In 2019, neuroscientists and doctors from Yale University managed to recover some of the brain functions of a pig that had been slaughtered four hours earlier. Now, that same group has repeated the achievement, this time in all the vital organs of several pigs that were dead for an hour. The research, recently published in Nature, is based on a complex injection system of a kind of synthetic superblood that reverses cell death. This breakthrough opens a new path for organ transplantation, but also raises questions about the timing of death.
After the last heartbeat, a chain of events begins: the lack of blood supply (ischemia) implies the absence of oxygen and other essential elements that lead to the death of cells, tissues and organs. In this investigation, scientists caused cardiac arrest in dozens of pigs who had previously been anesthetized. After an hour without blood supply – an hour of being considered medically dead – they were divided into three study groups. Some were connected to an ECMO life support system used in severe cases in which the heart and lungs stop working, while others were left as a control group and didn’t receive any resuscitation technique whatsoever. A third group was connected to a perfusion system (the slow and continuous introduction of liquids) called OrganEx, which was designed by the research team. After six hours, the researchers examined the state of the pigs’ cells and tissues, as well as the functioning of their vital organs.
David Andrijevic, a neuroscientist at the Yale University School of Medicine and co-author of the experiment, explained in a virtual press conference that “not all cells die immediately – there are a series of events that take their time.” What the researchers simply did was take advantage of this period of time. “It’s a process in which you can intervene, stop and restore some cellular function.”
They had not resurrected the pigs… rather, they had resurrected their organs
“OrganEx is made up of two components. The first is a perfusion system similar to cardiac and respiratory support systems that connect to the circulatory system. The second part is a synthetic cellular fluid that is pumped and contains different elements optimized to promote cell health and reduce inflammation and cell death throughout the body. The base of this fluid is a modified hemoglobin, the protein that transports oxygen.”
After having about 20 pigs connected to OrganEx for six hours, the team analyzed various parameters at the cellular level in the brain, lungs, heart, liver and kidneys. On virtually every metric, OrganEx outperformed ECMO. The scientists found that certain key cellular functions were active in many areas of the pigs’ bodies and that some organ functions had been restored. Thus, they observed that neurons and astrocytes in two brain regions recovered their pre-ischemia state. They also detected electrical activity in the heart, which retained the ability to contract. Furthermore, they saw that the different organs recovered the glucose levels present in the artificial blood. Finally, they found that, at the genetic level, the cellular machinery restarted its repair mechanisms. But – and this is what they wanted to emphasize, both in the published study and in the press conference – the team did not detect a recovery of general brain activity. That is, they had not resurrected the pigs… rather, they had resurrected their organs.
“Basically, our findings highlight a previously overlooked ability of the large mammalian body to recover after cessation of blood flow. This could be used to increase the availability of organs for transplants or to treat localized organ failure,” Andrijevic concluded.
His colleague, Stephen Latham, is director of the Yale Interdisciplinary Center for Bioethics and a co-author of the study. For him, this work has and will have many applications, especially when it comes to organ transplants.
“I think the technology holds great promise for our ability to preserve organs after harvesting them from a donor. You could take the organ and hook it up to this perfusion system so [that it can be] transported over a long distance, for a long period of time, to a recipient in need.”
On the possibility of connecting a human after cerebral, myocardial or renal ischemia, Latham cut speculation short: “This is very far from [being used] on humans. The goal here was to see if using perfusate (the fluid they created) could restore metabolic and cellular function in a wide range of organs. We have discovered that it can. But it does not restore all functions in all organs,” he clarified.
Future application in living humans would require, he added, “much more to be studied about the extent to which ischemic damage is undone in different types of organs before one even comes close to thinking of trying an experiment like this [with] humans.”
Sam Parnia, the director of research in resuscitation and critical care at New York University, commented: “This study shows that our social convention about death – that is, [the idea] of an absolute end – is not scientifically valid. On the contrary, death is a biological process that remains treatable and reversible for hours after it has occurred,” he explained to the Science Media Center (SMC).
Anders Sandberg, a researcher at the Institute for the Future of Humanity at the University of Oxford, also weighed in on the study:
“Ethically, [the experiments] seem to bring good news without collateral problems. In the future, such methods could also make a treatment after a very serious stroke or trauma more effective: by saving patients who would otherwise have died, it could reduce the number of transplants available. This may still be good news… but there is a risk that it will essentially prevent people from dying rather than [help them] recover.”
Sandberg also noted that there is an increasingly challenging ethical problem surrounding the idea of reviving organs, but not consciousness.
“As technology advances, we will be able to find more ways to keep bodies alive, despite not being able to revive the person we really care about.”