My road to a possible future

My experiences with death began in 1974, when I was age 10.

On Labor Day Sunday, while watching the Jerry Lewis MDA telethon, my father told me to turn the TV off.

When I asked why, he said my grandfather, age 74, died.

I would learn years later that he had emphysema and heart trouble.

I did not know my grandfather well, and, being a grammar school student, I didn’t understand death that well.

I was just told he would go to a better place.

Over the years, I would be to more funerals: a schoolmate who died in a skiing accident, three of my grandparents, a friend of a co-worker, and so on.

Man has been hard-wired to accept death, as horrible as it is, for millennia.

I was not alone.

Then, about a month or so after my 43rd birthday in August 2007, my life would change.

First, a co-worker who had been in poor health since an accident several years ago passed away.

Then I encountered several sleepless nights, fearing that I would not wake up again.

I then broke down in tears one Friday at work and was evaluated at hospital.

A second trip a couple of weeks later, this one for several days, followed.

I eventually entered several weeks of group therapy.

Then my mother, age 66, informed the family that she had liver cancer.

The news prompted me to investigate alternative therapies and medicines on the web in what would eventually become a vain attempt to save my mom, who died a week before Thanksgiving.

It was during this search that I learned about life extension and cryonics.

I began paperwork with Alcor, and initiated correspondence with Regina Pancake and Diane Cremeens, who were very helpful.

I still communicate regularly with Regina.

I also conferred with Rudi Hoffman, an insurance agent from Florida who specializes in dealing with cryonicists.

Everything seemingly went well until I received word from Rudi that AIG turned me down, because of a “bi-polar episode” which sent me to hospital on Super Bowl Sunday.

I should have known at that moment that the New England Patriots were going to have a bad day.

Several other minor health issues apparently caused AIG to throw up red flags.

I then employed my backup plan: I switched the beneficiary of my group life policy at my place of work, which is portable, to Cryonics Institute, upon Rudi’s recommendation.

I then contacted Andy Zawacki and Ben Best at CI and eventually filled out the appropriate forms.

Late this past spring I was accepted.

It took the death of a college schoolmate at 45 from heart failure in April to add more urgency to a serious issue.

I eventually declared CI the beneficiary of my 401K funds, which have lately taken a beating.

It’s been over a year since I began my research into cryonics.

I said so long to my career as a starving artist on the “open-mike” comedy circuit.

I waved goodbye to my stalled career as a football coach, a job I had on several occasions during the 1990s.

I found out that a couple of friends stopped being so when I told them of my desire for a longer life.

They used the same deathist argument, which goes, as the comic Bob Newhart would say, something like this:

“Why do you want to live forever? I don’t want to come back and be without my family and friends.”

“What if I come back and the world is much worse than it is today?”

“Why don’t you live your life today and make the most of it?”

It’s easy for anyone to say this, but look at an 80-year lifespan, for argument’s sake, and look at the everyday issues that one must address (work, family, economics, etc.) and one does not have that much time with which to begin.

My family is not crazy about my wishes.

They don’t believe in cryonics, but they will respect my wishes, or so they have said.

Even though my younger sister has power of attorney and is my estate’s executor, and despite the fact that I have paperwork completed with an attorney, I don’t know if I can trust anyone in my family if and when the need arises.

My mom’s death was not the only bell-weather event that I experienced over the last year.

I turned 44 in June.

My high school class celebrated its 25th year reunion.

I didn’t go because, as one who was not considered very popular, I didn’t want to risk having old wounds re-opened. I didn’t want to see classmates trying to impress each other with what they did with their lives after graduation, and I feared seeing some classmates who I did like suffer from the aging process.

I walked through my old grammar school for the first time in almost 35 years recently, and realized two things: first, it is scheduled to be torn down and replaced with a stadium on my local college’s campus, and I could no longer act like a child at heart.

I do not look forward to turning 50 and seeing my body and mind eventually break down.

I dread the prospect of seeing more of my family, friends and heroes fade from images and voices to echoes and memories.

I visited my high school football coach several weeks ago.

He, like my father, is in his early-70’s and has been recovering from a serious auto accident.

I told him that, despite what I may have learned from him in the classroom or on the football field, he unknowingly taught me the most important lesson one can learn: do not be afraid to think outside the normal bounds of society.

I would say “thinking outside the box” would have been a bad pun, considering the subject in mind.
I have no problem telling people of my interest in cryonics because I don’t want to see suffering and death.


Sadly, I have realized that I can’t save everyone in my own little world but myself.

I follow many technological web sites and read as much as I can about life extension.

Today, Bob Ettinger, Ray Kurzweil and Ben Best hold greater importance in my life than Muhammad Ali, the boxing legend, Jim Kelly, the Buffalo Bill quarterback who played in four straight Super Bowls, or Bret “Hitman” Hart, the pro wrestler who earned the right to say he’s “the best there is, the best there was, and the best there ever will be.”

I had to rethink my views on religion and spirituality.

How can one’s mind or spirit take one to Heaven or Hell when science says you go nowhere but oblivion?

I have heard people speculate that it may be from 20 to 100 years before the first resident of a cryostat or dewar leaves his or her confines for a renewed and greatly expanded life.

When that event happens, I am sure that much of what mankind has taught itself about so many things will be changed forever.

I don’t want to be left behind.

I want to contribute as much as I can to the cryonics and life extension communities as I can before my time comes to enter the cryostat (that is, if no cures for aging and related diseases are found by then).

I fear death, not only for myself, but for others.

This fear, plus my interest in cryonics and life extension, is what drives me today.

I’m not sure whether I will commemorate the holidays this year or in the years to follow.

What good are toys, games, appliances and other things when we, as a community and, I hope, as a race, should work toward giving and preserving life, which is the greatest gift of all?

Refractometry in cryonics

Contrary to popular opinion, in cryonics the blood of the patient is replaced with a cryoprotective agent to reduce freezing, or more recently, to eliminate ice formation altogether through vitrification. This procedure requires surgical access to the circulatory system of the patient to wash out the blood and replace it with a cryoprotective agent. But how do we know what the concentration of the cryoprotective agent is in the brain of the patient?

There are a number of methods to estimate the concentration of the cryoprotective agent including specific gravity (SG) and freezing point depression osmometry. Such methods can be impractical and time consuming. In the following article from Long Life Magazine (1978), Mike Darwin introduced refractometry as a method to determine cryoprotective agent concentration. Measuring the refractive index of the perfusate to estimate the concentration of the cryoprotectant in the patient is still practiced in cryonics today by taking samples of the arterial, venous, and burr hole effluent.

The sort of handheld refractometer that is discussed in Darwin’s article was used by Alcor  for manual refractometry measurements until the  organization obtained a benchtop refractometer in the mid-2000’s.  Alcor also collects continuous refractive index measurements using LabView and in-line industrial refractometers.  In 2007, Aschwin de Wolf  recommended the Reichert AR2000, a digital handheld refractometer, which is convenient to use, offers a wide reading range and a choice of different scales, and can be used with software to automatically record data.  The Reichert AR2000 is currently used by the Cryonics Institute.

Mike Darwin – Refractometric Determination of Cryoprotective Agent Concentration PDF

Interview with Cryonics Institute president Ben Best

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:

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:

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:

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:

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:

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:

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.

Vitrification agents in cryonics

Today’s post on 21st Century Medicine’s vitrification agent M22 completes the series on vitrification agents in cryonics. To date, three different vitrification agents have been used for cryopreservation of humans: B2C (at Alcor from 2001-2005), VM-1 (at the Cryonics Institute since 2005) and M22  (at Alcor since 2005).

Perhaps the most encouraging development in cryonics is that Alcor’s current vitrification agent, M22, is not only the least toxic cryoprotectant in the history of cryonics, it is also the state of the art in mainstream cryobiology research for vitrification of complex organs.

It is doubtful if the state of the art in vitrification in cryobiological research would be where it is today without the incentives provided by cryonics to search for a cryoprotectant that enables reversible vitrification of the brain without ice formation and minimal toxicity.

The first vitrification agent in cryonics: B2C

Vitrification agents in cryonics: VM-1

Vitrification agents in cryonics: M22

Vitrification agents in cryonics: VM-1

A major public misperception is that cryonics involves the freezing of dead people. The objective of cryonics is not to preserve dead people with the hope of future revival but to place critically ill patients in a state of biostasis until a time when more advanced medical technologies might be available to treat and cure them. Currently, all major cryonics organizations induce metabolic arrest of the brain by attempting vitrification rather than freezing.

Unless a patient has suffered a long period of circulatory arrest, after which perfusion of the body or brain is no longer possible, metabolic arrest is induced by cooling down the patient to cryogenic temperatures. Vitrification can be defined as “the process of converting a material into a glass-like amorphous solid that is free from any crystalline structure.” Because vitrification of pure water would require extremely rapid cooling rates, vitrification in cryonics is achieved by substituting the water of patients with a highly concentrated cryoprotectant agent before cooling.

In 2001, Alcor introduced its first vitrification agent (B2C) for neuropatients and extended this technology to whole body patients in 2005 with the introduction of M22. The Cryonics Institute introduced its own vitrification agent, VM-1, to its membership in 2005. VM-1 was developed by Dr. Yuri Pichugin and stands for Vitrification Mixture-1, which indicates that it was the first vitrification agent to be introduced at CI. Before VM-1, CI generally used the cryoprotective agent glycerol. VM-1 consists of 35% ethylene glycol and 35% dimethyl sulfoxide (w/w). It is introduced in a carrier solution called m-RPS-2, consisting of potassium chloride, glucose, and TRIS (alternatively called THAM). A more detailed review of the research and components of the solution can be found on the Cryonics Institute website.

VM-1 has been formulated and validated specifically for cryonics patients. Although encouraging viability results have been obtained in brain slices, the agent first and foremost reflects the search for a vitrification agent that is an affordable, but also strong and stable, glass former. M22 is the culmination of many years of research (mostly on kidney slices) by Greg Fahy et al. to find vitrification agents that can successfully recover organs from cryogenic temperatures for organ transplantation. M22 is being licensed to Alcor by the cryobiology company 21st Century Medicine.

An interesting similarity between the two agents is that both contain the same core components: ethylene glycol and DMSO. 21st Century Medicine solutions additionally contain formamide, which has a low toxicity in the presence of DMSO, allowing formulation of solutions of lower overall toxicity. Solutions containing DMSO, an amide, and ethylene glycol are protected by 21st Century Medicine’s M22 patent.

The strong glass forming ability and stability of VM-1 is further evidenced by the following research findings. Pichugin did not observe ice formation or devitrification when 20 ml glass vials of 60% and 65% VM-1 were cooled and warmed with cooling and warming rates as low as 0.1 degrees Celsius per minute. 65% VM-1 solutions with “homogenized rat brain tissues containing natural nucleators” did not show visible ice crystals after 14 days at dry ice temperature (-78.5 degrees Celsius). The stability of large volumes (2 liters — unfiltered) of VM-1 was investigated and no ice crystals were observed after 21 days of storage at dry ice temperature. These results raise the intriguing question of whether patients can be perfused with high concentration VM-1 in the field and shipped to a cryonics facility on dry ice. In cryonics we do not ship vials of cryoprotectant solution, or fully equilibrated brain slices, but patients that have been exposed to variable degrees of warm and cold ischemia. Questions about the nature and extent of ice damage of poorly perfused areas during long holding and transport periods at dry ice temperature still remain.

Unlike M22, VM-1 is not a suitable agent for perfusion of whole body patients. In CI patients where whole body perfusion was attempted with one of the components, ethylene glycol, serious edema resulted. Similar results have been encountered in the past with DMSO as a mono-agent. Improved results may be obtained by modifying the carrier solution of VM-1 to include an oncotic agent and/or using glycerol for the rest of the body. Although high molar glycerol can be perfused in (non-ischemic) patients without serious edema, CI currently discourages members from choosing whole body perfusion in order to ensure optimal perfusion of the brain.

The current carrier solution of VM-1, m-RPS-2, is basically a stripped down and modified version of Fahy’s Renal Preservation Solution-2. As such, it does not contain components that reduce free radical damage (such as glutathione) or ATP precursors (such as adenine) to assist energy generation during hypothermia. Perhaps a more controversial choice is the lack of an oncotic agent to prevent and counter edema during perfusion. Pichugin questions the value of such agents for perfusion of the brain. In practice, CI has not encountered much edema during brain perfusion of its patients, many of which have been exposed to considerable periods of warm and cold ischemia. m-RPS-2’s lack of hypertonicity does not seem to make the carrier solution suitable to inhibit chilling injury.

There are still some open questions about VM-1. Although VM-1 is designed as a low cost agent to allow preservation of the brain without ice formation, no published electron micrographs are available that show the quality of ultrastructural preservation that can be obtained with VM-1. VM-1 has been validated solely on the basis K+/Na viability assays. As electron micrographs of brains perfused with vitrification agents B2C and M22 indicate, agents that can inhibit ice formation can still produce strikingly visible differences in terms of ultrastructural alterations. Although good hippocampal slice viability results imply good ultrastructural preservation, actual empirical evidence of this could make a stronger case.

During the final step of cryoprotective perfusion at CI, the current protocol is to introduce 70% VM-1 at -7 degrees Celsius to reduce the time required to achieve a minimum target concentration of 60% as measured by refractometry. It is not clear what the biochemical effects of exposing the patient to such concentrations of VM-1 are, although the “ideal” temperature for the final step is lower than what is currently used by Alcor for M22. In practice, it is doubtful that the patient’s brain is at such temperatures during a typical perfusion. Such a protocol would require more rigorous control of the perfusate and brain temperature using a subzero chiller.

Another advantage would be to introduce VM-1 in a more “linear” fashion using a “closed circuit” in which the concentration is gradually increased. Because such a protocol requires a more expensive, complicated, and challenging perfusion circuit, the costs and risks of such a protocol need to be weighed against the potential advantages. One straightforward compromise might be to do “open circuit” perfusion but to close the circuit after target concentration has been reached to allow for good equilibration of the cells before terminating perfusion.

With VM-1, CI seems to have introduced an extremely cost effective and stable vitrification solution. If CI will find the resources to do new experiments to improve its composition and protocol, obtaining actual images of brain slices perfused (and vitrified) with the solution seems to be an important priority. It also needs to be stressed that results obtained in brain slice experiments in different species are not necessarily a good indicator of what can be expected in actual human cryonics patients who generally have been exposed to long terminal periods, warm and cold ischemia, and longer perfusion times at higher temperatures. It is clear that is there is an urgent need for a research program that investigates the relationship between such variables and outcome in terms of ice formation, viability and ultrastructure. Investigations that have been done by Darwin and Pichugin under more realistic conditions will be discussed in the future.