On 06 May, 2012 responses were solicited to what was termed The Cryonics Intelligence Test which was posted here on Chronosphere (see: http://wp.me/p1sGcr-vV). Two people responded to this public request to “take the test” and provide input on possible solutions to the problems posed by the resource material that accompanied the test. The test consisted of the resource materials and the following  instructions:

Dear ______,

If you can figure out the scientific take home message for cryonics in what is to follow, you will have demonstrated extraordinary insight into “thinking in a cryonics-medical context.”

You will also have the tool to be able to understand why I believe that cryonics must, on a purely scientific-medical basis, be pursued in a fundamentally different way, both biomedically and socially.

The Test: The test resource materials are available for download at ___________, you will find a number of full text peer reviewed scientific papers. In addition, you will be sent several cryopatient case Hxs. Together, these resources contain data which should give a reasonably intelligent person with a properly prepared mind a fundamentally new insight into a major, indeed overwhelming flaw in how cryonics has been, and currently is practiced.

Your task is to:

a) identify the problem(s)

b) identify one or more possible solutions

You have 5 days to complete this task. Your response should be in the form of a succinct statement of the problem, and an itemization, and if you like, a discussion of possible solutions.

Thanks for your patience and cooperation.

Mike Darwin

Purposes

The reasons for  this exercise were as follows (in no particular order):

To answer the question posed to me by Alcor CEO on what was the most important research to be undertaking in cryonics at this time.

To determine if a representative cross section of people not actively employed in cryonics, or working in cryonics-related research, would independently reach the same or same similar conclusions about a heretofore not understood or appreciated major problem in cryonics and propose the same possible solutions (or novel ones) to said problem.

To evaluate the caliber of the intellects (who chose to participate) who read Chronosphere.

To attempt to determine the number of Chronosphere readers who were willing to accept the challenge of  exposing their judgment and intellectual performance to scrutiny, either by myself, publicly, or both.

To determine the approximate number of people who took the time and exerted the effort to at least peruse the article and download the Test Resource Materials.

To attempt to get a preliminary idea of the nature of the readers of Chronosphere and their interest in highly technical topics of serious relevance to cryonics.

To gauge the impact and reaction of both the leadership of the cryonics community, and the cryonics community itself, to the revelations that result from this exercise and the commentary that is to shortly follow it.

To solicit novel solutions to the central problem posed in the exercise.

To inform the community at large, both the cryonics community and the public, of this serious problem in the way human cryoprerservation is currently being pursued (e.g., informed consent).

Participants

Two people (Alexander McLin and Gerald Monroe ) responded to the public request on Chronosphere to take the test. Prior to publicly soliciting responses, fifteen individuals of diverse backgrounds in cryonics were privately asked to take the test. Of these, eleven agreed to do so and of those eleven, ten completed the test. Of the ten privately solicited respondents, three agreed to allow publication of their answers; two with the use of their names. One individual, a young academic pursuing advanced graduate degrees, asked for and was granted anonymity, due to the likelihood that open involvement in cryonics could prejudice his academic career.

Since it is not possible for the responses of those who chose not to allow publication to be evaluated here, I will not make any comment on them beyond noting that they exist and that they, along with those of the respondents who did allow publication, were material in making the decision to pursue an open solicitation here for additional respondents.

At this time, the answers of the respondents are being presented absent any biographical/background information, so as not to bias the reader as he reads and considers each response. At a later date, I will edit this post to add a brief (few sentences) background description on each of the participants in order to provide demographic data on the participants as a group (e.g., how many were biomedically sophisticated, laypersons, long-time cryonicists, novices, etc.).[1]

 Responses

Responses are presented in alphabetical order (by name of the respondent). The only editing that has been done is to to correct typographical errors.

Alexander McLin

After studying the test materials, I have come to the following conclusions about how cryonics is currently practiced today and the problem with its current standards of practice. The problem is that cryonics isn’t effectively managing ischemia, nor it doesn’t seem to be incorporating medical findings about how the brain is affected by hypotension, hypoventilation, and hyperventilation.

Moreover, research in determining a method to predict onset of cardiac death after life-saving treatments is withdrawn indicate that this is difficult to do so, this in conjunction with other papers, show that the brain damage begins almost as soon as a patient’s circulatory system begins to fail. This is problematic from the cryonics point of view, because long before cardiac death is declared, the brain may have already suffered irreversible ischemia damage preventing optimal cryonics suspension.

The research materials furthermore show that hyperventilation when administrated for whatever reason actually makes things worse and that hypoventilation is preferred. With this in mind, do cryonics providers incorporate that finding when administrating oxygen to patients as part of the stabilization protocol?

To summarize, the conclusions I arrived at are that current cryonics providers are failing to manage ischemia, failing to research ways to predict the degree of severity of ischemia, failing to engage in proactive activities to minimize ischemia pre- and post-deanimation, and not incorporating medical findings in improving brain survivability in presence of hypotension and hypoventilation. In addition, there appear to be a lack of an attempt to maintain extensive database of patient medical history, collection of body fluids for pre and post-deanimation, and pre- and post-suspension which is essential for research intended to improve cryonics practices.

Here I will discuss solutions I have come up to address some of the conclusions I have arrived at. The biggest problem is the issue of ischemia and how likely it is to occur once oxygen is interrupted and also how sensitive the brain is to reperfusion injury. I would review the existing protocols to ensure whether they’re adequately taking the reperfusion injury into account, whether medicines need to be updated(add or remove medicines) with respect to the latest medical findings. It should be verified via meaningful actual research whether the cool-down equipment is really minimizing ischemia.

Finally, how can cryonics address the crucial issue of the existing medical-legal atmosphere that require patients to be declared dead according either to the cardiac or brain death definitions. Both which ensure that the brain will suffer ischemia damage before suspension occurs. How can cryonicists safely arrange for optimal cryonic suspension free of problematic legal implications? This suggests a need to engage in policy lobbying and pushing for legislation aimed towards changing the legal situation for the betterment of cryonics. To put it so bluntly, it appears that voluntary euthanasia is a cryonicist’s best friend, as distressing and stressful it may sound.

Lastly, cryonics providers need to establish a medical database and engage in much more data collection than they are doing at present. Some of the patient histories show recurrent problems with their collection equipment, do they need to be upgraded or replaced? Research in minimizing or preventing ischemia should be undertaken to determine how to optimize brain preservation prior to beginning suspension.

Mark Plus

Many cryonicists in hospice conditions currently deanimate and are pronounced after agonal periods similar to shock which result in prolonged hypoperfusion and hypoxia of the brain. These lead to significant compromises of the brain’s vasculature (e.g., the brain’s ability to self-regulate its blood flow to certain regions like the hypothalamus when the arterial pressure drops below 40 mm Hg) and interfere with cardiopulmonary support, washout and especially perfusion with cryoprotectants, not to mention the havoc they must cause to the brain’s fine structure.

Also, the trend towards harvesting organs from patients who are pronounced cardiac-dead after as little as two minutes of asystole is probably not a good thing for cryonicists, if the laws change to make it harder to opt out of such donations which will have the effect of ensuring thorough brain death.

My suggestions:

Use people with professional training in shock medicine and anesthesiology to perform the cardiopulmonary support after pronouncement. Monitor the level of brain perfusion with the proprietary bispectral index technology (which I had to look up and I’d like to read more about) to determine if brain hypoperfusion happens. Hypoventilate the patients.

Premedicate cryonicists before pronouncement with drugs like piracetam, arginine vasopressin and NO inhibitors, mentioned in the papers you sent me. You also wrote that Jerome White had attempted to premedicate himself with over the counter supplements until a few weeks before his suspension.

Cryonicists with terminal illnesses should consider moving to places where the laws allow assisted euthanasia so that they can go into arrest and undergo the suspension procedure well before their agonal decline.

Cryonics organizations need to gather a lot more data when they perform suspensions based on the current state of the medical art. The S-100B assay should be used along with other assays to measure brain injuries. These assays plus the bispectral index data can provide badly needed feedback on the effectiveness of brain perfusion procedures.

If the patient can’t deanimate at the time of his choosing, use some of the medical models developed by the DCD researchers to better estimate the patient’s time of cardiac death during standby.

I hope my answers and recommendations are not too off the mark, and I suspect I’ve misunderstand or failed to notice some key points. You gave me a lot of unfamiliar material to absorb in a short amount of time. After a few more weeks of study, I could probably understand it better. Some kind of primer would also help. A few years ago I speculated that based on actuarial considerations, the ideal candidate for cryosuspension would have to be a healthy ten year old who could walk into the lab and lie down on the table. That leaves the rest of us somewhere away from optimal candidacy for cryosuspension. But then, what can we do about it?

And I do plan to study this further, so thank you very much for the scientific background information, and feel free to send me additional papers.

Other observations:

I notice the contrast between the thorough reports you’ve written for the suspensions you’ve performed versus the ones written by Alcor’s “pod people,” which apparently includes Aaron Drake. Several things seem to go wrong with about every suspension Alcor has done lately, including basic preparations like not having the tray of all the necessary surgical tools ready for Dr. Nancy or the surgeon. I knew in a vague way that things had gotten bad, but you’ve given me some idea of how bad.

The scientific literature started to report the effects of shock and hypoperfusion decades ago, but you wouldn’t know that from the “official” cryonics propaganda. It seems like the cryonics movement should have incorporated this knowledge from the very beginning, but then physicians, surgeons and neuroscientists have mostly avoided cryonics and deprived us of their expertise. Dr. Ravin Jain, a neurologist, sits on Alcor’s board, and he should know this stuff, but I don’t get the impression that he’s done anything to incorporate his knowledge into Alcor’s suspension procedures. The neglect gives cryonics a reputation for “scienciness” and pseudoscience which it doesn’t necessarily have to have.

Gerald Monroe

a. The current techniques practiced for all the cryonics cases most likely result in long periods of ischemic hypoperfusion to the brain. Instruments now exist to detect this, combining the bispectral index with near infrared spectroscopy, and apparently even when top notch experts support cardiac surgeries on children, the hypoperfusion is common.

The ischemia and the hypoperfusion are very, very bad. Of course, so is the freezing. And the storage in liquid nitrogen where dissolved oxygen can reach the tissues and oxidize them. And the shoestring budget (compared to even a single hospital) the cryonics organizations have to do everything on.

b. It doesn’t sound like these problems are insoluble if there were real resources (compared to those spent to delay death from cancer by a few months, for instance) dedicated to the problem. Tomorrow, if cryonics had the resources of a single major metropolitan hospital, it could actually solve these problems in a systemic way.

There have to be experiments done on animals, where many different techniques* are attempted and evaluated. Evaluations should be done by preparing synapses of slices of the subject’s brain following the freezing. Also, rewarming and function tests (of slices), once the state of the art reaches the point that this is practical.

The human patients have to be part of this evaluation. If no one looks, the mistakes made will never be corrected. Somehow very small pieces need to be removed as samples from the human patients, following each cryonics procedure, small portions mostly taken from sections of the patient’s brain not thought to contain unique personality information.

And so on. Real improvements don’t come easily or cheaply – they come incrementally, with great effort, and honest evaluation of the results of each change. The last element is probably the most important of all.

The history of medicine is littered with many, many examples where something becomes common practice without honest testing of the results. Pretty much universally it fails.

With all that said, for those of us right here, alive in an era where cryonics does not have the resources it deserves, it is simply Pascal’s wager. No matter how dim the odds are, some chance of a form of survival is better than none. Information is probably duplicated inside the human brain many times over, and all of the decay processes that work against cryonics are things that happen according to predictable laws of physics. In a future world where a brain could be scanned at the molecular level, there is probably at least some recoverable memory and personality data for even the worst cryonics case.

For some, the prospective of saving even an incomplete fragment of yourself is better than the guaranteed destruction by rotting in the ground or burning in an incinerator.

Why it is like it is : the cryonics organizations don’t have any money. There’s probably a hundred new things that could be tried, and most of them are not better than what is being done now. Every dollar spent now is a buck less that could go to protecting the existing patients over many more decades.

Moreover, without any way to evaluate the current baseline : how effective is cryonics actually preserving the patients, right now? Making changes blindly is stupid. In the history of medicine, time and time again, it has been found that when a simple and dumb medical technique is compared honestly to a more expensive and advanced technique, almost universally the difference is minimal to none. A few examples : diuretics work as well as the far more expensive and specific beta blockers, film X-rays provide basically the same therapeutic improvement as the vastly more expensive CTs and MRIs, physical therapy works about as often as spine surgery, etc.

This is why in countries with socialized medicine, with outdated equipment and techniques and long wait lists, the patients live almost as long. (and the population lives years longer due to better lifestyles)

* A few ideas that might or might not work :
1. More rapid cooling by exposing the brain to coolant with burr holes and connecting pumps directly to cerebral perfusion
2. Drugs to prevent the cerebral arterioles from closing when exposed to cold perfusate.
3. Calcium blockers to prevent apoptotic pathways from triggering
4. Oscillating magnets like the Japanese claim work for transplanting teeth
5. Skipping cryonics entirely and plastinating the brain

Jordan Sparks, DMD

Well, I’ve read all the papers. I’ve attached the notes I made. I know you said I could skim them a little more quickly, but I was having trouble understanding and remembering. I needed to use a more aggressive approach this time. I did the references to help me get organized, and if I had to do that again I would do it without listing out all the names. Anyway, this is where I’m at.

I have a tentative answer which I may refine later. I’m continuing to think about it. You only gave me one cryopatient case Hx. I notice that it’s rich with hematology and chemistry data. Repeated samples were taken and charted over time. Both the TBW circuit and the cryoprotective perfusion circuit are well documented. Pressures and flow rates are nicely charted. Also, glycerol, blood gas, and pH were monitored during cryoprotective perfusion. The lab samples, in particular, are notable because that is not the current practice of Alcor or CI. It would take me some time to look back through case reports to see when was the last time this was done.

a) Cryonics providers are currently disregarding complexity associated with the biochemical milieu. I’m not quite sure how to state it, but all of the 22 papers treated their problems as a complex interplay of the mechanical issues as well as the biochemistry. Reading current Alcor and CI reports, on the other hand, there is a total disregard for the role of biochemistry.

That’s my first stab at it. I wish I could state it better, and I might try to rewrite it. I might wait for feedback from you before I go much further in case I’ve missed your point.

1.  Fast recovery from shock used vasopressor combined with hypertonic saline starch.  Slow recovery used fluid resuscitation.  Propofol and Hb concentrations were comparable in both groups.  The fast recovery resulted in better cerebral perfusion and a higher BIS that was likely due to the better perfusion.  CPP =MAP−ICP.

2.  Three resuscitation protocols: 1=FR (fluid resuscitation), 2=NA/HS (noradrenaline/ hypertonic starch), and 3=AVP/ HS (arginine vasopressin/HS).  The AVP/HS group had faster and higher increase in MAP and CCP as well as better survival.  Also, ICP was lower.

3.  After significant hypervolemia, cerebral circulation decompensation occured.  There were significant regional variations in cerebral blood flow.  The redistribution favored the areas related to cardiovascular control.

4.  Patients in shock can have normal physiological, hematological, fluid, and electrolyte balance but still die due to metabolic abnormalities.

5.  In spite of mechanisms for preferential shunting of blood to the brain, low MAP will result in poor perfusion.  This results in inadequate oxygenation as well as inadequate lactate washout.  Decreased perfusion leads to ischemic damage.

6.  Hemorrhagic hypotension was induced in dogs which was still above the lower limit of cerebral autoregulation.  This resulted in an increased turnover of free fatty acids in the CSF.

7.  Moderate reduction of MAP in anesthetized cats resulted in no significant EEG changes.  Below 40 mm Hg, cortical rhythms slowed and then stopped.  Cell damage was only found below 40 mm Hg.

8.  Baboons were pretreated with Phenoxybenzamine (PBZ) before hypovolemic shock, and it prevented the fall in cerebral blood flow.  EEG does not normally return after reinfusion.

9.  Bispectral index (BIS) dropped to 0 during cerebral hypoperfusion.

10.  For donation after cardiac death (DCD) kidneys, prolonged severe hypotension was a good predictor of subsequent organ function.  Donor age also correlated with worse outcome.

11.  Dogs anesthetized and hypovolemic shock induced for 2 hours.  NMR used to monitor phosphate metabolism.  Upon fluid resuscitation, phosphate pools quickly returned to near baseline values, but intracellular acidosis persisted.

12.  Hemorrhagic shock combined with increased ICP is particularly damaging.  Increased ICP leads to cerebral ischemia which causes release of thromboxane A2 (TxA2), a potent vasoconstrictor and hypertenstive agent.  The increase in TxA2 persists for at least two hours after reperfusion and results in further cerebral hypoperfusion.  Pretreatment with COX inhibitor ibuprofen decreases TxA2 levels and improves total cerebral blood flow after global cerebral ischemia.

13.  Brain is vulnerable during hypotension and shock, especially long-lasting shock.  Patchy areas of ischemia developed through sludge formation and persisted even after hyperperfusion, indicating the role of local factors.  Phenoxybenzamine pretreatment significantly reduced rCBF changes during shock.

14.  DCD livers result in inferior graft survival compared to donation after brain death (DBD).  A DCD risk index was developed.  The lowest risk is with donor age <= 45 years,  warm ischemia time (DWIT) <= 15 minutes, and cold ischemia time (CIT) <= 10 hours.

15.  CNS activity was measured during hemorrhagic shock under light central anesthesia.  After reinfusion, if neurons failed to recover electrical activity, this was an early indication of eventual irreversibility.  There is a relationship between irreversibility and cumulative oxygen debt and excess lactate.

16.  Rats were subjected to hypoxia and hypotension followed by resuscitation.  Rather than the no reflow that the authors were expecting, they observed hyperemia in some areas for at least two hours.  They concluded that therapy aimed at increasing cerebral blood flow and oxygenation would be insufficient.

17.  Guidelines for controlled DCD are given.  DBD is superior.

18.  DCD score system is described.  Kidneys may benefit from therapeutic interventions before transplantation.

19.  Average values for basal respiratory functions in adolescents and adults.

20.  Severe hypotension causes brain damage.  Microvascular damage results in hemorrhage upon reinfusion.

21.  Prolonged agonal time did not influence kidney transplantation outcome when other variables were closely considered instead.  For example, elderly donors were not included.

22.  During hypovolemic shock, electrical activity and ICP was minimally altered.  The authors interpret this as a lessening of the role of the brain in the genesis and perpetuation of irreversible shock.

References

1: Cavus E, Meybohm P, Doerges V, Hoecker J, Betz M, Hanss R, Steinfath M, Bein B.  Effects of cerebral hypoperfusion on bispectral index: A randomized, controlled animal experiment during haemorrhagic shock.  Resuscitation.  2010;81:1183-1189.

2: Cavus E, Meybohm P, Doerges V, Hugo HH, Steinfath M, Nordstroem J, Scholz J, Bein B.  Cerebral effects of three resuscitation protocols in uncontrolled haemorrhagic shock: a randomized controlled experimental study.  Resuscitation.  2009;80:567-572.

3: Chen RY, Fan FC, Schuessler GB, Simchon S, Kim S, Chien S.  Regional cerebral blood flow and oxygen consumption of the canine brain during hemorrhagic hypotension.  Stroke.  1984;15:343-350.

4: Cowley RA, Attar S, LaBrosse E, McLaughlin J, Scanlan E, Wheeler S, Hanashiro P, Grumberg I, Vitek V, Mansberger A, Firminger H.  Some significant biochemical parameters found in 300 shock patients.  J Trauma.  1960;9:926-938.

5: Feldman RA, Yashon D, Locke GE, Hunt WE.  Cerebral tissue lactate in experimental oligemic shock.  J Neurosurg.  1971;34:774-778.

6: Fritschka E, Ferguson JL, Spitzer JJ.  Increased free fatty acid turnover in CSF during hypotension in dogs.  Am J Physiol.  1979;236(6):H802-H807.

7: Gregory PC, McGeorge AP, Fitch W, Graham DI, MacKensie ET, Harper AM.  Effects of hemorrhagic hypotension on the cerebral circulation.  II.  Electricocortical function.  Stroke.  1979;10:719-723.

8: Hamar J, Kovach AGB, Reivich M, Nyary I, Durity F.  Effect of phenoxybenzamine on cerebral blood flow and metabolism in the baboon during hemorrhagic shock.  Stroke.  1979;10:401-407.

9: Hemmerling TM, Olivier JF, Basile F, Le N, Prieto I.  Bispectral index as an indicator of cerebral hypoperfusion during off-pump coronary artery bypass grafting.  Anesth Analg.  2005;100:354-6.

10: Ho KJ, Owens CD, Johnson SR, Khwaja K, Curry MP, Pavlakis M, Mandelbrot D, Pomposelli JJ, Shah SA, Saidi RF, Ko DSC, Malek S, Belcher J, Hull D, Tullius SG, Freeman RB, Pomfret EA, Whiting JF, Hanto DW, Karp SJ.  Donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation.  Transplantation.  2008;85:1588-1594.

11: Horton JW, McDonald G.  Heart and brain nucleotide pools during hemorrhage and resuscitation.  Am J Physiol.  1990;259:H1781-H1788.

12: Kong DL, Prough DS, Whitley JM, Taylor C, Vines S, Deal DD, DeWitt DS.  Hemorrhage and intracranial hypertension in combination incresae cerebral production of thromboxane A2.  Critical Care Medicine.  1991;19:532-538.

13: Kovach A, Sandor P.  Cerebral blood flow and brain function during hypotension and shock.  Ann Rev Physiol.  1976;38:571-596.

14: Lee KW, Simplins CE, Montgomery RA, Locke JE, Segev DL, Maley WR.  Factors affecting graft survival after liver transplantation from donation after cardiac death donors.  Transplantation.  2006;82:1683-1688.

15: Peterson CG, Haugen FP.  Hemorrhagic shock and the nervous system.  1. Spinal cord reflex activity and brain stem reticular formation.  Annals Surgery.  1965;485-496.

16: Proctor HJ, Wood JJ, Palladino W, Woodley C.  Effects of hypoxia and hypotension on oxygen delivery in the brain.  J Trauma.  1979;19:682-685.

17: Reich DJ, Mulligan DC, Abt PL, Pruett TL, Abecassis MMI, D’Alessandro A, Pomfret EA, Freeman RB, Markmann JF, Hanto DW, Matas AJ, Roberts JP, Merion RM, Klintmalm GBG.  A J Transplant. 2009;9:2004-2011.

18: Plata-Munoz JJ, Vazques-Montes M, Friend PJ, Fuggle SV.  The deceased donor score system in kidney transplants from deceased donors after cardiac death.  European Society Organ Transplant.  2010;23:131-139.

19: Shock NW, Soley MH.  Average values for basal respiratory functions in adolescents and adults.  J Nutrition.  1939;143-153.

20: Tamura H, Witoszka MM, Hopkins RW, Simeone FA.  The nervous system in experimental hemorrhagic shock: morphology of the brain.  J Trauma.  1972;12:869-875.

21: van Heurn LWE.  Prolonged agonal time–not a contraindication for transplantation.  Nat Rev Nephrol.  2011;7:432-433.

22: Yashon D, Locke GE, Bingham WG, Wiederholt WC, Hunt WE.  Cerebral function during profound oligemic hypotension in the dog.  J Neurosurg.  1971;34:494-499.

“Synaptic”

As you wrote in 1994, the three sources of damage to cryopatients are 1) the underlying disease process, 2) shock and global and trickle flow ischemia secondary to dying and cardiac arrest, and 3) cryoprotectant toxicity and cryoinjury from freezing. This, as far as I can tell, has not changed. So, a flaw in how cryonics is practiced would have to mean that providers are not minimizing the damage from these processes as well as they could be. #1 is out as that is not the primary mission of cryo providers, although I agree with the arguments on your blog that they could add some value here too. #3 is also basically out, because gains over M22 seem unlikely to come in the near future, at least outside of 21CM.

That leaves #2. A number of the papers you sent me study animal models of hemorrhagic shock, and the results are not pretty for preservation of cellular structure. For example, the amount of necrotic cells in Ozkan et al’s paper is pretty high–up to 50% necrotic in the temporal lobe, after just 3 hours. The natural question is: if a cell undergoes necrosis, has it irretrievably lost the information coded in its cellular state? The answer is unclear. On one hand, it may be possible to reverse engineer the process of cell degradation from the surviving clues and thus recover the position of crucial membrane receptors and/or neurites. On the other hand, if the degradation process is random enough, that may not be the case. Probably it depends on the specifics — “cell necrosis” is a broad class.

A number of the other papers look at the acceptability of donors who died of cardiac death. It seems that kidneys can last up to 4 hr’s of warm ischemia with similar function post-transplant, while lungs following can hardly withstand 15 mins of warm ischemia time and still offer good function post-transplant. Meanwhile, it is practically common knowledge that the organ which is least able to survive following ischemic time is the brain. Finally, there is regional susceptibility variation within the brain, and there are reasons to think that regions like CA1 that may be especially important for identity (i.e., memory) are especially vulnerable to ischemia.

To me, this emphasized how quick the interventions must be and how essential it is to maximize the time period during which oxygen perfusion in the brain is high. There’s no reason why neurons have to be able to withstand lack of oxygen for long before randomly decaying — evolution has little reason to select for it. It is a bias of operating on human timescales to think that not much can happen within five minutes, but molecular timescales unfold much faster.

You also sent a few papers that evaluated measures to query brain activity via EEG. You seem to have a particular interest in one EEG-derived algorithm called the Bispectral Index, which in a few fascinating cases actually went to zero in the absence of cerebral blood flow during surgery. These are interesting in part because they could potentially be used to monitor CBF in cryo patients.

Which brings me to the major problem that we see in many of the case reports you sent me. That is, we have good reason to believe that all of them had already experienced a very low brain oxygen perfusion prior to clinical death. The signs of this are many, and include the hyperventilation of A2435 and A2361, the terrible peripheral perfusion of A1556, the hypotension and fluid loss of A1614, ACS9577′s poor perfusion and very low coma scale score, and the long periods of apnea and low blood pressure of A2420. One of the papers that you sent me called the period after removal from life support and cardiac death the “agonal phase”, and this phrase has been aptly used in cryonics to describe the period during which a patient is known to be eminently terminal but has not yet reached cardiac death.

One key question is whether these patients are ever in fact technically brain dead, meaning no neural activity at all, as measured by EEG or CT. If they are, then it is possible that clinical death could be pronounced and preservation techniques could be started much sooner. When I first thought of this, I was hopeful that I had discovered your “problem.” But on further contemplation I’m not so sure, in part because it seems like people would have thought of this. So, I am going with the more obvious, and indeed in some senses more troubling, problem that many or most cryonics patients experience torrents of brain damage during their agonal period.

What to do about this?

1) Somehow establish, in the US, legal recognition of the rights of cryo patients to initiate procedures to preserve brain-encoded identity when the patient is diagnosed by independent physicians to be terminal, in a similar way that organ transplants are.

2) Use a workaround by going to a country like Switzerland that already allows assisted suicide in such cases, perform the cryopreservation there, and then ship the patients back on dry ice to the US.

3) #2, except establish a new storage facility in the foreign country.

4) Develop, drawing off of the “normal” biomedical literature, substantially improved methods for preserving brain oxygen perfusion in agonal cryonics patients, and implement these on a routine basis.

One of the interesting things about this problem is that it is not specific to cryopreservation but would also apply to plastination, and may even be more pronounced there. So this is one area where progress, if any is made on either front, would certainly be synergistic.

A meta thought of mine about this assignment is that I didn’t like the assumption that I would be able to diagnose problems and suggest solutions so quickly to a problem that many people have spent lots of time thinking about. I doubt that what I have written above is at all novel.

Still, I did find it to be a very worthwhile exercise to learn about some details of cryopreservation and its associated medical concepts, and for that, I thank you for offering it to me.

——————————————————————————————————

I want to extend a sincere thank you to all who participated in this exercise, and especially to Alexander McLin, Mark Plus, Gerald Monroe, Jordan Sparks, DMD, and “Synaptic” for publicly participating. It takes an enormous amount of courage to undertake such an exercise on the Internet, where it both is and will remain open to public scrutiny, more or less indefinitely. Congratulations gentlemen, you have my unreserved admiration for your courage and for your willingness to take a personal risk in pursuit of the truth. — MD

Footnote

Reception area of the Alcor Life Extension Foundation in Riverside, CA in April of 1987. The photos above the refreshments cart were of some of the patients in Alcor’s care at that time.

Sometimes we get defeated by technology, sometimes by cluelessness and sometimes by a most unexpected intersection of the two.

In 1981 I conceived of the idea of hanging the picture of each patient cryopreserved at Alcor on the wall of the facility. I intended the practice to start, not in the place where it might seem obvious for it to; in the patient care bay (PCB) as a memorialization of the patient for his family and friends, but rather, in the reception area and offices, where the organization’s staff dwelt on a daily basis. It was my intention that as the patients accumulated in the PCB, the photos would begin accumulating in the offices, laboratories, corridors and workspace of the Alcor staff.  The intention was to provide a not so subtle reminder that there were people in those big stainless steel tanks, people who were desperate to get out of there.

Photos of Alcor patients apparently spilling off  (?) the walls in the conference room at the Alcor Foundation’s facility in Scottsdale, AZ in April of 2011. Photo courtesy of Stan Lipin

My intention was that, over time, there would an inverse and very adverse relationship between “success” in terms of patient population growth and “failure” in terms of growth in the number of pictures on the wall. In time, I envisioned (with some glee) the framed photos multiplying like locusts, becoming ever more oppressive and occupying ever more wall space.  I foresaw that they would likely encroach into the PCB. I also thought it likely they would be downsized. But mostly, I hoped they would serve their primary function, which was that each one was to serve as a reminder to those working at Alcor: “Hey, I’m still waiting, get me out of here! I want to get back to living, just like you are, too!”

This was not an idea which I kept secret. It was frequently discussed with other Directors, with staff, even with the officers and directors of other cryonics organizations. In fact, I now believe it is a practice which has become universal at cryonics organizations around the world. Or should I say, had become universal.

Alas, I hadn’t counted on technological advance. Technological advance is almost always a “two sided blade” and is this case, the blade cut in a way I hadn’t at all foreseen. The digital photo frame makes it possible to store essentially an “infinity” of images, and display them all in the physical space occupied by just one, over short sequences of time. In so doing, it removes the clutter, and thus the annoyance of hundreds or even thousands of actual framed, photographic images. One problem solved.

And another created. The purpose of institutions is to attempt to overcome the most damaging consequences of human mortality to civilizations: the destruction of knowledge, wisdom and the values they enable. In short, the loss of memory and accumulated experience that comes with the death of individuals.

Enter the halls of any civilization’s venerable institutions and you will see the images of the individuals they treasure on their walls and of those individuals’ ideas encoded in the books lining their shelves and engraved in the form of quotes and aphorisms on their walls. Stroll their great cities, or the corridors of their museums and you will see statues and likeness of the persons they treasure and admire cast in bronze and carved in stone; all these things are feeble attempts at conserving the ideas and values of the individuals who created the intellectual capital that sustains their civilizations. It is not just that they owe these men personally (they do) it is that these civilizations survive by remembering and living by the ideas that these men created.

Unfortunately, it turns out that ideas, standing alone and absent the context of memory, are weak things. It is one thing to know that fire burns, and another thing altogether to know that fire burns having been burnt by it. It is the power of knowledge in the context of experience that is wisdom, and it is wisdom that is destroyed by death. Knowledge contained in books, or nowadays in digital form, is but a shadow compared to that contained in the mind of a man who knows the real truth of a thing in the context of personal, hard won experience. Feeling, guided by reason over time, is the most powerful tool in the universe; and death is its ultimate enemy.

The human institution (first as oral tradition) followed by the written word, were man’s initial tools against death. Poor instruments that they were, they were used to fight valiantly in an attempt to conserve the memory of what was – a story of people, places and events over time. They were, to a remarkable degree, successful. The Royal Society is almost unbelievable in this regard, with every scrap of correspondence and every minor triumph and squabble being recorded and preserved. So are many neighborhood British garden societies – many going back hundreds of years. This will be true of every successful human institution from enduring religious institutions such as St. Catherine’s monastery in the Sinai, to the fraternal organizations such as the Masons in the US.

Robert Ettinger (left).

With the advent of scientific medicine and Ettinger’s book in 1964, it has become scientifically credible for human beings to reach for personal biological immortality and thus, for the first time, for a credible and a definitive “end to death.” Because what death really is, is the destruction of human knowledge and wisdom, and that is always and necessarily rooted in the destruction of individual humans. Wisdom, in particular, is uniquely a property of individual persons, and so is creativity. Neither of these fantastical properties which create and drive civilization can be distilled into books, carved into stone, or molded into bronze or plastic.

To achieve immortality for individuals it will be necessary to utilize the structure of institutions. It should be abundantly evident that such institutions will necessarily have to be the most stable and durable of those which human beings have so far managed to engineer. As such, they will have to most emulate that property which human institutions were created for in the first place: the conservation of memory of persons, places and events in order to conserve values over time. This why institutions incessantly speak of things like “grand old traditions” and “institutional memory.”  Admittedly, it is a hard thing to do. And it is a perilous thing to do, because it relies upon successful prognostication of the future; that the ideas and values selected for conservation and propagation over the ages are the ones essential for success; and that the ones not essential, do not discredit those that are.

Inherent in cryonics is a terrible arrogance and optimism which attracts a kind of people who seem to possess an inborn contempt for, or incomprehension of the value of the past. This is evident in their own disregard for it. There is a shocking lack of historical conservation at both CI and Alcor. In fact, it is so shocking and all pervasive that I know that my words here will have virtually no impact on almost all who read them, because no one,[1] at either place has any idea of what I’m talking about. It is, literally, the equivalent of talking to people who have never seen books, about how shocking it is that they don’t have libraries.

Organizations that are clueless about their own (recent) historical past should, not surprisingly, also be clueless about the deeper reasons for things like pictures of patients hanging on the walls. A few years ago, I was talking with one of the (many) former Presidents of Alcor who had a question for me about  something in a member’s paperwork. This President wanted to know what “BACS” was? Now, I am old. In fact, I’m a little older than cryonics (by about 9 years). But that still only makes me 56, not 156.  I felt a little like I do when I see anyone in the US being stopped on the street and asked questions like, “Who is the Secretary of State?” or “Who was Abraham Lincoln?” and the response is an utterly clueless answer.

If you’re an average reader here, and you don’t have a clue, that’s OK, because there really is no cryonics community to get acculturated in. The answer is that the Bay Area Cryonics Society (BACS, they changed their named to the American Cryonics Society, ACS, in 1985) was the dominant cryonics organization in the world from ~1974-1984! That’s a third of all of cryonics history and it’s not that long ago.  To not know that and to be running the world’s largest cryonics organization seemed wrong to me. Not because it was wrong per se, but because it was inevitably a marker for what had to be a veritable iceberg of other missing information that was of far greater import. And even that isn’t necessarily a fatal flaw. Realizing a deficiency of knowledge or character or resources, even a spectacular one, and working hard to remedy it is the oldest heroes’ tale in the world.

By CryoX

{This is a work of fiction  {or is it?}

Mirror mirror hanging on the wall
You don’t have to tell me who’s the biggest fool of all
Mirror mirror I wish you could lie to me
And bring my baby back, bring my baby back to me – m2m

My frequent flier card isn’t a card at all, it’s Parthenocissus tricuspidata (some would argue it’ the Roman numeral IV, instead). Whatever. For me it’s the magic weed that evaporates the financial distance between the coasts three or four time a year. Most of my frat buddies have their business junkets, we academics have our conferences. Alcor and Mike Darwin. Both on the West Coast, as  was my upcoming conference. Doable.

I hadn’t seen Max More since my undergraduate days, which I realized were rapidly becoming, no pun intended, a chillingly long time ago. My girlfriend (at the time) and I had attended some cryo/extro/CR get-together’s, and I met Max and his wife Natasha several times.  Max was this earnest, muscular, ginger, intellectual type who tried just a little too hard, was just a little too rehearsed and was more than a little too rigid. His wife Natasha? In some slightly different AU, Kurzweil has his Ramona. To me there is something artificial, slightly off and s-t-r-e-t-c-h-e-d t-a-u-t about her.  The only time I met Max without her around, I noticed a big difference in him; he was visibly insecure.

Now, Max More is President of Alcor.

I should have called to be sure Max was going to be there instead of just booking for the tour. Stupid. My flight was delayed out of LAX, and with the crazy delay from the limo, I barely made it from Sky Harbor to the Alcor building in time to meet the rest of the group. Unbelievably, the traffic in Phoenix is worse than it is in L.A.

The Alcor building is drab and unimpressive which, because of the idiodyssey of my limo driver, I really don’t understand. There are two Acoma Drives in Scottsdale and the moron (or his company) driving me from the airport had no GPS. We spent half an hour cruising around the Scottsdale Air Park before I finally became desperate enough to shove my Droid in his face and demand he call someone for instructions (shame on me for not having my GPS enabled for travel). The Air Park has lots of architecturally attractive buildings – some quite stylish if you like that Frank Lloyd Desert Look. The Alcor building is Brutalist Bad; plain-ugly-anywhere.

As soon as we were admitted to the lobby/reception area, a bomb went off in my head: Natasha! I don’t know if she had anything to do with it, but that was my reaction.  That kind of space is, by definition, supposed to welcome and draw you in. Instead, there is this big, cold, crystalline blob in the form of an “Infinity Mirror” almost immediately inside the door on the wall to your right, as you walk in.

There are all kinds of problems with this. First, it causes a distraction. The visitors aren’t interacting or socializing with each other, or the Alcor staffer (who should be a scantily clad voluptuous blonde). Instead, they are looking at the “pretty” on the wall, and some of them are even ape-touching it. One Merkeley woman in the group poked me in the ribs and said in an excited whisper, “Oh look into it, look into it.” That was my undoing. Fun-house mirrors, looking down tall glass buildings, certain angles at the Las Vegas  strip: all provoke intense, uncontrollable vertigo and nausea. Instantly, I was an undergrad in a dorm room staring up at an empty case of Dos Equis from the floor.  In one direction was the door to the outside, which the lady who had let us in had locked with a key. In the other direction was a mass of sharp angled stainless steel and glass furniture which I could see myself impaled upon and dying in a pool of my own blood and vomit.  I was paralyzed in front of the magic mirror. All I could do was shut my eyes and think of cool sea breezes. It worked.

The Alcor reception area is done up in grays, icy whites and shiny metals. This is a cryonics company. Its two most obvious and predominant negative images to overcome are death and the cold.  I didn’t really need the rest of the tour because even before the nausea had fully subsided, I realized that the special expertise Max had been hired to ply on Alcor was a new, high technology “preservative” skill called techsodermy, which is the cryonics equivalent for “dead” high technology companies. It was invented in the 1980s in Silicon Valley, and while I just made the analogy to cryonics, it really owes it origins more to taxidermy, because it was invented in order to fill dead tech companies with fluff in the hopes of convincing someone to buy them. (When we were waiting for our rides, the Merkeley Lady said the lobby reminded her of Benihana, and that she expected an “Oriental gentleman” with sizzling liquid nitrogen and  steak and shrimp to come out and start “chopping our meal” with a Ginzu knife at any moment. At least, she hoped it was steak and shrimp.)

My Old Man is all about money. In fact, he is money. He makes money appear and disappear. He moves money. He cleans it, he packages it, he inventories it, he “handles” it. That means that his clients are, mostly, people who rarely, if ever touch the filthy stuff. Some of them don’t even want to touch the little pieces of plastic that serve as markers for it. It’s an irony that the people who have the most money are the most visibly invisible of the super rich. If there is anyone reading this who knows what a Smythsons Diary is, I’d be very surprised. Perhaps a few more would know how to assess a man’s station by looking at his shoes, or his writing utensil? Today, casual dress is so commonplace and so comfortable…and if you want to be somewhere reasonably economically and you have commonsense and a lot of money, you book first class and you dress sensibly and comfortably. But, if you are in the know – then you know who’s who, and you don’t need a ledger book to tell you.

If you want peace and privacy, then you don’t travel by commercial means at all. That’s for the peasants. You use Flight Centres and privates jets, and there is no security screening. And if you want a blow job or a massage, or both en route, that can be arranged for a few hundred dollars more; a small part of the cost of coach ticket the flying public pays, and that after taking off their shoes and belts and switching planes in Houston and Dallas.

The people at Alcor are clueless about how to get the customers that matter. Not just the rich and the super rich (the people my Old Man services day-in and day-out), but the “good-judgment” segment of every demographic of the population. You may be a working class stiff from Boston in a cloth coat, but you know what the genuine trappings of quality, durability and class are, regardless of the style. Warmth, wealth, style, elegance, quality; whether understated or overstated, they always come through. So does Costco warehouse gray.

My Old Man wanted me to get an M.B.A. But he wasn’t altogether disappointed that instead of the usual frequent flier card I got that Mark IV. He’s interested in cryonics and he thinks it has a technical and (less so) a financial chance of working. But Alcor? I may be that desperate, but unfortunately for me (and him), he’s not.