Biotechnology: Science, Engineering, and Ethical Challenges for the Twenty-First Century (1996)
Chapter: INDEX
Page 269
Index
A
Academic-industry collaborations
benefits for students in, 148, 149
benefits of, 153-154
conflict of interest issues, 130, 150-151, 154-155
culture of research in, 144
current status, 132-133
distribution of research funding, 133
exploitation of students in, 131-132
funding issues, 131
funding trends, 141-143
future directions, 144-146
historical development, 129, 138-139
Howard Hughes Medical Institute research policy, 155-160
issues of concern, vii, 131-132, 147-148
National Science Foundation perspective, 147-151
opportunities for enhancing, 149-150
patent law and practice, 139-140, 143
recent significant agreements, 141-143
university mission and, 140-141
Acquired immune deficiency syndrome (AIDS), 2, 30
dementia, 24
enzyme targeting in treatments for, 24-26, 30-33
nucleotide analog therapy, 106
obstacles to vaccine development, 24
plant-derived drugs for, 107
See also Human immunodeficiency virus (HIV)
Adenomatous polyposis coli, 18
Adenovirus, 69
gene therapy delivery systems using, 77-86
Advanced Technology Program, 242
Alpha-1-antitrypsin deficiency, 51-52
Alzheimer disease, 87
animal experimentation, 90
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Antisense molecules, 65, 67, 104
Artificial organs
bioartificial hybrids, 90-92
biotechnology applications, 62
liver, 91-92
pancreas, 90-91
skin, 89-90
vascular system, 92-96
Aspartic proteases, 30
Atherosclerosis, 92
Azidothymidine, 169
B
Basic research
core principles, 153
historical development, 1-2, 3-4, 135
in Howard Hughes Medical Institute, 155-160
patents on research tools, 170-171
public interest issues in, 152-154
Bayh-Dole Act, 139-140, 150, 152, 153, 154, 155, 165-166
definition, 114
EPA assessment, 246
ex situ, 116
future prospects, 125-127
hydraulic conductivity, 119
limitations, 118-119
market potential, 117
organisms used in, 114
performance evaluation criteria, 122
process fundamentals, 119-121
in situ strategies, 116-117
successful applications, 121-125
technical challenges, 114
technological status, 113, 114
in underground environment, 115-116
Biotechnology
cross-disciplinary linkages, 238-239
research development, 43-46
See also Genetic science
Biotechnology industry
biotechnology science and, 239-240
capital markets, 243
company characteristics, 110-111
confidentiality issues, 109
government partnerships, 243
international competition, 240
issues of concern, vi-vii
market characteristics, vi, 63
NIH cDNA patents and, 168-170
obstacles to manufacturing, 62
recombinant DNA technology in, 12
regulatory environment, 244, 248-249
regulatory process, 252-256
skills for, 110-111
tax environment, 243-244
See also Academic-industry collaborations
Biotechnology Research Subcommittee, 240-241
Blood products, 54
Bone marrow transplantation, alternatives to, 54
Bovine growth hormone, 197
Brain tumors, gene therapy for, 81-86
Bulbar muscular atrophy, 48
C
Cancers/tumors
epigenetic model, 104-106
genetic-based treatments, 19-23
genetic mutations in, 17-19, 105
solid, gene therapy for, 81-86
taxol therapy, 107-110
tumor suppressor genes, 18-19
See also specific cancer type; specific site
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Carbohydrate drugs, 104
Cardiovascular disease, 71
gene therapy for, 86
Cartilage, 97
Clinton administration
national science policy, 233-234, 240, 241
regulatory environment, 244
research and development budget, 235-236, 241
Cloning, 195-196
Clotting factor VIII, 53-54
Confidentiality
in biotechnology industry research, 109, 155
of genetic information, 51-53, 193-195, 203-204, 206
international research agreements, 227-228
Consultants/consulting, 158-159
Coronary heart disease, 51
Cost of care, eugenic pressures in, 202-203
Creutzfeldt-Jakob disease, 54
Criminal investigations
DNA testing, 10
genetic personal identification, 55
Cross-disciplinary linkages, 238-239
Cystic fibrosis, 50
Cytokines
agonists/antagonists, design of, 41-42
signaling pathways, 39-41
structure, 38-39
D
Dentatorubral-pallidoluysian atrophy, 49
Department of Agriculture, U.S., 248, 255
Diabetes mellitus, bioartificial pancreas for, 90-91
Diethylstilbestrol, 215-216
DNA
antisense therapy, 67
base pairs, 5
composition, 4-5
current understanding of, 63
fragmentation and separation, 7-11
individual differences, 10, 55
mutations, 6-7
patent applications, 167-170
polymerase chain reaction, 10-11, 43-44
protein encoding, 5-6
restriction fragment length polymorphism, 10-11
tracking human historical migration patterns, 55
See also Recombinant DNA technology
Duchenne muscular dystrophy, 49
E
Economics
access to prenatal genetic testing, 201-202
biotechnology market size, vi
cost of patent system, 163-164
drug pricing and reimbursement, 228-230
federal investment in biotechnology, 241-244
federal research budget, 235-236, 241
Human Genome Project funding, 205, 236-238
of regulation, 250-251
research funding in universities, 133, 138-139, 153
university finances, 133-134
Education and training
benefits for students in academic-industry collaboration, 148, 149
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exploitation of students in academic-industry collaboration, 131-132
faculty/student perception of ethical practice, 177-179
transmission of professional ethics, 173, 179-181, 204
values systems in, 175-177
Embryonic stem cell, 64-65
Engineering perspective
in biopharmaceutical industry, 100
in biotechnology, 98
on living systems, 100
Environmental Protection Agency, 224
authority and responsibility, 246-247, 248-249, 251
biotechnology regulations, 256
policy development, 250-251, 252-256
regulation of transgenic plant pesticides, 251-252
Ethics in research
access to genetic services, 201-202, 206
access to/ownership of data, 187-189
biotechnology issues, 174
current policy, 187
definitions of misconduct, 184-185
eugenic pressures, 202-203
faculty/student perception of current practice, 177-179
genetic enhancement, 202
genetic testing for behavioral traits, 203
guidelines for academia, 188-189
human subjects research, 189-190, 196-197, 214-215
implications of Human Genome Project, 193-195, 199-201
inappropriate assignment of authorship, 178
institutional review boards, 189-190
interventions that perpetuate serious illnesses, 195-196
investigating and sanctioning misconduct, 173-174, 178-179, 183-184, 185-187
misuse of research funds, 178
near term issues, 205-207
objectivity/subjectivity of science, 209-210
public perception/understanding, 174, 191-192, 197-198, 204
reporting of misconduct, 178
sloppy use of data, 178, 184-186
transmission of, in science education, 173, 179-181
unsafe practice, 178
Europe, 225-226, 227, 228-229, 230
F
F-actin, 94
Farnesyl, 21
Federal Food, Drug and Cosmetic Act, 249, 256
Federal Insecticide, Fungicide and Rodenticide Act, 248-249, 254, 256
Fetal monitoring, 210-211
Fialuridine, 106
Food and Drug Administration, 89, 248, 255
Future of biotechnology
academic-industry collaborations, 144-146
biological engineering, 98
bioremediation, 125-127
biotechnology industry, 110-111
biotechnology policy, 244-245
gene therapy, 65-66, 70-71, 85-87
health science, 61-62, 85-86, 208
pharmaceutical industry, 110
pollution control technologies, 256-258
tumor treatment, 85-86
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G
-Galactosidase, Ganciclovir, in gene therapy, 81-86
Gaucher's disease, 66
Gene therapy
adenoviral vector delivery systems, 77-86
anti-cancer, 23
applications, 23, 54-55, 61-62, 68, 86
for brain tumors, 85-86
delivery systems, 69-70, 71, 72, 74-86, 88, 89
ex vivo strategy, 72-74
for immunodeficiency diseases, 68-69
for neurological disorders, 86-87, 91
plasmid DNA in, 69-70
process, 68-69
prospects for, 61, 65-66, 70-71
regulation of expression, 72
research origins, 64-65
retrovirus delivery system, 74-77
for solid tumors, 81-85
source genes, 72
technical basis, 68
tissue engineering for delivery systems, 88, 97
in vivo strategy, 74
General Agreement on Tariffs and Trade, 231
Genetic risk, vi
diagnostic procedures, 49-50
diseases associated with, 68
epigenetic model, 104
insurance practice and, 194-195, 206
possibilities for disease prevention, 50-51, 193
privacy issues, 51-53, 203-204, 206
trinucleotide repeat diseases, 46-49
workplace discrimination and, 206
Genetic science
cloning, 195-196
drug production, 53-54
early DNA research, 3-4
effects on social attitudes and behavior, 205
genetic enhancement, 202
near-term ethical issues, 205-207
tissue engineering and, 97
understanding of plant biology, 108
Genetic screening
for behavioral traits, 203
for colon cancer, 19
effects on interpersonal relations, 202
implications for people existing with disorders, 202
Genome mapping
basics, 13
microbiological research, 15-17
research development, 44-46
similarity among organisms, 13
Glucocerebrosidase, 66
Government interventions/policy
allocation of research resources, 218-220
authority for biotechnology regulation, 248-249
in biotechnology, vii, 223-224, 247, 256
case study, 251-252
drug development, international comparison of, 223, 225-226
drug pricing and reimbursement, 228-230
federal research budget, 233-236, 241
future prospects, 258
human subjects research, 214-216, 217-218
interagency efforts, 255
international agreements, 227-228
investigating and sanctioning scientific misconduct, 184-190
investment in biotechnology, 241-244
limitations of law, 246-247
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national science policy, 233-234, 244
patent law, 139-140
policy development process, 250-251, 252-256
to promote technology transfer via patent system, 165-167, 171
promoting university-industry collaborations, 139-141, 153-154
prospects for, 244-245
role of, 109
transgenic plant pesticide regulation, 251-252
in university research, 136-139
See also specific governmental organization
Growth factors, in oncogene transcription, 20-21
Growth hormone, 53
H
Helsinki Declaration, 214
Hereditary nonpolyposis colon cancer gene, 18, 19
Herpes simplex virus thymidine kinase gene, 81-85
HIV. See Human immunodeficiency virus
Howard Hughes Medical Institute
conflict of interest policies, 157-159
research contributions, 156-157
research policy and practice, 155-156, 160
cost-benefit analysis, 205
current status, 46
economic development benefits from, 237
epigenetic system and, 105
ethical issues in, 193-195, 199-201
Ethical, Legal and Social Implications Program of, 199-200
federal funding, 236-238
goal, 13
medical applications, 46, 50, 72, 193, 194-195, 198, 236, 238, 239
patent issues, 164
Human growth hormone, 38
Human immunodeficiency virus (HIV)
binding structures, 33-36
design drugs for, 28-38
infection mechanism, 24
life cycle, 24
protease inhibition, 30-33, 37-38
in women, 209
See also Acquired immune deficiency syndrome (AIDS)
Human subjects research, 189-190, 196-197
gender/reproductive issues in, 214-218, 219
historical development, 214-215
women's health issues, 174, 208-209, 212-214, 219-220
I
Immunodeficiency. See Acquired immune deficiency syndrome (AIDS)
Immunodeficiency, gene therapy for, 68-69
Immunoglobulin M, 102
Informed consent, 189, 212 women in clinical trials, 217
Institutional review boards, 189-190
Insulin, 53
production in bioartificial pancreas, 90-91
Insurance industry, genetic science and, 194-195, 206
Interleukins, 38
See also Cytokines
International comparison
biotechnology industries, 240
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drug pricing and reimbursement, 228-230
patent system, 162, 165, 230-231
J
L
Life expectancy, 193-194
Ligase enzyme, 11
Liver
bioartificial, 91-92
gene therapy, 72-73, 76-77, 78-79
Lung cancer, 107
M
Machado-Joseph disease, 49
Malpractice, 217
Massachusetts Institute of Technology, 135-136
Mathematical modeling, 106
change vs. progress in, 210-211
contributions of Howard Hughes Medical Institute, 156-157
diagnostic imaging technology, 66
DNA-based diagnostic techniques, 43, 49-50
genetic diagnostic testing, 49-50
genetic science for disease prevention, 50-51
Human Genome Project in, 46, 50
patient decision-making and, 212
research on women's health issues, 208-209
Metabolic control theory, 103-104
Microcephalic infants, 196-197
Molecular cell biology
AIDS/HIV research, 24-26
biomaterials development, 96-97
in bioremediation, 126
of cancer, 17-19
cancer treatment, 19-23
limitations of research, 16
mathematical modeling, 106
prospects for technical development, 26
research contributions, 15-16, 64
vascular system mechanical environment, 92-94
Mutations
in colon cancer, 18-19
diagnostic screening, 49-50
DNA in, 6-7
trinucleotide repeats, 47-49
Myoscint, 66
Myotonic dystrophy, 47-49
N
National Institute for Standards and Technology, 242
National Institutes of Health
applications for cDNA patents, 167-170
biotechnology industry collaborations, 243
funding trends, 153
research guidelines, 12-13, 188, 189, 213, 219
National Research Council, 136
National Science and Technology Council, 241
National Science Foundation, 137, 140-141
on academic-industry collaboration, 147-151
centers for academic-industry collaboration, 148-149
on patents, 150
on technology transfer, 150
Neurological disorders, gene therapy for, 86-87, 91
NIH. See National Institutes of Health
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North American Free Trade Agreement, 231
Nuremburg Code, 214
O
Ornithine transcarbamylase deficiency, 54-55
Orphan Drug Act, 226
Ovarian cancer, 107
P
Pancreas, bioartificial, 90-91
Patents, 130
from academic-industry collaboration, 143, 154
access to potentially patentable research, 188-189
for cDNA sequences, 167-168
cost of regulatory system, 163-164
for government-sponsored research, 139-140
Howard Hughes Medical Institute research policy, 157-158
international comparison, 230-231
issues of concern, 166-167
legal protections, 162-163
National Science Foundation policy, 150
policy trends, 165-166
in promoting technology diffusion, 162-163, 164-165, 168-170, 171
rationale for legal approach, 161-162
on research tools, 170-171
unique features of intellectual property, 161
Patient rights, 212
Perchlorethylene, 124-125
Pesticides, 248-249
biotechnology applications, 256-257
transgenic, 251-252
Pharmaceuticals
biological synthesis, 106
carbohydrate drugs, 104
cytokine agonists/antagonists, design of, 38-42
development process, 223, 225-226
development time, 226-227
different effects in population subgroups, 212-213
DNA testing for drug resistance, 10
drug pricing and reimbursement, 228-230
engineering perspective in industry, 100
epigenetic model, 104-106
genetic science in, 53-54
mammalian cells in, 102-103
market characteristics, 63
mathematical modeling, 106
p53-based, 105
patent law, 230-231
from plant products, 107-110
product quality issues, 101, 103
protease inhibition, 30-33, 37-38
protein agonists/antagonists, 66-67
recombinant therapeutic proteins, 66
reproductive effects in males, 216
safety issues, 102
taxol, 107-110
therapeutic proteins, 101-103
use of small molecules, 103-104
See also Gene therapy
Phenylketonuria, 193
Plant biology
biopesticides, 256-257
epigenesis in, 110
pharmaceutical development and, 107
risks of recombinant DNA technology, 251-252
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taxol synthesis, 107-110
transgenic plant pesticides, 251-252
Plasmid DNA, 69-70
Pollution
biotechnology applications for managing, 246, 256-257
hazard materials sites, 117
See also Bioremediation
Polymerase chain reaction
application, 43-46
for disease screening, 49
mechanism, 10-11
Polyproteins, 28-30
Popovic, Mikulas, 183-186
President's Committee of Advisors on Science and Technology, 241
Proteins
agonists/antagonists, 66-67
antisense, 67-68
DNA encoding mechanism, 5-6
gene therapy, 69-70
oncogene signal transcription, 20-21
recombinant therapeutic, 66
retrovirus encoding, 28-30
targeted drugs, 66
therapeutic, 101-103
Public perception/understanding
of ethics issues in science research, 174, 191-192, 197-198
of implications of genetic science, 204, 240
in regulatory policy development, 250, 252, 255-256
R
ras oncogene, 18
inhibition of, 21-23
signal transcription, 20-21
Recombinant DNA technology
applications, 2
basics of, 11-12
medical applications, vi
regulatory approach, 247
regulatory responsibility, 248-249
research development, 2
somatic gene thereapy, 13
transgenic embryos, 12-13
Recombinant proteins, 66
Recombinant viruses, 74-86
Reproductive science
genetic engineering, 195-196
male-mediated outcomes, 216
microbiological research, 15-16
pharmaceutical research, 214-218
transgenic embroys, 12-13
Research
allocation of federal resources, 218-220
concept of historical progress in, 210-211
cross-disciplinary linkages, 238-239
development of national policy on, 233-234
distribution of university revenues, 133-134
ethical practice guidelines, 188-189
federal support for, 235-236, 241
government-industry cost-sharing agreements, 243
government involvement, 136-139
historical development, 134-139
international agreements, 227-228
objectivity/subjectivity of, 209-210
pharmaceutical development, 226-227
public interest issues in, 152-154
regulatory environment, 224, 244, 247
women's health issues, 174, 208-209, 212-219
See also Academic-industry collaborations; Ethics in research
Restriction fragment length polymorphism, 10-11
Retroviruses
Page 278
protein encoding, 28-30
research development, 30
Rheumatoid arthritis, 68
Risk assessment
regulatory, 250
transgenic plant pesticides, 251-252
RNA/messenger RNA
in antisense therapy, 67-68
in genetic mutations, 6
in protein encoding, 5
retrovirus gene therapy delivery systems, 74-77
S
Sickle cell anemia, 6
Signal transcription
in cancer, 20-21
Skin, artificial, 89-90
Somatic gene therapy, 13
Spinal atrophy, 48
Spinocerebellar ataxia, 49
Stem cell gene therapy, 73-74
Structural biology, contributions of, 28, 30
T
Taxol, 107-110
Technology transfer
issues of concern, vi-vii, 129-130
National Science Foundation policy, 150
promoted by patent system, 162-163, 164-165, 168-170, 171
Thalidomide, 215
Tissue engineering, vi
applications, 89
artificial skin, 89-90
bioartificial organs, 90-92
biomaterials development, 96-97
current state, 97-98
drug delivery systems, 96, 97-98
FDA approvals, 89
goals, 88
market characteristics, 97
mechanical environment, 89
technical requirements, 89
three-dimensional structures, 88
vascular system applications, 92-96
Toxic Substances Control Act, 249, 254, 256
Transgene, 12
Transgenic animals, 66
Transgenic embryos, 12-13
Transgenic plants pesticides, 251-252
Transplantation from microcephalic infants, 196-197
Trinucleotide repeats, 46-49
Tumor suppressor genes, 18-19
U
Underground pollution, 115-116, 117
V
Vaccinations, AIDS, 24
Vascular system
mechanical environment, 92-94
tissue engineering applications, 92-96
Viruses
retroviral action, 28-30
See also Adenovirus; Human immunodeficiency virus (HIV)
W
Wastewater bioremediation, 114
Women's health issues
allocation of federal research resources, 218-220
doctor-patient relationship, 212
inclusion in research trials, 174, 208-209, 212-214, 218-220
medical technology, 210-211
pregnancy and pharmaceutical research, 214-218, 219
Y
Yew tree, 107-108