With the inevitable end in sight – and with the cancer continuing to spread throughout her brain – Kim made the brave choice to refuse food and fluids. Even so, it took around 11 days before her body stopped functioning. Around 6:00 am on Thursday January 17, 2013, Alcor was alerted that Kim had stopped breathing. Because Kim’s steadfast boyfriend and family had located Kim just a few minutes away from Alcor, Medical Response Director Aaron Drake arrived almost immediately, followed minutes later by Max More, then two well-trained Alcor volunteers. As soon as a hospice nurse had pronounced clinical death, we began our standard procedures. Stabilization, transport, surgery, and perfusion all went smoothly. A full case report will be forthcoming.The hidden horror of this defies imagination. There's suffering, there's anxiety, there's fear, and there's burden of choice - anxiously reading about the procedures, second-guessing yourself - are you deluding yourself, are you grasping at straws, or are you being rational? When is the tipping point where you'll deny life support? This kind of decision hurts. I really hope that she simply believed it to be worth a shot and did not have to suffer from the ambiguity of the evidence, but I don't know, and its scary to imagine facing such choices.
Then if she is awakened - sadly, it seems exceedingly likely that almost everyone she knew will be dead, or aged beyond recognition, it is exceedingly likely that she will largely not be herself. No one ever looked if vitrification solution reaches the whole of the human brain - in the parts it won't reach, will be shredded, the parts it does reach, proteins denature. Tossing a book with pictures into a bucket of solvents is not a good way to preserve it's contents when you don't know what the paint is made of, especially if parts of the book not reached by solvents are then shredded.
If you're an altruist, well, there's a lot of people to save via more reliable, not so mentally painful, vastly cheaper methods, to which the majority of the population lacks access. Altruism doesn't explain cryonics promotion. Selfishness does - you believe in cryonics and you want confirmation, cryonics is your trade so you'll pitch it, or you're signed up and you need volunteers to test methods for your own freezing, or you want to feel exclusive and special... A lot of motives, but altruism is not one of them. Promoting cryonics, like any expensive, unproven, highly dubious medical procedure, is not a good thing to do. As far as beliefs go, "you'll almost certainly die but there's a chance you won't" is not the most comforting one.
Speaking of brains. Currently, among other things, I develop software for viewing serial block-face microscopy data, on a contract. This is my private opinion, of course - and I am not a neurologist, my main specialization is graphics, I look at neurons to tune and test the software, I don't quite know what all the little bits around are - I look at a bit and I'm like, what is it? And then I go to re-read description by one of other people at the project, and I am like, ohh, I think it's a mitochondrion inside a dendrite. And then I wonder - why is it here? What does it matter where it is? What is this thing that connects it to the wall? Is it some weird imaging artifact? I do not claim to speak for everyone. I'm doing my part which, among other things, can help to figure out how to preserve brains or how to digitize them.
And my opinion is, in TL;DR; form: "do not promote cryonics for use by humans now". If you want to promote something, malaria vaccines are a good idea, if you want to defend something controversial, there's DDT to kill mosquitos, if you want to defend something overly fancy, there's the mosquito shooting laser. And that's just malaria. There's a lot of other diseases that have well proven cures which aren't available to everyone.
When we have better understanding of the brain, the preservation will almost certainly be cheap and chemical, rather than cryogenic. Cryogenic preservation requires pumping brain full of vitrification solution which prevents ice from forming even at the slow cooling speed of an object as big as human brain. Those concentrations denature proteins, distort things, likely detach things. It is more rational to find right set of chemical fixatives, than to use solvents at denaturing concentrations. Especially if solvents do not even reach the whole brain. Liquid nitrogen is wrong, too - liquid nitrogen is much too cold, different parts of the brain have different thermal expansion coefficient, the whole thing cracks as it cools from the glass transition temperature down to liquid nitrogen temperature. One could write pages about such issues.
Hi Dmytry,
ReplyDeleteFirst of all, the notion that altruism cannot be a motive for promoting cryonics strikes me as just plain wrong. The altruist who thinks cryonics is highly probable would be the obvious exception. Also, different altruists will probably have different utility functions and thus different attitudes towards the prospect of life extension or brain preservation. Generally, those who think dramatically longer lives are a very good thing would prefer cryonics whereas those preferring natural lifespans would prefer malaria vaccines.
As to the chance that chemical fixation will work better in the near future, that remains to be seen. You are to be commended for working in a field that benefits this approach. However there are some pretty strong arguments in favor of the cold, or at some variant of vitrification. It is the only known way to preserve with some degree of viability.
Dessication, slow-freezing approaches to cryopreservation, etc. rely on vitrification of the intracellular fluid. Some microbes survive in amber (high-temperature vitrification), and resin embedding is common for histological applications, but reversibly inducing that state in the brain on a large scale is speculative. Fixation is much harsher than this, and results in zero viability.
There are possible engineering approaches to speeding up cooling or reducing toxicity of cryoprotectants (the two most critical variables). We need more research being done to investigate them and turn them into medical procedures. The cooling rate cannot be brought fast enough to induce cryopreservation without cryoprotectants, but it can reduce exposure time and hence toxicity. (Cryoprotectants are not toxic at or below the glass transition temperature.)
* Low-viscosity fluids such as fluorine could be perfused to cool quickly by rapid perfusion.
* Carbon nanotubes could be delivered throughout the tissue via perfusion, improving thermal conductivity.
* Genetic therapies could deliver synthetic biological components, e.g. facilitating trehalose import or interfering with toxicity mechanisms.
* Cryoprotectant solutes are known to interfere with each others' toxicity mechanisms. Studying these could lead to better ways of interfering with the toxicity mechanisms.
* Ice blockers that interfere with nucleation can be used to reduce needed concentrations, letting you get below the glass transition temperature at realistic rates (with a higher freezing point.)
The blood-brain barrier is also an important obstacle, as it leads to dehydration of brain tissue. Therapies that make the brain more resistant to/better able to recover from dehydration could be significant.
As to cost, the cost of the cryogenic approach also tends to be vastly overestimated because we are dealing with small scales at present. Large scale cryogenic storage is less expensive as the surface area to volume ratio changes. The costs apart from storage are comparable to or cheaper than the costs of an equivalent room-temperature protocol.
Hi Luke.
Delete> First of all, the notion that altruism cannot be a motive for promoting cryonics strikes me as just plain wrong. The altruist who thinks cryonics is highly probable would be the obvious exception. Also, different altruists will probably have different utility functions and thus different attitudes towards the prospect of life extension or brain preservation. Generally, those who think dramatically longer lives are a very good thing would prefer cryonics whereas those preferring natural lifespans would prefer malaria vaccines.
When you save someone young, they live for a while afterwards, while technological and medical progress keeps going on - this also has a shot at a very long life. At which point, you're back to cryonics being a really expensive way to save a life.
> As to the chance that chemical fixation will work better in the near future, that remains to be seen. You are to be commended for working in a field that benefits this approach. However there are some pretty strong arguments in favor of the cold, or at some variant of vitrification. It is the only known way to preserve with some degree of viability.
No degree of brain viability is currently preserved by cryonics. None at all. The viability preserved in small groups of cells must not be confused with complete lack of viability for anything approaching brains. Worse than that, structural detail is not preserved either (shredding by ice in at least some of the brain regions). Meanwhile, chemical fixation - after slicing - is something that preserves structural detail for present day analysis - it actually works.
> There are possible engineering approaches to speeding up cooling or reducing toxicity of cryoprotectants (the two most critical variables). We need more research being done to investigate them and turn them into medical procedures. The cooling rate cannot be brought fast enough to induce cryopreservation without cryoprotectants, but it can reduce exposure time and hence toxicity. (Cryoprotectants are not toxic at or below the glass transition temperature.)
Yeah, if we are to speak of freezing people in the future.
> * Low-viscosity fluids such as fluorine could be perfused to cool quickly by rapid perfusion.
What? Fluorine as in fluorine gas? Or some fluoride of something?
> * Carbon nanotubes could be delivered throughout the tissue via perfusion, improving thermal conductivity.
Ridiculous. They're sharp and literally cut through things.
> * Genetic therapies could deliver synthetic biological components, e.g. facilitating trehalose import or interfering with toxicity mechanisms.
Not dying of natural causes and cancer in the first place is a better target for genetic approach.
> * Cryoprotectant solutes are known to interfere with each others' toxicity mechanisms. Studying these could lead to better ways of interfering with the toxicity mechanisms.
> * Ice blockers that interfere with nucleation can be used to reduce needed concentrations, letting you get below the glass transition temperature at realistic rates (with a higher freezing point.)
Maybe, someday, and the real progress is in cryobiology, not cryonics.
> As to cost, the cost of the cryogenic approach also tends to be vastly overestimated because we are dealing with small scales at present. Large scale cryogenic storage is less expensive as the surface area to volume ratio changes. The costs apart from storage are comparable to or cheaper than the costs of an equivalent room-temperature protocol.
Large scale cryonics use can come only after there's new cryonics that works and sufficient evidence that it works. Currently the proponents of cryonics speak of miraculous future technologies, as if that would somehow allay the question of whenever cryonics actually preserves sufficient information.
> When you save someone young, they live for a while afterwards, while technological and medical progress keeps going on - this also has a shot at a very long life.
ReplyDeleteA lot depends if you think medical procedures to extend lifespan are within our grasp. The more unlikely curing aging in a short timeframe is, the more attractive the prospect of cryonics/future-cryonics for someone who prefers long lifespans.
> No degree of brain viability is currently preserved by cryonics. None at all. The viability preserved in small groups of cells must not be confused with complete lack of viability for anything approaching brains.
My understanding is that small slices of rabbit brains have demonstrated organized electrical activity.
> Worse than that, structural detail is not preserved either (shredding by ice in at least some of the brain regions). Meanwhile, chemical fixation - after slicing - is something that preserves structural detail for present day analysis - it actually works.
You are comparing slice work with whole brain work. Slice work in fixation is going to be favorable to whole brain work in cryopreservation and vice versa.
> Yeah, if we are to speak of freezing people in the future.
[Nitpick: Vitrifying, not freezing -- unless you want to be extremely casual. "Cryopreserving" is a better general term.] Yes, talking about cryopreserving people in the future is equally as valid as talking about extending maximum lifespan in the future. Malaria vaccines could e.g. keep someone alive long enough to benefit from better cryopreservation.
> What? Fluorine as in fluorine gas? Or some fluoride of something?
Terminology bungle on my part. Fluorine based inert fluids. See: http://www.google.com/patents/US6274303
> Ridiculous. They're sharp and literally cut through things.
The devil's in the details. I was thinking of a slurry of shorter ones. Some slight endothelial damage could be an acceptable tradeoff for faster cooling. They don't have to get inside cells, just speed up heat transmission.
> Not dying of natural causes and cancer in the first place is a better target for genetic approach.
It all depends where the lowest-hanging fruit is. Cryonics has the benefit that you can accept riskier tradeoffs, for example a therapy that would ordinarily kill you within a matter of weeks could be worth the risk if it puts you in good cryostasis until better countermeasures can be developed.
With cancer, you need a permanent fix that doesn't incur any fatal side effects over the course of the following weeks, because that would defeat the purpose.
> Maybe, someday, and the real progress is in cryobiology, not cryonics.
They aren't exclusive. Most of the research salient to neural cryobiology seems to be done by labs funded and supported by cryonics. The major financial incentives outside cryonics tend to be towards issues like fertility.
> Large scale cryonics use can come only after there's new cryonics that works and sufficient evidence that it works. Currently the proponents of cryonics speak of miraculous future technologies, as if that would somehow allay the question of whenever cryonics actually preserves sufficient information.
You can't get "sufficient" evidence without sufficient technology to measure it. This is a false dilemma. The whole point of doing cryonics in the here and now is to benefit from future technology that doesn't exist yet. If we wait for such technology to exist, we stand to miss a major window of opportunity. We can calibrate towards more optimal results somewhat based on existing technology/evidence, and that is what cryonics does.
In any case, dragging our feet on cryonics seems to drag down enthusiasm on the research side of things. We aren't getting to the point of reversible cryopreservation of patients faster by listening to the naysayers.
>A lot depends if you think medical procedures to extend lifespan are within our grasp. The more unlikely curing aging in a short timeframe is, the more attractive the prospect of cryonics/future-cryonics for someone who prefers long lifespans.
ReplyDeleteSounds like you have to do some serious tweaking on your forecasts to make cryo effective vs regular healtcare. Cryo has to be perfect as it is with no significant room for improvement, yet it must take more than the expected remaining lifetime until any solutions to ageing, etc etc.
> My understanding is that small slices of rabbit brains have demonstrated organized electrical activity.
For sufficiently small value of small, anything works.
> You are comparing slice work with whole brain work. Slice work in fixation is going to be favorable to whole brain work in cryopreservation and vice versa.
Whole brain does not work. Slices work. All you can presently do if you want to save yourself for the glorious future, is to have your brain cut up and then preserved, and it will still be a long shot.
> Vitrifying, not freezing -- unless you want to be extremely casual.
No, right now, it's freezing - it is not demonstrated that the solution reaches whole of the brain. The temperatures are far too low, as well, producing cracking due to thermal stress. It is an expensive pseudo-scientific procedure, albeit that doesn't make it entirely clear how much future can learn from the modern ice mummies.
> The devil's in the details.
Precisely, and details are why things that seem to some people like they work do not actually work, because details are not gotten right.