Transcript Slide 1

Ethics in Genetics
Associate Professor Martin Delatycki
Director Bruce Lefroy Centre
Murdoch Childrens Research Institute
Consultant Clinical Geneticist
Genetic Health Services Victoria
MCRI
• Largest paediatric research institute in
the Southern Hemisphere
• 60 research groups in 6 themes
• ~900 staff
• Located at the Royal Children’s Hospital
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
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.
Principles
• Autonomy
• Benificence
• Non malificence
• Justice
Autonomy
• Self-rule
• Ability to make decisions for oneself on the
basis of deliberation
Beneficence
• Acting so as to benefit others
Non maleficence
• Not harming others
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
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 ----> ?duty to warn
• confidentiality/disclosure measured by the greatest
potential harm
Case studies
1:2 Chance of
the condition
in child of
affected parent
Prenatal Options
• Traditional prenatal diagnosis
– Chorionic villus sampling
• Preimplantation genetic diagnosis
Chorion Villous Sampling
CVS
•11-15 weeks
•Diagnosis
– Chromosome abnorm.
– DNA Studies
– Biochemical studies
•1:100 miscarriage
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
PGD
+
PGD
- DNA extracted
and mutation
detection testing done
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.
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
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 Alan’s 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
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?
Pre-implantation selection for deafness - the
views of hearing children of deaf adults
Cara Mand
Martin Delatycki
Rony Duncan
Lynn Gillam
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”
Defining deafness
d/deaf
D/deaf
•medical model (disability) •social model (linguistic
minority)
• d/deaf individuals
- minority in hearing world • D/deaf individuals
separate cultural group
• often deaf later in life or -often
deaf from birth
have partial hearing loss
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)
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
• “We’d 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)
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” (MunzoBaell 2000)
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
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)
Deafness as a Disability vs.
Culture
Categories
Distinct culture /
Difference
Disability
Both
Unsure
Other
No. of
Participants
(n = 66)
30
Percentage
(%)
0
33
0
3
0
50
0
4.5
45.5
PND
Situations
Options
Male
% of males
Female
% of females
X2
P-value
Deaf parents
wanting deaf
children
Deaf parents
wanting hearing
children
Hearing parents
wanting hearing
children
Hearing parents
wanting deaf
children
Y
N
Y
N
3
11
2
12
21.4% 78.6% 14.3% 85.7%
6
46
4
48
11.5% 88.5% 7.7%
92.3%
0.92
0.58
Y
N
2
12
14.3% 85.7%
7
45
13.5% 86.5%
0.01
Y
N
3
11
21.4% 78.6%
4
48
7.7%
92.3%
2.20
1.0
0.16
0.39
0.6
PGD
Situations
Options
Male
% of males
Female
% of females
X2
P-value
Deaf parents
wanting deaf
children
Deaf parents
wanting hearing
children
Hearing parents
wanting hearing
children
Hearing parents
wanting deaf
children
Y
N
Y
N
3
11
2
12
21.4% 78.6% 14.3% 85.7%
10
42
7
45
19.2% 80.8% 13.5% 86.5%
0.03
0.01
Y
N
3
11
21.4% 78.6%
9
43
17.3% 82.7%
0.13
Y
N
2
12
14.3% 85.7%
7
45
13.5% 86.5%
0.01
0.71
1.0
1.0
1.0
Huntington Disease
•
•
•
•
•
Neurodegenerative
Onset on average in 40’s (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
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?
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
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
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
Empirical Evidence
• Very little
• Following studies by Rony Duncan, Martin
Delatycki, Bob Williamson, Julian
Savulescu, Lynn Gillam
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
22 Tests in Immature Minors
•
•
•
•
•
•
HD- 4
DM- 4
CMT- 3
BMD- 2
VHL- 2
SCA- 2
27 Tests in Mature Minors
•
•
•
•
•
HD- 14
DM- 5
BRCA- 3
FSHD- 2
SCA- 2
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
? Agree with Guidelines
• The majority of respondents agree with the
existing guidelines, but feel that each case
needs to be assessed individually
Views on existing guidelines
•
•
•
•
•
47% strongly agree
35% agree
3% don’t know
5% disagree
2% strongly disagree
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 don’t 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”
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
Thinking Gene-Positive
“I’m a very pessimistic person, I was always saying it’s going to be positive, it’s
going to be positive… it wouldn’t have been so much of a shock because
I’ve sort of said to myself, you know, I’m going to be positive anyway”
Travis:M:24:HD:20:-ve
“Knowing that there’s a 50:50 chance, it’s just, like it’s always in your head that
yes I have it, rather than no I don’t have it”
Zach:M:26:HD:23:-ve
“I just thought I had it, obviously I didn’t have signs or anything, but like, in my
head, yeah”
Poppy:F:24:HD:17:-ve
Living Again
“I’ve gotten off drugs since I found out”
Nina:F:23:HD:23:-ve
“Since I’ve been tested I’ve been pretty good… I haven’t 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”
Troy:M:26:HD:25:-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”
Travis:M:24:HD:20:-ve
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, didn’t feel like I was living kind of thing, like I had a life
but I wasn’t 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.”
Belinda:F:25:HD:21:+ve
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 didn’t, you
know, so for 19 years it feels like I’ve held my
breath, thinking that I’m going to get this illness, and
now it feels like I’m 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 didn’t
have the gene… and I felt like I could breathe for the
first time in 19 years”
Ella:F:20:HD:18:-ve
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?