“Disruption” is a fashionable concept that’s been in the news for some time now, to such an extent that the word is being criticized as “Silicon Valley jargon”. Award winning journalist and Political Editor of The Guardian Australia, Katharine Murphy, would not agree. She has just released her book On Disruption, which looks at how technologies, such as the Internet, have radically changed our professional and personal lives.
Now we are faced with unprecedented 21st century reproductive technologies which can be used to change the genetic essence of ourselves (our DNA) when we are embryos and in such a way that the changes will be passed on to our future descendants. Should we do this?
In other words, is it ethical to disrupt our modern-human genetic heritage which has evolved naturally over at least the last 200,000 years? That is just one of the ethical issues raised by “three-parent IVF” which has also been in the news, most recently, because the Senate Community Affairs References Committee of Federal Parliament has released a report, dated June 2018, Science of mitochondrial donation and related matters. The report considers calls to change State and Federal Australian laws, which currently prohibit such donation.
The Prohibition of Human Cloning for Reproduction Act 2002 and the Research Involving Human Embryos Act 2002 both make it a serious crime to create a human embryo other than for reproduction, or with more than two biological parents, or who has inheritable alterations of the human germ line (the genes passed on from generation to generation), or to implant such an embryo in a woman’s uterus.
“Three-parent IVF” — a term which, to calm down ethical fears, proponents of the technology want replaced by the less alarming and more normal and familiar sounding “mitochondrial DNA transplants” — could breach these prohibitions.
So, should Parliament change the law? What ethics should inform our answer to that question? Good facts are essential to good ethics, so let’s look first at the scientific facts.
An embryo results from the union of a man’s sperm and a woman’s ovum. The ovum has a DNA nucleus and, external to that, mitochondrial DNA (mtDNA) in the cytoplasm surrounding the nucleus. The mtDNA is inherited only from the woman and, from the time we are conceived until we die, converts energy from nutrients to energy for the cells that constitute every human being. Some women have defective mtDNA which can result in mild to very serious disease in their children.
“Three-parent embryos” are created using IVF and replacing the defective mtDNA of the woman who will have the child with the healthy mtDNA of another woman. This is known as mitochondrial replacement therapy (MRT) which can be carried out in four different ways, but the two most prominent are maternal spindle transfer (MST) and pronuclear transfer (PNT).
MST involves using a donor ovum with healthy mtDNA, extracting its nuclear DNA and replacing it with the nuclear DNA removed from an ovum of the intended mother, resulting in a “combination ovum” with mostly healthy mtDNA, which is fertilized with the father’s sperm to create an embryo. Importantly, MST does not involve creating an embryo from the donor’s ovum and then destroying that embryo by enucleating it. The embryo’s mtDNA is only “mostly healthy”, because some of the mother’s defective mtDNA in her ovum’s cytoplasm is ordinarily attached to the nuclear DNA and transferred with it.
In contrast, PNT does involve creating an embryo with the intention of destroying it. An embryo is created from the future mother’s ovum and the father’s sperm (“mother’s embryo”) and another embryo from a healthy mtDNA ovum donor and the father’s sperm (“donor embryo”). The nuclear DNA is removed from the “donor embryo”, destroying it, and the nuclear DNA from the “mother’s embryo” is transferred to the enucleated donor embryo creating an embryo with mostly healthy mitochondria.
So what are the ethics of these procedures?
“Three-parent embryos” can only be created through IVF in a laboratory. Consequently, those who regard IVF as morally unacceptable would reject this procedure from the outset.
Other people believe that IVF used in compliance with certain limiting conditions can be ethically acceptable. The limitations they require vary but can include not creating more embryos than will be implanted in a woman’s uterus and giving all embryos a chance at continuing life. These people might be willing to consider the ethics of MST, but would certainly reject PNT as it involves creating an embryo with the intention of destroying it.
Yet, other people do not accept the need for any major limitations on creating or using human embryos, which they see as having no moral status, that is, as “just a bunch of cells” or, as one Princeton University genetic scientist said to me, “no different from the cells inside your nose”. Consequently, they would not reject these procedures as unethical because of the treatment of human embryos they involve.
What other ethically relevant considerations should be taken into account?
The list is long and sobering and only a very few examples can be mentioned here. They go beyond the ethical issues raised by the technology itself to matters such as claims of rights to have a genetically related child, the ethics of alternative means of founding a family, and so on.
A technology-related consideration includes the ethics of alteration of the human germline, a possibility that for many elicits intense fear and for some great hope.
Until very recently, when we didn’t have the technology to alter the germline, there was almost universal agreement among bioethicists that such alteration would always be ethically wrong. Rather, we agreed that we had obligations to hold the germline intact for future generations as the common heritage of human kind.
Now, when human germline alteration has become possible, some bioethicists see it as ethically acceptable in order to avoid serious genetically transmitted diseases. Heartbreaking stories of individuals and families affected by such diseases, many of which are recounted in the Senate report, make the strongest case possible for allowing genetic modification.
The report also opens up the possibility of finessing the ethical concern about altering the human germline, by recommending we explore whether “mitochondrial donation is distinct from germline genetic modification”. In fact, because the intervention involves the transfer of nuclear DNA, many scientists call it “nuclear DNA transfer”, which sounds much less alarming. Words are not neutral and affect what we see as ethical or unethical.
If germline genetic modification were allowed, we would need to consider whether its use as therapy for serious, otherwise untreatable, genetic diseases is ethically different from its use for enhancement, that is, creating designer children. Another issue is whether “three-parent IVF” would establish a precedent of the ethical acceptability of “designer children”.
We must also consider the risks and harms of this experimental medical procedure, first of all to the child and the child’s future descendants. It poses multiple questions regarding its safety in terms of the long term health of the baby and the baby’s descendants. This is unknown territory, and consequently creating “three-parent babies” is human experimentation.
There are also risks and harms to others, such as women who donate “healthy mtDNA ova” – often they are vulnerable and easy to exploit – and to society, especially to its shared foundational values of respect for life and the dignity of each person. Is creating a “three-parent embryo” manufacturing a child, that is, a contravention of human dignity?
What would constitute informed consent to this procedure? Couples desperate to have a child will consent to unwarranted risks to try to realize that goal. Can we reasonably anticipate that the child would consent if he or she were present? If not, it would be unethical to create a “three-parent embryo”. What are the psychological risks to the child? Does the child have the right to know the identity of the mtDNA donor? We have belatedly recognized that children born from donated sperm and ova and adopted children have a right to know who their biological parents are.
It’s to be expected the “fertility industry” will support “three-parent IVF” as part of its continuing expansion globally. It was a $9.3 billion (US) a year business in 2012 and is estimated to reach $21.6 billion (US) by 2020. And governments are also likely to support it, but for cost saving reasons, rather than profit generating ones. The Senate report notes that the high healthcare and social services costs of children born with mtDNA diseases could be avoided.
Finally, here’s how a highly respected Canadian bioethicist Francois Baylis concluded her article warning of the risks and harms of “three-parent IVF”:
“Taken together, these ethical objections are cause for serious concern. Yet, despite their cumulative weight, the development and future use of mitochondrial replacement technology is likely inevitable (Baylis and Robert, 2004). Why is this so? Because in our world – a world of heedless liberalism, reproductive rights understood narrowly in terms of freedom from interference, rampant consumerism, global bio-exploitation, technophilia and hubris undaunted by failure – no genetic or reproductive technology seems to be too dangerous or too transgressive.”