On 24 March 2021, the Government introduced the Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021 (the Bill) to the House of Representatives. The Bill amends existing legislation to allow mitochondrial donation techniques to be used for research, training and human reproductive purposes. The overall aim is for women at risk of passing on mitochondrial disease, to have reproductive options for biological children without the increased risk of their child having mitochondrial disease.

This FlagPost is a snapshot of the Bills Digest (due to be published shortly) and provides an overview of the key elements of mitochondrial donation and the Bill.

What are mitochondria?

Mitochondria are small DNA-containing structures found in human cells. They produce roughly 90 per cent of the energy our body needs to function and also support a number of other functions. As outlined in the National Health and Medical Research Council (NHMRC) Mitochondrial Donation Issues Paper, DNA within mitochondria (mtDNA) is different from nuclear DNA (nDNA), namely:

• mtDNA is inherited primarily from the biological mother, nDNA is inherited from both biological parents
• mtDNA contains 37 genes (approximately 0.1 per cent of our genes), nDNA contains 20,000 to 30,000 genes
• a single cell can contain numerous mitochondria, and each of these can contain multiple copies of mtDNA; a single copy of nDNA is contained in the nucleus of most cells and there is usually just one nucleus per cell (pp. 6–7).

What is mitochondrial disease?

Mitochondrial disease is a group of inherited conditions that can cause serious health issues and, in severe cases, can cause death in childhood. The disease is caused by mutations in mtDNA or mutations in nDNA that impact the function of mitochondria, meaning it reduces their ability to produce energy. The disease particularly affects organs that have a higher energy use, such as the heart, muscles and brain. Currently, there is no known cure and treatment is mostly limited to the management of symptoms.

In Australia, approximately:

• one in 200 babies are born with some level of mtDNA mutation that could lead to mitochondrial DNA disease in their lifetime
• between one in 5,000 and one in 10,000 Australians are estimated to develop severe or life‑threatening mitochondrial DNA disease during their lifetime
• the average lifespan of children born with mitochondrial DNA disease is estimated to be between three and 12 years of age (NHMRC Issues Paper, p. 8).

What is mitochondrial donation?

Mitochondrial donation is an assisted reproductive technology that can assist women to avoid passing mitochondrial disease to their biological child (NHMRC Issues Paper, p. 3). This technology is not a cure for the disease, nor can it prevent the disease caused by mutations in nDNA. Instead, it is a way to prevent children from inheriting mitochondria that can cause the disease. In Australia, it is estimated that mitochondrial donation may be able to assist in the prevention of mitochondrial DNA disease in 60 births per year (NHMRC Issues Paper, p. 12).

Mitochondrial donation works by creating an embryo using the nDNA from the prospective mother and father and healthy mtDNA from a donor. Currently, several different mitochondrial donation techniques exist that can achieve this outcome (NHMRC Expert Statement, pp. 12–3).

The United Kingdom introduced amendments to its existing legislation to allow mitochondrial donation for reproductive purposes in 2015. To date, it is the only country to have done so. At the time of writing, only one facility is licenced to treat patients using mitochondrial donation, and only individuals with a very high risk of passing on serious mitochondrial disease are eligible for treatment.

Mitochondrial donation is still a relatively new technology and the long-term consequences are still unknown. Before introducing mitochondrial donation, the UK undertook several reviews and consultations that spanned multiple years. More recently in Australia, the NHMRC Mitochondrial Donation Expert Working Committee was tasked with reviewing the evidence on the safety and efficacy of mitochondrial donation that had emerged since the 2016 scientific review undertaken by the UK’s Human Fertilisation and Embryology Authority (Community Affairs References Committee Report, p. ix). The Committee concluded that there was no new significant evidence since the 2016 HFEA review (NHMRC Expert Statement, p. 32).

How would the Bill introduce mitochondrial DNA donation?

Under Australia’s current legislative framework, mitochondrial donation is illegal under the Prohibition of Human Cloning for Reproduction Act 2002(Cth) and the Research Involving Human Embryos Act 2002 (Cth). The Bill amends the relevant Acts and associated Regulations to make mitochondrial donation legal for research and human reproductive purposes.

Primarily, the Bill makes changes to ensure that it is no longer an offence to create, for the purposes of reproduction, a human embryo that:

• contains the genetic material of more than two people and
• contains heritable changes to the genome.

Given mitochondrial donation is a new medical technology, the Bill introduces a two-stage implementation approach. This is intended to allow for the expansion of scientific evidence to ensure the techniques are safe and effective and undertaken in an ethically appropriate manner.

Stage 1 would only allow three of the potential five licences types to be available from the NHMRC. These initial licences would authorise pre-clinical and clinical trial research and training, and clinical trial activities to take place. This approach would seek to determine the ‘safety, efficacy and feasibility of mitochondrial donation for reducing the risk of transmission of serious mitochondrial disease in humans’ (Explanatory Memorandum the Bill, p. 71).

Stage 2, which would permit mitochondrial donation in clinical practice, is dependent on the success of the licenced techniques and the findings of the Stage 1 review. As such, the two types of clinical practice related licences are subject to further amendments to legislation before they can be made available.

In acknowledgement of the ethical issues and concerns raised by the new technology endorsed by this Bill (including privacy, embryo creation and destruction, consent and donor rights) the Minister for Health has stated that the ‘Prime Minister, the cabinet, the party room and the opposition have all agreed to endorse a rare free vote, where people can vote with their conscience and free of their party's position’. Further discussion of these issues is available in the Bills Digest.

Funding to support the introduction of mitochondrial donation

To support the implementation of mitochondrial donation in Australia’s research and clinical settings, the Australian Government has committed $4.4 million over four years (part of a $10.3 million commitment over ten years) in the 2021–22 Federal Budget (pp. [223–4]).