linear model of innovation

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The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race by Walter Isaacson

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In June 2009, they published their discovery in a paper that was the Doudna Lab’s initial contribution to the CRISPR field. It was the first explanation of a CRISPR mechanism based on a structural analysis of one of its components.15 Rodolphe Barrangou Philippe Horvath CHAPTER 12 The Yogurt Makers Basic research and the linear model of innovation Historians of science and technology, including myself, often write about what is called the “linear model of innovation.” It was propagated by Vannevar Bush, an MIT engineering dean who cofounded Raytheon and during World War II headed the U.S. Office of Scientific Research and Development, which oversaw the invention of radar and the atom bomb.

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., 231 contact tracing, 257 Conti, Elena, 84–85 continuum conundrum, 337–38 Copenhagen (Frayn), 224 Coppola, Francis Ford, 352 coronaviruses, 47, 90, 270, 339, 365, 451 CRISPR systems to detect, 118 name of, 404 PAC-MAN and, 454–57, 460 RNA of, 65, 403–4 RNA interference and, 66–67 SARS, 65, 403, 441 SARS-CoV-2, 403–4 see also COVID-19 pandemic coronary heart disease, 251 Costolo, Dick, 219 Council of Europe, 278 Count Me In, 177 COVID-19 pandemic, xiii, xv, xvii, 251, 257, 262, 335, 373, 399–475, 477 Berkeley and, xiii–xv Innovative Genomics Institute, 401–5, 413–18, 419 China origin of, 263, 403, 452 Cold Spring Harbor conference and, 459–62 CRISPR cures and, xviii, 449–57 PAC-MAN, 454–57, 460 deaths in, 404, 449 legacies of, 473–75 SARS-CoV-2 in, 403–4 testing and, xiv–xv, 405, 406, 407–11, 413–18, 427–33 antigen tests, 430–31 Broad Institute and, 410–11, 429 CDC and, 407–10 CRISPR and, 413, 417, 421–25, 427–33, 453 Fauci and, 410 FDA and, 407–10 first person in U.S. to test positive, 407 Mammoth Biosciences and, 423–25, 429–32 PCR tests, 408, 413, 416, 421, 425, 428, 430 Sherlock Biosciences and, 428, 430 Trump administration and, 411 University of Washington and, 409–10, 415 Zhang and, 421, 427–32 vaccines and, 434, 435–47, 449 clinical trials of, 435–36, 440–41, 445–46, 461 Fauci and, 442 FDA and, 446 Isaacson in trial of, 435–36, 440–41, 445–46 cowpox, 436 Crichton, Michael, 271 Crick, Francis, 20–28, 47, 166, 389, 475 at Asilomar, 269 on central dogma of biology, 44 in DNA double-helix structure discovery, xviii, 7, 11, 26–28, 29–31, 46, 51, 58, 159, 423, 470 with DNA model, 16 Franklin’s work and, 25, 26 Nobel Prize awarded to, 28, 470 Watson’s meeting of, 20 CRISPR (clustered regularly interspaced short palindromic repeats), 69–149, 449–50, 477, 480 anti-CRISPRs, 260–61 as bacterial immune system, xiv, xviii, xix, 67, 86, 87 Banfield’s enlistment of Doudna to work on, xviii, 77, 79–80, 81, 93, 471 Barrangou and Horvath’s work on, 90–93, 143–44, 177, 178, 220, 223, 470 diagram of mechanism of, 133 discovery of, 71–77 DNA targeting in, xiv, xviii, 67, 76–77, 86, 87, 93–94, 106, 111, 131, 132, 133, 146, 217 Doudna’s creation of team for studying, 103–11 enzymes in, see CRISPR-associated enzymes in vitro vs. in vivo studies of, 80, 94–95, 183, 191, 202 Koonin’s study of, 76–77, 80, 92 and linear model of innovation, 90 Mojica’s study of, 71–76, 80, 91, 92, 220, 223, 224, 470, 479 naming of, 73 RNA in, 79, 108, 133 Cas13 targeting of RNA, 423–25, 429, 451, 452, 454–57 CRISPR RNA (crRNA), 86, 106, 124–26, 131–35, 137–39, 143, 146, 147, 180, 184, 186, 217 RNA interference, 77, 79, 93 single-guide RNA (sgRNA), 134–35, 139, 186, 190, 191, 195, 198 trans-activating CRISPR RNA (tracrRNA), 124–27, 131, 134, 135, 139, 146–47, 179–80, 182, 184–86, 217–18, 225 viruses’ disabling of, 260–61 yogurt starter cultures and, xviii, 90–92, 133, 143 CRISPR applications, 243–63 affordability of, 247–48 biohacking, 253–57, 263, 285, 288, 443–44 coronavirus testing, 413, 417 cures for viral infections, 449–57 CARVER, 452–53, 455–57 PAC-MAN, 454–57, 460 defense against terrorists, 259–63 diagnostic tests for cancers, 250 diagnostic tests for viruses, 115, 118, 421–25, 431–32, 451 at-home tests, 430–32, 460 coronavirus, 413, 417, 421–25, 427–33, 453 HPV, 422–23 ex vivo and in vivo, 246, 250 germline (inheritable) editing, see human germline editing somatic editing, 246, 276–77, 288, 329, 336, 338, 341 therapies, 233, 245–51 blindness, xviii, 250 cancer, xviii, 249–51 safe viruses as delivery method in, 456 sickle cell, xviii, 245–49, 329, 340 CRISPR-associated (Cas) enzymes, 73, 76, 84, 86, 92 Cas1, 86–87, 106, 128 Cas6, 106–7, 113, 128 as diagnostic tool, 115, 118 Cas9, 86, 92, 119, 124–25, 127, 128, 129–36, 133, 422–24, 440 purchasing of, 380 see also CRISPR-Cas9 gene editing Cas12, 86, 422–24, 429 Cas13, 86, 379, 423–25, 429, 451, 452, 454–57 CASCADE array of, 111 fluorescence microscopy and, 107–8 Zhang’s work with multiple proteins, 181 CRISPR babies, 245–47, 297–332, 325–32, 335, 337 birth of, 311–13, 315, 318 He Jiankui’s conviction and sentencing for his work, 332 He Jiankui’s removal of HIV receptor in, xv–xvi, 251, 303–13, 316–24, 369, 404 CRISPR-Cas9 gene editing, xiii, xiv, xvii–xix, 60, 90, 94, 97–98, 132–36, 151–241, 272 applications of, see CRISPR applications codons and, 190, 191–92, 194 companies formed to commercialize applications of, 203–13, 430 CRISPR Therapeutics, 207, 213, 245, 465 Editas Medicine, 209–13, 250, 454 Intellia Therapeutics, 213 competition to prove human application of, xv, 64, 143–49, 155–56, 157–60, 201–2, 374 Church in, 64, 160, 173–74, 192–95, 197–99, 201, 202 Doudna in, xv, 64, 160, 173–74, 179, 187–90, 197–202 Lander in, 64, 160 Zhang in, xv, 64, 159–60, 174, 175–86, 191–95, 197, 199–202, 227 Doudna and Charpentier’s 2012 paper on, 126, 137–41, 144–46, 148, 149, 156, 172–73, 179, 180, 182–86, 191, 192, 194–95, 202, 227, 233, 237–38, 374–75 in eukaryotic cells, 148–49, 184, 237–38 as inevitable, 202 in vitro vs. in vivo, 184, 382 Isaacson’s learning of, xiv, 378, 379–83 licensing of, 208, 211 moral questions concerning, see moral questions patents for, 92, 94, 115, 135–36, 144, 156, 232–41 of Doudna, Charpentier, and Berkeley, 207–8, 210, 219, 224, 233–40 Doudna’s battle with Zhang over, 184, 194, 208, 224, 234–40, 425, 470 pool idea for, 207–8 of Zhang and the Broad Institute, 192, 207–8, 210–11, 219, 224–27, 233–40 regulation of, 255, 361 Šikšnys’s paper and, 144 transposons and, 374, 375 virus infections and, xv, xix CRISPR conferences, 93, 129 in Berkeley (2012), 140, 141, 145–49 at Cold Spring Harbor, 302, 304, 385, 391, 393, 397, 415, 458, 459–67 in Quebec (2019), 373–77 CRISPR Journal, 85, 309, 319 CRISPR Therapeutics, 207, 213, 245, 465 crowdsourcing, 256–57, 285, 464 cryocooling, 57, 63 crystallography, 84, 187 Cas1 and, 86–87 DNA and, 19–23, 51 “photograph 51,” 25, 25, 395 phase problem in, 57 RNA and, 53, 55–57, 66, 171, 181 Cumberbatch, Benedict, 219 Cure Sickle Cell Initiative, 248 Curie, Marie, 8, 470 curiosity, 478–79 of Doudna, xix, 4, 5, 8, 31, 46, 51, 479 science driven by, xix, 89, 90, 457, 473, 479 Current Contents, 72 cystic fibrosis, 248 cytosine, 26, 27 Daley, George, 282, 316, 324, 369 Danisco, 90–92, 143, 148, 177, 220 Dantseva, Dariia, 434, 443–45 DARPA, 259–62, 351, 452, 454 Safe Genes project of, 260, 262, 380 Darwin, Charles, 10, 11–14, 28, 159, 292, 302, 364, 475 Davenport, Charles, 37 Davies, Kevin, 85, 309, 320 Davis, Miles, 345 Davos, World Economic Forum in, 368 deafness, 346–48 Decoding Watson (PBS documentary), 384, 386, 389–90, 392, 393 Deem, Michael, 298, 300, 301, 307–9 Defense Advanced Research Projects Agency (DARPA), 259–62, 351, 452, 454 Safe Genes project of, 260, 262, 380 Defense Department, U.S., 4, 259, 262 Defoe, Daniel, 414 Deisseroth, Karl, 167 Delbrück, Max, 37 Deltcheva, Elitza, 125–26 Dengue virus, 424 depression, 166, 352–53 bipolar disorder, 177, 327, 352–53 Derain, André, 395 designer babies, 355–56 see also CRISPR babies Desmond-Hellmann, Sue, 100 DETECTR (DNA endonuclease targeted CRISPR trans reporter), 422–23, 429, 460 Dhanda, Rahul, 428 diabetes, 99 Diana, Princess, 100 Diaz, Cameron, 219 Dicer enzyme, 66, 79 Didion, Joan, 7 digital technology, xvii, 28, 114 disabilities, 345–48 diversity, 362, 376, 480 DNA (deoxyribonucleic acid), xvii, xviii, 17–28, 43–47 bases in, 26, 27, 37, 71, 382, 480 in central dogma of biology, 44, 47, 270 cloning, 34–35, 98, 153, 280, 313, 415–16 CRISPR sequences of, see CRISPR crystallography and, 19–23, 51 discovery of double-helix structure of, xviii, 7, 11, 26–28, 29–31, 46, 51, 58, 159, 386, 390, 395, 397, 423, 470 editing of, see gene editing Franklin’s work on, xviii, 7, 22–26, 28, 31, 46, 51, 53, 227, 389, 459, 470 “photograph 51,” 25, 25, 395 Human Genome Project and, 37–41, 43, 45, 74, 172, 175, 280, 330, 352, 388, 390, 391 “junk,” 416 model of, 16, 27 mutations in, 41, 302 Pauling’s work on structure of, 21–25, 51, 159, 391 “photograph 51” of, 25, 25, 395 race to discover structure of, 21–28, 159, 390, 391 reverse transcription and, 270, 408 sequencing of, 71–72, 74, 79, 80, 83, 172 vaccines, 439–41, 444–45, 456 in viruses, 65 in yeast, 35, 45 Dolly the sheep, 280, 313, 415–16 Double Helix, The (Watson), xix, 6–8, 9, 20, 21, 27, 29–31, 50, 157, 328, 391, 397, 398, 414, 459, 477–78 Doudna, Dorothy (mother), 2, 4, 5, 32, 98, 472–73 Doudna, Ellen (sister), 2, 472–73 Doudna, Jennifer, 2, 62, 130, 138, 158, 188, 204, 214, 282, 298 as bench scientist, 103 at Berkeley, xiii–xv, xvii, 64–65, 83, 98, 101, 107 Berkeley lab of, 103–11, 104, 117 Isaacson learns to edit at, xiv, 378, 379–83 birth of, 4 business school considered by, 98 Caribou Biosciences, 113–18, 203, 207–8, 213 Intellia Therapeutics, 213 chemistry studied by, 31–34, 478 childhood of, xix, 2, 3–8, 31, 123 Charpentier’s rift with, 215–21, 464, 466 Church’s email to, 173, 197 coauthors on papers of, 48 at conferences, 287–90, 292, 303, 332, 367, 373, 375, 385, 459–61 at congressional hearing, 325, 328–29 CRISPR work of Banfield calls and invites her to collaborate, xviii, 77, 79–80, 81, 93, 471 Breakthrough Prize in Life Sciences awarded for, 219–21 Church’s paper and, 197, 234 collaboration with Charpentier, 135, 140, 160, 183, 199–200, 206, 215–21, 464–67, 475 company formations and, 203–13 competition to adapt CRISPR into tool for gene editing in humans, xv, 64, 160, 173–74, 179, 187–90, 197–202 creation of lab team, 103–11 defense applications and, 259–61 diagnostic tests and, 422–23 Editas Medicine and, 209–13 ethical considerations of, 367–70 Kavli Prize awarded for, 221 Lander’s “Heroes of CRISPR” and, 223–29, 388 medical applications and, 247–49, 251 meeting Charpentier, 119, 122, 127–28, 200 Nobel Prize awarded for, xix, 468, 469–73 paper for eLife, 198–201, 215, 225, 237 paper written with Charpentier (2012), 126, 137–41, 144–46, 148, 149, 156, 172–73, 179, 180, 182–86, 191, 192, 194–95, 202, 227, 233, 237–38, 374–75 patent for, 207–8, 210, 219, 224, 233–40 patent battle with Zhang, 184, 194, 208, 224, 234–40, 425, 470 possible partnership with Zhang, 207–8 publicity for, 216–17, 220, 223 review article written with Charpentier (2014), 215 Zhang’s emails and, 200–201, 207 see also CRISPR-Cas9 gene editing curiosity of, xix, 4, 5, 8, 31, 46, 51, 479 The Double Helix read by, xix, 6–8, 29–31, 157, 328, 391, 397, 398, 414, 459, 477 first marriage of, 54–56, 63 Genentech and, 97–102, 103, 105, 107, 113, 114 on gene therapy, 279 germline editing views of, 331–32, 367–70 at Harvard, 34–35, 40, 64, 208 He Jiankui and, 298, 302–4, 315–17, 319, 321–24, 328, 332 in high school, 31 Hitler nightmare of, 283, 286 at Hong Kong summit (International Summit on Human Gene Editing, 2015), 282, 292–93, 366 husband of, see Cate, Jamie Innovative Genomics Institute, 248, 261, 380–82, 401–3 COVID and, 401–5, 413–18, 419 Mammoth Biosciences and, xv, 249–50, 423 medical school considered by, 98 midlife crisis of, 97, 101 Napa Valley conference organized by, 287–90, 292, 303, 332, 367 in National Academy video, 355 at Pomona College, 30, 31–34 Qi and, 453–56 at Quebec conference, 373, 375 RNA work of, xviii, 45–49, 51–61, 63, 65–67, 134, 181, 220, 435–36, 446 son of, see Cate, Andrew Watson and, xviii, 8, 29, 48–50, 396 Watson visited by, 395–98 at Yale, 52, 57, 60–61, 63 Doudna, Martin (father), 2, 3–8, 32, 34, 58–60, 397–98, 472–73 cancer of, 58–59 death of, 59–60 Watson’s The Double Helix given to Jennifer by, xix, 6–8, 477 Doudna, Sarah (sister), 2, 3, 472–73 Down’s syndrome, 337 Doxzen, Kevin, 255 dragonflies, 170 Dr.

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Morgan, 210 jumping genes (transposons), 49, 373–76 June, Carl, 249 Jurassic Park, xviii, 164 Kass, Leon, 280–81 Kass Commission, 280–81 Katz, Deborah, 238 Kavli Prize, 221 Ketchens, Doreen, 480 Kilby, Jack, 240–41 Kim, Jin-Soo, 202 Kingsley, David, 385 Kissinger, Henry, 4 Klee, Paul, 395 Klompe, Sanne, 375 Knoepfler, Paul, 356 Knott, Gavin, 260, 378, 379–81, 402–3, 462 Kolter, Roberto, 34–35 Koonin, Eugene, 76–77, 80, 92, 423 Krauthammer, Charles, 281 Lam, Wifredo, 395 Lander, Eric, 39, 175–77, 193, 207, 209, 211, 212, 216, 222, 374, 388 as Broad Institute director, 64, 144, 160, 175, 216, 220, 223, 225–28 Charpentier and, 220, 223–24 Church and, 172, 227–28 in competition to adapt CRISPR into tool for gene editing in humans, 64, 160 COVID and, 410–11 Doudna and, 144–45 Doudna and Charpentier’s Nobel and, 471–72 “The Heroes of CRISPR,” 182, 223–29, 388 moratorium issue and, 330–32 prizes and, 219–20 Zhang and, 182–83, 220 Larson, Christina, 310 Lasky, Larry, 115 Lassa fever, 425 Lawrence Berkeley National Laboratory, 64, 87, 117, 456–57 Leber congenital amaurosis, 250 Leibniz, Gottfried Wilhelm, 159 Leonardo da Vinci, xix, 4, 259, 338, 375, 457, 478, 479 Lessing, Doris, 7 Levy, John, 165–66 Levy, Steven, 454 licensing COVID and, 405 of CRISPR technology, 208, 211 life, origin of, xvii, 45–49 Lifton, Richard, 47 light-sensitive proteins, 167 Lin, Shuailiang, 184, 192 Lincoln, Abraham, 64–65 linear model of innovation, 89–90 Lin Shiao, Enrique, 412, 415–18 Linux, 163, 256 lipid nanoparticles, 441 lipitoids, 456–57 Litton Industries, 114 Locke, John, 357 Lord of the Rings, The (Tolkien), 415 Lovell-Badge, Robin, 314, 316–22 Liu, David, 209, 321–22, 461–62, 472 Luria, Salvador, 19, 37 MacFarlane, Seth, 219 Mahler, Gustav, 352 Makarova, Kira, 376 malaria, 343, 390 Malthus, Thomas, 12–13 mammoth, woolly, 160, 169, 172 Mammoth Biosciences, xv, 249–50, 423–25, 429–32, 460 Manson, Charles, 352 Mäntyranta, Eero, 348 Marchione, Marilynn, 310, 313 Mardi Gras, 476, 480 Marletta, Michael, 101 Marraffini, Luciano, 70, 93–94, 176, 213, 220, 376, 470 Doudna’s meeting of, 180–81 patent and, 234–35, 240 Zhang and, 180–82, 186, 192, 200, 213, 234–35, 240 Marson, Alex, 440, 456 Max Planck Institute, 123–24, 140 May, Andy, 203–7, 235–36, 240 Mayo Clinic, 410 McCarthyism, 23 McClintock, Barbara, 49, 463 McCullough, Candy, 346–47 McGovern Institute, 428 McGwire, Mark, 349 Medical Research Council, 26 medical tourism, 291, 329 Mello, Craig, 66 memory, 354 Mendel, Gregor, 10, 11, 13–15, 292, 475 mental illness, 166–67, 177, 352–54 bipolar disorder, 177, 327, 352–53 depression, 166, 352–53 schizophrenia, 177, 352–53 of Rufus Watson, 38, 277, 352, 386, 389, 393 MERS (Middle East respiratory syndrome), 409, 438, 441 Mezrich, Ben, 171 Mic, 227 mice, 74, 122, 167, 259, 260, 348, 354 microchips, xvii, xix, 117, 201, 432, 473 patent rights for, 240–41 microfluids, 460 Microsoft, 206, 450 Middle East respiratory syndrome (MERS), 409, 438, 441 military defense, 260–63 Mill, John Stuart, 357 Milner, Yuri, 219 Miró, Joan, 395 MIT, 63, 64, 89, 117, 235n, 269 McGovern Institute, 428 see also Broad Institute of MIT and Harvard MIT Technology Review, 227, 312 Moderna, 441–42, 447 Moineau, Sylvain, 148, 220 Mojica, Francisco, 70, 71–76, 79, 80, 81, 90–93, 220, 223, 224, 470, 479 molecules, 7, 8, 29, 34, 51, 473 Moore, Henry, 395 moral questions, xvi, 268–69, 273, 333–70 continuum conundrum and, 337–38 diversity, 362, 376, 480 decision making, 355–65 Doudna and, 367–70 Engineering the Human Germline conference and, 276–78 enhancements, 276, 281, 302, 303, 326–27, 355–56, 360, 365, 376 absolute vs. positional improvements, 350–51 attractiveness, 386 cognitive skills, 354, 376 height, 349–51, 361, 376 intelligence, 354, 360–62, 376 memory, 354 muscle mass and athletic ability, 253–55, 348–49, 361, 376 super-enhancements, 339, 351–52 treatments vs., 338–39, 341, 350, 369–70, 376 free market, 331, 357–59, 363 eugenics, 360–63 germline editing, 245–47, 276–77, 287–93, 332, 341 He Jiankui and, 304 Napa Valley conference and, 287–90, 292, 332, 367 as red line, 276–77, 322, 324, 336–38 individual choice, 331, 358, 359, 369 community vs., 356–59 free-market eugenics and, 360–63 inequality, 274, 288, 358, 360, 362–63, 369, 376–77, 391–92 National Academy of Sciences and, 355–56 playing God, 269, 273, 333, 363–65, 480–81 preventions, 339 red lines, 335–39 germline as, 276–77, 322, 324, 336–38 slippery slope, xvi, 277, 289, 361, 481 societal discussion about, 355–56 Splicing Life report and, 273–74 thought experiments, 339, 341–54, 361, 362 character, 345–46 cognitive skills, 354 deafness, 346–48 disabilities, 345–48 Huntington’s disease, 341–42, 361, 365 psychological disorders, 352–54 sexual orientation, 347–48, 361 sickle cell, 343–45, 361 skin color, 347–48 unintended consequences, 277, 290, 364 Moreau, Sylvain, 93 Morrill Land-Grant Act, 65 mosquitoes, 122, 260, 261 Mount Sinai Medical Center, 381 Moviegoer, The (Percy), 345 MSTN gene, 348 Mukherjee, Siddhartha, 20–21 Muller, Hermann, 19 Mullis, Kary, 408 muscles and sports, 253–55, 348–49, 361, 376 Musunuru, Kiran, 312 Myhrvold, Cameron, 448, 450–54, 457, 460 Myhrvold, Nathan, 448, 450 myostatin, 253 Napa Valley conference, 287–90, 292, 303, 332, 367 Napolitano, Janet, 417 NASA, 254 Apollo program, 417 Nash, John, 352 National Academy of Medicine, 363 National Academy of Sciences, 143, 262, 269, 292–94, 309, 329 video of, 355–56 National Center for Biotechnology Information, 376 National Council of Churches, 273 National Human Genome Research Institute, 309 National Institutes of Health (NIH), 39, 56, 94, 117–18, 248, 294, 329, 331, 364, 390, 410, 423, 442, 446, 461 National Science Foundation, 89 National Transportation Systems Center, 206 Natural Science Society, 14–15 natural selection, 12, 13, 302 nature, xviii, xix, 5, 7, 8, 12, 17, 29, 33, 46, 51, 69, 75, 157, 280, 294, 310, 336, 342, 343, 364–65, 367, 375, 447, 457, 481 Nature, 47, 75, 108, 111, 198, 290, 291, 330, 374, 376, 469, 470, 474 Charpentier’s 2011 paper in, 125–27, 131, 147, 179–80, 185, 218 He Jiankui and, 309, 311, 312, 315, 316 Nazi Germany, 356, 359 Neanderthal, 205 nematodes, 66, 187 neurons, 167 Newton, Isaac, 159 New York Times, 40, 172, 289, 304, 307, 390, 427 New York University, 122 1984 (Orwell), 358–59 NMDA receptors, 354 Nobel Prize, 19, 20, 21, 44, 49, 53, 66, 100, 219, 221, 226, 270, 305, 470, 472 awarded to Doudna and Charpentier, xix, 468, 469–73 awarded to Watson, Crick, and Wilkins, 28, 470 Nogales, Eva, 111 Novak, Rodger, 122, 204, 205–7, 213, 216 Novartis, 206 Noyce, Robert, 240–41 Nozick, Robert, 353, 357–58 NPR, 245, 247, 290 nuclear location signal or sequence (NLS), 182, 189–90, 191, 194, 380, 440 nuclear power, xvii atom bomb, xvii, 89, 117, 224, 265, 338 attacks or disasters, 262, 351 nucleases, 155, 177 TALENs (transcription activator-like effector nucleases), 155, 167, 177–79, 187, 190 ZFNs (zinc-finger nucleases), 155, 178, 179 nucleic acids, 17 see also DNA; RNA nucleofection, 382 Nuffield Council, 293, 294 Obama, Barack, 294 Ochsner Hospital, 445 ODIN, The, 255 Office of Scientific Research and Development, 89 oil spills, 232 On the Origin of Species (Darwin), 11, 28 open-source software, 163, 256 optogenetics, 167 Orwell, George, 358–59 osmium hexamine, 57 Our Posthuman Future (Fukuyama), 281 Oviedo Convention, 278 Oxford University, 438, 439 P53 gene, 250–51 PAC-MAN (prophylactic antiviral CRISPR in human cells), 454–57, 460 Palievsky, Julia, 414 Panasenko, Sharon, 33–34 pandemics, 256–57, 263, 357, 405, 447 Black Death, 447 COVID, see COVID-19 Pasteur, Louis, 123, 231–32 Pasteur Institute, 119–22, 471 patents, xv, 39, 76, 98, 99, 114, 231–41 on biological processes, 231–32 for CRISPR systems, 92, 94, 115, 135–36, 144, 156, 232–41 of Doudna and Charpentier at Berkeley, 207–8, 210, 219, 224, 233–40 Doudna’s battle with Zhang over, 184, 194, 208, 224, 234–40, 425, 470 pool idea for, 207–8 of Zhang and the Broad Institute, 192, 207–8, 210–11, 219, 224–27, 233–40 effects on collaboration and competition, 219, 234, 375 for genetic engineering techniques, 392 for microchips, 240–41 of Pasteur, 231–32 universities and, 232, 473 Pauley, Jane, 352 Pauling, Linus, 21–25, 51, 159, 391 Pauling, Peter, 23–24 Pawluk, April, 261, 376 PBS, 384, 386, 389–90, 392, 393 PCR (polymerase chain reaction), 408, 413, 416, 421, 425, 428, 430 PCSK9 gene, 251 PD-1 protein, 249 Peacock Initiative, 301 Pei, Duanqing, 295, 317–19 penicillin, 56, 122 Penrose, Roger, 469–70 People’s Daily, 318 Percy, Walker, 345 Personal Genetics Education Project, 220–21 Pfizer, 435, 441, 442, 445, 447 Phage Group, 19, 479 phages (bacteriophages; viruses that attack bacteria), 19, 37, 75 bacteria’s use of CRISPR against, xiv, xviii, 67, 76–77, 86, 87, 93–94, 106, 111 see also CRISPR number of, 75 philanthropic foundations, 118 Phillips Academy, 171 physics, xvii, xix, 89 Pinker, Steven, 291–92 Pisano, Gary, 114 Pixar, 463 Plague, The (Camus), 399 Planck, Max, 471 Plath, Sylvia, 352 playing God, 269, 273, 333, 363–65, 480–81 PNAS, 143–44 pneumonia, 121 pneumonic plague, 159 Poe, Edgar Allan, 352 Poincaré, Henri, 69 Polaris Partners, 209 polio, 345, 437 polymerase chain reaction (PCR), 408, 413, 416, 421, 425, 428, 430 Pomona College, 30, 31–34 Porteus, Matthew, 344 He Jiankui and, 306–7, 314, 321, 323 preimplantation genetic diagnosis, 274–76, 285, 327, 337, 342, 361–62 prizes, see scientific prizes procreative beneficence, 360 Project Lightspeed, 441 Project McAfee, 443 Prometheus, 268, 286, 363, 365 Prometheus Bound (Aeschylus), 243 Protein & Cell, 290 proteins, 17, 43, 44, 45, 47, 51, 59, 61, 65 enzymes, see enzymes fluorescent, 165–67, 382–83 light-sensitive, 167 Pauling’s work on, 21 psychological disorders, see mental illness PubPeer, 226 Putin, Vladimir, 294 Quake, Stephen, 300, 301, 307 Quebec conference, 373–77 Qi, Stanley, 448, 453–57, 460 Quiz Kids, 18 race African Americans COVID vaccines and, 461 as researchers, 461 and skin color as disadvantage, 347–48 Watson’s comments on, 37, 49, 386–92, 394 radiation exposure, 260, 351 Rakeman, Jennifer, 409 Ramsey, Paul, 268–69 Rawls, John, 281, 357–58 Raytheon, 89, 117 Reader, Ruth, 227 Reagan, Ronald, 309 Rebennack, Mac, 479 Redesigning Humans (Stock), 278 Reed, Jack, 328 Reed, Lou, 352 Regalado, Antonio, 227, 312–13 religious organizations, 273 Remaking Eden (Silver), 277 reprogenetics, 277 reverse transcription, 270, 408 ribozymes, 44–45, 47, 53, 60 Rice University, 300, 307–9 Ridley, Matt, 90 crystallography and, 19–23, 51 Rifken, Jeremy, 269 RNA (ribonucleic acid), xvii, xviii, 17, 43–50, 85, 105, 385, 435–36, 446–47 in central dogma of biology, 44, 47, 270 of coronavirus, 65, 403–4 in CRISPR, 79, 108, 133 Cas13 targeting of RNA, 423–25, 429, 451, 452, 454–57 CRISPR RNA (crRNA), 86, 106, 124–26, 131–35, 137–39, 143, 146, 147, 180, 184, 186, 217 RNA interference, 77, 79, 93 single-guide RNA (sgRNA), 134–35, 139, 186, 190, 191, 195, 198 trans-activating CRISPR RNA (tracrRNA), 124–27, 131, 134, 135, 139, 146–47, 179–80, 182, 184–86, 217–18, 225 crystallography and, 53, 55–57, 66, 171, 181 Doudna’s work on, xviii, 45–49, 51–61, 63, 65–67, 134, 181, 220, 435–36, 446 first, origin of, 47 interference, 65–67, 77, 79, 85, 87, 93, 107 introns, 44–45, 49, 53, 55, 66 messenger (mRNA), 43–44, 65, 66, 77, 85, 439–42, 445 and origin of life, 45–47 replication in, 45, 47, 49, 51, 55 reverse transcription and, 270, 408 ribozymes, 44–45, 47, 53 structure of, xviii, 48, 51–61, 63, 65, 66, 134, 181, 220 self-splicing, 45, 47–49, 53–55, 60, 66 vaccines, 439, 440–42, 445–47, 449 in viruses, 65, 451–53 Rockefeller University, 17, 121, 181, 200, 205, 234–35, 270 Rogers, Michael, 270 Rolling Stone, 270 Roosevelt, Franklin, 345, 346, 386 Rossant, Janet, 369 Rothkopf, Joanna, 227 Royal Swedish Academy, 470 Russia, 294, 414 Sabeti, Pardis, 450–52 Sabin, Albert, 345, 437 Safe Genes, 260, 262, 380 Şahin, Uğur, 441 St.

The Innovators: How a Group of Inventors, Hackers, Geniuses and Geeks Created the Digital Revolution by Walter Isaacson

1960s counterculture, Ada Lovelace, AI winter, Alan Turing: On Computable Numbers, with an Application to the Entscheidungsproblem, Albert Einstein, AltaVista, Alvin Toffler, Apollo Guidance Computer, Apple II, augmented reality, back-to-the-land, beat the dealer, Bill Atkinson, Bill Gates: Altair 8800, bitcoin, Bletchley Park, Bob Noyce, Buckminster Fuller, Byte Shop, c2.com, call centre, Charles Babbage, citizen journalism, Claude Shannon: information theory, Clayton Christensen, commoditize, commons-based peer production, computer age, Computing Machinery and Intelligence, content marketing, crowdsourcing, cryptocurrency, Debian, desegregation, Donald Davies, Douglas Engelbart, Douglas Engelbart, Douglas Hofstadter, driverless car, Dynabook, El Camino Real, Electric Kool-Aid Acid Test, en.wikipedia.org, eternal september, Evgeny Morozov, Fairchild Semiconductor, financial engineering, Firefox, Free Software Foundation, Gary Kildall, Google Glasses, Grace Hopper, Gödel, Escher, Bach, Hacker Ethic, Haight Ashbury, Hans Moravec, Howard Rheingold, Hush-A-Phone, HyperCard, hypertext link, index card, Internet Archive, Ivan Sutherland, Jacquard loom, Jaron Lanier, Jeff Bezos, jimmy wales, John Markoff, John von Neumann, Joseph-Marie Jacquard, Leonard Kleinrock, Lewis Mumford, linear model of innovation, Marc Andreessen, Mark Zuckerberg, Marshall McLuhan, Menlo Park, Mitch Kapor, Mother of all demos, Neil Armstrong, new economy, New Journalism, Norbert Wiener, Norman Macrae, packet switching, PageRank, Paul Terrell, pirate software, popular electronics, pre–internet, Project Xanadu, punch-card reader, RAND corporation, Ray Kurzweil, reality distortion field, RFC: Request For Comment, Richard Feynman, Richard Stallman, Robert Metcalfe, Rubik’s Cube, Sand Hill Road, Saturday Night Live, self-driving car, Silicon Valley, Silicon Valley startup, Skype, slashdot, speech recognition, Steve Ballmer, Steve Crocker, Steve Jobs, Steve Wozniak, Steven Levy, Steven Pinker, Stewart Brand, Susan Wojcicki, technological singularity, technoutopianism, Ted Nelson, Teledyne, the Cathedral and the Bazaar, The Coming Technological Singularity, The Nature of the Firm, The Wisdom of Crowds, Turing complete, Turing machine, Turing test, value engineering, Vannevar Bush, Vernor Vinge, Von Neumann architecture, Watson beat the top human players on Jeopardy!, Whole Earth Catalog, Whole Earth Review, wikimedia commons, William Shockley: the traitorous eight, Yochai Benkler

His introduction deserves to be reread whenever politicians threaten to defund the research needed for future innovation. “Basic research leads to new knowledge,” Bush wrote. “It provides scientific capital. It creates the fund from which the practical applications of knowledge must be drawn.”8 Bush’s description of how basic research provides the seed corn for practical inventions became known as the “linear model of innovation.” Although subsequent waves of science historians sought to debunk the linear model for ignoring the complex interplay between theoretical research and practical applications, it had a popular appeal as well as an underlying truth. The war, Bush wrote, had made it “clear beyond all doubt” that basic science—discovering the fundamentals of nuclear physics, lasers, computer science, radar—“is absolutely essential to national security.”

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J.

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The Entrepreneurial State: Debunking Public vs. Private Sector Myths by Mariana Mazzucato

Apple II, banking crisis, barriers to entry, Bretton Woods, business cycle, California gold rush, call centre, carbon footprint, carbon tax, Carmen Reinhart, circular economy, clean tech, computer age, creative destruction, credit crunch, David Ricardo: comparative advantage, demand response, deskilling, dual-use technology, endogenous growth, energy security, energy transition, eurozone crisis, everywhere but in the productivity statistics, Fairchild Semiconductor, Financial Instability Hypothesis, full employment, G4S, general purpose technology, green transition, Growth in a Time of Debt, Hyman Minsky, incomplete markets, information retrieval, intangible asset, invisible hand, Joseph Schumpeter, Kenneth Rogoff, Kickstarter, knowledge economy, knowledge worker, linear model of innovation, natural language processing, new economy, offshore financial centre, Philip Mirowski, popular electronics, Post-Keynesian economics, profit maximization, Ralph Nader, renewable energy credits, rent-seeking, ride hailing / ride sharing, risk tolerance, Robert Solow, shareholder value, Silicon Valley, Silicon Valley ideology, smart grid, Solyndra, Steve Jobs, Steve Wozniak, The Wealth of Nations by Adam Smith, Tim Cook: Apple, Tony Fadell, too big to fail, total factor productivity, trickle-down economics, vertical integration, Washington Consensus, William Shockley: the traitorous eight

Myth 1: Innovation is about R&D The literature on the economics of innovation, from different camps, has often assumed a direct causal link between R&D and innovation, and between innovation and economic growth. While the systems of innovation literature referred to above has argued strongly against the linear model of innovation, much innovation policy still targets R&D spending at the firm, industry and national levels. Yet there are very few studies which prove that innovation carried out by large or small firms actually increases their growth performance – that is, the macro models on innovation and growth (whether ‘new growth’ theory models or the ‘Schumpeterian’ models) do not seem to have strong empirical ‘micro foundations’ (Geroski and Mazzucato 2002a).

America in the World by Robert B. Zoellick

Albert Einstein, anti-communist, banking crisis, battle of ideas, Berlin Wall, Bretton Woods, British Empire, classic study, Corn Laws, coronavirus, cuban missile crisis, defense in depth, Deng Xiaoping, Donald Trump, Douglas Engelbart, Douglas Engelbart, energy security, European colonialism, facts on the ground, Fall of the Berlin Wall, foreign exchange controls, Great Leap Forward, guns versus butter model, hypertext link, Ida Tarbell, illegal immigration, immigration reform, imperial preference, Isaac Newton, Joseph Schumpeter, land reform, linear model of innovation, Mikhail Gorbachev, MITM: man-in-the-middle, Monroe Doctrine, mutually assured destruction, Nixon triggered the end of the Bretton Woods system, Norbert Wiener, Paul Samuelson, public intellectual, RAND corporation, reserve currency, Ronald Reagan, Ronald Reagan: Tear down this wall, scientific management, Scramble for Africa, Silicon Valley, Strategic Defense Initiative, The Wealth of Nations by Adam Smith, trade liberalization, transcontinental railway, undersea cable, Vannevar Bush, War on Poverty

Second, Bush wanted the country to invest in basic research, the “seed corn” of future technologies. He understood that scientific experimentation needed the freedom to test ideas without considering immediate utilitarian purposes. Neither the military nor industry had the patience—or vision—to back pure scientific research. Bush’s plans reflected a linear model of innovation that began with scientific knowledge, translated into engineering practice, and led to practical products and processes. He could probably see that in reality the stages of this progression blurred into a network of feedback loops among theory, applied research, testing, refinements, new discoveries, and new processes and tools.