Ethics in Genetics

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Ethics in Genetics

• Associate Professor Martin DelatyckiDirector
  Bruce Lefroy CentreMurdoch Childrens Research
  InstituteConsultant Clinical GeneticistGenetic
  Health Services Victoria

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MCRI

• Largest paediatric research institute in the
  Southern Hemisphere
• 60 research groups in 6 themes
• 900 staff
• Located at the Royal Childrens Hospital

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Bruce Lefroy Centre

• 28 staff
• Research into neurogenetic diseases (Friedreich
  ataxia, Parkinson disease, Huntington disease,
  dystonia)
• Community genetic research (haemochromatosis,
  cystic fibrosis, Tay Sachs disease)
• Genetic ethics research

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THE HIPPOCRATIC OATH

• I swear the following Oath To consider dear to
  me as my parents him who taught me this art .
• I will prescribe regimen for the good of my
  patients according to my ability and my judgment
  and never do harm to anyone. To please no one
  will I prescribe a deadly drug, nor give advice
  which may cause his death. Nor will I give a
  woman a pessary to procure abortion. ... In
  every house where I come I will enter only for
  the good of my patients, keeping myself far from
  all intentional ill-doing and all
  seduction.... All that may come to my
  knowledge in the exercise of my profession ...
  which ought not to be spread abroad, I will keep
  secret and will never reveal. If I keep this oath
  faithfully, may I enjoy my life and practice my
  art, respected by all men and in all times but
  if I swerve from it or violate it, may the
  reverse be my lot.

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Principles

• Autonomy
• Benificence
• Non malificence
• Justice

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Autonomy

• Self-rule
• Ability to make decisions for oneself on the
  basis of deliberation

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Beneficence

• Acting so as to benefit others

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Non maleficence

• Not harming others

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Justice

• Moral obligation of fairness.
• Treating people equally in relation to criteria
  acknowledged to be morally relevant.
• Great variability in different societies,
  cultures and religions

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In 2008 what has changed?

• Options of genetic testing provide new choices
• the type of children we have
• information (management ) - future health
• Doctor patient relationship in genetics
• patient/client
• gene affects the family who is the patient
• Duty of care ----gt ?duty to warn
• confidentiality/disclosure measured by the
  greatest potential harm

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Case studies
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12 Chance of the condition in child of affected
parent
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Prenatal Options

• Traditional prenatal diagnosis
• Chorionic villus sampling
• Preimplantation genetic diagnosis

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Chorion Villous SamplingCVS

• 11-15 weeks
• Diagnosis
• Chromosome abnorm.
• DNA Studies
• Biochemical studies
• 1100 miscarriage

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Preimplantation Genetic Diagnosis- PGD

• In the context of IVF
• Testing by embryo biopsy
• Chromosomal abnormalities
• Selected single gene disorders
• Most common reason an objection to TOP or
  previous TOP following PND.
• No apparent increase in birth defects

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PGD

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PGD
- DNA extracted and mutation detection testing
done
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Method of embryo biopsy

• The hole in the zona allows entry of a micro
  pipette to aspirate 1 or 2 cells from the embryo.
• The cell can then be fixed to a slide, or placed
  in solution to allow genetic analysis.

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PGD for single gene disorders

• Requested by couples wishing to avoid TOP
• 97 diagnostic accuracy
• 20 pregnancy rate per cycle
• Cystic fibrosis most common indication
• Counselling by both Genetics and IVF team

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Client 1

• Alan and his partner Helen are both deaf and they
  are planning to have children.
• Alan has severe deafness as do both his father
  and his paternal grandfather. He grew up
  surrounded by deaf people.
• Genetic testing has shown that Alans deafness is
  due to an autosomal dominant mutation.
• Helen is the first in her family with deafness
  and this was thought to be due to exposure to a
  drug as baby.
• The couple communicate by sign language

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Client 1

• They come to you seeking prenatal diagnosis. They
  know that there is a 50 chance for each child to
  be deaf based on the dominant mutation found in
  Alan.
• They state that they want their children to be
  deaf like them so they can experience the D/deaf
  culture they live in. They request prenatal or
  preimplantation genetic diagnosis with selection
  for deafness.
• Can you help them?

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Pre-implantation selection for deafness - the
views of hearing children of deaf adults

• Cara Mand
• Martin Delatycki
• Rony Duncan
• Lynn Gillam

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Background

• Duchesneau and McCullough deaf lesbian couple
• Wanted a deaf child
• Congenital deafness is precisely the sort of
  condition that disqualifies would be donors
  (Spriggs 2002)
• Sperm from friend with 5 generations of deafness
• a hearing baby would be a blessing. A deaf
  baby would be a special blessing

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Defining deafness
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D/deaf

• Deaf people like being deaf, want to be deaf,
  and are proud of their deafness they claim the
  right to personal diversity, which is something
  to be cherished rather than fixed or erased
  (Tucker 1998)

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Current debate / controversy

• Against selection for deafness
• selecting deafness denying the child of an open
  future
• Often
• Medical professionals
• Hearing community
• d/deaf individuals
• Ethicists
• Wed like to be able to hear our children and
  grandchildren laugh and cry, listen to the radio
  the list is endless. Why would any human being
  want to deny such pleasure to herself or her
  children? (Tucker 1998)

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For selection for deafness

• Deafness not a disability
• Their choice to make
• Often (but not always)
• Ethicists
• Geneticists/ genetic counsellors
• D/deaf individuals
• Deaf people are disabled more by their
  transactions with the hearing world than by the
  pathology of their hearing impairment
  (Munzo-Baell 2000)

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Project

• To gain insight into the attitudes of hearing
  children of deaf adults, to selection for
  deafness
• Already know the views of both the hearing and
  Deaf community towards selection for deafness
• Hearing children of deaf adults
• Ideally placed, experience in both hearing and
  deaf world

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Project

• 2 Stage process, adopting qualitative and
  quantitative research methods
• 1st individuals from CODA and health
  professionals. Semi-structured interviews.
  Answers analysed and used to compile a survey for
  second group of participants .
• 2nd Anonymous survey broadcast electronically.
  Answers explored and similarities extracted and
  analysed.
• Through CODA (worldwide organisation)

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Deafness as a Disability vs. Culture
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PND
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PGD
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Huntington Disease

• Neurodegenerative
• Onset on average in 40s (4-80)
• Death on average 15 years from onset
• Chorea, dementia, personality change
• No treatment known to change outcome
• Autosomal dominant- all due to one mutation

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Client 2

• Max has a family history of Huntington disease.
  He has predictive testing that shows that he has
  inherited the condition.
• Max has two children- Ben is 8 and Nancy is 6.
  He requests that they be tested- do you test the
  children?

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Genetic Testing of Children

• To make diagnosis- uncontroversial (eg Duchenne
  muscular dystrophy)
• Where preventative treatment in childhood is
  proven- relatively uncontroversial
• Where no treatment is available and onset is
  adulthood- predictive testing- controversial

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Predictive Genetic Testing of Children

• Genetic societies- should not do so as it removes
  the right of that person to make their own
  decision
• Most adults choose NOT to have this testing
• The child may be treated differently to their
  detriment if their genetic status is known

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Predictive Genetic Testing of Children

• Alternate view eg Prof Julian Savulescu-
• Knowing status from childhood will allow that
  person to grow up with the knowledge of their
  genetic status and adjust to this

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Empirical Evidence

• Very little
• Following studies by Rony Duncan, Martin
  Delatycki, Bob Williamson, Julian Savulescu, Lynn
  Gillam

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Clinical Geneticist Survey

• Web-based survey sent to
• - Members of the Australasian Association of
  Clinical Geneticists (98)
• - Members of the Clinical Genetics Society of
  the UK (400)
• - All Medical Doctors who are members of the
  American Society of Human Genetics (1732)
• The target was Clinical Geneticists
• Responses were received as anonymous e-mails

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22 Tests in Immature Minors

• HD- 4
• DM- 4
• CMT- 3
• BMD- 2
• VHL- 2
• SCA- 2

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27 Tests in Mature Minors

• HD- 14
• DM- 5
• BRCA- 3
• FSHD- 2
• SCA- 2

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Follow-up

• 18/27 some follow-up
• 2 adverse events
• Initial depression and rebellion but eventual
  acceptance HD ve 17 year male
• No psychological disturbance but worry and
  responsibility for affected mother and untested
  brothers HD -ve 17 year female
• 9 reports of benefits

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? Agree with Guidelines

• The majority of respondents agree with the
  existing guidelines, but feel that each case
  needs to be assessed individually

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Views on existing guidelines

• 47 strongly agree
• 35 agree
• 3 dont know
• 5 disagree
• 2 strongly disagree

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Views on existing guidelines

• A strong theme of each case must be assessed on
  its own merits
• I support informed consent for testing and
  some minors are capable of providing it, others
  are not
• I dont believe in a rigid cut-off age as I
  believe obtaining maturity to gain informed
  consent is a gradual process
• Occasionally there are exceptions to the age
  limit and one has to be flexible

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Interviews with Young People

• 18 interviews with young people who had undergone
  predictive genetic tests
• 8 young people who were tested for HD
• 2 gene-positive 6 gene-negative
• Tested between ages of 17 and 25 yrs

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Thinking Gene-Positive

• Im a very pessimistic person, I was always
  saying its going to be positive, its going to
  be positive it wouldnt have been so much of a
  shock because Ive sort of said to myself, you
  know, Im going to be positive anyway Tra
  visM24HD20-ve
• Knowing that theres a 5050 chance, its just,
  like its always in your head that yes I have it,
  rather than no I dont have it ZachM26HD23
  -ve
• I just thought I had it, obviously I didnt have
  signs or anything, but like, in my head, yeah
• PoppyF24HD17-ve

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Living Again

• Ive gotten off drugs since I found out
• NinaF23HD23-ve
• Since Ive been tested Ive been pretty good I
  havent been in trouble with the police or
  anything I seem to have changed a bit, just come
  out of me shell.. You know.. A bit happier and
  stuff I want to start me own business
  TroyM26HD25-ve
• I thought well, if I can go through this whole
  process of getting tested for this thing, I can
  pretty much do anything I respected myself a lot
  more for that
• TravisM24HD20-ve

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Living Again

• It stopped me from living effectively at the
  time, I mean, I did the day to day things, I went
  to school, I ate dinner but, didnt feel like I
  was living kind of thing, like I had a life but I
  wasnt living. Once I had the knowledge, that was
  it, ok, fine, you know knowing but not knowing
  in a way knowing that if I live long enough I
  will develop symptoms one day, um, but now
  knowing exactly what the rest of my life has in
  store for me and allowing me just to accept that
  and just live. BelindaF25HD21ve

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Holding Your Breath

• All my life I thought I was going to get this
  illness, all my life, and last year I found out I
  didnt, you know, so for 19 years it feels like
  Ive held my breath, thinking that Im going to
  get this illness, and now it feels like Im a
  newborn child, you know, like, I can live a life
  I never knew I could. It seems really weird to
  adjust to, like, the whole time I thought I was
  going to get it and then she told me I didnt
  have the gene and I felt like I could breathe
  for the first time in 19 years
• EllaF20HD18-ve

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Client 3

• Sonya requests prenatal diagnosis (PND) for HD as
  her partner Colin is at 50 risk
• Colin has stated that he does not wish to know
  his HD status and he would suicide if he found he
  had the mutation
• Sonya says if the PND is positive she would tell
  Colin she miscarried
• Do you offer Sonya PND?