One of the most predictable features of public debates about cryonics is that those arguing in favor of cryonics are held to more rigorous standards than those seeking conventional medical treatment. Advocates of cryonics do not just have to prove that cryonics will work, they are also supposed to solve problems like overpopulation and the presumed boredom arising from expended lifespans. To some, people who make cryonics arrangements have an inflated perception of their own importance and should just forgo such selfish attempts to extend their lives. The default position seems to be that people should not exist and that life needs justification. Could you imagine such antinatalist rhetoric being employed when a person seeks conventional medical treatment to extend their life? We can’t, and such responses are quite indicative of the fact that people are not interested in serious evaluation of the cryonics argument.

The most striking case of cryonics being held to higher standards than conventional medicine concerns the requirement that “cryonics” needs to “work.” Even people who have made cryonics arrangements routinely say something like, “I estimate the probability of cryonics working as 5% but life insurance premiums are low and I have nothing to lose if it does not work.” To see how strange such a statement is, let’s look at these two terms, “cryonics” and “working.”

Cryonics is an experimental medical procedure to stabilize critically ill patients at low temperature to benefit from future advances in medicine. Such a definition can include a wide variety of cases, ranging from ice-free cryopreservation (vitrification) as an elective medical procedure in a hospital to the freezing of a person who is found days after circulatory arrest. Considering the enormous variability under which people can be cryopreserved, to claim that “cryonics” will not work without specifying under what conditions a cryopreservation is performed is akin to saying that “emergency medicine” or “chemotherapy” does not work — an absurd claim.

Usually when people argue that cryonics does not work they refer to the mistaken view that cryopreservation that is not initiated within hours, or even within minutes, after death does not make sense because the brain has “died” at that point. Such a view completely ignores the fundamental cryonics argument that lack of function of the brain does not imply that the neuroanatomical basis of identity is irreversibly destroyed.

But let us accept this position the sake of the argument. What such a critic is basically saying is that cryonics cannot work because cryonics patients are cryopreserved under conditions that do not allow it to work. To see how strange such a position is, imagine a country where law would prohibit CPR until 15 minutes of death. Would anyone be impressed if someone would argue that CPR does not work because patients suffer irreversible brain damage after 15 minutes of circulatory arrest? Of course not. We would instead insist that such obstacles should be removed so that these life-saving technologies can be employed as soon as needed. Clearly, whatever the merits of cryonics are, it is not reasonable to conflate the conditions under which cryonics is often conducted with the idea of cryonics as such.

Now let’s look at the second term. What does it mean for cryonics to “work?” Naturally, we would like a medical procedure to cure the disease and restore the patient to the condition than he was in prior to the disease. In real life this often happens, especially in the case of minor infections and minor insults. But there are also many cases where (heroic) medical interventions are aimed at keeping the patient alive without expecting a full recovery without side effects. This is often the case in acute cardio-respiratory arrest and stroke. Would we prefer a complete recovery for such patients? Of course. But would we say that interventions that aim to save a patient’s life did not work if we fail to meet such an ideal – say, a permanent loss of movement in one arm or reduced memory function? No, our first concern would be with the patient’s survival and his perception of the quality of his “new” life.

In the case of cryonics things are not much different. We hope that advanced cell repair technologies will be successful in completely restoring the patient to good health in a rejuvenated state. For some patients complete inference of the original structure of the brain might not be possible, but advanced neural archeology and neurogenomics may restore a significant degree of the original person. We do not heap scorn on such scenarios in today’s medicine and there is no reason to hold cryonics to higher standards, especially if one also advocates the very restrictions that are responsible for such less than perfect outcomes. In fact, there is no reason to be scathing about any credible attempts to save or prolong a life, even if the attempt will not necessarily succeed. Such a perspective is a given in conventional medicine or rescue operations.

One objection to this position is to argue that cryonics cannot work even under the most favorable conditions. Such an argument would basically entail that if a critically ill patient is stabilized without ischemic delays, without ice formation, and without fracturing, it should be categorically ruled out that technologies will ever be developed to repair the original disease of the patient and any form of injury that occurs during the cryopreservation process itself. I personally would consider such a position extremely dogmatic (would anyone argue such a position of long-term technological stasis if the cryonics context were dropped?) but it raises a fundamental question about the burden of proof. Should it rest with the person who aims to prolong life or should it rest with the person who aims to prohibit such attempts? Asking the question is answering it.

On the evening of Thursday, May 19 and on Friday, May 20, I attended the 2011 (2nd annual) Teens & Twenties young cryonicists gathering which preceded the Suspended Animation, Inc. conference in Fort Lauderdale, Florida. The Teens & Twenties gathering (for young cryonicists having human cryopreservation contracts in place with some cryonics organization) is an offshoot of the cryonics Asset Preservation Group. Like the Asset Preservation Group, this event was created-by and is run-by Cairn Idun. Bill Faloon funds Teens & Twenties through a Life Extension Foundation education grant. Members of the Asset Preservation Group, such as myself, are permitted to attend despite being more than 30 years old. Of the 52 people who attended, ten were Asset Preservation Group members, and 42 were young cryonicists.

When asked who did not want to be photographed, only one person in the group raised his hand. I will refrain from mentioning any of the young cryonicists by name. Writing about this very people-oriented event without mentioning individual young cryonicists is like writing about lemonade without mentioning lemon. Some of the personalities were particularly colorful and memorable. But I know that many of the individuals do not want the publicity, and in my experience people get very emotional about what is said and not said about them. Even with explicit permission I am concerned that many of the young cryonicists might not fully appreciate the kinds of problems writing about them in connection with cryonics might cause for their future careers.

This year the demographics of the young cryonicists more closely matched what is typical of cryonicists. Last year about one third of those attending were female, and there was a high representation of people from the entertainment industry. This year, the attendees were overwhelmingly male, with most of the females being companions of males (which is not to say they were not cryonicists). Many members of this group were impressively highly educated, mostly in computer technologies, and secondarily in biotechnologies.

EXCELLENT MEALS WERE INCLUDED IN THE SCHOLARSHIPS

There were six Russians: five from KrioRus, and one from CryoFreedom. KrioRus is located near Moscow, whereas CryoFreedom is further south in Russia, closer to Ukraine. Dr. Yuri Pichugin (formerly the Cryonics Institute’s cryobiologist, is associated with CryoFreedom. CryoFreedom advertises neuropreservation for $7,500. Although it currently has no human patients, two pets are in liquid nitrogen. (I also learned that there is a man named Eugen Shumilov who is working to start a new cryonics company in St. Petersburg, Russia, but there was no representation of Shumilov’s organization at this event.

There are two overlapping goals of the Teens & Twenties event. One is the opportunity for members of the Asset Presevation Group to meet the young cryonicists. The other is the opportunity for the widely dispersed young cryonicists to become acquainted with each other, and to build lasting networks (community building). Cairn Idun has designed a number of “getting to Know You” exercises to facilitate the networking.

There are two self-introductions: the first lasting one minute, and the second lasting two minutes. I was the most anal-retentive of any of the participants in these exercises. I wrote-out my self-introductions, and practiced reading them to myself until I was sure I was within a few seconds of the one and two minute allocations. The one-minute self-introductions were on Thursday evening, and the two-minute self-introductions were Friday morning.

The Thursday evening self-introductions were followed by the exercise wherein participants classified themselves by “color”: (Green:Conceptual, Curious, Wise, Versatile), (Red:Adventuresome, Skillful, Competitive,Spontaneous), (Gold:Responsible, Dependable, Helpful, Sensible), and (Blue:Warm, Communicative, Compassionate, Feeling), as described in my write-up of last year’s Teens & Twenties event.

Once again, Greens were most numerous, followed by Reds. Cairn directed the participants to gather into groups by color. No directions were given for these meetings, so it was to foster socialization between “like-colored” individuals.

Last year a number of people had little to say in their second self-introductions, imagining that they had said all that could be said about themselves in their first self-introduction. I concerned myself quite a bit about how to prevent this from happening again. I made a number of suggestions in the Young Cryonicists Facebook Group, as did others. Cairn had participants list wants and “not-wants” of various kinds before the second self-introductions as a means of facilitating self-awareness. I tried to make my second self-introduction very personal in the hope that it would inspire others. There weren’t too many who were at a loss for words in the second self-introductions this year. Many of the participants passed-out business cards or other self-descriptive materials in conjunction with their second self-introduction.

There was a breakout session in which those with special interests had an opportunity to discuss their interests or how they might work together on those interests. The interest areas were entertainment, research, computer sciences, communication networking, and psychology/philosophy of self.

INTEREST GROUPS

Bill Faloon encouraged the participants to share thoughts about types of research that could lead to reanimation — with the thought that many of the young cryonicists would be in charge of large revival trust funds with income that can be used for research on reanimation technologies. I won’t attempt to summarize the thoughts of others, but I can say a few things about what I said.

Some people don’t want cryonics because they are afraid that they will not be restored in their original condition. The mother of one cryonicist is a stroke victim, and she has had a frightening first-hand experience of losing mental & movement capacity. Hollywood plays into this vision by depicting reanimated beings as zombies who are criminally insane.

Few people want to be the first of those reanimated — they would prefer that many others be reanimated first to ensure that the process works perfectly. I suggested that the first people reanimated might be brought back by next-of-kin who are overly eager to see their loved-ones as soon as possible. The idea of reviving pets first would not be popular with many pet owners. Reanimation technologies might be perfected on non-pet animals, although even today there is increasing sentiment against animal research. Animal rights activists seek legislation to protect animals from “unnecessary research”, which would likely include anything cryonics-related. Austria banned research on apes in 2006, and the number of countries with similar legislation continues to grow [SCIENCE; 332:28-31 (April 2011)]. Even if reanimation research was conducted on apes, the extrapolation of restoring ape consciousness/identity to restoring of human consciousness/identity is non-trivial.

I worry that as more wealthy cryonicists are cryopreserved, their only concern will be for reanimation research. Many of them will not appreciate that improved cryopreservation methods will advance cryonics and thereby enhance their chances of reanimation.

The next “getting to know you” exercise was what Cairn calls “speed dating”. Each participant is to spend two minutes with every other participant having a one-to-one conversation. For myself, it gave me an opportunity to talk to many people I would not have spoken with otherwise, and to have personal conversations with many individuals that I cannot imagine happening in any other way. Spontaneous socializing more often results in people talking only to those they already know. This exercise is a good ice-breaker, but it does involve some effort. It can be a strain to be starting conversations again-and-again, and again-and-again having to break them off once they become interesting — but the result was well worth the effort for me. Having a personal connection with individuals enables me to interact with them more productively, and this must also be true of the others. I rate speed-dating as the most valuable of all of the exercises, along with self-introductions.

Participants filled out a sheet indicating their interest level in cryonics — including such things as whether they planned to have a cryonics-related career, do volunteer work for a cryonics organization, or simply be a consumer.

GATHERING FOR THE GROUP PHOTO

he final event was the group photo, after which was a dinner and then reception for the Suspended Animation conference. The photographer who made the group photo was employed to make photographs only intended sor private use of Suspended Animation, Inc., but we did not learn this until later (even the photographer did not know).

All the young cryonicists had the fees, hotel expenses, and meals associated with the Suspended Animation conference paid-for. The opportunity for some of the young cryonicists who have an interest in science to directly interact with current cryonics researchers could eventually lead to large scientific dividends for cryonics research in the future.

There were reportedly many exaggerated rumors about what happened in the evening hot-tub sessions in the 2010 Teens & Twenties gathering. I brought my bathing suit this year, but did not spend a great deal of time in the hot tub. The conversation was a bit more playful than it was in other contexts, and there was more of a party-spirit in the hot tub — which some of the participants relished. I would guess that about half of the Teens & Twenties participants spent at least some time in the hot tub.

Despite all of the intensive social interaction and “getting to know you” exercises, I would have a hard time making a connection between names, faces, and biographies of at least a third of the young cryonicists. I don’t believe that I am unique in that regard. The “speed-dating” exercise was particularly helpful in strengthening and deepening the name/face/biography connections. Memories of the individuals and their personalities are likely to be more easily refreshed in the future thanks to the meetings and exercises of this gathering.

YOUNG CRYONICISTS VISIT WITH SAUL KENT

Gerald Feinberg, a Columbia university physicist who, among other things, hypothesized the existence of the muon neutrino, had a strong interest in the future of science and life extension. In 1966 he published the article “Physics and Life Prolongation” in Physics Today in which he reviews cryobiology research with the aim of realizing medical time travel. Unlike most of his scientific colleagues, Feinberg recognized that it might be possible for people dying today to benefit from future advances in science in the absence of perfected techniques:

For the living it is necessary to await successful completion of freezing research before attempting to freeze them. For the newly dead this consideration is irrelevant since the dead have nothing to lose by being frozen, even by imperfect methods…

He doubts, however, whether “the primitive freezing techniques now available” would be good enough to permit successful resuscitation in the future.  Although his article ends in endorsing cryonics as a procedure, Feinberg did not make cryopreservation arrangements himself, despite his familiarity with molecular nanotechnology and his association with the Foresight Institute.

In the June 1992 issue of Cryonics magazine, Mike Perry writes:

Only a few days ago, as I write this, Gerald Feinberg, aged 58, died of cancer.  He was not frozen.  It appears  that he didn’t lack the means to make the arrangements, nor the time. Somehow, he was just not interested enough.  Friends or acquaintances I’ve talked to could give little in the way of definite reasons for the lack of  interest, but I get the impression that, when all was said and done, the  interest he did show was mainly academic after all.  Another factor may  have been hostility from colleagues and family members.  Apparently he was well criticized for the Physics Today article on the prolongation of life, though not for something really scientifically daring, like the tachyon  theory.

Human cryopreservation procedures have changed considerably since 1992 and cryonics researcher Mike Darwin has composed an ambitious article to answer the question whether current cryopreservation techniques can preserve identity. One of the most important observations in this article is that we do not need to wait until the future to get a better understanding of how good our current procedures are in this regard.

As long as we keep in mind that the absence of ultrastructural evidence for the preservation of identity-critical information does not necessarily mean the absence of this information as such (after all, future imaging and data gathering technologies may be more powerful than today’s) it is very important for cryonics advocates to recognize that preliminary work to infer the original structure of the brain from (3D) images of ischemic and cryopreserved tissue can start right now. Even in the absence of physical technologies to restore those structures to their native state, demonstrating that we can infer the original state, and visually reconstruct it, can be another argument in favor of human cryopreservation.

Further reading: Gerald Feinberg – Physics and Life Prolongation

Introduction

Ongoing legal challenges and hostile interference of relatives have increased awareness among cryonicists that addressing the likelihood that one will be cryopreserved at all should take center stage among other strategies for survival. As a consequence, a number of individuals have recently taken on the task of working out the conceptual and legal challenges to minimize hostile interference (for a contribution on the ethical aspects of cryonics interference, look here).

One aspect of cryonics optimization planning that has received little attention to date is to develop legal strategies to deal with medical and legal issues surrounding one’s death, terminal illness, and the dying phase. In this memo I will outline some of the most important medical and medico-legal issues, how cryonicists could benefit from recognizing them, and suggest some legal and practical solutions. Before I get to the substance of these issues I would like to briefly identify all the stages in which proactive cryonics planning can improve our odds of personal survival.

Opportunities for cryonics optimization

The first and most obvious decision is to make cryonics arrangements. Alcor members face complicated decision making because the organization offers both whole body cryopreservation and neuro cryopreservation. From the perspective of cryonics optimization many members choose neuropreservation because it enables the organization to exclusively focus on what matters most; the brain. There is also a logistical advantage. In case transport of the whole body across state lines is delayed the isolated head can be released in advance as a tissue sample. Additionally, a number of Alcor members have recognized that it is possible to have the best of both worlds and combine neuro-vitrification and separate cryopreservation of the trunk. This allows the member to take advantage of the superior preservation of the brain that is available for neuro patients without having to forego whole body cryopreservation. This option is not widely advertised so one is encouraged to contact Alcor about revisions in funding and paperwork.

The other obvious decision is to have secure funding in place. Many members have given extensive thought about funding mechanism and wealth preservation so there is little need to discuss this here. From the perspective of cryonics optimization it is important to emphasize the importance of over-funding your cryopreservation. This not only protects you against future price increases, but also enables you to take advantage of technical upgrades that cannot be offered at the current preservation minimums. Another aspect to consider is leaving money to cryonics research. Although it is reasonable to expect that general progress in science will include general cell repair, there may be areas that will only be pursued by those who have a scientific or personal interest in resuscitation of cryonics patients. As in many areas in life, diversification is key. One should not solely depend upon Alcor or CI for successful resuscitation research or efforts.

Another important opportunity for cryonics optimization is to recognize the importance of proximity. From a technical point of view, there is simply no comparison to de-animating near the cryonics facility of your choice. This is not just a matter of reducing ischemic time. Remote standby and stabilization is a fertile ground for all kinds of logistical and legal complications. Most cryonics members do recognize the importance of reducing transport times but it is an established fact that as soon people become terminally ill they become more resistant to the idea of relocating and often prefer to die among friends at home. It is important to anticipate this scenario and to not delay relocation plans until the last minute. Another advantage of relocating at an earlier stage is that one is better protected in case of a terminal disease with rapid decline or sudden death.

As mentioned above, one issue that is getting increasing attention is how to protect oneself against hostile relatives and third parties. The take-home message is to alter cryopreservation contracts and your paperwork in such a matter that there is an incentive *not* to interfere.

Last but not least, something should be said about community building. Cryonicists can greatly benefit from becoming active in their local cryonics group. Often these meetings are open to members of all cryonics organizations. Most cryonics groups organize standby and stabilization trainings where members can familiarize themselves with the basics of the initial cryonics procedures. Such groups may not only play a part in your own future cryopreservation but are also useful to get a basic understanding about what you can do in the case a local member or a loved one needs to be cryopreserved. Another important aspect of participation in a local cryonics group is that one remains in contact with other cryonicists. When people get older their friends and family members die and the member has little communication with those who are aware of his desire to be cryopreserved. If you live in an area where there are no local cryonics groups contact your cryonics organization and/or start your own local group.

Physician-assisted dying

If there was more widespread acceptance of cryonics the harmful delay between pronouncement of legal death and the start of cryonics procedures would not exist. After a determination of terminal illness, preparations would be made to ensure a smooth transition between the terminal phase and long term care at cryogenic temperatures.

Some states have enacted legislation that allows a terminally ill patient to request the means to terminate their life.  Assisted suicide is currently legal in the following three states: Oregon, Washington, and Montana. Physician-assisted dying does not remove the current obstacle that cryonics procedures can only be started after legal pronouncement of death but it can bring the timing of death (and thus of standby) under the patient’s control. Utilizing such laws can also greatly reduce the agonal phase of dying and its associated risk of damage to the brain.

The legal requirements for utilizing physician-assisted suicide can vary among states but, as a general rule, require that a patient has been diagnosed with a terminal illness with no more than six months to live, that the patient is of sound mind, and that the request is made in written form and witnessed. The State of Oregon has a residency requirement to discourage physician-assisted dying tourism.

Since cryonics procedures are performed after legal death, there is no reason why cryonics patients are exempt from utilizing these laws. Despite rumors to the contrary, there is no evidence that utilization of these laws require mandatory autopsy. After all, the cause of death in physician-assisted dying is clear; self- administration of the lethal drug. To avoid any possible accusations that cryonics organizations encourage the use of such laws, it is recommended that no person associated with the cryonics organization should be a witness, let alone be the physician that prescribes the lethal drugs.

Sudden death and autopsy

One of the worst things that can happen to a cryonics member is sudden death. Especially when the patient is young with no prior heart conditions, an autopsy is almost guaranteed. There is little one can do to avoid sudden death aside from choosing a lifestyle that reduces cardiovascular pathologies. The only preparation for dealing with sudden death is to become a religious objector to autopsy. Some states (including California, Maryland, New Jersey, New York and Ohio) have executed laws to restrict the power of the state to demand an autopsy. Although exceptions can still be made in cases of homicide or public health there is little to lose in using such provisions. The websites of Alcor and CI have links to the relevant forms to execute. The Venturists are offering a card for their members stating that they object to autopsy. This card can be requested from Michael Perry (mike@alcor.org) at Alcor. An example of such a card is provided below.

Sudden cardiac death is not the only reason for ordering an autopsy. An autopsy is typically ordered if there are criminal suspicions (homicide) or suicide. There is also a greater risk of autopsy when a patient dies in absence of other people. Since many old cryonicists are single and spent a lot of time alone they are also at an increased risk for autopsy. This is another good argument to remain involved with local cryonics groups and in frequent contact with other cryonicists.

If autopsy cannot be avoided it is important that the cryonics organization is notified promptly. Cryonics organizations can make another attempt to persuade the authorities to abstain from an autopsy or to request a non-invasive autopsy that exempts and protects the brain. The cryonics organization can also issue instructions for how the patient should be maintained prior, during and after autopsy. It might be worthwhile to generate a template of general autopsy instructions for cryonics patients. Such a document may not be binding but it could be useful in limiting the amount of ischemia and injury.

The dying phase and Advance Directives

Most cryonics members have a basic understanding of the importance of time and temperature to protect a cryonics patient after legal pronouncement of death. Fewer people recognize the effect of the dying process itself on the outcome of a cryonics case. In best case scenarios (physician-assisted dying, withdrawal of ventilation) the dying phase is relatively rapid while in worst case scenarios extensive ischemic injury to the brain is possible. Little work has been done to outline recommendations for the terminally ill cryonics patient. One of the main objectives of this article is to recognize that cryonics members could benefit from a general template that can be used in their Advance Directives and to guide surrogate decision makers.

At this point it is useful to briefly describe how the dying phase itself can affect the outcome of cryonics procedures (for a more detailed treatment see the appendix at the end of this article). A useful distinction is that between terminal illness and the agonal period. A patient is classified as terminal when medical professionals establish that the patient cannot be treated with contemporary medical technologies. During this period the patient is usually still of sound mind and able to breathe and take fluids on his/her own. Unless the patient has suffered an insult to the brain or a brain tumor, there is no risk for ischemic injury to the brain yet. At some point, however, the body’s defense mechanisms will be overwhelmed by the patient’s disease and the patient enters the agonal phase. The agonal phase, or active dying phase, can be characterized as a form of general exhaustion. The body is still fighting but with decreasing success and efficiency. One of the biggest concerns for cryonics patients is the development of (focal) brain ischemia while the (core) body is still mounting its defense.

It would be impossible to design an Advance Directives template that is optimal for all cryonics patients, but there are a number of general guidelines that can inform such a document:

* All health care decisions should be guided by the objective of preserving the identity of the patient throughout the terminal and dying phase.

* Measures to prolong dying should only be initiated or accepted if they result in less ischemic injury to the brain.

* Life-sustaining measures should be withheld in case of traumatic or ischemic insults to the brain.

To ensure that sensible decisions are made in situations that are not covered by these Advance Directives, a Health Care Proxy can be executed that designates a person to make those decisions. It is understandable to give such power to the person closest to you but in the case of cryonics it is recommended that this responsibility should be given to a person with a strong commitment to your desires and a detailed understanding of the medical needs of cryonics patients.

Pre-medication of cryonics patients

If a critically ill cryonics member is at risk of ischemic brain injury during the dying phase it stands to reason that some palliative treatment options are better than others. One possibility for cryonics patients is to specify such options in one’s Advance Directives. Another scenario in which pre-medication is possible is where the medical surrogate is strongly supportive of such measures. It should be noted that such a decision rests solely with the member or his/her medical representative. Cryonics organizations should not be involved in the pre-mortem treatment of the patient.

There are two important questions about pre-medication of cryonics patients:

1. Is it safe?

2. Is it beneficial?

The answer to the first question has a lot to do with the status of the pharmaceutical agents in question. For example, a supplement like melatonin is less controversial than a prescription drug like heparin. The most important thing to keep in mind is that drugs that may be beneficial after legal pronouncement of death could have adverse effects in critically ill patients. Good examples are drugs that have effects on blood rheology and clotting. One would rather forego the hypothetical benefit of a drug if there is a non-trivial change of triggering major controversies about drugs taken during the dying phase. This leaves only certain supplements as relatively safe options for pre-medication of cryonics patients.

The answer to the second question is not clear. The rationale behind pre-medication is that it can protect the brain during agonal shock and its associated ischemic events. Evidence for this belief is usually found in the peer reviewed literature on neuroprotection in ischemia. However, there is a clear difference between the administration of neuroprotective agents during the dying phase and the administration of neuroprotective agents prior to artificially-induced acute ischemia. One perspective is that such agents are beneficial but only delay the ischemic phase of the dying period. In this case supplements have little neuroprotective effect. An alternative perspective is one where such supplements do not alter the agonal course as such but provide more robust protection after circulatory arrest. Obviously, this matter is not of concern to conventional medicine so there is little evidence to make rational decisions. In light of the previous discussion, the current (tentative) verdict should be that a case can be made for pre-administration of neuroprotective agents but that these agents should be confined to “safe” supplements like melatonin, Vitamin E and curcumin. Whether such a regime would be beneficial needs to be decided on a case by case basis and is, therefore, more in the domain of the Health Care Proxy than Advance Directives.

Do Not Resuscitate Orders

Do Not Resuscitate (DNR) orders present one of the most challenging issues for cryonics optimization. On the one hand, we would like to benefit from any attempt to resuscitate us in case of sudden cardiac arrest (or any other acute events that can lead to death). On the other hand, we would not like to be subject to endless rounds of futile resuscitation attempts that can damage the brain.

One would be inclined to think that resuscitation attempts should be made in case of sudden insults or during surgery but that no resuscitation attempts should be made during terminal illness. In reality things are not that simple. For example, resuscitation may be possible after 8 minutes of cardiac arrest but the patient can suffer severe brain damage as a consequence. Such a scenario can be minimized by executing a DNR at the cost of foregoing any resuscitation attempts at all. Would this outweigh the benefits of successful resuscitation attempts? It is hard to see how an objective answer to this question can be given without taking a specific person’s views on risk and treatment into account. One way to mitigate this dilemma is to make a distinction in your Advance Directives between pre-arrest emergencies (for example, resuscitation should be permitted in the case of labored breathing but presence of heart beat) and full arrest. An in-hospital situation where resuscitation of a critically ill patient would be helpful would be where it would allow a cryonics standby team to deploy at the bedside of the patient. As can be seen from these examples, good resuscitation instructions for cryonics patients require a lot of attention to context. Because confusion could arise whether Advance Directives would include pre-hospital emergency procedures it is recommended to execute an explicit document if you want these cases to be covered – such a document could be complemented by wearing a bracelet.

Creating a general template

This article has identified a number of important medico-legal issues that need to be addressed by cryonicists to optimize their cryopreservation. It has become clear that in the case of many topics we would all benefit from uniform and effective language. The next step is to translate the concerns discussed in this document in clear legal language so that templates can be offered to all members of cryonics organizations to draft their own Living Will and Advance Directives. One potential problem of such a general template is that it may not conform to state regulations and needs additional tweaking to make it valid in the state where the person lives.

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Appendix :  Neurological damage during the dying phase

Securing viability of the brain by contemporary criteria is the most important objective of cryonics standby and stabilization. Recognition of how pathological events in the central nervous system can defeat this objective is of great importance. As a general rule, the risk for increased brain damage is higher during slow dying. For example, when the ventilator is removed from the patient who is not able to breathe on his own the time between this action and circulatory arrest can be short. Conversely, when a patient is going through a prolonged terminal and agonal phase (regional) injury to the brain can occur while the body itself is still fighting for its survival.

The human brain has little storage of excess energy. As a result, hypoxia causes the brain to deplete its oxygen reserves within 30 seconds. The energy depletion that follows cerebral hypoxia during the dying phase has a number of distinct effects: 1) excitation or depression of certain processes in the brain, 2) alteration in the maintenance of structural integrity of tissues and cells, and 3) alteration of neuromediator synthesis and release. The depletion of oxygen leads to a switch from aerobic to anaerobic energy production. As a consequence, there is an increase in the metabolic end-products of glycolysis such as lactic acid which decreases pH in the brain. After 5 minutes no useful energy sources remain in the brain, which can explain why the limit for conventional resuscitation without neurological deficits is put at 5 minutes as well. Because the dying phase leads to progressively worse hypotension and hypoxia the metabolic state of the brain after the agonal phase is worse than if there would have been sudden cardiac arrest.

Light microscopic changes have been observed in brain cells after 5 minutes of ischemia. Prolonged hypotension, as can occur in the agonal patient, can lead to the appearance of “ghost cells” and disappearance of nerve cells. Such observations provide evidence that structural changes, including cell death, can occur prior to clinical death. Another manifestation of hypoxia (or hypotension) is the progressive development of cerebral edema. The resulting narrowing of vessels and decrease of intercellular space can, in turn, aggravate energy delivery to tissues. Of particular importance for cryonics stabilization procedures is the development of no-reflow which can prevent complete restoration of perfusion to parts of the brain during cardiopulmonary support. There is no consensus as to whether no-reflow can occur as a result of prolonged hypotension (as opposed to complete cessation of blood flow), but an extended dying phase can set the stage for cerebral perfusion impairment after circulatory arrest.

The central nervous system does not shut down at once. Throughout the terminal and agonal phase alternations in the brain progress from minor changes in awareness and perception to deep coma. As a general rule, more recent and complex functions of the brain disappear earlier than the most basic functions of the brain. The uneven brain response to hypoxia may reflect different energy requirements, biochemical and structural differences, and/or the activation of protective mechanisms to preserve the “core” functions of the brain. The CA1 region of the hippocampus has been demonstrated to be uniquely vulnerable to ischemia. This presents a problem for contemporary cryonics since the objective of human cryopreservation is to preserve identity-relevant information in the brain.

This article is a slightly revised version of a paper that was submitted for the 4th Asset Preservation Meeting near Gloucester, Massachusetts.

It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death….

Cryonicists have named their favorite conception of death “information-theoretic death.” In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person’s memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death.

In contemporary medicine, death can be pronounced using two distinct criteria; cardiorespiratory arrest or brain death. A lot of ink has been spilled over the co-existence of those criteria and its bioethical implications but I think that most people would agree that the practice of medicine requires this kind of flexibility. What is interesting for us is that clinical brain death (or brain stem death) is defined as “the stage at which all functions of the brain have permanently and irreversibly ceased.” There are a number of ways how such a diagnosis can be made, but in this context I want to focus on the absence of organized electrical activity in the brain.

We first should note the use of the word “irreversible.” After all, if a patient is cooled down to a low core temperature to permit complicated neurosurgical procedures most of us would not say that this person is “temporarily brain dead.” As a matter of fact, one could argue that cryonics is just an experimental extension of clinical hypothermic circulatory arrest in which there is a temporal separation of stabilization and treatment. Now, we could argue that what may be irreversible by today’s standards may not be irreversible by future standards but then, again, we are trying to persuade the other person to accept our view of future medicine. It would be much better, and I hope much easier, to argue that contemporary cryopreservation techniques can preserve organized electrical activity in the brain. The advantage of this approach is obvious. Instead of arguing in favor of our own criterion of death we can argue that, according to mainstream criteria for determination of death, cryonics patients are not dead. This is an interesting case in which a scientist (i.e., a cryobiologist) may be able to make a major contribution to the legal recognition and protection of cryonics patients.

So where are we standing right now? How good are our preservation techniques? If we aim for reversible whole brain cryopreservation a cryoprotective agent should have two properties: (1) elimination of ice formation, and (2) negligible toxicity. In the early days of cryonics, we were not able to satisfy both criteria at once. Using just a little bit of glycerol would not be toxic but it would still allow massive ice formation. Using a lot of a strong glass former such as DMSO would eliminate ice formation but at the price of severe toxicity. Mostly due to the groundbreaking work of cryobiologists Gregory Fahy and Brian Wowk, in the year 2000 the Alcor Life Extension Foundation introduced a vitrification agent called B2C that eliminated ice formation and had a more favorable toxicity profile. In the year 2005, the separation between the state of the art in experimental cryobiology and cryonics practice was further narrowed when Alcor introduced M22 as their new vitrification agent. M22 is the least toxic vitrification agent in the academic cryobiology literature that permits vitrification of complex mammalian organs at a realistic cooling rate.

M22 and other solutions derived from the same cryobiological principles have been validated in the brain as well. Former Cryonics Institute researcher Yuri Pichugin and collaborators used a related vitrification solution for the preservation of rat hippocampal brain slices without loss of viability after vitrification and rewarming. At a cryonics conference in 2007, 21st Century Medicine announced that the use of M22-based solutions permitted the maintenance of organized electrical activity in rabbit brain slices. So, at this stage we can argue that our existing vitrification solutions have a reasonable chance of maintaining organized electrical activity in brain slices. The next challenge is to demonstrate this property in whole brains.

Whole brain cryopreservation is not just the cryopreservation of a great number of individual brain slices. Brain slices can be cryopreserved by (step-wise) immersion in the vitrification solution. Vitrification of whole brains (even small brains such as rodent brains) requires the introduction of the vitrification solution through the circulatory system. This aspect of whole brain vitrification presents a number of technical challenges. Electron micrographs of vitrified tissue from whole brains, however, indicate that these challenges can be overcome. The current research objective is to perfect perfusion techniques and optimize vitrification solutions to maintain organized electrical activity in whole brains. We know that this objective is possible in principle because the famous surgeon Robert White demonstrated retention of electrical activity in whole isolated brains after cooling them to ~2-3°C. Isolated brain perfusion is a complicated surgical procedure, but the current writer and cryobiologist Brian Wowk have recognized that validation of whole brain activity is also feasible in situ.

Reversible cryopreservation of the whole brain without losing organized electrical activity is not a trivial research objective but it should be easier to achieve than reversible cryopreservation of the whole body and, perhaps, some other organs. If and when we accomplish this, we will no longer be dependent on “rationalist” arguments that appeal to logic and optimism about the future. We can argue that our patients should not be considered dead by the most rigorous criterion for determination of death in current medical practice. We can then even mount some smart legal challenges to seek better protection for cryonics patients. If we can make this step forward we should also aim at improved protection of existing cryonics patients, which will allow them, among other things, to own assets and bank accounts. This is how science can be employed in legal strategies for asset preservation.

This article is a slightly revised version of a paper that accompanied a recent presentation on neural cryobiology and the legal recognition of  cryonics at the 5th Asset Preservation Meeting in Benicia, California.

Robert Ettinger‘s book Youniverse: Toward a Self-Centered Philosophy of Immortalism and Cryonics is a book containing many insights and deep thoughts, yet has such an informal writing style that many readers might not take it seriously. I know of no other work of philosophy in which the author begins a sentence with “Anyway,”. Ettinger writes that the first cryonics-related organization was founded “in 1962 or 1963, I forget which”, then says “Why don’t I look it up?” and justifies himself by reference to a Woody Allen movie. This is not the kind of writing one expects from a philosophy treatise.

Ettinger may not take himself too seriously, but he is even more dismissive of most of the world’s foremost philosophers and religious figures. The writings of Aristotle are called “ramblings”. In describing William James’s statement that James was only able to understand Hegel while under the influence of nitrous oxide, Ettinger notes how appropriate it is that nitrous oxide is also called laughing gas. Ettinger wrote that “Rousseau has been extravagantly praised, and not only by himself”, but dismisses Rousseau as unoriginal, incoherent, not profound, and frequently wrong. Ettinger describes the philosopher G.E. Moore as being “definitely confused as well as confusing, abounding in contradictions and non-sequiturs, sometimes substituting assertions for arguments.” Ettinger often seems himself guilty of the last accusation. He faults Isaac Asimov for the “absurdity” that without the “saving grace of death” the rigid views of the old would prevent further progress — but leaves a critique of Asimov’s argument “as an exercise for the reader”. Ettinger writes that “Paeans of praise have poured from the pens of platoons of panting pundits” concerning Godel’s Incompleteness theorem, which he dismisses as a linguistic trick associated with the failure of physics to correspond identically with formal (mathematical) systems. By finding the quote from Wittgenstein “I don’t know why we are here, but I am pretty sure that it is not in order to enjoy ourselves”, Ettinger has massively deflated my respect for the philosopher Ludwig Wittgenstein. Ettinger describes the modern “self-styled bioethicist” as a “new type of vermin or parasite” whose major accomplishment has been to create “the illusion of looking down on people far above them.”

Ettinger wrote that “fear of God” is generally really fear of parents, neighbors, and a lifetime of conditioning. He says people too readily submit to tradition rather than use reason. To be “normal” is to have the same delusions as the neighbors. He says loyalty “is frequently a worthy habit”, but sometimes nothing more than an unjustified habit. Ettinger says faith is arrogant certainty in the absence of evidence, which ultimately “boils down to sacrificing your integrity for a bit of comfort”. To Ettinger it is obvious that non-human animals have consciousness and feelings, and that a God that disregarded the suffering of animals on the grounds that animals have no soul “would have less compassion than the average human”. Like many physicists, Ettinger seems accepting of the idea that time and the universe began with the Big Bang, but wonders where God would be before He created time and the universe. Ettinger can make no sense of an omniscient, omnipotent God creating people who need to live their lives to prove whether they deserve Heaven or Hell. Ettinger says that a benevolent God would forgive the skeptics, who should therefore have no reason to compromise their integrity and disbelief.

Ettinger’s irreverence extends to the legal system. Frequent use of appeals courts and split decisions in the Supreme Court are given as evidence that laws are unclear or that bias is pervasive. He describes juries as “ignorant, stupid and readily swayed by irrelevancies and by histrionics”. In connection with the adversarial system, Ettinger wrote “All lawyers are frightening, and specialty litigators are terrifying. Some firms are said to keep their lead litigators chained in a tower room and fed raw meat until needed.” I asked Mr. Ettinger what his beloved son (a lead litigator at a prestigious law firm) had to say about the law chapter, but I got no definitive response.

As the book title YOUNIVERSE implies, Ettinger believes that “me-first” and “feel-good” are the only possible basis for conscious motivation. He also states that a person ought to want whatever will maximize future “feel-good”, and that people do not always want what they ought to want. Ettinger believes that “figuring out what we ought to want is the primary problem of philosophy”. He says that a main aim of YOUNIVERSE is to debunk the views that values are arbitrary or externally given.

Ettinger challenges the claim of David Hume that “You can’t derive an ‘ought’ from an ‘is'”, and — like Ayn Rand with her Objectivist Ethics — he does so by reference to values being rooted in biology. Ettinger disparagingly dismisses Rand’s views as narcissism, “me generation”, and “looking out for number one” without explaining how this differs from “me-first”. Rooted in biology, Rand makes survival the basis of her ethics, rather than “feel-good”. Ironically, Ettinger writes more approvingly of Nietzsche’s self-centeredness, although Ettinger faults Nietzsche’s belief in the importance of power over other people as a core value. (Ettinger notes that Nietzsche believed Russians and Jews, rather than Germans, would be the “master races” of Europe.)

I disagree with the arguments of Rand and Ettinger for deriving “ought” from biology. Biology dictates that animals value food and water, but many humans have committed suicide by refusing food and water. To assert that such people are “wrong” and did not do what they ought to have done would be attempting to externally impose values upon them. Ettinger could argue that such people were acting in such a way as to maximize their satisfaction — “me-first” and “feel-good” (he gives the examples of a woman rushing into a burning building to save her baby, or “saints” who gain personal satisfaction from ascetic service to others). But by that argument they were wanting what they ought to want. The point Ettinger seems to be making is that people should not allow others to impose their values upon them — should not be driven by guilt, social pressure, the need to conform. But if people are driven by these motives, they are nonetheless still maximizing their satisfaction. Ettinger might say that such people are acting without integrity by not being true to themselves, but why should people be blamed for valuing the opinions of others and for this being important to them? If it is “impossible to be motivated by anything other than self interest, because motivation means what is important to the self”, then the word “ought” is inappropriate. If “me-first” and “feel-good” are the only possible bases for conscious motivation, then the word “ought” is inappropriate. The only reason that people fail to want what they ought to want is because of matters of fact, not matters of value — people failing to appreciate the consequences of their actions in the context of their values.

The issue of determinism and free will is a subject about which I have thought, read, and written about considerably (see A Case for Free Will AND Determinism ), yet I found Ettinger’s chapter on this subject impressively thoughtful and informative. I mostly agree with Ettinger’s views, about which we are both very much in the minority. I won’t say much about the issues or insights I gained in the determinism chapter, but I will comment on how he applies determinism to cryonics. Ettinger notes that “determinism is very nearly equivalent to” conservation of information, which implies that any human who ever lived could be reconstructed without having been cryonically preserved — except that there may never be adequate computing power.

Although I can conceive of retaining my personal identity in the total absence of any memories that I have, I nonetheless find the idea hard to relate-to. I am even less comfortable about the idea that the essence of my personal identity is feeling. Ettinger has firmer opinions on these subjects than I do, but I sense that his emphasis on feeling as the essence of personal identity contradicts his admonishments about the use of reason against intuition, tradition, and conditioning.

Ettinger skims over the subject of ischemic damage in cryonics, and I think he is wrong to say that “cryothermic damage will in most cases be the most difficult to reverse”. Freezing damage is like broken pieces that are nonetheless intact, whereas ischemic damage is like dissolution or decomposition of structure. Nonetheless, I cannot quantify my argument in terms of “most cases”. I think Ettinger is wrong to cling to the word “immortality” as meaning “indefinitely extended life” when its literal meaning is “eternal life”. His use of the word “immortality” presents cryonics as an alternative to religion rather than an extension of medicine.

Although Ettinger acknowledges that death will mean an end to suffering, he sees a number of disadvantages, including
“…it’s hard to enjoy life when you’re dead.
…daisies are prettier when viewed from above.
…you can only vote in Chicago.
…you need extra strength deodorant.”
But mainly, “Life is better than death because it is more interesting.” (For my own views on the subject, see: Why Life Extension?)

In his lifetime of reading Ettinger has collected numerous notable quotes, and these gems are liberally sprinkled throughout YOUNIVERSE. Some of my favorites include “‘Love thy neighbor as thyself’ presupposes that you love yourself” (Miguel de Unamuno), “The greatest part of our happiness depends on our disposition, not our circumstances” (Martha Washington), and Will Rogers’s WWII suggestion for getting rid of German U-boats: “Boil the Atlantic Ocean. How do we do that? Hey, I’m just an idea man, I leave the details to the engineers.”

Ettinger also has a chapter called “Misunderstandings” which deals with his insights into a wide variety of subjects. Indicative of my “anti-intellectual” bias, is the fact that my favorite is Ettinger’s observation that torque (force X lever arm length) has identical units to work (newton-meters), despite the fact that work and torque are completely different. He offers no solution or explanation, however.

A consequence of Ettinger’s informal writing style is that there is much autobiographical material throughout YOUNIVERSE. But the last formal chapter (I am not counting the Appendix) is explicitly autobiographical. He says “I have perhaps a few thousand admirers, hardly any of whom give me much thought or attention”. Ettinger speaks of his loneliness in having experienced the loss of all his friends and family of his generation, and that there is nobody left whom he wants to impress. Indicative of Ettinger’s world-weariness is his quote of a comment made by his brother that all of life is “killing time and amusing oneself while waiting to die”.

Ettinger’s final comments concern his plan to have a pre-mortem “jolly wake” with music, speakers, toasts, and other festivities prior to a suicide intended to improve the conditions of his cryonic preservation. Ettinger notes earlier in the book that “many people are more afraid of seeming cowardly than of facing danger”, which is why suicide with an audience of friends and family would boost his courage. The last line of the chapter reads “If I never wake up, my last experience will have been better than most — a very brief comfort, to be sure.”

Although there are some cryonicists who believe that Robert Ettinger would be the perfect cryonicist to win sympathy for voluntary self-euthanasia to improve cryopreservation, I am not one of them. How can you justify voluntary euthanasia in a non-terminal person when there is no way of knowing how many years of life that person could be expected to live? How can you justify voluntary euthanasia for ANYONE not suffering from a terminal disease, or expect the public to be sympathetic to voluntary self-euthanasia under these conditions? Even for terminal cryonics patients, I would not be to eager to see a public association of cryonics with self-euthanasia or physician-assisted suicide. Cryonicists would be accused of taking advantage of mentally-compliant sick and elderly people for monetary reasons, which would lead to even more cryonics-unfriendly legislation.

And there are practical problems, not the least of which is the danger of autopsy. Many cryonicists, myself included, cling to life tenaciously — much more tenaciously than the average person. I would find it very difficult to euthanize myself or have myself euthanized. The ideal situation is when death is nearly certain to occur within a week. But this is the condition in which standbys are typically initiated, not the condition in which standbys fail to occur. Heart attack is a common cause of death, and this is most often unexpected. Most cryonicists who receive standby are people dying of cancer, and whose slide toward death is along a more predictable path. The ability of cancer victims to euthanize themselves would make the standby process easier, but that would have no effect on reducing the number of cryonicists who deanimate without standby, despite having arranged for standby. There are no convincing arguments that simplifying self-euthanasia or physician-assisted suicide will lead to the majority of cryonics cases having greatly improved cryopreservation by significantly reducing the number of cryonicists deanimating under unfavorable conditions.

What is striking about cryonics is that those who have taken serious efforts to understand the arguments in favor of its technical feasibility generally endorse the idea. Those who have not made cryonics arrangements usually give non-technical arguments (anxiety about the future, loss of family and friends, etc), lack funding or life insurance, or are (self-identified) procrastinators. In contrast, those who reject cryonics are almost invariably uninformed. They do not understand what happens to cells when they freeze, they are not aware of vitrification (solidification without ice formation), they think that brain cells “disappear” five minutes after cardiac arrest, they demand proof of suspended animation as a condition for endorsing cryonics, etc.

This does not mean that no serious arguments could be presented. I can see two major technical arguments that could be made against cryonics:

1. Memory and identity are encoded in such a fragile and delicate manner that cerebral ischemia, ice formation or cryoprotectant toxicity irreversibly destroy it. Considering our limited understanding of the nature of consciousness, and the biochemical and molecular basis of memory, this cannot be ruled out. Cryonics advocates can respond to such a challenge by producing an argument that pairs our current understanding of the neuroanatomical basis of identity and memory to a cryobiological argument in order to argue that existing cryonics procedures are expected to preserve it. An excellent, knowledgeable, response of this kind is offered in Mike Darwin’s Does Personal Identity Survive Cryopreservation? Cryonics skeptics in turn could produce evidence that existing cryonics procedures fall short of this goal.

2. The cell repair technologies that are required for cryonics are not technically feasible. This argument should be presented with care and rigor because the general argument that cell repair technologies as such are not possible contradicts existing biology. A distinct difference from the first argument is that it is harder, if not impossible, to use existing empirical evidence to settle this issue. After all, making cryonics arrangements is a form of decision making under uncertainty and such decisions are not straightforwardly “correct” or “incorrect,” “right” or “wrong.” What can be done is to provide a detailed scientific exposition of the nature and scope of the the kind of repairs that are necessary for meaningful resuscitation and to argue that both biological and mechanical cell repair technologies are not conceivable – or are conceivable.

One thing that becomes immediately clear from this exercise is that there is no single answer to the question of whether cryonics can work because the answer to this question depends on the conditions and technologies that prevail during the cryopreservation of a patient. This introduces a set of more subtle distinctions concerning the question of what kind of cryonics should be assessed. It also produces an argument in favor of continuous improvement of cryonics technologies, and standby and stabilization services.

This short examination of technical arguments that could be made against cryonics gives advocates of the practice two talking points in discussion with skeptics or hostile critics:

(a) If a critic flat-out denies that cryonics is technically feasible, it is not unreasonable to ask him/her to be specific about what (s)he means by cryonics. This simple question often will reveal a poor understanding of existing cryonics technologies and procedures.

(b) A decision made on the basis of incomplete knowledge cannot be “right” or “wrong” and should be respected as one’s best efforts to deal with uncertainty.

This book review was originally published in Cryonics magazine, 1st Quarter, 2011.

Editor-in-chief, cryobiologist, and aging researcher Gregory M. Fahy and his associate editors Michael D. West, L. Stephen Cole and Steven B. Harris have compiled what might be the most impressive collection of articles on interventive gerontology to date in their 866 page collection The Future of Aging: Pathways to Human Life Extension. The book is divided into 2 parts. The first part includes general, scientific, social and philosophical perspectives on life extension. The second part is a collection of proposed interventions, which are organized in chronological order, starting with the (projected) earliest interventions first. Of course, such an organization of the materials necessitates a subjective estimation of when such technologies will be available and is bound to be controversial. The collection closes with a number of appendices about contemporary anti-aging funding and projects (SENS, Manhattan Beach Project).

I have read the book with the following two questions in mind:

1.     Which approaches for increasing the maximum life span show clear near-term potential?

2.     Is meaningful rejuvenation possible without advanced cell repair technologies?

What follows are my comments on selected chapters of the book.

I cannot say that I am a big fan of Ray Kurzweil’s work. His general introduction to life extension, “Bridges to Life,” co-written with Terry Grossman, starts out on a restrained note, discussing the benefits of caloric restriction, exercise, basic supplementation, and predictive genomics. But it then ratchets up into bold claims about the future that rest on controversial premises: about biology and health following the same path as information technology; about the technical feasibility of molecular nanotechnology; and about the nature of mind. One thing that remains a mystery to me is how such an accelerating pace of anti-aging technologies could be validated considering the relatively long life expectancy of humans. Presumably we are expected to adopt a lot of these technologies based on their theoretical merits, success in animal studies, or short-term effects in humans.

Associate Editor Stephen Cole contributes a chapter on the ethical basis for using human embryonic stem cells. I suspect that his argument in favor of these therapies relies on adopting a definition of personhood that has more far-reaching, and more controversial, consequences than just permitting the use of human embryonic stem cells. One of the most disconcerting aspects of the bioethical debate on stem cell research is that many of its advocates seem to feel that if they do not see an ethical case against it, government funding for such research should be permitted.  In essence, this means that opponents of embryonic stem cell research are obliged to financially support it as well. This is a recipe for further aggravating what has already become a passionate political debate.

As someone with relatively limited exposure to the biogerontology literature I should be cautious in singling out one technical contribution for high praise, but Joshua Mitteldorf’s chapter on the evolutionary origins of aging is one of the best and most inspiring articles in the field of aging research I have read and worth the hefty price of the book alone. Mitteldorf outlines a case for the theory that evolution has selected aging for its own sake and presents experimental findings that falsify other explanations for aging such as wear-and-tear and metabolic trade-offs. That aging is firmly under genetic control may appear the most pessimistic finding in terms of the prospects of halting aging but in fact allows for the manipulation of a number of selected upstream interventions that can inhibit or mitigate these programs.

It is clear from this ambitious book that cryobiologist Greg Fahy also has a strong interest in biogerontology but nothing prepared me for the encyclopedic knowledge that he displays in his lengthy chapter on the precedents for the biological control of aging. Fahy’s chapter further corroborates the view that aging is under genetic control. He also reviews a great number of beneficial mutations and interventions in animals and humans that can extend lifespan. Reading all these inspiring examples, however, I found myself faced with the same kind of despair as when reading about all the neuroprotective interventions in stroke and cardiac arrest. There is great uncertainty how such interventions would fare in humans (or other animals) and, more specific to the objective of human life extension, how we ourselves can ascertain that there are no long-term adverse consequences. Fahy does not run away from the most formidable challenge of all, rejuvenation of the brain without losing identity-critical information, but points out that identity-critical information might be retained despite the turnover and replacement of components that a meaningful life extension program for the brain would most likely require. Fortunately, people who make cryonics arrangements can feel a little better about this issue because their survival is not dependent on safe technologies becoming available in their lifetime.

Zheng Sui’s report on using high potency granulocytes to cure cancer in mice is one of the more exciting chapters in the book and a fine example of the role of chance discoveries in biomedical research (Zheng by accident discovered a mouse innately resistant to cancer). With substantial support of the Life Extension Foundation and other private donors, Sui is aggressively pursuing Leukocyte Infusion Therapy (LIFT) human trials instead of pursuing the torturous path of trying to illuminate the biochemical and molecular mechanisms that drive the successful results in mice. I should mention that a unique concern for cryonicists is that eliminating cancer in the absence of other effective anti-aging technologies could increase the likelihood of dying as result of identity-threatening insults such as cardio-vascular complications, ischemic stroke, or Alzheimer’s disease.

I must admit being somewhat disappointed in the chapter about “evolutionary nutrigenomics” by Michael Rose and his collaborators. Michael Rose has always struck me as one of the more level-headed and empirical aging researchers, and his work with fruit flies is a resounding demonstration of using evolutionary tools to investigate and combat aging. His short contribution to this book reads more as a quickly thrown together status update of their company, Genescient, than a rigorous treatment of the issues. Dispersed throughout the text are a number of interesting perspectives on alternative approaches to aging research and the validation of anti-aging interventions, but these issues are not discussed in much detail. Michael Rose’s work is of great interest, but this chapter is neither a good introduction to his work nor an in-depth treatment of the practical applications of his research.

Anthony Atala’s chapter, “Life Extension by Tissue and Organ Replacement,” is a fascinating update on the current status and potential of regenerative medicine and tissue engineering. Unlike most of the chapters in this book, the author reports a number of examples of successful clinical applications. It is a good example of how working with nature (instead of trying to improve upon it) can have meaningful near-term benefits. Unfortunately, there is no discussion of the progress in regenerative medicine for the brain. Obviously, such strategies cannot involve a simple replacement of the brain with a newly grown brain but selected repair technologies can play an important role in brain-damaging diseases and insults. The inclusion of “life extension” in the chapter title seems somewhat artificial to me because there is no distinct treatment about how tissue and organ replacement will be expected to contribute to life extension. Additionally, there is little discussion of contemporary artificial and mechanical alternatives to organs (or biological structural components) in this chapter, or in any other chapters in the book, which I think is a minor oversight.

Robert J. Shmookler Reis and Joan E. McEwen contribute a chapter about identifying genes that can extend longevity. Their discussion of the prospects for mammals includes the sobering observation that “many of the gains we can attain by a single mutation in the simpler organism may already have been incorporated in the course of achieving our present longevities.” Then again, unless aging is firmly under genetic control in simple organisms but the result of wear and tear in humans there should be (unique) approaches in humans that should confer similar benefits as well.

The publication of this book came to my attention when I learned about Robert Freitas’s contribution, “Comprehensive Nanorobotic Control of Human Morbidity (PDF),” so I was quite interested in reading this final chapter of the book. I am not qualified to comment on the technical aspects of his vision of nanotechnology. I think it is fair to say, though, that if resuscitation of cryonics patients is possible they will most likely be resuscitated in a future that has nanomedical capabilities resembling those that are outlined in this chapter. For this reason alone, this chapter should be of great interest to readers of this magazine. Of particular interest is the discussion of cell repair technologies and brain rejuvenation, a topic of great interest to cryonics. Freitas devotes considerable space discussing how anti-aging strategies like SENS can be achieved with medical nanorobots but the chapter falls short of offering a distinct exposition of a nanomedical approach to aging and rejuvenation. With such profound molecular capabilities one would think that such an approach would not just consist of updating existing biotechnological approaches to eliminate aging related damage with more powerful tools. I think that the distinct capabilities that molecular technologies have to offer would have benefitted from a more extensive discussion of their transformative capabilities. In particular, the section on nanorobot-medicated rejuvenation could have benefitted from a more rigorous treatment of the question of how these interventions would produce actual rejuvenation. Rejuvenation will be a practical requirement for most cryonics patients and it would be interesting to see a more detailed technical discussion of this topic.

Robert Freitas introduces the phrase NENS (Nanomedically Engineered Negligible Senescence) for his vision of how the goals of SENS can be achieved through nanomedicine. This raises an important question: is there any reason to believe that the timeline for “conventional” SENS will be different from the timeline for mature molecular medicine? It is hard to tell, but one could argue that the development of mature nanotechnology is more comprehensive than any strategies designed to deal with the causes or effects of the aging process. So why not just fund the work of biological and mechanical molecular nanotechnologists to accelerate meaningful re-design of the human organism? I think that the best answer is that our current state of knowledge does not justify giving a privileged position to any particular approach and having these visions of the future compete may be the best hope that we have for seeing meaningful rejuvenation and the resuscitation of cryonics patients in the future.

If there is one serious omission in this impressive collection of articles it is a more comprehensive chapter on the topic of biomarkers of aging in humans. As reiterated throughout this review, the gold standard and most rigorous determination of the efficacy of anti-aging therapies and interventions is to empirically determine whether they increase maximum human lifespan. For obvious reasons, most medical professionals and healthcare consumers are pressed to make decisions based on less rigorous criteria and the development of a set of reliable biomarkers of aging is highly desirable. Of course, the most rigorous case for successful biomarkers would require the same kind of long-term studies, leading to an infinite regress problem. How to break out of this predicament while retaining a framework to make rational decisions about life extension technologies is not a trivial problem and can be the topic of a whole new volume of articles. Interestingly enough, one of the most insightful perspectives on this issue is given in Appendix A by SENS researcher Michael Rae when he points out that therapies aimed at rejuvenation can be tested at much more rapid timescales than therapies to retard the aging process or increase the maximum lifespan.

Michael Rae also notes that SENS’s “engineering heuristic” is well established in other fields of biomedicine. It is certainly the case that aging research could benefit from a stronger emphasis on solving problems and repairing damage instead of completely trying to understand the underlying pathologies but it also needs to be pointed out that the engineering approach has not fared much better in areas of research that are notoriously resistant to effective solutions such as neuroprotection in stroke. Ultimately, the SENS approach cannot completely escape studying the mechanisms and metabolic pathways involved when treatments are compared and side-effects are studied. In this sense, the difference between SENS and alternative approaches is a matter of degree, not principle.

I think that the editors are justified in claiming that the prospects for solving the aging challenge have never looked better. A close inspection of all the chapters, however, shows that no significant interventions in the aging process in humans are available now, and I doubt they will become available in the near future. And even if the aging process can be eliminated, there will still be medical conditions and accidents that require placing a person in cryostasis until effective treatment is available. For the foreseeable future there is good reason to agree with Thomas Donaldson’s advice* that making cryonics arrangements is the most fundamental and sensible decision one can make in order to reap the benefits of powerful future life extension therapies.

*Thomas Donaldson – Why Cryonics Will Probably Help You More Than Antiaging, Physical Immortality 2(4) 28-29 (4th Q 2004)


This article was originally published in Cryonics magazine, 4th Quarter, 2010.

Introduction

The most important reasons for writing case reports are:

1. To provide a transparent and detailed description of procedures and techniques for members of the cryonics organization and the general public. A cryonics organization that never writes anything about its cases and procedures should be treated with more caution than an organization that does.

2. To validate current protocol and procedures in general, and its actual implementation in particular. A case report should not only record what happened but should be used for guidance as to what should happen in the future. A detailed case report, especially when a variety of physiological data has been collected, contains a wealth of information that can be analyzed for the team members’ and patient’s benefit. Cryonics cases are relatively rare (compared with other medical procedures), so we should try to learn as much as we can from the cases we perform.

3. To serve as a medical record to assist with future attempts to revive the patient. Although advanced future medical technologies may make it possible to determine the physiological condition of the patient down to the molecular level, it is important to provide as much medical information as possible to help in efforts to revive patients. Having a detailed record of the patient’s condition prior to pronouncement, subsequent stabilization, and cryoprotection, may also help the organization in establishing the desired sequence of revival attempts.

4. To gain more scientific credibility. If we want scientists and physicians to take us seriously, we need to convince them that we attempting to cryopreserve our patients in a scientific manner.  Professional case reports can provide this kind of credibility.

This article will mainly concern itself with the general question of how a case report can help a cryonics organization in improving protocol, techniques and skills.

Protocol

To be able to assess the quality of patient care in a cryonics case, it is important to specify what the intended protocol was prior to writing about the case. Only if we know what the organization was supposed to do will we be able to assess how successful the care was. For example, if there is no mention of collecting (and analyzing) blood gases during a case this may have been because it is currently not a part of the organization’s protocol, but it may also be the result of a shortage of skilled personnel, defective equipment, or other problems or deficiencies. Unless the writer of the report specifies what should have happened, it is difficult to assess the quality of preparation and performance. If preparation for the case was poor and there was no (functional) extracorporeal perfusion equipment available, the case report should not simply state that the organization attempted to do a

case without substituting the blood with an organ preservation solution, but also why the blood washout was not attempted.

In reality there will be many deviations between the organization’s protocol and what actually happens. Human cryopreservation cases are not controlled laboratory experiments, and as many people who have extensive experience doing cases know, unique situations present themselves, including frustrating events that are beyond the control of even the most skilled medical professional. Nevertheless, the inherent unpredictability and uniqueness of cryonics cases is too often used as an excuse or justification for failing to follow established protocol, or for serious errors and omissions in the care of the patient. Documenting the prospective protocol will help us to gain a more systematic understanding of what is possible (or essential) and within our control, versus that which is not.

Detail

The importance of writing detailed descriptions of the procedures and techniques employed during a case cannot be overestimated. This not only enables the reader to gain a comprehensive understanding of the techniques used, it also allows detailed analysis of the difficulties that were encountered during a case that would not have been noticed if there is only a brief mention of it. For example, instead of simply noting that medications were administered, providing comprehensive details is essential. There are many reasons why this is the case.

Case reports should be prepared with the possibility in mind that what may seem mysterious, or inexplicable, to the writer may be crystal clear to an expert or perceptive reader when provided with sufficient detail.

Providing as much detail as possible also serves to allow for replication of the techniques used by others. This is a critical component of the scientific method. Other investigators or practitioners must be able to duplicate the procedures and obtain the same outcome. Yet another consideration is that factors not now perceived or considered to be important may become so in the future. There are many examples of this in the history of cryonics that have proved essential to improving patient care. For example (1), in the early days of cryonics bags of ice were used to facilitate external cooling. It was not until comprehensive and consistent core cooling data were collected that it became apparent that this technique required 6-8 hours to cool a patient to ~ +20°C (room temperature!) with the patient cooling at a rate of 0.064°C/min. Documentation of these appallingly slow cooling rates provided powerful incentive to develop stirred water ice baths which increased cooling rates to between 0.15°C/min  and 0.33°C /min, allowing cooling to ~15°C within 90 minutes to 2 hours after the start of cardiopulmonary support (CPS) (see graph below).

Comparison of Cooling Methods: Above are actual cooling curves for three adult human cryopreservation patients on Thumper support, using ice bags, the Portable Ice Bath (PIB), and the PIB augmented by SCCD (squid) cooling. Patient A-1133 weighed 56.8 kg, patient A-1169 weighed 57.3 kg, and patient A-1049 weighed 36.4 kg. As this data indicates PIB cooling is approximately twice as efficient as ice bag cooling. The SCCD appears to increase the rate of cooling by an additional 50% over that of the PIB (roughly adjusting for the difference in the patients’ body mass).

This example is even more instructive because continued diligent and comprehensive monitoring of cooling in multiple patients made clear other factors that were critically important to good outcome or, conversely, prohibited it. A large-framed obese male with heavy fat cover and a large amount of thermal inertia will not cool at anywhere near the rate that an emaciated, petite woman will. Evaluating the patient for fat cover and body mass index before deanimation allows reasonably accurate prediction of the cooling rate and may suggest the need for the addition of other cooling modalities such as peritoneal lavage with chilled fluid. Favorable results from application of peritoneal cooling in turn will suggest that even greater rates of cooling are possible for all patients and lead to the addition of the modality as a standard part of the protocol.

Failure to gather and promptly analyze data as basic as cooling rate precludes realization that problems exist as well as any possibility of solving them.

It is important to note that an incomplete case report doesn’t necessarily indicate failure on the part of a cryonics organization. In a case where the number of team members is limited, all resources may have to be devoted to doing the case, instead of collecting data, or assigning an essential person to the job of taking notes. In the case of limited personnel it is better to do a good case without documentation than to document a bad case. To some degree this conflict between tasks can be avoided by having some of the team members (the team leader, paramedic, etc.) use a voice recorder with a clip-on microphone. But if the number of team members is insufficient, and data collection is not possible, this should be reported in the case report and recommendations should be made and implemented to prevent this situation from occurring again in the future. Good data acquisition and scribe work are essential for a good case report and, if feasible, should be a full-time job during a case.

Analysis

Specifying the protocol and describing the case in great detail is necessary but is not sufficient. A critical review of the information and data culminating in a list of desired changes and specific plans to address them should complement this. Ideally every discrepancy between protocol and reality that has been observed during the case should be discussed. Even in a case where stabilization started promptly after pronouncement, and the protocol was followed to the letter, there is still a lot of (physiological) data that, once analyzed, may require a change in the protocol in future cases.

To assess skills, identify critical failures, formulate solutions, and compare cases in a meaningful and valid way, a consistent and systematic format of reporting cases is essential. A typical case report should be divided into sections describing protocol, patient assessment, preparation and deployment of standby assets, the details of the case (divided in sections such as  airway management, cardiopulmonary support, external and other cooling methods, blood washout, cryoprotective perfusion, and cooling to storage temperature), analysis, recommendations, and a variety of (public or non-public) appendices. Such appendices should include time-lines and graphic presentation of data, medications, cryoprotectants, and statistical analysis and comparisons to other cases.

Each case report should not only present solutions, or suggest tests and experiments to identify solutions, but provide a plan of action as to how these things can be accomplished. One approach to ensure that research and tests to validate solutions are implemented, and appropriate remedial action is taken, is to appoint an officer in the organization who is responsible for quality assurance and quality control. This individual’s job will be to ensure that case reports are written in a manner consistent with the guidelines as outlined by the organization, as well as to ensure implementation of required changes.

Another critical role of case reports is to educate the organization’s staff as well as consultants and, where appropriate, the patients’ physicians and other health care providers about protocol, procedures and techniques. Although case reports are not and should not be a substitute for comprehensive written protocols, standard operating procedures (SOPs), and thorough training of personnel, sometimes solutions to problems can only be found in case reports where a team member was presented with an unusual problem. Consistent and systematic organization of case reports will greatly enhance the utility of case reports for this purpose. For example, if a reader wants to know about surgical techniques, and problems encountered in gaining access to the circulatory system for blood washout, consulting a case report will be far easier if they’re organized in a consistent and predictable manner.

Answering Objections

One objection to writing up a case report is that it is not a controlled experiment and at best provides only anecdotal evidence. This is not the case for the following reasons.

Not all the mistakes and issues identified are of a hypothesis testing nature. For example, if a patient presents the human cryopreservation team members with a problem that could not be managed with the equipment at hand, the cryonics organization doesn’t necessarily need a larger number of cases to decide to make a change to their equipment, and to start teaching employees the necessary skills.

Similarly, what may be perceived as anecdotal evidence for the cryonics organization may be a consistent finding in nearly identical settings in mainstream medicine. For example, some issues during a human cryopreservation case may be well known in hemodynamic management of potential organ donors in hospitals, or, for example, a medication in the protocol that is undergoing trial as a stroke therapy may demonstrate the same adverse effects observed during transport of a cryonics patient.

Of course, such lessons are impossible to learn without both broad and deep knowledge of medicine and the relevant research literature. Considering the ever growing number of publications and hyper-specialization, case reports may increasingly become collaborations between numbers of people with expertise in diverse areas. The individuals with the most valuable input do not necessarily have to be the ones who did the case. A physician dealing with similar issues in a neuro-intensive care unit may identify problems and propose solutions not obvious to those delivering cryonics care to the patient.

Monitoring

We don’t know how our patient is going to fare in the future but we can know a lot about how our patient fared up to the point of long term low temperature care if we monitor his condition continuously. This starts from collecting detailed pre-mortem medical data to monitoring fracturing events during cooldown.

It is tempting to say that a case went very well if all the steps of the protocol were followed in a timely manner. This is not unreasonable because one would expect a strong correlation between an evidence based protocol and optimal care. But it is important to keep in mind that the goal of stabilization and cryopreservation is to treat the patient and not the book (as a saying in emergency medicine goes).

Without comprehensive monitoring of the patient through all parts of the procedures a case report will only document a predictable series of mechanical steps and some crude visual indicators of (relative) success at best. The things we are really interested in, like (quantitative) end-tidal CO2 measurements, cardiac output, pH, and cerebral oxygenation, cannot be observed without sophisticated equipment.

Not only do we want to know how the patient is doing after the fact, we would also like to be able to intervene during a case if we observe a trend that suggests (alternative) treatment. Only in-depth reporting and analysis combined with a sound understanding of the physiopathology and available treatments will enable us to do so.

Presentation

A comprehensive list of dos and don’ts in writing case reports is not something that can be explored in this article, but some things are worth mentioning. Stylistically, a human cryopreservation report should resemble a medical or research report rather than a sensationalized adventure for the patient or the standby team. This should apply to the organization of the material as well as the choosing of words. As a general rule mainstream medical terminology should be used instead of cryonics jargon. Editorializing should be limited, and if perceived necessary, be moved to the proper section of the report. For example, jumping from a technical description of procedures to quarrelling among relatives or complaining about government regulation doesn’t look very professional.

Protocol, procedures and techniques should be the subject of the report, not people. Cryonics preparation and procedures are very demanding and exhausting for all people involved and mistakes are made and will be made. Errors should be presented as dispassionately as possible to avoid a culture of blame and personal conflict. Experience also teaches that (potential) participants are more open to transparent reporting if a case report will not single out individuals in describing procedures.

No matter how competent the writer of the report is, each report should be proofread by most or all individuals who were involved in the case and, if possible, a variety of outsiders with appropriate technical and medical knowledge, before it is released to the general public.

Patient Care

Writing case reports as presented in this article may be more demanding and time-consuming than generally has been done in human cryopreservation, but the results may improve patient care to a degree not previously seen.  Ultimately, the most ambitious use of case reports will be one in which the case reports are analyzed as a series, measurements are compared, and patterns are established. Reading (and evaluating) a series of case reports in a systematic manner  will even enable us to answer some very fundamental questions as to whether, or the degree to which, protocol, procedures and techniques  have improved over the years.

Providing the best patient care possible for current and future patients is the reason why cryonics organizations exist, and considering how powerful a tool a good case report can be, a responsible cryonics organization should devote considerable resources and time to writing them.

As our members and resources increase, and human cryopreservation gradually becomes a part of mainstream medicine, the successful transition from basic algorithm, volunteer driven case to evidence-based cryonics will be an important mandate.

Case reports and increasing caseload

One of the biggest challenges facing a growing cryonics organization is that the organization will be faced with a growing number of cases per year. This challenge is further amplified if all these cases need to be documented. As a consequence, a cryonics organization will find itself allocating an increasing amount of time to writing case reports and falling behind publication schedule. One of the most unfortunate responses to such a development would be to make an attempt to keep writing case reports in the old style but to lower standards and take short cuts.

An alternative approach is to develop a new format for case reports that allows for a shorter report but still captures the essential objectives of case reporting. One approach is to eliminate all the narrative that is not essential for following the mechanics of the case and evaluating the quality of care. In the past there have been a number of case reports with excessive narrative but little technical reporting or analysis. For a cryonics organization with a growing caseload the opposite approach should be followed. Another approach is to eliminate detail about procedures that were performed without deviations from past protocol and expectations, provided that this is made explicit in the report. As a result, case reports will increasingly read as a description and commentary on events that diverged from protocol or new observations about existing procedures.

To establish a template for such case reports the following approach can be followed. First, it is established what kind of information is essential for doing a meta-analysis of all cryonics cases. Then these parameters are reverse-engineered to create a template for writing case reports that reconcile the need for economy of expression and documenting all the relevant aspects of a case.  One important advantage of producing such case reports is they permit easier consultation of the technical details of the case and still meet the fundamental objectives of writing case reports.

The history of case report writing in cryonics shows an erratic potpourri of approaches and styles. One of the most unfortunate victims has been the objective of using case reports to improve the practice of human cryopreservation and to formulate meaningful research questions for the sciences that inform cryonics. But if systematic thought is given to the objectives of case reporting outlined in this document, steps can be taken to leave this unsatisfactory situation behind while meeting the needs of a growing cryonics organization.

Notes

(1) I am grateful to Mike Darwin for this example and for reviewing earlier drafts of this article.

Paul Edwards concludes his chapter ‘The Semantic Challenge’ in his book God and the Philosophers with the following observation about logical positivism:

It is not uncommon nowadays to hear logical positivism dismissed as a set of crude errors and confusions. This is done with an air condescension by philosophers whose writings are usually models of obscurity. To people of my generation who came to philosophy in the 1940s, when traditional metaphysicians  were a dominating force, logical positivism was a liberating movement. Occasionally the leading figures were guilty of dogmatism, and on some important issues, such as the mind body problem and the question of free will, the logical positivists made no significant contributions, but the main doctrines seem to me substantially sound. The verification principle in particular, when stated with suitable amendments, is a powerful weapon against pretentious humbug.

Do life extensionists need to take an interest in philosophy of science and metaphysics? In his review of James Ladyman and Don Ross’s Every Thing Must Go: Metaphysics Naturalized, Alcor staff member Mike Perry notes that “as immortalists we hope to be in the world for a good long while, thus we are interested in the nature of reality. Reality determines, among other things, what our prospects are for our own longterm survival.”

Alternatively, one could argue that metaphysics is not a theoretically legitimate discipline and that the verifiable claims of physics exhaust what we can say about “reality.” Perhaps the most useful benefit of familiarizing oneself with philosophy of science and analytic philosophy is that it enables one to get a better appreciation of the difference between meaningful experimental science and sweeping generalizations deduced from shaky metaphysics.

Further reading: Five important empiricist philosophy books