1 Development and Purpose

Australia was in uncharted regulatory territory, faced with the task of developing a regulatory framework that was independent and transparent and promoted public engagement.^{Footnote 44} In the 1992 Standing Committee on Industry, Science and Technology’s Report, Genetic Manipulation: The Threat or the Glory?, the Chairman, Michael Lee, identified the challenge created by biotechnology: ‘… nations around the world are grappling with the legal and institutional changes which will be required to cope with the new technology’.^{Footnote 45} In response to the emerging field of biotechnology, it was determined that Federal Government intervention was necessary to enforce a regulatory regime to oversee the use and advancement of gene technology.^{Footnote 46} At the time, in the late 1990s, Government interventions were deemed ‘inadequate’ to respond to the rapid growth of gene technology.^{Footnote 47} Following consultation with the public and relevant stakeholders, the product was a regulatory regime underpinned by a precautionary approach.^{Footnote 48}

The primary focus of the Gene Technology Bill 2000 (Cth) concerned genetic modification within the agriculture and food industry — which is reflected in the ‘plant centric’ language of the legislation.^{Footnote 49} For example, in its most recent review, the Legislative and Governance Forum on Gene Technology concluded ‘[t]he Scheme was not designed to regulate humans’.^{Footnote 50} Genetic manipulation of humans, such as cloning or gene therapy, did not fall within the regulatory ambit of the Bill.^{Footnote 51} This was raised by former Attorney-General Nicola Roxon who noted the ‘legitimate focus’ of the proposed law was narrow in scope, excluding the technology’s potential application in humans.^{Footnote 52} She argued explicit and precise statutory language was required to ‘ensure the [regulatory] system is appropriate not just for handling and containment of genetically modified organisms in the plant and animal world, but also in the human area’.^{Footnote 53} Consistent with Michael Lee’s view, Ms Roxon acknowledged in the ‘not too distant future, we will have to grapple with how we legislate or regulate … the treatment of human cells in other areas’.^{Footnote 54} We are now facing this challenge, as HHGE inevitably continues to mature as a technology.

Although an objective of the Bill was to safeguard public health and the environment, its intention in offering this protection was balanced against risks associated with genetically modified foods.^{Footnote 55} Whilst the Bill represented Australia’s regulatory response to emerging biotechnologies, the need to future-proof the law to account for further advancements continues to be a recurring issue.

2 Regulation of HHGE

While this regime may have a ‘plant centric’ focus, there is ambiguity in relation to its application in humans, particularly in the context of clinical trials.^{Footnote 56} Under the current GT Act, a CRISPR-mediated genetic modification is classified as a gene technology and as such,^{Footnote 57} an organism subject to this modification is deemed a ‘genetically modified organism’ (‘GMO’).^{Footnote 58} Following a periodic review and amendments to the Gene Technology Regulations,^{Footnote 59} ‘site-directed nuclease (‘SDN’) techniques’ were introduced as an example of a genetic modification technique captured under the Act.^{Footnote 60} Techniques including CRISPR-Cas9 systems, zinc finger nucleases^{Footnote 61} and transcription activator-like effector nucleases were incorporated into the definition of an SDN.^{Footnote 62} This change signified the need to update definitions within the GT Act, prompted by developments of scientific techniques.^{Footnote 63} A distinction in the purpose of undertaking an SDN was also addressed (see Figure 1 below). SDNs which do not incorporate the introduction of a new nucleic acid template do not constitute a GMO.^{Footnote 64} This is referred to as an ‘SDN-1’ — whereby the organism does not carry new traits resulting from gene technology, indicating a double-stranded break has been induced, without the introduction of a repair DNA guiding template.^{Footnote 65} This indicates that any genetic manipulation inserting a new DNA sequence, induced through a technique such as CRISPR technology, produces a GMO which is regulated under the GT Act.

Figure 1. The classification of GMOs according to the purpose of undertaking CRISPR technology in an organism.

3 Governance and Regulatory Framework

The GT Act establishes a governance framework, enforced through the Gene Technology Scheme. The overarching body responsible for the operation of the regulator and the practical enforcement of the GT Act is the Legislative and Governance Forum on Gene Technology (‘LGF’), established by an intergovernmental agreement.^{Footnote 66} The LGF is a Ministerial Council, composed of Ministers from each state jurisdiction, managing portfolios relevant to gene technology.^{Footnote 67} The Gene Technology Regulator (‘GTR’) sits below the LGF in the governance framework. The GTR is an independent^{Footnote 68} statutory body which oversees the use of gene technology and ensures compliance with the regulatory regime.^{Footnote 69} As a result of the governance structure, the GTR sits within the purview of the LGF’s oversight function.^{Footnote 70}

The GTR is responsible for administering and operating the licensing system enforced by the GT Act.^{Footnote 71} In addition, when dealings with GMOs serve a therapeutic purpose or a therapeutic good contains a GMO, this requires collaboration between the GTR and the Therapeutic Goods Administration (‘TGA’).^{Footnote 72} The TGA retains sole responsibility to regulate therapeutic goods, ensuring their safety, quality and efficacy for use in humans.^{Footnote 73} The interactive effect of the GT Act and Therapeutic Goods Act 1989 (Cth) (‘TGA Act’) raises important considerations relating to the delineation of jurisdiction according to the nature and use of the GMO/product and the appropriateness of the appointed regulator.

Two statutory committees are also established under the GT Act: the Gene Technology Technical Advisory Committee (‘GTTAC’) and the Gene Technology Ethics and Community Consultative Committee (‘GTECCC’).^{Footnote 74} The GTTAC is composed of members with skills or experience in science, medicine and public health.^{Footnote 75} Their primary function is to provide scientific or technical advice to the GTR on matters relating to gene technology (including biosafety aspects), GMOs, genetically modified products, applications submitted to the GTR for proposed dealings with GMOs and the development of policy/procedural guidelines, principles and practice.^{Footnote 76} In contrast, the GTECCC offers diversity in its opinion, with members drawing upon experience or skills in a number of areas, such as law, ethics, religious practices, risk communication, community consultation, business and consumer affairs.^{Footnote 77} The Committee also provides advice to the GTR on ethical concerns pertaining to gene technology, the development of policy or procedures/guidelines and codes of conduct and community consultation.^{Footnote 78}

Australia’s governance approach aims to centralise day-to-day regulation and enforcement of statutory obligations to one federal regulator, the GTR. Guidance and oversight is facilitated by the LGF and Committees, which serves two purposes. First, it enforces accountability on behalf of the GTR to comply with statutory obligations and justify acceptable dealings with GMOs. Second, the provision of advice is a means to identify different perspectives and opinions in relation to the use of gene technology. This is imperative in the context of law and policy reform in the area of biotechnology.

The primary regulatory mechanism governing the use of gene editing is the enforcement of a licensing system.^{Footnote 79} This licensing system characterises dealings with a GMO into two groups: an exempt dealing or a notifiable low-risk dealing (‘NLRD’). A licence is required for dealings which fall outside the scope of either group.^{Footnote 80} In the context of HHGE, preclinical genetic modification of human cells will not be characterised as an exempt dealing.^{Footnote 81} However, it may be a NLRD, if physical containment is possible.^{Footnote 82} An Institutional Biosafety Committee (accessed through an accredited organisation) will assess the intended ‘dealing’ to determine whether it is one which falls within the NLRD regulatory scheme.^{Footnote 83} Criminal sanctions accompany a failure to obtain a licence or comply with conditions of a licence when dealing with GMOs.^{Footnote 84}

It is arguable the GT Act is an embodiment of Hume’s Law and Snow’s two cultures. The role of science as a factual instructor attempts to bridge the descriptive-normative divide. In light of science and law operating as two cultures, the advent of gene technology was the catalyst prompting the law to react to this development by implementing a framework for its regulation in plants. It is arguable that a precautionary approach is merely a reflection of the need for the law to monitor ongoing developments as the technology’s potential remained largely uncertain. Further, the ‘plant centric’ nature of the statute is indicative of a regulatory response that did not adequately apply a future-oriented lens, which was only raised by one member of Parliament, the former Attorney-General Nicola Roxon.^{Footnote 85}

Although the GT Act retains primary responsibility for the regulation of gene technology, its legislative objective did not consider the application of this technology in humans (in particular, for a therapeutic or enhancement purpose). The continued operation of the scheme remains largely ‘plant centric’, as reinforced by the GTR, and, as a result, was not created with the intention to regulate humans as GMOs. Where does this leave Australia regarding the regulation of HHGE? Should HHGE fall within the remit of the TGA Act?^{Footnote 86}

1 Development and Purpose

Advancements in research involving cloning, stem cells and ART prompted the introduction of the Research Involving Human Embryos Bill (‘RIHE Bill’) in 2002. The creation of Dolly the sheep in 1996 and the use of embryos and stem cells within the context of an ART in 1998 represented a new field of research with clinical and therapeutic potential in humans.^{Footnote 87} These developments raised a number of concerns including the possibility of human cloning, the use of cloning to treat disease and the ethics of embryo research.^{Footnote 88}

In the context of legislating in public policy areas that are emotionally and ethically provocative, such as biotechnology, the role of government was characterised as ‘uncontroversial’^{Footnote 89} by John Faulkner, Federal Senator and Shadow Minister for Public Administration and Home Affairs. Rather, the ‘regulatory principle embodied in [the RIHE Bill]’ encourages government to play an active role in ‘determining the ethical limits of medical research’.^{Footnote 90} Much like the introduction of the GT Act, this was a repeat of history. The law was reacting to another scientific advancement, prompting discussions regarding an appropriate national regulatory mechanism to govern and oversee a rapidly advancing field of research.^{Footnote 91}

The Research Involving Human Embryos Act 2002 (Cth) (‘RIHE Act’), in conjunction with the Prohibition of Human Cloning for Reproduction Act 2002 (Cth) (‘PHCR Act’),^{Footnote 92} creates a ‘complex regulatory and [prohibitive] landscape for research involving genome modification of human embryos’.^{Footnote 93} At the time of its introduction to Parliament, the RIHE Bill was described as ‘conservative’,^{Footnote 94} ‘careful’^{Footnote 95} and ‘strict’.^{Footnote 96} Despite this strict approach, it was noted the Bill was designed to adopt a ‘very responsible approach to licensing and monitoring’ of this new research field.^{Footnote 97} The practical effect of the RIHE Act led to the continuation of embryo research in a very limited capacity.

Unlike the GT Act, enquiries and debates concerning the RIHE Act were human centric and dominated by rhetoric surrounding the moral and human status of an embryo.^{Footnote 98} A primary issue raised in the context of this Bill was the application of research techniques on human embryos and possible uses in ART. Consequently, many stakeholders advocated for a strict and prohibitive regulatory regime.^{Footnote 99} Despite the presence of two irreconcilable and polarised views pertaining to the ethics and permissibility of embryo research and its uses in ART, the ‘broader duty to society’ was a prevailing factor in favour of allowing research to continue.^{Footnote 100} The need to proceed with caution and care represented a more accurate reflection of a pluralist society,^{Footnote 101} which encouraged flexibility in a regulatory approach to account for differences in opinion.^{Footnote 102} In addition, permissibility of embryo research was informed by an assessment of the potential benefits and risks to human health.

2 Regulation of HHGE

The primary regulatory mechanism governing the use of embryo research is a licensing regime,^{Footnote 103} enforced by the Embryo Research Licensing Committee (‘ERLC’), a statutory body created under the RIHE Act.^{Footnote 104} Failure to obtain a licence or adhere to licence conditions incurs criminal penalties, including imprisonment.^{Footnote 105}

The RIHE Act adopts a broad definition of an embryo,^{Footnote 106} which allows for research and training in ART clinics on egg culture, manipulation and maintenance, provided licence authorisation and approval is obtained. There are limited circumstances in which research involving CRISPR technology may be undertaken. First, pursuant to a licence, the ERLC may authorise the genetic manipulation of embryos to insert genetic material from a third person.^{Footnote 107} Second, research may be undertaken on embryos not suitable for implantation or excess ART embryos (if appropriately declared by the ERLC).^{Footnote 108} In order to lawfully use excess ART embryos, statutory requirements arguably impose burdensome practical barriers. For example, section 20 RIHE Act authorises the ERLC to grant a licence for the use of excess ART embryos,^{Footnote 109} on the proviso that express written authority from the woman and her spouse declares the embryos to be excess ART embryos.^{Footnote 110} In addition, consent must be obtained from the woman and her spouse and relevant ‘responsible persons’ prior to issuing the licence.^{Footnote 111}

Whilst these circumstances appear to facilitate a lawful avenue for embryo research involving CRISPR technology, the utility of such research is questionable, as an embryo that is unsuitable for implantation is significantly damaged.^{Footnote 112} The utility of any such research will be dependent on the aim of the experiment.^{Footnote 113} However, significant damage may limit the validity and utility of the research, as the embryo is not capable of proper functioning to sustain life.

It is clear there are significant barriers limiting CRISPR technology involving viable human embryos for research purposes. The restrictive regulatory approach inherent within the RIHE Act provides limited scope to lawfully create and use embryos for both clinical and basic research purposes.^{Footnote 114} This may be particularly problematic following the concluding statement of the Organising Committee at the Third International Summit on Human Genome Editing in March 2023. They recognised the progress of germline genome editing, which is not intended for reproduction, in the context of basic research, which uses human embryos or gametes. In light of these developments, it was concluded that basic research in this area should continue.^{Footnote 115} However, the Committee reiterated that the primary purpose of this research is to improve understanding of ‘aspects of early human development or exploring how the methods might be used to correct gene variants leading to genetic disorders’.^{Footnote 116} This further strengthens the argument to re-assess Australia’s legal framework in relation to embryo research. Specifically, to reduce the burdensome practical barriers imposed by the current regulatory system.

1 Development and Purpose

The need for legislation to address cloning was initiated by Dolly the sheep, which marked the success of somatic cell nuclear transfer in an animal model.^{Footnote 117} Upon its introduction in the House of Representatives, the Prohibition of Human Cloning Bill 2002 (‘PHC Bill’) originally formed part of the RIHE Bill. Due to the plethora of issues raised in the context of embryo research and unanimous support for the outright prohibition of cloning, the proposed Bill was split.^{Footnote 118} Given the ‘complex ethical and moral judgements’ raised in the context of embryo research and the inevitability of varying views on behalf of elected members, the Government did not oppose splitting the Bill.^{Footnote 119} As Senator Chris Ellison noted:

Much like the RIHE Bill, the PHC Bill was described as ‘conservative’,^{Footnote 121} adopting a strict prohibitive approach to address ethical concerns regarding scientific developments within the realm of human reproduction and the use of human embryos.^{Footnote 122} This Burkean^{Footnote 123} approach to reform advocates for change to occur incrementally, by ‘insensible degrees’,^{Footnote 124} such that it is ‘slow, deliberate, and measured’.^{Footnote 125} However, this approach must be balanced against the need to further progress research to enable refinement of technology and meet the safety threshold required for human use. This is illustrative of Hume’s Law, whereby the law must rely upon science to instruct its substantive or descriptive content. Once ascertained, the law may respond accordingly, by contextualising the technology and defining its boundaries for appropriate use/s. Snow’s two cultures are also reinforced, as lawmakers are tasked with responsibility to translate scientific developments into enforceable laws.

2 Regulation of HHGE

The clinical application of HHGE directly contravenes the PHCR Act. The legislation prescribes a number of outright prohibitions, which effectively criminalises HHGE.^{Footnote 126} There are two provisions of particular relevance. First, it is a criminal offence to undertake heritable alterations to the human genome, with a maximum penalty of 15 years imprisonment.^{Footnote 127} The criminalisation of heritable editing was not the focus of Parliamentary debate, only noted in passing by one Senator.^{Footnote 128} The effect of this provision bans germline gene therapy, which may be carried out in germ cells^{Footnote 129} or the cells of an early embryo.^{Footnote 130} Despite this ban, in the 2005 review of the RIHE Act and PHCR Act, most commonly known as the Lockhart Review, the Legislation Review Committee recommended that the creation of human embryos (by means other than fertilisation) subjected to HHGE could be undertaken under licence, for research purposes to ‘increase knowledge or treat diseases’.^{Footnote 131} The practical impact of this recommendation is yet to be known.

Second, it is a criminal offence to place a prohibited embryo into a woman to achieve pregnancy, with a maximum penalty of 15 years imprisonment.^{Footnote 132} For the purposes of this provision, an embryo subject to HHGE constitutes a ‘prohibited embryo’.^{Footnote 133} This bans the clinical application of HHGE — reinforcing the illegality of using HHGE as part of ART.

The PHCR Act represents a highly restrictive model of regulating HHGE in human embryos, for both clinical and research purposes. This approach is arguably consistent with Kranzberg’s utilitarian position which reinforces that technology has a moral identity. In the context of the PHCR Act, it is evident that the clinical application of CRISPR for HHGE has been defined as an unacceptable use.^{Footnote 134} This is reflected in the outright prohibition of clinical uses of HHGE, within the context of ART. Research uses of HHGE appear to be permitted in human embryos created by a means other than fertilisation, pursuant to a licence. However, the statutory language of section 15 PHCR Act creates confusion regarding its applicability to HHGE involving the creation of human embryos for research purposes. The need for clear and unambiguous statutory drafting is vital, given the serious criminal penalties accompanying prohibited uses of HHGE.

1 The Regulation of Genome Editing in Therapeutics

Genetically modified cells, including those subject to CRISPR technology, are classified and regulated as biologicals.^{Footnote 141} The regulation of biologicals was introduced in 2011 via the implementation of a new regulatory framework under the governing legislation.^{Footnote 142} The framework was designed and enforced to address the use of emerging technologies.^{Footnote 143}

Biologicals are defined as a distinct group of therapeutic goods which are made from, or contain, human cells and/or tissue.^{Footnote 144} Consequently, they introduce unique unforeseen risks that are not raised in the context of other therapeutic goods, such as prescribed medicines or medical devices.^{Footnote 145} Biologicals are regulated in accordance with a risk classification system, whereby class 1 represents ‘very low’ risk and class 4 ‘high’ risk.^{Footnote 146} On this spectrum, genetically modified cells are characterised as class 4 high risk biologicals.^{Footnote 147} The Therapeutic Goods Regulations 1990 (Cth) (‘TGA Regulations’) defines class 4 biologicals as products containing human cells or tissues that have been genetically modified to introduce a function that may or may not have been intrinsic to the cells and/or tissues upon retrieval from a donor.^{Footnote 148} Further, the purpose of the product must be used, or likely to be used, to treat or prevent disease, facilitate a medical diagnosis, inhibit, influence or modify a physiological process, test for susceptibility to a particular disease or replace/modify the anatomy of a person.^{Footnote 149} Biologicals confined to the parameters of the relevant legislative provisions and regulations can be used in Australia.^{Footnote 150}

A clinical trial involving a biological may proceed in Australia, with approval from the GTR, the TGA and relevant Institutional Human Research Ethics Committees (‘HRECs’).^{Footnote 151} This reflects the extent of the interaction between the TGA Act and GT Act with respect to the use of genetically modified products in humans. It also highlights the applicability of the GT Act, despite its ‘plant centric’ focus.^{Footnote 152} The RIHE Act and PHCR Act continue to operate at the periphery, to limit research uses of CRISPR technology and deter improper uses of genetically modified products in humans.

The use of a biological for special or experimental purposes is permitted under the TGA Act, provided the sponsor^{Footnote 153} adheres to the specified conditions of use imposed by the TGA Regulations.^{Footnote 154} These conditions may include compliance with specified HREC procedural protocols and guidelines, the National Statement on Ethical Conduct in Research Involving Humans and cessation of use if required by the HREC.^{Footnote 155}

The use of novel biological therapies or gene therapies in humans are subject to the TGA’s Clinical Trial Approval (‘CTA’) Scheme.^{Footnote 156} The CTA Scheme operates as an evaluative process for high risk or novel treatments, including gene therapy, with limited preclinical scientific data regarding its safety, risks and efficacy.^{Footnote 157} It involves a comprehensive review of the scientific and ethical issues posed by the novel therapeutic, undertaken by the TGA’s HRECs, prior to the commencement of a clinical trial.^{Footnote 158} It is the responsibility of the sponsor to submit a formal CTA application to the TGA, with the available data for review.^{Footnote 159} The sponsor must also ensure compliance with the relevant requirements under the GT Act, to obtain a licence or exemption for the use of a GMO.^{Footnote 160} In addition, adherence to the Guideline for Good Clinical Practice, the National Statement on Ethical Conduct in Human Research and any relevant protocol approved by the HREC is mandated.^{Footnote 161}

The HREC exercises the primary oversight function, which involves ongoing monitoring of a biological subject to approval for use in humans.^{Footnote 162} This function involves the review of the benefit-risk ratio, trial results, progress reports, ethical acceptability of its use, amendments to protocols, breaches of conditions and safety information.^{Footnote 163}

2 Contravention of the Therapeutic Goods Act 1989 (Cth)

The TGA Act codifies a number of criminal and civil penalties relating to the import, export, manufacture, supply and use of biologicals.^{Footnote 164} Criminal penalties are composed of three elements:

1. 1. The biological is for use in humans; and

2. 2. It is not subject to exclusions or exemptions; and

3. 3. The use of the biological:

   1. a. Has resulted in, or will result in, or likely to result in harm or injury to a person; or

   2. b. If used would result in or likely to result in harm or injury to a person.

A breach of the criminal provisions is accompanied by a term of imprisonment.^{Footnote 165} For example, the importation, exportation and supply of a biological incurs a penalty of 5 years imprisonment.^{Footnote 166} While the criminalisation of certain conduct acts as a deterrent, it also emphasises the strict regulation of biologicals, due to the inherent risks to human health. The TGA Act also enforces civil penalties.^{Footnote 167}

The potential use of HHGE must also consider the applicability of criminal and civil provisions under the TGA Act.