Human ventricular fibrillation victims subjected to only 1ºC of
hypothermia showed a substantial increase in both survival and favorable neurological
outcome [CRITICAL CARE MEDICINE; Don,CW; 37(12):3062-3069 (2009)].
Humans have been subjected to deep hypothermic cardiac arrest for aortic surgery for over an
hour without gross neurological deficits. The subjects reached complete electrocerebral
silence (zero electroencephalographic bispectral index) between temperatures of
16ºC and
24ºC [JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA; Hayashida,M; 21(1):61-67 (2007)]
and were re-warmed without neurological deficit,
confirming that dynamic brain activity can be lost and regained without loss of personal identity.
Many reptiles and invertebrates can withstand lower temperatures
than mammals, and thus achieve a more profound state of depressed
metabolism and suspended animation. The northern wood frog (Rana sylvatica)
can survive in a semi-frozen state down to −6ºC for
months with full recovery upon
rewarming [THE FASEB JOURNAL; Costanzo,JP; 9(5):351-358 (1995)].
Multicellular animals treated with cryoprotectants have
survived cooling to cryogenic temperatures. A variety of
parasitic helminths
have survived liquid nitrogen storage
after treatment with DMSO, glycerol or ethylene
glycol [CRYOBIOLOGY; James,ER; 49(3):201-210 (2004)].
Many varieties of nematode larvae have survived cryogenic
temperatures. The
C. elegans
nematode is
routinely stored in liquid nitrogen.
Plant nematodes treated with 25% ethylene
glycol, cooled rapidly and held in liquid nitrogen for a
few minutes before storage in a −140ºC freezer
for a month, showed 85%
survival [CRYOBIOLOGY; Irdani,T; 52(3):319-322 (2006)].
Survival rates up to 70% were achieved for parasitic nematode
larvae treated with 10% DMSO before 16 month storage in
liquid nitrogen [INTERNATIONAL JOURNAL FOR PARASITOLOGY; Gill,JH;
25(12):1421-1426 (1995)]. A majority of a variety of infective nematode
species larvae treated with sodium hypochlorite and saline
solution survived more than 15 years in liquid nitrogen,
although percent infectivity was less than half of percent
survival [VETERINARY PARASITOLOGY; van Wyk,JA; 88(3-4):239-247
(2000)]. The stress-sensitive tropical parasitic nematode Radopholus
similis treated
with a mixture of methanol, glycerol and glucose showed no reduction
of infectivity or reproduction after storage in liquid
nitrogen [CRYOBIOLOGY; Elsen,A; 55(2):148-157 (2007)].
A number of mammalian tissues and organs have been successfully vitrified.
Tissue-engineered blood vessels that were vitrified, stored at
−135ºC and rewarmed showed comparable metabolic activity
to fresh controls [TISSUE ENGINEERING; Dahl,SLM; 12(2):291-300 (2006)].
Rat hippocampal slices vitrified, cooled to −130ºC, and rewarmed
showed 100% viability within experimental
error [CRYOBIOLOGY; Pichugin,Y; 52(2):228-240 (2006)]. Rabbit
trachea that were vitrified, held in liquid nitrogen, and rewarmed were
comparable to fresh
specimens [CRYOBIOLOGY; Xu,H; 58(2):225-231 (2009)]. Complete
mouse ovaries have been vitrified, stored in liquid nitrogen, and
rewarmed to produce live pup birth rates comparable to that seen with
fresh ovaries [FERTILITY AND STERILITY; Hasegawa,A;
86(Suppl 3):1182-1192 (2006)].
The greatest accomplishment of vitrification to date has been the vitrification
of a rabbit kidney, cooling to −135ºC, rewarming, retransplatation into
the rabbit, and the kidney able to sustain the rabbit indefinitely as the
sole functioning
kidney [ORGANOGENESIS; Fahy,GM; 5(3):167-175 (2009)]. But this
falls far short of vitrifying a whole rabbit or a whole mouse.
Although cryogenic storage cannot prevent ionization by radiation
or the breaking of chemical bonds, cryogenic storage protects
against radiation damage by reducing the mobility and reactivity of
reactive species generated by
radiation [ULTRAMICROSCOPY; Knopek,E; 10(1-2):71-86 (1982)].
Cooling large molecular hydrated organic compounds to cryogenic
temperature has been shown to increase tolerable exposure to
ionizing radiation up to ten times in electron
microscopy [JOURNAL OF MICROSCOPY; Glaeser,RM; 112(1):127-138
(1978)]. Cells stored in liquid nitrogen
subjected to ionizing radiation a hundred times normal
background levels show no increase in cell death, nor
is there evidence of chromosomal or genetic change
after storage in liquid
nitrogen [AMERICAN JOURNAL OF PHYSIOLOGY; Mazur,P;
247(3 Pt 1):C125-C142 (1984)]. Frozen 8-cell mouse
embryos subjected to the equivalent of 2,000 years of background
gamma rays
during 5 to 8 months in liquid nitrogen showed no detrimental
effect on survival or
development [JOURNAL OF REPRODUCTION AND FERTILITY; Glenister,PH;
70(1):229-234 (1984)]. Chinese hamster ovary fibroblasts in 10% DMSO
show 3.5 times
less damage from 600 rad of x-ray irradiation at liquid nitrogen
temperature compared to
22ºC [CRYOBIOLOGY; Ashwood-Smith,MJ; 16(2):132-140 (1979)].
Calling the depressed metabolism by hydrogen sulfide "suspended animation"
is hyperbole insofar as metabolism at one tenth normal is still far above
absence of metabolism. Even if artificial hibernation of humans could allow
for maintenance temperatures close to 0ºC, the metabolic rate would
still be one-twentieth normal. A 200 day spaceflight would require
10 days worth of nutrient, oxygen and waste-handling for a mammal
hibernating at 0ºC. By contrast, if human cryopreservation were
possible at cryogenic temperatures, minutes of metabolism at normal
body temperatures would take tens or hundreds of thousands of
years [REJUVENATION RESEARCH; Best,B; 11(2):493-503 (2008)].
Moreover, cryopreservation at cryogenic temperature would afford
much greater protection against radiation damage. Maintaining
cryogenic temperature in space could require modest amounts
of energy.
Cryoprotectant toxicity using conventional cryoprotectants
remains the single greatest obstacle to vitrification of
organs larger than a rabbit
kidney [CRYOBIOLOGY; Fahy,GM; 6 June 2009].
If cryoprotectant toxicity could be eliminated, reversible
cryopreservation at cryogenic temperature of an entire human
could become possible. Alternatively, if all human cells could
be induced to produce a non-toxic cryoprotectant such as trehalose
(which does not cross cell membranes), whole body vitrification
might become possible. Human fibroblasts have already
been induced to synthesize cryoprotectant trehalose by
genes introduced using
recombinantadenovirusvectors [NATURE BIOTECHNOLOGY; Guo,N; 18(2):168-171 (2000)].
Cryonics is the cryopreservation
of legally dead humans at cryogenic temperatures in the hope that
future technology will not only repair damage resulting from
cryopreservation, but cure all diseases and
rejuvenate people to the prime of life. Cryonics
as it is practiced today uses vitrification, but although ice
can be eliminated in many organs, damage is nonetheless done
by cryoprotectant toxicity. There may also be freezing
damage due to incomplete perfusion of certain organs
or tissues. Nanotechnology
(nanomedicine)
is expected to be able to repair damage on a molecular level.
Future technology is not
science, but the idea that future technology will be
vastly superior to current technology should not be dismissed.
The emphasis of current technology in cryonics is to
cryopreserve with the least amount of damage so that
future technology has the best chance of repairing the
damage. Although some future molecular repair technology
could fix damage, but it is more prudent to minimize
damage in the first place. Therefore, cryonics
organizations first perfuse cryonics patients with anti-freeze
cryoprotectants to eliminate ice altogether (vitrification).
Electron micrographs of vitrified brain tissue at least indicate
that brain structure can be preserved on a fine level, which
makes future molecular repair more promising.
Humans in spaceflight would not require rejuvenation or
the curing of fatal diseases — nor should there be
any repair process require for cryoprotectant toxicity
or freezing damage. If something to increase tissue
thermal conductivity were developed, less toxic cryoprotectants
could be used because faster external cooling would be
feasible. Alternatively, something like a reverse microwave
technology for cooling rather than warming could have
some benefit.
Pure water can vitrify without cryoprotectants if cooled
at 3 million degrees Celcius
per second [JOURNAL OF MICROSCOPY; Bald,WB;143(Pt 1):89-102 (1986)].
Such a cooling rate would be impractical for mammalian tissues, at least
partially because cooling would be applied externally. If something
could be invented that acted like an inverse microwave that cools tissue
uniformly the way microwave heating warms uniformly, less cryoprotectant
could be used.
Adiabatic demagnetization is something like an
inverse microwave effect. A cryonics patient could be
perfused with a solution composed not only of cryoprotectant but of a paramagnetic
salt such as
ferric ammonium alum in a magnetic field. By gradually decreasing
the strength of the magnetic field the salt ions become disordered, uniformly
drawing heat throughout the body of the cryonics patient, not just from
the surface. This or other
novel mechanisms of cooling
could potentially be of great benefit in solving the problem
of rapidly cooling large biological objects.
![[GO TO BEN BEST'S HOME PAGE]](../homeback.gif)
HOME PAGE