancestry, and race might be only a poor
    predictor of genetic risk and therefore treatment response.
    References (abridged):
    1. Osborne NG, Feit MD. The use of race in medical research. JAMA.
    1992;267:275-279.
    2. Oppenheimer G. Paradigm lost: race, ethnicity, and the search for a
    new population taxonomy. Am J Public Health. 2001;91:1049-1055.
    3. Institute of Medicine. Unequal Treatment: Confronting Racial and
    Ethnic Disparities in Health Care. Washington, DC: National Academies
    Press; 2003
    4. Risch N, Burchard E, Ziv E, Tang H. Categorization of humans in
    biomedical research: genes, race, and disease. Genome Biol.
    2002;3:1-12
    5. Burchard EG, Ziv E, Coyle N, et al. The importance of race and
    ethnic background in biomedical research and clinical practice. N Engl
    J Med. 2003;348:1170-1175
    J. Am. Med. Assoc. http://www.jama.com
    --------------------------------
    Related Material:
    ANTHROPOLOGY: ON HUMANS AND RACE
    The following points are made by D.A. Hughes et al (Current Biology
    2004 14:R367):
    1) Systematists have not defined a "type specimen" for humans, in
    contrast to other species. Recent attempts to provide a definition for
    our species, so-called "anatomically modern humans", have suffered
    from the embarrassment that exceptions to such definitions inevitably
    arise -- so are these exceptional people then not "human"? Anyway, in
    comparison with our closest-living relatives, chimpanzees, and in
    light of the fossil record, the following trends have been discerned
    in the evolution of modern humans: increase in brain size; decrease in
    skeletal robusticity; decrease in size of dentition; a shift to
    bipedal locomotion; a longer period of childhood growth and
    dependency; increase in lifespan; and increase in reliance on culture
    and technology.
    2) The traditional classification of humans as Homo sapiens, with our
    very own separate family (Hominidae) goes back to Carolus Linnaeus
    (1707-1778). Recently, the controversial suggestion has been made of
    lumping humans and chimpanzees together into at least the same family,
    if not the same genus, based on the fact that they are 98-99%
    identical at the nucleotide sequence level. DNA sequence similarity is
    not the only basis for classification, however: it has also been
    proposed that, in a classification based on cognitive/mental
    abilities, humans would merit their own separate kingdom, the
    Psychozoa (which does have a nice ring to it).
    3) As for sub-categories, or "races", of humans, in his Systema
    Naturae of 1758 Linnaeus recognized four principal geographic
    varieties or subspecies of humans: Americanus, Europaeus, Asiaticus,
    and Afer (Africans). He defined two other categories: Monstrosus,
    mostly hairy men with tails and other fanciful creatures, but also
    including some existing groups such as Patagonians; and Ferus, or
    "wild boys", thought to be raised by animals, but actually retarded or
    mentally ill children that had been abandoned by their parents. In his
    scheme of 1795, Johann Blumenbach (1752-1840) added a fifth category,
    Malay, including Polynesians, Melanesians and Australians.
    4) Blumenbach is also responsible for using the term "Caucasian" to
    refer in general to Europeans, which he chose on the basis of physical
    appearance. He thought Europeans had the greatest physical beauty of
    all humans -- not surprising, as he was of course European himself --
    and amongst Europeans he thought those from around Mount Caucasus the
    most beautiful. Hence, he named the "most beautiful race" of people
    after their supposedly most beautiful variety -- a good reason to
    avoid using the term "Caucasian" to refer to people of generic
    European origin (another is to avoid confusion with the specific
    meaning of "Caucasian", namely people from the Caucasus).
    5) The extent to which racial classifications of humans reflect any
    underlying biological reality is highly controversial; proponents of
    racial classification schemes have been unable to agree on the number
    of races (proposals range from 3 to more than 100), let alone how
    specific populations should be classified, which would seem to greatly
    undermine the utility of any such racial classification. Moreover, the
    apparent goal of investigating human biological diversity is to ask
    how such diversity is patterned and how it came to be the way that it
    is, rather than how to classify populations into discrete
    "races".(1-4)
    References:
    1. Nature Encyclopedia of the Human Genome. (2003). Cooper, D. ed.
    (Nature Publishing Group),
    2. Fowler, C.W. and Hobbs, L. (2003). Is humanity sustainable?. Proc.
    R. Soc. Lond. B. Biol. Sci. 270, 2579-2583
    3. Encyclopedia of Human Evolution and Prehistory. (1988). Tattersall,
    I., Delson, E., and Van Couvering, J. eds. (Garland Publishing)
    4. World Health Organization Website http://www.who.int
    Current Biology http://www.current-biology.com
    --------------------------------
    Related Material:
    PUBLIC HEALTH: ON RACE-BASED THERAPEUTICS
    The following points are made by M. Gregg Bloche (New Engl. J. Med.
    2004 351:2035):
    1) Are we moving into a new era of race-based therapeutics? The recent
    publication of the African-American Heart Failure Trial (A-HeFT), a
    clinical trial of a medication intended for a single racial group,
    poses this awkward question. The study's most striking finding -- that
    the addition of isosorbide dinitrate and hydralazine to conventional
    therapy for heart failure reduced relative one-year mortality by 43
    percent among blacks -- has provoked wide discussion. The trial's
    sponsor, NitroMed, which holds a patent on the fixed-dose combination
    of isosorbide dinitrate and hydralazine that was used, posits that
    heart failure has a different pathophysiology in blacks than in
    whites, necessitating different treatment strategies.(1)
    2) The reported 43 percent relative decrease in the rate of death due
    to heart failure among blacks is cause for celebration. There is wide
    agreement that blacks die from heart failure at rates disproportionate
    to those among whites. But to assess A-HeFT's larger implications for
    the role of race in therapeutic design, it is important to be clear
    about what the study has not shown.
    3) First, A-HeFT has not established that adding isosorbide dinitrate
    and hydralazine to conventional therapy for heart failure yields
    greater benefits for blacks than for other racial or ethnic groups.
    The study, which enrolled only self-identified blacks, did not test
    this hypothesis. The clinical and economic logic behind A-HeFT's
    design has its roots in previous, multiracial studies that compared
    isosorbide dinitrate and hydralazine with other investigational drugs,
    administered in combination with different conventional therapies.
    These therapies were standard in their day but are inferior to the
    conventional therapy used today, which typically includes an
    angiotensin-converting-enzyme (ACE) inhibitor. Indeed, one of these
    previous studies helped to establish ACE inhibitors as standard
    treatment. This trial compared isosorbide dinitrate and hydralazine
    with the ACE inhibitor enalapril and demonstrated that enalapril
    resulted in a greater overall reduction in mortality.(2)
    4) An ill-defined subgroup of patients, though, did well when treated
    with isosorbide dinitrate and hydralazine and fared poorly with
    enalapril. Seizing on this opportunity, a biotechnology firm obtained
    intellectual-property rights to a fixed-dose combination of isosorbide
    dinitrate and hydralazine and sought approval from the Food and Drug
    Administration (FDA) in 1996 to market this formulation as a new drug.
    The FDA declined, citing statistical uncertainties in the trial
    data.(1) That is when race entered the picture. A group of
    investigators (including the holder of the patent on the combination
    treatment) reanalyzed the previous clinical-trial data according to
    race and concluded in 1999 that the combination treatment did as well
    as enalapril at prolonging the lives of black patients with heart
    failure.(3) Other work suggested that ACE inhibitors were less
    effective in blacks than in whites.
    5) At this point, it might have made clinical and scientific sense to
    add isosorbide dinitrate and hydralazine to conventional therapy
    (which by now typically included an ACE inhibitor) and to compare this
    combination to conventional therapy alone -- for all patients with
    heart failure, regardless of race. Such a trial had not been
    performed, since the standard therapies used in earlier trials did not
    include ACE inhibitors. But race consciousness offered a faster way
    through the FDA's regulatory maze. In 1999, NitroMed obtained
    intellectual-property rights to fixed-dose isosorbide dinitrate and
    hydralazine and said it would seek FDA approval to market the
    formulation as a therapy for heart failure in blacks. Two years later,
    the FDA indicated to NitroMed that successful completion of a clinical
    trial in black patients with heart failure would probably result in
    approval.(1) This commitment gave rise to A-HeFT, and the publication
    of this trial's results virtually ensures FDA approval.
    6) We need not shy away from the potential benefits of race-conscious
    therapeutics, but we should manage its downside risks. Greater
    awareness among physicians and the public that race is at best a
    placeholder for other predispositions, and not a biologic verity,
    would be a first step. Beyond such awareness, companies -- such as
    NitroMed -- that stand to gain from taking account of race could
    commit a substantial portion of their profits to research on genetic,
    psychosocial, and other mechanisms that might underlie racial gaps in
    clinical response.(3-5)
    References (abridged):
    1. Kahn J. How a drug becomes "ethnic": law, commerce, and the
    production of racial categories in medicine. Yale J Health Policy Law
    Ethics 2004;4:1-46
    2. Cohn JN, Archibald DG, Ziesche S, et al. A comparison of enalapril
    with hydralazine-isosorbide dinitrate in the treatment of chronic
    congestive heart failure. N Engl J Med 1991;325:303-310
    3. Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in
    response to therapy for heart failure: analysis of the
    vasodilator-heart failure trials. J Card Fail 1999;5:178-187
    4. Lifton RJ. The Nazi doctors: medical killing and the psychology of
    genocide. New York: Basic Books, 1986
    5. Cacioppo JT, Hawkley LC. Social isolation and health, with an
    emphasis on underlying mechanisms. Perspect Biol Med
    2003;46:Suppl:S39-S52
    New Engl. J. Med. http://www.nejm.org