The Gene

Home > Science > The Gene > Page 72
The Gene Page 72

by Siddhartha Mukherjee


  concerns about responsible use of genome engineering for treatment or cure of, 476

  creating a fate map for, 488–89

  mismatch between genome and environment in, 264–65, 482

  monogenic, 260–62, 295

  need to understand intersection between genetic information, behavioral exposures, and random chance in, 487

  neo-eugenics (newgenetics) to select against specific, 273–74

  pattern of inheritance as clue to genetic influences in, 298–300

  penetrance and expressivity of genes in, 263–64, 447

  polygenic, 262

  polygenic, caused by multiple genes at multiple locations, 262–63, 295

  problem of identifying actual genes causing, 278–79

  tendencies toward, identified by genome sequencing, 490–91

  genetic engineering, 291

  ban on federal funding for ES cells for, 469

  as beginning of a new era, 226

  Berg’s early work with recombinant DNA and, 206–08

  challenges to implementing, 467

  as conceptual shift, 294

  concerns about safety of, 226

  cystic fibrosis gene research using, 290n

  Genentech formed to explore, 239

  hemophilia treatment using, 466–67

  interest in future applications of, 222, 291, 417

  steps in achieving, in humans, 475

  genetic links

  in autism, 265, 276, 406, 444, 444n, 448, 449, 454, 482, 503

  in bipolar disease, 8, 388, 444, 447, 449, 453, 503

  in cancer, 9

  creativity and, 449

  criminal behavior and, 300–301

  development of genetic diagnosis and increase in number of, 437

  genes predictive of risk and, 447

  intergenerational family histories showing, 8

  possible use of technology for changing, 9

  in schizophrenia, 8, 129, 261, 262, 276, 298–300, 303, 442, 445n, 449, 453, 503

  genetic memory

  cell’s capacity to selectively silence, 403

  epigenetics used to alter, 406

  experience transmitted to next generation in, 395–96

  gene transmission in, 396

  histone marking of molecular memory on genes and, 401–02

  Hongerwinter experience and, 394, 395, 405–06

  nuclear transfer experiments and, 396–99, 402

  random inactivation of X chromosomes and, 399–400

  Yamanaka’s experiment to reverse, 404–05

  genetics

  agricultural fair booths on, 85

  Aristotle’s work in, 23, 24

  Bateson’s coining of word, 62

  central dogma on movement of, 169, 172, 221, 223

  coining of new words and language for, 71–72

  conceptual shifts in, 293–94

  diseases linked with, 260–61, 291

  dissatisfaction with slow rate of change in, 294–95

  four phases of quest to understand, 321

  power to determine “fitness” using, 461–62

  scale shifts in, 294

  shift from pathology focus to being science of normalcy, 330

  Soviet political ban on, 125–26, 127

  thematic focus of, 330–31

  Genetics Institute (GI), 247–48

  genetic screening. See also genetic diagnosis; genetic tests

  for BRCA1 gene, 13, 438, 439–40, 457

  for cystic fibrosis, 291

  for Down syndrome, 13, 269, 273, 275, 458, 490n

  for Gaucher’s disease, 291

  lawsuits over medical advice received after, 270–71

  neo-eugenics (newgenetics) and, 272–75

  parental right to choose not to have a child after, 271

  right to be born and, 269, 270, 272

  selective abortion after, 269, 269n, 273

  as social responsibility, 275

  genetic tests. See also genetic diagnosis; genetic screening

  for BRCA1 gene sequence, 439, 440

  diseases amenable to, 455

  genes predictive of risk and, 447

  as moral tests, 438

  principles guiding use of, 458–59

  for schizophrenia, 446–47, 449

  therapeutic abortion performed on basis of, 268

  genetic therapies, 491

  geniuses

  inheritance patterns and, 74

  schizophrenia and, 448

  sperm banks (repository) for choosing, 274, 276

  genome editing (genomic surgery), 472

  Genome Project. See Human Genome Project

  genomes

  cancer and, 9

  epigenetic system for functioning of, 402–03

  evolutionary history seen in, 333n

  mismatch between environment and, 264–65, 482

  publication of draft sequence of, 13

  sequencing of. See Human Genome Project; genome sequencing

  genome sequencing, 306–21

  choice of simple organisms to use in early research using, 303

  Clinton on success of, 318–19

  comparisons between human, worm, and fly genes in, 316–17

  conception of gene changed by, 294, 314–15, 321

  decision to use, after genetic diagnosis results, 461–62

  early evaluation of technical feasibility of, 301–03

  estimating number of genes in, 313n

  of fruit flies, 303, 315–17

  gene patent proposals for, 308–09, 312

  Haemophilus genome and, 309–11, 313

  of human genome. See Human Genome Project

  joint announcement about first survey of, 317–19

  joint publication of papers on, 321

  natural ambiguity in, 194

  noncoding genes in, 314, 455n

  overview of human genome in, 322–26

  rapid-sequencing machine for, 302, 306

  for schizophrenia, 461

  shotgun-sequencing technique in, 310, 311, 312, 316, 319

  single cell with multiple functions in, 313

  single function with multiple cells in, 313–14

  tendencies toward disease identified by, 490–91

  Venter’s gene-fragment technique in, 306–09, 308n

  of worms, 303, 312–14, 313n, 315, 316, 317

  genomic code, 325

  genomic engineering, 463–83

  ban on federal funding of new ES cells for, 469, 476

  Berg’s experiments with, 206–07, 226

  Chinese’s experiments with human embryos using, 478

  concerns about responsible enhancement of genomes in, 464, 477

  CRISPR/Cas9 system for adding genetic code into genome in, 472, 477, 478, 489

  draft of guide on “post-genomic” use of, 479–83

  establishment of reliable human ES cells needed for, 467–69, 475

  federal bans on aspects of, 476, 479

  first permanent human genome engineering experiment in, 478–79

  first targeted genome modification of human embryo in, 479

  gene-modified ES cells converted into reproductive cells before use in, 473–74

  genetic emancipation versus genetic enhancement in, 477

  hurdles to, 467

  incorporating genetic changes created in ES cells into human embryos in, 473–75

  interest in future applications of, 12, 14, 476

  IVF and, 475

  justification for adding information to the genome in, 477

  Medawar on possibilities of, 222

  method to create intentional genetic changes in genomes of ES cells needed for, 469–73, 475

  modern technologies for, 12, 14

  need for evaluation of, 12

  NIH prohibition on two kinds of research using human ES cells in, 476

  public support for lifting bans on, 479

  questions to be explored in, 475–76

  reproductive
cells modified in, 464–65, 467

  scientists’ proposal for a moratorium on use of gene editing and gene-altering techniques in, 476–77

  severe disease treatment or cure as responsible use of, 476

  steps needed for creating genetically modified humans using, 475–76

  virus genes inserted into composite embryos for, 418

  genotypes, 71

  environmental factors affecting phenotype outcomes with, 107

  eugenics and manipulation of, 74

  interactions between heredity, chance, environment, variation, and evolution and, 107–08

  phenotypes determined by, 106–07

  random change in phenotype outcomes with, 107

  social engineering using, 460–61

  geographic factors

  Darwin’s research on bird population evolution affected by, 37–38, 45n

  D4DR variant distribution and, 386

  development of twins reared apart, 382

  new species formation and, 45n, 108–09

  spread of early humans and, 339–41

  Wallace’s theory of bird population variants affected by, 39

  geology, 19, 28, 30, 32, 38, 47, 335, 336, 340

  Germany. See also Nazi Germany

  eugenics programs in, 76–77

  scientists’ migration from, as reaction to Nazism, 130, 131, 146

  germ cells. See also eggs; sperm

  conversion of ES cells into, 474

  gemmule theory of heredity with, 43

  Hongerwinter memory’s marking of, 405–06

  germplasm

  eugenicists on eliminating defects in, 83

  Weismann on inheritance of, 57–58

  Gilbert, Walter, 166n, 176n

  DNA sequencing by, 218, 219, 222, 243

  genome-sequencing evaluation by, 302–03

  insulin synthesis and, 241, 242, 244

  giraffes, evolution of, 42, 57, 395

  Gleick, James, 10n, 409

  glucose metabolism, genes turned on or off for, 174–76, 176n, 392

  Goeddel, David, 244–45, 247

  Goldstein, David, 450

  Goodfellow, Peter, 360–61, 362

  Goodship, Daphne, 382–83

  gorillas

  evolution and, 332

  pairs of chromosomes of, 322

  Gosling, Ray, 151, 153n, 158

  Gottesman, Irving, 298

  Gould, John, 34

  Gould, Stephen Jay, 348

  Graham, Robert, 274, 276

  Gray, Asa, 44

  Greece, ancient, inheritance theories in, 21–24, 27

  Griffith, Frederick, 112–15, 131, 133, 136, 158, 159, 212

  growth hormone gene, in humans, 421

  guanine, 135, 156

  Gurdon, John, 396–99, 398n, 402, 404

  Gusella, James, 286, 287

  Gypsies, Nazi extermination of, 124–25, 137

  Hadamar hospital, Germany, 123

  Haemophilus influenzae, genome sequencing of, 309–11, 313

  Hahn, Otto, 130

  Haiselden, Harry, 85

  Haldane, J. B. S., 292

  Hamer, Dean

  background and training of, 371–72

  homosexuality-related genes (gay genes) research of, 373–78, 379

  sexual orientation interest of, 372–73

  Hammarsten, Einar, 139

  Hartsoeker, Nicolaas, 26

  Haussler, David, 320

  hawkweed plant-breeding experiments of Mendel, 54–55

  height

  genetic links in, 66, 68, 68n, 74, 103, 104, 110, 128, 334, 480, 481

  genetic manipulations to increase, 76

  Mendel’s plant studies on, 48, 51, 95

  twin studies of, 374, 382

  variance distribution of, 66, 67, 68, 85, 103, 457

  hemochromatosis, 278–79, 281

  hemoglobin

  beta-thalassemia mutation and, 424n

  gene regulation of, 178, 307n

  oxygen binding by, 141–42, 164

  sickle cell anemia and, 170, 171, 173, 184

  hemophilia

  factor VIII therapy for, 246–47, 249

  gene therapy for, 466–67

  genetic inheritance of, 98–99, 100, 129, 260, 264, 278

  genetic map of, 291

  HIV infection with, 249

  Russian royal family with, 98, 99–100

  Henn, Brenna, 338

  Henslow, John, 28, 31

  hepatitis B vaccine, 251

  Hepburn, Audrey, 394

  Herbert, Barbara, 382–83

  Hereditary Disease Foundation, 283

  Hereditary Genius (Galton), 68, 72, 502

  Hereditary Health Courts (Germany), 122

  Hereditary Monstrosities (de Vries), 58

  heredity

  ancient Greek philosophers on, 21–24

  Bateson on power of genes in, 63, 74

  Bateson on transmission of units in, 70–71

  cancer as a genetic disease related to, 297

  Christian belief on Adam as First Parent in, 25

  coining of new words for units in, 71–72

  Darwin’s work on theory of, 41–43, 46, 57

  de Vries on particles of information in, 58, 60, 61, 62

  encoding of basic information in, 25–26

  epigenetics used to alter, 406

  eugenics and laws of, 74

  Galton’s research on, 65–70, 74, 103

  gemmule theory of, 43–44, 57, 66, 113, 395–96

  gene as basic unit of, 9–10, 485

  genetic information in, 101–02

  homunculus concept in, 25–26, 43, 337

  information flow of instructions in, 70–71

  Lamarck’s approach to, 42

  mathematical modeling of traits in, 103–04

  Mendel’s exploration of units of, 53–54, 62, 70, 71

  notion of human identity constructed using, 127–28

  phenotype as interactions between chance, environment, variation, and evolution and, 107–08

  shock therapy for plants to overcome, 126–27, 406

  theory of evolution needed with, 57, 65, 66

  variation in, 36

  Weismann on information passed in, 57–58

  Wolff on fertilized eggs in, 26–27

  Heredity in Relation to Eugenics (Davenport), 77

  Herrick, James, 170

  Herrnstein, Richard, 300, 343, 345, 346, 347

  Herschel, Sir John, 29, 30

  Hershey, Alfred, 139n

  Hess, Rudolf, 119n

  Heyneker, Herbert, 241n

  high-risk behavior, 5HTTLRP gene associated with, 459, 460

  Hiroshima, Japan, atomic bombing (1945) of, 301

  Hirsh, David, 194

  histones, 400–401, 405, 407

  Hitler, Adolf, 124

  eugenics and extermination policy of, 122–23, 275

  racial hygiene beliefs of, 120–21

  rise of, 119

  scientists leaving Germany as reaction to, 130, 131, 146

  HIV, 249, 418, 423

  Hobbes, Thomas, 75

  Hodgkin, Dorothy, 145, 150

  Holmes, Oliver Wendell Jr., 83–84

  homosexuality

  Bieber’s theory of, 370–71

  as choice, 370–71

  Freud on, 442

  gay gene and, 371

  Hamer’s research on genes related to, 373–78, 379

  psychiatrists on, in 1950s and 1960s, 370

  Homosexuality: A Psychoanalytic Study of Male Homosexuals (Bieber), 370

  homosexuals, Nazi extermination of, 125

  homunculus concept, in inheritance, 25–26, 43, 337

  Hongerwinter (Hunger Winter), Netherlands

  description of, 393–94

  gene expression and cellular memory affected by, 405–06

  grandchildren’s genetic memory of, 394, 395

  physical impact on grandchildren of survivors of, 394

  Ho
od, Leroy, 302, 306

  Hopkins, Nancy, 176n

  hormonal therapy in sexual reassignment, 364, 365–66

  Horne, Ken, 246

  Horvath, Philippe, 470

  Horvitz, Robert, 191, 192–94

  hospitals

  colonies in eugenics movement and, 77, 78–79, 80–81, 82, 84, 120, 304–05

  genetic screening in, 269, 291

  OTC deficiency gene-therapy trial in, 431–33, 434–35

  sexual reassignment in, 363–64

  Hox gene family, 324

  Huang, Junjiu, 478–79, 480

  Huberty, James, 298, 301

  Hughes, Everett, 329

  human embryos

  ethical issues about genomic engineering use of, 473

  experiments to derive stem cells from, 467–69

  federal limits on cell lines from, 469

  first permanent human genome engineering experiment using, 478–79

  human ES cells derived from discarded IVF embryos, 468–69

  targeted genome modification of, 479

  human genetics

  gene mapping as transformative moment in, 288, 291–92

  impact on medicine and health of new interest in, 259–60

  links between diseases and, 260–61

  monogenic diseases in, 260–62

  neo-eugenics (newgenetics) and, 272–77

  nuclear transfer technique using mitochondria and, 398n

  polygenic disease caused by multiple genes in multiple locations in, 262–63, 295

  polygenic syndromes in, 262

  Human Genome Project, 306–12, 315

  catalog of genes by, 330

  challenge of finishing sequence for, 311

  Clinton on success of, 318–19

  clone-by-clone assembly approach in, 311, 319

  conflicts between Celera and, 317, 319

  draft genome sequence publication by, 13

  federal control of, 303–04, 309

  funding for, 312

  initial meeting of, 304

  international collaborators on, 304

  joint announcement about first survey with Venter’s Celera, 317–19

  joint publication of papers by, 321

  polymerase chain reaction (PCR) used in, 302

  purpose of, 13–14

  Science publication of work of, 315

  as starting point in inquiry into the exact nature of information, 486

  Sturtevant’s research on gene linkages as basis for, 97

  technical hurdles encountered by, 319–20

  Watson as head of, 304, 308, 309, 310, 463–64

  human genomes

  concern about ability to alter, 464

  creating a fate map for, 488–89

  difficulty of deciphering combinations of variants in, 487

  Encyclopedia of DNA Elements (ENC-O-DE) on, 486–87

  future of research on, 330

  gene therapy on reproductive cells introduced into, 464–65

  need for direct study of, 486–87

  number of genes in, 322, 323

 

‹ Prev