GENOMIC MEDICINE AND PUBLIC HEALTH August 16, 2000 Alan E. Guttmacher, M.D. Senior Clinical Advisor to the Director National Human Genome Research Institute What We Will Consider • The “old genetics” • The Human Genome Project • The “new genetics” - genomic medicine • The new genetics and health • The new genetics and society The “Old Genetics” • About conditions wholly caused by: –An extra or missing chromosome or part of a chromosome • e.g., Down syndrome, Turner syndrome, cri-du-chat syndrome –A mutation in a single gene • e.g., cystic fibrosis, Marfan syndrome, phenylketonuria The “Old Genetics” • These conditions – Are of great importance to individuals and families with them – But, even when added together, are relatively rare – Most people not directly affected – Genetics thus played relatively small role in health care (and in society) The “Old Genetics” • These conditions are rare enough that: –Genetics care could be supplied primarily by medical geneticists and genetic counselors, with occasional involvement of primary care providers and other specialists The “Old Genetics” • In terms of research: –Because of their small impact on health, these genetic conditions of relatively limited interest –In past two decades, genetics of relatively little help in answering basic questions, but of increasing help as source of lab tools > 9 of the CDC’s 10 Leading Causes of U.S. Deaths Have Genetic Components • • • • ? • • • • • 1. Heart disease (31.0% of deaths in ‘98) 2. Cancer (23.2%) 3. Stroke (6.8%) 4. COPD (4.8%) 5. Injury (4.2%) 6. Pneumonia/Influenza (3.9%) 7. Diabetes (2.8%) 8. Suicide (1.3%) 9. Kidney disease (1.1%) 10. Chronic liver disease (1.1%) > 9 of the WHO’s 10 Leading Causes of Global Deaths Have Genetic Components • • • • • • • • • ? 1. Heart disease (13.7% of total in ‘98) 2. Stroke (9.5%) 3. Pneumonia (6.4%) 4. HIV/AIDS (4.2%) 5. COPD (4.2%) 6. Diarrhea (4.1%) 7. Perinatal (4.0%) 8. Tuberculosis (2.8%) 9. Trachea/bronchus/lung cancer (2.3%) 10. Traffic accidents (2.2%) The “New Genetics” Genomics • Comes largely from knowledge emanating from the Human Genome Project The Human Genome Project • An international government project that is ahead of schedule! • And under budget!! • And from its start has earmarked funds for consideration of its ethical, legal, and social implications (ELSI) - the largest funding ever devoted to bioethics!!! The Human Genome Project • The human genome consists of about three billion chemical bases • It would fill 150,000 telephone book pages with A’s, C’s, G’s and T’s • Disease is often caused by a single variation in the three billion bases one letter in the 150,000 pages • Our challenge is partly one of scale Human Genome Project Sequence Progress Asof of 6/25/00 6/11/00 As 6/18/00 Draft = 65.7% Finished = 21.1% Total = 86.8% The Human Genome Project • That is “only” the “race” for the human genome sequence - the alphabet –Vital tool, but of little impact itself –The real fun, and the real impact on peoples’ lives, comes from figuring out how words and sentences are formed and then creating new poetry The Human Genome Project • Which brings us back to the genomic medicine… Genomic Medicine • About conditions partly: –Caused by mutation(s) in gene(s) • e.g., colon cancer, breast cancer, atherosclerosis, inflammatory bowel disease, diabetes, Alzheimer disease, mood disorders, many others –Prevented by mutation(s) in gene(s) • e.g., HIV (CCR5), ?atherosclerosis, ?cancers, ?diabetes, many others Genomic Medicine • These conditions –Are also of great importance to individuals and families with them –But are quite common –Directly affect virtually everyone –Will make genetics play large role in health care and in society Genomic Medicine • So far, most success identifying genetic contributions to common disease has been for low frequency, high penetrance alleles, e.g.: – HNPCC (colon cancer) – BRCA1 and 2 (breast & ovarian Ca) – MODY 1,2,3 (diabetes) – Alpha-synuclein (Parkinson disease) Genomic Medicine • But, on a population level, most genetic contributions to common disease are from high frequency, low penetrance alleles, e.g.: – APC I1307K and colon cancer – ApoE and Alzheimer disease – Factor V Leiden and thrombosis – CCR5 and HIV/AIDS resistance Genomic Medicine • So, much more to come, in the next few years, as these genetic contributions to more common disease are identified… Genomic Medicine • These conditions are common enough that: –Genetics care will be supplied primarily by primary care providers from many health disciplines, with occasional involvement of medical geneticists and genetic counselors and other medical specialists Genomic Medicine • These conditions are common enough that: –Genetics rises to the level of a focus for public health professionals Genomic Medicine • These conditions are common enough that: –Genetics rises to the level of a focus for public health professionals –Might genetics be to public health in the 21st century what infectious disease was in the 20th? Genomic Medicine • In terms of research: –Because of their great impact on health, these conditions are of great interest –In next two decades, genetics will provide not only even better lab tools, but also answers to many basic biological questions Genomic Medicine • Will change health care by... –providing knowledge of individual genetic predispositions –creating pharmacogenomics –allowing population based screening for certain Mendelian disorders Genomic Medicine • Knowledge of individual genetic predispositions will allow: – Individualized screening, – Individualized behavior changes – Presymptomatic medical therapies, e.g., anti-colon cancer agents before colon cancer develops, antihypertensives before hypertension develops Genomic Medicine • Pharmacogenomics will allow: –individualized medication use based on genetically determined variation in effects and side effects –use of medications otherwise rejected because of side effects –new medications for specific genotypic disease subtypes Genomic Medicine • Will change health care by... –providing better understanding of non-genetic (environmental) factors in health and disease –emphasizing health maintenance rather than disease treatment –allowing genetic engineering Genomic Medicine • Will change both health care and research by creating… –a fundamental understanding of the etiology of many diseases, even “non-genetic” diseases Genomics • May include characteristics that most do not see as “diseases” and many do not see as innate – e.g., height, intelligence, sexual orientation, alcoholism, violence, happiness-sadness, confidence-anxiety, altruismgreed Genomics • Will also change our lives by… –Allowing everyone to know their own (and maybe others’) health and disease predispositions –Allowing everyone to know their own (and maybe others’) “characteristics” predispositions –Showing that we are all mutants Genomics • May also change society through –Social stratification by genetic status, e.g., in employment or marriage –Genetic engineering against (and for) diseases and characteristics –Cloning –Increased opportunity for “private eugenics” Genomics • Raises new concerns, such as: –Discrimination against individuals –Discrimination against groups –Genes run in families –Genetic determinism • Will we have false impression of our futures? • Nature over nurture? Genomics • And more concerns, such as: –Fairness in access –Confidentiality/privacy of information –Right not to know and not to act –What is appropriate informed consent process for genetic testing –Patenting and licensing How Do Health Professionals Prepare for Genomic Medicine? • Need to learn to “think genetically” - to: – realize when genetic factors play a role – effectively use family hx & genetic tests – be able to explain genetics concepts – deal with “risk” & genetic predisposition – realize personal and societal impact of genetic information – protect genetic privacy – use genetics to individualize patient care – use genetics to preserve health The National Coalition for Health Professional Education in Genetics (NCHPEG) • Seeks to: – integrate genetics into the knowledge base of health professionals & students – develop educational tools & information resources to facilitate health professional integration of genetics into practice – strengthen & expand the community committed to coordinated national genetics education for health professionals The National Coalition for Health Professional Education in Genetics (NCHPEG) • Over 100 member organizations (including the Association of Schools of Public Health) • Web site at: www.NCHPEG.org How Does Society Prepare for the Genomics? • Education to achieve understanding of: – the basics of the science of genetics – the eventual use of genetics in health care – how to deal with risk and predisposition – the personal impact of genetics information – the societal impact of genetics The Future (?2010) - Alzheimer Disease, for example • 5 or 6 genetic variations identified that strongly predispose for Alzheimer disease; another 10 or 12 with weaker association • Chip-based genetic test gives personal likelihood of developing the condition • Chip-based genetic test identifies the drug most likely to be effective for given individual • Chip-based genetic test determines individual likelihood of drug side effects The Future (?2010) - Asthma, for example • Genetic testing reveals which genetic subtype of asthma an individual has • Therapy, both environmental-protective and medical, chosen based on this subtyping • Another genetic test identifies the drug most likely to be effective for given individual • Another genetic test determines individual likelihood of drug side effects