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The recent “brain reanimation” experiment on pigs is fascinating but not for the reason you think

The real issue raised is not about brain transplants or sci-fi fantasies of reanimation of corpses. It is about how we define life and death

By Philip Ball  

Caption

Stories about scientists reanimating a brain in a jar, like those prompted by a paper published last week in Nature, have a long pedigree. In 1937 the Sunday Express reported “Lonely island experiments with machine that keeps a brain alive.” It went on: “In a guarded, walled laboratory… a machine is slowly being assembled [that] can even keep a brain alive after the animal it was taken from is dead.” The machine was allegedly being constructed by Nobel laureate surgeon Alexis Carrel (who bought the island retreat of St Gildas, off Brittany, with his prize money) and world-famous aviator Charles Lindbergh.

But the story was total fantasy, and so are any similar suggestions based on the new experiments. These were done at the Yale School of Medicine by a team led by neuroscientist Nenad Sestan. What they report is deeply interesting and rather surprising. Using an apparatus that “perfuses” brains with a blood-like fluid, pulsing it through the veins and arteries, they could see signs of tissue function in pigs’ brains taken from an abattoir—even though the pigs’ heads had been removed after the death of the animals up to four hours earlier. It has generally been thought that irreversible, debilitating damage of the cells and tissues of organs happens more quickly than this when blood circulation (and thus oxygen supply) is stopped, either by removal from the body or by death of the organism. That’s why people are pronounced brain dead minutes after the heart stops beating.

You can see where this is leading. Are we being too hasty to assume brain death in people who suffer fatal trauma? Might it even be possible to use a perfusion apparatus like this to keep brains alive—and perhaps even ultimately to transplant them to another body? Does the work offer hope for the many people (especially in Silicon Valley) who have paid large sums to have their heads cryogenically frozen after death, arresting cell decay, in the hope that one day they might be resuscitated?

The answer is a firm no. Despite breathless claims about “rebooting” or “bringing back to life” the pig brains, there is nothing in these experiments that gives any indication that a brain placed in the perfusion device could be brought back to conscious function. It’s not even a matter of this being “early days” for such a goal: it is very possible that, between seeing some activity in the cells of a perfused brain and restoring actual “brain function,” there is not just much ground to be navigated but a yawning gulf. The restoration of cell activity, say Sestan and colleagues, “should not be extrapolated to signify resurgence of normal brain function… at no point did we observe the kind of organised global electrical activity associated with awareness, perception, or other higher-order brain functions.”

That’s no surprise. Yet it would be tempting to suppose that such revival was on the cards: after all, the Yale team had anaesthetics at the ready to administer if they saw any evidence of brain activity (such as electrical “brain waves”) that could hint at a return of the ability to perceive sensations—like pain. This, however, was not because it seemed at all likely, but was merely a responsible ethical precaution. Indeed, despite the grisly sound of the experiments, the team was scrupulous about the ethics—in the view of bioethicists Nita Farahany and Henry Greeley and cognitive neuroscientist Charles Giattino, probably more so than many others would have been. No animals were killed for the work: the brains were sourced from livestock killed for meat.

The confusion potentially elicited by this work arises from an old and unresolved tension about what we mean by life, and in particular by the distinction between the life of cells and tissues and that of organisms. It is a tension that goes right back to the work of Carrel in the early 20th century on the laboratory culturing of living tissues and the preservation of organs. Carrel, working at the Rockefeller Institute for Medical Research in New York, perfected methods for keeping small samples of tissue “alive” in a glass dish by bathing them in a fluid that supplied the necessary nutrients and giving them access to dissolved oxygen. He claimed to have kept a specimen of chick heart tissue alive and pulsing for decades (although we now know this was not possible). Carrel was interested both in trying to grow tissues and organs artificially for transplantation and in keeping whole, surgically removed organs viable by perfusion for the same purpose.

At the time, this work seemed to hold the promise of immortality: we could simply replace our organs and tissues as they wore out. It was, of course, never quite as simple as that. Besides, continuity of the “self” would seem to demand continuity of the brain—and it is far from clear how that could be replaced. “Head transplants” (more properly they would be “body transplants”) are still mooted from time to time, but usually only by mavericks such as the Italian neurosurgeon Sergio Canavero, who has claimed to have transplanted the heads of monkeys and (dead) humans. These are merely exercises in connecting arteries other tissues: there’s not the slightest indication that life, let alone thoughts and memories, could be restored in such a process, and indeed Canavero did not even reconnect the spinal cord.

The tissue-culture experiments of Carrel and others showed that cells could be kept living separate from the body. But that is wholly different from preserving the “life of the organism.” Another early pioneer of tissue culture, Thomas Strangeways, working at the Cambridge hospital that later became a research laboratory bearing his name, made that point rather dramatically in a public lecture on the subject in 1926. Imagine, he said, grinding up a person’s body into mincemeat just after death and turning it into sausages. No one would doubt that the person was well and truly deceased. Yet if the sausages were kept cold to preserve them, a piece of the “flesh” could later be cultured in a dish into living cells. He even produced a sample of this sort, which he said had been made from sausages obtained from a butcher.

The parallels with the Yale experiment are clear enough (even without pointing out that Strangeways’s middle name was Pigg). Now, it’s true that the Yale team showed rather more than simply the ability of a few cells in the pig brains to resume metabolism. They saw that the pumped blood substitute could flow down even the smallest vessels in the brains’ circulation network, and that the vessels would even widen in response to a drug known to have this effect in living organisms. The structure of the brain tissues remained intact even down to the cell scale, and some of the neurons in the brains were capable of sending out the electrical pulses involved in mental processing: they could “talk” to one another.

Don’t get too exercised by that last finding, though. The “mini-brain” that I had grown last year from a piece of my arm, that was cultured in the lab first into stem cells and then into neurons, will also have contained neurons capable of this “firing” activity. It is what such cells are “designed” to do, if they are alive at all. It doesn’t mean they are in some sense “thinking.”

Farahany and her coauthors do feel that the Yale findings raise new ethical questions. For one thing, they say, “new guidelines are needed for studies involving the preservation or restoration of whole brains, because animals used for such research could end up in a grey area—not alive, but not completely dead.” They even wonder if this demonstration of the unexpectedly long persistence of some activity in the brain might one day mean that information—images or memories—might be retrieved from human brains shortly after death by decoding the residual neural activity. Meanwhile, bioethicists Stuart Youngner and Insoo Hyun say that the results might pose difficult questions for the harvesting of organs from people soon after death: “ultimately, more people could become candidates for brain resuscitation rather than for organ donation.” But while there is absolutely no sign that higher brain function can be recovered in treatments like this, one has to fear that such resuscitation would amount to no more than placing the person in a permanently vegetative state.

What all this really implies is really what Strangeways pointed out all those years ago: that in effect we still don’t have a good understanding or intuition of what death means for us as whole and sentient organisms. We are cooperative colonies of cells, and those cells can outlive us—witness the “immortal” cells of Henrietta Lacks, the Baltimore woman who died from cervical cancer in 1951 but whose cancer cells are still cultured and used today for research. That “us” is a higher-order notion, and we’re none too sure how it is woven out of the vitality of our cells, tissues and organs—or how and when they lose their ability to sustain it.

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