Recently, a new Bill on mitochondrial donation, the Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021, was tabled in the federal Parliament. Although a vote was scheduled for last June, circumstances conspired against the parliamentary agenda, and it has been held over until later in the year.
The Bill proposes to introduce mitochondrial donation — and to legalise the intervention, which would be unlawful under current law — into the Australian health system. One of the reasons the Bill was needed is that, under current law, an act that alters a human genome is unlawful in Australia and will result in a penalty of 15 years imprisonment — one of the strictest penalties for genome alteration in the world.
That penalty is set out in section 15 of the Prohibition of Human Cloning for Reproduction Act 2002 (Cth) (the ‘PHCR Act’). That provision has remained unchanged since 2002, despite huge advancements in science, including the invention and discovery of several completely new forms of editing and altering human genomes. One such advancement was the discovery of a way of editing the human genome with great precision; this was the CRISPR Cas-9 (and related) techniques, and the discoverers won joint Nobel prizes for chemistry in 2020 for their achievements.
How Mitochondrial Donation Works
Mitochondrial donation involves taking healthy mitochondria from the egg of a donor and transferring that healthy mitochondria into the egg of a mother who has defective or diseased mitochondria. Replacing the defective mitochondria in the mother’s egg with healthy mitochondria from another woman’s healthy egg means that the child who will issue from the mother will not have mitochondrial disease or any other disease associated with defective mitochondria (such as Leigh syndrome). Where the procedure is not undertaken, a child born of a mother with defective mitochondria is virtually guaranteed to inherit mitochondrial disease or a related condition. Most of these conditions are not well treatable, and certainly not curable. After all, imagine if every cell (or most cells) in your body had a defect! The health implications of any mitochondrial defect are serious indeed.
This figure is taken from this article, pulished in Harvard University’s Science in the News website (CC BY 4.0). The figure is by Rebecca Clements.
As may be seen in figure 1, mitochondrial donation involes a few steps. First, a medical practitioner will remove the nuclear DNA from the donor egg, leaving an ’empty egg’ (an egg sans nucleus) containing healthy mitochondria (purple). Second, the medical practitioner will then remove the defective mitochondrial DNA from the birth mother’s nuclear DNA (teal). This creates a healthy nucleus with all of the defective mitochondrial material removed. Then, the altered nuclear DNA from the mother is transferred into the empty donor egg that is free of any defective mitochondria. The result is a newly engineered egg comprising the donor’s mitochondrial DNA and the mother’s nuclear DNA. This new egg is then fertilised by the father’s sperm outside of the body (ex vivo) and, once fertilised, implanted into the mother’s womb.
Once this transfer, fertilisation, and implantation process has taken place, the mother will possess a new egg. As noted, this will be an engineered egg — a product of the mother, the father, and the donor. Inside that egg, an embryo will develop that will now possess (1) nuclear DNA from the mother, (2) nuclear DNA from the father, as well as (3) the donated mitochondrial DNA from the donor’s egg. The defective mitochondrial DNA has been removed and in its place we have only healthy mitochondrial DNA.
The reason this is possible is because, fascinatingly, mitochondria have their own chromosomes and their own DNA. This DNA is separate from the DNA that we find in the nucleus of cells (the nuclear DNA). As such, it is possible to swap out the mitochondrial DNA in an egg without disturbing the nuclear DNA.
Since the nuclear DNA is the trait-giving DNA (that is, the DNA of primary genetic inheritance, imparting such things as eye colour, height, bone density, etc.), the child’s primary genetic inheritance will remain undisturbed by the addition of the donated mitochondrial DNA from the donor. In fact, the mitochondrial DNA is just that: DNA that relates only to the mitochondria in the cells. The anatomy of a cell is visible in figure 2, below. As we can see, the nuclear DNA and mitochondrial DNA are separated and rarely interdigitate. But while the mitochondrial genome is separate from the nuclear genome, its volume is much lower. The mitochondrial genome is built of 16,569 DNA base pairs, while the nuclear genome is made up of some 3.3 billion DNA base pairs.
This figure is taken from this article, pulished in Harvard University’s Science in the News website (CC BY 4.0). The figure is by Rebecca Clements.
Hang on — what are mitochondria?
Mitochondria are known as the ‘energy powerhouses’ of our cells. They are membrane-bound organelles within our cells that generate enough energy to facilitate cellular activity. Mitochondria also contain their own chromosomes. They are essential in converting the energy we receive from exogenous sources (such as food and sunlight) into energy that the cell can use in the tissues or organs. Mitochondria create energy by storing it chemically in the form of adenosine triphosphate (ATP).
Different tissue and organ cells have varying numbers of mitochondria. A mature red blood cells or erythrocyte may have no mitochondria; by contrast, liver cells (hepatocytes) can have more than 2,000 mitochondria in a single cell. Mitochondria even exist in collagen-producing cells like fibroblasts (see figure 3, below).
Image taken by the Institute of Molecular Medicine I, University of Düsseldorf (CC BY 4.0) and obtained here via this Wikimedia Commons page.
What does the Maeve’s Law Bill do?
Among other things, the Maeve’s Law Bill amends section 15 of the PHCR Act to carve out an exception for mitochondrial donation, essentially decriminalising the procedure. Recall that altering the human genome is unlawful, and that mitochondrial donation would have to be deemed an unlawful alteration of the human genome under the existing law. This is because, when a mitochondrial donation intervention takes place, the medical practitioner will be altering the human genome by transferring the DNA contained in the mitochondria into a new egg that will ultimately be implanted into a mother. Precisely how and when the alteration occurs (for instance, is it unlawful to alter the genome ex vivo?) is probably not worth considering. The provision seems broad enough to capture almost any kind of alteration, at least potentially. So, without the amendment in the Bill to make an exception for mitochondrial donation (and the Bill proposes to makes a huge number of amendments across three separate Acts), a practitioner who administers the treatment would be liable for up to 15 years imprisonment.
The question I have is as follows: Is the Maeve’s Law Bill a sign of things to come? Could we see further carve outs for CRISPR-style interventions in the near future? While interesting to contemplate, I do not think we shall see any such change. The reason is that we are still too far away from wielding CRISPR (or other genome editing techniques) in ways that would be safe and effective. Somatic cell genome editing, however: that may be a different matter. But I digress. Somatic cell editing is a different case altogether.
Federalism and Mitochondrial Donation
Despite many good aspects, the Maeve’s Law Bill does have some issues. Some of those relate to the ways in which the treatment is to be made available across the state and federal levels of government. As always in health, the dualism of our federal republic — and the indelible separation of the state and federal tiers on matters of health — threaten to complicate the roll out of any medical treatment.
On my analysis, it is quite possible that certain states, for whatever reason (perhaps ethical ones), may in the future enshrine a law prohibiting mitochondrial donation in that state, despite a Commonwealth laws that permits the intervention (Maeve’s Law). In such an instance, the current Bill is powerless to overcome that issue. Of course, it is arguable that federalism would require that to be just so, since the Commonwealth lacks a power to legislate on health. However, I wonder whether a National Cabinet memorandum of understanding could not be reached, and whether the states and territories could not refer their powers to legislate on this narrow area of health law to the Commonwealth under s 51 (xxxvii) of the Constitution.
Submission to Senate Inquiry
I and my colleague Professor Ainsley Newson set out some of our perceptions of the Bill in our submission to the Legislation Committee of the Senate Standing Committee on Community Affairs. Our submission is available here; it is submission number 49.