Frankenswine: Pig brains partly revived by scientists 4 hours after pigs were killed

Well that seems like a big deal.

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I don’t mean to give you nightmares America but someone is eyeing up this technology for the future. If they only revived 10% of his neurons he would still be twice as smart as he is now and then you will never get rid of him, mwa ha ha ha.

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OK so I pulled the paper and skimmed through. A few things jump out:

  1. The cells weren’t necessarily dead. The brains come from pigs that have been killed via electrical shock (cardiac arrest) and exsanguination. They then circulated cold isotonic fluid throughout the brain to keep things going and kept it mostly on ice. While cells aren’t happy about it, they’ll usually survive being placed on ice for a while.

  2. Data past 6 hours post-mortem doesn’t appear to be shown. Would have been cool to include 12- and 24-hour time-points.

  3. I’m not seeing any measurements of apoptosis or necroptosis, which suggests a much bigger focus on preserving architecture and some cell function than on quantifying what percentage of cells overall were preserved or how well.

  4. I would really like to have seen scRNAseq data from several time-points along the way to get more into ensemble changes in gene expression. I realize that this is a tedious and expensive endpoint to include, but it was right there for the taking! Here’s hoping they banked samples and will be digging deeper soon.

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“It’s Frankensween!”

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I’ll just leave this here.

http://www.gregegan.net/DISTRESS/Excerpt/DistressExcerpt.html

Damn, I just love real science speak. I am pretty good at clinical stuff, but when it comes to basic science, I mostly just a fan boi. Thank you.

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Just because you have your jargon soup and I have mine doesn’t mean we can’t appreciate that they’re both damn good soups! This is irrelevant to the discussion at hand, but I am so fucking pumped for where medicine is headed! Not this pig brain revival (new band name) stuff, but cheap biologics, cell therapies, and way way way better patient stratification.

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Since we appear to have a medical scientist in our midst, I’m taking the opportunity to ask some questions: As sensational as the headline is, does the paper reveal any purpose behind this work? As in, what are they hoping to prove or do with this research?

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I prefer Larks Tongues in Aspic.

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I am not the said medical scientist; but aside from basic research interest this avenue of work seems like it would be of great interest for the cases where the patient is overall in pretty good shape; but we cannot presently reverse the effects of some cell death in the brain.

That’s fairly common(strokes, drowning/asphyxiation when recovered quickly but not quickly enough, some sorts of mechanical trauma, blood loss sufficient to deprive the brain of oxygen but repairable once you reach the trauma surgeon); and leads to a lot of tragically debilitating outcomes, from nontrivial mental impairments to “we could keep the body alive for years; but that patient is basically dead.” cases.

Something that allows you to reactivate neural tissue that hasn’t been inactive for too long lengthens the window to discover and correct the underlying problem and getting the patient back without dire loss of mental function.

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I’ll do some interpretive dancing with excerpts. From the paper:

Many mammalian species have large, energy-demanding brains that are highly susceptible to anoxia and cessation of blood flow. Studies in both humans and experimental animals have shown that oxygen stores, global electrical activity, and consciousness are lost within seconds of interrupted blood flow, while glucose and ATP stores are depleted within minutes. Unless perfusion is quickly restored, multiple deleterious mechanisms lead to widespread membrane depolarization, loss of ionic homeostasis, mitochondrial dysfunction, and excitotoxic accumulation of glutamate. The convergence of these factors has been widely proposed to initiate a progressive, and largely irreversible, cascade of apoptosis, necrosis, and axonal damage.

Translation: brain death is bad for you.

However, several observations have questioned the inevitability
of neural cell death minutes, or even hours, after cessation of brain
perfusion

Translation: what if we could make brain death less bad for you?

These data suggest that the initiation and duration of cell death after anoxia or ischaemia may span a longer temporal interval than is currently appreciated, allowing for a multifaceted intervention that could halt the progression of damaging cellular programs initiated by the global insult. Therefore, we postulate that, under appropriate conditions, certain molecular and cellular functions in the large mammalian brain may retain at least partial capacity for restoration after a prolonged post-mortem interval (PMI).

Translation: we don’t really understand how death works

Using this technology, we have shown that microcirculation and
specific molecular and cellular functions in the large mammalian
brain can be restored under ex vivo normothermic conditions after an
extended PMI (see Supplementary Discussion). 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 or ischaemic insult than is currently appreciated

Translation: we found that brain death wasn’t as permanent as we used to think it was

Our technology requires further development, optimization, and
implementation, including studies with longer perfusion times. This
experimental approach may have broader applications than those
described herein, and could potentially help to bridge the gap between
basic neuroscience and clinical research, especially as it pertains to the human brain. This possibility raises important ethical considerations that must be addressed by researchers, institutional boards, and funding agencies, requiring the establishment of unambiguous standard operating procedures to preclude the possibility of re-activating and maintaining remnant awareness or brain functions that may result in inadvertent suffering45. Additionally, it is imperative for investigators to procure mammalian brains in an ethical manner consistent with all current and future regulations

Translation: more grants, please

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That final translation can be found in pretty much any paper you choose to read. It is the one absolute constant in research. More money, please!

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Mainly, I think, they are trying to advertise the ‘BrainEx’ perfusion system and the ‘Hemopure’ blood-substitute perfusion fluid (which is an expensive technology in search of an application).

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This study is a year old. https://www.technologyreview.com/s/611007/researchers-are-keeping-pig-brains-alive-outside-the-body/

It is getting a second round of publicity because the Yale team sexed it up enough for a Nature paper, and sent out a well-coordinated wave of press-releases to all the usual churnalists. Whatever their prowess in ‘reviving’ pig brains. I cannot question their ability to revive a news story a long time after it should have died.

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Instead of “FrankenSwine,” it should be “ReHaminator.”

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This calls for me to ressurrect Commander Powell from Dark Star.

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Nice summary.

As I understood things, the brain goes phlibbbbttt! when the life support stuff goes. The longer it stays off, the less chance you have of getting back to the complex process you had before. Yale haven’t changed that at all, All they have done so far is to provide an argument that your quarterpounder can feel pain. But it is possible that their technique may let us track the decay process, and find out what, if anything, slows it down.

There was something on Robert Cornish in a recent Futility Closet.

He had no good measure of death, so when he ‘revived’ a dog (blind and brain damaged) it is likely he did not kill it properly in the first place. All rather horrid.

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Surely teaching it the rudiments of phenomenology will have no potential downsides whatsoever. It works on planet-killer sized nuclear warheads after all…

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