# Presentation: 174845

## GENOMIC MEDICINE AND PUBLIC HEALTH 

- 					 August 16, 2000
- Alan E. Guttmacher, M.D.
- Senior Clinical Advisor to the Director
- National Human Genome Research Institute National Institutes of Health

## 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

- Draft = 65.7%
- Finished = 21.1%
- Total = 86.8%

- As of 6/11/00

- As of 6/18/00

- As of 6/25/00

## 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, altruism-greed

## 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