The introduction of mitochondrial donation in Australia, as proposed by the bill, raises a number of ethical, social and scientific issues. Many of these issues are deeply personal and manifest in strong and opposing views.
The committee has heard from a range of submitters and witnesses who strongly support the introduction of mitochondrial donation to enable women with mitochondrial disease to bear biological children and reduce the risk of passing it on to future generations, and the burden of the disease on families and communities.
The committee also heard strong opposition to the bill, underpinned by concerns that mitochondrial donation would involve the creation and destruction of embryos, that there are existing legal options to have children thereby making this technology unnecessary, and that it would cause distress and confusion to a child born from the biological material of three people.
In addition, a range of scientific issues have been raised with the bill. The committee heard concerns about a lack of publicly available research on mitochondrial donation and its use in other jurisdictions, and the potential for unknown intergenerational effects. There were also strongly held concerns that legalising mitochondrial donation could open the door to human cloning or other inappropriate uses of the technology.
Ethical and social considerations
Reducing the risk of mitochondrial disease
Those in support of the bill told the committee that the introduction of mitochondrial donation would help reduce the risk of a woman with mitochondrial disease passing it on to her biological child.
Witnesses and submitters described the devastating impact of mitochondrial disease on individuals and multiple generations within families, and the desire to reduce the risk of the disease being passed on to future generations.
The Mito Foundation explained that the opportunity to have a healthy child through mitochondrial donation offers some families the only means to have a child genetically related to both parents who is healthy. One witness, who suffers from mitochondrial disease, told the committee:
This law would be an absolute ray of hope, a miracle, to me because I don't have any other options and I feel that I'm running out of time. This is the only way I would be able to have my own healthy biological child. If anything were to happen to me, I know that my husband would be able to see part of me in our own children, and this would mean the world—to have this legalised within my time frame or at least for future families.
This perspective was strongly reinforced by several submitters to the inquiry who shared their experiences living with mitochondrial disease, some with children who could potentially benefit from the option of mitochondrial donation.
The Mito Foundation noted that introducing mitochondrial donation in Australia could also address the risk of people traveling overseas for mitochondrial donation procedures in jurisdictions with unregulated health systems and for conditions not related to the avoidance of mitochondrial disease.
Mitochondrial donation is not a cure
However, some submitters and witnesses stressed to the committee that mitochondrial donation does not cure mitochondrial disease, and that some ‘diseased’ mitochondria can still be transferred through the procedure. Mrs Wendy Francis of the Australian Christian Lobby made the comment:
Mitochondrial transfer doesn't cure mitochondrial disease. It engages in genetic manipulation and it ensures that people with mitochondrial disease are not born.
Several witnesses noted that the introduction of mitochondrial donation will not prevent children being born of mitochondrial disease. This is because a mother may not know that she carries a mutation, or because a new mutation could appear, or because the mutation is in the woman’s nuclear DNA and therefore cannot be treated with this procedure. Associate Professor Megan Best, Director at Ethicentre, added:
Rather than spending our money and efforts on experimental ART techniques, I believe we should seek to develop genetic treatments for those born with mitochondrial disease. Children will still be born with mitochondrial disease, even if this bill is passed.
However, other witnesses gave evidence that mitochondrial donation, although not a cure, would significantly reduce the defective mitochondrial DNA in offspring, and overall, decrease the burden of the disease within the community.
The Murdoch Children’s Research Institute, argued that ‘[t]he fact that [mitochondrial donation] won't remove the disease burden entirely is clearly not a reason to oppose the legislation’. Professor David Thorburn explained:
This is offering families who know they are at risk of mitochondrial DNA disease a reproductive option. There's no expectation that one can wipe out genetic diseases from the community.
Although there is currently no cure for mitochondrial disease, the Department of Health noted that the Government has also spent considerable funding on research to find a cure.
On the issue of the potential carry over of defective mitochondria through the procedure, witnesses acknowledged that further research was needed. However they argued that current evidence already shows that mitochondrial donation significantly reduces the defective mitochondria.
According to Dr George Daley, a member of the International Society for Stem Cell Research (ISSCR):
What we're really encouraged by, however, is that the evidence to date is that these strategies actually do reduce the burden of defective mitochondria quite significantly—not perfectly, but quite significantly.
Options for building a family
The committee heard from several inquiry participants that introducing mitochondrial donation is unnecessary. This is because there are already legal options available to a woman with mitochondrial disease concerned about passing it on to her offspring. These options would include adoption, use of a donor egg, or pre-implantation genetic diagnosis (PGD).
Dr Bernadette Tobin of the Plunkett Centre for Ethics told the committee that families should be looking at ways to have a healthy child that are already legal in Australia:
It's perfectly possible to have a child, using a donated egg without then taking that egg, which is perfectly healthy, and then modifying it in ways that are very risky for future generations, and, therefore, the child will have three biological parents et cetera. That's my point, that someone in that position could simply use IVF with a donor egg.
However the committee heard a different perspective from those who suffer from mitochondrial disease and the organisations and clinicians that support them. The Mito Foundation summarised:
While some people do not consider genetic relationship to be of significant importance, evidence indicates that this is not the case for a large number of people. This was upheld throughout the consultations mentioned above and has also been highlighted by members of the Australian mitochondrial disease community who are clear that they are not seeking to have a ‘designer baby’ but simply a child related to both parents and one who will not suffer from mitochondrial disease.
A witness, who suffers from mitochondrial disease, gave evidence about her strong connection with her biological mother, and the desire to have that with her own biological child:
… when I do something in the day or I look in the mirror or I say something, I realise that that's come from my mum. That was her personality. She was conscientious, she was persistent and determined, she was compassionate. Those are all things that I inherited from her and that I'm so grateful for. For me, this process would allow me to continue to pass that on to my children and for us to have that unique bond in that biological way.
Creation and destruction of embryos
In the course of the inquiry, concerns were raised regarding the creation and destruction of human embryos involved in mitochondrial donation techniques.
As discussed in Chapter 2, inquiry participants specifically objected to some of the proposed mitochondrial donation techniques in the bill (pronuclear transfer and polar body transfer techniques), because they involve the creation of a human embryo ‘for its parts’, and would result in higher rates of embryo wastage.
According to the Australian Catholic Bishops Conference, mitochondrial donation techniques do not respect the human dignity of embryos:
The Conference objects to the disposing of any human embryos because such actions would instrumentalise human embryos, treating them as part of a production process where they can be kept or disposed of subject to arbitrary judgements.
The committee heard competing evidence on whether the introduction of mitochondrial donation would result in significantly more embryos being created or destroyed.
Professor David Thorburn of the Murdoch Children’s Research Institute argued there would not be a substantial number of excess embryos generated with the mitochondrial donation as compared to other assisted reproductive technologies.
‘Three parent child’
Inquiry participants told the committee that the techniques used for mitochondrial donation would result in a ‘three parent child’ because the individual born of the procedure would have three genetic parents (mother, father, donor).
Dr Bernadette Tobin of the Plunkett Centre for Ethics explained that a fundamental objection to mitochondrial donation is that the techniques would require three people to produce a child:
… the point is that the embryo will be formed from biological material from three people. That confuses the child's biological heritage. That's the point about the biological material from three people—it's genomically confusing. Children ought to be able to look back to their origins of one untampered-with sperm and one untampered-with egg.
According to the Australian Christian Lobby, mitochondrial donation represents a significant departure from current assisted reproductive technology (ART) practices:
Until the advent of mtDNA transfer, children have always been born as the result of two biological parents. Even the small minority conceived with the assistance of donor eggs or donor sperm still have only 2 genetic parents. This technology represents a significant change from the way ART is currently practiced in Australia. Children born of mtDNA transfer have two biological mothers and one biological father. This creation of an embryo with three biological parents crosses a new frontier in human experimentation.
Inquiry participants expressed concern about the confusion and distress that would be caused to a child born of mitochondrial donation who is trying to understand their origins and self-identity.
As discussed in Chapter 2, inquiry participants stressed that if the bill were to be passed, it would be important to retain the donor register which would allow a person born from mitochondrial donation to receive identifying information about their donor when they turn 18.
The Australian Catholic Bishops Conference argued that mitochondrial donation techniques would involve the transmission of personal characteristics between the donor and the resultant offspring. In their submission, they state:
A person’s identity depends on more than appearance and other characteristics, but mtDNA is also an important influence on characteristics such as ageing, memory and combatting disease.
However, other inquiry participants refuted the claim that mitochondrial donation would result in a ‘three parent child’. For example, Science and Technology Australia, argued that placing the DNA of a mother’s nucleus into a donor egg does not significantly change the genetic makeup of the child:
The nuclear genome contains just over 20,000 genes that encode for a protein, mitochondria only have 13 genes and code for proteins exclusively in the mitochondria (Salzberg 2018). While mitochondria do contain its own DNA, the function of this DNA is to allow the proper function of the mitochondria - to produce energy for the cell.
The Murdoch Children’s Research Institute acknowledged that the term ‘parent’ is obviously complex. According to Dr Christopher Gyngell, a research fellow in biomedical ethics with the institute, the distinction between nuclear DNA and mitochondrial DNA is relevant:
One reason we might refer to a provider of sperm or egg as a genetic parent is that they provide a lot of the personal characteristics of that person. The nuclear DNA codes personal characteristics and can explain things like our likes and dislikes. Mitochondrial donation doesn't provide for those personal characteristics, so for that reason it would be my view that it would be inappropriate to label a mitochondrial donor as a parent.
Commercial exploitation and risks to donors
The committee heard concerns about the potential for commercial exploitation by in vitro fertilisation (IVF) clinics through the introduction of mitochondrial donation. Inquiry participants highlighted a shortage of donor eggs in Australia, and the risk of commercialisation, and exploitation of women for their eggs.
The Australian Christian Lobby recommended that a clause be inserted in the bill to prohibit the use of human eggs obtained by commercial means, either in Australia or overseas. In addition, that IVF clinics should be banned from offering inducements to clients to donate excess eggs obtained through their own treatments.
Concerns were also raised about the health risks to donor women, and the lack of understanding of the long-term health risks involved in donation. According to the Australian Christian Lobby:
The call on egg donors also contributes to the objectification of women. Increasingly women are being called on to donate eggs for therapeutic practices as the applications of ART widen. Women are not ‘spare parts’ providers. The demands made of these women in these processes is costly in time and in terms of health risks.
Several inquiry participants raised concerns about the provisions of the bill that would enable a woman to select the sex of embryos.
The bill outlines that under a clinical trial licence and clinical practice licence, and following counselling, a woman and her spouse (if any) can request for only male embryos be selected for implantation. The rationale is that, experts consider there is potentially an additional risk of mitochondrial disease re-emerging in the children of daughters born through mitochondrial donation.
In the Mitochondrial Donation Expert Working Committee’s Statement to the National Health and Medical Research Council (NHMRC) CEO, sex selection was specifically addressed:
The Committee noted that, while there is scope to prevent the transmission of genetic changes resulting from mitochondrial donation by restricting the clinical procedure to male offspring only, there are ethical, scientific and practical considerations that make this practice problematic.
Inquiry participants told the committee that the United Kingdom (UK) does not allow sex selection in its mitochondrial donation regime. Several international submitters, the Wellcome Centre for Mitochondrial Research in the UK, and MitoCanada, were not supportive of mandatory male preferential sex selection.
In addition, according to the Wellcome Centre for Mitochondrial Research, sex selection would create a risk to the viability of the embryo and is unnecessary:
… determination of sex would currently require an additional manipulation of the embryo at an extremely early stage of development, potentially compromising viability of that embryo.
Several submitters recommended amending the bill to remove the ability to select the sex of embryos. One noted that, given the differences of opinion internationally and amongst ‘experts’, it is unreasonable to expect families contemplating mitochondrial donation to make this decision.
The Feminist International Network of Resistance to Reproductive and Genetic Engineering expressed strong opposition to the ‘selective erasure of female embryos, hence future girls and women’.
A key concern raised by those who object to the bill was the lack of publicly available scientific evidence about the safety and efficacy of mitochondrial donation, and the unknown risks to children subject to the procedure and to future generations.
The Australian Catholic Bishops Conference noted that mitochondrial donation has been legal in the UK for five years, with no reported live births, and no clear evidence the procedure is safe or practical.
The Australian Christian Lobby shared similar concerns about the lack of published evidence from the UK. They noted in their submission that:
… considerations regarding client confidentiality and parental wishes have also apparently obscured public insight into the outcomes of the UK scheme to some extent. This makes it difficult to assess other potential moral and ethical implications relating to the procedures which have been performed in the UK to date.
It was suggested that the Mitochondrial Donation Expert Working Committee’s Statement to the NHMRC CEO highlighted a lack of evidence regarding the safety of mitochondrial donation. The statement notes:
… incremental developments have been made on some aspects of the science since the 2016 UK Human Fertilisation and Embryology Authority (HEFA) scientific review. However, there is no significant new evidence about the safety and efficacy of mitochondrial donation since the 2016 HEFA scientific review.
Inquiry participants voiced strong concerns about the unknown impacts of mitochondrial donation on the health of the person born of the procedure. For example, the Australian Christian Lobby said:
Questions regarding the long-term implications of the procedure into adulthood may potentially remain under-researched in practice for many years’.
The Robinson Research Institute recommended further research in large animals to determine the relative safety and efficacy of mitochondrial donation techniques. It also recommended further research to understand the risk of mitochondrial disease re-emerging in children of mitochondrial donation and the consequences of any mitochondrial DNA being carried over to the prospective mother.
In contrast to these concerns, the committee heard from several witnesses arguing that there is sufficient scientific evidence to proceed with mitochondrial donation in Australia. The ISSCR told the committee that clinicians and scientists believe the preponderance of evidence suggests moving forward:
Our position at the International Society for Stem Cell Research is that there is sufficient evidence to justify first-in-human clinical studies.
Professor Megan Munsie, Member and past Chair of the ISSCR, added that preclinical experiments including those undertaken in large animals, demonstrate the safety of mitochondrial donation techniques:
Our guidelines stipulate the laboratory and clinical research involving mitochondrial replacement therapies for the purpose of preventing transmission of serious diseases is scientifically justifiable. We acknowledge that more research must be undertaken to refine optimised techniques but conclude that preclinical experiments performed to date, including the birth of healthy macaque monkeys, demonstrate adequate safety of mitochondrial replacement techniques to justify first-in-human clinical experiments.
Other submitters noted that the bill itself will allow for important research, which will help demonstrate the safety and efficacy of mitochondrial donation. Dr George Daley of the ISSCR told the committee:
Through the provisions of the bill before us, I think there's a reasonable approach to rigour, to prudence, to safety and to what we hope will ultimately advance our understanding so that it can be even safer and more effective in the future.
Human germline manipulation
Another key concern raised in the inquiry is that mitochondrial donation, if introduced through the bill, would result in human germline manipulation. That is, altering genetic material that is inherited by the next generation.
According to the Robinson Research Institute, mitochondrial donation is a form of genome modification combining the DNA of three people in the conception of a child:
… this genome modification is a heritable germline manipulation, meaning that the children of any females conceived by Mitochondrial Donation will inherit the two female genomes, as mtDNA is passed through the female germline relatively unchanged.
Submitters noted that there is currently an international moratorium on human germline manipulation, due to the limits of genetic knowledge in this area. Associate Professor Megan Best explained the rationale behind the moratorium:
The motivation behind this whole idea is that we really don't know what the full impact of changing the germ line would be on the human gene pool, because of the limits of our genetic knowledge.
It was also suggested that ‘interference with human germline has consequences for history, anthropology and the social sciences’. This is because research into human populations, migration and demographic history uses mitochondrial DNA analysis.
Inquiry submitters also raised issue with those who have equated mitochondrial donation to an organ transplant. One submitter noted that an organ transplant would only affect the recipient and not her descendants, and that mitochondrial donation makes heritable changes to a person’s genome that will be passed on to future generations.
The committee heard concerns around the current limits of human understanding of mitochondrial DNA, and that it may contribute to personal characteristics in a person in ways not yet recognised. The committee was directed to the Government’s consultation paper on the bill which acknowledges that ‘the immediate and long term risks for the child and longer-term implications for subsequent generations are not yet fully understood’.
Finally, submitters raised concerns that mitochondrial donation would ‘open the door to other germ-line manipulations’ which have been condemned internationally.
In contrast to these concerns, evidence was also presented to the committee which disputed the claim that mitochondrial donation would result in human germline manipulation.
At a hearing, the ISSCR told the committee that there is a clear distinction between the current scientific understanding of mitochondrial donation techniques and heritable editing of the human genome:
[ISSCR] scientists believes that heritable genome editing, where changes are made to nuclear DNA of an embryo, is not ready for clinical testing at this time. In contrast, mitochondrial replacement techniques as described in Maeve's Law are ready.
The Mito Foundation argued that the bill clearly rules out intentional modification of either nuclear or mitochondrial DNA during mitochondrial donation. That is, mitochondrial donation as outlined in the bill, can only be used to minimise the risk of Australian parents passing on mitochondrial disease to their children.
In their statement to the CEO of the NHMRC, the Mitochondrial Donation Expert Working Committee specifically addressed the question of whether mitochondrial donation is distinct from germline genetic modification. The committee advised:
… the term “germline genetic modification” has conceptual drawbacks and would not be appropriate for classifying mitochondrial donation… however, that it is essential to recognise that mitochondrial donation introduces changes to the genome of the embryo with the potential to be inherited by future generations.
The committee heard concerns about the bill amending the Prohibition of Human Cloning for Reproduction Act 2002 and enabling techniques to be practiced that are used in cloning. For example, the Feminist International Network of Resistance to Reproductive and Genetic Engineering submitted that such change would be ‘highly unethical’:
… it is less than 20 years since the Australian parliament voted against human cloning. This was a good decision because, as we predicted, cloning has not produced any of the ‘miracle cures’ that were promised at the time.
The committee heard that the use of Pronuclear Transfer and Second Polar Body Transfer techniques, proposed in the bill, use techniques similar to that used in cloning. At a hearing, Associate Professor Megan Best of Ethicentre argued:
It is true that pronuclear transfer as described in the bill is not cloning per se, however the technique used is a parallel of what is used in nuclear transfer, or cloning. Do we really want people to get better at the techniques? The difference between pronuclear transfer and cloning is just the cells that you use. The techniques are the same.
Other witnesses, however, stressed that mitochondrial donation is not cloning and its purpose is not to produce identical copies. According to Professor Megan Munsie of the ISSCR:
The distinction here is that in cloning technology you're attempting to make the copy of existing nuclear DNA, and in the case of mitochondrial replacement techniques you're either taking across the maternal chromosomes, the chromosomes of the woman with the diseased mitochondria, or the pronuclei—that is, before the male and the female chromosomes unite to form a new nucleus. So I don't see it as cloning an individual.
Scientists that gave evidence to the committee stressed the distinction between nuclear and mitochondrial DNA. Dr Christopher Gyngell of the Murdoch Children’s Research Institute explained that with mitochondrial donation:
… you're getting the mitochondrial DNA, which is shared by many, many different people, that only really affects the functioning of the mitochondria, not the personal characteristics that are contained in our nuclear DNA. I think the term 'designer babies' is really referring to changes in nuclear DNA, which affect our personal characteristics, rather than changes to our mitochondrial DNA.
Other uses for mitochondrial donation techniques
In addition to fears about cloning posed by the bill, concerns were raised that mitochondrial donation, if legalised, would open the floodgates for other uses of mitochondrial donation techniques that are outside the initially narrow remit in the bill.
The committee heard that the technology used in mitochondrial donation has been promoted as a way to address infertility. There were also concerns the technology would be used to treat other rare diseases or as a way to choose desirable traits in children.
In reply to these concerns, the Murdoch Children’s Research Institute argued that mitochondrial donation techniques are unlikely to be used as a viable option for infertility, and are completely irrelevant for the treatment of other diseases or the selection of desirable traits that might result in ‘designer babies’. According to Professor David Thorburn:
The concept of mitochondrial donation being used to treat infertility has been raised. I think most credible authorities conclude that there is no hard evidence that it would work and think that the risk-benefit ratio is inappropriate for mitochondrial donation to be used in that context. To me, that's the only spillover of mitochondrial donation into other uses, and that seems to me to be clearly blocked in the legislation, by requiring it to be only used for the prevention of severe disease. It cannot be used for the prevention of any other inherited disorders—Down syndrome, cystic fibrosis. It is completely irrelevant; changing the mitochondria would not do anything.
More broadly, as discussed in Chapter 2, inquiry participants told the committee that the changes to cloning and embryo research legislation proposed by the bill are sufficiently narrow to prevent any use of the techniques beyond the treatment of mitochondrial disease.
The Department of Health also gave evidence at the hearing that any further use of the techniques beyond mitochondrial donation would require additional legislative change and consideration by the Parliament.
The committee acknowledges the devastating impact of mitochondrial disease on individuals and whole families. The committee was deeply moved by evidence from those who suffer from mitochondrial disease, who have lost family members to the disease, and who have a strong desire to prevent the burden of the disease in future generations.
The proposed introduction of mitochondrial donation in Australia, as set out in the bill, engages difficult ethical, social and scientific issues. The committee notes that the changes proposed are significant and that the bill would amend existing laws that strictly control embryo research and prohibit cloning.
The committee acknowledges and respects the diverse views held in relation to the bill. This is reflective of broader views on mitochondrial donation in the community, and reinforces the importance of allowing for a conscience vote. The task of the committee in this inquiry has been to explore the issues raised by the bill, and present them to the Parliament to assist in its deliberations.
Should the bill be passed, the committee highlights several areas where additional clarification, amendment or further consideration may be appropriate. These include in relation to:
the proposed donor register, and exploring the possibility of enabling children under the age of 18 the right to information about the donor in appropriate circumstances;
pre-treatment counselling for all parties involved in mitochondrial donation, and providing further clarity on the requirements for counselling for donors;
in relation to sex selection, whether the provisions of the bill that would enable a woman the option of selecting the sex of embryos is necessary and appropriate; and
monitoring and evaluation of the outcome of the clinical trial, and providing further clarification on the requirements for longer term outcomes monitoring and reporting. In particular, ensuring that the privacy of families is protected, but also providing assurance that the evidence needed to consider the safety and efficacy of mitochondrial donation will be available for the community, and the Parliament, to assist in considering the possibility of clinical practice in Stage 2.
The committee makes no recommendations as this is a conscience matter. The report is simply a summary of the submissions and views available at the time of reporting.
Senator Wendy Askew