The Mix and Mash-up of Being Human A recent book tells us how genes explain us, partly and imperfectly.

Who We are and How We Got Here: Ancient DNA and the New Science of the Human Past

By David Reich (2018, Pantheon Books) 335 pages including endnotes, index, and 28 figures

This book explains the new technologies that researchers use to analyze DNA found in human fossils.  Those ancient bones are the grist that scientists mill in an attempt to discern relationships between early human populations and to reconstruct patterns of migration among them.

In his introduction, David Reich summarizes the career of the late Luca Cavalli-Sforza, whose History and Geography of Human Genes (1994) included an attempt to “reconstruct the great migrations of the past.” (xi)  Reich suggests that Cavalli-Sforza was like Moses who climbed to high ground to view the promised land over the horizon, but was left behind while others forged on beyond Jordan’s banks. When Reich then reminds us that his “ancient DNA laboratory at Harvard published more than half the world’s genome-wide human DNA,” (xxi) it becomes clear that he, successor to Cavilli-Sforza, hopes to stake his claim in the genetic land of milk and honey.

There is a bit of hubris in this positioning, even though Reich is, at points, properly humble in the face of the massive ignorance of just what our DNA can tell us.  He declares early on that “we are like kindergarteners in our ability to read the genome,” (9) and admits that he has worked with only “a handful” of samples from each culture he has studied. Reich also eventually concedes that he has only a “superficial knowledge of the historical and archeological and linguistic background of any topic we work on.” (282)   These insights might point to the need for caution, and to avoid overstating one’s conclusions. Yet there is a disconnect between the limitations Reich recognizes and the many triumphalist declarations he makes in his book about the power of DNA to explain so much about past populations.

When Reich then reminds us that his “ancient DNA laboratory at Harvard published more than half the world’s genome-wide human DNA,” (xxi) it becomes clear that he, successor to Cavilli-Sforza, hopes to stake his claim in the genetic land of milk and honey.

My first quibble is with his title.  I know that authors, particularly those working with mass-market trade presses, are often at the mercy of sales departments whose pressure to adopt eye-catching titles sometimes overwhelm a writer’s good sense.  But what exactly does it mean to say that a book will tell us Who We Are and How We Got Here?  The immediate tendency is to conclude that the author really thinks, in the most reductive sense, that the “open sesame” code that will release the answers to human questions of identity is buried in our DNA. I doubt that Reich believes this, since he so deliberately goes out of his way to distance himself from controversial comments of others like Nobel Laureate James Watson, who famously declared that “We used to think that our fate was in our stars. Now we know, in large measure, our fate is in our genes.”¹

Reich approaches an explanation for his title in the first chapter, which purports to tell us “How the Genome Explains Who We Are,” and explains his goal and his methods. He uses genome-wide association studies to elucidate patterns of similarity among population groups that left a skeletal record. That “who we are” turns out to be no kind of person in particular, but a mixture of different populations. Explaining “migration and population mixture” (10) is Reich’s goal.  “Mixture,” he says, “is fundamental to who we are” (97) “. . . we are mixtures all the way down.” (82) We Are All Mixtures might not have made such a snappy title, but it would have been a clearer indication of what the book is really about.

I also wondered who the audience for this book was.  In its first pages, Reich claims that the book is “intended for lay reader and specialist alike.” (xxi) Then, to bring his general reader up to speed on research methods, he uses the term “junk dna” to explain how noncoding regions of DNA function as critical markers in the studies this book details.

We Are All Mixtures might not have made such a snappy title, but it would have been a clearer indication of what the book is really about.

Why does he repeat the now seriously flawed concept of “junk” on the first page of his first chapter? Certainly, it is not for specialists, who presumably already understand the problems with that phrase. ² The use of jargon that is widely rejected because it signals a misleading and obsolete way of thinking about DNA will not benefit the uninformed “lay reader” either.

Reich goes on to further confound lay readers by using language like this: “Our initial approach was to carry out a principal component analysis, which can identify combinations of mutation frequencies that are most efficient at finding differences among samples.” (103) Prose like that may be acceptable in a specialty journal, but it is completely out of place in a book supposedly written for a general audience. Unfortunately, his chapters detailing migration patterns of Native Americans, and people in East Asia and Africa, suffer from a similarly ponderous style that hides more than it reveals.

At times Reich comes perilously close to using causal language—positing a “gene for” complex behavioral and medical reactions.  He talks of “a gene . . . that allows people in Tibet . . . to thrive in their oxygen poor environment” and genes “associated with the biology of keratins” that may have “helped Neanderthals adapt to new environments.” (65) Reich does his readers a disservice when he suggests relationships between single genes and intricate phenotypes. ³ He should label these musings clearly as speculation.

In his chapter on The Genomics of Race and Identity, Reich reminds us that studies of race and ethnicity are not new.  He echoes the fears of German archaeologists who worry about being linked to techniques they associate with Nazi science. (112) Indians are concerned about the “politically explosive” suggestion that there was a migration from West Eurasia to India. (134) But Reich insists the old ideas of race are wrong, and that there are no “primeval groups” “that separated tens of thousands of years ago.” African- Americans are only “latest in a long line of population mixtures.” (xxii) “Everyone in mainland India is a mix” of ancestry and “No group in India can claim genetic purity.” (135) The new DNA technologies reveal that “migration and mixture” between “divergent populations” has been a “key force shaping human history,” thus “ideologies that seek a return to a mythical purity are flying in the face of hard science.” (121)

Reich’s repeats his concern that people under study, in a display of ethno-cultural sensitivity, may react negatively toward researchers. He notes the grievances of indigenous groups, like the Havasupi, the Navajo and the Karitiana of Amazonia, who have been subject to DNA testing sometimes done without their fully informed consent. Those episodes made researchers hesitate to begin work that might later be blocked by controversy; they became “wary” of studying ancient cultures through DNA samples.

As he discusses the debate surrounding the skeleton of the Kennewick Man, Reich recalls the advice of a rabbi that “all graves are sacrosanct.” He then quickly seizes on a potential justification the rabbi provides for unearthing ancient bodies: it may be acceptable to open graves if your goal is “promoting understanding” or “breaking down barriers between people.” (286) This fits Reich’s earlier claim, that “Genetics offers the opportunity to rediscover lost stories, and has the potential to promote not just understanding but healing.” (185) But we are not told which philosopher king will decide how to determine whether one is “breaking down barriers” or merely promoting one’s own research.

Reich does his readers a disservice when he suggests relationships between single genes and intricate phenotypes. He should label these musings clearly as speculation.

Reich then boldly declares: “I am not aware of any cases in which research in molecular biology including genetics—a field that has arisen almost entirely since the end of the Second World War—has caused major harm to historically persecuted groups.” (163) That formulation, limiting research in genetics to post-WWII work in molecular biology, allows him to avoid a discussion of the history of eugenics, which cannot be so clearly divorced from a century of study in genetics. ⁴ Yet even with that qualification, he seems unaware of the problems, described in textbooks for three decades, which emerged from research into the genetics of sickle cell disease.

In the early 1970s, seventeen states passed laws authorizing, and in many cases mandating, sickle cell screening as a condition for receiving a marriage license or going to school. People–almost exclusively African-Americans– who refused the test for themselves or their children faced widespread discrimination. Some were denied insurance, employment, or the right to marry. Eventually, backlash from the negative impact of the tests led states to reverse course and they, along with the federal government, passed laws to prohibit such discriminatory behavior. ⁵ Fear about the use of genetic discrimination to target specific racial or ethnic groups was so well understood that it was specifically cited as a motive for passing the federal Genetic Information Nondiscrimination Act. ⁶ Minority groups remain alert to the potential for genetic testing to identify sickle cell trait, which has been used to exclude African-American job applicants, and more recently, was the justification for barring some African-Americans from intercollegiate athletics. ⁷ Every geneticist should know this important part of history.

It is possible to concur with the claim that his research with DNA “is providing definitive answers to questions about whether changes in the archeological record reflect movements of people or cultural communications” and still realize that genome-wide association studies are merely one tool of scientific analysis. Ancient DNA aside, no single discipline or technique will ever answer every question about the past.

I found the book fascinating for the suggestions it presented about the potential to understand the migration of language, culture and peoples, and other insights, like the statistical likelihood that Queen Elizabeth, despite descending from a line that traces William the Conqueror as a forbearer, may have no biological link to William as part of her own genome. As Reich says, “a person’s genealogy …  is not the same as his or her genetic inheritance.” (12)

But his tendency to oversell what we know right now about the prehistory of human groups left me ultimately frustrated. It is possible to concur with the claim that his research with DNA “is providing definitive answers to questions about whether changes in the archeological record reflect movements of people or cultural communications” (276) and still realize that genome-wide association studies are merely one tool of scientific analysis. Ancient DNA aside, no single discipline or technique will ever answer every question about the past. Reich is optimistic that his “pursuit of truth for its own sake” will be a force for good, not ill. But he would do well to follow his own admonition that the “history of science has revealed … the danger … of being too convinced that one knows the truth.” (264) 

¹ Allen Buchanan, Dan W. Brock, Norman Daniels, From Chance to Choice: Genetics and Justice (Cambridge: Cambridge University Press, 2001) 91.

² J Brosius, S J Gould, On “genomenclature”: a comprehensive (and respectful) taxonomy for pseudogenes and other “junk DNA” Proceedings of the National Academy of Sciences Nov 1992, 89 (22) 10706-10710.

³ See, for example, Kenneth S. Kendler, “A Gene for…”: The Nature of Gene Action in Psychiatric Disorders, Am J Psychiatry 2005; 162:1243–1252.

⁴ Lombardo PA, The power of heredity and the relevance of eugenic history. Genet Med. 2018 Jul 31. doi: 10.1038/s41436-018-0123-4. [Epub ahead of print]

⁵ E.G., North Carolina Acts of Assembly, 1975, c. 463, s. I. (Discrimination against any person possessing sickle cell trait or hemoglobin C trait prohibited). Congress also passed the 1972 National Sickle Cell Anemia Control Act, which makes receipt of federal funding to states contingent on sickle cell testing being voluntary. Public Law 92-294 (86 Stat. 136).

⁶ Neil Holtzman, Proceed with Caution: Predicting Genetic Risks in the Recombinant DNA Era (Baltimore: Johns Hopkins University Press, 1989) 219.

⁷ Jordan, et. al., “Screening U.S. College Athletes for Their Sickle Cell Disease Carrier Status,” American Journal of Preventive Medicine, vol. 41, Issue 6, Supp. 4, pg. S406-S412 (December 2011).