[extropy-chat] Cryonics is the only option?

[Robert Bradbury]

On 4/16/07, Brett Paatsch <bpaatsch at bigpond.net.au> wrote:

I know you asked Anders, but...

>  Would you classify yourself as a believer in cryonics?
>

I would argue that if you cannot make a reasonable case that the information
content is completely destroyed, as would be the case say with cremation,
then at some point we will have the technology to recover it.  Your question
is unclear as to whether you want cryonics to simply preserve the
information content or whether you expect it to lead to a full recovery of
the original biological body with most (or all) of the original atoms or
molecules where they were before undergoing cryonics.

My point about the caveat against believers btw is that believers reason
> differently and argue differently - by differently I mean fundamentally
> dishonestly and evasively.
>

I would argue that is a misstatement.  I think there are probably only about
a dozen people, at most a few dozen, in the world who have the depth of
knowledge required for an *informed* discussion of the topic.  Others aren't
so much arguing dishonestly or evasively but from a simple lack of
knowledge.

On what basis do you think machine phase chemistry is "definately"
> thermodynamically credible?
>

On the basis that *ALL* of biology is assembled molecule by small molecule.
(Drexler effectively argued this in his 1981 PNAS paper that most people
haven't read.)  The use of the term "machine phase chemistry" is
ill-defined.  What are DNA polymerase, RNA polymerase and the ribosome if
they are not machines conducting chemistry!?!  (And if you don't know what
they are and how they work go look them up in Wikipedia or Google.  Go read
[1], and then come back to the discussion.

What I think you mean to take issue with is precision general purpose
molecular assembly which is somewhat different from what is done in
biology.  And as has been pointed out elsewhere, Drexler *never* said that
you could assemble anything and everything -- he said that there were a lot
of things that you could assemble which cannot be assembled which could not
be assembled using current methods.  (And the entire history of chemistry
over the last 100 years is a fairly clear demonstration of that.)

I'm assuming you are aware of Smalleys fat and sticky fingers criticisms of
> Drexler.
>

I assume you know that Smalley's criticisms are a decade or more old and
haven't done a recent PubMed article review using the keyword "nanoassembly"
or "nanoassemblies" and are unaware of [2].

 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?
>

Not really.  It is "free radical based" chemistry that would be difficult to
do in water (or many other solutions).  A primary reason "water" is
undesirable other than the fact that it would interfere with free radical
based chemistry is that it is a solid below 32C.  There is nothing
preventing one from doing mechanical assembly in say LN2 or LH2 or LHe.  The
lower temperatures reduce the inaccuracies due to thermal motion of the
molecules.

To quote directly from Nanosystems, Section 1.2.2a:

   - A machine-phase system is one in which all atoms follow controlled
   trajectories (within a range determined in part by thermal excitation).
   - Machine-phase chemistry describes the chemical behavior of
   machine-phase systems, in which all potentially reactive moieties follow
   controlled trajectories.

There is no problem (at least in my mind) for assembling proteins (or
nucleic acids) at low temperatures in non-water based solutions (I would
love to know what fraction of enzymes still function properly in cooled
liquid ammonia (or how difficult it would be to evolve them)).

If you want proteins (which are sequences of amino acids) to "fold" properly
then you have to put them into the environment (water + temperature) for
which they evolved.  Even then some proteins will not fold properly without
the assistance of other proteins such as heat shock factors and chaperonins.

I've frozen and thawed cells. Have you?
>

I made cooked some frozen vegetables the other night, does that count?  I
think as a child I also may have fed frozen brine shrimp to my tropical
fish.  Don't know if I thawed them to bring them back to life however. (Just
as an FYI, since I'm doing research on it now, there are a number of species
of both plants and animals, including brine shrimp, tardigrades and rotifers
which can be dessicated and/or frozen and thawed and survive quite well
after such "death" events.  In mammals the best example may be arctic ground
squirrels which allow their temperatures to drop to near freezing for
extended periods during the winter.)

I've not personally frozen embryos but that can be done too, also not
> reliably
> in the case of a single embryo, as I understand - but that we (people,
> scientists)
> can do it at all speaks to the robustness of life in *simple* forms and
> yet says
> nothing at all about the freezing of organs like brains.
>

It is unclear from any studies I've seen whether it is the freezing &
thawing that destroys the embryos or whether the embryos were non-viable in
the first place.  You have to bear in mind that 60-70% of natural
conceptions seem to result in miscarriages.  Those eggs & sperm are not
"perfect" in from the get-go.


We can't do organs. I thinkI recall Eugen saying Greg Fahy is interested in
> that (perhaps kidneys).
>

I'd suggest you do a PubMed search on "Fahy GM [AU]" and read his paper from
~2003-6.

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.
>

The brains of tardigrades and rotifers aren't as big as ours but they
survive freezing and thawing.  The caveat would be that their genomes have
evolved to allow that.

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.
>

Actually, I've got some very large rhododendrons out in front of my house
and I'm reasonably certain that in spite of the fact that their leaves all
froze several times this winter that their cells (and mitochondria and
chloroplasts) will be fine in a couple of weeks.

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.
>

Perhaps not, but there are parasites which inhabit human cells, e.g. Toxoplasma
gondii  which have ~80 megabase genomes which is probably enough for
replacing a significant part of the human genome in human cells should it
become severely damaged.  (No need to wait for chromallocytes when you can
start building genome patches today (if one has enough imagination and $$$))
[3].

So talk to me like a cell biologist. Tell me your protocol or point me to a
> peer reviewed paper.
>

I don't understand the emphasis on creating a "synthetic cell".  Why is this
necessary?  Its much simpler to reprogram existing cells and deliver them
where needed (e.g. enhanced genome stem cell therapy).  More importantly if
you are going to develop "real" cryonic suspension reanimation methods one
probably wants precision delivery of proteins and genetic materials so one
is talking complex forms of gene therapy -- not synethetic cell therapy.


> > See it as a ridiculously detailed form of 3D printing, where you want
> > to write prepared molecules into a matrix of frozen water.
>
> Handwaving. Show me a paper or a protocol.
>

There are a number of published peer reviewed papers on 3D printing of cells
onto various matrices and having them grow into functional biological
systems.  I believe one of the more recent involved the growing of heart
valves.  The printing of molecules is more complex and we do not yet have
print heads capable of that level of resolution.  AFMs have the positioning
accuracy required and there is no reason to believe we can't produce tips
(or ink jets) capable of spitting out a few molecules at a time.  There is
no financial driver at this time to produce these methods.  In part because
organ transplants are still expensive and risky propositions.  Even if you
were able to manufacture (print) or grow new organs they are not an ideal
solution.

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'd suggest you might want to review [4-7].

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. And once they are like that they will
> start to die faster than your manufacturing fingers can build more cells
> onto the seed cells.
>

Do you think we can't get fingers around something 10 microns in size?  Hell
we are patterning hundreds of millions of devices at 45nm in
microelectronics (and planning to go below 30nm).  Do you think hydrogen
bonds stop working if you are using them at -190C?  Putting a frozen water
cell down on a cube of other frozen cells at -190C and getting it to stay
where you put it does not sound like a problem to me.  Putting a cell filled
with liquid N2 down on a cube of cells filled with liquid N2 doesn't sound
like a problem either.  The tricky part will be replacing the lN2 with lH2O.
You might be able to go from N2 to NH4 to H2O but the liquid phases don't
overlap unless you subject them to some pressure I would suspect (some I
guess some work needs to be done here...).

But we are getting ahead of ourselves. Putting together any old cell,
> (assembling
> it like a manufacturing process not growing it like in cell culture)
> rebuilding a
> single celled organism say that functions like a single celled organism,
> (eats,
> moves, divides to replicate) - that would be the Science or Nature paper
> of the
> year in which it was done.
>

Its also way beyond the technology we need to have.  I would say assembling
a eukaryotic cell from scratch would normally come *after* you have
assembled the first nanorobot from scratch.

Biological or theoretical?  What nanoscale dissassemblers are you talking
> about?
>

The biological ones clearly exist.  In your stomach, you intestines, certain
soil bacteria and particularly fungi have lots of them.

 Inside cells, biomolecules, proteins assemble and fold into the right
> shapes
> in water. Proteins won't fold the way they do out of water.
>

That isn't clear.  So long as you have a solvent which will form hydrogen
bonds I strongly suspect that at least some proteins will fold properly
(there's a PhD thesis or several idea for you...).  If you have a folded
protein and cool it down it doesn't become "unfolded" (they unfold on
heating because the increased atomic motion disrupts the hydrogen bonding
which holds them together).  Proteins (or membranes) primarily become
disrupted on cooling due to crystal growth in the liquids (primarily ice)
disrupting the physical structures, potentially in some cases causing
covalent bond breakage (but I know most of those covalent bonds aren't
broken otherwise my vegetables would have turned to mush when I boiled them
on the stove).

It is interesting that one of the primary methods used by organisms to
resist desiccation is to produce trehalose which appears to form lots of
hydrogen bonds with the biological molecules and sheltering them and perhaps
allowing them to resist structural distortions during from the removal of
the water.


> Dunno what you mean. Only working nanoSYSTEMS I know of are biological
> ones the others are purely speculative (fanciful even).
>

The nanoSYSTEMS of antarctic bacteria work down to at least -4C.  Though
they probably work a bit more slowly than those we commonly encounter.

[BIG SNIP -- because I've got limited time to critique emails to the ExICh
list]

Brett, I am glad that you are studying Cell Biology.  Its one of the fields
people will need to know to contribute to these efforts in the future.  But
I think it is reasonable to assume that Anders has studied it as well (as
well as god knows how many other subjects).  Its only when one has a good
grasp of one field that one begins to understand what is required to
integrate it with others of equal complexity.  That is why Nanosystems will
always go down in my book as one of the most brilliant books ever written.
Chapter 12 I could easily understand because it was my field of expertise
but its taken me more than a decade to begin to understand some of the other
areas and the kind of research that went into them.  So one can argue
against cryonics for a few more decades, perhaps you have the time and
energy to do so.  Or you can simply ask whether people like Eric D., Marvin
M., Ralph M. and Robert F. might be able to connect some insights together
better than people who seem to have focused in very narrow areas much of
their lives (e.g. Dr. Smalley).

Robert

1. Kornberg, A., "DNA Replication" (2005)
http://www.amazon.com/Dna-Replication-Arthur-Kornberg/dp/1891389440
2. Hickenboth, C. R. et al, "Biasing reaction pathways with mechanical
force<http://www.nature.com/nature/journal/v446/n7134/abs/nature05681.html>,"
Nature 466:423-427 (22 Mar 2007).
3. Note, I am not suggesting patches onto T. gondii, I am suggesting
assembly lines that produce T. gondii packages that deliver largely human
genome subsets. If one assumes only 2-2.5% of the 3 gigabase human genome
codes for useful sequence (particularly if one is delivering "organ"
specific genome subsets), then T. gondii could carry a complete human genome
set of genes.
4. "New light microscope sharpens scientists' focus" (10 Aug 2006)
http://www.physorg.com/news74439510.html
5. Betzig, E. et al, "Imaging intracellular fluorescent proteins at
nanometer resolution<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16902090&itool=pubmed_docsum>,"
Science 313:1642-5 (15 Sep 2006).
6. "Imaging Transparent Brains" (3 Apr 2007).
http://neurophilosophy.wordpress.com/2007/04/03/imaging-transparent-brains/
7 .Dodt HU et al, "Ultramicroscopy: three-dimensional visualization of
neuronal networks in the whole mouse
brain<http://http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17384643&itool=pubmed_docsum>,"
Nat. Meth 4(4):331-6 (Apr 2007).
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