Mitochondrial donation is a reproductive technology procedure to reduce
the chances of a woman passing on mitochondrial disease—a potentially life-threatening
condition—to her children.
Mitochondrial donation was legalised for use on humans in the United
Kingdom (UK) in 2015. The UK is the only jurisdiction in the world that has
legalised mitochondrial donation for clinical application, and to date, no
children have been born using this process in the UK. Since then, there have
been discussions in the Australian scientific and medical communities about the
possibility of this technique being made legal for clinical practice in
This report looks at the science of mitochondrial donation, the safety
and efficacy on the technique as well as the ethical considerations of such
technology, and evaluates whether the Australian Government should consider
making mitochondrial donation available within Australia, and if so, under what
kind of regulatory regime.
The report uses information provided in the course of this inquiry, and
relies on the significant body of evidence gathered during the 12
year process to evaluate and ultimately legalise mitochondrial donation in the
What is mitochondrial disease?
Mitochondria are found in the fluid surrounding the nucleus of cells.
They are responsible for making energy within the cell, without which the cells
would not survive. In order to work, the mitochondria have their own
mitochondrial DNA (mtDNA).
Mitochondrial disease can be caused by mutations in the mtDNA or in the nuclear
In some cases, mitochondrial disease is caused by genetic mutations in
the nuclear DNA – most of our DNA (over 99 per cent) is found in the nucleus of
the cell and we inherit this from our mother and our father. Mitochondrial
disease can also arise as a spontaneous genetic mutation at conception.
Mitochondrial disease varies in presentation. It can be mild with little
or no symptoms or can be severe enough to be life threatening. It tends to
affect parts of the body that require a lot of energy, like the brain, muscles,
kidney and heart. While some symptoms can be managed, there are no effective
treatments available for serious mitochondrial disease and there is no cure.
Common symptoms of mitochondrial disease include developmental delays,
seizures, weakness and fatigue, muscle pain, vision loss, and heart problems,
leading to morbidity and in some cases premature death.
Chapter two discusses mitochondrial disease and related illnesses in greater
Causes of mitochondrial disease
In about half of all known cases, mitochondrial disease is caused by
mutations in the mtDNA, which are inherited matrilineally, from mother to
children through multiple generations.
This is because the mother's oocytes (eggs) contain significant amounts of
mtDNA, while the mtDNA contained in a father's sperm is lost at fertilisation. The
level of mutated mtDNA a child will inherit, or the severity of any subsequent mitochondrial
disease, is unpredictable.
For women with a known mtDNA mutation who want to have a child with a
genetic link, there are currently two key options to reduce the chance of
passing on mitochondrial disease.
The first is to use prenatal diagnosis, conducted on a pregnant woman at
around 11–14 weeks gestation, usually by performing a genetic test on a
placental tissue biopsy. If an mtDNA mutation is found, parents then face a
choice of either continuing or terminating the pregnancy.
The other option is to use pre-implantation genetic diagnosis (PGD),
where embryos are created using in vitro fertilisation (IVF) and then tested
before implantation to look for embryos with the lowest proportion of mutated
There are limitations to this method because it cannot be used by all
women with mtDNA mutations and it can only reduce, not eliminate, the risk of
having a baby affected by mitochondrial disease. In some cases, there are no
embryos with an acceptably low mtDNA mutation load and the IVF cycle must be
Additionally, even if unaffected themselves, girls born after the use of
PGD may themselves still be at risk of having affected children, as some
abnormal mitochondria may be present in their oocytes.
The full range of reproductive choices available to people with a
mitochondrial mutation are discussed in greater detail in chapter two.
Mitochondrial donation (or mitochondrial replacement techniques) is
designed to prevent the transmission of mtDNA diseases from mother to child by
creating an embryo with nuclear DNA from the intended mother and mtDNA from a donor
with nonpathogenic mtDNA through modification of either an oocyte or zygote
mtDNA does not contribute to a person's genetic identity because mtDNA
only provides energy to the cells. Nuclear DNA is responsible for a person's
physical, cognitive and behavioural characteristics. A recipient of donated
mtDNA will not resemble the donor.
Mitochondrial donation only assists women with mtDNA mutations—the cause
of approximately half of mitochondrial disease—and assists in reducing the risk
of mothers with this form of mitochondrial disease passing it on to their
The various methods of mitochondrial donation and the benefits, risks and
ethical considerations of the differing techniques are discussed in greater
detail in chapters three and four.
Regulation of mitochondrial donation and related research
Under current Australian legislation, some forms of mitochondrial
research are prohibited entirely because it requires fertilising an egg with
the genetic material of more than two people, while others can be researched
under license but must be destroyed within 14 days.
There are two key pieces of legislation which prohibit the research and
clinical implementation of mitochondrial donation in Australia. Additionally,
there are a range of other regulatory instruments and bodies which are relevant
to mitochondrial donation.
The National Health and Medical Research Council (NHMRC) is Australia's
peak body for supporting health and medical research, including providing
advice on ethical behaviour in health care and in the conduct of health and
medical research. The NHMRC is responsible for administering the two pieces of
legislation relevant to mitochondrial donation – Research Involving Human
Embryos Act 2002 (Embryo Research Act) and the Prohibition of Human
Cloning for Reproduction Act 2002 (Cloning Act).
Two relevant committees of the NHRMC include the Australian Health
Ethics Committee (Health Ethics Committee) and the Embryo Research Licensing
Embryo Research Licensing Committee
The Embryo Research Licensing Committee of the NHMRC is responsible for administering
the Cloning Act and the Embryo Research Act. Both Acts regulate activities that
relate to mitochondrial donation and would have to be amended if mitochondrial
donation was to be permitted in Australia.
A detailed discussion of what is currently allowed under legislation and
the amendments required to permit the implementation of mitochondrial donation in
clinical practice is included in chapter five.
Health Ethics Committee
The Health Ethics Committee of the NHMRC provides advice on ethical
issues relating to health, and develops human research guidelines. Guidelines
relevant to mitochondrial donation include the Ethical Guidelines on the use
of assisted reproductive technology in clinical practice and research (ART
and the National Statement on Ethical Conduct in Human Research (Human
While the Health Ethics Committee is responsible for guidelines on how Assisted
Reproductive Technologies (ART) such as IVF should be implemented, it is not
responsible for the regulation and monitoring of ART use in clinical practice. The
Embryo Act requires all ART clinics to be accredited by the Reproductive
Technology Accreditation Committee (RTAC) of the Fertility Society of Australia
Regulation of ART clinics
The Fertility Society is the peak body for those professionals involved
in reproductive medicine in Australia, including gynaecologists, scientists,
nurses and counsellors.
The reproductive medicine sector is self-regulating under the Fertility Society
accreditation scheme managed by the RTAC, which regulates and licenses the 88
clinics across Australia which perform ART techniques for individuals.
As part of the RTAC assessment process, ART clinics are assessed for
compliance with the RTAC Code of Practice, which in turn requires compliance
with the NHMRC ART Guidelines.
The Fertility Society includes the scientists' sub-group Scientists in
Reproductive Technology (SIRT), with over 500 members in Australia, New Zealand
and internationally. The goals of SIRT are to:
[P]romote professional excellence through education,
training, research and dissemination of scientific information; to increase the
profile and professional status of scientists in assisted reproduction; and,
finally, to act as a resource for formulating a consensus on scientific issues
and guidelines for best scientific practice, predominately for the Fertility
Society of Australia but also for other professional bodies.
Dr Nadine Richings, Vice Chair of SIRT, told the committee that embryologists
working in ART clinics are not currently required to be certified in Australia,
although SIRT is currently developing a certification scheme for embryologists
to be accredited by a third party.
Suggestions from the Fertility Society and SIRT on an appropriate
certification and regulation framework for mitochondrial donation in Australia is
discussed in further detail in chapter five.
Overseas status of mitochondrial donation
The UK undertook a 12 year process to allow for the research of
mitochondrial donation from 2005, leading to the legalisation of this technique
for clinical implementation in 2015, and a licence to administer this as a treatment
being granted to a fertility clinic in 2017.
There were a significant number of scientific and ethical reviews, as
well as community consultations to ensure that the technology could be safely
and ethically undertaken and that there was public support for the measure.
The timeline below gives a brief outline of the process:
||The Human Fertilisation and Embryology Authority (HFEA) is
created to review information relating to embryos and advise the Secretary of
||HFEA grants research licence for pronuclear transfer.
||HFEA releases first scientific review and recommends
||HFEA's Ethics and Law Committee considers ethical issues.
|January 2012 – March
||HFEA undertakes public dialogue work on the ethics and
public attitudes towards mitochondrial replacement. Public were generally
supportive of these techniques, although concerns around safety, the donor
role and the regulation of the techniques were highlighted.
||Nuffield Council on Bioethics publishes its ethical
|September 2012 –
||Open consultation questionnaire, meetings and patient
focus group takes place.
||HFEA releases second scientific review.
||The Government announces it will move forward with public
consultation on draft regulations for the use of mitochondrial donation to
prevent mothers passing on serious mitochondrial diseases to their children.
||HFEA releases third scientific review on safety and
||Legislation to legalise mitochondrial legislation put
before UK Parliament.
||The Human Fertilisation and Embryology (Mitochondrial
Donation) Regulations 2015 passes.
||The Human Fertilisation and Embryology (Mitochondrial
Donation) Regulations 2015 come into force. Requires both the clinic and the
patient to be licenced by the HFEA.
||Final regulations governing
mitochondrial donation are endorsed by the HFEA.
||HFEA grants licence to provide
mitochondrial donation to the Newcastle Fertility Centre.
||HFEA grants licence to undergo
mitochondrial donation to two UK women carrying mtDNA mutations.
|As of 30 April 2018
||HFEA's Statutory Approvals
Committee has considered 6 applications to carry out mitochondrial
Source: HFEA, Third
scientific review of the safety and efficacy of methods to avoid mitochondrial
disease through assisted conception: 2014 update, additional information
received 30 May 2018, pp. 6–8; AMDF, Submission 26,
pp. 6–7 and AMDF, Mitochondrial donation, https://www,amdf.org.au/mitochondrial-donation/ (accessed 15 June 2018).
United States of America
The consultation process for mitochondrial transfer in the United States
of America (USA) to date has been less structured than in the UK, mostly due to
the lack of a specialised agency for human reproduction and fertility.
In 2014 the USA Food and Drug Administration requested the Institute of
Medicine of the National Academies of Sciences, Engineering and Medicine to
review the broader implications of mitochondrial transfer. The review was quite
cautious, recommending that future clinical trials are restricted to women with
serious risks of transmitting mitochondrial disease to their children, and for
which the mitochondrial mutation is pathogenic and highly likely to be
manifested in a severe clinical way; and that mitochondrial transfer only be
made to male embryos to prevent any transfer of the donated mitochondria to
However, federal restrictions on funding and research 'in which a human
embryo is intentionally created or modified to include a heritable genetic
modification' mean that clinics in the USA cannot currently conduct research in
Singapore is currently carrying out public consultation on whether or
not mitochondrial donation should be permitted to prevent heritable
Following this introductory chapter, this report consists of four
Chapter two outlines the impact of mitochondrial disease on
individuals and their families, the rates of mitochondrial disease and mtDNA
mutations and the cost to the health sector;
Chapter three discusses the science of mitochondrial donation;
Chapter four discusses the ethics and possible health risks; and
Chapter five reviews the regime recently introduced in the UK to
regulate the clinical implementation of mitochondrial donation, and compares
that to the existing regulatory regime in Australia. Chapter five also provides
the recommendations and conclusions of the Senate Community Affairs References
Conduct of the inquiry
On 21 March 2018 the Senate referred the science of mitochondrial
donation to the committee for inquiry and report by 19 June 2018 with the
following terms of reference:
the science of mitochondrial donation and its ability to prevent
transmission of mitochondrial disease;
the safety and efficacy of these techniques, as well as ethical
the status of these techniques elsewhere in the world and their
relevance to Australian families;
the current impact of mitochondrial disease on Australian families and
the healthcare sector;
consideration of changes to legal and ethical frameworks that would be
required if mitochondrial donation was to be introduced in Australia;
the value and impact of introducing mitochondrial donation in Australia;
other related matters.
On 19 June 2018 the Senate granted an extension of time for reporting to
27 June 2018.
The inquiry was advertised on the committee's website and the committee
wrote to stakeholders inviting them to make submissions.
The committee also issued media releases to promote public awareness
about ways individuals could engage with the inquiry. Media releases were
published on the committee's website and were tweeted using the @AuSenate
The committee invited submissions to be lodged by 11 May 2018.
Submissions continued to be accepted after this date.
The committee published 53 submissions from government agencies,
organisations and individuals. A further 7 submissions were accepted as
confidential submissions. A list of submissions provided to the inquiry is
available on the committee's website
and in Appendix 1.
The committee held a public hearing on 17 May 2018 in Sydney, NSW. A
list of witnesses who provided evidence at the public hearing is available at
Notes on references
In this report, some references to Committee Hansard are to proof
transcripts. Page numbers may vary between proof and official transcripts.
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