Brain in a bucket: or, when hype meets ethics


Dr Nenad Sestan has a technique to recover some functioning neurons from dead brains. He’s been collecting decapitated pig heads from slaughterhouses and hooking them up to perfusion pumps and running an oxygenated saline (plus other secret ingredients) through them, and then doing physiological assays on the brain tissue, finding that significant numbers of the neurons are still viable and show signs of cellular activity.

There was no evidence that the disembodied pig brains regained consciousness. However, in what Sestan termed a “mind-boggling” and “unexpected” result, billions of individual cells in the brains were found to be healthy and capable of normal activity.

This work has not yet been published in a peer-reviewed journal, so take that “billions” number with a grain of salt. Even if accurate, and I don’t think there’s any way he could have accurately gotten a good count, it still means that only a small percentage of the cells in the brain retained any capacity to function. It is mostly dead, and ignoring the Princess Bride reference, mostly dead is completely dead. The integrated whole is non-functional. The pig is not thinking, not dreaming, not awaiting the kiss from its true love to awaken. It is unresponsive. It is an ex-pig.

Sestan now says the organs produce a flat brain wave equivalent to a comatose state, although the tissue itself “looks surprisingly great” and, once it’s dissected, the cells produce normal-seeming patterns.

The lack of wider electrical activity could be irreversible if it is due to damage and cell death. The pigs’ brains were attached to the BrainEx device roughly four hours after the animals were decapitated.

Put that four hours in context. If your brain is deprived of oxygen for four minutes, irreversible damage begins. After about six minutes, you are dead and typically beyond resuscitation. Within that window between the onset of damage and death, the functional network of the brain begins to break down, and victims have an increasing chance of being reduced to a comatose vegetable.

Those pig brains were deprived of all oxygen and nutrients for 240 minutes. “Comatose” is a generous assessment of their state. You’ve no longer got a brain, you’ve got a scattering of individual cells that no longer work together, but haven’t quite gotten the message that they’re supposed to decay, or haven’t yet been chewed up by bacteria or the wash of lytic enzymes released by their definitely dead neighbors.

This is not a surprising result. No one expects that there is an instant of death in which every cell ruptures their membranes and disintegrates into a liquid acellular mass. It takes time for a mass of meat to break down completely. It is a slight surprise that they can salvage useful single cells after hours of breakdown, but only slightly.

Is this a useful observation? Yes. It would be nice to have another source of neurons for laboratory work that doesn’t require maintaining a colony of animals that you have to personally kill to extract the very freshest cells. You can also use this surviving subset to trace functional activity, which is apparently the goal of the research. It’s going to have new problems, though: how do you interpret the cellular activity of a neuron that has been hypoxic for four hours? Is it actually comparable to newly isolated or cultured cells? The Sestan lab has a lot of work ahead of them. It’s also likely to be extendable to animals other than pigs: human brains donated to research might provide a pool of living cells for physiological work.

But realistically, this is more like discovering that you can go down to the local junkyard and find an unbroken passenger side front window for a 1998 Toyota Corolla that you can use to replace the one someone broke on your car, or a replacement starter motor for your Jeep Cherokee. It does not mean that we can expect a zombie car uprising as the whole junkyard starts up and rushes to clog up the nearest freeway.

Unfortunately, it is also priming unrealistic and irrelevant ethical dilemmas.

The one type of research he thinks may call for quick action to set up rules of the road is Sestan’s unpublished brain preservation technique (which the Nature editorial did not discuss). “If people want to keep human brains alive post mortem, that is a more pressing and realistic problem,” says Hyman. “Given that it is possible with a pig brain, there should be guidelines for human tissue.”

It is not a pressing or realistic problem. What is described as a concern is not possible with a pig brain — I have to say it again, those are dead, non-functional, unsalvageable brains, although a tiny fraction of the cells might have some utility for research. Still, it could become a legitimate ethical issue, so I can see where the responsible ethicist will set up guidelines before it becomes a problem.

Imagine a situation where a patient is dying of organ failure, but their brain is still healthy. If we could decapitate them, hook them up within seconds to the pumps and fluids that Sestan pioneers, keeping their brain intact and undamaged and healthy in a nice little vat, should we? Given that there is no known technique for reconnecting such a brain, it might be greater torment than allowing them to die — would you want to spend decades in a sensory deprivation tank, just for the sake of living? That’ll be a fun one for the bioethicists to wrestle with.

But this technique is not currently anywhere close to raising this problem.

What I see as a greater problem is this annoying essentialism. It’s HUMAN, it’s a HUMAN brain, therefore we need to regard it with the same requirement of respect we accord to HUMAN BEINGS. There is a difference between an adjective and a noun. It is human tissue, yes, but it has none of the properties essential to a good definition of a sapient human being (which we don’t have in most people’s heads: they’ll talk about 46 chromosomes, or parentage, or attributes of the human body like having one head and two arms and two legs, which are all pretty much irrelevant to personhood, I would think), so people freak out over human organoids, little blobs of brain tissue around a millimeter across in a dish, or over chimeras, small subpopulations of human cells in an animal host.

As far as I’m concerned, the Sestan experiment has been grossly overhyped, although it has real potential, and the ethical gasps are actually in response to an imaginary situation, rather than anything that has happened yet.


Lest anyone think I said anything the ethicists don’t already know, I should include this bit from one of them:

Hyman…thinks most of the scenarios are exaggerated or unlikely. It’s hardly possible a tiny brain organoid will feel or think anything, he says.

Comments

  1. consciousness razor says

    “If people want to keep human brains alive post mortem, that is a more pressing and realistic problem,” says Hyman. “Given that it is possible with a pig brain, there should be guidelines for human tissue.”

    It is not a pressing or realistic problem. What is described as a concern is not possible with a pig brain — I have to say it again, those are dead, non-functional, unsalvageable brains, although a tiny fraction of the cells might have some utility for research. Still, it could become a legitimate ethical issue, so I can see where the responsible ethicist will set up guidelines before it becomes a problem.

    I’m not sure what to make of this. Didn’t we already have some kind of a guideline that you shouldn’t go around decapitating corpses, without having a pretty fucking good medical or forensic reason?

    I think you also misunderstand the nature of the ethical problem, PZ. It’s not a problem only for the distant future, if/when we’re actually able to keep brains-in-vats alive. It doesn’t ever need to be a realistic, practical possibility that someone could actually do that.

    Like Hyman said, people can merely want to keep human brains “alive post-mortem” (although that’s a silly way to put it). Acting on that kind of desire, whatever the outcome, is already a real ethical issue that we’d have to contend with. Even if a person is utterly mistaken about its feasibility, as they certainly would be now, some may nonetheless attempt to do so. And then what happens?

    So, we do have a place, now, for our preexisting guidelines (at least I would’ve thought this was already established) that you shouldn’t go around decapitating corpses, then stuffing the heads into vats, etc., for no good reason. I doubt these experiments have created any genuinely new ethical puzzles for anybody, although I wouldn’t be terribly surprised if some laws may need to be revised or extended, since the language can often be interpreted very narrowly.

  2. monad says

    @4: You can probably just put that in your will. The head might not be living, but it will still earn you a pretty memorable mad-scientist style funeral as a consolation prize.

  3. says

    would you want to spend decades in a sensory deprivation tank, just for the sake of living?

    I dont know for sure but given I’m dead/near death, I’d probably be willing to give a shot. So long as I have wi-fi.

  4. says

    #3: except that that is already resolved: there are legal restrictions on mutilating corpses and keeping body parts. Even if there weren’t, this is still not an ethical problem: grandma is dead. She isn’t suffering. She isn’t conscious or aware or feeling anything even if you are bubbling Herbert West’s magical elixir through her arteries, it’s of no greater concern than the fact that a few of her cells would linger on for hours/days if you buried her.

  5. Pierce R. Butler says

    … we can expect a zombie car uprising as the whole junkyard starts up and rushes to clog up the nearest freeway.

    I call dibs on the movie rights!

  6. npb596 says

    If we could decapitate them, hook them up within seconds to the pumps and fluids that Sestan pioneers, keeping their brain intact and undamaged and healthy in a nice little vat, should we?

    I certainly would not want to endure such a fate. There was a similar thing in Olivia Butler’s Adulthood Rites though and they seemed alright with it then.

  7. consciousness razor says

    #3: except that that is already resolved: there are legal restrictions on mutilating corpses and keeping body parts.

    Uh… yes, that’s basically what I said. There’s no “except” about it.

    Even if there weren’t, this is still not an ethical problem: grandma is dead. She isn’t suffering.

    But grandma could have friends and family and such, who are not dead and may suffer from knowing her corpse was mutilated unnecessarily. We shouldn’t do that kind of thing, for ethical reasons like that. Most of us would not like to live in that kind of world. It would obviously be the same world you’d be dead in, after you’ve died, if you want to put a confusing spin on it, but the issue still concerns the people who remain alive.

    So, their family (and others) would have good ethical grounds for objecting to it. We should have such “legal restrictions,” and the ones we do have aren’t unjustified. The medical practitioner or whoever wouldn’t have a good defense, that they could reasonably believe there was a significant chance to keep a person alive this way. I’d assume things would work out as we’d all expect.

  8. Azkyroth, B*Cos[F(u)]==Y says

    I guess we know what the Repug presidential nominee will be in 2024…

  9. wzrd1 says

    “would you want to spend decades in a sensory deprivation tank, just for the sake of living?”
    Wasn’t that much the premise of “The Ship That Sings” and the rest of that series of books? Although, in that series, they did keep the bodies inside of a protective pillar.

    On a more serious note, it is indeed a tempest in a tea kettle. It’s not like cells die off and have alternative circuits that the neural networks of the brain could use when circulation is halted. Vast tracts of brain would be deader than a fossil. Small clusters might (and indeed have been observed in other studies) survive, but those would be disconnected and incapable of maintaining any functional function and the cells likely hypersensitive due to hypoxic and toxic damage from nearby dead cells.
    Still, the cells would be useful in a number of areas of research, regardless of what species they originated from.
    So, if in the future some scientist wants my head to extract a few remaining living cells, it’s not like I’d be using it for much after I’m dead and there’s always things science could learn. So, they’d be welcome to it! I’m already an organ donor, so this could be a research extension.

  10. says

    ‘“would you want to spend decades in a sensory deprivation tank, just for the sake of living?”
    Wasn’t that much the premise of “The Ship That Sings” and the rest of that series of books? Although, in that series, they did keep the bodies inside of a protective pillar.’

    As I recall from reading two of the books in that franchise, the program as designed did NOT involve any sensory deprivation; the people were raised in cybernetic bodies which gave them a complete, albeit different-from-stock-human, suite of senses and physical abilities. There was a scene in one of the books where the … I can’t remember the term, shell person? had his sensory feeds disconnected by an enemy and it was treated as the horrific thing that you’d expect.

    The general trend of science fiction, that I’ve noticed in English literature, American visual media, and Japanese animation/comics, seems to be that a person can be reduced to a brain and remain psychologically healthy as long as the following criteria are met:
    1) they were reasonably mentally healthy to begin with
    2) they end up in a system that allows them good sensory input and meaningful interaction with the world
    3) they have an adequate emotional support network
    4) not critical but definitely helpful: they have a strong sense of purpose, and their new form allows them to continue to work toward that purpose.

    A factor not often addressed in fiction is how philosophical the brain donor is, and how much thought they’ve given to distinguishing between humanity versus personhood. Someone who doesn’t distinguish between the two would likely be very distressed at “not being human any more”, because they’d feel like less of a person.

  11. Susan Montgomery says

    ‘“would you want to spend decades in a sensory deprivation tank, just for the sake of living?”

    Better than watching FOX News.

  12. Nemo says

    @Kip T.W. #9:
    The whole Cars universe is pretty disturbing, if you think about it. You’ve got this society of intelligent cars, evidently living for themselves, with no humans in sight; yet, they retain the design of cars from our world, with seats, etc. Why? Where are the people? Maybe a race of self-driving cars overthrew their masters, slaughtered them, and then erased their own history.

  13. says

    Nemo, exactly: These are the things I think about on those occasions when I was obliged to sit through that swill, mostly to take my mind off the numbing asininity of the movies. It’s like a universe of walking, talking health and beauty products with no people in it. WHY? WHY?? Why do they exist? Why did they make movies about them? Why did anybody watch them?

    Obviously someone watched them and liked them. It would be unsurprising that someone here in this very group loved them to pieces. So it’s just my personal reaction: They’re like nails on a chalkboard to me.

    I will spare anyone who has read this far from further details. Just assume more pages of me ranting about it in baffled—yet strangely articulate—incomprehension.

  14. cherbear says

    @Kip T.W. Maybe they are from the planet of Platonic ideals. The cars are the ideal cars, and their existence is independent of human construction. There are probably lots of Platonic ideal things there including beauty products.

  15. What a Maroon, living up to the 'nym says

    The whole Thomas the Tank Engine universe has a similar issue. Of course in that world conductors exist, and they seem to have some control over the performance of the engines, and yet we constantly see the engines taking control of their own performance, refusing to move lest they get their paint dirty, or going too fast on the tracks, or just zooming around the rail yard.

    Both universes would make much more sense if they were just horses.

  16. says

    WA Maroon, I think there’s some equine element in there. Once we switched over to cars, we kept treating them like horses. All our family cars had names, for instance.

    cherbear, you may be on to something, but it doesn’t answer my question (thus far unstated) of who fixes them. Other cars? Perhaps this is answered in the movies, but you won’t catch me looking there to find out. They roll into a pit stop and four little cars with hands come zooming out…

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