04/08/23

Legal and Policy Issues Concerning Access to Genetic Information

Philip R. Reilly, M.D., J.D.Philip R. Reilly, M.D., J.D.

ASLME Public ForumASLME Public Forum

DNA Fingerprinting and Civil LibertiesDNA Fingerprinting and Civil Liberties

Cambridge, MACambridge, MA

September 17, 2004September 17, 2004

04/08/23

DNA is THE Information Molecule

All the genetic information coding for a human is present in All the genetic information coding for a human is present in the first cell (union of sperm and egg)the first cell (union of sperm and egg)

The information is a long sequence written in a four letter The information is a long sequence written in a four letter alphabet (A, T, G, C)alphabet (A, T, G, C)

The DNA sequence in germ cells is 3,100,000,000 letters The DNA sequence in germ cells is 3,100,000,000 letters

The human genome has about 24,000 genesThe human genome has about 24,000 genes

Our cells use more than 100,000 proteins Our cells use more than 100,000 proteins

04/08/23

The DNA Paradox

Your DNA is 99.9 percent like that of the person Your DNA is 99.9 percent like that of the person next to younext to you

The .1 percent difference is immensely importantThe .1 percent difference is immensely important

It means we differ at 6 million letters It means we differ at 6 million letters

We are both very alike and very differentWe are both very alike and very different

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Laws of Inheritance

Genes are units of information that are Genes are units of information that are transmitted with high fidelity through time transmitted with high fidelity through time (an error rate of only about 1 in 100,000 per (an error rate of only about 1 in 100,000 per gene per generation)gene per generation)

Genes may have dominant, recessive or X-Genes may have dominant, recessive or X-linked effectslinked effects

04/08/23

We Have Tools to Decode DNA

Enzymes that can cut the DNA molecule in precise locationsEnzymes that can cut the DNA molecule in precise locations

Enzymes that permit us to amplify (make billions of copies Enzymes that permit us to amplify (make billions of copies of) a DNA sequence of interestof) a DNA sequence of interest

Technologies that permit us to sequence vast stretches of the Technologies that permit us to sequence vast stretches of the DNA moleculeDNA molecule

Research methods that permit us to associate tiny variations Research methods that permit us to associate tiny variations in the DNA molecule with risk for a diseasein the DNA molecule with risk for a disease

04/08/23

Why Should We Be So Interested in Our DNA?

Insights into causes of important diseases in humans, animals, Insights into causes of important diseases in humans, animals, and plantsand plants

New tools to assess risks in advance, permitting intervention New tools to assess risks in advance, permitting intervention

New tools in drug developmentNew tools in drug development

New approaches to therapyNew approaches to therapy

Powerful identification technologyPowerful identification technology

04/08/23

Major Areas of DNA Research

Understanding DNA VARIATIONUnderstanding DNA VARIATION

Single DNA letter changes are known as SNPsSingle DNA letter changes are known as SNPs

atagca…………………….ataccaatagca…………………….atacca

Two or more SNPs can be combined into haplotypesTwo or more SNPs can be combined into haplotypes

New tool - SNP chips with disease focusNew tool - SNP chips with disease focus

Understanding the genetic profile of cells (use of microarrays Understanding the genetic profile of cells (use of microarrays with thousands of molecules anchored to a slide to detect with thousands of molecules anchored to a slide to detect what genes are turned on).what genes are turned on).

04/08/23

Trends in Applied Genomics

New Genetic TestsNew Genetic Tests

Pharmacogenetics Pharmacogenetics

Behavioral genetics (genes that create risk for Behavioral genetics (genes that create risk for autism) autism)

Pharmaceutical Industry - Drug developmentPharmaceutical Industry - Drug development

Agriculture - Genetically engineered cropsAgriculture - Genetically engineered crops

Nutrition - genomics as an approach to wellness Nutrition - genomics as an approach to wellness

04/08/23

Inexpensive to Test

From 1990 to 2004 the cost of performing a DNA From 1990 to 2004 the cost of performing a DNA test for cystic fibrosis dropped 75 percent while test for cystic fibrosis dropped 75 percent while the number of mutations tested rose from 5 to 25.the number of mutations tested rose from 5 to 25.

Tandem Mass Spectrometry screens newborns for Tandem Mass Spectrometry screens newborns for 20-30 single gene disorders for $1.00 per disease 20-30 single gene disorders for $1.00 per disease per child per child

DNA forensic testing is on the order of $30-$50 for a DNA forensic testing is on the order of $30-$50 for a clean sample.clean sample.

04/08/23

Some Ethical Issues in Genomic Medicine Moral status of fetus and embryoMoral status of fetus and embryo

prenatal diagnosis and selective abortionprenatal diagnosis and selective abortiontherapeutic cloningtherapeutic cloning

Population based carrier screeningPopulation based carrier screeningimpact on parentingimpact on parenting

Safety of genetically modified foodsSafety of genetically modified foods

Genetic PrivacyGenetic Privacy doctor-patient relationshipdoctor-patient relationship

iimpact of risk assessment testing for insurance and mpact of risk assessment testing for insurance and employmentemployment

long term storage of DNA and datalong term storage of DNA and data

04/08/23

Genetics and Confidentiality

Genetic information is familialGenetic information is familial

The physician may discover facts that are of great The physician may discover facts that are of great importance to other family membersimportance to other family members

What issues arise when a doctor discovers that a What issues arise when a doctor discovers that a serious disorder arose for genetic reasons?serious disorder arose for genetic reasons?

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Case: Risk of Colon Cancer

DNA test may indicate that a person carries a mutation that DNA test may indicate that a person carries a mutation that increases cancer riskincreases cancer risk

Inference: his siblings and other relatives may have this Inference: his siblings and other relatives may have this mutation toomutation too

Opportunity: early screening and curative surgeryOpportunity: early screening and curative surgery

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Ethical Problem: Disclosure within Families

The patient states that he will not disclose his test results to The patient states that he will not disclose his test results to relatives, and he forbids the physician to do so.relatives, and he forbids the physician to do so.

What is the proper ethical conduct for the physician?What is the proper ethical conduct for the physician?

Is there a duty to warn? A limited right?Is there a duty to warn? A limited right?

Why or why not?Why or why not?

04/08/23

New Tests for Developmental Disorders

It has been impossible in many cases to explain why a child It has been impossible in many cases to explain why a child has developmental delayhas developmental delay

DNA tests may soon greatly improve our diagnostic and DNA tests may soon greatly improve our diagnostic and prognostic skills in autism, mental retardation, ADHD and prognostic skills in autism, mental retardation, ADHD and other disordersother disorders

04/08/23

Challenge: Genetics and Self-Image

New DNA tests to diagnose DD/MR will sometimes cause: New DNA tests to diagnose DD/MR will sometimes cause:

Parental guilt Parental guilt

Diminished self-worthDiminished self-worth

StigmatizationStigmatization

How will genetic labels affect educationHow will genetic labels affect education

Is there a risk for genetic determinism?Is there a risk for genetic determinism?

04/08/23

Opportunity: Warning Healthy People about Risk for Future Disease

Cancer: about 5 -10 percent of people who develop cancer Cancer: about 5 -10 percent of people who develop cancer are born with a significantly increased riskare born with a significantly increased risk

Tests available for breast and colon cancer now.Tests available for breast and colon cancer now.

04/08/23

Who Has a Claim on Your Genetic Data?

Spouse?Spouse?

Siblings?Siblings?

Children?Children?

Physician?Physician?

Teacher?Teacher?

Life Insurer?Life Insurer?

Employer?Employer?

Department of Public Health?Department of Public Health?

US Military?US Military?

Parole BoardParole Board

04/08/23

How Public is Your Genetic Information?

Virtually everybody born in the US since 1968 has had a Virtually everybody born in the US since 1968 has had a genetic test. A few states save the tissue; others the data. genetic test. A few states save the tissue; others the data.

US Military operates the largest tissue bank in the world. US Military operates the largest tissue bank in the world. They retain the sample long after the soldier musters out. They retain the sample long after the soldier musters out.

Many of the people in the room who have had surgery have a Many of the people in the room who have had surgery have a tissue sample in storage somewhere. By one estimate tissue sample in storage somewhere. By one estimate there are 320 million stored samples in the US.there are 320 million stored samples in the US.

04/08/23

Universal DNA Banking?

In Iceland, Decode Genetics has access to virtually all medical records in In Iceland, Decode Genetics has access to virtually all medical records in the country.the country.

Estonia plans to sell access to its population’s DNA samples and medical Estonia plans to sell access to its population’s DNA samples and medical records. (So does its neighbor, Latvia)records. (So does its neighbor, Latvia)

The Marshfield Clinic (Wisconsin) seeks to enroll 40,000 volunteers in a The Marshfield Clinic (Wisconsin) seeks to enroll 40,000 volunteers in a gene-environment study. Mayo Clinic has even bigger plans.gene-environment study. Mayo Clinic has even bigger plans.

The UK seeks to enroll 500,000 volunteersThe UK seeks to enroll 500,000 volunteers

Many other groups considering the same approachMany other groups considering the same approach

Pharmaceutical companies store DNA on all persons in clinical trials.Pharmaceutical companies store DNA on all persons in clinical trials.

Every state has universal newborn screening.Every state has universal newborn screening.

Every state has a DNA felon data banking law. Every state has a DNA felon data banking law.

04/08/23

Genetics and Health Insurance

Almost all states have laws prohibiting group health plans Almost all states have laws prohibiting group health plans from using genetic data to deny coverage for pre-existing from using genetic data to deny coverage for pre-existing conditionsconditions

The federal HIPAA (Sect. 703) also forbids thisThe federal HIPAA (Sect. 703) also forbids this

Although there is little evidence of genetic discrimination, Although there is little evidence of genetic discrimination, public concern is highpublic concern is high

04/08/23

Will Genetics Change the Definition of Disease?

Is a person who carries a mutation that increases his or her Is a person who carries a mutation that increases his or her risk for a disease or disorder healthy or ill?risk for a disease or disorder healthy or ill?

Consider: a 42 year old woman seeks oophorectomy because Consider: a 42 year old woman seeks oophorectomy because of her family history of ovarian cancer. Her insurer of her family history of ovarian cancer. Her insurer refuses to pay for the surgery because it was not performed refuses to pay for the surgery because it was not performed to treat a “bodily disease.” Should she be reimbursed? to treat a “bodily disease.” Should she be reimbursed? (Katskee v. Blue Cross of Nebraska)(Katskee v. Blue Cross of Nebraska)

04/08/23

What are the Risks of Genetic Discrimination?

access to health insuranceaccess to health insurance

access to life insuranceaccess to life insurance

access to long-term care insuranceaccess to long-term care insurance

employmentemployment

04/08/23

Genetics and Life Insurance

Genetic tests rarely used in underwritingGenetic tests rarely used in underwriting

About 10 states have laws regulating some aspect of this About 10 states have laws regulating some aspect of this

Insurers will not demand tests because they do not need to. Insurers will not demand tests because they do not need to. Theywill see results of tests that applicant has taken when Theywill see results of tests that applicant has taken when they review medical recordsthey review medical records

It will be difficult to prohibit life insurers from gaining access It will be difficult to prohibit life insurers from gaining access to genetic test datato genetic test data

04/08/23

Genetics and Long Term Care Insurance

Les than 10 percent of Americans purchase it, but the Les than 10 percent of Americans purchase it, but the number is risingnumber is rising

What if there were a predictive test for Alzheimer’s What if there were a predictive test for Alzheimer’s disease?disease?

04/08/23

Genetics and Employment

The ADA forbids using pre-employment medical The ADA forbids using pre-employment medical testing testing

The EEOC has said that ADA rules protect persons The EEOC has said that ADA rules protect persons denied employment on the basis of a genetic test denied employment on the basis of a genetic test

OSHA exists to promote a safe workplaceOSHA exists to promote a safe workplace

May employers use genetic tests for risk for May employers use genetic tests for risk for occupational disease?occupational disease?

04/08/23

What is a Serious Genetic Disorder?

In the period from 1965 to 1995 the number of live born In the period from 1965 to 1995 the number of live born children with spina bifida in England and Wales declined children with spina bifida in England and Wales declined by 95 percent.by 95 percent.

This was because of a screening test that could identify This was because of a screening test that could identify women with “high risk” pregnancieswomen with “high risk” pregnancies

For most fetuses with spina bifida we cannot really predict For most fetuses with spina bifida we cannot really predict future medical problems.future medical problems.

04/08/23

Predictions: Genetics in 2020

Universal DNA banking under state protectionUniversal DNA banking under state protection

Routine use of genetic information to guide wellness Routine use of genetic information to guide wellness

Routine sue of genetic information in premarital screeningRoutine sue of genetic information in premarital screening

Routine use of genetic screening in pregnancyRoutine use of genetic screening in pregnancy

Routine use of genetic data in making prognostic statements Routine use of genetic data in making prognostic statements

Routine use in choice of drug therapyRoutine use in choice of drug therapy

DNA data will play a central role in crime resolutionDNA data will play a central role in crime resolution

Routine use of DNA testing in invocation of insanity defenseRoutine use of DNA testing in invocation of insanity defense

People will talk about their genetic risks the way they do People will talk about their genetic risks the way they do about family history todayabout family history today

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The End

04/08/23

What’s Next?

PharmacogeneticsPharmacogenetics Nutritional geneticsNutritional genetics Use of genetic profiling in choice of skin Use of genetic profiling in choice of skin

care productscare products Search for anti-aging genesSearch for anti-aging genes Human behavioral geneticsHuman behavioral genetics

04/08/23

Pharmacogenomics

Most drugs do not work in a significant fraction of patients.Most drugs do not work in a significant fraction of patients.This is in part due to genes that influence drug metabolism.This is in part due to genes that influence drug metabolism.

The era of one drug fits all will end in the next 10 years.The era of one drug fits all will end in the next 10 years.Drug choice will be matched to patients’ genetic backgroundDrug choice will be matched to patients’ genetic background

First use will be to avoid giving drugs that cause severe First use will be to avoid giving drugs that cause severe adverse effects in some patients. Next use will be to choose adverse effects in some patients. Next use will be to choose the right drug for the patient.the right drug for the patient.

Genomic knowledge will permit efficient development of Genomic knowledge will permit efficient development of drugs that will have greater efficacy and fewer side effects.drugs that will have greater efficacy and fewer side effects.

04/08/23

Nutritional Genomics

Goal: Guide consumers to the most effective nutritional Goal: Guide consumers to the most effective nutritional supplement based on their genotypessupplement based on their genotypes

Example: Some people have a “pro-inflammatory” genotype. Example: Some people have a “pro-inflammatory” genotype. The use of an anti-inflammatory nutritional supplement to The use of an anti-inflammatory nutritional supplement to dampen the inflammatory response may help reduce the dampen the inflammatory response may help reduce the risk of or delay the age of onset of chronic inflammatory risk of or delay the age of onset of chronic inflammatory disorders such as coronary artery disease and osteoarthritis disorders such as coronary artery disease and osteoarthritis

04/08/23

Genetic Variation and Skin Care

Some researchers now studying differential aging Some researchers now studying differential aging of skinof skin

On the horizon – much better products against On the horizon – much better products against photoaging, better protections against skin cancerphotoaging, better protections against skin cancer

04/08/23

Genes for Longevity?

Studies in lower organisms have shown that one can build Studies in lower organisms have shown that one can build strains that are long lived.strains that are long lived.

Longevity is a familial trait.Longevity is a familial trait. One company collects DNA samples and medical histories One company collects DNA samples and medical histories

on people (and their sibs) who have lived to be 100. It has on people (and their sibs) who have lived to be 100. It has mapped a longevity gene chromosome 4. The company mapped a longevity gene chromosome 4. The company dreams of creating anti-aging productsdreams of creating anti-aging products

04/08/23

Human Behavioral Genetics

The search for genes that influence risk for autism, The search for genes that influence risk for autism, schizophrenia, bipolar disorder, and other schizophrenia, bipolar disorder, and other common mental illnesses is underway.common mental illnesses is underway.

Claims linking genes with intelligence will Claims linking genes with intelligence will proliferate.proliferate.

What will we do with such knowledge?What will we do with such knowledge?

04/08/23

Do We Need to Regulate?

What are we regulating?What are we regulating? Research projects?Research projects? Individual choice in sue of technology?Individual choice in sue of technology? State access to genetic data?State access to genetic data? Private use of genetic data?Private use of genetic data?

04/08/23

Why are we here?

Society has a powerful new set of tools…tools to analyze Society has a powerful new set of tools…tools to analyze (and, ultimately, change) the genetic structure of any (and, ultimately, change) the genetic structure of any organism on earth.organism on earth.

This technology is as world changing as nuclear energy. This technology is as world changing as nuclear energy.

Sixty years into the Nuclear Age, its immense dangers are not Sixty years into the Nuclear Age, its immense dangers are not yet under our controlyet under our control

Tonight we will consider just a few of many important Tonight we will consider just a few of many important societal issues created by the Genomic Age…which, like societal issues created by the Genomic Age…which, like nuclear power, offers immense benefits poses great risks.nuclear power, offers immense benefits poses great risks.

04/08/23

The Human Genome Project

A government program that finished three years ahead of A government program that finished three years ahead of schedule and well under budget!schedule and well under budget!

It gave us the consensus DNA sequence of humanity … the It gave us the consensus DNA sequence of humanity … the operating system for the hardware … the blueprint.operating system for the hardware … the blueprint.

It told us a great deal about who we are, and it made us realize It told us a great deal about who we are, and it made us realize once again the profound beauty of life and consciousness. once again the profound beauty of life and consciousness.

But it did not tell us exactly how many genes there are or what But it did not tell us exactly how many genes there are or what they dothey do

04/08/23

The Biggest Impact of Genomics so far? Agriculture? Examples:

In the USA tens of millions of acres are planted with corn, soy In the USA tens of millions of acres are planted with corn, soy beans and cotton that are genetically engineered to resist a beans and cotton that are genetically engineered to resist a certain non-chemical pesticide.certain non-chemical pesticide.

The rice genome has been sequenced and Chinese scientists The rice genome has been sequenced and Chinese scientists have developed several strains of genetically modified rice.have developed several strains of genetically modified rice.

Golden rice may prevent blindness from lack of vitamin AGolden rice may prevent blindness from lack of vitamin A

In October 2002 plans were set out to create an onion that will In October 2002 plans were set out to create an onion that will not make a person cry when he or she cuts it.not make a person cry when he or she cuts it.

04/08/23

Biggest Event in Genomics in 2002?

Complete sequence of the Malaria parasite Complete sequence of the Malaria parasite (P.falciparum)(P.falciparum)

Complete sequence of the mosquito vector Complete sequence of the mosquito vector (Anopheles gambiae)(Anopheles gambiae)

In 2002 more than 100 million people developed In 2002 more than 100 million people developed malaria which killed 3 million.malaria which killed 3 million.

Sequencing has already suggested an important new Sequencing has already suggested an important new approach to treatment.approach to treatment.

04/08/23

Trends in Applied Genomics

Cost of acquiring genetic data continues to fall.Cost of acquiring genetic data continues to fall.

DNA testing will be cheap compared to many medical tests.DNA testing will be cheap compared to many medical tests.

Correlation of gene variants with important aspects of human Correlation of gene variants with important aspects of human health will uncover many new insights into the etiology of health will uncover many new insights into the etiology of common diseases.common diseases.

Major advances in microarray technologies in study of Major advances in microarray technologies in study of proteomics.proteomics.

04/08/23

Genes and Environment

Genes determine very little, but they influence a Genes determine very little, but they influence a great dealgreat deal

The challenge is not to untangle nature from nurtureThe challenge is not to untangle nature from nurture

It is to understand how genes and the environment It is to understand how genes and the environment interactinteract

04/08/23

Molecular Medicine is Coming to Your Hospital

DNA tests in use now to diagnose causes of severe infection.DNA tests in use now to diagnose causes of severe infection.

Many hospitals have started cancer genetics clinicsMany hospitals have started cancer genetics clinics(about 5-10% of all cancers arise due to a mutation with (about 5-10% of all cancers arise due to a mutation with

which the person was born).which the person was born).

2005: Microarrays in use in your hospital’s laboratories2005: Microarrays in use in your hospital’s laboratories

2010: We will routinely ask vast numbers of questions about 2010: We will routinely ask vast numbers of questions about an individual’s DNA or proteins as an aid in maintaining an individual’s DNA or proteins as an aid in maintaining wellness, making diagnoses and choosing drug therapieswellness, making diagnoses and choosing drug therapies

04/08/23

The Power of Genetic Data

Impact of genetics on prenatal diagnosisImpact of genetics on prenatal diagnosis

Impact of genetics on confidentiality in medicineImpact of genetics on confidentiality in medicine

Impact of genetics on the insurance industryImpact of genetics on the insurance industry

Consequence of government having access to your Consequence of government having access to your genetic records recordsgenetic records records