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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
Overview
1. Why (yet) more on pre-birth testing and screening?- Why is this important to bioethics? Why now?
- What I aim to achieve today
2. What is happening scientifically?
3. Concepts at stake
4. The challenge for bioethics; and some initial claims
5. Next steps and conclusion
smh.com.au
Why (yet) more on pre-birth testing and screening? 1
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)
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:
i. Existing bioethical concepts ill-equipped to respond to prenatal WGS- Consent as an example
ii. Some practicalities to help resolve the dilemma
iii. How bioethics might approach such problems
thinkbigmagazine.com
Prenatal context remains ethically contested
› 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
Existing aspects of the debate
babble.com
What is happening scientifically? 2
› 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
Existing debates
Whole Genome / Next generation sequencing
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
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
Concepts that are at stake (and what we might do with them) 3
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
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
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”
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Example: debates over consent
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
The challenge for bioethics; and some initial claims 4
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
A pragmatic suggestion
› 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
WGS may be method; does not have to be result…
www.hernandocountygis-fl.us
A pragmatic suggestion (2)
› Use ‘filters’ to create a “results return model” (Dondorp & de Wert 2012; Yu et al 2013; Donley et al 2012; Netzer et 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
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
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)
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
Next steps 5
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
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
What have I proposed?
› Two main claims:1. 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
What have I proposed?
2. 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?