X-Message-Number: 33149
From: 
Date: Tue, 28 Dec 2010 03:05:51 EST
Subject: Scoring Cases

Content-Language: en

From: Gerald Monroe _ 
(mailto:) 
Date: Mon,  27 Dec 2010 12:42:20 -0600
Subject: Re: CryoNet #33139 - #33144
 
This is a pretty good summary, Gerald. I've interlaced some points that I  
think are important.
 
>>Simplifying it: the edema damages neurons enough that they won't  

restart. (nor will a flooded engine, or a jammed machine).  But since  
biological 
enzymes aren't functional near 0 degrees C, neurons have probably not  been 
able to catalyze the self destructive processes that neurons perform when  
they think they are damaged beyond repair.>> 

Edema is  certainly a major factor in compromising cellular viability in 
ischemic and  nonischemic hypothermia, but it isn't the only factor. 

Substrates necessary for  the cells to restart function get used up, free 
radical 
damage occurs due to  multiple factors (including uncoupled electron transport 
in the mitochondria)  and there is undoubtedly biochemical injury of the 
same kind, if not to the same  degree, as occurs in warm ischemia.
 
Many enzymes have rather abrupt inactivation temperatures; in other words  
they stop working altogether if cooled or heated above a given temperature.  
However, others behave "erratically' or even continue to function as 
predicted  by the Arrhenius equation. To the extent that these enzymes are 

mobile, and  capable of driving chemical reactions, they will continue to do so:
near 0 deg C  or even far below it. Catalase, the enzyme that decomposes 
hydrogen peroxide, is  active at dry temperature. I found this out a kid by 
preparing a liver  homogenate in 70% v/v glycerol and adding that to a mixture 
of hydrogen peroxide  in 70% v/v glycerol - with both solutions cooled to dry 
ice temperature. Within  a few seconds, fine white foam begins to appear in 
the interface between the two  solutions. That foam is oxygen from the 
decomposing H2O2. This only happens when  a liver homogenate is added to the 
peroxide.So, some enzymes, for good or ill,  will continue to do their duty as 
long as they can diffuse to the substrates  they are configured to act upon.
 
Another problem is "uncoupling' of linked enzyme systems. Enzymes often  
function as part of a complex chain of catalyzed reactions, and if one enzyme 
 drops out, or becomes more or less active than it should be, that can 

result in  the failure of the "system,' or worse, in the production of toxic or
 metabolically problematic compounds. These compounds can inhibit other 
important  reactions, cause direct injury (such as free radicals species do by 
damaging  cellular molecules), or result in excessive consumption of an 

essential  substrate for energy production...  Most of the enzymes that degrade
cell  structure, proteases and lipases, are typically sequestered inside 

cells; many,  but not all of them, in organelles called lysosomes. One positive
effect of  ultraprofound hypothermia (0 to +5 deg C) is that it greatly slows 
rupture of  the lysosomes. For one thing, the lysosomal membranes are 
frozen solid at these  temperatures - as are most other cellular membranes 

(including the organelle and  plasma membranes). Indeed, it may well be the 
phase 
transition of the lipids in  the membranous structures of cells that provide 
a great deal of the protection  that is "unexpected' on the basis of the 
Arrhenius equation (or the Q10 rule) in  conditions of hypothermia above the 
freezing point of water. 
 
Nonhibernating mammals, such as humans, are made up mostly of saturated  
fats which have a freezing point at or above room temperature. When our cells  
are cooled to a few deg C above freezing, the saturated fats in our cell  
membranes crystallize, and this not only renders these lipids unavailable for 
 metabolism and more resistant to catabolism, it also has profound effects 
on the  many cellular proteins (including enzymes) that are complexed with 
those lipids  *and with the complexing molecules that attach them to the 

lipids*, as well. As  far back as the mid-1960s, it was understood that cooling
can cause  destabilization of both the protein-lipid complexes and of their 
complexing  molecules, resulting not only in inactivation of enzymes, but in 
some instances,  possibly "inactivation' of the substrate molecules (upon 
which enzymes act), as  well (Ushakov, B., J. Gem PhysioL 44, 518-560 (1964).
 
>>Hence, if a patient were stored at near 0 C for 24 hours, there's  still 
a reasonable chance that their brain contains the information that  cryonics 
tries to preserve.  But it isn't ideal : ideal cryonics  preservation 
freezes the brain before an hour of cold ischemia has occurred  (before that 
point CPR and bypass machines are used to actively prevent  ischemia).  The 
reason this is ideal is that the maximum chance of survival  according to 
current science would be to put the brain in state at low  temperature that we 
know is revivable, and then to freeze it preventing any  further biochemical 
change at all from that start.  Since the brain is  composed of complex 
molecular structures, even though we cannot prove for  certain that revival is 

possible, we can show that it is virtually certain that  the information needed
to perform a revival has been preserved.>>
 
It is here that I must disagree with you - principally for the *certainty  
*with which you make the statement:
"Since the brain is composed of complex  molecular structures, even though 
we cannot prove for certain that revival is  possible, we can show that it 
is virtually certain that the information needed  to perform a revival has 
been preserved."

I wish that this were so; that it was proven.  But that is not the  case. 
We do not yet know what the "information necessary to perform a revival  is.'
 We are increasingly in a position to make educated guesses, but that is 
not  the same as knowing with proven certainty.  And it is critically 
important  to define what you mean by "revival.' For instance, it is not too 
terribly  uncommon for people to suffer severe head injury that results in 

prolonged  cerebral edema - brain swelling - who go on to "recover,' but with 
one 
teensy  little problem: their declarative memory is completely wiped. They 
have no  memory of their name, of growing up, of being married or having 
children (if  such was the case) and most of these people never recover their 
declarative  memories. Generally, their procedural memories are intact: they 
know how to  walk, drive a car, read and so on.  Often people so injured 
will undergo  dramatic changes in personality, almost always becoming more, 

rather than less  disinhibited. They may take up profanity, and drink or drugs,
become sexually  promiscuous, or just generally be more garrulous and 
obnoxious. This is believed  to be due to heavy losses of neurons in the 
prefrontal cortex. 
 
The relevance of such individuals to this discussion is that they raise the 
 question of just WHO exactly survived the accident that caused their brain 
 injury. At what point of memory loss, or personality change, do you stop 
being  you, or become someone else? Or are you just the neuronal circuits 
that generate  your consciousness - and if so, then why is YOUR death such a 
big deal - since  those same circuits will continue to exist in other humans, 
presumably long  after you are dead? In fact, they may well exist in all 
vertebrates! Cryonics is  likely to force the issue of personal identity and 
personal survival in ways  that have previously not been much of an issue, 
either for individuals, or for  society. Cloning of humans is now illegal, but 
it is patently clear that almost  all cryonics patients have sufficiently 
intact nuclear DNA to allow them to be  cloned. 
 
Given that medicine and society currently treat amnestic head injured  

patients who also have profound changes in personality as the SAME person they
were before the injury, how is that different from a cryopatient who is  "
revived' from a single intact nucleus *and who is not afflicted with the  
frontal neuron loss and accompanying personality alterations that some  

contemporary brain injury patients experience?* Indeed, by cloning criteria, it
is 
possible to begin reviving almost all of today's cryopatients! The 
experiment  has been a success!
 
While admittedly taking a long way to get here, my point is that we do not  
yet understand the neurobiology of memory, learning, or personality. We 

have  some ideas, but they are not proven, and there is plenty of room for the
possibility that we are doing something with contemporary cryopreservation  
procedures that wipes memory, or degrades it. While this seems unlikely to 
me  under conditions of "good' cryopreservation (and maybe unlikely to you, 
too), as  a scientist, I've learned to be skeptical; and the older I get 
the more  conservatively skeptical I get - and this despite the loss of so 
many frontal  cortex neurons from aging.
 
Mike Darwin


 Content-Type: text/html; charset="UTF-8"

[ AUTOMATICALLY SKIPPING HTML ENCODING! ] 

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=33149