12 ms·

Aldehyde-Stabilized Cryopreservation Procedure Wins Brain Preservation Prize

75 points by nikolay 11y ago

nikolay 11y ago
This is the third aspect I post on the subject and I'm surprised that there's zero engagement regarding such a great scientific achievement!
- ddorian43 11y ago
  We gotta chase the latest photo-sharing apps bro. Also check what time it is when you post.
- jacquesm 11y ago
  I'll give you some engagement. I really think it is sad that you see this as a 'great scientific achievement' when in actual fact nothing of note has been achieved. The whole article reads like a puff-piece pretending this is a major breakthrough when in fact as far as I can see it not much of note has been achieved, yes, it's a mammal but certain types of frogs have been known to be able to freeze and thaw and their neurological systems are working just fine afterwards. In this case all we have is some visual inspection which makes the claim that the brain has been recovered a bit doubtful, it's not as if a rabbit using that previously frozen brain is hopping around. (That probably would be a breakthrough.) Cryopreservation, uploading, life extension technology and related fields are for the most quack science taking money from the gullible (or their estates) and spending it on un-productive areas of research. I sincerely wished that HN would stick to discussing things with a bit more solidity, if we afford these subjects the amount of space their proponents would like then HN would go the same way as renewable energy fora that allowed 'zero point energy' enthusiasts to run unchecked. I'm happy for you that you wish to live for ever (who doesn't?) and that you believe that in your lifetime we'll see a major change in this respect but I'm a bit tougher to convince and I've seen enough bs during my lifetime to solidly vote against giving this stuff more airtime than it already has. Historically, anybody that tried to peddle life eternal turned out to have been lying. FWIW you're going to die, get used to it and make the most of the time that you have. If and when the future dictates otherwise you'll be able to adjust with grace and on the off chance that it does not you'll be happy you followed my advice.
  - wodencafe 11y ago
    That's a bit insulting of you, to presume that anyone who forms an opinion of Cryonics beyond "It's Quack Science" is only interested in "living forever", and not to be taken seriously. The essence of your argument is circular: it doesn't work because it's quack science, and it's quack science because it doesn't work - but it doesn't matter, because you're going to die anyway. What a cop out. One would think you got your information on Cryonics from watching an old VHS of "The Re-Animator"
    - jacquesm 11y ago
      > One would think you got your information on Cryonics from watching an old VHS of "The Re-Animator" That's a bit insulting of you. And to answer, no, I get my information from reading articles such as those linked, hence my comment on it. I've seen enough of the groups pushing these kind of pieces to see them as no better than religious groups selling 'the afterlife' and associated goodies with zero chance of actually delivering on their promises. And just like those religious groups they always need a little bit more money. It's quack science because none of it works. It will be science once someone can freeze a very small mammal (say a tiny rodent), keep it frozen for a while and then thaw that creature again and it will live a long and healthy life. It will be science when someone scans a very small brain to a very high resolution, will build a functioning simulation of that brain in a computer to such an extent that the simulation exhibits all of the traits of the original. Until then it's all just purposefully soft-balled problems that pretend to solve some crucial aspect of the whole chain without actually addressing the main problems head on, just enough 'progress' to keep the funding coming. I make my living debunking bs and this stuff is - to me - a very high grade of it, all I see here is a cynical attempt at getting funding by for instance linking Alzheimer research to this group (which they have absolutely nothing to do with). Feel free to have a different opinion.
      - MikeNomad 11y ago
        "It will be science when someone scans a very small brain to a very high resolution, will build a functioning simulation of that brain in a computer to such an extent that the simulation exhibits all of the traits of the original." And that science will not happen until we have (among several things) the ability to stabilize a brain sufficiently (when no longer being used for its original purpose) to have a very high resolution scan performed and stored. I would think getting this first part correct would be of the utmost importance. Scan resolutions will continue to improve for any number of reasons beyond this application. It would appear that the primary subject of the OP is both quite relevant, and an important building block, allowing research to move further along this particular approach.
camillomiller 11y ago
What I find confusing is that (from a quick skim) there's no mention on how easy it would be to actually bring back the brain in, say, 50 years. Does this method make reviving brain tissue easier?
- omgtehlion 11y ago
  No. This method is used to micro-image the brain cells, not to revive it. Essentially it kills it (and kills it fast), then binds all proteins so they remain intact.
- mackman 11y ago
  The breakthrough here was injecting a poison that makes revival impossible but allows freezing with synaptic structure intact. Then hypothetically you can slice and scan the brain and simulate it later when computers are powerful enough. Personally that seems more likely tha figuring out a new reversible freezing process.
- imaginenore 11y ago
  Do you expect an actual answer of what will be possible in 50 years? It's just a logical development. Less damage => more chance of recovery.
nickledave 11y ago
jacquesm is right, there's no actual scientific breakthrough here. We already know glutaraldehyde does a good job of preserving synaptic structure, that's why we have used it to fix brains for electron microscopy analysis for roughly a century. I guess it's cool that you can freeze a glut-fixed brain and then unfreeze it and that won't have a dramatic effect on the structure. I'd be interested to know how quantitative their analysis was. Absence of evidence (of deformed synapses) is not evidence of absence. But anyways the synaptic ultrastructure probably isn't everything. It's necessary but not sufficient.
reasonattlm 11y ago
The comments suggesting that this is unimportant are pretty silly. People have been objecting to cryonics on the basis that it hasn't been proven beyond a doubt to preserve fine structure, versus only having had a reasonable set of evidence to preserve fine structure. They have objected on the basis that proven methods of preservation in small scale tissue samples hadn't been rigorously demonstrated to work in large organs. Now that the fine structure and scaling doubts are dispelled, they move on to objecting for other reasons, and even suggest that it was obvious in hindsight that the fine structure was preserved, or that methods would scale. Denying that cryonics is relevant or useful or a valid area of research and development because no-one has yet completely implemented the full loop of technologies for reversible full body cryopreservation is missing the point. (But note that it has been done for a single organ, which was transplanted, and functioned). The point is that we could be saving lives, and we are not, largely because of irrational objections that are not really based on technological or scientific positions, but grasp at a those positions as a shield for the real nebulous feelings on the matter. The reversal of cryonics in the future has been written on extensively. There are very detailed treatments of what would be required. There is no sound reason to think it impossible; it's just a matter of sufficient control over chemistry and biochemistry. If you believe that there is some sound reason that it is impossible, then publish a paper - it would be influential if correct, because it would demolish the work of much of the cryobiology community in their initiatives to create reversible cryopreservation of organs and tissues. Here is the paper for this research by 21st Century Medicine: "Aldehyde-stabilized cryopreservation": http://dx.doi.org/10.1016/j.cryobiol.2015.09.003 http://dx.doi.org/10.1016/j.cryobiol.2015.09.003
- jacquesm 11y ago
  What a load of bull. Cryopreservationist walks into a bar. Goes 'Hey, everybody, pay me $50 and I'll show you a fantastic trick, I take your watch, put it in a bag, smash it up with a hammer, then open the bag and out comes your watch'. Fascinated a number of patrons sign up and pay their $50, hand over their watches. Audible gulps as the watches go into a nice silver velvety bag and a very large hammer smashes down on the bag with the bar serving as temporary anvil. The bag with the remains of the watches gets carefully pocketed and some of the money goes towards ordering a round of drinks for everybody. So, how about my watch, asks one of the people that handed over his watch and his money. "Oh, that's the hard part, I haven't really studied that yet, come back in a few 100 years and I might have your watch again. But I'm getting better at smashing watches, that's for sure." > The point is that we could be saving lives, and we are not, largely because of irrational objections that are not really based on technological or scientific positions, but grasp at a those positions as a shield for the real nebulous feelings on the matter. What makes you believe that we could be saving lives?
dnautics 11y ago
Aldehydes covalently bond and crosslink the proteins and irreversibly kill all of the fixed cells. There is zero hope that this provides a solution to cryopreservation except in the slice it up and look at it under the microscope sense.
- jimrandomh 11y ago
  True! But slicing it up and looking at it under microscopes is, in fact, the most likely means of restoring cryopreserved brains, either as computer simulations or as nanobot-constructed replicas. Doing it this way is easier because such techniques could handle cases where molecules are damaged in ways that make them not function but which make it obvious (from a good microscope reading) what they were before.
- lsparrish 11y ago
  > Aldehydes covalently bond and crosslink the proteins and irreversibly kill all of the fixed cells. That is the textbook answer, however these bonds are only "irreversible" as a matter of biochemistry. You can actually break any chemical bond by increasing the temperature enough. The problem for our purposes is that this means destroying the structure. > There is zero hope that this provides a solution to cryopreservation except in the slice it up and look at it under the microscope sense. The trick to reversing the bond without damaging the structure would be in delivering high enough amounts of energy with high enough precision to have only the intended effects. This may or may not be physically possible. However, to rule out the possibility completely, we would need to consider a wide variety of physical interactions that are well outside the range of biology and wet-solvent chemistry, in addition to the full spectra of potential biomimetic and biological approaches.
  - dnautics 11y ago
    Good luck. When you make an imine with an aldehyde the principal mechanism of irreversability is that a stray reductant (available in spades in biochemical settings) takes the imine down to a primary amine. (This is not found in most textbooks, you just have to know that). Now, a primary amine is a relatively stable covalent bond, and getting selective deamination is going to be especially difficult since there's plenty of amines around. Not the least of which is the other side of the lysine that the aldehyde attached to in the first place.
zimpenfish 11y ago
PZ Myers had a good take on this a few days ago - http://scienceblogs.com/pharyngula/2016/01/29/how-can-you-protect-a-brain-by-destroying-it/ http://scienceblogs.com/pharyngula/2016/01/29/how-can-you-pr... > 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.
- lsparrish 11y ago
  His criticism bad (as ever), since he assumes all information needed for nervous system function is the same as all information needed to replicate a given nervous system. Most of the information needed for function in any system is generic across similar systems. We are only interested in the information that is specific to the individual.
  - kanzure 11y ago
    > We are only interested in the information that is specific to the individual. Not necessarily; there's a lot of value to be had in the non-specific information, too.
    - lsparrish 11y ago
      This technique is useful for general neuroscience purposes, yes. My point was just that it isn't what is critical to preserve for the sake of cryonics.
- cbr 11y ago
  The question of whether the physical structure is enough to preserve the information that makes you you is the key thing, and Myers is right to say we should be trying to figure out how to read the information off of very small brains. On the other hand, if you think that the physical structure is sufficient (I don't) then figuring out how to preserve whole human brains is pretty important. There's a long time to figure out how to read the information off the preserved brains, but any unpreserved (or improperly preserved) ones are gone for good. So I see why Hayworth etc are interested in high-quality preservation of larger and larger animals and aren't focusing on the reading portion. "I'm more inclined to believe their goal is to pocket lots of money exploiting people’s fear of death. ... 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." I've met Hayworth, this really doesn't fit him. He is genuinely interested in better preservation methods as a way to fight death. As a neuroscientist working in connectomics his association with cryonics only hurts him professionally.

75 points by nikolay 11y ago

This is the third aspect I post on the subject and I'm surprised that there's zero engagement regarding such a great scientific achievement!

ddorian43 11y ago
We gotta chase the latest photo-sharing apps bro. Also check what time it is when you post.
jacquesm 11y ago
I'll give you some engagement. I really think it is sad that you see this as a 'great scientific achievement' when in actual fact nothing of note has been achieved. The whole article reads like a puff-piece pretending this is a major breakthrough when in fact as far as I can see it not much of note has been achieved, yes, it's a mammal but certain types of frogs have been known to be able to freeze and thaw and their neurological systems are working just fine afterwards. In this case all we have is some visual inspection which makes the claim that the brain has been recovered a bit doubtful, it's not as if a rabbit using that previously frozen brain is hopping around. (That probably would be a breakthrough.) Cryopreservation, uploading, life extension technology and related fields are for the most quack science taking money from the gullible (or their estates) and spending it on un-productive areas of research. I sincerely wished that HN would stick to discussing things with a bit more solidity, if we afford these subjects the amount of space their proponents would like then HN would go the same way as renewable energy fora that allowed 'zero point energy' enthusiasts to run unchecked. I'm happy for you that you wish to live for ever (who doesn't?) and that you believe that in your lifetime we'll see a major change in this respect but I'm a bit tougher to convince and I've seen enough bs during my lifetime to solidly vote against giving this stuff more airtime than it already has. Historically, anybody that tried to peddle life eternal turned out to have been lying. FWIW you're going to die, get used to it and make the most of the time that you have. If and when the future dictates otherwise you'll be able to adjust with grace and on the off chance that it does not you'll be happy you followed my advice.
- wodencafe 11y ago
  That's a bit insulting of you, to presume that anyone who forms an opinion of Cryonics beyond "It's Quack Science" is only interested in "living forever", and not to be taken seriously. The essence of your argument is circular: it doesn't work because it's quack science, and it's quack science because it doesn't work - but it doesn't matter, because you're going to die anyway. What a cop out. One would think you got your information on Cryonics from watching an old VHS of "The Re-Animator"
  - jacquesm 11y ago
    > One would think you got your information on Cryonics from watching an old VHS of "The Re-Animator" That's a bit insulting of you. And to answer, no, I get my information from reading articles such as those linked, hence my comment on it. I've seen enough of the groups pushing these kind of pieces to see them as no better than religious groups selling 'the afterlife' and associated goodies with zero chance of actually delivering on their promises. And just like those religious groups they always need a little bit more money. It's quack science because none of it works. It will be science once someone can freeze a very small mammal (say a tiny rodent), keep it frozen for a while and then thaw that creature again and it will live a long and healthy life. It will be science when someone scans a very small brain to a very high resolution, will build a functioning simulation of that brain in a computer to such an extent that the simulation exhibits all of the traits of the original. Until then it's all just purposefully soft-balled problems that pretend to solve some crucial aspect of the whole chain without actually addressing the main problems head on, just enough 'progress' to keep the funding coming. I make my living debunking bs and this stuff is - to me - a very high grade of it, all I see here is a cynical attempt at getting funding by for instance linking Alzheimer research to this group (which they have absolutely nothing to do with). Feel free to have a different opinion.
    - MikeNomad 11y ago
      "It will be science when someone scans a very small brain to a very high resolution, will build a functioning simulation of that brain in a computer to such an extent that the simulation exhibits all of the traits of the original." And that science will not happen until we have (among several things) the ability to stabilize a brain sufficiently (when no longer being used for its original purpose) to have a very high resolution scan performed and stored. I would think getting this first part correct would be of the utmost importance. Scan resolutions will continue to improve for any number of reasons beyond this application. It would appear that the primary subject of the OP is both quite relevant, and an important building block, allowing research to move further along this particular approach.

camillomiller 11y ago

What I find confusing is that (from a quick skim) there's no mention on how easy it would be to actually bring back the brain in, say, 50 years. Does this method make reviving brain tissue easier?

omgtehlion 11y ago
No. This method is used to micro-image the brain cells, not to revive it. Essentially it kills it (and kills it fast), then binds all proteins so they remain intact.
mackman 11y ago
The breakthrough here was injecting a poison that makes revival impossible but allows freezing with synaptic structure intact. Then hypothetically you can slice and scan the brain and simulate it later when computers are powerful enough. Personally that seems more likely tha figuring out a new reversible freezing process.
imaginenore 11y ago
Do you expect an actual answer of what will be possible in 50 years? It's just a logical development. Less damage => more chance of recovery.

nickledave 11y ago

jacquesm is right, there's no actual scientific breakthrough here. We already know glutaraldehyde does a good job of preserving synaptic structure, that's why we have used it to fix brains for electron microscopy analysis for roughly a century. I guess it's cool that you can freeze a glut-fixed brain and then unfreeze it and that won't have a dramatic effect on the structure. I'd be interested to know how quantitative their analysis was. Absence of evidence (of deformed synapses) is not evidence of absence. But anyways the synaptic ultrastructure probably isn't everything. It's necessary but not sufficient.

reasonattlm 11y ago

The comments suggesting that this is unimportant are pretty silly. People have been objecting to cryonics on the basis that it hasn't been proven beyond a doubt to preserve fine structure, versus only having had a reasonable set of evidence to preserve fine structure. They have objected on the basis that proven methods of preservation in small scale tissue samples hadn't been rigorously demonstrated to work in large organs. Now that the fine structure and scaling doubts are dispelled, they move on to objecting for other reasons, and even suggest that it was obvious in hindsight that the fine structure was preserved, or that methods would scale. Denying that cryonics is relevant or useful or a valid area of research and development because no-one has yet completely implemented the full loop of technologies for reversible full body cryopreservation is missing the point. (But note that it has been done for a single organ, which was transplanted, and functioned). The point is that we could be saving lives, and we are not, largely because of irrational objections that are not really based on technological or scientific positions, but grasp at a those positions as a shield for the real nebulous feelings on the matter. The reversal of cryonics in the future has been written on extensively. There are very detailed treatments of what would be required. There is no sound reason to think it impossible; it's just a matter of sufficient control over chemistry and biochemistry. If you believe that there is some sound reason that it is impossible, then publish a paper - it would be influential if correct, because it would demolish the work of much of the cryobiology community in their initiatives to create reversible cryopreservation of organs and tissues. Here is the paper for this research by 21st Century Medicine: "Aldehyde-stabilized cryopreservation": http://dx.doi.org/10.1016/j.cryobiol.2015.09.003 http://dx.doi.org/10.1016/j.cryobiol.2015.09.003

jacquesm 11y ago
What a load of bull. Cryopreservationist walks into a bar. Goes 'Hey, everybody, pay me $50 and I'll show you a fantastic trick, I take your watch, put it in a bag, smash it up with a hammer, then open the bag and out comes your watch'. Fascinated a number of patrons sign up and pay their $50, hand over their watches. Audible gulps as the watches go into a nice silver velvety bag and a very large hammer smashes down on the bag with the bar serving as temporary anvil. The bag with the remains of the watches gets carefully pocketed and some of the money goes towards ordering a round of drinks for everybody. So, how about my watch, asks one of the people that handed over his watch and his money. "Oh, that's the hard part, I haven't really studied that yet, come back in a few 100 years and I might have your watch again. But I'm getting better at smashing watches, that's for sure." > The point is that we could be saving lives, and we are not, largely because of irrational objections that are not really based on technological or scientific positions, but grasp at a those positions as a shield for the real nebulous feelings on the matter. What makes you believe that we could be saving lives?

dnautics 11y ago

Aldehydes covalently bond and crosslink the proteins and irreversibly kill all of the fixed cells. There is zero hope that this provides a solution to cryopreservation except in the slice it up and look at it under the microscope sense.

jimrandomh 11y ago
True! But slicing it up and looking at it under microscopes is, in fact, the most likely means of restoring cryopreserved brains, either as computer simulations or as nanobot-constructed replicas. Doing it this way is easier because such techniques could handle cases where molecules are damaged in ways that make them not function but which make it obvious (from a good microscope reading) what they were before.
lsparrish 11y ago
> Aldehydes covalently bond and crosslink the proteins and irreversibly kill all of the fixed cells. That is the textbook answer, however these bonds are only "irreversible" as a matter of biochemistry. You can actually break any chemical bond by increasing the temperature enough. The problem for our purposes is that this means destroying the structure. > There is zero hope that this provides a solution to cryopreservation except in the slice it up and look at it under the microscope sense. The trick to reversing the bond without damaging the structure would be in delivering high enough amounts of energy with high enough precision to have only the intended effects. This may or may not be physically possible. However, to rule out the possibility completely, we would need to consider a wide variety of physical interactions that are well outside the range of biology and wet-solvent chemistry, in addition to the full spectra of potential biomimetic and biological approaches.
- dnautics 11y ago
  Good luck. When you make an imine with an aldehyde the principal mechanism of irreversability is that a stray reductant (available in spades in biochemical settings) takes the imine down to a primary amine. (This is not found in most textbooks, you just have to know that). Now, a primary amine is a relatively stable covalent bond, and getting selective deamination is going to be especially difficult since there's plenty of amines around. Not the least of which is the other side of the lysine that the aldehyde attached to in the first place.

zimpenfish 11y ago

PZ Myers had a good take on this a few days ago - http://scienceblogs.com/pharyngula/2016/01/29/how-can-you-protect-a-brain-by-destroying-it/ http://scienceblogs.com/pharyngula/2016/01/29/how-can-you-pr... > 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.

lsparrish 11y ago
His criticism bad (as ever), since he assumes all information needed for nervous system function is the same as all information needed to replicate a given nervous system. Most of the information needed for function in any system is generic across similar systems. We are only interested in the information that is specific to the individual.
- kanzure 11y ago
  > We are only interested in the information that is specific to the individual. Not necessarily; there's a lot of value to be had in the non-specific information, too.
  - lsparrish 11y ago
    This technique is useful for general neuroscience purposes, yes. My point was just that it isn't what is critical to preserve for the sake of cryonics.
cbr 11y ago
The question of whether the physical structure is enough to preserve the information that makes you you is the key thing, and Myers is right to say we should be trying to figure out how to read the information off of very small brains. On the other hand, if you think that the physical structure is sufficient (I don't) then figuring out how to preserve whole human brains is pretty important. There's a long time to figure out how to read the information off the preserved brains, but any unpreserved (or improperly preserved) ones are gone for good. So I see why Hayworth etc are interested in high-quality preservation of larger and larger animals and aren't focusing on the reading portion. "I'm more inclined to believe their goal is to pocket lots of money exploiting people’s fear of death. ... 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." I've met Hayworth, this really doesn't fit him. He is genuinely interested in better preservation methods as a way to fight death. As a neuroscientist working in connectomics his association with cryonics only hurts him professionally.