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Yale scientists restore cellular function in 32 dead pig brains
Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.
- Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
- They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
- The research raises many ethical questions and puts to the test our current understanding of death.
The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?
But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.
What's dead may never die, it seems
The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.
BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.
The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.
As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.
The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.
"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.
An ethical gray matter
Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.
The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.
Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.
Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?
"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."
One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.
The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.
"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.
It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.
Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?
The dilemma is unprecedented.
Setting new boundaries
Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."
She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.
- Why Cryogenics Is Bogus - Big Think ›
- Factory farm death rate of pig sows increases sharply - Big Think ›
Some mysteries take generations to unfold.
- In 1959, a group of nine Russian hikers was killed in an overnight incident in the Ural Mountains.
- Conspiracies about their deaths have flourished ever since, including alien invasion, an irate Yeti, and angry tribesmen.
- Researchers have finally confirmed that their deaths were due to a slab avalanche caused by intense winds.
a: Last picture of the Dyatlov group taken before sunset, while making a cut in the slope to install the tent. b: Broken tent covered with snow as it was found during the search 26 days after the event.
Photographs courtesy of the Dyatlov Memorial Foundation.<p>Finally, a <a href="https://www.nature.com/articles/s43247-020-00081-8" target="_blank">new study</a>, published in the Nature journal Communications Earth & Environment, has put the case to rest: it was a slab avalanche.</p><p>This theory isn't exactly new either. Researchers have long been skeptical about the avalanche notion, however, due to the grade of the hill. Slab avalanches don't need a steep slope to get started. Crown or flank fractures can quickly release as little as a few centimeters of earth (or snow) sliding down a hill (or mountain). </p><p>As researchers Johan Gaume (Switzerland's WSL Institute for Snow and Avalanche Research SLF) and Alexander Puzrin (Switzerland's Institute for Geotechnical Engineering) write, it was "a combination of irregular topography, a cut made in the slope to install the tent and the subsequent deposition of snow induced by strong katabatic winds contributed after a suitable time to the slab release, which caused severe non-fatal injuries, in agreement with the autopsy results."</p><p>Conspiracy theories abound when evidence is lacking. Twenty-six days after the incident, a team showed up to investigate. They didn't find any obvious sounds of an avalanche; the slope angle was below 30 degrees, ruling out (to them) the possibility of a landslide. Plus, the head injuries suffered were not typical of avalanche victims. Inject doubt and crazy theories will flourish.</p>
Configuration of the Dyatlov tent installed on a flat surface after making a cut in the slope below a small shoulder. Snow deposition above the tent is due to wind transport of snow (with deposition flux Q).
Photo courtesy of Communications Earth & Environment.<p>Add to this Russian leadership's longstanding battle with (or against) the truth. In 2015 the Investigative Committee of the Russian Federation decided to reopen this case. Four years later the agency concluded it was indeed a snow avalanche—an assertion immediately challenged within the Russian Federation. The oppositional agency eventually agreed as well. The problem was neither really provided conclusive scientific evidence.</p><p>Gaume and Puzrin went to work. They provided four critical factors that confirmed the avalanche: </p><ul><li>The location of the tent under a shoulder in a locally steeper slope to protect them from the wind </li><li>A buried weak snow layer parallel to the locally steeper terrain, which resulted in an upward-thinning snow slab</li><li>The cut in the snow slab made by the group to install the tent </li><li>Strong katabatic winds that led to progressive snow accumulation due to the local topography (shoulder above the tent) causing a delayed failure</li></ul><p>Case closed? It appears so, though don't expect conspiracy theories to abate. Good research takes time—sometimes generations. We're constantly learning about our environment and then applying those lessons to the past. While we can't expect every skeptic to accept the findings, from the looks of this study, a 62-year-old case is now closed.</p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a> and <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a>. His most recent book is</em> "<em><a href="https://www.amazon.com/gp/product/B08KRVMP2M?pf_rd_r=MDJW43337675SZ0X00FH&pf_rd_p=edaba0ee-c2fe-4124-9f5d-b31d6b1bfbee" target="_blank" rel="noopener noreferrer">Hero's Dose: The Case For Psychedelics in Ritual and Therapy</a>."</em></p>
As patients approached death, many had dreams and visions of deceased loved ones.
One of the most devastating elements of the coronavirus pandemic has been the inability to personally care for loved ones who have fallen ill.
Research reveals a new evolutionary feature that separates humans from other primates.
- Researchers find a new feature of human evolution.
- Humans have evolved to use less water per day than other primates.
- The nose is one of the factors that allows humans to be water efficient.
A model of water turnover for humans and chimpanzees who have similar fat free mass and body water pools.
Credit: Current Biology
Being skeptical isn't just about being contrarian. It's about asking the right questions of ourselves and others to gain understanding.