CRISPR’d pig kidneys for xenotransplantation

Last week, the biotech firm eGenesis supplied a donor kidney sourced from a genome-edited pig to a surgical team at Massachusetts General Hospital (MGH) in the US. The donated kidney was transplanted into a patient with end-stage renal disease whose existing kidney transplant (‘allotransplanted’ from a human) was wearing out. The FDA had granted an expanded access authorisation for the procedure and, as of today’s date, the patient is reported to be doing well.

It is not clear to me from any of the materials online how exactly the pig was edited, other than that it was broadly subject to CRISPR/Cas9 editing of three kinds. First, there was so-called knock out editing of the glycan antigens (which lead to hyperacute rejection); second, there was knock in editing of seven human transgenes, which are thought to help with ‘acceptance’ (or which mitigate immunogenic rejection); and, finally, there was editing directed towards inactivating the genes known to cause porcine endogenous retroviruses (PERVs).

In total, eGenesis and MGH report that sixty-nine (69) discrete gene edits were made. That appears to be a record for a xenotransplantation, because the previous two pig-derived heart xenotransplants from 2022 and 2023 in the US are reported to have only been subject to about 10 edits.

I am assuming that the edits were made to the germline cells of a pig embryo fertilised in the laboratory, as opposed to being made on primordial germ cells or embryonic stem cells, but I am not able to find any specific protocols for this firm’s method. I suspect that somatic cell nuclear transfer (SCNT; ie, cloning) was not used, even though SCNT is technically legal in the US. In any event, I wrote a piece for the Conversation on some of the issues arising in relation to this recent news item here.

A Generational Miscalculation: Unpicking Centrelink’s Unlawful Income Apportionment

Today on Welfare Law in Australia, Darren O’ Donovan analyses an internal document released under the Freedom of Information Act 1982 (Cth) just a few days ago. That document reveals the inner working of Services Australia as it continues in its efforts to remediate a multi-decade calculation blunder likely affecting more than 100,000 people. What is more, the calculation blunder was also unlawful — well, at least according to the Commonwealth Ombudsman.

The post comes only a day after Charlesworth J of the Federal Court of Australia found, in Patrick v Attorney-General (Cth) [2024] FCA 268, that governments will no longer be able to deny information requests that are determined at a date after the relevant Minister’s term has expired because (among other things) a document will be viewed as an ‘official document’ as it exists as such at the time of the request rather than at the time of the determination [8].

Case note: Fidge v Pfizer Australia Pty Ltd [2024] FCA 161

On 1 March 2024, Rofe J of the Federal Court of Australia (FCA) delivered a decision concerning an application brought by a medical practitioner, Dr Julian Fidge, in July 2023, against the pharmaceutical companies Pfizer Australia Pty Limited and Moderna Australia Pty Limited (the respondents).

The applicant sought an injunction under s 147(1) of the Gene Technology Act 2000 (Cth) (GT Act), which permitted an ‘aggrieved person’ to obtain an injunction from the FCA as against any conduct that was or would be an offence under the GT Act or the Gene Technology Regulations 2000 (Cth) (GT Regulations). An injunction so ordered would restrain the offending party from engaging in the conduct.

It is important to note that the applicant had formed the view that the vaccines sponsored by the respondents, which are generally known as mRNA vaccines (mRNA vaccines), were, or had contained, genetically modified organisms (GMOs) as defined under s 10 of the Gene Technology Act 2000 (Cth) (GT Act). While the meanings of these words might well be ‘at large’ in the scientific literature, the application in this case was framed in terms of the legal meaning of this expression, which was provided under s 10 the GT Act, as follows:

genetically modified organism means:

(a) an organism that has been modified by gene technology; or

(b) an organism that has inherited particular traits from an organism (the initial organism), being traits that occurred in the initial organism because of gene technology; or

(c) anything declared by the regulations to be a genetically modified organism, or that belongs to a class of things declared by the regulations to be genetically modified organisms;

but does not include:

(d) a human being, if the human being is covered by paragraph (a) only because the human being has undergone somatic cell gene therapy; or

(e) an organism declared by the regulations not to be a genetically modified organism, or that belongs to a class of organisms declared by the regulations not to be genetically modified organisms.

As I have argued elsewhere, the applicant’s submission appeared to completely omit any reference the GT Regulations. This was unusual, since the GT Regulations declare a broad range of organisms to to be not GMOs (notwithstanding s 10 of the GT Act) pursuant to the subsection (e), above. For instance, ‘Schedule 1: Organisms that are not genetically modified organisms’ contains 10 items; and Schedule 1A: Techniques that are not gene technology’ contains 11 items, which appear to affect many GMOs. Indeed, it might be argued, as I have argued, that the applicant’s failure to consider the applicability of these exemptions rendered the submissions inadequate.

In any event, the applicant had formed the view that the mRNA vaccines were GMOs under the GT Act as a result of reading various sources. These included some refereed articles, some preprint publications concerning the genetic profile of the mRNA vaccines, various online documents, and other sources (many of which were presented on a webpage published by the Australian Medical Professional Society in respect of the proceedings). However, none of these sources appeared to consider the legal meaning of the expression GMO under the GT Act.

Nevertheless, on the basis of the above view, the applicant asserted that the respondents were required to obtain licenses under the GT Act from the Office of the Gene Technology Regulator (OGTR) to ‘deal with’ those mRNA vaccines pursuant to s 40 of the GT Act. The requirement to obtain licences in respect of the mRNA vaccines followed from the asserted conclusion that they were GMOs under the GT Act. Since the respondents had not obtained those licences, the applicant submitted, the importation, distribution and transportation of the vaccines (among other acts) constituted offences under ss 32 and 33 of the GT Act. In committing the offences, the conduct of the respondents could now be restrained by the FCA under s 147(1) of the GT Act — although it was not clear whether the relief sought (the injunction) was intended to apply to the impugned activities in general or only insofar as they related to the applicant.

While the evidence relating to the applicant’s belief that the mRNA vaccines were, or contained, GMOs was submitted to the FCA, Rofe J disregarded this evidence because the question of law underlying the applicant’s action — were the mRNA vaccines GMOs? — was unneccessary to determine in these summary judgment proceedings. That was because the proceedings really concerned the anterior procedural question whether the applicant had standing to make the application.

The reason a summary judgment was delivered was because summary judgment had been sought by the respondents. They averred that the applicant lacked standing in reliance of s 147(1) of the GT Act, which effectively defined what an ‘aggrieved person’ was in respect of the GT Act:

If a person has engaged, is engaging, or is about to engage in any conduct that is or would be an offence against this Act or the regulations, the Federal Court of Australia (the Court) may, on the application of the Regulator or any other aggrieved person, grant an injunction restraining the person from engaging in the conduct.

The respondents submitted that the purpose of s 147(1) was to confine standing to persons aggrieved by actions done contrary to the GT Act [42]. Pfizer submitted, in effect, that not any person affected by (or even especially affected by) any product regulated or partially regulated by the GT Act would attain standing by virtue of their status as an affected person; instead, s 147(1) is drafted so as to narrow the scope of standing to those persons who are aggrieved directly by regulated dealings under the GT Act and where the regulation of those dealings are virtually the sole province of the GT Act. In other words, the provision, as Rofe J summarised the argument (at [42]),

is not intended to afford a broad remedy for any person with either general or specific grievances with GMOs arising from activities, uses or conduct not regulated by the GTA. This includes health and safety risks to consumers that may only be indirectly related to dealings under the Act, especially where such risks are specifically regulated by other statutory regimes or bodies.

As against this submission, the applicant contended that the GT Act has a far broader purpose, which includes the protection of the health and safety of the public. It thus followed that the applicant would have standing because, if the mRNA vaccines were or contained GMOs as the applicant submitted, and if this meant the mRNA vaccines had the potential to harm patients, then the applicant, as a person who had consumed the mRNA vaccines and had administered the mRNA vaccines, was a person protected by the GT Act, and in particular its object to regulate ‘risks to the end user or recipient of a GMO product, in particular the safety and efficacy of a therapeutic GMO product’ [43].

Given the above submissions, Rofe J understood the task of the proceedings as resolving the question of law whether the applicant was an aggrieved person based on the characterisation of the GT Act averred by the applicant. In this way, the case revolved not so much on whether the mRNA vaccines were, or contained GMOs, but on whether the applicant was protected as a consumer of a therapeutic good by the GT Act, whose purpose, as the applicant contended, was protective of such a class of persons.

On top of that, the applicant had to show that, even if this was accepted, that he, above others, had a ‘special interest’ in the alleged protective purpose of the Act, as was required by the general (common law) of standing [43]. This was always going to be a difficult thing to prove, because, after all, the applicant was one of millions of consumers of the mRNA vaccines, as well as one of thousands of health practitioner to have administered them to patients.

In the end, Rofe J found that the applicant did not have standing. The authority most analogous and relevant to the applicant’s submissions was Ogle v Strickland (1987) 13 FCR 306 (Ogle). That case involved a Christian ministers of religion identifying themselves as persons aggrieved by a decision by a censorship agency to permit an allegedly blasphemous film into Australia (see [129]). Although the authority of Ogle has been questioned several times since — including as observed by Jagot J in Australian National Imams Council Ltd v Australian Communications and Media Authority (2022) 404 ALR 323 at [91] — Rofe J found that her Honour was bound to follow the decision because it had not been overturned and the respondents did not challenge it.

Again, Ogle was a case in which certain Christian ministers argued that they were, and were found to be, persons aggrieved in respect of a decision of a censorship agency to permit an allegedly blasphemous film to be imported into Australia. The relevant statutory provision regarding aggrieved persons in that case appeared in s 5(1) of the Administrative Decisions (Judicial Review) Act 1977 (ADJR Act). That provision simply stated that certain aggrieved persons would be able to apply to the (then) federal court in various circumstances. Lockhart J found that the clergymen were persons aggrieved (at 318) notwithstanding that they did not have any legalistic special interest in the subject matter of the proceeding. As Lockart J wrote,

It is true that the appellants have no special interests in the subject matter of the decision in the sense of legal or equitable rights or proprietary or pecuniary interests; but they are persons aggrieved because to repel blasphemy is a necessary incident of their vocation. To deny them standing would deny an important class in the community an effective means and procedure for challenging decisions of the kind involved in this case.

When applied to the facts in this matter, Ogle enlivened an important test, which might be called the ‘necessary incident of the profession’ test. Applied to the medical profession, that question became ‘whether the matters agitated by Dr Fidge are a necessary incident of being a medical practitioner’ [131]. Rofe J’s consideration of this question is instructive for cases involving medical practitioners who seek remedies in circumstances where they allege a general legal breach and take action to protect patients generally. Rofe J found, in this case, that challenging decisions or actions of regulators did not form an incident of the medical profession in the same way as challenging a censorship decision did form an incident of the clergy in Ogle.

As Rofe J writes,

it is not a necessary incident of the medical profession that doctors oppose any or every breach of legislation that may (in their view) pose a risk to the health and safety of people. The sources of obligation referred to by Dr Fidge — the AHPRA Code of Conduct, Hippocratic Oath and AMA Code of Ethics — do not require doctors to challenge alleged breaches of legislation in order to “do no harm” or properly inform their patients. It is certainly not a necessary incident of being a doctor to challenge alleged breaches of the GTA. Nor do doctors have a professional obligation to “speak for all members of the Australian community” about potential health risks.

In my capacity as a legal scholar, I agree with Rofe J that neither the various ethical codes (Codes) regulating health practitioners in Australia, nor the Hippocratic Oath, go so far as to require, compel, or even permit health practitioners to challenge alleged offences under law to protect their patients. While the Codes do not explicitly prevent practitioners from challenging laws, they do not explicitly support such actions either. And consideration of the disciplinary actions taken by regulators responsible for enforcing the Codes soon indicates that, with respect to vaccines, health practitioners have been expected to have been bound to comply with the law in respect of protecting patients: see, eg, Health Care Complaints Commission v Parmenter [2023] NSWCATOD 136. In general, it might be said that compliance with the law to protect patients is an incident of the profession whereas challenging laws to allegedly protect patients is not.

In divining the legal character of Dr Fidge’s action, Rofe J concluded that it derived from an ethical position — one of ‘strong personal beliefs’ [135] — rather than a professional or legal duty:

Dr Fidge’s concern ultimately arises from a sense of moral obligation, not professional obligation or legal duty imposed on him as a medical practitioner. Although the ministers in Ogle may have felt that they had a moral obligation to challenge the decision of the Censorship Board, the majority in Ogle did not hold that a moral obligation is sufficient to establish standing.

Given that the applicant failed to demonstrate that he was an aggrieved person, the question of whether the mRNA vaccines were, or contained, GMOs did not arise. However, as I plan to explore in much more detail in future writing on this case, the decision does indicate that the purpose of the GT Act is to regulate GMOs on a ‘gap-filling’ basis, the result of which is that the GT Act does not regulate every therapeutic good that may or does contain a GMO, or something akin to a GMO. Rofe J ascertained this conclusion by means of a detailed purposive analysis of the GT Act as a whole, which included an independent construction of the text and (historical and legislative) context of the GT Act, as well as its interaction with other statutes, such as the Therapeutic Goods Act 1989 (Cth).

Indeed, the idea that the GT Act would be a ‘super regulator’ whose purpose was to become a ‘one stop shop’ for the regulation of GMOs and GM products in Australia, ‘regardless of whether the GMOs or GM products were also therapeutic goods, foods, agricultural and veterinary chemicals or industrial chemicals,’ was explicitly rejected by the Commonwealth Parliament when the GT Act was enacted (see [66]).

Instead, the GT Act was enacted explicitly as a gap filler directed at filling gaps related to ‘dealings with live viable organisms,’ such as ‘laboratory research involving the genetic modification of animals, plants, bacteria and viruses and the growing of crops, animals and fish.’ Where the Therapeutic Goods Administration (TGA) had approved a therapeutic product that contained certain gene-related products, the GT Act was not intended to, and did not, per force of its objects or legislative purpose, also apply as a second layer of regulation. Indeed, as I have argued in respect of this proceedings and more generally, the risk-based regulation (RBR) approach adopted to product regulation in Australia and abroad has always stood against duplication of this kind.

Thus, although Rofe J’s decision did not answer the question as to whether Dr Fidge, if found to have been aggrieved, would have been correct in identifying the respondents’ failure to obtain licences as breaches of the GT Act under ss 32 and 33, it is certainly apparent from her Honour’s analysis of the GT Act that such alleged breaches are unlikely to be made out by any future litigant.

In the media: VAD in Victoria; the thalidomide assistance scheme; sexual misconduct reforms in health care

This post is just a brief discussion of three media contributions I have made in the last few months.

Interview on SIX News about Victorian VAD laws

I was interviewed in December last year for the Six News Australia program Between Parkes Place and Capital Hill about a judgment of November 2023, delivered by Abraham J as a single judge of the Federal Court of Australia. The judgment concerned the validity and operation of certain provisions of the Victorian euthanasia law — the Voluntary Assisted Dying Act 2017 (Vic) (VAD Act).

That decision of Abraham J, in the case of Carr v Attorney-General (Cth) [2023] FCA 1500 (30 November 2023), found that certain sections of the VAD Act (s 57(a); and ss 19(1)(d)–(e) and 28(1)(d)–(e)) were inoperative because they authorised a form of assisting suicide that was inconsistent with sections of the Commonwealth Criminal Code Act 1995 (Cth) — namely, ss 474.29A and 474.29B. Those criminal provisions, which were inserted into the Code in 2005 by the Howard government in the context of an earlier stage of the euthanasia debate, made aiding and abetting suicide by a carriage service a criminal offence. See, eg, section 474.29A(1) below (noting that the many subsections that follow sub (1) are omitted here):

It was unsurprising, I guess, in view of the legislative history of the Code provisions that, on a purposive analysis, Abraham J would find that the criminal Code was intended to criminalise the very thing authorised by the Victorian VAD Act.

The implications for the applicant doctor in this case, and for the operation of the VAD Act in Victoria, were considerable. That’s no surprise, however, as this was really a test case to determine a question of law: namely, whether a doctor discussing assisted dying with a patient over the phone would be prosecutable under the Cth criminal law. In other words, the doctor-applicant here saw his and his peers’ exposure to criminal liability as a possibility and was proved correct in going to the FCA to ensure that he would (or would not) be so exposed if he were to discuss suicide with any of his relevant patients under the Victorian law.

The interview is about 30 minutes’ long, and I thank the presenters for their detailed discussion. Oh — and one last note. I was alerted just yesterday that Kate Chaney MP has moved a Bill — which is here — that would amend the Criminal Code so as to make the Victorian law operative again.

Comments on the thalidomide inquiry and the federal government’s response

Also in December, my brief comments appeared in a short news story on thalidomide, which was published in the wake of a report published by the Senate Community Affairs References Committee about thalidomide, titled Support for Australia’s thalidomide survivors, and following the apology in Parliament by the Prime Minister to those who survived thalidomide and their families for the trauma and harms caused them in the 1960s.

There is a lot to say about the Australian thalidomide episode; however, what is unusual about the Senate Report is its discussion of and request for legal advice received by Australian MPs regarding the question of the Commonwealth’s liability or ‘obligations’ after it permitted thalidomide to be supplied in the Australian therapeutic goods market. Ultimately, the Report recommended that the legal advice be published to the public. However, that recommendation was not accepted by the government; it was merely noted, with no reasons or any response.

As the Senate report states (footnotes removed):

2.87. Early in the inquiry the committee was advised that the former Minister for Health, the Hon. Sussan Ley MP, commissioned advice from Maddocks Lawyers about Australia’s obligations to its thalidomide survivors.

2.88. On 19 June 2018, the Senate agreed that a copy of the document should be provided to the Senate by 20 June 2018. On 16 August 2018, Senator the Hon. Bridget McKenzie, representing the Minister for Health in the Senate, made a public interest immunity claim over the document. Senator McKenzie’s public interest immunity claim was based on the fact that the document was legal advice to government:

It has been the long-standing practice of successive Australian Governments to not disclose privileged legal advice, including advice that canvasses possible constitutional issues.

2.89 In the interim report the committee requested that a copy of the advice be
made available to the committee to help it to understand the options available
to the Australian Government.

2.90 The Maddocks Lawyers’ advice was not made available to the committee and
the committee was unable to verify or consider the contents of the advice. This
is important as the advice could have provided the committee with a better
understanding of the legal context in which the Australian Government is
being asked to respond to the Thalidomide Group Australia’s requests. The
advice could have also provided the committee with important information
regarding the current options available to the Australian Government for
supporting thalidomide survivors.

2.91 Instead, the only evidence the committee has about the advice comes to it
indirectly. The committee received some evidence that a ministerial adviser
revealed some of the content of that advice to the Director of the Thalidomide
Group Australia, Ms Lisa McManus. According to Ms McManus, the adviser
provided her with the following information about the advice:

– the advice is 23 pages long;
– it provided five possible options;
– one of the options was to ‘do nothing’; and
– it concluded that the Australian Government had no legal obligation, but
that the Australian Government has a ‘moral responsibility’ to assist
thalidomide survivors.

Committee view
2.92. The committee considers that Australian governments have a moral obligation
to Australia’s thalidomide survivors. The committee notes that both the
Australian Government and the state governments failed to monitor drug
safety at a time when other governments around the world did so. Documents
provided to the committee demonstrate that the Australian Government was
aware that more could be done to safeguard public health from dangerous
drugs. The committee notes that the formation of the Therapeutic Goods
Administration was a direct result of the thalidomide disaster and notes
evidence to the inquiry that suggests such a body could have been, and should
have been, established earlier.

Parl Info

Obviously, whether the Maddocks advice might have suggested or explored any cause of action against the Commonwealth for historical negligence is of immense interest to victims (and to a lesser extent legal scholars). It does seem to me that there would not be very high prospects of a case on today’s law. However, if the Maddocks advice included five possible courses of action, one of which was ‘do nothing,’ what were the others? Are any of those options not canvassed by the Senate Committee?

What really strikes me as difficult about this issue is that the Committee was not itself able to review the advice, in circumstances where one might expect that Senators, as sworn officers of the Commonwealth, might be entrusted with such documents. After all, the lawyers who wrote the advice, while also bound by legal professional privilege, are not sworn officer of the Commonwealth. But I digress. It may be left to negligence scholars such as myself to guess and theorise about what liability might, on a given historical account, be affixed to the Commonwealth — if any.

Sexual misconduct reforms to health practitioner law

Proposed reforms to the Health Practitioner Regulation National Law, or National Law, have been circulated for consultation recently. The National Law is an Act separately enacted in most of the different states as part of a national scheme for regulating health practitioners called the National Registration and Accreditation Scheme, or NRAS. Technically, the NRAS is designed as an applied laws scheme, because the template is a Queensland law that then gets ‘applied’ in other jurisdictions. But because not every state applies the Queensland law (NSW enacts the law itself), it’s actually probably best described as a ‘combination scheme.’ In any event, it’s a co-operative scheme between the states and Commonwealth; however, there is no Commonwealth-level legislation.

I wrote about these promising reforms for The Conversation here. In essence, the reforms aim to put a stop to the rising rates of notified sexual misconduct and boundary violations that are emanating from the clinical practices of health practitioners nationwide. However, a few notes I might now add include the following.

First, much credit for the shape and substance of the reforms should be duly extended to Prof Jenni Millbank of UTS, whose several detailed publications on the National Law have really unearthed the difficulties that these reforms attempt to address. For instance, the second proposal, which is about bringing other states’ reinstatement processes up to the same level of strictness as the process in NSW, would probably not have been possible to float unless Millbank had identified and argued about this problem in one of her excellent refereed articles.

Second, the NSW version of the National Law has been stricter from the very beginning (2009), and the reform processes hence have — in my view inevitably — been a slow and somewhat agonising process of watching all the other states catch up to where NSW began.

In my view, this has also really been the consequence of the National Registration and Accreditation Implementation Project (NRAIP) team not really clicking with the NSW participants in its original discussion in 2008. While the NSW advocates were clear and compelling in arguing for the preferability of the existing NSW practitioner law (and on that basis ‘carved out’ parts of the NRAS to retain those preferable laws), the NRAIP team seemed wedded to the template, and may have failed to identify all the real virtues of the stricter NSW system. That was the NSW system which had developed, in short, in response to several scandals — principally, Chelmsford, “Butcher of Bega,” and Dr Sood, and which, in 1983, created the first ‘HCE’ (health complaints entity) — namely, the HCCC — in the world.

Alright — thanks for reading.