The Wandering Gene and the Indian Princess

by Jeff Wheelwright

  I am especially obliged to two dedicated men who shared their research and patiently answered questions: Harry Ostrer and Stanley Hordes. Many others I don’t have space to name responded to my queries, for which I am grateful. I thank my steadfast, beautiful wife, there at the beginning and at the end.

  Finally I must acknowledge the members of the Medina and Martinez families. They were always gracious, forthcoming, and kind, even as their losses continued. I admire you and wish you peace.

  NOTES

  * * *

  PROLOGUE

  PHOTO: Mount Blanca, San Luis Valley, Colorado. All photos by the author unless otherwise noted.

  2Hispano, the Spanish word for Hispanic, is a term used by historians and social scientists. It denotes people whose forebears lived in what became U.S. territory after the Mexican-American War. Most other professionals, including medical professionals and geneticists, tend not to distinguish Hispanos from the larger class of Hispanics. Hispanos themselves usually say they are Spanish or Spanish American, and sometimes they will call themselves Mexican, but only when they are speaking in Spanish, not English. In English, Mexican is reserved for later immigrants.

  As for Hispanos’ perceptions of their Native American blood, see “Genetic Admixture, Self-Reported Ethnicity, Self-Estimated Admixture, and Skin Pigmentation among Hispanics and Native Americans,” Yann C. Klimentidis et al., American Journal of Physical Anthropology, Vol. 138, 2009, pp. 375–83.

  6My edition of Don Quixote is the 1755 translation by Tobias Smollett: The Adventures of Don Quixote de la Mancha, Miguel de Cervantes, Farrar, Straus and Giroux, New York, 1986. The discussion of Dulcinea’s origins, which I have partly quoted but mainly paraphrased, appears in Volume I, Book 3, pp. 190–92.

  CHAPTER 1: GIRASOL

  PHOTO: Wild sunflowers, San Francisco, Colorado.

  EPIGRAPH (Spanish verse only): The People of El Valle: A History of the Spanish Settlers in the San Luis Valley, Olibama Lopez Tushar, El Escritorio Press, Pueblo, CO, 2007.

  Chapter 2: Predestination

  PHOTO: Stations of the Cross Shrine, San Luis, Colorado.

  27For information on sporadic breast cancer, see the American Cancer Society guide: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/index.

  For BRCA inheritance and penetrance I consulted: “Breast Cancer Risk Associated with BRCA1 and BRCA2 in Diverse populations,” James D. Fackenthal and Olufunmilayo I. Olopade, Nature Reviews/Cancer, Vol. 7, December 2007, pp. 937–48; “Cancer risks among BRCA1 and BRCA2 mutation carriers,” E. Levy-Lahad and E. Friedman, British Journal of Cancer, Vol. 96, 2007, pp. 11–16; “Hereditary Breast Cancer in Jews,” Wendy S. Rubinstein, Familial Cancer, Vol. 3, 2004, pp. 249–57. See also “Genetics of Breast and Ovarian Cancer,” by the National Cancer Institute: http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional.

  A good book for the lay reader concerned about heritable breast and ovarian cancer: Positive Results: Making the Best Decisions When You’re at High Risk for Breast and Ovarian Cancer, Joi L. Morris and Ora K. Gordon, MD, Prometheus Books, New York, 2010.

  32A catalog of BRCA1 and BRCA2 mutations is maintained by the National Institutes of Health, accessible at: http://research.nhgri.nih.gov/projects/bic.

  The 185delAG mutation of BRCA1 also goes by the name 187delAG. The former entered the literature first, but for technical reasons many scientists have adopted the latter. “The naming confusion is a result of the fact that the sequence from nucleotides 185–188 is ‘AGAG,’ so that it is impossible to tell if the deletion is caused by removal of the nucleotides at positions 185–86 or at positions 187–88, as both would produce the same final sequence.” Source: http://www.pharmgkb.org/search/annotatedGene/brca1/variant.jsp.

  CHAPTER 3: THE WANDERING GENE

  PHOTO: Culebra Range, Sangre de Cristos.

  37I found the following surveys of Jewish history and Jewish genetics helpful: Wanderings: History of the Jews, Chaim Potok, Knopf, New York, 1978; The Chosen People in America, Arnold M. Eisen, Indiana University Press, Bloomington and Indianapolis, 1983; “A Genetic Profile of Contemporary Jewish Populations,” Harry Ostrer, Nature Reviews/Genetics, Vol. 2, November 2001, pp. 891–98; “The Jewish People: Their Ethnic History, Genetic Disorders and Specific Cancer Susceptibility,” Inbal Kedar-Barnes and Paul Rozen, Familial Cancer, Vol. 3, 2004, pp. 193–99; “A Mosaic of People: The Jewish Story and a Reassessment of the dna Evidence,” Ellen Levy-Coffman, Journal of Genetic Genealogy, Vol. 1, 2005, pp. 12–33; Abraham’s Children: Race, Identity, and the DNA of the Chosen People, Jon Entine, Grand Central Publishing, New York, 2007.

  40For an example of a DNA test for Jewish ancestry, see: “A Genome-Wide Genetic Signature of Jewish Ancestry Perfectly Separates Individuals with and without Full Jewish Ancestry in a Large Random Sample of European Americans,” Anna C. Need et al., Genome Biology, 2009. Available at: http://genomebiology.com/2009/10/1/R7. Using less strict criteria, direct-to-consumer companies such as 23 and Me offer Jewish ancestry testing.

  40The 2001 paper by Harry Ostrer is cited above. For his latest work in this vein, see: “Abraham’s Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry,” Gil Atzmon et al., American Journal of Human Genetics, Vol. 86, No. 6, June 2010, pp. 850–59.

  42For the dating of the 185delAG mutation, see: “The 185delAG BRCA1 Mutation Originated before the Dispersion of Jews in the Diaspora and Is Not Limited to Ashkenazim,” Revital Bruchim Bar-Sade et al., Human Molecular Genetics, Vol. 7, No. 5, 1998, pp. 801–5. The senior author and lead investigator, Eitan Friedman, has since refined his estimate of the mutation’s age to 2,200 years ago. Source: E. Friedman, personal communication, June 2011.

  43Myriad Genetics, which controls BRCA testing, has statistics on the non-Jewish carriers of 185delAG. Thus: “In the clinical genetic testing setting, a small percentage of individuals who tested positive for the 185delAG mutation were not of Ashkenazi Jewish descent. Of 709 individuals who were identified by Myriad Genetics Laboratories, Inc. (as of the summer of 2002) as carrying the 185delAG mutation in BRCA1, 77 individuals (11%) indicated a non-Ashkenazi ancestry. The remaining 632 individuals indicated Ashkenazi Jewish ancestry.” Source: “Identification of Germline 185delAG BRCA1 Mutations in Non-Jewish Americans of Spanish Ancestry from the San Luis Valley, Colorado,” Lisa G. Mullineaux et al., Cancer, Vol. 98, No. 3, August 2003, p. 600.

  44For the finding of 185delAG in non-Jewish families in Yorkshire, England: “Haplotype and Phenotype Analysis of Six Recurrent BRCA1 Mutations in 61 Families: Results of an International Study,” S. L. Neuhausen et al., American Journal of Human Genetics, Vol. 58, No. 2, February 1996, p. 275. In June 2011, at a conference in Israel, investigator Eitan Friedman stated that the mutation in England had been analyzed and found to be of independent (non-Jewish) origin. A scientific publication is forthcoming.

  45The ancient Muslim city of Medina is described in No god but God: The Origins, Evolution, and Future of Islam, Reza Aslan, Random House, New York, 2005.

  46The Ashkenazim arose a millennium ago from admixture between Jewish pioneers and their European hosts, but the direction of the matings and the fractions of the admixture have been unsettled issues. Research by David B. Goldstein and his colleagues has suggested that Middle Eastern Jewish men mated with local women, e.g., “Founding Mothers of Jewish Communities: Geographically Separated Jewish Groups Were Independently Founded by Very Few Female Ancestors,” Mark G. Thomas et al., American Journal of Human Genetics, Vol. 70, 2002, pp. 1411–20. Goldstein developed this idea in his book Jacob’s Legacy: A Genetic View of Jewish History, Yale University Press, New Haven, 2008.

  A contrary scenario emphasizing the founding role of Middle Eastern females was put forward in “The Matrilineal Ancestry of Ashkenazi
Jewry: Portrait of a Recent Founder Event,” Doron M. Behar et al., American Journal of Human Genetics, Vol. 78, March 2006, pp. 487–97. About the population’s growth, the authors observed that the “unique, well-documented overall demography [of the Ashkenazim] is consistent with several founding events, repeated bottlenecks, and dramatic expansions, from an estimated number of ~25,000 in 1300 A.D. to >8,500,000 around the turn of the 20th century.”

  These studies were based on rather limited Y-chromosome and mitochondrial DNA assays. More recently, broad, whole-genome analyses of the Ashkenazim have been undertaken, showing their links to other European, Middle Eastern, and other Jewish populations. See: “Genomic Microsatellites Identify Shared Jewish Ancestry Intermediate Between Middle Eastern and European Populations,” Naam M. Kopelman et al., BMC Genetics, Vol. 10, No. 8, December 2009 (available at http://www.biomedcentral.com/1471-2156/10/80); “The Genome-Wide Structure of the Jewish People,” Doron M. Behar et al., Nature, Vol. 466, July 2010, pp. 238–42; “Abraham’s Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry,” Gil Atzmon et al., American Journal of Human Genetics, Vol. 86, No. 6, June 2010, pp. 850–59. (The last paper is by Ostrer and his team.)

  The bottom line of the population research: Jews, wherever they may live today, share Middle Eastern ancestry, and for that reason their disparate populations show a high degree of genetic relatedness. An Ashkenazi Jew in Poland is more like a Sephardic Jew in Turkey or Spain than he is like his non-Jewish neighbors in Poland. This is what Harry Ostrer meant when he spoke of genetic threads that were recognizably Jewish.

  47A popular treatment of the Khazar theory of Ashkenazi origins is The Thirteenth Tribe: The Khazar Empire and its Heritage, Arthur Koestler, Random House, New York, 1976. See also, more recently, Levy-Coffman, op. cit., and Entine, op. cit., and the rebuff of the theory by Atzmon et al., 2010, op. cit.

  49There are many sources of information on the Jewish genetic disorders. Among those I consulted: Jewish Genetic Disorders: A Layman’s Guide, Ernest L. Abel, McFarland & Co., Jefferson, NC, 2001; “Prenatal Genetic Screening in the Ashkenazi Jewish Population,” Randi E. Zinberg, Ruth Kornreich, Lisa Edelmann, Robert J. Desnick, Clinics in Perinatology: Metabolic and Genetic Screening, Vol. 28, No. 2, June, 2001, pp. 367–82; “A Genetic Profile of Contemporary Jewish Populations,” Ostrer, op. cit. Up-to-date information can be found at the websites of the Jewish Genetic Disease Consortium, http://jewishgeneticdiseases.org, and of the Israeli National Genetic Database, www.goldenhelix.org/server/israeli, which lists 43 Ashkenazi disorders.

  50This chapter’s treatment of race science and Jews benefited from the following: Fishberg, op. cit.; “‘The Coefficient of Racial Likeness’ and the Future of Craniometry,” R. A. Fisher, Journal of the Royal Anthropological Institute, Vol. 66, 1936, pp. 57–63; “Geneticists and the Biology of Race Crossing,” William B. Provine, Science, Vol. 182, 1973, pp. 790–96; The Mismeasure of Man, Stephen Jay Gould, W. W. Norton, New York, 1981, 1996; Defenders of the Race: Jewish Doctors and Race Science in Fin-de-siècle Europe, John M. Efron, Yale University Press, New Haven, 1995; “The Persistence of Racial Thinking and the Myth of Racial Divergence,” S. O. Y. Keita and Rick A. Kittles, American Anthropologist, Vol. 99, No. 3, 1997, pp. 534–44; Statement on ‘Race,’ American Anthropological Association, Arlington, VA, 1998 (available at http://www.aaanet.org/stmts/racepp.htm); “Racial Science, Social Science, and the Politics of Jewish Assimilation,” Mitchell B. Hart, The History of Science Society, University of Chicago Press, Vol. 90, No. 2, June 1999, pp. 268–97; Mengele: The Complete Story, Gerald L. Posner and John Ware, Cooper Square Press, New York, 2000; “Race, Ancestry, and Genes: Implications for Defining Disease Risk,” Rick A. Kittles and Kenneth M. Weiss, Annual Review of Genomics and Human Genetics, Vol. 4, 2003, pp. 33–67; “If There Are No Races, How Can Jews Be a ‘Race’?,” Steven Kaplan, Journal of Modern Jewish Studies, Vol. 2, No. 1, 2003, pp. 79–96; “The Meaning and Consequences of Morphological Variation,” Richard L. Jantz, American Anthropological Association, Arlington, VA, 2004; “In the Name of Public Health—Nazi Racial Hygiene,” Susan Bachrach, New England Journal of Medicine, Vol. 351, No. 5, July 29, 2004, pp. 417–20; “The Measure of America: How a Rebel Anthropologist Waged War on Racism,” Claudia Roth Pierpont, The New Yorker, March 8, 2004, pp. 48–63; “Race and Reification in Science,” Troy Duster, Science, Vol. 307, February 2005, pp. 1050–51; Studying the Jew: Scholarly Antisemitism in Nazi Germany, Alan E. Steinweiss, Harvard University Press, Cambridge, 2006; The Price of Whiteness: Jews, Race, and American Identity, Eric L. Goldstein, Princeton University Press, Princeton, NJ, 2006; “Human Genetics and Politics as Mutually Beneficial Resources: The Case of the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics During the Third Reich,” Sheila Faith Weiss, Journal of the History of Biology, Vol. 39, No. 1, 2006, pp. 41–88.

  52The estimate of 0.5 percent Ashkenazi outbreeding per generation was taken from: “Jewish and Middle Eastern Non-Jewish Populations share a Common Pool of Y-chromosome biallelic haplotypes,” M. F. Hammer et al., Proceedings of the National Academy of Sciences, Vol. 97, No. 12, June 2000, p. 673. This paper was among the first to establish the Middle Eastern roots of the Ashkenazim.

  Maurice Fishberg’s finding that Jews were more like their immediate neighbors than they were like Jews in other countries is not contradicted by research, mentioned earlier, showing that Jewish populations share Middle Eastern DNA and that Jews across the Diaspora are more similar to each other than to their hosts. That’s because Fishberg compared physical traits or phenotypes, while contemporary scientists compare genotypes, the one not necessarily capturing or corresponding to the other.

  54For Ostrer’s important 2010 paper, see the note for page 40.

  55Scientists have conjectured for decades whether carriers of a single Tay-Sachs mutation may have gained an evolutionary advantage through natural selection. The opposing argument is that genetic drift can explain the mutation’s spread among Ashkenazi Jews. Thus: “Founder Effect in Tay-Sachs Disease Unlikely,” N. C. Myrianthopoulos et al., American Journal of Human Genetics, Vol. 24, 1972, pp. 341–42; “Role of Genetic Drift in the High Frequency of Tay-Sachs Disease among Ashkenazic Jews,” S. Yokoyama, Annals of Human Genetics, Vol. 43, 1979, pp. 133–36; “Heterozygote Advantage in Tay-Sachs Carriers?,” B. Spyropoulos et al., Annals of Human Genetics, Vol. 33, 1981, pp. 375–80; “Curse and Blessing of the Ghetto,” Jared Diamond, Discover, Vol. 12, March 1991, pp. 60–66; “Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection,” Neil Risch, Josef Ekstein et al., American Journal of Human Genetics, Vol. 72, 2003, pp. 812–22; “The Possibility of a Selection Process in the Ashkenazi Jewish Population,” Joel Zlotogora and Gideon Bach, American Journal of Human Genetics, Vol. 73, No. 2, 2003, pp. 438–40.

  The paper proposing a causal connection among Tay-Sachs carriers, BRCA carriers, and intelligence was “Natural History of Ashkenazi Intelligence,” G. Cochran et al., Journal of Biosocial Science, Vol. 38, No. 5, September 2006, pp. 659–93 (first published online in 2005). See, for a rebuttal, “Haplotype Structure in Ashkenazi Jewish BRCA1 and BRCA2 Mutation Carriers,” Kate Im et al., Human Genetics, May 20, 2011 (e-publication ahead of print). The senior author, Bert Gold, started his investigation as a believer in the selective benefits of Jewish BRCA, but his analysis of the mutations changed his mind. Source: B. Gold, personal communication, June 2011.

  CHAPTER 4: EL CONVENTO

  PHOTO: El Convento, San Luis, Colorado.

  61For a physical inventory (buildings and terrain) of San Luis and its sister villages, see: “The Culebra River Villages of Costilla County, Colorado,” prepared by Maria Mondragon-Valdez for the State Historic Preservation Office, Colorado Historical Society, June, 2000. Available at: http://www.coloradohistory-oahp.o
rg/publications/pubs/614.pdf. My cultural overview of Hispanos drew upon The Hispano Homeland, Richard L. Nostrand, University of Oklahoma Press, Norman, 1992. The folkways of Culebra are described in The People of El Valle: A History of the Spanish Settlers in the San Luis Valley, Olibama Lopez Tushar, El Escritorio Press, Pueblo, CO, 2007, and La Cultura Constante de San Luis, edited by Randall Teeuwen, The San Luis Museum and Cultural Center, San Luis, CO, 1985.

  62The area’s vermilion hills: Death Comes for the Archbishop, Willa Cather, Knopf, New York, 1927, p. 305.

  63About the figure of Doña Sebastiana: Tushar, op. cit., p. 117. References for the penitentes are given in chapter 6 notes.

  65For an analysis of the depiction of suffering in Spanish Catholic religious painting, see “Images of Power and Salvation,” Rosemary Mulcahy, in El Greco to Velazquez: Art During the Reign of Philip III, edited by Sarah Schroth, Distributed Art Publishers, Inc., New York, 2008, pp. 123–45.

  66The genetic proximity of the Sephardim and the Ashkenazim is explored in Atzmon et al., 2010, op. cit.

  66In addition to Potok, Fishberg, and Entine, all op. cit., my treatment of the Jewish and crypto-Jewish experience in medieval Spain benefited from: The Battle for God: A History of Fundamentalism, Karen Armstrong, Ballantine, New York, 2001; To the End of the Earth: A History of the Crypto-Jews of New Mexico, Stanley M. Hordes, Columbia University Press, New York, 2005; Juggling Identities: Identity and Authenticity Among the Crypto-Jews, Seth D. Kunin, Columbia University Press, New York, 2009; “How Muslims Made Europe,” Kwame Anthony Appiah, The New York Review of Books, November 6, 2008, pp. 59–62, “A Flogging for the Lucky Ones,” Stefan C. Reif, The Times Literary Supplement, Feb. 20, 2009, p. 8; “Modernizing the Marranos,” J. H. Elliott, The New York Review of Books, March 11, 2010, pp. 22–24.