Genomic advances and testing and screening before birth: what’s at stake?

1. Genomic advances and testing and screening before birth: what’s at stake? AABHL Conference | Sydney, July 2013 Centre for Values, Ethics and the Law in Medicine (VELiM) Dr Ainsley Newson | Senior Lecturer in Bioethics

2. Overview • Why (yet) more on pre-birth testing and screening? • Why is this important to bioethics? Why now? • What I aim to achieve today • What is happening scientifically? • Concepts at stake • The challenge for bioethics; and some initial claims • Next steps and conclusion smh.com.au

3. 1 Why (yet) more on pre-birth testing and screening?

4. Why is this important to bioethics? Why now? • Prenatal context remains interesting • Time restrictions; limitations on decision-making; psychological investment • WGS could bring unprecedented complexity to PND or IVF • More information; obtained faster; obtained earlier • Genetic risk could become relevant to more women and couples • Could “change norms and expectations of pregnancy” (Donley et al 2012) “[A]ll this is possible before we’ve figured out whether we should be doing it” (Jay Shendure, genome scientist, University of Washington)

5. What I aim to achieve today… Problem: literature on prenatal WGS tends to: • Raise questions but not address them; • Discuss issues in familiar rhetoric • too limited here • Include empirical claims, especially re: harms I will suggest: • Existing bioethical concepts ill-equipped to respond to prenatal WGS • Consent as an example • Some practicalities to help resolve the dilemma • How bioethics might approach such problems thinkbigmagazine.com

6. Prenatal context remains ethically contested Existing aspects of the debate • Moral and legal status of the embryo/foetus • Assumptions about the value of life for those with the condition being tested/screened for • Threshold of ‘seriousness’ to justify testing; definitions of health and illness • Genetic determinism babble.com

7. 2 What is happening scientifically?

8. Whole Genome / Next generation sequencing Existing debates • Then: • US$10-$50m per genome • Time consuming • Poor accuracy • Now: • <US$10K per genome • Fast & accurate • Meaning of information gained? • Soon: • US$1K per genome • Really, really fast • Know (a little) more about meaning

9. Microarrays • Glass slide with known small DNA fragments (SNPs) attached • Determine whether a particular known gene/mutation is present/absent • Allow finer resolution mapping than chromosomal analysis alone • Fast and cheap • Simultaneously detect hundreds of thousands (or millions?) of SNPs Credit: Wellcome Images

10. Emerging prenatal / preimplantation technologies Noninvasive prenatal testing (NIPT) • Analyses cell-free fetal DNA • Obtained via blood test: no risk • 3-6% of all cell-free DNA in pregnant woman • Test reliably from ~week 7 • Available clinically now • WGS and Microarray testing can be used in NIPT • More data needed on clinical use Preimplantation Genetic Screening (PGS) • Not PGD, but a wide-ranging screen on embryos prior to implantation • Goal: boost chances of IVF success • Clinical validity contested, RCTs currently underway • WGS and Microarray testing can be used in PGS • More data needed on clinical use

11. 3 Concepts that are at stake (and what we might do with them)

12. How ‘bioethics’ might tend to tackle WGS • We might talk about ‘reproductive autonomy’ • Should there be wholly ‘individualised choice’ for prenatal WGS? • Who should set the limits on testing? • Should reproductive autonomy override the future child’s ‘right not to know’? • In bioethics we might also talk about ‘informed consent’ • How could informed consent to WGS be gained in a meaningful way? • These are of course interesting questions • But they also lead to intractable debates

13. Example: debates over consent • Traditional models of informed consent focus on: • Being fully specific • Being fully explicit (Manson & O’Neill, 2007) • WGS and Microarrays will challenge this • More novel genetic information of uncertain clinical significance; • Right ‘not to know’ (future child? couple?); • Decision perhaps needed quickly; • Vulnerable groups, e.g. couple facing repeated IVF genengnews.com

14. Example: debates over consent • Consent process is detailed, time consuming but necessarily incomplete • Criticisms: (Manson & O’Neill, 2007) • Mere information transfer, ignoring transactional context • Explicit and specific consent necessitates standards impossible to attain • Consent for WGS/Microarrays in NIPT or PGS needs different approach • Focus: “communicative transaction” • Intelligible, relevant, successful and bidirectional communication • Draw on each party’s “inferential competencies” • Give “adequately accurate” information not “illusory completeness”

15. What might we do with concepts like consent and autonomy in this discussion? • Aspects of consent to WGS in a prenatal context are obviously important • E.g. Is more information better than less? • Determining scope of reproductive autonomy also important • However, volume of information and other complexity arising from WGS shows limits of these concepts. • Are we asking the right questions? Need: • To think about the practicalities • To think about the structure of bioethical debate

16. 4 The challenge for bioethics; and some initial claims

17. So how does WGS challenge bioethics? • Have claimed that popular concepts will not help resolve problems of prenatal WGS/Microarray analysis • Challenges are to: • Resolve the problems WGS raises; and • Do so in a way that does not lead to more empirical claims or intractable problems wired.com

18. A pragmatic suggestion WGS may be method; does not have to be result… • WGS/Microarrays will provide more information than know how to interpret for some time to come • Until information has clinical utility akin to that in current prenatal or preimplanation genetic diagnosis, seems unreasonable to provide it • Counterpoints: • Information obtained belongs to person’s health record and should be reported • Information will become certain/settled • Assumes we can (at some point) make objective judgements about what information to provide • So need a flexible, deliberative approach www.hernandocountygis-fl.us

19. A pragmatic suggestion (2) • Use ‘filters’ to create a “results return model” (Dondorp & de Wert 2012; Yu et al 2013; Donley et al2012; Netzeret al, 2009 [not PND]) • Don’t view WGS as a test from which results have to be ‘returned’ • Rather, view WGS as a dynamic information resource • Results should be dynamically ‘managed’ over time by the individuals to whom the information pertains, consistent with personal attitudes and values, in conjunction with clinical care • ? Resource implications • ? Process implications • ? Health care professional relationshipimplications… icondig.com

20. A pragmatic suggestion (3) • Dynamic information in PND: • Use WGS approach • Filter information so consistent with that currently reported in PND or embryo replacement • Be mindful of ‘specification creep’ • Can help mitigate ethical concerns with WGS prenatally • Issues like clinical utility, privacy, open future, couples’ expectations, technological imperatives etc. are explicitly considered first • Imposes time and methodological discussion

21. A suggestion as to the kind of reasoning we might do “The ideal of allowing autonomous reproductive choices appears less suitable… than the idea of making future parents… responsible for making a good choice.” (Dondorp and de Wert 2013) • Parents (or prospective parents) should ‘act parentally’ (McDougall 2005 & 2007) • Action is right iff it’s what a virtuous parent would do • Virtuous parent has and exercises parental virtues • Parental virtues are conducive to child’s flourishing • E.g. acceptingness, committedness, future-agent focus, [‘responsableness’?] • Has been used to argue: • Selecting disability may be acceptable if promotes flourishing (McDougall 2009) • Selecting disability is not acceptable (Malek 2013)

22. Possible problems with this approach • Debate over what should constitute the standard of virtuous conduct • And what this might mean for PND… • “Virtue implies excellence” (Saenz 2010, p504) • ‘Acting parentally’ is more a minimal threshold than the excellence virtue requires • Only those actions that fail to promote flourishing will be precluded, too low a standard (Children are resilient!) • Is this (arguable) vagueness enough to prevent a role for virtue? • It DOES allow for a broad cultural discussion about how we should parent

23. 5 Next steps

24. Consider additional elements • Direct to consumer aspect • Privacy and data management • ‘Non-medical’ applications of data • Today I have provided an initial framework; there are more questions to answer gcs.com.au

25. So what is at stake? • Informed decision-making is at stake • Rhetoric on conceptions of health and disease and perfection is at stake • Requirement to accept fallibility is at stake • Bioethics methodology is at stake • Practical management of genetic information is at stake hubpages.com

26. What have I proposed? • Two main claims: • WGS may not be as problematic as first inspections suggest; if we manage data according to a “dynamic information resource” model • Existing issues in PND will still be relevant to this, but WGS/Microarrays in NIPT or PGS may not make them worse • Managing information will mitigate the issues with volume of information • There are other issues with NIPT which are relevant but beyond scope of this presentation

27. What have I proposed? • WGS offers a great opportunity to re-invigorate bioethics debates in a prenatal choice context. I have suggested that this could be by way of a virtue-responsibility model • Attempt to avoid problems with harm-benefit analysis, such as empirical claims • This will help to shape a view of parenthood that accepts imperfection We also need to continue with public engagement about genetic information, its value and its pitfalls. Ultimately: will technologies such as WGS help couples make ‘accepting’ decisions that they can live with in the longer term?