Genomics and World Health

252 Pages·2002·15.1 MB·English

THE ADVISORY COMMITTEE ON
HEALTH RESEARCH
Genomics
andWorld
Health
WHO
WORLD HEALTH ORGANIZATION
GENEVA
Genomics and World Health
Genomics and World Health
Report of the Advisory Committee on
Health Research
Chaired by Jeffrey D. Sachs
Presented to Dr. Gro Harlem Brundtland,
Director-General of the
World Health Organization,
on 20 December 2001
World Health Organization
Geneva
2002
WHO Library Cataloguing-in-Publication Data
World Heath Organization. Advisory Committee on Health Research.
Genomics and world health / report of the Advisory Committee on Health Research.
1. Genomics 2. Genome 3. World health 4. Delivery of health care
5. Developing countries
ISBN 92 4 154554 2 (NLM Classification: QZ 50)
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Contents
Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
2. Genomics and the Genome Projects . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
2.2 What are genes and how do they function? . . . . . . . . . . . . . . . . . . . . . . . . . . . .19
2.3 The development of molecular genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24
2.3.1 Classical genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24
2.3.2 Molecular genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28
2.4 Characterizing the human genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30
2.4.1 The identification of human disease genes . . . . . . . . . . . . . . . . . . . . . . . .30
2.4.2 The Human Genome Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31
2.4.3 Mapping the human genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32
2.5 Functional genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32
2.5.1 Annotation of the human genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32
2.5.2 Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33
2.5.3 Transcriptomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .34
2.5.4 Gene regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35
2.5.5 Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36
2.6 The genomes of other organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36
2.6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36
2.6.2 The pathogen genome project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36
2.6.3 The genomics of disease vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39
2.6.4 The genomes of the worm, fruitfly, yeast and various animals . . . . .39
2.6.5 The central importance of the mouse genome project . . . . . . . . . . . . .39
2.6.6 Plant genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40
2.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41
3. The Potential of Genomics for Health Care . . . . . . . . . . . . . . . . .43
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43
3.2 Monogenic disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43
3.3 Communicable disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47
3.4 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .51
3.5 Complex multifactorial disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55
3.6 Developmental abnormalities and mental retardation . . . . . . . . . . . . . . . . . . .58
3.7 Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .60
3.8 Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61
3.9 Gene therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63
3.10 Stem cell therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .64
3.11 Plant genomics and human health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .66
3.12 Forensic medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67
3.13 Biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69
3.14 Broader issues of biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69
3.15 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .70
4. Relevance and Time-Scale of Advances in Genomics for
Global Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71
4.1 Genomics in the context of current world health problems . . . . . . . . . . . . . .71
4.2 When will the medical promises of genomics be fulfilled? . . . . . . . . . . . . . . .73
4.3 Maintaining the balance of research planning and health care . . . . . . . . . . .75
4.4 Will the medical applications of genome research be affordable? . . . . . . . .77
4.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .78
5. The Potential of Genomics for the Health of the
Developing Countries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79
5.2 Examples of what is feasible now . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .80
5.2.1 The inherited disorders of haemoglobin. . . . . . . . . . . . . . . . . . . . . . . . . .81
5.2.2 Genetic resistance to communicable disease . . . . . . . . . . . . . . . . . . . . . .84
5.2.3 The introduction of DNA diagnostics for communicable disease . .86
5.2.4 Drug-resistant organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86
5.2.5 Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .89
5.2.6 Non-communicable disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90
5.3 The development and provision of services in clinical genetics
and DNA technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92
5.4 Genomics for the control of communicable disease: future directions . . . .93
5.5 Forging international partnerships in academia . . . . . . . . . . . . . . . . . . . . . . .102
5.6 Regional collaboration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
5.7 Information technology and bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . .104
5.8 Summary and future possibilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105
6. Potential Risks and Hazards of the Applications of
Genomics and their Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107
6.2 Genetic manipulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .108
6.3 Risks in non-human genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109
6.3.1 Animals and insects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109
6.3.2 Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
6.4 Changing the genetic constitution of individuals or populations . . . . . . . .111
6.5 Genetic databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .113
6.6 Biological warfare and other political misuses . . . . . . . . . . . . . . . . . . . . . . . . .118
6.7 Stem cell gene therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .120
6.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .122
7. Justice and Resource Allocation: Implications for the
Post-Genomic Era . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123
7.2 Current inequities in the provision of health care . . . . . . . . . . . . . . . . . . . . . .124
7.2.1 Inequities in health status and disease burden . . . . . . . . . . . . . . . . . .124
7.2.2 Issues of development and poverty alleviation . . . . . . . . . . . . . . . . . . .125
7.3 Research priorities and access to the benefits of research . . . . . . . . . . . . . .127
7.3.1 The gap between developed and developing countries in
health research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127
7.3.2 Redressing the developed-developing country gap . . . . . . . . . . . . . . .131
7.3.3 Developing research capacities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .133
7.4 Intellectual property and sharing the benefits of research . . . . . . . . . . . . . .135
7.4.1 Patents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135
7.4.2 Patenting genetic material . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .136
7.4.3 The TRIPS agreement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .140
7.4.4 Biological resources and benefit sharing . . . . . . . . . . . . . . . . . . . . . . . .142
7.5 Ownership and access to genetic databases . . . . . . . . . . . . . . . . . . . . . . . . . . .144
7.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .146
8. Ethical Issues in Genetic Research, Screening, and Testing,
with Particular Reference to Developing Countries . . . . . .147
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .147
8.2 Informed consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .149
8.2.1 Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .149
8.2.2 Genetic testing in health care and research . . . . . . . . . . . . . . . . . . . . . .150
8.2.3 Other approaches to regulating genetic testing, screening
and research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .153
8.2.4 Genetic databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .153
8.3 Confidentiality of genetic information to prevent discrimination and
stigmatization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155
8.3.1 Confidentiality and its appropriate limits . . . . . . . . . . . . . . . . . . . . . . .155
8.3.2 Discrimination and stigmatization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157
8.4 Gender issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .160
8.5 Eugenics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162
8.6 The disability rights movement’s challenge to genetic screening
and testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
8.7 Nontherapeutic genetic interventions: genetic enhancements . . . . . . . . . . .167
8.8 Gene therapy, stem cell therapy and human cloning . . . . . . . . . . . . . . . . . . .170
8.9 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .173
9. Education and Public Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175
9.2 Level of knowledge about genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175
9.3 Public perceptions of biotechnology and genetic engineering . . . . . . . . . . .177
9.4 Lack of organizations for setting public policy and ethical standards
for genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .180
9.5 Requirements for education and policy-making in the genomics era . . . .183
9.5.1 Public education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .183
9.5.2 Health care professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .184
9.5.3 The educational role of clinical genetics services . . . . . . . . . . . . . . . . .184
9.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .185
10. Recommendations for WHO and Its Member States . . . . . . . .187
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .187
10.2 Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .188
10.2.1 Technical cooperation between WHO and its Member States . .188
10.2.2 WHO’s normative function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .193
10.2.3 An advocacy role for WHO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .195
10.3 Closing Summary and Key Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .198
Annex A Glossary of Technical Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .201
Annex B Consultation Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .209
Annex B1: Outline of consultation process and timeline . . . . . . . . . . . . . . . . . . . . .209
Annex B2: Consultations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .210
B2.1 Consultation on the ACHR Report on Genomics and Health . . . .211
B2.2 Brasilia Regional Consultation on Genomics and World Health . .216
B2.3 The Bangkok Multiregional Consultation on Genomics and
World Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .218
Annex B3: List of contributing WHO staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .224
Annex B4: List of relevant background WHO work on genetics,
genomics and biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .225
Annex B5: Profiles of Report writers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .227
Annex C References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . .229
Acknowledgements
The writing team for this Report was comprised of David Weatherall
(Principal/Lead Writer), Dan Brock and Heng-Leng Chee. Members of
the WHO Advisory Committee on Health Research (Zulfiqar Bhutta,
Barry Bloom, Mahmoud Fathalla-Committee Chair, Marian Jacobs,
Gerald Keusch, Maxime Schwartz, Gita Sen, Fumimaro Takaku, Cesar
Victora, Lars Walloe, Judith Whitworth) provided extensive comments
and inputs to various drafts of the Report prepared by the writing team.
David Carr provided invaluable editorial support throughout the
preparation of the Report. Williamina Wilson provided expert editori-
al assistance on the final draft of the Report. Tikki Pang coordinated
the process for preparation and development of the Report and the
Department of Research Policy & Cooperation, WHO, Geneva,
Switzerland acted as secretariat. Invaluable secretarial assistance was
provided throughout by Liz Rose and Daniéle Doebeli. Important
inputs were also received from a large number of individuals who par-
ticipated in the various consultations and from WHO staff members
(listed in Annexes B2 and B3). Additional material, advice and assis-
tance on various aspects of the Report and its preparation were pro-
vided by Bob Cook-Deegan, Jo Cooper, Sigurdur Gudmundsson, Eva
Harris, Juntra Karbwang, Victor McKusick, Alex Mauron, Richard
Moxon, Chris Newbold, Tim Peto, Abha Saxena, Manju Sharma,
Sacha Sidjanski, John Sulston and Andrew Simpson. William R.
Brinkley was responsible for the cover design and Marc Kaufman for
lay-out design and production.
This Page Intentionally Left Blank
Foreword from the Director General
The announcement of the sequencing of the human genome in 2001 rep-
resents an unprecedented milestone in the advancement of our knowledge
on the molecular basis of life itself. Together with the advances made in
the deciphering of the genomes of many disease-causing microorganisms
and their vectors, it is clear that the science of genomics holds tremendous
potential for improving health globally.
The information generated by genomics will, over time, provide
major benefits for the prevention, diagnosis and management of commu-
nicable and genetic diseases as well as other common killers or causes of
chronic ill health including cardiovascular diseases, cancer, diabetes, and
mental illnesses. It is thus timely and appropriate for WHO to examine the
implications of advances in genomics and other critical areas of biotech-
nology. For this reason, I have asked the Advisory Committee on Health
Research (ACHR) to prepare this Report.
The Report focuses on the expectations, concerns and possibilities for
the use of new genomic knowledge in improving world health. The spe-
cific challenge is how we can harness this knowledge and have it con-
tribute to health equity, especially among developing nations. It is a reali-
ty that most genomic and biotechnology research is presently carried out
in the industrialized world, and is primarily market-driven. Genomics also
needs to be applied to the health problems of the developing world. It is
crucial that we actively seek means to involve developing country scien-
tists in innovative biotechnology.
The present Report points out that the genomics revolution has
brought with it many complex scientific, economic, social and ethical con-
cerns. These need to be carefully addressed, debated and considered.
Recent developments in cloning and stem cell therapy, for example, have
raised serious ethical, moral and safety concerns. It follows that societies
also need to be better prepared for the era of genomics and its conse-
quences. Public education, understanding and trust on the key issues in
genomics is a basic pre-requisite. It is also vital that genomics be consid-
ered in the wider context of health and that a relevant balance is main-
tained in research, development and health care provision between the
more conventional and well-tried approaches of clinical research, epi