Xenotransplantation and the law: Mexico as a case study on regulatory barriers

Lisandro Herrera Aguilar
Galicia Abogados, Mexico City
lherrera@galicia.com.mx

Martha J Contreras Secchi
Galicia Abogados, Mexico City
mcontreras@galicia.com.mx

The life sciences sector is undergoing an extensive transformation, driven by the race between biotechnology, genetics, rising global health demands and the law. Among the most disruptive developments in recent years is xenotransplantation, which, simply put, involves the transplantation of living cells, tissues or organs from animals into humans. As global human organ shortages persist, often compounded by bureaucratic obstacles, xenotransplantation could emerge as a promising alternative. Recent advances in gene editing, immunology and regenerative medicine have brought this once-distant possibility within reach, while regulatory frameworks around the world still need to catch up with the scientific progress being made.^[1]

This article analyses xenotransplantation from a global perspective, highlighting the relevant technological drivers, ethical debates, regulatory frameworks and clinical milestones. Additionally, this article uses Mexico’s legal framework as a practical case study, showing how existing health laws can inadvertently create barriers to interspecies organ transplantation (animal to human), even though the laws themselves do not explicitly prohibit it.

The origins of xenotransplantation

The United States Food and Drug Administration (FDA) defines xenotransplantation as ‘any procedure that involves the transplantation, implantation, or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs.’^[2]

Among several potential donor species, recently pigs have emerged as the preferred candidates. Some studies have shown that their anatomical and physiological similarities to human beings, relatively fast breeding cycles and amenability to genetic modification make them an ideal species for organ donation. Historically, xenotransplantation has faced significant barriers to its implementation, namely immune rejection, the risk of infectious diseases and ethical concerns, which have limited its clinical application. However, the application of CRISPR-Cas9 gene-editing technology has dramatically accelerated the progress made in regard to addressing these barriers. This gene-editing technology has enabled precise genomic modifications to be made to reduce immune rejection and, therefore, improve the compatibility between the donor tissue and the patient.^[3]

As a result, xenotransplantation now represents the integration of several different scientific advances: genetic engineering to mitigate immunogenicity, immunosuppressive therapies to prevent rejection and regenerative medicine techniques to enhance graft survival.^[4]

This integration has moved the application of xenotransplantation from theoretical research into reality in the form of approved clinical trials, which has raised urgent questions about the regulatory readiness of jurisdictions that might want to use it and what ethical and legal oversight is needed.

Scientific and clinical breakthroughs

Pig-to-human organ transplants

In 2024, the first successful pig-to-human kidney transplant was performed in the US.^[5] A 62-year-old patient at Massachusetts General Hospital received a genetically modified kidney developed by eGenesis, co-founded by Harvard geneticist, George Church, and former postdoctoral fellow, Luhan Yang.^[6] The kidney underwent 69 genomic edits using CRISPR-Cas9, aimed at:

• removing the pig genes that produce sugars, triggering human immune rejection;
• introducing human genes to enhance immune compatibility; and
• turning off porcine endogenous retroviruses to reduce infection risk.^[7]

This milestone demonstrated not only the technical feasibility of the procedure, but also that a path exists towards addressing the chronic organ shortage. Following this success in the US, shortly after, in 2025, China made a similar breakthrough when the Xijing Military Hospital transplanted a pig’s liver into a brain-dead human patient.^[8]

Regulatory milestones

However, scientific progress alone does not guarantee that xenotransplantation is ready for adoption within clinical trials. Consequently, regulatory frameworks are essential to ensure the relevant safety, efficacy, ethical oversight and legal standards are adopted to support this breakthrough.

In the US, a leader in innovation, the FDA approved the first official xenotransplantation clinical trial, led by United Therapeutics. This trial involves patients with end-stage renal disease and genetically engineered pig kidneys (‘UKidneys’).^[9]

Key features of the clinical trial include:

• a multicentre, open-label, adaptive design, combining phases 1–3;
• long-term monitoring of the graft function and potential zoonotic infection risks; and
• the integration of immunological and genomic data to optimise the outcomes.^[10]

The ethical debate on xenotransplantation

Unlike some countries that already conduct clinical trials involving animal-to-human organ transplantation, Europe has adopted a more cautious approach, prioritising ethical scrutiny and public safety over rapid scientific progress. Even though the European Medicines Agency (EMA) issued guidelines on xenogeneic cell-based medicinal products in 2009, it has yet to approve xenotransplantation trials, reflecting its cautious stance.^[11] This caution highlights Europe’s views on bioethics, animal welfare and human safety, as a core pillars when dealing with emerging medical technologies.

Even though xenotransplantation has the potential to solve many of the burdens related to donor transplantation, it raises profound moral questions that extend well beyond its technical feasibility, touching on the welfare of sentient animals, the integrity of human identity and the public health consequences.

Animal welfare

One of the most, if not the most, contested ethical issues related to xenotransplantation concerns the deliberate breeding of animals for donation purposes and the genetic modification of organs for donation, particularly as not many attempts at breeding such animals have been successful. It has been argued that, even when rigorous welfare standards are applied, using animals for the purpose of breeding organs, as mere medical instruments, and subjecting them to confinement, genetic manipulation and ultimately sacrificing them, cannot be justified merely to produce organs that may be compatible.^[12]

Zoonotic risks

Xenotransplantation introduces the possibility of cross-species disease transmission, including infection by porcine endogenous retroviruses (PERVs) and other pathogens. While genome-editing technologies like CRISPR-Cas9 can reduce such risks, it has not yet been proven that it is possible to fully eliminate them. This situation could lead to public health risks deriving from potential outbreaks; therefore, to mitigate these risks it is necessary to develop comprehensive risk mitigation-related clinical and legal protocols to protect the recipients.^[13]

These two examples highlight some of the most relevant ethical complexities surrounding xenotransplantation. However, on the other hand, advocates emphasise xenotransplantation’s life-saving potential. Currently, millions of patients worldwide die each year while waiting for organ transplants, due to a shortage of available organs and the lengthy bureaucratic proceedings involved, underscoring the urgent need for alternative organ sources. To address these challenges, animal-derived organs, developed through the use of advanced genetic engineering like CRISPR-Cas9 gene-editing technology, could be a solution to reduce the reliance on scarce human donors.

That said, the proponents of xenotransplantation defend the use of these practices by arguing that the pursuit of methods capable of saving the lives of patients who would otherwise die waiting for viable human organs, provides a moral justification for the use of such measures. Nevertheless, the question of which prevails, animal wellbeing or human survival, remains an ongoing ethical dilemma.

Practical challenges and legal complications: the case of Mexico

Despite remarkable scientific achievements, the relevant legal and regulatory frameworks still lag behind scientific innovation. Most transplantation laws worldwide have been developed with human-to-human organ donation in mind, meaning that xenotransplantation remains in a legal and ethical grey area. In this context, Mexico provides a particularly illustrative example.

In the case of Mexico, the law does not explicitly prohibit xenotransplantation; however, existing regulation effectively limit its implementation. Several applicable laws and regulations are outlined below, which provide a pertinent example:

• Resolution WHA57.18 (2004). Mexico does not currently have an institutional or regulatory position opposing the future implementation of xenotransplantation. The country’s adoption of the World Health Organization’s Resolution WHA57.18 in 2004 demonstrates a degree of openness to the practice, as it recognises xenotransplants as a potential solution when human material is unavailable.^[14]
• NOM-253-SSA1-2012 ‘For the disposal of human blood and its components for therapeutic purposes’, defines xenotransplantation as a therapeutic procedure involving the transfer of organs, tissues or cells from another species into a human. This official standard acknowledges the existence of xenotransplantation procedures, although it does not constitute a comprehensive regulatory framework.^[15]
• The General Health Law (GHL). Under the GHL, an ‘organ’ is defined as a morphological entity composed of a group of different tissues that autonomously maintain its structure, vascularization and capacity to perform physiological functions.^[16] Similarly, the term ‘transplant’ is defined as the transfer of an organ, tissue or cells from one part of the body to another, or from one individual to another, in a way that integrates into the recipient’s body.^[17] This general definition also does not explicitly exclude the possibility of xenotransplants.

Notably, these definitions do not explicitly restrict the origin of the organ to human sources. This broad and function-based description could arguably allow for the inclusion of animal-derived organs (ie, xenotransplantation), provided that such organs meet the functional criteria described.

However, despite these broad definitions, the GHL and the related Regulations on Transplants impose a critical legal and ethical condition: no organ, tissue or cell may be used for transplantation against the will of the donor. In the case of living donors, the Regulations require that the donor’s informed and voluntary consent is documented and reviewed by the institution’s Internal Transplant Committee. The law clearly outlines that this consent must include, at a minimum, the donor’s full name and an explicit expression of their willingness to donate.

Given that animals cannot provide informed consent, this provision presents a significant barrier to the implementation of xenotransplantation as a transplant under the current regulatory regime. While the framework does not explicitly prohibit xenotransplantation, the consent requirement effectively renders it impermissible in practice.

Mexico’s situation, as an example, illustrates a broader global regulatory challenge: legal systems have not yet evolved to effectively implement ethical xenotransplantation procedures, forcing potential patients to navigate legal grey areas in pursuit of a healthier life.

Future outlook and recommendations

Recent breakthroughs have proved the technical feasibility of genetically engineered pig-to-human organ transplants and its capacity to save lives, yet regulatory, ethical and operational barriers remain. Mexico exemplifies this dilemma: although xenotransplantation is not explicitly prohibited by law, its implementation is hindered by consent requirements, among others, grounded in humancentric laws.

To ensure the safe implementation of xenotransplantation it is essential to harmonise the relevant legal definitions, ethical oversight, animal welfare standards and zoonotic risk management procedures, at a minimum. Ultimately, xenotransplantation will serve as a test case for how effectively regulatory frameworks can adapt to the rapidly advancing field of biomedical technology, which demands that scientific innovation work in tandem with our ethical responsibilities, to create safe and ethical health regulations.^[18]

Notes