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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 ›
- You may be dead, but your brains cells aren’t. Yet. - Big Think ›
Evolution doesn't clean up after itself very well.
- An evolutionary biologist got people swapping ideas about our lingering vestigia.
- Basically, this is the stuff that served some evolutionary purpose at some point, but now is kind of, well, extra.
- Here are the six traits that inaugurated the fun.
The plica semilunaris<img class="rm-lazyloadable-image rm-shortcode" type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NjgwMS9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTY3NDg5NTg1NX0.kdBYMvaEzvCiJjcLEPgnjII_KVtT9RMEwJFuXB68D8Q/img.png?width=980" id="59914" width="429" height="350" data-rm-shortcode-id="b11e4be64c5e1f58bf4417d8548bedc7" data-rm-shortcode-name="rebelmouse-image" />
The human eye in alarming detail. Image source: Henry Gray / Wikimedia commons<p>At the inner corner of our eyes, closest to the nasal ridge, is that little pink thing, which is probably what most of us call it, called the caruncula. Next to it is the plica semilunairs, and it's what's left of a third eyelid that used to — ready for this? — blink horizontally. It's supposed to have offered protection for our eyes, and some birds, reptiles, and fish have such a thing.</p>
Palmaris longus<img class="rm-lazyloadable-image rm-shortcode" type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NjgwNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMzQ1NjUwMn0.dVor41tO_NeLkGY9Tx46SwqhSVaA8HZQmQAp532xLxA/img.jpg?width=980" id="879be" width="1920" height="2560" data-rm-shortcode-id="4089a32ea9fbb1a0281db14332583ccd" data-rm-shortcode-name="rebelmouse-image" />
Palmaris longus muscle. Image source: Wikimedia commons<p> We don't have much need these days, at least most of us, to navigate from tree branch to tree branch. Still, about 86 percent of us still have the wrist muscle that used to help us do it. To see if you have it, place the back of you hand on a flat surface and touch your thumb to your pinkie. If you have a muscle that becomes visible in your wrist, that's the palmaris longus. If you don't, consider yourself more evolved (just joking).</p>
Darwin's tubercle<img class="rm-lazyloadable-image rm-shortcode" type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NjgxMi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0ODUyNjA1MX0.8RuU-OSRf92wQpaPPJtvFreOVvicEwn39_jnbegiUOk/img.jpg?width=980" id="687a0" width="819" height="1072" data-rm-shortcode-id="ff5edf0a698e0681d11efde1d7872958" data-rm-shortcode-name="rebelmouse-image" />
Darwin's tubercle. Image source: Wikimedia commons<p> Yes, maybe the shell of you ear does feel like a dried apricot. Maybe not. But there's a ridge in that swirly structure that's a muscle which allowed us, at one point, to move our ears in the direction of interesting sounds. These days, we just turn our heads, but there it is.</p>
Goosebumps<img class="rm-lazyloadable-image rm-shortcode" type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NzMxNC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNzEyNTc2Nn0.aVMa5fsKgiabW5vkr7BOvm2pmNKbLJF_50bwvd4aRo4/img.jpg?width=980" id="d8420" width="1440" height="960" data-rm-shortcode-id="8827e55511c8c3aed8c36d21b6541dbd" data-rm-shortcode-name="rebelmouse-image" />
Goosebumps. Photo credit: Tyler Olson via Shutterstock<p>It's not entirely clear what purpose made goosebumps worth retaining evolutionarily, but there are two circumstances in which they appear: fear and cold. For fear, they may have been a way of making body hair stand up so we'd appear larger to predators, much the way a cat's tail puffs up — numerous creatures exaggerate their size when threatened. In the cold, they may have trapped additional heat for warmth.</p>
Tailbone<img class="rm-lazyloadable-image rm-shortcode" type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NzMxNi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY3MzQwMjc3N30.nBGAfc_O9sgyK_lOUo_MHzP1vK-9kJpohLlj9ax1P8s/img.jpg?width=980" id="9a2f6" width="1440" height="1440" data-rm-shortcode-id="4fe28368d2ed6a91a4c928d4254cc02a" data-rm-shortcode-name="rebelmouse-image" />
Image source: Decade3d-anatomy online via Shutterstock<p>Way back, we had tails that probably helped us balance upright, and was useful moving through trees. We still have the stump of one when we're embryos, from 4–6 weeks, and then the body mostly dissolves it during Weeks 6–8. What's left is the coccyx.</p>
The palmar grasp reflex<img class="rm-lazyloadable-image rm-shortcode" type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NzMyMC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNjY0MDY5NX0.OSwReKLmNZkbAS12-AvRaxgCM7zyukjQUaG4vmhxTtM/img.jpg?width=980" id="8804c" width="1440" height="960" data-rm-shortcode-id="67542ee1c5a85807b0a7e63399e44575" data-rm-shortcode-name="rebelmouse-image" />
Palmar reflex activated! Photo credit: Raul Luna on Flickr<p> You've probably seen how non-human primate babies grab onto their parents' hands to be carried around. We used to do this, too. So still, if you touch your finger to a baby's palm, or if you touch the sole of their foot, the palmar grasp reflex will cause the hand or foot to try and close around your finger.</p>
Other people's suggestions<p>Amir's followers dove right in, offering both cool and questionable additions to her list. </p>
Fangs?<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Lower mouth plate behind your teeth. Some have protruding bone under the skin which is a throw back to large fangs. Almost like an upsidedown Sabre Tooth.</p>— neil crud (@neilcrud66) <a href="https://twitter.com/neilcrud66/status/1085606005000601600?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Hiccups<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Sure: <a href="https://t.co/DjMZB1XidG">https://t.co/DjMZB1XidG</a></p>— Stephen Roughley (@SteBobRoughley) <a href="https://twitter.com/SteBobRoughley/status/1085529239556968448?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Hypnic jerk as you fall asleep<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">What about when you “jump” just as you’re drifting off to sleep, I heard that was a reflex to prevent falling from heights.</p>— Bann face (@thebanns) <a href="https://twitter.com/thebanns/status/1085554171879788545?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script> <p> This thing, often called the "alpha jerk" as you drop into alpha sleep, is properly called the hypnic jerk,. It may actually be a carryover from our arboreal days. The <a href="https://www.livescience.com/39225-why-people-twitch-falling-asleep.html" target="_blank" data-vivaldi-spatnav-clickable="1">hypothesis</a> is that you suddenly jerk awake to avoid falling out of your tree.</p>
Nails screeching on a blackboard response?<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Everyone hate the sound of fingernails on a blackboard. It's _speculated_ that this is a vestigial wiring in our head, because the sound is similar to the shrill warning call of a chimp. <a href="https://t.co/ReyZBy6XNN">https://t.co/ReyZBy6XNN</a></p>— Pet Rock (@eclogiter) <a href="https://twitter.com/eclogiter/status/1085587006258888706?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Ear hair<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Ok what is Hair in the ears for? I think cuz as we get older it filters out the BS.</p>— Sarah21 (@mimix3) <a href="https://twitter.com/mimix3/status/1085684393593561088?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Nervous laughter<blockquote class="twitter-tweet" data-lang="en"><p lang="en" dir="ltr">You may be onto something. Tooth-bearing with the jaw clenched is generally recognized as a signal of submission or non-threatening in primates. Involuntary smiling or laughing in tense situations might have signaled that you weren’t a threat.</p>— Jager Tusk (@JagerTusk) <a href="https://twitter.com/JagerTusk/status/1085316201104912384?ref_src=twsrc%5Etfw">January 15, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Um, yipes.<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Sometimes it feels like my big toe should be on the side of my foot, was that ever a thing?</p>— B033? K@($ (@whimbrel17) <a href="https://twitter.com/whimbrel17/status/1085559016011563009?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Ultimately, this is a fight between a giant reptile and a giant primate.
The 2021 film “Godzilla vs. Kong" pits the two most iconic movie monsters of all time against each other. And fans are now picking sides.
The more you see them, the better you get at spotting the signs.