In 2019, neuroscientists and doctors at Yale University managed to recover some of the brain function of a pig that had been slaughtered four hours earlier. Now, this same group has repeated the feat, this time in everything the vital organs of several pigs that have been 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 avenue for organ transplantation, but also raises questions about the time of death.
After the last heartbeat, a chain of events begins: the lack of blood supply (ischemia) involves the absence of oxygen and other essential elements which lead to the death of cells, tissues and organs. In this investigation, scientists caused cardiac arrest in dozens of previously anesthetized pigs. After an hour without a blood supply – an hour when they were considered medically dead – they were divided into three study groups. Some were hooked up 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 received no resuscitation techniques. A third group was connected to an infusion system (the slow, continuous introduction of liquids) called OrganEx, which was designed by the research team. After six hours, the researchers examined the condition of the pigs’ cells and tissues, as well as the functioning of their vital organs.
David Andrijevic, a neuroscientist at Yale University School of Medicine and co-author of the experiment, explained during a virtual press conference that “not all cells die immediately – there is 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 certain cellular functions.”
They didn’t resurrect the pigs…rather they resurrected their organs.
“OrganEx is made up of two components. The first is an infusion system similar to cardiac and respiratory support systems that connects to the circulatory system. The second part is a synthetic cellular fluid that is pumped and contains different elements optimized to support cellular health and reduce inflammation and cell death throughout the body. The basis of this fluid is modified hemoglobin, the protein that carries oxygen.
After connecting around 20 pigs 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 cell functions were active in many areas of the pigs’ bodies and that certain organ functions were restored. Thus, they observed that neurons and astrocytes in two regions of the brain returned to their pre-ischemic state. They also detected electrical activity in the heart, which retained the ability to contract. In addition, they saw that the different organs recovered the glucose levels present in the artificial blood. Finally, they discovered that at the genetic level, the cellular machinery restarts 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 in general brain activity. That is to say, they had not resurrected the pigs… but rather, they had resurrected their organs.
“Fundamentally, our findings highlight a previously overlooked ability of large mammalian bodies to recover after blood flow has ceased. 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 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 removing them from a donor. You could take the organ and hook it up to this infusion system to [that it can be] transported a long distance, for a long time, to a recipient in need.
On the possibility of connecting a human after cerebral, myocardial or renal ischemia, Latham cut short speculation: “It’s very far from being [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 is possible. But it does not restore all functions in all organs,” he said.
Future application in living humans would require, he added, “many more studies of the extent to which ischemic damage is repaired in different types of organs before one even thinks of trying an experiment. like this one”. [with] humans.”
Sam Parnia, Director of Research in Resuscitation and Critical Care at New York University, commented: “This study shows that our social convention about death, i.e. [the idea] of an absolute end – is not scientifically sound. Rather, death is a biological process that remains treatable and reversible for hours after it occurs,” he told the Science Media Center (SMC).
Anders Sandberg, a researcher at the Institute for the Future of Humanity at the University of Oxford, also commented on the study:
“Ethically, [the experiments] seem to bring good news without collateral problems. In the future, such methods could also make treatment after a stroke or very serious trauma more effective: by saving patients who would otherwise have died, this could reduce the number of transplants available. That might still be good news… but there’s a risk that it will essentially stop people from dying rather than [help them] retrieve.”
Sandberg also noted that there is an increasingly difficult ethical issue surrounding the idea of reviving organs, but not consciousness.
“As technology advances, we’ll be able to find more ways to keep bodies alive, even if we’re not able to revive the person we really care about.”