From: merkle@parc.xerox.com (Ralph Merkle)
Subject: The Technical Feasibility of Cryonics; part #5
Organization: Xerox PARC
Date: 22 Nov 92 21:18:04 GMT

The Technical Feasibility of Cryonics

PART 5 of 5.

by

Ralph C. Merkle
Xerox PARC
3333 Coyote Hill Road
Palo Alto, CA 94304
merkle@xerox.com

A shorter version of this article appeared in:
Medical Hypotheses (1992)  39, pages 6-16.


----------------------------------------------------------
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FOOTNOTES

1) Peter Mazur, a well known cryobiologist and critic of cryonics, has 
said: "Cryobiologists are often asked how long cells can remain viable 
at -196 degrees C, the temperature of boiling liquid nitrogen (which is 
the usual cryogenic fluid).  The answer is clear - more than 1000 years.  
The reason is that direct ionizations from background radiation are the 
only source of damage at such temperatures.  Ordinary chemical reactions 
cannot occur.  The pertinent question then is not storage stability, it 
is how can one get cells down to -196 degrees C and back without killing 
them."[42]  The record for storage is held by Leonard Hayflick, who has 
kept normal fibroblasts from embryonic human lungs in liquid nitrogen 
for 28 years (as of June 1990) without noticeable deterioration[96].

2) There is no implication here that the most powerful repair method 
either will (or will not) be used or be necessary.   The fact that we 
can kill a gnat with a double-barrelled shotgun does not imply that a 
fly-swatter won't work just as well.  If we aren't certain whether we 
face a gnat or a tiger, we'd rather be holding the shotgun than the fly-
swatter.  The shotgun will work in either case, but the fly-swatter 
can't deal with the tiger.   In a similar vein, we will consider the 
most powerful methods that should be feasible rather than the minimal 
methods that might be sufficient.  While this approach can reasonably be 
criticized on the grounds that simpler methods are likely to work, it 
avoids the complexities and problems that must be dealt with in trying 
to determine exactly what those simpler methods might be in any 
particular case and provides additional margin for error.

3) An atomic mass unit is the same as a Dalton.  Different authors in 
different fields have different preferences for the name used to 
describe this unit, and so no single abbreviation will satisfy everyone.  
The use in this paper of the atomic mass unit, abbreviated as amu, was a 
compromise intended to be most easily understood by the widest audience.

4) A wide variety of mechanical computer designs are feasible.  Perhaps 
the most famous proposal for a mechanical computer was made by Charles 
Babbage[98] in the early to mid 1800's.  Mechanical systems can be 
scaled down to the molecular size range and still function, although the 
analysis of such molecular mechanical systems requires the use of 
(appropriately enough) molecular mechanics: a thriving field which 
models molecular behavior by the use of force fields to describe the 
forces acting on the individual nuclei[99].  The time evolution of the 
locations of the nuclei can be followed using relatively straightforward 
computational methods.

5) To fully specify the state of each atom would, strictly speaking, 
require that we specify the states of all its electrons.  For the most 
part, however, these states are known or can be readily inferred once 
the type of atom is given.  For example, a sodium atom in solution will 
normally be the ion, Na+.  Likewise, the bonding structure of two carbon 
atoms separated by a certain distance can normally be inferred from the 
distance.  The state of magnetization, while relevant for computers (the 
state of magnetization of a floppy disk is obviously of importance) is 
of negligible importance in biological systems.  People are routinely 
exposed to magnetic fields of several Tesla to make diagnostic images, 
and appear none the worse for the experience.  While coordinate 
information should be sufficient in almost all cases, we can always add 
a few bits of additional information if there is some ambiguity.  This 
won't increase our estimate of 100 bits per atom by very much, and 
because 100 bits is a conveniently round number we'll continue to use 
it.

6) Because proteins are always produced as a linear chain, they must of 
necessity be able to adopt an appropriate three dimensional 
configuration by themselves.  Usually, the correct configuration is 
unique.  If it isn't, it is usually the case that the molecule will 
spontaneously cycle through appropriate configurations by itself, e.g., 
an ion channel will open and close at appropriate times regardless of 
whether it was initially started in the "open" or "closed" 
configuration.  If any remaining cases should prove to be a problem, a 
few additional bits can be used to describe the specific configuration 
desired. 

7) "For many years, it was thought that irreversible cellular damage 
unavoidably occurs after only a few minutes of complete cerebral 
ischemia.  This opinion has been modified during the past decade 
[omitted reference].  Provided that the conditions for recovery are 
optimal, short-term restoration of brain functions may be achieved after 
periods of ischemia lasting as long as 60 minutes..."[93].
"Most clinical and experimental studies suggest that the normothermic 
brain is not able to withstand complete ischemia of >8 to 10 min.  There 
is, however, firm experimental evidence of functional and biochemical 
recovery of a substantial part of the brain after complete 
cerebrocirculatory arrest of one hour [omitted references]."[97].
"It turned out in fact that appropriate treatment of post-ischemic 
recirculation disturbances led to recovery of energy metabolism and 
neuronal excitability after complete cerebro-circulatory arrest of as 
long as 1 hour at normal body temperature [omitted reference]"[95].

8) Definitions that are similar or identical to the one given here are 
well known in the cryonics literature[23].

9) This issue is of great concern to computer users.  A variety of tools 
and techniques exist for recovering information from damaged or 
otherwise inoperative disk drives, with the intent of recovering the 
memory and "personality" of the computer so that the user will not 
suffer a (sometimes traumatic) loss.

10) Cryonics will also fail if a person is prematurely thawed.  This 
failure mode, however, is not an argument against cryonics, rather it is 
an argument for reliable refrigerators.  A person injured in a car crash 
might die if their ambulance was struck by a train.  This is not an 
argument that we should cremate accident victims rather than use an 
ambulance to transport them to a hospital!

11) There is fairly general agreement that death by the information 
theoretic criterion wil not occur during storage of tissue at the 
temperature of liquid nitrogen, confer footnote 1.  For this reason we 
neglect the possibility that significant information loss occurs during 
storage even though this might be viewed as theoretically possible.

12) Criticisms of cryonics are not supported by the extant literature.  
Interestingly (and somewhat to the author's surprise) there are no 
published technical articles on cryonics that claim it won't work.  As 
one might suspect, there are also no articles in the neuroscience 
literature that address the issue of erasure of memory in the 
information theoretic sense, and there are no articles in the 
cryobiological literature that address the impact of freezing on the 
retention of long term memory in the information theoretic sense.  There 
is an almost absolute conceptual failure to either understand or 
consider the implications of the information theoretic criterion of 
death.  This conceptual failure is a severe impediment to research in 
this area.
Even worse, the Society for Cryobiology has gone so far as to adopt by-
laws calling for the expulsion of members who support cryonics.  Members 
in good standing who support cryonics have been threatened with firing 
if they discuss their views publicly.  Open discussion and review has 
proven to be a remarkably effective engine for driving scientific 
advance.  The suppression of open discussion by a scientific society 
runs counter to one of the most central principles of scientific 
research and seriously impedes progress.

13) Many non-mammalian animals can be frozen to temperatures as low as 
-50 degrees C and survive[57].

14) A majority of the population favor "death with dignity" laws which, 
once enacted, would give the individual control over the conditions of 
their own legal death.  Once such laws are enacted it should be possible 
in many cases to eliminate the ischemic interval entirely.

15) There are various reasons for delay when a person is cryonically 
suspended, ranging from purely pragmatic issues such as delay following 
abrupt and unexpected accidents to legal and social forces that mandate 
that suspension not be started until after a legal declaration of 
"death."  Whatever the cause, the effect is to increase the level of 
damage that takes place prior to suspension.

16) It should be clear that the claim of "irreversibility" is 
unsupported.  Mitochondrial function is well understood: they provide 
energy for the cell.  Even the complete absence of mitochondria would 
not cause death by the information theoretic criteria.

17) Much current work advances the (correct) claim that cellular, organ, 
and body function is lost under certain conditions.  This loss of 
function is incorrectly and misleadingly labeled "death," "irreversible 
injury," etc.  This work forms the backdrop against which tissue damage 
to cryonically suspended patients is measured by most biologists, 
cryobiologists, doctors and other health care workers.  Clearly, this 
work predisposes such workers to dismiss cryonics because, by these 
criteria, much "irreversible" damage has occurred in most cryonically 
suspended patients.  The implications of adopting the information 
theoretic criterion of death have simply not been considered, and we can 
reasonably expect a delay of several years to a few decades before they 
are.  This would be consistent with historical data concerning the slow 
acceptance of new ideas.  Ignaz Semmelweis demonstrated in 1848 that 
washing your hands in chlorinated lime after leaving the autopsy room 
and before entering the maternity ward reduced maternal deaths from 
childbed fever from as high as 25% to about 1%.  Despite this, his 
proposal was widely ridiculed and little practiced for several more 
decades[60].
Interestingly, few of even the most severe critics of cryonics claim 
that death by the information theoretic criterion is likely to have 
occurred when the question is posed to them directly.

18) It is interesting to note that current research into the three-
dimensional structure of neurons often embeds neural tissue in plastic, 
and then produces a series of thin sections (typically 50 to 100 
nanometers thick in electron microscopic reconstruction work) by using 
an ultramicrotome.  The serial sections are then examined by a person 
(typically a graduate student) and the structures of interest in each 
section are outlined on a digitizing tablet and entered into a computer.  
The resulting data-base is used to build a three-dimensional image of 
the neuron[54].  This work has been quite successful at determining the 
three-dimensional structure of small volumes (small enough for a 
graduate student to examine in a few weeks or months) despite the 
adverse effects of tissue preparation and sectioning.  Sections vary in 
thickness.  They also buckle, fold, and tear.  Despite these 
difficulties, the human visual system can reconstruct the original shape 
of the object in three dimensions.  Current electron microscopic 
reconstructions are quite capable of analyzing even the finest dendrites 
and thinnest axons, as well as determining the location and size of 
synapses[27,28], and even finer detail[29].  It seems reasonable that 
the less damaging method of inducing a fracture at low temperature, and 
the more informative and less damaging analysis possible with 
nanotechnology (as opposed to destructive analysis of thin sections by a 
high energy electron beam) will produce more information about the 
structure being analyzed.

19) Under favorable circumstances, we might be able to terminate the 
division process sooner.  That is, it might be that a relatively large 
piece of tissue (several tens of microns or larger) was relatively 
intact, and required little if any repair.  Devising methods to take 
advantage of the minimal damage that might occur under favorable 
circumstances is beyond the scope of this paper. 

20) For those concerned about the omission of water molecules and the 
like, we could just as easily store the coordinates of every molecule.  
This would increase the storage requirement, but would still be entirely 
feasible.

21) Despite the notorious difficulty in obtaining accurate information 
about specific aspects of brain "hardware," as discussed by 
Cherniak[115], it is still the case that rather rough bounds can be 
usefully derived.

22) A literature search on cryonics along with personal inquiries has 
not produced a single technical paper on the subject that claims that 
cryonics is infeasible or even unlikely.  On the other hand, technical 
papers and analyses of cryonics that speak favorably of its eventual 
success have been published.  It is unreasonable, given the extant 
literature, to conclude that cryonics is unlikely to work.  Such 
unsupported negative claims require further analysis and careful 
critical evaluation before they can be taken seriously.
Newsgroups: sci.cryonics