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.
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The idea of 'absolute time' is an illusion. Physics and subjective experience reveal why.
- Since Einstein posited his theory of general relativity, we've understood that gravity has the power to warp space and time.
- This "time dilation" effect occurs even at small levels.
- Outside of physics, we experience distortions in how we perceive time — sometimes to a startling extent.
Physics without time<p>In his book "The Order of Time," Italian theoretical physicist Carlo Rovelli suggests that our perception of time — our sense that time is forever flowing forward — could be a highly subjective projection. After all, when you look at reality on the smallest scale (using equations of quantum gravity, at least), time vanishes.</p><p style="margin-left: 20px;">"If I observe the microscopic state of things," writes Rovelli, "then the difference between past and future vanishes … in the elementary grammar of things, there is no distinction between 'cause' and 'effect.'"</p><p>So, why do we perceive time as flowing <em>forward</em>? Rovelli notes that, although time disappears on extremely small scales, we still obviously perceive events occur sequentially in reality. In other words, we observe entropy: Order changing into disorder; an egg cracking and getting scrambled.</p><p>Rovelli says key aspects of time are described by the second law of thermodynamics, which states that heat always passes from hot to cold. This is a one-way street. For example, an ice cube melts into a hot cup of tea, never the reverse. Rovelli suggests a similar phenomenon might explain why we're only able to perceive the past and not the future.</p><p style="margin-left: 20px;">"Any time the future is definitely distinguishable from the past, there is something like heat involved," Rovelli wrote for the <a href="https://www.ft.com/content/ce6ef7b8-429a-11e8-93cf-67ac3a6482fd" target="_blank"><em>Financial Times</em></a>. "Thermodynamics traces the direction of time to something called the 'low entropy of the past', a still mysterious phenomenon on which discussions rage."</p>
The strange subjectivity of time<p>Time moves differently atop a mountain than it does on a beach. But you don't need to travel any distance at all to experience strange distortions in your perception of time. In moments of life-or-death fear, for example, your brain would release large amounts of adrenaline, which would speed up your internal clock, causing you to perceive the outside world as moving slowly.<br></p><p>Another common distortion occurs when we focus our attention in particular ways.</p><p style="margin-left: 20px;">"If you're thinking about how time is <em>currently</em> passing by, the biggest factor influencing your time perception is attention," Aaron Sackett, associate professor of marketing at the University of St. Thomas, told <em><a href="https://gizmodo.com/why-does-time-slow-down-and-speed-up-1840133782" target="_blank">Gizmodo</a></em>.<em> "</em>The more attention you give to the passage of time, the slower it tends to go. As you become distracted from time's passing—perhaps by something interesting happening nearby, or a good daydreaming session—you're more likely to lose track of time, giving you the feeling that it's slipping by more quickly than before. "Time flies when you're having fun," they say, but really, it's more like "time flies when you're thinking about other things." That's why time will also often fly by when you're definitely <em>not</em> having fun—like when you're having a heated argument or are terrified about an upcoming presentation."</p><p>One of the most mysterious ways people experience time-perception distortions is through psychedelic drugs. In an interview with <a href="https://www.theguardian.com/books/2018/apr/14/carlo-rovelli-exploding-commonsense-notions-order-of-time-interview" target="_blank"><em>The Guardian</em></a>, Rovelli described a time he experimented with LSD.</p><p style="margin-left: 20px;">"It was an extraordinarily strong experience that touched me also intellectually," he said. "Among the strange phenomena was the sense of time stopping. Things were happening in my mind but the clock was not going ahead; the flow of time was not passing any more. It was a total subversion of the structure of reality."<br></p><p>It seems few scientists or philosophers believe time is completely an illusion.</p><p style="margin-left: 20px;">"What we call <em>time</em> is a rich, stratified concept; it has many layers," Rovelli told <em><a href="https://physicstoday.scitation.org/do/10.1063/PT.6.4.20190219a/full/" target="_blank">Physics Today</a>.</em> "Some of time's layers apply only at limited scales within limited domains. This does not make them illusions."</p>What <em>is</em> an illusion is the idea that time flows at an absolute rate. The river of time might be flowing forever forward, but it moves at different speeds, between people, and even within your own mind.
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Controversial physics theory says reality around us behaves like a computer neural network.
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- The theory claims that natural selection produces both atoms and "observers".
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