New research is confusing conventional wisdom about life and death.
Researchers at Yale University have used new technology to restore cells from some recently dead pig organs, restoring the animal’s cells to function. The findings, published Wednesday in the scientific journal Nature, raise deep ethical questions about how medicine defines death, but also anticipate new possibilities for harvesting human organs for transplantation.
“My eyes went wide,” said Brendan Parent, an assistant professor of bioethics at NYU Grossman School of Medicine, when he first read the new findings. “My brain has gone 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 comment discussing the implications of the new technology.
The research is still in an early experimental phase and many years from its potential use in humans. It could ultimately help extend the lives of people whose hearts have stopped beating or who have suffered a stroke. The technology also shows the potential to drastically change the way organs are harvested for transplantation and increase their availability for 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 from the tissues. The cells begin to die. It is a path to death that causes damage that scientists have considered irreversible.
The new research challenges that idea.
“Cell disappearance can be stopped,” said Dr. Nenad Sestan, a neuroscience professor at Yale School of Medicine and author of the new research, at a news conference. “We have restored some cell functions on multiple organs that should have died.”
Yale researchers accomplished this feat by building a system of pumps, sensors and tubes that connect to pig arteries. They also developed a formula with 13 drugs that can be mixed with blood and then pumped into the cardiovascular systems of animals. The research builds on previous work at Yale, which showed that some damage to brain cells could be reversible after blood flow is 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 the new system, called OrganEx, worked, the researchers caused heart attacks in pigs that had been anesthetized. The pigs have been dead for an hour, and the researchers cooled their bodies and used neural inhibitors to make sure the animals did not regain consciousness during subsequent experiments.
Then, the researchers started using the OrganEx system. They compared its performance to ECMO, a life support technology used in hospitals today where a machine oxygenates the blood and circulates it throughout the body.
OrganEx restored circulation and prompted the repair of damaged cells. For example, scientists have seen heart cells contract and resume electrical activity. Other organs, including the kidneys, also showed improvements, the study says.
The pigs treated with OrganEx surprised the researchers. During the experiment, the heads and necks of the dead pigs moved under their own power. The animals remained under heavy anesthesia.
“We can say that the animals were not conscious during these moments and we don’t have enough information to speculate as to why they moved,” Sestan said.
Researchers believe the snapping of the neck is an indication that some muscle functions have been restored after death.
The OrganEx research is a single study in a laboratory setting where researchers had total control over the circumstances of the death and treatment of the pigs. Even so, the first results open up possibilities that would have sounded like science fiction a few years ago.
“The assumption that the loss of oxygen to the brain or organs in seconds or minutes means those organs are hopelessly damaged and leaking – that’s not true,” said Nita Farahany, a neuroethics and law professor at Duke University, who is not been involved in the study.
The definition of death is a moving target that has changed with the development of new life support technologies such as ventilators or ECMO. Ethics experts see OrganEx as ECMO on steroids and something that could change the definition of what medical death means.
“Death is a process. Technology, at several critical moments over the past few decades, has shifted the focus for when that process begins and when we can say the death process is over, “said NYU bioethicist Parent.” All machine iterations in being able to 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. “
Yale researchers do not foresee the use of OrganEx to cure people anytime soon.
“Before you connect it to a person to try to undo whole-body ischemic damage in a human, you would need to do a lot more work. Not that it can’t be done, but it will take a long time, ”said Stephen Latham, director of Yale’s Interdisciplinary Center for Bioethics. “There is a lot more experimentation that would be needed.”
The implications of only partially reversing the damage to a patient who suffered a fatal heart attack or drowned are immense, he said.
“You should think about what state a human would be in if he was severely damaged by ischemia and you gave him some kind of perfusate that reversed some but not all of that damage. That could be terrible, right? ”Latham said.
Instead, researchers see more immediate avenues for real-world use for research. Today, transplant surgeons have to struggle to keep up with ischemia and prevent organs from running out of blood for too long.
OrganEx could help transplanted organs travel greater distances and reach people who would otherwise be out of reach for a transplant, Latham said. It could also prevent organ loss due to ischemic damage, potentially expanding the supply of organs.
“From a transplant point of view, when is every second critical, and if it isn’t? What if we have more time? ”Farahany said.
The potential of the new technology opens up new and compelling medical ethics questions and adds a new twist to some that remain unsolved.
Ethics experts have debated whether it is appropriate to use a technology such as ECMO to preserve organs in patients declared dead based on cardiorespiratory criteria.
“If we decide that someone has died because their heart is still, but we use a technology to restart their heart, including organ preservation, does that undermine the determination of death?” Parent asked, outlining the subject of what remains a rare practice.
There is no regulation for how long doctors must wait to determine death before restarting the technology as an ECMO to preserve organs for transplants, Farahany said. OrganEx could allow more time between death and organ preservation.
It is also possible that OrganEx may change the threshold for when it is ethical for doctors to let a patient die and thus preserve their organs for donation.
“In the short term, it’s not a treatment. But if it’s that effective, it could be a treatment – you certainly wouldn’t be able to recover organs from someone if you could keep doing things to save their life, ”Farahany said.
It’s a technology that remains in its early stages, but it could have such an impact that it redefines the line between life and death.