Subject: Re: [extropy-chat] Cryonics is the only option?

From: "Anders Sandberg" <[email-masked]>
Date: Tue, 17 Apr 2007 12:55:10 +0200 (MEST)

Brett Paatsch wrote:
> Saying you wouldn't call yourself a disbeliever doesn't amount to a
> positive
> asserting of belief.  You could be a sceptic or agnostic on the matter.
> Let
> me invite you off the fence. Would you classify yourself as a believer in
> cryonics?

I think that cryonic suspension does preserve synaptic structure (when
done right and fast enough) and that the frozen brain contains enough
information that it could in principle be reconstructed. Given that the
information loss is not total, that subcellular scanning appears
physically feasible and a result of many development paths and that there
is a finite chance that a stored brain could end up in a future where such
scanning methods are present, I think that there is a chance that at least
some of current cryonics patients will end up uploaded.

Does that make me a cryonics believer in your eyes?

While I defend a lot of reconstruction methods below, my heart is more in
analysing scanning and emulation methods.

> On what basis do you think machine phase chemistry is "definately"
> thermodynamically credible?
>
> I'm assuming you are aware of Smalleys fat and sticky fingers criticisms
> of
> Drexler. Life molecules like proteins assemble in compartments containing
> water.  Machine phase chemistry as I understand it is essentially
> watery-solution free chemistry.  Without a watery solution how do you see
> machine phase chemistry managing the folding of proteins?

You can always build hybrids. One simple model would be to assemble
proteins in a watery environment and then transfer them to a machine phase
environment (with water around them, if needed) for assembly if you are
(say) restoring a frozen brain.

Smalleys fat and sticky fingers criticism seems to be disproven by DNA
repair enzymes, and they are working in a liquid environment. Even if
general atomic assembly is impossible or too inefficient it is clearly
possible to make more specialized forms of moiety assembly, it would just
make the systems messier and less easy to do armchair design of.

>>Given that frozen cells can be thawed with viability intact,
>
> I've frozen and thawed cells. Have you?

No. But if you are referring to the fact that quite a lot of the cells die
in the process, I don't consider that to be any form of counterargument to
my previous argument. I was merely showing that there existed a method
that had a high likeliehood of assembling a viable cell if implemented,
not the best possible such method.

> It is
> important to get that the brain is an organ of a multicellular life form.
> It grows as
> a result of the actions of cells but it isn't just a big lump of cells. I
> know you know
> that as a neuroscience guy but I don't know how well you know that and I
> don't
> accept expertise on the part of others until I see evidence of it.

Well, you can always call me a theoretical neuroscientist. I know about
the brain structure, but the closest I get is looking over the shoulders
of experimenters doing rat brain slice work.

Brain tissue is terribly complex and labyrinthine, and I think standard
cryo suspensions do nasty things to it. That is why I'm not so much of a
believer of bodily cryonic revival but rather in uploading - I can see how
that could in principle be done, and it is even possible to get down to
gritty details already to callibrate our predictions. (actually, I really
ought to be working on that paper right now)

> I don't think its (organs like kidneys have been done). I'd want to see a
> peer
> reviewed journal to give it (say a kidney thawing) credit as having been
> really
> been done because scientists too are excellent at kidding themselves.
> Thats
> why peer review matters it helps take out the garbage.

Sure. We all want peer reviewed studies of our favorite fields.

Cryonics suffers because it is proactive. If the neanderthals had foreseen
genomics they might have preserved some of their DNA for future testing
(let's say in amber or by putting it into glacier caves). Tens of
thousands of years later genomics might indeed scan the DNA as desired,
finding whatever answers once desired ("Is Groo really the son of Ugh?")
But a neanderthal critic would of course have been able to both criticise
the project on the grounds of the faith in genomics and in the assumption
that amber or glacier caves were a good way of going about it - even if
those assumptions (in this thought experiment) were entirely right. Would
that have made Ughs paternity test project irrational (beside the issue
that he would never know the answer, but lets assume he felt there was a
good reason anyway)? It doesn't seem so. Faith in future genomics may be
impossible to prove, but one can develop methods that are the best
possible given one's technology to preserve tissue. They may very well
have other good spinoffs (imagine the neanderthals inventing the ice box
and then the refrigerator 40,000 years ago) and may in any case not be a
huge drain of resources from stone science and spear ballistics.

We are in a better position than the neanderthals because we have a bit
better information about the effects of our suspension methods, the
physiology of tissues, can do simple experiments etc. It is still a very
uncertain research project, that is true, but it doesn't strike me as
inherently irrational.

> Though we can grow cells in quantity in E.coli, we can't build as opposed
> to
> growing a just a single frozen cell. A growing cell can preserve the
> integrity
> of mitochondrial membranes. You can't do that working from the outside
> to built the membrane.

Hmm, suppose you were putting down phospholipids in a matrix of vitrified
water, starting from the bottom and adding layer after layer. Why couldn't
you just print the inner membrane? It would be just like the 3d printing
of the nested spheres in the middle of this page:
http://www.georgehart.com/rp/rp.html

> We can produce in vitro cell free systems to do research on. We can create
> liposomes - lipid enclosed spheres that aren't cells. But we can't create
> a
> living cell as a manufacturing process.

No, not yet. But unless you believe in vitalism, you would agree that is
*somehow* the molecules making up a cell were just placed in the right
pattern it would become a living cell, right?

Now it is just up to us arguing that it can be done to show that it is
possible to achieve this using a physical system, and for the people
arguing that it is likely to be done to show why such a system is likely.

> At this stage, we, science, don't know how for instance the first cell
> that
> was the progenitor of all life on earth formed. Not exactly. We don't even
> know that much in principle yet.

Or even that it was a cell. I'm pretty convinced that it was more akin to
a ribozyme.

>>  Cells are pretty robust (otherwise they wouldn't survive, and
>> temperature changes and thermal noise would instantly kill them), so you
>> only need to get close enough to the attractor state(s) that correspond
>> to
>> a working cell to get it to spontaneously do the final pieces of
>> selforganisation.
>
> "only"   "attractor state(s) that correspond to a working cell" :-)
>
> So talk to me like a cell biologist. Tell me your protocol or point me to
> a peer reviewed paper.
>
> "attractor state(s) that correspond to a working cell" sounds like
> believer psuedo-explanation handwaving to me.

I am a computational biologist. At best I can explain my thinking and
results to you, but I dont do "protocols" and attractor states are my
bread and butter.

A bilayer is an attractor state in the configuration space of phospholipid
molecules in water (e.g. see S.J. Marrink, E. Lindahl, O. Edholm, and A.
Mark. Simulation of the spontaneous aggregation of phospholipids into
bilayers. J. Am. Chem. Soc., 123:8638-8639, 2001. )

Membrane biophysics is not my field, but I'm pretty certain there are
characterizations of how far lipids can be displaced before the structure
breaks. And I know there are molecular dynamics simulations of membranes
(such as the one above) that would allow you to experiment with jittering
their positions. So unless it has already been done, there is a nice paper
in characterizing the probability of reforming properly from  different
levels of positional (and rotational) uncertainty. In fact, one could also
try changing the simulation temperature to see if there is any phase
transitions or other troubles if one starts with a vitrified ice state and
move up to physiological temperature (I'd love to do that paper if I had
the time, simulator and some more expertise).

[In fact, given results such as the animation at the bottom of
http://www.memphys.sdu.dk/~besold/research.html a more proper
characterization would be: does this organisation happen fast enough to
not cause significant leaks or topological defects of the membrane. ]

Locations of biomolecules is an interesting chapter. Given the rapid
diffusion of most small molecules and proteins not bound to anything, they
can essentially be put in the right compartment and they will extremely
quickly spread out. More care is needed for membrane-bound molecules that
have to be placed on the right membranes and macromolecular structures
such as microtubuli. My guess is that it is the later that are going to be
the most troublesome objects to reconstruct. Again, if it has not been
done yet it is not a terribly hard research project to characterize how
much noise in position these structures can handle, and how quickly they
relax into correct (or incorrect) configurations.

Cells are stable to thermal noise and other minor distortions due to e.g.
mild sound waves. Most of this I would expect is because of the bilayers.
To me it makes sense to regard a living cell as a particular set of points
in the configuration space of all its molecules. We know small deviations
from this set like an indentation of the membrane will relax away, so it
is an attracting set. What needs to be characterized is the distance to
the boundaries of the basin of attraction for this set: if an intervention
or recreation manages to stay within that distance from the "true" cell it
will converge back to the proper state.

> You say that as though you have done it. But you haven't actually done it
> have you. Had you done it you'd have had a lead paper in Science and
> Nature.

Them's fighting words. Let's race you to the cover? :-)

> That sort of handwaving is highly characteristic of  what transhumanists
> do when they prentend to actually discuss technology. It works to give
> the illusion of knowledge without demonstrating any. It poo poos whats
> necessary to be done without either demonstrating that it has been
> done and without giving a protocol that demonstrates that it can be
> done even in principle.

Have you seen Nick Szabo's essay on falsifiable designs?
http://unenumerated.blogspot.com/2007/02/falsifiable-design-methodology-for.html
I think he has a good idea for an antidote.

>>To have a realistic chance of doing it right you first need to have
>> scanned
>> a cell,
>
> With current technology, cryo EM one can't scan a single cell. You scan
> lots of them and get an aggregated averaged out picture. Fair warning
> handwaving about future technology will prompt me to want to see what you
> know about the relevant small scale physics.

I think cryo EM is changing quite rapidly, and given some of the
references I'm adding to my paper it seems that making pretty good 3D
models of single cells is within the near future. The biggest problem is
that EM cannot distinguish protein types, and that is of course what we
really want. Would you think Raman spectroscopy would enable that?

>> picking it apart molecule by molecule and recording the locations and
>> type. If that can be done piling them together seems to be equally hard.
>
>
> I disagree. I think it is much much harder. I even think it is impossible.
> Because
> you have to get your manufacturing fingers around the cell clusters whilst
> the
> cells in the centre of the cluster have to be at the right temperature to
> act like
> cells and bind to the other cells.

My assumption was -170 C. It seems that your view is that cells at this
temperature do not correspond to viable cells at all?

> Your brain and mine would at one level be variations on the theme of homo
> sapiens male brains. But what makes me me and you you is in the
> nanoscale details. Knowing how to build Bretts brain as a manufacturing
> process wouldn't give you an algorithm for building an Anders brain. At
> the
> nanoscale where the synapse make their connections our individual brains
> would be too different.

Sure. The differences are actually far larger than nanoscale, you can see
different folding patterns even in twin brains.

>> Maybe it would be worthwhile doing a careful critique of nanoscale
>> dissassemblers?
>
> Biological or theoretical?  What nanoscale dissassemblers are you
> talking about?

Theoretical. Since many of the wilder projects discussed here tend to be
based on the assumption that they can work, clearly analysing the
underlying assumptions and constraints would help constrain the
handwaving.

> That I think is ultimately what transhumanism is. Its not the successor to
> humanism its a cultural support system for cryonicists and technological
> religious types that can't find salvation in the normal religions. Thats
> why
> transhumanism doesn't produce anything except writers and entertainers
> - although individual transhumanists do produce some things those things
> are
> in their capacities as people not as transhumanists.

That is an interesting criticism. And one that I actually agree with to
some extent. However, I'm much more hopeful about the usefulness of
transhumanism.

> The wheels came off the transhumanist movement when transhumanists did
> not take a strong enough stand when US political conservatives turned into
> religious regressives.

Actually, that might have been the breakthrough. Because it made
bioethicists much more transhumanist, and that will make a major change in
policy and funding in the long run.

>
>> That a lot of entropy is being pushed around (making unordered atoms
>> into
>> an ordered cell) adds a bit to the heat problem, but can still be
>> managed
>> by slowing things down or dividing the workpieces so that radiating the
>> entropy into the environment is easy.
>
> No offense Anders but conversation needs a lot more credibility
> established
> before we can do the handwavey stuff.

Excuse me, but where is the handwaving *here*? You might slap my fingers
on cell biology, but it seems pretty strange that you find *these*
statements handwaving. Or do you think that Brillouin's inequality or the
various heat laws do not apply?

>> That molecules are dancing around isn't an enormous problem at -170,
>> since the cryonic brain is essentially a crystal lattice with thermal
>>  vibrations are on the order of 0.01 nm.
>
> The resolution of electron microscopes are about 2 nanometres from memory
> perhaps 0.2. Its not the state of the brain when frozen as a block of
> tissue
> thats the (or rather a) problem its that each brain is so massively unique
> in
> its arborial structures to very low resolutions. Lipid bilayers are only
> around
> 6 nanometres thick and if the bilayers are breached the ions leak and the
> organelle will not work. You have to be able to manufacture to place your
> lipids to that degree of precision whilst keeping the heat out that would
> change
> the chemistry of the lipids. It can't be done not.

Hmm, and why shouldn't I start to accuse you of handwaving and asking you
to refer to peer reviewed papers here? It is one thing to state that it
looks very unlikely, another to categorically state that it cannot. The
latter actually suggests some kind of scientific evidence against the
possibility.

Now, our big disagreement really seems to be the constructability of
bilayers. I say they probably can be put together according to fairly
complex specifications by working a LN temperatures and then thawing, you
say it cannot be done. Maybe we should start a separate thread to actually
hash it out freshly, stating assumptions and all that?

[ this paper seems relevant, but I haven't found the full text yet:
http://journals.cambridge.org/action/displayAbstract;jsessionid=2DB1538444172C5407EB5A708E22DA6E.tomcat1?fromPage=online&aid=365124
]

> Nature grows her brains as one-offers
> she
> doesn't manufacture them and she doesn't build in service laneways for
> repair.
> That we do know.

And my approach would be to add layer after layer rather than trying to go
from the outside in.

> Granted. I ranted.

We all do. Sometimes it is useful.

> You ask other questions in your post which are fair ones and I drafted
> answers
> to them but I can't spend more time on this right now so I'll post this
> much.

Same here, but I mean the thing about a thread on bilayers. As I said, not
my main area of expertise but likely cruicial for a lot of arguments here.

> I'm studying cell biology currently. Actually I should be writting up my
> research
> project.  I mostly interested in seeing what you have under the bonnet as
> a
> neuroscientist rather than as a ethical philosopher anyway.

Right now I get to do neuroscience to some extent, since I'm preparing a
review of what we know today for a workshop on the feasibility of
uploading.

-- 
Anders Sandberg,
Oxford Uehiro Centre for Practical Ethics
Philosophy Faculty of Oxford University

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