Genetics Screens, Tests

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Genetics Screens, Tests Therapies

• Philip Boyle, Ph.D.
• Vice President, Mission Ethics
• www.CHE.ORG/ETHICS

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Goals for todays conversation

• To explore the ethical issues unique to genetics
  screens, tests, and therapies
• To understand the Church teaching on genetics
• To consider the differences between informed
  consent and counseling

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THE GENETICS SCENE

• A tidal wave of genetic data Human Genome
  Project (HGP)
• Researchers can now routinely identify genetic
  mutations associated with common diseases like
  CANCER, ALZHEIMERS, and certain kinds of
  CARDIOVASCULAR disease.
• PREDICTIVE testing for monogenic, late-onset
  disorders such as HUNTINGTONS disease
• SUSCEPTIBILITY testing for late-onset disorders
  of complex genetic and environmental interaction
  such as BREAST CANCER.

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THE GENETICS SCENE

• The next decade will see
• testing to identify the genetic basis of disease
• rapid increase in the number of tests to detect
  numerous illnesses (multiplex testing)
• Diagnostic micro-chip technology that can
  simultaneously analyze DNA from 6500 patients for
  the presence of 106 different mutations on seven
  genes has been available for some time and its
  range is expanding.
• test kits and diagnostic products readily
  available to the public
• individualized therapies

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Genetics Across the Life Span

• Pre-implantation (PGS)
• Carrier screening
• Testing for lethal diseases / gender
• Prenatal
• MSAFP / Ultrasound
• Amniocentesis / CVS
• Neonatal
• Inborn errors of metabolism
• Adolescents and adults
• Carrier screening
• Pre-symptomatic testing
• Predictive testing
• Therapies
• Enhancement therapies
• Individualized medicine

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Genetics applications Ethical Issues

• Screening
• Population
• Testing
• Accuracy of test
• Expressions of condition
• Age of onset
• Probabilities
• Uses of tests
• Private
• Personal and family uses in marriage
• Reproductive uses
• Health decisions
• Social uses
• Employment
• Insurances
• Public health
• Therapy
• Targeted cells
• Therapeutic research with embryonic stem cells
  (SCNT)

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Unique ethical questions?

• Probabilistic information
• Affecting the family
• Should some science not be pursued?
• Somatic v germ-line
• Embryonic stem cell
• Enhancement therapy human identity
• Labeling / stigma
• The nature of disease illness

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Unique ethical questions?

• Geneticize health
• Cause of disease fully explainable by genes?
• Contribution of gene to health?
• Nature v. nurture
• Genetic penetration The nature of disease?
• Medicalization of daily life
• Justice
• Less expensive means?
• Privilege some diseases not others?

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NIH Task Force on Genetic Testing

• Despite remarkable progress
• No effective interventions are yet available to
  improve the outcome of most inherited diseases
• Negative (normal) test results might not rule out
  future occurrence of disease
• Positive test results might not mean the disease
  will inevitably develop
• Promoting Safe and Effective Genetic Testing in
  the US (Sept. 1997)

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Carrier Testing and Prenatal Diagnosis

• George and Carol recently married
• Both had cousins with Cystic Fibrosis (CF)
• Sought counseling
• 1 in 2500 live births
• 1 in 25 (4) are heterozotes (asymptomatic)
• Detection rate 85 in screening
• In screening if 1 partner is negative there is a
  1 in 10,100 chance of CF
• If both partners are negative 1 in 39,200 chance
  of CF
• If one partner is carrier and other test
  negative 1 in 396 chance
• Positive predictive value not high in general
  population
• Life expectancy of CF is rising
• Population is not well informed about probability

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Decisions with implications

• How much information is needed?
• Should they be told when nothing can be done?
• What are the benefits of the info before, during,
  and after pregnancy?
• What are the harms?
• Anxiety
• Stigma / labeling / discrimination
• Acting on probable information
• When in life should a person be told they are a
  carrier?
• Who should make the decision?
• Should MDs inform all patients or some subset?
• Can the state mandate the test?

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Religious-Ethical Questions

• Shall we marry? Conceive? Adopt?
• What is the cause of it? Did God cause it?
• Is this punishment?
• Guilt / Shame/ Anger
• Sins of the parents
• Medical choices
• Contraception, sterilization, IVF,
  pre-implantation
• Full disclosure?
• Cooperation?

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Directive 28

• Each person or the person's surrogate should
  have access to medical and moral information and
  counseling so as to be able to form his or her
  conscience. The free and informed health care
  decision of the person or the person's surrogate
  is to be followed so long as it does not
  contradict Catholic principles.
• Two actions
• Informed Consent
• Acting on the information

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Critical Decisions Genetic Testing

• Genetic testing can assist sound decision-making
  in a wide range of situations. It is most
  commonly employed to detect problems with
  newborns. Moreover, millions of Americans are
  hospitalized every year because of hereditary
  disease and congenital defects. To the extent
  that genetic testing sets the stage for a cure or
  effective therapy, it is a blessing. USCCB,
  1996

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Directive 54

• Genetic counseling may be provided in order to
  promote responsible parenthood and to prepare for
  the proper treatment and care of children with
  genetic defects, in accordance with Catholic
  moral teaching and the intrinsic rights and
  obligations of married couples regarding the
  transmission of life.

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Should the test be made widely available?

• 10 minutes counseling pre and post test
• If 3 million couples annually 2,820,00
  uneffected
• Totaling 471,00 hours
• 180,000 families with 1 or 2 carriers 180,000
  hours
• 2000 genetic counselors or 650 hr/ 16 wks of
  counseling

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Issues

• Adequate informed consent (with counseling) and
  implications for non-consenting relatives
• Families should not be coerced or intimidated
• Potential consequences should be described and
  understood before testing begins
• Care should not be contingent on testing
• Parents should understand reasons for newborn
  screening give written consent for tests
• Market implications as prices fall and access
  increases

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Issues

• Confidentiality
• Release results only to those the patient has
  given consent for information release
• Protect information from third parties (including
  insurers?)
• Dont usually inform other family members
• Discrimination and stigmatization by insurers,
  employers
• Just dont do it!
• Patient/consumer/health plan member involvement
  in policy making is desirable

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Church considerations

• Testing
• To the extent it sets stage for cure or therapy
• Counseling
• Promote responsible parenthood
• Prepare for treatment of care of affected child
• Informed consent
• Full disclosure
• Cooperation
• Immediate v mediate
• Placing information in context

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Prenatal testing

• Amy is a 27-year-old woman
• 16 weeks pregnant with male
• Abusing alcohol
• History of alcohol and drug abuse.
• Genetic counselor suggested there could be fetal
  harm if she continued to drink.
• Family history
• Nephews were hyperactive and one seemed slow.
  Aunt had some form of mild retardation.
• If tested, might show Fragile-X

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Fragile-X Syndrome

• Common form of inherited retardation.
• X-linked disorder
• 1 in 850 people carry this chromosome.
• 1 in 1250 males are affected,
• Milder cases occur 1 in 2000 females.
• Gene is not totally penetrant or expressive which
  means that the spectrum of the disorder moves
  from severe mental retardation such as Down's
  Syndrome to mild disability.
• 20 with Fragile-X are asymptomatic.
• Variable expression cannot be predicted.
• Imprinting occurs between generations, that is,
  an asymptomatic father passes the gene to his
  daughter who is also asymptomatic but in the
  third generation the gene expresses itself.
• Highly accurate DNA test (5 percent error rate)
  for fragile-X is available.

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What needs to be decided?

• Should Amy have her fetus tested?
• What is Amy obligation to inform her spouse?
• Is Amy obligated to tell her sisters?
• Should all newborns be tested for fragile-X?
• Should prenatal diagnosis be considered a
  routine feature of the testing package offered to
  pregnant women?
• Suppose the woman refuses the test?
• What is the likely impact of the diagnosis of
  fragile-X on a child's education?

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Religious-ethical Questions

• Marital problems created by genetics
• Conflicts between options and religious
  convictions
• Identity
• Guilt / shame / suffering / punishment / grief

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Issues

• Prenatal and Carrier Testing
• Respect for individuals/couples values is vital
• In RC settings, all medical options should be
  presented, even if they cannot be endorsed or
  provided
• Testing of children and adolescents
• Generally should not test for adult onset
  diseases unless direct medical benefit will
  accrue to the child and this benefit would be
  lost by waiting until adulthood

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Gift of Life Evangelium Vitae

• Is prenatal diagnosis morally licit? If
  prenatal diagnosis respects the life and
  integrity of the embryo and the human fetus and
  is directed toward its safeguarding or healing as
  an individual, then the answer is affirmative
  (sec. I, no. 2). 1987

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Gospel of Life

• Prenatal diagnostic techniques are morally
  permissible when they do not involve
  disproportionate risks for the child and the
  mother, and are meant to make possible early
  therapy or even to favor a serene and informed
  acceptance of the child not yet born (no. 63).

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Gospel of Life

• But since the possibilities of prenatal therapy
  are today still limited, it not infrequently
  happens that these techniques are used with a
  eugenic intention which accepts selective
  abortion in order to prevent the birth of
  children affected by various types of anomalies..
  (no. 63)

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Summary of Church Teaching

• The mother is given informed consent
• Neither the fetus of mother is subject to
  disproportionate risk. Some proportion between
  risk to fetus and mother and benefits to be
  expected from tests.
• There is benefit to be derived from testing
• Therapeutic intervention for fetus
• Prepare parents for birth
• Diagnosis of genetic mutation does not result in
  abortion.

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Pre-symptomic Testing

• Mr. P is a 29-year-old college educated married
  man with one child
• Preparing to enter medical school
• Fathers renal failure is secondary to adult poly
  cystic kidney disease (APKD)
• APKD autosomal-dominant disorder or 50 at risk
  for this disorder.
• Has a small-term life insurance policy and sound
  benefits through his employer.
• Mr. P is asymptomatic
• He is aware that a DNA test is available
• Undecided about pursing his diagnosis
• First inclination--seek increased disability
  benefits and to set up a 250,000 trust fund with
  whole life insurance

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Ethical questions

• Is he diseased?
• Is he obligated to be tested?
• Should he tell his wife?
• Should he have his son tested? At what age?
• Should he inform his physician?
• What information must he disclose to the insurer?
• What must he tell others? School? Employer?

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• Mr. P is laid off and it is four month before he
  lands a job. As part of the new job he must join
  the companys health plan.
• Is his risk of AKPD a pre-existing disorder?
• Can he not be hired because of his disorder?
• Can they hire him, but exclude coverage on his
  pre-existing disorder?

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Religious-Spiritual Questions

• Eclipsed futures
• Disorders that create chronic illness
• End-of-life decisions
• Did God cause it?
• Is this punishment?
• Guilt / Shame/ Anger
• Sins of the parents

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Case and Discussion

• Roger Patton is a first year biology teacher.
  When Roger was preparing to teach a class on
  genetics, he read a pamphlet on Huntingtons
  Disease (HD) and began to suspect his fathers
  strange behavior might be the beginning signs of
  the disease. Roger was tested himself and it was
  confirmed that he has the gene for HD himself.

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Case and Discussion

• HD is a dominant disorder, with symptoms
  appearing between the ages of 35 and 50.
• Each child of the HD patient has a 50 chance of
  inheriting the HD gene.
• It can be diagnosed, but there is nothing that
  can be done therapeutically to ameliorate the
  symptoms.
• It is always fatal.
• He has just learned his wife is pregnant with
  their first child.

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Case and Discussion

• HD is a dominant disorder, with symptoms
  appearing between the ages of 35 and 50.
• Each child of the HD patient has a 50 chance of
  inheriting the HD gene.
• It can be diagnosed, but there is nothing that
  can be done therapeutically to ameliorate the
  symptoms.
• It is always fatal.
• He has just learned his wife is pregnant with
  their first child.

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Vatican Sec of State, 1997

• There exists respect for the right of each
  person to decide whether or not to be informed of
  the results of genetic examinations. Yet the
  right of the individual concerned cannot be
  absolute in this regard there is need to
  consider cases where the information has
  consequences for the health of other persons
  (e.g., family member)

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Obligations

• Obligations to other
• Accurate test
• Serious harm
• Effective treatment
• Cannot wait
• Employer obligations
• Is the condition detriment to doing the job?
• Will the condition be exacerbated by the job?

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Conclusions

• Genomics created under explored issues
• Multiplex testing
• Individualized therapies
• Use of embryonic stems cells alternatives
• Common human morality has some theory to address
  ethical problems
• Church teaching
• Often general rules 10,000 feet
• Some rules without exception
• ERDs under defined in some areas