“It seems that no supposedly scientific criticism of cryonics has ever addressed the real issues involved or ever been based on a grasp of them.” — The Cryobiological Case for Cryonics (1988)
Q: How can something that cannot be demonstrated be scientific?
A: Cryonics is a technological proposition, not a new natural phenomenon. Its feasibility can be examined using known science just as spaceflight was proven theoretically possible decades before it was actually demonstrated.
Q: Where does the burden of proof lie when attempting to determine the scientific truth of a proposed claim, such as the claim that cryonics will work?
A: The burden of proof lies with those who make a claim that is inconsistent with existing well established scientific theory. Cryonics is not inconsistent with well-established scientific theory. The laws of physics, neuroscience, biochemistry, biology, cryobiology, chemistry, or any other science do not require either that the structures that encode human personality and long term memory be preserved, or not be preserved, by cryopreservation. At no point does cryonics require that existing physical law be altered in any way. Published articles about cryonics say it's not only consistent with physical law, it's likely to work under reasonable conditions (see the Alcor FAQ question What do experts say?) There is, therefore, no a priori reason to believe that preservation of personality relevant information is either to be expected or not expected. Neither claim would be extraordinary, and the scientific question should be addressed by looking at the preponderance of the evidence.
When a terminally ill patient requests to be cryopreserved, the burden of proof shifts to those who oppose the request (see the Alcor FAQ question Isn’t the burden of proof on Alcor to show that cryonics will work?).
Q: What science supports cryonics?
A: Cryonics is an attempt to preserve the physical basis of the human mind. Cryonics is not a belief that whole people can be frozen and revived with any near-term technology. The science that most directly supports cryonics is neural cryobiology. If a brain can be preserved well enough to retain the memory and personality within it, then restoring health to the whole person is viewed as a long-term engineering problem.
This reliance on future technology for restoring health is often cited as evidence that cryonics is based on faith, not science. This is an incorrect argument since the necessary technologies are foreseeable, and even widely anticipated in other fields. They are no different than the expected advances in materials and control systems assumed by early theoretical studies of spaceflight.
The key scientific question of cryonics is whether information essential to personhood can be preserved with current technology. This question is virtually never addressed by critics, despite being the most essential contemporary component of cryonics.
Q: Can a brain stop working without losing information?
A: It is a well-established fact that long-term memories are encoded in durable physical and chemical changes.
“We know that secondary memory does not depend on continued activity of the nervous system, because the brain can be totally inactivated by cooling, by general anesthesia, by hypoxia, by ischemia, or by any method, and yet secondary memories that have been previously stored are still retained when the brain becomes active once again. Therefore, secondary memory must result from some actual alterations of the synapses, either physical or chemical.” — Textbook of Medical Physiology by Arthur C. Guyton (W.B. Saunders Company, Philadelphia, 1986), page 658.
“Procedural and declarative memories differ dramatically. They use a different logic (unconscious vs. conscious recall) and they are stored in different areas of the brain. Nevertheless, these two disparate memory processes share several molecular steps and an overall molecular logic. Both are created in at least two stages: one that does not require the synthesis of new proteins and one that does. In both, short-term memory involves covalent modification of preexisting proteins and changes in the strength of preexisting synaptic connections, whereas long-term memory requires the synthesis of new proteins and the growth of new connections. Moreover, both forms of memory use PKA, mitogen-activated protein kinase (MAPK), CREB-1, and CREB-2 signaling pathways to convert short-term to long-term memory. Finally, both forms appear to use morphological changes at synapses to stabilize long-term memory.” — “Synapses and Memory Storage” by Mayford M, Siegelbaum SA, and Kandel ER. Cold Spring Harbor Perspectives in Biology, April 10, 2012, page 10.
“Can memory be retained after cryopreservation? Our research has attempted to answer this long-standing question by using the nematode worm Caenorhabditis 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 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.” — “Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans” by Natasha Vita-More and Daniel Barranco, Rejuvenation Research, October 1, 2015; 18(5): 458–463.
Loss of brain activity is not only survivable, but sometimes even beneficial for the prevention and treatment of ischemic injury. Further discussion and references can be found in the article Medical Time Travel.
Q: Does natural freeze tolerance in animals teach anything about cryonics?
A: While animals that survive partial freezing illustrate the principle that brain activity can stop and later resume, the condition of such animals is quite different from cryonics. Overwintering animals do not cool very far below 0ºC, and they still contain liquid between ice crystals. Cryonics involves more extreme dehydration, and complete solidification at cryogenic temperatures. With the possible exception of some insects and nematodes, no animal can naturally survive temperatures required for cryonics. The technology used in cryonics is derived from cryogenic tissue banking methods, not natural freeze tolerance.
Q: What data support brain cryopreservation?
A: Prior to the 1990s, estimations of freezing damage in the brain relied mostly on indirect information. This information included numerous studies showing recovery of neuronal cells and synapse metabolism following freezing to cryogenic temperatures with modest cryoprotection. Even whole brains were known to briefly recover normal electrical activity after freezing to -20ºC for five days with glycerol cryoprotection.
In 1995, a study showing excellent preservation of brain structure following perfusion with 7.4 Molar (68% w/v) glycerol and freezing to -90ºC was published on the Internet and in a cryonics periodical. The study essentially duplicated in large dogs the best cryonics protocols used on humans at that time. Although cooling was only to -90ºC, no further ice formation would be expected during cooling to liquid nitrogen temperature (-196ºC) because the remaining unfrozen solution is too concentrated to freeze.
70% w/v glycerol is almost unfreezable. This means that after forming interspersed pockets of ice, the remaining concentrated solution vitrifies (solidifies without freezing) when cooled below a “glass transition temperature”. The majority of tissue becomes solidified in this glassy matrix with minimal damage, as the micrographs below show.
Glycerolized frozen-thawed brain tissue: Typical appearance of gray matter at 6700x magnification. Note intact capillary endothelial cells (A) and particles of carbon (B) in the capillary lumens. The overall appearance of the neuropil and of the axons and neurons is excellent.
Glycerolized frozen-thawed brain tissue: White matter from the corpus collosum at 6700x magnification. Note the excellent preservation of the capillary (A) and its endothelial cell plasma membranes. The nucleus (B) shows typical loss or reorganization of nucleoplasm; this is seen more frequently in frozen-thawed brains than in brains just perfused with glycerol and fixed without freezing. Several axons (C) exhibit typical skrinkage of axoplasm and alteration in myelin structure. The increase in free space between axons and other structures is the result of glycerol-induced dehydration.
Glycerolized frozen-thawed brain tissue: A synapse in gray matter from the hippocampus at 40,200x magnification. The presynaptic junction contains small packets of neurotransmitter (A) visible as granules. Note the overall crisp appearance of both the synaptic membranes and adjacent structures of the neuropil. This degree of preservation at the synaptic level was uniformly observed in all samples examined.
Areas affected by ice and other damage can be seen in the original study. In addition, high concentrations of glycerol have toxic effects that are currently not understood. What effect, if any, this toxicity has on the biochemistry of stored memory is currently unknown.
In 2001 Alcor switched from glycerol to a proprietary mixture of cryoprotectants designed to eliminate ice formation completely, ideally achieving vitrification of the entire brain. At the time of writing (2005), Alcor is in the process of switching to another mixture of cryoprotectants for vitrification called M22. The toxicity of M22 is considerably lower than that of 70% glycerol. Whole kidneys perfused with M22 and cooled to -45°C and even vitrified at -135°C have been successfully transplanted with long term survival. Micrographs documenting brain vitrification with M22 are shown in this talk and this published paper.
Q: Doesn’t vitrification require small tissue pieces and high cooling rates?
A: No. Vitrification can happen on any scale at any cooling rate if enough water is replaced by cryoprotectant. The paper that first proposed the modern approach to vitrification included a photograph of a vitrified organ (rabbit kidney). The first paper showing successful vitrification of living cells used a cooling rate of only 20 degrees per minute. Other papers have been published studying the vitrification of volumes as large as 1.5 liters.
It’s true that vitrification followed by return of normal metabolism can only be done for small tissue pieces, such as blood vessels, at this time. Slow heat transfer in large organs causes an accumulation of toxic effects with current technology. Nevertheless, tissue structure can be preserved. Thus Alcor’s vitrification is a morphological vitrification that preserves the structure and much biochemistry of the brain, but not sufficient biochemistry for spontaneous return of normal metabolism. Future repair or replacement of molecules altered by the vitrification process will be required.
Solidification without freezing. Two liters (5 pounds) of M22 solution cooled until vitrified as a solid at a temperature of -124ºC. All molecules are locked in position as an amorphous solid. The belief that only small samples can be vitrified is a myth.
Q: How can imperfect preservation be reversed?
A: Any cell that has ever survived freezing or vitrification has recovered from imperfect preservation. Cells cooled below -100ºC enter an alien state in which most cell water is replaced by solutes, molecules deform from normal shapes, and even cell membranes undergo phase transitions. After warming and removal of cryoprotectant, cells engage in considerable self-repair before operating normally again.
It is a premise of cryonics that natural self-repair is not all that will ever exist in medicine. And indeed, it already is not, since molecular intervention in cell death following cryopreservation has already begun in mainstream cryobiology. Cryonicists have been envisioning cell repair augmentation by drugs, synthetic enzymes, viruses, and macrophages since the 1960s. These ideas, part of a biological tradition of diffusion-driven chemistry, are now termed “wet nanotechnology”. In the 1980s, a new type of nanotechnology based on positional control of chemical reactions was proposed in a mechanical tradition. The utility of such technology in cryobiology was recognized early.
Today the potential of wet and dry nanotechnology in medicine is collectively termed “nanomedicine”. According to the U.S. National Institutes of Health, nanomedicine will eventually bring “synthetic biological devices” that could heal diseases and “fix the ‘broken’ parts in the cells”. Any honest scientific assessment of the utility of long-term preservation, be it gametes from an endangered species or an entire human being, must consider the impact of future technology.
Exactly what technology is expected? Since preservation can be continued indefinitely, even centuries, one must consider the limits of what is physically possible. It’s already known that every tissue and organ in the body can in principle be regenerated. The most elegant application of such technology will be in situ regeneration of injured tissue, including regrowth of lost limbs and organs. For treatment of severe traumatic injuries, it’s theoretically possible that even an entire body could be regenerated around an unconscious brain maintained in a fluid life support system.
The brain must be repaired, not replaced. If mature nanotechnology is assumed, then very sophisticated repair strategies can be envisioned as explained in the references below. In the worst case, it’s theoretically possible to scan the entire molecular structure of a cryopreserved brain into a computer for analysis and direction of repair processes. For cryopreservation under good conditions with modern technology, and without fracturing, less extreme forms of cell repair should suffice.
Cell Repair and Nanomedicine References
Q: What is the impact of clinical death on cryonics?
A: Theoretically clinical death need not have any impact on cryonics because blood circulation and breathing can be artificially restored when the heart of a terminally-ill patient stops beating. In practice, procedures for treating ischemia (stopped blood circulation) in cryonics differ greatly between organizations. Even for organizations that advocate aggressive intervention, such as Alcor, logistical factors and limitations of closed-chest cardiopulmonary support during cooling mean that all cryonics patients will suffer some cerebral ischemic injury. Ideally, this injury can be limited to the equivalent of several minutes of ischemia at normal body temperature.
It’s well known that 4-6 minutes of normothermic ischemia (circulatory arrest at normal body temperature) can be survived. It’s less well known that experimental protocols involving post-resuscitation hypothermia, hypertension, and hemodilution can reverse up to 13 minutes of normothermic ischemia without serious harm. Other protocols combining drugs with post-resuscitation hypothermia have reversed 16 minutes of normothermic ischemia in dogs without neurological deficit. Even one hour of normothermic ischemia has been reversed in cats with only loss of hippocampal and striatal tissue. Even these losses are likely caused by programmed cell death triggered by ischemia rather than acute destruction during the ischemic interval.
The brain “dies” after several minutes without oxygen not because it is immediately destroyed, but because of a cascade of processes that commit it to destruction in the hours that follow restoration of warm blood circulation. Restoring circulation with cool blood instead of warm blood, reopening blocked vessels with high pressure, avoiding excessive oxygenation, and blocking cell death with drugs can prevent this destruction. Clinical use of these laboratory methods will someday extend cerebral ischemia survival far beyond the 4-6 minutes of today.
Dismissing cryonics as preservation of “dead” people is a misrepresentation of biological reality. It’s especially disingenuous given that viability is not even strictly necessary for the contemporary objective of cryonics, which is the preservation of basic neurological information. The biological situation is best summarized by the National Human Neural Stem Cell Resource website:
“It is quite clear that clinically defined death, which in most states is simply the cessation of cardiac and respiratory activity, does not mean that all of the cells of the body have died. It simply means that the cells required to maintain/sustain life, namely, cardiac muscle cells and diaphragmatic muscle cells no longer function adequately.”
Q: Why is cryopreservation sometimes attempted hours after clinical death?
A: Cryonics procedures are ideally begun by restoring circulation and breathing within moments of cardiac arrest. If this should not be possible, most people who choose cryonics choose to proceed with cryopreservation anyway. This is scientifically justified by the generally good appearance of brain tissue in electron micrographs during the early hours of clinical death. Much of what is known about neurodegenerative diseases is actually based on histochemical studies of brains obtained hours after clinical death, so clearly much chemical information still exists. Living neurons can sometimes be cultured as long as 4 hours, or even 8 hours after clinical death. Further discussion and references concerning post-mortem brain changes are available within this article, and also this one. These data suggest that the early stages of what we consider death today may actually be a treatable injury. This is not because death is reversible, but because what we think of as death today might not really be death at all. Rather than spontaneous return of function, death may ultimately be determined by information theoretic criteria.
There is a school of thought within cryonics that says apparently dead people should always be cryopreserved as matter of medical ethics, regardless of how badly damaged they appear based on current knowledge. In other words, short of complete brain destruction, death should never be presumed. Obviously cryonics by this definition is hard to falsify, making this view normative rather than scientific.
Q: What should all scientists be able to agree on about cryonics?
A: Matters of fact:
Q: What can scientists disagree on about cryonics?
A: Matters of judgment and ethics: