[ExI] Alcor's new statement on ASC

[Stuart LaForge]

John Clark wrote:


>
> I was disappointed in Alcor?s official statement about ASC on page 8 of
> the current issue of Cryonics, although it started well when Alcor
> recognized there is "strong proof" that if ASC is used then:
>
>> *"Aldehyde  Stabilized Cryopreservation (ASC)  brains can be preserved
>> well enough at cryogenic temperatures for neural connectivity (the
>> connectome) to be completely visualized "*
>
> To me that is a pretty huge development but its even better than that
> because not only is the connectome information retained when the brain is
> frozen solid it can be completely visualized even when it has been warmed
>  back up to room temperature. This is especially impressive because, for
> various technical reasons I can get into later if anybody is interested,

If you consider your connectome to be the essential you, then your
argument does  follow in a narrow sense. But keep in mind that your
connectome is a malleable ever evolving thing. Every second of every day,
you are making new memories and also forgetting old ones. In a continual
state of becoming.

Maybe by placing so much stock in a frozen snapshot of your connectome you
would lose the information of who you were becoming. Kind of like a
Heisenberg uncertainty principle of identity. Which memories were just
starting to form? Which were on the verge of being forgotten. Life and
consciousness are not just nouns, they are also verbs i.e. dynamic
processes.


> I
> think the warming up process almost certainly causes even more damage than
>  the freezing process.

>From a biomedical standpoint, absolutely. Especially if the warming comes
too fast. Also from ischemia considerations, it would be better to warm
the person from the inside out. But I am sure you had more reductive
reason so let's hear it. I am curious. :-)


>> *?Current brain vitrification methods without fixation leads to
>> dehydration?*
>
> And more important the current method leads to the shrinkage of the brain
>  by 50%.

All cryobiotic organisms that survive freezing undergo a certain amount of
dehydration in the process. The hardiest are also anhydrobiotic. They
accomplish this in general by replacing a good deal of their water with
sugars. For example tardigrades use trehalose but less hardy wood frogs
use simple glucose and keep their water in their extracellular spaces with
glucose and urine operating to keep ice crystals small instead of drying
out like tardigrades.

The best explanation I have heard to date is that all the hydroxyl groups
available in  sugars serve to maintain hydrogen bonds with all the
proteins, lipids, and nucleic acids in cells thus "hydrating" them without
water and keeping them stably functional. The relatively concentrated
sugar solution then itself vitrifies. Less water => less ice => less
damage.

>From a reversible cryonics POV, the challenge will be getting the sugar
into all the necessary cells during freezing and then out of those cells
during rewarming without damage to those cells. Cell dehydration happens
with extracellular vitrification alone and the cell membranes and
intracellular compartments lose their structure without sugar to prop it
up.

A wood frog can survive if its cells can retain 60% of its water.
Tardigrade cells can survive while retaining on the order of 1% of their
water. Both do so using a combination of sugars to scaffold biomolecules
and antifreeze proteins to help inhibit ice formation.


> That statement makes no sense to me. If we can see  the connectome with
> an Electron Microscope using ASC but we can?t see it with Alcor?s method
> then obviously ASC has done less damage to it. I agree that doesn?t prove
> that Alcor's method has produced unrecoverable damage, maybe a technology
> more advanced than a Electron Microscope can still recover it, but I?d
> rather not stake my life on a ?maybe" if there is an alternative. In
> general the very scale used to determine the degree of damaged something
> has sustained is how hard it is to figure out what something looked like
> before the damage occurred, and its easier to figure that out with ASC.

If you are that worried about your connectome, just get a picture or
better yet a movie of it while you are still alive. The data will be far
easier to stably store than a biologically useless head.

http://www.humanconnectomeproject.org/gallery/

Hell a tabula rosa clone of you could probably have that digitized engram
of you downloaded into its brain in a few hundred years. Your DNA won't
survive covalently bonding with every nitrate group in its vicinity. But
your DNA can survive boiling water. Think on that before you pickle
yourself in glutaraldehyde for posterity.

> And yes
> aldehyde is toxic, but it is not very toxic, it is the active ingredient
> in wart removing lotion that you can get at the drug store without a
> prescription; I wouldn?t want to drink it but I wouldn?t want to drink
> Alcor?s vitrification solution either.

Are you kidding me? Tardigrades can survive outer space but cant survive
aldhehyde. Aldehyde is one of the most toxic substance known. It
inactivates *viruses* which is why it works on that wart. And it is so low
a concentration that you don't notice the hundreds of thousands of skin
cells it kills along with it.

> Preserving all the molecules in the brain can?t be very important if long
>  term preservation of your personal identity is what you?re after because
>  most of molecules in the brain are small and don?t last long. For example
> NO ( Nitrous oxide ) is a very small intermediary molecule that is
> important in cell communication, but in the normal course of life any
> particular NO molecule probably only exists for a few seconds at best. I
> am more interested in preserving things that are not so ephemeral, like
> the connectome and large proteins that should still be recognizable (but
> I
> admit no longer functional) even after it has become cross linked with
> aldehyde.

Again, you are not just poisoning your cells with aldehyde, you completely
cross-linking all your biomolecules into one gigantic covalently bonded
molecule. You will be will still be able to see the forest, you just won't
be able to see where one tree ends and another one begins.

> The term "cell viability? can be misleading because it often involves
> super fast flash freezing of a microscopic cell by direct contact with a
> thing as cold as liquid nitrogen, something not possible to do with a
> macroscopic object like a human brain. And if cell viability was the only
> consideration Alcor should have stayed with the method it used 10 years
> ago and not have switched over to vitrification. In this study
> conventional cryopreservation did a better job at preserving cell
> viability than vitrification in which only 10% of the cells were viable.
> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895516/

Well comparing the two media used in your cited experiment:

"The conventional cryopreservation media was prepared by mixing 80%
F-medium with 10% fetal bovine serum (FBS) and 10% dimethyl sulfoxide
(DMSO) (Me2SO; Sigma Chemical, St. Louis, USA)."

"Vitrification media was prepared according to the formula developed by
Kasai and Mukaida [6] named ESF40. This comprises 40% ethylene glycol (EG)
(WAKO Pure Chemical Industries Ltd., Osaka, Japan), 18% Ficoll 70 (SIGMA,
St. Louis, USA), and 0.3 M sucrose (Junsei Chemical Co. Ltd., Tokyo,
Japan) dissolved in F-medium."

That doesn't surprise me at all. DMSO in their first medium helps get the
sugars in the F-medium into the cells. DMSO crosses cell membranes very
easily. The second contains no DMSO and while Ethlyene glycol, sucrose,
and Ficoll by themslves can't get into cells for crap. The idea is not
just to vitrify the outside of the cells but their interiors as well.

If I remember correctly Alcor's current brew does contain some DMSO.

>
> Nevertheless I think Alcor made a smart decision a decade ago when they
> switched to vitrification because it produced better Electron Microscope
> pictures than the previous method did. It?s now time to make another
> smart decision.

Again, take a picture of your connectome before you die and let Alcor do
its thing. Don't turn your brain into a paperweight just to keep it
looking pretty. Their tech will get better, I am certain of it. Why would
you want your connectome preserved at the moment of your death anyway? So
you can live forever with PTSD?

> I think it's a pipe dream to expect reversible brain preservation to be
> demonstrated by ANY method before full scale Drexler style Nanotechnology
> is developed. If somebody manages to bring even a mouse back from liquid
> nitrogen temperatures in the near future using Alcor's method I?ll eat my
>  words and forget about ASC. I would be delighted if that happened but
> I?m
> not holding my breath.

Dozens of examples of proof of principle of vitrification already exist in
nature. I can't show you a mouse at liquid nitrogen temps but I can show
you a frog at -16 C:

https://www.youtube.com/watch?v=pLPeehsXAr4

I was pleasantly surprised to discover Natasha Vita-More did it in the lab
with nematodes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620520/

Way to go, Natasha! :-)

I can't show you a single example of *anything* surviving getting dipped
in aldehyde at *any* temperature. Not even viruses, and they are not even
really alive to begin with.

So I think Alcor is on the right track. It just needs work and time.


> By the way, Drexler was ahead of his time in more ways than one, in his
> book "Engines Of Creation? he talks about something that sounds very much
> like ASC, and that was 30 years ago.
>
>> *?Certainly fixation results are likely to be much harder to reverse so
>> as to restore biological viability?*
>
> I disagree, I am very far from certain about that, in fact I am about as
> far as its possible to get. To restore biological viability you?re going
> to need information about what atom goes where, and from everything I?ve
> seen ASC does a better job preserving that information than Alcor?s
> current method. Electron Microscopes don?t lie.

What goes where is not enough. You need to be able to distinguish between
hydrogen bonds and covalent bonds. Scanning electron microscopes don't
have the resolution to distinguish hydrogen bonding from covalent bonding.
You need an STM for that. I think what you see would be a lot messier with
ASC under an STM.

Nanosanta will thank you for not cross-linking your molecules into a
Gordian knot. I am only telling you this because I like you. But in the
end, its your brain at stake so do what you want.

>> *"Robert McIntyre, the lead researcher at 21st Century Medicine , made
>> a point during his presentation at the Alcor 2015 conference of
>> recommending adoption of ASC in cryonics at this time.?*

> I frankly can?t make heads or tails out of Robert McIntyre. He says we
> should not use ASC until it undergoes the same exhausted testing that the
> FDA insists any new drug must undergo, and that costs on average about a
> billion dollars and takes at least a decade to finish; presumably he wants
>  to make sure it won?t make people worse by making them even deader than
> they otherwise would be. In fact McIntyre?s company ?Nectome? which he
> cofounded says on the first page of its website that they are
> recommending against using Alcor?s vitrification method too, "We believe
> that rushing to apply vitrification today would be extremely
> irresponsible?. Apparently McIntyre believes Alcor hasn't gone through a
> sufficient amount of red tape and hasn't had enough "thoughtful
> discussions from medical ethicists?, so people who have terminal cancer
> today are supposed to just wait until those ethicists are satisfied. And
> that should happen sometime in the next decade, or maybe the decade after
> that.

What? A for-profit company that is competing with a non-profit company
suggests they both undergo expensive FDA testing? I wonder why they would
do that?

> I think that?s just nuts. I won't mind waiting to be revived once I am
> frozen, one year or a thousand years it will all seem the same to me; but
> I
> most certainly will mind if I need to be frozen right now but have to wait
>  because those super-ethical people haven?t finished their thoughtful
> discussions yet.

The argument is not really about ethics. Its about rational self-interest
on multiple levels for both cryonicists and the companies involved.

Stuart LaForge