2.1
The inquiry heard a range of views regarding the bill from people who strongly support the introduction of mitochondrial donation, and those who strongly oppose it.
2.2
This chapter focuses on how the bill intends to introduce mitochondrial donation and the key issues identified with the proposed approach. They include removing the existing prohibitions in embryo research and cloning legislation, the design and implementation of the staged approach, and aspects of the governance arrangements and safeguards proposed in the bill.
2.3
The next chapter outlines some of the broader ethical considerations that apply to the introduction of mitochondrial donation, and the moral, scientific and social issues raised by witnesses and submitters during the inquiry. It also provides concluding comments from the committee and lists areas for possible clarification or amendment in the bill.
Exemption for mitochondrial donation
2.4
As discussed in Chapter 1, the use of mitochondrial donation techniques is currently prohibited under the Prohibition of Human Cloning for Reproduction Act 2002 (PHCR Act) and the Research Involving Human Embryos Act 2002 (RIHE Act).
2.5
Currently, under the PHCR, it is an offence to create or develop embryos through fertilisation with genetic material from more than two people. It is also an offence to make heritable changes to the genome of a human embryo for reproductive purposes.
2.6
The Department of Health (department) told the committee that the bill creates a narrow exemption in the existing laws to enable mitochondrial donation to be introduced in Australia.
2.7
In addition, the department said that in order to legalise any other techniques outside of mitochondrial donation, a further legislative process would be required. According to Ms Bronwyn Field, First Assistant Secretary:
… we have not lifted the prohibitions in any of the current laws that are in place. What we've done is actually to provide an exemption so that mitochondrial donation can occur. So this really does narrow and limit the extent of what we're legalising, and there is no other legal change to allow for any other techniques to occur, outside of mitochondrial donation.
2.8
Several inquiry participants told the committee they considered the bill would appropriately narrow the legislative changes to introduce mitochondrial donation solely for the purpose of avoiding transmission of mitochondrial disease.
2.9
Others, as discussed further in Chapter 3, felt strongly that the amendments to embryo research and cloning legislation are risky and not justifiable, and could leave the door open for mitochondrial donation techniques to be misused in the future.
Staged approach
2.10
Of the inquiry participants that were in favour of the introduction of mitochondrial donation, the committee heard broad support for the staged approach outlined in the bill.
2.11
Inquiry participants were also supportive of the bill’s cautious and strict regulatory framework for introducing mitochondrial donation, with a robust licencing and oversight regime.
2.12
Many expressed their hope that through the proposed staged approach, families could soon gain access to mitochondrial donation, within a safe and highly regulated framework.
2.13
One witness, who works with people suffering from mitochondrial disease, told the committee:
… it's vitally important for, say, the caring physicians that the patients are allowed to access safe procedures to help them have family when they're planning their families. This legislation and the proposed tiered introduction to it does allow for the safe introduction of mitochondrial donation as a procedure in the way that it has formal licensing at the various stages of the introduction.
2.14
However, as discussed in further detail in Chapter 3, for those who are opposed to the introduction of mitochondrial donation, the staged approach proposed by the bill does not address some key ethical, moral or scientific concerns.
Stage 1 clinical trial phase
2.15
As discussed in the previous chapter, during stage 1, the Department of Health proposes to undertake a competitive grants process to identify a suitable organisation to undertake the clinical trial. The clinical trial is anticipated to take approximately 10 years. The explanatory memorandum notes:
… [w]hile there is a relatively small number of women that may be assisted through the trial, it will not be a fast process due to the potential for participants to require multiple IVF procedures before a successful pregnancy is achieved.
2.16
Those in favour of introducing mitochondrial donation expressed overwhelming support for a clinical trial in stage 1. For example, Research Australia commented:
The approach of initially allowing mitochondrial donation as part of a clinical trial is an appropriate recognition of the stage of development of this technology. It ensures that mitochondrial donation will only occur with the informed consent of participants and in a highly regulated environment.
2.17
The Mito Foundation told the committee that the two-stage implementation process would provide multiple opportunities for mitochondrial donation to be considered and any changes to be made before it is introduced into clinical practice.
2.18
The International Society for Stem Cell Research (ISSCR) noted that the bill would enable a cautious introduction of mitochondrial replacement therapy that will provide access for eligible Australian families while monitoring safety and efficacy through the National Health and Medical Research Council’s (NHMRC) licencing committee.
2.19
However, the committee also heard a range of concerns about the proposed clinical trials in stage 1. Some concerns were around the limited number of licences for clinics available during the clinical trial stage. Others noted the need for training to develop the appropriate expertise in Australia in mitochondrial donation.
2.20
More broadly, however, many inquiry participants expressed concerns about proceeding to a clinical trial phase at all on the basis of current scientific evidence on the safety and efficacy of mitochondrial donation. These concerns are discussed in further detail in Chapter 3.
Stage 2 clinical practice
2.21
The bill contemplates that under stage 2 there will be a national regulatory framework which will allow for licenced clinical practice of mitochondrial donation in participating states and territories. This would be overseen by the NHMRC.
2.22
However, before mitochondrial donation can be introduced into clinical practice, several preconditions would need to be met:
that the safety and efficacy of any mitochondrial donation techniques would need to be demonstrated; and
further legislative changes would need to be introduced at the Commonwealth, State and Territory levels.
2.23
The Department of Health outlined what is required to introduce mitochondrial donation into clinical practice in stage 2:
… stage 1 involves clinical trials, and so evaluation of those trials would be required before we went to stage 2. There's also a seven-year review point for the legislation, so that would be likely to happen as well, prior to movement to stage 2. And then, when we get to stage 2 … there has to be agreement by the parliament to do that … In addition, states and territories will also have to opt in.
Reviewing the clinical trial
2.24
The Department of Health told the committee that the focus of reviewing the outcome of the clinical trials is to determine the safety and efficacy of mitochondrial donation.
2.25
Inquiry participants argued for longitudinal data on a minimum number of participants to demonstrate the safety and efficacy of mitochondrial donation techniques before it becomes clinically available.
2.26
Commenting on the lack of publicly available data on the UK mitochondrial donation regime, Associate Professor Megan Best of Ethicentre, said:
A requirement needs to be written into the legislation of how many people have to be followed up, a minimum number of participants needs to be stipulated as having data collected over time, and also intergenerational safety needs to be looked at before it is approved by parliament as a clinically safe technique.
2.27
The committee also heard that more detail is needed regarding the process for the five listed mitochondrial donation techniques in the bill to be considered and potentially approved through stage 1 for introduction into clinical practice.
2.28
The Department of Health told the committee that an evaluation program for the clinical trial will be developed with the NHMRC, in conjunction with the licencing scheme. According to Ms Angela Wallbank, Assistant Secretary from the Department of Health, a cautious approach will be taken:
We're very, very conscious of how sensitive this issue is and we want to do it as well as we can, with a view to things like privacy, whilst also being sure that we can say whether the techniques are safe and they have efficacy.
National regulatory framework
2.29
The bill contemplates that there will need to be legislation introduced by states and territories in order to implement mitochondrial donation into clinical practice.
2.30
This is because, in clinical practice, mitochondrial donation techniques are expected to be classified as an assisted reproductive technology (ART), which is the responsibility of states and territories.
2.31
At the Commonwealth level, there will also need to be further regulations to specify the permitted mitochondrial donation techniques for clinical practice. This will be a disallowable instrument to be put before the Parliament following the outcomes of the clinical trial and having regard to expert advice.
2.32
One submitter noted the risk that states and territories might choose to opt out of a national regulatory framework, raising issues with equity of access:
… it will be important for State and Commonwealth governments to prepare for the possibility that, if not coordinated well with each of the States and Territories, this approach may lead to a disuniform regime across the country, with different access rights to mitochondrial donation.
Licencing framework
2.33
As discussed in Chapter 1, the bill allows for five types of mitochondrial donation licences to be administered by the NHMRC’s Embryo Research Licencing Committee (ERLC).
2.34
The bill sets out what is authorised under each kind of licence, what conditions can be attached, and other administrative requirements. It also applies offence provisions to certain conduct outside the authorisation of a licence.
2.35
Inquiry participants noted that the ISSCR has recently recommended that research and clinical use involving mitochondrial donation is permissible, but only when subject to strict regulatory oversight and limited to patients at high risk of transmitting serious mitochondrial DNA based diseases to their offspring. Witnesses commented that the licencing measures in the bill would provide the required limitations and oversight outlined by the ISSCR.
Licencing decisions
2.36
The committee heard broad support for the ERLC’s role in the licencing and approval processes. However there were concerns the ERLC lacks the specific expertise in clinical and genetic aspects of mitochondrial disease.
2.37
There was support amongst submitters for the use of clinical experts in mitochondrial disease to support licencing decisions. For example, the Murdoch Children’s Research Institute suggested that the ERLC be supported in its licencing decisions by a small expert group to provide advice on an ongoing basis. Australian Genomics suggested that an expert clinical panel could be used to review referrals.
2.38
The NHMRC submitted that the bill will allow the ERLC to call on external expertise, including people with expertise in mitochondrial disease, people with expertise in clinical trials, and other experts as required.
2.39
According to the Department of Health there is no need to establish specific membership requirements or have a standing advisory committee. It explained that the bill will enable the ERLC to access to the advice they need to administer the licencing regime:
… it may not be appropriate just to have someone who has expertise in mitochondrial disease, for example; they might need more information than that. It was also to assist with ensuring that there's no conflict of interest, given the small pool of experts in this area.
Licence requirements and ongoing monitoring
2.40
Inquiry participants commented on the important ongoing monitoring requirements for licence holders.
2.41
The NHMRC submitted that the ERLC are already contemplating the need to ensure authorised embryologists are competent, and remain so, for the duration of their authorisation under a licence.
2.42
According to the NHMRC the bill places significant requirements on licence holders to collect a body of data relating to the clinical trial and its outcomes:
The bill is quite explicit that the holder of the clinical trial licence—so at the clinical trial stage—must monitor the outcomes, including pregnancies, any childbirth resulting and the ongoing health and development of the child born as a result of such pregnancies… So there will be quite a lot of outcomes monitoring that takes place.
2.43
Several submitters and witnesses commented on the need for long term monitoring of persons born from mitochondrial donation. These submitters reiterated concerns about the lack of published data on the efficacy and safety of the clinical trials in the UK, and information on the health outcomes of children (and future generations) born from mitochondrial donation.
Accessing mitochondrial donation
2.44
In order for a family to access mitochondrial donation during the clinical trial, the clinic must apply to the ERLC for approval. The bill sets out a range of factors the ERLC must be satisfied of before granting approval, including:
that there is a particular risk that mitochondrial disease will occur in the child;
that there is significant risk of serious illness or other serious medical condition occurring in that child as a result;
that other available techniques to minimise risk would be inappropriate; and
that the woman and her spouse have attended counselling and are fully informed of the risks and alternatives.
2.45
One witness noted that the bill recognises that mitochondrial donation will not be appropriate in every case:
This type of intervention will not be suitable for all people with mitochondrial disease who wish to have their own child. In fact, there are other techniques that could be used for some people, so it will be done on a case-by-case basis.
2.46
Some inquiry participants were concerned about ambiguity in the bill regarding what the ERLC must consider before it gives approval for a woman to have mitochondrial donation. For example, one witness commented on the requirement that there be a significant risk of serious illness or other serious medical condition occurring in the child. They argued that it is not clear what is meant by ‘other serious medical condition’ or how this is different from a ‘serious illness’.
2.47
It was suggested that further evidence could be required from women that they carry a homoplasmic mitochondrial DNA mutation before they become eligible for mitochondrial donation. One witness explained:
One way [the bill] could be tightened is to specify that the women involved, to be eligible for admission into the clinical trial, must provide evidence of carrying homoplasmic mitochondrial DNA mutations. That is the severe form of the disease.
2.48
Several submitters suggested that the bill could have the unintended consequence of excluding surrogacy arrangements, which could be necessary for women who suffer from mitochondrial disease who are too sick to carry a child, or for male couples using a surrogate.
Avoiding delays
2.49
The committee heard of the need for timeliness in the delivery of the clinical trials, and to avoid delays for families attempting to access the treatment.
2.50
Under the bill, where the ERLC provides approval for a woman to undergo a mitochondrial donation procedure, that approval lasts five years or until the birth of a live child from the procedure, whichever is earliest.
2.51
Several submitters noted that the bill’s approach to giving ‘approval’, over the issuing of an individual licence, is preferable, and could help avoid the kinds of delays experienced in the UK.
2.52
The Progress Education Trust told the committee that ‘time is of the essence’ for those wanting to start a family:
… particularly for prospective mothers who will need to undergo treatment and carry a pregnancy. Each delay can be a bitter blow to those who wish to have a child free from life-limiting mitochondrial disease.
2.53
Time limits and reporting requirements were suggested to improve transparency and accountability around the timeliness of ELRC decisions.
The need for equitable access
2.54
Amongst those supportive of the bill, there was a call for equitable access to mitochondrial donation, noting the demand around Australia. One witness described the situation for her patients:
There are many patients around Australia who have mitochondrial disease, and at my clinic we see patients from all different states and territories within Australia. So I can tell you from that experience that there are patients across the country who would be seeking this type of technique as part of their family planning.
2.55
It was suggested that clinical trials should be required to offer mitochondrial donation in all states and territories, or, that support be provided to families to access a clinical trial even if they live in another state or territory. The committee also heard the suggestion that priority populations should be identified to access mitochondrial donation.
Permitted techniques
2.56
As discussed in Chapter 1, the bill prescribes five mitochondrial donation techniques:
maternal spindle transfer (MST);
pronuclear transfer (PNT);
germinal vesicle transfer (GVT);
first polar body transfer (first PBT); and
second polar body transfer (second PBT).
2.57
All five are permitted techniques for a pre-clinical research and training licence. However, only two mitochondrial donation techniques would be permitted under a clinical trial licence. These are the MST and PNT techniques.
2.58
Inquiry participants expressed support for the bill limiting the permitted techniques to MST and PNT during clinical trials, having regard to the current state of the research into mitochondrial donation. The explanatory memorandum also notes these techniques are considered safe for clinical use in humans the UK.
2.59
There was also support for the bill recognising GVT and PBT techniques, and acknowledgement of the possibility of techniques being developed into the future.
2.60
Several submitters from the scientific community argued the bill should not limit the potential for future techniques to be developed. It was suggested that the bill may have the unintended consequence of limiting future pre‑clinical research and clinical use of techniques currently under development.
2.61
The committee heard that the licencing regime and training requirements outlined in the bill will provide important safeguards for the use of the techniques during the clinical trials:
… the techniques themselves have been used but do require a skilled hand. I would like to draw your attention to the licensing that recognises and requires, before a clinical trial licence is granted, that the embryologist who would be performing the technique must first apply for a training and research licence and be able to justify their skill before applying for a clinical trial licence.
2.62
However, the committee also heard concerns about some of the permitted techniques outlined in the bill, specifically, PNT and Second Polar Body Transfer. It was argued that these techniques are problematic for two reasons:
that the techniques used in PNT and Second Polar Body Transfer are similar to that used for human cloning; and
these techniques necessitates the creation of a human embryo ‘for its parts’ which once harvested destroy the embryo.
2.63
According to a number of submitters, the bill should be amended to only allow the use of MST. Ethicentre told the committee that:
… [a]s other techniques are available and show promise, for example, Maternal Spindle Transfer, this project can proceed without including Pronuclear Transfer and Second Polar Body Transfer.
2.64
The Australian Christian Lobby noted their concerns with the PNT technique and destruction of embryos:
Pronuclear transfer and similar techniques lead to higher rates of embryo wastage and should not be pursued at the outset when alternatives exist. Maternal spindle transfer should be the focus of research.
2.65
Overarching concerns regarding the use of mitochondrial donation techniques, including the creation and destruction of embryos and concerns about human germline manipulation, are discussed in further detail in Chapter 3.
Donor register
2.66
The donor register proposed by the bill was widely supported by inquiry participants, including those with concerns about the potential confusion and distress for children born of ‘three biological parents’.
2.67
Under the bill, the donor register would not be publicly available, and would allow any person over 18 born as a result of mitochondrial donation to access identifiable information regarding their mitochondrial donor. The donor would also have access to information on the register about themselves, and whether a child has been born of their donation.
2.68
Submitters suggested that the bill be amended to give children under the age of 18 the right to information from the donor register in some circumstances to be consistent with the approach in states and territories.
2.69
It was also suggested that the donor register be able to facilitate a donor notifying a donor-conceived children of any potential heritable medical issues as they become known.
Other safeguards
Consent
2.70
Under the bill, proper consent is required from the prospective mother, father and donor before proceeding with mitochondrial donation.
2.71
The NHMRC in its submission highlighted the importance of appropriate processes for obtaining proper consent.
2.72
However, the committee heard some concerns about families consenting to the risks of mitochondrial donation. It was suggested that informed consent will be difficult due to the ‘complexity of the procedures’ involved. It was also suggested that the future generations of children born of this technique are not able to consent to the intervention. The Australian Christian Lobby explained:
Included in the ‘consent’ is a high level of risk-taking for a procedure that is still largely experimental. Couples are dependent on experts to make an informed decision and concepts of mitochondrial inheritance are particularly difficult.
2.73
In response, the Australian and New Zealand Infertility Counsellors Association (ANZICA) stressed the importance of counselling for all parties:
Given the clinical and psychosocial complexities associated with mitochondrial donation, ANZICA strongly recommends that rigorous counselling and regulatory conditions (currently in place for third party reproduction) be applied.
2.74
The explanatory memorandum also notes the importance of counselling to help parents make informed decisions. It further stated that using a medical procedure which could prevent that child from having a debilitating illness meant that consent could be anticipated.
Counselling
2.75
Under the bill, a condition of a clinical trial licence and clinical practice licences requires an individual and their spouse to attend pre-treatment counselling.
2.76
The Mito Foundation told the committee that mandatory counselling would allow families to make informed decisions about mitochondrial donation and permit them appropriate reproductive choice.
2.77
ANZICA suggested that counselling requirements for donors should be explicitly recognised. Best practice, according to ANZICA, would require each party having at least two counselling sessions – plus an additional joint session in the case of known donation.
2.78
The committee heard that there are currently different requirements for counselling in states and territories, and it was suggested that there should be further clarification about counselling requirements at a national level.
2.79
According to the NHMRC, the Australian Health Ethics Committee (AHEC) will be reviewing its Ethical guidelines on the use of assisted reproductive technology in clinical practice and research to incorporate guidance specifically for mitochondrial donation.
2.80
The guidelines cover information counselling and consent and the use of donated gametes in assisted reproductive technology. The NHMRC told the committee:
… whether there's anything specific that needs to be considered for mitochondrial donors—will be picked up as part of the targeted review that the Australian Health Ethics Committee will do if the legislation passes. The committee intends to do a limited, targeted review to pick up mitochondrial donation implementation considerations to support the implementation of the bill.
2.81
The Department of Health noted that there is no limit in the bill as to the number of counselling sessions that could be required.
2.82
Finally, several inquiry participants recommended the bill should require pre-treatment counsellors to be independent and not involved in the research program. ANZICA commented that rather than require independent counsellors, there should be a requirement for counsellors to be accredited.
Privacy
2.83
Submitters were supportive of the protections for individual privacy in the bill. It was noted that children born of mitochondrial donation may attract media and public attention, and that the privacy wishes of families must be respected and upheld.
2.84
The committee also heard support for the bill not requiring children born of mitochondrial donation to be subject to ‘unnecessary or routinely invasive monitoring’.
Reporting and review
2.85
The committee heard from several submitters that there should be a parliamentary review before proceeding to Stage 2.
2.86
Currently in the bill, there would be a requirement for an independent review every seven years.
2.87
This is in addition to any review of the outcome of the clinical trial, which, as discussed above, is expected to run over 10 years, and will be used to inform any further legislative changes that would be required to progress to clinical practice.