Scientists Are Giving Dead Brains New Life. What Could Go Wrong? – The New York Times

Every morning for several weeks, the scientists woke up around 4:30 to be at the slaughterhouse as the first pigs were led to the killing floor. While they waited, the animals were stunned, killed, eviscerated and stripped of usable meat; later, Daniele and Vrselja would run carrying a bloody pig head in a bag to the manager’s office, where they would use a pump to empty the excess blood from it. Finally, placing the skull on ice, they would drive it back with them to the lab in Blacksburg.

It was difficult not to get discouraged. The architecture of the brains was only half of it: The scientists also had to learn to remove the skull in a way that preserved the organ’s vital architecture, like the arteries. And initially they were working without neurosurgical tools. “We had an oscillating saw from Home Depot,” Daniele said. “It was like sawing into the unknown, because you had to go millimeter by millimeter, and the whole key was to go as close as possible to the brain but not pierce into it, because you actually didn’t know where the floor was, where the brain was.”

With every two steps forward, they seemed to be taking another one back. By running food coloring through the arteries of the brain, Vrselja and Daniele could see how blood traveled through the organ, but the arteries split and joined at such irregular intervals that it took days to figure out how each one influenced the circulation of blood. “Every time we thought that we had it down,” Daniele told me, “a weird branch would come up and steal the circulation from the brain, and then it would leak out that way.”

By the 20th brain, they had a sense of which arteries connected to which; by the 40th, they had worked out what vessels needed to be closed off — and what sections of the skull needed to remain attached. “I remember feeling like shit, physically, because we were up at 4 every morning, going to bed at midnight and doing the same thing again,” Vrselja told me. “But eventually, there was progress.”

Sestan and his team would end up modifying nearly every aspect of BMI’s machine. Still, both the original and the current iteration, which Yale is seeking a patent for using the name BrainEx, work in fundamentally the same way. First, the brain is mostly freed from the skull; all the dangling arteries, save the carotids, are cauterized or sutured. Next, the organ is flushed of residual blood. At the same time, an amount of perfusate equivalent to a bottle of wine is brought to body temperature in the machine’s reservoir and oxygenated — as with real blood, oxygenation turns the perfusate a darker, scarlet red.

Once the fluid — the present form of which includes antibiotics and nine different types of cytoprotective agents — is ready, the brain is lowered into a plastic case the scientists have nicknamed “the football” and connected via the carotids. A small thermal unit (a miniature air-conditioner and heater) sits under the football, controlling the temperature of the organ; the pressure and speed of the perfusate, meanwhile, are governed by a type of pump. With a dull whir, the fluid begins to circulate across the arteries, capillaries and veins of the brain in a loop, exiting on each circuit through a dialysis unit that “cleans” any waste products and through a filter that removes any naturally occurring bubbles.

Perhaps the most innovative modification involved fluid mechanics, one of Vrselja’s specialties in graduate school. As the British mathematician John Womersley managed to quantify more than half a century ago, blood does not circulate through our arteries at a uniform rhythm — it circulates in pulses, in concert with the shudder of our hearts. To account for that dynamic, the BMI unit had shipped with an automated “pulse generator,” a device that replicates the heartbeat’s pulsatility in the organs.

After the N.I.H. meeting, Sestan was invited to Duke University to speak with the members of the school’s bioethics faculty and others. “People were aghast,” one person familiar with the meeting told me, “because everyone had this image of a pig’s head on a lab cart, attached to a bunch of hoses and tube, and the pig’s head coming back to life. There was a lot of concern,” the person went on, “that if this was to be made public in the wrong way, it could really be a setback for brain research. Like, decades of setback. It was so easily caricaturized.”

That summer, after a source told me about the Duke meeting, I reached out to Sestan. In a phone call, he called the experiment “the most important thing I’ve ever done, and the most important thing I will ever do,” and mentioned he was preparing to submit a paper to Nature. Once it had been accepted, he went on, he would get back in touch with me; until then, he wasn’t able to comment on the record.

In March 2018, Sestan met again with the N.I.H. Under the impression that everything he said would be kept confidential, he had put together a presentation on his experiment, and while the dozen or so attendees looked on, he clicked through a series of slides showing restored cells from the perfused brains. According to later reports, Sestan, referring to the most recent ECoG data, stressed that he was confident that the brains in his experiment were “not aware of anything.” Still, he went on, he could not speak to what other scientists might do with the research. “Hypothetically, somebody takes this technology, makes it better and restores someone’s [brain] activity,” he said. “That is restoring a human being. If that person has memory, I would be freaking out completely.”

With each meeting, the number of people aware of the project was growing, and Sestan, despite what he described to me as “begging and pleading,” was unable to prevent the publication last spring of an article in the MIT Technology Review, which was apparently based on video of Sestan’s 2018 N.I.H. presentation. Published with a still of a scene from the Steve Martin comedy “The Man With Two Brains,” the article framed Sestan’s work as “a step that could change the definition of death” — a “feat” that “inaugurates a bizarre new possibility in life extension.”

Within hours, the news had been picked up by media outlets around the world. “Scientists keeping pig brains ‘alive’ inside their SEVERED heads in Frankenstein-style research,” read the headline in the British tabloid The Mirror. The conspiracy theorist Alex Jones brought up the experiment on his radio show.

The email flooded in to Sestan’s office. “In case a study comes up and I find myself dying at that time, I volunteer for the brain study,” one read. “That’s right, I give you permission to, upon my untimely death, extract my brain and keep it ‘alive’ as long as you can outside the context of my body.” Another writer chided Sestan for taking measures to prevent the emergence of consciousness. “Progress cannot and should not be held back. … I suggest you seek private research funding from Silicon Valley, there is many a great powers and influential men who would fund this line of research and see it through to its full potential.” Finally, and most tragic, there were the relatives of patients who suffered brain trauma. What Sestan’s project proved, a mother in New England wrote hopefully, was that “there is no way to know when someone is truly dead.” Sestan told me: “You want to respond to each email, you want to try to explain the science, but you can’t. There are just too many.”

This spring, I flew to New Haven to tour Sestan’s lab. In a show of ceremony, he saved a viewing of the BrainEx for last. “You,” he said proudly, throwing open the door to a converted supply closet, “are the first member of the public to see it.” Roughly eight feet wide and mounted on the shelves of a long metal hospital-style cart, the BrainEx was less a single machine than a bristling collection of individual machines, each connected to the next, in a simulacrum of the human body. Here, the pulse generator — the equivalent of a heart. Here, the filters — mechanized kidneys. There, the device that, like lungs, helped oxygenate the perfusate. “We’ll do our dance,” Daniele said, and he commenced a dry run — sans brain — of the process, miming each step.

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