Ethics in Genetics

1. Ethics in Genetics Associate Professor Martin DelatyckiDirector Bruce Lefroy CentreMurdoch Childrens Research InstituteConsultant Clinical GeneticistGenetic Health Services Victoria

2. MCRI • Largest paediatric research institute in the Southern Hemisphere • 60 research groups in 6 themes • ~900 staff • Located at the Royal Children’s Hospital

3. 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

4. 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.

5. Principles • Autonomy • Benificence • Non malificence • Justice

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

7. Beneficence • Acting so as to benefit others

8. Non maleficence • Not harming others

9. 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

11. 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

12. Case studies

13. 1:2 Chance of the condition in child of affected parent

14. Prenatal Options • Traditional prenatal diagnosis • Chorionic villus sampling • Preimplantation genetic diagnosis

15. Chorion Villous SamplingCVS • 11-15 weeks • Diagnosis • Chromosome abnorm. • DNA Studies • Biochemical studies • 1:100 miscarriage

16. 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

17. PGD +

18. PGD - DNA extracted and mutation detection testing done

19. 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.

20. 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

21. 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

22. 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?

23. Pre-implantation selection for deafness - the views of hearing children of deaf adults Cara Mand Martin Delatycki Rony Duncan Lynn Gillam

24. 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”

25. Defining deafness

26. 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)

27. 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)

28. 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)

29. 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

30. 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)

31. Deafness as a Disability vs. Culture

32. PND

33. PGD

34. 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

35. 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?

36. 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

37. 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

38. 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

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

40. 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

41. 22 Tests in Immature Minors • HD- 4 • DM- 4 • CMT- 3 • BMD- 2 • VHL- 2 • SCA- 2

42. 27 Tests in Mature Minors • HD- 14 • DM- 5 • BRCA- 3 • FSHD- 2 • SCA- 2

43. 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

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

45. Views on existing guidelines • 47% strongly agree • 35% agree • 3% don’t know • 5% disagree • 2% strongly disagree

46. 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”

47. 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

48. 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

49. 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

50. 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