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

EDITOR’S NOTE: The following text has been edited from a machine translation. I have tried to be as faithful to the original as possible. The title is mine – MD

I came to visit the United States, and specifically to visit California, earlier this year. Before my visit I wrote to Mike Darwin and to some others in cryonics to learn where the underground facility was where the Cryonics Society of California (CSC) cryonics patients were found decomposed in 1979. No one could tell me where to find the facility. I went to Oakwood Cemetery in Chatsworth, and inquired of the management as to where the facility had been located. The cemetery management was not of any help and they informed me that, unless I had relatives interred there, I would have to leave the premises.

I returned to the cemetery the next day, this time on foot (without a driver) and spent the day from the time the cemetery opened until nearly sunset looking for the place where the CSC facility had been, but I was unable to find any trace of it. There is nothing there to show where the CSC patients were lost. There is nothing to memorialize their attempt to survive via cryonics. There is nothing to commemorate them, either as individuals, or as tragic reminders to others in cryonics.

Mike Darwin writes about the importance of memory and not forgetting the history of cryonics. He says that lessons from the past must be learned and not forgotten. My point here is that people need help to do this; they cannot do it unaided. They need instructions on how to remember and constant reminders which are enduring.

After much effort, I finally found out where the CSC facility was. I went back to Oakwood Cemetery and there is nothing on that spot – just a bend in the road and grass. This made me very angry and I said to myself, “What is the matter with the cryonicists in the United States that they have no hearts and no sorrow about what happened in this place? How can you remember your history if you never knew it in the first place? How can you learn what you have already forgotten?” This makes me very sad.

Mike Darwin says it must be remembered, but he does not say how to remember it.

When I returned home I continued to think about that unmarked place in Oakwood Cemetery where those cryonics patients were abandoned, and where they lost their lives forever, and I began to make a plan to remember them. I went to Chatsworth to remember and to honor them, and I could not even find the place where they lost their chance at continued life. There must be marker there. There must be a tool to make us remember. So, I have devised a tool for keeping memory alive and for making cryonicists learn this lesson from the past.

My proposal is for a memorial on the spot where the CSC facility is now buried. This tool for remembering will be buried in the earth and it will be unknown and unseen, except by people who know where to look for it. The memorial is level with the earth and buried in it just as were (and are) the CSC cryonics patients. It is sunken in earth and forgotten as they now are, and will forever be, without this tool.

The memorial is an inverted decagonal pyramid placed into earth above vault. Each side of the pyramid is in memory of one of the cryonics patients lost at there. The top opening of the decagon has a surface area of 1.61803399 meters (the Golden Mean) and bottom has a surface area of 0 meters. This makes a catch-basin in which leaves, grass clippings, insects and all other matter, dead and alive, will be trapped and remain. The catch-basin will fill up to the top and become invisible and lost. The names and faces of the lost cryonics patients that are engraved on each facet of the dodecagon will be covered with dead matter and soil.

To stop this from happening, every person who is a true cryonicist must do as I did and go to the Oakwood Cemetery in Chatsworth one time before they too are cryopreserved. They must reach past the metal grate covering the opening in the memorial and remove the dead matter in the catch basin. They must do this to preserve the memory of and to learn the lesson that the mistake at Chatsworth has to teach. They must do this because to be a cryonicist is to have a duty to remember and a duty to learn from past mistakes. It is also required that all cryonicists honor the patients lost at Chatsworth, because in becoming a cryonicist, each person accepts some of the responsibility for the loss of the patients at Chatsworth. Becoming a cryonicist means accepting some responsibility for that terrible mistake and in that way the forgetting is hard. Only if such a terrible lesson is costly and unpleasant will the memory, and the lesson to be learned from it, endure.

Each cryonicist keeps the accumulating debris in the memorial from erasing the memory of the patients who were lost there. It is a task that is unending – and that is as it should be. If we forget those patients we will have forgotten ourselves and we will surely make the same mistake again (or others will make it on us). We must never forget!

* Hamlet: Act 3, Scene 1: In your prayers be all my sins remembered, or remember my sins in your prayers to God, so that I may be forgiven them.

Steven B. Harris, M.D.

In September of 1988, Steve Harris, M.D., published an essay entitled The Day the Earth Stood Still: Cryonics and the Resurrection of the Mythic Hero. It was one of his best in a formidable roster of insightful articles that he wrote dealing with the likely cultural requirements and cognitive limitations that inform humanity’s acceptance, or lack thereof, of cryonics.  I strongly recommend cryonicists read it. Steve’s articles had a great deal of influence on my thinking,  and both Steve and I were, in turn,  influenced by  the philosopher-mythologist-historian Joseph Campbell. I don’t know how Steve was introduced to him, but I first heard of Campbell as a result of the PBS series THE POWER OF MYTH WILL BILL MOYERS, (downloadable here)  which aired in the late 1980s.

I remember breaking out in goose bumps (I have them now) many times during Campbell’s program and, subsequently, when reading his books. His book of the same title as the series is an excellent introduction to his work. I had the same reaction when reading  Steve Harris’ brilliantly insightful articles dealing with issues critical to human perception of, and reaction to cryonics when I read them for the first time in manuscript form, before they were published in Cryonics And I had it again when I read them in “in print” as the final, published product. These works bear reading and rereading and reading again.

The Dead Ant Heap & Our Mechanical Society: http://www.alcor.org/Library/html/DeadAntHeap.html

The Return of the Krell Machine: http://www.grg.org/charter/Krell2.htm

Will Cryonics Work?: http://www.alcor.org/Library/html/probability.html

The Society for the Recovery of Persons Apparently Dead: http://www.alcor.org/Library/html/PersonsApparentlyDead.htm

Many are Cold But Few Are Frozen: http://www.cryocare.org/index.cgi?subdir=&url=humanist.html

Frankenstein and the Fear of Science (Lecture), VHS tape: http://www.worldcat.org/title/frankenstein-and-the-fear-of-science/oclc/043933281

There are very powerful ideas and insights in these essays which should be a source of influence and inspiration to many more cryonicists, than to those relatively few who have read them, to date.

One of my central points about the reason for the continued “failure” of cryonics, and for its very slow growth, both absolutely and relatively,  is the near total lack of any kind of memory of what has gone before, let alone a sorting out of what part of that history is vitally important to be remembered. It’s as if most cryonicists live only in the present, looking forward to a future exclusively of their own imagining, with just a dim halo of memory extending, perhaps 5 years back, at most.

A few days ago, I had my nth practical example of that. I was contacted by some people interested in establishing cryonics Elsewhere. One of the interesting (and depressing) things they had been told by “cryonics people in the US,” was that it was a “good idea to establish companion for profit and non-profit organizations” to carry out the various functions of the cryonics undertaking with minimal liability.

Really?

Maybe that is the best system, but if it is, there is no evidence I know of to support it, and substantial empirical evidence to refute it.

This is an edited version of my response t0 that recommendation:

“I can only tell you what I have observed here over and over again. Maybe you can figure a way around it, or maybe you won’t have the same problems in the first place, owing to cultural differences. I just don’t know.

You will notice that all of the cryonics organizations in the US consist of fully integrated providers. Suspended Animation is the (recent) exception. What’s remarkable about this situation is that it is the polar opposite of what all of us intended when we started cryonics operations here (myself included). There were always paired for profit and not for profit companies, and for just the reasons you’ve stated. CSNY & Cryo-Span, CSC & Cryonic Interment, BACS & Trans Time, IABS & Soma, Cryovita, Manrise & Alcor… And yet there are only single entities around today. Why?

I do not know about your local law, but in the US, it is forbidden for non-profit organizations (NPOs) and for-profit corporations (FPCs) to have interlocking directorates. In fact, it is generally prohibited for corporations related to, or doing business with each other to have interlocking directorates, unless one is mostly or wholly owned by the other, regardless of their status as FPCs, or NPOs. The reasons for this are many and are deeply rooted in corporate law, but mostly can they be reduced to “conflict of interest” issues. In the early days of cryonics, this ban on interlocking directorates was flagrantly disregarded. The inevitable result was that the FPCs completely dominated the NPOs. In fact, FPCs used the NPOs as a convenient shill for doing all the things that were unprofitable, risky, or otherwise not desirable, such as being stuck with the open-ended custody of the patient!

While the initial reason for this was the use of the Uniform Anatomical Gift Act (UAGA) to accept the patients, the eventual reason for it became (obviously), proprietary interest. People in the FPCs got paid for their work (usually in shares in the FPC) and people in the NPO didn’t – couldn’t, in fact. Valuable work, work that would earn shares, got done by the FPCs, and everything else got shuffled off onto the NPOs. You can actually  see this happening at the time, if you take a look at the issues of “Life Extension”/”Long Life Magazine” on the CryoEuro Wiki, because people didn’t talk about BACS, they talked about Trans Time… And where the reward, or the potential for reward exists is also typically where all the time, attention and money will flow.

Eventually, as visibility increased, the state began to menace, and the directorates were fully separated. That’s when all hell broke loose! The people running the NPOs had to be disinterested directors, and they did not stand to make money (or shares), or gain in any way from giving advantage to the FPCs. Contracts, fee increases, and all the other “taken for granteds” between the FPCs and NPOs were now up for debate and consideration. And since they were now two truly separate organizations, jealousy, resentment, and plain old proprietary interest and territoriality took over.

I pretty much thought the FPCs would win, primarily because they did have that huge advantage of proprietary interest on their side. But what I hadn’t figured on was the patients! The NPOs had control of the patients; and it was with the patients that the real loyalties ultimately rested. TT and BACS pretty much destroyed each other. In the case of Alcor, Alcor prevailed, and in the case of CI, well, there was never an issue in the first place, since CI was always an integrated operation. And yet, why this happened remains a mystery to many, even to those who have put some effort into finding out what happened.

In a large, diverse and robust marketplace, commercial service providers servicing NPOs could possibly work. SA may be the first of these, but only time will tell.

However, while cryonics is small and not subject to normal market forces, the two organizations model has not been proven workable. It becomes particularly vicious when there is only one service provider and one NPO, but totally different directors (as the law here requires), because then it becomes like a long-married couple who hate each other, but because of children, fiances and other reasons, cannot divorce. Far from creating the checks and balances it was anticipated to, this set-up created a state of gridlock and animosity. Ultimately, it degenerated to people on both sides screaming that the other was trying to screw them. And since they couldn’t stop dealing with each other and go to the “competition,” it just ground on until there was little or nothing left. That is, in fact, in significant measure, how Alcor was reborn.

Finally, you will encounter this problem: the FPC will be absolutely essential to the NPO, because the FPC will hold all the assets for delivering the up-front (immediately legally riskiest) part of cryopreservation (CP). They will own the equipment, employ the people, own the vehicles…. So the NPO eventually finds itself not just held hostage to FPC , but at risk if the FPC screws up.

I’ll give you a highly personal example. I was a major shareholder in Cryovita, the service provider to Alcor, but Jerry Leaf held most of the shares. Alcor relied on Cryovita completely for rescue and perfusion and there were no alternative service providers available – none. Alcor didn’t own so much as a cannula, or a set of scrub clothes. Cryovita was a shares corporation and the shares were distributed in a complex and potentially problematic way. It seemed possible that if Jerry were to suddenly experience medico-legal death, that the continued smooth functioning of Cryovita could be at risk of being disrupted. That became one of several causes of a major split between Jerry and I, because I realized, as President of Alcor (which I was, at that time), that if Jerry dropped “dead,” Alcor’s ability to deliver CP could be at risk of disruption. Alcor didn’t have cash lying around to go buy all the required equipment in a hurry! It had taken Jerry and me many years to patiently accumulate it, and to do so at well below market rates.

But it was worse than that, because over the years, Cryovita had generated patents, made exclusive agreements, and otherwise done all kinds of normal business things that corporations do. The problem was, all that “stuff” was also needed and used by Alcor! So, I began acquiring those same capabilities for Alcor, which was, of course, a costly duplication of capital equipment and it caused a feeling of resentment in Jerry/Cryovita.

So, what actually happened when Jerry did have a heart attack and was CPed? Well, exactly what I thought might happen, but in a way I never could have imagined. Cryovita did split from Alcor (kindly selling Alcor some of the most critical assets Alcor needed to stay in business), but the people who took Cryovita away were Kathy Leaf (Jerry’s widow), Saul Kent, Paul Wakfer, Brenda Peters and myself – the very people who had been the most ardent advocates of Alcor for so hard and long.

What happened to Cryovita? Well, it morphed in various ways, but today it is known as 21st Century Medicine!

Naturally, this version of events will be strongly biased by my point of view, so I would suggest you ask others and check it out for yourself. Look at the back issues of “Life Extension” and “Long Life” magazine on the CryoEuro Wiki to get a feel for the “Trans Times” of the 1970s and ’80s. Jim Yount, John Day and especially Frank Rothacker of ACS, may also be able to provide you with valuable perspective.”

My guess is that almost all of the newcomers to cryonics over the past decade, or so, have not read any of Steve Harris’ essays. And they clearly know little of the actual history of cryonics, let alone have any distillation (regardless of the direction of its bias) of what is important in that history to remember and act upon.

If you Google “history of cryonics” this what comes up on the first page (and subsequent pages offer no greater resources). Ben Best’s article is actually the most popular (longitudinally). It’s a fine, bare-bones factual narrative. But it is bloodless and lesson-less; it provides no instruction for others striving to create cryonics without recreating our errors. [I want to be very clear here that this is not a criticism of Ben's article: it was not written to be a tutorial on the lessons to be learned from the history of cryonics.]

What makes history both “teachable” and “leanable” is the humanity of it. We are, as Campbell so eloquently said, “story creatures”; we learn through guided narrative informed by the power of the mythic. BACS, TT, CSNY, Cryo-Span, Alcor, Manrise, CI, these entities were created by individual people for very personal reasons, as well as for the visible and easily understood public ones. Most contemporary cryonicists seem to recoil from any consideration of the “messy” and “untidy” aspects of the personal motivations and dynamics that drove (and drive) organizations, in and out of cryonics. And yet, that’s where a lot of the most important reasons and answers are to be found that will lead on to successes, or doom us to repeated failures.

Adapted from Source Document: http://www.docstoc.com/docs/88919930/Cryostat-Preparation—Cryonics-Institute

PURPOSE: To detail the procedures used for set-up and final preparation of Almax fiberglass-composite resin long-term patient care cryostats. This standard operating procedure (SOP) (aka Best Practices) details the vendors, materials and techniques used to prepare the Almax cryostats for full operational status after receipt from the manufacturer.

1.0. Detail of configuration and a brief overview of the manufacturing procedure used to produce cryostats.

Almax cryostats are cylindrical, double walled vessels that employ perlite and low vacuum (1-12 torr) insulation to facilitate highly efficient long-term liquid nitrogen refrigeration of cryopatients. Each unit has an overall height of 327.7 cm, an external diameter of 182.9 cm, an internal diameter of 121.9 cm and a useable internal height of 218.4 cm. The static liquid nitrogen capacity of Almax cryostats is approximately 2550 liters with a static boil-off rate in the range of 10.5 to 12.5 liters per day. Adult, human, whole body patient capacity is between 4 and 6 patients, depending upon patient diameter and the method of packaging used.

1.2.  Engineering details are presented Figure 1.1-1.2.

Figure 1.1: Detailed engineering specifications for the Almax long-term patient care Cryostats.

The cryostats are fabricated from a fibreglass mat-modified vinyl ester (Hetron 922, Ashland Chemical Co.) composite. The basic procedure for fabrication consists of building up layers of glass mat saturated with a resin monomer that is reinforced with carboxyl-terminated butadiene-acrylonitrile copolymer. The resin is polymerized (cured) using methyl ethyl ketone peroxide (2-butanone peroxide, or MEK-peroxide), which initiates free-radical cross-linkage of the monomer. This technique avoids incorporation of the MEK peroxide catalyst into the finished polymer, rendering it more stable, more corrosion resistant and less chemically reactive. Five millilitres of MEK peroxide are used per pound of Hetron 922. The inner vessel (can) of the cryostat is an open- topped cylinder with a concave bottom made from of vinyl ester resin and glass mat with a wall thickness of ~13 mm. The outer cylinder (can) is comprised of the same material, has a wall thickness of ~15 mm and is connected to the inner can only by a glue bond where the two are joined at the opening of the inner can on the top of the cryostat.

The opening of each cryostat is closed with a snug-fitting insulating neck-plug with an external cover of 14 gauge grade #2, 304 stainless steel. The insulating neck-plug is made from 22 layers of 2.5 cm thick Owens-Corning high density extruded polystyrene insulating foam board (~121.9 cm in diameter by 55.9 cm thick.) which are sandwiched between the stainless steel cover and an inner cover of painted chip board or marine plywood using 4 threaded nylon rods to compress and secure the foam to the inner and outer covers of the cryostat lid. A section of 5.1 cm diameter PVC plastic pipe penetrates the neck-plug and external cover in the center allowing access to the inside of the cryostat for temperature and liquid level monitoring.

Figure 1.2: Detailed engineering specifications for the Almax long-term patient care cryostats.

1.3.  Cryostats are manufactured under contract with Almax Products, a company owned and operated by Bruce Alter, located in Bearsville, New York:

Almax Products                    Mailing address:  Almax Products

363 Coldbrook Road                                            P.O. Box 441

Bearsville, NY 12409                                           Bearsville, NY 12409

Phone: 845-679-4615  FAX: 845-679-8620   email: Almax441@aol.com

Almax subcontracts the work of building the cryostats shells to Polymil Products, (contacts Sam Yacuzzo and Tammy Shultz) of LeRoy, NY:

Polymil Products, Inc                 585-768-8170

51 North Street

Leroy, NY 14482

Purchase price for 1 cryostat, ordered in May 2009 was $23,000 US, half payable on issuance of the purchase order and half payable by 45 days after delivery.

Perlite insulation is for the units is obtained from:

Noble Perlite                             405-872-5660

312 W Chestnut

Noble, OK 73068-8545

On average, 70 thirty-pound bags of perlite are used by Almax in a preliminary filling of the annular space prior to shipment of the cryostat. An additional 14 bags of perlite are shipped with the unit and used to top-up the annular space after shipping; the perlite settles en route due to handling and movement of the cryostat. Cost per bag as of 16 May, 2009 was ~ $20 US, per bag, including wrapping and palletizing, in preparation for shipment.

Currently shipment is being arranged by Almax and charges for the last load of perlite were $__________ US.

The stainless steel cover for the cryostat is manufactured by:

Beck Industries, Inc.

24462 Sorrentino Court,

Clinton Township,MI, United States, 48035
(586) 790-4060 PHONE
(586) 790-4982 FAX
EMAIL: mbeck6@sbcglobal.net

Figure 1.3: Stainless steel cryostat covers manufactured by Beck Industries, Clinton Township, MI.

The covers are 127 cm in diameter x 7.6 cm deep with a 20.3 cm circular central access port cover. The cover has 1/8″ diameter holes at 116.8 cm bolt circle, 22.9 cm bolt pattern with 1/8″ screw holes and 7.6 cm sides which are skip welded around the 127 diameter of the cover. The covers are fabricated from 14 gauge, grade #2, 304 stainless steel.

Price is $860.00 US per cover. Charge for palletizing and shipping to Bearsville, NY is $200.00 US.

TOTAL PRICE $_________ US

Figure 1.4: Removal of cryostat from shipping vehicle/container.

1.4  Atmospheric air is withdrawn from the annular space of the cryostat in order to create a vacuum in two stages. The first stage employs a roughing pump which is capable of reducing pressure in the annulus to ~ 5 x 10^-2 torr, however it will only be necessary to achieve a stable vacuum of ~ 500 torr before switching to the polishing/ maintenance vacuum pump. The roughing pump used is  in an Alcatel ACP-15, 8.2 cubic ft/min with a peak pumping speed of 14 m³ /hr and a final vacuum capacity of 5 x 10^-2 torr. The ACP-15 employs Roots blower technology. Roots pumps are positive displacement machines using two synchronized rotors rotating in opposite directions. The rotors feature profiles usually shaped like the figure 8.During the rotation, molecules of gas are isolated between the lobes and the stator and then led to the exhaust side of the pump without variation of volume.

Figure 1.5: Alcatel ACP-15 roughing pump.

The ACP-15 features a frictionless pumping module that is optimized for operation without internal lubrication. Complete technical specifications, operation and servicing instructions for the ACP-15 are present as Appendix 1 to this SOP.

Figure 1.6: Welch 1376C-03, DUOSEAL®, two-stage, belt drive high vacuum pump.

Final ‘polishing’ evacuation of the cryostat annulus as well as maintenance of the vacuum, is achieved using a Welch 1376C-03,DUOSEAL®, two-stage, belt drive high vacuum pump. The Welch pump has a peak pumping capacity of 300 LPM (10.6 CFM) with a final achievable vacuum of 1 x10^-4 torr. The Welch pump motor is configured to operate on 220V, 50 Hz,1 PH and is supplied with Schuko plug which must be replaced with a ____________ plug prior to be being placed into service.

Complete technical specifications, operating and servicing instructions for the Welch Welch 1376C-03,DUOSEAL® pump are present as Appendix II to this SOP.

2.0.  Shipment and unloading of the cryostat.

2.1.  The cryostats is palletized and prepared for shipment via commercial freighter in a sea-land container. It is then shipped, either by semi-trailer, or by truck, within the sea-land container, on wooden skids (generally skids of very poor quality). Drag chains are placed around the skids and they are pulled to the end of the trailer. Then they are pulled out further with the forklift so that the rear end of the skid rests firmly on the trailer and the opposite end of the skid is then lowered to rest on a wooden support frame so that the pallet holding the cryostat can be can be picked-up from the side with the forklift, removed from the  truck and moved into the facility where the cryostat is placed on custom made steel frame castered trolley for additional preparation, prior to placement into service.

Figure 2.2: The forklift is repositioned at the side of the cryostat/pallet and the unit is removed from the vehicle and placed on the ground..

 Figure 2.3: The evacuation port cover plate used to hold perlite in place and prevent contamination of the perlite with moisture during shipping is unbolted and removed.

 Table 2.1: Equipment, Tools and Supplies Required to Remove Cryostats from Delivery Vehicle

2.2.  The cryostat is shipped from the manufacturer with a resin-composite cover plate and sealing gasket secured to the evacuation port opening of the unit with 12 bolts (Figure 1.3). This cover plate serves both to contain the perlite insulation material and keep it dry during shipment. Perlite is moderately hygroscopic and will absorb water from the atmosphere in high humidity environments. Once the cryostat is in the storage facility, the cover plate is unbolted and the cover plate and the neoprene rubber gasket that seals it to the evacuation port flange are removed and set aside. The evacuation port opening is then immediately covered with a heavy-duty, 3 mil plastic refuse bag that is tightly secured in place with a ratchet-type nylon tie-down strap. It is important to immediately and tightly cover this opening to prevent moisture from entering the annular space and contaminating the perlite, since this would make subsequent evacuation of the annulus difficult, or impossible.

  Figure 2.4:  A custom built trolley fabricated from powder coated welded steel tube stock and high quality 3″ diameter urethane casters is used to safely move the  cryostat around the facility in the horizontal position during post -manufacturing preparation. Wooden skids are used to protect the cryostat from damage by the steel frame of the trolley.

 2.3.  The cryostat is transported to the work-area at the facility by placing it on a custom built metal trolley. The unit is left on the trolley until all preparative work (prior to hoisting the unit into the upright position) is completed.

3.0 Topping up the cryostat with perlite.

3.1 Protective clothing consisting of a heavy-duty, hooded Tyvek work coverall, fabric reinforced vinyl gloves and a full face N-100 respirator are donned. Duct tape is used to secure the hood opening of the of Tyvek suit to the edges of the respirator, the sleeves of the Tyvek suit to the work gloves and the tops of the work boots to the leggings of the Tyvek coverall, as shown in Figure 3.1, below. It is important to achieve a seal at all joints in the protective clothing in order to prevent the highly irritating perlite dust from contaminating the worker’s skin.

3.2  The plastic bag covering the evacuation port is removed and perlite is poured from the bags into the evacuation port opening as shown in Figure 3.2. The perlite is spread out inside the annular space and packed tight with wooden spreading and tamping paddles that are made in-house, as shown in Figure 3.3, below. Considerable force is required to tamp the perlite solidly into place, and typically the full weight of the worker must be brought to bear on the tamping paddle.

Figure 3.1: Duct tape is used to secure and seal the respirator, gloves and boots to the protective Tyvek coverall in order to prevent perlite dust from coming into contact with the workers’ skin. An full-face N-100 respirator is to provide respiratory protection from the perlite dust. Note perlite spreading and tamping tools resting on the cryostat at the middle left of the photo.

 Figure 3.2: Perlite is poured from the 20 lb bags into the cryostat annular space with the workman standing atop the cryostat.

Figure 3.3: A spreading and tamping tool are fabricated from plywood and a 24 x 24 x 61 cm piece of lumber (which serves as the handle). The spreading tool has the handle offset to one side of the plywood plate, while the tamping tool has the handle secured to the center of the plate allowing for stability and even distribution of load when compressing the perlite. The handles are secured to the plywood plates using  1/4″  by 3″ wood screws reinforced with quick-set epoxy adhesive.

Figure 3.5: Perlite is tamped into place in the annulus of the cryostat using the wooden tamping tool.

Figure 3.6: When the annular space is filled with packed perlite to the level of the bottom of the evacuation port no additional perlite is added and the top of the cryostat is brushed off with a household broom.

Figure 3.7: The evacuation port is again tightly covered with a plastic bag to prevent entry of water vapor into the annular space.

Figure 3.8: A jet of compressed air is used to clean the perlite dust off of the cryostat.

4.0.  Preparation of the evacuation port and evacuation valve assembly.

The first step in preparing the evacuation plumbing assembly is to sweat solder a 27 cm long x 3/4″ piece of copper onto a 3/4″ NPT Stainless Steel Ball Valve Full Port WOG1000 SS304 SUS304 0.75 .75 Female Ports.

Assemble the tools and supplies required for sweating the section of pipe into the valve. Prepare the copper pipe by sanding both ends using fine grit sand paper. Apply solder paste to the end to be sweated to the ball valve and insert the pipe into the 3/4″ copper T-connector. Don gloves and heat the copper pipe and connector with the torch for approximately 30 seconds. Apply solder by touching a J-shaped piece of solder to the joint 7 times; the solder will be drawn into the joint between the pipe and connector by capillary action. If the metal is not hot enough, reheat it with the torch as necessary. Allow the solder to cool and set-up for 60 seconds and then wipe the joint clean with a shop towel. Any remaining excess solder may be removed with a wire brush.

The threaded copper NPT to pipe slip fitting is then attached to the vacuum shut-off valve using Teflon thread sealing tape to insure a gas-tight seal.

Table 4.1 Tools and Supplies Required for Sweating Joints in Copper Pipe

Figure 4.1: A section of copper pipe is sweat-soldered into the female end of a brass NPT connector which is then screw threaded into a ball type shut off valve using Teflon pipe joint sealing tape.

The valve and pipe assembly are then attached to the evacuation port cover plate by drilling a hole just large enough to admit the copper pipe in the center of the 41.9 cm diameter cover plate. It is important that the hole be a tight fit to the valve and pipe assembly so that the pipe can be securely cemented into place without any possibility of leaks (there must be a gas-tight seal). The copper pipe is prepared for cementing into place by sanding with fine grit sand paper, after which it is degreased using acetone and a clean rag (or lint-less disposable shop towel). The end of the pipe to be attached to the evacuation port cover is then painted with Special Blend MFR-10 lb laminating resin (low volatile organ compound, mixed 100 to1 with methyl ethyl ketone (MEK) peroxide (supplied by Michigan Fiberglass Sales, St. Claire Shores, MI)  and the pipe is inserted into the previously drilled hole. Additional coats of laminating resin and glass mat, as needed, are used to secure the evacuation pipe in place, with care being taken to ensure that the pipe opening remains clean and unobstructed by resin. Each coat of applied resin is allowed to fully cure before the next coat is applied.

Figure 4.2: Top: the evacuation port cover plate with the stub of copper pipe to which the vacuum valve will be attached already in position. Bottom: schematic of the evacuation port, vacuum valve and T assembly housing the thermocouple vacuum gauge.

The back of evacuation port cover plate and the tip of the copper evacuation pipe assembly is then prepared for bonding to the flange of the evacuation port by being sanded with fine grit sandpaper. Once the plate has been “roughed-up” so that the adhesive epoxy will adhere, it is blown clean of particulates with a jet of compressed air, and then wiped with a clean rag dampened with acetone. Seven 6”x6” squares of cotton batting for filtration are painted with special blend MFR-10 lb laminating resin, low V.O.C. mixed  100/1 with MEK Peroxide (both from Michigan Fiber Glass Sales, St. Claire Shores) for hardening and adhesion.

Figure 4.3: Cotton batting filter pads are shown being cemented in place on back of evacuation port cover plate.

Figure 4.4.: The edges of the cotton bats are saturated with adhesive resin and smoothed onto the back of evacuation port cover plate.

The neoprene rubber gaskets that were between the evacuation port cover plates and the evacuation port flanges during shipment from Almax are used as templates for cutting the 3/4 ounce chopped strand FG-03438 fiberglass cloth rings.

Figure 4.5: The rubber sealing gaskets used to protect the annulus from the ingress of dirt and moisture during transport of the cryostat from the manufacturer are used as templates for cutting rings of fiberglass cloth which will act as the permanent sealing gasket.

Figure 4.6: It is important to wear respiratory protection whenever working with or around fiberglass. N-95 masks are suitable for such work, whereas a full-face N-100 respirator is required for work where perlite dust is being generated.

The fiberglass cloth rings are then applied to the cryostat evacuation plate flange using the same laminating resin that was used to adhere the cotton filter pads.

Figure 4.7: This illustrates proper preparation for cementing the fiberglass cloth rings to the evacuation port plate flange. Note the presence of a piece of protective (black) plastic to prevent damage or marring of the surface of the cryostat with the resin being used to cement the rings in place.

Figure 4.8: Household fiberglass building insulation (Owens-Corning) is used to plug the opening of the evacuation port. This prevents the perlite from migrating into the vacuum line, and it also serves as a coarse pre-filter for the larger particles of perlite dust, preventing them from entering the vacuum pumps.

Owens-Corning fiberglass “wool”  building insulating is packed against the perlite to prevent the perlite from plugging the filter.  The edges are then painted with laminating resin to facilitate adherence of the fiberglass cloth rings.

Figure 4.9: The edges of the evacuation port flange are carefully painted with resin to insure adhesion of the fiberglass cloth rings and to facilitate a thorough seal when the port cover is applied and clamped in place for final bonding to the flange.

 4.10: A small paint application roller is used to evenly apply (and assure saturation of) the fiberglass cloth rings to the flange.

A roller applicator is used to apply more laminating resin to the fiberglass cloth  rings. Three fiberglass “cloth” rings are applied in this manner to each cryostat. [The non-disposable parts of the roller may be cleaned up with acetone after use.] Once preparation of the fiberglass cloth rings is completed, the back surface of the evacuation port cover plate is painted with resin, taking care not to contaminate the cotton batting filters.

Figure 4.11: After the prep of the filter is completed and the final coat of adhesive has been applied, the back of the evacuation port cover plate is carefully and completely painted with adhesive resin taking care not to get resin on the cotton filter pads.

Figure 4.12: The evacuation port cover is then attached to the flange and held in place tightly with 4 equidistantly spaced C-clamps which are left in place until the resin has dried and fully hardened (~72 hours under normal working conditions).

The evacuation port cover with its integral filter (i.e., glued-on assembly of 3 cotton bats) is then clamped onto the flange opening and held in position for the adhesive resin to set up and cure.

5.0 Initial (rough) evacuation of the cryostat

 Initial evacuation of the cryostat is undertaken using the Alcatel ACP-15 roughing pump to a stable vacuum of ~ 500 torr. The Welch 1376C-03,DUOSEAL®, two-stage, belt drive high vacuum pump. must not be used for initial evacuation of the cryostat.  Failure to pre-evacuate the cryostat using a roughing pump will result in contamination of the oil in the two-stage pump with water and can damage the pump mechanism. Additionally, two-stage vacuum pumps are not designed to pump high density atmospheric gas – they are to be used only as “polishing” pumps to  harden and subsequently maintain the vacuum to ~ 1.0 torr.

Figure 5.1: Initial evacuation of the perlite filled annulus is accomplished using the Alcatel roughing pump. An inexpensive Bourdon tube vacuum  gauge (VG350-14CBM) is interposed in the vacuum line (mounted on a 3/4″ copper T-connector) to monitor the progress of the initial pump-out.

Figure 5.2: Once a vacuum of ~ 1.0 torr is achieved, the vacuum valve is closed, the roughing pump is removed, and the 2-stage vacuum pump is connected to the annulus. For this preliminary hardening of the vacuum a thermocouple vacuum gauge is used and is placed near the pump, for convenience.

 6.0 Preparing the base of the cryostat prior to erection upright.

A five foot diameter circle of 3/4″ plywood is used to seal and secure the bottom of the cryostat. The plywood circle has three 5″diameter holes cut in it, arranged as shown in Figure 6.1, to allow for 2-part  urethane foam resin to be poured into the space between the plywood circles and the bottom of the cryostat. Once the urethane resin foams, expands and sets, it serves to stabilize and reinforce the plywood so the bottom of the cryostat and ensure that  it is well supported and stable on the floor when the unit is finally filled with liquid nitrogen.

Figure 6.1:Circles of 3/4″ plywood are cut so as to fit into the opening of the base of the cryostat’s outer cylinder. Three 5″ diameter holes, spaced equidistant from each other are cut into the plywood to allow for filling of the space between the plywood discs and the bottom of the cryostat with urethane foam. The discs are placed with the holes at the top of cryostat base so that the urethane resin-activator mixture does not leak out onto the floor during loading into the base of the cryostat.

 Figure 6.2: The plywood disc is initially held in place with duct tape until it can be firmly anchored with steel tube stock or metal bars to prevent it from being displaced by the expanding urethane foam.

The plywood disc is initially secured to the bottom of the cryostat with duct tape and then clamped firmly into place using rigid steel tube stock or metal bars and heavy-duty C-clamps, as shown in Figures 6.2 and 6.6

The  space between the plywood disc and the bottom of the cryostat can now be filled with supporting, rigid, closed-cell urethane foam. The foam used for this is MF-1002 1.2 lb density urethane foam (from Michigan Fiberglass Sales). The foam is prepared from a two component kit consisting of  urethane resin (part-A) and activator (Part-B) which are mixed in equal parts using a wooden paint mixing-type stick in disposable 2-gallon paper pails. The resin, activator, paper pails and wooden mixing paddle are included with each MF-1002  kit.

Figure 6.3: The two (A&B) components of the urethane foam are mixed in disposable paper pails using a wooden mixing paddle (also disposable). The foaming reaction begins almost immediately and is well underway within a minute.

Figure 6.4: Foaming action of the combined resin and activator less than a minute after being combined and thoroughly mixed in the mixing-dispensing pail.

Once the components are mixed, the activated urethane resin will expand to ten times its starting volume and will subsequently harden into dense foam. The foaming action begins within 60 seconds of the start of mixing of the resin and activator, so it is necessary to quickly pour the mixture into the holes in the plywood. The activated urethane resin is poured into the headspace using disposable funnels made from lightweight aluminum sheet metal (~22 gauge). The resulting urethane foam requires approximately an hour to set and  is fully cured in 24 hours.

Figure 6.5: Lightweight flexible aluminum sheet metal is formed into half-cones which are taped in place to form funnels. These disposable funnels are then used to facilitate pouring the mixture into the 5″ holes cut into the plywood discs, starting with the lower holes and finishing up with the top holes.

Figure 6.6:Once the urethane foam has filled the headspace and has stopped exhausting from the filling holes, the holes are covered with squares of plywood which are screwed into place. The plywood disc should then be primed and painted with a waterproof oil-based, or two-part epoxy concrete floor paint, to prevent subsequent water damage due to efflorescence from the concrete slab, or insect (termite) infestation.

Four to six 2-gallon pails of the activated resin mixture is typically enough for each cryostat. [ The density of the foam may be altered by changing the ratio of resin and activator: more part-B than part-A results in a larger final volume of foam with less density.]

The cryostat is now ready for movement to the patient storage area of the facility for erection to a vertical position, fire-retardant coating, final hardware outfitting, painting and placement into service.

_______________________________________________________

By  Mike Darwin

SPECIMEN PROPOSED INTERNATIONAL PURCHASE CONTRACT AS OF 2009

TERMS AND CONDITIONS OF CONTRACT FOR PURCHASE OF ALMAX LIQUID NITROGEN CRYOPATIENT STORAGE CRYOSTAT

These Conditions may only be varied with the written agreement of the Purchaser.. No terms or conditions put forward at any time by the Supplier (Almax)  shall form any part of the Contract unless specifically agreed in writing by the Purchaser.

1. DEFINITIONS

In these Conditions:

“Purchaser” means the Purchaser, a limited liability company located at OOO “Purchaser_______________________________________________, hereinafter referred to as ‘Purchaser.’

“Supplier” means Almax Products, 363 Coldbrook Road, P.O. Box 441, Bearsville, NY, United States of America, 12409, Phone: 845-679-4615, FAX: 845-679-8620   email: Almax441@aol.com hereinafter referred to as ‘Almax.’

“Goods” means any goods as are to be supplied to Purchaser by Almax Products (or by any of the Supplier’s subcontractors) pursuant to or in connection with this Contract, as detailed in the Purchase Order attached to this contract and in Section 2.4, below.

“Contract” means the Contract between Purchaser and the Almax consisting of the Purchase Order, these conditions and any other documents (or parts thereof) specified in the Purchase Order and in A.

“Purchase Order” means the document setting out Purchaser’ requirements for the Contract.

2. GOODS

2.1       The Goods shall be to the reasonable satisfaction of Purchaser and shall conform in all respects with any particulars specified in the Contract and in any variations thereto.

2.2       The Goods shall conform in all respects with the requirements of any statutes, orders, regulations or bye-laws from time to time in force.

2.3       The Goods shall be fit and sufficient for the purpose for which such Goods are ordinarily used and for any particular purpose by Almax in the supply of the Goods and the execution of the Contract.

2.4       Specifically, Almax agrees to provide the following goods and services:

2.4.1   A double walled, cylindrical, composite vinyl ester resin fiberglass, perlite and vacuum (10^-3 mm Hg) insulated cryogenic liquid nitrogen biological specimen storage container (cryostat) based on the engineering drawings provided by Almax Products and attached to this Contract as Exhibit A. The inner vessel diameter is 1220 mm, and the inner vessel height is 2440 mm (tolerance ± 2 mm). The outer vessel diameter is 1830 mm, and the outer vessel height 2740 mm (without stand). With the stand the overall height of the cryostat is 3200 mm. The empty weight with the stand attached is 1814 kg. The inner cylinder wall thickness is a minimum of 12.7 thick. The approximate working volume for liquid nitrogen of the cryostat is 2142 liters.

All drawings are included in the price. Almax will send detailed drawings, blueprints and photos as requested, upon signing the contract.

Materials of construction for the cryostat are as follows:

Outer cylinder or shell: H-992  MEKP/COBALT STRUCT

Inner cylinder or shell:  H-992 MEKP/COBALT STRUCT

Heads:  H-992 MEKP/COBALT STRUCT

Flanges: H-992 MEKP/COBALT STRUCT

Nozzle necks: H-992  MEKP/COBALT STRUCT

External nuts/bolts: CS

CS Gaskets: 11 mm Neoprene rubber

Corrosion Barrier: 1-ply “C” backed W 2-ply chopped strand fiberglass laminate

Exterior: Five (5) coats of FireFree FF88 tumescent fire protective coating as supplied by FIREFREE Coatings, Inc., 580 Irwin Street, Suite 1, San Rafael, CA 94901, Phone: (888) 990-3388, USA and applied per the manufacturer’s specifications and instructions attached as Exhibit B to this Contract.

Design Pressure: (4′) + 15 PSIG, (6′) – 15 PSIG

Design standards: ASTM-D3299

2.4.2   A stand for the cryostat is provided equipped with 4 casters capable of easily rolling over finished concrete floors with the unit fully loaded with liquid nitrogen at  a gross weight of 2,430 kg including the cryostat stand, neck-plug and cover.

2.4.3   Cryostat will be loaded with perlite prior to shipment. Additional perlite will be furnished for “top off” as per 2.4.4, below. Price of cryostat inclusive of above: $25,000 with $3,000 discount on a second cryostat if ordered with 90 days of the receipt of the unit specified in this Contract.

2.4.4   Fourteen (14) bags Grefco Minerals HP-500 grade perlite as supplied Noble Perlite, 312 W Chestnut, Noble, OK 73068-8545 USA, phone:405-872-5660.@ $ 30 a bag (30 pound bag) plus a $15.00 pallet charge, price: $435.00

2.4.5   One (1) each resin kit to include: 2 ea: 10″ wide x 50 yards rolls of 1.5 oz FRP mat and 1 each 5-gallon drum of 411-400 resin, price: $545.00

2.4.6   Annular space vacuum burst disc to be provided by Purchaser or Purchaser’ designated vendor FOB to Almax.( Rupture disc set pressure: 15 psi rupture temp: ambient (-20 to +45 deg C) normal operating pressure: 2.5 x 10-5 torr (high vacuum) on one side, ambient pressure (1 atmosphere) Almax installation charge: $175.00

2.4.7   One (1) each extra 41.9 cm diameter evacuation port/filter cover plate to be supplied by Almax, price $245.00

2.4.8   One (1) each 41.9 cm diameter evacuation port/filter cover plate fully outfitted with 7-ply cotton filter and 3/4″ copper pipe and fittings, including Mueller brand 3/4″ ball brass ball valve (Home Depot part #06P115) sealed and assembled per the procedure detailed in Exhibit C, attached to this Contract, price included in base cryostat price.

2.4.9   Five (5) each: steel clevises for lifting cryostat capable of bearing a weight of at least 1,000 kg each, price: $148.50.

2.5.0   One (1) each R-06413-30 Tygon® vacuum tubing, 3/8″ID x 7/8″OD, 10 ft/pack, price $115.00

2.5.1   One (1) each 10 ft length Fischer Scientific red rubber vacuum tubing 9.5mm ID 22.3mm OD, 3/8″ ID 7/8″ OD., price: $69.90

2.5.2   Almax agrees to work with the subcontractor selected for the cryostat cover, Beck Industries of 24454 Sorrentino Court, Clinton Township,MI, 48035, USA, Phone number (586)790-4060, to ensure that the stainless steel cover fabricated by Beck Industries fits the cryostat supplied by Almax. In the event the cover does not fit due to incorrect specification supplied to Beck Industries by Almax, then Almax shall be fully liable for the replacement cost of said cover.

3. PRICE

3.1       The price of the Goods shall be as stated in the Contract and no increase will be accepted by Purchaser unless agreed by them in writing before the execution of the Contract.

3.2       Unless otherwise agreed in writing by Purchaser, Almax shall render a separate invoice in respect of each consignment delivered under the Contract. Payment shall be due 30 days after receipt of the Goods or the correct invoice therefore, whichever is the later.

3.3       Taxes, where applicable, shall be shown separately on all invoices as a strictly net extra charge.

3.4       The cost of palletizing and preparing the cryostat for shipment and for shipping the container is to be paid by Almax. Shall employ a licensed and bonded forwarder to handle the entire shipping procedure to include arranging the pick-up and delivery of Goods, filing and completing all required paperwork, and clearing of  the Goods through customs.

3.5       The total price is $27,733.34

3.6       The price shall be paid as follows:

•           1/3rd deposit upon initiation of this Contract and issuance of the Purchase Order

•           1/3rd upon completion of unit/system and or photo or inspection at factory

•           Final 1/3rd prior to ship and confirming positive test results done by Purchaser at its facility in Moscow, Russian federation

•           Prices are FOB shipping point.

•           All payments are in US dollars.

4. DELIVERY

4.1       The Goods shall be delivered to Purchaser, _________________________. Any access to premises and any labor and equipment that may be provided by Purchaser in connection with delivery shall be provided without acceptance by the Purchaser of any liability whatsoever and Almax shall indemnify Purchaser in respect of any actions, suits, claims, demands, losses, charges, costs and expenses which the Purchaser may suffer or incur as a result of or in connection with any damage or injury (whether fatal or otherwise) occurring in the course of delivery or installation to the extent that any such damage or injury is attributable to any act or omission of the Supplier or any of his subcontractors.

4.2       Where any access to the premises is necessary in connection with delivery or installation, the Supplier and his sub contractors shall at all times comply with the reasonable requirements of the Purchaser’ staff.

4.3       The time of delivery shall be of the essence and failure to deliver within eighty (80) days shall enable Purchaser (at its option) to release itself from any obligation to accept and pay for the Goods and/or to cancel all or part of the Contract therefore, in either case without prejudice to its other rights and remedies.

5. PROPERTY AND RISK

5.1       Property and risk in the Goods shall without prejudice to any of the rights or remedies of the Purchaser (including Purchaser’ rights and remedies under condition 7 hereof) pass to Almax at the time of delivery.

5.2       The property in the Goods shall pass to Purchaser upon payment for the Goods unless delivery of the Goods is made prior to payment, when it shall pass to Purchaser once the Goods have been delivered.

5.3       Any Goods for which the Supplier has received payment but which have not been delivered will, for the avoidance of doubt, remain the exclusive property of Purchaser and may be removed at any time by Purchaser or its representatives from wherever they are stored.

6. DAMAGE IN TRANSIT

6.1       On dispatch of any consignment of the Goods Almax shall send to Purchaser at the address for delivery of the Goods an advice note specifying the means of transport, the place and the date of dispatch, the number of packages and their weight and volume. Almax  shall free of charge and as quickly as possible either repair or replace (as the Purchaser  shall elect) such of the Goods as may either be damaged in transit or having been placed in transit fail to be delivered to Purchaser provided that: (a) in the case of damage to such goods in transit the purchaser shall within 30 days of delivery give notice to Purchaser that the Goods have been damaged, (b) in the case of non delivery Purchaser shall (provided that Almax has been advised of the dispatch of the Goods) within 10 days of the notified date of delivery give notice to the Supplier that the Goods have not been delivered.

7. INSPECTION, REJECTION AND GUARANTEE

7.1       Almax Products guarantees and warrants that the cryostat will maintain a vacuum of 10^-3 mm Hg between inner and outer containers with no more than 24 hours of pumping (using a standard laboratory vacuum pump with a minimum of 20 LPM of free air displacement and capable of delivering an ultimate vacuum of 1 x10 ^-4) per 30 day period. Almax further warrants that the cryostat (inner and outer containers and joint  at the neck-tube) will retain their structural integrity without leaking or cracking at a pressure difference of one atmosphere while storing a full load of liquid nitrogen (at least 2142 liters) and that the cryostat will conform to the description and drawings attached hereto as exhibit

7.2       Almax shall permit Purchaser or his authorized representatives to make any inspections or tests they may reasonably require and Almax shall afford all reasonable facilities and assistance free of charge at his premises. No failure to make complaint at the time of such inspection or tests and no approval given during or after such tests or inspections shall constitute a waiver by Purchaser’ of any rights or remedies in respect of the Goods.

7.3       Purchaser may by written notice to Almax reject any of the Goods which fail to meet the requirements specified herein. Such notice shall be given within a reasonable time after delivery to Purchaser of Goods concerned. If Purchaser shall reject any of the Goods pursuant to this Condition, Purchaser shall be entitled (without prejudice to his other rights and remedies) either (a) to have the Goods concerned as quickly as possible either repaired by Almax or (as the Purchaser shall elect) replaced by Almax with Goods which comply in all respects with the requirements specified herein, or (b) to obtain a refund from Almax in respect of the Goods concerned with no charge, either in materials or labor, to Purchaser.

7.3       The guarantee period applicable to the cryostat shall be 3 years from putting into service or 3 years from delivery, whichever shall be the shorter (subject to any alternative guarantee arrangements agreed in writing between Purchaser and Almax). If Purchaser shall within such guarantee period, or within 30 days thereafter, give notice in writing to Almax of any defect in any of the Goods as may have arisen during such guarantee period under proper and normal use Almax shall (without prejudice to any other rights and remedies which Purchaser may have) as quickly as possible remedy such defects (whether by repair or replacement as the Purchaser may elect) without cost to Purchaser.

7.4       Prior to shipment of the cryostat Almax shall perform a successful vacuum confirmation and spark test and provide detailed results of these test to Purchaser.

7.5       Any Goods rejected or returned by Purchaser as described in paragraph 7.2 or 7.3 shall be returned to the Almax at Almax’s risk and expense.

8. LABELLING AND PACKAGING

8.1       The Goods shall be packed and marked in a proper manner and in accordance with the Purchaser’s instructions and any statutory requirements and any requirements of the carriers. In particular, the Goods shall be marked with the Purchase Order number, the net gross and tare weights, the name of the contents shall be clearly marked on each container and all containers of hazardous goods (and any documents relating thereto) shall bear prominent and adequate warnings. Almax shall indemnify Purchaser against all actions, suits, claims, demands, losses, charges, costs and expenses which Purchaser may suffer or incur as a result of, or in connection with, any breach of this Condition.

8.2       All packaging materials will be considered nonrefundable and will be destroyed unless Almax’s advice note states that such materials will be charged for unless returned. The Purchaser accepts no liability in respect of the non-arrival at the Supplier’s premises of empty packages returned by Purchaser unless Almax shall within 10 days of receiving notice from the Purchaser that the packages have been dispatched notify Purchaser of such non-arrival.

8.3       Almax agrees to accept for placement in the sea-land container transporting the Goods to Purchaser at ____________________________ such other accessory items and equipment as will reasonably fit in the container upon the mutual agreement of both parties at no additional charge to Purchaser.

9.0 CORRUPT GIFTS OR PAYMENTS

Almax shall not offer or give or agree to give, to any employee or representative of Purchaser any gift or consideration of any kind as an inducement or reward for doing or refraining from doing or having done or refrained from doing, any act in relation to the obtaining or execution of this or any other contract with Almax or showing or refraining from showing favor or disfavor to any person in relation to this or any such contract.

10. PATENTS AND INFORMATION

10.1    It shall be a condition of the Contract that the Goods are made up in accordance with designs furnished by Almax that none of the Goods will infringe any patent, trademark, registered design, copyright or other right in the nature of industrial property of any third party and Almax shall indemnify Purchaser against all actions, suits, claims, demands, losses, charges, costs and expenses which Purchaser may suffer or incur as a result of or in connection with any breach of this Condition.

10.2    All rights (including ownership and copyright) in any specifications, instructions, plans, drawings, patterns, models, designs or other materials (a) furnished to or made available to Almax Purchaser pursuant to the Contract, shall remain vested solely in Purchaser (b) prepared by or for Almax for use, or intended use, in relation to the performance of this Contract are hereby assigned to and shall be vested in the Purchaser solely and (without prejudice to condition 14.2). Almax shall not, and shall procure that his servants and agents shall not (except to the extent necessary for the implementation of the Contract) without the prior written consent of Purchaser, use or disclose any such specifications, instructions, plans, drawings, patterns, models, designs or other materials as aforesaid, or any other information (whether or not relevant to the Contract) which Purchaser may obtain pursuant to or by reason of this Contract, except information which is in the public domain, otherwise than by reason of a breach of this provision, and in particular (but without prejudice to the generality of the foregoing) Almax shall not refer to Purchaser or the Contract in any advertisement without Purchaser’ prior written agreement.

10.3    The provision of this Condition 10 shall apply during the continuance of this Contract and after its termination, howsoever arising.

11. HEALTH AND SAFETY

Almax represents and warrants to Purchaser that Purchaser has satisfied itself that all necessary tests and examinations have been made or will be made prior to delivery of the Goods to ensure that the Goods are designed and made so as to be safe and without risk to the health and safety of persons using the same, and that Almax has made available Purchaser adequate information about the use for which the Goods have been designed and which have been tested and about any Conditions necessary to ensure that when put to use the Goods will be safe and without risk to health. Almax shall indemnify Purchaser against all actions, suits, claims, demands, losses, charges, costs and expenses which Purchaser may suffer or incur as a result of or in connection with any breach of this Condition.

12. INDEMNITY AND INSURANCE

12.1    Without prejudice to any rights or remedies of Purchaser’ (including Purchaser’ rights and remedies under condition 7 hereof) Almax shall indemnify Purchaser, its agents and employees against all actions, suits, claims, demands, losses, charges, costs and expenses which Purchaser may suffer or incur as a result of or in connection with any damage to property or in respect of any injury (whether fatal or otherwise) to any person which may result directly or indirectly from any defect in the Goods or the negligent or wrongful act or omission of the Almax.

12.2    Purchaser shall have in force and shall require any sub-contractor of Almax to have in force; (a) employer’s liability insurance in accordance with any legal requirements for the time being in force, and (b) public liability insurance for such sum and range of cover as Almax deems to be appropriate but covering at least all matters which are the subject of indemnities or compensation obligations under these Conditions in the sum of not less than $1,000,000 for any one incident and unlimited in total, unless otherwise agreed by Almax in writing.

12.3    The policy or policies of insurance referred to in paragraph 12.2 shall be shown to Purchaser whenever it requests, together with satisfactory evidence of payment of premiums.

13. CONFIDENTIALITY

13.1    Almax’s shall take all reasonable steps to ensure that all persons engaged in any work in connection with this Contract have notice that the statutory provisions apply to them and will continue so to apply after the expiry or termination of this Contract.

13.2    Almax shall keep secret and not disclose and shall procure that his employees shall keep secret and do not disclose any information of a confidential nature obtained by him by reason of the Contract except information which is in the public domain otherwise than by reason of a breach of this Provision.

13.3    The provisions of paragraphs 14.1 and 14.2 shall apply during the continuance of this Contract and after its termination howsoever arising.

14. TERMINATION

14.1    Almax shall notify Purchaser in writing immediately upon the occurrence of any of the following events:

a) where Almax is an individual and if a petition is presented for Almax’s bankruptcy or the sequestration of its estate or a criminal bankruptcy order is made against Almax  or Almax is apparently insolvent or Almax  makes any conveyance or assignation for the benefit of creditors, or if an administrator is appointed to manage his affairs; or b) where Almax is not an individual but is a firm; or a number of persons acting together in any capacity, if any event in (a) or (c) of this Condition occurs in respect of any partner in the firm or any of those persons or a petition is presented for Almax to be wound up as an unincorporated company; or c) where the Almax is a company, if the company passes a resolution for a winding-up or dissolution (otherwise than for the purposes of and followed by an amalgamation or reconstruction) or the court makes an administration order or a winding-up order, or the company makes a composition or arrangement with its creditors, or an administrative receiver, receiver or manager is appointed by a creditor or by the court, or possession is taken of any of its property under the terms of a floating charge.

14.2    On the occurrence of any of the events described in paragraph 15.1, or if Almax shall have committed a material breach of this contract and (if such breach is capable of remedy) shall have failed to remedy such breach within 30 days of being required by Purchaser in writing to do so, or, where Almax is an individual, if he shall die or be adjudged incapable of managing his affairs by determination of a court of law, Purchaser shall be entitled to terminate this Contract by notice to Almax with immediate effect. Thereupon, without prejudice to another of its rights, Purchaser may itself complete the Services or have them completed by a third party using for that purpose (making a fair and proper allowance therefore in any payment subsequently made to Almax) all materials, plant and equipment on the Premises belonging to the Almax, and the Purchaser shall not be liable to make any further payment to Almax until the Services have been completed in accordance with the requirements of this Contract, and shall be entitled to deduct from any amount due to the Almax the costs thereof incurred by Purchaser (including the Purchaser’ own costs). If the total cost to the Purchaser exceeds the amount (if any) due to Almax, the difference shall be recoverable by the Purchaser from Almax.

14.3    In addition to his rights of termination under paragraph Purchaser shall be entitled to terminate this contract by giving to Almax  not less than 30 days’ notice to that effect. In the event of such termination Almax shall, if required to do so by Purchaser , prepare and submit to  Purchaser a report on the work done prior to the termination and making such recommendations as may be based on the work done prior to termination.

14.4    Termination under paragraphs 14.2 or 14.3 shall not prejudice or affect any right of action or remedy which shall have accrued or shall thereupon accrue to Purchaser and shall not affect the continued operation of Conditions 10 and 14.

15. RECOVERY OF SUMS DUE

Wherever under the Contract any sum of money is recoverable from or payable by Almax, that sum may be deducted from any sum then due, or which at any later time may become due, to the Supplier under this Contract or under any other agreement or contract with Purchaser

16. ASSIGNATION AND SUB CONTRACTING

16.1    Almax shall not assign or sub-contract any portion of the Contract without the prior written consent of Purchaser. Sub-contracting any part of the Contract shall not relieve Almax of any obligation or duty attributable to it under the Contract or these conditions.

16.2    Where Purchaser has consented to the placing of subcontracts, copies of each sub-contract shall be sent by the Supplier to the Purchaser immediately it is issued.

16.3    Where Almax enters a sub-contract with a supplier or contractor for the purpose of performing the Contract, Almax shall cause a term to be included in such sub-contract which requires payment to be made to the supplier or contractor within a specified period not exceeding 30 days from receipt of a valid invoice as defined by the sub-contract terms.

17. FORCE MAJEURE

17.1    For the purposes of this Contract the expression “force majeure” shall mean any cause affecting the performance by a party of its obligations arising from acts, events, omissions, happenings or non happenings beyond its reasonable control including (but without limiting the generality thereof) governmental regulations, fire, flood, or any disaster or an industrial dispute affecting a third party for which a substitute third party is not reasonably available. In the case of Almax, each cause will only be considered force majeure if it is not attributable to the willful act, neglect or failure to take reasonable precautions of Almax, its agents or employees.

17.2    Neither party shall, in any circumstances, be liable to the other for any loss of any kind whatsoever including, but not limited to, any damages or abatement of charges whether directly or indirectly caused to or incurred by the other party by reason of any failure or delay in the performance of its obligations hereunder which is due to force majeure.

17.3    If either of the parties shall become aware of circumstances of force majeure which give rise to or which are likely to give rise to any such failure or delay on its part, it shall forthwith notify the other by the most expeditious method then available and shall inform the other of the period which it is estimated that such failure or delay shall continue.

17.4    It is expressly agreed that any failure by Almax to perform or any delay by Almax in performing its obligations under this Contract which results from any failure or delay in the performance of its obligations by any person, firm or company with which Almax shall have entered into any contract, supply arrangement or sub-contract or otherwise shall be regarded as a failure or delay due to force majeure only in the event that such person, firm or company shall itself be prevented from or delayed in complying with its obligations under such contract, supply arrangement, subcontract or otherwise as a result of circumstances or force majeure.

17.5    For the avoidance of doubt, it is hereby expressly declared that the only events which shall afford relief from liability for failure or delay shall be any event qualifying for force majeure hereunder

18. REFERENCES

Almax shall provide details of two reference bodies including names and telephone numbers of contacts, for whom similar work has been, or is currently, undertaken.

19. WAIVER

19.1    The failure of either party to insist upon strict performance of any provision of the Contract, or the failure of either party to exercise any right or remedy to which it is entitled under the Contract, shall not constitute a waiver thereof and shall not cause a diminution of the obligations established by the agreement.

19.2    A waiver of any default shall not constitute a waiver of any subsequent default.

19.3    No waiver of any of the provisions of the Contract shall be effective unless it is expressly stated to be a waiver and communicated to the other party in writing.

20. SEVERABILITY

If any provision of the Contract is held invalid, illegal or unenforceable for any reason by any court of competent jurisdiction, such provision shall be severed and the remainder of the provisions hereof shall continue in full force and effect as if the Contract had been executed with the invalid, illegal or unenforceable provision eliminated. In the event of a holding of invalidity so fundamental as to prevent the accomplishment of the purpose of the agreement, the Purchaser and Almax shall immediately commence good faith negotiations to remedy such invalidity.

21. NOTICES

Any notice given under or pursuant to the Contract may be sent by hand or by post or by registered post or by the recorded delivery service or transmitted by telex, telemessage, facsimile transmission or other means of telecommunication resulting in the receipt of a written communication in permanent form and if so sent or transmitted to the address of the party shown in the Purchase Order, or to such other address as the party may by notice to the other have substituted therefore, shall be deemed effectively given on the day when in the ordinary course of the means of transmission it would first be received by the addressee in normal business hours.

22. ARBITRATION

Any controversy or claim arising out of or relating to this Contract, or the breach thereof shall be settled by binding arbitration in accordance with the Commercial Arbitration Rules of the American Arbitration Association, and judgment upon the award entered by the arbitrator(s) may be entered and enforced by any court having jurisdiction thereof. Additionally, the parties intend that the arbitrators have power to issue any provisional relief appropriate to the circumstances, including but not limited to: temporary restraining orders, injunctions and attachments. The parties intend that this agreement to arbitrate be irrevocable and agree that either party is entitled to injunctive relief to quash litigation by the other part which breaches the agreement

21. HEADINGS

The headings to Conditions shall not affect their interpretation.

22. GOVERNING LAW

The Contract shall be governed by and construed in accordance with United States of America law and Almax hereby irrevocably submits to the jurisdiction of the US courts. The submission to such jurisdiction shall not (and shall not be construed so as to) limit the right of the Purchaser to take proceedings against Almax  in any other court of competent jurisdiction, nor shall the taking of proceedings in any one or more jurisdictions preclude the taking of proceedings in any other jurisdiction, whether concurrently or not.

IN WITNESS WHEREOF, the parties hereto have executed this

Agreement as of the date and year indicated below.

______Month _______Day ___________Year

Purchaser

By : _____________________________

XXXXX X. XXXXXXX,

Title: General Director, “Purchaser”

Date__________________________

Almax Products, Inc.

_________________________________

Bruce Alter

Title: President, Chief Executive Officer

Date____________________________

—————————————————————————————–

PURCHASE ORDER

Almax Products agrees to supply

At this time Price for one (1) complete unit, per contract to include:

double wall fiberglass liquid nitrogen storage system complete with required load of perlite, fill/load service fitting installed and 4 extra bags of perlite for “toping off” system…

Lifting lugs (3) placed per details

Stand:

PRICE $ 25,000 USD

2 plus units:

@ $ 22,000  Each  USD

***IF A SECOND UNIT IS PURCHASED WITHIN 3 MONTHS OF THE FIRST P.O. THEN DEDUCT $ 3,000 USD…

***AGAIN, THESE PRICES WILL CHANGE IF RESIN IS NOT AVAILABLE AT OLD PRICE..

_____________________________________________________________________________________

Options:

55 gallons Hetron 922 Resin** @ $ 595  USD

** Catalyst can not be shipped due to regulations.

This can be obtained via web site or local hardware or DIY store.

Extra Perlite: 14 bags Grefco Minerals HP-500 grade   @ $ 30 a bag ( 30 pound ) plus a $ 15 pallet charge

5-layers of Fire Flame 88 equal  Flame Control 20-20 A @ $ 1320  USD

1-Extra sealing Filter Plate Fiberglass @ $ 540 USD

1-Welch Model # 1376C-03  Vacuum pump wired for 220V, 50Hz 1 phase with Schuko Plug @ $ 4480 USD

5-clevises for lifting with a capacity 2,000 kg @ $ 29.70 each USD

By Mike Darwin

Sometime in the next few months, it seems likely that Director Errol Morris’ take on Bob Nelson’s account of the cryopreservation of James H. Bedford, We Froze the First Man, retitled Freezing People is Easy, will go into production. The title is at once sarcastic, brilliant, inspired and accurate, because, as readers of Chronosphere already (should) know, freezing people is anything but easy. While there have been many movies made that touch on cryonics, use it as a plot element, or even rely on it  as a major enabler of the story, this will be the first film about cryonics. It is, of course, quiet possible for a film about  cryonics to be good – even great – and still be bad for it. This film offers substantial possibilities for both of those elements to be in play.

Perhaps the most important thing to beware of is that the script is not based solely upon Nelson’s heavily (positively) biased and often inaccurate memoir, but also upon the searingly acerbic episode of Ira Glass‘ popular Public Radio International (PRI) radio show, This American Life (full program at this link). What’s more, Glass is also a co-producer of Freezing People is Easy. It is possible to listen to the This American Life episode, entitled Mistakes Were Made, and forget the context in which it was aired on PRI – as part of a series of pieces on scumbags in public life who refuse to take responsibility for their bad acts.To know that this so, one has only to read this excerpt from the review of that broadcast by cryonicist, author and social psychologist Ronald G. Havelock, published in the May, 2009 issue of  Long Life, the news organ of the Cryonics Institute/Immortalist Society:

“First of all, I think we should absolve Nelson of blame for what happened. This poor
man was struggling with a task which was way over his head. He deceived himself, as
others have before and since, with the notion that many people would flock to cryonics
once they realized that it had a real possibility of working. he greatly underestimated
the length of time it would take for cryonics to become popular. We are still
waiting. More importantly, he also greatly underestimated the basic requirements for
making it work, the first of which is to have an adequately funded and competently
staffed facility with the ability to maintain itself over long periods. I think he gambled
that, something like that mythical ball field, if he started it and had real capsules
filled with liquid nitrogen, they would come. Those who actually came, including the
famous Dr. Bedford, came with hope and desperation in their hearts but they came
empty-handed. How could they imagine that this service would be free? Simply put,
they took advantage of this man, and he returned the favor by promising much more
than he could possibly deliver.” [1]

It is also possible to forget that, first and foremost, Errol Morris (The Thin Blue Line, The Guardian, The Fog of War: Eleven Lessons from the Life of Robert S. McNamara: center photo in montage above) is a documentarian with a clever, often indirect, but always ruthless approach to making film show the truth and expose hypocrisy.

Zach Hem authored the script and while his narrative talent might be questioned on the basis of his botched effort in Mr. Magorium’s Wonder Emporium, he also wrote the script for the 2006 film Stranger Than Fiction, which is a surprisingly intellectual meditation on life, death and the power of the mundane to make life worth living. Helm’s take on Nelson and Chatsworth should be especially interesting, because his perspective in Stranger Than Fiction and Mr. Magorium’s Wonder Emporium suggest he may favor the intrinsic value of the individual life; the issue which makes or breaks a viable approach to a “cryonics friendly” perspective in any work of art.

 Somehow I doubt it though, and the casting of Paul Rudd (Clueless, Anchorman, Halloween: The Curse of Michael Myers, The 40-Year-Old Virgin, Knocked Up, Forgetting Sarah Marshall, Dinner for Schmucks) to play Nelson does nothing to reassure me. It has also been reported that Owen Wilson and Christopher Walken are on-board – one wonders what their respective roles will be; Norman Bedford and Robert Prehoda?  Or perhaps Walken will play Bob Ettinger? If, as rumored, Saturday Night Live’s Kristen Wiig also joins the cast, will she play Nelson’s then wife, or the author of We Froze the First Man, Sandra Stanley, to whom Nelson was confiding the details of Dr. Bedford’s cryopreservation and with whom he was reportedly having an affair at that time?

The book is rich in characters familiar to those with any history in cryonics: Saul Kent, Curtis Henderson, Bob Ettinger, Robert Prehoda, Dick Jones (aka Dick Clair), Dante Brunol, MD, Stella Gramer…and many more. It should be a fascinating exercise to see which, if any, of these supporting characters makes it into the film by name, or in a clearly recognizable way.

But will Freezing People is Easy get made, and if so, what will be its fate? Cryonics has been around for 50 years and attracting international attention for almost all of them. Thus, it should come as no surprise that there were two previous efforts to make movies where cryonics was the subject of the film, most notably, a film of Norman Spinrad’s darkly comedic and politically (left) loaded science fiction novel, Bug Jack Barron. For over 30 years, there were regular reports from the Hollywood intelligentsia (an oxymoron, I know) that Bug Jack Barron was to be made by Universal Studios, directed by Costa-Gavras, with the script written by Harlan Ellison. The story of why Bug Jack Barron never made it onto film has the same bizarre, cursed and insane quality to it as does the history of cryonics itself.

The story of why Thomas Berger’s (Little Big Man) novel Vital Parts never made it into production is even more tragic,  and the links with cryonics go deeper. The first go-round at Vital Parts the movie, was in 1971, with a when director Hal Ashby (Being There ,  Harold and Maude,  The Landlord and Let’s Spend the Night Together ), with Walter Matthau was slotted to play the principal character in the novel, Carlo Rheinhart (a long running character of Berger’s whose middle aged make over in this novel was reportedly inspired by Bob Nelson), the loser in the midst of a mid-life crisis who is seduced into involvement in the bizarre world of cryonics by the seemingly transtemporal Bob Sweet – a man from Rheinhart’s distant past who seemingly knows too much to be merely human.

Berger had visited the Cryonics Society of new York (CSNY) repeatedly to gather background information for his book, so it is no accident that a Mr. Softy ice cream  truck features prominently in the novel; Gillian Cummings (aka Beverly Greenberg), who was later to die tragically in the CSNY facility, drove a Jolly Tim’s ice cream truck to help pay the liquid nitrogen bills for her father, Herman Cummings (aka Herman Greenberg). And it is also probably no accident that the creepily mysterious bob Sweet shares the same last name with on the most prominent cryonics patients of the time; the liberal (“negro rights”) activist Marie Phelps Sweet, later lost at Chatsworth, along with the other Cryonics Society of California (CSC’s) patients who were also in the custody of Bob Nelson. Matthau’s son, and the apple of his eye, Charlie Matthau, was later to become a signed up, bracelet wearing cryonicist who was condemned to watch his father die by inches while doing everything in his power to both keep him alive (he kept portable defibrillators in his father’s home, car and work places) and unsuccessfully persuade him to make cryonics arrangements.

Left to Right: Walter Matthau, Charlie Matthau and Hal Ashby.

The next go round at turning Vital Parts into a movie was in 1987, with the irascible, reclusive and heavily drug abusing Ashby trying to make a comeback from his exile to television with another important, quirky film. This time Danny deVito had been recruited to play Rheinhart, and, in an inspired bit of casting, Gene Hackman had agreed to play Bob Sweet. During a meeting between Ashby and the producer Jerome Hellman to discuss finalization of the production of Vital Parts, Hellman became aware of what appeared to be “traveling phlebitis” in Ashby and shortly thereafter actor Warren Beatty became aware of Ashby’s symptoms, ultimately resulting in Ashby’s seeing an oncologist who diagnosed him with pancreatic cancer, from which he subsequently died in December of 1988.

The two other films which feature cryonics as cryonics (e.g., medical time travel) are screenwriter Mark Andrus’ and director W.D. Richter‘s  1991 Late For Dinner; a treacley, train wreck of a film which reviewer Owen Gleiberman aptly described as a film “so meticulously scrubbed of what we generally think of as entertainment value that the result is mostly a quirky, dawdling snooze,” and the truly, irredeemably awful 1985 film Stitches, starring the late Eddie Albert, Parker Stevenson, Geoffrey Lewis, and Brian Tochi. Oh yes, and I almost forgot to include the garbled and largely incoherent Vanilla Sky (starring Tom Cruise and Penelope Cruz) by the otherwise brilliant director Cameron Crowe, of which Stephan Zacharek of Salon.com said: “Who would have thought that Cameron Crowe had a movie as bad as Vanilla Sky in him? It’s a punishing picture, a betrayal of everything that Crowe has proved he knows how to do right….But the disheartening truth is that we can see Crowe taking all the right steps, the most Crowe-like steps, as he mounts a spectacle that overshoots boldness and ambition and idiosyncrasy and heads right for arrogance and pretension — and those last two are traits I never would have thought we’d have to ascribe to Crowe.” While I am no superstitious mystic, the ill fated bad luck attached to cryonics – in an out of film – makes me want to shout out a warning to all and sundry involved with Freezing People Is Easy, to “Run as far and as fast from the project as you can for both your personal and professional lives.“

Any way you look at it, the film promises to be a deep wallow in black comedy. That’s normally a genre I really appreciate, and often enjoy. This time, I’m not so sure. Robert F. Nelson (aka Frank Bucelli) is a bad man – a man who did enormous damage to cryonics, but more importantly, to the lives of the many people he defrauded and destroyed; not the least of which are the 10 cryonics patients whose loss were a direct or indirect result of his actions.  It is probably too much to hope that Helm’s and Morris’ effort could be as dark and well executed a black comedy as Peter Berg’s Very Bad Things, which Roger Ebert aptly summed up as not “a bad movie, just a reprehensible one. It presents as comedy things that are not amusing. If you think this movie is funny, that tells me things about you I don’t want to know.” That’s the movie that should be made about Nelson. The question is, should it be a movie, let alone the first movie, made about cryonics?

Footnote

[1] This statement is so wrongheadedly stupid on so many levels, it is hard to know where to begin in critiquing it. A good place to start would be by noting that Dr. Bedford hardly came “empty handed” to Nelson, or to cryonics. Instead, he came bearing $250,000 1967 US dollars ($1,714,832.83 in 2012 dollars) all of which was subsequently spent on his cryopreservation. It should also be pointed out that the majority of the families of the patients lost at Chatsworth, and at the Cryonic Interment facility on the East Coast (as well as some of the patients themselves), paid exactly what Nelson asked of them at the time: $10,000 to $15,000 in ~1973 US dollars, or $53,099.29 in 2012 dollars; substantially more than what the Cryonics Institute now charges for whole body cryopreservation today. Finally, this statement neglects the finding of the civil court that found Nelson guilty of fraud and for “intentional infliction of emotional distress.”

I have followed the saga of Mike Darwin beginning back in the day of Usenet where Mike maintained a cryonics list. I came upon this list while “surfing the ‘net” and found his editorials interesting. I wrote him an idle question and he wrote back, initiating a sixteen-year roller coaster friendship.

Now in 2012, I hope to make some observations from one who knows him intimately (not too intimately).

18 or so years ago, none of us could have predicted where the miracle of the Internet would take us.  Would any of you have believed ago that many global health care providers would have embraced a hard-core cryonicist as an authoritative voice in medicine?  By “embraced”, I mean they all hang on his every word.  Back in about 2000 they all took up a collection to purchase him a new computer to keep him on-line. Small denomination money came in from all over the world.

Because of that miracle, Mike has most assuredly entered the arena of “legitimate” medicine more than any of you can imagine.  Certainly more than anyone in the self-limiting field of cryonics.  His writings enjoy wide readership among working physicians and health care providers. He has contributed to several articles in a world-class clinical journal “Critical Care” with a journal “impact rating” (lots of clinicians read it) near the top three Critical Care journals in the world.

But it wasn’t an easy task.  As most of you know, Mike is a very unusual person on almost every level. I’ve known him for a very long time and I’ve seen the patterns emerge and descend in his life and I think I know him better than most, if for no other reason than he doesn’t keep friends long.  Like many of the rest of us, Mike has very potent talents combined with demons that keep those talents from wide expression.

Mike’s passion is what most physicians consider the pseudoscience of Cryonics, and he lives for little else. It is his passion and his obsession. At some point years ago, he reached a point in his life where his demons fully expressed themselves and he burned many bridges to those doing administrative and research Cryonics. To this day, those factions exclude him from those activities.

So for a few years around the turn of the century, he didn’t have lot to do with his time. Mike decided that he liked conversing with the members of CCM-L because it allowed him to pontificate about science and other things in life, and all always enjoyed his missives. As time progressed, he got more involved in Cryonics again, and slowly withdrew from CCM-L.

As a practical matter, his baseline default is to be culturally and socially isolated and he seems to be at home there. He works hard to maintain that isolation. He has an extensive history of effectively burning bridges over issues that could probably be resolved with even rudimentary diplomacy; an alien concept to him.

Over the years I have tried to understand why former friends and colleagues so relentlessly exclude him.  Conversations with some of them wondering why his strengths cannot be mined as his (perceived) shortcomings managed. The universal answer is that his (perceived) shortcomings have the capability of being so malignant that they are either afraid of him or any potential benefit isn’t worth the effort.

But Mike is an authentic Genius in Aspic (my term).  He chose to pursue a course of science that: 1. Limited his colleagues to a relatively small culturally isolated group, and 2.  Almost completely excludes him from many of the goals in life he would like to have in a perfect world. He is a genius trapped in Aspic and the “Richest Man in Bogota” ( H.G Wells).  His formidable talents are trapped.  Had he chosen to pursue righteous scientific disciplines, he would be mentioned in the same breath as Feynman.

My role in all this was to try to keep him visible to (for want of a better term) “traditional” science by keeping doors open for him as a writer in the literature of and speaker at meetings attended by scientists of the real world that righteously excludes Cryonics. To some degree, I have been successful in that endeavor, but it hasn’t been easy. Mike’s boundless energy, enthusiasm and confidence is pretty much limited to Cryonics, for which he writes extensive blogs and argues endlessly with critics thereof. His interest in mainstream science has dwindled, and that includes the mainstream scientists of CCM-L, for which he hasn’t much time or energy or interest in being a part of.

I’ve seen this coming for a while which is Why I chose to compile a history of his contributions to CCM-L for posterity. His response was that this volume was a waste of time and of no value to anyone, which is completely in character. I find it curious that this volume is the only book ever written about him that is complimentary.  He rejected all this and quickly evolved attempts to divert or stop altogether any involvement in these projects.

OK, he can be hard to get along with and he can be abrasive and irritating and emotional. We deal with these types with surgeons all the time, but if their benefit exceeds their detriment, we simply manage them more effectively.  Darwin is an authentic genius with a passionate and encyclopedic knowledge of medicine and science. There isn’t enough gold in Ft. Knox to buy that. It’s a gift from God.

I will tell you that I continue to use my influence to get him further inducted into the global medical community because I sincerely believe he is a valuable resource. He’s honest to a fault, beyond intelligent, has impeccable scientific integrity, works hard and has uncanny ability to communicate complex concepts to an eclectic audience. For those reasons, he has the potential to get the ear of clinical medicine.  He has great potential as a writer for medical subjects, and speaker at international meeting. Mike sitting in a 2 X 4 shack in Arizona spending his days grooming the surrounding desert is a waste when his knowledge base and communication abilities have such potential benefit to science.

There is a window of opportunity here to re-think former misadventures in terms of the current needs of science and medicine. The world evolves and we all need to evolve with it, or we’ll become extinct. Mike needs to evolve to something other than lethal or self-limiting iterations.  Who knows, he may be the ticket infiltrating the legitimacy of Cryonics in the global medical community. Weirder things have happened. We, in clinical medicine, learned long ago that the mission transcends personal problems. We learn to manage them better to facilitate a greater good.

*If you are British, yes, he is related to that Crippen, and no, I’m not related to that Darwin.

Screening for the Risk of Deanimation

The term “screening” is used in medicine to describe routine examinations or diagnostic procedures of a defined group of individuals to identify diseases or risk factors for same at an early stage. Screening is usually categorized as a  “preventive medical examination” or a  “checkup,” and its aim is to increase the life expectancy of those examined  by reducing the incidence or severity of life threatening disease and enhancing the quality of life. The most accurate examination methods possible should be used to identify as many diseases as possible still in their non-symptomatic phase, so that early treatment or change in life style can be initiated.

It is critically important to understand that the purpose of a “deanimation screening scan” (DSS) is not primarily to interfere with the course of disease or to extend the duration of life during this life cycle. Rather, it is to predict or to warn of impending  deanimation with increased accuracy and precision. Any contemporary medical or health benefits are thus incidental. Indeed, it is precisely when DSSing is used to determine or influence current medical interventions that it becomes dangerous. Knowing when you are likely to deanimate with greater precision, for sole purpose of improving your cryopreservation, carries little if any risk of iatrogenesis beyond that which would be present if you found out you were dying at a later time, or didn’t find out and suddenly collapsed in cardiac arrest from a heart attack, or suffered a massive stroke. It is only when the course of treatment is altered by obtaining the data, or looking at it (see “The Black Box of the Baseline,” below) that DSSing becomes either a practical or an ethical conundrum.

The first problem we confront in a screening test for deanimation risk is that we are moving in completely uncharted waters. We have no benchmarks or baselines on which to structure our screening program, save for a modest number of pilot programs that have been undertaken to evaluate full body scanning as a primary tool for the detection of cancer and atherosclerosis in the general population, or in selected subpopulations. For now, these will have to serve as the basis for our protocols, as well as the important cautionary lessons learned from other screening programs.

For reasons of safety, (see Radiation & Risk, below) Magnetic Resonance Imaging (MRI) is preferred over Computerized Tomography (CT), because no ionizing radiation is employed in making the image. MRI has some important limitations at this time, most notably only a few centers have devices that image the coronary vessels with sufficient precision  to allow risk  assessment for coronary artery disease (CAD).  Similarly, screening for Alzheimer’s Disease (AD),(beta amyloid deposits) also requires CT-PET scanning and the associated exposure to ionizing radiation.  So, for the present, CT is the only way to screen for CAD and AD. For this reason, and for those who for economic reasons may need to use CT imaging, it is worthwhile to briefly discuss the much hyped “risks” of radiation from whole body CT scans and this is done in some detail below.

Figure 25: Typical finding in an elderly woman who under prophylactic full body MRI scanning during a clinical trial in Germany to determine if full body scanning would reduce morbidity and mortality from cardiovascular disease and cancer. (Gohde, et al.)

A specimen imaging protocol is presented as Appendix 1 and is taken from the study by Gohde, et al., “Prevention without radiation – a strategy for comprehensive early detection using magnetic resonance imaging,” which was itself a pilot study in the use of MRI as a screening tool for cancer and cardiovascular disease.

The Mechanics

Currently, there is only one way to get a  DSS and that is to do it yourself.  There are several reasons, which will be discussed directly, why that is not a good idea, or certainly not the ideal way  to pursue DSSing. There are a number of reasons for this, starting with the potential for harm. Primum non nocere is the first dictum in medicine: first do no harm. Information is the most powerful force in the universe and information concerning you own health and welfare is especially important. It is also information that you cannot be objective about. It just isn’t possible. It is for this reason that no good physician treats himself or his immediate family in life or death matters as the sole or usually even the primary caregiver. In fact, speaking from experience as a person knowledgeable in medicine, I have found that wise counsel and advice I can (and do) easily give to others  is strangely absent from my own ears when I am the patient.

This lack of objectivity is more than a nuisance, it can be truly dangerous; and here I will have recourse to an actual example. The first four people to undergo DSSing have done so over the past 11 months. These were all individuals who were over 60 and who had not had consistent (or recent) “physicals.” All were counseled about the dangers of VOMIT and about the negative psychological impact of potentially finding out “something was wrong.” All four individuals had significant anomalies on their scans – two of which were life threatening and these were (or are) being medically managed.

In the other two cases, the scans revealed anomalies that might merit further medical evaluation in testing, and in both cases, the decision was wisely made not to pursue those tests. Why? That’s a complicated question, and I’ll answer it by explaining the circumstances of one of these people:

Mr. Ling is an 82 year old man who is in excellent health. He is physically active, mentally sharp and still working part time in his profession of many years.  He underwent a DSS five months ago. The findings were, overall, very good. His coronary calcium score was roughly a third lower than expected for his age, he had no signs of neoplasms, or of peripheral or central atherosclerosis, and the only abnormal cardiovascular finding was evidence of mitral valve regurgitation, which was deemed not serious and not likely to progress rapidly. However, a number of nodules were found in his right lung, along with some enlarged lymph nodes. The radiologist who reviewed the scan suggested a possible biopsy, with or without “bronchoalveolar lavage” (BAL).

While Mr. Ling is in good health, he is an 82 year old man and BAL requires sedation with propofol or a similar drug, and carries with it the risk of significant complications.  As to a CT-guided needle biopsy of the lung masses or the lymph nodes, this is this discussion that took place between Mr. Ling and the radiologist who interpreted his scan: “OK, let’s consider what this could be? I’m not sick – never felt better, so it’s not TB or something infectious? And if it’s cancer, well, what kind of treatment options would I have at my age for lung cancer with lymph node involvement?”

Those were great questions, and as it turned out, the radiologist was only playing it safe – he doesn’t want to get sued if Mr. Ling finds out he has cancer and a lawyer says to  a jury, “The doctor who imaged him said, ‘You’re in you 80s, I see this kind of thing all the time. Don’t worry about it.”  The radiologist ended by noting, “Since you are planning on following up in a year with another scan, we’ll see if anything has changed then.” And Mr. Ling is fortunate to have sufficient financial means that if he wants to pop in for a scan two months later, he can do that, too.

The problem is, most people aren’t in Mr. Ling’s position, and many will be unable to reason their way past the information that they have “masses” or “lumps” in their lungs and “enlarged lymph nodes in their chests!” That kind of worry cannot only be expensive, it can be damaging to one’s health, and corrosive to one’s quality of life. The information from DSSing should be given in the proper context, in the proper way, by the proper people, with the proper knowledge.  Absent that, it can do real harm. And if the scan does reveal a grave or untreatable medical condition, then there is all the more reason for the person to have the necessary resources at hand to help him cope and plan.

Ideally, this program would be part of a comprehensive Member Survival Program (MSP) administered by the cryonics organization (CO) and there would be a staff person whose job it would be to maintain communications with members, encourage compliance with MSP protocols (including the preferred imaging protocol) and collect and manage the resulting data stream.

Under such a scheme, upon intake (approval of cryopreservation arrangements) all members would have (at their option) completed a comprehensive health history and demographic information questionnaire, most of which would be completed as part of their membership application. The data from this questionnaire, as well as any electronic medical records the member may choose to provide, would be entered into the CO’s comprehensive member data base. The availability of this data would then allow for downstream refinement of the “one size fits all” scan protocol being proposed here, by allowing for individual risk assessment for CVD and cancer. This would flag members at elevated risk of early onset of these diseases to consider commencing scanning surveillance at an earlier age.

The Schrödinger Scan: the Black Box of The Baseline

Unless otherwise indicated, the first (baseline) scan would be done at age 45 for men and age 50 for women. In order to completely avoid any deleterious negative psychological effects, as well any potentially harmful effects from VOMIT (as discussed above), the baseline scan remains blinded and unexamined for 1 year after it is made. This done by providing written instructions to the radiologist reviewing the scan to seal the report unless there are unequivocal findings of life threatening pathology.

At the end of the year long blind period, the scan is examined and any anomalies noted. If the member chooses, a repeat scan can be done to resolve any questions or concerns raised by the baseline imaging. For example, if what appears to be a suspicious mass or nodule was found, a rescan a year later will very likely disclose if it is a neoplasm e.g., it will have grown or spread). It may seem counter intuitive to not look at data which you have paid for, experienced inconvenience to get, and which “might” save your life, but that is the necessary price that must be paid for this intervention to be used safely.

The baseline scan must be regarded as the first part of something that will not “happen,” or be completed for another year – like a bulb that has been planted to bloom in the spring, or a bond that will not mature for another 12  months. The scan itself is only a part of the process: the necessary information to safely interpret it does not appear until the required interval of time has elapsed. After all, before this protocol was proposed, no one ever got scanned and they felt just fine about it (until they dropped over in cardiac arrest).  For those of a quantum bent, consider it an extended version of Schrödinger’s famous experiment, except instead of the cat in the box, it’s a CAT scan in the box.

Scan Intervals & Exceptions

If the baseline is “negative,” showing no evidence of evolving pathological processes that merit intervention or further monitoring, then it is being proposed that the next scan take place 5 years later. Similarly, with each subsequent negative “healthy” scan, the next scan would be 5 years hence until age 81, at which point scans would be done every 2 years until cryopreservation ensues.

Figure 26: Proposed algorithm for Deanimation Screening Scan intervals and actions.

These scan intervals are arbitrary and will no doubt need to be refined over time as experience is gained. Intuitively, it seems that there should be a relationship between scan intervals and increasing age, and it is possible to configure scan intervals based on things like increasing risk of SCA or terminal illness with age. However, until some real world experience is gained, a conservative approach which minimizes costs and maximizes the opportunity for benefit, seems best. There are lots of programmers, mathematicians and similarly qualified people in cryonics and if any are interested in working with me, I am interested in generating scan interval algorithms based on the rising risk of disease and death with age (if you are interested, contact me at m2darwin@aol.com)

Going it Alone?

If a decision is made to proceed with DSSing on an individual basis, there are a number of important things to keep in mind and to do:

* Do consider carefully the possible impact this decision will have on you and on your family. In fact, give some thought to discussing this with your spouse or significant other before moving ahead.

* Do select a good imaging center with competent and caring staff who can give you good counsel about the procedure and the results. Imaging centers that offer full body scans are often used to counseling patients: make sure the one you select is a good one. Talk with the staff about your concerns before you commit to being imaged.

* Do explain to the radiologist who will interpret your images that you are having a baseline scan done and you only want to know if there is unequivocal pathology present that requires immediate or urgent medical intervention. If you can’t get that assurance from him, ask for your results only in writing on the same disk on which your scan is written.

* Don’t look at your scan or the written report that accompanies it. If you have a reliable and willing CO, send a copy to them and ask them to send you the results a year from when they receive the media with the images and the report on it. Duplicate CDs are typically made and given upon request at no charge, or for a small fee at the time you are imaged, or when you come for your results. Bring your own media to save money!

* Do provide a copy of the disk with the scan on it to your medical surrogate and to anyone who is on you ICE (in case of emergency) contact list on your mobile phone. The reason for doing so is that, should you experience SCA during the blinded waiting period, the scan may still save you from autopsy if it documents the presence of CAD, or some other pathology that could have caused your sudden and unexpected deanimation.

* Don’t  rely on the DSS to keep you out of trouble, or to reassure that everything is OK, should you develop serious health concerns. Just because a scan shows no indication of pathology does not necessarily mean that there is none. If you have signs or symptoms that would have prompted medical attention absent scanning, act on them in the same way after scanning. Let your physician decide if the scan is significant in the context of any illness or concerns.

* Don’t forget that the scan intervals are 5 years and that is more than enough time for serious disease to develop. Indeed, the 5 year window is a long one, especially where cancer is concerned. A DSS is not a health promotion or a disease prevention program. It’s primary purpose is to let you know you are terminally ill, not to assist you in avoiding that eventuality.

* Do know that if you have atherosclerosis, “vasculopathy” and you want to monitor progression of the disease, your scan intervals will have to be much shorter than 5 years – probably 6 months to 1 year, depending upon the severity, your response to medical intervention, and so on.

Economies of Scale?

Medical imaging is a highly competitive, non-monolithic industry consisting of many operators, large and small, both independent and institutionally affiliated. Such market environments inevitably encourage the drive to survive, and thus typically offer the discriminating consumer the opportunity for real bargains. I made a number of calls to imaging centers around the US and discussed the possibility of group discounts and “scan plans” wherein members of an organization or group, even just a group of like minded individuals, could get deep discounts on scans. The majority of centers I spoke with were receptive to this idea, and several discussed specific numbers which were anywhere from 20% to 60% lower than their standard walk-in fee.

Thus, it should be possible for groups of cryonicists in a given geographical area to make arrangements with a local imaging center for scans. The same was also true when I inquired about group or institutional discounts for carotid and abdominal ultrasound screenings, with the difference being that in some cases, prices went from ~ $350 per screen to ~ $60 per screen, providing the group could be scheduled for the same time and place.

The Pre-Cryopreservation Baseline CT Scan

Figure 27: A hypothetical pre- and post-cryopreservation  CT cerebral angiogram. The post-perfusion image would be obtained by administering radiocontrast agent(s) into the perfusate immediately, or shortly before discontinuing cryoprotective perfusion, prior to deep cooling to storage temperature.

If it is at all possible, a final vital CT scan of the head (at least) should be done as close to the time of cryopreservation as possible. This scan should be done with contrast and with no concerns about clinical radiation dose limitations, since the member will be terminal. The objective of this scan is to document, in as much detail (highest resolution) possible, the morphology of the brain and its vasculature. The imaging technique used should be one that optimizes resolution of the cerebral angiogram. The reason for making these images is that they should allow for many important determinations about the quality of initial stabilization and cryoprotective perfusion and cryoprotectant distribution in the brain to be made, at leisure, during the period the patient is in storage.

If contrast agent(s) is injected into the perfusion circuit shortly, or immediately prior to the discontinuation of perfusion, it should be possible to obtain a post-vitrification angiogram, which in turn should allow for evaluation of cerebrovascular patency, as well as assist in determining the anatomical landmarks within the cryopreserved tissue. It should also be possible to add other kinds of tracers to the perfusate, which might allow for quantification of regional distribution of cryoprotectants, or of other molecular species of interest not only within the brain vasculature, but within the brain parenchyma, as well. Again, the presence of a baseline pre-cryopreservation scan will likely be of great importance in allowing accurate interpretation of post-cryopreservation images.

This scan must be a CT, as opposed to an MRI, since MRI scans are unobtainable in deep hypothermia, or in the solid state.

Radiation & Risk

When the mass media talk about the “risks” from radiation associated with CT scanning, the first question that should spring to mind is, “Risks to who?” Sensitivity to ionizing radiation varies based on the cell age and mitotic cycle, and what this means in practical terms is that the younger you are, the greater the risk radiation presents to you.  Children thus have a much higher relative risk when compared to adults due to their rapid cell division and cell differentiation rate.

Figure 28: The risk of developing cancer as a result of radiation exposure is strongly age dependent and decays dramatically as people age. By the time an individual is in his 60s, 70s or 80s, the risk of neoplastic disease from medical imaging becomes negligible. Adapted from ICRP Publication 60 (1990).
 

These data also demonstrate that you cannot simply use the average relative risk shown in Table 1 to estimate the increased incidence of cancer due to radiation exposure. In order to do this analysis correctly, you need take into consideration the age of all individuals in the irradiated group. For instance, a man of 80 has a life expectancy of about 8 years, versus 33 years for a man of 45. Thus the risk to individuals over the age of 70 is, for all practical purposes, essentially nil. Table 2 illustrates what the  American College of Radiology considers minimal to high radiation doses in “absolute” terms.

This is why there is an increase in the relative risk values for the “entire population”  if children are included in that evaluation. However, even a quick glance at Figure 28 (above), where the estimated lifetime risk that radiation will result in cancer (carcinogenesis) is presented relative to the person’s age, shows that children have a 10% – 15% lifetime risk from radiation exposure, while individuals over the age of 60 have minimal to no risk (due to the latency period for cancer and the person’s life expectancy).  The accepted latency period is, by the way ~ 10 years.

Table 1 shows the relative risk of developing cancer per sievert (Sv) unit of radiation exposure. Tables 3 and 4 provide some comparison benchmarks of radiation exposure both in relative terms (low, medium, high) and in terms of common, specific medical imaging procedures used in regional CT.

So, let’s put this information in the context of a cryonicist wishing to reduce his risk of unexpected deanimation. The protocol being proposed here assumes a baseline scan at age 45 for males (50 for females) which, if free of any indication of ongoing morbid processes, is to  be repeated in 5 years, at age 51. If than scan is negative, subsequent scans would be performed at intervals of 5 years (if negative) until age 81, at which time the scan interval would decrease to 2 years. If we assume a lifetime cancer risk of approximately 1 in 1000 and a total of 7 scans  until age 81, at which point any further risk from radiation exposure becomes irrelevant, we might expect to see an increase in the lifetime risk of cancer from approximate 33% to 34%.  Even if the number of scans were more than doubled to 20; one per two years during the interval between age 50 and age 80, the lifetime risk of cancer would increase at most to ~ 35%.[1] This of course, assumes that all DSSs are CT, as opposed to MRI.

These risk calculations are based on the linear no-threshold (LNT) model of radiation risk.  This model assumes that the carcinogenicity of radiation is proportional to dose, even down to the lowest levels.  No one really knows how carcinogenic low-dose radiation is, because the carcinogenicity of low doses is so small that it’s practically impossible to measure. The official position of the Health Physics Society is that quantitative estimates of risk for doses below 50 mSv per year (100 mSv lifetime) cannot be made.[2]

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As useful aside, if you are interested in the progress being made in medical imaging, I would highly recommend the blog Magnetic Resonance Imaging: To See and Be Amazed: http://limpeter-mriblog.blogspot.com/ The site contains many beautiful images and is a treasure trove of information on both the mainstream progress, and the esoterica of MRI

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End of Part 4

(ischemia) ~85% of the time!

By Mike Darwin

Removing a Central Objection to Cryonics

In case you missed it, what I just said in that slim paragraph at the end of the preceding part of this article has profound implication because it has the potential to remove what is unarguably one of  the largest and the most rational objections that there are to cryonics. That objection is that roughly two-thirds of those who have made cryonics arrangements will not be cryopreserved under good conditions, and that half of all those signed up will be cryopreserved under very adverse conditions, such as autopsy or long (greater than 12 hours) post cardiac arrest delay. The recent advances in non-invasive medical imaging I’m about to discuss here offer the opportunity to we cryonicists to make many, if not most such losses all but unnecessary.

Figure 17: False color CT 3-D reconstruction of a patient’s intracranial arterial vascular tree. The orange-red, cheery shaped anomaly behind the right eye is a large aneurysm. The brain and other intracranial soft tissues have been digitally subtracted to facilitate a complete and unobstructed view of the patient’s arterial vasculature.

The image that you see in Figure 17 is now a perfectly pedestrian medical image that can be obtained from a garden variety CT scanner available at most diagnostic imaging centers in mid-sized cities anywhere in the world. This particular image has the brain, the soft tissue and everything digitally subtracted from it but the patient’s arterial tree and skull. The cherry shaped protrusion on the right is an aneurysm which, if were to rupture, could cost the patient his life or leave him profoundly disabled.

Figure 18: Many brain aneurysms can be treated non-surgically by passing a very thin platinum wire within the aneurysm where the wire coils up to form a yarn-like ball inside the weakened, ballooned-out area of the vessel wall. A clot subsequently forms around the coil and the vessel eventually closes off the opening to what was once the aneurysm.

Fortunately, there is a procedure  called “coiling” (Figure 18) which allows most such aneurysms to be successfully treated. Sadly, very people with brain aneurysms know that they have one until it ruptures – by which time it is almost always too late treat it effectively.

Scan Your Troubles Away?

The question logically arises, “Why not look inside everyone’s head if we have the technology to do so? Wouldn’t that allow us to identify not only the people who have aneurysms they don’t know about, but also everyone who has a tumor, or a narrowed coronary or carotid artery, or a gallstone, or anything else wrong with them that they don’t know about? In fact, why not scan their whole bodies and see if anything is amiss? Wouldn’t that allow us to nip most slowly progressing degenerative diseases in the bud?”

The answer to that question is a qualified “Yes and no.” The first and most important qualification to consider is the very substantial difference between them and us. They are going to die and, hopefully, we are not. Once you are content to die, it doesn’t really make a great difference exactly how it happens and it certainly doesn’t make any difference what happens to you afterwards. They will pay exactly nothing to avoid laying around dead for x-hours, or to avoid being autopsied. We, on the other hand, will pay something. That is a huge divide, because, as it turns out, the first and greatest barrier to such universal screening using CT and/or MRI is its adverse cost to benefit ratio.

Figure 19:  The rapid advance of computing and the high demand for ever more sophisticated medical images has driven the cost of 3-D CT and MRI scanning down to ~ $200 for a head scan $800 for a whole body scan.  http://www.superiorbodyscan.com/?gclid=CP_d5Neyiq8CFWwGRQodsHQX-w

While there are many CT and MRI machines, they are kept adequately busy, or perhaps just a little less busy than some of their owners would like, imaging sick and the worried well or hypochondriacal people. If the entire population, or even some modest fraction of it were to suddenly present for imaging, the system would crash. CT and MRI machines are very expensive and while the cost of scans has dropped dramatically, they are still not free. On the macro-level, governments, insurance companies and economists are constantly struggling to determine which therapeutic and diagnostic interventions offer the best return for the money invested in them.

The Problems of Bite Back and VOMIT

Surprisingly, information obtained from diagnostic tests can sometimes not only fail to yield any benefit, in which the case the money spent on the test is wasted, they can also cause harm. A recent example of this, much in the news, is the Prostate Specific Antigen (PSA) test used as a screening tool for prostate cancer (Figure 20). (http://www.pbs.org/newshour/rundown/2011/10/psa-testing-controversy-reignites-over-screening-debate.html) The problem with the PSA test as a screening tool is that to be effective in that capacity it requires a fairly long baseline, a good deal of contextual information (the patient’s race, family history, medications, and so on) and it requires good clinical judgment as well as a ‘patient’ patient.

Figure 20: It was anticipated that the PSA test, used as a screening tool for prostate cancer, would significantly reduce both the morbidity and mortality from the disease. It has so far failed to do so.

A single high PSA reading, or even several, may mean nothing. Most often it is the trend, rather than the absolute number; this is particularly true for black men.  In short, it’s a test that takes a lot of time and thought to interpret and use well and as such is probably not well suited to mass screening where a “yes” or “no” answer is sought before proceeding to costly, invasive and possibly injurious further evaluation.  Yet another problem is that even when prostate cancer is found and treated, it turns out that very few lives are saved because most of those cancers are slow growing and in men who will die of something else before the cancer kills them. Thus, the cost to benefit ratio of the PSA is being questioned, not the least of which because it causes many men to suffer and even die from treatments from which they did not benefit!

This is very much where medicine is today with respect to the “medical imaging singularity.” While it is possible to “look inside” just about everybody, the cost to benefit ratio for the health care system and for the “man on the street” would not justify it. In fact, it would be a medical catastrophe.

To understand why this is so it is necessary to understand three things. The first and most important of these is something called VOMIT, which is a very serious form of bite back associated with our new found ability to see inside patients with increasing exactitude. VOMIT stands for Victim of Medical Imaging Technology and refers to patients who suffer unnecessary interventions for abnormalities observed by imaging or other investigational technology, but which were not found during surgery or subsequent invasive diagnostic interventions. (Hayward, 2003) Here, I will go further and extend the definition of VOMIT to include any diagnostic finding which result in a diagnostic or therapeutic intervention which is not cost effective or causes harm to the patient. That is a very important caveat and tall order to fill, as we shall soon see.

The second is the relatively straightforward one of the ratio of the dollar benefit of resources expended to dollar benefit returned in years of productive life saved as a result of the intervention. Even in cases where early diagnosis saves lives, such as in breast cancer screening, the economic returns are equivocal. It is also often the case that “early” diagnosis with existing imaging technology is still not early enough to cure the disease. As a result, the patient suffers a longer, more miserable course of treatment and the healthcare system is subjected to greater expense with no return.

The third is the problem of information overload and it is somewhat related to VOMIT. The truism that a picture is worth a thousand words is probably a vast understatement. A single 3-D medical image contains a vast wealth of information – information which has heretofore been unavailable to both the clinician and his patient.  This might seem like a good thing, and in the long run it will be, but for now, and for a long while to come the details of the landscapes being revealed will, to a great extent, be terra incognito.

The Danger of TMI

When advances in microelectronics allowed for 24-hour ECG monitoring in the 1970s,  it became possible for clinicians for the first time to see the beat by beat electrical activity of their patients’ hearts for up to a day at a time, or longer. Prior to that, they were limited by the enormous quantities of paper tracings that would be required and the need to confine the patient to the clinic or laboratory. Now, with the advent of the compact and mobile “Holter monitor,” it was possible to capture the patient’s ECG data continuously under ambulatory, real-world conditions (Figure 21). Physicians were awash in a veritable sea-tide of data!

Figure 21: The Model 445 Mini-Holter Recorder which was released in 1976 allowed clinicians for the first time to “see” their patients’ ECGs under real-world conditions and for prolonged periods of time.

The problem was , they assumed, quite understandably, that they knew what it all meant. After all, doctors had been looking at patients’ ECGs for decades in their offices, in hospitals, at bedsides in homes and in physiology laboratories. They knew how to read  an ECG! So, when they discovered that some of their patients had periodic bouts or “runs” of very worrisome arrhythmias, they did the prudent and rational thing – they treated them for these arrhythmias with medications. Unfortunately, the result was the opposite of that expected; a significant increase in morbidity and mortality in these patients, because it turns out that in a subpopulation of healthy people, those arrhythmias were benign and not indicative of any health problem.  Thus, misinterpretation of the “same” information they were confident in dealing with in small chunks, presented in bulk and in a different context, was one of the unforeseen and arguably unforeseeable bite back consequences of Holter monitoring technology. (Harrison, 1978)

The Last Heart Attack?

If you assemble and then read over the Alcor case summaries of the last 40 years it is impossible not to be shocked by the seemingly high incidence of sudden and unexpected cardiac arrests. Because my data set is incomplete for Alcor, I can’t be definitive, but the number seems to be somewhat higher than for the same subpopulation of people from the general population (white, middle class, etc). Until, that is, you consider that most cryonicists are male. So, as you read accounts of cryonicists in their 40s and 50s arresting while scuba diving, while taking a nap or watching television, in part what you are seeing is selection bias at work. The point is, no one ever died of “sudden heart disease” a “sudden aneurysm” or, for that matter “a sudden cancer.” These are degenerative disease that takes years to decades to develop. While still difficult to detect in their nascent stages, their terminal lesions are usually very visible many months and sometimes for even for many years before they end lives.

Figure 22: Coronary artery calcium scoring using computed tomography and carotid intima media thickness and plaque using B-mode ultrasonography offer the prospect of detecting almost all coronary artery disease before it reaches the stage where it can cause a heart attack or sudden cardiac arrest.

There has been a great deal of media attention lately to an initiative called SHAPE; The Society for Heart Attack Prevention and Eradication,  which aims to all but eliminate heart attacks by combining CT of the heart to obtain a “myocardial calcium score” (a powerful risk predictor of heart attack)(Figure 22) and carotid intima media thickness and plaque using B-mode ultrasonography as part of a three step program to eliminate heart disease. The next two steps in SHAPE’s plan are a “polypill” combination of blood pressure and anti-atherosclerosis drugs and finally, perhaps, a vaccine. A similar “Last Heart Attack in America” initiative focused on coronary scanning along with dietary interventions to reverse atherosclerosis has been the focus of a feature length documentary on CNN in which former US President Bill Clinton is prominently  featured as a spokesman and advocate. The common ground of these two initiatives is that almost no one dies of a heart attack without there being  glaring evidence present in their hearts years before the infarct occurs. It is only necessary to look for it!

There can be no question that as imaging technology evolves, and as medical acumen catches up with what is available, that such imaging will become a routine part of any checkup  for patients whose age and risk profile merit it (and eventually, if they live long enough, that means most patients). As it stands right now, if you are a middle aged man or woman with a significant risk profile for heart disease, and you have a heart attack, it’s my personal opinion you have ample grounds to sue your physician for negligence.  Right now, that’s just my opinion, so it doesn’t count for anything, but the point is that sooner or later this, or a better coronary imaging modality is going to become the standard of care and heart attacks will become a rare event – a thing of the past – a relic from a time when doctors couldn’t see inside of you.

Ultrasound Investigations

There are cheaper, simpler and completely risk free ways (in terms of radiation) to  find out whether you have atherosclerosis or not.  The most predictive of these for money is the carotid ultrasound (CUS) test.

Figure 23: The carotid ultrasound scan is  a simple, non-invasive diagnostic investigation that employs sound waves to create an image of the two large blood vessels in the neck that supply most of the blood to the brain. If there is a buildup of plaque or a thickening of the limning of these two arteries the person is at increased risk of stroke and there is a high probability that there is also systemic atherosclerosis present. If there is evidence of severe narrowing of one or both of the vessels, then it becomes urgent that medication and possibly surgery be used to correct the condition in order to avoid the likelihood of a crippling or lethal stroke.

This simple, non-invasive test takes just a few minutes and uses ultrasound waves to image the carotid arteries and the blood flowing through them (Figure 23). If there is thickening of the arterial wall, or plaque present, then it is a virtual certainty that the person has systemic atherosclerosis and warrants a more extensive workup. This test is often also “packaged”  with a quick “look-see” at the abdominal aorta also using ultrasound, to rule out the possibility of an abdominal aortic aneurysm – something that is more common in smokers once they reach middle age, and beyond.

If you shop around diligently, the cost a CUS can be as little as your transportation costs to the health fare or community center where it is being offered, often as a “loss leader” by health care providers or medical imaging companies seeking more remunerative business opportunities (if they find something amiss during the CUS).  The cost of such an evaluation can range from as little as $60, to as much as $380.

A CUS is ideal for people on a budget and for those under age 45 with no history of heart disease, cancer or other pathology or risk factors that might put them at increased risk of sudden cardiac arrest.

Why Full Body Scans?

Figure 24: The full body CT or MRI scan is often offered as “add-on” to the complete or the “executive’s” physical. Many imaging centers offer these scans without the need of the patient’s person physician prescribing the scan using their in-house radiologists to write the order for the test. http://www.prevenium.com/contact.asp

 Put simply, there is no substitute for seeing, or to put a new twist on an old adage: a picture is worth a thousand medical tests. While the origins of all of the degenerative diseases that kill us are at the molecular level, mostly we die as a consequence of the macro-level changes they inflict on our bodies, even if the coup de gras is rooted in the action of things like adhesion molecules and inflammatory pathways; as is the case with most heart attacks. It is the large, easily “seen” bulges of aneurysms, masses of plaque or tumor that kill, and these almost always take years to develop. What this means practically is that, with a few exceptions, aside from suicide, homicide and accident, virtually no one has to die – or to deanimate without plenty of advance warming. The implications for cryonics are as obvious as they are profound.

End of Part 3

(ischemia) better than ~85% of the time!

By Mike Darwin

Ischemia: The Problem of “Long Down Time”

 Almost every cryonicist I’ve ever spoken with envisions his cryopreservation will occur under ideal circumstances. He will be diagnosed with  some vague and ill defined terminal illness, bravely decide to end futile treatment and then enter hospice with a team of skilled and caring cryonics personnel at his bedside. He will nap, read, watch TV, and then, near the end, nod off surrounded by loved ones as the cryonics personnel hover nearby. This may not be the most attractive picture in any absolute sense, but it is certainly as reassuring a one as it is possible to find in contemporary cryonics. And while many, or even most cryonicists may find this scenario credible, much of the rest world doesn’t.

 Figure 10:  Approximate U.S. distribution of predictable deaths by cause based on 2004 data. Note that ~57% of all deaths occur sufficiently suddenly, or under circumstances such as accidents, which preclude standby or other cryonics stabilization measures. Chart derived from data: [National Vital Statistics Report, Volume 53, Number 5 (October 2004)]. This data may be compared to the data in Figure 10 to see how closely the US national incidence of sudden and unpredictable death map that of Alcor’s experience (Figure 11).

One likely reason for the scarcity of biomedical people involved in cryonics is that their actual, day-to-day experience is at sharp odds with the scenario I’ve just laid out above.  In countless hours of both focused and casual conversations with such individuals, what emerges is a sense of incredulity about the reversibility of the damage these professional and technical people witness as a part of their duties caring for the very old, and the critically ill dying; not to mention that large fraction of people who die suddenly and without warning, end up as DOAs in the emergency department or coroner’s cases. Regardless of whether their opinions prove the valid ones, we are clearly failing to communicate to them and to the community at large, an experience of cryonics which is not so biomedically adverse.

To do that, it is first necessary to move beyond  anyone’s scenarios or suppositions and evaluate the reality of what is actually happening to the patients we cryopreserve. That turns out to be a hard thing to determine with any degree of precision, because none of the cryonics organizations maintain any kind of statistical database on their members’ cryopreservations. How many cryopatients have dementia? How many were autopsied? What is the mean ischemic time from cardiac arrest to the start of cardiopulmonary support (CPS)? How many patients have ischemic times of 2-5 minutes, 5-10 minutes, 15-30 minutes, 12 hours, 14 hours, 5 days? What is the mean age at cryopreservation? [Absence of data on this last question I find particularly amusing in a group of people supposedly preoccupied with longevity and "life extension": how long are they living, on average?]  There is currently no way to tell.

There is not even any way to determine the age, gender, or any of dozens of other potentially critically important demographic details that are, or could be vital in assuring quality cryopreservations, reducing ischemic times, or reducing known iatrogenenic events. A concern of mine for onto three decades now is that we have no way to spot adverse epidemiological events that might be associated with our unique dietary supplement or other lifestyle practices. Perhaps most incredibly, there are no written criteria, however arbitrary, to assign any degree of quality, or lack thereof, to the cryopreservation a given patient has received (let alone that a given Cryonics Organization (CO) provides, on average). This had lead to what has become known as “the last one is always the best one” to date rating system, wherein each case that is not either an existential or an iatrogenic disaster, is pronounced by the staff who carried it out as, “the best case we’ve done so far!”

We cryonicists may be in some kind of willful, data free fog about what our situation is, however, it’s a safe bet to assume that most of the rest of the world, based on their own professional and personal experiences, are not so ignorant. The first step towards a solution is to understand the scope and severity of the problem by getting reliable numbers. While that is not easy to do, the Alcor Life Extension Foundation does maintain a crude, if incomplete accounting of all the patients they have placed into cryopreservation: http://www.alcor.org/cases.html. A cursory analysis of this yields the following breakdown. Even basic data such as cause and mode of death are missing from ~20 of the cases listed there – these have necessarily been excluded from the analysis below.

Figure 11: A major hurdle to evaluating quality in cryonics operations is the lack of any outcomes (e.g., reanimation followed by evaluation) or of any surrogate markers or scoring systems to serve as evaluation tools to determine not only the quality of cryopreservation care being given, but also the objective neurocognitive status of the patients when they enter cryopreservation. For the purposes of this analysis very crude criteria were used to assess the quality of the patient as a finished product at the end of cryopreservation. These were normothermic ischemic time between cardiac arrest and the start of CPS, catastrophic peri-arrest brain injury such as an intracranial bleed followed by prolonged cerebral no-flow before pronouncement of medico-legal death, very long warm ischemic times (> or = to 12 hours) and autopsy.

Using the criterion of “minimal ischemia” (≤15 minutes)[1], 48% of Alcor’s patients are cryopreserved under these conditions (Figure 10).  Thirty-nine percent of their patients suffer long ischemic periods of 6-12 hours or more (mostly as a result of SCA and UDA); and 13% suffer very long periods of ischemia (> or = to 24 hours) which are not currently preventable, or which conclude in autopsy prior to cryopreservation.  Put more cogently, you have less than a 50% chance of being cryopreserved (with Alcor) under conditions of minimal ischemia. While this number is discouraging, it is spectacular when compared to the Cryonics Institute, where it is somewhere in the low single digits.

Figure 12: The graph above is the same as in Figure 11, with the difference being that the losses have been expanded to include those that would be expected if the population wide incidence of end-stage, GDS-7 dementias were imposed on all the groups. The result is that percentage of patients who might reasonably be expected to have both minimal ischemia and no pre-cryopreservation GDS-7 dementias drops to just 26%.

But once again, these numbers are misleading if the criterion is cryopreservation under minimal ischemia conditions, because they do not take into account the number of patients who enter cryopreservation with dementia, or severe brain injury due to stroke, other neurovascular disease, or massive head trauma. If only dementia, at the current incidence for the general population is factored into the analysis, then the picture becomes considerably more bleak, as can be seen in Figure 10, with only 26% of  Alcor cryonics patients being preserved with relatively intact brains under reasonably good conditions.[2]

Impact of the BDDs on the Likely Survival of Personhood

Figure 13: The effect of advanced Alzheimer’s Disease on the macroscopic appearance of the brain is evident when coronally sectioned brains from an AD (R) patient and a healthy person in their mid-20s (L) are compared side by side.

Deaths from AD are typically deaths from end-stage AD, which usually implies severe global destruction of both cerebral hemispheres (Figures 13 & 14) on both a macro and microscopic level. Death due to AD is a prolonged process (~8 years from diagnosis to death), and the neurological deterioration that occurs as the disease progresses is often scored using the global deterioration scale (GDS) of primary degenerative dementias, which ranges from 1 (least) to 7 (worst) in severity. GDS scores in excess of 5 are associated with major loss of macro- and micro-scale brain structure and will be assumed here to represent serious compromises to, or the destruction of personhood.

Figure 14: The histological appearance of the brain in AD is shown in panels b and c above. In many areas of the brain there is virtually complete loss of the neuropil; the synaptic weave that interconnects neurons which can be seen in its normal state in c, the panel at the far left. The majority of the neurons and many of their supporting glial cells have died and been scavenged by macrophages and histiocyytes.  There are abundant deposits of proteinaceous plaque containing the  neurotoxin protein beta amyloid neurofibrillary tangles which are the remnants of neuronal long processes such as axons and dendrites. The extent and uniformity of the changes seen above varies from patient to patient during the course of the disease, but becomes increasingly uniform throughout both hemispheres of the cortex the longer the patient survives with a GDS score of 7 (end stage dementia).

A Deanimation Warning Device?

Figure 15: The medical imager as a deanimation prediction device?

 In his 1939 science fiction story Life-Line,” Robert Heinlein envisions a device that can predict, with considerable precision, when a person is going to die. While none of us cryonicists wants to die, most of us could certainly profit from knowing when we are going to deanimate. Better still would be also finding out how to postpone our cold dip in liquid nitrogen for a while, if it was possible to do so.

Many cryonicists will be familiar with this graph of Ray Kurzweil’s showing the impending arrival of the singularity (Figure 16).

Figure 16: Ray Kurzweil’s graph showing the exponential increase in neuro-image reconstruction which has occurred largely as a function of the exponential growth in computing capacity since 1970.

Well, if you are a cryonicist, I’m here to tell you that insofar as non/minimally-invasive medical imaging is concerned, the singularity is here.

From the earliest days of medicine physicians have desired one thing almost above all others and that is to possess the power to peer into their patients bodies and observe the goings on there. Since the discovery of x-rays by Wilhelm Conrad Röntgen in 1895 (Crane, 1964) there has been steady progress towards the satisfaction of that desire. The development of contrast media, endoscopy, computerized axial tomography (CAT or CT) scanning and magnetic resonance imaging (MRI) scanning have allowed increasingly exact and impressive images of the interior of the living body to be made.

However, a number of serious limitations have, and to a great extent still do prevent the full realization of the physician’s idealized desire to see inside his patients at will. Those barriers are field, dimensionality and point of view, as well as resolution, color, contrast and the dollar cost of the imaging.

In the case of CT and MRI those barriers have been breached to such a degree that it is now possible for cryonicists to be able to determine with a very high degree of accuracy and precision both of what and when they are going to experience medico-legal death. A corollary of this is that in many cases it will be possible for them to avoid what would have otherwise been an unavoidable very long period of ischemia and quite likely a medico-legal autopsy  as well.

End of Part 2

How to avoid autopsy and long ‘down-time’

(ischemia) better than ~85% of the time!

By Mike Darwin

It’s easy to concentrate on the biggest and most obvious reason that cryonics hasn’t attracted wider acceptance, principally the fact that it doesn’t work “yet” and it will be a long time before we know if does. But there’s a clue to another capital reason for its slow adoption which is to be found in the failure of cryonics to attract much enthusiasm or activism within its own ranks. Why is this?

I believe a central reason for this failure is that cryonics, even as it is currently configured and accepted by those who embrace it, performs dismally. Everyone seriously involved with cryonics is painfully aware, either consciously or subconsciously, that cryonics is at least a two tier lottery. Sure, everyone knows that we’re taking a “chance” on being recovered in the future by being cryopreserved in the first place. But to even get to that round of the lottery, you have to get cryopreserved, and it would seem material whether or not you are cryopreserved well.

For some, perhaps cryonics is a ritual exercise. As long as there are remains, a freezer, someone to take the money and hang picture on the wall, then you have a chance; and all chances are created equal. Their position seems to be same as that of the millions of lottery ticket holders before the winning number is announced: we all have the same chance at the prize. If that’s your attitude, you can stop reading this right now, there’s nothing more here to interest you – not even in terms of idle entertainment value, because this discussion, from here on out is deadly serious, and brass tacks practical.

 Figure 1: The autopsy rate has declined by half in the United State between 1972 and 2007, although it has shown a slight increase since these data were collected. Source: http://www.cdc.gov/nchs/data/databriefs/db67.pdf

As Figure 1 shows, the autopsy rate, which can serve as the ultimate, population wide indicator of a very bad cryopreservation,  constituted 8.5% of all deaths in 2007. That percentage has risen slightly since then and is now at ~ 9%. The situation isn’t quite as grim as it might first appear if you break down the reasons for autopsy and note that 55.4% of autopsies were conducted as a result of deaths due to “external causes,” which means suicide, accident or homicide. If you think you are in a “lower risk” category for these, you may  be right, in which your case your risk may be fractionally smaller. And of course, not all of these autopsies were state mandated: some were requested by the next of kin, or even the decedents themselves. Still, 9% seems a reasonable, overall unavoidable loss number currently confronting cryonicists given the culture we inhabit.

Figure 2: Since the first man was cryopreserved in 1967, the demographics of autopsy have shifted increasingly from the aged to those in younger population cohorts. Source: http://www.cdc.gov/nchs/data/databriefs/db67.pdf

If the age distribution of autopsies in the US is examined, the picture gets even more uplifting if you are, or you expect to live in into old age (which is, incidentally, medically defined as 65 years of age, or older). In this age group, the incidence of autopsy has declined dramatically from 37% of all postmortems since 1972,  near the time cryonics began, to only 17% as of 2007.

However autopsy is only one of a number of factors that can and do interfere with  cryonicists achieving “good,” or even “acceptable,”  (forget  ideal), cryopreservations. The other three factors which loom large are sudden cardiac arrest (SCA), unexpected death (UD, which is different than SCA) and brain destroying diseases ( BDDs, or dementias). While Alzheimer’s Disease is the most common of the BDDs, there are others such as Pick’s, Lewy Body, Parkinson’s and the vascular dementias, which together account for 20-30% of all age-associated BDDs.

Brain Destroying Diseases (Dementias)

Autopsy is only one of a number of factors that can and do interfere with  cryonicists achieving “good,” or even “acceptable,”  (forget  ideal), cryopreservations. The other three factors which loom large are sudden cardiac arrest (SCA), unexpected death (UD, which is different than SCA) and brain destroying diseases (BDDs).

 Figure 3: Incidence of dementias as a percentage of all cause mortality in males, females and the United States population as a whole. Prepared from data in the National Vital Statistics Report Volume 59, Number 10 December 7, 2011Deaths: Final Data for 2008: 2008http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_10.pdf

 Currently, the BDDs in aggregate (including catastrophic stroke) account for ~3.2% of all deaths in the US (Figure 3). However, insofar as cryonicists are concerned, this number is likely to be misleadingly low, because most cryonicists enter cryopreservation at or after age 65, the point at which the incidence of BDDs begin to climb exponentially. (Evans DA, 1990) This number is expected to, and in fact is exploding as a consequence of both the demographic shift due to an aging population in the West and increasingly longer life spans (Figure 4).

 Figure 4: The large increase in Alzheimer’s Disease as a cause of death in the United States is largely a function of the increasing average age of the population and the survival of many additional individuals into advanced old age. Source: http://www.alz.org/downloads/Facts_Figures_2012.pdf

 Figure 5: A breakdown of dementias by type shows that Alzheimer’s Disease accounts for 47% of the total as the sole cause of the dementia and is a major contributing factor in another 28% making it by far the most common pathological mechanism in play as the cause of dementia in the elderly.  [S. Seshadri, S, Wolf, PA, Beiser, A,  Au, RU, McNulty, K, White,R, et al. Lifetime risk of dementia and Alzheimer's disease: The impact of mortality on risk estimates in the Framingham Study. Neurology, 49:1498-1504,1997.]

 Figure 6: Incidence of Alzheimer’s Disease by age cohort in the US population as of 1988.[ Evans D, et. al. Prevalence of Alzheimer' s Disease in a community population of older persons. JAMA, 262:18;2551-6, 1989.]

In the 74-84 age cohort, 19% of that population has AD (exclusive of other dementias) and in those individuals over the age of 85, the diagnosed incidence is 47%. These numbers are almost certainly low, because many of the elderly are who are institutionalized for falls, or other issues not ostensibly related to primary brain disease, go on to develop brain disease in an institutional setting and ultimately have listed as their causes of death, pneumonia, urosespsis, sepsis  secondary to decubitus ulcers, or other causes that escape epidemiological surveillance for AD. Currently, AD is responsible for 2.8% of deaths in white males men aged 65  or older and 4.7% of white males who are 85 years of age, or older. These numbers are expected to triple by the year 2050.

 Figure 7: The incidence of Alzheimer’s Disease rises roughly exponentially with age such that over 1,100 people out of 100,000 aged 86 or older have the disease.

When cryonics was launched in the mid-1960s the problem of BDDs as a threat to the workability of cryonics was not even considered.  In 1967, the year the first man was cryopreserved, the average life expectancy in the US was ~70 years and the problem of dementias was a fraction of what it currently is.  Additionally, comparatively little was known about the pathophysiology of the BDDs at that time, and there was little or no awareness within the cryonics community of their potential to degrade or altogether destroy personal identity, perhaps even years in advance of the pronouncement of medico-legal death. The problem of BDDs and of age-associated destruction of the brain is arguably the foremost biomedical obstacle confronting cryonics in the long term, and it is for this reason that I will return to this topic again later in this article in the context of discussing its early detection, with a brief discussion of treatment, and ultimately, definitive interventions to halt and reverse it.

Figure 8: The Siemens Biograph mCT PET is a positron emission tomography/computed tomography (PET•CT) scanner that enables precise measurement of metabolic processes and data quantification, including the assessment of neurological disease and malignant tissues (resolution and molecular characterization of neoplasms as small 3 mm in diameter). The device can provide quantitative measurements of brain beta amyloid protein burden.

For now, I will note that because AD is by far the most common of the BDDs and because it has a unique pathophysiological feature, a remarkable advance in early diagnosis via noninvasive  computerized tomography (CT) and positron emission tomography (PET) imaging has recently become clinical available. Beta amyloid is the protein found in the plaques characteristic of AD, and there has been intensive research over the past decade to identify radiolabeled tracer compounds that will safely cross the blood brain barrier (BBB) and bind to both beta amyloid and tau proteins. (Barrio 2008), (Black, 2004)  In February of this year, the US FDA approved the Siemens Biograph mCT, a positron emission tomography-computed tomography (PET-CT) scanner capable of not only detecting, but of quantifying  amyloid in the brain. The Biograph mCT has been very well received, and within the space of a few months the machines have appeared in most major cities in the US. The Biograph mCT in conjunction with the recently developed FDDNP, (2-(1-6-[(2-[F-18] fluoroethyl)(methyl)amino]-2-naphthylethylidene) malonitrile) tracer allows for calculation of total brain amyloid burden (Wang, 2004) and visualization of discrete amyloid containing lesions as small as ~ 3 mm in diameter (tracers for tau protein, the other primary pathological protein in AD are currently in the pipeline for FDA approval).

 Figure 9: Top: PET scan of beta amyloid deposits in the brain of a patient with early moderate Alzheimer’s disease appear in red in the image above. The beta amyloid deposits are concentrated, as expected, in the frontal and prefrontal cortices as well as in the hippocampus. Bottom: Beta amyloid distribution in the brain of a patient with early moderate AD (L) versus normal control (R). One important consequence of this imaging is the growing realization of the global range of AD’s impact on the brain. As recently as a decade ago it was believed that the destruction of brain tissues was confined largely to the hippocampus and the prefrontal cortex, especially early in the disease. It is now understood that the histological destruction of AD is widespread and that during the end-stage of the disease few if any areas can be expected to be spared.

Very early detection of AD may turn out to be critical to achieving effective treatment, or even slowing progression of the disease, since significant beta amyloid and tau deposition seem to promote ongoing inflammation and interfere with putative therapeutic drugs. A good example of this is the recent fate (Vellas, 2010) of the investigational drug  tarenflurbil ((R)-flurbiprofen ) which inhibits gamma-secretase, the enzyme that produces beta amyloid AB-42, the species of beta-amyloid that forms fibrillary plaques. (Black, 2008) Unfortunately, the drug does nothing to remove existing existing AB42 deposits, which presumably continue to exert their neuron killing and pro-inflammatory actions.

(R)-flurbiprofen is highly effective in animal models of very early AD and the drug showed significant promise in Phase I & II clinical trials. However, development of (R)-flurbiprofen was dropped when it became apparent in Phase III trials that the drug would likely only be effective in a clinical setting if it its administration was begun before clinical signs of AD developed; in other words, when beta amyloid levels were very low and would be detectable only by testing cerebrospinal fluid or, now with sensitive CT molecular imaging techniques involving the screening of subpopulations of healthy individuals at risk.

This kind of effort and application of technology and pharmacotherapy may not profitable for pharmaceutical companies, but that does not mean that it would be be worthwhile for us cryonicists. (R)-flurbiprofen  is a close chemical relative of the OTC NSAID ibuprofen and it is a metabolite of the prescription NSAID flubiprofen.  (R)-flurbiprofen  is an enantiomer of flurbiprofen (~ 5%  of (L) flubiprofen is metabolized into (R) flubiprofen by the liver after ingestion) which is completely inactive as  a COX inhibitor, and is thereby free of the anti-COX side effects associated with NSAIDS.  Despite it’s lack of both COX-I and COX-II activity, the drug does have strong anti-inflammatory activity by acting through inhibition of NF-κB and AP-1 activation pathways, and this may provide added benefit in controlling the inflammatory processes associated with AD. (Tegeder, 2001)  As an interesting aside,  (R)-Flurbiprofen has also been shown to suppress prostate tumor cells by inducing p75NTR protein expression. (Quann, 2007)

(R)-Flurbiprofen is an example of a drug with considerable therapeutic potential that will almost certainly not see clinical application due to the high cost associated with regulatory burden and the logistical hurdle of needing to start therapy years before symptoms of AD manifest themselves. (R)-Flurbiprofen might also conceivably be useful as combination therapy with  the already FDA approved skin cancer drug bexarotene (Targretin), an antineoplastic, which has been shown to reverse beta amyloid deposition in a rodent model of AD as well as to improve cognitive function. Targretin rapidly cleared beta amyloid from the brains of animals in a variety of models of AD (<2 months) and while it is not a cytotoxic chemotherapeutic agent, the drug has sufficient adverse effects that it would be problematic to administer over a period of years or decades. A combination of short term therapy with Targretin to remove beta amyloid, followed by long term administration of (R)-Flurbiprofen is a possible treatment strategy that would seem attractive to explore. The ability to dynamically monitor beta amyloid levels in the brains of patients undergoing such novel therapeutic regimens, especially outside the confines of the medical-industrial establishment, is yet another advantage of this evolving singularity in medical imaging.

End of Part 1