(Crossposted from Depressed Metabolism)

On September 6, 2007 we launched the blog Depressed Metabolism for a number of reasons. The most important one was to launch a blog with a strong emphasis on cryonics. Although there are a number of good blogs on aging and life extension, there was not such a blog for cryonics. Another reason was to revive the spirit of Alcor's Cryonics Magazine of the 1980s and early 1990s, which had a strong emphasis on technical discussion of cryonics and related sciences. The Internet, and the blog format in particular, enabled to create such a forum again at reduced cost. The third reason was that the blog also enabled the authors to organize their thoughts and make contributions to a number of technical issues in cryonics. Although this objective has often produced long and technical entries, Depressed Metabolism has documented and, sometimes, contributed to the science of human cryopreservation on topics ranging from reperfusion injury to cryoprotectant toxicity.

One of the important themes of the blog has been that experimental science is hard. What appears to be a  good idea in theory, can die an unexpected death in the lab.  For this reason we have restrained ourselves from reporting hot-off-the-press discoveries in bioscience. There does not seem to be a single theory in science that is not supported by one research paper or another. To the extent that we have reported on new research, we generally have used a (new) paper to discuss the topic in a broader context. Another reason why we exercise moderation on this front is because without looking into detail at the research design and methodology of a study, it is hard to assess its credibility.

When we started in September 2007, our statistics showed a couple of unique visitors a day. Since then, visits to Depressed Metabolism have picked up a great deal and exceed 100 unique visitors on an average day. The bulk of them seem to be either people with a strong interest in life extension and cryonics or biomedical researchers who stumbled upon the website as a result of Googling technical terms. Some of this traffic would not have been possible without the attention we got from websites and blogs such as Longetivity Meme, Al Fin, and Alcor News. It is not surprising that some of the most popular entries are also the more accessible ones. The most popular entries to date include:

Hydrogen sulfide does not induce hypometabolism in sheep

Fever and brain injury

Why is cryonics so unpopular?

Albert Einstein’s brain and information-theoretic death

Immortality and cryonics

Singularity economics and the future of money

Interview with Cryonics Institute President Ben Best

What is cryonics?

Since we started the blog we have not enabled comments but we do encourage thoughtful and informed responses and will consider publishing them as blog entries. A recent example was Mike Darwin's reponse to a post on structure-function analysis of neuroprotectants. We also created a Facebook Depressed Metabolism Readers Group where readers of the blog can connect and discuss posts and related issues. Unless implied in discussion of technical matters, we have generally refrained from participating in cryonics politics on our blog. Although we are very concerned about the future of cryonics, and that of Alcor in particular, we believe that the best long term strategy to deal with the problems facing cryonics is to set an example. Answer incompetence with excellence, amateurism with professionalism, and secrecy with transparency and accountability. As evidenced by our entry on Alcor's non-democratic self perpetuating board of Directors, we do believe there is a benefit to encouraging debate on the legal and organizational aspects of cryonics. The quality of operations in cryonics organizations suffers from not being subject to market mechanisms, not having a  clear endpoint of care, and wishful thinking on the part of members and donors. One of the guiding considerations for Depressed Metabolism has been to disseminate the knowledge and tools to evaluate the technical operations of cryonics organizations, and that of patient care in particular.

Depressed Metabolism is not the official blog of the cryonics community and as such allows contributors to post on other topics of personal interest. During the last couple of months we have published on such diverse topics as Iceland's Blue Lagoon, science in H.P. Lovecraft's stories, the future of money, rationality and ethics, common political fallacies, human rights, the demonization of oil speculators, dietary supplements, the ideology of death, the chemistry of spontaneously fermented beers, education, children and caloric restriction, the art of Edvard Munch, social scientists, and the world's best vegetarian restaurants. Obviously, the opinions in these pieces are those of the authors only and not of the organizations and companies with which they are associated. Neither do we believe that our opinions on such topics are necessarily part of a broader philosophy. Since we started this blog we have taken great care to emphasize that cryonics should be presented as a form of critical care medicine and not as one element in a broader "transhumanist" or "immortalist" philosophy. Having said this, it is clear to us that cryonics  (and cryonics research) has a better chance of growing and surviving in a culture that values privacy, private property, and freedom of contract.

Looking forward, the cause of cryonics and life extension will remain the primary focus of the blog.  We will continue to publish on the technical aspects of cryobiology, cryonics, critical care medicine, neuroscience, and life extension. We also intend to make additional historical documents available and uncover writings that have never been published before. Expect more publications on epistemology and skepticism, molecular cooking and drinking, practical health issues, local features (Portland, OR), and the arts. Please do not hesitate to write us in case you have something of interest to contribute.

Thanks to all those who have authored or reviewed entries for the blog: Gregory Jordan, Veronique Struis, Shannon Vyff, Mike Perry, Ben Best, Mike Darwin, and Brian Wowk. And thanks to all those who have linked to our posts and articles and/or promoted the blog on their websites or through private correspondence.

Running a blog is less expensive than publishing a paper magazine but not costless (e.g., website hosting, domain registration, reproduction of papers and book chapters, etc). The work we have done for the blog has been very rewarding but often very labor-intensive and time consuming. Please help us keep the blog running and click on the "donate" button on the right sidebar (below) to give a Paypal donation. Thanks for your support!

(Crossposted from Depressed Metabolism)

A recent study in Rejuvenation Research reports that a combination of dietary supplements confer neuroprotection in stroke. Over a 2 week period rats received either a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine  called NT-020 or vehicle (i.e., the same solution minus the compounds of interest) before stroke was induced through middle cerebral artery occlusion (MCAo). Two weeks after the insult the rats were subjected to behavioral tests and histological examination. Rats treated with the dietary supplements scored better on behavioral tests, had less histological damage, and showed evidence of neurogenesis.

This study is interesting for a number of reasons. Foremost, it highlights the possibility that dietary choices can positively affect outcome after ischemic insults. These findings complement research that found that caloric restriction improves behavioral and histological outcome after stroke.  The findings also reinforce that some of the most effective neuroprotective agents to date are ordinary nutrients, vitamins, and hormones. In this study the investigators combine a number of these agents to greater effect. Although the authors do not present specific data on bioavailability in the brain for these compounds, they argue that a multi-agent approach relaxes the dosage requirements for individual agents.

The paper reviews assays that demonstrate improved neurogenesis in the rats that received NT-020 such as endogenous birth of new neurons, neuronal phenotype expression of newly formed cells, and alterations in neurogenic factors. Pharmacological modulation of neurogenesis after ischemia is a young research field and the results reported in this paper provide additional evidence for the (only recently accepted) phenomenon of adult neurogenesis. Unresolved questions at this point include how neurogenesis differs among species and whether post-ischemic neurogenesis can improve long term outcome in humans.

The  design of the current study does not allow a rigorous answer to the question of whether neurogenesis contributed to or accompanied improved outcome. The possibility that other mechanisms (such as  increased free radical scavenging) were primarily responsible for the observed improvements cannot be ruled out based on this study.

Link: Dietary Supplementation Exerts Neuroprotective Effects in Ischemic Stroke Model

(Crossposted from Depressed Metabolism)

Just a superficial look at the history of the life extension movement will suffice  to show the rise and fall of numerous fads and trends in ideas about the mechanisms and “treatment” of aging.  Psychological meliorism and simplistic visions of biochemistry create overly optimistic expectations about extending the maximum human lifespan.  But how can we know if a treatment is able to extend the maximum lifespan of humans without giving it to them and waiting….

In his article “Why Cryonics Will Probably Help You More Than Antiaging” (2004), cryonics activist Thomas Donaldson contrasts cryonics with antiaging as a means to life extension and argues that a major advantage of cryonics is that cryobiology research can move at a much faster pace than anti-aging research, especially as it pertains to humans:

The best possible proof that a treatment will indefinitely prolong the lives of human beings must come from a demonstration of its effects on human beings. Not fruit flies, worms, mice, or rats, but human beings. Yet there’s a small problem here: we are human beings ourselves, and a proof that a treatment prolongs the lifespan of people will take … at least the lifespan of some people…cryobiology can progress much faster than antiaging. Not only that, but its progress almost totally lacks the problems of proving that an advance has happened. The state of a brain, or even a section of brain, after vitrification and rewarming to normal temperature, shows directly whether or not the method used improved on previous methods.

What about treatments that have been shown to extend the maximum lifespan in small mammals? Or using  treatments that have been shown in humans to stop or slow down the aging process?

“It takes a long time and the actual reports on clinical use of a drug for physicians to get an idea of the effects of longterm use of that drug.  Very few drugs of any kind get formal tests for the entire lifespan of normal people taking them.”

Even if people are not prevented from experimenting with various life extension technologies, these epistemological and practical problems cannot easily be overcome.

“No matter what some scientists say, a cure for aging involves many problems all of which will need time for their solution. Even now, you may be young and feel that you need not think about cryonics because some means to slow your aging will come before you’ve gotten very old, and from that still other means to slow your aging even more … and so to true agelessness. In this article we have seen why such dreams of a rapid solution to aging cannot come fast for any of us. At the same time, cryonic suspension able at least to preserve our brains in a reversible form, allowing restoration of vital functions, looks likely to come much sooner.”

And as Robert Prehoda pointed out in an old interview, successful treatment of aging will still leave an individual vulnerable to accidents:

Immortality is statistically impossible because accidents would eventually eliminate all individuals in any non-aging population.

Despite these arguments, the life extension and “transhumanist” movement remains many times larger than the people who have made cryonics arrangements.  Some reasons for this are explored in another entry, but the mystery remains.

(Crossposted from Depressed Metabolism)

This is the first in a series of interviews with individuals in the life extension and cryonics movement. We start off with an interview with Ben Best, president of the Cryonics Institute.

What is your philosophy toward life?

I think that “sense of life” or emotional involvement  in life is the most crucial determinant of orientation toward life per se. I can rationalize and try to  understand my sense of life — and probably exert  influence — but to assert that I have “control” of  it would be saying too much. Existentially, although I sometimes feel “thrown” helplessly into the world,  for the most part I have a conviction that I must accept responsibility for my conditions and exert  effort & intelligence to improve — and that effort  & intelligence can produce results.

I have an immense appreciation of my life and  experiences whether those experiences are positive or negative. I certainly don’t enjoy negative or  painful experiences at the time I am experiencing them (and do not seek them out), but I am glad to have  them in my history. My greatest regrets in life are not so much things that I have done or that have  happened to me, but things that I have not done. The great evils of life are aging and death. If  these two evils could be remedied there would be  time enough to use all that has been learned from  the negative experiences and to create positive experiences that fulfill the promises of life  which I have experienced in tantalizing tastes.  (This is not to say that I have not already  experienced life in a wide variety of ways.)

But regrets aside, I love all that I have  gotten from life, and I simply want more, more,  more… And I am sad that there aren’t more  people who feel the same way. I have written on  these themes on my website:

http://www.benbest.com/lifeext/whylife.html

Are you still a practitioner of caloric restriction?

I practice calorie restriction only to the  extent of eating fewer calories than I would  eat were I not so conscious of benefits of  restricting calories. I was once far more  aggressive in restricting my calories than I currently am. My CRAN (Caloric Restriction with  Adequate Nutrition) practices have been described on my website:

http://www.benbest.com/calories/cran98.html

Do you believe that taking supplements can extend life?

Yes, I think there is no question that supplements  can “square the curve” and extend average lifespan. A major breakthrough occurred in the mid-1990s when  the AMA published a study showing that selenium supplements caused a 50% reduction in cancer  incidence [JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION;  Clark,LC; 276(24):1957-1963 (1996)]. Formerly the  medical establishment insisted that dietary supplements  are of no benefit. My website contains considerable  evidence of supplements reducing the incidence of  various disease conditions:

http://www.benbest.com/nutrceut/nutrceut.html

More controversial is the claim that supplements  can extend maximum lifespan. Unfortunately, too many people believe that lack of convincing evidence  that supplements can extend maximum lifespan is equivalent to evidence that supplements do not  extend lifespan in any way. “Squaring the curve” and preventing disease may be a means to live long  enough (and healthy enough) to benefit from rejuvenation technologies — whether or not  supplements can extend maximum lifespan.

How did you get involved in cryonics?

I was very interested in my health from an  early age — and not because I had serious health problems (I haven’t). I also had an early aversion  to death, and later, as a teenager, enjoyed science fiction stories that described  immortality and endless youth. I found  the PROSPECT OF IMMORTALITY in a health  food store and I also read Alan Harrington’s  THE IMMORTALIST. I argued in favor of the idea  of cryonics years before I became seriously  involved. After getting my computing science degree  and beginning work as a programmer in Toronto  in 1987 I seriously studied life extension and less seriously got involved in cryonics  (became a Director of the Cryonics Society of Canada). My emphasis was more on life  extension, because I did not give cryonics a very good chance of working. Since that time  I have become much more optimistic about the chances of cryonics working. And hopefully I am improving  the chances of cryonics working.

Do you think humans can achieve immortality?

Sadly, no. Forever is forever, and something will  eventually kill every human. I have written about this subject in detail on my website:

http://www.benbest.com/lifeext/immortal.html

What do you consider the most important reasons why  not many people sign up for cryonics?

They don’t enjoy life enough or they discount the reality/proximity of death or they believe that cryonics is in opposition to religion. The third reason is probably  the most important for the most people, but I believe that  it is important to mention the first two reasons as an  explanation for the attitudes of people who do not  use religion as an argument against cryonics.

Do you agree that cryonics should be presented as a form  of long term critical care medicine?

This is a far more reasonable approach than  opposing cryonics to religion, especially because cryonics can only hope to extend life, not guarantee  immortality. I more often describe cryonics as “experimental medicine” to emphasize that it is  unproven and not guaranteed to work.

Have you talked to children about cryonics?

Not much. I did have a recent experience in  which I spoke to about a hundred middle school  students about cryonics in five classes (groups of  20) for about an hour per class. The students were mostly silent, asking very few relevant questions,  so I can’t say much about what it is like to discuss cryonics with children. I was later told  that the next day the children came to class with many relevant questions.

What are your other interests besides cryonics and life extension?

My website shows a range of my interests:

http://www.benbest.com/

which include travel, history, philosophy, economics,  computing, business, and science in general. I have interests, like massage and humanistic psychology, which  I have not discussed on my website. I have some good  friendships, and I am interested in my friends. I am actually  interested in almost everything to some extent and my love  of learning, thinking and understanding has much to do with  my love of life.

I have made a hobby of learning about every element in the periodic table. I have cards with information about each element, and I study these cards while I work-out on my stairmaster, which is my main form of exercise. (I have tried running, but injured myself too often. Stairmaster allows study while getting low-impact aerobic exercise.) A large portion of my Wikipedia edits (aside from cryonics and life extension) are clarifications of information about elements and compounds — questions that occurred to me while studying on my stairmaster.

I have also recently become more interested in planetary science and space travel. Formerly, a desire to see the world of the future did not play much of a role in my craving for extended youth, but increasingly I add a disappointment for not being able to see and participate in all of the exciting things that will happen.

The only sport that interests me very much is women’s tennis. Some of my best friends are women. I am fascinated by women  and hope that I will someday have a lasting and fulfilling  relationship with one. However, I am too much of  a workaholic devoted to cryonics and life extension to  spend much effort on that project.

What kind of jobs did you work before being elected President of CI?

I had many odd jobs before working as a taxi-driver  and teamster (including semi-trailer driver). I also worked as a computer operator, tutor/teaching assistant  and as a pharmacist. Then I became a computer programmer  for a bank and taught computer programming languages  (APL and Java) at night school in Toronto.

What made you decide to run for president of CI?

I decided that the time had come for me to devote my  life to cryonics. I felt that I could make a unique and profound contribution to the workability of cryonics.  Although work as a computer programmer paid well, the  product of my labor was not personally meaningful to  me (which is not the same as satisfaction with doing a good job). It is extremely satisfying to me to be  able to do the work I do as CI President. I cannot think of any other work I would rather be doing. And  I have no desire to not be working as long as I can  do this work.

How did you meet Saul Kent, and to what extent does Mr. Kent  currently influence your actions and behaviors?

I met Saul Kent at the October 1989 Cryonics Conference held near Detroit Michigan:

http://www.cryonet.org/cgi-bin/dsp.cgi?msg=109

Although Saul has been very influential in other cryonics  organizations, this was not the case with the Cryonics  Institute. I am not often in communication with Saul, but I respect what he has done for cryonics and on a few  occasions I have deferred to his wishes on matters  that were not of great significance. I am not conscious  that he influences my actions and behaviors aside  from my appreciation of his financing of cryonics-related  research. Saul is certainly influential in terms of his  authority at Suspended Animation, Inc., with whom many  CI Members (including me) have contracts for  standby/stabilization. But for the most part I have not  dealt with him directly.

What do you consider your biggest failures and achievements at CI?

I failed to get the IRS to grant 501(c)13 status to the  Cryonics Institute. I failed to get a patent for CI-VM-1. I failed to change CI policy to allow acceptance of  neuro patients. I have failed to restore the ability of CI to perfuse in the CI facility.

I succeeded in going through all of the CI Member files  and creating a computer database that provides a means of  quantifying and quickly accessing Member information (and in  the process eliminating bad records of lost and deceased members).  I have greatly improved the content (not the appearance)  of the Cryonics Institute website. I have made significant  revisions to the paperwork and I created contracts for Standby/Transport services for CI Members with  Suspended Animation. I have created computer control for patient cooling. I have placed all of the financial  bookkeeping on CI’s computer, relieving the CI Treasurer of most of the chores of gathering data  for financial statements and payment of taxes. I have written case reports for all new CI patients. I have caused prepayments  to be treated as liabilities rather than income. I have  changed the fiscal year to be the calendar year.  I continue to make improvements in CI perfusion  equipment and procedures. Among other things…

CI encourages member involvement through elections and  mailing-lists. Do you think CI benefits from this?

I co-created the CI Members’ forum with John de Rivaz  and I am pleased with the channel of communication that it has promoted. The forum has put CI Members in touch  with CI Members, Directors, Officers and Staff. I am  usually a very active participant in the CI Members’ forum.

I have actively encouraged CI Members to be candidates  in the Board of Director elections. I think that voting  and running for office increases Member participation  in the Cryonics Institute — which I believe is a  good thing.

What kind of improvements would you like to implement  at CI in the coming years?

I want to improve the efficiency of patient cooling and add the capability to cool two patients simultaneously.  I want to be able to create financial statements more  quickly and easily. I want to improve perfusion methods  and equipment, with a particular eye toward reducing edema.  I want to improve the safety associated with operations in  the patient care area. I want to restore the ability of CI  to perfuse at the CI facility. I want better documentation  for what is done at CI. I need to address the challenges of growth, including adding physical capacity and  additional staff. For CI (and in the cryonics community in general), I would like to see more fruitful attention  and effort devoted to wireless vital signs alarm systems.  Too many cryonicists living alone have suffered massive  ischemia, autolysis and decomposition due to the absence  of such systems. Cryonicists who have a cardiac arrest  while sleeping next to a spouse would also benefit.

What is a typical day like at CI?

Most days involve a reasonable amount of answering  the phone and e-mail. Readings are taken of liquid nitrogen levels in the cryostats daily, which I only  do when Andy is away. Filling of some cryostats is done twice weekly by Andy — only once weekly are all of the  cryostats re-filled. Andy does the member paperwork and  building maintenance. I do the bookkeeping/tax payments  and website updates. A large part of the time I am researching and writing. When we get a patient, the  patient becomes the center of attention.

You have investigated the issue of molecular mobility at low  temperatures. Has this made you more or less skeptical about  intermediate temperature storage for cryonics patients?

I am more skeptical about the value of intermediate  temperature storage, but I am skeptical of my skepticism  because my results are so inconclusive.

At the recent CI training, Alcor’s Readiness Coordinator Regina Pancake attended and led a successful case simulation. Do you think it would be a positive development if there was more mutual assistance and cross-training between staff and members of cryonics organizations?

The co-operation between CI and Alcor in the last few years has been reasonably good. A CryoSummit was held between Alcor, ACS and Alcor in August 2002. After some wrangling I was permitted to attend an Alcor training in October 2003. In the summer  of 2007 Tanya and I co-led a training in Alberta. Dr. Pichugin  gave some training to your wife Chana when she was an Alcor  employee in December 2007. In May 2008 Alcor sent Regina  to attend the CI Cryonics Rescue Training. I would like to witness/participate in an Alcor case, but the  opportunities for doing this seem limited.

The thorniest issue related to co-operation between CI and Alcor has to do with local response in areas where there is a mix of Alcor and CI Members, such as in Toronto and the UK. The UK has set a good example (with Alcor approval) of allowing both CI Members and Alcor Members to participate in the trainings. But where proprietary information is involved such as the Critical Care Research meds, even signing a non-disclosure agreement would not be an option for CI Members insofar as they are the people the non-disclosure agreements are designed to “protect” against. Worse, if a CI Member becomes terminal and the local group decides to do volunteer standby and stabilization, how much Alcor equipment can be used? Alcor invests a great deal of money in that equipment, and proprietary sentiments are completely appropriate. In practice, this has not been a problem thus far, but if both cryonics organizations continue to grow, situations of this nature are bound to arise and I hope that reasonable solutions can be found.

How do you feel about competition in cryonics?

I believe that arrogance and complacency are poison  for cryonics organizations, and competition is of value in shaking complacency (sometimes). I definitely think  that it would be a bad idea for cryonics to have all the eggs in one organizational basket. I opposed the  idea of a merger between Alcor and CI when the issue was raised at the CryoSummit in 2002. There is already  too much vulnerability to lawsuits and legal/political  threats. More organizations in more locations  (including more countries) would reduce this vulnerability.

Some people say that CI should offer its own standby and  stabilization services. Do you agree with this?

CI does not have the resources to provide standby  and stabilization in the Detroit area, much less anywhere else. There is very little demand for these services by  CI Members — and very little willingness to pay more than  the minimum. CI Members interested in contracting for  standby and stabilization do so with Suspended Animation.

I have attempted to provide both local and remote CI  Members with support in volunteer standby and stabilization.  The May 2008 training was given as part of this support,  although only six CI Members attended. I have obtained and  discussed equipment that local groups could use, but very few CI Members showed any interest. I will continue to  support volunteer effort by CI Members, but my expectations  are not high.

What are the prospects of CI Members coming to the CI area  to retire, create mutual support communities and start  cryonics hospices?

A few CI Members have shown an interest in creating  a mutual support community near CI, but for the most part CI Members would rather remain near home and family  when they become terminal. In a couple of cases, CI Members  with serious health problems have recently moved to be  near CI. This creates the potential for faster  response, but in both cases the Members are living  alone and may not benefit without alarm systems.

Dr. Yuri Pichugin resigned his post at CI several months ago.  Are there any plans to hire a new researcher or to continue  research at CI in some way?

There are no plans for a new researcher. Concerning  R & D, I think the most immediate need is for greater Development, rather than Research — except to the  extent that my own studying & experimentation with equipment & procedures is considered research.

In the recent past you have stated that there should be the  equivalent of a “Manhattan Project” for cryoprotectant toxicity. Can you elaborate on this? How do you think cryonics can realize this goal?

I have elaborated on this in the March/April 2008  issue of LONG LIFE magazine. Eliminating or greatly reducing  cryoprotectant toxicity would be the greatest possible step  toward suspended animation through cryopreservation with  vitrification. If suspended animation through cryopreservation  became a reality there would be immediate acceptance and  adoption by conventional medicine. Patient stabilization  would be perfected by researchers all over the world and  adopted in hospitals and other medical facilities.

I think that too much research effort in cryonics is devoted  to whole body vitrification, which is a side issue.  Cryoprotectant toxicity needs to be the focus of attention,  and studied with experiments directed toward understanding  the molecular mechanisms on a theoretical level — not simply  trial and error. Whole body vitrification could very well be  achieved more quickly if cryoprotectant toxicity was the  focus of study.

CI is regulated as a cemetery, you are not allowed to cryoprotect patients in your own facility, and neuropreservation seems to be controversial in Michigan. Is it not time to relocate CI to another state?

It would be far too costly and risky to attempt to move to another state.

(Crossposted from Depressed Metabolism)

Although critical philosophers like Herbert Marcuse (1898 – 1979) are not known for their contributions to economics or analytical philosophy, Marcuse’s essay “The Ideology of Death” (1952) should appeal to those who think that death is not a necessary part of existence, let alone something to celebrate. In this essay, the author discusses the phenomenon that prominent Western philosophers (Plato, Hegel, Heidegger) have not just accepted death as a biological fact that may be overcome, but have elevated its status to something that gives meaning to life. Unfortunately, this line of thinking persists today.  Although Herbert Marcuse lived through the 60’s and 70’s, he did not seem to have an interest in investigating scientific means to prolong life and overcome death.

In the history of Western thought, the interpretation of death has run the whole gamut from the notion of a mere natural fact, pertaining to man as organic matter, to the idea of death as the telos of life, the distinguishing feature of human existence. From these two opposite poles, two contrasting ethics may be derived; On the one hand, the attitude toward death is stoic or skeptic acceptance of the inevitable, or even the repression of the thought of death by life; on the other hand the idealistic glorification of death is that which gives “meaning” to life, or is the precondition for the “true” life of man…

It is remarkable to what extent the notion of death as not only biological but ontological necessity has permeated Western philosophy–remarkable because the overcoming and mastery of mere natural necessity has otherwise been regarded as the distinction of human existence and endeavor…

A brute biological fact, permeated with pain, horror, and despair, is transformed into an existential privilege. From the beginning to the end, philosophy has exhibited this strange masochism–and sadism, for the exaltation of one’s own death involved the exaltation of the death of others…

How can one protest against death, fight for its delay and conquest, when Christ died willingly on the cross so that mankind might be redeemed from sin? The death of the son of God bestows final sanction on the death of the son of man…

The fight against disease is not identical with the fight against death. There seems to be a point at which the former ceases to continue into the latter. Some deep-rooted mental barrier seems to arrest the will before the technical barrier is reached. Man seems to bow before the inevitable without really being convinced that it is inevitable.

Published in The Meaning of Death, Herman Feifel, Editor (1959)

(Crossposted from Depressed Metabolism)

The two most popular technical arguments against human cryopreservation are that cryonics causes irreversible freezing damage and that the delay between pronouncement of legal death and the start of cryonics procedures causes irreversible injury to the brain. Such arguments can be countered by pointing out that freezing damage and prolonged periods of warm ischemia do not necessarily produce information-theoretic death. The argument that cryonics procedures themselves produce additional forms of injury which cannot be treated with contemporary technologies misses the point that cryonics involves stabilization of critically ill patients so that they can be treated with future technologies. In the case of freezing damage, this argument has also lost most of its value because today’s cryonics organizations employ vitrification agents to stabilize a patient at cryogenic temperatures without ice formation.

The criticism that delays between pronouncement of legal death and start of cryonics procedures will cause irreversible injury to the brain is also unfair because it treats the current social and legal obstacles to perform better stabilization of cryonics patients as an intrinsic element of cryonics itself. But cryonics does not necessarily involve cryopreservation of persons who have been pronounced legally dead. The current Wikipedia entry on cryonics defines cryonics as follows:

Cryonics is the low-temperature preservation of humans and other animals that can no longer be sustained by contemporary medicine until resuscitation may be possible in the future.

As can be deduced from this definition, cryonics constitutes a form of medical time travel that uses cryogenic temperatures to allow a terminally ill patient to reach a time when more advanced treatments may be available. As such, it would be premature to declare a cryonics patient “dead.” In most cases, pronouncing a person dead only reflects our current inability to treat the patient and our psychological need for definitive answers to questions of life and death. The limitation that cryonics procedures can only be started after pronouncement of legal death reflects the unfortunate fact that the current medical establishment does not recognize cryonics as a credible form of advanced critical care.

As a result, cryonics is currently practiced as a form of emergency medicine in which conventional resuscitation technologies such as chest compressions and ventilations are used to avoid the kinds of injury that follow after cardiac arrest. Although there will always be a place for cryonics as a form of emergency medicine to treat cases of trauma and  sudden circulatory arrest, most patients who currently present for human cryopreservation would benefit from more hospital cooperation in choosing cryonics as an elective medical procedure.

Although current cryonics organizations such as Alcor try to make the best of a bad situation by employing standby teams that allow rapid intervention after cardiac arrest to reduce brain injury, much improved quality of care of cryonics patients would be possible if cryonics procedures would start at a point where medical professionals (with informed consent of the patient and/or family) would determine that further treatment of the patient with contemporary technologies would be futile, or even counter-productive.

When this determination is made, conventional life support for the patient would be terminated and deep hypothermia would be induced using cardiopulmonary bypass. At deep hypothermic temperatures, the patient’s blood would be substituted with an organ preservation solution to reduce blood complications associated with lower temperatures. When the patient’s core temperature approaches the freezing point of water, the organ preservation solution would be replaced by a vitrification agent to allow an ice-free descent to cryogenic temperatures for long term care. After lowering the patient’s temperature below the glass transition point (Tg), the patient is maintained at intermediate temperatures to reduce the risk of thermal stress and fracturing that would occur at lower cryogenic temperatures.

If such hospital based human cryopreservation will be available, most of the injury that is currently incurred by cryonics patients can be eliminated. No longer do cryonics patients have to suffer harmful periods of shock, cerebral ischemia, and circulatory arrest before intervention is possible. Cryonics as emergency medicine will be confined to cases that constitute unexpected life-threatening events.

As this brief, but simplified, description of hospital based (or assisted) cryonics makes clear, ischemic brain injury is something that can be eliminated from cryonics procedures if the current restriction to limit cryonics procedures to clinically dead people were lifted. Such a change will not only improve the quality of cryonics procedures, it will also make cryonics available to cardiac arrest and stroke victims who can be resuscitated with contemporary technologies but will suffer delayed brain injury (often leading to higher-brain death) if they are allowed to resume life at normothermic temperatures.

Contemporary cryonics procedures do not need to cause “irreversible” brain injury or  massive freezing damage. There is good reason to believe that in ideal cases existing cryonics procedures can be successfully reversed up to the point of cryoprotective perfusion. The major limiting factor in cryonics is not “brain death” or freezing  but cryoprotectant toxicity. But even in this area cryonics associated research  companies are setting the standard for conventional cryobiology, as demonstrated by Alcor’s implementation of the vitrification agent M22 to cryopreserve its patients.

(Crossposted from Depressed Metabolism)

Most life extensionists and transhumanists do not buy into many of the myths about cryonics. But one perspective that is sometimes voiced by futurists is that cryonics is a rational backup plan until aging is cured. This position has some serious shortcomings and potentially lethal implications.

Human cryopreservation is the practice of placing terminally ill patients who have exhausted contemporary medical treatments into long term cryogenic care, allowing them to benefit from future medical treatments. Although aging-associated diseases are an important cause of death, they are not the only cause of death. Even when biological aging becomes optional, a person will still be vulnerable to accidents and violence.

The mindset that cryonics will become redundant as soon as aging is conquered is especially dangerous when it leads (young) people to forgo or postpone making cryonics arrangements because they expect to benefit from  rejuvenation technologies and dietary supplementation during their lifetime. This may not only reflect wishful thinking regarding the rate of progress in overcoming aging, but it will also leave them vulnerable to other causes of death.

As long as humans (or post-humans) are vulnerable to injury that cannot be treated with contemporary medical technologies, human cryopreservation will remain important as a form of critical care. In other words, as long as there can be situations that warrant metabolic arrest to avoid information-theoretic death, there is a need for cryonics or similar technologies to induce metabolic arrest, like molecular warm biostasis.

There are a lot of people who believe in the technical feasibility of cryonics and intend to make cryonics arrangements….when necessary. As cryonics observers know, this is an extremely risky attitude because when people need cryonics the most, they often are unable to communicate their wishes, may meet resistance from relatives who benefit from their not making cryonics arrangements, or lack financial resources because life insurance is no longer an option to fund cryonics.

The best time to make cryonics arrangements is when it seems least likely that you need them soon. This is also evidenced by the fact that young healthy people can get excellent rates on life insurance.

(Crossposted from Depressed Metabolism)

One problem in assessing the merits of taking a specific dietary supplement (ranging from vitamins to  exotic multi-ingredient compounds) is widespread selection bias in the documentation that is supposed to support the use of the supplement in question.  The sheer number of scientific studies combined with variation in research methodologies virtually guarantees that for every supplement a supporting study can be found. For example, the recent issue of Life Extension Magazine (August 2008) has an article on the multiple health benefits of melatonin with 81 references. All these studies discuss either the biochemical properties of melatonin or show beneficial effects. This is what is what is seen. What is not seen are the studies in which melatonin is not effective or has adverse effects.  Or the studies that never got published as a result of “publication bias.” Granted, melatonin seems to be a remarkably effective agent for a diverse number of conditions, including its use as a neuroprotective agent in stroke, but such selective presentation of biomedical research seems to be a mainstay in the marketing of dietary supplements.

Another limitation of such documentation is that the studies that are used to recommend the taking of a supplement often solely address the (short-term) effects of that compound on the medical condition in question. Although it would not be practical to report on all the studies that investigate (chronic)  administration of the compound on other systems in the body, such unrelated adverse effects should not be ruled out when considering prolonged use. It is a major leap from demonstrating beneficial effects of a compound in rodents and preliminarily studies in humans to “recommending” the use of that compound for prolonged use in humans. And it is a giant leap to go from such studies to combining different effective compounds in very high dosages in a single product.

Promoting the use of supplements with a hodgepodge of  encouraging in-vitro studies, small animal studies, and observations in humans is not necessarily wrong, nor constitutes deliberate selection bias. Human biochemistry is extremely complex, and rigorous  research would require enormous resources and longitudinal experiments.  In real life there is a need to make informed decisions based on the evidence at hand. Still, our current state of knowledge and our ignorance about how all that we know adds up for specific individuals should induce modesty and, perhaps, moderation. For those who take supplements as a means to radical life extension, making cryonics arrangements remains the irreplaceable  cornerstone of such a program because it increases the odds to reach a time where truly meaningful (molecular) life extension technologies will be available, aside from the protection cryonics offers against most “lethal” accidents.

(Crossposted from Depressed Metabolism)

“Ethically, what is the correct thing to do when medicine encounters a difficult problem? Stablize the patient until a solution can be found? Or throw people away like garbage? Centuries from now, historians may marvel at the shortsightedness and rationalizations used to sanction the unnecessary death of millions.” - Brian Wowk Ph.D, 9th May 2006

Introduction

In contemporary medicine terminally ill patients can be declared legally dead using two different criteria: whole brain death or cardiorespiratory arrest. Although many people would agree that a human being without any functional brain activity, or even without higher brain function, has ceased to exist as a person, not many people realize that most patients who are currently declared legally dead by cardiorespiratory criteria have not yet died as a person. Or to use conventional biomedical language, although the organism has ceased to exist as a functional, integrated whole, the neuroanatomy of the person is still intact when a patient is declared legally dead using cardiorespiratory criteria.

It might seem odd that contemporary medicine allows deliberate destruction of the properties that make us uniquely human (our capacity for consciousness) unless one considers the significant challenge of keeping a brain alive in a body that has ceased to function as an integrated whole. But what if we could put the brain “on pause” until a time when medical science has become advanced enough to treat the rest of the body, reverse aging, and restore the patient to health?

Metabolic Arrest

Putting the brain on pause is not as far fetched as it seems. The brain of a patient undergoing general anesthesia has ceased being conscious. But because we know that the brain that represents the person is still there in a viable body, we do not think of such a person as “temporarily dead.”

One step further than general anesthesia is hypothermic circulatory arrest. Some medical procedures, such as complicated neurosurgical interventions, require not only cessation of consciousness but also complete cessation of blood flow to the brain. In these cases the temperature of the patient is lowered to such a degree (≈16 degrees Celsius) that the brain can tolerate a period without any circulation at all. Considering the fact that parts of the human brain can become irreversibly injured after no more than five minutes without oxygen, the ability of the brain to survive for at least an hour at these temperatures without any oxygen is quite remarkable.

Again, because we know that in such cases the brain that represents the person is still there in a viable body, we do not think of such a person as “temporarily dead.” These examples illustrate that the medical community already recognizes and accepts the fact that a medical procedure that produces loss of consciousness, and even loss of circulation, does not constitute irreversible death.

Unfortunately, general anesthesia and hypothermic circulatory arrest cannot be used to pause the brain long enough to find a treatment for a person who has been declared legally dead by cardiorespiratory criteria. A person under general anesthesia may require tens, if not hundreds, of years of artificial circulation to keep the brain viable until medical science is able to return him to health. Leaving financial considerations aside, artificial circulation of an organ, let alone such a vulnerable organ as the brain, will produce increasing brain injury over time, and ultimately, destruction of the person.

Hypothermic circulatory arrest eliminates the need for metabolic support of the brain, but only for a limited period of time. Current research into hypothermic circulatory arrest indicates that the brain might tolerate up to 3 hours of complete circulatory arrest if the temperature is lowered close to the freezing point of water (zero degrees Celsius). This is not nearly long enough to put the brain on pause to allow the patient to reach a time where his current medical condition may be treatable. In light of these limitations, it is understandable that no serious attempts are currently being made to continue long-term care for a patient whose body has stopped functioning as an integrated organism.

But if low temperatures can extend the period that the brain can survive without circulation, much lower temperatures should be able to extend this period even further. At -196 degrees Celsius molecular activity has become so negligible that it can be said that the brain has been put on pause in the literal sense of the word. This allows the patient to be “transported” to a time when more advanced medical technologies are available, even if this would require hundreds of years. Advocates of human cryopreservation argue that long-term care at cryogenic temperatures offers a rational alternative to the current practice of burial and cremation of persons no longer treatable by contemporary medicine.

Contrary to popular views of cryonics, cryonics is not about preserving dead people but about long-term care of critically ill patients. The objection that cryonics is an attempt to resuscitate dead people reflects a misunderstanding of the rationale behind cryonics. The arguments supporting human cryopreservation are not radically different than the already established arguments behind general anesthesia and hypothermic circulatory arrest; it merely introduces lower temperatures and longer care. Therefore, the difference between contemporary medicine and cryonics is quantitative, not qualitative, in nature. Likewise, the relationship between cryonics and religion is not qualitatively different than that between contemporary medicine and religion. In both cases medical technology is used to preserve life.

Vitrification

But does the procedure of cooling a patient to cryogenic temperatures not cause injury in itself? Most of the human body consists of water and lowering the body below the freezing point of water will produce massive ice formation. For this reason, patients who present for cryonics are protected from ice damage by using a cryoprotective agent to reduce, or even eliminate, ice formation. Conventional extracorporeal bypass technologies are used to circulate the solution throughout the body. When enough water is replaced with the cryoprotective agent the patient is maintained at cryogenic temperatures for long-term care. Historically the cryoprotective agents that were used in cryonics are mainstream cryoprotective agents such as DMSO and glycerol. High concentrations of glycerol or DMSO can significantly reduce ice formation, but cannot eliminate it altogether.

A better alternative to conventional cryoprotection is vitrification. Vitrification offers the prospect of cooling an organ to cryogenic temperatures without ice formation. Although vitrification of pure water requires extremely high cooling rates, these cooling rates can be greatly reduced if high concentrations of cryoprotective agents and “ice blockers” are added. Ice blockers are synthetic variants of naturally occurring anti-freeze proteins used by hibernating animals to protect themselves from freezing injury. The vitrification agent is introduced within a so-called “carrier solution” which includes molecules to prevent cell swelling, support metabolism, maintain physiological pH, and prevent oxidative damage. The vitrification agent is introduced in a gradual fashion to prevent excessive volume changes in cells. During the final stages of cryoprotectant perfusion the temperature is dropped below zero degrees Celcius to protect the cells from toxicity caused by high concentrations of the vitrification agent at higher temperatures.

The current generation of vitrification agents can preserve the fine details (ultrastructure) of the brain without requiring unfeasible cooling rates. Although electrical activity has recently been demonstrated in vitrified rabbit brain slices, reversible vitrification of the human brain without loss of cellular viability is currently not possible. The current research objective, therefore, is to improve on these vitrification agents to allow for reproducible vitrification and recovery of organs with complete long-term viability. Such a breakthrough would not only lead to cryogenic organ banking for transplantation and research but would remove the most fundamental obstacle to suspended animation of humans.

Brain death and cryonics

Although a vitrified patient cannot be rewarmed and restored to health with contemporary technologies, the extremely low temperatures at which a patient is maintained permit possible resuscitation of a patient in the future without any risk of deterioration during long-term care. In this sense it compares favorably to procedures such a hypothermic circulatory arrest which allow for only a few hours to treat a patient. This not only offers the option to treat patients who cannot be treated with contemporary medical technologies, it also offers the possibility to treat medical conditions where successful resuscitation is possible but higher brain function will be lost if care is resumed at normal body temperature.

A good example of this is cardiac arrest. Patients who have suffered more than 5-7 minutes of cardiac arrest can often be resuscitated, but some of the most vulnerable cells in the brain (such as the hippocampal CA1 neurons) will die within days of the insult. There are currently no effective medical interventions or neuroprotective agents that will prevent such damage. As a result, today’s medicine can restore viability to such patients, but only by losing some, or most, higher brain functions.

If one believes that the objective of medical care is not just to preserve life in the sense of integrated biological function, but also to preserve the person, then one would agree that such patients might be better served by interventions that place them under long-term care in the form of cryonics. Although there is no guarantee that such patients will be restored to full functionality in the future, the certainty of higher brain death is an alternative that many people would prefer to avoid.

Conclusion

Cryonics does not involve the freezing of dead people. Cryonics involves placing critically ill patients that cannot be treated with contemporary medical technologies in a state of long-term low temperature care to preserve the person until a time when treatments might be available. Similar to such common medical practices as general anesthesia and hypothermic circulatory arrest, cryonics does not require a fundamental paradigm shift in how conventional medicine thinks about biology, physiology, and brain function. Although current cryopreservation methods are not reversible, under ideal circumstances the fine structure that encodes a person’s personality is likely to be preserved. Complete proof of reversible vitrification of human beings would be sufficient, but is not necessary, for acceptance of cryonics as a form of long-term critical care medicine. The current alternative is death; or for persons who are at risk of suffering extensive brain injury, loss of personhood.

For very old and fragile patients, meaningful resuscitation would require reversal of the aging process. Obviously, the objective of cryonics is not to resuscitate patients in a debilitated and compromised condition, but to rejuvenate the patient. Ongoing research in fields such as biogerontology, nanomedicine, and synthetic biology inspire optimism that such treatment will be available in the future. The fortunate thing for cryonics patients is that even if fundamental breakthroughs in these fields will be the result of long and painstaking research, the cold temperatures allow them time — a lot of time.

The first minutes after “death”

As currently practiced, cryonics procedures can only be started after legal death has been pronounced by a medical professional. To prevent brain injury between pronouncement of legal death and long-term care in liquid nitrogen all major cryonics organizations offer standby services to ensure that the time of circulatory arrest is minimized. In ideal circumstances the cryonics organization of which the patient is a member will deploy a standby team consisting of cryonics professionals to stabilize the patient immediately after pronouncement of legal death.

A mechanical device is used to restart blood circulation and ventilate the patient. Because the objective of this intervention is not to resuscitate but to stabilize the patient this is called cardiopulmonary support (CPS). At the same time the patient is lifted into a portable ice bath to induce hypothermia to slow metabolic rate. A number of medications are also given to support blood flow to the central organs, reverse and prevent blot clotting, restore physiological pH, prevent edema, and protect the brain from ischemic injury.

If the patient is pronounced legally dead at a remote location an additional step to this protocol is added and the patient’s blood is washed out and replaced with an organ preservation solution to preserve viability of the tissue during transport at low temperatures. The organ preservation solution that is currently used by cryonics organizations is similar to the cold organ preservation solutions that are used in conventional medicine (such as Viaspan) to preserve organs for transplantation.

At the cryonics organization the patient’s blood (or the organ preservation solution) is replaced with the vitrification agent to prevent ice formation during cooldown to liquid nitrogen temperatures for long-term care.

(Crossposted from Depressed Metabolism)

In “Heritage of Horror,” Lovecraft scholar S.T. Joshi writes that Lovecraft’s short story “Cool Air” “anticipates cryogenic research.” We can forgive Joshi the common mistake of writing “cryogenics” when he means “cryonics,” but how much cryonics is there really in Lovecraft’s “Cool Air?”

“Cool Air” (1926) tells the story of a struggling writer who has secured affordable housing in a converted brownstone on West 14th Street in New York City to devote himself to “dreary and unprofitable magazine work.” Around three weeks pass when an incident in the room above introduces the reader to the character of Dr. Muñoz, whose “complication of maladies” requires an environment of constant cold. When the main character experiences a sudden heart attack, his initial repugnace for the eccentric doctor changes to admiration when Dr. Muñoz is able to offer him relief with a suitable combination of drugs.

Dr. Muñoz, we learn, is the “the bitterest of sworn enemies to death, and had sunk his fortune and lost all his friends in a lifetime of bizarre experiment devoted to its bafflement and extirpation.” He believes that “will and consciousness are stronger than organic life itself, so that if a bodily frame be but originally healthy and carefully preserved, it may through a scientific enhancement of these qualities retain a kind of nervous animation despite the most serious impairments, defects, or even absences in the battery of specific organs.” As the story develops we learn about the doctor’s own (increasing) need for a cold environment to preserve his bodily frame.

Just as in cryonics, Dr. Muñoz employs cold to prevent decomposition. And decreased temperatures confer increased benefits in slowing down the rate of decomposition. In cryonics these benefits of low temperatures are exploited by reducing the temperature of the patient to a point of complete metabolic arrest. At the temperature of liquid nitrogen (-196 degrees Celcius) biological time stands still for all practical purposes.

But what is remarkable about Dr. Muñoz’s approach is that he reaps the metabolic advantages of induced hypothermia without these temperatures preventing his mind from functioning. Dr. Muñoz seems to be unusually “alive” at ultra-profound, or even, high subzero temperatures! Because the EEG of a human brain becomes flat below 20 degrees Celcius, some other process must be involved, perhaps the “incantations of the mediaevalists, since he believed these cryptic formulae to contain rare psychological stimuli which might conceivably have singular effects on the substance of a nervous system from which organic pulsations had fled.”

Unless Dr. Muñoz’s treatment induced profound changes in the body’s biochemistry that allowed it to operate at much lower temperatures, his philosophy of life seems less “materialistic” and coherent than that of Lovecraft’s other enemy of death, Herbert West. Lovecraft never anticipated the practice of cryonics in a systematic fashion, but if Dr. Muñoz and Herbert West could have put their brilliant minds together, the benefits of cold temperatures could have been reaped to induce metabolic arrest in anticipation of future resuscitation of the “dead.”