Mixed Race Studies

Human Variation: A Genetic Perspective on Diversity, Race, and Medicine

Cold Spring Harbor Laboratory Press
2014
131 pages
(21 4C, 5B&W), index
Hardcover ISBN: 978-1-621820-90-1
Paperback ISBN: 978-1-936113-25-5

Edited by:

Aravinda Chakravarti, Professor of Medicine, Pediatrics, Molecular Biology & Genetics, and, Biostatistics
Johns Hopkins University School of Medicine, Institute of Genetic Medicine

Since the appearance of modern humans in Africa around 200,000 years ago, we have migrated around the globe and accumulated genetic variations that affect various traits, including our appearance, skin color, food tolerance, and susceptibility to different diseases. Large-scale DNA sequencing is now allowing us to map the patterns of human genetic variation more accurately than ever before, trace our ancestries, and develop personalized therapies for particular diseases. It is also reinforcing the idea that human populations are far from homogeneous, are highly intermixed, and do not fall into distinct races or castes that can be defined genetically.

This book provides a state-of-the-art view of human genetic variation and what we can infer from it, surveying the genetic diversity seen in Africa, Europe, the Americas, and India. The contributors discuss what this can tell us about human history and how it can be used to improve human health. They also caution against assumptions that differences between individuals always stem from our DNA, stressing the importance of nongenetic forces and pointing out the limits of our knowledge. The book is thus essential reading for all human geneticists and anyone interested in how we differ and what this means.

Contents

• Preface
• Perspectives on Human Variation through the Lens of Diversity and Race / Aravinda Chakravarti
• What Type of Person Are You? Old-Fashioned Thinking Even in Modern Science / Kenneth M. Weiss and Brian W. Lambert
• Social Diversity in Humans: Implications and Hidden Consequences for Biological Research / Troy Duster
• Demographic Events and Evolutionary Forces Shaping European Genetic Diversity / Krishna R. Veeramah and John Novembre
• Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease / Felicia Gomez, Jibril Hirbo and Sarah A. Tishkoff
• A Genomic View of Peopling and Population Structure of India / Partha P. Majumder and Analahba Basu
• How Genes Have Illuminated the History of Early Americans and Latino Americans / Andres Ruiz-Linares
• Can Genetics Help Us Understand Indian Social History? / Romila Thapar
• Race in Biological and Biomedical Research / Richard S. Cooper
• Personalized Medicine and Human Genetic Diversity / Yi-Fan Lu, David B. Goldstein, Misha Angrist, and Gianpiero Cavalleri
• Index

Do Races Differ? Not Really, Genes Show

The New York Times
2000-08-22

Natalie Angier, Science Columnist

In these glossy, lightweight days of an election year, it seems, they can’t build metaphorical tents big or fast enough for every politician who wants to pitch one up and invite the multicultural folds to ”Come on under!” The feel-good message that both parties seek to convey is: regardless of race or creed, we really ARE all kin beneath the skin.

Yet whatever the calculated quality of this new politics of inclusion, its sentiment accords firmly with scientists’ growing knowledge of the profound genetic fraternity that binds together human beings of the most seemingly disparate origins.

Scientists have long suspected that the racial categories recognized by society are not reflected on the genetic level. But the more closely that researchers examine the human genome — the complement of genetic material encased in the heart of almost every cell of the body — the more most of them are convinced that the standard labels used to distinguish people by ”race” have little or no biological meaning.

They say that while it may seem easy to tell at a glance whether a person is Caucasian, African or Asian, the ease dissolves when one probes beneath surface characteristics and scans the genome for DNA hallmarks of “race.”…

Read the entire article here.

Genetic analysis strongly suggests that early humans first arose in Africa and emerged out of Africa only ~100,000 years ago, a fairly recent development, evolutionarily speaking, which explains why we are all closely related. Any classification of biological races within our species is arbitrary because there are no major discontinuities in our diversity across the globe. Importantly, genetic data show that currently populous groups are not necessarily reflected by their past abundance, and human history is one of repeated admixture, not maintenance of purity. It is this genetic admixture that has left an imprint on every human disease with a genetic component, including common chronic ones. Thus, it is quite unlikely that the genetic variations underlying our diseases, which represent only a small fraction of our genetic diversity, will vary markedly across humanity.

Aravinda Chakravarti, “Racial profiling in medicine,” Nature Medicine, Volume 19, Number 7 (July 2013), 808. http://dx.doi.org/10.1038/nm.3254

Racial profiling in medicine

Nature Medicine
Volume 19, Number 7 (July 2013)
page 808
DOI: 10.1038/nm.3254

Aravinda Chakravarti, Professor of Medicine
McKusick-Nathans Institute of Genetic Medicine
Johns Hopkins University

Jonathan Kahn, Race in a Bottle: The Story of BiDil and Racialized Medicine in a Post-Genomic Age, Columbia University Press, 2012. 28 pp., ISBN: 0231162987

The field of human genetics is moving beyond using genomics as a tool for deeper understanding of human disease pathophysiology to the possibility of translating this knowledge for efficient treatment. A particular emphasis is being placed on Individualized medicine’, promising to tailor treatment based on each of our genomes. This ideal vision, however, can cause unease when our notions of genetic individuality intersect with those of ancestry and race. Jonathan Kahn’s book, Race in a Bottle, is a contemporary medical story born of this nexus. In it, he skillfully uses the story of the drug BiDil, a therapeutic for heart failure marketed specifically for African Americans (but whose use has declined markedly because it provides no unique benefit in comparison to similar drugs), as the backdrop for examining the expanding role of race in medical genomics, even when the same science has called the existence of race into serious doubt.

As Kahn highlights in the book, the innocuous birth of BiDil in 1992 was no predictor of its contorted history. BiDil is a combination of two vasodilators, hydralazine and isosorbide dinitrate (H-I), which are presumed to act through the nitric oxide pathway to provide benefit to patients with congestive heart failure. They were combined into one pill for easier administration, although each was already available in generic form. Between 1980 and 1991, two major clinical trials in the United States, involving patients of both European and African ancestries, clearly established that angiotensin-converting-enzyme inhibitors should be the preferred drug for patients with heart failure and that the H-1 combination should be used in individuals who did not benefit from this frontline therapy. Sensing a market opportunity, Medco Research obtained the intellectual property rights to BiDil, demonstrated its bioequivalence to the H-1 formulation and approached the US Food and Drug Administration(FDA) in 1996 for approval to market this ‘new’ drug. The FDA refused, arguing that clinical trials showing the utility of H-1 for heart failure did not meet the stiff criteria for such approval.

There was a suspicion that the nitric oxide response, and heart failure, was somehow different in blacks than in whites. So Jay Cohn, a respected cardiologist and owner of the original BiDil patent, reanalyzed the original clinical trial data to demonstrate that H-1 did work better in blacks than whites, a contention described and contested in the book. This finding not only led to a new patent but prompted its new owner, NitroMed, to conduct a fresh clinical trial in 2001, involving only African-American patients with heart failure, to demonstrate BiDils utility in this group. None of these facts are in doubt. What is doubted, however, is the implicit assumption that BiDil is not useful for white patients, the chronology of key events and the motivations of various actors in medicine, industry and government—factors that morphed an otherwise convenient drug formulation into a race-specific drug. Kahn makes the charge that “BiDil was not about personalizing medicine; it was about exploiting race to obtain cheaper, quicker FDA approval for a drug.”…

…Genetic analysis strongly suggests that early humans first arose in Africa and emerged out of Africa only ~100,000 years ago, a fairly recent development, evolutionarily speaking, which explains why we are all closely related. Any classification of biological races within our species is arbitrary because there are no major discontinuities in our diversity across the globe. Importantly, genetic data show that currently populous groups are not necessarily reflected by their past abundance, and human history is one of repeated admixture, not maintenance of purity. It is this genetic admixture that has left an imprint on every human disease with a genetic component, including common chronic ones. Thus, it is quite unlikely that the genetic variations underlying our diseases, which represent only a small fraction of our genetic diversity, will vary markedly across humanity…

Read or purchase the article here.