CryoNet #33139 - #33144

CryoNet - Mon 27 Dec 2010

    #33139: Re: Max More: find the right dog whistle to grow cryonics [MARK PLUS]
    #33140: Signing up older people [Brian Wowk]
    #33141: Cryoburn [David Stodolsky]
    #33142: a request [Chris Manning]
    #33143: Just a thought [Chris Manning]
    #33144: Scoring Cases  [M2darwin]

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Message #33139
Date: Sun, 26 Dec 2010 09:18:57 -0700
Subject: Re: Max More: find the right dog whistle to grow cryonics
From: MARK PLUS <[email protected]>

In Cryonet #33135,, un person writes:

>But that sure wasn't the persona bush had when he ran for president twice. Oh,
no. You see, Bush is smart, and he had smart advisors. He knows that a more
homespun, "country", HUMBLE, a more SPIRITUAL persona is what wins over more
people. So he became an actor, and he played a part. He found a dog whistle that
more people could hear.

I think you underestimate the Americans who matter. The American
people, at least the ones with some intelligence, have warmed up to
Christopher Hitchens, like Max an Oxford-educated British immigrant
with controversial views and an uninhibited way of speaking and
writing. Who could have predicted that Americans would turn Hitchens's
pro-atheism book into a best seller, and elevate Hitchens into a
sought-after public intellectual (now unfortunately dying from
cancer)?

Of course, Max has a different role to play now than public
intellectual. But his education, published world view and way of
expressing himself don't carry the costs you seem to think they do.

-- 
Mark Plus
Life is short: Freeze hard!

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Message #33140
Date: Sun, 26 Dec 2010 12:52:31 -0800
Subject: Signing up older people
From: Brian Wowk <[email protected]>

"Unperson" wrote:

> We have to concentrate on OLDER people. Young people do not generally sign up. We have to look to those we really realize they are indeed going to die. Young people do not really realize this viscerally enough to get them to sign up.

     This is not a good idea.  Aside from living down to the worst
negative stereotypes of cryonics, there are real issues with financial
hardship, informed consent, and patient burden in deliberately seeking
to sign up older people for cryonics.  The idea seems to be based on a
false premise that having lots of cryopreserved people in need of
future revival is a good thing.  Living members make cryonics
organizations strong.  Cryopreserved patients are a tremendous
obligation for ongoing care and revival at an expense and difficulty
that is still unknown.  I understand that the point of cryonics is to
cryopreserve people and get them back, but for cryonics to work at all
there will have to be a sufficient number of young living people
interested enough in cryonics to keep it going vs. cryopreserved
people.

     As a matter of cryonics history, the greatest interest in
cryonics has actually been among the young.  Proportionately more
cryonics activists became activists while they were young rather than
old.

---BW

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Message #33141
From: David Stodolsky <[email protected]>
Subject: Cryoburn
Date: Sun, 26 Dec 2010 22:13:01 +0100

<http://www.amazon.com/Cryoburn-Vorkosigan-Saga-McMaster-Bujold/dp/1439133948>

>From Publishers Weekly
Fans have been clamoring for Hugo winner Bujold to pen a new Vorkosigan Saga novel since 2002's Diplomatic Immunity, and they will not be disappointed by this thoughtful tale. Only five days after arriving on Kibou-daini for a cryonics conference, interplanetary diplomat Miles Vorkosigan narrowly escapes kidnapping. Drugged, dazed, and alone, he is taken in by Jin Sato, whose mother was the leader of a cryonics reform movement until being declared mentally ill and involuntarily frozen. Now Jin lives in a building full of squatters running an illegal cryonics clinic. Under imperial orders to investigate the shady dealings of the cryo cartels, Miles connects the far-flung pieces and exposes a sneaky plot. Bujold introduces appealing characters to join familiar ones in exploring the ramificat
 ions of a planet-wide culture of postponing death, and her deft and absorbing writing easily corrals the complex plot and softens the blow of a tear-jerking conclusion. (Nov.) (c) 
Copyright C PWxyz, LLC. All rights reserved.




David Stodolsky
[email protected]  Skype: davidstodolsky

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Message #33142
From: "Chris Manning" <[email protected]>
Subject: a request
Date: Mon, 27 Dec 2010 09:23:31 +1100

If you post a message to CryoNet that contains a quote from a previous message that happened to be the last message in its digest, could you please ensure that you do not include the words 'End of CryoNet Digest' in the quote?

I am often tired when I am reading CryoNet digests (which arrive daily at 9 p.m. local time) and I don't want to have to have the presence of mind to remember to check whether it is indeed the end of the digest.

The situation reminds me of that Monty Python sketch where the credits roll, purporting to be the end of the show, and then a voice says "And now, another 6 minutes of Monty Python's Flying Circus!"


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Message #33143
From: "Chris Manning" <[email protected]>
Subject: Just a thought
Date: Mon, 27 Dec 2010 10:10:50 +1100

Just a thought I had recently which I will share with other cryonicists for what it may be worth (maybe 2c Australian).

There are many possible scenarios in which revival from cryopreservation will be technically possible but problematic for other reasons, e.g. revival may be outlawed due to overpopulation. I am surprised that these possibilities aren't being canvassed more in the cryonics community. Anyway, the thought I had is as follows:

During the time when revival technology is being developed, there will of course be progress in other areas of human endeavour. This other progress could include both the discovery of earth-like planets of other stars and the development of faster space travel, making it easier to reach them.

If revival does prove technically possible but problematic, it may prove feasible to transport cryopreserved bodies to such a planet, where the people would be revived and live their future lives. After all, there would be no need for life-support systems on the ship! The maintenance of the dewars during the voyage could probably be automated. 

We would probably need to know in advance the attitude of the cryopreserved people to this possibility. I hereby let it be known that I am agreeable in principle to my body being transported to another world as per the above scenario.

More generally, I think readers ought to be asking themselves in what possible future circumstances they do or do not wish to be revived.


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Message #33144
From: [email protected]
Date: Sun, 26 Dec 2010 21:20:03 EST
Subject: Scoring Cases 

Content-Language: en

>Any attempt to quantify damage  is, I think, valuable, so long as we 
realize that it's partly >handwaving at this point. And of  course those who have 
the greatest  confidence in molecular >repair of the brain will feel that 
it's mostly irrelevant  anyway.
 
 
Careful reading of what I wrote should make it clear that the  scoring 
system I generated is an approximation to the point of being  almost arbitrary. 
And I suppose it is fair to call it hand  waving; in precisely the same way 
the first attempts to catalog the stars, or  explain the motion of heavenly 
bodies was hand waving.   
This will be the case with any attempts to score injury or  project 
survival based on surrogates, absent the kind of feedback that is  really required: 
recovery of a living system which exhibits functions that can  be assessed. 
Even the most sophisticated imaging technology currently  available can't 
show us a memory, or describe the structural determinants of  personal 
identity - or if they can, we don't yet know it. This is, in fact,  the critical 
Achilles heel of cryonics because it both enables its existence  by providing 
hope, and generates the principal cause of its downfall:  over-optimism to 
the point of self destruction. We should be mindful that  there is no such 
thing as a quantum of hope. Hope, by its very nature, is  infinite: and 
therein lies its great power to  nourish and sustain, and its even greater power 
to delude and  corrupt. 
>The frustrating part is that Steve Harris made the most  sophisticated 
attempt to  >quantify ischemic inujury, but never finished writing the  paper, 
so far as I know. He  >derived a number that he referred to as the "E-HIT" 
score, meaning Equivalent >Homeothermic Ischemic  Time. See 
>http://www.depressedmetabolism.com/2008/07/10/critical-cooling-rate-to-prev
ent->ischemic->brain-injury/ 
Steve Harris' E-HIT paper is indeed valuable, and it is  unfortunate that 
he did not complete  it. 
>The  problem with Darwin's approach is that he is applying a linear  
formula to a >phenomenon  which cannot be linear. That is, the damage caused by 
the tenth minute >of warm ischemia is >highly  unlikely to be the same as the 
 damage caused by the >first. 
Actually, this  is the key flaw in Steve Harris' approach, as well as in  
Mike Perry's effort to quantify  ischemic injury with his "Measure of 
Ischemic Exposure "(MIX). Both of these  approaches to quantifying ischemic injury 
rely on the "Q10 rule" which posits  that each 10oC decrement of temperature 
reduction (below 37oC) results in an  approximate halving of metabolic rate 
(in man), or to be more precise, a  reduction of metabolic activity by a 
factor of ~2.2 (where Q is oxygen  consumption (O2 used per unit of time) 
which decreases by 1/2.2 with each 10oC  drop in body temperature).[2] BTW, its 
important to keep in mind that Q10 is a  unit-less quantity, as it is the 
factor by which a rate changes, and is thus a  useful way to express the 
temperature dependence of a  process. 
In point of fact,  the Q10 rule (or more accurately, the Arrhenius equation 
from which it was  derived) serves as one of the three pillars upon which 
human cryopreservation  rests; [*] i.e., continued reduction in temperature 
eventually results in the  slowing of metabolic and catabolic activity to the 
extent where, at  approximately the boiling point of liquid nitrogen (-196 
oC ), all biochemical  change is arrested, more or less indefinitely.[3] 
[*] The other two pillars are the information theoretic criterion  of death 
and the assumed continued advance of technology and  medicine. 
The Q10 rule shows surprising constancy across species, with the  value 
being typically between 1 and 3 and, under conditions of hypothermia,  has been 
verified as operational in the brains of rats, dogs and men to ~5oC,  at a 
value of ~2.2.[2] The decrease in metabolic rate predicted by the Q10  rule 
is exponential; thus, a decrease in body temperature from 37oC to 17oC  
results in a decrease in metabolic rate by a factor (1/2.2)2 = 1/4.8. If the  
Q10 rule is applied to the human brain, using the tolerable limit of cooling  
before ice formation occurs inflicting freezing damage (~0oC), the predicted 
 slowing of catabolism during ischemia would be such that each hour spent 
at  0oC would be the equivalent of approximately three and a quarter minutes 
spent  under conditions of normothermic ischemia ([60 min]* 2.2-3.7 =  
3.24). [I would like to pause to note  that the Q10 rule is much abused in 
biology, but that's another pot at another  time.] The Q10 rule has  important 
implications for surgery employing deep hypothermic circulatory  arrest (DHCA) 
where there is the need to bound the safe period of cold  ischemia with a 
high degree of confidence. In 1991 Greeley, et al.,[2] derived  an equation 
for approximating the safe circulatory arrest time at any  temperature; the 
Hypothermic Metabolic Index (HMI)  
Two important caveats accompany the HMI, and they are that  the hematocrit 
(HCT) and pH be taken into consideration when making  the calculation. HCT 
determines the hemoglobin decay curve that will take  place during the period 
of hypothermic circulatory arrest (in essence the  stored oxygen available 
in the blood at the time that circulation is  interrupted). The pH strategy 
management strategy management employed during  cardiopulmonary bypass (CPB) 
will affect cerebral blood flow and thus may  impact brain metabolic 
housekeeping. Use of pH stat management[*] results in  higher cerebral blood flow 
(CBF) during CPB and thus, typically, better brain  oxygenation and overall 
metabolic status at the time circulatory arrest  begins.[4] The advantage 
that the HMI enjoys over the Q10 rule is that it has  been empirically "proved"
 in humans via the Boston Circulatory Arrest  Trial.[5],[6] 
[*] The Boston Circulatory Arrest Trial was carried out using  alpha stat 
pH management which is no longer used by most centers for pediatric  cardiac 
surgery involving DHCA. 
The Importance of Cold Scission: 
Applying the Q10 rule to cryopatients, or to dogs or rats for  that matter, 
would suggest that 3 hours of cold ischemia is the limit beyond  which 
recovery (absent reparative therapies) would be impossible, and this is  indeed 
the case. Application of the Q10 rule to cryopatients who experience  
prolonged periods of cold ischemia during Transport, on the order of 24 to 72  
hours, would suggest a grim situation pertains; indeed one where decomposition  
has begun. However, there are problems in extending the Q10 rule over long  
periods of time at temperatures close to 0oC; with apparent contradictions  
surfacing in the form of successful preservation of meat and other 
foodstuffs  by simple refrigeration (~4-10oC) for prolonged periods of time,[7] and 
of  even more relevance, the successful storage of human organs (which are  
comparably sensitive to the brain in terms of cold ischemic injury), for  
periods of 48 to 72 hours at  1-4oC[3].[8],[9],[10],[11] 
Preservation of ischemia-intolerant organs such as the liver and  kidney is 
made possible not by any sophisticated interruption of metabolism,  but by 
the use of intracellular organ preservation solutions which act  primarily 
by inhibiting cellular edema and scavenging free radicals.[12]  So, while the 
Q10 rule predicts the  mammalian brain's response to ischemia (at least to 
 ~5oC) reasonably  well,[13],[14],[15],[16] it does not predict the behavior 
of other ischemic  mammalian organs under the conditions of cold storage for 
transplantation.  Similarly, preservation of foodstuffs by refrigeration 
and prolonged storage  of organs near 0oC are possible because the Q10 rule 
does not take into  account several important facts; the first, and probably 
most important of  which, is that much of  the  metabolic and catabolic 
activity characteristic of biological systems is  facilitated by the catalytic 
action of enzymes. In fact, biology as we know it  is largely an artifact of 
the greatly accelerated speed of chemical reactions  made possible by 
enzymes, as compared to the rate of reaction predicted on the  basis of the 
Arrhenius equation.[17]  
Enzymes are proteins with complex shapes - shapes that are essential to  
their action as facilitators of chemical reactions - and these shapes are  
critically dependent upon the structure of the enzymes - in particular, their  
folding pattern. Profound and ultraprofound hypothermia can destabilize the  
folding of proteins resulting in a loss of stereospecificity in the case of 
 many enzymes. This phenomenon was first described during cooling of 
enzymes to  below 10oC by Irias and Olmstead in 1969, who referred to it as "cold  
scission," or "cold lability," and noted its effectiveness in halting 
their  biochemical activity.[18]    Additionally, phase changes in the 
non-aqueous lipid components of  cells, brought on by deep cooling, can also relieve 
these molecules of their  normal physical mobility and thus their 
availability for biochemical  activity.[19] Additionally, enzymes embedded in lipds 
that undergo phase  change upon cooling to below room temperature may be 
spatially inhibited by  being confined in the solidified membrane.[20]  
Another factor that critically effects cell viability in both  hypothermia 
and in ischemia is the   Gibbs-Donnan Equilibrium; an unstable situation 
occurs in a solution if  one side of a semi-permeable membrane contains a 
solution consisting of a  permeable cation such as K+ with an impermeable anion 
(negatively charged  protein), whilst the other side contains a solution of 
K+ and Cl-, both of  which are permeable to the membrane with the K+ 
concentrations being equimolar  on both sides of the membrane. 
The effectiveness of intracellular organ preservation solutions  provides a 
clue that, at least near 0oC, it may be the case that much of the  cold 
ischemic injury predicted by the Q10 rule (and which is in fact observed  to 
occur) results from not from biochemical activity, per se, but rather from  
biophysical changes which proceed in the absence of metabolism or catabolism.  
Under normal metabolic conditions approximately 1/3rd of resting cellular  
energy expenditures are on ion homeostasis. The protein rich intracellular  
milieu is positively charged, and the sodium chloride (NaCl- ) rich  
extracellular milieu is negatively charged. Because NaCl- is osmotically  active, 
movement of NaCl- from the extra- to the intracellular space across  the cell 
membrane (to balance the charge difference represented by the  positively 
charged intracellular protein; the Gibbs-Donan Equilibrium), the  result is 
cellular edema. It is cellular edema, and the biophysics of the  Gibbs-Donan 
Equilibrum, that appear to be a major driver of cold ischemic  injury. This 
is antagonized by intracellular organ preservation solutions by  removing 
most of the offending sodium from the extracellular spaces and  replacing it 
on a roughly equimolar basis with cell membrane impermeable  osmotically 
active species; typically sugars such as lactobionate and  raffinose or the 
sugar-alcohol, mannitol.  
Because of enzymatic inhibition due to chilling, and especially  if 
impermeant species have been used to replace the edema causing small  extracellular 
ions in cold stored brains, simple metrics that employ the  Arrhenius 
equation cannot be used to quantify warm or cold ischemic injury in  cryonics (or 
in organ preservation). Much as is the case when biological or  chemically 
reacting systems are rendered into the solid state by vitrification  or 
desiccation,  the Arrhenius equation ceases to be of direct  use. 
Mike  Darwin 
References 
1.          Hillyard Industries I: Vindicator+ Technical Data Sheet #168. 
In. St.  Joseph, MO: Hillyard Industries, Inc; 2010. 
2.          Greeley W, Kern, FH, Ungerleider, RM. et al.: Cerebral 
metabolic  suppression during hypothermic circulatory arrest in humans. The Annals 
of  Thoracic Surgery 1999, 67(6):1895-1899. 
3.         Hixon H: The question  column: How cold is cold enough? Cryonics 
1985,  6(1):19-25. 
4.          Bellinger DC WD, duPlessis AJ, Rappaport LA, Jonas RA, 
Wernovsky G,  Newburger JW.: Neurodevelopmental status at eight years in children 
with  dextro-transposition of the great arteries: the Boston Circulatory 
Arrest  Trial. J Thorac Cardiovasc Surg 2003,  126(5):1385-1396. 
5.          Wypij D, Newburger, JW, Rappaport, LA, duPlessis, AJ, Jonas RA, 
 Wernovsky, G, Lin, M, Bellinger, DC.: The effect of duration of deep  
hypothermic circulatory arrest in infant heart surgery on late  
neurodevelopment: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc  Surg 2003, 
126(5):1397-1403. 
6.          Ungerleider R, Gaynor,   JW.: The Boston Circulatory Arrest 
Study: An analysis. J Thorac  Cardiovasc Surg 2004, 127:1256-1261. 
7.          Lorentzen G: Food preservation by refrigeration, a general  
introduction. International Journal of Refrigeration 1978,  1(1):9-12. 
8.          Ross H MV, Escott ML.: 72-hr canine kidney preservation without 
 continuous perfusion. Transplantation 1976,  21(6):498-501. 
9.          Sung D, Woods, JE.: Forty-Eight-Hour Preservation of the Canine 
Liver.  Ann Surg 1974, 199(4):422-426. 
10.       Monden  M, Fortner, JG.: Twenty-four- and 48-hour canine liver 
preservation by simple  hypothermia with prostacyclin. Ann Surg 1982,  
196(1):38-42. 
11.       Todo S,  Hamada, N,  Zhu, Y,  Zhang, S,  Subbotin, V, Nemoto, A,  
Takeyoshi, I,  Starzl, TE.: Lazaroid U-74389G for  48-hour canine liver 
preservation. Transplantation 1996,  61(2):189-194. 
12.       Belzer  F, Southard, JH.: Principles of solid-organ preservation 
by cold storage.  Transplantation 1988, 45(4):673-676. 
13.        Michenfelder J, Milde, JH.: The effect of profound levels of  
hypothermia (below 14 degrees oC) on canine cerebral metabolism. J Cereb Blood 
 Flow Metab 1992, 12(5):877-880. 
14.       Haneda  K, Thomas, R, Sands, MP, Breazeale, DG, Dillard, DH.: 
Whole body protection  during three hours of total circulatory arrest: an 
experimental study.  Cryobiology 1986, 23(6):483-494. 
15.       Drabek  T, Fisk, JA, Dixon, CE, Garman, RH, Stezoski, J, 
Wisnewski, SR, Wu, X,  Tisherman,, SA K, PM.: Prolonged deep hypothermic circulatory 
arrest in rats  can be achieved without cognitive deficits. Life Sci 2007,  
8(7):543-552. 
16.        Goldzveig S, Smith, AU.: A simple method for reanimating rats 
and mice.  J Physiol 1956, 132(2):406-413. 
17.        Benjamin-Cummings T: Chemical Kinetics, Third Edition. Weinheim: 
 Wiley-VCH Verlag GmbH & Co. KGaA; 1997. 
18.       Irias J,  Olmsted, MR.: Pyruvate carboxylase. Reversible 
inactivation by cold. Pyruvate  carboxylase. Biochemistry 1969, 19:91-98. 
19.       Avery S,  Lloyd, D, Harwood, JL.: Temperature-dependent changes 
in plasma-membrane lipid  order and the phagocytotic activity of the amoeba 
Acanthamoeba castellanii are  closely correlated. Biochem J 1995, 312((Pt  
3)):811-816. 
20.       Zakim D,  Kavecansky, J, Scarlata, S.: Are membrane enzymes 
regulated by the viscosity  of the membrane environment? . Biochemistry 1992,  
31(46):11589-11594. 
21.       Perry R:  Towards a measure of ischemic injury. . Cryonics 1996,  
17(2):21. 
22.       Harris  S: Initial cooling in cryonics from body temperature to 
ice temperature:  Physiologic and physics theory, quality control proposals, 
historical cryonics  case analysis examples, lab experimental results, 
literature review, numerical  recipe examples, and practical summaries and 
recommendations for the future.  In. Rancho Cucamonga, CA: Critical Care Research; 
 2003. 
--- 



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