Mixed Race Studies

In the past, the belief that human races had substantial and clearly delimited biological differences contributed to justify discrimination and was used to oppress and foment injustices, even within the medical context. The concept of race is still loaded with ideology and carries within it relationships of power and domination. It is similar to a banana peel: empty, slippery and dangerous.

S. D. J. Pena, “The fallacy of racial pharmacogenomics,” Brazilian Journal of Medical and Biological Research, Volume 44, Number 4 (April 2011): 272.

The fallacy of racial pharmacogenomics

Brazilian Journal of Medical and Biological Research
Volume 44, Number 4 (April 2011)
pages 268-275
DOI: 10.1590/S0100-879X2011007500031

S. D. J. Pena
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais
Belo Horizonte, MG, Brasil
GENE – Núcleo de Genética Médica, Belo Horizonte, MG, Brasil

Personalized pharmacogenomics aims to use individual genotypes to direct medical treatment. Unfortunately, the loci relevant for the pharmacokinetics and especially the pharmacodynamics of most drugs are still unknown. Moreover, we still do not understand the role that individual genotypes play in modulating the pathogenesis, the clinical course and the susceptibility to drugs of human diseases which, although appearing homogeneous on the surface, may vary from patient to patient. To try to deal with this situation, it has been proposed to use interpopulational variability as a reference for drug development and prescription, leading to the development of “race-targeted drugs”. Given the present limitations of genomic knowledge and of the tools needed to fully implement it today, some investigators have proposed to use racial criteria as a palliative measure until personalized pharmacogenomics is fully developed. This was the rationale for the FDA approval of BiDil for treatment of heart failure in African Americans. I will evaluate the efficacy and safety of racial pharmacogenomics here and conclude that it fails on both counts. Next I shall review the perspectives and the predicted rate of development of clinical genomic studies. The conclusion is that “next-generation” genomic sequencing is advancing at a tremendous rate and that true personalized pharmacogenomics, based on individual genotyping, should soon become a clinical reality.

Introduction

The American astrophysicist Neil deGrasse Tyson defined the “perimeter of ignorance” as the boundary where scientists face a choice: continue the quest for knowledge or invoke a deity or other supernatural forces. He used as an example no less than Isaac Newton himself, whose law of gravity enabled calculation of the force of attraction between any two objects. When computing the orbits of the planets around the sun, Newton feared that the mutual attraction between them would render the solar system unstable. He then concluded that God occasionally stepped in to make things right. A century later, the French astronomer Pierre-Simon de Laplace created a new mathematical tool called perturbation theory and used it to demonstrate that the solar system is in fact stable over periods of time much longer than Newton could predict. Laplacian science, therefore, no longer needed to postulate the interference of supernatural forces to explain astronomical facts.

Newton’s appeal to God, however unnecessary, may at first sight appear as a humble attitude of a great man. However, Tyson demonstrates that, on the contrary, it represented presumptuousness on his part: if his mathematics was not good enough to explain the phenomenon, then the problem was too complicated for any other human mind to figure out, then or anytime in the future. By “embracing ignorance” Newton’s attitude negatively infused a temporary stage of incomplete knowledge with a false permanency, running counter to the philosophy of open-mindedness and discovery that characterizes Science.

Pharmacogenetics and pharmacogenomics are likewise in a dilemma right at the edge of the perimeter of ignorance…

…To try to deal with this situation it has been proposed to use interpopulational variability as a reference for drug development and prescription, leading to the development of “race-targeted drugs”, as exemplified by the case of BiDil for treatment of heart failure in African Americans. The rationale for such strategy is that, since we still lack the pharmacogenomic knowledge necessary to implement true personalized treatment, we make do by using the race or the ethnic-geographic affiliation of a given patient as the replacement of the germane individual genotyping at critical loci.

Therein lies the fallacy of racial pharmacogenomics – being predicated on the idea that individual genotyping will be impossible to achieve in the near future, it “embraces ignorance”. Moreover, it often does so under false premises. For instance, in the FDA news release entitled “FDA Approves BiDil Heart Failure Drug for Black Patients” it is stated that this represents “a step toward the promise of personalized medicine”. But racial medicine is group medicine – most definitely it is not personalized medicine…

…I propose that, rather than thinking about populations, ethnicities or races, we should focus on the unique genome of a particular individual, which is structured as a mosaic of polymorphic haplotypes with diverse genealogical histories. This shifts the emphasis from populations to persons. We should strive to see each individual as having a singular genome and a unique life history, rather than try to impose on him/her characteristics of a group or population. Under this model, ideas such as that of human races or “race-targeted drugs” become meaningless and vanish like smoke.

The safety of racial pharmacogenomics

The adoption of racial pharmacogenomics by the FDA has serious implications that extend much beyond the restricted limits of the medical arena. Thus, it has to be evaluated not only scientifically, but also within a historical, sociological and philosophical context.

In the past, the belief that human races had substantial and clearly delimited biological differences contributed to justify discrimination and was used to oppress and foment injustices, even within the medical context. The concept of race is still loaded with ideology and carries within it relationships of power and domination. It is similar to a banana peel: empty, slippery and dangerous.

Thus, our final conclusion is that racial pharmaco-genomics fails on grounds of insufficient benefit/cost ratio: it has much to recommend against it and very little scientific justification in its favor.

To use racial pharmacogenomics as a palliative measure is tantamount to “embracing ignorance”. It erroneously confers persistence and credence to the idea that human races do exist. As pointed out by the sociologist Paul Gilroy, such persistence is toxic, contaminating and weakens all society…

Read the entire article here.

DNA tests probe the genomic ancestry of Brazilians

Brazilian Journal of Medical and Biological Research
Volume 42, Number 10 (October 2009)
pages 870-876
DOI: 10.1590/S0100-879X2009005000026

S .D. J. Pena
GENE, Núcleo de Genética Médica, Belo Horizonte, MG, Brasil
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil

L. Bastos-Rodrigues
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil

J. R. Pimenta
GENE, Núcleo de Genética Médica, Belo Horizonte, MG, Brasil

S. P. Bydlowski
Laboratório de Genética e Hematologia Molecular (LIM-31), Faculdade de Medicina, Universidade de São Paulo, Hospital das Clínicas, São Paulo, SP, Brasil

We review studies from our laboratories using different molecular tools to characterize the ancestry of Brazilians in reference to their Amerindian, European and African roots. Initially we used uniparental DNA markers to investigate the contribution of distinct Y chromosome and mitochondrial DNA lineages to present-day populations. High levels of genetic admixture and strong directional mating between European males and Amerindian and African females were unraveled. We next analyzed different types of biparental autosomal polymorphisms. Especially useful was a set of 40 insertion-deletion polymorphisms (indels) that when studied worldwide proved exquisitely sensitive in discriminating between Amerindians, Europeans and Sub-Saharan Africans. When applied to the study of Brazilians these markers confirmed extensive genomic admixture, but also demonstrated a strong imprint of the massive European immigration wave in the 19th and 20th centuries. The high individual ancestral variability observed suggests that each Brazilian has a singular proportion of Amerindian, European and African ancestries in his mosaic genome. In Brazil, one cannot predict the color of persons from their genomic ancestry nor the opposite. Brazilians should be assessed on a personal basis, as 190 million human beings, and not as members of color groups.

Introduction

Brazilians are one of the most heterogeneous populations in the world, the result of five centuries of interethnic crosses between peoples from three continents: Amerindians, Europeans and Africans. Little is known about the number of indigenous people living in the area of what is now Brazil when the Portuguese arrived in 1500 (1), although a figure often cited is that of 2.5 million individuals. The Portuguese-Amerindian admixture started soon after the arrival of the first colonizers and later became commonplace, being even encouraged after 1755 as a strategy for population growth and colonial occupation of the country….

From the middle of the 16th century, Africans were brought to Brazil to work on sugarcane farms and, later, in the gold and diamond mines and on coffee plantations. Historical records suggest that between circa 1550 and 1850 (when the slave trade was abolished), around four million Africans arrived in Brazil (2)…

Uniparental genetic markers in Brazilians

…To learn about the maternal counterpart, we analyzed mtDNA, which revealed a different reality. Considering Brazil as a whole, 33, 39, and 28% of matrilineages were of Amerindian, European and African origin, respectively (9,12). As expected, the frequency of different regions reflected their genealogical histories: most matrilineal lineages in the Amazon region were of Amerindian origin, while African ancestrality was preponderant in the Northeast (44%) and European haplogroups were prevalent in the South (66%). These data have since been amply confirmed by numerous other studies. For instance, we recently analyzed the mtDNA haplogroup structure of 242 self-identified white individuals from São Paulo and ascertained 24% Amerindian, 22% African and 54% European matrilineal proportions (Dornelas HG, Bydlowski SP, Pena SDJ, unpublished data).

Next, for further confirmation, we studied mtDNA lineages in 120 black individuals from the city of São Paulo. The results, as expected, showed a mirror image of those previously found in white Brazilians: on the one hand, 85% of the lineages originated in Sub-Saharan Africa, 12% were from Amerindians and only 3% were from Europe; on the other, only 48% of the Y chromosome lineages originated from Sub-Saharan Africa (the vast majority belonging to haplogroups E3a7 and E3a*). Studies on black individuals from the cities of Rio de Janeiro and Porto Alegre produced very similar results.

Taken together, these numbers disclose a picture of very strong directional mating between European males and Amerindian and African females, which agrees perfectly with the known history of the peopling of Brazil since 1500. These studies also reveal that the genomes of most Brazilians are mosaic, having mtDNA and NRY of different phylogeographical origins.

Biparental genetic markers and ancestry in Brazilians

In Brazil, notwithstanding relatively large levels of genetic admixture and a myth of “racial democracy”, there exists widespread social prejudice that seems to be particularly connected to the physical appearance of an individual. Color (in Portuguese, cor) denotes the Brazilian equivalent of the English term race (raça) and is based on a complex phenotypic evaluation that takes into account, besides skin pigmentation, also hair type, nose shape and lip shape. The reason why the word color is preferred to race in Brazil is probably because it captures the continuous aspects of phenotypes. In contrast with the situation in the United States, there appears to be no racial descent rule operational in Brazil and it is possible for two siblings differing in color to belong to completely diverse racial categories.

Based on the criteria of self-classification of the 2000 census of the Instituto Brasileiro de Geografia e Estatística (IBGE), the Brazilian population was then composed of 53.4% Whites, 6.1% Blacks and 38.9% Brown (“pardos” in Portuguese). How do these numbers correlate with genomic ancestry?..

Read the entire article here.