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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 ›
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Astronomers find these five chapters to be a handy way of conceiving the universe's incredibly long lifespan.
- We're in the middle, or thereabouts, of the universe's Stelliferous era.
- If you think there's a lot going on out there now, the first era's drama makes things these days look pretty calm.
- Scientists attempt to understand the past and present by bringing together the last couple of centuries' major schools of thought.
The 5 eras of the universe<p>There are many ways to consider and discuss the past, present, and future of the universe, but one in particular has caught the fancy of many astronomers. First published in 1999 in their book <a href="https://amzn.to/2wFQLiL" target="_blank"><em>The Five Ages of the Universe: Inside the Physics of Eternity</em></a>, <a href="https://en.wikipedia.org/wiki/Fred_Adams" target="_blank">Fred Adams</a> and <a href="https://en.wikipedia.org/wiki/Gregory_P._Laughlin" target="_blank">Gregory Laughlin</a> divided the universe's life story into five eras:</p><ul><li>Primordial era</li><li>Stellferous era</li><li>Degenerate era</li><li>Black Hole Era</li><li>Dark era</li></ul><p>The book was last updated according to current scientific understandings in 2013.</p><p>It's worth noting that not everyone is a subscriber to the book's structure. Popular astrophysics writer <a href="https://www.forbes.com/sites/ethansiegel/#30921c93683e" target="_blank">Ethan C. Siegel</a>, for example, published an article on <a href="https://www.forbes.com/sites/startswithabang/2019/07/26/we-have-already-entered-the-sixth-and-final-era-of-our-universe/#7072d52d4e5d" target="_blank"><em>Medium</em></a> last June called "We Have Already Entered The Sixth And Final Era Of Our Universe." Nonetheless, many astronomers find the quintet a useful way of discuss such an extraordinarily vast amount of time.</p>
The Primordial era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTEyMi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNjEzMjY1OX0.PRpvAoa99qwsDNprDme9tBWDim6mS7Mjx6IwF60fSN8/img.jpg?width=980" id="db4eb" class="rm-shortcode" data-rm-shortcode-id="0e568b0cc12ed624bb8d7e5ff45882bd" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="1049" />
Image source: Sagittarius Production/Shutterstock<p> This is where the universe begins, though what came before it and where it came from are certainly still up for discussion. It begins at the Big Bang about 13.8 billion years ago. </p><p> For the first little, and we mean <em>very</em> little, bit of time, spacetime and the laws of physics are thought not yet to have existed. That weird, unknowable interval is the <a href="https://www.universeadventure.org/eras/era1-plankepoch.htm" target="_blank">Planck Epoch</a> that lasted for 10<sup>-44</sup> seconds, or 10 million of a trillion of a trillion of a trillionth of a second. Much of what we currently believe about the Planck Epoch eras is theoretical, based largely on a hybrid of general-relativity and quantum theories called quantum gravity. And it's all subject to revision. </p><p> That having been said, within a second after the Big Bang finished Big Banging, inflation began, a sudden ballooning of the universe into 100 trillion trillion times its original size. </p><p> Within minutes, the plasma began cooling, and subatomic particles began to form and stick together. In the 20 minutes after the Big Bang, atoms started forming in the super-hot, fusion-fired universe. Cooling proceeded apace, leaving us with a universe containing mostly 75% hydrogen and 25% helium, similar to that we see in the Sun today. Electrons gobbled up photons, leaving the universe opaque. </p><p> About 380,000 years after the Big Bang, the universe had cooled enough that the first stable atoms capable of surviving began forming. With electrons thus occupied in atoms, photons were released as the background glow that astronomers detect today as cosmic background radiation. </p><p> Inflation is believed to have happened due to the remarkable overall consistency astronomers measure in cosmic background radiation. Astronomer <a href="https://www.youtube.com/watch?v=IGCVTSQw7WU" target="_blank">Phil Plait</a> suggests that inflation was like pulling on a bedsheet, suddenly pulling the universe's energy smooth. The smaller irregularities that survived eventually enlarged, pooling in denser areas of energy that served as seeds for star formation—their gravity pulled in dark matter and matter that eventually coalesced into the first stars. </p>
The Stelliferous era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTEzNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMjA0OTcwMn0.GVCCFbBSsPdA1kciHivFfWlegOfKfXUfEtFKEF3otQg/img.jpg?width=980" id="bc650" class="rm-shortcode" data-rm-shortcode-id="c8f86bf160ecdea6b330f818447393cd" data-rm-shortcode-name="rebelmouse-image" data-width="481" data-height="720" />
Image source: Casey Horner/unsplash<p>The era we know, the age of stars, in which most matter existing in the universe takes the form of stars and galaxies during this active period. </p><p>A star is formed when a gas pocket becomes denser and denser until it, and matter nearby, collapse in on itself, producing enough heat to trigger nuclear fusion in its core, the source of most of the universe's energy now. The first stars were immense, eventually exploding as supernovas, forming many more, smaller stars. These coalesced, thanks to gravity, into galaxies.</p><p>One axiom of the Stelliferous era is that the bigger the star, the more quickly it burns through its energy, and then dies, typically in just a couple of million years. Smaller stars that consume energy more slowly stay active longer. In any event, stars — and galaxies — are coming and going all the time in this era, burning out and colliding.</p><p>Scientists predict that our Milky Way galaxy, for example, will crash into and combine with the neighboring Andromeda galaxy in about 4 billion years to form a new one astronomers are calling the Milkomeda galaxy.</p><p>Our solar system may actually survive that merger, amazingly, but don't get too complacent. About a billion years later, the Sun will start running out of hydrogen and begin enlarging into its red giant phase, eventually subsuming Earth and its companions, before shrining down to a white dwarf star.</p>
The Degenerate era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE1MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNTk3NDQyN30.gy4__ALBQrdbdm-byW5gQoaGNvFTuxP5KLYxEMBImNc/img.jpg?width=980" id="77f72" class="rm-shortcode" data-rm-shortcode-id="08bb56ea9fde2cee02d63ed472d79ca3" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="810" />
Image source: Diego Barucco/Shutterstock/Big Think<p>Next up is the Degenerate era, which will begin about 1 quintillion years after the Big Bang, and last until 1 duodecillion after it. This is the period during which the remains of stars we see today will dominate the universe. Were we to look up — we'll assuredly be outta here long before then — we'd see a much darker sky with just a handful of dim pinpoints of light remaining: <a href="https://earthsky.org/space/evaporating-giant-exoplanet-white-dwarf-star" target="_blank">white dwarfs</a>, <a href="https://earthsky.org/space/new-observations-where-stars-end-and-brown-dwarfs-begin" target="_blank">brown dwarfs</a>, and <a href="https://earthsky.org/astronomy-essentials/definition-what-is-a-neutron-star" target="_blank">neutron stars</a>. These"degenerate stars" are much cooler and less light-emitting than what we see up there now. Occasionally, star corpses will pair off into orbital death spirals that result in a brief flash of energy as they collide, and their combined mass may become low-wattage stars that will last for a little while in cosmic-timescale terms. But mostly the skies will be be bereft of light in the visible spectrum.</p><p>During this era, small brown dwarfs will wind up holding most of the available hydrogen, and black holes will grow and grow and grow, fed on stellar remains. With so little hydrogen around for the formation of new stars, the universe will grow duller and duller, colder and colder.</p><p>And then the protons, having been around since the beginning of the universe will start dying off, dissolving matter, leaving behind a universe of subatomic particles, unclaimed radiation…and black holes.</p>
The Black Hole era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMjE0OTQ2MX0.ifwOQJgU0uItiSRg9z8IxFD9jmfXlfrw6Jc1y-22FuQ/img.jpg?width=980" id="103ea" class="rm-shortcode" data-rm-shortcode-id="f0e6a71dacf95ee780dd7a1eadde288d" data-rm-shortcode-name="rebelmouse-image" data-width="1400" data-height="787" />
Image source: Vadim Sadovski/Shutterstock/Big Think<p> For a considerable length of time, black holes will dominate the universe, pulling in what mass and energy still remain. </p><p> Eventually, though, black holes evaporate, albeit super-slowly, leaking small bits of their contents as they do. Plait estimates that a small black hole 50 times the mass of the sun would take about 10<sup>68</sup> years to dissipate. A massive one? A 1 followed by 92 zeros. </p><p> When a black hole finally drips to its last drop, a small pop of light occurs letting out some of the only remaining energy in the universe. At that point, at 10<sup>92</sup>, the universe will be pretty much history, containing only low-energy, very weak subatomic particles and photons. </p>
The Dark Era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE5NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0Mzg5OTEyMH0.AwiPRGJlGIcQjjSoRLi6V3g5klRYtxQJIpHFgZdZkuo/img.jpg?width=980" id="60c77" class="rm-shortcode" data-rm-shortcode-id="7a857fb7f0d85cf4a248dbb3350a6e1c" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="810" />
Image source: Big Think<p>We can sum this up pretty easily. Lights out. Forever.</p>
Dr. Katie Mack explains what dark energy is and two ways it could one day destroy the universe.
- The universe is expanding faster and faster. Whether this acceleration will end in a Big Rip or will reverse and contract into a Big Crunch is not yet understood, and neither is the invisible force causing that expansion: dark energy.
- Physicist Dr. Katie Mack explains the difference between dark matter, dark energy, and phantom dark energy, and shares what scientists think the mysterious force is, its effect on space, and how, billions of years from now, it could cause peak cosmic destruction.
- The Big Rip seems more probable than a Big Crunch at this point in time, but scientists still have much to learn before they can determine the ultimate fate of the universe. "If we figure out what [dark energy is] doing, if we figure out what it's made of, how it's going to change in the future, then we will have a much better idea for how the universe will end," says Mack.
A unique exoplanet without clouds or haze was found by astrophysicists from Harvard and Smithsonian.
- Astronomers from Harvard and Smithsonian find a very rare "hot Jupiter" exoplanet without clouds or haze.
- Such planets were formed differently from others and offer unique research opportunities.
- Only one other such exoplanet was found previously.
Munazza Alam – a graduate student at the Center for Astrophysics | Harvard & Smithsonian.
Credit: Jackie Faherty