X-Message-Number: 33155
Date: Tue, 28 Dec 2010 17:12:39 EST
Subject: Scoring Cases

Content-Language: en

Gerald, These are very good questions and are  certainly not the kind of 
questions  asked by people who have been recruited into cryonics over the past 
15 years, or  so. Could you tell me more about yourself, either here on 
CryoNet, or via  personal communication? 
References: <_ 
(mailto:) > 
From: Gerald Monroe <_ 
(mailto:) > 
Date: Tue, 28 Dec 2010 06:04:06  -0600 
Subject: Re: CryoNet #33145 -  #33149 
>>I'm still stuck on the following.  If we cool the patient down while  

preventing hypoxia, and then do not leave them 'liquid' and in a hypoxic state
longer than proven guidelines for possible recovery, freezing the brain 
solid  and then chilling it to the point that molecular motion almost ceases, 
what  could go wrong?  What physical  structure COULD neurons store 

information in that would not be retained in this  manner?  The functional 
systems of 
 the brain may contain many mysteries, but it's still an object made of 
ordinary  matter.>> 
Yes, the brain is made up of ordinary matter, and for  the record, no, I am 
not a mystic: I think it almost certainly the case that  memory, 
personality and identity can be fully explained on the basis of the  physical 

structure of the brain/body. And if we had a way to render those  structures 
into a 
solid state, devoid of meaningful biophysical change, then we  would indeed 
be preserving the individual in a viable state - and if we could  reverse 
that process without harm, then we would have suspended animation and  
survival of the treated individual. 
But there's the rub, we do NOT have such a method at  hand. When you write: 
"freezing the brain solid and then chilling it to the  point that molecular 
motion almost ceases, what could go wrong?" you put your  finger on the 
kernel of the problem. Currently, we have two ways to achieve  durable 

(indefinite) biopreservation, and those are freezing and vitrification.  Both of
these processes cause enormous perturbation of brain structure on both  the 
tissue and the molecular level. Currently, we believe that vitrification  

causes less perturbation to the structures we think are the best candidates for
encoding memory and personal identity, and so that is why it now considered 
the  "best' treatment. However, there is substantial evidence that most 
patients who  are being "vitrified' are in fact only partially vitrifying and 
in many cases  may be freezing - and freezing under conditions that may be 
far worse than had  they been frozen using conventional methods of 

cryoprotection and slow cooling.  But before I discuss the biophysical changes 
may attend vitrification, I  want to discuss freezing injury, in part because 
there is some overlap between  it and freezing in terms of the injury 
WHAT COULD GO WRONG: It is probably no accident that a  large fraction of 
the people recruited to cryonics since its inception have been  engineers, 
mathematicians, computer scientists, programmers, and, in general,  physical 
science types. I believe one reason for this is that there is a  fundamental 
difference in the way biological machines and electromechanical  machines 
are structured and operate. Almost all electromechanical systems may be  

fairly described as solid state - even those in existence before the advent of
electronics, and before the advent of the transistor. By solid state I mean 
that  virtually all their components are, literally, solid at their normal 
operating  temperatures.  
A consequence of this is that I can take a  21st Century Android phone or a 
17th century clock, and  whack them with a sledgehammer and the end result 
would broadly be the same: I'd  have a bunch of solid pieces of varying 

sizes and shapes that just sat there -  and of course, neither the phone nor the
clock would work any longer. But, all  the pieces would still be there and 
they would retain their individuality and  unique identity. And such will be 
the case indefinitely, as long as they are  protected from the elements. 
Biological systems are NOT solid state devices, and  they operate in very 
different ways. The core of biological systems is the  membrane; and 

membranes in living systems are not just passive walls or  "compartment makers':
they are the engines of chemistry and action in living  systems. They have 
enormous complexity and they derive a great deal of their  unique ability to 
function as living systems from their liquidity and  plasticity. If I were to 
reach for a meaningful physical analogy in the everyday  macro-world, the 
analogy would be that of soap bubbles. Cell membranes are very  much like soap 
bubbles, and they behave in broadly similar ways when stressed.  If you 
osmotically stress a cell by shrinking or swelling it too much, it does  not 
behave like a glass sphere and shatter into discrete pieces which can be  

collected and reassembled. Rather it buds and blebs and behaves like what it is,
 a liquid. And if you stress it enough, it simply comes apart into little  
droplets and into smaller "cells,' vesicles that have formed from the 
original  membrane.  
Before such dramatic changes occur, the structure of  the membrane can 

undergo reorganization in many ways, and the proteins embedded  in the membrane
may be rearranged as well. This is true not just for the plasma  membrane 
that encases the cell, but also for the membranes that comprise the  cellular 
organelles. In fact, it is rearrangement of mitochondrial membrane  
structure that underlies some of the damage that occurs in ischemia. Freezing  
causes enormous mechanical stress to the plasma membrane, and to organelle  
membranes, and some of the response to this stress is to radically alter  
membrane structure. In the worst case, the cell membrane(s) disappear as the  
structures they were, and reappear as new structures; droplets of membrane  
material, brand new micro-cells and so on. And they shed structures that were  
embedded or enclosed in them; thus the debris fields seen in frozen thawed  
Biological systems are NOT solid state devices and if  you damage them 

badly enough they do not sit around as discrete, broken pieces  waiting to have
their pre-injury, functioning structure inferred from the broken  pieces. 
And it is important to understand that some of this "remorphing' goes on  
during the freezing process as a consequence of the enormous osmotic and  
mechanical stresses imposed by ice formation. Further, there are significant  
changes to membrane structure, such crystallization of the lipids that occur  
solely as a result of cooling, and completely independent of freezing. To 
return  to the Android phone analogy, it would be as if the Android were made 
up of  liquids encased in soap bubbles and you squashed it.   
Imagine a soap bubble with an exquisitely detailed  painting embedded into 
its surface. A painting made up of millions of tiny  pixels comprised of 
colored nanoparticles. If you burst the bubble, some of the  bubble wall 
material will return to a simpler, all-fluid state, and some of it  may reform 
into new bubbles. But in any event, the painting is gone and what's  more, it 
is not obvious that it can be inferred from the puddle of particles in  

liquid and the new bubbles that result. So that is one thing that can go wrong.
I think it likely that procedural memory is encoded in  hard connections 
between neurons. But it is possible that declarative memory  relies on a 

different mechanism; perhaps changes in the character of the  synapses, neuronal
cell membranes, number or distribution of vesicles or other  membrane-based 
structures, or discrete changes in the chemistry of the neuronal  membranes. 
BOTH freezing and vitrification have the potential to disrupt those  kinds 
of structures in ways that would leave them uninferrable. Vitrification  may 
do this by the expedient of altering membrane structure irreversibly by  
dehydration, or by changing the molecular structure of the membranes or 
membrane  components by directly perturbing their structure. Vitrification 
solution is NOT  water, and water is critical to the structure of many of the 
molecules inside  cells. Indeed, a good part of the science behind designing 

tolerable  vitrification solutions is to make them behave as much like water as
possible -  while at the same time behaving as good glass forming agents 
when  cooled. 
As I said before, we simply don't how memories are  encoded in the brain 
and far more profoundly, we do not have a solid proven  theory of what 

comprises human identity - leaving particular structures out of  it. This is one
many reasons why we should be striving mightily to achieve  fully 
reversible suspended animation; because we JUST DON'T KNOW ENOUGH  YET. 
>>Storage at near 0 C during transport might be  a big mistake.  You  could 
easily be  correct.>> 
>>But it we were hypothetically presenting the  science of cryonics to an 
unbiased review board and we say : step ONE patient's  brain is 

revivable,therefore it contains the long term memory data.  Step TWO : a short 
time after 
step ONE,  we have frozen the brain and the larger molecules are completely 
unable to go  anywhere.  They have not budged from  where they were located 
in Step ONE.  Step THREE is of course the brain after a century in liquid  
nitrogen...hopefully almost the same as steps 1 and  2.>> 
This is all fine and dandy as long as you can posit  that the molecules 
have not budged from where they were whist in a fully  functional state. But 
you cannot do that, and neither can anyone  else. 
>>It seems like it ought to be possible to write  equations describing the 
information state of the brain in step one followed by  step two, and 

mathematically PROVE that a negligible amount of information has  been lost in 
transition.  We  would need to know nothing at all about memory storage, 
except that it is  performed by large durable molecules above a certain number 
of  daltons.>> 
Yes, that is correct: now, define "negligible' and  prove that the 

molecular structure is essentially unperturbed. Do that, and your  statement 
as correct. 
>>This is under ideal circumstances: patient has  good standby care by a 
competent medical team, and chooses to be suspended a  short drive from the 
cryonics lab.  One way to ensure this would be to have the patient on an 

active life  support machine that the patient could order switched off, causing
the patient  to legally die when the team is ready.  That would be a 

frightening moment, and one that I hope all of us here  have a chance to 
(assuming a method for keeping the brain alive in  it's current form is not 
developed in the next 50-80  years).>> 
Well, it might be frightening to you, but having seen  countless dying 

patients in this condition, and knowing the distress and  hopelessness they feel
(after all, many know they are DYING), I would not find  the "switch off' 
of "life support' frightening at all - indeed it would be the  prospect of 
CONTINUED life support that might render my brain into an  unrecoverable 
state that I would find - not frightening - but  terrifying. 
>>Your clinical examples aren't very  illustrative because you're talking 
about edema for a period of days killing  billions of neurons, and now the 
patient cannot retrieve their memories.  Are the memories gone?  Did neurons 
involved in the process of  searching and retrieving declarative memory data 
get destroyed?  Who knows, but the patient has been  allowed to fester in a 
hospital bed for weeks while the damaged neurons are  eaten by macrophages, 
and none of the damage has been repaired or the missing  cells replaced.  If 
I go attack your  desktop computer with a soldering iron and short a few 
hundred randomly chosen  circuits, you would not necessarily conclude that the 
data on your computer was  destroyed past any method of recovery.  

Especially if your computer stored it's  data in hundreds of distributed storage
chips scattered all across the  mainboard.>> 
I think my clinical example of cerebral edema and  declarative memoery loss 
is very much on point because it COULD imply that it is  NOT the death of 
brain cells that cause's memory loss, but rather some  alteration in membrane 
structure as a result of edema. In fact, we can be sure  that neuronal cell 
death, either from apoptosis or necrosis is NOT the cause of  such memory 
loss. These patient do not experience global loss of neurons and the  areas 
where they suffer the most neuron loss, the prefrontal cortex, is not  
generally associated with memory storage or retrieval. Nor are there visible  
losses in the white matter connections in the inflow/outflow tracts to the  
hippocampus - nor is the hippocampus catastrophically injured (e.g. by MRI  
Certainly it is possible that they have lost access to  their memories, 

rather than the memories themselves. But this hypothesis fails  to explain why,
after they make a recovery from the acute injury, they can form,  store and 
retrieve new declarative memories, but still not access the ones  create 
prior to the trauma? Thus, there is much we don't know.   
are not like transistors in a microchip; that analogy  holds only where they 
do non-unique tasks. It might be better to think of them  as microscopic 
flash drives written on soap  bubbles. 
Finally, the quality of cryopreservation most patients  are now receiving 
is dismal and has, on average, deteriorated since 1990.  Optimal pretty much 
is a thing of the past in cryonics anywhere in the world  today. 
Mike  Darwin

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


Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=33155