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Cryonics Takes Another Big Step Toward the Mainstream

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Rejuvenation Research
© Mary Ann Liebert, Inc.
DOI: 10.1089/rej.2020.2356
Rejuvenation Research
Cryonics takes another big step towards the mainstream (DOI: 10.1089/rej.2020.2356)
This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Cryonics takes another big step towards the mainstream
Aubrey D.N.J. de Grey
SENS Research Foundation, Mountain View, USA
“You're dead when a doctor says you're dead.” – James Bernat
A lot progress, both technological and political, has occurred in cryonics since Ben Best
made his scientific case for cryonics in this journal in 2008.1 Among the most encouraging
examples were the demonstration of retention of memory in nematode worms after
cryopreservation and revival, also published in RR,2 and the emergence of an
unprecedentedly authoritative consensus around the feasibility of preserving complex
mammalian tissues.3
One common objection to the theory and practice of human cryopreservation is that it can
only work under ideal circumstances because the brain “dies” within minutes. This issue of
Rejuvenation Research contains a comprehensive study to understand the ultrastructural
effects of circulatory arrest on the mammalian brain.4 The authors of this paper show that
ischemia-induced damage to the brain is a time- and temperature-dependent process. It
takes many hours of normothermic global ischemia, and several weeks of cold global
ischemia, to damage the fine structure of the brain to a degree that the original structure
of the brain cannot be recognized or inferred. The researchers also introduce a novel deep
learning algorithm that can distinguish the early stages of permanent cerebral ischemia
from the late stages of permanent cerebral ischemia by looking at electron micrographs
alone. The paper concludes by speculating that future computational technologies can re-
construct the pre-ischemic state of the brain from the ischemic state. They call this
discipline “reconstructive connectomics” and its methods could also be used to infer the
non-frozen state from the frozen state (if there is freezing damage), providing an
important tool-set to permit biological repair and revival of cryonics patients preserved in
non-ideal circumstances.
Today, human cryopreservation is practiced as a form of experimental emergency
medicine in which standby teams are deployed to the bedside of a terminally ill person to
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Page 2 of 4
Rejuvenation Research
Cryonics takes another big step towards the mainstream (DOI: 10.1089/rej.2020.2356)
This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
start their procedures as soon as the person is pronounced legally dead. The delays and
complex logistics entailed in this process are often perceived as intrinsic to the process of
human cryopreservation. In principle, however, human cryopreservation can be practiced
as an elective medical procedure in which the transition between the decline of a terminal
patient and the start of cryonics procedures is managed by medical professionals. The aim
of human cryopreservation as an elective medical procedure is distinctly different from
palliative care or euthanasia because the objective would be to save a life, not end it.5 The
degree to which human cryopreservation as a hospital-based procedure draws upon
mainstream disciplines such as critical care medicine, anesthesiology, extracorporeal
perfusion, and cryobiology, warrants the name Medical Biostasis for this emerging
In 2019, for the first time, a detailed human Medical Biostasis Protocol was published to
document what such a procedure could entail.6 This document is the culmination of a
collaborative effort of cryobiology researchers and medical professionals. The protocol
does not just provide a detailed set of guidelines for hospital-based medical biostasis but
also suggests lab-based methods to evaluate the efficacy of the procedure and identifies
areas for further experimental research. The introduction to the document reads as
Medical biostasis is an experimental procedure that induces metabolic arrest at
cryogenic temperatures to allow terminally ill patients to benefit from future
medical advances and restore them to good health. Practiced as a hospital-based,
elective medical procedure, medical biostasis consists of three distinct procedures:
induction of hypothermic circulatory arrest, cryoprotection, and long-term care at
intermediate temperatures (between -120
and -130
). This document sets out a
detailed protocol for medical biostasis, outlines a variation of this protocol for out-
of-hospital emergency cases, and outlines research directions to further optimize
this protocol.
In ideal circumstances this protocol permits maintaining viability of a patient’s brain by
contemporary medical criteria until about halfway of cryoprotectant perfusion, after which
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Page 3 of 4
Rejuvenation Research
Cryonics takes another big step towards the mainstream (DOI: 10.1089/rej.2020.2356)
This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
point the aim of the procedure is preservation of the fine structure of the brain for long-
term cryostasis.
Given the slow mainstream medical acceptance of human cryopreservation, it is not likely
that this document will be fully used by a hospital in the West in the foreseeable future.
Having an evidence-based protocol for clinical human cryopreservation, however, can
assist researchers and medical professionals to review medical biostasis procedures and
understand the rationale for various components. This protocol also is useful for critics to
recognize the difference between what “good cryonics” would look like and the protocols
that existing cryonics providers currently are compelled to do.
Existing human cryopreservation providers can also draw upon this protocol to further
improve and refine their procedures because not all procedures outlined in the document
require a hospital-based elective medical procedure (for example, improved monitoring of
the brain cryopreservation).
The difference between “old school” cryonics and medical biostasis is not black and white
as evidenced by the fact that the new Chinese cryonics provider Yinfeng uses rapid
extracorporeal perfusion technologies for its initial stabilization part of a patient.
The current COVID-19 pandemic has drawn unambiguous attention to the social and
economic costs of immunosenescence, one of the main targets for rejuvenation
biotechnologies in the SENS program. Rejuvenation technologies are not likely to be
available in time for very old and terminally sick people. Medical biostasis presents the
only practical and evidence-based means of survival for them. The case for using “The
Arrest of Biological Time as a Bridge to Engineered Negligible Senescence” has further
grown in credibility since its 2004 exposition in The Annals of the New York Academy of
Sciences7 and warrants further scientific and medical scrutiny. Exposition of a detailed
protocol to conduct human medical biostasis by medical professionals is an important
contribution to this endeavor.
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Page 4 of 4
Rejuvenation Research
Cryonics takes another big step towards the mainstream (DOI: 10.1089/rej.2020.2356)
This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
1. Best BP. Scientific justification of cryonics practice. Rejuvenation Res 2008;
2. Vita-More N, Barranco D. Persistence of Long-Term Memory in Vitrified and Revived
Caenorhabditis elegans. Rejuvenation Res 2015; 18(5):458-463.
3. Lewis JK, Bischof JC, Braslavsky I, Brockbank KGM, Fahy GM, Fuller BJ, Rabin Y,
Tocchio A, Woods EJ, Wowk BG, Acker JP, Giwa S. The Grand Challenges of Organ
Banking: Proceedings from the First Global Summit on Complex Tissue
Cryopreservation. Cryobiology 2016; 72(2):169-182.
4. de Wolf A, Phaedra C, Perry RM, Maire M. Ultrastructural Characterization of
Prolonged Normothermic and Cold Cerebral Ischemia in the Adult Rat [published
online ahead of print, 2020 Mar 12]. Rejuvenation Res. 2020; this issue.
5. Minerva F, Sandberg A. Euthanasia and Cryothanasia. Bioethics 2017; 31(7):526‐533.
6. de Wolf, A. Medical Biostasis Protocol. 2019;
7. Lemler J, Harris SB, Platt C, Huffman TM. The arrest of biological time as a bridge to
engineered negligible senescence. Ann N Y Acad Sci 2004;1019:559‐563.
Downloaded by Dr. Aubrey de Grey from at 06/04/20. For personal use only.
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
The ultrastructural effects of prolonged normothermic and cold ischemia on the cerebral cortex of the adult rat were investigated. Complete cerebral ischemia was produced by cardiac arrest and the animals' temperature was maintained at 37°C for periods ranging from 0 to 81 hours prior to electron microscopy preparation. Electron micrographs of cold cerebral ischemia were generated after stabilizing the rat's temperature at 0°C after cardiac arrest for periods ranging from 0 hours to 6 months. A qualitative examination of the electron micrographs shows structural signatures of energy depletion such as vessel leaking and chromatin clumping after 1 hour at 37°C and after 24 hours at 0°C, followed by synapse degradation after 6 hours at 37°C and 1 week at 0°C. Evidence of advanced necrosis is observed after 36 hours at 37°C and 2 months at 0°C. A deep learning algorithm is introduced that demonstrates the temperature-dependence of ischemia-induced ultrastructural changes and that can also successfully distinguish between early ischemic changes and advanced necrosis.
Full-text available
The first Organ Banking Summit was convened from Feb. 27 - March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery - and even space travel. Key scientific challenges were discussed including ice nucleation and growth, cryoprotectant and osmotic toxicities, chilling injury, thermo-mechanical stress, the need for rapid and uniform rewarming, and ischemia/reperfusion injury. A variety of opportunities to overcome these challenge areas were discussed, i.e. preconditioning for enhanced stress tolerance, nanoparticle rewarming, cyroprotectant screening strategies, and the use of cryoprotectant cocktails including ice binding agents.
Full-text available
Can memory be retained after cryopreservation? Our research has attempted to answer this long-standing question by using the nematode worm Caenorhabditis elegans (C. elegans), a well-known model organism for biological research that has generated revolutionary findings but has not been tested for memory retention after cryopreservation. Our study's goal was to test C. elegans' memory recall after vitrification and reviving. Using a method of sensory imprinting in the young C. elegans we established that learning acquired through olfactory cues shapes the animal's behavior and the learning is retained at the adult stage after vitrification. Our research method included olfactory imprinting with the chemical benzaldehyde (C6H5CHO) for phase-sense olfactory imprinting at the L1 stage, the fast cooling SafeSpeed method for vitrification at the L2 stage, reviving, and a chemotaxis assay for testing memory retention of learning at the adult stage. Our results in testing memory retention after cryopreservation show that the mechanisms that regulate the odorant imprinting (a form of long-term memory) in C. elegans have not been modified by the process of vitrification or by slow freezing.
Full-text available
Biological systems can remain unchanged for several hundred years at cryogenic temperatures. In several hundred years, current rapid scientific and technical progress should lead to the ability to reverse any biological damage whose reversal is not forbidden by physical law. We therefore explore whether contemporary people facing terminal conditions might be preserved well enough today for their eventual recovery to be compatible with physical law. The ultrastructure of the brain can now be excellently preserved by vitrification, and solutions needed for vitrification can now be distributed through organs with retention of organ viability after transplantation. Current law requires a few minutes of cardiac arrest before cryopreservation of terminal patients, but dogs and cats have recovered excellent brain function after 16-60 min of complete cerebral ischemia. The arrest of biological time as a bridge to engineered negligible senescence, therefore, appears consistent with current scientific and medical knowledge.
Full-text available
Very low temperatures create conditions that can preserve tissue for centuries, possibly including the neurological basis of the human mind. Through a process called vitrification, brain tissue can be cooled to cryogenic temperatures without ice formation. Damage associated with this process is theoretically reversible in the same sense that rejuvenation is theoretically possible by specific foreseeable technology. Injury to the brain due to stopped blood flow is now known to result from a complex series of processes that take much longer to run to completion than the 6 min limit of ordinary resuscitation technology. Reperfusion beyond the 6 min limit primarily damages blood vessels rather than brain tissue. Apoptosis of neurons takes many hours. This creates a window of opportunity between legal death and irretrievable loss of life for human and animal subjects for cryopreservation with possibility of future resuscitation. Under ideal conditions, the time interval between onset of clinical death and beginning of cryonics procedures can be reduced to less than 1 min, but much longer delays could also be compatible with ultimate survival. Although the evidence that cryonics may work is indirect, the application of indirect evidence is essential in many areas of science. If complex changes due to aging are reversible at some future date, then similarly complex changes due to stopped blood flow and cryopreservation may also be reversible, with life-saving results for anyone with medical needs that exceed current capabilities.
In this article we discuss the moral and legal aspects of causing the death of a terminal patient in the hope of extending their life in the future. We call this theoretical procedure cryothanasia. We argue that administering cryothanasia is ethically different from administering euthanasia. Consequently, objections to euthanasia should not apply to cryothanasia, and cryothanasia could also be considered a legal option where euthanasia is illegal.
  • F Minerva
  • A Sandberg
  • Cryothanasia Euthanasia
Minerva F, Sandberg A. Euthanasia and Cryothanasia. Bioethics 2017; 31(7):526-533. 6. de Wolf, A. Medical Biostasis Protocol. 2019;