The Code Breaker, page 45
3. Author’s interviews with Rodolphe Barrangou.
4. Rodolphe Barrangou and Philippe Horvath, “A Decade of Discovery: CRISPR Functions and Applications,” Nature Microbiology, June 5, 2017; Prashant Nair, “Interview with Rodolphe Barrangou,” PNAS, July 11, 2017; author’s interviews with Rodolphe Barrangou.
5. Author’s interviews with Rodolphe Barrangou.
6. Rodolphe Barrangou… Sylvain Moineau… Philippe Horvath, et al., “CRISPR Provides Acquired Resistance against Viruses in Prokaryotes,” Science, Mar. 23, 2007 (submitted Nov. 29, 2006; accepted Feb. 16, 2007).
7. Author’s interviews with Sylvain Moineau, Jillian Banfield, and Rodolphe Barrangou. Conference agendas 2008–2012 provided by Banfield.
8. Author’s interview with Luciano Marraffini.
9. Author’s interview with Erik Sontheimer.
10. Author’s interviews with Erik Sontheimer, Luciano Marraffini; Luciano Marraffini and Erik Sontheimer, “CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA,” Science, Dec. 19, 2008; Erik Sontheimer and Luciano Marraffini, “Target DNA Interference with crRNA,” U.S. Provisional Patent Application 61/009,317, Sept. 23, 2008; Erik Sontheimer, letter of intent, National Institutes of Health, Dec. 29, 2008.
11. Doudna and Sternberg, A Crack in Creation, 62.
Chapter 13: Genentech
1. Author’s interviews with Jillian Banfield and Jennifer Doudna.
2. Eugene Russo, “The Birth of Biotechnology,” Nature, Jan. 23, 2003; Mukherjee, The Gene, 230.
3. Rajendra Bera, “The Story of the Cohen-Boyer Patents,” Current Science, Mar. 25, 2009; US Patent 4,237,224 “Process for Producing Biologically Functional Molecular Chimeras,” Stanley Cohen and Herbert Boyer, filed Nov. 4, 1974; Mukherjee, The Gene, 237.
4. Mukherjee, The Gene, 238.
5. Frederic Golden, “Shaping Life in the Lab,” Time, Mar. 9, 1981; Laura Fraser, “Cloning Insulin,” Genentech corporate history; San Francisco Examiner front page, Oct. 14, 1980.
6. Author’s interview with Rachel Haurwitz.
7. Author’s interview with Jennifer Doudna.
Chapter 14: The Lab
1. Author’s interviews with Rachel Haurwitz, Blake Wiedenheft, Jennifer Doudna.
2. Author’s interview with Rachel Haurwitz.
3. Rachel Haurwitz, Martin Jinek, Blake Wiedenheft, Kaihong Zhou, and Jennifer Doudna, “Sequence- and Structure-Specific RNA Processing by a CRISPR Endonuclease,” Science, Sept. 10, 2010.
4. Samuel Sternberg… Ruben L. Gonzalez Jr., et al., “Translation Factors Direct Intrinsic Ribosome Dynamics during Translation Termination and Ribosome Recycling,” Nature Structural and Molecular Biology, July 13, 2009.
5. Author’s interviews with Sam Sternberg.
6. Author’s interviews with Sam Sternberg, Jennifer Doudna.
7. Author’s interviews with Sam Sternberg, Jennifer Doudna; Sam Sternberg, “Mechanism and Engineering of CRISPR-Associated Endonucleases,” PhD thesis, University of California, Berkeley, 2014.
8. Samuel Sternberg,… and Jennifer Doudna, “DNA Interrogation by the CRISPR RNA-Guided Endonuclease Cas9,” Nature, Jan. 29, 2014; Sy Redding, Sam Sternberg… Blake Wiedenheft, Jennifer Doudna, Eric Greene, et al., “Surveillance and Processing of Foreign DNA by the Escherichia coli CRISPR-Cas System,” Cell, Nov. 5, 2015.
9. Blake Wiedenheft, Samuel H. Sternberg, and Jennifer A. Doudna, “RNA-Guided Genetic Silencing Systems in Bacteria and Archaea,” Nature, Feb. 14, 2012.
10. Author’s interviews with Sam Sternberg.
11. Author’s interviews with Ross Wilson, Martin Jinek.
12. Marc Lerchenmueller, Olav Sorenson, and Anupam Jena, “Gender Differences in How Scientists Present the Importance of Their Research,” BMJ, Dec. 19, 2019; Olga Khazan, “Carry Yourself with the Confidence of a Male Scientist,” Atlantic, Dec. 17, 2019.
13. Author’s interviews with Blake Wiedenheft, Jennifer Doudna; Blake Wiedenheft, Gabriel C. Lander, Kaihong Zhou, Matthijs M. Jore, Stan J. J. Brouns, John van der Oost, Jennifer A. Doudna, and Eva Nogales, “Structures of the RNA-Guided Surveillance Complex from a Bacterial Immune System,” Nature, Sept. 21, 2011 (received May 7, 2011; accepted July 27, 2011).
Chapter 15: Caribou
1. Author’s interview with Jennifer Doudna and Rachel Haurwitz.
2. Gary Pisano, “Can Science Be a Business?,” Harvard Business Review, Oct. 2006; Saurabh Bhatia, “History, Scope and Development of Biotechnology,” IPO Science, May 2018.
3. Author’s interviews with Rachel Haurwitz, Jennifer Doudna.
4. Bush, “Science, the Endless Frontier.”
5. “Sparking Economic Growth,” The Science Coalition, April 2017.
6. “Kit for Global RNP Profiling,” NIH award 1R43GM105087-01, for Rachel Haurwitz and Caribou Biosciences, Apr. 15, 2013.
7. Author’s interviews with Jennifer Doudna, Rachel Haurwitz; Robert Sanders, “Gates Foundation Awards $100,000 Grants for Novel Global Health Research,” Berkeley News, May 10, 2010.
Chapter 16: Emmanuelle Charpentier
1. Author’s interviews with Emmanuelle Charpentier. This chapter also draws from Uta Deffke, “An Artist in Gene Editing,” Max Planck Research Magazine, Jan. 2016; “Interview with Emmanuelle Charpentier,” FEMS Microbiology Letters, Feb. 1, 2018; Alison Abbott, “A CRISPR Vision,” Nature, Apr. 28, 2016; Kevin Davies, “Finding Her Niche: An Interview with Emmanuelle Charpentier,” CRISPR Journal, Feb. 21, 2019; Margaret Knox, “The Gene Genie,” Scientific American, Dec. 2014; Jennifer Doudna, “Why Genome Editing Will Change Our Lives,” Financial Times, Mar. 24, 2018; Martin Jinek, Krzysztof Chylinski, Ines Fonfara, Michael Hauer, Jennifer Doudna, and Emmanuelle Charpentier, “A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity,” Science, Aug. 17, 2012.
2. Author’s interview with Emmanuelle Charpentier.
3. Author’s interviews with Rodger Novak, Emmanuelle Charpentier; Rodger Novak, Emmanuelle Charpentier, Johann S. Braun, and Elaine Tuomanen, “Signal Transduction by a Death Signal Peptide Uncovering the Mechanism of Bacterial Killing by Penicillin,” Molecular Cell, Jan. 1, 2000.
4. Emmanuelle Charpentier… Pamela Cowin, et al., “Plakoglobin Suppresses Epithelial Proliferation and Hair Growth in Vivo,” Journal of Cell Biology, May 2000; Monika Mangold… Rodger Novak, Richard Novick, Emmanuelle Charpentier, et al., “Synthesis of Group A Streptococcal Virulence Factors Is Controlled by a Regulatory RNA Molecule,” Molecular Biology, Aug. 3, 2004; Davies, “Finding Her Niche”; Philip Hemme, “Fireside Chat with Rodger Novak,” Refresh Berlin, May 24, 2016, Labiotech.eu.
5. Author’s interview with Emmanuelle Charpentier.
6. Elitza Deltcheva, Krzysztof Chylinski… Emmanuelle Charpentier, et al., “CRISPR RNA Maturation by Trans-encoded Small RNA and Host Factor RNase III,” Nature, Mar. 31, 2011.
7. Author’s interviews with Emmanuelle Charpentier, Jennifer Doudna, Erik Sontheimer; Doudna and Sternberg, A Crack in Creation, 71–73.
8. Author’s interviews with Martin Jinek, Jennifer Doudna. See also Kevin Davies, interview with Martin Jinek, CRISPR Journal, Apr. 2020.
Chapter 17: CRISPR-Cas9
1. Author’s interviews with Martin Jinek, Jennifer Doudna, Emmanuelle Charpentier.
2. Richard Asher, “An Interview with Krzysztof Chylinski,” Pioneers Zero21, Oct. 2018.
3. Author’s interviews with Jennifer Doudna, Emmanuelle Charpentier, Martin Jinek, Ross Wilson.
4. Author’s interviews with Jennifer Doudna, Martin Jinek.
5. Author’s interviews with Jennifer Doudna, Martin Jinek, Sam Sternberg, Rachel Haurwitz, Ross Wilson.
Chapter 18: Science, 2012
1. Author’s interviews with Jennifer Doudna, Emmanuelle Charpentier, and Martin Jinek.
2. Jinek et al., “A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity.”
3. Author’s interview with Emmanuelle Charpentier.
4. Author’s interviews with Emmanuelle Charpentier, Jennifer Doudna, Martin Jinek, and Sam Sternberg.
Chapter 19: Dueling Presentations
1. Author’s interview with Virginijus Šikšnys.
2. Giedrius Gasiunas, Rodolphe Barrangou, Philippe Horvath, and Virginijus Šikšnys, “Cas9–crRNA Ribonucleoprotein Complex Mediates Specific DNA Cleavage for Adaptive Immunity in Bacteria,” PNAS, Sept. 25, 2012 (received May 21, 2012; approved Aug. 1; published online Sept. 4).
3. Author’s interview with Rodolphe Barrangou.
4. Author’s interview with Eric Lander.
5. Author’s interviews with Erik Lander, Jennifer Doudna.
6. Author’s interview with Rodolphe Barrangou.
7. Virginijus Šikšnys et al., “RNA-Directed Cleavage by the Cas9-crRNA Complex,” international patent application WO 2013/142578 Al, priority date Mar. 20, 2012, official filing Mar. 20, 2013, publication Sept. 26, 2013.
8. Author’s interviews with Virginijus Šikšnys, Jennifer Doudna, Sam Sternberg, Emmanuelle Charpentier, and Martin Jinek.
9. Author’s interviews with Sam Sternberg, Rodolph Barrangou, Erik Sontheimer, Virginijus Šikšnys, Jennifer Doudna, Martin Jinek, and Emmanuelle Charpentier.
Chapter 20: A Human Tool
1. Srinivasan Chandrasegaran and Dana Carroll, “Origins of Programmable Nucleases for Genome Engineering,” Journal of Molecular Biology, Feb. 27, 2016.
Chapter 21: The Race
1. Author’s interviews with Jennifer Doudna; Doudna and Sternberg, A Crack in Creation, 242.
2. Ferric C. Fang and Arturo Casadevall, “Is Competition Ruining Science?,” American Society for Microbiology, Apr. 2015; Melissa Anderson… Brian Martinson, et al., “The Perverse Effects of Competition on Scientists’ Work and Relationships,” Science Engineering Ethics, Dec. 2007; Matt Ridley, “Two Cheers for Scientific Backbiting,” Wall Street Journal, July 27, 2012.
3. Author’s interview with Emmanuelle Charpentier.
Chapter 22: Feng Zhang
1. Author’s interviews with Feng Zhang. This section also draws from Eric Topol, podcast interview with Feng Zhang, Medscape, Mar. 31, 2017; Michael Specter, “The Gene Hackers,” New Yorker, Nov. 8, 2015; Sharon Begley, “Meet One of the World’s Most Groundbreaking Scientists,” Stat, Nov. 6, 2015.
2. Galen Johnson, “Gifted and Talented Education Grades K–12 Program Evaluation,” Des Moines Public Schools, September 1996.
3. Edward Boyden, Feng Zhang, Ernst Bamberg, Georg Nagel, and Karl Deisseroth, “Millisecond-Timescale, Genetically Targeted Optical Control of Neural Activity,” Nature Neuroscience, Aug. 14, 2005; Alexander Aravanis, Li-Ping Wang, Feng Zhang… and Karl Deisseroth, “An Optical Neural Interface: In vivo Control of Rodent Motor Cortex with Integrated Fiberoptic and Optogenetic Technology,” Journal of Neural Engineering, Sept. 2007.
4. Feng Zhang, Le Cong, Simona Lodato, Sriram Kosuri, George M. Church, and Paola Arlotta, “Efficient Construction of Sequence-Specific TAL Effectors for Modulating Mammalian Transcription,” Nature Biotechnology, Jan. 19, 2011.
Chapter 23: George Church
1. This section is based on author’s interviews and visits with George Church and also Ben Mezrich, Woolly (Atria, 2017); Anna Azvolinsky, “Curious George,” The Scientist, Oct. 1, 2016; Sharon Begley, “George Church Has a Wild Idea to Upend Evolution,” Stat, May 16, 2016; Prashant Nair, “George Church,” PNAS, July 24, 2012; Jeneen Interlandi, “The Church of George Church,” Popular Science, May 27, 2015.
2. Mezrich, Woolly, 43.
3. George Church Oral History, National Human Genome Research Institute, July 26, 2017.
4. Nicholas Wade, “Regenerating a Mammoth for $10 Million,” New York Times, Nov. 19, 2008; Nicholas Wade, “The Wooly Mammoth’s Last Stand,” New York Times, Mar. 2, 2017; Mezrich, Woolly.
5. Author’s interviews with George Church and Jennifer Doudna.
Chapter 24: Zhang Tackles CRISPR
1. Josiane Garneau… Rodolphe Barrangou… Philippe Horvath, Alfonso H. Magadán, and Sylvain Moineau, “The CRISPR/Cas Bacterial Immune System Cleaves Bacteriophage and Plasmid DNA,” Nature, Nov. 3, 2010.
2. Davies, Editing Humanity, 80; author’s interview with Le Cong.
3. Author’s interviews with Eric Lander, Feng Zhang; Begley, “George Church Has a Wild Idea…”; Michael Specter, “The Gene Hackers,” New Yorker, Nov. 8, 2015; Davies, Editing Humanity, 82.
4. Feng Zhang, “Confidential Memorandum of Invention,” Feb. 13, 2013.
5. David Altshuler, Chad Cowan, Feng Zhang, et al., Grant application 1R01DK097758-01, “Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease Mutations,” National Institutes of Health, Jan. 12, 2012.
6. Broad Opposition 3; UC reply 3.
7. Author’s interviews with Luciano Marraffini and Erik Sontheimer; Marraffini and Sontheimer, “CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA”; Sontheimer and Marraffini, “Target DNA Interference with crRNA,” U.S. Provisional Patent Application; Kevin Davies, “Interview with Luciano Marraffini,” CRISPR Journal, Feb. 2020.
8. Author’s interviews with Luciano Marraffini and Feng Zhang; Zhang email to Marraffini, Jan. 2, 2012 (given to me by Marraffini).
9. Marraffini email to Zhang, Jan. 11, 2012.
10. Eric Lander, “The Heroes of CRISPR,” Cell, Jan. 14, 2016.
11. Author’s interviews with Feng Zhang.
12. Feng Zhang, “Declaration in Connection with U.S. Patent Application Serial 14/0054,414,” USPTO, Jan. 30, 2014.
13. Shuailiang Lin, “Summary of CRISPR Work during Oct. 2011–June 2012,” Exhibit 14 to Neville Sanjana Declaration, July 23, 2015, UC et al. Reply 3, exhibit 1614, in Broad v. UC, Patent Interference 106,048.
14. Shuailiang Lin email to Jennifer Doudna, Feb. 28, 2015.
15. Antonio Regalado, “In CRISPR Fight, Co-Inventor Says Broad Institute Misled Patent Office,” MIT Technology Review, Aug. 17, 2016.
16. Author’s interviews with Dana Carroll; Dana Carroll, “Declaration in Support of Suggestion of Interference,” University of California Exhibit 1476, Interference No. 106,048, Apr. 10, 2015.
17. Carroll, “Declaration”; Berkeley et al., “List of Intended Motions,” Patent Interference No. 106,115, USPTO, July 30, 2019.
18. Author’s interviews with Jennifer Doudna and Feng Zhang; Broad et al., “Contingent Responsive Motion 6” and “Constructive Reduction to Practice by Embodiment 17,” USPTO, Patent Interference 106,048, June 22, 2016.
19. Author’s interviews with Feng Zhang and Luciano Marraffini. See also Davies, “Interview with Luciano Marraffini.”
Chapter 25: Doudna Joins the Race
1. Author’s interviews with Martin Jinek and Jennifer Doudna.
2. Melissa Pandika, “Jennifer Doudna, CRISPR Code Killer,” Ozy, Jan. 7, 2014.
3. Author’s interviews with Jennifer Doudna and Martin Jinek.
Chapter 26: Photo Finish
1. Author’s interviews with Feng Zhang; Fei Ann Ran, “CRISPR-Cas9,” NABC Report 26, ed. Alan Eaglesham and Ralph Hardy, Oct. 8, 2014.
2. Le Cong, Fei Ann Ran, David Cox, Shuailiang Lin… Luciano Marraffini, and Feng Zhang, “Multiplex Genome Engineering Using CRISPR/Cas Systems,” Science, Feb. 15, 2013 (received Oct. 5, 2012; accepted Dec. 12; published online Jan. 3, 2013).
3. Author’s interviews with George Church, Eric Lander, and Feng Zhang.
4. Author’s email interviews with Le Cong.
5. Author’s interview with George Church.
6. Prashant Mali… George Church, et al., “RNA-Guided Human Genome Engineering via Cas9,” Science, Feb. 15, 2013 (received Oct. 26, 2012; accepted Dec. 12, 2012; published online Jan. 3, 2013).
Chapter 27: Doudna’s Final Sprint
1. Pandika, “Jennifer Doudna, CRISPR Code Killer.”
2. Author’s interviews with Jennifer Doudna and Martin Jinek.
3. Michael M. Cox, Jennifer Doudna, and Michael O’Donnell, Molecular Biology: Principles and Practice (W. H. Freeman, 2011). The first edition cost $195.
4. It was Detlef Weigel, at the Max Planck Institute for Developmental Biology.
5. Author’s interviews with Emmanuelle Charpentier and Jennifer Doudna.
6. Detlef Weigel decision letter and Jennifer Doudna author response, eLife, Jan. 29, 2013.
7. Martin Jinek, Alexandra East, Aaron Cheng, Steven Lin, Enbo Ma, and Jennifer Doudna, “RNA-Programmed Genome Editing in Human Cells,” eLife, Jan. 29, 2013 (received Dec. 15, 2012; accepted Jan. 3, 2013).
8. Jin-Soo Kim email to Jennifer Doudna, July 16, 2012; Seung Woo Cho, Sojung Kim, Jong Min Kim, and Jin-Soo Kim, “Targeted Genome Engineering in Human Cells with the Cas9 RNA-Guided Endonuclease,” Nature Biotechnology, Mar. 2013 (received Nov. 20, 2012; accepted Jan. 14, 2013; published online Jan. 29, 2013).
9. Woong Y. Hwang… Keith Joung, et al., “Efficient Genome Editing in Zebrafish Using a CRISPR-Cas System,” Nature Biotechnology, Jan. 29, 2013.
Chapter 28: Forming Companies
1. Author’s interviews with Andy May, Jennifer Doudna, and Rachel Haurwitz.
2. George Church interview, “Can Neanderthals Be Brought Back from the Dead?,” Spiegel, Jan. 18, 2013; David Wagner, “How the Viral Neanderthal-Baby Story Turned Real Science into Junk Journalism,” The Atlantic, Jan. 22, 2013.
3. Author’s interview with Rodger Novak; Hemme, “Fireside Chat with Rodger Novak”; Jon Cohen, “Birth of CRISPR Inc.,” Science, Feb. 17, 2017; author’s interviews with Emmanuelle Charpentier.
4. Author’s interviews with Jennifer Doudna, George Church, and Emmanuelle Charpentier.
