Jews and Genes

by Alan McGowan What is a Jew? What has kept the Jewish people, descendants of the ancient Israelites, together for such a long time? Who are the descendants of the “lost tribes?” Two recently published books, one by a writer who has written extensively on genetics, the other by a distinguished geneticist and “genetic historian,” provide intriguing insights into these and other questions. The two books, Abraham’s Children: Race, Identity and the DNA of the Chosen People, by Jon Entine (the writer), and Jacob’s Legacy: A Genetic View of Jewish History, by David Goldstein (the geneticist), raise many questions and appropriately provide only tentative answers. Goldstein essentially speaks for both of them, however, when he concludes: “Being Jewish is about culture, not DNA.” The massive Human Genome Project, which published its initial working draft sequence with great fanfare on February 12th, 2001, was funded based chiefly on the promise of dramatic improvements in health. Yet the Project and its allied activities have produced a huge amount of data useful for many activities other than medical analysis. Among these is the use of DNA sequences to determine ethnic and racial histories. The new profession of “genetic historian” has thus been born. In 1953, James Watson and Frances Crick published their seminal paper describing the structure of deoxyribonucleic acid, or DNA. DNA had for some time been understood to be the chemical of genetics, since the chromosomes — the small bodies found in in the nucleus of every human cell that show a different color when stained (hence their name) — were basically composed of it. The discovery of the double helix structure gave a clue as to how the molecule could be replicated so that copies of genes could be transferred from parent to child. The Y chromosome can be used in a similar way to trace the genetic history of males. Mammalian males have one X and one Y chromosome; females have two X chromosomes. Because the Y has fewer than a hundred genes, whereas the X has approximately a thousand, the Y is also less subject to natural selection pressure, and is passed down largely intact from father to son. Mitochondria and Y chromosomes provide powerful tools for the analysis of genetic history, particularly given the rapid sequencing that is now possible (sequencing means determining the exact sequence of DNA nucleotides on the chromosome). The August, 2008 issue of Scientific American, for example, has a fascinating article describing the routes of human migration out of Africa that have already been discovered using this technology. Both Jon Entine and David Goldstein add zest to their books by seeking to trace their own Jewish origins. As they both point out, however, there is a greater, more scientific reason, to be interested in the genetics of the Jewish people. Hundreds of diseases have now been determined to have some genetic influence, from so-called monogenic diseases such as Huntington’s Disease, where just one gene variation (called an “allele”) can cause the disease, to those diseases such as early-onset breast cancer in which a specific allele is not causative but greatly increases the chance of the disease developing. Many more of these disease alleles wait to be discovered. The first step in the discovery process is to find a “marker” or set of markers associated with the disease. Once this has been done, the particular mechanism by which the alleles cause or predict the disease has to be determined, to demonstrate that the alleles are, indeed, the actual cause. Simply finding such markers is a huge challenge, since there are hundreds and hundreds of diseases and some twenty thousand genes in the human genome (the exact count is in dispute, based in part on a 2004 paper by John Dupre,“Understanding Contemporary Genomics,” which even questions the notion of a singular “gene”). In comparing genomes, it would be very helpful, of course, if people’s genomes were identical except for that one allele or set of alleles we think might be a marker for the disease. This would require, however, that everyone be an identical twin! Instead, we must look for the next best thing: a population that is genetically similar. When Nancy Wexler, for example, was looking for the allele that caused Huntington’s Disease — which had killed her mother and represented a risk to her — she went to a remarkable village, San Luis on Lake Maracaibo in Venezuela, where (as she had seen in a film) a very large number of people appeared to have the disease. The setting was perfect for her research, since everyone was closely related, with very similar genomes. It was possible, therefore, to compare their genomes, find the relatively few alleles that were different, and match those differences with people who had the disease. (Although no cure has yet resulted from the discoveries made by Wexler and the geneticists with whom she worked, there is now, at least, a test that at-risk people can take to determine whether they will get the disease.) Jews also fit the bill for such genetic research. Although 50 percent of American Jews are nowmarrying non-Jews, there has been, until very recently, a remarkable genetic cohesiveness to Jewish communities worldwide, produced by their disinclination to proselytize and the social pressures on them, from within and without, to marry fellow Jews. Genetic research raises interesting ethical issues, however. In Jacob’s Legacy, Goldstein relates the story of deCODE Genetics, a biopharmaceutical company based in Reykjevik that took genetic samples from native Icelanders, all of whom are descendants of a relatively few Norwegians who settled in Iceland centuries ago. The assumption was that this “founder effect” would produce a population with very similar genomes and therefore provide opportunities for the discovery of disease alleles. The original intent of deCODE was to establish a Health Sector Database, with complete medical, genetic, and genealogical information on the whole population — from which the company ultimately hoped to make a profit. While the plan was effectively quashed by the Icelandic Supreme Court, the controversy remains: What responsibility did deCODE have towards the Icelanders? What piece, if any, of the profit should be shared by the population, and in what form? Should Icelanders have a voice in how their data are used? Given the history of the Jews, the same issues are certainly going to be raised should there ever be an attempt to establish a Jewish health database. Who will have access to the data? How will privacy be maintained? What protection will there be against abuses? How will people avoid being discriminated against? What voice should the Jewish people have in the use of their data? These are all part of the larger questions concerning genetic privacy for the entire human population. Jon Entine is particularly interested in using one’s personal genome to trace ancestry. Henry Louis Gates has made this technology famous by presenting a television series in which he had a variety of well-known people test a swab of their DNA. The results indicated what percentage of their ancestry is African, Jewish, Irish, or whatever. Within the scientific community, such analyses are very controversial, especially since they give no indication as to their accuracy or the size of their data base. As David Goldstein notes, “individual genotypes — that is, one person’s DNA signature at any place or places on the genome — rarely carry much information about geographic ancestry. Why? Populations are generally similar and rarely show more than slight statistical differences.” Goldstein explained further to me in an e-mail: “A variant at a single site in the genome does not carry very precise information about geographic ancestry because population genetics is stochastic [non-deterministic or random]. Let’s imagine that an African American carries out one of those ancestry tests and finds a match, at some degree of resolution, for his Y chromosome in a particular place in Africa. Does that mean that the individual’s ancestors came from that precise village? No. It could have been another place where that kind of Y chromosome was found in the past [but] no longer due to chance changes. As you look farther back in time, these stochastic changes magnify. “On the other hand,” he continued, “when you pile up many differences throughout the genome then you can get more precise information about geographic ancestry . . . thus, you can tell whether an individual is from north Europe versus Africa with a very high degree of confidence, or from Africa or East Asia, and so on. Indeed, you can even tell with high confidence if an individual has Ashkenazi Jewish ancestry [or is] European without such ancestry.” In short, the accuracy of genetic history depends on the number of specific places one looks on the genome. Since none of the commercial databases disclose how much of the genome they examine to come up with their numbers, there is no way to determine the accuracy of their findings. Sequencing one’s entire genome costs about $5,000. A commercial company will provide your “genetic history” for between $219 and $650. How much of your genome is used? You do the math. (An article in the July 3rd, 2009 edition of Science called for standardization and regulation of such ancestry testing and noted that the American Society of Human Genetics has issued recommendations urging the “need for greater responsibility, research, explanatory clarity and accountability” in the field.) Implicit in this ancestry discussion is the controversial issue of the validity of “race” as a genetic category in human beings. Goldstein deals only indirectly with this by equating “race” in the beginning of his book with geographic ancestry (a much less loaded term). Entine, however, tackles the issue head on. (Readers interested in the debate over race may well want to turn to Revisiting Race in a Genomic Age, edited by Barbara A. Koenig, Sandra Soo-Jun Lee, and Sarah S. Richardson.) He first lists the many legitimate reasons to distance oneself from the racist past, when scientists spent a good deal of time “proving” that non-white populations were innately inferior. Entine details the faults and difficulties of eugenics, the pseudo-science of the first half of the 20th century that called for the “superior” races — primarily whites — to propagate mightily while preventing the “inferior” races from doing so. Ultimately, however, Entine believes that scientists who today reject the validity of race as a biological category are simply recoiling from this history. “Shadowed by the racist ideologies [of Nazi Germany and eugenics],” he writes, “common sense was sacrificed to the new ideology of environmental determinism.” It is true that the eugenics period in American and European history was sad and degrading, with nobody involved looking very good. Many leading progressive thinkers, including Margaret Sanger, H. G. Wells, and John Maynard Keynes, fell prey to the seductions of the notion that improving the human condition was simply a matter of having the right people have children. Entine is right in criticizing the excesses and errors of that time, but wrong in his assessment of the “politically correct” attitudes of scientists today who question the validity of the biological race concept. There is much more substance to their arguments. Harvard University’s Richard Lewontin, for example, in a 1972 paper, “Apportionment of Human Diversity,” which Entine actually highlights, points out that genetic differences between races must be compared to genetic differences within races. Populations may differ in the frequency of allelic distribution, for example — African-Americans have more of the sickle cell allele than do non-African Americans, and Ashkenazi Jews have a higher frequency of the BRCA1 allele, which predisposes to early-onset breast cancer, than do non-Jews — but there is not one allele that is exclusive to one population. “As a biological rather than a social construct,” Lewontin reiterated in 2006, “ ‘race’ has ceased to be seen as a fundamental reality characterizing the human species.” Lewontin notes that 85 percent of our genetic variation actually occurs “among individuals within local national or linguistic populations” and that there is “continuous [genetic] variation over the whole world with no sharp boundaries and with no greater similarity occurring between Western and Eastern Europeans than between Europeans and Africans! Thus, the classically defined races do not appear from an unprejudiced description of human variation. Only the Australian Aborigines appear as a unique group.” Entine’s treatment of Franz Boas (1896-1942), who is widely viewed as the founder of modern American anthropology and pioneered the idea that race is a statistical artifact, is especially unkind. Entine calls Boas’ ideas “discredited,” and bolsters his criticism by suggesting that Boas fudged the data in one of his important studies about the craniology of different populations. Boas’s paper attempted to show the plasticity of head shape and to attribute it predominantly to the influence of the particular environment in which children grow up. However, even Corey S. Sparks and and Richard L. Jantz, two important modern critics of Boas’ paper, note that the more sophisticated methods of analysis needed to show that the size and shape of human heads result from genetics, not environmental factors, were not available to Boas, and “make no claim that Boas made deceptive or ill-conceived conclusions” (Proceedings of the National Academy of Sciences, 99.23, 2002). Moreover, Entine fails to note that other scientists have challenged the view of Sparks and Jantz. The controversy was aired in several papers in the American Anthropologist; in one (Gravlee, Bernard, & Leonard, 2003), three leading anthropologists state: “When we clarify Boas’s position and place the immigrant study in historical context, Sparks and Jantz’s renalysis supports our conclusion that, on the whole, Boas got it right.” We have learned a great deal since the completion of the Human Genome Project in 2001, including the fact that the complexity of the genome is far greater than we thought. We tend to look for simple answers — a “gene” for everything — when the truth is much more complicated. Part of this complexity has to do with “gene regulation.” We all carry every part of our genome in most cells in our body — including the alleles, for example, that determine eye color. Clearly that set of genes cannot express itself in the fingernails, however fashionable blue nails might be. Therefore, part of the genomic structure has to tell the genes when to be operative, and when to lie dormant. Furthermore, just as in a crossword puzzle, in which a single letter may be part of two words, a single strip of DNA can actually be part of several “genes.” Part of the complexity of the genome is the stitching together all of these pieces to produce the correct genetic information. Notwithstanding this complexity, and the fundamental agreement between Goldstein and Entine that Jewishness is history and culture far more than DNA, there are certain aspects of Jewish history on which DNA can shed some fascinating light. Tradition has it, for example, that after the exodus of the Jews from Egypt, Aaron, brother of Moses, was selected as the first “Cohen,” or priest, and that his sons were also so designated. Since the Y chromosome is passed from father to son, it might be possible for DNA in that chromosome to give evidence of such a priestly hereditary tradition. Indeed, some 90 percent of contemporary Cohanim do have some genetic features in the Y chromosome that are different from those of other Jews. This is the Cohen Modal Haplotype. (A haplotype, shortened from “haploid genotype,” is a cluster of alleles that exist on the same chromosome, although at different places, and tend to be inherited together. Many inherited characteristics are thought to be related to haplotypes rather than to individual genes.) The Cohen Model Haplotype is found in individuals among both Ashkenazic and Sephardic populations around the world, as well as among the Bene Israel in India. This phenomenon speaks to great sexual fidelity among Jewish women (at least those married to Cohens!) since only a few sons born from extramarital unions, and therefore without the Cohen Modal Haplotype, would have lowered the percentage a great deal. The Lemba people of South Africa, who follow Jewish traditions and claim to be descended from the Israelites, also displays the Cohen Modal Haplotype, although at a slightly lower frequency than among Ashkenazim or Sephardim. A sub-clan, the Buba, are held to be the priestly clan of the Lemba, and most of the haplotype found in the Lemba are among the Buba. However, the Cohen Modal Haplotype is also the most common haplotype found among southern and central Italians, Hungarians, Iraqi Kurds, and (to a lesser extent) Armenians. Does this call into question the basic thesis? Not really — but it does underline the essential point that while DNA, with other pieces of evidence, may be indicative of Jewish ancestry, it is chiefly culture, far more than genetics, that defines a person as a Jew. With science advancing all the time, along with sophisticated statistical methods of analysis, there are fascinating stories to be told, questions to be asked, and more books to be written in the immediate future. Alan H. McGowan is a faculty member of the Science, Technology, and Society Program at Eugene Lang College, The New School for Liberal Arts. He was founder of the Gene Media Forum and president of the Scientists’ Institute for Public Information, a major bridge between scientists and the media. McGowan is an executive editor of Environment magazine and a member of the Council on Foreign Relations.