erythropoietin, 308
ES cells. See embryonic stem cells
Escherichia coli (E. coli), 173, 174, 175, 180, 207, 209–10, 211, 212, 228–29
Essay on the Principle of Population, The (Malthus), 37, 38
estrogen
sexual reassignment using, 363, 365
in women with Swyer syndrome, 363
ethical issues. See also moral issues
death in gene-therapy trial in OTC deficiency and, 432–33, 434–35, 465
ES cells and genetic changes and, 473, 477
fetal testing for homosexuality and, 377
gene cloning and, 233
gene-therapy trials in children and, 430, 434, 435, 465
human genome engineering and, 478
patenting recombinant DNA techniques and, 237
preimplantation genetic diagnosis (PGD) and, 456–57, 464
propagating genetic hybrids in bacterial cells and, 209
recombinant DNA technology and, 233
scientists’ proposal for a moratorium on use of genomic engineering due to, 477
sexual selection for male children and, 456–57
transgenic animals in gene research and, 421
ethnic cleansing, 138. See also genetic cleansing; racial cleansing
eugenic camps, 120, 227. See also colonies
eugenics, 64–77. See also neo-eugenics (newgenetics)
American programs for, 77, 344
critics of, 73–74
early public support for, 73, 74, 75–77
equality in social conditions needed for, 116–17
fear of racial degeneration and, 75
fittest babies contests and, 85
Galton’s coining of word, 65, 72, 502
Galton’s promotion of, 64–65, 72–75, 110, 116, 120, 159, 273, 343, 502
gene therapies and, 464
Muller’s mutation research and opinions on, 116–17, 274
Nazi racial extermination programs justified by, 124–25, 138
Nazi sterilization programs based on, 120, 121–22, 123, 124, 125
neo-eugenics (newgenetics) differentiated from, 272–73, 275
racial hygiene theory and, 76–77, 120–21
radiation-induced genetic changes for, 116
renunciation of, after Nazi’s use of, 138, 259
selective breeding proposals for, 73, 74, 75
sexual selection for male children and, 456–57
sterilization proposals for, 74, 75–76
Eugenics Court (Germany), 121
Eugenics Record Office, 77, 85, 116, 138
Eugenics Review (journal), 76
Eumenides (Aeschylus), 21
European Early Modern Human (EEMH), 333
euthanasia program for genetic defectives, in Nazi Germany, 13, 122–24
Evans, Martin, 419
evolution
Agassiz’s theory of multiple origins and theory of, 331
cancer as a genetic disease related to, 297
Darwin’s gemmule theory of, 43–44, 57, 66, 113, 395–96
early modern humans and, 332–33
genetic memory as challenge to, 395
genetics reconciled with, 102, 104–08
genomic information for, 333n
information theory on impact of mutations on, 413
natural selection and, 40–41, 104–05, 331
Neanderthals’ place in, 332–33
phenotype as interactions between heredity, chance, environment, variation and, 107–08
theory of heredity needed with, 57, 65, 66
Wallace’s general theory of, 39
exome sequencing, 443
exons, 219, 295, 323, 443
“Experiments in Plant Hybridization” (Mendel), 46, 60
extermination camps, in Nazi Germany, 124–25, 129–30, 137–38, 226
factor VIII gene, in humans, 197, 247–48
factor VIII therapy, 246–47, 249
factor IX gene therapy, 466
Falkow, Stan, 212, 213
familial schizophrenia, 8, 442, 444–45, 446n, 461
fantasies
human genome encoded with, 483
in schizophrenia, 4
sexual behavior related to, 365, 366
Fantastic Four (comic-book series), 266
fate map for individual genomes, 191, 488–89
fear extinction, 492n
fears, in schizophrenia, 2, 4, 5
FBI, 117
FDA, 249, 434, 435
feebleminded
eugenics and sterilization of, 77, 78–79, 80, 81, 116, 120
Nazi racial cleansing program for, 124
Feldburg, Wilhelm, 131
Feldman, Martin, 336, 338, 342
Fermat, Pierre de, 56–57
fetal cell tests, 267
films
eugenics education using, 85
Nazi propaganda using, 121
Fisher, Ronald, 103–04, 399
fittest babies contests, 85
fittest concept. See survival of the fittest
5HTTLRP gene, in humans, 459–60
fly genetics. See fruit flies
“For Whom the Bell Curves” (Patterson), 348
fossils
Darwin’s collection of, 32, 33–34, 221n
Herschel’s origin theory and, 30
human origin and migration theory and, 336
Foucault, Michel, 462
Franklin, Rosalind
background and training of, 143–44
criticism of Watson and Crick’s double-helix DNA model by, 151–52
imaging research on DNA structure by, 13, 144–45, 149–50, 153, 153n, 155, 158, 159, 314, 502
Watson’s reaction to research of, 149–50, 150n, 154
fraternal twins. See twins; twin studies
Freud, Sigmund, 442
Friedman, Richard, 491, 492n
frogs
gene insertion experiments with, 229, 231, 236
nuclear transfer experiments with, 396–99, 402, 404
Yamanaka’s cell-fate reversal experiment in, 404–05
fruit flies
cell-fate determination in embryonic development studies using, 186–91, 195
chromosome research using, 93–94, 95, 96–97
comparisons between human and worm genes with, 316–17
environmental triggers for gene actualization in, 263–64
gene action research using, 162
genetic variant experiments using, 105–08, 110
genome sequencing of, 303, 315–17
as model system for research, 259
number of genes in, 316
Science publication of genome of, 316–17
Fruit Fly Genome Project, 303
“Funes the Memorious” (Borges), 403
Future of Genomic Medicine conference (2013), Scripps Institute, La Jolla, California, 450
Galápagos Islands, 33, 38, 41
Galen, 356
Galton, Francis, 62, 64–70
Ancestral Law of Heredity of, 68–69, 72
background and training of, 65
Bateson’s criticism of, 69, 72
Darwin on work of, 68
Darwin’s research studied by, 65, 66
eugenics promoted by, 64–65, 72–75, 110, 116, 120, 159, 273, 343, 502
nature versus nurture research of, 67, 128
sterilization (negative eugenics) and, 76
twin studies used by, 128, 298
units of information in inheritance and, 68–70, 74, 103
variation measurements of, 66–68, 70
Gamow, George, 164
Gardner, Howard, 345
Garrod, Archibald, 260–61
gastric cancer, 405
Gaucher’s disease, 269, 291
Gelsinger, Jesse
impact of death of, 434–35, 465
OTC deficiency gene-therapy trial and, 431–34, 464, 465, 466, 503
OTC deficiency variant i
n, 429, 430
Gelsinger, Paul, 431, 432, 433–34, 465
gemmule theory of heredity
Darwin’s statement of, 43–44
experimental proof against, 57, 66, 113
genetic memory related to, 395–96
GenBank, 320
gender
amniocentesis to predict, 267
ancient Greek beliefs on, 356–57
genes in determination of, 355–56, 366–67
preimplantation genetic diagnosis (PGD) to predict, 456
sexual selection for male children and, 456–57
use of term, 356
gender identity
continuum of, 367
genes in determination of, 355–56, 367–68
sexual reassignment and, 363–67
transgender identity and, 368
use of term, 356
of women with Swyer syndrome, 363
gene activation
epigenetic marks and, 403n, 418
external triggers for, 107
gene regulation using, 401
gene-silencing and, 399–400, 401
histone marking of molecular memory and, 401–02
human embryogenesis and, 407
mapmaker genes for, 189–90
promoters for, 307n
proteins for, 189, 196, 403n
random chance for, 107
selective, at different times and in different circumstances, 177
gene cloning, 218, 220, 221, 292
Asilomar II conference (1975) on, 233
“Berg letter” on benefits and hazards of, 228
Berg’s recombinant DNA research involving, 208–09
of BRCA1 gene in breast cancer, 439
coining of phrase, 222
as conceptual shift, 294
concerns about using, 227, 230, 231, 232, 233, 237
of cystic fibrosis gene, 288–91
of Dolly, the sheep, 397
early research on linked genes and, 97
of factor VIII gene, 247–48, 249
finding disease-linked genes using, 276–77
gene libraries for, 224
Genentech’s use of, in medicine, 238, 241, 242, 243, 244, 251
of hemochromatosis gene, 279
Human Genome Project’s use of clone-by-clone assembly approach, 311, 313, 319
impact of, 222, 224
mapping genes to chromosomal locations using, 287, 288
nuclear transfer experiments using, 397
patent for, 237
positional cloning technique in cystic fibrosis mapping, 288–91
protein manufacture using, 250–51
reverse transcriptase used with, 248
scientists’ suggestions for regulating, 227, 229, 230, 232–33
use of term, 13, 222
gene editing
intentionally changing human genome using, 489
issues raised by, 476
permanent and heritable changes on human embryonic stem cells using, 475
scientists’ proposal for a moratorium on use of, 476–77
gene expression
epigenetic marks and, 403n
gene-silencing and, 400
genomic code controlling multiple genes for, 325
Hongerwinter experience and reformatting of, 405–06
incomplete penetrance and variability in, 389n
intergenic DNA and introns for, 307, 324
in schizophrenia, 447
starvation-induced alterations in, 405
virus genes in composite embryos and lack of, 418
gene families, 324
gene-fragment genome sequencing technique, 306–09, 308n
gene mapping, 278–92
chromosome jumping technique in, 289–90, 294
as conceptual shift, 294
in cystic fibrosis, 13, 289–90
dissatisfaction with slow rate of change in, 294–95
early research on linked genes and, 97
failure of gene-by-gene approach in, for polygenic disorders, 295, 300
families with genetic trait markers needed for, 281, 286
in hemochromatosis, 278–79
in Huntington’s disease, 13, 283–84, 361
linkage analysis in, 109, 286, 378, 439, 445, 445n
polymorphisms as signposts in, 280–81, 301
positional cloning technique in, 288–91
process of identifying gene in, 279–80, 286–88
in schizophrenia, 445–46
search for sex-determining gene on the Y chromosome using, 361
as transformative moment in human genetics, 288, 291–92
Genentech
biotech research by, 251–52, 466
factor VIII gene cloning by, 247–48
federal guidelines and, 243
founding of, 239, 241
insulin synthesis by, 243–45, 243n, 251, 308
somatostatin research of, 241–42
Generation of Animals (Aristotle), 23
gene recombination, 181–82, 184, 208, 227, 229, 231, 278, 360n
genes
as basic unit, 9–10, 485
Bateson on power of, 63
changes in conception of, due to genome sequencing, 314–15, 321
crossing over of, 96, 97, 182, 208, 334–35, 502
discontinuous nature of information on, 63, 103, 413
DNA as master molecule of, 291
embryonic development and, 102
environmental influences on, 402–03
eugenics and manipulation of, 74
evolution reconciled with, 102, 104–08
families of, 324
flow of biological information with, 410
four phases of quest to understand, 321
identity and, 368–69
information carried by, 101–02
information theory on formation of, 412–13
interplay of epigenes with, 407
Johannsen’s coining of word, 71–72, 172, 502
number of human, 322, 323
origins of human beings seen in, 331–33
patents for, 308–09
perception of ourselves as assemblages of, 485–86
Schrödinger on molecular structure of, 132
shift from pathology focus to normalcy in research on, 330
speculations about molecular identity of, 133–34
Szostak’s experiment using micelles to generate self-replicating forms of, 411–12
transcription of RNA copies of, 166–67, 182
transformation of. See transformation
translation of, 71–72, 164–65, 166–67, 314
as units of selection in neo-eugenics (newgenetics), 273
variation in. See variation
Genes, Dreams and Realities (Burnet), 379
gene sequencing, 13, 292
as conceptual shift, 294
dissatisfaction with slow rate of change in, 294–95
gene diversity in cancer and, 297
Human Genome Project for, 13
impetus for sequencing entire human genome using, 295–97
potentially treatable condition identified by, 453
scale shift in, 293
in schizophrenia, 443, 445, 447
template of normal cancer genome needed in, 297–98
use of term, 13
gene-silencing, 399–400
gene splicing, 219, 248, 323
gene splitting, 219, 294
gene therapy, 423–36
ADA deficiency treatment using, 423–25, 426–28
ban on trials of, 435, 437
criticisms of approach to trials of, 433–34, 435–36
delivery of genes into nonreproductive cells in, 422–26
discovery of embryonic stem cells (ES cells) for, 418–19
enthusiasm for using, 428
ES cells and, 418
factor IX in hemophilia and, 466
first known attempt in humans, with beta-thalassemia, 424n
gene-modified T cells used in, 425–27
germ-line, 465, 467, 469, 474
for hemophilia, 466–67
inserting corrected gene directly into the body in, 430, 431–32, 434, 435, 436, 466
new technologies introduced for, 465–66
nonreproductive cells modified in, 464
ornithine transcarbamylase (OTC) deficiency treatment using, 429–36
permanently modified genomes in, 467–68
positive eugenics and, 464
reproductive cells modified in, 464–65, 467
retroviral gene-delivery vector in, 423–25
return of, after introspection following trial death in, 465
two types of, 464–65
virus genes inserted into composite embryos for, 418
viruses for gene delivery in, 465–66
genetically modified organisms (GMOs), 14n, 245, 418, 475
genetic alteration, 116, 301, 421, 428, 437
genetic cleansing, 85
colonies for feeblemindedness and, 124
heredity basis for, 129
Nazi approach to racial cleansing based on, 121–22, 124, 138
Ploetz’s theory of, 120
Genetic Courts (Germany), 122
genetic diagnosis, 437–62, 491. See also genetic screening; genetic tests of bipolar disorder, 450, 453, 461
BRCA1 gene in breast cancer and, 438–40, 453
conundrums in using, 453
discovery of genetic links to diseases as impetus for development of, 437
diseases selected for, 458
example of two rare syndromes superposed on each other in, 451–52
extraordinary suffering as condition for using, 458, 459, 461, 462, 464
family and personal choices after variant identification in, 461, 462
of fetal mutations using maternal blood, 450
fundamental questions about uncertainty, risk, and choice and, 450
gene management using, 457–58
genes predictive of risk and, 447
high-penetrance genes in, 458, 459, 461, 462, 464
justifiable, noncoerced interventions used after, 458, 459, 461, 462, 464
medical and moral conundrums with, 437–38
penetrance and expressivity as factors in, 447
power to determine “fitness” using, 461–62
predictive determinants in, 438, 454–55
preimplantation genetic diagnosis (PGD) used for, 456–57
previvors and, 441, 453–54
renaissance in use of, 437
of schizophrenia, 442–47, 449–50, 453, 455, 492
selective abortion after, 269, 269n, 273, 452, 458
of a severe, progressive degenerative neuromuscular disease, 450–52, 453
triangle of principles guiding use of, 458–59, 461–62, 464
unpredictable nature of some genes and, 454
genetic disorders
combination of mutations and penetrance in, 299