GENOMIC MEDICINE AND PUBLIC HEALTH Alan E. Guttmacher, M.D.

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
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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
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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