How can you protect a brain by destroying it?


Last week, Simon Davis wrote to me with questions about this cryonic brain preservation technique, which has now been published as How to Freeze Your Brain and Live Forever (Maybe). Unfortunately, my comments did not make it into the story, because, Simon politely explained, there are length restrictions and perhaps, I assume, also because my extended dismissive scorn does not translate well to polite journalism. And that's OK! Because I have a blog, and I can rant here!

The Brain Preservation Society has a goal: to preserve dead brains today, so they can be reanimated at some distant time in the future. At least, that's what they say -- I'm more inclined to believe their goal is to pocket lots of money exploiting people's fear of death. Their immediate plan, though, is to develop more thorough mechanisms of locking down the fine structure of brains.

Extending today’s existing small-volume neural preservation techniques to whole brains is essential to the scientific goal of mapping neuronal connectivity across an entire human brain – a goal that has been identified by the NIH and others as crucial to furthering of our knowledge of brain function – see for example the NIH’s Human Connectome Project. Furthermore, advances in neuroscience today strongly suggest that appropriately preserved brains will contain our memories, identity, and a substrate for future consciousness, so that an appropriately verified preservation technology may allow future reanimation of the memories and identity of the preserved individual, if desired.

Lovely. I'm all in favor of mapping neuronal connectivity -- I did some small-scale stuff in that field decades ago. But they make extravagant claims.

The technology they are using is straightforward and useful.

We describe here a new cryobiological and neurobiological technique, aldehyde-stabilized cryopreservation (ASC), which demonstrates the relevance and utility of advanced cryopreservation science for the neurobiological research community. ASC is a new brain-banking technique designed to facilitate neuroanatomic research such as connectomics research, and has the unique ability to combine stable long term ice-free sample storage with excellent anatomical resolution. To demonstrate the feasibility of ASC, we perfuse-fixed rabbit and pig brains with a glutaraldehyde-based fixative, then slowly perfused increasing concentrations of ethylene glycol over several hours in a manner similar to techniques used for whole organ cryopreservation. Once 65% w/v ethylene glycol was reached, we vitrified brains at -135 °C for indefinite long-term storage. Vitrified brains were rewarmed and the cryoprotectant removed either by perfusion or gradual diffusion from brain slices. We evaluated ASC-processed brains by electron microscopy of multiple regions across the whole brain and by Focused Ion Beam Milling and Scanning Electron Microscopy (FIB-SEM) imaging of selected brain volumes. Preservation was uniformly excellent: processes were easily traceable and synapses were crisp in both species. Aldehyde-stabilized cryopreservation has many advantages over other brain-banking techniques: chemicals are delivered via perfusion, which enables easy scaling to brains of any size; vitrification ensures that the ultrastructure of the brain will not degrade even over very long storage times; and the cryoprotectant can be removed, yielding a perfusable aldehyde-preserved brain which is suitable for a wide variety of brain assays.

But first of all, you need to understand that their current methods don't involve simply freezing brains. They are freezing brains and perfusing them with glutaraldehyde to fix them, better preserving the ultrastructure of the tissue. Every microscopists does this; I was fixing zebrafish brains with a cocktail of acrolein, glutaraldehyde, and paraformaldehyde in the 1980s, trying to capture detailed images of synapses in the spinal cord. It worked pretty well, too. They know what they are getting out of this: an aldehyde-preserved brain.

What I didn't do with my experiments in aldehyde-preserved brains was claim that I was preserving all the information necessary for nervous system function. I was quite aware that I was chemically nuking all the proteins in the tissue; I was washing out most of the chemistry; I was destroying most of the physiological information to preserve a structural skeleton of what was there, so I could see the physical arrangement of the pieces. Nothing more.

Neuroscience does not suggest that fixing a brain in aldehydes will preserve "memories, identity, and a substrate for future consciousness". There's no reason to think their methods create "appropriately preserved brains".

There is a respectable question to be answered with their techniques about the structure of the brain, but it is only one tiny step forward in understanding how the brain functions and generates a mind. Ultrastructure is something we can study, so it's an issue of chasing the question that can be answered while telling everyone you're trying to address a completely different question that can't.

The pattern of synaptic connections is an essential part of the story, but it is not sufficient. A simple counterexample: consider the effect of MAO inhibitors and various antidepressants. They modulate the activity of the brain by affecting the intercellular concentration of neurotransmitters. Consider hormonal effects: your brain is profoundly altered by the chemical signals in your blood (and recursively, secretes hormones of its own). There's this whole phenomenon called non-synaptic plasticity, in which the behavior of ion channels and pumps is modified by, for instance, phosphorylation, or binding of cofactors.

These things are all destroyed by fixation. The information is no longer there.

If this organization is so confident that they have preserved all the necessary information, I'd like to know why they're playing around with just the first step of the problem, doing so in impractically complex organisms, and not working on the necessary step of recovering that information. That's the real test.

Take a simpler organism, like a fruit fly or a nematode. Kill it, fix it, freeze it, vitrify it. That should be trivial at their tiny scale. Then rebuild a fly brain from the extracted information and show me that it still knows how to walk, fly, eat, court, and mate.

Nobody's even close to accomplishing any of that.

Until then, any talk of an adequate preservation method is simply wishful thinking, especially when it relies on the kind of obliteration of the molecular information in the brain that the Brain "Preservation" Society is doing.

Of course, I actually know why they don't do any of that. Fruit flies and nematodes won't pay them a substantial annuity to have their brains vitrified and stored, and their gratitude upon being resurrected wouldn't be at all remunerative.

But for now, they've got really good EM technique and can show off pretty pictures of well-fixed cells. Bravo! Who knew that I was so cutting-edge 30 years ago?


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"Take a simpler organism, like a fruit fly or a nematode. Kill it, fix it, freeze it, vitrify it. That should be trivial at their tiny scale. Then rebuild a fly brain from the extracted information and show me that it still knows how to walk, fly, eat, court, and mate" That is exactly the type of experiment that would be convincing for scientists. May be even with 1) bigger animals such as mice and 2) with artificial small brains made in culture with stem cells.

By claude paul Malvy (not verified) on 30 Jan 2016 #permalink

More Transhumanist quackery, on par with Deepak Chopra's stuff about conscious gut bacteria and fizzy magnesium hydride pills.

Agreed, "...their goal is to pocket lots of money exploiting people’s fear of death."

But this time, instead of uploading souls to God-boxes, we're back to good old cryogenic limbo: the "Freezers for Geezers" plan. And, since it's too expensive to freeze your whole body, you can just freeze your brain. Which only goes to show that "if you can't get a life, at least you can get a head";-)

Re. neglecting the chemistry of consciousness: That's a common oversight by Transhumanists, whose official dogma is that brains are nothing more than assemblages of binary electrical switches that can be replicated in silicon. All those pesky neurotransmitters and neurohormones can be entirely dispensed with in the quest for resurrection and immortality. Since we don't need the neurochemicals, we can just wash them away with aldehydes. Yes, that would be "brainwashing," though a bit more sophisticated than what the Moonies do.

Transhumanism is nothing more than a new religion wrapped in "high tech" to make it look sciencey. I see from the linked article that Humai even calls its "learn everything about you" app Soul. Presumably the fine print says they can sell everything they learn about you to Big Data, which is only one step better than selling it to identity theft rings in Moscow. Speaking of "selling your Soul." The jokes write themselves.

It's good to read your take-down of this crap. Atheists, rationalists, and skeptics need to get much more vocal, since Transhumanism has caught on in Silicon Valley and is starting to percolate into the culture at-large. This resembles the 1970s when wacko religious cults were on the rise: the Moonies, Hare Krishna, Scientology, etc.

PZ, if you had to solve the problem that cryonicists want to solve, given your expertise as a neuroscientist, how would you go about trying to solve it?

By Mark Plus (not verified) on 06 Feb 2016 #permalink

Seems like most of the chemistry would be preserved, though, including hormones, ion pumps, phosphorylation, etc. Even if proteins are altered, their locations should still be preserved just fine. The whole idea is to preserve as much of the complexity as possible. Objections about revival should be kept entirely separate from objections about preservation quality.

By Jordan Sparks (not verified) on 06 Feb 2016 #permalink

I put $500k of my own money into this technology every single year, and it's quite clear I will never get any of it back. Does that sound to you like someone who is trying to take advantage of others? At worst, it's delusional, but it's quite obviously not exploitative.

By Jordan Sparks (not verified) on 06 Feb 2016 #permalink

Hasn't anyone watched Futurama? Kids these days...

The whole conclusion to this piece is bizarre. Has PZ never spoken to someone involved with Cryonics before? Obviously actually reviving a cryonically stored life form is not on the agenda in the near term, or probably even the medium term. The thing is, if we can find a way to preserve the brain pretty exactly, it won't matter how long it takes to develop that technology, since frozen heads in jars can afford to be very patient. You don't even have to preserve the head very well, just make sure that it's possible for people with technology far, far ahead of what we have now to reconstruct how the brain looked before the preservation process.

By Quite Likely (not verified) on 09 Feb 2016 #permalink

"Quite Likely" and others: Lots of IFs there. IF I invent a perpetual motion machine, and IF homeopathy works, THEN all of our problems will be solved. Right. That's faith, not reason. (For all you know, if Singularity robots take over the Earth, they might discover Alcor and treat it like the frozen food aisle in the supermarket.)

Jordan: As a free person, you have the right to do whatever you like with your money, and as a free person, I have a right to tell you that you're burning your children's inheritance for the sake of a delusion, which in the end is selfish and therefore immoral. You may as well be donating it to Scientology in the hope of getting all those pesky Thetans scrubbed out of your soul.

BTW, speaking of homeopathy, Singularity founder Ray Kurzweil is also into all manner of quack medicine including taking @ 150 supplements a day and subscribing to the "acid/alkaline" theory of health, one of whose proponents just got convicted of practicing medicine without a license. If he's so far from reality on those kinds of things, how is it that anyone takes the rest of his prophesies seriously?

Face this: You're going to die, and when you die, one of two things will be true. Either your mind will shift to another state of existence, or your mind will cease to exist entirely. Interestingly, you only get to find out which is true, if the former is true. So the only answer you can possibly get, to the "what happens when I die?" question, is, "you shift to another state of existence." Because if what happens is that your mind ceases to exist, you won't be around to reflect on the cessation of your existence.

If that sort of thing terrifies you, I'd strongly suggest practicing Buddhist meditation exercises daily (no belief in a deity is needed) until you lose your fear of nothingness. Because in the end, there's nothing to be afraid of.

The Brain Preservation Foundation is not in the business of preserving brains for future revival. They are a non-profit organization dedicated to advancing brain preservation research. As a first step towards a brain preservation technology, they are focusing on preservation of the structural connectome. As you say, preserving the brain's structure is a necessary part of preserving the brain's information. The BPF's website is quite clear on this: "Disclaimer: We don’t preserve people at BPF, and we don’t advocate any particular preservation method or company."

As far as I can tell, the BPF's position is totally reasonable: They think that a working brain preservation technology would be of great benefit to humanity, so they funded a tech prize to motivate the first step of the process: good-looking structure. Now that the prize has been won it's important to take stock of what current neuroscience research says about memory storage, and what other conditions a brain preservation protocol would need to satisfy to preserve a person's memories. In parallel, Dr. Hayworth, president of the Brain Preservation Foundation, is working on the FlyEM project, attempting to do exactly what you suggest -- upload a fly brain.

Do not confuse the Brain Preservation Foundation with current cryonics practice. No one is currently offering aldehyde-stabilized cryopreservation to people for money. The Brain Preservation Foundation folks think that brain preservation technology is valuable and are working to encourage its development. If you thought brain preservation was important, how would you go about encouraging its development?

Also, why do you think that the phosphorylation states of ion channels would be modified by aldehyde fixation?

PZ, you're saying that capturing the information about synaptic connectivity is not sufficient. Sufficient for what? For the brain to function? Sure, but the goal here is not to recreate a functional brain, it's to recreate a personality, most likely in a new carrier. This new carrier, a substrate for consciousness, might not even be a biological brain. It could be a computer. Do we need all that physiological information to preserve a personality? It seems like they think so, and you disagree, but is there a definite answer?