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).

16. October 2014 · Comments Off · Categories: Cryonics

Cryonics Magazine, August, 2013

Why Reversible Cryopreservation Matters

[The following is a text adaptation of a PowerPoint presentation given on Sunday, May 12, 2013 at the Resuscitation and Reintegration of Cryonics Patients Symposium in Portland, Oregon.]

Let’s start with the following definition of cryonics:

“Cryonics is the stabilization of critically ill patients at ultra-low temperatures to allow resuscitation in the future.”

As you can see, nothing in this definition says that repair is an intrinsic feature of cryonics. But is this a reasonable perspective? Let’s think about a number of aspects of cryonics that could be classified as “repair.”

• Critically ill patients are sick and will need medical treatment in the future.
• Most cryonics patients will require
rejuvenation.
• The cryopreservation process itself causes (irreversible) damage.

Yes, cryonics patients will require a second look at their condition by a future doctor who will have more advanced medical technologies at his/her disposal. This could conceivably be called “repair.” Most cryonics patients will also require rejuvenation biotechnologies. After all, it makes little sense to cure the patient’s disease but leave him/her in a fragile, debilitated state. This could be called “repair” too, in particular if you believe that aging is the progressive accumulation of damage. The repair that I want to discuss here is repair of the damage that is associated with the cryopreservation process itself. If we can eliminate this kind of damage, and the associated requirement of repair in the future, we will make the idea of cryonics a whole lot more attractive. What would be the advantages of being able to offer such “cryonics without repair?”

Perhaps the most obvious advantage is that cryonics could not be dismissed solely by pointing to the (irreversible) damage caused by the cryopreservation process itself. In essence, such a form of cryonics would be akin to putting a critically ill patient in a state of true suspended animation. This would strengthen the legal position of cryonics patients because a decision to abandon a patient in such a condition would be more akin to murder (or at least serious neglect). Another advantage would be that the absence of cryopreservation damage would increase the likelihood of the patient being restored to good health in the future. Less damage is also likely to translate into lower costs, too, and it is rather obvious that such an advantage can mean more security for the patient. Reversible cryopreservation may also lead to earlier treatment and resuscitation attempts, which may reduce challenges associated with re-integration. Cryonics without repair also matters in the here-and-now. Without the goal of reversible cryopreservation there are no objective, empirical criteria to evaluate the quality of care in a cryonics case. Last, but not least, we should do no harm. Allowing unnecessary injury of the patient because future advanced technologies should be able to fix it is a morally suspect gamble with a person’s life.

That is an impressive list of arguments in favor of offering reversible human cryopreservation. Now let’s try to be more specific about what cryonics without repair means. Clearly, the condition of the patient should not worsen relative to the critical condition the patient was in at the time of pronouncement of legal death. In fact, a rarely recognized possibility in a good cryonics case is that it might even be feasible to slightly improve the condition of the patient through the administration of cerebroprotective medications and washing out the blood, provided these procedures do not restore spontaneous circulation and consciousness, of course. A common perspective at Alcor to look at the objective of stabilization procedures is to say that these procedures should be aimed at maintaining viability of the patient by contemporary criteria. In the past I have characterized this objective as securing viability of the brain, but I think it would be better to aim for complete viability of the body unless there is a clear trade-off between viability of the brain (the most important organ in cryonics) and the rest of the body. Ultimately, though, we do not just want to be able to reverse the stabilization procedures but all cryonics procedures.

Before we walk through basic cryonics procedures to identify obvious and notso- obvious opportunities for cryonics procedures to produce additional damage, let’s look at circumstances in which the patient suffers additional damage that cannot be attributed to the cryonics organization. The most obvious situation is where there is a long delay between pronouncement of legal death and the start of cryonics procedures because hours go by before the patient is discovered or hospital administrators do not allow immediate access. It is important to recognize that the goal of maintaining viability can be defeated before we even start our procedures. Critics of cryonics often talk about compromising circumstances as if they are intrinsic aspects of cryonics instead of the result of tragic but avoidable events or hostile authorities. Reversible cryopreservation is only possible if the cryonics organization is notified in time and receives good cooperation from hospital administrators and other authorities.

The first real opportunity for a cryonics organization to “screw up” is to allow substantial periods of warm and cold ischemia. This can happen in a number of ways including, but not limited to, not restoring adequate circulation, inadequate ventilation, allowing blood pressure and cerebral perfusion to drop (restoring blood pressure does not guarantee good cerebral blood flow), suboptimal induction of hypothermia, or conducting surgery at high temperatures without metabolic support. In ideal circumstances a cryonics stabilization is conducted so that suboptimal results in one of these areas are offset by gains in the other protocols.

If a cryonics organization is able to provide metabolic support and rapidly cool down the patient to close to the freezing point of water the next challenges involve the cryopreservation process. The best known form of damage here is, of course, ice damage. While today’s vitrification agents are formulated to inhibit ice formation at realistic cooling rates, there are still a number of things that can go wrong. The distribution of cryoprotectant in the brain can be incomplete as a result of surgical errors or flaws during cryoprotective perfusion (e.g., vessels not properly cannulated, extremely low or high pressures, pumping air, etc.) The cryoprotectant can also be introduced at temperatures that are too warm or introduced too rapidly to allow the cells to maintain volume in an acceptable range. Even if none of these mistakes are made, we run into other challenges that cryonics organizations cannot successfully overcome yet.

Successful vitrification requires the use of high concentrations of organic solutes (such as DMSO and formamide) and non-penetrating polymers. While much progress has been made by cryobiology researchers Gregory Fahy and Brian Wowk to formulate solutions with low toxicity, and such solutions have been shown to successfully cryopreserve brain slices, our current understanding is that it is not likely that the brain of a cryonics patient remains spontaneously viable after being equilibrated with these agents. This is partly because the “blood brain barrier” leads to a situation in which solutes naturally present in the brain become concentrated during cryoprotective perfusion (dehydration) as discussed in the next paragraph. This causes cells inside whole brains to be cryoprotected by a mixture of natural solutes and some components of the perfused cryoprotectant solution rather than just the carefully-formulated cryoprotectant solution. Sometimes natural is not good.

It is sometimes said that eliminating cryoprotectant toxicity is the “holy grail” of cryonics research. While there is good empirical evidence to suggest that despite this toxicity good ultrastructure of the brain is still possible, true reversible human cryopreservation without reliance on sophisticated repair will require cryoprotectants with much lower toxicity. The need for less toxic cryoprotectants is especially tied into the problem of achieving concurrent and adequate distribution of cryoprotectant to all parts of the body that are vulnerable to freezing injury, which requires many hours of perfusion. In addition to cryoprotectant toxicity there are a number of other poorly-understood phenomena that could frustrate the ideal of cryonics without repair such as “chilling injury” and “thermal shock.”

An interesting form of injury that is not well known by the general public but that triggers a lot of discussion among cryonics researchers is dehydration of the brain. Without exception, a wellconducted cryopreservation of the brain with present technology produces severe shrinking. In fact, this shrinkage, and the corresponding increase in concentration of salts and proteins naturally present in the brain, appears to be a key mechanism by which whole brains vitrify despite limited permeability to perfused cryoprotectants. Evidence of substantial dehydration (obtainable by direct inspection of the brain inside the skull or via CT scans) is often considered an indicator of good care in cryonics. Of course, this leaves the question unanswered whether such a degree of dehydration is compatible with viability of the brain. Yuri Pichugin, the researcher who developed the Cryonics Institute’s current vitrification agent, VM-1, considered such extreme cerebral dehydration an obstacle to restoring viability after vitrification and identified a number of blood brain barrier modifiers that allowed him to recover brain slices after whole brain cryoprotective perfusion with improved viability. Whether such agents are of benefit or actually harmful is still an open research question.

Even if we could cryopreserve a human being without ice formation, toxicity, chilling injury, or other forms of injury associated with cryoprotection, there is still one remaining obstacle for reversible  cryopreservation: fracturing caused by thermal stress. While fracturing has been recognized as a problem and observed as an empirical phenomenon in patients as far back as the early 1980s, this form of injury has pushed itself to center stage (together with cryoprotectant toxicity and cerebral dehydration) since cryonics organizations started using vitrification agents aimed at eliminating ice formation altogether. If ice formation is eliminated, fracturing is the only mechanical form of damage left. While the significance of fracturing damage is sometimes downplayed by molecular nanotechnology experts, and fracturing at cryogenic temperatures doesn’t result in actual fragmentation, letting a human brain form fractures is not what most people would consider appropriate treatment of a critically ill patient.

What is striking, however, is how little we actually know about fracturing in cryonics patients. Fracturing has been observed in patients that were cryopreserved with (relatively) low concentrations of cryoprotectants. Such protocols produced ice formation and we should therefore not be surprised about observing cracking in those patients. Even in patients who have been cryopreserved using modern vitrification agents acoustic fracturing events (which may or may not correspond with actual fractures) have been detected above the glass transition temperature (Tg) of the pure vitrification solution. But even these observations have little relevance to the question of what we should expect in a good case. Many cryonics patients are perfused under sub-optimal conditions due to delays after clinical death. It is therefore likely that many of these fracturing events, if real, can be attributed to ischemia-induced perfusion impairment and ice formation. And that cooling frozen tissues to very low temperatures can cause fracturing is something we already know.

There are some encouraging preliminary research results suggesting that under ideal circumstances (i.e., good equilibration, controlled cooling) fracturing is not as serious a problem as it has been made out to be. The current practice of long term care at liquid nitrogen temperature may not be salvaged by such observations, but the intermediate temperature storage (ITS) systems that have been developed might be sufficient to eliminate this problem under good conditions at temperatures not too far below Tg. A related intriguing question is what the effect of severe cerebral dehydration is on the occurrence and frequency of fractures in the brain.

Let’s say that one agrees with the objective of “cryonics without repair” (or very limited repair), and the identification of the biggest scientific and technical obstacles to achieve this. What should our research and clinical objectives be? For starters, cryonics organizations should continue to cultivate an interest in personal alarm systems and securing good legal and logistical cooperation with providers of medical care. One technical development that deserves to be introduced is “field vitrification.” Strictly speaking, the phrase is a misnomer because we are not really talking about the patient being vitrified in a remote location; it is the cryoprotective perfusion part of the procedure that is done prior to transport to Alcor (in remote cases). Evidence from at least three labs indicates that perfusing the patient in the field with a vitrification solution and shipping on dry ice is safe, practical, and superior to blood substitution in most scenarios. While remote blood substitution (“washout”) is clearly demonstrated to be better than shipping the patient without removing the blood, it is not likely that hypothermic organ preservation solutions capable of keeping the brain viable for longer than 24 hours, and capable of inhibiting whole body edema, will be developed any time soon. Field vitrification is simply the next logical development in high-quality evidence-based cryonics. Other important improvements include better cooling efficiency (e.g., using cyclic cold lung lavage), improved cardiopulmonary support protocols, a renewed emphasis on monitoring during casework, and the introduction of intermediate temperature storage.

The most formidable challenge will be to develop what I call “brain-friendly” cryoprotectants. What needs to be accomplished? These agents should have no, or tolerable, toxicity, eliminate chilling injury and other poorly-understood forms of cryopreservation injury, allow safe and fracture-free storage at intermediate temperatures, and allow cryoprotective perfusion with greater penetration of agents into brain tissue with less dehydration so that results in whole brains can more closely match the high viabilities now obtainable in brain slices.

At my own company, Advanced Neural Biosciences, we have successfully developed a rat EEG model to screen for such brain-friendly cryoprotectants. As I write up this presentation, we have been successful in recovering integrated whole brain electrical activity after hypothermic circulatory arrest at 0° Celsius. Our next objectives are to recover EEG activity in the brain after cooling to subzero temperatures and to understand the relationship between cryoprotectants, the blood brain barrier, dehydration, and viability. It is too early to report any significant findings yet, but one thing that has become quite clear to us is that adequate ventilation during cool down is essential to recovery of whole brain activity. This is rather important because cryonics organizations have not been that concerned about meeting the brain’s demand for oxygen during stabilization, and during blood washout and blood substitution in particular. No doubt, if we continue this research we will learn other things that have direct relevance to the practice of cryonics.

The whole brain cryopreservation research project has been made possible by the generous support of the Life Extension Foundation. The author also wishes to thank the Immortalist Society, Cryonics Institute, Alcor, LongeCity, 21st Century Medicine, Alan Mole, York Porter, Jordan Sparks, David Ettinger, Ben Best, Mark Plus, Peter Gouras, James Clement, Luke Parrish, and John Bull for additional support.

15. October 2014 · Comments Off · Categories: Cryonics, Science

Cryonics Magazine, July 2013

[The following is a text adaptation of a PowerPoint presentation given on Sunday, May 12, 2013 at the Resuscitation and Reintegration of Cryonics Patients Symposium in Portland, Oregon]

An understanding of probable future repair requirements for cryonics patients could affect current cryostorage temperature practices. I believe that molecular nanotechnology at cryogenic temperatures will probably be required for repair and revival of all cryonics patients in cryo-storage now and in the foreseeable future. Current nanotechnology is far from being adequate for that task. I believe that warming cryonics patients to temperatures where diffusion-based devices could operate would result in dissolution of structure by hydrolysis and similar molecular motion before repair could be achieved. I believe that the technologie for scanning the brain/mind of a cryonics patient, and reconstructing a patient from the scan are much more remote in the future than cryogenic nanotechnology.

Cryonicists face a credibility problem. It is important to show that resuscitation technology is possible (or not impossible) if cryonicists are to convince ourselves or convince others that current cryonics practice is not a waste of money and effort. For some people it is adequate to know that the anatomical basis of the mind is being preserved well enough ― even if in a very fragmented form ― that some unspecified future technology could repair and restore memory and personal identity. Other people want more detailed elaboration.

Books have detailed what nanotechnology robots (nanorobots) will look-like and be capable-of, including (notably) Nanosystems by K. Eric Drexler (1992) and Nanomedicine by Robert A. Freitas, Jr. (Volume I, 1999; Volume IIA, 2003). The online Alcor library contains articles detailing repair of cryonics patients by nanorobots at cryogenic temperature, in particular, “A Cryopreservation Revival Scenario using Molecular Nanotechnology” by Ralph Merkle and Robert Freitas as well as “‘Realistic’ Scenario for Nanotechnological Repair of the Frozen Human Brain.” Despite the detailed descriptions, calculations, and quantitative analyses that have been given, any technology as remote from present capabilities as cryogenic nanotechnology is certain to be very different from whatever anyone may currently imagine. It is difficult to argue against claims that all such descriptions are nothing more than handwaving, blue-sky speculations.

Current medical applications of nanotechnology are mainly limited to the use of nanoparticles for drug delivery.1 Nanomachines are being built, but they are little more than toys ― including a rotor that can propel a molecule2 or microcantilever deflection of DNA by electrostatic force.3 In classical mechanics and kinetic theory of gases, on a molecular level, temperature is defined in terms of the average translational kinetic energy of molecules, which means that the lower the temperature the slower the motion of the molecules. According to the Arrhenius Equation, the rate of a chemical reaction declines exponentially with temperature decline. It would be wrong to conclude that nanomachines would barely be able to move at cryogenic temperatures, however. Nanomachines operate by mechanical movement of constituent atoms, a process that is temperature-independent. In fact, nanomachines would probably operate more effectively at cryogenic temperature because there would be far less jostling of atoms in the molecular structures upon which nanomachines would operate. Nanomachines would also be less vulnerable to reactions with oxygen at cryogenic temperature, although it would nonetheless be preferable for cryogenic nanorepair to occur in an oxygen-free environment.

Although under ideal circumstances ice formation can be prevented in cryonics patients, circumstances too often result in at least some freezing―such as inability to perfuse with vitrification solution, or poor perfusion with vitrification solution because of ischemia due to delayed treatment. Past cryonics patients were perfused with the (anti-freeze) cryoprotectant glycerol, whereas cryonics patients are currently perfused with cryoprotectant solutions that include ethylene glycol and dimethylsulfoxide (DMSO). Unlike water, which forms crystalline ice when solidifying upon cooling, cryoprotectants form an amorphous (non-crystalline, vitreous) solid (a “hardened liquid”) when solidifying upon cooling. The “hardened liquid” is a glass rather than an ice. The temperature at which the solidification (vitrification) occurs is called the glass transition temperature (Tg).

For M22, the cryoprotectant used by Alcor to vitrify cryonics patients, Tg is typically between −123°C and −124°C (depending on the cooling rate). Tg is about the same for the cryoprotectant (VM-1) used for cryonics patients at the Cryonics Institute. Although freezing can be reduced or eliminated by perfusing cryonics patients with vitrification solution before cooling to Tg, eliminating cracking is a more difficult problem. Cryonics patients are cooled to cryogenic temperatures by external cooling. Thermal conductivity is slow in a cryonics patient, which means that the outside gets much colder than the inside. When the outside of a sample cools more quickly than the inside of the sample, thermal stress results. A vitrified patient subjected to such thermal stress can crack or fracture. No efforts have been made to find additives to M22 that would have a similar effect as boron oxide has on allowing Pyrex glass to reduce thermal stress.

If a vitrified sample is small enough, and if cooling is slow enough, the sample can be cooled far below Tg ― down to liquid nitrogen temperature ― without cracking. A rabbit kidney (10 milliliter volume) can be cooled down to liquid nitrogen temperature in two days without cracking/fracturing.6 Cryonics patients are much too large to be cooled to liquid nitrogen temperature over a period of days without cracking. The amount of time required for cooling vitrified cryonics patients to liquid nitrogen temperature without cracking is unknown, and would probably be much too long.

In 1990 cryobiologist Dr. Gregory Fahy published results of cracking experiments that he performed on samples of the cryoprotectant propylene glycol.4 Tg for propylene glycol is −108°C, but in RPS-2 carrier solution the Tg is −107°C. In one experiment he demonstrated that cracking began at lower temperatures for smaller samples, specifically: −143°C for 46 mL, −116°C for 482 mL, and −111°C for 1412 mL. (The last volume is comparable to the volume of an adult human brain.) Dr. Fahy also demonstrated that cracking could be delayed by cooling at slower cooling rates. But when cracking did occur, the cracks formed at the lower temperatures were finer and more numerous.

Based on evidence that large cracks formed at higher temperatures by more rapid cooling results in a relief of thermal stress that prevents the fine and more numerous cracks formed when cracking begins at lower temperature, the Cryonics Institute (CI) altered its cooling protocol for cryonics patients. CI patients are cooled quickly from −118°C to −145°C, and then cooled slowly to −196°C.5 In order to minimize or eliminate cracking in cryonics patients, proposals have been made to store the patients at temperatures lower than Tg (−124°C), but higher than liquid nitrogen temperature (−196°C).6 Such a cryo-storage protocol is described as Intermediate Temperature Storage (ITS). Alcor currently cares for a number of ITS patients at −140°C, but a consensus has not yet been reached about what ITS temperature will be chosen when this service is made available to all Alcor members.

Although Alcor’s vitrification solution M22 can prevent ice formation with some samples and protocols, M22 cannot prevent ice nuclei from forming at cryogenic temperatures. Ice nuclei are local clusters of water molecules that rotate into an orientation that favors later growth of ice crystals when a solution is warmed. Ice nuclei are not damaging, but the fact that ice nuclei can form indicates molecular mobility which could be damaging. Specifically, between the temperatures of −100°C and −135°C, ice nuclei can form in M22, with the maximum ice nucleation rate occurring near Tg. At −140°C the ice nucleation rate for M22 is undetectable. But nuclei will be probably formed in cooling to −140°C.

Although cryostorage at −140°C is an attempt to minimize cracking and minimize nucleation, this ITS neither eliminates cracking nor ice nuclei formation. Cryonics patients slowly cooled from Tg to −140°C will surely experience some ice nucleation. Alcor places a listening device (“crackphone”) under the skull of its cryonics patients for the purpose of monitoring cracking events. My understanding is that for most Alcor patients the crackphone detects cracking at Tg or only slightly below Tg, although there was reportedly one M22-perfused patient for which the first fracturing event occurred at −134°C. The propylene glycol experiments would support the view of cracking occurring slightly below Tg, but vitrified biological samples resist cracking better than pure cryoprotectant solutions.

With ice formation, cracking could occur at temperatures higher than Tg. Although ITS may prevent the formation of cracking that could occur in cooling below −140°C, it does not prevent the cracks that occur in cooling from Tg to −140°C. I have wondered whether there are forms of damage which would occur in a cryonics patient stored at −140°C that would not occur during storage at −196°C. A solid cryogenic state of matter does not prevent molecular motion. Molecular motion in a biological sample held at cryogenic temperature could result in damage to that sample.

Ions generated by radiation are much more mobile than molecules. An ionic species (probably protons) in trimethylammonium dihydrogen phosphate glass is nine orders of magnitude more mobile than the glass molecules—and sodium ions in sodium disilicate glass are twelve orders of magnitude more mobile than the glass molecules.9

Cryobiologist Peter Mazur has stated that below −130°C “…viscosity is so high (>1013 Poise) that diffusion is insignificant over less than geological time spans.” He adds that “…there is no confirmed case of cell death ascribed to storage at −196°C for some 2-15 years and none even when cells are exposed to levels of ionizing radiation some 100 times background for up to 5 yr.”10 Frozen 8-cell mouse embryos subjected to the equivalent of 2,000 years of background gamma rays during 5 to 8 months in liquid nitrogen showed no evident detrimental effect on survival or development.11

In attempting to evaluate damaging effects of temperature and radiation, it could be valuable to analyze chemical alterations, rather than complete cell death or viability. Acetylcholinesterase enzyme subjected to X-ray irradiation shows conformational changes at −118°C, but no conformational changes when irradiated at −173°C.12 X-ray irradiation of insulin and elastase crystals resulted in four times as much damage to disulfide bridges at −173°C compared to −223°C.13 Another study showed a 25% crystal diffraction lifetime extension for D-xylose isomerase crystals X-ray irradiated at less than −253°C compared to those irradiated at −173°C.14

One study showed that lettuce seeds show measurable deterioration when stored at liquid nitrogen temperature for periods of 10 to 20 years. Rotational molecular mobility was quantified. A graphical plot was generated showing increasing times for when 50% of lettuce seeds would fail to germinate as a function of decreasing temperature. Those times were estimated to be about 500 years for −135°C and about 3,400 years for −196°C.15 Translational vibrational motion has been given as an explanation for seed quality deterioration at cryogenic temperatures.16 The mean square vibrational amplitude of a water molecule is not even zero at 0 Kelvins (−273°C), and has been determined to be 0.0082 square Angstroms. The mean square vibrational amplitude is 0.0171 square Angstroms at −173°C and 0.0339 square Angstroms at −73°C.17

Realistically, however, 3,400 years is much longer than cryonics patients are likely to be stored. Storage in liquid helium at −269°C or in a shadowed moon crater at −235°C18 would certainly be more trouble than it is worth. Northern wood frogs spend months in a semi-frozen state at −3°C to −6°C, and are able to revive with full recovery of heartbeat upon re-warming.19 An empirical study of a cryoprotectant very similar to M22 (VS55)
showed viscosity continuing to increase exponentially below Tg, just as viscosity increases exponentially with temperature decrease above Tg.20 The exponential decrease in viscosity (molecular mobility) that makes ice nucleation cease at −135°C indicates that there is probably little molecular mobility at −140°C, despite the possibility of damage from ionic species or vibrational motion. All things considered, however, my personal preference is for storage in liquid nitrogen, rather than some intermediate temperature above −196°C. I would also prefer for cryogenic nanorobot repair to be at liquid nitrogen temperature.

I am by no means a nanotechnology expert, but I can give a brief description of my own views of how cryogenic nanotechnology repair of a cryonics patient would proceed. I must thank Ralph Merkle for his assistance in allowing me to consult with him to formulate and clarify many of my views. I believe that repair of cryonics patients at cryogenic temperature would be a combination of nano-mining and nanoarcheology. Nanorobots (nanometer-sized robots) would first clear blood vessels of water, cryoprotectant, plasma, blood cells, etc. The blood vessels would become mining shafts that would provide access to all body tissues. Nanometer-sized conveyor belts or trucks on rails could remove blood vessel contents. Where freezing or ischemia had destroyed blood vessels, artificial shafts would be created. Unlike the nano-mining that simply removes all blood vessel contents, the creation of artificial shafts would have the character of an archeological dig. Care would be taken in removing material to avoid damaging precious artifacts that might indicate original structure ― which could
be discovered at any unexpected moment.

Section 13.4 of K. Eric Drexler’s book Nanosystems provides diagrams and details of a nanorobot manipulator arm. Such a “diamondoid” component would contain about four million atoms, and could be fitted with a variety of tools at the end of the arm. A variety of tips with varying degrees of chemical reactivity could allow for reversible, temporary chemical bonds that could be used for grabbing and moving molecules. These could range from radicals or carbenes that would form strong covalent bonds, to boron that can form relatively weak and reversible bonds to nitrogen and oxygen, to simple O-H groups that can form even weaker hydrogen bonds. Tools for digging need not be so refined. The manipulator arm is depicted as being 100 nanometers long and 50 nanometers wide, although nanorobots would need to be larger to include capability for locomotion, computation, and power. A complete nanorobot could be as large as a few thousand nanometers in size. A capillary is between 5,000 to 10,000 nanometers in diameter, so there should be plenty of room for many such nanorobots to operate. Ralph Merkle estimates that 3,200 trillion nanorobots weighing a total of 53 grams could repair a cryonics patient in about 3 years.21,22 Like many of the calculations associated with nanotechnology, I take these figures with a pound of salt. It is certainly true, however, that it could take years to repair a patient, and that there should not be a rush to finish the job.

Merkle & Freitas have suggested that nanorobots be powered by electrostatic motors. Stators and rotors would be electric rather than magnetic. Tiny moving charged plates are easier to fabricate than tiny coils and tiny iron cores, but more fundamentally, magnetic properties do not scale well with reduced size (i.e., molecular-scale magnetic motors don’t work), whereas electrostatic properties do scale well with reduced size. Electrostatic actuators are already being used in microelectromechanical systems (MEMS).23 High density batteries could provide power for days, and recharging stations could be located throughout the patient. Alternatively, nanotube cables could bring power to the patient from the outside. Such cables could also be a means of transmitting and receiving computational data. Nanotube cables could also be used to reunite fracture faces
created by cracking. Scanning and image processing capabilities would need to evaluate what needs to be fixed.

As much as possible I would favor replacement rather than repair, which would greatly simplify the process. It would be much easier to replace a kidney than to repair the diseased kidney of an elderly patient who died of kidney disease. Curing disease and rejuvenation would thus become part of the repair of a cryonics patient. Of course, neuro patients would require an entirely new body. The brain would be the major exception to replacement strategy because the brain could not be replaced without loss of memory and personal identity.

Even within the brain, however, it could be feasible to replace many components without loss of memory and personal identity. It could be feasible to replace many organelles such as mitochondria, lysosomes, etc., and many macromolecules such as proteins, carbohydrates, and lipids. DNA could be repaired, and possibly even modified to cure genetic disease, but epigenetic expression in neurons may be critical for reconstruction of synaptic structure. Synaptic connections would not only be restored, but the quantity and quality of neurotransmitter contents should be restored. It is not simply a matter that some neurotransmitters are inhibitory and others are stimulatory. There are more than 40 different neurotransmitters used in the brain, and there must be a good reason why such variety is necessitated.

Part of the repair process could involve removal of ice nuclei, nearly all of which would be extracellular. Re-created blood vessel contents would include fresh cryoprotectant, water, plasma, and blood cells without the original ice nuclei. Although some repair scenarios favor different types of repair above cryogenic temperature, I doubt that this is necessary or desirable. Alternative repair scenarios involve splitting the brain in half, and halving the halves repeatedly at cryogenic temperature—with digitization at each step—until the brain has been totally digitized.21,22 Or digitization could be done by repetitive nano-microtomes at cryogenic temperature. The digital data could be used for full reconstruction. Some people might object that if one individual could be created from digital data, many such individuals could be created—raising questions of which are duplicates and
which is the original. There is detailed discussion of the duplicates problem/ paradox in the philosophy section of my website BENBEST.COM.

Although other repair scenarios could prove to be feasible, I believe that cryogenic nanotechnology will be required for all cryonics patients in the foreseeable future until the problem of cryoprotectant toxicity can be solved. With effective nontoxic cryoprotectants, sufficient cryoprotectant could be used to prevent ice nuclei formation at all temperatures, prevent devitrification (freezing) upon rewarming, and eliminate all toxic damage. In such a case, there could be true reversible cryopreservation (suspended animation).

What is needed to create the nanotechnology required for repair of cryonics patients? Small machines will need to build parts for smaller machines, which would in turn build even smaller machines. Many details of machine
operation must be perfected at each stage. Current modern technological civilization began with cave people pounding on rocks. Ralph Merkle has said that compared to future technology, current technology is pounding on rocks.

References

1. Chi AH, Clayton K, Burrow TJ, Lewis R, Luciano D, Alexis F, D’hers S, Elman NM. Intelligent drug-delivery devices based on micro- and nano-technologies. Ther Deliv. 2013 Jan;4(1):77-94.

2. Kudernac T, Ruangsupapichat N, Parschau M, Maciá B, Katsonis N, Harutyunyan SR, Ernst KH, Feringa BL. Electrically driven directional motion of a four-wheeled molecule on a metal surface. Nature. 2011 Nov 9;479(7372):208-11.

3. Zhang J, Lang HP, Yoshikawa G, Gerber C. Optimization of DNA hybridization efficiency by pH-driven nanomechanical bending. Langmuir. 2012 Apr 17;28(15):6494-501.

4. Fahy GM, Saur J, Williams RJ. Physical problems with the vitrification of large biological systems. Cryobiology. 1990 Oct;27(5):492-510.

5. Best B. The Cryonics Institute’s 95th Patient. Long Life. 2009 Sept-Oct; 41(9- 10):17-21.

6. Wowk B. Systems for Intermediate Temperature Storage for Fracture Reduction and Avoidance. 2011 Third Quarter;32(3):7-12.

7. Okamoto M, Nakagata N, Toyoda Y. Cryopreservation and transport of mouse spermatozoa at -79 degrees C. Exp Anim. 2001 Jan;50(1):83-6.

8. Angell CA. Entropy and Fragility in Supercooling Liquids. Journal of Research of the National Institute of Standards and Technology. 1997 March-April; 102(2):171-185.

9. Mizunoa F, Belieresa J.-P, Kuwatab N, Pradelb A, Ribesb M, Angell CA. Highly decoupled ionic and protonic solid electrolyte systems, in relation to other relaxing systems and their energy landscapes. 2006 Nov;352(42/49):5147- 5155.

10. Mazur P. Freezing of living cells: mechanisms and implications. Am J Physiol. 1984 Sep;247(3 Pt 1):C125-42.

11. Glenister PH, Whittingham DG, Lyon MF. Further studies on the effect of radiation during the storage of frozen 8-cell mouse embryos at -196 degrees C. J Reprod Fertil. 1984 Jan;70(1):229-34.

12. Weik M, Ravelli RB, Silman I, Sussman JL, Gros P, Kroon J. Specific protein dynamics near the solvent glass transition assayed by radiation-induced structural changes. Protein Sci. 2001 Oct;10(10):1953-61.

13. Meents A, Gutmann S, Wagner A, Schulze-Briese C. Origin and temperature dependence of radiation damage in biological samples at cryogenic temperatures. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1094-9.

14. Chinte U, Shah B, Chen YS, Pinkerton AA, Schall CA, Hanson BL. Cryogenic (<20 K) helium cooling mitigates radiation damage to protein crystals. Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):486-92.

15. Walters C, Wheeler L, Stanwood PC. Longevity of cryogenically stored seeds. Cryobiology. 2004 Jun;48(3):229-44.

16. Wowk B. Thermodynamic aspects of vitrification. Cryobiology. 2010 Feb;60(1):11-22.

17. Leadbetter AJ; The Thermodynamic and Vibrational Properties of H$_2$O Ice and D$_2$O Ice. 1965 Sep;A287:403-425.

18. Paige DA, Siegler MA, Zhang JA, Hayne PO, Foote EJ, Bennett KA, Vasavada AR, Greenhagen BT, Schofield JT, McCleese DJ, Foote MC, DeJong E, Bills BG, Hartford W, Murray BC, Allen CC, Snook K, Soderblom LA, Calcutt S, Taylor FW, Bowles NE, Bandfield JL, Elphic R, Ghent R, Glotch TD, Wyatt MB, Lucey PG. Diviner Lunar Radiometer observations of cold traps in the Moon’s south polar region. Science. 2010 Oct 22;330(6003):479-82.

19. Costanzo JP, Lee RE Jr, DeVries AL, Wang T, Layne JR Jr. Survival mechanisms of vertebrate ectotherms at subfreezing temperatures: applications in cryomedicine. FASEB J. 1995 Mar;9(5):351-8.

20. Noday DA, Steif PS, Rabin Y. Viscosity of cryoprotective agents near glass transition: a new device, technique, and data on DMSO, DP6, and VS55. Exp Mech. 2009 Oct;49(5):663-672.

21. Merkle, RC. The Molecular Repair of the Brain. Cryonics. 1994 Jan;15(1):16-31.

22. Merkle, RC. The Molecular Repair of the Brain. Cryonics. 1994 Apr;15(2):18-30.

23. Fennimore AM, Yuzvinsky TD, Han WQ, Fuhrer MS, Cumings J, Zettl A. Rotational actuators based on carbon nanotubes. Nature. 2003 Jul
24;424(6947):408-10.

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

08. September 2014 · Comments Off · Categories: Health, Society

When advocates of radical life extension discuss the social benefits of humans having much longer lifespans, it is often just a footnote to a personal desire to prolong life. As a consequence, cynicism from critics is often encountered. It hard to counter such skepticism effectively because people may believe you are just trying to make an essentially selfish desire look socially desirable.

There is an alternative. We can approach the topic from the other direction if we ask what kind of lifespans would be desirable if we want to increase social welfare and reduce human suffering. Let’s look at a number of issues.

There is a large literature about coping with the death of loved ones, relatives, and friends. While many people find support from such self-help books, most people would agree that no amount of anticipation or coping can eliminate the suffering and devastation that follows the death of a loved one. Is there an upside? I am not aware of any serious writer pontificating about the positive aspects about a person dear to you dying or suffering from aging-related disabilities. A society in which humans have control over the aging process would be desirable because it would eliminate the dominant cause of death (age-associated diseases) and the suffering it brings to survivors.

It is not uncommon to hear people being accused of not caring about the effects of their actions on future generations. This complaint is particularly prominent in discussions about the environment and the use of natural resources. If humans were not born to die on a predictable schedule this whole dynamic would change because the distinction between current and future generations would cease to exist. If consideration of the long-term consequences of our actions requires a prominent place in human life, we should not want humans to replace each other but generations to coexist in time and space.

Age discrimination involves discrimination of individuals on the basis of their age. In most instances, however, this discrimination concerns biological age and its effects on appearance, physical health, and mental skills. Biological age is not hard to observe and can usually be inferred from chronological age. If we prefer that people are not treated differently because of their date of birth we should want to live in a society where rejuvenation biotechnologies sever the link between chronological age and biological age.

What about economic welfare? Ageless people would be able to remain productive and generous, medical costs associated with the debilitating health and mental effects of biological aging would be substantially reduced, and highly talented people would not cease to exist.

Reasoning backwards from what morality and welfare would “dictate” about human lifespans is not just a talking point in discussions about the bioethics of life extension. One can imagine the rise of a social movement that seeks to educate the general public about the social benefits of biological control over the aging process. Such a social movement would not be in the business of making excuses for eccentric individual desires but would recommend that the reduction of suffering, sustainable growth, and more virtuous conduct would require that humans do not have a fixed expiration date.

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

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

17. August 2014 · Comments Off · Categories: Health, Science

The idea that aging is a choice will strike many readers as preposterous and I will admit at the outset that such a position can ultimately not be maintained. But in a milder sense, it should be recognized that we can make decisions in life regarding diet and lifestyle that can mitigate or accelerate the aging process. This “wiggle room” may turn out to be of great importance for reaching a time when serious rejuvenation biotechnologies will become available.

According to biologist Michael R. Rose (see the interview in Cryonics magazine, September 2013) aging is not an immutable process of wear and tear that unfolds through iron logic without being sensitive to lifestyle and diet. Aging begins after the start of reproduction and the forces of natural selection decline with chronological age, eventually stopping at late age (which raises the possibility that aging stops).

Some things that we associate with aging are not inevitable physiological processes but choices or decisions to conform to expectations. For example, when people reach adulthood, and pursue a family and career, they often conform to a lifestyle that involves more time sitting at a desk or in cars, more time spent inside, less time socializing with friends, and are subject to increasing amounts of stress and sleep deprivation.

As the physiological consequences of such a lifestyle (obesity, higher blood pressure, declining free hormone levels) express themselves many people tell themselves such things are the inevitable effects of getting older. But alternative scenarios may be possible if we remain aware of our environment, lifestyle, and diet.

In the case of diet, the dominant opinion remains that a healthy diet can be identified regardless of age, sex, and population group. There is increasing evidence, however, that such a perspective leaves a lot to be desired and that too much reductionism in these matters is not a good thing. There are, however, a number of observations that can be made. Restriction of calories (or intermittent fasting or meal skipping) seems to trigger a beneficial stress response that improves health and perhaps even extends life. Similarly, adopting a diet that more closely mimics that of hunter gatherers in conjunction with giving up a sedentary lifestyle has been successful in improving the lives (and looks!) of many people, in particular in the case of obesity.

What makes it rather difficult to adopt such lifestyle changes is that we are almost continuously exposed to an environment that makes it rather difficult to effect such changes. Most of our food is highly processed, loaded with carbs and sugar, and served in portion sizes that always seem to increase. When we move from one location to another the emphasis is on minimizing energy expenditure and eliminating resistance. We work in dark and confined spaces during the day and are exposed to light until we go to sleep (or sometimes even during sleep!). When we come home we turn on the television or the computer to “socialize.” It should not surprise us that such an “unnatural” lifestyle translates into the classic signs of aging and functional deterioration.

There is a lot at stake here. As daunting as it may seem, the idea that aging is not a uniform “process” that swallows us up at a constant rate opens up the possibilities of positive change. Armed with the latest findings in evolutionary biology and medicine we can start pushing back, stabilize the situation as best as we can, and reach a time when more radical rejuvenation biotechnologies will become available. Start moving, start lifting, go camping, make new friends, eat organic and fermented foods, skip the occasional meal, and cut the sugar!

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, October, 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.