Are the proposed mtDNA transfer techniques ethical?

Media coverage on “3 person IVF” has admittedly eased up a bit after the House of Commons voted in favor of the proposed mitochondrial DNA (mtDNA) techniques that I talked about in my blog post from last week. However women affected with mitochondrial diseases as well as members of the bioethics community know the debate is far from over.

As the astute reader may have noticed, I deliberately tried to leave any firm opinion out of my previous ‘news update’ from last week. As safe as it may feel to hide behind a news report, one of the most reiterated lessons during my studies in bioethics is that we cannot be afraid to make normative statements.  Translated into syllabus requirements: each week 2 students have to present an ethical analysis of a case study (10 minutes presentation, 10 minutes Q&A).

This week was my turn, and I had the timely opportunity to present on mtDNA transfer.  To add to the excitement, this week we had class at the Nuffield Council on Bioethics— which meant that I was presenting on the turf of people who published a extensive (98 page) bioethical review of these techniques before publishing their endorsement in 2012.

If the PNT and MST techniques are proven to be acceptably safe and effective, on balance it would be ethical for families wishing to use them to do so. [5.2, p88]

After a quick hello, I cut to the chase: “my presentation today will look at a subset of concerns that challenges this conclusion.”

Needless to say, adrenaline was running high.

 

My assessment: UNETHICAL

There are long lists of points to consider in reviewing these new techniques, but since I only had 10 minutes, I tried to focus on areas that I felt have largely been brushed over in the publicized discussion.

 

1. The novel use of the human embryo

For some people… the merging of the [pronuclear] DNA from the parents to create an embryo with a unique genetic identity is morally significant. Those holding this view are likely to find [pronuclear transfer] morally preferable [to nuclear transfer] because of the higher moral status afforded to the embryo once this stage of development has been reached. Given, however, that the law permits research up to 14 days after fertilisation where it is ‘necessary and desirable’,  and the BMA supports this position, the BMA does not consider this to be a relevant distinction in terms of developing policy for mitochondrial transfer. [4.58, p63]

I acknowledged the obvious question (Is the outcome of mtDNA transfer ‘necessary and desirable’?) but for time sake marked it for Q&A. Instead I focused on the assertion that this point was irrelevant to policy making.

Pronuclear Transfer (PNT) uses embryos in a way that is significantly different from previous reproductive treatments such as preimplantation genetic diagnosis (PGD) with in vitro fertilization (IVF)— a technique used to select embryos to reduce the probability of passing on deleterious genetic conditions.  An oft cited argument (ie: Savulesco) in support of such technologies is that it is not logical to think that all embryos should deserve to live because (if we reference natural procreation with sexual intercourse) approximately 3-5 embryos are created and lost for every live birth.

Both proposed mtDNA transfer techniques would utilize this same selection step before implanting embryos in a woman.  However, PNT first requires the creation of a ‘donor embryo’ for the specific purpose of harvesting its healthy mitochondria.  This embryo is NOT created with the chance of being selected.

Those of you that have seen The Island (2005) in which wealthy people can create a spare body from which they can harvest necessary transplants, may understand why I cringe at this thought.

In evaluating the ethics of novel techniques like this, it may be most appropriate to return to first principles.

Instead of / in addition to asking: How can we match moral value with a quantifiable measurement (ie: number of cells, number of days old)?

Perhaps we ought to ask: Is it ethically acceptable to create embryos for the means of other embryos?

 

2. The increased need for egg donation

When compared with current artificial reproductive technologies (ie: PGD / IVF, donor egg) the proposed techniques require 2x as many eggs– one from the affected mother and one from the female mitochondrial donor.

The BBC reported… “HFEA says people should feel the same about [gamete donation] as they do about altruistic, or living, organ donation.” HFEA Chair Lisa Jardine was quoted in the Daily Telegraph as saying that she wanted egg donation to become ‘as obvious as blood donation’. [4.95, p72]

In a society that promotes a woman’s right over her body and sexual organs through widespread use of artificial reproductive technologies, contraception, and abortion (and paid for under NHS!) this assertion that altruistic women donate eggs is dubious.

But this is not just a discussion of societal norms, and the medical risks of egg extraction. (Note: There is ~10-14% risk of ovarian hyperstimulation syndrome for women that have eggs extracted.) This is also a discussion of justice.

We do not consider it appropriate for a regulator to set a limit on the number of times a mitochondrial donor can donate eggs for research or reproduction, other than to protect her from repeated ovarian stimulation. [4.149, p84]

Since 2012, NHS will pay women a flat sum of £750 (+ compensation for travel, childcare, accomodation, etc) per donation cycle. Currently, there is a ’10 family limit’ to prevent the dystopian situation where children produced from donor gametes might unknowingly have children with half-siblings.  Without a limit on the number of donations that women could make, we amplify the concerns that we’ve had about incentivizing kidney donations– it bears a great risk of exploiting the poor.

One interesting analogy shared by a previous egg donor and published by Center for Genetics and Society is that “saying that financially struggling young women donate eggs out of the goodness of their hearts is like saying that poor men work in coal mines because they are so concerned that the rich have enough electricity.”

I give the UK the benefit of the doubt and say that it does not want to end up in a situation where we are shipping in donated eggs from women in impoverished countries where £750 could stretch a lot further than it does in London.  So, are we willing to increase the commodification of our own English women? And mind you, because of our understanding of medical tourism, these English eggs will NOT just serve English people, but the wealthy.

 

3. The role of the affected woman’s voice

[Our son] was 2yr and 4 mths old [when he died of Leigh’s disease]. He had very little quality of life and was very ill and suffered greatly, as did the entire family. These last couple of years have been devastating beyond belief for all of us. We have one healthy daughter who is nearly 5. We would love more children to make our family complete but cannot take the risk this could happen again, so until our gene is found, we are pursuing donor egg options… We would 100% inform any child born of the techniques used, and feel strongly that the child would be grateful to have a genetic link to myself (mother) rather than no genetic link at all (with the donor eggs we are currently using). I believe the impact on the child would be minimal. It only takes me telling them the story of how our son died to make them realise why we would have pursued this technique to ensure another child didn’t suffer this way. We would 100% travel abroad for this technique, we are already going to Spain for our donor eggs… [4.99, p73-74]

I don’t think anyone would debate that this is a powerful account. And a history of patriarchy in medicine demonstrates why it is important to listen to the voice of the patient.

But while narrative accounts are not necessarily confined to rules of rationality, the arguments of bioethicists must be based in reason.  We must recognize these voices as a member of the orchestra, NOT the director.  The implication of letting emotion rule is not just detrimental to our arguments, but also to the affected group. Passion feeds on passion.  If affected women were constantly told that this is unsafe or at least that the safety / efficacy cannot be accurately assessed because of many unknowns, I don’t think we would have statements like: I believe the impact on the child would be minimal.

So my final question: Is it ethical to emphasize an emotional narrative such that sincere risks are made less prominent?

 

Summary:

1. When evaluating the ethical nature of novel biotechnologies, it may be necessary to return to first principles. As demonstrated with the examples of creating donor embryos via PNT and increasing the call for egg donation, relying on previous standards is inadequate.

2. Incorporating the patient’s voice into ethical debate is powerful. I contend that it is important to keep this voice, but we must proceed with much caution lest we let emotion overpower reason.

3. Based on the interplay between the patient’s voice and an ethical assessment– bioethicists must take responsibility for the endorsements they offer.

I braced myself for a brutal round of Q&A…so I was pleasantly shocked when the majority of responses agreed that I managed to address some important concerns.  I hope by sharing this I have managed to provide some additional points for your consideration.

Over and out.

– ASB

 

Some end notes:

– Featured image courtesy of Silvia Camporesi.

– Many thanks to the people that listened to my musings and helped me refine my arguments over pretzels in the park, through email, and via homing pigeon over this past week. Your support is greatly appreciated!

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Pre-Vote News: “Mitochondrial Donation: Is it safe? Is it ethical?”

Last night I had the amazing privilege to attend a debate in the Houses of Parliament regarding today’s vote about whether or not to amend their 2008 Human Fertilisation and Embryology Act (HFEA). The debate was hosted by the Progress Educational Trust (PET), an independent organization that “urge(s) you to vote in favour of the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015.”

I’m rushing this post to press, so please forgive the lack-luster writing quality– I thought you might enjoy an update while the news is fresh. My understanding of biology is helpful, but please understand that I am no expert on this.  All information provided is correct to the best of my knowledge– but if you see some errors, please let me know!

What is mitochondrial disease?

Most info in this section can be double checked on Wikipedia.

  • A set of diseases caused by faulty mitochondria, the “powerhouse” organelle in the body responsible cellular metabolism– converting the food we eat into energy that is usable by our body (ATP — adenosine triphosphate)
  • Symptoms: mostly effects organs that need a lot of energy such as brain (seizures, demintia); heart (cardiomyopathy “heart muscle disease”); muscles (weakness, cramping); ears / eyes / nerves (deafness, blindness, neuropathic pain)
  • Although in 5th grade we learned that all our DNA is stored in chromosomes in the nucleus of our cells that we received from our parents — half from Mom (egg), half from Dad (sperm)– this is only mostly true. It’s more like 49% from Dad (stored in the sperm’s chromosomes) and 51% from Mom (49% stored in the egg’s chromosomes, 2% stored in the egg’s mitochondria). This 2% is exclusively passed through the maternal line. (eg: George’s mitochondrial DNA came from his mom, which came from her mom, which came from her mom… George’s wife will pass on mitochondrial DNA to their children.)
  • While 85% of these mitochondrial diseases are caused by genetic mutations in chromosomal DNA, ~15% of mitochondrial diseases are caused by mutations in the mitochondrial DNA. This subset of mitochondrial diseases is where we focus our attention.

What is mitochondrial donation?

“A type of in vitro fertilization (IVF) that involves conceiving a child using biological material from three people — the child’s parents, plus a mitochondrial donor” (PET briefing).

You may have heard about this in the media as a “3 parent” embryo.  a somewhat misleading description since parents are not just defined by genetic relations. (Think about parents of adopted children.)  Even if emphasize the importance of genetic lineage, the embryo would only receive ~2% of its DNA from the “3rd parent” (the woman who donates mitochondrial DNA). Remember: 98% of the DNA is from the chromosomes of the egg & sperm.

The HFEA is proposing two specific techniques:

1. maternal spindle transfer (MST)

Mitochondria from a donor egg is transferred to the Mom’s egg. The Mom’s egg (now containing healthy mitochondrial DNA from the donor) is then fertilized with Dad’s sperm using IVF techniques.

2. pronuclear transfer (PNT)

Mom’s egg is fertilized with Dad’s sperm using IVF. A donor embryo is formed using donor egg and potentially (though not necessarily) donor sperm. The healthy mitochondrial DNA from the donor embryo is transferred to the embryo formed from the Mom’s egg and the Dad’s sperm. This technique results in the death of the donor embryo, the ethics of which are briefly outlined below.

See the HFEA’s website for more info on these two techniques.

What are the main ethical considerations?

Lots of things to consider! But for time sake (I have to run to class!) I’ll talk about two:

1. Is mitochondrial transfer safe?

Again, this is contested. Based on the debate yesterday, my understanding is that these techniques have been researched for 30+ years. The majority of this time has been spent with animal research, but the last 5 years have used human embryos. The results are promising, but we wouldn’t understand the effects until it is tested in humans.

This technique is unique in the fact that it changes the germ line. It is very difficult to predict the social and biological harms / benefits of this type of alteration. There have been a few experiments in humans that use similar techniques, (US — late 1990s, China — 2003) but the results have either been unsuccessful or indeterminate.

Note: In the US, the FDA has NOT yet approved mitochondrial donation for clinical trials. This takes for-eh-ver, so even if / when this advances to the stage of clinical trials, it will be a long time before it is available to the general public.

2. What is the moral status of an embryo?

A highly contested question. According to UK parliament (2002) the embryo has some non-negligible moral value that is less than the moral value of person after birth. This matches their policy that permits the use of IVF to select against severe genetic disease and states that embryos may be used for research purposes only when they are ≤ 14 days (“early embryos”).

One of the strongest voices on the other side of the fence is the Catholic Church, which states that “human life must be respected and protected absolutely from the moment of conception” (2270). Contrary to popular belief, the Catholic Church does encourage “research aimed at reducing human sterility” (2375). However, it opposes “techniques involving only the married couple… that dissociate the sexual act from the procreative act” (2377 — eg: artificial insemination / fertilization) and strongly opposes “techniques that entail the dissociation of husband and wife, by the intrusion of a person other than the couple” (2376).  This understanding matches the Catholic teaching that sympathizes with infertile couples but maintains that a child is gift– there is no “right to a child” (2379).  As such, the Catholic Church does not support the proposed changes– especially PNT which creates and destroys the donor embryo, a means to the end of creating a healthy embryo.

The vote will take place this afternoon (London time) so stay tuned to the news!  Based on the views exchanged at the debate yesterday and the fact that IVF is permitted in the UK with costs covered under the National Health Service, I’m betting that this proposal will pass at least in part– definitely for MST, but perhaps not for PNT because of the ethical reasons explained above.

And if you made it through that whole post, here are some photos for your enjoyment.