New research is confounding conventional wisdom about life and death.
Researchers at Yale University used a new technology to restore cells in some organs of pigs that had just died, bringing the animals’ cells back to function. The findings, which were published Wednesday in the scientific journal Nature, raise profound ethical questions about how medicine defines death but also teases new possibilities for the collection of human organs for transplant.
“My eyes went wide,” Brendan Parent, an assistant professor of bioethics at the NYU Grossman School of Medicine, said about the moment he first read the new findings. “My brain went to all the crazy places we could go in 20 or 30 years.” Parent was not involved in the study, but was asked by Nature to write a commentary discussing the implications of the new technology.
The research is still in an early, experimental phase and many years from potential use in humans. It could ultimately help to extend the lives of people whose hearts have stopped beating or who have suffered a stroke. The technology also shows potential to dramatically shift how organs are collected for transplant and increase their availability to patients in need.
When the heart stops beating, blood flow is cut off from the body in a process called ischemia and a cascade of biochemical effects begins. Oxygen and nutrients are cut off from tissues. Cells begin to die. It’s a path toward death that causes damage that scientists have considered irreversible.
The new research challenges that idea.
“The demise of cells can be halted,” Dr. Nenad Sestan, a professor of neuroscience at the Yale School of Medicine and an author of the new research, said during a news conference. “We restored some functions of cells across multiple organs that should have been dead.”
The Yale researchers accomplished this feat by constructing a system of pumps, sensors and tubing that connects to pig arteries. They also developed a formula with 13 medical drugs that can be mixed with blood and then pumped into the animals’ cardiovascular systems. The research builds on previous work at Yale, which demonstrated that some damage to brain cells could be reversible after blood flow was cut off. Yale has filed a patent for the new technology, but is making its methods and protocols freely available for academic or nonprofit use, the study says.
To evaluate how well the new system, called OrganEx, works, the researchers caused heart attacks in pigs that had been anesthetized. The pigs were dead for an hour, and the researchers cooled their bodies and used neural inhibitors to ensure the animals did not regain consciousness during subsequent experiments.
Then, the researchers began to use the OrganEx system. They compared its performance against ECMO, a life-support technology used in hospitals today in which a machine oxygenates blood and circulates it throughout the body.
OrganEx restored circulation and prompted the repair of damaged cells. For example, the scientists saw heart cells contract and electrical activity return. Other organs, including kidneys, also showed improvements, the study says.
The pigs treated with OrganEx startled researchers. During experimentation, the dead pigs’ heads and necks moved under their own power. The animals remained under heavy anesthesia.
“We can say that animals were not conscious during these moments and we don’t have enough information to speculate why they moved,” Sestan said.
The researchers do view the neck jerk is an indication some muscle function was restored after death.
The OrganEx research is a single study in a laboratory setting in which researchers had total control over the circumstances of the pigs’ death and treatment. Even so, the early results open up possibilities that would have seemed like science fiction a few years ago.
“The assumption that loss of oxygen to the brain or organs within seconds to minutes means those organs are irretrievably damaged and loss — that’s not true,” said Nita Farahany, a neuroethicist and law professor at Duke University, who was not involved in the study.
The definition of death is a moving target that has shifted as new life-support technology like ventilators or ECMO were developed. Ethicists view OrganEx as ECMO on steroids and something that could change the definition of what medical death means.
“Death is a process. Technology has, at several critical moments in the course of the last several decades, shifted the goal posts for when that process begins and when we can say that the process of death has ended,” Parent, the NYU bioethicist, said. “All the iterations of machines that can sustain or restart lung function and or heart function have changed our perception, our experience, of when we can say it’s worth trying to save someone’s life.”
The Yale researchers don’t foresee the use of OrganEx to treat people anytime soon.
“Before you hook this up to a person to try to undo whole body ischemic damage in a human being, you’d need to do a lot more work. Not that it couldn’t be done, but that’s going to be a long ways away,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “There’s a great deal more experimentation that would be required.”
The implications of only partially reversing damage to a patient who suffered a deadly heart attack or who had drowned are immense, he said.
“You’d have to think about what is the state to which a human being would be restored, if they had been seriously damaged by the ischemia and you gave them kind of a perfusate that reversed some but not all of that damage. That could be a terrible thing, right?” Latham said.
Instead, the researchers see more immediate avenues for real-world use for the research. Today, transplant surgeons must scramble to stay ahead of ischemia and prevent organs from going too long without blood supply.
OrganEx could help transplant organs move longer distances and reach people who would otherwise be out of range for a transplant, Latham said. It could also prevent organs from being lost to ischemic damage, potentially expanding organ supply.
“From a transplant perspective, when every second is critical — what if it’s not? What if we have more time?” Farahany said.
The new technology’s potential opens new and compelling medical ethics questions — and adds a new twist to some that remain unresolved.
Ethicists have been debating whether it’s appropriate to use technology like ECMO to preserve organs in patients who are declared dead under cardiorespiratory criteria.
“If we decide someone is dead because their heart is stopped, but we use a technology to restart their heart — even for organ preservation — does that undermine the determination of death?” asked Parent, outlining the argument about what remains a rare practice.
There is no regulation for how long doctors must wait to determine death before restarting technology like ECMO to preserve organs for transplant, Farahany said. OrganEx could allow for more time between death and organ preservation.
It’s also possible OrganEx could change the threshold of when it’s ethical for doctors to let a patient die and then preserve their organs for donation.
“In the short run, it’s not a treatment. But if it is so effective it could be a treatment — you certainly couldn’t recover organs from somebody if you could continue to do things to save their life,” Farahany said.
It’s a technology that remains in its earliest stages, but could be impactful enough to redefine the line between life and death.