Title: Ethical Issues in Personalized Medicine
1Ethical Issues in Personalized Medicine
- Jeffrey R. Botkin, M.D., M.P.H.
- Professor of Pediatrics and Medical Ethics
- Associate Vice President for Research
2The Human Genome
February, 2001
3Consequences of Human Genome Project
- Technology available for detailed sequencing
- Normal and abnormal sequence information
available - Proliferation of genetic tests for DNA sequences
associated with clinical conditions - Testing available before effective treatments or
prevention available
4ELSI Issues in Genetic Halfway Technologies
- Challenges for genetic tests
- Genome research many new tests
- 1715 diseases for which there are tests
- 1435 clinical tests
- 280 research tests
- Limited FDA oversight
- Rapid transition from bench to bedside
- Direct marketing of recreational genetic tests
- Public/professional confidence in benefits of
medical technology
5Ethics and Genetics
- 1990 Dr. James Watson announces that 3 - 5 of
new human genome project budget will be devoted
to ethical, legal, and social implications - ELSI Program
- Why this allocation in genetics research?
6Why the public concern over genetic technology?
7Genetic Concepts
- Genetic determinism
- The notion that our genes determine our biology
and behavior - Generally false even for Mendelian conditions
- Genetic exceptionalism
- The notion that genetic knowledge is different
than other forms of knowledge in biology and
medicine - Differences Family relationships, a history of
abuse, beliefs in genetic determinism (genes as
the blueprint)
8Lewis Thomas, M.D.
- The Technologies of Medicine
- Non-technologies
- Decisive technologies or high technologies
- Immunizations
- Halfway technologies
- Dialysis
- Human Genetics?
(1913-1993)
9High Technology Power?
- Gene therapy
- Somatic
- Germline
- Designer babies
- Reproductive cloning
- Tissue engineering
- Personalized medicine
Chris Blair
10Single Gene vs Complex Diseases
- Successful identification of genes associated
with Mendelian disorders - Diagnostic testing
- Predictive testing
- Carrier testing
- Prenatal diagnosis
- Limited success with identifying major genes
associated with complex conditions
11Genetic Determinants of Obesity
- Researchers Discover New Genetic Risk Factors
Involved in Adult and Childhood Obesity - Comprehensive Study Uncovers Six Genetic Variants
Associated With Body Mass Index
http//www.genome.gov/27529231 December 2008
12Obesity Study
- 32,000 individuals of European ancestry
- 15 genome wide association studies identified
and analyzed - 35 genetic variants identified that are
associated with BMI - Results
- The 1 of the population with the most
obesity-causing variants estimated to be 10 lbs
heavier than the 1 with the least number of
variants
13Common, Complex Conditions
- To date, limited progress on identifying single
genes or small gene sets that are strongly
associated with common, important health
conditions - Genetic tests may not provide valuable
predictive information for these conditions - Genetics may provide better understanding of
pathophysiology and therapeutic targets
14Systems Biology
- Institute for Systems Biology, Seattle
Washington - Systems biology is the study of an organism,
viewed as an integrated and interacting network
of genes, proteins and biochemical reactions
which give rise to life.
http//www.systemsbiology.org
15Social and Policy Issues
- Challenges will emerge from the complexity of
individual technologies as applied in specific
research, clinical, social, and public health
contexts
16ELSI Issues in Genetic Non-technologies
- Information management -- Social and Policy
Issues - Education and standards for MDs
- Genetic counselors
- Implications for family members
- Responsibilities of physicians/counselors
- in clinical care
- Responsibilities of investigators in research
- Privacy of genetic information
17Evaluation of Genetic Tests
- ACCE Framework
- Analytic validity
- Does the test detect what it is designed to
detect? - Analytic sensitivity and specificity
- False positives and false negatives
- Clinical Validity
- Does the test correctly identify those with the
condition and those without the condition? - False positive and false negatives
- Clinical Utility
- Does screening/testing for the condition improve
the outcome for the individual? - ELSI considerations
- EGAPP initiative (CDC)
18Validity/Utility
From Burke et al. AJMG 2001106233
Clinical Utility
Yes
No
MEN2
HD
Clinical Validity
High
HFE
ApoE
Low
MEN2 multiple endocrine neoplasia type 2 HD
Huntington disease HFE hereditary
hemochromatosis ApoE apoliproprotein alleles to
predict Alzheimer
19Research Challenges
- Development of research protocols to demonstrate
the clinical validity and clinical utility of
genetic tests - Requires an assessment of the impact of
information on behavior and secondary impacts on
morbidity and mortality - Questions about whether information per se, or
non-patient impacts, have sufficient value to
justify testing or screening - Newborn screening context
20ELSI Concerns over Predictive Testing
- Concerns over negative psychological impacts
from genetic testing have not been borne out in
research to date - Individual situations may justify concern
- Individuals generally use genetic information in
appropriate ways - The risk of insurance and employment
discrimination is low - Fears over risks are a significant barrier to
use of genetic tests
21Insurance Discrimination
- Long-standing concern of policy makers that
predictive genetic testing will lead to insurance
discrimination - The single most consistent concern expressed by
those declining genetic testing - Health insurance a primary concern
- Life and disability insurance also a concern
- Isolated instances of insurance and employment
discrimination
22Insurance and Employment Discrimination
- Genetic Information Non-discrimination Act
(GINA) passed in 2008 - Protects against use of genetic information in
insurance and employment - HIPAA had protected against group discrimination
- Federal employees protected
- Many state laws in place
- Efficacy of GINA remains to be demonstrated
23Genetic information vs Privacy
Lin Z, et al. Science 2004305183
24Re-Identification based on DNA sequence
information
- Sequences are not intrinsically identifiable
- Necessary to have a reference database that links
sequence information to individual identifiers - Re-identification only important if sequence
information carries important health information - Important health information must be revealed to
someone who can use the information to harm the
source individual
25Group Discrimination/Stigma
- Concerns about impacts of genetic information on
social groups - Stigmatizing clinical conditions associated with
defined social groups (Jewish mutations) - Return to genetic explanations for social
problems - Poor mans pharmacogenomics presuming
genotypes based on racial or ethnic background
26ELSI for Genetic Testing
- Genetics currently has limited power for the
prevention and treatment of disease - Likely to provide more contributions over time
perhaps through a systems approach - High value in better understanding basic biology
- Expanded use of poorly validated tests due to
limited oversight - Test validity and utility are serious concerns
- Group impacts from genetic research