By Richard B. Gibson.
Nature recently published a study by a team at Yale University in which the circulation and cellular activity of a pig’s vital organs – pancreas, liver, kidney, heart, lungs, and even brain – were restored over an hour after death. While exploratory, the study’s results are nonetheless remarkable, challenging the intuition of death’s irreversibility and having potential severe downstream implications for organ donation practicalities and policies.
In short, the researchers developed OrganEx from the 2019 BrainEx system. While BrainEx demonstrated the potential to preserve anatomical and neural cell integrity, this 2022 update develops this potential, seeking to maintain cellular function within multiple vital organs within the porcine body posthumously. OrganEx comes in two parts, an infusion device and a synthetic solution. An hour after the pig’s demise from an induced cardiac arrest, the Yale team connected the animal’s body to the infusion device. It then began circulating the perfusate – containing an artificial oxygen carrier, vitamins, amino acids, and a complex drug cocktail – around the pig’s body, alongside its blood. After six hours, the team observed that oxygen had begun flowing to multiple tissues and that the heart had demonstrated some electrical activity. Additionally, tissue integrity appeared preserved, there was a decrease in cell death, some cells were metabolising glucose and synthesising proteins, and some cellular repair mechanisms appeared active. In other words, compared to the control groups, OrganEx successfully initiated posthumous cell repair in damaged organs.
Nevertheless, OrganEx raises multiple ethical issues. So, I want to give a snapshot of two of them. The first being the use of animals in research and the second being our understanding of death.
Animal ethics
As with all research involving animals, we need to acknowledge concerns regarding the avoidance of harm and respect for autonomy. In the OrganEx case, simply put, was it right to use pigs as the objects of the study?
As far as can be told, the pigs didn’t suffer subjective harm due to their participation. Following recommendations from Yale’s Institutional Animal Care and Use Committee, in addition to external advisory and ethics groups, the pigs were fully sedated before death. As such, they never experienced the heart attack, any pain resulting from it, or the rest of the experiment. Additionally, the pigs didn’t demonstrate any neural activity measurable via an EEG whilst connected to OrganEx.
However, beyond the animal’s subjective experience, the fact that they were deliberately killed for this experiment might cause some consternation as death itself can be considered harmful, especially given the abundance of evidence suggesting that pigs have complex internal worlds.
A slaughterhouse provided the brain for the 2019 BrainEx study. So, the animal would have died regardless of study participation. But, this is not the case in OrganEx, as the pigs used here were killed explicitly for the study’s purposes. If not for their participation, they could have continued living. So, we might want to question whether this was necessary and whether an alternative to the porcine model could have been used, thereby sparing the pigs’ lives. One counterintuitive option could have been to jump straight to posthumous human experimentation. This might seem odd given that research structures typically place human experimentation at the latter stages, after animal involvement. However, the OrganEx study had, as its focus, a corpse. And, given that a live pig arguably has a stronger claim to moral consideration than an already dead person, it seems reasonable to skip the former and go straight for the latter. After all, a deceased person has already experienced the harm of death.
And death is?
Death’s often considered irreversible. This makes someone who’s just drowned different from Napoleon – the former’s demise might be undone while the latter’s cannot. So to say that someone is dead is to say they will remain so. This idea is even reflected in legal and regulatory contexts, with irreversibility invoked in legislation like the USA’s 1981 Uniform Determination of Death Act and codes of practices like that of the UK’s Academy of Medical Royal Colleges.
OrganEx, however, potentially shifts what we understand to be irreversible radically. Previously, it would seem evident that a body kept at around 36°C for over an hour without any medical intervention would be unrevivable. Yet, as OrganEx demonstrates, albeit in a specific context, this doesn’t seem necessarily accurate. Posthumous cellular degradation doesn’t seem as inevitable as once thought. While the OrganEx study’s application is geared towards cellular activity, further research might reveal similar revelations concerning tissues and whole organs.
Now, OrganEx isn’t the first innovation to demonstrate a capacity to challenge commonly held ideas of death. For example, the advent of ventilators and heart transplants did the same concerning the cardiopulmonary criterion. Nevertheless, its potential to alter our perception of irreversibility presents a significant challenge regarding our understanding of mortality. After all, we ascribe different social, ethical, and legal considerations based on whether someone’s alive or dead. Ensuring that such considerations – like when to harvest organs or when defiling a corpse becomes murder – are assigned correctly is of fundamental importance.
Ultimately, OrganEx seems to have displayed the potential, like many innovations before it, to highlight irreversibility not as a concrete fact of biology but as a medical perspective seen through the lens of technological capacity.
Author: Richard B. Gibson
Affiliation: University of Texas Medical Branch
Competing interests: None declared
Social media accounts of post author: @RichardBGibson