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?