By Anthony Merlocco

Due to the ongoing struggle to obtain organs for those in need, and the resulting morbidity and mortality while awaiting organs, renewed efforts to study transplantation between species, or xenotransplantation (XTx), have emerged. Gene editing has been used to enhance human graft survival or to make animal organs better suited for a human host. This strategy has not advanced enough to permit clinical trials in humans, which is highlighted by the emergency use authorization for the first modern-era human XTx in January of 2022 wherein a pig-to-human heart transplant was completed. While this patient later died, and it was not clear whether this was actually from organ rejection, the receipt of this animal organ has refocused attention on the reality that were transplantation successful, further work is needed to address improving feasibility and outcomes in adult patients and how to foresee and respond to ethical issues and guide ethical translation to clinical trials.

Broadly, issues arising in the creation of xenotransplantation can span an ever widening breadth including strategies to make humanoid chimeric organs and arguments related to moral status of borderline personhood or issues raised in animal rights and welfare. However, three topics rooted in clinical research have elicited significant attention: 1) justice and harm evaluations arising from potential interspecies disease transmission to the recipient, or the human population, 2) questions surrounding research ethics, consent, and long-term research obligations, and 3) policymaking for allocation, costs, and equitable access.

However, there is a very important topic that so far has received close to zero attention: xenotransplantation and paediatric health. Even when no hard line separates the ethical issues surrounding xenotransplantation in adults and children, there are some issues which call for us to stop and think more deeply about how they may apply in children uniquely. Let us remember that children are not simply “little adults”, and the ethical issues that stem from the unique psychology and biological characteristics require distinct approaches. So far there has been focus on how to approach the right to withdraw from clinical trials in this population, and whether legislation should accompany XTx clinical trials to ensure follow-up. This attention has initiated an important step forward and we must further expand the analyses of additional ethical issues to support arguments that we have good reason to develop paediatric xenotransplantation, particularly in neonates who may benefit uniquely.

Paediatric ethical issues arising in xenotransplantation will be unique but may or may not preclude development of paediatric xenotransplantation in concert with adult xenotransplantation. There are specific reasons children will benefit from xenotransplantation and in some cases more so than adults. Compared with adults, children may be uniquely advantaged by XTx because of 1) organ size considerations, 2) more significantly limited alternatives, 3) an immunologic advantage, and 4) an opportunity to transplant children with genetic diseases that currently limit allotransplantation. How we approach the introduction of XTx to children is thus itself an important consideration.

Of the three possible approaches to developing xenotransplantation research – developing it first in adults, developing it first in children, and developing it in both populations simultaneously – current efforts appear directed at adult development. We cannot presume development of adult xenotransplantation will be readily translatable to children as some issues they face will differ, thus we cannot presume the first approach above will inevitably lead to application in children. Children have much to gain from xenotransplantation, perhaps even more than adults. Thus, we must minimize any delay in developing xenotransplantation in this population, but this must be balanced against harms that could result from not awaiting adult results.

Some unique issues to children are not necessarily new, as evidenced through the first baboon heart transplant in Baby Fae in 1984, highlighting issues of safety, harm, and perceptions of xenotransplantation that now require re-examination. Experimentation on children and informed consent may elicit controversy today much as they did then, however, paediatric surgeons are revisiting physician attitudes and finding high acceptance if the health outcomes are similar to allotransplantation. Since crossing species barriers between animals and humans might create feelings of discomfort we should plan ahead about how to provide the necessary psychological support. Psychosocial support is already an integral component of pre- and post-transplant paediatric care, but this is generally focussed on promoting follow-up rather than addressing the experience of having another’s organ internalized. The very idea of having living animal parts integrated into one’s body is a distinctive ethical issue and how a toddler or teen will process or wrestle with this and how it may impact identity is unknown. Indeed, already, large and disfiguring scars lead to insecurity and embarrassment. Might we expect an even more visceral reaction due to XTx? It might be that the experience of having a “pig heart” may only exacerbate this both from challenges to self-conception from feeling “part-pig” and from the potential for bullying by other children.

XTx in children may open a world of benefit that we have a moral imperative to study, yet, we also have several unique issues to solve and must balance potential harms with probabilities that are hard to assess. If we proceed, we must do so with caution because of unique paediatric ethical challenges from 1) increased paediatric susceptibility to infection (xenozoonosis), 2) possible psychological challenges with identity, mental health, and maturity, risk, and moral hazard, and 3) issues arising from assent, consent, and research. Given that adult XTx development has already begun, it may be such that the ethical balance tips toward starting here and (maybe) only next moving on to children. Ultimately when all the paediatric advantages and risks are weighed, we should favour piloting xenotransplantation in adults but must advocate development of paediatric specific protocols.

Author: Anthony Merlocco

Affiliations: Associate Professor at the University of Tennessee Health Science Center

Competing interests: None

Acknowledgements: The author would like to thank Dr. César Palacios-González for his important contributions and feedback.