Once upon a time, there were three little piggies (in fact, more than 100) who had no idea they would achieve worldwide fame because some of their brain function was resurrected hours after their death.
The pigs did not realize what happened when vascular circulation and certain cellular functions in their brains were revived. As lead author Zvonimir Vrselja of Yale’s neuroscience department and the team reassure in their paper in Nature: They found no sign that the brains had regained consciousness in any way, shape or form. This is probably just as well.
The scientists weren’t trying to bring the pigs back to life anyway. “It was the opposite of the goal to have consciousness restored,” spelled out co-author Nenad Sestan of Yale.
“There was no evidence for awareness, perception or other higher-order brain functions,” the paper stated.
The scientists themselves had no idea how their experiment would go. But the researchers were apparently just as horrified as anybody would be by the sheer possibility of inadvertently creating zombie swines or that the brains of the deceased pigs would have some sort of consciousness induced.
Their preventative measures included intensely monitoring signals from the severed brains and preparing to knock out the undead brains at any glimmering of perception — using anesthetic, that is. The team was also prepared to cool the brains (dampening biological activity) if they discerned any sign of organized global electricity activity.
Happily, they did not observe any such signs.
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Why on earth would anybody do this? Because we all want to know if we can be brought back from the dead. But that is way, way in the future, if ever, and is NOT what this team set out to do with these pigs. Their immediate goals were much more modest.
“We wanted to know what happens in brains when the blood flow stops, and if cells can have functions restored like in culture. If it can be done in a petri dish — could it be done in an intact brain?” Sestan explained to reporters. (In 2017, scientists cultured cells from a brain stem tumor taken from a deceased child because of limited availability of tumor tissue for study. This team found that the post-mortem interval for successful harvest of cells for a durable culture should be “less than 6-8 hours (from the time of death to the time that the tissue is placed in ice cold shipping and transportation media).” And back in 2002, other scientists proved they could keep human brain cells harvested post-mortem alive in culture for weeks.)
There is no scientific consensus on what “dead” is. Merriam-Webster unhelpfully defines death as “a permanent cessation of all vital functions: the end of life.” A 2017 paper published in the Quarterly Journal of Medicine on how doctors define death cited two basic premises: breakdown in the functioning of the organism as a whole; and neurological death, “namely, that the person has lost the capacity for consciousness secondary to irreversible brain (or brain stem) injury.”
But that doesn’t cover all cases doctors encounter, wrote QJM Editor-in-Chief Seamas Donnelly. It is “nigh impossible” to achieve a single universal definition that covers all manners of death, he concluded.
That said, these pigs were definitely deceased when the Yale experiment began.
“The brains used in the study were obtained from the Newhaven food processing plant,” explained Dr. Stephen Latham, an ethicist associated with the scientific team. The brains were obtained from pigs slaughtered for consumption - “No animals were sacrificed for the study,” he told reporters.
So what was the experiment? The team started with brains from pigs that had been (definitely) dead for four hours. In place of hearts, the brains were “fed” by perfusion systems. In place of blood, the team infused the brains with an artificial perfusate spiked with hemoglobin that, among its other characteristics, could support the energy requirements of the brains.
Result: Four hours after the pigs had died, and throughout the next six hours, the scientists restored and sustained micro-circulation and molecular and cellular functions in the intact pig brains. All this was done at room temperature.
Why did they stop this groundbreaking experiment after six hours? Because by that time the control brains not “fed” the special perfusate were mush: Nothing much was left of the control brains, Latham explained, so, in the absence of a comparator, they stopped. Only at some much later stage in research can we learn if brain function can be sustained for longer.
Mammalian cells are highly vulnerable to changes in oxygen level and blood flow, Sestan observed. But the results indicate that isolated intact mammalian brains have “an underappreciated capacity” for restoration of “micro-circulation and molecular and cellular activity after a prolonged post-mortem interval.”
OK, but did they actually prevent cellular damage? Postpone it? Reverse it?
“We don’t know whether we are reversing completely some of the damage in the cells molecular, at the cellular level, or just postponing the inevitable,” Sestan said. “We don’t know if after longer profusion the cells would die anyway. But just being able to show that with our technology, we can see dramatic differences with three groups of control brains — even postponement could be valuable to clinical studies.”
Not a pig apocalypse
In case you want to do this at home, Sestan explained that their technology involved three key components: The first was their synthetic cyto-protective solution; the second their custom profusion device to pump it into the brains; and third, the surgical procedure to isolate the intact brains.
The perfusate they invented had the property of blocking neuronal activity, just in case; they thought that brain cells might be better preserved, and their molecular and cellular functionality better restored, if the cells were not actively performing their usual neuronal functions.
Indeed, their novel technique sustained tissue and cellular structures, some molecular and cellular functionality, and glial and vascular response to stimuli. “We observed dramatic differences between our brains and the control brains,” Sestan shared.
Sestan reassured, again, that they did not recreate living brains. They recreated cellularly active brains. The conclusion is that improvement might be made to techniques aimed at restoring the functionality of brain cells in damaged — not dead — brains.
At this stage, nobody can say what could potentially start from a dead pig brain and make it a living brain that could make the pig oink. We do not know if this technology, suitably developed, could be used to resurrect actual consciousness. That was not the goal. Their techniques do not have medical applications, Sestan stressed.
Frankenpork does not rise
And if the pig brains had somehow come to life or if any sign of consciousness was witnessed? They would have had to stop the experiment immediately, ethicist Latham spelled out. This is unbroken ground and there is nothing even approaching an ethics consensus about this kind of research, he elaborated. There is zero institutional oversight about creating zombie swine.
It can’t even fall into the category of animal research, because the brains were from dead animals, Latham explained. And if consciousness had somehow been restored, no ethics committees exist to even think about how to do the kind of trade-offs one does when experimenting, such as: Is the suffering justified by the end goal of the research?
The whole thing would have had to stop until ethics expertise develops that can give guidance, Latham summed up, adding that there is no evidence whatsoever that any kind of consciousness or perception can be restored in dead brain tissue.
But this work was not merely curiosity. The truth is that it has shed new light on what really happens to the brain after death.
One major takeaway from the study is we now realize that hours after circulatory arrest — not just seconds or a few minutes — circulation in the brain and some cellular and molecular activities can be restored, Sestan explained.
“Cellular death in the brain occurs after a longer time window than we had thought. We had thought that cells undergo cell death within minutes. We are now showing that the process is a gradual, stepwise process — and that some of those processes can be either postponed, preserved or reversed,” he said, stressing yet again that they did not recover brain function; just postponed cell deaths.
“We hope to be able to better understand how the brain reacts to circulatory arrest and how to intervene and salvage cells,” he summed up.
And this can help how? “It could potentially help victims of stroke and other maladies or events that cause brain cell death,” Sestan speculated.
Or other organs, Latham pointed out. The “BEx system,” suitably adjusted and adapted, could conceivably be used to keep other organs alive or to reverse post-mortem decomposition of the organs, which are generally even less sensitive than brain tissue. But the system would have to be tinkered with a great deal, he said.
Finally, it bears pointing out that while pet pigs are people to their doting owners, a pig brain is not a human brain. Just as rodent studies may not be directly migrated to humans, and what works on a mouse may not work on the kids, success in resurrecting molecular function in a pig brain doesn’t mean it would work on human tissue or that, one day, life could be restored to the clinically, categorically dead.