The Drug Hunters
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biochemistry, 92, 119, 149, 157, 163, 187–88, 210
Biogen, 167
biogenic amine substances, 241
bipolar disorder, 232
birth control, 207, 211, 213, 214, 216, 247
anti-contraception laws, 213, 216
birth control clinics, 207, 210
Catholic opposition, 214–15, 217
birth control pill, 191f, 193–23
Boston trials, 217
old pottery shed in Mexico City, 220
Puerto Rico trials, 217–19
Swiss dairy farmers, 194–95
synthesis of progesterone, 196–02
black death. See bubonic plague
blood acidity, 180–82
blood infections, 81, 99, 141
blood proteins, 90
blood serum, 84
blue death. See cholera
Boehringer Ingelheim, 63
bone marrow, 110, 122
Borges, Jorge Luis, 9–10
“Library of Babel, The,” 9–10
Vindications. See Vindications
botany, 31–34, 39, 43
Boyer, Herb, 163
Bristol Myers, 55, 133, 190
Bristol-Myers Squibb, 142
British Journal of Experimental Pathology, 129
broad-spectrum antibiotics, 98
Bruckheimer, Jerry, 246
bubonic plague, 80
Calhoun, Dr. Archibald, 101
Candida vaginitis, 5
captopril, 186–88
carbonic anhydrase, 180–82
cardiovascular disease, 179–80
Carl Duisberg. See Bayer Company
carminative. See anti-flatulents
Cat’s Cradle, 196–97
cells, 10, 35, 84, 86, 90, 93, 110, 122, 152, 154–55, 162, 167–68, 228, 269
animal cells, 84, 86
bacteria cells, 84, 128, 162, 165
blood cells, 35
cancer cells, 110, 164
cytotoxity, 122
muscle cells, 93
pancreatic cells, 154–55
plant cells, 86
Center for Drug Evaluation and Research, 142
Centers for Disease Control and Prevention, 183
Chain and Florey, 130–33
Chain, Ernst Boris. See Chain and Florey
chemical suppliers, 52
chemotherapy, 110, 122
Chesapeake Bay, 13
chickens, 44, 138, 204
childbed fever. See puerperal fever
chinchona. See quinine
Chinese Herbal Medicine: Materia Medica, 147
Chinese medicine, 117, 147–48
Chinese workers, 117
chloramphenicol, 140
chloroform, 11–12, 58
chlorpromazine, 234–41
Jacques L., 235
release in the USA, 236
chlortetracycline, 140
chocolate, 38, 39
cholera, 80, 173–77
cholera pandemics, 173–74
cholesterol, 11, 141, 180, 199
Cialis, 248
Ciba-Geigy, 8
Clark University, 205, 211, 213, 214
clotting factor VIII, 167
Clowes, Alec, 150–52, 157–60
clozapine, 237
cocaine, 38
Cold Spring Harbor Symposium on Quantitative Biology, 163
collagen, 230, 232
Collip, James, 156–57, 160–61
Columbus, 35, 80
coma, 180
combinatorial chemistry, 249
Comstock Act of 1873, 207–8, 216
congenital insensitivity to pain, 26
conium, 58
Connaught Laboratories, 158, 161
consumption. See tuberculosis
contraception. See birth control
Cordus, Valerius, 32–34, 39, 44, 52, 120, 200, 250
death, 34, 250
Dispensatorium, 33, 120
corn, 136
Corpora non agunt nisi ligata. See Ehrlich, Paul
corpus luteum, 195–96
Creutzfeldt-Jakob disease, 136
Crick, Francis, 82–83
curare, 38, 122–23
Cushman and Ondetti, 186–89
Cushman, Dave. See Cushman and Ondetti
Cyanamid, 39–40, 56, 63, 105, 112
cyclosporine, 5
cystotomy, 46
cytotoxicity, 122
Dalton, John, 64
atomic theory of, 64
De Materia Medica. See Dioscorides
degradation (chemical), 199
de Isla, Ruy Diaz, 80
Denmark, 89
Depp, Johnny, 247
depravity theory. See moral depravity theory
depression, 38, 39, 232, 238–41
diabetes, 151–54, 156, 159, 160, 165
diaphragms, 207
diarrhea, 19, 173, 213, 250
Die Ätiologie der Begriff und die Prophylaxis des Kindbettfiebers, 82
diethylene glycol, 100, 101, 102
digitalis, 149
Dinesen, Isak, 89
Dioscorea composita. See Mexican yam
Dioscorides, 32–33
De Materia Medica, 32
diosgenin, 200–1
diphtheria, 128, 129
Dispensatorium, 33, 120
diuretics, 181–82, 185
Diuril, 180–82
DNA, 82, 136, 162–66, 168, 249
recombinant DNA, 162–66, 168, 249
Dogmatists, 36
dopamine, 211, 240–41
dopamine receptors, 110–11, 240–41
Dover, Thomas, 20–21
Dover’s Powder, 20–21
drug development, 39, 68, 106, 111–13, 119, 151, 157, 163, 168, 188, 208, 217, 223, 245–52
average cost of developing a new drug, 8, 111
comparison to filmmaking, 245–52
drug trials, 189, 212–30, 239
FDA role in, 111–13
rational design, 187–88, 249
self-experimentation, 212–13
drug discovery stories
aspirin, 63–76
birth control pill, 193–224
captopril, 186–88
chloroform, 11–12, 58
chlorpromazine, 234–41
Diuril, 180–82
ether, 43–56
imipramine, 237–42
insulin, 150–63
opium, 19–25
penicillin, 127–34
propranolol, 184–85
quinine, 35–38
rapamycin, 5–7
Salvarsan, 84–93
streptomycin, 136–39
sulfanilamide, 97–100
drug discovery team, 133, 138, 140, 156–61, 186–88, 237
drug interactions, 109–10
drug potency, 4, 25, 129, 140–42, 161
drug resistance, 140–42
erythromycin, 140
tetracycline, 140
druggable protein. See druggable target
druggable target, 10–11, 85–86, 167–68, 240–41, 258–59
drugs
dirty drugs, 259
New World drugs, 35, 36, 38
Stone Age drugs, 4
total number of possible drug compounds, 9
dwarfism, 166
dyes, 63–67, 84–88
aniline purple, 65, 98
German dye industry, 63–64
methylene blue, 85
trypan red, 86
dyskinesia, 240
E. coli, 141, 162, 166
E. R. Squibb and Sons, 55–56, 58, 67, 70, 133, 142, 164–66, 186–90, 212
acquired by Bristol-Myers, 190
edema, 260
Ehrlich, Paul, 84–93, 97–98, 127, 188, 227
Corpora non agunt nisi ligata, 79, 90
side-chain theory, 90–91
the four G’s, 89
Eli Lilly, 133, 142, 150–53, 157–61, 164–66
Elixir S
ulfanilamide, 100–6, 108–9, 112, 118
guilty of violating a minor regulation, 104
Nidiffler, Maise, 102
Watkins, Harold, 103–104
Empirics, 36
endorphin, 23
Engel-Apotheke, 21
Enovid, 220
epidemics, 79, 173–74, 177
epidemiology, 177–78, 183
epidemiological studies, 177, 179
epinephrine. See adrenalin
erectile dysfunction, 221, 248
ergot, 58, 149
erythromycin, 140
erythropoietin, 167
ethambutol, 139
ether, 34, 43–56
Eben Frost, first ether patient, 48
ether frolics, 45
John Collins Warren, first ether surgeon, 49
ethyl alcohol. See alcohol
Ethyl Corporation, 197
ethylamine, 241
FDA, 7, 8, 26, 70, 103–4, 105–9, 111–13, 212–14, 219, 220, 223, 251
Center for Drug Evaluation and Research, 142
FDA approval, 7, 8, 26, 70, 217, 219, 220, 223
FDA field inspectors, 103–4
fenfluramine. See fen-phen
fen-phen, 106–10
fish or cut bait, 69–70
Fleming, Alexander, 127–29, 131
Florey, Howard. See Florey and Chain
Florey and Chain, 130–34
fluoroquinolones, 98
Food and Drug Administration. See FDA
Food, Drug and Cosmetic Act of 1938, 105
formulators, 20, 67,
the four G’s. See Ehrlich, Paul
Framingham Heart Study, 179–81
Freud, Sigmund, 232–33, 236
Friedrich Bayer and Company. See Bayer Company
Frolich, Theodor. See Holst and Frolich
fungus, 128–34, 137, 252
athlete’s foot, 5, 7, 167, 250
birch fungus, 3–4
G 22355. See imiprimazine
G. D. Searle, 218–20
Galen, 36
gangrene, 46
gaseous surgical anesthetics, 227
Geigy, 237–40
genes, 26, 162–68
insulin gene, 165
rabbit gene that creates hemoglobin, 162
sodium channel gene, 26
Genentech, 162–68
collaboration with Lilly, 165
General Motors, 245–46
genetic medicine, 162–69
Genetics Institute, 167
germ theory of disease, 45, 174
germs. See pathogens
Gillette, King C., 209
Gilman, Alfred. See Goodman and Gilman
GlaxoSmithKline, 105
glucocorticoids, 219–20
glucose, 101, 152, 155
gonorrhea, 127, 141
good laboratory practices (GLP), 105
Goodman and Gilman, 119–24
The Pharmacological Basis of Therapeutics, 121–24
Goodman, Louis. See Goodman and Gilman
guarana, 58
guinea pigs, 231
Harris, Sir Henry, 164–65
Harvard Medical School, 44, 214
hashish. See marijuana
Heinrich Dreser. See Bayer Company
hemophilia, 167
herbarizing, 52
heroin, 19, 22, 70, 72, 75
Bayer heroin, 22, 70, 72, 75
heroin kit, 22
HGH. See human growth hormone
high blood pressure. See hypertension
high-throughput screening, 249
Hippocrates, 228
HIV. See AIDS
HMG-CoA reductase, 11
Hoechst AG, 64, 88
Hoenikker, Felix, 196–97
Hoffman, Felix. See Bayer Company
Hoffmann-La Roche, 63
Holst and Frolich, 231
Holst, Alex. See Holst and Frolich
homeopathy, 68
Hopi medicine men, 117
hormones, 23, 93, 153, 166, 187, 202
human growth hormone (HGH), 166–67
human trials, 189, 212–30, 239
Humanae Vitae, 222
hydrocarbon science, 197–98
hydrocortisone, 219
hypercholesterolemia, 180
hypertension, 178–85
essential hypertension, 178–79
link between hypertension and stroke, 179
hypodermic needles, 22, 159–61
ICI Pharmaceuticals, 184
imipramine, 237–42
Paula I, first patient, 239
Boehringer, Robert, 240
immune system, 5, 90–91, 149, 178, 280
animal immune systems, 5
plant immune systems, 149
immunity, 90
impetigo, 128
impotence, 185
in vitro fertilization, 205, 208, 215
in vivo fertilization, 205
informed consent, 71
Institute for Infectious Diseases in Berlin, 86
Institute of Cell Biology and Genetic Engineering, 40
insulin, 152–66, 168–69, 233, 247
interferon, 148
International Union for Conservation of Nature, 148
Irish potato famine, 173
isoniazid, 139
Italian disease. See syphilis
Jackson, Charles T., 47–48
Journal of the American Medical Association, 101
Jungle, The, 104
Kekulé, August, 63
Kenya, 89
King James Bible, 120
Koch, Robert, 85, 135, 174
Kuhn, Roland, 237–40, 241–42
La Bohème, 134
La Traviata, 134
Laboratorios Hormona S. A., 202
laboratory animals, 87, 205, 213–15, 231
guinea pigs, 231
rabbits, 87, 205, 213–15
Laborit, Henri, 234–36, 241–42
Largactil. See chlorpromazine
League of Women Voters, 210
library of animals, 147–49
library of dirt, 270, 272
library of genes, 166
library of plants, 29f, 34–40, 93, 148
library of synthetic chemistry, 39, 166
Librium, 109
Lilly (company). See Eli Lilly
Lilly, Colonel Eli, 150
Lilly, Eli (Jr.), 150
Lilly, Josiah, 150
limes, 231
Lind, James, 225f, 229–32
Linnaeus, Carl, 35
Lipitor, 11
Liston, Robert, 46
lock-and-key (drug targeting), 91
Lone Ranger, The (movie), 247
Louis XIV, 37
lymphoma, 122
M. smegmatis. See bacteria
M. tuberculosis. See bacteria
Macleod, J. J. R., 154–59, 168–69
madhumeha. See diabetes
magic bullets, 75, 86–89, 93, 127,
malaria, 34–38, 85–86, 148
Manhattan Project, 8, 196–97
MAO inhibitors, 110
marijuana, 25
Marker degradation method, 203, 213
Marker, Russell, 197–02, 220
Massachusetts General Hospital, 49
Massengill, Samuel Evans, 100, 102–05, 108
McClintock, Barbara, 136
McCormick, Katherine Dexter, 209–13, 220
McCormick, Stanley, 209–11
medical schools, 44, 47, 49, 54, 85, 100, 118, 119, 123, 189, 214
Merck (company), 4, 21, 63, 133, 138, 180–82
Merck, Friedrich Jacob, 21
Merck, Emanuel, 21
mercury, 43, 80
metabolites, 111
methylene blue. See dyes
Mexican yam, 200–1
miasma theory, 80–83, 175
microbes. See microorganisms
microbiology, 119, 136
microbus. See Monobacvan
microorganisms, 136
soil microorganisms, 136
microscopes, 84, 91
midwives, 81
MIT, 209, 210
mitral valve dysfunction, 107–9
modafinil, 228
molecular biology, 92, 166
Monardes, Nicolas, 38
Monobacvan, 13, 142
moon shot, 8
moral depravity theory, 175
morphine, 19, 21–23, 58, 69–70, 149,
commercial production, 21
Morton, William T. G., 47–50, 52, 54
Motrin, 73
MRSA, 141, 142
multiple sclerosis, 168
Mycobacterium tuberculosis. See bacteria
nadolol, 188
narcolepsy, 228
Nardil, 110
narrow-spectrum antibiotic, 98
National Science Foundation, 211
Nav1.7, 26
Naval Laboratory, 54
Nazis, 73–75, 130, 132, 134, 232–33
Neisseria gonorrhoeae. See gonorrhea
neural receptors, 240, 241
neurodegenerative diseases, 136
New England Journal of Medicine, 44, 49, 88
Nipah, 135
nitrogen mustard, 122
Nobel Prizes, 67, 124, 135, 136, 137, 168, 185
Banting, Frederick, 168
Baeyer, Adolf von, 67
Black, James, 185
Gilman, Alfred Goodman, 124
Hoenikker, Felix, 196
Koch, Robert, 135
Macleod, J. J. R., 168
McClintock, Barbara, 136
Prusiner, Stanley, 136
Waksman, Selman Abraham, 137
norepinephrine, 241
Novartis, 4, 8, 63, 237
NSAIDs, 26,
numerus clausus, 205
octane rating system, 198
olanzapine, 237
Ondetti, Miguel. See Cushman and Ondetti
opiates. See opium
opium, 3, 9, 19–25
ancient formulation, 19
endorphin receptors, 23
operation, 23
opiate addiction, 22
origins, 19
optical chemistry, 198
organ transplant therapy, 5–6
organophosphate, 122
Oryctolagus cuniculus (laboratory rabbit). See laboratory animals
Ötzi the Iceman, 3–4
Out of Africa, 89
ovulation, 195, 212, 215, 222
painkillers, 27
pancreas, 152–57, 159, 160, 162
pancreatic duct, 154–55, 169
Papaver somniferum. See opium
Paracelsus, 20, 44
parasites, 3–4, 18, 35, 85, 86, 87, 167
paregoric, 20
Parke Davis, 133
Pasteur Institute, 91, 99
Pasteur, Louis, 83–84, 174
pathogens, 11, 80, 83–91, 98, 99, 127, 129, 135, 136–38, 140–41, 167, 175, 177
highly evolved pathogens, 135
newly evolved pathogens, 135
pathology, 10, 120, 130, 131
PDE5 enzyme, 110, 248
PDE6 enzyme, 110
penicillin, 11, 98, 127–34
Albert Alexander, first patient, 131
deep vat fermentation method, 133
manufacture penicillin on a large scale, 132–33
moldy cantaloupe, 133
“penicillin club” consortium, 133