Source material includes interviews by the author with George Daley: May 29, 2001; June 21, 2001; August 16, 2002; October 3, 2003; January 19, 2004. Kenneth Kenyon: November 1, 2003; January 16, 2004. William Lensch: August 16, 2002; October 8, 2002; August 21, 2003. Susan Singer: April, 10, 2002; May 16, 2002. Richard Vulliet: March 22, 2004.
p. 3 “The essence of a stem cell”: Kenneth Kenyon, interview by the author, November 1, 2003.
pp. 3-4 But each of these cells is much tinier: One plant seed, in fact, can contain hundreds of thousands of stem cells.
p. 4 that a sperm from his “aged, decrepit body”: George Daley, “Stem Cells: Medicine and Myth,” “New Horizons in the Post-Genome World,” press conference, Whitehead Institute, May 4, 2001.
p. 6 to restore a full complement of red blood cells: One such study: M. Osawa … H. Nakauchi, “Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell,” Science, Vol. 273 (1996), pp. 242-45.
p. 7 by a bipartisan group of U.S. senators: Sam Brownback (R-KS), Orrin Hatch (R-UT), and Chris Dodd (D-CT) announced the proposal of the Cord Blood Stem Cell Act of 2003 in the fall of ’03. (The act contains two bills—S1717 and HR 2852—the latter bill previously proposed by Christopher Smith [R-NJ]). Congress has not yet reached a decision. For an update, or to read both bills, go to www.thomas.loc.gov.
p. 9 “Even the dumbest stem cell is smarter”: Evan Snyder, inter-
viewed by Carl T. Hall, “Harvard researcher mines stem cell riches in West,” The San Francisco Chronicle, January 6, 2003, p. A6.
p. 9 Similar to the animal kind, meristem cells: The numerous biological elements that plants and animals have in common, which include stem cells, lead many scientists to believe that plants and animals are descended from a common ancestor. Embryologist Scott Gilbert comments in a footnote in Developmental Biology (6th edition, p. 635): “The similarities between plant meristem cells and animal stem cells may extend to the molecular level, indicating that stem cells existed before plants and animals pursued separate phylogenetic pathways.”
p. 9 “If you go into a field”: Susan Singer, interview by the author, April 10, 2002.
p. 10 “it brings to mind amphibians”: Biologist from Novartis, conversation with the author, June 9, 2003. Several other scientists made similar comments to the author, among them Mark Keating, who studies amphibian regeneration: “I think for a long time regeneration has been in the badland of science.” Keating, interview by the author, May 14, 2003.
p. 12 Stem cells injected into the coronary artery of dogs: P.R. Vulliet … M.D. Kittleson, “Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs,” Lancet, Vol. 363 (2004), pp. 783-84.
Source material includes interviews by the author with Hans Bode: March 11, 2002; March 12, 2002. Richard Campbell: October 2002. Charles Dinsmore: March 15, 2002. Howard Lenhoff: February 9, 2002; May 5, 2002; June 10, 2002.
p. 13 “If there were no regeneration”: Richard J. Goss, Principles of Regeneration (New York: Academic Press, 1969), p. 1.
p. 13 Many Junes ago: Howard and Sylvia Lenhoff and their wonderfully written and elegantly produced book Hydra and the Birth of Experimental Biology—1744 (The Boxwood Press, 1986), were an invaluable source for many of the historical details in this chapter. The Lenhoffs’ volume includes engaging accounts of Trembley and his times, his experiments with hydra, and his era’s fascination with regeneration. It also contains the Lenhoffs’ translation of Trembley’s four memoirs, which overflow with Trembley’s character as a scientist and his meticulous observations of the small green creatures he was so taken by.
p. 13 countless little green nubs: This particular species of freshwater hydra is green because of algae living inside one layer of its cells. Howard Lenhoff, interview by the author, February 9, 2002.
p. 15 He would cut his “insecte”: A History of Regeneration Research: Milestones in the Evolution of a Science, edited by Charles E. Dinsmore (Cambridge/New York: Cambridge University Press, 1991), p. 27. “For example, they used the term ‘insect’ for any small invertebrate and even for some large vertebrates that appear segmented”—the crocodile, for example.
p. 15 as Trembley stood witness with his magnifying glass: In their Scientific American article, Vol. 258 (1988), pp. 108-13, Howard and Sylvia Lenhoff made this observation about Trembley: “Amazingly, he made scores of findings in the short span of four years from 1740 to 1744. Moreover, he did it long before the development of sophisticated tools, relying mostly on a magnifying glass and occasionally on a simple single-lens microscope.”
p. 16 “… one of the heads was immortal and the others almost as bad”: Edith Hamilton, Mythology (New York: Mentor Books, The New American Library, 1942), p. 164.
p. 18 “Apparently these gentlemen have some cherished system”: John R. Baker, Abraham Trembley of Geneva, Scientist and Philosopher 1710-1784, (London: Edward Arnold, 1952), p. 43.
p. 19 Réaumur referred to the animal as a “polyp”: Hydra and the Birth of Experimental Biology—1744, p. 5: “Trembley’s attitude toward nomenclature appears to have been one of nearly total indifference. He allowed Réaumur, with the collaboration of another colleague, Bernard de Jussieu, to name his animals ‘polyps,’ with the addition of one ecological (‘freshwater’) and one morphological (‘arms shaped like horns’) trait to distinguish them from the octopus and other ‘polyps of the sea.’”
p. 19 “His own eyes and skills”: Charles Dinsmore, “The Foundations of Contemporary Regeneration Research: Historical Perspectives,” Monographs in Developmental Biology, Vol. 23 (Basel, New York: Karger, 1992), pp. 11-12.
p. 20 Voltaire was said to be so confident: A History of Regeneration Research, p. 13.
p. 20 Hoards of naturalists went tromping: A History of Regeneration Research, p. 13.
p. 21 it may in fact have been Abraham Trembley who first witnessed: John Baker, Trembley’s first biographer, suggests that Trembley was “the first human being to witness cell-division and in the same act the first to see the multiplication of a single-celled plant.” Abraham Trembley of Geneva, p. 156. Also see pp. 102-3, 154-69. Howard Lenhoff brought this buried piece of history to the author’s attention.
p. 22 “Trembley didn’t like theories”: Howard Lenhoff, interview by the author, June 10, 2002.
p. 23 “In order to extend our knowledge of natural history”: Hydra and the Birth of Experimental Biology—1744, Fourth Memoir, p. 187.
Source material includes interviews by the author with Sabine Brauckmann: April 5, 2002. John Gearhart: June 28, 2001; January 8, 2002; August 30, 2003. Barbara Knowles: January 23, 2002. Gail Martin: February 13, 2002. Virginia Papaioannou: February 12, 2002; May 9, 2002. Barry Pierce: February 2, 2002; March 10, 2002. Davor Solter: February 13, 2001. Roy Stevens and Anne Wheeler: January 23, 2002; August 9, 2002. Anne Wheeler: May 7, 2001; July 8, 2002. Donald Varnum: May 7, 2001.
p. 25 “The stem cell, I believe, is the interpretation of regeneration”: John Hearn, interview by the author, May 18, 2003.
p. 25 “I felt perfectly free”: Roy Stevens, interview by Susan Mehrtens, The Jackson Laboratory Oral History Collection, June 14, 1986, p. 5.
p. 26 when he noticed that a chinchilla-colored: Stevens began his job at the Jackson Laboratory on June 1, 1952, and reports in his oral history (p. 5) that “Maybe it was six months after I had got here” that he saw his first teratoma-burdened mouse. Stevens confirmed to the author (August 9, 2002) that, although the strain has both albino and chinchilla mice, the first one he saw was chinchilla.
p. 26 Greek for “swollen monster”: “monster” from teras, and “swollen” from onkoma, from The Human Teratomas (New Jersey: Humana Press, 1983), p. 23.
pp. 26-27 teratomas represent but a small fraction: Several of Stevens’s teratoma papers make for interesting reading. Among them: “Embryology of testicular teratomas in Strain 129 mice,” Journal of the National Cancer Institute, Vol. 23 (1959), pp. 1249-95; “The biology of teratomas including evidence indicating their origin from primordial germ cells,” Année Biologique (1962), pp. 586-610; and “The origin and development of testicular, ovarian, and embryo-derived teratomas,” Teratocarcinoma Stem Cells, Cold Spring Harbor Laboratory, Conferences on Cell Proliferation, Vol. 10 (1983), pp. 23-36.
p. 27 the first ever described in the testis: In their paper “Experimental teratoma,” Current Topics in Pathology, Vol. 59 (1974), pp. 76-77, Ivan Damjanov and Davor Solter note how exceptionally rare spontaneously occurring teratomas are in mammals, including laboratory mice.
p. 27 indentations shaped like eye sockets: The Human Teratomas; Experimental and Clinical Biology, edited by I. Damjanov, B. Knowles, and D. Solter (New Jersey: Humana Press, 1983), p. 9.
p. 28 Roy Stevens was instantly captivated by the teratoma: During the nineteenth century, sightings of these tumors were all the rage in pathology. Writes one historian, “As if competing for the Guinness Book of Records, reports of the dermoid with the most teeth [well over 300 …], of the greatest
weight [over 52 lbs …], of the greatest diameter [45 cm], or with different kinds of hair … followed.” The Human Teratomas, p. 2.
p. 29 an inherited teratoma had never been glimpsed in a mouse: Stevens’s Jackson Laboratory oral history, p. 5. Prior to Stevens’s finding, occasional teratomas had been seen in the ovaries of female mice; they might have been inherited, but there was no concrete evidence.
p. 29 “Prexy” Little was a mouseologist: Clarence Little acquired his nickname “Prexy” during his years as a college president, for which Prexy was “accepted slang.” Martha Harmon, C.C. Little and the Founding of the Jackson Laboratory, May 2000.
p. 29 It was while he was a student at Harvard: Lee M. Silver, Mouse Genetics, adapted for the Web by Mouse Genome Informatics, the Jackson Laboratory. Also, George Snell’s online portrait of C.C. Little: Biographical Memoirs, Vol. 46 (1975), p. 242. Online version: http://www.nap.edu.
p. 30 Only one percent of Mouse Strain 129: The initial paper by Stevens and C.C. Little: “Spontaneous testicular teratomas in an inbred strain of mice,” Proceedings of the National Academy of Sciences, Vol. 40 (1954), pp. 1080-87. Also, Stevens’s Jackson Laboratory oral history, p. 5.
p. 31 “I could have abandoned the project then and there”: JAX, inhouse publication of the Jackson Laboratory, Vol. 18 (3), (Fall 1970), p. 6. Many details about Stevens’s multiyear attempt to find a mouse teratoma’s cell of origin are chronicled in this issue of JAX and the Spring 1971 issue, Vol. 19 (1).
p. 31 “He was decorated several times”: Barry Pierce, interviewed by the author, February 2, 2002. Stevens received the Legion of Merit and the Silver Star; from daughter, Anne Wheeler to author.
p. 35 “But things turned out”: Driesch’s quote appears in Joseph Needham’s Order and Life (Cambridge, England: Yale University Press, 1936),
p. 52. The quote originated in Driesch’s “The Science and Philosophy of the Organism,” Gifford Lectures (2nd edition, London: Black, 1929). Notes Needham (p. 51), “Considerable astonishment was … caused by Driesch’s announcement in 1891….”
p. 35 “prospective potency,” as he called it: Order and Life, pp. 53-54. Continues Needham, “This condition of multiple potency of the parts of the early egg-cell has been termed Pluripotence.”
p. 36 “The examination of serial sections”: Francis Herrick, The American Lobster: A Study of Its Habits and Development (Washington, DC: Government Printing Office, 1895), p. 108.
p. 38 “very insignificant complexes of indifferent cells”: Eugen Korschelt, Regeneration and Transplantation (Berlin: Gebrudes Borntraeger, 1927); republished by Watson Publishing International, 1990, p. 626.
p. 38 “Some facts concerning the regressive differentiation”: Henry V. Wilson, “On the behavior of the dissociated cells in hydroids, alcyonaria, and asterias,” Journal of Experimental Zoology, Vol. 11 (1911), p. 285.
p. 38 “fine bolting cloth such as is used for tow nets”: Henry Wilson, “On some phenomena of coalescence and regeneration of sponges,” Journal of Experimental Zoology, Vol. 5 (2), (1907-08), p. 246.
p. 39 “other animals besides sponges and hydroids”: Henry Wilson, Journal of Experimental Zoology, Vol. 11 (1911), pp. 281-87.
p. 39 “from his single-mindedness”: “Confidential report on candidate for fellowship,” the Jackson Laboratory, December 6, 1960.
p. 40 Thirty percent of his mouse offspring: Karl Illmensee and Leroy C. Stevens, “Teratomas and chimeras,” Scientific American (April 1979), p. 123.
p. 40 “By tracing the testicular teratoma back”: Roy Stevens, JAX, Vol. 19 (1), (Spring 1971), p. 13.
p. 41 “Well we tried, but we couldn’t get it to work”: Donald Varnum, interview by the author, May 7, 2001.
p. 42 “Roy or I formed a rather small, but intensely interested”: Barry Pierce, Teratomas and Differentiation, edited by M.I. Sherman and D. Solter (New York: Academic Press, 1975), p. 3.
p. 43 Kleinsmith and Pierce had: L.J. Kleinsmith and G.B. Pierce, “Multipotentiality of single embryonal carcinoma cells,” Cancer Research, Vol. 24 (1964), pp. 1544-51.
p. 43 Pierce and Dixon uncovered: G.B. Pierce and F.J. Dixon, “Testicular teratomas, I. Demonstration of teratogenesis by metamorphosis of multipotential cells,” Cancer, Vol. 12 (1959), pp. 573-83.
p. 43 “took dogma right by the throat”: Barry Pierce, interview by the author, February 2, 2002.
p. 44 “The cells were made tumorous simply by activation”: Armin C. Braun, “The reversal of tumor growth,” Scientific American (November 1965), p. 79. Also of interest by Braun: “Plant cancer,” Scientific American (June 1952), pp. 66-72.
Source material includes interviews by the author with Jane Barker: January 23, 2002; January 31, 2002; February 7, 2003. Seldon Bernstein: January 30, 2002; September 6, 2002. William Lensch: November 2003. Ernest McCulloch: July 16, 2001; December 19, 2001; January 9, 2002; February 16, 2003. James Till: June 19, 2001; January 18, 2002; September 5, 2002; December 20, 2002. Irving Weissman: January 11, 2001; February 6, 2002.
p. 47 “There is a lot of biology between the stem cell and mature cell”: Harvey Patt, paraphrased: “It was Harvey Patt who once said that there is a lot of biology between the stem cell and mature cell.” L.F. Lameston, from his “Concluding Address.” See Stem Cells of Renewing Populations, edited by
A.B. Cairnie, P.K. Lala, and D.G. Osmond (New York: Academic Press, 1976), p. 375. Patt was a radiobiologist at the University of California, San Francisco.
p. 47 Signs abounded that regenerative cells: Barry Pierce described (interview by the author, February 2, 2002) the thinking in the 1950s. “Cell biologists knew that basal cells in skin were regenerative tissue, but it wasn’t known what happened in many other organs” in regard to tissue renewal. “In the gut, there was nothing that would lead you to believe there were stem cells. Yet the average-sized human being will slough in their feces about forty kilograms of dead gastrointestinal cells every year, and about ten kilograms of dead white blood cells. That means there has to be a tremendous effort to maintain these tissues in their adult functioning state. We’re talking about before stem cells were really thought about in cell biology.”
p. 48 had been planted in people’s minds back in 1909: T.M. Fliedner, “Characteristics and potentials of blood stem cells,” Stem Cells, Vol. 16 (1998), suppl 1, pp. 13-29.
p. 49 “If they gave 200 rads, that wasn’t enough to kill mice”: Irving Weissman, interview by the author, February 6, 2002.
p. 50 The first effective animal-to-animal bone marrow transplants: One of the first such papers was E. Lorenz … E. Shelton, “Modification of irradiation injury in mice and guinea pigs by bone marrow injections,” Journal of the National Cancer Institute, Vol. 12 (1951), pp. 197-201.
p. 50 a British team led by Charles Ford: C.E. Ford … J.F. Loutit, “Cytological identification of radiation-chimaeras,” Nature, Vol. 177 (1956), pp. 452-54.
p. 51 a thousand of the laboratory’s 100,000 mice had perished: JAX, Vol. 15 (4), (Winter 1967), p. 8.
p. 53 “we were fumbling at the edge of the known”: Seldon Bernstein, email to the author, April 10, 2004.
p. 53 Russell’s experiment lifted off in 1956: Seldon Bernstein, interviews by the author, January 30, 2002, and September 6, 2002.
p. 54 “It was the first rescue for anemia”: Jane Barker, interview by the author, January 23, 2002.
p. 54 Russell and Bernstein went on to: S.E. Bernstein and E.S. Russell, “Implantation of normal blood-forming tissue in genetically anemic mice, without X-irradiation of host,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 101 (1959), pp. 769-73.
p. 54 “The hypothesis was that stem cells existed”: Ernest McCulloch, interview by the author, July 16, 2001.
p. 57 “One of the things Ernest and I agreed upon”: James Till, interview by the author, January 18, 2002.
p. 58 “When I saw those lumps, it occurred to me at once”: Ernest McCulloch, interview by the author, January 9, 2002.
p. 60 in 1962 Becker produced an elegant set of experiments: A.J. Becker, E.A. McCulloch, and J.E. Till, “Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells,” Nature, Vol. 197 (1963), pp. 452-54.
p. 61 they could at least propose a definition: Jim Till believes that the first paper in which his group offered a definition of stem cell was: L. Siminovitch, E.A. McCulloch, and J.E. Till, “The distribution of colony-forming cells among spleen colonies,” Journal of Cellular and Comparative Physiology, Vol. 62 (1963), pp. 327-36. “Lou Siminovitch made crucial conceptual contributions to the work that led to this paper,” noted Till in an email to the author.
p. 62 The current belief is that an average-weighted adult: Science News, June 16, 2001, p. 378.
pp. 62-63 Till and McCulloch had pocketed: J.E. Till and E.A. McCulloch, “A direct measurement of the radiation sensitivity of normal mouse bone marrow cells,” Radiation Research, Vol. 14 (1961), pp. 213-22. The report was reprinted in The Journal of NIH Research, Vol. 4 (June 1992), pp. 73-78, with commentary by McCulloch and Till included.
p. 63 Weissman and his team achieved: G.J. Spangrude, S. Heimfeld, and I.L. Weissman, “Purification and characterization of mouse hematopoietic stem cells,” Science, Vol. 241 (1988), pp. 58-62.
p. 64 The valuable insight that scientists learned by: See E. Donnall Thomas’s Nobel Lecture, “Bone marrow transplantation—past, present and future,” December 8, 1990, which is available online at: http://www.nobel.se/medicine/laureates/1990/thomas-lecture.pdf. Thomas cites (p. 579) the late ’60s as “the beginning of the ‘modern’ era of human allogeneic marrow grafting.”
p. 64 In 2002, an estimated 30,000 autologous transplants: International Bone Marrow Transplant Registry, IBMTR/ABMTR Newsletter, Vol. 10, Issue 1, November 2003. See: http://www.ibmtr.org.
Source material includes interviews by the author with: Carolyn Compton: September 30, 2002. Howard Green: May 1, 2002; September 17, 2002; September 19, 2002; September 25, 2002. James Rheinwald: February 27, 2002; November 1, 2002; November 6, 2002. Pamela Robey: April 23, 2002.
p. 67 “If you can’t grow something, you can’t improve its growth, because there’s nowhere to start”: Howard Green, interview by the author, May 1, 2002.
p. 67 “I was doing it for the very reason”: John Gearhart, interview by the author, January 8, 2002.
p. 72 Historians claim that the first person to successfully graft: Howard M. Lenhoff and Sylvia G. Lenhoff, “Tissue grafting in animals: Its discovery in 1742 by Abraham Trembley as he experimented with hydra,” Biological Bulletin, Vol. 166 (February 1984), pp. 1-10.
p. 73 “I cannot explain what became of the body”: Abraham Trembley, Fourth Memoir, p. 175, Sylvia and Howard Lenhoff, Hydra and the Birth of Experimental Biology—1744 (The Boxwood Press, 1986).
p. 75 So successful were they in fine-tuning their methods: An article by Howard Green in the November 1991 issue of Scientific American (“Cultured cells for the treatment of disease,” pp. 96-102) provides fuller detail about Green’s growing of keratinocytes. Also refer to J.G. Rheinwald and H. Green, “Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma” (pp. 317-30) and “Serial cultivation of strains of human epidermal keratinocytes: The formation of keratinzing colonies from single cells” (pp. 331-44), Cell, Vol. 6 (1975).
p. 78 whose wounds proved more problematic: G.G. Gallico … H. Green, “Permanent coverage of large burn wounds with autologous cultured human epithelium,” The New England Journal of Medicine, Vol. 311 (1984), pp. 448-51.
Source material includes interviews by the author with Marie Di Berardino: January 30, 2004. Alan Bradley: February 4, 2004. Martin Evans: May 9, 2002; February 18, 2003; February 9, 2004. Matthew Kaufman: December 10, 2002. Gail Martin: February 2, 2002; February 13, 2002; March 17, 2004. Virginia Papaioannou: February 12, 2002; May 9, 2002; January 14, 2004. Elizabeth Robertson: April 13, 2004.
p. 83 “The concept of an embryo”: Scott F. Gilbert, Developmental Biology (Sixth edition, Massachusetts: Sinauer Associates, Inc., 2000), p. 3.
p. 83 The first gene ever identified in an organism: The LacZ gene of the bacteria E. coli was reported in 1969 by Jonathan Beckwith’s laboratory at Harvard Medical School.
p. 83 Nobel laureate François Jacob cogently offered at a scientific meeting: Jacob, who received a Nobel Prize in 1965 in medicine for his inroads into genes in bacteria, made these comments at a teratoma meeting held at Cold Spring Harbor in 1982: “Concluding remarks,” Teratocarcinoma Stem Cells, edited by L.M. Silver, G. Martin, and S. Strickland (New York: Cold Spring Harbor Laboratory, 1983), pp. 683-88.
p. 85 In the late ’60s: Martin Evans, interview by the author, May 9, 2002.
p. 86 they’d never grown their stem cells long-term: Pierce, interview by the author, March 26, 2004. Pierce said they grew bits of teratoma, but never attempted to make cell lines with EC cells.
p. 88 One notable example was organ transplants: The first heart transplant was done in ’67, the patient surviving another eighteen days. That same year the first successful liver transplant was performed by Dr. Thomas Starzl at the University of Colorado Health Sciences Center, Denver. Indicative of how far organ transplantation has come, doctors at the Jackson Memorial Hospital in Miami announced on March 18, 2004, that they had transplanted, as a unit, eight organs into a six-month-old baby with a smooth-muscle disorder. Coralie Carlson, Associated Press, March 18-19, 2004.
p. 89 Retinoic acid, for instance: Anton Jetten, director of the Cell Biology Section, National Institute of Environmental Health Sciences, NIH, interview by the author, December 1, 2003.
p. 90 a longtime question about the embryo had found some answers: John Gurdon, conversation with the author, October 18, 2002. For further background, see: J.B. Gurdon and J.A. Byrne, “The first half-century of nuclear transplantation,” Proceedings of the National Academy of Sciences (USA), Vol. 100 (2003), pp. 8048-52. This paper can be found at PNAS Online, Classics of the Scientific Literature: http://www.pnas.org/misc/classics.shtml.
p. 90 Marie Di Berardino, an eminent developmental geneticist: John Gurdon, in an email to the author (April 6, 2004), notes the following: “Marie Di Berardino was a member of the Briggs and King research group that first successfully transplanted living cell nuclei to eggs. Marie made a major contribution by discovering the chromosome abnormalities that arise from nuclear transplantation. Over many decades she has contributed greatly to the field of nuclear transfer in amphibia, well before mammalian nuclear transplantation was successful. In particular she has been by far the most important contributor to nuclear transfer work with the American frog Rana pipiens.”
p. 91 Robert Briggs and Thomas King at the Institute for Cancer Research: Briggs and King began their collaboration in February 1950. Marie Di Berardino, interview by the author, March 29, 2004. See Marie Di Berardino’s memoir of Briggs: Biographical Memoirs, Vol. 76 (1999), pp. 50-63. Online version: http://stills.nap.edu/html/biomems/rbriggs.html.
p. 92 would a research team vindicate Gurdon: K. Hochedlinger and R. Jaenisch, “Monoclonal mice generated by nuclear transfer from mature B and T donor cells,” Nature, Vol. 415 (2002), pp. 1035-38.
p. 92 “Briggs and King, and then Gurdon showed us”: Virginia Papaioannou, interview by the author, May 9, 2002.
p. 92 “No one had ever even guessed”: John R. Baker, Abraham Trembley of Geneva, Scientist and Philosopher 1710-1784 (London: Edward Arnold, 1952), p. xviii.
p. 95 Scientists’ new found ability to grow: For more about the keen interest in stem cells from teratomas at the time, and how they might assist biologists in exploring the mammalian embryo and human genetic diseases, see Gail Martin’s paper, “Teratocarcinomas and mammalian embryogenesis,” Science, Vol. 209 (1980), pp. 768-76.
p. 96 lying in a dish and “marking time”: Martin Evans, interview by Virginia Papaioannou, Albert Lasker Award for Basic Medical Research, 2001: http://www.laskerfoundation.org.
p. 97 Five months after Evans and Kaufman published: The Evans-Kaufman study: “Establishment in culture of pluripotential cells from mouse embryos,” Nature, Vol. 292 (1981), pp. 154-56. Gail Martin’s study: “Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells,” Proceedings of the National Academy of Sciences (USA), Vol. 78 (1981), pp. 7634-38.
p. 97 Martin Evans persevered toward this goal: Additional accounts of how Martin Evans went from his early studies of teratoma-burdened mice in the late ’60s to engineering a mouse with a genetic modification include: M. Evans, “The cultural mouse,” Nature Medicine, Vol. 7 (2001), pp. 1081-83. Also of interest: press releases and interviews on the Lasker Foundation’s Web site: http://www.laskerfoundation.org.
p. 98 By ’83, they had injected embryonic stem cells: Allan Bradley, email to the author, April 13, 2004.
p. 98 Mario Capecchi at the University of Utah: For a full telling by Capecchi about the milestone of engineering mice that have specific genes knocked out of them, refer to his article “Targeted gene replacement” in Scientific American (March 1994), pp. 52-59.
Source material includes interviews by the author with Joseph Altman: April 25, 2004. Arturo Alvarez-Buylla: March 13, 2003. Shirley Bayer: April 25, 2004. Fred Gage: April 15, 2002; March 19, 2003. Steven Goldman: November 27, 2001; December 7, 2001; February 17, 2002; May 8, 2002; February 5, 2003. Peter Marler: March 17, 2003; May 14, 2003. Fernando Nottebohm: May 10, 2001; January 9, 2002; February 21, 2003; March 3, 2003; March 4, 2003. Stewart Sell: February 4, 2003.
p. 101 “Stem cells can divide many times”: Fernando Nottebohm, interview by the author, January 9, 2002.
p. 102 alongside the stem cell in the bone marrow … lived a cousin stem cell: S.A. Kuznetsov and P.G. Robey, “A look at the history of bone marrow stromal cells: The legacy of Alexander Friedenstein,” Graft, Vol. 3 (2000), pp. 278-83.
p. 105 trained as a psychologist, Altman: Joseph Altman, interview by the author, April 25, 2004.
p. 105 “The first paper I published was a question mark”: J. Altman, “Are new neurons formed in the brains of adult mammals?” Science, Vol. 135 (1962), pp. 1127-28.
p. 107 She and her Purdue team reported in Science: S.A. Bayer … P.S. Puri: “Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life,” Science, Vol. 216 (1982), pp. 890-92.
p. 107 Accounts of new neurons forming: M. Cayre … A. Strambi, “The common properties of neurogenesis in the adult brain: From invertebrates to vertebrates,” Comparative Biochemstry and Physiology, Part B, Vol. 132 (2002), pp. 1-15. R.H. Nordlander and J.S. Edwards, “Postembryonic brain development in the monarch butterfly,” Wilhelm Roux’ Archive, Vol. 164 (1970), pp. 247-60. P.R. Johns and S.S. Easter, “Growth of the adult goldfish eye,” Journal of Comparative Neurology, Vol. 176 (1977), pp. 331-41.
p. 108 a student of the field’s originator, William Thorpe: The details about William Thorpe came from Peter Marler, interviewed by the author, March 17, 2003. Marler recounted that the first person to apply the sound spectrograph to the study of birdsong was actually Donald Borror, a distinguished field biologist at Ohio State University. Yet once Thorpe encountered the first of these instruments in England in the late ’40s, it was Thorpe, more than Borror, who grasped “its tremendous potential for studying birdsong and took the lead in applying it in a general way,” explains Marler. Describes Thorpe in his Nature paper titled “The process of song-learning in the chaffinch as studied by means of the sound spectrograph” (March 13, 1954), p. 465, “For the first use of the ‘Sonograph’ I have been greatly indebted to the kindness and courtesy of the Superintendent and staff of the Admiralty Research Laboratory at Teddington, whose ‘Sonograph’ was for a long time the sole instrument of its kind in England.”
p. 109 “We all believe it’s there”: Fernando Nottebohm, interview by the author, February 21, 2003.
p. 110 three to four times larger than a female’s: F. Nottebohm, “From bird song to neurogenesis,” Scientific American, Vol. 260 (1989), p. 75.
p. 110 From decades past came a handful of reports: Several of these reports (that testosterone elicits song in female birds) are referenced in Fernando Nottebohm’s paper “Testosterone triggers growth of brain vocal control nuclei in adult female canaries,” Brain Research, Vol. 189 (1980), pp. 429-
36. One paper refers to the pet-store scam: E.H. Herrick and J.O. Harris, “Singing female canaries,” Science, Vol. 125 (1957), pp. 1299-1300. A different paper by Herrick describes how several months’ worth of testosterone injections caused a “broad Breasted Bronze” turkey hen to start “gobbling” like a male. “The influence of androgens in a female turkey,” Poultry Science, Vol. 30 (1951), p. 758.
p. 111 It was the first time that a hormone: Nottebohm’s resulting paper: “Testosterone triggers growth of brain vocal control nuclei in adult female canaries,” Brain Research, Vol. 189 (1980), pp. 429-36.
p. 112 In various papers, including … in Science in 1981: “A brain for all seasons: Cyclical anatomical changes in song control nuclei of the canary brain,” Science, Vol. 214 (1981), pp. 1368-70.
p. 115 “I was sure they were neurons because”: Steven Goldman, interview by the author, February 5, 2003.
p. 115 “There seemed to be no question we were looking at neurons”: Fernando Nottebohm, interview by the author, February 21, 2003.
p. 116 and in his papers mentioned others before him: J. Altman, “Autoradiographic and histological studies of postnatal neurogenesis IV,” Journal of Comparative Neurology, Vol. 137 (1969), p. 433. To quote Altman in that paper: “Several investigators (Allen, ’12; Bryans, ’59; Globus and Kuhlenbeck, ’44; Opalski, ’34; Rydberg, ’32) reported the presence in adult animals and man of a mitotically active ‘subependymal layer’ (Kershman, ’38) around the ependymal wall of the anterior lateral ventricle.”
p. 116 “These facts would suggest a high rate of cell proliferation”: J. Altman and G.D. Das, “Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats,” Journal of Comparative Neurology, Vol. 124 (1965), p. 329.
p. 117 They announced their exceptional news: S. Goldman and F. Nottebohm, “Ependymal neurogenesis in adult female canaries,” Society for Neuroscience Abstracts, Vol. 8 (140), 1982. F. Nottebohm and S. Goldman, “Connectivity and kinetics of neurons born in adulthood,” Society for Neuroscience Abstracts, Vol. 8 (140), 1982. Steven Goldman, email to the author, April 19, 2004.
p. 117 Their paper followed in April: “Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain,” Proceedings of the National Academy of Sciences (USA), Vol. 80 (1983), pp. 2390-94.
p. 121 They were en route to Jerusalem: See Nottebohm’s “A white canary on Mount Acropolis,” which contains the lecture (series: The King Solomon Lectures) that he gave at the Hebrew University, Jerusalem; Journal of Comparative Physiology, Vol. 179 (1996), pp. 149-56.
Source material includes interviews by the author with Ariff Bongso: April 9, 2003; April 24, 2003. Doug Powers: April 3, 2003; April 11, 2003.
p. 123 “I guess I have never felt that knowledge is scary”: Ralph Brinster, interview by the author, August 20, 2003.
p. 123 to make better sense of a hierarchy: Beatrice Mintz, for one, was investigating “a hierarchy of stem cells” in the ’70s. See “Gene expression in neoplasia and differentiation,” Harvey Lectures Series 71 (New York: Academic Press, 1978), p. 217.
p. 124 Researchers had pried similar cells: Ariff Bongso’s 1994 paper in Human Reproduction (Vol. 9, pp. 2110-17) cites rabbits as the first animals from which ES cell lines were obtained, in 1965 (p. 2110). Bongso’s paper also includes (p. 2114) several other reports of cell lines made from cells taken from the inner cell mass of other species.
p. 125 literally, “in the glass” of a petri dish: Nowadays the term “in vitro,” as it applies to in vitro fertilization, is actually a misnomer, given that today’s petri dishes are usually made of plastic.
p. 126 Tens of thousands of test-tube babies later: According to the American Society for Reproductive Medicine, since 1981 more than a million ART (assisted reproductive technology) babies, which includes IVF babies, have been born worldwide. Of those, over 250,000 were born in the United States.
p. 128 An estimated two-thirds or more of egg-and-sperm unions: “What is an embryo?” by H.W. Jones Jr. and L. Veeck, Fertility and Sterility, Vol. 77 (April 2002), p. 659, “but a conservative estimate is that at least two-thirds of the products of oocyte and sperm fusion are in some way defective, either chromosomally or perhaps more subtly at the molecular level. The carrier of these abnormalities is so abnormal that it never implants, or, if it does implant, usually perishes very early in development.”
p. 128 A survey published in 2003: “Cryopreserved embryos in the United States and their availability for research,” Fertility and Sterility, Vol. 79 (2003), pp. 1063-69.
p. 129 “that it seemed to come from God’s own whisper”: Asiaweek, August 24, 2001, p. 34.
p. 131 “The embryo is not a person”: Lewis Wolpert, email to the author, April 16, 2003. About his well-known maxim, Wolpert communicated (in a second email to the author, November 20, 2002), “I did actually say it to a doctor at a meeting in Belgium who clearly irritated me; and my friend Jonathan Slack—now Prof at University of Bath—wrote it down and published it. I have a poster of it—the actual quote is ‘It is not birth, marriage,
or death, but gastrulation that is the most important event in your life’. A little exaggeration but even so … Lewis.”
p. 131 Bongso and his crew had carved: A. Bongso … S. Ratnam, “Isolation and culture of inner cell mass cells from human blastocysts,” Human Reproduction, Vol. 9 (1994), pp. 2110-17.
Source material includes interviews by the author with Alta Charo: March 28, 2003; March 26, 2004. Norman Fost: December 15, 2002; January 19, 2003; May 2, 2003; March 11, 2004. John Hearn: May 18, 2003; June 7, 2003. Jennifer Kalishman: July 10, 2003; July 22, 2003. Colin Stewart: April 29, 2003. James Thomson: August 10, 2002; May 30, 2003. Michael West: June 2, 2003; July 9, 2003; April 22, 2004.
p. 133 “As he told me, he is interested”: From a second-grader’s interview with James Thomson that appeared in Falk Kids Press, a supplement produced by Falk Elementary School in Madison, Wisconsin, that ran in the Wisconsin State Journal on April 14, 2002.
p. 134 “In short, the unborn have never been recognized”: Roe v. Wade, 410 U.S. 113, January 22, 1973.
p. 134 “to systematically address the issue of research on conceptuses”: Lori B. Andrews, “Regulation of experimentation on the unborn,” Journal of Legal Medicine, Vol. 14 (1993), p. 25.
p. 135 Newsweek spotlighted the “new hope”: Sharon Begley, “Cures from the womb: Fetal tissue promises new hope for incurable diseases and beguiling questions of science,” Newsweek, February 22, 1993, pp. 49-51.
p. 135 research into transplanting fetal tissue had carried on: From the NIH’s Office of Science Policy: “Chronology—Human Fetal Tissue Research,” draft August 29, 2002, footnote 3: “The moratorium also did not affect other types of research (i.e., basic and preclinical research) involving human fetal tissue obtained from induced or spontaneous abortions or stillbirths.”
p. 136 Each year in the early ’90s as many as 1.5 million fetuses: L.B. Finer and S.K. Henshaw, “Abortion incidence and services in the United States in 2000,” Perspectives on Sexual and Reproductive Health, Vol. 35 (2003), p. 8.
p. 140 As he told an audience years later: “Stem Cells on Land and at Sea” conference, Mt. Desert Island Biological Laboratory and the Jackson Laboratory, Bar Harbor, August 10, 2002.
p. 140 to grow a whole plant from a single mature corn cell: James Thomson, email to the author, June 2003: Mature cell, not a stem cell.
p. 140 Frederick Steward … had been the first to achieve this feat: Marc Cathey, “Good breeding curbs invasiveness,” The American Gardener, Vol. 82 (2), (March-April 2003).
p. 141 as one Michigan zoologist described: Susan Douglas Hill, “Origin of the regeneration blastema in polychaete annelids,” American Zoologist, Vol. 10 (1970), pp. 101-12. Hill at the University of Michigan noted in this paper that “the origin of cells of the regeneration blastema has long been a source of controversy,” but that “it has become quite well-established that in amphibians the limb blastema”—the knot of cells at the stump of a missing limb—“arises from previously differentiated cells in the immediate vicinity of the amputation site.” These cells appeared to undergo “dedifferentiation.” Continued Hill, “Gurdon’s (1964) revealing experiments with nuclear transplants have shown that in at least some cells the genome is not irreversibly altered or blocked by differentiation but retains its capacity to support development if placed in a suitable environment.”
p. 141 “I was never sure we would survive it”: Davor Solter, “James Thomson and the holy grail,” by Leslie Whitaker, The Pennsylvania Gazette (Jan-Feb 2002).
p. 142 “Once you put a blastocyst in culture”: Colin Stewart, interview by the author, April 29, 2003.
p. 142 “We chatted about how it would be interesting”: James Thomson, interview by the author, August 10, 2002.
p. 143 Problem solving was right up this Phi Beta Kappa’s alley: Thomson conveyed that he might have ended up a mathematician had it not been for his teacher Frederick Meins at the University of Illinois, who taught Thomson in the honors biology program. Thomson, in notes emailed to the author, July 17, 2003: “Fred certainly has a right to claim me as his intellectual progeny if he cares to, as, if he had not popped up in my life at that point, I probably would have continued to study Mathematics. One of his graduate students went on to make the first transgenic plant, so given the current controversy over GMO organisms in Europe, and the controversy over human ES cells, Fred can really claim to have influenced world events.”
p. 146 “made me think we could outsmart aging”: Michael West, interview by the author, July 9, 2003.
p. 146 aim of Geron’s scientists became … telomerase: Michael West, interview by the author, April 22, 2004. As West describes, Elizabeth Blackburn’s lab had found the “footprint” of the telomerase molecule, but it had not been isolated.
p. 148 Wisconsin Alumni Research Foundation: Not to be confused with the University of Wisconsin’s alumni office, its patent office WARF is a
story unto itself. WARF was founded in 1925 as a result of Professor Harry Steenbock’s then-controversial idea of providing the university with the patent rights to his discovery of how to activate vitamin D in food products. His innovation virtually eliminated the bone disease rickets while raking in millions of dollars in patent profits. WARF went on to fund the research of university scientists from proceeds derived from a growing pool of lucrative patents. See “Commercializing university research,” The New England Journal of Medicine, Vol. 314 (1986), pp. 1621-26.
p. 148 “a week later Mike West visited”: James Thomson, email to the author, July 17, 2003.
p. 152 how can its beginning be any less important: New scientific evidence in 2002 would support this pro-life stance, in Doerflinger’s opinion, which was the finding that within twenty-four hours of conception fertilized mammalian eggs have body-plan features previously undetected, and so weren’t just blobs of cells. See Nature, Vol. 418 (July 4, 2002), p. 14.
p. 152 “In his great novel The Brothers Karamazov”: Joseph A. Fiorenza, letter to Congress, July 10, 2001. U.S. Catholic Bishops, Office of Communications: http://www.nccbuscc.org/prolife/issues/bioethic/stemcell71001.htm.
Source material includes interviews with Marc Cathey: August 12, 2003. Peter Donovan: May 21, 2004. David Gardner: July, 1, 2003. John Gearhart: April 9, 2001; June 11-13, 2001; June 28, 2001; January 8, 2002; November 6, 2002; May 23, 2003; August 3, 2003; August 30, 2003. Robert Griesbach: December 11, 2003. Jeffrey Jones: September 8, 2003. Bruce Lahn: April 18, 2003. Beatrice Mintz: November 2, 2003; November 11, 2003. Virginia Papaioannou: May 9, 2002. Michael Shamblott: April 23, 2001; June 13, 2001; September 3, 2003. Susan Singer: April 10, 2002. Michael West: April 22, 2004.
p. 155 “The field of developmental biology has changed dramatically”: Virginia Papaioannou, interview by the author, December 12, 2002.
p. 155 Professor Shunong Li: Information about Shunong Li was provided by Bruce Lahn, a geneticist at the University of Chicago and an acquaintance of Li. Bruce Lahn, interview by the author, April 18, 2003; and emails to author, May 22, 2003, and August 7, 2003. According to Lahn, Li started to derive human embryonic cells in 1997.
p. 155 Mediterranean anemia, an inherited blood disease: Alternative names include thalessemia and Cooley’s anemia. This group of inherited conditions interfere with the production of hemoglobin, leading to too few red blood cells.
p. 156 Christopher Graham at Oxford: In an email (June 6, 2003) to the author, Graham stated that the title of his first stem cell-related “licence application [1987] was ‘Derivation of cell lines from the human conceptus to investigate the growth regulation of embryonic and tumour cells for the development of effective preimplantation diagnosis.’” Graham said in an earlier email (June 5, 2003) to the author, “It is possible that there seemed to be more people trying to derive human ES cells than were actually doing so. I obtained my material from two IVF clinics and consequently had to go through two ethical cttees in two different hospitals.”
p. 156 “their inner cell masses … screamed stem cells”: Robert Edwards, email to the author, May 20, 2003.
p. 157 a roughly six-day-old embryo: Jeffrey Jones, email to the author, February 13, 2004: “Actually, the very 1st stem cell line was created from a DAY 7 embryo. The other 4 cell lines came from DAY 6 embryos.”
p. 158 The very term embryology had been growing stale: Developmental biologist J.D. Ebert, in a talk at the Taniguchi Symposium on Developmental Biology, April ’97, remarked that “the term ‘developmental biology’ did not come into common usage until the early 1950s.” From the symposium catalogue, p. 86.
p. 158 larger-than-life Cecil B. De Mille figure: Marc Cathey, who worked in Frederick Steward’s lab, provided this depiction of Steward in a telephone interview by the author, August 12, 2003. He recalled Steward as saying “we only do epics” and further described Steward as “all drama-and-hell.”
p. 158 Steward’s precedent of cloning a carrot plant: According to Cathey, Steward’s lab-grown carrot was the first plant cloned from a single cell. See The American Gardener (March/April 2003), p. 13. Author could find no further confirmation. Over time, botanists have found that Steward’s technique of growing a plant from a single adult cell is less efficient than growing a plant from a group of meristem cells taken from an adult plant’s organ, according to Robert Griesbach of the U.S. National Arboretum. The latter is the method most often used nowadays for cloning plants. One of Steward’s claims to fame, however, is his use of the special coconut-milk culture. The vast majority of blooms that greet one at a flower market have been grown in a similar coconut-milk medium, confirms Griesbach, which means that “Steward’s experiment is part of every birth, wedding, and funeral,” says Cathey, interview by the author, August 12, 2003. Robert Griesbach, interview by the author, December 11, 2003; and email, December 15, 2003.
p. 159 “possesses a power of its own”: Theodor Schwann, Microscopical Researches into the Accordance in the Structure and Growth of Animals and Plants,” translated from German by Henry Smith (London: The Sydenham Society, 1847), p. 192. (Of interest: pp. 186-215.)
pp. 159-160 Robert Briggs and Thomas King had set the stage: R. Briggs and T.J. King, “Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs,” Proceedings of the National Academy of Sciences (USA), Vol. 38 (1952), pp. 455-63.
p. 160 Beatrice Mintz … and Tibby Russell … had determined: “Gene-induced embryological modifications of primordial germ cells in the mouse,” Journal of Experimental Zoology, Vol. 134 (1957), pp. 227-37.
p. 161 “invisible developmental history”: Beatrice Mintz, interview by the author, September 11, 2003.
p. 167 “the collaboration was really a hedge”: Michael West, interview by the author, June 2, 2003.
p. 171 Ian Wilmut and his team at the Roslin Institute: I. Wilmut … K.H. Campbell, “Viable offspring derived from fetal and adult mammalian cells,” Nature, Vol. 385 (1997), pp. 810-13.
p. 172 They included “Huxleyish scenarios”: Johns Hopkins Magazine, November 1997.
p. 173 “If we are successful in genetically manipulating our cells”: John Gearhart, notes emailed to the author, July 30, 2003.
p. 173 “When Dolly happened”: James Thomson, interview by the author, May 30, 2003.
p. 174 Thomson and Jeffrey Jones finally started growing: Jeffrey Jones, in an email (September 22, 2003) to the author: “My records also show that the first human embryo donated to Jamie’s IRB protocol was donated on 5/10/96 but not thawed and cultured until a few months later on 8/23/96. For the next year and a half (from this date until December ’97), an additional 32 embryos were donated to this protocol. However no hES [human ES] cell lines were created until we switched to David Gardner’s sequential embryo culture system in January of 1998.”
p. 174 Working in a small room: James Thomson’s early IVF embryo work, done in a small room at the University of Wisconsin Hospital, was isolated from federally-funded projects. The research later moved off-campus to WiCell Research Institute. As Alta Charo cites, a ruling in the fall of ’01 would verify that, in fact, it is not illegal to do private work in the same lab as federally-funded work. Rather, the problem that presents itself, says Charo, is that it’s so logistically difficult to comply with the legal need to keep every petri dish and pipette purchased with private funds separate from materials purchased with public funds “that many researchers choose to create a separate location.”
p. 174 the two papers were published: J.A. Thomson … J.M. Jones, “Embryonic stem cell lines derived from human blastocysts,” Science, Vol. 282 (1998), pp. 1145-47. M.J. Shamblott … J.D. Gearhart: “Derivation of
pluripotent stem cells from cultured human primordial germ cells,” Proceedings of the National Academy of Sciences (USA), Vol. 95 (1998), pp. 13726-31.
p. 175 Professor Li lost his cell line: Bruce Lahn, in an email to the author, May 22, 2003: “Professor Shunong Li published his human ES cell line in January of 1998, in Academic Journal of Sun Yat-Sen University of Medical Science 19(1):77-78. He is still at the University, and I have frequent contact with him. In the paper, he passaged his line 5 times, and showed that his cells are positive for alkaline phosphotase, a marker for undifferentiated human ES cells. The line was lost when, during summer vacation, the liquid nitrogen tank dried up.”
p. 176 Gearhart observed in a 1999 letter to Roy Stevens: Letter from John Gearhart to Roy Stevens, March 16, 1999.
p. 176 “There is almost no realm of medicine”: Harold Varmus quoted by Sharon Schmickle, Star Tribune, April 11, 1999.
p. 177 “Research and demonstrations of clinical efficacy”: Paul Berg, testimony, U.S. Senate Committee on the Judiciary, “Drawing the line between ethical regenerative medicine research and immoral human reproductive cloning,” March 19, 2003.
Source material includes interviews by the author with Alejandro Sánchez Alvarado: March 15, 2002; January 27, 2004. Diana Clarke: April 15, 2002; April 18, 2002. George Daley: May 29, 2001; June 21, 2001; August 16, 2002; October 3, 2003; January 19, 2004. Curt Freed: October 24, 2003. Mark Keating: May 14, 2003. Jordana Lenon: July 30, 2003. Éva Mezey: April 24, 2002; September 23, 2003. Timothy Moffitt: May 31, 2001. Shannon Odelberg: March 10, 2004. Charles Peters: October 13, 2003. Catherine Verfaillie: May 20, 2002; November 4, 2003. Frances Verter: November 13, 2003.
p. 179 “But extraordinary claims require extraordinary evidence”: Carl Sagan, Broca’s Brain: Reflections on the Romance of Science (New York: Random House, 1979), p. 62.
p. 180 they “could transform the practice of medicine”: George Daley, “Stem cells: Debunking the myths, developing the medicine,” Museum of Science, Boston, March 14, 2001.
p. 180 during a press seminar at Whitehead: “New Horizons in the Post-Genome World,” a Whitehead Institute Press Seminar, May 2-4, 2001. Daley’s talk “Stem Cells: Medicine and Myth” was on May 4, 2001.
p. 182 Harvard Medical School’s Evan Snyder: B.D. Yandava … E.Y. Snyder, “Global cell replacement is feasible via neural stem cell transplanta-
tion: Evidence from the dysmyelinated shiverer mouse brain,” Proceedings of the National Academy of Sciences (USA), Vol. 96 (1999), pp. 7029-34.
p. 182 scientists at the Salk Institute in California and Sweden’s Sahlgrenska University Hospital: P.S. Eriksson … F.H. Gage, “Neurogenesis in the adult human hippocampus,” Nature Medicine, Vol. 4 (1998), pp. 1313-17.
p. 182 London taxi driver study: E.A. Maguire … D.C. Frith, “Navigation-related structural change in the hippocampi of taxi drivers,” Proceedings of the National Academy of Sciences (USA), Vol. 97 (2000), pp. 4398-403.
p. 183 Weissman’s Stanford lab had persevered: G.J. Spangrude … I.L. Weissman, “Purification and characterization of mouse hematopoietic stem cells,” Science, Vol. 241 (1988), pp. 58-62. C.M. Baum … B. Peault, “Isolation of a candidate human hematopoietic stem-cell population,” Proceedings of the National Academy of Sciences (USA), Vol. 89 (1992), pp. 2804-08.
p. 184 “We can do this”: John Gearhart, Oncology Seminar Series, Dana-Farber Cancer Institute, April 10, 2001.
p. 185 the first adults to benefit from this new technology: Two adults with chronic myelogenous leukemia. See: A.L. Pecora et al., “Prompt and durable engraftment in two older patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated umbilical cord blood,” Bone Marrow Transplantation, Vol. 25 (2000), pp. 797-99. Frances Verter, writer and keeper of the outstanding Web site “A Parent’s Guide to Cord Blood Banks,” noted the following in an email (November 13, 2003) to the author: “The small volume of cord blood collections, and hence the insufficient number of stem cells, was once a barrier to adult usage, but this has now been overcome by either multiplying the cells in vitro prior to transplant (J Jaroscak, et al., Blood 2003; 101:5061), or by transplanting multiple cord blood units simultaneously (JR Wingard, Medscape [TM]2001; Medscape Conf Covereage, Amer Soc Hem 43rd Annual Meeting).” See http://www.parentsguidecordblood.com for more information on the subject. Also refer to issue #51 of the newsletter on the Blood & Marrow Transplant Information Network (http://www.bmtinfonet.org), another top-notch Web site.
p. 186 how effectively can a baby’s banked umbilical cord blood treat an illness: For in-depth information about cord blood’s medical uses and how to evaluate the public/private banks that collect it, visit “A Parent’s Guide to Cord Blood Banks” at http://www.parentsguidecordblood.com. This Web site provides insights into the pros and cons of cord blood banking, the diseases treated with cord blood, and how the stem cells in cord blood compare with those in bone marrow.
p. 188 “We really had a hard time convincing ourselves”: Angelo Vescovi, quoted by John Travis, “Cellular conversion turns brain into blood,” by John Travis, Science News, January 23, 1999. The reported study: C.R.
Bjornson … A.L. Vescovi, “Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo,” Science, Vol. 283 (1999), pp. 534-37.
p. 189 in the lab of Éva Mezey: “Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow.” Ran in the December 1, 2000, issue of Science, Vol. 290.
p. 190 claim by Helen Blau and coworkers at Stanford: “From marrow to brain: Expression of neuronal phenotypes in adult mice.” Ran in the December 1, 2000, issue of Science, Vol. 290.
p. 190 A collaboration orchestrated by Diane Krause: D.S. Krause … S.J. Sharkis, “Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell,” Cell, Vol. 105 (2001), pp. 369-77.
p. 190 This finding was soon eclipsed by another: Catherine Verfaillie first announced the finding of her bone marrow stem cells at a meeting of the American Society of Hematology, December 1999. Her lab would publish several papers about the nature of these cells. One of the most notable: “Pluripotency of mesenchymal stem cells derived from adult marrow,” Nature, Vol. 418 (2002), pp. 41-49.
p. 191 A journal article had lately reminded scientists: The article was by Darwin Prockop, then at Allegheny University of the Health Sciences in Philadelphia: “Marrow stromal cells as stem cells for nonhematopoietic tissues,” Science, Vol. 276 (April 4, 1997), pp. 71-74.
p. 193 This seemed to strongly validate her cell’s multipotent versatility: Verfaillie called her cell a “multipotent adult progenitor cell,” or MAPC.
p. 193 Numerous studies now indicate: Two such studies showing the brain’s recruitment of new cells soon after injury: H. Nakatomi … M. Nakafuku, “Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors,” Cell, Vol. 23 (2002), pp. 429-41. J. Liu … F.R. Sharp, “Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils,” Journal of Neuroscience, Vol. 18 (1998), pp. 7768-78.
p. 196 “Are there in this Insect”: History of Regeneration Research, p. 74. Original source: V.P. Dawson, “Nature’s enigma: The problem of the polyp in the letters of Bonnet, Trembley, and Reaumur,” American Philosophical Society, Philadelphia, 1987.
p. 196 an excerpt from one lengthy report: T.H. Morgan, “The physiology of regeneration,” Journal of Experimental Zoölogy, Vol. 3 (1906), pp. 458-59. Before long, Morgan would become so discouraged by his failure to figure out regeneration, that he would switch to studying genetics and wind up just about the most famous geneticist of his day.
p. 197 Either these immature cells were holdovers: In his two-volume work Regeneration and Transplantation (1927, 1931), Eugen Korschelt fre-
quently cites these two possible explanations for limb replacement. In one passage, he refers to the “redifferentiation of cells or reactivation of available reserves” (p. 2). Elsewhere he cites these prerequisites for the regrowth of lost parts: “Sufficient indifferent cellular material must be available for this, be it that cells which have actually remained indifferent are present, being left over from embryonic development, and which proceed to divide when the occasion arises, or that it is possible for already differentiated cells to return to the indifferent state” (p. 620). Some scientists of his day, Korschelt notes, felt that “once cells have developed along specific lines, they are in no case able later to change tack and to continue along different lines” (p. 334). Korschelt, however, maintains that “in view of the facts at our disposal, there can scarcely be any denying the possibility that developmental processes are reversible” (p. 335).
p. 197 “Either it’s a very early stem cell”: Catherine Verfaillie, interview by the author, May 20, 2002.
p. 198 Max Planck Institute team in Dresden: shows cells in salamander’s tail dedifferentiating into embryonic cells: K. Echeverri and E.M. Tanaka, “Ectoderm to mesoderm lineage switching during axolotl tail regeneration,” Science, Vol. 298 (2002), pp. 1993-96.
p. 198 “The ability to regrow missing parts”: Alejandro Sánchez Alvarado, interview by the author, April 15, 2002.
p. 199 “Any cell in the body can behave as any other cell”: Christopher Potten, conversation with the author, March 24, 2003.
p. 200 Mark Keating … and his postdoc Shannon Odelberg: suggest that specialized mammalian cells can dedifferentiate: S.J. Odelberg … M.T. Keating, “Dedifferentiation of mammalian myotubes induced by msx1,” Cell, Vol. 103 (2000), pp. 1099-1109.
p. 200 “I don’t think there’s any reason”: Mark Keating, interview by the author, May 14, 2003.
p. 201 George Daley and Rudolf Jaenisch collaborated: W.M. Rideout … R. Jaenisch, “Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy,” Cell, Vol. 109 (2002), pp. 17-27.
p. 201 On August 9, 2001, George W. Bush … to announce: For press release, see http://www.whitehouse.gov/news/releases/2001/08/print/20010809-2.html.
p. 201 Thomson himself “was reportedly hang gliding”: Jordana Lenon, interview by the author, July 30, 2003.
p. 202 The August decision was neither an executive order: Lana Skirboll, email to the author, July 20, 2004.
p. 203 He had received an experimental transplant: Curt Freed, interviews by the author, October 24, 2003; March 2004.
Source material includes interviews by the author with Douglas Cotanche: March 19, 2002. Marie Filbin: May 3, 2004. Rebecca Folkerth: October 9, 2001. Donald Gash: January 15, 2003. Emanuela Gussoni: January 7, 2003. Kenneth Kenyon: November 1, 2003; January 16, 2004. Ronald McKay: November 11, 2001; January 31, 2002; January 20, 2004. Donald Orlic: February 20, 2004. Thomas Reh: January 4, 2002; January 15, 2002; January 13, 2004. Simon Tran: October 22, 2003. Ann Traynor: February 2, 2004. Henriette van Praag: January 5, 2004. Michael Young: March 29, 2001; April 3, 2001; March 20, 2002; October 9, 2003; January 26, 2004.
p. 205 “The challenge is to move basic cell biology”: George Daley, lecture: “Stem cells: Debunking the myths, developing the medicine,” Boston’s Museum of Science, March 14, 2001.
p. 207 The University of Toronto researchers: V. Tropepe … D. van der Kooy, “Retinal stem cells in the adult mammalian eye,” Science, Vol. 287 (2000), pp. 2032-36.
p. 209 In his talk—which was titled “Is the potential of stem cells”: Ruben Adler, lecture, Schepens Eye Research Institute, May 17, 2001.
p. 211 Parkinson’s patient who had traveled to China: The journal paper that reviews this case: R.D. Folkerth and R. Durso, “Survival and proliferation of nonneural tissues, with obstruction of cerebral ventricles, in a Parkinsonian patient treated with fetal allografts,” Neurology, Vol. 46 (1996), pp. 1219-25.
p. 213 notes Kenneth Kenyon, who developed limbal cell transplants: K.R. Kenyon and S.C. Tseng, “Limbal autograft transplantation for ocular surface disorders,” Ophthalmology, Vol. 96 (1989), pp. 709-22.
p. 216 FDA approval cannot be taken as a true indicator: Paul Richards, interview by the author, March 8, 2004; email to the author, April 20, 2004.
p. 221 Approximately one in every 400 to 500 children: National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), NIH. See http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm#8.
p. 221 “Eighty percent of patients”: James Shapiro, email to the author, January 28, 2004. Shapiro also noted in his email that “over 300 patients have received islet transplants worldwide since the introduction of the Edmonton Protocol. An international multicenter trial is currently underway at the nine sites, funded by the Immune Tolerance Network.”
p. 225 Henriette van Praag at the Salk Institute made a discovery: H. van Praag … F.H. Gage, “Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus,” Nature Neuroscience, Vol. 2 (1999), pp. 266-70. Also see: H. van Praag … F.H. Gage, “Running enhances
neurogenesis, learning and long-term potentiation in mice,” Proceedings of National Academy of Sciences (USA), Vol. 96 (1999), pp. 13427-31.
p. 226 It refers to mouse studies conducted by Donald Orlic: One such Orlic study is: “Bone marrow cells regenerate infarcted myocardium,” Nature, Vol. 410 (2001), pp. 701-05.
p. 226 In recent investigations: Strauer et al., Circulation, Vol. 106 (2002), pp. 1913-18; Assmus et al., Circulation, Vol. 106 (2002), pp. 3009-17; Stamm et al., Lancet, Vol. 361 (2003), pp. 45-46; Tse et al., Lancet, Vol. 361 (2003), pp. 47-49.
p. 229 “Being able to control transitions”: Ron McKay, interview by the author, April 23, 2002.
p. 229 Two years later, they went a step further: J.H. Kim … R. McKay, “Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease,” Nature, Vol. 418 (2002), pp. 50-56.
p. 229 “up to a fifty percent reduction”: M. Barinaga, “Fetal neuron grafts pave the way for stem cell therapies,” Science, Vol. 287 (2000), p. 1422.
p. 230 They derived these regenerative progenitor cells: Charles Vacanti, emails to the author, March 22 and March 23, 2004. Charles Vacanti is one of four brothers who together are known for pioneering the field of tissue engineering. They have been called the “stem cells for the entire field.”
p. 231 stem cells from sheep bone marrow: T.E. Perry … J.E. Mayer, “Bone marrow as a cell source for tissue engineering heart valves,” The Annals of Thoracic Surgery, Vol. 75 (2003), pp. 761-67.
p. 231 approximately 2.5 million people living: International Campaign for Cures of Spinal Cord Injury Paralysis.
p. 233 researchers have identified a patch of cells: These experiments were done by Michael Zuber in the laboratory of William Harris at the University of Cambridge.
Source material includes interviews by the author with Ariff Bongso: April 9, 2003. Timothy McCaffrey: December 19, 2003. Andrew McMahon: March 29, 2004. Douglas Melton: March 5, 2002; November 20, 2002. Terry Mock (Champion Tree Project): April 4, 2004. Jonathan Tilly: March 29, 2004.
p. 235 “We are now in the center of biology itself”: Ronald McKay, “Medical evolution” by Gregg Easterbrook, The New Republic, March 1, 1999, p. 20.
p. 235 a study by Japanese scientists that involved planarians: F. Cebria … K. Agata, “FGFR-related gene nou-darake restricts brain tissues to the hea region of planarians,” Nature, Vol. 419 (2002), pp. 620-24.
p. 235 shown by Thomas Hunt Morgan: “Experimental studies of the regeneration of Planaria maculata,” Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, Vol. 7 (1898), pp. 364-97.
p. 236 the Champion Tree Project International: For more information visit: http://www.championtreeproject.org.
p. 236 a Massachusetts General Hospital team unfurled its surprise finding: F. Johnson … J.L. Tilly, “Germline stem cells and follicular renewal in the postnatal mammalian ovary,” Nature, Vol. 428 (2004), pp. 145-50. “It’s true that new markers very much helped with this work, though we were led into this by studying cell death.” Jonathan Tilly, interview by the author, March 29, 2004.
p. 236 what has tended to be “over-hyped”: Christopher Potten, conversation with the author, March 24, 2003.
p. 237 Possibly as many as ten percent of a cell’s genes: Ron McKay, interview by the author, April 23, 2002.
p. 237 stridently opposed to human reproductive cloning: Many researchers who oppose the reproductive cloning of humans nevertheless support the cloning of nonhuman animals. Cloning cows and sheep, an alternative to the lengthy process of breeding, is seen as a valuable source of agricultural products; and, if made to carry foreign genes, cloned animals might be useful producers of important human proteins. Cloning might also help to increase the numbers of certain endangered species. Note that the world’s first such clone, a male banteng, was born at the San Diego Zoo in January 2004.
p. 238 In the United States, scientists … who rely on government funding: The National Institutes of Health alone “supports an extramural research community of over 200,000 research personnel who are affiliated with approximately 1,700 organizations.” Lana Skirboll, director of the Office of Science Policy, NIH, email to the author, April 1, 2004.
p. 240 Singapore’s bioethics committee: “Ethical, legal and social issues in human stem cell research, reproductive and therapeutic cloning,” June 2002, http://www.bioethics-singapore.org/resources/reports1.html.
p. 241 a South Korean team reported: W.S. Hwang … S.Y. Moon, “Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst,” Science, Vol. 303 (2004), pp. 1669-74.
p. 242 They maintain that they have developed culture techniques: Aside from TriStem, other groups that have reported turning one type of mature cell into another includes a team at the Scripps Research Institute in San Diego that announced in 2004 that it has a chemical that can induce muscle cells from mice to dedifferentiate into immature status, from which state the cells can be directed into other cell types.
p. 242 The British company TriStem: I.S. Abuljadayel, “Induction of stem cell-like plasticity in mononuclear cells derived from unmobilised adult human peripheral blood,” Current Medical Research and Opinion, Vol. 19 (2003), pp. 355-75.
p. 243 “If we say any cell has the potential”: Harold Varmus, “Medical evolution,” by Gregg Easterbrook, The New Republic, March 1, 1999, p. 23.
p. 243 “The Dolly experiment says that any cell”: James Thomson, interview by the author, May 10, 2003.
p. 243 “It would be surprising if the first lines were any good”: Doug Melton, interview by the author, March 5, 2002.
p. 244 Massachusetts had passed a law in 1974: Massachusetts General Laws, Chapter 112, Section 12J.
p. 245 grown in the company of mouse cells: Andrew McMahon, interview by the author, March 29, 2004.
p. 247 Author’s note: When I asked Hans Bode whether a hydra really is an immortal animal, his response was: “Well, it might be, but obviously you can’t prove it’s immortal.”