"without first getting some kind of serious ethical guidance."
April 17, 2019 12:35 PM   Subscribe

Scientists revive pig brains somewhat in the lab. "a surprising amount of cellular function was either preserved or restored." (Caution: does involve some discussion of animal slaughter, not gratuitous)
posted by Rufous-headed Towhee heehee (47 comments total) 9 users marked this as a favorite
So there's hope for [insert your least favorite politician here]....
posted by DreamerFi at 12:52 PM on April 17, 2019 [3 favorites]

I believe this is exactly the situation "Your scientists were so preoccupied with whether or not they could, they didn't stop to think if they should" was meant to address.
posted by ChuraChura at 12:58 PM on April 17, 2019 [19 favorites]

"Your scientists were so preoccupied with whether or not they could, they didn't stop to think if they...... BRAIIIIIIINS!!!!!!!!!!"
posted by thelonius at 1:01 PM on April 17, 2019 [5 favorites]

"In a commentary that accompanied the research paper in Nature, Farahany and her colleagues Henry Greely and Charles Giattino say the work reminds them of a line from the 1987 movie The Princess Bride: "There's a big difference between mostly dead and all dead. Mostly dead is slightly alive."
posted by Making You Bored For Science at 1:02 PM on April 17, 2019 [13 favorites]

This has horrifying implications. I hope bioethicists are more effective than techbros at reining in the enthusiasm for this research.
posted by Johnny Wallflower at 1:03 PM on April 17, 2019 [8 favorites]

Miracle Max was right after all!
posted by Greg_Ace at 1:03 PM on April 17, 2019 [3 favorites]

After deciding on the final version of their technology, which they call BrainEx...

That sounds like a old-timey patent medicine that purports to eliminate unwanted brain tissue, which it technically can do over the long term because it's mostly alcohol.
posted by mandolin conspiracy at 1:04 PM on April 17, 2019 [8 favorites]

why tho
posted by bondcliff at 1:05 PM on April 17, 2019 [1 favorite]

You can count on humanity to spend its last years figuring out how to kill something twice
posted by Rust Moranis at 1:06 PM on April 17, 2019 [27 favorites]

This season of The Walking Dead is really struggling for good villains.
posted by haileris23 at 1:08 PM on April 17, 2019

"What do I have to lose? My jar?"
posted by They sucked his brains out! at 1:10 PM on April 17, 2019 [8 favorites]

The Porcine Dead
posted by randomination at 1:12 PM on April 17, 2019 [1 favorite]

So you're saying Ted Williams' head might still be able to hit when they thaw him out? Maybe? No? Then I guess I'm still not clear what the point was of freezing it.
posted by Cris E at 1:20 PM on April 17, 2019

"What do I have to lose? My jar?"
posted by They sucked his brains out!

posted by GenjiandProust at 1:33 PM on April 17, 2019 [6 favorites]

This is ripe for jokes about zombies or the cryonics folks, but studies like this help the general understanding of the brain. Much more likely is advances in how we respond to stroke or aid recovery after brain surgery.

Which is not to say that this is no joking matter, because jokes are fun, but this could have some pretty cool results.
posted by explosion at 1:53 PM on April 17, 2019 [22 favorites]

"Once a human dies and their tissue is in a laboratory, there are many fewer restrictions on what can be done," Grady says. "It is interesting to think about this issue in light of this experiment."

This is interesting because it would need to be demonstrated that the dead's brains could be resurrected, which would really open up a lot of difficult questions about rights of the living and the dead. There are also a ton of things about brains and consciousness we simply do not know and I think it would be extremely relieving to finally get some hard answers to those age old questions. If they ever need volunteers for human research in this way, sign me up. I don't want to live forever, hell, I don't always even want to live at all, but I truly believe understanding the nature of consciousness and brain functions could radically change humanity for the better and would totally be down to be a guinea pig in that regard.
posted by GoblinHoney at 2:20 PM on April 17, 2019 [3 favorites]

paging Ron Popeil
posted by jkaczor at 2:55 PM on April 17, 2019

I remember where I was in 1997 when I was reading about the cloning of Dolly the sheep, thinking how the future wonders I'd always heard about were beginning to come forward. Today, I see this and the first thing I think is all this will do is keep some Peter Thiel or Elon Musk on this planet long after our own loved ones have fallen away, and contribute to the rising problem of politicians in their late 70s and 80s.

It comes to something, you know? Clearly, there's a part of me that the scientists ought to bring back to life, but I'm afraid it can never be done.
posted by Countess Elena at 2:55 PM on April 17, 2019 [2 favorites]

I don’t think reanimating brains riddled with plaques and tangles is going to teach us much about Alzheimer’s disease. I have a lot more faith in in vivo amyloid and tau imaging techniques, which are a reality now.

It might teach us something about how information is stored, though. Maybe. However, when I read this I thought immediately of organ donation, and the uneasy fact that that rests on a fairly recent redefinition of what it means to be dead... one which, at first blush, this pig work seems to complicate.
posted by eirias at 3:01 PM on April 17, 2019 [2 favorites]

Also, I’m someone who has a relative who recovered from an irrecoverable coma! So I already have some feels about what doctors say they know, and what they actually know, about brain death.
posted by eirias at 3:06 PM on April 17, 2019 [2 favorites]

I'll let some doctors poke around with my mostly dead brain if it might reduce some of that in the world. I imagine it would not be hard to keep the brain vat full of a sedative if there was actually any risk of the brain booting back up conscious.

I would just give the brains their own MeFi accounts.
hey, wait a sec...
posted by Barack Spinoza at 3:07 PM on April 17, 2019 [2 favorites]

“Once a human dies and their tissue is in a laboratory, there are many fewer restrictions on what can be done," Grady says.

Next stop: Necrophilia City!
posted by dr_dank at 3:18 PM on April 17, 2019 [1 favorite]

I imagine it would be a tragic, hellish existence, to have immortality at the cost of being a brain in a jar, and nearly all the sensations you experience are disconnected "phantoms", uncontrolled memories from back when you had a body with eyes, skin, ears, and so on. The rest of your interactions with the natural world come from some lab techs interrupting your coma-like state, turning electrodes on and off here and there, letting you know that your credit is still good and that they can keep the lights on. Death would be a gift.
posted by They sucked his brains out! at 3:37 PM on April 17, 2019 [3 favorites]

My initial reaction was positive because of the obvious implications for basic science and advanced medicine, yet on further thought, I don't like how crude the experiment is. Temporarily reviving a whole dead brain at the tissue and cell level is a pointless unimpressive project, unless the researchers had some motivating context to do it. Is it routine scientific practice to keep other intact organs alive in laboratory conditions? Has that been beneficial? They don't (or the article doesn't) explicitly provide a compelling and ethically justified story why this approach is worth building their careers on.
posted by polymodus at 4:13 PM on April 17, 2019

on further thought, I don't like how crude the experiment is

I mean, you have to start somewhere.
posted by grumpybear69 at 4:26 PM on April 17, 2019 [1 favorite]

The article says "The scientists constantly monitored the pig brains' electrical activity, Latham says. If they had seen any evidence that signals associated with consciousness had emerged, they would have used anesthesia and cooling to shut that down immediately." But consciousness is such a mystery now, I mean...how would they know? Especially, as otbers have noted, since our rules about brain death and vegetative states are not always correct NOW.
And also, if consciousness is an emergent property of the brain then reactivating any of the architecture means really reactivating some conciousness, doesn't it? Things I ponder.
posted by Rufous-headed Towhee heehee at 4:40 PM on April 17, 2019 [4 favorites]

"How's it feel?"

"It doesn't."

"Bother you?"

"What bothers me is, nothin' does."
posted by wildblueyonder at 4:40 PM on April 17, 2019 [4 favorites]

Viral marketing for Pet Cemetery is impressive this time...

But the cat came back. He wouldn't stay away. He was sitting on the porch - BRAINS!
posted by Nanukthedog at 4:57 PM on April 17, 2019 [5 favorites]

I mean, you have to start somewhere.

So what I was saying is, without a clear context (and thus readers left to fill it in themselves), that "somewhere" is really nowhere. The experiment is crude because it lacks intellectual context, not because it's simple or basic or gross.
posted by polymodus at 5:00 PM on April 17, 2019

There is MRI imaging that give some indication that thought is occurring vs sleep or unconsciousness.
posted by sammyo at 5:33 PM on April 17, 2019

Horrifying and repugnant.

But I'll simply add it to the vast roster which will make what's about to happen to us feel like justice — mild justice.
posted by jamjam at 5:42 PM on April 17, 2019 [2 favorites]

Oh yeah, this will end well
posted by Pinback at 6:08 PM on April 17, 2019

Everything in Futurama is coming true. Heads in jars, Oprahism as an organized religion...
posted by Slarty Bartfast at 6:46 PM on April 17, 2019 [4 favorites]

and i, for one, welcome our zombie pig overlords
posted by entropicamericana at 7:25 PM on April 17, 2019

Hoo boy. Lot to unpack here. I don't have expertise with everything in this study, but the electrophysiological component is in my wheelhouse.

So first, my own summary of what this study is about based on my reading of it. The brain is the most metabolically demanding organ in the human body (and in that of most other large, complex animals). This makes it the most vulnerable of any organ to a loss of oxygen and nutrients, and in general after even a few minutes without blood flow, the brain suffers irreversible damage. However, there are a variety of reasons to think that this damage isn't an all-or-nothing kind of phenomenon, and some aspects of this damage may be recoverable even hours after loss of blood flow. Understanding whether and how this is possible is really important for treating stroke and other ischemic damage, and also for understanding the prognosis of patients in coma, persistent vegetative state, or even brain death. This research is an attempt to learn what kinds of cellular or even tissue-wide processes might be recoverable up to hours after total loss of oxygenated blood flow.

What they did
Basically, the took the brains of dead pigs and pumped a specially designed artificial blood through them, and tried to determine what physiological processes would recover on their own. They measured a variety of things, from structure to metabolism to electrophysiology.

What they found
Overall, their experiment seemed to arrest the normal cell death that would occur following death of the animal. (Note that in general, individual cells in the body, including individual neurons in the brain, can continue to live many minutes to hours after death of the organism.) Artificially pumping an oxygen-carrying medium mixed with neuroprotective drugs seems to stop the death of these individual cells. This was accompanied by a preservation of some larger-scale structure in the brain tissue. Additionally, various cell-level processes that would stop after the death of the organism were restored. The brains appeared to resume a certain level of metabolic activity, and individual neurons resumed spontaneously generating action potentials (the electrical signals they use to communicate). However, the global electrical activity that is characteristic of healthy brains was unaffected by their treatment. By the standard measures used to characterize brain death in humans, these brains were exactly as dead as they were prior to treatment. Individual neurons may have resumed their activity, but the tissue as a whole remained nonfunctional.

What they concluded
I think the best summary from the paper is this:
These findings indicate that molecular and cellular deterioration in the brain after circulatory arrest seems to follow a protracted process, instead of occurring within a singular, narrowly defined temporal window. Perhaps most importantly, with the appropriate intervention, the mammalian brain retains a greater capacity for metabolic and neurophysiological resilience to anoxic [loss of oxygen] or ischaemic [loss of blood flow] insult [physiological trauma] than is currently appreciated.
(My emphasis.)

How it's reported
The first sentence in the NPR article is technically correct:
The brains of dead pigs have been somewhat revived by scientists hours after the animals were killed in a slaughterhouse.
But that "somewhat" is doing a lot of work. The brains started as dead, and by the electrophysiological measures that are used to identify brain death, they remained exactly as dead throughout the experiment. I'm not a clinician and I have no personal experience with using EEG to diagnose brain death, but as I understand it there are cases in which the EEG results can be equivocal. What's reported in the paper is unequivocal. There is no activity consistent with a functioning brain. I've seen recordings of gelatin with more activity than what they show. What they've shown is that individual cells and some tissue-wide metabolic activity are revived, but this doesn't seem to yield a revived brain.

The rest of the article is pretty good as far as giving a decent explanation of the study and what was found, but I think overall the tone of the article, and the comments provided by other experts not directly affiliated with the study, give the impression that this is much closer to a "revive a brain in a vat" situation than it actually is.

What the bioethicists say
(Full disclosure, I've met Nita Farahany, the first author of the commentary cited above and one of the people quoted in the NPR piece, a few times while I was in grad school, though she probably doesn't remember me.) Farahany is quoted by NPR as saying "It's a groundbreaking discovery, but it also really fundamentally changes a lot of what the existing beliefs are in neuroscience about the irreversible loss of brain function once there is deprivation of oxygen to the brain." I don't entirely agree with this, actually. The recovery of cell-level function seen in this study is really interesting, but I don't think it by itself fundamentally changes what a lot of people think about what's possible for the brain to recover from. The lack of any sign of recovery in EEG or other systems-level functional recovery is completely consistent with what most people think about recovery from loss of blood flow and oxygen under these conditions, that is, it's not happening.

In their commentary, Farahany et al. noted that the researchers consulted with Yale's IACUC, which determined that no oversight was required because the pigs were already dead (which is generally true; IACUCs are only concerned with what happens before an animal dies). However, the researchers recognized that there was a risk that they were entering into a new gray area that the existing ethics rules and regulators might be poorly equipped to address, and so they took additional steps to avoid the possibility of resuscitating a dead pig brain to a state of experiencing suffering, for example, including anesthetics in their "artificial blood" medium, and being prepared to shut down the experiment at the first sign of any positive EEG signal if it were to occur (which apparently it didn't). They also directly engaged the bioethics community, seeking out input from various ethicists before beginning the work. I think the most important bit of Farahany et al.'s commentary on the study is this:
In our view, discussion about the appropriate path for this research should not wait for follow-up studies. The Yale group was conscientious and consulted the local institutional IACUC, Yale bioethicists, NIH programme officers and even the NIH Neuroethics Working Group. The researchers did what they could, and probably more than many would have done, to ensure that they were acting appropriately in a void of ethical analysis on the issue.

Now is the time to fill that void.
(My emphasis.)

In other words, the current ethics regulations have not considered the case of restoring any kind of function to dead, intact brains, and Yale's IACUC is essentially correct that there is no oversight required for dead animal tissue. This lack of oversight seems to be, well, an oversight, and Farahani et al. call for the bioethics community to address it. While Vrselja et al. appear to have met a standard above and beyond the regulatory requirements, the regulations and ethical standards should probably be adjusted to at minimum equal what they did, and consider the case of future scientific and technological developments that could actually restore systems-level functionality to a dead, currently-unregulated brain. I strongly agree with this opinion.

A few further thoughts
I actually don't think this represents a particularly strong step towards a "brain-in-a-vat" scenario, though I enjoy the jokes about it. Restoring function to individual neurons and restoring function to a system of nervous tissue are very different things, and I don't see anything in this study that suggests the latter is possible using their technique. Farahani et al. suggest that the lack of EEG may be due to the inhibitory drugs included in the media they perfused the brain with, but I don't buy that. Living brains on anesthesia have distinct, clearly identifiable EEG/ECoG patterns. These brains were dead, and had no systemic activity whatsoever.

Regarding sense of creepiness a lot of people here seem to have from this study, I think that makes sense, particularly when thinking about possible future applications that the NPR article seems to suggest are on the horizon. But I think there is less to be concerned about or creeped out by than it may first seem. When Luigi Galvani discovered in 1780 that electrical stimulation of a dead frog's legs could cause its muscles to contract in a life-like fashion, people were understandably creeped out then, as well. Mary Shelley was inspired to write Frankenstein in part by his experiments. But almost 240 years later, we're still not reanimating corpses, but we are using bioelectrical phenomena to regulate faulty heart rhythms, stabilize the tremor of people with Parkinson's, and develop neural prostheses to allow paraplegics to walk. Is it possible that this work could enable some kind of horrific brains-in-vats dystopia? Probably not, but we should definitely prepare ethics regulations to avoid it just in case. Will it enable new treatments for neurological trauma or better diagnosis of true brain death? Maybe not, but I think it's vastly more likely than the brain-in-vat scenario.

Finally, there's potentially a really positive research ethics outcome here that seems not to have been discussed much. Some studies of neurophysiology don't require a functioning brain, but they do require healthy, living neurons in their proper neural circuit. At the moment, these studies require euthanizing animals (usually rats or mice) in order to be able to gain access to the tissue quickly after death, before the cells begin to degrade or die. If this technique can be applied broadly, it's possible that some, maybe even most, of these studies could be done using brains acquired from slaughterhouses, where animals are being killed anyway, reducing the number of animals required for biomedical research. Reduction in numbers is one of the "three R's" of animal research ethics, generally one of the primary goals of ethical considerations, and this could be a powerful tool to achieve that goal in some cases.
posted by biogeo at 7:47 PM on April 17, 2019 [73 favorites]

posted by mwhybark at 8:12 PM on April 17, 2019 [3 favorites]

wait, the pig character is totes someone else, my bad
posted by mwhybark at 8:12 PM on April 17, 2019 [1 favorite]

molecular and cellular deterioration in the brain after circulatory arrest seems to follow a protracted process, instead of occurring within a singular, narrowly defined temporal window

So what you're saying here is that when we die it happens slowly and gradually, mental functions slipping away over minutes or hours? Great. That's just great. Really something to look forward to.

BRB patenting my Just Get It Over With™ instant-squish euthanasia machine
posted by ook at 5:10 AM on April 18, 2019 [3 favorites]

Good question, but I don't think so. Rather, our mental functions are supported by a complex interplay of molecular and cellular processes which require coordination that appears to be lost relatively quickly, even when those processes can persist in individual cells. We still have a long way to go to understand the "secret sauce" that makes the difference between a truly living, functioning, conscious brain versus a technically living but nonfunctional brain that is incapable of consciousness.
posted by biogeo at 6:22 AM on April 18, 2019 [2 favorites]

Giant Meteor 2020: Just Get It Over With™
posted by Johnny Wallflower at 7:47 AM on April 18, 2019 [2 favorites]

The pig's name was Abby... Abby... Abby Someone.
posted by slkinsey at 7:57 AM on April 18, 2019 [3 favorites]

Will this lead to a new paragraph in Do Not Resuscitate orders?
posted by StickyCarpet at 8:24 AM on April 18, 2019

"Refrigerate after opening."
posted by They sucked his brains out! at 10:34 AM on April 18, 2019 [3 favorites]

So in this case they took dead brains and put them in an artificial blood solution to provide nutrients and oxygen to the cells. The brains stay dead because that's how that works.

But what if we could find a way to switch a living brain directly from real blood to artificial blood without it dying in between the two? If that's possible, it doesn't necessarily need to lead to a brain-in-a-vat, but that depends on how much separation you need from the rest of the body to do it. Speaking in a sci-fi sort of extrapolation, I'm imagining a scenario where the body is badly injured. In the ER, the blood vessels leading to the brain are severed and used to circulate artificial blood separately from the rest of the body, protecting the brain. Are there different medicines that you can use on the rest of the body if you know the blood won't circulate to the brain? Maybe we even want to stop circulation in the rest of the body for a bit during surgery, which we can get away with for longer because the brain is separate. And at the end, the brain's blood vessels are reconnected to the body and the artificial blood flushed out.

This has about as much to do with the experiment as the brain-in-a-vat scenario, but it's a thought.
posted by vibratory manner of working at 2:57 PM on April 18, 2019 [5 favorites]

but it's a thought.

I see what you did there.
posted by Greg_Ace at 3:16 PM on April 18, 2019 [2 favorites]

You know, it turns out "somewhat" is exactly how far I've always wanted pigs' brains to be revived.
Thanks, science!
posted by Chitownfats at 4:46 PM on April 18, 2019 [1 favorite]

I see what you did there.

I perceive what you did there, with my meat-eyes.

There! Better!
posted by GenjiandProust at 4:56 PM on April 18, 2019 [1 favorite]

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