Ethics of mitochondrial donation
A number of submitters to this inquiry expressed ethical concerns about
the techniques used in mitochondrial donation. Noting that different people
have different ethical frames of reference, this chapter examines the ethical
issues that have been raised during the inquiry.
The ethical issues can be broadly categorised under three themes:
Moral issues: including questions about the moral status of
embryos and who should be considered to be a parent;
Medical and health ethics: including questions about whether a
child has a right to know the genetic contributors; how donors are treated;
whether consent can be anticipated and the degree to which medical science
intervenes in the life of a child born to the technique; and
Scientific ethics: including questions about when a technology
should be considered to be safe for use; whether the technology will affect future
generations and the degree of risk to them and whether the technology could
inadvertently be used for other things.
All witnesses and submitters to this inquiry agree that mitochondrial
disease is a terrible disease, with devastating impacts to individuals and
their families. Submitters with an ethical objection to mitochondrial donation
expressed great compassion for families impacted by mitochondrial disease:
Our hearts go out to families dealing with these diseases and
who have the understandable desire that their children should not also be born
with these burdens. It is a natural human longing to spare children of illness
Moral status of human embryos
As discussed in chapter three, the pronuclear transfer technique
requires two fertilised eggs, one from the mother with the mutated mitochondrial
deoxyribonucleic acid (mtDNA) and one from a donor with healthy mtDNA. The pronuclear
transfer technique results in a reconstituted egg with the parents' nuclear
DNA, but it requires the disposal of the fertilised pronuclei that were
contained in the donor egg.
Submitters such as the Social Issues Committee of the Anglican Church
Diocese of Sydney, the Plunkett Centre for Ethics, the Australian Catholic
Bishops Conference and Catholic Health Australia raised an ethical concern that
the creation of an embryo for the purpose of destroying it violates the dignity
that is owed to the embryo.
The legislative changes required to permit the pronuclear transfer technique of
mitochondrial donation in Australia would represent the only permissible
creation of an embryo with no potential to develop into a viable pregnancy,
outside of somatic cell nuclear transfer (SCNT) research conducted under
The Australian Catholic Bishops Conference explained that its objection
about the ethical use of embryos was not limited to mitochondrial donation, but
was a common concern about all forms of assisted reproductive technology (ART):
Human beings have inherent dignity and their rights as people
must be respected including their right to life from the moment the first cell
of the human zygote is formed by whatever means it comes to be.
A logical ethical sequence of this dignity is that the life
of each human embryo is to be considered inviolable. [ART] may involve the
discarding of human embryos and may involve the formation of an embryo of a laboratory
procedure replacing...marital intercourse...with a technical procedure.
The Plunkett Centre for Ethics raised a similar concern about the
creation of an embryo to obtain the donor egg and mitochondria:
Treating an embryo merely as a means and not also as
an end in itself violates the respect owed to embryonic human life.
For these submitters, the end to which the procedure is directed is
Their belief in the dignity of the embryo means that their opposition is not
specific to mitochondrial donation, but to any interference with human embryos
that leads to their destruction:
I think, of course, that we should never have legalised
research on human embryos that involves their destruction, and I have no doubt
there will be plenty more destructive research on human embryos to develop any
of these techniques. There's no doubt about that.
Other submitters recognised that questions about the moral status of
embryos were neither new nor particular to mitochondrial donation.
As noted in earlier chapters, one current option that is available to
women who live with a mitochondrial disease who are considering having children
is to have the embryos tested through a process known as pre-implantation
genetic diagnosis. In their submission to the committee, Mr Ash Howlett and Dr
Steve Mercer explained that they could see little ethical difference between
the mitochondrial donation techniques and other procedures that had already
been legalised, such as pre-implantation genetic diagnosis:
Perhaps the most similar technique on ethical terms currently
employed in Australia is Preimplantation Genetic Diagnosis (PGD). With PGD,
many embryos are created for the purpose of removing cells for genetic testing.
Embryos that are deemed unfit are destroyed, likely many more than are
destroyed during a single mtDNA donation process depending on the number of
embryos tested during PGD. This leads us to an ethical area that is contested
by people who believe that life begins at the embryonic stage of development,
and those that believe that it is more ethically justifiable to suggest that
life begins later on during pregnancy, around when neural structures are
forming. A government that allows PGD as well as other embryo or foetal
destroying procedures such as abortion, should not be swayed by appeals to the
moral status of an embryo.
Bioethicist Dr Ainsley Newson also noted that current ART already
requires the destruction of a number of embryos and the introduction of
mitochondrial donation would not add substantially to the number of embryos
that are destroyed each year:
We also have quite small numbers here. This is a background
of a technology where fewer than 100 people a year are likely to use it,
compared to the 13,000 cycles of assisted reproductive techniques. Embryo
discard in that context would be significantly higher. If your position is one
where that is problematic too then that is not going to be information that is
convincing or of comfort.
In summary, while there are a range of views about the moral status of
embryos, there is little about mitochondrial donation that is different to
other forms of ART. As Dr Newson submitted to the committee:
There are a range of views on embryo moral status in
Australia. Mitochondrial donation does not add anything new to existing issues
regarding the ethics of the use of embryos in research and clinical treatment,
from the perspective of the moral status of the embryo.
The committee understands that some people will have ethical concerns
about the destruction of human embryos. That is an understandable concern;
however, the question is whether those concerns should preclude the progression
of mitochondrial donation techniques. The committee has reached a view that the
ethical concerns should not prohibit further scientific review and community
consultation on the use of mitochondrial donation in Australia.
The committee has received evidence that all forms of ART result in some
destruction of embryos and pregnancy screening techniques present parents with
a choice of continuing a pregnancy or undergoing a termination. As concerning
as that may be, ART has been available in Australia for a number of decades and
is well accepted. The committee accepts that arguments against mitochondrial
donation based solely on the absolute moral status of the embryo are a
continuation of an older debate over reproductive rights.
However, mitochondrial donation does potentially raise new and different
ethical concerns regarding embryos that must be considered. The legislative
changes required to permit the pronuclear transfer technique of mitochondrial
donation in Australia would represent the only permissible creation of unique
and potentially viable embryos with no potential to develop into a viable
pregnancy outside of SCNT research conducted under license. This is a new moral
question that would require community consultation as well as a change to the
legal prohibition of such activity under current law.
The committee considers that mitochondrial donation techniques do not
present new ethical concerns, but they do present a scientifically supported
source of hope that future generations of Australians may be able to live free
of the diseases that have plagued generations of their families.
mtDNA parent or mtDNA donor?
One of the ethical concerns about mitochondrial donation is the
inclusion of genetic material from a third person in the creation of the
embryo. The phrase that has sometimes been used in the media is that
mitochondrial donation creates 'three-parent babies'.
The ethical concern about the use of a third person's genetic material
was expressed by Dr Bernadette Tobin, Director of the Plunkett Centre for
Ethics as a violation of 'the child's right to a natural biological heritage'.
This argument can be separated into two parts: the first part is an
argument that the introduction of a third genetic donor violates the dignity of
the unborn child and the second is that the child will be confused or will
experience distress because they are uncertain about their parentage.
Central to both arguments is a question about whether an mtDNA donor is or
should be considered to be a parent.
Dr Newson notes that there is a difference between genetic and social
...the term 'three parent baby' has numerous problems. It
conflates genetic and social parenting. It overlooks that the genetic
contribution from the 'third parent' is vastly smaller than the commissioning
couple's and that an epigenetic contribution from a woman pregnant with a
foetus conceived via oocyte donation could also be said to be a 'genetic
From a genetic perspective, some submitters suggested that the phrase is
misleading. The Wellcome Trust, in an attachment to its submission, explained
that children who are born using these techniques will only have nuclear DNA
from the mother and the father:
In mitochondrial donation, almost all of the child's genes
will come from its parents; the mitochondrial donor will only contribute 37
genes (0.1% of total DNA), which enable the mitochondria to produce energy. The
donor mitochondrial DNA will not affect the child's appearance, personality or
any other features that make a person unique – it will simply allow the
mitochondria to function normally and the child to be free of mitochondrial DNA
disease. Mitochondrial donation involves two-parent fertilisation in the same
way that IVF does, and any child would be genetically unique, with a natural combination
of nuclear genes from both parents...
The term "three-parent children" is misleading.
These children will only have two biological parents...
Professor John Christodoulou, Chair of Genomic Medicine at the
Department of Paediatrics at the University of Melbourne suggested that the
fact that mtDNA does not contribute to physical, cognitive or behavioural
characteristics was relevant to considering whether the mtDNA donor should be
considered to be a parent:
Certainly, it's DNA that is different from the parent's, but
it is 0.1 per cent of the total amount of genetic material in terms of what
makes us us. As I said, the mitochondrial DNA really is only involved in making
energy; it's not about other physical, cognitive or behavioural
Associate Professor Damian Dowling from the School of Biological
Sciences at Monash University also thought that the genetic contribution of the
mtDNA donor was so small that the donor should not be considered to be a third
From a technical genetic point of view, if we just consider
the nuclear chromosomes and ignore the mtDNA, the children produced will
clearly be two-parent babies. But, as others have pointed out, if we consider
all of the unique protein-coding genes dispersed across the nuclear and
mitochondrial genome—of which there are 37 mitochondrial and close to 20,000
nuclear genes—the children produced would be 2.002-parent babies.
If the three-parent issue is considered from a social perspective, in
the United Kingdom (UK) the mtDNA donor is not considered to be a parent, but
the equivalent of an organ donor.
Some submitters observed that organ donation and tissue donation
includes a complement of DNA being placed into the body of the recipient.
Professor Christodoulou noted that the additional genetic complement does not
change the way society views that person:
Bone marrow transplantation can be considered to have DNA
from three individuals. That's very acceptable; we don't call that person a three-person
bone marrow recipient.
Similarly, according to Professor Carolyn Sue, Director of the
Mitochondrial Research Centre at the Kolling Institute of Medical Research
based at the Royal North Shore Hospital in Sydney, surveys of patients who live
with mitochondrial disease indicates that they conceive of the procedure as
being similar to organ or tissue donation:
When you hear the 'three parent' terminology, I guess they
want you to hear that it's like a bone marrow transplant or a heart transplant.
Those patients also have three components of DNA within their body, but really
that doesn't impact on their day-to-day lives, apart from the fact that it's
improved their health outcomes.
Fears that transplantation or an infusion might change a person are also
not new. Dr John Duley, a scientist who has worked in the area of mitochondrial
disease, recalled that similar fears were raised when heart transplants were
In people's minds this organ was endowed with almost mystical
qualities—it was the seat of love and other emotions... Its transfer from one
person to another was regarded as an unnatural act, meddling with 'personhood'
and trespassing into territory that had a spiritual quality.
Science and the ethical debates about transplantation have evolved since
that time and transplants are now a standard part of medical practice. The
broader Australian community accepts that organ donation is ethical and it is
something that the medical community actively promotes:
In Australia, we already support organ donation; it is legal,
it is common practice and we actively promote it. Somebody who has an organ
donated has more DNA from somebody else than we are talking about in
Concepts around the genetic contribution of mtDNA versus nuclear DNA
have broader application than simply a question of contribution to the
parentage of a particular child. It also reflects on whether mtDNA donation is
considered to be a germline genetic modification in the same way that some
nuclear DNA modifications can be. This is an issue that will be considered in
greater detail below.
The committee understands that there are people who have concerns that
mitochondrial donation techniques may lead to children having three genetic
parents. This is not the case. The benefit of mitochondrial donation is that it
affords people living with mitochondrial disease the opportunity to have a
genetically related child whilst dramatically reducing the child's chance of
developing a serious mitochondrial disease.
The committee considers that an mtDNA donor should be conceptualised as
being similar to an organ donor. The committee notes that there are already
procedures being performed, such as bone marrow or organ transplants, that
results in genetic material being transferred to a person who needs it for a
medical reason. These do not appear to have led to adverse consequences for the
individuals involved in the transplant procedures. There may be reasons to hold
concerns about mitochondrial donation, but the committee does not have any
reservation that the children born of this technique will have only two
parents. The question of whether mtDNA donation should be anonymous, similar to
organ donation, is discussed below.
Medical and health ethics
Four main ethical questions were raised by submitters that can be
broadly categorised as concerning medical and health ethics:
should mtDNA donation be anonymous?
will the mtDNA donors be exploited?
would a child consent to be conceived by mitochondrial donation?
should a child be required to participate in ongoing follow up?
Each of these questions is considered below.
Should mtDNA donation be anonymous?
Another ethical concern raised by submitters was whether mtDNA donors
should be anonymous or whether the child has a right to know the identity of
the donor. This question needs to be considered from the perspective of the
donor and from the perspective of the child who may be born of the technique. In
the UK, the regulations allow a child born of the technique to discover only
non-identifying information about the donor from the age of 16, making mtDNA
A donor is entitled to know how many children have been born from their donated
material, the sex of those children, and what years the children were born.
Dr Newson explained that the rationale for making mtDNA anonymous in the
UK was that mitochondrial donation is more akin to organ or tissue donation
than reproductive donation and the preference for anonymity reflects that fact.
However, opinions on whether mtDNA donors should be anonymous vary. Professor
John Christodoulou supported anonymous mtDNA donation because he considered it
to be important to the donor.
Professor Sue informed the committee that some people living with mitochondrial
disease have indicated that they would prefer mitochondrial donation to be
anonymous because they considered that the techniques were akin to organ or
tissue donation and because they were concerned about the risk of stigma.
Other submitters to the inquiry argued that, if Australia allowed mtDNA
donation, the child should be entitled to know the identity of the mtDNA donor.
Dr Petra Wale, a board member of the Fertility Society of Australia told
the committee that most donor-conceived people want to know their genetic
People want to know where they come from. As a society and as
a practice we don't have anonymous donation anymore. Anybody donating in the
current climate, and this has been for many years—whether it be a sperm donor,
an egg donor or an embryo donor—is made aware that that resulting offspring
will know who you are and have the opportunity to have identifying information
about you. I struggle to think that there will be a lot circumstances where
this would be anonymous. There would probably be a lot of people who have
people helping them out. That's what happens now with egg donation. It's
usually altruistic from other family members and from best friends. There are
always stories. Their best friends and other people help them out. Making it
anonymous will come back to bite us.
Some submitters, such as the Australian Christian Lobby and the
Australian Catholic Bishops Conference, considered that the child's right 'to
know and be cared for by his or her parents' includes a moral right to know the
circumstances of a person's conception.
Archbishop Fisher drawing on the experiences of adopted children,
pointed to the psychological distress that can result from a lack of knowledge
about their genetic history:
When we think of what confusion that might create in a child
regarding their lineage, their genetic heritage, the families they belong to,
we know already the problem of genealogical bewilderment or children that go
searching for donor parents or searching for their natural parents when they
been adopted. We would risk creating another group of children in search of
Dr Tobin from the Plunkett Centre agreed the move away from
anonymous donation was to be commended and that it should not be considered for
To add to what you said, that we have gotten rid of anonymous
donation is a great Australian ethical development that has been picked up in
some parts of the world. This was a wonderful achievement of the NHMRC 10 or 15
years ago. I do hope that nothing that the legislators consider will have us
back-sliding on that one.
In her submission, Dr Newson explained that she conducted a
citizen's jury to understand community attitudes to mitochondrial donation.
According to Dr Newson, one of the issues that many of the jurors were concerned
about was ensuring that children had a right to know their donor if they wished
to do so.
Dr Newson noted that allowing the mtDNA donor to be known also validates
the contribution that the mtDNA donor made to the child's life:
Women who choose to donate oocytes for mitochondrial donation
are making a small but very fundamental contribution to this process and also
to the genetic complement of any children who are born as a result. The
presumption that this complement is too small to warrant recognition of the
donor, to me, overlooks the significance of the physical process of donation
and also that the donated material makes a significant difference between
someone having mitochondrial disease and not in the future.
Professor John Christodoulou told the committee that, like other ethical
issues involving mitochondrial donation, the committee needs to consider
carefully about community morals and expectations regarding the process:
[T]his is an area where we need to understand what the
community by and large wants or finds acceptable. Certainly, everyone is
entitled to their own individual want and desire, but I guess if we are talking
about changing legislation for the whole community we have to take into account
what the whole community's desire is.
The committee understands that people have different views about whether
mtDNA donation should be anonymous. The committee considers that a child's
right to know their biological heritage should be paramount. The committee
acknowledges that there has been a shift in Australian attitudes towards making
information about a person's biological heritage known in both the adoption
space and in other forms of ART. The committee considers that children who are
born from a mitochondrial donation technique should be entitled to know their
donor if they want to.
The committee notes that it proposes treating mtDNA donation differently
from either gamete or organ donation. The committee considers that an mtDNA
donor should be conceptualised as being similar to an organ donor because they
are donating non-nuclear genetic material. However, recognising that biological
or heritage questions may arise for children born of this process, the
committee considers that mtDNA donors should not be anonymous.
Women who donate their mtDNA should be made aware that if a child is
born from their donated mtDNA then the child may be given identifying
information about the donor at an appropriate time.
Will mtDNA donors be exploited?
Mitochondrial donation requires human eggs that contain healthy
mitochondria. Some submitters expressed concerns about where the eggs would
come from and whether the egg donor would be exploited.
The Social Issues Committee of the Anglican Church Diocese of Sydney
raised concerns that women may be financially coerced into donating their eggs
for this purpose:
...there are also ethical issues pertaining to the egg donor
herself. It is known that egg donation is potentially dangerous due to the
risks of associated hormonal stimulation. As a result, egg donors can be
difficult to find. This leads to pressure from lobby groups to introduce
payment for gamete donation, which leads to vulnerable women being financially
coerced into undergoing a potentially life-threatening harvesting procedure.
This is unethical.
This concern was shared by the Catholic Church. Archbishop Anthony
Fisher, the Catholic Archbishop of Sydney and Chairman of the Bishops
Commission for Family, Youth and Life told that committee that he was concerned
that eggs needed to be obtained from women through invasive procedures:
The availability of human ova is often assumed when people
talk about reproductive technology as if they were somehow there in a cupboard
to be used. In fact, it means women have to be used to obtain these eggs. They
are extracted by invasive procedures that do carry some risk.
Professor David Thorburn, Head of Mitochondrial Research and Diagnostic
Laboratories at the Murdoch Children's Research Institute and Victorian
Clinical Genetic Services told the committee that the eggs required for these
procedures would most likely come from excess eggs that were donated after in
vitro fertilisation procedures or from women who were close to the family.
Professor Sue told the committee that her research indicated that most
women would be happy to be able to donate their excess eggs after in vitro
In this case it is going to be donor women, who are
presumably and most commonly donating their eggs because they've had an IVF
procedure themselves. When we asked those patients, we found a huge level of
altruism about this. The women who were having IVF procedures for infertility
reasons, for example, would most commonly be the donors, and the excess eggs
would probably be the donor material. There was this altruistic feeling. They
were delighted, happy, that their excess eggs had, first of all, a purpose or
could have a legal purpose and also that they would be helping other people who
faced a similar but slightly different dilemma from theirs.
The Ethical guidelines on the use of assisted reproductive technology
in clinical practice and research, 2017 (ART Guidelines) made by the
National Health and Medical Research Council (NHMRC) relevantly provides that
both commercial trading and direct and indirect inducements are prohibited by
legislation to prevent this type of exploitation:
The current situation in Australia is that gamete donation
must be altruistic, and that commercial trading in human gametes or the use of
direct or indirect inducements is prohibited by legislation. This position
reflects concerns about the potential exploitation of donors (particularly egg
donors) and the potential risks to all parties.
However, the ART Guidelines permit the reimbursement of some
out-of-pocket expenses that are directly incurred by the donor.
Another potentially concerning form of exploitation could stem from
overuse of the same donor's genetic material. Currently, the ART Guidelines
specify that only a limited number of families can be created from a single egg
or sperm donor and that consideration must be given to the number of persons
already born from the donor's donated genetic material in deciding whether to
use that donor's material.
The same standards may be applied to egg donors who donate eggs for mtDNA
The committee understands the concerns about the potential exploitation
of mtDNA donors. However, the committee has confidence that the existing
ethical standards for egg donation are consistent with community expectations.
The committee expects that the same ethical safeguards that protect egg donors
would be applied to egg donors who donate their eggs for mtDNA donation if it
was introduced in Australia. The regulatory aspects of mitochondrial donation
are discussed in greater detail in chapter five.
Would a child consent to
Consent is an important ethical principle that is derived from the
rights of autonomy and dignity. Some submitters raised concerns that a child
that is yet to be born cannot, and, if they had the requisite capacity, may not
consent to such a procedure.
The Australian Christian Lobby noted that anticipated consent is an
important principle in considering whether mitochondrial donation should be
...children with three biological parents are a brave
experiment which will have a significant effect on a person not-yet-born who is
unable to consent to the procedure. Ethicist Margaret Sommerville speaks of the
principle of 'anticipated consent' where a person is affected by a decision to
which they cannot give consent. Such a decision, made by the parents on behalf
of the child, may have serious consequence for the child and their sense of
This is a principle that can have practical implications and can be an
important ethical guide for people who are making decisions about the care of
people who are unable to provide consent. However, Dr Tobin questioned whether
the principle would apply in the case of a person born because of a
mitochondrial donation technique:
We came up with a formula which said: ... if you could
anticipate that they would consent—then it would be legitimate... it's
obviously very relevant here. All we can really do is do thought experiments,
because, if you ask me what I think a child so manufactured will think when he
or she grows up, I don't know.
People who live with a mitochondrial disease and their children had
little difficulty imagining whether a person who was born from a mitochondrial
donation technique would consent. Mary, a person living with a mitochondrial
disease, asked her children whether they thought they would have consented to
In the process of preparing my submission, I talked to my
children about this and I said to them: 'What do you think?' They said, 'If we
had a child with mitochondrial disease, we would love that child we would
understand what the child was going through.' But their view was that everyone
who has mitochondrial disease, their families that are affected by it, should
have this choice.
Justin, who also lives with a mitochondrial disease, told the committee
that he believes that a child who was born of the technique would understand
the choice that had been made for them:
What I have learned over the last 2½ years is that having a
disability or a sickness like we've got is about compromise. You are
compromising the whole time about what you used to have in your life that you
don't have anymore. Being part of a family where the other members of the
family are disabled or are sick and is also about compromise—you can't do the
things you need to do. So I'm confident that any child, if this technology was
to go forward, born through mitochondrial donation would understand that life
is about compromises when you are in this situation. If that means that I can't
participate in recreational genetics, if that means that a second woman gave me
the slightest part of my DNA, I think that would be a compromise I would be
able to live with.
The committee acknowledges that some submitters have ethical concerns
about whether a child would consent to a medical procedure that had the
potential to prevent it from having a debilitating illness. The committee
considers that the child's consent could be anticipated. Whilst we cannot know
for certain, the evidence from submitters living with the disease is that they
and their children would like to have the choice to determine whether or not
the technique is right for them and their child.
Ongoing follow up
Scientific and medical research depends on data. Submitters told the
committee that they considered that follow up should be conducted with the
children who are born to these techniques. A number of submitters told the
committee that there should be a rigorous follow-up study conducted by the
fertility clinics to inform the scientific evidence base.
The NHMRC told the committee that obtaining the best data about people
born to this technique will requires significant long-term follow up,
potentially over multiple generations:
Ideally, this monitoring would be multi-generational, that
is, children born following mitochondrial donation would be monitored into adulthood
and their children, if any, would also be monitored.
In the UK, the team at the Wellcome Centre for Mitochondrial Research
developed an innovative clinical method through the National Health Service's
Feedback from [patient focus] groups states that patients
wanted to be involved in long term follow up but at the same time, did not want
to 'medicalise' an otherwise healthy child. Taking this into consideration, the
follow up pathway takes advantage of the routine NHS health checks offered to
all children born in the UK, with only a small amount of extra information
collected during these appointments.
In Australia, the NHMRC acknowledged that obtaining data may be
difficult to obtain if a child does not wish to be monitored into the future:
However, while the parents may have consented to ongoing
monitoring on behalf of the child, the child has not been involved in this
decision and may not consent to long-term follow-up. Therefore, while the
importance of follow-up for the safety and well-being of the child can be
emphasised, there are significant ethical issues associated with ongoing
monitoring that would need to be explored further.
Dr Newson raised concerns regarding the child's right to privacy, noting
that 'the balance between monitoring and invasiveness should be carefully
Professor Sheryl de Lacey, a Professor of Nursing at Flinders
University, noted that it may be possible to ask the parents to participate in
a study about the health and wellbeing of their children:
Taking part in a clinical trial necessitates an agreement to
participate in follow-up studies. This is a view that a child should not be
created so as to be identifies as 'different' and subjected to mandatory
procedures in the interests of science. However my experience in social
research suggests that it is possible to track the progress and development of
children through enrolment of the parents in the trial.
Professor de Lacey noted that the failure to conduct a long-term study
can make it challenging to understand the effects of a particular technology
for a substantial period of time:
Follow up of children was never successfully achieves when
IVF was introduced and we are now reliant on retrospective epidemiological
studies to indicate the health outcomes for children.
The NHMRC's ART Guidelines currently require clinics to record and
retain certain information for the purposes of follow up.
Clinics are required to make this data available in a non-identifiable format
to ensure accountability and for research purposes.
Similar and additional requirements may be imposed if mitochondrial donation is
legalised for clinical use in Australia.
The committee considers that clinical follow-up is important to monitor
the health of children born to the technique and for epidemiological health
reasons it is important to know about the risks that may be presented by the
technology. The committee acknowledges the concerns that unnecessary or
intrusive follow up risks 'medicalising' an otherwise healthy child. The
committee considers that this is a matter that needs to be considered in the
regulatory design if the government decides to legalise mitochondrial donation.
Scientific ethical considerations
The most important stakeholder in any discussion about mitochondrial
donation is the child whose life will be affected by the use of the technique.
In this section, the following questions will be discussed:
should the technology be used if there is a potential for harm?
is mitochondrial donation germline genetic modification?
is it ethically relevant that mitochondrial donation is not a
could allowing mitochondrial donation lead to a 'slippery slope'?
Should the technology be used if
there is a potential for harm?
In chapter three, it was noted that there are still some aspects of the
science of mitochondrial donation that are not completely known and that there
could potentially be some harm to the children born to the technique if some of
the concerns are realised.
The question that needs to be considered is whether the technology
should be authorised for use if there is some risk of harm. The Murdoch
Children's Research Institute and Victorian Clinical Genetic Services consider
that the potential risks and the potential benefits need to be weighed up in
considering whether to authorise any technique:
It is unlikely that any IVF technique or most other medical
advances could ever have been introduced if absolute certainty was a
pre-condition of their application to human subjects. It is thus necessary to
consider the balance of potential benefits and potential harms to decide
whether application to human subjects is appropriate and what types and
duration of monitoring should be in place to assess safety and efficacy if the
benefits outweigh the harms.
The Biomedical Ethics Research Group at the Murdoch Children's Research
Institute noted that the potential to avoid passing on a devastating and
life-threatening illness to an unborn child was a clear ethical imperative that
weighed in favour of allowing mtDNA donation.
The countervailing factor that the Biomedical Ethics Group at the
Murdoch Children's Research Institute pointed out was that there were factors
that suggested that the science was not yet certain and potentially unsafe:
[Mitochondrial Replacement Therapy] is a new technology. It
could have unexpected and harmful consequences, which should be fully
investigated before MRT is used clinically. Concerns have been raised about the
potentially harmful effects that could arise as a result of a genetic
misalignment between mitochondrial and nuclear DNA.
Distinguished Professors Jenni Millbank and Isabel Karpin and Professor
Anita Stuhmcke argued that a harm minimisation approach balanced the rights of
parents against the potential safety risks:
In the interests of protecting and supporting Australians we
believe that a harm minimisation approach is urgently needed that ensures the
health and well-being of both the family and their future offspring. Such an
approach accords with human rights principles and the well accepted right to
form a family. In the case of those seeking treatment for mitochondrial disease
a legal prohibition is both onerous and discriminatory towards people who carry
the gene for this disabling condition.
The committee considers that a harm minimisation approach is appropriate
in the circumstances. The committee accepts that the potential to alleviate
significant suffering is a morally compelling reason to permit mitochondrial
donation, though it notes that the hope for the technology needs to be balanced
against the potential risks. At this point, the risks appear to be sufficiently
manageable to allow the use of the technology. However, it is not the role of a
Senate committee to make definitive scientific or medical findings. The
committee considers that formal review and potential endorsement of the UK scientific
findings should be made by a panel of Australian experts with relevant
scientific and medical knowledge. The committee considers that an independent
panel of Australian scientists and medical practitioners should be asked to
consider whether the science is sufficiently certain for clinical use.
Some submitters raised ethical concerns about whether mitochondrial
donation would alter the human germline and whether that should be permitted. In
gene therapy, a distinction can be drawn between somatic gene therapy, an
alteration of a cell that only affects the current generation, and germline
gene therapy which alters a gene that is passed on to future generations.
In most jurisdictions, heritable gene alteration, or germline gene therapy, is
It is thought of as a 'bright line' in terms of both safety and ethics.
Different jurisdictions have come to different positions on whether
mitochondrial donation should be considered to be an inheritable gene
alteration or replacement. In chapter three it was noted that the National
Academies of Sciences, Engineering and Medicine in the United States of America
proposed the implantation of only male embryos for a period of time to monitor
the effects of mitochondrial donation while effectively removing the potential
for the mitochondria to passed on to future generations.
In the UK, mitochondrial donation was considered to be a germline therapy
because the mitochondria will be inherited by future generations from a female
born to the technique if she has children, but it was not considered to be a
form of human genetic modification.
However, these terms generally relate to nuclear genes rather than organelles,
Submitters to the inquiry who supported mitochondrial donation
considered that the question about whether mitochondrial donation was a germline
alteration did not arise because it was separate from the nuclear genes. Dr
Newson suggested that mitochondrial replacement should be considered neither
germline or somatic gene therapy but as 'conditionally inheritable genomic
Mitochondria is conditionally inheritable because it can only by passed through
the female line; in a male embryo the mitochondrial donation is similar to
somatic gene therapy. In a female embryo, the mitochondria is inheritable and
forms part of the genetic information that is passed on to future generations.
Professors Thorburn, Christodoulou, Sue, Carroll, Ryan and Filipovska
noted that mitochondrial donation should be thought of ethically as being
distinct from germline genetic modification because mtDNA is distinct from the
These submitters also noted that mtDNA was not unique to individuals,
but was shared with the other members of the maternal haplogroup.
Submitters who were concerned about germline alteration were most
concerned about the effects of mtDNA donation on future generations.
For these submitters, the scientific uncertainty raised a moral concern about
whether the lives of people who are not yet born may be affected by the
carrying out of the mitochondrial donation procedure.
These concerns were prompted by some of the scientific questions that were
raised in chapter three, such as questions about possible mito-nuclear
Dr Tobin from the Plunkett Centre told the committee that she had no
principled objection to altering a person's genes to correct a genetic defect
even if there was a risk that the modification could be inherited, if it could
be shown it could be done safely:
It may be that with some of the new genetic techniques,
so-called CRISPR, where, at least theoretically, it may be possible to correct
a genetic defect in a young human being or adult human being such that that
person no longer has that disease or susceptibility to disease, and that
affects that person's germ line, a time comes when that is safe. If so, I don't
see an in-principle objection to that. I don't think we're there now.
Dr Newson told the committee that mitochondrial donation was the first
process that would be permitted to deliberately alter heritable characteristics,
but it was up to the committee to determine whether that was ethically
Senator Brockman's question was around if this is the first
thing that we know of that will lead to these kind of changes in a deliberately
intervening way; my answer to that is yes. The questions from an ethical perspective
are, 'What does that matter? What do we make [of] this from a moral
Whether Australia determines that mtDNA amounts to germline modification
or not will have implications for how mitochondrial donation can be legalised
in Australia. This will be discussed in greater detail in chapter five.
The committee recognises that there are many ethical views regarding
mitochondrial donation. In particular, the committee understands that some
submitters have concerns about whether mitochondrial donation constitutes a
form of germline gene therapy. The committee understands mtDNA is inherited
from the mother and that changes to mtDNA of an egg or embryo will affect
future generations. However, the committee accepts that there is an ethical
difference between the manipulation of nuclear DNA and the manipulation of
mtDNA, primarily because mtDNA does not contribute to the characteristics of
inheritable genetics in the manner traditionally thought of, at the time such
manipulations were prohibited through anti-cloning laws.
The committee acknowledges that there is a degree of scientific
uncertainty as to how to characterise the modification of mtDNA, and that these
definitions might have unanticipated impacts, such as legalising other techniques
of gene manipulation. As with other areas of science discussed in this report,
the committee acknowledges it does not have the expertise to make a formal
finding, but recognises that further exploration is required.
Therefore, the committee considers that the questions of whether mtDNA
should be considered a germline genetic modification, and does that preclude it
use, should be considered by a panel of expert Australian scientists and
bioethicists as a foundational question to be answered prior to any
legalisation of mitochondrial donation.
Does it matter if it is not a cure
for mitochondrial disease?
There is currently no cure for mitochondrial disease.
Mitochondrial donation is also not a cure for mitochondrial disease; it
prevents the transmission of the mitochondrial disease to the next generation.
Some submitters considered that it was morally relevant that
mitochondrial donation was not a 'cure' for mitochondrial disease. For these
submitters, a distinction could be drawn between alleviating the suffering of a
living person and intervening to prevent a person from acquiring a
The Australian Christian Lobby clearly told the committee that
interference at a genetic level was of concern:
Mitochondrial donation does not cure mitochondrial disease.
It is not 'treatment'. It is genetic manipulation to ensure that mutant mtDNA
is not transmitted to future generations. This has serious ethical
Dr Tobin from the Plunkett Centre elaborated on this concern:
I think it is important to note that, were you to recommend
the legalisation of this procedure, it is a procedure that doesn't cure anyone
of this disease, even in its mild forms let alone in its severe forms. The
risks that it involves are, strictly speaking, unnecessary. I think there are
alternative ways in which people with this disease, which can be so
debilitating, can have children.
For these submitters, the fact that mitochondrial donation was not a
cure militated against its legalisation, but the Australian Mitochondrial
Disease Foundation (AMDF) argued that the lack of any cure for mitochondrial
diseases gave ethical weight to the argument in favour of legalising
Unfortunately at this time there is no cure and few
treatments for mitochondrial disease which is one of the reasons its impacts on
patients and families are so devastating and why the community is seeking the
opportunity for Australia to adopt mitochondrial donation as an option for
AMDF's argument was supported by a number of leading scientists in the
field who told the committee:
The fact that there is no cure for mitochondrial disease
emphasizes the need and the urgency for allowing women from affected families
to have the best chance of having biologically related children who are unaffected
by mitochondrial disease...Like almost all assisted reproduction approaches, it
should be regarded as mitigating risk, rather than eliminating it. It is worth
noting that about 3% of all births are affected by a serious genetic anomaly or
The committee understands that mitochondrial donation is not a cure, but
it presents an opportunity to prevent a child from developing a specific
disease. Whilst there are ethical questions about whether this should be
permitted for nuclear cells, the committee considers that correcting the mtDNA may
be ethically permissible.
The start of the slippery slope?
Some submitters raised concerns that the same reasoning that is used to
allow the replacement of mtDNA to avoid a disease could be used to justify the
alteration of nuclear genes of unborn children to alleviate disease. These
submitters were concerned that this would be a step towards genetic engineering
and a lack of human diversity.
While the committee understands this argument, it is not the proposition
before the committee. The committee is satisfied that mitochondrial donation
can be legalised in a manner that does not permit the alteration of nuclear
Concluding committee view
The report, so far, has considered the evidence presented to the
committee by submitters, including prominent members of the scientific and
medical community who work in fields relevant to mitochondrial disease, and
concluded that mitochondrial donation is a safe and effective treatment to
prevent transmission of mitochondrial disease to the next generation in cases
where the disease develops because of mutated mtDNA.
Chapter one outlined that this treatment has been legalised in the UK,
after an extensive 12 year path of scientific and ethical review, combined with
community education and consultation.
Chapter two discussed mitochondrial disease and its impact to
individuals and families, as well as provided some estimates of the health
costs associated with this disease. Compelling evidence was presented to this
committee on the devastating impacts of this disease on families, particularly
as its genetic nature means it tends to impact multiple members of the same
family, with high child mortality.
Chapter three discussed the evidence provided on the science and safety
of mitochondrial donation. Evidence to the committee noted that while there are
still some unknown risks associated with mitochondrial donation, they are far
outweighed by the known risks of mitochondrial disease.
The committee recognises the clinicians' argument that most new medical
therapies involve a degree of risk and the last stage of the development of medical
treatments usually involve controlled clinical trials. The committee considers
that mitochondrial donation has reached this stage. As discussed in chapter
three, the committee believes that a formal determination that the science of
mitochondrial donation is ready for clinical trial in Australia should be made
by independent experts with relevant scientific and medical expertise.
This chapter discussed the ethics of mitochondrial donation. Many of the
ethical concerns considered the mechanics of mitochondrial donation because it
necessitates the destruction of embryos and interferes with dignity of natural
conception. The committee recognises that these concerns are not specific to
mitochondrial donation, and can be applied to any form of ART. However, the
committee acknowledges that the creation of viable, distinct embryos with no
potential to develop into a viable pregnancy is a new moral question that would
require community consultation as well as a change to the legal prohibition of
such activity under current law.
One key ethical concern specific to mitochondrial donation remains
unresolved: whether or not mitochondrial donation is genetic engineering of the
human genome similar to germline modification, and if so, whether that in
itself is enough to reject mitochondrial donation as a medical therapy to
prevent children being born with a high risk of developing mitochondrial
The committee heard evidence that mitochondrial donation is not a form
of germline modification as that term was understood at the time genetic
modification was prohibited under Australian law. However, the committee
recognises that an independent determination that mitochondrial donation is not
a form of germline modification would most appropriately be made by a panel of
scientists and bio-ethicists.
These foundational questions remain to be answered before the committee
can make a finding that mitochondrial donation is a medical therapy that is
safe to be introduced into Australia in the form of a clinical trial, which
could lead to clinical practice.
To achieve this, legislative change must occur at commonwealth and state
level to make mitochondrial donation lawful, and a regulatory regime must be
created to oversee research, clinical trial and later public rollout. The next
chapter discusses the evidence presented to the committee on the most effective
ways to regulate for Australia.
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