[extropy-chat] Alternative to Cryo was The Amazing Cellular Repair device

[Eugen Leitl]

On Tue, Oct 11, 2005 at 02:48:14PM -0700, The Avantguardian wrote:

> I don't like the term cryonics. Whatever the "truth"
> of the matter may be, that word has a bad reputation
> in mainstream scientific circles. Since I am a in
> mainstream science, I prefer to use a different label
> that has less of a stigma. No offense to anyone
> intended, but words carry political baggage. 

But cryogenics is already taken, and with a different meaning.
Cryopreservation is neutral, and mainstream. Suspension
is not yet tainted. Both are good alternatives.
 
> That's my point. I am aiming at viability, a harsher
> metric yes, but the only one I would pay for.

Brain vitrification is assessed by viability.
Current viability (cortical slices Na/K ratio) is 
however insufficient, if structural disruption on the
neuron periphery is considerable.

The problem with viability is that it is artificial metjric,
because no one can afford to warm unprocessed tissue
in the first place, because it's not going to last on animal
scale. Organ scale, maybe. But notice that you still need
to fix cryofractures for perfusion. This is not possible
without extensive reprocessing.

> Mechanists might disagree with me but I am a vitalist.
> Structure without the spark is a corpse. Chemically
> equivalent to the living, but not alive.  

I agree that if there are low-toxicity alternatives
that we should be choosing those. Fortunately, the recent
progress says that the current recipes are almost good
enough for indefinitely viable renal implant. The brain
is different, however. We might or might not soon get word on
how well that is going.
 
> Not in the lab, but I have eggs go bad on me. That
> sulfer smell of rotten eggs is H2S. Many bacteria
> release it as a waste product.

I've worked with H2S. It's more toxic than HCN,
and it's toxic *by the same route*. If you think irreversibly
removing iron from Cytochrome C (among other things) is a good 
way to suspend, you're pretty isolated with that opinion.
 
> According to this toxicology article by Reiffenstein
> et al. , 50-100 ppm of H2S (the concentration used by
> Blackstone et al. was 80 ppm) results in "irritation
> of the respiratory tract" whereas 500-1000 ppm results
> in unconsiousness, neural paralysis, and death. I
> would *personally* take my chances with 80 ppm.

We're talking to a chronic exposure to an agent which
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12767687&dopt=Abstract

Toxicology. 2003 Jun 30;188(2-3):149-59. 	Related Articles, Links
    
Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures.

    Thompson RW, Valentine HL, Valentine WM.

    Department of Pathology and Center in Molecular Toxicology, Vanderbilt University Medical Center, Rm 109 MCS Annex Bldg., 1401 21st Ave South, Nashville, TN 37232-2561, USA.

    Hydrogen sulfide and hydrogen cyanide are known to compromise mitochondrial respiration through inhibition of cytochrome c oxidase and this is generally considered to be their primary mechanism of toxicity. Experimental studies and the efficiency of current treatment protocols suggest that H(2)S may exert adverse physiological effects through additional mechanisms. To evaluate the role of alternative mechanisms in H(2)S toxicity, the relative contributions of electron transport inhibition, uncoupling of mitochondrial respiration, and opening of the mitochondrial permeability transition pore (MPTP) to hydrosulfide and cyanide anion cytotoxicity in primary hepatocyte cultures were examined. Supplementation of hepatocytes with the glycolytic substrate, fructose, rescued hepatocytes from cyanide anion induced toxicity, whereas fructose supplementation increased hydrosulfide anion toxicity suggesting that hydrosulfide anion may compromise glycolysis in hepatocytes. Although inhibitors of the MPTP opening were protective for hydrosulfide anion, they had no effect on cyanide anion toxicity, consistent with an involvement of the permeability transition pore in hydrosulfide anion toxicity but not cyanide anion toxicity. Exposure of isolated rat liver mitochondria to hydrosulfide did not result in large amplitude swelling suggesting that if H(2)S induces the permeability transition it does so indirectly through a mechanism requiring other cellular components. Hydrosulfide anion did not appear to be an uncoupler of mitochondrial respiration in hepatocytes based upon the inability of oligomycin and fructose to protect hepatocytes from hydrosulfide anion toxicity. These findings support mechanisms additional to inhibition of cytochrome c oxidase in hydrogen sulfide toxicity. Further investigations are required to assess the role of the permeability transition in H(2)S toxicity, determine whether similar affects occur in other cell types or in vivo and evaluate whether this may provide a basis for the design of more effective therapeutic measures for hydrogen sulfide intoxication.

    PMID: 12767687 [PubMed - indexed for MEDLINE]

Rodents are not people. Check out
Tvedt, B; Skyberg, K; Aaserud, O; et al. (1991b) Brain damage caused by hydrogen sulfide: a follow-up study of six patients. Am. J. Ind. Med. 20:91-101.
 
> I don't know. I hope Blackstone and his colleagues try
> it out at colder temps and longer times. They aren't
> my mice, I wish they were.

I'm glad I'm not your rodent ;p
 
> I am pretty familiar with hypothermia. It has actually
> been purposely induced in patients undergoing open
> heart surgery, to slow down ischemic damage to the

Mild hypothermia. This is a good thing. Severe hypothermia
means accumulating additional damage while not even
being able to homeostate existing structures, which 
deteriorate. 

Severe hypothermia is a good thing only in stabilizing
patients heading for cryopreservation. I don't think anyone
will ever recover a human primate from a day of severe
hypothermia. Maybe a couple of days, tops.

> I think that if 1% BMR can be achieved, than it would
> be transhumanism's ticket to SENS. Go to sleep, a

You age in your sleep. Hibernation causes damage of its
own, though I'm not enough of a biologist to pull up
a few references.

> hundred years go by in the outside world, you age 1
> year, wake up and bingo, they have a cure for what
> ails you, possibly even old-age. Then again, you might
> wake up to find that medicine has been banned and you
> have a bunch luddites praying for your soul. It would
> still be a gamble.
> 
> > 
> > With vitrification, no damage occurs beyond of the
> > original caused during the suspension. And it quite
> > easy to measure what that damage is, and to gauge
> > how much of it is irreversible information erasure,
> > and which can be transformed back at structure
> > descriptor
> > level.
> 
> We don't even have a structure descriptor for memory

I'm talking about ultrascale structure and below.

> let alone consciousness in humans. If 20 years from
> now, we find out that consciousness is all volatile
> RAM, it aint gonna do much good for all the frozen
> heads. 

We already know that flat EEG lacunes (even prolonged ones
in medicated hypothermia) do not destroy
the person, both in humans and animals. It is really 
the structure, not electrochemical activity of the structure,
which is transient, and regenerated by the structure
once it's reperfused and warmed up.
 
> 
> > No way. 
> 
> Hey, nobody is twisting your arm to be a believer. All
> I am saying is that *I* would sign up for this and
> that *I* would invest what chump change I can scrape
> together in a company that does this. They're
> rationale and mouse demonstration has me sold.
> Especially if someone else can verify. *You* are free
> to do what *you* want.

I might be mistaken. But I do not think H2S is going to
work in primates, human or otherwise for the purpose
intended (inducing hibernation).

I would not invest in hibernation for the purpose of
skipping centuries, anyway. It only buys you years,
maybe a decade. It will not buy you even half a century.

Now a decade might to matter towards our life's end,
but right now it does not.
 
> If preserving my structure is all that mattered, why
> not just fossilize myself in epoxy like a bug in
> amber? That way my relatives can use me as a doorstop

Because preservation in amber isn't. Nor is plastination.
Look at it in TEM and at molecular scale, and you see something
which looks very bad. These things are like plastic dummies.
They only look like a human as long as you don't look too close.
Mummies look like people, too. So do statues.

> or something else useful. Why bother to have a hard to
> maintain cryonics facility keep me at liquid N2 temp
> if there is no intention of ever thawing me out?

Because your reconstruction does not require devitrification
by thermal ascent, whether RF-heated or otherwise which
does not require extensive reprocessing (such as integrating
fractal heat exchanges into the bulk of vitrified tissue --
which is not something we can do within the next 50 years). 
It a major source of damage.
 
> > I wish a had a subscription. Does anyone have
> > institutional
> > access to Cryobiology?
> 
> I do. Send me a reasonably short wish list of articles
> and I can help you out.

Thanks lots. I will contact you offlist, but it might take time
(work things are a bit crazy right now).

-- 
Eugen* Leitl <a href="http://leitl.org">leitl</a>
______________________________________________________________
ICBM: 48.07100, 11.36820            http://www.leitl.org
8B29F6BE: 099D 78BA 2FD3 B014 B08A  7779 75B0 2443 8B29 F6BE
-------------- next part --------------
A non-text attachment was scrubbed...
Name: signature.asc
Type: application/pgp-signature
Size: 189 bytes
Desc: Digital signature
URL: <http://lists.extropy.org/pipermail/extropy-chat/attachments/20051012/d2d495cc/attachment.bin>