Reversible cryopreservation

On the forum of the Immortality Institute there is an interesting exchange about the feasibility and time line for reversible cryopreservation. Cryobiologist Brian Wowk weighs in with some interesting observations:

I think in the next 20 years more small animal organs, and perhaps some human organs, may be reversibly cryopreserved. The best scenario for cryonics would be improved, and possibly demonstrably reversible, cryopreservation of animal brains. It has been long observed that if reversible solid-state brain preservation could be demonstrated, then cryonics revival becomes a purely technical problem (albeit very complex one) of tissue regeneration. There would be no remaining doubt about whether the preservation itself was viably preserving human beings….Reversible solid-state cryopreservation of whole mammals is a very difficult problem with existing technology. This is why when asked about it people will often defer to nanotechnology. References to nanotechnology as a solution to a medical problem basically say, “We have no idea how to solve this problem with existing tools, but future abilities to completely analyze and repair tissue at the molecular level will be implicitly sufficient.” It’s a valid argument, but saying that a medical problem will be solved when someday technology exists to solve *every* medical problem is not very illuminating about time lines or nature of the problem.

Advocates of cryonics often push for demonstration of reversible small animal cryopreservation as  a means to persuade the medical establishment and the general public of the technical feasibility of cryonics. The limitation of this approach, however, is that this goal cannot be achieved until we are able to successfully vitrify all vital organs of the animal, including such difficult organs  as the lungs and the kidney. A more promising approach is to keep improving vitrification of the central nervous system. As argued in a recent piece for Alcor’s Cryonics Magazine, if organized electrical activity can be demonstrated after whole brain cryopreservation a strong case can be made for the acceptance of cryonics as a medical procedure and improved legal protection of cryonics patients.  It should be noted, however, that these research efforts constitute only one objective in cryonics. Another objective of cryonics research is to optimize procedures and protocols for existing patients, who invariably suffer some degree of circulatory arrest.

The future of Alcor

Alcor’s recent news item about its 2009 Annual Board Meeting and Strategic Meeting contains a number of encouraging statements. On the front of institutional reform, however, there is not much news to report. The passage about the need to balance recruiting new Board members and preserving institutional memory reads as a rather uninspired defense of the Board’s recent decisions. In light of the growing recognition that most of Alcor’s problems over the years can be tracked back to the composition and functioning of the Board of Directors, one would have expected more innovation on this front.  A major problem with a self-perpetuating Board of Directors remains that there are few mechanisms available in case a competent Board of Directors would change in an incremental fashion into a contra-productive Board. Perhaps the idea of term limits could prevent such scenarios.

In particular, there is an urgent need to adopt institutional changes that can prevent the highly variable quality of patient care that has been observed in the history of the organization.  Another challenge that remains is the recruiting of  additional Board members with a strong knowledge of Alcor’s technical operations and the delivery of standby services. Without this knowledge (and some degree of common sense) it is highly unlikely that the Board can do a serious job of overseeing such matters.

One of the most positive items in Alcor’s report is the recognition that Alcor would benefit from substantial cost savings in its operations.  Throughout most of Alcor’s history the organization has been dependent on (unpredictable) donations from wealthy members to sustain normal operations.  Obviously, this way of funding the operations of a cryonics organization (as opposed to long term patient care) constitutes an irresponsible gamble. Donors should be commended for being reluctant to contribute to Alcor (any further) until Alcor has shown evidence of getting its financial house in order. A number of sensible proposals were discussed to generate more structural income for the organization such as increasing membership dues, raising cryopreservation minimums, introducing a recommended funding level (as opposed to just a minimum funding level), and creating income-generating endowments.

One aspect that is largely ignored in this report, however, is the potential for substantial cost reductions in Alcor’s daily operations itself. For most of its history Alcor used to be rather transparent about staff member salaries in its communications and the magazine. It may not be a coincidence that this practice disappeared  during the period when Alcor saw substantial increases in compensation for (some of) its staff members. To give some perspective, the old Tim Freeman Cryonics FAQ included the following question and answer:

7-2.  Is anyone getting rich from cryonics?  What are the salaries at these organizations like?

In December 1990, Cryonics magazine reported that the Board of Directors of Alcor voted a 25% pay cut for all of the staff, so they could keep their budget balanced.  Many of the Directors are also on the staff.  The salaries after the cut ranged from $22,500 annually for the highest paid full-time employee (the President) to $14,400 for the lowest-paid full-time employee.  None of the Alcor staff are getting rich from their salaries.

It would be a worthwhile undertaking to do a comprehensive study of Alcor’s staff and consultant compensation history and policies (or lack thereof). There is never a shortage of arguments to justify higher compensation and ad-hoc decision making in cryonics, but it is doubtful that generous salary increases in the industry over the years were necessary to recruit or retain competent staff members. It might even be argued that a number of problems in cryonics are actually linked to offering wages that exceed what the employees who receive them would otherwise earn in the market place. Similarly, substantial cost savings can be obtained by increasing productivity and decreasing staff members. Issues of compensation and staff efficiency should be essential topics of consideration in any serious discussion about Alcor becoming more self-sustaining and less dependent on wealthy donors.

Another topic that deserves attention in this context is that all of Alcor’s major technologies (medications protocols, organ preservation solutions, vitrification agents) are licensed to the organization by independent research labs. Although Alcor itself is mostly to blame for not having developed competing technologies of its own since the mid-1990s, it is important to recognize this dependence. At the very least, Alcor could benefit from a cost-benefit analysis of some of these technologies and from developing contingency plans to deal with scenarios in which these technologies would no longer be available or cost-prohibitive.

During most of its history Alcor (and later, CryoCare) promoted the idea of cryonics as a medical procedure and criticized other cryonics organizations like the Cryonics Institute for being overly optimistic and reckless.  In an ironic twist of fate, some critics of Alcor now use this perspective to criticize the organization for not living up to the idea of cryonics as medicine. As a general rule, this is to be welcomed. Where this criticism can go off track, however, is when it is insufficiently recognized that knowledge of conventional medicine is a necessary, but not a sufficient, condition to do good cryonics. One of the worst scenarios for the future of cryonics is one in which regulators impose standards upon cryonics organizations that  actually increase the challenges of providing good patient care; something that has happened already in the case of the Cryonics Institute when the organization was forced to perform a complex technical procedure like cryoprotective perfusion at a funeral home.

Faced with the technical complexities of ramped cryoprotective perfusion, Alcor has decided to develop a system that not only uses software to record perfusion parameters (concentration, pressure, temperature, refractive index etc.) but to use the same software to control them as well. Provided that this new system lives up to its expectations, this development will be a major step towards a system that can use real-time feedback to adjust perfusion parameters in a manner that so far has only been available in small organ cryobiological research. The data that will be generated during cases can, in turn, be used to create cases reports that follow a consistent, formal standard. When these reports are used in an intelligent fashion, the prospect of developing technologies and protocols that can reduce the high variability in patient care will be feasible.

The 2009 SENS Conference

Once a year I try to attend at least one biogerontology conference. Although I attend biogerontology conferences out of personal interest, and at my own expense, they are the most fruitful grounds for promoting cryonics I have found, and this is especially true of SENS conferences.

I have missed none of the four SENS conferences that have been held at Cambridge University. “SENS” is Dr. Aubrey de Grey’s “Strategies for Engineered Negligible Senescence.”

SENS conferences attract scientists who are eager for science to achieve rejuvenation, and who have a strong belief that science has the capacity to do so. Not surprisingly, such people are often receptive to the idea that future science may be capable of reanimating humans who have been well cryopreserved.

Recently I have heard regret expressed about the aging of the cryonics community and the absence of a next generation of cryonics activists to replace the current ones. My experiences at the 2009 SENS conference dispelled much of my concern about this.

I took about a hundred CI brochures, but these were quickly taken by the 290 SENS conference attendees. I was continually approached by young scientists and researchers who were eager to meet me and who said they would make cryonics arrangements when they got out of graduate school and could afford to do so. Insofar as many of the attendees were Europeans, I was often asked whether the shipping delays to the United States would make cryonics not worth doing, and whether there were any plans by the Cryonics Institute to create a storage facility in Europe. (I was told about a group wanting to establish a storage facility in Switzerland, but I did not get any details. Apparently it is not a project with serious hope of success in the near future.)

I was astounded when a British student approached me and said that he would be devoting all of his graduate school work to the problem of cryoprotectant toxicity. He had already gotten Dr. Fahy to send him a copy of “Cryoprotectant toxicity neutralization,” a new paper to be published in an upcoming issue of CRYOBIOLOGY. The student is in the process of collecting other cryobiology publications that address the subject. I directed him to a relevant webpage in the cryonics section of my www.benbest.com website.

A number of people from KrioRus were at the conference, notably Igor Artyuhov, who is their technical guru. The group also does life extension research. Igor showed me their poster showing extended lifespan of mice administered heat-shock protein through nose-drops. I was interviewed by a journalist who writes for the Russian edition of SCIENTIFIC AMERICAN.

I had met Nick Mayer, a Terasem employee, at the previous SENS conference, and Nick introduced himself to me again at this meeting. Nick manages “cyberbiological systems”, specifically a website that is being used like an on-line personal diary. As Nick described it to me, the website would be useful to store personal information that could be used to help in the reconstruction of someone who has been reanimated from cryopreservation. But when I looked at his website, it appears to be a project for reconstructing people from their diaries alone — without any saved biological material.

To my surprise, one of the presenters, Dr. Gunther Kletetschka, had a poster and an oral presentation dealing with eliminating the cracking problem in cryonics.

Cracking of vitrified tissue at cryogenic temperatures is a consequence of the fact that external cooling causes superficial tissue to contract more than deep tissue (thermal conductivity is low). Dr. Kletetschka’s approach is based on the idea that if a cryonics patient were perfused with a solution containing gadolinium (nanoparticles would be best), an entire vitrified brain could be cooled uniformly by the magnetocaloric effect.

From a practical point of view, his sample size was apparently very small, and he did his testing on ice rather than vitrified tissue. I had many other criticisms of his approach, which I attempted to discuss with him in a constructive, supportive manner. He was interested in what I had to say, and was very receptive. Insofar as he is so enthusiastic about doing cryonics-related research, and insofar as he lives in Maryland (not so far from Michigan) I suggested that he attend the CI Annual General Meeting on Sunday, September 27. He expressed an interest in doing so.

A European student told me that his mother is a stroke victim, but that he has not been able to induce her to consider cryonics. Having experienced the debilitating effects of stroke she is worried that faulty reanimation procedures would bring her back into an even more debilitated condition. I suggested asking her to assess the probability of that happening and how bad the downside would matter if the probability is small. I think that in the context of all of the other repairs that would be essential to cryonics working that it is unlikely that all such defects would not be fixed.

A middle-aged European woman wanted to speak with me about how to convince her husband that cryonics is a good idea. The couple are both religious, but she thinks “heaven can wait” because she enjoys life here on earth and she would like to share earthly life for a very long time with her husband. I gave her many arguments against the claim that cryonics is against religion, including the one concerning refusing a lifesaving medical treatment being equivalent to suicide (a sin).

I was reminded of the Depressed Metabolism posting about the “hostile wife phenomenon” in cryonics:  It occurs to me that when a male spouse is interested in cryonics, but his wife is not, that he can go ahead and make the arrangements. A financially dependent woman (as this woman is), less often has that option. I have also often seen cases of women interested in cryonics, but who dropped the interest when it became clear that their spouse would not join them in cryostasis. They would rather not live if they cannot be with their husbands. It reminds me of studies of working couples that show that a wife is much more likely to quit her job to follow her husband in a career change that involves moving — whereas the opposite happens much less frequently.

I won’t say much about the SENS conference itself, but I had lots of meetings and discussions that taught me a lot about biogerontology issues. I was particularly interested in discussing my recent article “Nuclear DNA Damage as a Direct Cause of Aging” which had been published in Rejuvenation Research, because it is a direct challenge to one of the tenets of SENS (that nuclear DNA damage only matters for cancer).

Not only was I able to have two private sessions in which I discussed the matter with Aubrey de Grey, but I was able to eat breakfast several times with Vera Gorbunova and her husband Andrei Seluanov, two DNA repair experts who were attending the conference. Vera and Andrei have written the only other review (other than my own) supporting the thesis that nuclear DNA repair capability declines with age.

I had cited that review in my own review. Vera had sat across from me at my first breakfast by chance. She had read my review and told me that she agreed with it. Most of the times that I went for a meal I was very pleased by at least one person randomly sitting near me, and had an interesting and productive discussion with them on a matter of interest. I discussed my cryonics alarm system problems with a woman who is getting a PhD in biomedical engineering.

I was very surprised and pleased to meet Kristen Fortney at the conference. Kristen is a University of Toronto student who attended some of our cryonics meetings in Toronto. She was a physics student and was planning to do graduate work in quantum physics. At the conference she told me she had changed to a PhD program focused on computational work with the human genome, focused on anti-aging strategies. She wrote a blog of the conference as it progressed on the Ouroboros academic blog for aging research.

Basile J. Luyet on the instability of solidified solutions

Basile J. Luyet (1897-1974) can be considered the father of modern cryobiology. His book “Life and Death at Low Temperatures” is a classic in the field and his journal “Biodynamica” evolved into a publication solely dedicated to the study of low temperature biology. Luyet identified the possibility of solidification without crystallization at low temperatures (vitrification) of biological materials, an approach that was later worked out as a practical method for organ preservation by the cryobiologist Greg Fahy.  Vitrification solutions are also used in human cryopreservation to prevent ice formation in patients during cooldown and storage at liquid nitrogen temperature.

In the following Biodynamica study (1966) Luyet investigates the issue of structural instability and molecular mobility in solidified aqueous solutions. In these initial investigations he anticipated the phenomena of re-crystallization and de-vitrification upon rewarming, which later would present formidable challenges during the early years of applied vitrification research in large organs. Although Luyet briefly mentions the possibility of molecular mobility as such at temperatures down to absolute zero, his main focus is on ice formation that can occur during the rewarming of solutions. Cryonics Institute President Ben Best has done some theoretical explorations into the issue of molecular mobility at low temperature, a topic that raises important questions about the desirability of intermediate temperature storage (ITS) of cryonics patients.

B. Luyet – The Problem of Structural Instability and Molecular Mobility in Aqueous Solutions “Solidified” at Low Temperatures (1966) PDF

5 dangerous ideas about cryonics

The cryonics organizations Alcor and the Cryonics Institute have taken great care to correct some of the persistent myths about cryonics. With so much widespread misinformation being circulated in the media it seems trivial to pay attention to some of the misconceptions that some people who are sympathetic to cryonics hold. But the price of ignoring these opinions is that progress in the science of cryobiology and practice of human cryopreservation is adversely affected. What follows is a list of 5 “dangerous” ideas (or misconceptions) about cryonics and their consequences.

1. First in, last out.

A popular expression in cryonics is that the first person who was cryopreserved will require the most extensive repair technologies and therefore will be the last person to be resuscitated. The underlying assumption in this view is quite reasonable: when advances in cryopreservation technologies are made, demands on advanced future repair technologies will be lessened. The problem with this view, however, is that it assumes that advances in cryobiology and neuroprotection are the only factor influencing the quality of care in cryonics. Unfortunately, advances in the science of cryopreservation will not automatically translate into better patient care.  Other factors, such as the delay between time of “death” and start of procedures, and the protocols, equipment and personnel of the responding cryonics organizations, matter as well. For example, if a cryonics standby team is not able to get to a patient before 24 hours after cardiac arrest, pumps him full of air during remote blood washout, and ships him back to the cryonics organization at subzero temperatures, that patient will not benefit from advances in human cryopreservation such as rapid induction of hypothermia, neuroprotection and vitrification.

A professional cryonics organization with “old” technologies may on average do better than an incompetent cryonics organization with “new” technologies. The important lesson to be drawn here is that the concept of “patient care” is a meaningful concept  in cryonics and consumers of cryonics services need to evaluate their cryonics providers on their ability to provide good care.

2. Only the future will tell us how good our cryonics procedures are.

It is true that only the future will tell us whether cryonics patients will be resuscitated or not; but that does not mean that we cannot say anything meaningful about the quality of care in individual cryonics cases. The most obvious point is that we can compare actual patient care to the published protocols and objectives of the cryonics organization. More specific observations can be made during a cryonics case using medical equipment. In a well-run cryonics case a number of physiological and chemical measurements are made to determine the response of a patient to various interventions. As a general rule, the objective of cryonics stabilization procedures is to keep the brain of the patient viable by contemporary medical criteria. The danger of thinking of cryonics as one single experimental procedure that can only be evaluated in the future is that it ignores the fact that actual cryonics procedures consist of various separate procedures that can be monitored and evaluated using existing medical tools. The least that a cryonics consumer should expect from his cryonics organization is that it discloses its cryonics procedures to the general public and produces detailed case reports.

3. Cryonics patients are no longer being frozen.

Because not all cryonics patients will be “ideal” cases, this view is vulnerable to the same objections as the “first in, last out” rule, but there are some other issues that are important to mention in this context. The most important fact to be stressed is that ice formation is not a binary all or nothing thing but a continuum ranging from straight freezing (cryopreservation without cryoprotection) to complete elimination of ice formation. Although there have been many cases where patients have been frozen without the use of a cryoprotective agent, its opposite, complete vitrification, should be considered  a theoretical ideal. The degree of ice formation is determined by the nature and concentration of the cryoprotective agent. For example, low concentrations of the cryoprotectant glycerol will result in more ice formation than higher concentrations of glycerol.

What has changed in the recent years is that both major cryonics organizations are now offering cryopreservation using vitrification agents. Although these vitrification agents are formulated to eliminate ice formation, it is generally believed that such a result is not achievable in all tissues and organs in the human body at the moment.  Another important point to be made is that not all solutions that can eliminate ice formation are equal because they can differ greatly in toxicity.  The technical challenge in cryonics is not so much to eliminate ice formation but to develop vitrification solutions with no or limited toxicity. Although it is correct that contemporary vitrification solutions  can solidify without ice formation, delays in response time, poor patient care, and high toxicity can offset most of these advances.

4. The probability that cryonics will work is X.

Both critics and supporters have made specific probability estimates about how likely cryonics is to work. In its worst form such probability assessments convey nothing more than putting a number on overall feelings of pessimism or optimism. More serious attempts have been made to calculate a specific probability that cryonics will work. Such attempts usually go as follows: A number of independent conditions (or events)  for cryonics to work are distinguished, these conditions are “assigned” a probability, and the total (or joint) probability is calculated by multiplying them. Although such calculations give the semblance of objectivity, they are  equally vulnerable to the fundamental objection that assigning one single number to the probability that cryonics will work is just a lot of hand waving.  How many independent events are there and how do we know that they are independent? What is the basis for assigning  specific probabilities to these conditions? What are the effects of minor changes in the numbers?

Probability calculations are not completely useless.  They can help us in identifying important conditions that need to be satisfied for resuscitation. They can also help identify weak links  that can be improved. But probability estimates can be dangerous as well when we take them too seriously and discourage people from making cryonics arrangements. The point here is not that we should refrain from being skeptical but that if we make quantitative estimates we should be able to back up our statements with rigorous arguments or just confine ourselves to more qualitative statements. Another objection to  making cryonics probability estimates was made by the cryonics activist and mathematician Thomas Donaldson. He makes the common sense point that many of these conditions are not independent of what we do. We can make a contribution to increasing the probability that cryonics will work.

Last but not least, what does it mean when we talk about “cryonics working?” It is conceivable that cryonics will work for one person but not for another, reflecting improved technologies and protocols. Perhaps asking the question if cryonics patients can be “revived” is the wrong question. As the cryobiologist Brian Wowk has pointed out,  the real question is how much original personality would survive the many possible damage/repair scenarios, not revival per se.  Survival in medicine is not a simple black-and-white issue, as evidenced by people who recover from stroke or cardiac arrest but with personality and memory alterations.  And it is worth  mentioning once more that how much of our personality survives is depended on what we do to improve the quality and long-term survival of our cryonics organizations.

5. I will sign up for cryonics when I need it.

It should be obvious without much reflection why this is a dangerous idea. At the time a person really needs cryonics, he may no longer be able to communicate those desires, lack funding to make arrangements, or encounter hostile relatives. A more subtle variant concerns the person who expects that aging will be solved before cryonics will be necessary. This person may or may not be right, but such optimism may not make him more immune to accidents than other people. This mindset is often observed among young “transhumanists” and practicing life extensionists. A related, but rarer, variant is to postpone making cryonics arrangements until the cryonics organization makes a number of changes including, but not limited to, hiring medical professionals, stop wasting money, becoming more transparent, giving members the right to vote, etc. Such issues are important, and need to be addressed, but a safer response would be to join the organization and influence its policies, or, if this will be necessary, combine with others to start a competing cryonics organization without such flaws.

There are not many people who think that it is sensible to make cryonics arrangements, but there are even fewer people who have actually made such arrangements.

As we have seen, some of these dangerous ideas share the same or related assumptions and produce identical effects: decreased scrutiny of cryonics organizations and a decreased chance of personal survival. An important common theme is that cryonics cannot be treated as one single monolithic technology and that the fate of our survival depends as much on the state of the art in human cryopreservation technologies as on the competence of cryonics providers. Caveat emptor!

The red blood cell as a model for cryoprotectant toxicity

Various approaches are available to investigate cryoprotectant toxicity, ranging from theoretical work in organic chemistry to  cryopreservation of complete animals. Because resuscitation of complex organisms after cryopreservation is not feasible at the moment, such investigations need to be confined to viability assays of individual cells and tissues or ultrastructural  studies.

One simple model that allows for “high throughput” investigations of cryoprotectant toxicity are red blood cells (erythrocytes). Although the toxic effects of various cryoprotective agents may differ between red blood cells, other cells, and organized tissues, positive results in a red blood cell model can be considered the first experimental hurdle that needs to be cleared before the agent is considered for testing in other models.  Because red blood cells are widely available for research, this model eliminates the need for animal experiments for initial studies. It also allows researchers to investigate human cells. Other advantages include the reduced complexity of the model  (packed red blood cells can be obtained as an off-the-shelf product) and lower costs.

Red bloods cells can be subjected to a number of different tests after exposing them to  a cryoprotective agent. The most basic test is gross observation of the red blood cells in a cryoprotectant solution. When high concentrations of a cryoprotectant are used (such as in vitrification), a stepwise approach is necessary to avoid  osmotic  injury. If a cryoprotectant solution is extremely toxic rapid hemolysis will follow, which often can be observed by a noticeable change of the color of the solution,  red cell debris sinking to the bottom of the test tube, or negligible difference between the pellet (if there is one at all) and the supernatant after centrifugation. But if the researcher is interested in agents that are not extremely toxic, or wants to compare variants of  similar agents with each other, quantitative methods and detailed observations are required using respectively spectrophotometry and light microscopy.

In 1996, Bakaltcheva et al. used the red blood cell model for an elegant and thoughtful study  of cryoprotective toxicity. The authors did not only use spectrophotometry to measure hemolysis  but also used microscopy to study the morphology of the red blood cell after exposure to various agents at different temperatures. The results of these different measurements were in turn correlated with each other in order to determine if there are general properties  affecting cryoprotectant toxicity. The authors propose that reduced toxicity can be achieved by keeping the dialectric constant of the medium and membrane close to that of an aqueous solution without solutes.  These findings can also explain why cryoprotective mixtures  of various agents (such as DMSO and formamide) can reduce toxicity.  A general rule of thumb for formulating vitrification agents with reduced toxicity seems to be to maintain most properties of water but eliminating the posibility of ice formation. It should not be a surprise that such an approach has guided the choice of solvents in areas such as cryoenzymology.

Robert White on brain death

Robert J. White is most known, or perhaps most notorious, for his work on primate head transplants. Less known, but more relevant to the practice of human cryopreservation, is his work in cerebral ischemia, hypothermia, and brain preservation. Most of White’s innovative work was published in the 1960s and 1970s. White also published a substantial number of opinion pieces on a variety of topics. One of these topics is brain death.

In an 1972 editorial for the publication Hospital Progress, “The Scientific Limitation of Brain Death,” White notes that:

…we have to acknowledge the probability that eventually all of the major cellular complexes of the human body will be replaceable either by transplanted organs (man or animal) or by sophisticated engineering modules.

As a consequence, the clinical definition of death is shifting from cardiopulmonary criteria to the central nervous system. But unlike other organs,

…this system is not replicatable, representing as it does the repository of the highest functions of man…when this elite cellular system fails it would seem reasonable to assume that what is characteristically ‘human’ is also being lost from the body.

But just as the cardio-respiratory definition of death has evolved and changed with the clinical practice of cardiopulmonary resuscitation,  a similar fate may be in store for the definition of brain death. The clinical use of general anesthesia and hypothermic circulatory arrest, in which the brain can be put “on pause,” emphasize how important the aspect of “irreversibility” is.

As presently defined, the definition of brain death puts much emphasis on brain function upon physical examination. A major limitation of this definition is that it categorically ignores the prospect that brain function could be restored in the future by technologies more advanced than practiced today, provided the material basis of brain function is preserved.

Another challenge is that the science of cryobiology has advanced to such a state where brain slices can be preserved at subzero temperatures and recovered without loss of viability through vitrification. When recovery of organized electrical activity can be demonstrated in vitrified mammalian whole brains, the prevailing definition of brain death will need to be challenged again because it will open the practical possibility to maintain critically ill people in a state of low temperature circulatory arrest without producing one of the indicators of irreversible brain death. Such advances would be an extension of the  experiments Robert White did on isolated hypothermic brains.

As White stresses in the final paragraph of his paper:

…like all biological activity, life and death merge into one another representing a continuum and the neuro-scientist can only in the final analysis determine the point of irreversibility of this highly complex system at which the possibility of organized activity that characterizes human behaviour  has been exceeded.

Human cryo-anabiosis

Recent advances with the use of hydrogen sulfide, carbon monoxide and “hibernation induction triggers” to depress metabolism in animal models have  renewed interest  in the possibility of human hibernation.  The ability to drastically depress human metabolism without the use of cold (or in combination with cold) would have a number of important medical and scientific applications including the stabilization of trauma patients, prolonging the time of safe circulatory arrest in surgery, and space travel.

In 2007, the author published a review of the field of depressed metabolism for Alcor’s Cryonics Magazine and expressed skepticism about the prospect of real hibernation in humans any time soon. But this does not mean that we cannot learn from natural hibernators to identify metabolic pathways that can be inhibited to prolong the period the brain can sustain circulatory arrest at normothermic and hypothermic temperatures. As evidenced by the remarkable period myocardium can sustain energy deprivation and still recover, there is still a lot about human metabolism that remains obscure.

Like many ideas in biogerontology, the idea of chemically manipulating human metabolism as a medical procedure to prolong or save lives has gone through various cycles of optimism and disillusion. In his 1969 book Suspended Animation, the author Robert Prehoda presented a number of proposals to manipulate  metabolism in humans. Another person who wrote about depressed metabolism, or “human anabiosis,” was the cryobiologist Armand Karow (1941-2007). During the year 1967 Karow wrote a 5 part series on the science and prospect of depressed metabolism in humans for Cryonics Reports which is made available for this first time online. Although Karow devotes most of his series to the technical obstacles to achieve real suspended animation using cryogenic temperatures, he also discusses the use of metabolic inhibitors to protect vulnerable organs during cooldown to cryogenic temperatures.

Armand Karow – Goal: Human Cryo-Anabiosis (1967)

Cloning of frozen mice and cryonics

Japanese scientists have managed to clone a mouse that had been frozen without any cryoprotection for 16 years at minus 20 degrees Celsius. The researchers used the researchers used brain cell nuclei, and planted it into an egg of another living mouse, leading to the birth of the cloned mouse.

Although the objective of cryonics is not to be resuscitated as a genetic copy of oneself but to resume life as the same individual, this is encouraging news because it  reinforces the idea that cold can be used to preserve life and identity relevant information. If such feats are possible without any cryoprotection, the prospects for vitrification to preserve the identity of a person are strengthened.

These new cloning techniques also hold promise for preservation of endangered species and, as some speculate and hope, may even allow the possibility of resurrecting extinct animals such as the woolly mammoth.

What is unfortunate is that these type of discoveries draw attention to the negative sentiments and  ignorance many people have when it comes to cryonics. In one article critics were quoted as ‘saying how undesirable this type of research is’, that ‘it brings the world closer to the day when people try to clone long- dead relatives stored in cryopreservation clinics’ and ‘that it could even lead to a macabre new industry – in which people leave behind ‘relics’ of their bodies in freezers in the hope that they could one day be cloned’.

Although such arguments do not directly apply to contemporary cryonics, which involves the resuscitation of the same person and requires consent of the patient, such reactions are further evidence that most of the resistance against the idea of human cryopreservation may not be technical but psychological in nature.

We can only hope that when the resuscitation of cryonics patients becomes a reality we all live in a much more open-minded and tolerant society.

Link: DNA / Tissue freezing at the Cryonics Institute

Armand Karow on Isamu Suda's brain cryopreservation experiments

In 2007, cryobiologist Armand M. Karow passed away. Unlike many contemporary cryobiologists, Karow offered cautious support for the objectives of cryonics. In the mid-1960s, Karow served on the Scientific Advisory Council of the Cryonics Societies of America (CSA). He also published a regular column titled “Scientifically Speaking” in Cryonics Reports, a publication by the Cryonics Society of New York (CSNY).

One of these columns, “The Suda Experiment,” contains his comments on   Isamu Suda’s cat brain experiments. Suda perfused whole cat brains with low concentrations of glycerol and recorded electrical brain wave activity (EEG) after storage at high subzero temperatures and rewarming. But as Karow points out, “the generation of EEG’s is not necessarily an indication of organized, coherent activity… The EEG tracings obtained by Suda probably could have been generated even if a large number of the cells were damaged.”

A similar point can be made about studies that demonstrate viability in brain tissue after long periods  (1 hour) of warm ischemia. Although such studies are helpful to persuade critics of cryonics that cryopreservation or warm ischemia do not (instantly) destroy the brain, there is a tendency in cryonics to selectively highlight studies that are “outliers” in their field to make the case for cryonics. A related issue is the scientific meliorism implicit in the view that whatever can be imagined as not contradicting the laws of chemistry and physics will occur, a view of which the scientific, psychological, and social  aspects will be discussed here in more detail in the future.

Armand Karow – The Suda experiment (Cryonics Reports, 1967)

Cryobiologist Brian Wowk on the Suda experiments and cryonics (Immortality Institute Forum, 2006)