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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 ›
Inventions with revolutionary potential made by a mysterious aerospace engineer for the U.S. Navy come to light.
- U.S. Navy holds patents for enigmatic inventions by aerospace engineer Dr. Salvatore Pais.
- Pais came up with technology that can "engineer" reality, devising an ultrafast craft, a fusion reactor, and more.
- While mostly theoretical at this point, the inventions could transform energy, space, and military sectors.
The U.S. Navy controls patents for some futuristic and outlandish technologies, some of which, dubbed "the UFO patents," came to light recently. Of particular note are inventions by the somewhat mysterious Dr. Salvatore Cezar Pais, whose tech claims to be able to "engineer reality." His slate of highly-ambitious, borderline sci-fi designs meant for use by the U.S. government range from gravitational wave generators and compact fusion reactors to next-gen hybrid aerospace-underwater crafts with revolutionary propulsion systems, and beyond.
Of course, the existence of patents does not mean these technologies have actually been created, but there is evidence that some demonstrations of operability have been successfully carried out. As investigated and reported by The War Zone, a possible reason why some of the patents may have been taken on by the Navy is that the Chinese military may also be developing similar advanced gadgets.
Among Dr. Pais's patents are designs, approved in 2018, for an aerospace-underwater craft of incredible speed and maneuverability. This cone-shaped vehicle can potentially fly just as well anywhere it may be, whether air, water or space, without leaving any heat signatures. It can achieve this by creating a quantum vacuum around itself with a very dense polarized energy field. This vacuum would allow it to repel any molecule the craft comes in contact with, no matter the medium. Manipulating "quantum field fluctuations in the local vacuum energy state," would help reduce the craft's inertia. The polarized vacuum would dramatically decrease any elemental resistance and lead to "extreme speeds," claims the paper.
Not only that, if the vacuum-creating technology can be engineered, we'd also be able to "engineer the fabric of our reality at the most fundamental level," states the patent. This would lead to major advancements in aerospace propulsion and generating power. Not to mention other reality-changing outcomes that come to mind.
Among Pais's other patents are inventions that stem from similar thinking, outlining pieces of technology necessary to make his creations come to fruition. His paper presented in 2019, titled "Room Temperature Superconducting System for Use on a Hybrid Aerospace Undersea Craft," proposes a system that can achieve superconductivity at room temperatures. This would become "a highly disruptive technology, capable of a total paradigm change in Science and Technology," conveys Pais.
High frequency gravitational wave generator.
Credit: Dr. Salvatore Pais
Another invention devised by Pais is an electromagnetic field generator that could generate "an impenetrable defensive shield to sea and land as well as space-based military and civilian assets." This shield could protect from threats like anti-ship ballistic missiles, cruise missiles that evade radar, coronal mass ejections, military satellites, and even asteroids.
Dr. Pais's ideas center around the phenomenon he dubbed "The Pais Effect". He referred to it in his writings as the "controlled motion of electrically charged matter (from solid to plasma) via accelerated spin and/or accelerated vibration under rapid (yet smooth) acceleration-deceleration-acceleration transients." In less jargon-heavy terms, Pais claims to have figured out how to spin electromagnetic fields in order to contain a fusion reaction – an accomplishment that would lead to a tremendous change in power consumption and an abundance of energy.
According to his bio in a recently published paper on a new Plasma Compression Fusion Device, which could transform energy production, Dr. Pais is a mechanical and aerospace engineer working at the Naval Air Warfare Center Aircraft Division (NAWCAD), which is headquartered in Patuxent River, Maryland. Holding a Ph.D. from Case Western Reserve University in Cleveland, Ohio, Pais was a NASA Research Fellow and worked with Northrop Grumman Aerospace Systems. His current Department of Defense work involves his "advanced knowledge of theory, analysis, and modern experimental and computational methods in aerodynamics, along with an understanding of air-vehicle and missile design, especially in the domain of hypersonic power plant and vehicle design." He also has expert knowledge of electrooptics, emerging quantum technologies (laser power generation in particular), high-energy electromagnetic field generation, and the "breakthrough field of room temperature superconductivity, as related to advanced field propulsion."
Suffice it to say, with such a list of research credentials that would make Nikola Tesla proud, Dr. Pais seems well-positioned to carry out groundbreaking work.
A craft using an inertial mass reduction device.
Credit: Salvatore Pais
The patents won't necessarily lead to these technologies ever seeing the light of day. The research has its share of detractors and nonbelievers among other scientists, who think the amount of energy required for the fields described by Pais and his ideas on electromagnetic propulsions are well beyond the scope of current tech and are nearly impossible. Yet investigators at The War Zone found comments from Navy officials that indicate the inventions are being looked at seriously enough, and some tests are taking place.
If you'd like to read through Pais's patents yourself, check them out here.
Laser Augmented Turbojet Propulsion System
Credit: Dr. Salvatore Pais
Scientists do not know what is causing the overabundance of the gas.
- A new study looked to understand the source of methane on Saturn's moon Enceladus.
- The scientists used computer models with data from the Cassini spacecraft.
- The explanation could lie in alien organisms or non-biological processes.
Something is producing an overabundance of methane in the ocean hidden under the ice of Saturn's moon Enceladus. A new study analyzed if the source could be an alien life form or some other explanation.
The study, published in Nature Astronomy, was carried out by scientists at the University of Arizona and Paris Sciences & Lettres University, who looked at composition data from the water plumes erupting on Enceladus.
The particular chemistry, discovered by the Cassini spacecraft which flew through the plumes, suggested a high concentration of molecules that have been linked to hydrothermal vents on the bottom of Earth's oceans. Such vents are potential cradles of life on Earth, according to previous studies. The data from Cassini, which has been studying Saturn after entering its orbit in 2004, revealed the presence of molecular hydrogen (dihydrogen), methane, and carbon dioxide, with the amount of methane presenting a particular interest to the scientists."We wanted to know: Could Earthlike microbes that 'eat' the dihydrogen and produce methane explain the surprisingly large amount of methane detected by Cassini?" shared one of the study's lead authors Régis Ferrière, an associate professor in the department of Ecology and Evolutionary Biology at the University of Arizona.
Earth's hydrothermal vents feature microorganisms that use dihydrogen for energy, creating methane from carbon dioxide via the process of methanogenesis.
Searching for such microorganisms known as methanogens on the seafloor of Enceladus is not yet feasible. Likely, it would require very sophisticated deep diving operations that will be the objective of future missions.
So, Ferrière's team took a more available approach to pinpointing the origins of the methane, creating mathematical models that attempted to explain the Cassini data. They wanted to calculate the likelihood that particular processes were responsible for producing the amount of methane observed. For example, is the methane more likely the result of biological or non-biological processes?
They found that the data from Cassini was consistent with either microbial activity at hydrothermal vents or processes that have nothing to do with life but could be quite different from what happens on Earth. Intriguingly, models that didn't involve biological entities didn't seem to produce enough of the gas.
"Obviously, we are not concluding that life exists in Enceladus' ocean," Ferrière stated. "Rather, we wanted to understand how likely it would be that Enceladus' hydrothermal vents could be habitable to Earthlike microorganisms. Very likely, the Cassini data tell us, according to our models."
Still, the scientists think future missions are necessary to either prove or discard the "life hypothesis." One explanation for the methane that does not involve biological organisms is that the gas is the result of a chemical breakdown of primordial organic matter within Enceladus' core. This matter could have become a part of Saturn's moon from comets rich in organic materials.
It marks a breakthrough in using gene editing to treat diseases.
This article was originally published by our sister site, Freethink.
For the first time, researchers appear to have effectively treated a genetic disorder by directly injecting a CRISPR therapy into patients' bloodstreams — overcoming one of the biggest hurdles to curing diseases with the gene editing technology.
The therapy appears to be astonishingly effective, editing nearly every cell in the liver to stop a disease-causing mutation.
The challenge: CRISPR gives us the ability to correct genetic mutations, and given that such mutations are responsible for more than 6,000 human diseases, the tech has the potential to dramatically improve human health.
One way to use CRISPR to treat diseases is to remove affected cells from a patient, edit out the mutation in the lab, and place the cells back in the body to replicate — that's how one team functionally cured people with the blood disorder sickle cell anemia, editing and then infusing bone marrow cells.
Bone marrow is a special case, though, and many mutations cause disease in organs that are harder to fix.
Another option is to insert the CRISPR system itself into the body so that it can make edits directly in the affected organs (that's only been attempted once, in an ongoing study in which people had a CRISPR therapy injected into their eyes to treat a rare vision disorder).
Injecting a CRISPR therapy right into the bloodstream has been a problem, though, because the therapy has to find the right cells to edit. An inherited mutation will be in the DNA of every cell of your body, but if it only causes disease in the liver, you don't want your therapy being used up in the pancreas or kidneys.
A new CRISPR therapy: Now, researchers from Intellia Therapeutics and Regeneron Pharmaceuticals have demonstrated for the first time that a CRISPR therapy delivered into the bloodstream can travel to desired tissues to make edits.
We can overcome one of the biggest challenges with applying CRISPR clinically.
"While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," she continued.
What they did: During a phase 1 clinical trial, Intellia researchers injected a CRISPR therapy dubbed NTLA-2001 into the bloodstreams of six people with a rare, potentially fatal genetic disorder called transthyretin amyloidosis.
The livers of people with transthyretin amyloidosis produce a destructive protein, and the CRISPR therapy was designed to target the gene that makes the protein and halt its production. After just one injection of NTLA-2001, the three patients given a higher dose saw their levels of the protein drop by 80% to 96%.
A better option: The CRISPR therapy produced only mild adverse effects and did lower the protein levels, but we don't know yet if the effect will be permanent. It'll also be a few months before we know if the therapy can alleviate the symptoms of transthyretin amyloidosis.
This is a wonderful day for the future of gene-editing as a medicine.
If everything goes as hoped, though, NTLA-2001 could one day offer a better treatment option for transthyretin amyloidosis than a currently approved medication, patisiran, which only reduces toxic protein levels by 81% and must be injected regularly.
Looking ahead: Even more exciting than NTLA-2001's potential impact on transthyretin amyloidosis, though, is the knowledge that we may be able to use CRISPR injections to treat other genetic disorders that are difficult to target directly, such as heart or brain diseases.
"This is a wonderful day for the future of gene-editing as a medicine," Fyodor Urnov, a UC Berkeley professor of genetics, who wasn't involved in the trial, told NPR. "We as a species are watching this remarkable new show called: our gene-edited future."