Pardee, Jacob, and Monod published: Arthur B. Pardee, François Jacob, and Jacques Monod, “The genetic control and cytoplasmic expression of ‘inducibility’ in the synthesis of β=galactosidase by E. coli,” Journal of Molecular Biology 1, no. 2 (1959): 165–78.
“The genome contains”: François Jacob and Jacques Monod, “Genetic regulatory mechanisms in the synthesis of proteins,” Journal of Molecular Biology 3, no. 3 (1961): 318–56.
1953 paper: Watson and Crick, “Molecular structure of nucleic acids,” 738.
“He called it DNA polymerase”: Arthur Kornberg, “Biologic synthesis of deoxyribonucleic acid,” Science 131, no. 3412 (1960): 1503–8.
“Five years ago”: Ibid.
From Genes to Genesis
In the beginning: Richard Dawkins, The Selfish Gene (Oxford: Oxford University Press, 1989), 12.
Am not I: Nicholas Marsh, William Blake: The Poems (Houndmills, Basingstoke, England: Palgrave, 2001), 56.
Lewis studied mutants: Many of these mutants had initially been created by Alfred Sturtevant and Calvin Bridges. Details of the mutants and the relevant genes can be found in Ed Lewis’s Nobel lecture, December 8, 1995.
“Is it sin”: Friedrich Max Müller, Memories: A Story of German Love (Chicago: A. C. McClurg, 1902), 20.
In Leo Lionni’s classic children’s book: Leo Lionni, Inch by Inch (New York: I. Obolensky, 1960).
“We propose to identify every cell in the worm”: James F. Crow and W. F. Dove, Perspectives on Genetics: Anecdotal, Historical, and Critical Commentaries, 1987–1998 (Madison: University of Wisconsin Press, 2000), 176.
“like watching a bowl of hundreds of grapes”: Robert Horvitz, author interview, 2012.
“There is no history”: Ralph Waldo Emerson, The Journals and Miscellaneous Notebooks of Ralph Waldo Emerson, vol. 7, ed. William H. Gilman (Cambridge, MA: Belknap Press of Harvard University Press, 1960), 202.
131 extra cells had somehow disappeared: Ning Yang and Ing Swie Goping, Apoptosis (San Rafael, CA: Morgan & Claypool Life Sciences, 2013), “C. elegans and Discovery of the Caspases.”
he called it apoptosis: John F. R. Kerr, Andrew H. Wyllie, and Alastair R. Currie, “Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics,” British Journal of Cancer 26, no. 4 (1972): 239.
In another mutant, dead cells: This mutant was initially identified by Ed Hedgecock. Robert Horvitz, author interview, 2013.
Horvitz and Sulston discovered: J. E. Sulston and H. R. Horvitz, “Post-embryonic cell lineages of the nematode, Caenorhabditis elegans,” Developmental Biology 56. no. 1 (March 1977): 110–56. Also see Judith Kimble and David Hirsh, “The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans,” Developmental Biology 70, no. 2 (1979): 396–417.
But even natural ambiguity: Judith Kimble, “Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans,” Developmental Biology 87, no. 2 (1981): 286–300.
The British way, Brenner wrote: W. J. Gehring, Master Control Genes in Development and Evolution: The Homeobox Story (New Haven, CT: Yale University Press, 1998), 56.
began to study the effects of sharp perturbations on cell fates: The method had been pioneered by John White and John Sulston. Robert Horvitz, author interview, 2013.
As one scientist described it: Gary F. Marcus, The Birth of the Mind: How a Tiny Number of Genes Creates the Complexities of Human Thought (New York: Basic Books, 2004), “Chapter 4: Aristotle’s Impetus.”
The geneticist Antoine Danchin: Antoine Danchin, The Delphic Boat: What Genomes Tell Us (Cambridge, MA: Harvard University Press, 2002).
Some genes, Dawkins suggests: Richard Dawkins, A Devil’s Chaplain: Reflections on Hope, Lies, Science, and Love (Boston: Houghton Mifflin, 2003), 105.
PART THREE: “THE DREAMS OF GENETICISTS”
Progress in science depends on new techniques: Sydney Brenner, “Life sentences: Detective Rummage investigates,” Scientist—the Newspaper for the Science Professional 16, no. 16 (2002): 15.
If we are right . . . it is possible to induce: “DNA as the ‘stuff of genes’: The discovery of the transforming principle, 1940–1944,” Oswald T. Avery Collection, National Institutes of Health, http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/157.
“Crossing Over”
A biochemist by training: Details of Paul Berg’s education and sabbatical are from the author’s interview with Paul Berg, 2013; and “The Paul Berg Papers,” Profiles in Science, National Library of Medicine, http://profiles.nlm.nih.gov/CD/.
a “piece of bad news wrapped in a protein coat”: M. B. Oldstone, “Rous-Whipple Award Lecture. Viruses and diseases of the twenty-first century,” American Journal of Pathology 143, no. 5 (1993): 1241.
Unlike many viruses, Berg learned: David A. Jackson, Robert H. Symons, and Paul Berg, “Biochemical method for inserting new genetic information into DNA of simian virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli,” Proceedings of the National Academy of Sciences 69, no. 10 (1972): 2904–09.
Peter Lobban, had written a thesis: P. E. Lobban, “The generation of transducing phage in vitro,” (essay for third PhD examination, Stanford University, November 6, 1969).
Avery, after all, had boiled it: Oswald T. Avery, Colin M. MacLeod, and Maclyn McCarty. “Studies on the chemical nature of the substance inducing transformation of pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III,” Journal of Experimental Medicine 79, no. 2 (1944): 137–58.
“none of the individual procedures, manipulations, and reagents: P. Berg and J. E. Mertz, “Personal reflections on the origins and emergence of recombinant DNA technology,” Genetics 184, no. 1 (2010): 9–17, doi:10.1534/genetics.109.112144.
In the winter of 1970, Berg and David Jackson: Jackson, Symons, and Berg, “Biochemical method for inserting new genetic information into DNA of simian virus 40,” Proceedings of the National Academy of Sciences 69, no. 10 (1972): 2904–09.
In June 1972, Mertz traveled from Stanford: Kathi E. Hanna, ed., Biomedical politics (Washington, DC: National Academies Press, 1991), 266.
“You can stop splitting the atom”: Erwin Chargaff, “On the dangers of genetic meddling,” Science 192, no. 4243 (1976): 938.
“My first reaction was: this was absurd”: “Reaction to Outrage over Recombinant DNA, Paul Berg.” DNA Learning Center, doi:https://www.dnalc.org/view/15017-Reaction-to-outrage-over-recombinant-DNA-Paul-Berg.html.
Dulbecco had even offered to drink SV40: Shane Crotty, Ahead of the Curve: David Baltimore’s Life in Science (Berkeley: University of California Press, 2001), 95.
“In truth, I knew the risk was little”: Paul Berg, author interview, 2013.
“Janet really made the process vastly more efficient”: Ibid.
Boyer had arrived in San Francisco in the summer of ’66: Details of the story of Boyer and Cohen come from the following resources: John Archibald, One Plus One Equals One: Symbiosis and the Evolution of Complex Life (Oxford: Oxford University Press, 2014). Also see Stanley N. Cohen et al., “Construction of biologically functional bacterial plasmids in vitro,” Proceedings of the National Academy of Sciences 70, no. 11 (1973): 3240–44.
Late that evening, Boyer: Details of this episode are from several sources including Stanley Falkow, “I’ll Have the Chopped Liver Please, Or How I Learned to Love the Clone,” ASM News 67, no. 11 (2001); Paul Berg, author interview, 2015; Jane Gitschier, “Wonderful life: An interview with Herb Boyer,” PLOS Genetics (September 25, 2009).
The New Music
Each generation needs a new music: Crick, What Mad Pursuit, 74.
People now made music from everything: Richard Powers, Orfeo: A Novel (New York: W. W. Norton, 2014), 330.
In the early 1950s, Sanger had solved: Frederick Sanger, “The arrangement of amino acids in pr
oteins,” Advances in Protein Chemistry 7 (1951): 1–67.
Frederick Banting, and his medical student: Frederick Banting et al., “The effects of insulin on experimental hyperglycemia in rabbits,” American Journal of Physiology 62, no. 3 (1922).
In 1958, Sanger won the Nobel Prize: “The Nobel Prize in Chemistry 1958,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1958/.
his “lean years”: Frederick Sanger, Selected Papers of Frederick Sanger: With Commentaries, vol. 1, ed. Margaret Dowding (Singapore: World Scientific, 1996), 11–12.
In the summer of 1962, Sanger moved: George G. Brownlee, Fred Sanger—Double Nobel Laureate: A Biography (Cambridge: Cambridge University Press, 2014), 20.
On February 24, 1977, Sanger used: F. Sanger et al., “Nucleotide sequence of bacteriophage Φ174 DNA,” Nature 265, no. 5596 (1977): 687–95, doi:10.1038/265687a0.
“The sequence identifies many of the features”: Ibid.
In 1977, two scientists working independently: Sayeeda Zain et al., “Nucleotide sequence analysis of the leader segments in a cloned copy of adenovirus 2 fiber mRNA,” Cell 16, no. 4 (1979): 851–61. Also see “Physiology or Medicine 1993—press release,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1993/press.html.
The “arsenal of chemical manipulations”: Walter Sullivan, “Genetic decoders plumbing the deepest secrets of life processes,” New York Times, June 20, 1977.
“Genetic engineering . . . implies deliberate”: Jean S. Medawar, Aristotle to Zoos: A Philosophical Dictionary of Biology (Cambridge, MA: Harvard University Press, 1985), 37–38.
“By learning to manipulate genes experimentally”: Paul Berg, author interview, September 2015.
T cells sense the presence of invading cells: J. P Allison, B. W. McIntyre, and D. Bloch, “Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody,” Journal of Immunology 129 (1982): 2293–2300; K. Haskins et al, “The major histocompatibility complex-restricted antigen receptor on T cells: I. Isolation with a monoclonal antibody,” Journal of Experimental Medicine 157 (1983): 1149–69.
In 1970, David Baltimore and Howard Temin: “Physiology or Medicine 1975—Press Release,” Nobelprize.org. Nobel Media AB 2014. Web. 5 Aug 2015. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1975/press.html.
In 1984, this technique was deployed: S. M. Hedrick et al., “Isolation of cDNA clones encoding T cell-specific membrane-associated proteins,” Nature 308 (1984): 149–53; Y. Yanagi et al., “A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains,” Nature 308 (1984): 145–49.
“liberated by cloning”: Steve McKnight, “Pure genes, pure genius,” Cell 150, no. 6 (September 14, 2012): 1100–1102.
Einsteins on the Beach
I believe in the inalienable right: Sydney Brenner, “The influence of the press at the Asilomar Conference, 1975,” Web of Stories, http://www.webofstories.com/play/sydney.brenner/182;jsessionid=2c147f1c4222a58715e708eabd868e58.
In the summer of 1972: Crotty, Ahead of the Curve, 93.
“the beginning of a new era”: Herbert Gottweis, Governing Molecules: The Discursive Politics of Genetic Engineering in Europe and the United States (Cambridge, MA: MIT Press, 1998).
“Asilomar I,” as Berg would later call: Details of Berg’s account of Asilomar come from conversations and interviews with Paul Berg, 1993 and 2013; and Donald S. Fredrickson, “Asilomar and recombinant DNA: The end of the beginning,” in Biomedical Politics, ed. Hanna, 258–92.
The Asilomar conference produced an important book: Alfred Hellman, Michael Neil Oxman, and Robert Pollack, Biohazards in Biological Research (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1973).
summer of 1973 when Boyer and Cohen: Cohen et al., “Construction of biologically functional bacterial plasmids,” 3240–44.
“ ‘safe’ viruses, plasmids and bacteria”: Crotty, Ahead of the Curve, 99.
“Well, if we had any guts at all”: Ibid.
“Don’t put toxin genes into E. coli”: “The moratorium letter regarding risky experiments, Paul Berg,” DNA Learning Center, https://www.dnalc.org/view/15021-The-moratorium-letter-regarding-risky-experiments-Paul-Berg.html.
In 1974, the “Berg letter” ran: P. Berg et al., “Potential biohazards of recombinant DNA molecules,” Science 185 (1974): 3034. See also Proceedings of the National Academy of Sciences 71 (July 1974): 2593–94.
“are specious”: Herb Boyer interview, 1994, by Sally Smith Hughes, UCSF Oral History Program, Bancroft Library, University of California, Berkeley, http://content.cdlib.org/view?docId=kt5d5nb0zs&brand=calisphere&doc.view=entire_text.
On New Year’s Day 1974: John F. Morrow et al., “Replication and transcription of eukaryotic DNA in Escherichia coli,” Proceedings of the National Academy of Sciences 71, no. 5 (1974): 1743–47.
Asilomar II—one of the most unusual: Paul Berg et al., “Summary statement of the Asilomar Conference on recombinant DNA molecules,” Proceedings of the National Academy of Sciences 72, no. 6 (1975): 1981–84.
“You fucked the plasmid group”: Crotty, Ahead of the Curve, 107.
He was promptly accused of: Brenner, “The influence of the press.”
“Some people got sick of it all”: Crotty, Ahead of the Curve, 108.
“The new techniques, which permit”: Gottweis, Governing Molecules, 88.
To mitigate the risks, the document: Berg et al., “Summary statement of the Asilomar Conference,” 1981–84.
two-page letter written in August 1939: Albert Einstein, “Letter to Roosevelt, August 2, 1939,” Albert Einstein’s Letters to Franklin Delano Roosevelt, http://hypertextbook.com/eworld/einstein.shtml#first.
As Alan Waterman, the head: Attributed to Alan T. Waterman, in Lewis Branscomb, “Foreword,” Science, Technology, and Society, a Prospective Look: Summary and Conclusions of the Bellagio Conference (Washington, DC: National Academy of Sciences, 1976).
Nixon, fed up with his scientific advisers: F. A. Long, “President Nixon’s 1973 Reorganization Plan No. 1,” Science and Public Affairs 29, no. 5 (1973): 5.
“was to demonstrate that scientists were capable”: Paul Berg, author interview, 2013.
“The public’s trust was undeniably increased”: Paul Berg, “Asilomar and recombinant DNA,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1980/berg-article.html.
“Did the organizers and participants”: Ibid.
“Clone or Die”
If you know the question: Herbert W. Boyer, “Recombinant DNA research at UCSF and commercial application at Genentech: Oral history transcript, 2001,” Online Archive of California, 124, http://www.oac.cdlib.org/search?style=oac4;titlesAZ=r;idT=UCb11453293x.
Any sufficiently advanced technology: Arthur Charles Clark, Profiles of the Future: An Inquiry Into the Limits of the Possible (New York: Harper & Row, 1973).
“may completely change the pharmaceutical industry’s”: Doogab Yi, The Recombinant University: Genetic Engineering and the Emergence of Stanford Biotechnology (Chicago: University of Chicago Press, 2015), 2.
In May, the San Francisco Chronicle ran: “Getting Bacteria to Manufacture Genes,” San Francisco Chronicle, May 21, 1974.
Cohen also received: Roger Lewin, “A View of a Science Journalist,” in Recombinant DNA and Genetic Experimentation, ed. J. Morgan and W. J. Whelan (London: Elsevier, 2013), 273.
Cohen and Boyer filed a patent: “1972: First recombinant DNA,” Genome.gov, http://www.genome.gov/25520302.
“to commercial ownership of the techniques for cloning all possible DNAs”: P. Berg and J. E. Mertz, “Personal reflections on the origins and emergence of recombinant DNA technology,” Genetics 184, no. 1 (2010): 9–17, doi:10.1534/genetics.109.112144.
Swanson came to see Boyer in January 1976: Sally Smith Hughes, Genentech: The Beginnings of Biotech (Chicago: University of Chicago Press, 2011), “Prologue.”
br /> Boyer rejected Swanson’s suggestion of HerBob: Felda Hardymon and Tom Nicholas, “Kleiner-Perkins and Genentech: When venture capital met science,” Harvard Business School Case 813-102, October 2012, http://www.hbs.edu/faculty/Pages/item.aspx?num=43569.
In 1869, a Berlin medical student: A. Sakula, “Paul Langerhans (1847–1888): A centenary tribute,” Journal of the Royal Society of Medicine 81, no. 7 (1988): 414.
Two decades later, two surgeons: J. v. Mering and Oskar Minkowski, “Diabetes mellitus nach Pankreasexstirpation,” Naunyn-Schmiedeberg’s Archives of Pharmacology 26, no. 5 (1890): 371–87.
Ultimately, in 1921, Banting and Best: F. G. Banting et al., “Pancreatic extracts in the treatment of diabetes mellitus,” Canadian Medical Association Journal 12, no. 3 (1922): 141.
In 1953, after three more decades: Frederick Sanger and E. O. P. Thompson, “The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates,” Biochemical Journal 53, no. 3 (1953): 353.
To synthesize the somatostatin gene: Hughes, Genentech, 59–65.
“I thought about it all the time”: “Fierce Competition to Synthesize Insulin, David Goeddel,” DNA Learning Center, https://www.dnalc.org/view/15085-Fierce-competition-to-synthesize-insulin-David-Goeddel.html.
“Gilbert was, as he had for many days past”: Hughes, Genentech, 93.
460 Point San Bruno Boulevard: Ibid., 78.
“You’d go through the back of Genentech’s door”: “Introductory materials,” First Chief Financial Officer at Genentech, 1978–1984, http://content.cdlib.org/view?docId=kt8k40159r&brand=calisphere&doc.view=entire_text.
Gilbert recalled. The UCSF team: Hughes, Genentech, 93.
In the summer of 1978, Boyer learned: Payne Templeton, “Harvard group produces insulin from bacteria,” Harvard Crimson, July 18, 1978.
August 21, 1978, Goeddel joined: Hughes, Genentech, 91.
On October 26, 1982, the US Patent: “A history of firsts,” Genentech: Chronology, http://www.gene.com/media/company-information/chronology.