The Future of Aging: Pathways to Human Life Extension

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)


Philosophy of science and life extension

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

The RhinoChill: A New Way to Cool the Brain Quickly

We scientists are difficult, cranky, and above all, maddeningly frustrating people. Want to turn lead into gold? No problem, we can tell you how to do that, and in fact have even done it already: the only catch is that the cost of such ‘nuclear transmutation’ is many times that of even the most expensive mined gold. You say you want to travel to the moon? Done! That will be ~$80 billion (in 2005 US dollars). Want to increase average life expectancy from ~45 to ~80 years? Your wish is our command, but be mindful, you will, on average, spend the last few of those years as a fleshpot in the sunroom garden of an extended care facility.

And so it has been with an effective treatment for cerebral ischemia-reperfusion injury following cardiac arrest. Thirty years ago, laboratory scientists found a way to ameliorate most (and in many cases all) of the damage that would result from ~15 minutes of cardiac arrest, and what’s more, it was simple! All that is required is that the brain be cooled just 3oC within 15 minutes of the restoration of circulation. The catch? Well, this is surprisingly difficult thing to do because the brain is connected to the body and requires its support in order to survive. And the body, as it turns out, represents an enormous heat sink from which it is very difficult to remove the necessary amount of heat in such short time. Thus, the solution exists and has been proven in the laboratory, but it has been impossible to implement clinically.  This may be about to change as a variety of different cooling technologies, such as cold intravenous saline and external cooling of the head begin to be applied in concert with each other. Separately, they cannot achieve the required 3oC of cooling, but when added together they may allow for such cooling in a way that is both effective and practical to apply in the field.  A newly developed modality that cools the brain via the nasal cavity may provide the technological edge required to achieve the -3oC philosopher’s stone of cerebroprotection.

Read the complete article in PDF here.

Prospects for Mild Therapeutic Hypothermia and Improved CPR in Cardiopulmonary Cerebral Resuscitation

There are two kinds of hypothermia: protective or preservative hypothermia, and therapeutic hypothermia. The former is easy and straightforward to understand for most, clinicians and laymen, alike.  However, therapeutic hypothermia has proved to be a far more difficult idea to communicate, probably because it is so easy to conflate it with protective hypothermia.

Anyone who has had any contact with refrigeration will at once understand the concept of protective hypothermia. Foodstuffs, and other biological materials that are cooled, experience protection against spoilage and decay roughly in proportion to the degree to which they are cooled. A little cooling slows decomposition a bit, and enough cooling will stop it altogether. Again, the temperature-induced decrease in the rate of chemical reaction is a fundamental property of chemistry which is understood intuitively by anyone who lives where it gets cold, or where refrigeration is in use.

By contrast, therapeutic hypothermia does not rely primarily upon the slowing of metabolism or the rate of chemical reactions that occurs as a result of cooling, but rather upon the effects very modest degrees of cooling have on gene activation and signal transduction in mammals. Controlled, mild therapeutic hypothermia (MTH) is generally understood to constitute a reduction in body temperature from ‘normal’ for the species being treated, to 3oC below normal. In the case of humans, this would mean a reduction in body temperature from 37oC to 34oC. Such a modest reduction in temperature results in profound down-regulation of pro-inflammatory cell-signaling pathways and causes the inactivation of genes involved in a multiplicity of deleterious cellular and systemic processes. Similarly, MTH can inhibit apoptosis of brain cells, and slow or halt the downward spiral of excessive metabolic demand by injured cells, causing yet more non-productive hyper-metabolism, and consequently even more cell death. In this article, the biomechanics of MTH are briefly explored, as well as the prospects for improved outcomes in patients who suffer anoxic-ischemic brain injury as a result of cardiac arrest as a result of the rapid application of MTH following the insult.

Read the complete paper in PDF here.

Suspended Animation Conference 2011

The cryonics company Suspended Animation “will sponsor the conference, “Suspended Animation – The Company and The Goal,” which will be held in Fort Lauderdale in May, 2011. The conference will feature speakers on the latest strategies and advances toward perfecting reversible human suspended animation. During the conference, SA will also host tours and demonstrations at its facility in Boynton Beach.”

More information about the program, registration, and the free live webcast can be found on the Suspended Animation 2011 conference page.

From the conference brochure:

“The Whole-Body Vitrification Project – Greg Fahy, PhD — 21st Century Medicine, Inc. Major new findings from Phase I of a revolutionary longterm project to achieve reversible whole-body solid state suspended animation in humans. This project, conducted at 21st Century Medicine, is the only whole body vitrification research being conducted in mammals and was funded entirely by a $5.6 million dollar grant from the Life Extension Foundation. Cryobiologist Greg Fahy will discuss how well whole animals can be cryopreserved right now, the possibility of using a single advanced vitrification solution to cryopreserve entire animals and, eventually, humans, and a unique, newly-invented technology to produce large, cryopreserved tissue slices for scanning and transmission electron microscopy. A proposal and budget for Phase II of the Whole-Body Vitrification Project will also be presented.”

Is a life worth starting? Some personal views

For life—the life of any sentient creature—to be worth living, there must, as Robert Ettinger has often said, be a preponderance of satisfaction over dissatisfaction. If this overall slant toward good rather than bad is maintained, it seems reasonable that one stands to gain by continued existence. I am not sure what fraction of the human (or other sentient) population achieves this positive balance and will not speculate except to note that by appearances there are many humans who do achieve it, along with other creatures, pets in particular, so at least for them, life is worth continuing. To say that life once started is worth continuing does not, as David Benatar points out, imply that it was worth starting in the first place, or should have been started. But I think that, barring certain problematic cases,  it is fair to conclude that a human life at least is worth starting, if there are responsible prospective parents who would like to start it. Here I think it is reasonable to expect that the resulting person will feel that life is overall a benefit, and additionally, that others, the parents in particular, will stand to gain from the new life that has entered their lives. I don’t accept Benatar’s arguments that by and large life is pretty terrible and people delude themselves who think otherwise.

Also I reject his “asymmetry” argument, that it is “good” if a life that would be bad does not come into existence, but merely “not good” rather than “bad” if a life that would be good does not come into existence. (It is easy to see how this asymmetry supports the argument that life should not start in the first place and Benatar refers to it often.) Benatar’s main rationale for this argument seems to be that, while we would consider someone morally at fault for deliberately bringing into existence someone who would be miserable and just want to die, we would not similarly hold someone culpable who elected not to bring into existence someone who would be happy and want to remain alive. This I think should not be the only consideration, for it is based only on the idea of when we should regard an action as bad, and not at all on when we should regard it as good and commendable. (Why this particular asymmetry?) Instead, weighing both sides of the issue as I think is justified, I would opt for the fully symmetric position that it is “not bad” if a life that would be bad does not come into existence, and similarly, “not good” if a life that would be good does not come into existence. On the other hand, I question and doubt whether a life that comes into existence would be bad in the long run, given the prospect of immortality, which I think is a possibility through science (see below).

Life does, of course, have its problems, death in particular, that might call in question whether it is worthwhile after all and thus, whether the life of any sentient being is worth starting.  For this one problem there are a number of possible answers that will be satisfying to different people, and thus can serve as ground for a feeling that life is worthwhile and was worth starting despite one’s own mortality. There is the famous Epicurean argument that death is not really a problem because before it happens it causes no harm, and after it happens there is no victim. There is the Buddhist argument that, more fundamentally, the self is an illusion anyway, so that in fact no persons exist and death never really happens, though bliss can still occur through states of enlightenment which thus are worth seeking. There are various religious traditions that promise an afterlife and a happy immortality for those who prove worthy, or, in some versions, all who are born. Then there is scientific immortalism, which holds that at least substantial life extension through science and technology is possible, so that, irrespective of any supernatural or mystical process, persons of today have more to hope for as they get older than the usual biological ruin and oblivion.

The scientific possibilities for overcoming death come in different varieties that each have their own advocates. Some of these hopefuls, particularly younger ones, focus on the prospect that aging and now-terminal illnesses will be remedied in their natural lifetime, so that they will escape clinical death and need not specially prepare for it. Others who are not so confident have made arrangements for cryopreservation after clinical death, in hopes of resuscitation and cure of aging and diseases when the requisite technology becomes available. Still others hold out for advances on a more cosmic scale that will eventually make it possible to raise the dead comprehensively. (Some possible scenarios for this using multiple, parallel time streams rather than revisiting or recovering a hidden past are considered in my book, Forever for All, and the article at http://www.universalimmortalism.org/resurrection.htm.) The three possibilities are not mutually exclusive, so that, for example, persons who have chosen cryonics may also place varying hopes in the other two. In fact, my personal viewpoint as a scientific immortalist grants some validity to all three possibilities, but I think it is imperative now to be engaged in cryonics, which is almost unique and the clear favorite as a proactive, interventive strategy against death. Passive acceptance of the dying process simply does not feel right, whatever the prospects for near-term medical progress, or on the other hand, resurrections in a more distant, technologically superior future. It goes without saying that I also think future life will be worth living—it should be possible to make it so, if future developments can provide the opportunity.

Non-existence is hard to do

A review of  contemporary antinatalist writings

Originally published in Cryonics, 2nd Quarter, 2010 (PDF)

“Coming into existence is bad in part because it invariably leads to the harm of ceasing to exist.” David Benatar

If they could get a corpse to sit up on an operating table, they would jubilantly exclaim, “It’s alive!” And so would we. Who cares that human beings evolved from slimy materials? We can live with that, or most of us can.” Thomas Ligotti

The persistence of pessimism

When I sent out an email message soliciting contributions on the topic of philosophical pessimism and antinatalism one person declined with the reasonable response that such positions are only taken seriously by a handful of far-out philosophers. Humans have evolved to procreate and seek happiness. What is the point?

The reason why I have not been inclined to so easily dismiss the recent renaissance of philosophical pessimism is because negative and tragic views about life are woven throughout human history and culture. Most dominant religions have little positive to say about the state of humanity (after the fall) and the prospects for a life devoid of suffering on earth. Despite its relative sophistication, even Buddhism presents a picture of the universe as a source of suffering. Much can be said about pessimism but not that its influence is outside the mainstream.

Even the antinatalist position that it is better never to have been and that we have a moral obligation not to procreate is not completely obscure. Who has not had the experience of talking to the grumpy old lady who wonders why anyone would want to bring children into this world? We routinely dismiss such positions as being out of touch with reality but modern culture persists in linking intellectualism to pessimism. This perhaps should not be surprising because, as a general rule, excessive thinking comes at the expense of sensual experience. One reason why many intellectuals are biased towards pessimism is because it provides them the opportunity to rescue us with their ideas. Antinatalism offers the triumph of Reason against existence itself; the ultimate triumph of the Intellectual.

Philosophical aversion to pessimism can be found among the finest thinkers in the history of philosophy. There is David Hume, the great empiricist thinker, and an amiable and optimistic person. Then there is Friedrich Nietzsche, who, despite a life of disease and isolation, recognized that pessimism is not an objective feature of the universe but the expression of a weak and oversensitive mind. The twentieth century witnessed a strong renaissance of the empiricism of David Hume in the form of logical positivism. These philosophers rightly abstained from putting forward a “philosophy of life,” but optimism about science and humanity’s potential is clear in their foundational writings. It is also interesting to note that the most recent forceful responses to pessimism have not come from professional philosophers but from libertarian economists who do not display the slightest intellectual embarrassment in claiming that life is getting better all the time.

In my opinion, the most obvious question that can be raised about philosophical pessimism is whether its supporting claims are factual descriptions of reality or just expressions of temperament. Another interesting question is whether philosophical pessimism necessarily obliges us to the antinatalist position. In seeking answers to these questions we turn to the literature of contemporary antinatalism.

Jim Crawford’s Confessions of an Antinatalist is a highly readable autobiographical exposition of antinatalism. Thomas Ligotti’s book The Conspiracy Against the Human Race is more ambitious in scope and contains a wealth of historical information on pessimism, discussions of modern science, and, not surprisingly, a review of the theme of pessimism in horror literature. David Benatar’s Better Never to Have Been: The Harm of Coming into Existence is the most rigorous exposition of antinatalism to date. This book covers a lot of ground and I will confine myself to some of its main topics only.

The harm of coming into existence

In its purest form antinatalism may not be attainable but the framework that informs this position rests on a couple of sound premises: (1) we do not impose a harm (or withhold a benefit) by not bringing someone into this world; (2) we do impose a harm by bringing someone into the world when this person’s life will be bad. Jim Crawford believes that these premises are evident and I see little reason to dispute him. The real debate about antinatalism is how to determine that a person’s life is (or will be) bad, and how much consideration the interests of parents should be given.

One of the most problematic aspects about the work of Crawford and other antinatalists is that they have little patience for the argument that life is better than they think it is. In some passages it is hard to distinguish the antinatalist from the Marxist. If people think that life is much better than Crawford makes it out to be, the standard rejoinder is that these people suffer from a form of false consciousness (pessimists frequently use words like “truly” and “really”). In some passages this attitude borders on intolerance. A prime example can be found in Crawford’s discussion of childhood. For many people growing up was a period of great happiness and discovery. Crawford’s agitated dismissal of such accounts introduces an element of illiberalism in what is otherwise a humanistic endeavor. It is in these passages that antinatalism turns into bitter ideology.

The way the term “bias” is employed is deeply problematic. It is used as if there is an objective perspective that can reached were it not for those pesky evolutionary biases coming between the person and the universe. At times the author appears to be saying that if evolution did not select in favor of those wanting to survive we would not want to survive. This is not particularly helpful. Some of these “biases” do not cover up anything but just make us happier.

Let us assume here the metaphysical premise that there is an objective, material reality that can be known through the use of reason and empirical observation. This does not mean that there is one “correct” fit between an organism and the world. A person who is manically depressed perceives the world in a different matter than a person who is not. How we are “wired” and respond to our environment is not a matter of “correct” or “incorrect.” Thinking otherwise would be hard to reconcile with an evolutionary outlook in which life is just the outcome of random interactions of organic molecules.

One argument that remains available to the pessimist would be that the probability of creating a miserable life is too high to warrant procreation. But it is at this point that the “transhumanist” can enter the debate and claim that our expected quality of life is no longer just the outcome of a “random” evolutionary process but can be brought under rational control. We should endeavor to make happy children.

In my opinion, the short response to empirical pessimism can take the following form. Pleasure and pain are both part of existence. For some sentient beings pleasure outweighs pain, for other sentient beings pain outweighs pleasure. A moral agent cannot add up, subtract, or divide these elements for life as a whole to produce an objective quality-of-existence function. The antinatalist runs into the same problems as all the utilitarians and welfare economists who have tried to define a social utility function as a guide for public policy. As Thomas Ligotti notes in his book, “…the reason for the eternal stalemate between optimists and pessimists, is that no possible formula can be established to measure proportions and types of hurt and happiness in the world. If such a formula could be established, then either pessimists or optimists would have to give in to their adversaries.” I think that the best response available to the antinatalist would be to follow David Benatar’s example and present a strictly formal argument, or simply argue that in case of doubt, we should abstain from procreation.

Escape strategies

After spending the bulk of his book persuading the reader that life is suffering, Crawford discusses what he calls “Escape Strategies.” In his treatment of Buddhism as an escape strategy he could simply have made the obvious internal critique that desire may be sufficient, but not necessary for suffering. Crawford’s treatment of Christianity is scathing, which may indicate regret because the author himself was a Christian for awhile. Why have children if there is the prospect of eternal damnation? Good question, but I think that a Christian can respond by saying that following Scripture is more important than applying human morality to God’s creation.

The last escape strategy that Crawford reviews is hope, which turns into a discussion of futurism and transhumanism. The argument that many of those pursuing life extension will not be around to benefit from it is too simplistic. Unless the brain is completely destroyed at death, the neuro-anatomical basis of identity can be preserved at cryogenic temperatures for a very long time. No delusional expectations about the future are required. People in cryostasis have time. But then the author delivers a critique that I think deserves serious treatment by transhumanists (discussions about “friendly AI” do not exhaust this topic by any means). In a nutshell, we should not expect that technological progress will necessarily produce moral progress. And even if it will, accidents happen. Technologies that can be designed to produce great joy can be used to create great suffering as well. If humanity can manufacture hell without God, the case for pessimism and antinatalism may be strengthened.

Interestingly enough, the anticipation of such dark future technologies may present a (subconscious) obstacle for many people considering cryonics. Hundreds of millions of people believe in the craziest things like astrology and psychoanalysis, but only a handful of people (around 1500) have made cryonics arrangements. This lack of interest can  hardly be attributed to ignorance, and perhaps the most persuasive answer may be hidden in Crawford’s book. Cryonics basically forces people to deal with the question whether they would like to be “born again” in a far and unknown future. As a general rule, the answer seems to be “no.” Antinatalists may find additional ammunition for their position in studying the reasons for the low sign-up rate for cryonics.

Mahayana antinatalism

Antinatalists should expect a lot of obvious questions such as “are most people not glad to be alive?” or “why not kill yourself?” I fear that Crawford’s answer to the question “why not kill yourself?” risks undermining the orthodox antinatalist project. If empathic sensibility can make an enlightened antinatalist who wants to stick around it is arguable  that antinatalists should make an effort to remain alive in an effort to reduce the amount of (future) suffering in the universe. Antinatalists then become life extensionists. To use conventional Buddhist terminology, perhaps at some point there will be a Theravada version of antinatalism (focused primarily on non-procreation) and a Mahayana version of antinatalism (concerned with the elimination of the suffering of all sentient beings).

David Benatar runs into a similar problem when he ponders the question whether bringing new people into the world could be justified to reduce the suffering of the last remaining people. It seems to me that how an antinatalist deals with such practical moral issues depends on how the ethics of antinatalism is conceived. Do we have a “right” not to come into existence or is the objective of antinatalism to juggle with small and great suffering towards the ultimate end of its complete abolition?

If antinatalism is conceived as a strictly individualistic endeavor, concerns about the suffering of all humans can be easily dismissed. But in that case antinatalism would just collapse into individualist pessimism. Who cares about suffering, as long as it is not me! This is not the kind of sentiment that is generally found in antinatalist writings. I do not think that the question whether there might be moral reasons to remain alive, and, yes, bring into being forms of life that are benevolent but ruthless towards suffering, can be easily dismissed.

At one point Crawford observes that secular and smart people are having fewer children. This does not look good for the inevitable triumph of antinatalism. Under such scenarios antinatalism produces dysgenics, and if one believes that stupidity and evil go hand in hand, increased suffering for more people.

To me it is not unlikely that, in practice, antinatalism leads to more suffering because it will only be adopted by sympathetic human beings such as Crawford. The antinatalist cannot argue that the amount of suffering in the universe cannot be increased nor decreased. The whole point of antinatalism after all is that suffering can and should be decreased. But how to go about this may be more complicated than it appears. A sober assessment of the practical implications of antinatalism may require revision of the antinatalist position itself.

Confessions of an Antinatalist is a fine and humane book, but in the end it is also a book of the converted written for the non-converted. Thomas Sowell has noted that in economics there are no solutions but only trade-offs. I would not be surprised if antinatalists will come to a similar conclusion at some point.

Suffering without meaning

Thomas Ligotti is a contemporary horror writer whose fiction work  is marked by cosmic nihilism, alienation and the fragile nature of reality. As a great admirer of the work of Ligotti I have been reluctant to comment on his non-fiction. Fortunately, unlike many other artists, Ligotti has little interest in “critical theory” or “progressive” politics. His book The Conspiracy Against the Human Race: A Contrivance of Horror is not concerned with such trivial topics but with the bleak fate of humanity in a deterministic and indifferent universe.

The book starts off with an introduction by obscurantist philosopher Ray Brassier, whose work would certainly qualify for the description that Ligotti gives to Schopenhauer’s oeuvre (“too overwrought in the proving to be anything more than another intellectual labyrinth for specialists in perplexity”).

Reading Ligotti’s account of why humans reject truly bleak views about life it would be interesting to see how antinatalists respond to the existence of orthodox Calvinism. Accepting a universe without free will that is ruled by an omnipotent God who has decreed that the majority of people will suffer in hell for His self-glorification seems a lot more terrifying to me. Nonetheless, millions of people have accepted this theological perspective. The existence of Reformed theology lays to rest the view that humans have an intrinsic desire to avoid doctrines that are too terrible too contemplate.

When Ligotti discusses the work of antinatalist Peter Wessel Zapfe once more we find the view that there is an objective predicament of mankind that is hidden by false consciousness. It is remarkable to see the similarities between those who argue that we do not want look our “oppression” straight in the face and those who argue that we avoid coming to terms with the horror of existence. What  is often lacking here is the recognition that there is also a wealth of literature about human suffering that supports the idea that we would be happier if we did look nature straight in the face. No nonsense about “moral responsibility,” “sin,” “duty,” “the greater good” etc. Marquis de Sade, Friedrich Nietzsche, and Max Stirner are representatives of this school of thought.

What is intriguing about Ligotti’s book is that it reads like a rather delicate balancing act. On one hand, we have the detached observer (my favorite) who is bemused at the show business of both the optimists and pessimists. On the other hand, it is unmistakable that Ligotti feels affinity with the philosophers of cosmic horror and pessimism. His fiction does not leave much room for any other conclusion. But The Conspiracy Against the Human Race contains more than a few (unintended) suggestions how someone who declines to take sides would present his argument.

Hard determinism and the illusion of the self

I have a hard time relating to the Ligotti’s discussion about determinism and pessimism. Hard determinism (or hard imcompatibilism) is just a part of the “scientific worldview” and it is not obvious to me why it should be a source of despair. Ligotti then discusses the existence of the “self.” I am inclined to think there is an important difference between free will and the self. Modern science can make sense of the world and human action without assuming free will. I am  not convinced that this is possible if the concept of the self is rejected. Unlike free will, the recognition of a “self” comes at a later stage in evolution. It has been argued that primitive people could not clearly distinguish the self from its surroundings and thus were not able to discover the laws of physics and manipulate it to their benefit. The philosopher Hans Reichenbach developed a pragmatic case for the existence of the external world and the self in his seminal work Experience And Prediction: An Analysis of the Foundations And the Structure of Knowledge. Ultimately, the Kantian question whether something “really” exists (or what something “really” looks like) does not seem particularly helpful in the study of reality, as the early logical positivists of Vienna understood well.

Why would anything that neuroscientists discover about the self and how it is constructed be a source of dread? If you believe that life is just the result of random meetings of organic molecules, it stands to reason that the physical basis of consciousness and the self reflects such a process. Why would accepting such ideas make one a “heroic pessimist?” Why the pessimism at all? Ligotti even agrees. “One would think that neuroscientists and geneticists would have as much reason to head for the cliffs because little by little they have been finding that much of our thought and behavior is attributable to neural wiring and heredity rather than to personal control over the individuals we are, or think we are. But they do not feel suicide to be mandatory just because their laboratory experiments are informing them that human nature may be nothing but puppet nature. Not the slightest tingle of uncanniness or horror runs up and down their spines, only the thrill of discovery. Most of them reproduce and do not believe there is anything questionable in doing so.”

Ligotti also discussed transhumanism, but not in much depth. As a transhumanism skeptic myself, I found little to object to but it seems that Ligotti’s real target is what is called Singularitarianism. This part in the book seems something of a missed opportunity because there is substantial overlap between Ligotti’s fiction and themes that are discussed by transhumanist writers: living in a computer simulation, parallel universes, alternate realities etc.

When Ligotti reviews near-death experiences and ego-death, the common-sense neurological explanations that were invoked in discussions of free will and the self are largely absent (a notable exception is his discussion of the possibility that a brain tumor can cause such an “enlightened” state). For critical-care physicians it is a given that many people suffer (regional) cerebral ischemia during the dying process. As such, it is surprising (but encouraging) that not more people claim enlightenment after they recover. These periods of  transient oxygen deprivation can produce long term damage and a “re-wiring” of the brain, which can explain the new perspectives these people adopt. From a physicalist perspective, death of the ego is (partial) death of the brain, something one may or may not want to celebrate.

In Ligotti’s book the reason for pessimism is multi-factorial. It includes the lack of meaning in an indifferent universe, the reality of hard determinism, and the illusion of the self. The works of Benatar and Crawford are more restricted in scope and mostly focus on more mundane suffering. Ligotti’s philosophical horror is much richer, but I wonder how much of it will resonate with people who embrace a scientific view of the universe. The Conspiracy against the Human Race may not have been designed as an argument against “unweaving the rainbow” (to use Richard Dawkin’s useful phrase) but it sometimes reads like one.

There is a lot in Ligotti’s fine book that I have not discussed such as the extensive treatment of pessimism in horror fiction, loads of interesting philosophical and scientific references, plus illuminating discussions of obscure authors such as Peter Wessel Zappfe and Philipp Mainlander. As such, it can also be considered as an indispensable reference for philosophical pessimism and cosmic horror.

Empiricism and non-existence

David Benatar is a rigorous philosopher. His work can be situated in the analytic tradition and he makes an honest attempt to anticipate objections to his own views. When he argues for positions using mainly logical arguments he is quite persuasive. A being that does not exist can neither be harmed nor benefited. I cannot see how this argument (or  tautology?) can be successfully refuted. But when Benatar attempts to argue that the quality of life of most people is much worse than they think it is, multiple challenges arise. I do not think this is the result of Benatar’s poor reasoning but because the fields that he relies on – evolution, social psychology, happiness research and the study of cognitive biases – are notorious for allowing competing views. It seems to me that ultimately Benatar cannot escape the charge that he pays excessive attention to theories that claim that we think we are happier than we really are. Perhaps I have spent too much time in the wrong subculture but it seems to me that the phenomenon of people claiming to be less happy than they really are should not be ignored either.

Like Crawford, Benatar cannot completely escape the charge of illiberalism. Classical liberalism takes very seriously the challenges in reaching satisfactory conclusions about the quality of other people’s lives. In practice this means that we exercise restraint in making strong cognitive and moral claims about the feelings and preferences of other people. This is a mindset that does not seem to come easily to antinatalists. Benatar is on more agreeable ground when he simply derives his antinatalism from uncertainty; “some know that their baby will be among the unfortunate. Nobody knows, however, that their baby will be one of the allegedly lucky few.”

Benatar believes that even if his empirical argument about the poor quality of our lives fails, his formal argument from asymmetry is still left standing. He thinks that even if there is one single painful pinprick in an otherwise good life, we still harm that person by bringing him into existence. I think that Benatar is “proving” too much here. We can agree that anyone who conceives a child cannot escape the prospect that this person will experience some harm. But from this it does not follow that the person is harmed in a meaningful moral sense without considering the expected overall quality of that life. Perhaps Benatar would respond that I have not understood his argument, and I will admit that I have a difficult time understanding why the possibility that a person’s pleasures are expected to outweigh the pains do not alter his argument. I think that both bringing into existence a life that is invariably good and a life that is generally good can be morally defended on the grounds that there will not be any post-natal moral objections from the person involved. Of course, we are not morally obliged to do so, because we will not deprive the unborn of such a good life if we don’t have children. But since most parents have a positive interest in having children, in practice this tips the scales in favor of some (but not all!) procreation. One problem I can see with my argument is that it might permit the creation of a life form that would experience great suffering but with an unalterable survival instinct and no cognitive possibility of moral blame or regret. Some antinatalists might even claim that this is a rather accurate description of the human race as it exists today.

As an empiricist, I generally give the benefit of doubt to empirical observations when they appear to conflict with logical reasoning. I think that this preference itself can be justified on historic and pragmatic grounds. The claim that coming into existence is always a harm is not consistent with the reports of all those who have come into existence. That seems to be a non-trivial epistemological roadblock for antinatalism.

When Benatar discusses the moral duty not to have children he runs into the obvious problem of how the interests of the parents should be weighed against the interests of the child. One does not need to be an ethical egoist to believe that the interests of the parents count for something. In this case the question returns to how bad the life of most people is and, as discussed, this is a rather vulnerable part of antinatalism. Benatar attempts to answer the obvious objection that most people who have been born do not regret this or blame their parents. But when I read his thoughts on “indoctrination” I only see further evidence of the anti-liberalism in his writings.

In fairness to Benatar (who seems to identify himself as a liberal of some sorts), he does defend the legal right to procreation because he admits that there can be reasonable disagreement about his views. I think this point is particularly important for antinatalism since reasonable objections often come from the very people whose lives Benatar characterizes as very bad. That is not to deny that society can choose to be less supportive of people who engage in reckless procreation. Such behavior can be substantially decreased by withholding benefits that encourage or reward such behavior. Benatar correctly argues that if one subscribes to a consistent interpretation of the Kantian argument that future people should not be treated as means, then all reproduction is morally dubious. But whether that highlights the virtues or defects of Kant’s ethics I leave to the reader to ponder.

Benatar highlights the importance of making a distinction between the decision to bring someone into existence and the decision to continue life. Even if we commit to the idea that it is better never to have been we can still have reasons for wanting to continue life. As a matter of fact, Benatar entertains the argument that the prospect of death itself is one of the reasons why existence is bad. Those who follow Epicurus believe that death cannot be experienced and thus cannot be a bad thing for the person. This is an extremely difficult argument to refute, but Benatar’s discussion of this topic is quite illuminating because he points out that those who hold this position may also have to commit to the view that death can never be good for a person. One only needs to imagine a person whose life is one of continuous suffering to see that this is not a plausible argument.

As an academic Benatar is less hostile to religion than Crawford and Ligotti but I do not think he can successfully escape the objection that antinatalism requires an atheist perspective. One does not have to be a scripturalist to note that Benatar is only concerned with the fate of humans and not with the interests of God. Perhaps Benatar cannot see any positive value in human suffering because his information about Creation is incomplete. Theodicies that reconcile the existence of God and the existence of Evil are not difficult to generate. As Plotinus has observed, “We are like people ignorant of painting who complain that the colours are not beautiful everywhere in the picture: but the Artist has laid on the appropriate tint to every spot.”

Antinatalists and life extensionists

One would think that cryonicists and life extensionists should be repulsed by antinatalism. I think such a view would be mistaken. All the antinatalist authors discussed here are motivated by empathy for the suffering of all sentient life. We should also welcome the analytical and physicalist perspectives that underpin their writings. Too much (Continental) philosophy is simply an insult to the intellect and a waste of time. If a case should be made for pessimism it needs be stated in a form that is amenable to reasoned debate and empirical investigation.

Of more specific interest to life extensionists is the plausible prospect that our abilities to decrease suffering will (necessarily?) be matched by our abilities to increase suffering too. This is a possibility that should be studied in great detail by advocates of molecular nanotechnology, strong AI, and Substrate Independent Minds.

It is no secret that cryonicists are underperforming in terms of reproduction. But as Howard V. Hendrix discusses in the article “Dual Immortality, No Kids: The Dink Link between Birthlessness and Deathlessness in Science Fiction,” this may not be a coincidence. If biological immortality becomes a credible option, having children as a substitute for personal survival will lose much of its appeal.

Most rewarding for cryonicists is the unique perspective that antinatalists can bring to the debate concerning why so few people have made cryonics arrangements. The hostility of many people towards cryonics cannot be explained if people categorically believe that  meaningful resuscitation (revival) is impossible. It is the prospect that cryonics may actually work that induces severe anxiety. If the antinatalists are correct in their assessment that coming into existence is always a harm, the unpopularity of cryonics might be indirect evidence for their position.

I want to close this review with one word of advice to those who engage in debates with antinatalists. Most antinatalists waste little time reminding their readers how controversial their ideas are. They think that they have uncovered the greatest taboo of all time. As an empirical matter, this is doubtful. Antinatalist ideas can be freely discussed in modern Western countries, something that cannot be said about a number of other controversial ideas. Antinatalists are also quick to point out that their pessimism should not be dismissed as an expression of weakness and depression. But then the antinatalists commit a similar error by too easily viewing optimism as a defense mechanism or a form of bias. But is it completely unreasonable to look for the neurophysiologic and genetic basis of pessimism and optimism? The uncompromising naturalism in the work of the antinatalists  supports such an inquiry.

Jim Crawford: Confessions of an Antinatalist (Nine Banded Books 2010)

Thomas Ligotti: The Conspiracy Against the Human Race: A Contrivance of Horror (Hippocampus Press 2010)

David Benatar: Better Never to Have Been: The Harm of Coming into Existence (Oxford University Press 2006)

Thanks to Dr. Michael Perry for discussing some of the topics in this review and proofreading an earlier version of this document.

At last, a sure-cold way to sell cryonics with guaranteed success!

A humorous romp through a promising new technique in aesthetic medicine from one cryonicist’s (warped) point of view.

Figure 1: Before cryopreservation (L) and after cryopreservation (R).

As everyone involved in cryonics for more than a fortnight is sadly aware, cryonics doesn’t sell. Indeed, if we were pitching a poke in the eye with a sharp stick, we’d more than likely have more takers than we’ve had trying to ‘market’ cryonics to the public. To see evidence that this is so, you need only wander around a shopping mall on a weekend and observe all the (painfully) stainless steel lacerated and brightly colored needle-pierced flesh sported by the young and trendy and increasing by the old and worn, as well.

Yes, it’s clear; we misread the market, to our lasting detriment.

It’s true that we’ve tried the ‘you’ll be rich when you wake you up line,’ and heaven knows we’ve beaten the ‘you’ll be young and beautiful forever’ line, well, virtually beaten it to death. And while people are certainly interested in great fortune and youth, both of these things share the same unfortunate shortcoming, namely that they are things that people either don’t have but want, or do have and don’t want to lose. As anyone who is really savvy at marketing will tell you, the best way to sell something is to promise (and preferably be able to deliver) that you can get rid of something that people have and really don’t want – something that is ruining the quality of their life, destroying their health, draining their pocketbook and, worst of all, making them really, really ugly.

So, it turns out that for onto 50 years now, we’ve missed the real selling point of cryonics that’s been there all along: IT WILL MAKE YOU THIN! Guaranteed!

Can such a claim be true? Well, surprisingly, the answer would seem to be an almost unqualified, “Yes!”

Recently it’s been discovered that adipocytes, the cells responsible not only for making you fat, but for making you hungry, as well, are particularly susceptible to a phenomenon in cryobiology that has proved a nettlesome (and only recently (partially) overcome) barrier to solid organ cryopreservation: chilling injury. Quite apart from freezing damage due to ice crystals forming, adipocytes are selectively vulnerable to something called ‘chilling injury.’ 1-5 Chilling injury occurs when tissues are cooled to a temperature where the saturated fats that comprise their cell membranes (external and internal) freeze. You see, saturated fat, which is the predominant type of fat in us humans, freezes well above the temperature of water – in fact, it freezes at just below room temperature. That’s why that big gash of fat on the edge of your T-bone steak is stiff and waxy when it is simply refrigerated, and not frozen.

Figure 2: Chilling injury is thought to result from crystallization of cell membrane lipids.

Chilling injury isn’t really well understood. In the days before both cryobiology and indoor heating, humans used to experience a very painful manifestation of it in the form of chilblains – tender swelling and inflammation of the skin due to prolonged cold exposure (without freezing haven taken place). In the realm of organ preservation it is currently thought that chilling injury occurs when cell membranes are exposed to high subzero temperatures (-5oC to -20oC), again, in the absence of freezing.

There is evidence that the lipids (fats) that make up the smooth, lamellar cell membranes undergo crystallization when cells are cooled much below 0 deg C. Since the crystals are hexagonal in shape and have a hole in the middle, this has the effect of creating a pore or hole in the membrane. Cells don’t like that – those holes let all kinds of ions important to cells keeping their proper volume and carrying on their proper metabolic functions leak in and out, as the case may be. This isn’t merely an inconvenience for cells, it’s downright lethal. Without boring you with technical details, it is possible to partially address this state of affairs in organ preservation by adjusting the ‘tonicity’ of the solution bathing the cells: oversimplifying even more, this means by increasing  the concentration of salts to a concentration higher than would normally be present

Figure 3: Contouring of the skin in a pig subjected to brief, subzero cooling of subcutaneous fat.

But, to return to our chilled adipocytes and the promise not only of weight loss, but of a fat-free future; adipocytes are killed, en masse, when their temperature is dropped to between 0 and -7oC. Within a few days of exposure to such temperatures they undergo programmed cell death (apoptosis) and within a couple of months they are phagocytized by the body; and all that ugly and unwanted fat is carted off to be used as fuel by the liver. Now the rub would seem to be that this effect is most pronounced when the temperature of the tissue is cooled to below the freezing point of water and held there – preferably for a period of 10 minutes or longer.

That sounds dire, doesn’t it? What about the skin, the fascia, blood vessels, and the other subcutaneous tissues that will FREEZE (in the very conventional sense of having lots and lots of ice form in them)? Well, the answer, as any long-time experimental cryobiologist will know (even if he won’t tell you) is: pretty much nothing. Way back in the middle of the previous century, a scientist named Audrey Smith and her colleagues at Mill Hill, England found that you could freeze hamsters ‘solid’ – freeze 70+% of the water in their skin and 50% of the water in their bodies – and they would recover from this procedure none the worse for wear. Similarly, those of us who have carelessly handled dry ice for a good part of our lives will tell you that we see parts of our fingertips turn into stiff chalky islands of ice all the time, with the only side effect being a bit of temporary numbness that resolves in a few days to a week – certainly a side effect well worth it to avoid the considerable inconvenience of rummaging around to find a pair of protective gloves.

Figure 4: The Zeltiq Cool Sculpting Cryolipolysis device.

But alas, we scientists (most of us, anyway) are not a very entrepreneurial lot, and so we never thought either of inventing the ZeltiqTM cryolipolysis system, or using ‘the thin-new-you’ as a marketing tool for cryonics.

Yes, that’s right; some very clever folks have found a way to make a huge asset out of a colossal liability – to organ preservationists, anyway. Around 2004 a Minneapolis dermatologist named Brian Zellickson, MD, who specialized in laser and ultrasonic skin rejuvenating procedures, made a not so obvious connection. Both laser and skin ‘face-lifting’ and skin ‘rejuvenation’ procedures rely on the subcutaneous delivery of injuring thermal energy to the tissues of the face, or other treated parts of the body (cellulite of the buttocks and thighs are two other common areas for treatment). These energy sources actually inflict a second degree burn in a patchy and well defined way to the subdermal tissues.

Now this may seem a very counterintuitive thing to do if you are trying to induce ‘rejuvenation’ or ‘lift’ a sagging face. But if you think about it, it makes a great deal of sense. As any burn victim will tell you, one of the most difficult (and painful) parts of recovery is stretching the highly contracted scar tissue that has formed as a result of the burn injury. Indeed, for many patients with serious burns over much of their body, the waxy, rubbery and very constricting scar tissue prevents the return of normal movement, and can lock fingers and even limbs into a very limited range of motion. Many burn victims must do painful stretching exercises on a daily basis to avoid the return of this paralyzing skin (scar) contracture.

And it must be remembered that aged skin – even the skin of the very old – can still do one thing, despite the many abilities it has lost with age, and that thing is to form scar tissue in response to injury. Thus, laser and ultrasonic heating of normal (but aged) skin induces collagen proliferation and large-scale remodeling of the skin. For all the bad things said about scar tissue it is still a remarkable achievement in that it does constitute regenerated tissue. Regenerated tissue which does the minimum that normal skin must do to keep us alive: provide a durable covering that excludes microbial invasion, and prevents loss of body fluids. By injuring the tissue just below the complexly differentiated layer of the dermis (with its hair follicles, sweat glands and highly ordered pigmentation cells) much of the benefit of ‘scarring’ is obtained without the usual downsides.

The injured tissues respond by releasing collagen building cytokines as well as cytokines that result in angiogenesis (new blood vessel formation) and widespread tissue remodeling. And all that newly laid down collagen contracts over time, tightening and lifting the skin – and the face it is embedded in. These techniques may justly be considered much safer versions of the old fashioned chemical face peel, which could be quite effective at erasing wrinkles and achieving facial ‘rejuvenation,’ but was not titrateable and was occasionally highly unpredictable: every once in awhile the result was disastrous burning and accompanying long term scarring and disfiguration of the patient’s face.

St some point Dr. Zellickson seems to have realized that the selective vulnerability of adipocytes to chilling offered the perfect opportunity for a truly non-invasive approach to ‘liposuctioning’ by using the body’s own internal suctioning apparatuses, the phagocytes, to do the job with vastly greater elegance and panache than any surgeon with a trocar and a suction machine could ever hope to do. Thus was invented the Zeltiq Cool SculptTM cryolipolysis machine.6

Figure 5: The cooling head of the Zeltiq devive equipped with ultrasonic imaging equipment and a suction device to induce regional ischemia and hold the tissue against the cooling surface.

The beauty of cryolipolysis is that it is highly titrateable, seems never to result to in excessive injury to, or necrosis of the overlying skin, and yields a smooth and aesthetically pleasing result. Not unjustifiably for this reason it is marketed under the name Cool SculptingTM. The mechanics of the technique are the essence of simplicity. The desired area of superficial tissue to be remodeled is entrained by vacuum in a cooling head equipped with temperature sensors, an ultrasonic imaging device, and a mechanical vibrator. The tissue in the cooling head is sucked against a conductive surface (made evenly conductive by the application of a gel or gel-like dressing to the skin) where heat is extracted from it. The tissue is cooled to a temperature sufficient to induce apoptosis in the adipocytes, while at the same time leaving the overlying skin untouched. The depth of cooling/freezing is monitored by ultrasound imaging and controlled automatically by the Zeltiq device.  At the appropriate point in the cooling process the tissue is subjected to a 5 minute period of mechanical agitation (massage) which helps to exacerbate the chilling injury, perhaps by nucleating the unfrozen fat causing it to freeze.7 When the treatment is over, the device pages an attendant to return to the treatment room and remove it.

The tissue under vacuum is also made ischemic – blood ceases to flow, and this has the dual advantage of speeding the course of the treatment by preventing the blood borne delivery of unwanted heat – and more importantly, by making the cooling more uniform, predictable and reproducible. It also has the effect of superimposing ischemic injury on top of the chilling injury which is something that seems to enhance adipocyte apoptosis. The whole treatment, in terms of actual cooling time, takes about 60 minutes. In the pig work which served as the basis for the human clinical treatments, the duration of treatment was only 10 minutes: but the cooling temperature was also an ‘unnerving’ -7oC. The degree of temporary and fully reversible peripheral nerve damage (that temporary numbness us ‘dry ice handlers’ know so well) was more severe at this temperature, although it resolved in days to a week or two, without exception.

As previously noted, cryolipolysis causes apoptosis of adipocytes and this results in their subsequently being targeted by macrophages that engulf and digest them. This takes time, and immediately after treatment there are no visible changes in the subcutaneous fat. However, three days after treatment, there is microscopic evidence that an inflammatory process initiated by the apoptosis of the adipocytes is underway, as evidenced by an influx of inflammatory cells into the fat of the treated tissues. This inflammatory process matures between seven and fourteen days after treatment; and between fourteen and thirty days post-treatment, phagocytosis of lipids is well underway. Thirty days after treatment the inflammatory process has begun to decline, and by 60 days, the thickness of interlobular septa in the fat tissue has increased. This last effect is very important because it is weakness, or failure of the interlobular fat septae that is responsible for the ugly ‘cottage cheese’ bulging that is cellulite. Three months after the treatment you get the effect you see below on the ‘love handles’ of this fit, and otherwise trim fellow. Thus, it is fair to say that Cool SculptingTM is in no way a misnomer.

Figure 6: Art left is a healthy, fit young male who has persistent accumulation of fat in the form of ‘love handles’ that are resistant to diet and exercise and the same man 3 months after cryolipolysis.

Does cryolipolysis really work? The answer is that it works extremely well for regional remodeling or sculpting of adipose tissue – those pesky love handles, that belly bulge around the navel, that too plump bum, or those cellulite marred thighs. So far it has not been used to try and ablate large masses of fat – although there seems no reason, in principal, why this could not be done using invasive techniques such as pincushioning the fat pannus with chilling probes, as is done with cryoablation in prostate surgery. However, this would be invasive, vastly more expensive, and likely to result in serious side effects.

And that was one of the really interesting things about the research leading up to FDA approval of cryolipolysis: it seems to cause no perturbation in blood lipids, no disturbance of liver function (the organ that has to process all that suddenly available fat) and no global alterations in immune function. It seems to be safe and largely adverse effect free. There is some localized numbness (as is the case in freezing of skin resulting from handling dry ice) but it resolves without incident with a few weeks of the procedure.8

So, all of this makes me wonder, since human tissues tolerate ice formation and respond to it in much the same way as they do to laser or ultrasound ‘rejuvenation’ (depending upon the degree of damage) a logical question is, “would it be possible to use partial freezing of the skin – just enough to provoke the remodeling response – as a method of facial rejuvenation?” It should be safer than a chemical people and it is, like laser and ultrasound therapy, titrateable.

Figure 7: “Gad darn it, this shiny gold stuff keeps getting into the silt I’m tryin to git out of this here river!”

Which returns me to the whole subject of cryonics: fat is very poorly perfused and it seems unlikely that things done to moderate or abolish chilling injury will be nearly so effective for the adipocytes in fat (if it they are effective at all). That means that we might well all come back from our cryogenic naps not only young, via the magic of nanotechnology and stem cell medicine, and rich via the miracle of compound interest (which none other than Albert Einstein once remarked was “the most powerful force in the universe”), but also THIN! For all these years organ cryopreservationists, like Fahy and Wowk, have been panning for the mundane silt of a way around a chilling injury9 all the while discarding the gleaming nuggets of gold that were persistently clogging up their pans.

We cryonicists should not repeat their error and should realize a good thing when we see it. Now, for the first time, we can credibly claim that if you get cryopreserved you’ll come back not only young and rich, but young and rich and beautiful and thin!

Methinks there must be very few in the Western World today, man woman or child, who can resist a product that has all that to offer – and which, by the way, bestows practical immortality in the bargain.

Ok, Ok, maybe we shouldn’t mention that last part about immortality; it might scare the children.

REFERENCES:

1)     Wiandrowski TP, Marshman G. Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia. Australas J Dermatol 2001;42:207–10.

2)     Diamantis S, Bastek T, Groben P, Morrell D. Subcutaneous fat necrosis in a newborn following icebag application for treatment of supraventricular tachycardia. J Perinatol 2006;26:518–

3)     Lidagoster MI, Cinelli PB, Levee´ EM, Sian CS. Comparison of autologous fat transfer in fresh, refrigerated, and frozen specimens: an animal model. Ann Plast Surg 2000;44:512–5.

4)      Wolter TP, von Heimburg D, Stoffels I, et al. Cryopreservation of mature human adipocytes: in vitro measurement of viability. Ann Plast Surg 2005;55:408–13.

5)      Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D, Anderson RR. Selective cryolysis: a nivel method of noninvasive fat removal. Lasers Surg Med 2008;40:595–604.

6)     Avram MM, Harry RS. Cryolipolysis for subcutaneous fat layer reduction. Lasers Surg Med. 2009 Dec;41(10):703-8. Review. PubMed PMID: 20014262.

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The diminishing returns of reactive medicine

In an article for Slate, Jay Olshansky argues in favor of a position that one would expect to be common sense at this point:

While we can extend life in aging bodies through behavioral improvements and medical treatments, the time has arrived to acknowledge that our current model of reactive medicine, of trying to treat each separate disease of old age as it occurs, is reaching a point of diminishing returns.

So what is the reason why vast amounts of money are spent on research to treat age-associated diseases but so little on eliminating or mitigating aging as such? Why is this “one-disease-at-a-time model” so dominant? One reason might be that most people believe that overcoming one specific manifestation of aging is easier to do than overcoming aging itself. Not surprisingly, most academic and commercial research is shaped by short term ambitions or short-term financial interests.

Many people who deal with serious age-associated diseases hope that a cure can be found within their lifetime.  This is not so strange if you consider that many people who do advocate meaningful rejuvenation research are technological optimists who think the same thing about overcoming aging. In that sense, people show little interest in supporting research that has little personal benefit to them or close relatives. This is further evidenced by the fact that people are more inclined to contribute to anti-aging efforts that promise benefits in their lifetime. This in turn provokes criticism from mainstream scientists of not being realistic, which further discredits the field.

But as Olshansky indicates, the diminishing returns of the approach to just fight the symptoms of aging should force people to change perspective. Olshansky also observes  that “manufacturing survival time in the absence of decelerated aging” can produce a lot of hardship and suffering in old age:

It’s important to acknowledge the fundamental differences between disease and aging. Although age-associated changes in the body produce an increased risk of disease, the reverse is not true. That is, reducing the risk of disease has no influence on biological aging. Thus, if a population is preserved with increasing efficiency by advances in technology that reduce the risk of disease, those saved will live into increasingly later sections of the lifespan where aging takes a greater toll on body and mind. Life extension achieved in this way could extend old age by exposing survivors to the high-risk conditions of frailty that are common, and largely immutable, near the end of life—the very outcome that medicine and public health practitioners are trying to avoid.

For people who have made cryonics arrangements, there is another danger; the possibility of life extension at the price of increased vulnerability to identity-destroying diseases.  There is no shortage of cryonics patients with Alzheimer’s or impaired brain function. As much as we would like to deny it, there could be a disturbing trade-off between life extension and true personal survival as long as treatments for neurodegenerative diseases are not available.

Meta-research and medical skepticism

The Atlantic features an important article about “meta-researcher” Athina Tatsioni, who has published a number of influential papers about the quality of biomedical research:

He and his team have shown, again and again, and in many different ways, that much of what biomedical researchers conclude in published studies—conclusions that doctors keep in mind when they prescribe antibiotics or blood-pressure medication, or when they advise us to consume more fiber or less meat, or when they recommend surgery for heart disease or back pain—is misleading, exaggerated, and often flat-out wrong. He charges that as much as 90 percent of the published medical information that doctors rely on is flawed. His work has been widely accepted by the medical community; it has been published in the field’s top journals, where it is heavily cited; and he is a big draw at conferences…

He chose to publish one paper, fittingly, in the online journal PLoS Medicine, which is committed to running any methodologically sound article without regard to how “interesting” the results may be. In the paper, Ioannidis laid out a detailed mathematical proof that, assuming modest levels of researcher bias, typically imperfect research techniques, and the well-known tendency to focus on exciting rather than highly plausible theories, researchers will come up with wrong findings most of the time. Simply put, if you’re attracted to ideas that have a good chance of being wrong, and if you’re motivated to prove them right, and if you have a little wiggle room in how you assemble the evidence, you’ll probably succeed in proving wrong theories right.

This raises a number of important issues from a life extension perspective. For starters, these findings reinforce that it is just not credible for mainstream researchers and medical professionals to sustain these arrogant attitudes towards serious research efforts in life extension and cryonics. Good research is hard to do, and there is little of it.  This applies particularly to research that translates into meaningful medical benefits.  It  may be hard to swallow that a lot of  what constitutes conventional medicine is based on flawed studies and interest-driven research, but there is no escaping this conclusion.

Having a strong interest in the results is a double-edged sword. On the one hand, it makes one more susceptible to bias and cherry-picking. On the other hand, it can produce a determined mindset to tackle ambitious research goals (rejuvenation, vitrification). For example, the breakthroughs in vitrification technology at a company like 21st Century Medicine would have been unthinkable if the principal researchers would not have had an enduring strong personal interest in the technologies they are researching. This phenomenon can  also throw some light on the observation that often committed amateurs have more knowledge than professional researchers. Academic researchers often move from one (grant-funded) fad to another without obtaining a wide and deep understanding of the fields they are investigating. Unfortunately, such fashionable researchers are often featured in the media as “experts.”

Athina Tatsioni’s findings should also have a sobering effect on those who think we are in a period of accelerating medical progress. Even the  more credible medical research often fails to contribute to the expected clinical breakthroughs. To those familiar with the complex biochemistry of life, and the opportunity to introduce (long term) side-effects along with beneficial interventions (including attempts to just “repair” something), this should not be a surprise.

Naturally, Athina Tatsioni does not have a high opinion on research that claims benefits for vitamins and supplements:

For starters, he explains, the odds are that in any large database of many nutritional and health factors, there will be a few apparent connections that are in fact merely flukes, not real health effects—it’s a bit like combing through long, random strings of letters and claiming there’s an important message in any words that happen to turn up. But even if a study managed to highlight a genuine health connection to some nutrient, you’re unlikely to benefit much from taking more of it, because we consume thousands of nutrients that act together as a sort of network, and changing intake of just one of them is bound to cause ripples throughout the network that are far too complex for these studies to detect, and that may be as likely to harm you as help you. Even if changing that one factor does bring on the claimed improvement, there’s still a good chance that it won’t do you much good in the long run, because these studies rarely go on long enough to track the decades-long course of disease and ultimately death.

The take-home message is that skepticism is a useful disposition when looking at all research, medical practice, and triumphant claims about accelerating technological progress. One advantage of those who have made cryonics arrangements have is that they have time and, in theory (!), should be less prone to wishful thinking and jumping on the latest bandwagon. As Michael Anissimov writes, “When I talk to older transhumanists that are into cryonics, I see people who are psychologically calmer than those who endlessly obsess over their food, questionable supplements, and other minutiae that will mean jack squat if they get into a simple car accident.” It also reinforces the approach of arguing in favor of cryonics using skeptical arguments (about our arbitrary and evolving concepts of death)  instead of making bold claims about existing and future science.

Further reading: John P. A. Ioannidis – Why Most Published Research Findings Are False.