20. October 2014 · Comments Off · Categories: Neuroscience, Science

Cryonics Magazine, February 2013

This is the first entry in a new series of short articles about neuroscience and its implications for the field of human cryopreservation and life extension. In this article I discuss the relationship of the brain to consciousness and knowledge acquisition before venturing into more specific and practical topics

What is consciousness? Most of us understand the word in context, but when asked to define it we are suddenly at a loss for words or at best we offer a description that seems wholly inadequate. Scientists, philosophers, and religious scholars have debated the source, meaning, and nature of consciousness for all of recorded history. But with the rise of neuroscience over the past few decades, it now seems as though explaining the nature and mechanisms of conscious experience in neurobiological terms may be an attainable goal.

The recent work on consciousness by neuroscientists has left certain philosophers more frustrated than ever before, including the likes of Thomas Nagel and David Chalmers. They suspect that consciousness may be quite different and separate from the brain circuitry proposed to underlie it.

Consciousness has appeared to be a strange and undefinable phenomenon for a very long time. Daniel Dennett captured the feeling very nicely in the 1970s:

“Consciousness appears to be the last bastion of occult properties, epiphenomena, immeasurable subjective states — in short, the one area of mind best left to the philosophers. Let them make fools of themselves trying to corral the quicksilver of “phenomenology” into a respectable theory.”(1)

Consciousness no longer appears this strange to many researchers, but the philosophers just mentioned continue to hold that it may not be reduced to brain processes active in cognition. A common philosophical complaint is that any neurobiological theory of consciousness will always leave something out. What it will always leave out is the feeling itself — the feeling of what it is like to be aware, to see green, to smell flowers, and so on (Nagel 1974; Chalmers, 1996). These are so-called qualia — the experiences themselves — and these are what are important about consciousness. The philosopher making this argument may go on to conclude that no science can ever really explain qualia because it cannot demonstrate what it is like to see green if you have never seen green. Ultimately, they argue, consciousness is beyond the reach of scientific understanding.

By contrast, neuroscientists take for granted that consciousness will be domesticated along with the rest of cognition. Indeed, this work tends to assume that neuroscience will not only identify correlates of consciousness, but will eventually tell us what consciousness is. By and large, these neuroscientific efforts have been directed toward cortical regions of the brain, cortical pathways, and cortical activity. This is due, in part, to the prevalence of clinical studies of human patients with region-specific cortical lesions that are correlated with deficits in specific kinds of experiences. This tendency to focus on the cortex may also reflect the common knowledge that humans possess the highest level of consciousness of all animals and have proportionally more cortex than our closest relatives (and — so the supposition goes — therein lies the difference in levels of consciousness).

Another theory of consciousness, offered by Dr. Gerald M. Edelman, aims to resolve this “divorce” between science and the humanities over theories of consciousness. The premise of Edelman’s theory is that the field of neuroscience has already provided enough information about how the brain works to support a scientifically plausible understanding of consciousness. His theory attempts to reconcile the two positions described earlier by examining how consciousness arose in the course of evolution.

In his book on the topic, Second Nature: Brain Science and Human Knowledge, Edelman says:

“An examination of the biological bases of consciousness reveals it to be based in a selectional system. This provides the grounds for understanding the complexity, the irreversibility, and the historical contingency of our phenomenal experience. These properties, which affect how we know, rule out an all-inclusive reduction to scientific description of certain products of our mental life such as art and ethics. But this does not mean that we have to invoke strange physical states, dualism, or panpsychism to explain the origin of conscious qualia. All of our mental life, reducible and irreducible, is based on the structure and dynamics of our brain.

In essence, Edelman has attempted to construct a comprehensive theory of consciousness that is consistent with the latest available neuroanatomical, neurophysiological, and behavioral data. Calling his idea Neural Darwinism, Edelman explains that the brain is a selection system that operates within an individual’s lifetime. Neural Darwinism proposes that, during neurogenesis, an enormous “primary repertoire” of physically connected populations of neurons arises. Subsequently, a “secondary repertoire” of functionally defined neuronal groups emerges as the animal experiences the world. A neural “value system,” developed over the course of evolution and believed to be made up of small populations of neurons within deep subcortical structures, is proposed to assign salience to particular stimuli encountered by the animal in order to select patterns of activity.

For example, when the response to a given stimulus leads to a positive outcome the value system will reinforce the synaptic connections between neurons that happened to be firing at that particular moment. When a stimulus is noxious, the value system will similarly strengthen the connections between neurons that happened to be firing at the time the stimulus was encountered, thus increasing the salience of that stimulus. When a stimulus has no salience, synaptic connections between neurons that fired upon first exposure to that stimulus will become weaker with successive exposures.

Importantly, the mapping of the world to the neural substrate is degenerate; that is, no two neuronal groups or maps are the same, either structurally or functionally. These maps are dynamic, and their borders shift with experience. And finally, since each individual has a unique history, no two individuals will express the same neural mappings of the world.

This brings us to the three tenets of Edelman’s theory:

1. Development of neural circuits leads to enormous microscopic anatomical variation that is the result of a process of continual selection;

2. An additional and overlapping set of selective events occurs when the repertoire of anatomical circuits that are formed receives signals because of an animal’s behavior or experience;

3. “Reentry” is the continual signaling from one brain region (or map) to another and back again across massively parallel fibers (axons) that are known to be omnipresent in higher brains.

Edelman thus believes that consciousness is entailed by reentrant activity among cortical areas and the thalamus and by the cortex interacting with itself and with subcortical structures. He suggests that primary consciousness appeared at a time when the thalmocortical system was greatly enlarged, accompanied by an increase in the number of specific thalamic nuclei and by enlargement of the cerebral cortex — probably after the transitions from reptiles to birds and separately to mammals about a quarter of a billion years ago. Higherorder consciousness (i.e., consciousness of consciousness), on the other hand, is due to reentrant connections between conceptual maps of the brain and those areas of the brain capable of symbolic or semantic reference — and it only fully flowered with hominids when true language appeared. Regarding language and its relationship to higher-order consciousness, Edelman explains:

“We do not inherit a language of thought. Instead, concepts are developed from the brain’s mapping of its own perceptual maps. Ultimately, therefore, concepts are initially about the world. Thought itself is based on brain events resulting from the activity of motor regions, activity that does not get conveyed to produce action. It is a premise of brain-based epistemology that subcortical structures such as the basal ganglia are critical in assuring the sequence of such brain events, yielding a kind of presyntax. So thought can occur in the absence of language….

The view of brain-based epistemology is that, after the evolution of a bipedal posture, of a supralaryngeal space, of presyntax for movement in the basal ganglia, and of an enlarged cerebral cortex, language arose as an invention. The theory rejects the notion of a brainbased, genetically inherited, language acquisition device. Instead, it contends that language acquisition is epigenetic. Its acquisition and its spread across speech communities would obviously favor its possessors over nonlinguistic hominids even though no direct inheritance of a universal grammar is at issue. Of course, hominids using language could then be further favored by natural selection acting on those systems of learning that favor language skills.”

Such a theory is attractive because it does not simply concentrate on conscious perception, but it also includes the role of behavior. We do well to keep in mind that moving, planning, deciding, executing plans, and more generally, keeping the body alive, is the fundamental business of the brain. Cognition and consciousness are what they are, and have the nature they have, because of their role in servicing behavior.

An important element of Edelman’s theory that consciousness is entailed by brain activity is that consciousness is not a “thing” or causal agent that does anything in the brain. He writes that “inasmuch as consciousness is a process entailed by neural activity in the reentrant dynamic core it cannot be itself causal.” This process causes a number of “useful” illusions such as “free will.”

Edelman’s theory of consciousness has further implications for the development of brain-based devices (BBDs), which Edelman believes will be conscious in the future as well. His central idea is that the overall structure and dynamics of a BBD, whether conscious or not, must resemble those of real brains in order to function. Unlike robots executing a defined program, the brains of such devices are built to have neuroanatomical structures and neuronal dynamics modeled on those known to have arisen during animal evolution and development.

Such devices currently exist — such as the “Darwin” device under development by The Neurosciences Institute. Darwin devices are situated in environments that allow them to make movements to sample various signal sequences and consequently develop perceptual categories and build appropriate memory systems in response to their experiences in the real world.

And though Edelman recognizes that it is currently not possible to reflect the degree of complexity of the thalmocortical system interacting with a basal ganglia system, much less to have it develop a true language with syntax as well as semantics, he nevertheless suggests that someday a conscious device could probably be built.

More ambitiously, Edelman also thinks that contemporary neuroscience can contribute to a naturalized epistemology. The term “naturalized epistemology” goes back to the analytical philosopher Willard Quine and refers to a movement away from the “justification” (or foundations) of knowledge and emphasizes the empirical processes of knowledge acquisition. Edelman is largely sympathetic towards Quine’s project, but provides a broader evolutionary framework to epistemology that also permits internal states of mind (consciousness).

1 Daniel C. Dennett, “Toward a Cognitive Theory of Consciousness,” in Brainstorms: Philosophical Essays on Mind and Psychology (Montgomery, VT: Bradford Books, 1978).

13. October 2014 · Comments Off · Categories: Cryonics, Neuroscience, Science

First published in Cryonics, 4th Quarter 2011

Robert Ettinger on Substrate-Independent Minds

Introduction and Afterword by Aschwin de Wolf

Introduction

Robert Ettinger, the “father of cryonics,” was cryopreserved on July 23, 2011. While Ettinger’s book Man into Superman (1972) is considered an important contribution to transhumanism, he increasingly came to recognize that most people do not desire a hard break with the past and resist radical transformation. During the last years of his life he became a vocal critic of ‘mind uploading’ as a means of personal survival and spent a considerable amount of time refining his arguments why mind uploading is not likely to work. This document organizes excerpts from his last book Youniverse and mailing list messages on the topic of substrate-independent minds. In the afterword, I make a brief attempt to place his contributions in a broader philosophical context.

The title of this document refers to a message that Robert Ettinger sent to the Cryonics Institute mailing list on July 21, 2011. In response to the claim that the human mind is a machine, and that the function of any machine can be duplicated by a machine built of another material, Ettinger asked, “Can you build a locomotive out of helium?”

Mind Uploading

“A large and burgeoning group of scientists, including some of the brightest, believe that—in principle—computers will fairly soon be able to think in the fullest sense of the word. They will be living, conscious entities with feelings and subjective experiences.

“A corollary—many believe—is that your persona could be uploaded into a computer and you could then live an incomparably bigger and better life as a simulation or emulation.

“I think the uploading thesis is probably wrong, although (as usual) it’s too soon to be sure. But the issue is a significant part of modern philosophy, and potentially has enormous practical importance.

“…I am among the radicals in the expectations for AI. But intelligence is not life. It is by no means proven that life as we know it with subjective experience can exist on an arbitrary substrate, such as silicon.” (Youniverse)

Information

“One extreme school of thought holds that information and its processing constitute everything that is important. In particular, you are essentially just a collection of information, including a program for processing that information. Your ‘hardware’—the nervous tissue that embodies and handles the information—is only secondary.

“My conclusion will be that it is not necessarily possible—even in principle—for consciousness to exist on an inorganic substrate, and in fact that it is unlikely.

“Sometimes the doubters are accused of dualism—the increasingly discredited belief that the living and inanimate worlds, or the material and the spiritual worlds, are separate.

“This certainly is not true of me or of many others who question the information paradigm. I am a thoroughgoing materialist and reductionist. I will not feel in the least dehumanized if it turns out the information paradigm is right…I have strong doubts, but they are based entirely on the evidence, or lack thereof.

“The most radical of the ‘strong AI’ people believe that all thinking is information processing, and all information processing is thinking; and they appear to believe that consciousness is just an expression of complexity in thinking.

“People who talk this way must be admired for boldness and strength of conviction, but I think not for clarity of thought.

“The point is, all physical phenomena, all interactions, involve information processing in some sense. But that isn’t all they do. A computer, or a person with pencil and paper, could figure out—describe or predict—what the atoms do, and that would be an analog of the information processing part of the phenomenon; but only the actual, physical atoms can form an oxygen molecule. And to anthropomorphize or analogize ‘feelings’ and ‘thoughts’ into these phenomena is simply unjustified. It amounts to declaring, by fiat, that thinking and feeling are inherent in information processing; but saying so doesn’t make it so.” (Youniverse)

Turing Tests and Zombies

“Alan Turing was a brilliant mathematician and computer pioneer. He played an extraordinary part in winning World War II through his work in cryptography for British Intelligence. He also showed many of the potential capabilities of general computers. But one of the works for which he is most famous is badly flawed or has been badly misused—the ‘Turing test’ for intelligence/- consciousness.

“Again, I am a firm materialist and reductionist: I readily concede the possibility that a machine could (conceivably) have life and consciousness. But I deny that we can assume that (inorganic) machines have this potential; and with still more help from Turing I think I can make the case persuasive.

“‘Uploaders’ or ‘upmorphists’ or patternists generally maintain that our identity resides in our information content. Their most extreme position is patently absurd—that ‘we’ literally persist, in some degree, if any of the information about us is preserved, even our writings or biographical data. (Shades of Woody Allen! ‘I don’t want to live on in my works; I want to live on in my apartment.’) Anyone who believes this needs more help than I can provide.

“Turing ingeniously showed that a strip of paper tape marked in squares, with zeroes or ones marked on the squares according to certain rules, along with a simple mechanism for moving the tape and making or erasing marks, could be a universal information processor—i.e., it could accomplish any information processing task that any digital computer (serial or parallel) could do, given enough time. It could even produce any result that a quantum computer might, albeit at a teeny-tiny fraction of the speed.

“You certainly can’t claim that a paper tape (even when it is moving) is alive or conscious! Yet that tape, in theory, could produce any response that a person could to a particular stimulus—if by ‘response’ we mean a signal sent to the outside world, suitably coded. It could converse with perfect fidelity to an individual’s character, and over a teletype could fool that person’s husband or wife.

“My original objection to the uploading assumption was simply that we don’t know anything about consciousness or feeling, hence it is premature to assume that it can exist other than where we know it exists, viz., in organic brains. It is entirely possible that meat machines (as opposed to machines of silicon or metal etc.) have some unique quality that allows the emergence of feeling and consciousness. Until we can isolate and define the mechanisms of feeling—of the subjective condition—we must reserve judgment as to the possibility of inorganic people. (Youniverse)

“Uploaders tend to put faith in the Turing Test  for human intelligence, and to believe that zombies cannot exist. Let’s  take a quick look.

“Communicating (say) by email, a testor tries to determine whether the testee is a human or a computer program. Passing the test supposedly proves the  testee is human or equivalent. But the test is clearly worthless, since it  produces both false positives and false negatives. As much as 50 years  ago Eliza, a program pretending to be a psychiatrist, fooled many people—false positives. And of course a child or a retarded person could perform below par and produce a false negative. The Turing test is baloney.

“In similar vein, uploaders tend to believe that something which outwardly behaves like a person must be a person. They reject the possibility of zombies, systems that by their actions appear to be sentient but are not. Yet it  is often easy to fool people, and, as already noted, programs have fooled  people even though no one claims the programs were alive.” (Cryonics Institute Mailing List, September 9, 2010).”

Imperfect Simulations

“..any simulation created in the foreseeable future will be imperfect, because it will necessarily reflect current theories of physics, and these are known to be incomplete and almost certainly in error to some extent or in some domains. Whether this would necessarily result in material deviations of the simulation from the course of nature, and in particular whether it would preclude feeling, we don’t yet know. But we do know that the simulation would be wrong, which in itself is enough to justify withholding judgment on the possibility of living computers.” (Youniverse)

Analog Failures

“The uploading thesis depends on the assumption that any organic process in the brain can be duplicated by analog in some other medium but this not only isn’t obvious; it’s nonsense.

“For example, suppose a certain process depends on magnetism, and all you have to work with are the mechanical forces transmitted by rigid bodies. Can you make an electric motor out of tinker toys? Can you build a synchrotron out of wooden boards and nails? Uploaders think a computer (of the electronic variety) can be a person: how about a Babbage mechanical computer made of rods and gears? Presumably, any kind of information processing and storage can be done by a collection of rods and gears but could rods and gears conceivably be conscious? I doubt it; not all media are created equal. So it is entirely possible that organic brains have potentialities not realizable anywhere else in the universe.” (Youniverse)

“Just ask yourself what consciousness is—what physical condition or process constitutes consciousness. You don’t know, hence you cannot know that a simulation  fills the bill.” (Cryonics Institute Mailing List, September 16, 2010)

Petitio Principii

“It seems to me that all the computer-metaphor people… keep making the same error over and over again—assuming as a premise the very hypothesis they are trying to establish. When the premise is the same as the conclusion, naturally the conclusion follows from the premise. They refer repeatedly to ‘all computational devices’ etc., implying that the brain is just that—another computational device—when in fact that is precisely what is at issue: Is the brain possibly something more than a computational device? The computer metaphor is plausible (and I am not in the least uncomfortable with it) but plausibility isn’t proof.” (Youniverse)

The Map is not the Territory

“Adherents of the ‘information paradigm,’ I believe, are deceived in part by glibness about  ‘information’ and hasty ways of looking at it.

“Apprently it needs to be said again and again: a description of a thing or a process—no matter how accurate and how nearly complete—is not the same as the thing or the process itself. To assume that isomorphism is enough is just that—an assumption, not self-evidently permissible.

“Even though (for example) a computer program can in principle describe or predict the behavior of a water molecule in virtually all circumstances, a water molecule for most purposes cannot be replaced by its description or program. If you pile up 6.02 x 1023 computers with their programs, you will not have 18 grams of water, and you will have a hard time drinking it or watering your plants.” (Youniverse)

“Eliezer Yudkowsky (and other uploaders) claim that mapping a system results in a map that effectively has the same properties as the original. Well, look again at one of my counter-examples. I write down with pencil and paper the quantum description of a hydrogen atom in its ground state. It could hardly be more obvious that the marks on paper do not constitute a hydrogen atom. And if you put side by side two papers describing two hydrogen atoms, they will not combine to form a hydrogen molecule. In principle, of course (the math is difficult) you could write down expressions corresponding to the formation of hydrogen molecules from hydrogen atoms, but you will still have just marks on paper.

Once more, a simulation is just a coded description of a thing, not the thing itself.” (Cryonics Institute Mailing List, September 18, 2010)

Identity

“The term ‘identical’ is used in different ways by different people. To  some, two systems are identical if they differ only in location, e.g. two  hydrogen atoms in ground state. But I have pointed out that a difference in location necessarily implies other differences as well, such as gravitational fields. Hence my position is that, if the question arises, are A and B  identical, then they are not.

“If two systems differ in spatial or temporal location, then they may be identical to most observers for most purposes, but survival of one does not  imply survival of the other. Suppose you, as you are now according to local  observation, also exist at a great distance in space or time (either past or  future), just by accident. I see no reason for the survival of B to imply the survival of A.” (Cryonics Institute Mailing List, September 16, 2010)

Afterword

Robert Ettinger presented a number of distinct arguments (no fewer than fifteen, by his own count!) against mind uploading and I cannot pretend to have presented them all in this document. I think there are a number of core positions associated with Ettinger’s argument that can be stated quite succinctly, however.

  1. Whether mind uploading is possible is ultimately an empirical question and cannot be settled conclusively by analogies or thought experiments.
  2. A description of a material object is not necessarily the same as the object.
  3. A simulation must be erroneous because the program necessarily is based on our incomplete knowledge about physics.
  4. Consciousness may be substrate-dependent.
  5. A copy of a person may not constitute personal survival.

The common denominator that runs through Ettinger’s critique of substrate-independent minds is a thorough empiricism about knowledge. Ettinger does not categorically rule out the feasibility of mind uploading but takes people to task for dogmatic claims on these topics in absence of empirical corroboration.

Ettinger was particularly irritated by the claim that materialism commits a person to the acceptance of mind uploading. He could not see how a rejection of the soul excludes the view that certain materials are uniquely suitable, or even exclusively suitable, for a certain function. One might add that it is even conceivable that the mind is substrate-independent but that existing organic chemistry provides the most versatile basis for advanced consciousness and survival.

Most of the issues that Ettinger was concerned about may be resolved by the time he will be resuscitated but it is possible that some of the issues that are at stake in this debate are ultimately un-falsifiable or even pseudo-problems. For example, how could we settle the question of whether a copy is “really you?” Obviously, a copy of something will always confirm that (s)he is really him- or herself but that is of little help in resolving the question. Similarly, we may never be able to conclusively verify (or falsify) that a computer has consciousness or feelings. Is it even conceivable that new super-intelligent life forms will replace humans without being conscious or having feelings! Evolution selects for fitness, and whether this implies consciousness is an open question.

So who is right, Robert Ettinger or his critics? I think what captures Ettinger’s perspective the best is to say that if you expect an answer right now, you have not paid close attention to his argument.

11. October 2014 · Comments Off · Categories: Cryonics, Neuroscience

Cryonics MagazineSeptember-October 2012

On Saturday, July 7, 2012, I attended the Symposium on Cryonics and Brain-Threatening Disorders in Portland, Oregon. The symposium was the “brain child” of Aschwin de Wolf, who also kindly invited me to give a presentation on treatments to mitigate Alzheimer’s Disease (AD). The symposium was organized by the Institute for Evidence-Based Cryonics and Cryonics Northwest.

It has been said that cryonics arrangements are made by people who think about things other people would rather not think about – in this case, one’s personal mortality. Like the sun in the sky, we can be aware of its presence, but prefer not to look at it. Dementia is in the same category. Despite the fact that anyone who lives long enough (cryonicists are usually life-extensionists) is much more likely than not to get dementia, even cryonicists are often reluctant to plan for becoming demented. Aschwin deserves a lot of credit for not only being a cryonicist, but for organizing (with his wife Chana) the world’s first symposium/conference dealing with the subject of cryonics and dementia. It is all the more impressive because Aschwin is a man in his 30s.

The symposium required no registration, registration fee, or notification of attendance. One man attended because another attendee had informed his wife of the event while on an airplane to Portland. There were only about 30 people at the event, but the quality of the attendees and presenters was very high. The event was held at Kaos Softwear, a manufacturing company where Chana is a manager. All the talks were allotted one full hour.

Chana, who has a master’s degree in neuroscience, was the first presenter. Her topic was neurogenesis — the creation of new neurons. Although neurogenesis was discovered in 1965, because neurons are post-mitotic (are non-dividing cells), the discovery was viewed with skepticism until the discovery of neural stem cells in 1992. Neurogenesis only occurs in two discrete areas of the mammalian brain: in the olfactory system and in the hippocampus. The latter is more crucial, although the exclusion of the cerebral cortex is of great concern insofar as that is the probable location of memory, identity, and decision-making. The hippocampus prepares new memories for long-term storage in the cerebral cortex. Chana asked lots of questions for which there are yet no answers. Why does the hippocampus need to create new neurons in the creation of new memories? How is neurogenesis used? How is neurogenesis regulated? Neurogenesis declines with age, and is enhanced with exercise or ischemia. Ultimately, endogenous neurogenesis does not appear to hold much promise as a repair strategy for AD or other forms of dementia. However, it is a worthwhile endeavor to understand neurogenesis in order to guide our own attempts at neuronal repair and/or replacement.

Aubrey de Grey began his talk by acknowledging that none of the work being funded in the 2012 $4.5 million budget of his SENS (Strategies for Engineered Negligible Senescence) Foundation is focused on repairing the brain, although there is a project determining the rate of accumulation of epimutations, that is not focused on repair. He spent the first half-hour reviewing the SENS program, and the next 15 minutes explaining why 3 of the 7 SENS strategies are particularly applicable to dementia: (1) Neurofibrillary tangles and soluble amyloid in Alzheimer’s disease (AD), and their counterparts in other neurodegenerative diseases, are intracellular junk, (2) amyloid plaque in AD is extracellular junk, and (3) late-stage neurodegeneration involves cell loss. Dr. de Grey said that intracellular junk shows signs of failed autophagy. He said that most of the intracellular junk in dementia is protein. It should be easier to dispose of than the cholesterol degradation products which are the focus of SENS lysosome work on atherosclerosis, but which are not properly delivered to the lysosome. He outlined the circumstantial evidence that the main problem may be the same as in atherosclerosis, i.e. oxidized cholesterol poisoning the lysosome. He spoke of the current clinical trials for having microglia eliminate extracellular junk (amyloid plaques). The first human clinical trials had shown great promise, but were halted because 5% of the patients developed brain inflammations. The newer trials have apparently corrected that problem. Aubrey noted the widespread belief that the amyloid would be removed without being of much benefit – expressing his belief that this misses the point, because major postponement or reversal of AD will require fixing all three main problems, hence lack of benefit from fixing one is not evidence that that one need not be fixed. I am one of the skeptics because follow-up autopsies on the first trials showed that even when amyloid plaques had been completely removed, no reduction in degeneration had occurred [THE LANCET; Holmes,C; 372:216 (2008)]. By the time AD is diagnosed, neurodegeneration is too far along to be helped by removing amyloid (though there is rapid progress in improving very early diagnosis). Immunization to remove amyloid would be more effective if begun in the 20s or 30s, much like shots for measles or polio — as prevention rather than cure. Although amyloid may serve a positive function in repair or it would not have evolved. [Aubrey notes: who says it evolved? "Aging is a product of evolutionary neglect, not evolutionary intent" (Hayflick)]. Concerning cell loss, Aubrey was sanguine about Jean Hebert’s work exploiting the fact that certain neural progenitor cells are highly migratory, potentially facilitating widespread distribution of new neurons throughout the neocortex via stem cell therapies. Even if neurons can be replaced in the neocortex, I wonder how that would compensate for the loss of synaptic connections and strength of synaptic connections. Of the three approaches mentioned by Dr. de Grey, I would say that removal of intracellular junk has the best chance of being of benefit on its own, because it is the neurofibrillary tangles that tend to cause cell death rather than the amyloid plaques, which are an upstream event.

My talk was basically a summary of the “Alzheimer’s Disease: Molecular Mechanisms” page in the life extension section of my website BENBEST.COM. I wrote the page in 2003 between leaving my job as bond database support for Scotiabank in Toronto, Canada, and becoming president of the Cryonics Institute in Michigan. For the subsequent 9 years I have become increasingly displeased about how out-dated the webpage was becoming. So I was pleased at the opportunity to do the massive research required to update that webpage for this symposium. Unfortunately, it was all I could do to finish the updating before catching my flight to Portland. Aschwin and Chana allowed me to crash at their condominium. I missed the Friday evening social for those attending the symposium because I spent all evening and a couple of hours the next morning creating my PowerPoint. I was pleased with the result, however, and pleased with the presentation I was able to deliver.

I encourage anyone interested in the content of my talk to consult my Alzheimer’s webpage because that page has detailed linkable references which I could not include in my presentation. I believe that the most promising therapy is the targeting of copper with PBT2, which removes copper from amyloid without chelating essential element metals. Etanercept, which antagonizes the inflammatory cytokine TNF-alpha has also shown promising results. Possibly also, passive immunization with tau antibodies would be of greater benefit in stopping neurodegeneration than immunological approaches against amyloid. Concerning prevention, exercise, curcumin, pomegranate juice, and folic supplementation have shown good results. Seemingly conflicting results would indicate that ginko biloba can slow cognitive decline in Alzheimer’s patients, but is of no benefit in preventing the disease.

Mike Perry’s topic was Early Detection of Alzheimer’s Disease. On that subject he reported that the CerebroSpinal Fluid (CSF) is low in amyloid beta and high in phosphorylated tau protein. I had put much more detail on this subject into the biomarkers section of my webpage on Alzheimer’s Disease – which I showed to Mike later in the day. In his presentation Mike noted even for people who do not get AD, dementia of some kind is still very probable with aging. He commented that AD is not a terminal illness, which is defined as an illness in which two physicians have certified that the patient probably has no more than six months left to live. No AD patient dies of AD — the cause of death is usually infection (pneumonia, bedsores, urinary tract infection, etc.). I expressed concern that suicide by VSED (Voluntary Stopping of Eating and Drinking, as Mike calls it) by an AD victim could lead to autopsy. Mike denied that this was necessarily the case.  I was told that for anyone who had died by refusing food and water the cause of death would be obvious, and no autopsy would be required, though circumstances and policies will vary. Mike Darwin, however, noted that VSED could be harmful to the brain as cardiac arrest draws near, due to low respiration rates. Aschwin responded that this kind of brain damage is still relatively benign in comparison to the alternative (advanced dementia). James Swayze, who is a paraplegic with cryonics arrangements and was in attendance at this event, has expressed concerns that dehydration causes brain damage. Dehydration may reduce brain functionality, but brain dehydration is a key process in removing water from the brain in the vitrification point of view and is probably a benefit rather than a harm for cryonics purposes.  Alzeimer’s patients nearly always die of infection, and because infection may also occur early in the disease,  Mike Darwin recommended that anti-microbial treatment be refused by an Alzheimer’s victim as a way of hastening cryopreservation. If infection does not occur early in the disease, however, refusing antibiotics may not produce the desired result.

Keegan Macintosh, who recently graduated from a Canadian law school, presented on the subject of Thomas Donaldson’s 1988 lawsuit in California to be cryopreserved before his brain cancer destroyed too much of his brain to make cryonics a worthwhile effort. Keegan criticized the attorneys involved in the appeal for arguing that Donaldson’s right to “premortem cryopreservation” stemmed from a constitutionally-protected right to assisted suicide, rather than the right to pursue a risky, but potentially life-saving procedure. By framing the case this way, the Court was able to avoid having to consider Donaldson’s unique and crucially relevant motive, and thus the possibility of cryonics succeeding, for him or anyone else. Acknowledging, however, that options for assisted suicide could be of use to cryonicists with brain-threatening disorders, Keegan examined developments in American law on the issue, and then turned to Canadian jurisprudence. He pointed out a number of potentially significant differences between the U.S. Supreme Court’s substantive due process analysis in the more recent physician-assisted suicide cases, Washington v. Glucksberg and Vacco v. Quill, and Supreme Court of Canada’s approach to section 7 of Canada’s Charter Rights and Freedoms (right to life, liberty and security of the person) in Rodriguez v British Columbia, and cases since. The government’s position is presumably influenced by a desire to avoid a “slippery-slope” that disvalues human life. Keegan noted that although formerly other countries looked to the American Constitution for guidance, Canada’s constitution is now the world’s most popular role-model. Section 2 of Canada’s Charter of Rights and Freedoms emphasizes “freedom of conscience and religion.”

What would be the effect of someone acting on the belief that pre-mortem cremation is the road to salvation? “Freedom of conscience” implies that secular morality is as important as religious belief and there is some emerging jurisprudence to that effect. Would the belief that good-quality cryopreservation is necessary to live again at some future time not then receive equal protection to analogous beliefs and practices of religious origin? Keegan believes that an appeal such as Donaldson’s – and indeed any constitutional challenge against a law impeding access to cryonics – would have a better chance of success in Canada than in the United States.

Max More spoke without slides on the subject of “Survival, Identity, and Extended Mind.” The objective of Max’s talk was to consider how it could be possible to back-up personal identity-relevant information and then reintegrate that information to restore personality if cryopreservation has been imperfect. If cognitive processes and their inputs can be external to the brain, Max would like to take advantage of this to improve the chances of reviving people suffering from brain-threatening disorders. Andy Clark and David Chalmers wrote an authoritative paper entitled “The Extended Mind.” According to Max, for an outside object or process to be considered part of the mind, it has to produce results that are reasonably comparable to the components normally seen internally and biologically/neurologically. Clark and Chalmers propose three conditions for considering externally-located processes to be part of an individual’s cognitive processes: 1) constancy (the external component has to be there reliably); 2) accessibility (a natural ease of use of that component); and 3) automatic endorsement (the person must trust the component as they would trust any comparable part of their natural body). Max noted that a few years before the Clark/Chalmers paper he had considered the related issue of when an external technology could be considered part of the self (in chapter 4 of his dissertation: “Technological Transformation and Assimilation”). Although Max doubted Ray Kurzweil’s claim that an externally-convincing simulation of his father (made out of traces available) would actually have a self, Max did not argue that no well-simulated person could have a self. Max suggested that a notebook could be part of the thinking process, rather than just a tool. Nonetheless, he was dubious about the value of keeping lots of diaries, although it has been suggested that biographical information could assist in reconstruction of a cryonics patient and that cryonics organizations should take a more proactive role in fasciliting storage of identity- and memory relevant information. Max was also dubious that a computer that could convincingly simulate a person would have a self. He raised the question “What is self?” He referred to David Hume’s claim to introspectively only be able to discover thoughts and feelings, but no self. Dennett called self an illusion. This would lead me to believe that neither Hume nor Dennett should have much concern with their own survival (like most people?). Max said that he could lose a few memories without feeling his self was compromised — because he believes that personal identity is more than memory. It includes dispositions, values, and so on.

After the presentations there was a panel of all the presenters, plus Aschwin the host. I requested that each panelist explain what they would do if diagnosed with AD. Aschwin said he would immediately proceed to terminate his life under conditions favorable to cryopreservation provided that the diagnosis was credible and there are no short-term cures on the horizon. Keegan said that he would see first what, if any, time he had before symptoms such as apathy and denial would be expected to set in, and take some conservative portion of that time remaining to spend some quality time with family and friends. Keegan noted that, despite our best efforts, cryonics may not work, and thus it is rational to seek meaningful experiences in the moments one knows they have left, if such can be done without irreparably compromising one’s cryopreservation. I noted that Robert Ettinger also said he would terminate life by hypothermia in a cold bathtub at the end of a party with friends – but delayed such an action to the point where he lost consciousness and lost the ability to do any such thing at the age of 92 when he deanimated. I said that I would probably spend about a year attempting to confirm the diagnosis, and might delay further trying to determine if a cure was possible or forthcoming soon. Max said that he would want a second opinion, but like Keegan wanted to have some joyful time before self-termination. Chana said that she would be very concerned about how the decision to self-terminate would affect others, in particular how to explain to her family why she was ending her life while outwardly being in good health. Chana and Aschwin spoke of being sensitive to each other’s feelings about the matter. Aschwin noted that those who care for AD family members to a natural death often suffer from severe caregiver depression. Chana said that once she had decided to pull the plug that she would “find a way to take a bath in Agent Orange and take advantage of Oregon laws.” By this she meant she would find a way to give herself an aggressive form of cancer that would cause two Oregon physicians to declare that she is a terminal patient. Once this is done, an Oregon physician can write a prescription for phenobarbital which the patient can use for suicide by overdose at the time and place of their choosing. Aubrey said that he would delay the decision without worrying too much about loss of neurons. In addition to delaying because of diagnosis confirmation and evaluating hope for a cure within a short time period, Aubrey added evaluating the likelihood that cryopreservation procedures would be improved by waiting. Mike Perry said that he would try to confirm the diagnosis and if sure about it, “get it [deanimation] over with as soon as possible.”

I mentioned the case of a CI Member dying of cancer who, with her husband, called Suspended Animation, Inc., to be present at their suicide. Her 30-year-old husband was in good health, but did not want to live without his wife and planned to die along with her. CI terminated both their memberships and established a policy of reserving the right to cancel cryonics contracts in cases of suicide. Aschwin strongly disapproved of this CI policy. In his opinion, cryonics organizations should never encourage or condone suicide but should not refuse cryopreservation to those who have taken their own lives. I believe cryonics organizations cannot be seen as encouraging the hastening of death on the ground that cryonics may work, and must ensure that others do not get that impression. Not enough was said about what policies would be most appropriate for cryonics organizations.

I asked Aubrey if he thought that an AD patient would ever be so advanced that SENS could not save the self. Aubrey agreed that could happen, but it would be difficult to say when. The case is similar with straight frozen patients or patients with varying amounts of ischemic damage. The concept of “information theoretic death” is meaningful, but difficult to determine. Even if SENS methods could not recover enough memory and identity to save a person, some future molecular archeology might be able to do so.

There was some discussion about the most promising treatments for Alzheimer’s disease. Aschwin pointed out that both early-onset Alzheimer’s and late onset Alzheimer’s have a strong genetic component, which should favor the use of gene therapy.

Mike described the activities of the Venturists, which is offering to save Venturist Members who are being cryopreserved by a cryonics organization that fails. Another project of the Venturists is that they are seeking $50,000 for Mike Darwin, who lost his cryopreservation arrangements with Alcor due to financial difficulties.

04. October 2014 · Comments Off · Categories: Cryonics, Neuroscience, Science

Connectome: How the Brain’s Wiring Makes Us Who We Are by Sebastian Seung, Houghton Mifflin Harcourt Trade, 384 pages, 2012.

[This review originally appeared in Venturist News and Views, June-July 2012, 6-7 and Cryonics, September-October 2012]

The scientific perspective that informs Sebastian Seung’s bestselling popular neuroscience book Connectome is so familiar to cryonicists that the bulk of this book could be mistaken for an extensive introduction to the philosophy of mind embodied in cryonics. His book offers a rigorous exposition of the view that our identity is encoded in the connections between neurons, the “connectome,” which itself is shaped by our genes and life experience. The strength of this book is not only its review of the empirical evidence that supports this outlook but its encouraging the reader to think about its implications.  Readers who are intimately familiar with the argument in favor of cryonics should not assume that there is little to learn from this book. As imaging and storage technologies evolve, cryonicists can do more now than in the past to learn about their individual connectome, strengthening the likelihood of successful resuscitation.

One important element of the connectionist premise that structures Seung’s book is that it does not completely resolve competing theories about how the brain works. For example, the recognition that long-term memory (and identity) does not depend on transient electrical activity but has a more robust long-term physical basis that persists during cessation of brain activity (examples are hypothermic circulatory arrest and short periods of cardiac arrest) does not imply a single perspective on how the genome provides the neurological bases for memory formation, retention, recollection, and re-prioritization. One interesting perspective, “neural Darwinism,” which was anticipated by the multi-talented classical-liberal economist Friedrich Hayek, proposes a theory of brain function in which a genetically determined wiring of the brain is subject to competing experiences that strengthen or weaken populations of synapses throughout life. One of the interesting implications of this theory is that consciousness can be treated as an emergent outcome of micro-events in the brain, instead of a mysterious, autonomous property of the brain (think of the curious concept of “free will”).

Seung devotes two chapters to the nature-nurture debate through a connectionist perspective. One of the unfortunate effects of the nature-nurture distinction is that it masks the obvious point that what we call “nurture” (upbringing, environment, etc.) is not exempt from biology but simply concerns the relationship between biological systems and between a biological system and its physical environment. Social scientists who have a strong “nurture”-bias should therefore not be exempted from describing “nurture” in verifiable physical terms, something that many of them do not feel the slightest obligation to do. Another unattractive feature of this debate is that it is routinely portrayed as one between genetic determinists and “environmentalists.” In reality, the debate is mostly between serious scholars who acknowledge that behavior and learning are shaped by both genetics and the environment and those who basically consider the mind a blank slate—a position that is clearly contradicted by existing science but remains popular as a premise in contemporary public policy and certain political ideologies. One of the interesting topics that Seung discusses in these chapters is whether the plasticity of the brain changes over time.

From the perspective of cryonics, the relationship between the genome and the connectome is of great importance. If some of the basic wiring of the brain that encodes personality and temperament is determined by genes and is fixed (or mostly fixed) at an early age, then some parts of the connectome might be inferred from a person’s genome, which opens up an exciting research program for cryonics. A systematic study of the field where genetics meets neurodevelopment might help in understanding the relationship between the genome and brain ultrastructure. This in turn could assist in future resuscitation attempts. To date, the assumption in cryonics has been that the complete ultrastructure of the patient must be preserved (or at least preserved in such a manner that it can be inferred), but if some of it can be inferred from the genome the repair requirements for resuscitation of cryonics patients may be relaxed. Looking for such invariable features in variable brains is an important element of a credible cryonics resuscitation research program.

The power of comparing connectomes is also recognized by Seung in a separate chapter (“Comparing”). There he reviews technologies and approaches to compare connectomes with the goal of understanding personality differences and understanding neuropathologies or “connectopathies.” This chapter is one of several in which the author reviews the existing and emerging technologies that are enabling us to produce a complete connectome, including the innovative equipment of cryonicist and Alcor member Kenneth Hayworth to perform serial electron microscopy. Also discussed are technologies such as diffusion MRI (dMRI), which allows for non-invasive mapping of the connectome at the macro scale using water as a probe. This technology may not be adequate to map the connectome at the cellular level but its contribution to comparative connectomics has already been recognized. It may also hold promise as a means to collect identity-critical information about an individual while alive, which again may lessen the computational challenges involved in cryonics resuscitation. One of the exciting prospects of the field of connectomics is that it can contribute to a further narrowing of the challenges involved in restoring cryonics patients to good health.

Seung closes his chapters on emerging technologies with a review of the prospects of connectomics for the treatment of neurological diseases. One of the potential treatments involves the re-programming of a person’s own (skin) cells to neurons, which can then be introduced in the brain to treat a disease or enhance brain function. Such an approach may also be used to fill the “missing gaps” in the brain of a cryonics patient (alternative technologies include molecular construction of neurons by advanced molecular nanotech­nology).

At this point, I think we can foresee a rather optimistic future for cryonics research and the prospect of resuscitation. Instead of conceptualizing cryonics as the preservation of clinically dead people in the hope that future medicine can restore these people to good health, we can envision a more complex, but more encouraging, path. The work of resuscitation and restoring identity is not something that is expected to occur exclusively in the future but rather will be an ongoing process that starts as soon as the patient is cryopreserved. And with the rise of advanced genomics and non-destructive imaging technologies, some of the initial work can be done while the person is still alive. One of the exciting aspects of being a cryonicist today is that you can take proactive steps to learn about your own connectome and other identity-relevant information.

Seung devotes no less than a whole chapter to human cryopreservation (and the associated idea of chemopreservation). The author recognizes that his own views about the connectome are so similar to the philosophy of mind that underpins cryonics that he needs to do some justice to the rationale of cryonics. One unfortunate aspect is that he situates his discussion of cryonics in the context of religion and immortality. It is undeniable that some cryonicists are motivated by visions of personal immortality but this idea is not intrinsic to cryonics (neither is mind uploading or transhumanism.) Properly conceived, cryonics is an experimental medical procedure that aims to stabilize patients at cryogenic temperatures in anticipation of future treatment. What really distinguishes cryonics from mainstream medicine is not uncertainty (which is a fact of life), but the temporal separation of stabilization and treatment. One regrettable implication of attributing religious motives to people who make cryonics arrangements is that it cheapens the use of the word ‘religious.’ Instead of referring to worship of a higher being, it is here used as a strong belief in something in the absence of conclusive evidence. But by putting the bar so low, Seung (unintentionally) classifies many aspects of life, including choosing novel experimental treatments in mainstream medicine, as “religious.”

At one point Seung writes that research aimed at demonstrating that contemporary vitrification technologies can preserve the connectome will “finally bring some science to Ettinger’s wager.” This is a remarkable statement because even the earliest arguments in favor of cryonics were never presented in the form of a pure wager. In his book The Prospect of Immortality, Robert Ettinger reviews existing evidence from cryobiology and neuroscience and argues that, combined with the expectation that medicine will continue to evolve, the choice to be cryopreserved is a rational decision. Since Ettinger’s book cryonics organizations and wealthy donors have expended a lot of money and time in perfecting preservation techniques and looking at the effects of new technologies on the structure and viability of the brain.  Compared to the state of, let’s say, interventive biogerontology, the scientific progress that has been made in cryonics is not trivial. For example, it is doubtful whether the widespread adoption of vitrification in mainstream cryobiology would have been possible without sustained research into using this approach for complex organs by cryonics supporters. To my knowledge, cryonicists have always been quite eager to generate experimental knowledge to inform their decision making. Now that more advanced technologies to map the human brain are becoming available, cryonics organizations are eager to use them instead of just passively maintaining their “faith.”

Ultimately, Seung still fails to recognize that cryonics inherently involves an element of uncertainty that cannot be eliminated without it not being cryonics anymore (i.e., elimination of uncertainty makes it suspended animation). For example, the author recognizes that it is not necessary for a preservation technology to perfectly preserve the connectome as long as it remains possible to infer the original state (or missing information) from what has been preserved. We can speculate what the limits of such “neural archeology” will be, but I do not think anyone can make conclusive arguments. In this sense, cryonics cannot be completely moved from the realm of informed decision making into the realm of indisputable fact. An element of uncertainty will always be associated with it, even if the experimental evidence in favor of this medical procedure keeps mounting.

The author also discusses alternative preservation approaches such as chemical fixation and plastination. One major disadvantage of existing chemical preservation technologies is that they are irreversible by contemporary techniques (literally a “dead end”) and they do not allow for viability assays to distinguish between worse and better preservation techniques. In contrast, in cryobiology, evidence of good ultrastructural preservation is often a starting point (or independent corroboration) to identify cryoprotectants that are able to store complex organs at cryogenic temperatures and restore them without loss of viability. There is one other formidable challenge that will inevitably arise if chemical preservation is offered as a means of personal survival. It is how to deal with the fact that if chemical fixation is delayed perfusion impairment will prevent complete cross-linking of biomolecules. Even more so than cryonics, chemopreservation requires that the procedure be started prior to, or immediately following, circulatory arrest. In absence of this, the fate of a person’s connectome is uncertain, and may even worsen during storage—a problem cryonics is exempt from.

The book ends with a chapter about mind uploading. One misconception about cryonics is that people seek it as a means to mind uploading, or that reviving the person in a computer is the aim of cryonics. In fact, the late Robert Ettinger became a vocal critic of mind uploading in his final years. He offered a lot of arguments for his skepticism but his main concern was that questions about the feasibility of mind uploading are ultimately empirical questions which cannot be settled by deductive reasoning and dogmatic claims about the nature of the mind or consciousness. One of the amusing aspects of the debate about mind uploading is that proponents and skeptics both accuse the other of not being consistent materialists. Interestingly enough, Seung makes an observation relevant to this debate when he writes how the idea that “information is the new soul” is implied in the mind uploading project.

Despite some misgivings about how Seung presents and conceptualizes cryonics, I am unaware of another book that offers such a clear exposition of the relationship between brain and identity that informs human cryopreservation (and chemopreservation). The most rewarding thing for me was a stronger recognition that the idea of the connectome is not just a premise but opens the door to multiple fruitful research programs aimed at personal survival.

About the Author: Sebastian Seung is Professor of Computational Neuroscience and Physics at MIT and Investigator at the Howard Hughes Medical Institute. He has made important advances in artificial intelligence and neuroscience. His research has been published in leading scientific journals and also featured in the New York Times, Technology Review, and the Economist. (From the dust jacket.)

Dr. Seung was also a speaker at the Alcor-40 conference in October 2012

19. August 2014 · Comments Off · Categories: Cryonics, Death, Neuroscience

On October 11, 2013, the Wall Street Journal featured a cover story about the unintended consequences of Norway’s long-time insistence on “plastic graves” (“Grave Problem: Nothing is Rotting in the State of Norway”). You see, after World War II the Norwegians wrapped the dead in plastic prior to burial and now they are faced with…corpses that are not decomposing. Since cemetery real estate is scarce in Norway this creates a rather complicated and sensitive problem. One of the solutions is to poke holes in the ground and plastic to inject a lime-based solution to accelerate decomposition.

Not many people would expect the brains of these plastic-preserved Norwegian corpses to be in pristine condition at the ultrastructural level but this strange story does illustrate that decomposition is a process that is highly sensitive to variables like the presence of oxygen, water, microorganisms, and temperature. Of course, some of these variables are related. When temperatures are lower there will be reduced microbial activity. As a consequence, at cold temperatures the rate of decomposition can be even slower than what one would predict based on the decrease of the brain’s metabolism alone. Cold ischemia is not just warm ischemia slowed down (and vice versa).

My company, Advanced Neural Biosciences, Inc., is currently collaborating with Alcor to produce a series of electron micrographs of brain tissue exposed to very long times of cold ischemia (0 degrees Celsius). One of the reasons we are doing this project is to bring actual data to the decision making process concerning the question when to accept and when no longer to accept a patient who has been stored at low temperatures prior to contacting Alcor for cryonics arrangements.

Ultimately, what we are looking for is an ultrastructural signature of “information-theoretic death.” This presents a formidable problem because information-theoretic death is not an unambiguous identifiable property of an image but concerns our best guestimate about how much structure a future technology might still be able to infer from a given state of damage. For existing patients and members who want to be preserved under any conditions this is not a directly relevant question (the future will tell). But when you have to make a decision whether to accept a third-party “post-mortem” patient, arbitrary decisions have to be made because Alcor simply cannot accept every case brought to its attention.

We have now produced electron micrographs of up to 1 month of cold ischemia. When we shared these 1 month images with the Alcor Research and Development committee one member remarked that he “would not have guessed that so much structure could remain after one month.” When we presented an image from this series at a recent conference, attendees were also surprised about this level of preservation.

Of course, this is not the end of the story because a patient with such a long period of cold ischemia will still need to be cooled to cryogenic temperatures for long-term care and a “straight freeze” on top of such extensive ischemic damage could tip the balance towards informationtheoretic death. These results raise one interesting possibility, however. If the damage of a straight freeze is a lot worse than the damage from moderate times of cold ischemia, cryoprotecting the brain (or both hemispheres separately) by soaking it in cryoprotectant could be a superior protocol for a select number of Alcor cases. There is still much to be learned.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, November, 2013

26. November 2013 · Comments Off · Categories: Cryonics, Neuroscience, Science, Society

[This interview was originally published in Cryonics magazine September 2013]

By Stephen Cave

This magazine generously reviewed my book Immortality: The Quest to Live Forever and How it Drives Civilization in the November/December 2012 edition. But the reviewer argued that I didn’t properly understand cryonics — so I decided to speak to a leading expert. This interview, with Cryonics Magazine’s editor Aschwin de Wolf, is the result. Parts of the interview appeared originally in Aeon Magazine (http://www.aeonmagazine.com)

What is cryonics?

(Stephen Cave) Cryonics is sometimes described as “medical time travel” – is that how you see it?

(Aschwin de Wolf) Yes, that is a good characterization. What sets cryonics apart from other medical procedures is not uncertainty (which is an element of many experimental medical treatments) but the temporal separation of stabilization and treatment. Cryonics reflects the recognition that a disease considered terminal today might be treatable in the future.

Does/will cryonics work?

What is the largest (or most complex) organism (or tissue) that has been successfully cryopreserved and revived (or reversibly vitrified)?

A rabbit kidney has been vitrified and successfully transplanted with long-term survival. Another major achievement that supports the practice of cryonics is the successful vitrification and functional recovery of rat hippocampal brain slices.

In terms of whole organisms, tardigrades and certain insect larvae have been successfully recovered after cryopreservation at low sub-zero temperatures.

What breakthroughs in cryopreservation are still required? When do you think they might come?

Recovery of organized electrical activity in the whole brain (EEG) after vitrification and rewarming would provide further support for the practice of cryonics. This may be achieved in about 5 to 10 years. Long term, the aim should be true suspended animation of a mammal.

It is important to recognize, however, that the damage associated with today’s cryonics procedures only excludes meaningful future resuscitation if the original state of the brain cannot be inferred. Damage-free cryopreservation would be sufficient but it is not necessary to justify practicing cryonics today.

Cryonics depends upon faith in technological progress and social stability (such that well-disposed scientists and physicians in the future will be both able and inclined to revive cryonics patients). Why do you believe the future will be so utopian?

In my opinion, it is more reasonable to ask why anyone would make decisions on the premise that medical progress would come to a screeching halt. Cryonics patients have time, and successful resuscitation does not necessarily require fast or accelerated progress. Cryonics does not rest on an utopian, but on a very conservative, premise.

Resuscitation of cryonics patients is the foremost responsibility of a cryonics organization. That is why organizations like Alcor set aside substantial amounts of money in a separate trust to allow for the maintenance and eventual resuscitation of the patient.

Social acceptance

Why do you think cryonics is not more popular?

It would be tempting to say that cryonics is not more popular because most people do not think it will work. The problem with this explanation is that hundreds of millions of people believe in all kinds of things for which there is no strong empirical evidence at all, such as astrology. In addition, when faced with a terminal prognosis people have a really low threshold for believing in the most implausible treatments.  If the popularity of cryonics would be a function of its scientific and technical feasibility, we should have seen major increases in support when new technologies, such as vitrification, were introduced.

The most likely explanation, in my opinion, is that people fear social alienation and solitary resuscitation in an unknown future. In fact, writers such as Arthur C. Clark, who strongly believed that cryonics will work, personally admitted as much. This is a real challenge for cryonics organizations but there is a growing interest in topics such as reintegration of cryonics patients.

Do you think there might be a tipping point in its popularity? What might bring such a tipping point about?

Scientific and technological breakthroughs in cryobiology (suspended animation) and cell repair will certainly help, but if fear of the future holds most people back there may not be such a tipping point. It is possible, however, that in certain demographical groups making cryonics arrangements will be recognized as the normal, rational, thing to do. Something like is already happening in subcultures that are interested in human enhancement or reducing bias in decision making.

Do you think there will be a day when cryonics is the normal procedure for treating those with diseases incurable by contemporary medicine?

Yes, or at least some kind of long term stabilization procedure will be used for people that cannot be treated by contemporary medicine. I find it hard to imagine that people will persist in burying or burning a person just because there is no treatment today. That is just irrational and reckless.

Philosophy and legal status of cryonics

Are those who are currently cryopreserved, in your view, actually dead?

No. But I do not think we can just claim that they are alive in the conventional sense of the word either, although that may change if we can demonstrate that cryopreservation can preserve viability of the brain.

If not, what state do you consider them to be in?

If the original state of the brain, what some scientists call the “connectome,” can be inferred and restored, cryonics patients are not dead in a more rigorous sense of the word. Their identities are still with us in an information-theoretical sense.

What legal status do you think those who are cryopreserved should have?

They should have much stronger legal status than the deceased have today. While a meaningful philosophical/technical distinction could be made between conventional patients and cryonics patients I think we need to err on the side of caution and give them the same kind of protection as other patients with terminal diseases.

At the very least, obstacles to conducting good human cryopreservation in hospitals should be eliminated because a lot of reservations people have about cryonics are not intrinsic features of the procedure but the results of cryonics organizations being forced to practice cryonics as a form of emergency medicine.

When should it be legal for someone to have themselves cryopreserved (eg, any time? when diagnosed with a terminal illness? or only when brain-dead according to current definitions? etc)

If a patient has been diagnosed as “terminal,” that is basically an admission of the physician that (s)he has exhausted contemporary medical treatment options. At that point it is prudent to identify other means of saving the patient’s life, including stabilizing them at lower temperatures for future treatment. This is particularly important if the patient is in a condition where continued metabolism will progressively destroy the brain. Such a procedure would be the opposite of assisted suicide because its aim would be to preserve life, not to end it.

Ethical considerations

The overpopulation problem: if a few generations of people do all have themselves cryopreserved, then when technology permits them to be revived and healed, will there not be an enormous population boom? How will this be managed?

There are several responses to this question. The most obvious one is to draw attention to the fact that today’s socio-economic debates in the West are about the consequences of a decline in population in the future as a consequence of people having fewer children.

It is also important to recognize that cryonics does not operate in a sociological, psychological, and technological vacuum. If support for the procedure changes so will our views on reproduction and sustainability.

Of course, it should not even be assumed that future generations will be confined to one planet (Earth). 

What do you say to the idea that death gives meaning or shape to life?

Cryonics is not a permanent cure for death. There may always be catastrophic events that could irreversibly kill a person or whole populations. In fact, it may never be possible to know that we will not die for the simple fact that this would require absolute knowledge about the infinite future.

Having said this, no, I do not think that death gives meaning to life. That is just an admission that the things that matter do not have intrinsic value but are experienced with mortality as a framework. Neither introspection nor observation of ordinary life suggests this.

In fact, I suspect that short human life-spans have an adverse effect on morality because it fosters instant gratification and indifference about long-term reputation and/or consequences.

On the other hand, do you think we are morally obliged to practice cryonics (as we might be to try to prolong life in other ways)?

My qualified answer is “yes.” If we believe that the aim of medicine is to preserve life and reduce suffering, cryonics is a logical extension of this thinking. Cryonics is not only a rational response to the recognition that science and technologies can evolve, but it also can be important to stabilize devastating cases of acute brain trauma.

You

When did you first become interested in life-extension technology?

In my case, my interest in life extension was a consequence of making cryonics arrangements.

When did you first hear about cryonics? When did you sign up for it?

I first read about cryonics on the internet in the mid-1990s. The idea seemed quite reasonable to me but I did not consider it as something that had direct personal relevance to me at the time. This changed in 2002 when a rather trivial medical condition prompted me to think more seriously about my remaining life and mortality. I read a lot of cryonics literature in a short period of time, attended the Alcor conference that autumn, and finalized making cryonics arrangements in January 2003.

Do you proselytize among friends and acquaintances? Have you had much luck in persuading others to sign up for cryonics?

Unless I know that a person has a strong interest in making cryonics arrangements, I generally do not explicitly try to persuade them. This is partly because I do not want people to get defensive in response to the idea. In cases where I know that the person is very open to cryonics, I put more effort into it. I think I have been successful in persuading around 4 people to make cryonics arrangements. There may be more that I am unaware of because of all the writing that I do.

Are you pursuing life-extension practices in the hope that you won’t need to be cryopreserved?

Yes. As most people with cryonics arrangements, I have a strong interest in life extension and rejuvenation research. I am not very optimistic about short-term breakthroughs so I try to eat healthy, exercise, and avoid dangerous activities and excessive stress.

What is your educational background?

I graduated in political science at the University of Amsterdam and have a strong interest in economics and philosophy as well. Over time my academic interests have mostly shifted to biology and neuroscience – also because of the experimental research that I am involved in.

What is your involvement with Alcor or other cryonics institutes/firms?

I have been an Alcor member for 10 years and have been employed in cryonics either as an employee or on a contract basis since 2004. My main activities right now are to conduct neural cryobiology research in my lab at Advanced Neural Biosciences and to edit Alcor’s monthly magazine, Cryonics.

I have always had a good relationship with the other major cryonics organization, the Cryonics Institute, too. In fact, without its support, and its individual members’ support, our research would not have been possible.

What would be your best guess for the year when you will be revived by the scientists of the future? What might the world look like then?

I do not think that there is a uniform year for all cryonics patients. Much will depend on the condition of the patient and prevailing technologies and capabilities at the time. For a typical patient, I doubt we are going to see meaningful resuscitation attempts before 2075.

If the past is any guidance, the (far) future will be a combination of things that have always been with us and things we cannot even imagine right now. I suspect that the most characteristic change in the future will be a seamless integration of human technology and biology and greater control over the aging process. 

04. October 2013 · Comments Off · Categories: Cryonics, Neuroscience

A major obstacle to strengthening the case for cryonics is the perception that meaningful research aimed at resuscitation of cryonics patients cannot be done today. Attempts to be more specific than evoking the need for a technology that can manipulate matter at the molecular level are considered to be vague and unproductive. Clearly, such a stance is an open invitation for skeptics to claim that cryonics advocates have not much more to offer than hope and optimism. Nothing could be further from the truth. Not only is there a lot of relevant empirical research that can be conducted today, a focused investigation into the technical and logistical challenges of resuscitation can also define cryonics research priorities and refine the stabilization and cryopreservation procedures that we use today.

The first thing that needs to be recognized is that if we want to say something specific about the nature and limits of repair we need to be able to characterize the damage in detail. There has been a lot of general discussion of damage but there have been few writers that have systematically characterized the forms of damage that can occur prior to and/or during cryopreservation and then linked those forms of damage to contemporary or envisioned repair strategies. A notable exception is the 1991 article “‘Realistic’ Scenario for Nanotechnological Repair of the Frozen Human Brain” where the individual forms of mechanical and biochemical damage (ice formation, protein denaturation, osmotic damage etc.) are catalogued and repair strategies are discussed in biological terms.

Describing the various forms of damage at such a detailed level provides a meaningful context within which to discuss the technical feasibility of cryonics in rather specific terms, too. If someone would claim that cryonics is hopeless because of the “toxicity” of the vitrification agents we can ask for more specifics about what kind of biochemical damage is being alleged and why such alterations irreversibly erase identity-critical information.

Even when it is admitted that theoretical and empirical investigations into damage associated with (crude) cryonics technologies is possible it surely would be preposterous, wouldn’t it, to claim that repair of the damage itself can be done today. Well, not quite. Granted, we do not have the biological or mechanical cell repair technologies that would be required for repair of the brain at the molecular level but we can simulate a specific kind of damage (ice formation, ischemia) and create three dimensional neural wiring maps that can be compared to controls. Often this is not even necessary because we understand the universal language of biology and, for example, if we observe a ruptured cell membrane wall we know how it is supposed to look.

From here it is a short step to what I would call “reconstructive connectomics,” a sub-discipline of the field of connectomics that studies pathological changes of neural connections in the brain with the aim of in silico repair. Computational limitations currently constrain the scale and complexity at which we can do these reconstructions but it is not necessary to do reconstructive connectomics in a human-sized brain to obtain a much greater understanding of the mechanisms of damage, the type of repair required, and the empirical content of concepts like information-theoretic death.

It is important to point out here that the idea that resuscitation research can start today does not require taking sides in debates about the relative merits and limitations of biological versus mechanical cell repair technologies. The primary objective here is to show that meaningful resuscitation research can be done today and that the absence of such research only provides our critics easy targets.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, May, 2013

14. January 2013 · Comments Off · Categories: Cryonics, Neuroscience, Science

Some observers believe that cryonics advocates are reluctant to subject their theories to experimental scrutiny because this could damage their (uncritical) belief in future resuscitation. Similarly, one might think that cryonicists would react with a mix of hostility and dismissal to alternative strategies for personal survival. Nothing could be further from the truth. In fact, it is exactly because our personal survival is at stake that forces us to be wary of dogmatism.

For this reason, I have always been interested in chemical fixation as a (low cost) alternative for cryonics. In fact, years before all the talk about the “connectome” and “plastination” I spent considerable time exchanging messages with Michael Perry at Alcor about the technical and practical feasibility of chemical brain preservation. But no matter how open minded I tried to be about this approach, I kept running into the same challenges over and over again.

The challenge that has concerned me the most is whether a delayed start of chemical brain fixation will produce incomplete distribution of the chemical fixative in the brain because of ischemia-induced perfusion impairment. Thinking about the technical problem of “no-reflow” is not the first thing on the mind of someone who first hears about the idea of using chemical fixatives to preserve the brain. In my case, this concern was not just “theoretical.” In my lab I have spent many years looking at the effects of cerebral ischemia on cryopreservation and chemical fixation. Last year we decided to broaden our investigations to delayed chemical fixation and we have not been pleased at what we have observed so far. After 1.5 years of room temperature storage the delayed aldehyde fixed brains are falling apart and continue to decompose. In small animals one might imagine that such perfusion impairment could be overcome by immersing the brains in the fixative instead but human brains are simply too large. By the time that the fixative would have reached the core of the brain, extensive autolysis will have occurred.

Another complex problem is to identify a fixation and polymerization protocol that fixes all identity-critical parts of the brain. If aldehydes do not completely fix the lipids in the brain, should we add strong oxidizing heavy metals to stabilize lipids? This is possible in theory but, as a general rule, these chemicals are either very expensive or dangerous to use (or both). Even if we are able to identify a chemical fixation protocol for the brain that can do the job, how can we know that such brains are stable for very long periods of time? Should we follow fixation by embedding with a polymer to inhibit residual biochemical activity? To my knowledge, there is no known embedding protocol that is scalable to human brains due to the extreme viscosity of these plastics.

Recently these issues took a more personal nature for me when I had to think really hard about a reasonable but affordable longterm preservation protocol for a companion animal. I spent many days reading the electron microscopy and fixation literature to come up with a protocol that was better than aldehyde fixation and low temperature storage. Adding calcium to the fixative? What about phenol? Post-fixation perfusion of a viscous cryoprotectant to allow storage at subzero temperatures? That is when I really started appreciating the “magic” of cold temperatures.

Absent a vitrification agent, cryogenic temperatures can cause extensive damage to cells. But one thing we know: whatever the nature of this damage, as soon the brain is below the glass transition temperature of -130°C, all water is either frozen or a vitrified rigid solid. We do not have to worry about any damage getting worse over time, or whether some biomolecules have not been fixed. Cold may be “crude” in its effects but it is exactly because no biochemical process can escape inhibition at very low temperatures that makes it such a powerful personal survival technology.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, January, 2013

25. July 2012 · Comments Off · Categories: Cryonics, Health, Neuroscience

The recent symposium on cryonics and brain-threatening disorders was a major success. On Saturday, July 7, 2012, around 30 people attended the first ever symposium on dementia and cryonics in Portland, Oregon. The symposium started with a brief introduction by Institute for Evidence Based Cryonics President Aschwin de Wolf, who emphasized why people with cryonics arrangements have a clear interest in understanding and avoiding dementia. The first speaker, Chana de Wolf, introduced the audience to the topic of adult neurogenesis, the two areas in the brain where it occurs, and how little we still understand about it. Aubrey de Grey then talked about the SENS approach to rejuvenation and how some emerging damage repair bio-technologies might be able to also reverse neurodegenerative diseases such as Alzheimer’s disease. Cryonics Institute President Ben Best followed Aubrey’s presentation with a technical introduction about the pathophysiology of Alzheimer’s disease and the treatments that are currently being investigated. Ben is maintaining a page about the molecular mechanisms of Alzheimer’s disease on his personal website.

After the break Alcor staff member Mike Perry presented a detailed analysis of a recent paper in which cerebrospinal fluid samples could predict the onset of Alzheimer’s diseases many years before the first signs of cognitive impairment, a finding that holds great promise for life-extensionists, and those with an increased risk for Alzheimer’s disease in particular. Institute for Evidence Based Cryonics Board member Keegan Macintosh then presented a rigorous legal analysis of the Thomas Donaldson case and indicated how the case could have been argued more persuasively then and now. The last speaker of the day was Alcor President Max More who introduced the concept of the extended mind and its relevance to cryonics and neurodegenerative diseases, which prompted a useful exchange about the desirability of cryonics organizations facilitating members to store identity-critical information. The official meeting ended with a panel discussion moderated by Aschwin de Wolf in which all the speakers took questions from the audience and other speakers.

The program and panel left ample time for interaction between speakers and the audience. The topic of avoiding dementia and what to do when a cryonicist is diagnosed with a brain threatening disorder received a lot of attention. Despite the rather disturbing subject of the symposium there seemed to be a general recognition that it was extremely valuable to explore this topic in the context of cryonics. Some suggestions of how to deal with dementia were made that had not been previously discussed in cryonics publications.

It is not likely that we will organize a symposium about this topic every year but there was a strong interest in organizing meetings about other topics on a regular basis in the Pacific Northwest.

The slides of all but one of the presenters are available on the symposium page and a video recording of Aubrey de Grey’s talk was made by one person in the audience. A more detailed report of the symposium will appear in an upcoming issue of Alcor’s Cryonics magazine.

20. June 2012 · Comments Off · Categories: Cryonics, Death, Neuroscience

It is generally not the task of scientists to consider the legal, financial, and logistical limitations when searching for biomedical breakthroughs but there are good examples where considering the real-world applications of a technology can be instructive. Research aimed at preservation of brains (or the “connectome”) is such an example. Even if chemopreservation can be demonstrated to preserve the intricate wiring of the brain, it can be safely assumed that there will not be a massive change in demand for brain preservation technologies (especially if the technology is too strongly tied to mind uploading). As a consequence, providers of chemopreservation will most likely operate in the same environment as providers of cryonics. That means that, as a general rule, there will be a delay between pronouncement of legal death and the start of procedures.

There is now more than 40 years of mainstream biomedical research demonstrating that even short interruptions of circulation (under normothermic conditions) can produce perfusion impairment in the brain. As has been demonstrated by cryonics researcher Mike Darwin and my own lab, Advanced Neural Biosciences, this “no-reflow” can produce poor distribution of cryoprotectants (including vitrification agents) and associated freezing. One serious concern that cryonics researchers have about chemopreservation-in-the-real-world is that poorly chemically fixed brains will be prone to autolysis during long-term storage. This limitation of chemopreservation applies to both “conventional” biological resuscitation scenarios as to whole brain emulation. One can only recover (or “upload”) what is preserved – or can be inferred. And as far as we understand things today, the advantage of temperature as a long-term preservation method is that it does not depend on a healthy, non-ischemic circulatory system. Cryopreservation of an ischemic brain can produce ice formation, but as soon as it is placed in liquid nitrogen, cold will “fix” whatever there is without further degradation. The same thing cannot be said about chemopreservation under poor conditions.

There is an understandable tendency to compare brain preservation protocols under ideal conditions and favor the method that produces the best preservation. But support for either technology cannot be solely based on results produces under controlled lab conditions. Personal survival technologies should be evaluated under conditions that are most likely to be encountered by organizations that will offer them. Demonstrating that chemical fixation (and plastination) can preserve the connectome is a laudable goal but the case for chemopreservation as a clinical experimental preservation method requires a persuasive response to the objection that delays in fixation can frustrate the aims of chemopreservation in the most fundamental manner.

One interesting aspect of the cryonics vs chemopreservation debate, though, is that it appears that some people simply feel more comfortable with one of the approaches. People who have shown the slightest interest in human cryopreservation can get really excited about the idea of chemical brain preservation. This indicates that if both approaches would be pursued actively, the growth of chemopreservation would not necessarily be at the expense of cryonics but there would be a growth in the total number of people making bio-preservation arrangements aimed at personal survival. But as Mike Darwin has recently pointed out, chemopreservation is not at the stage where it can be responsibly offered. The growth of this field requires a committed group of individuals who will research, develop, and implement this program. Chemopreservation does not need to be perfected before being offered (neither was cryonics) but so far most advocacy has been mostly at the conceptual level.