// Depressed Metabolism: The Science of Personal Survival

In “Heritage of Horror,” Lovecraft scholar S.T. Joshi writes that Lovecraft’s short story “Cool Air” “anticipates cryogenic research.” We can forgive Joshi the common mistake of writing “cryogenics” when he means “cryonics,” but how much cryonics is there really in Lovecraft’s “Cool Air?”

“Cool Air” (1926) tells the story of a struggling writer who has secured affordable housing in a converted brownstone on West 14th Street in New York City to devote himself to “dreary and unprofitable magazine work.” Around three weeks pass when an incident in the room above introduces the reader to the character of Dr. Muñoz, whose “complication of maladies” requires an environment of constant cold. When the main character experiences a sudden heart attack, his initial repugnace for the eccentric doctor changes to admiration when Dr. Muñoz is able to offer him relief with a suitable combination of drugs.

Dr. Muñoz, we learn, is the “the bitterest of sworn enemies to death, and had sunk his fortune and lost all his friends in a lifetime of bizarre experiment devoted to its bafflement and extirpation.” He believes that “will and consciousness are stronger than organic life itself, so that if a bodily frame be but originally healthy and carefully preserved, it may through a scientific enhancement of these qualities retain a kind of nervous animation despite the most serious impairments, defects, or even absences in the battery of specific organs.” As the story develops we learn about the doctor’s own (increasing) need for a cold environment to preserve his bodily frame.

Just as in cryonics, Dr. Muñoz employs cold to prevent decomposition. And decreased temperatures confer increased benefits in slowing down the rate of decomposition. In cryonics these benefits of low temperatures are exploited by reducing the temperature of the patient to a point of complete metabolic arrest. At the temperature of liquid nitrogen (-196 degrees Celcius) biological time stands still for all practical purposes.

But what is remarkable about Dr. Muñoz’s approach is that he reaps the metabolic advantages of induced hypothermia without these temperatures preventing his mind from functioning. Dr. Muñoz seems to be unusually “alive” at ultra-profound, or even, high subzero temperatures! Because the EEG of a human brain becomes flat below 20 degrees Celcius, some other process must be involved, perhaps the “incantations of the mediaevalists, since he believed these cryptic formulae to contain rare psychological stimuli which might conceivably have singular effects on the substance of a nervous system from which organic pulsations had fled.”

Unless Dr. Muñoz’s treatment induced profound changes in the body’s biochemistry that allowed it to operate at much lower temperatures, his philosophy of life seems less “materialistic” and coherent than that of Lovecraft’s other enemy of death, Herbert West. Lovecraft never anticipated the practice of cryonics in a systematic fashion, but if Dr. Muñoz and Herbert West could have put their brilliant minds together, the benefits of cold temperatures could have been reaped to induce metabolic arrest in anticipation of future resuscitation of the “dead.”

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The practice of balneotherapy, also known as water treatment or spa therapy, has experienced a resurgence in popularity in recent years, especially amongst those with skin diseases such as psoriasis and atopic dermatitis. Salts, minerals, and bacteria particular to certain geothermal springs in various locations throughout the world have long been touted as having beneficial effects on skin, including significant reductions in lesions associated with psoriasis.

Of particular interest is the Blue Lagoon on the peninsula of Reykjanes in Iceland. A heating plant was built on the penninsula in 1976 to take advantage of naturally occurring geothermal activity. The Blue Lagoon was formed when hot water was discharged into an adjacent lava field. The lagoon water has an average temperature of 37°C, a pH of around 7.5, and a salt content of 2.5%. One of the plant workers with psoriasis began bathing in this new lagoon and his condition was greatly improved; this led to an instant and quickly growing interest in the healing potential of the Lagoon amongst sufferers of many types of skin diseases.

The Lagoon’s unique chemical and bacterial composition is found nowhere else in the world. The chemical composition of the Lagoon is (in mg/kg of Lagoon fluid): SiO2 137, Na 9280, K 1560, Ca 1450, Mg 1.41, CO2 16.5, SO4 38.6, H2S 0.0, Cl 18500, and F 0.14. The Lagoon waters also contain coccoid and filamentous blue-green algae not found under similar conditions anywhere else.

Early studies of the Blue Lagoon’s effect on both diseased and healthy skin has proven that bathing in the lagoon, and particularly applying the Lagoon’s white silica mud to the body, results in a significant reduction — oftentimes complete elimination — of even the most severe symptoms of psoriasis. Recent research published by Grether-Beck, et al. shows that these beneficial effects are not limited to diseased skin, and in fact the lagoon waters and mud have an anti-aging effect on healthy, normal skin.

While these initial studies demonstrated a beneficial effect of the Blue Lagoon on the skin, it remains to be discovered exactly what properties of the fluid and mud confer this benefit. In their recent paper, Grether-Beck, et al. prepared silica mud and microalgae extracts from Blue Lagoon mud and water samples to study their effects on in vitro epidermal keratinocytes and dermal fibroblasts (i.e., skin cells) as well as in vivo effects after topical treatment in healthy volunteers.

Since skin conditions like psoriasis and atopic dermatitis are characterized by reduced skin barrier function, and keratinocyte differentiation is a key component in determining the quality of the skin barrier, it is interesting to note that silica mud extracts stimulated expression of keratinocyte differentiation markers, as did both algae types, albeit to a lesser extent.

Extracts from silica mud and Blue Lagoon coccoid and filamentous algae also significantly inhibited ultraviolet (UV) radiation-induced metalloproteinase-1 (MMP-1) expression, which was associated with a concomitant inhibition of UV-induced interleuken-1 (IL-1) and IL-6 expression. Additionally, Blue Lagoon coccoid and filamentous algae extracts significantly upregulated expression of Collagen 1A1 (COL1A1) and COL1A2 in dermal fibroblasts — two genes which are critically involved in collagen synthesis.

Upregulation of keratinocyte differentiation markers was associated with a significant reduction in transepidermal water loss of treated skin areas in vivo; COL1A1 and COL1A2 expression also increased in treated skin after 4 weeks of treatment.

While such research is exciting, further investigation of the effects of the combination of Lagoon chemicals and bioactive molecules is necessary for a complete understanding of the therapeutic potential of the Blue Lagoon. Additionally, some data about the longevity of its beneficial effects on skin is warranted as well.

Medical tourism to the Blue Lagoon is growing. In 1994 Blue Lagoon opened an outpatient psoriasis clinic (renovated in 2005) with two dermatologists and three nurses on staff. Treatment consists of twice-daily dips in the Lagoon, during which silica mud is applied to psoriatic lesions, and UVB treatment in a phototherapy cabinet. Blue Lagoon skin care products can be purchased in Iceland, Nordic capitals, and online.

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Because the current generation of vitrification agents permit cryopreservation of the brain without ice formation, the current objective of cryonics research is maintenance of viability of the brain during cryopreservation. The most popular viability assay that has been used in cryonics and cryonics-associated cryobiology research is the potassium/sodium ratio (K+/Na+ ratio). Because the ability of a cell to regulate its ionic composition reflects and affects many other biochemical processes, the K+/Na+ ratio is a good measurement of viability in general. For example, all the brain slice experiments to validate the Cryonics Institute’s vitrification agent VM-1, were assessed using the K+/Na+ ratio as a measure of viability.

In the case of the brain, demonstrating such “basic” viability after vitrification is a necessary, but perhaps not sufficient, condition for reversible vitrification of the brain without adverse (long term) effects. Recovery of function in the brain is a more subtle concept than in other organs. In 2007, 21st Century Medicine reported maintenance of long-term potentiation (LTP) in vitrified brain slices. Chana de Wolf proposed more specific experiments to demonstrate maintenance of memory after cryopreservation. And more specific molecular assays could assist in illuminating the effects of cryoprotective perfusion, cryoprotectant toxicity, and cryogenic cooling on the brain. Such viability and functional assays can be correlated and combined with structural assays to assist in developing cryoprotectant solutions, and perfusion and cooling protocols that will permit successful resuscitation of whole brains after vitrification.

Further reading: Securing Viability of the Brain in Cryonics

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Cryonics Reports was the publication of the Cryonics Society of New York (CSNY). In April 1968 a call to arms to conquer aging was published. This editorial stressed that the problems of aging will not be solved until we decide that we want to conquer aging and extend our lives.

Heart disease and cancer are not isolated phenomena, but merely manifestations of the general progressive degeneration of our bodies. We call this progression aging because it affects our entire organism and is time dependent. It is the ultimate disease.

Read the complete editorial.

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In his January 2008 Journal of Emergency Medical Services (JEMS) article, “Nothing but the Truth,” Criss Brainard provides examples of two cases where voice recording technology could aid in clearing the names of emergency personnel who had been accused of inappropriate conduct during patient transport. While cryonics standby team members may not need to worry about such allegations, it is obvious that voice recording can be useful in clarifying any questions regarding the specifics of a case. In fact, nearly every aspect of a cryonics case can be voice recorded including logistical operations, start of procedures, medication administration, physiological measurements, descriptions of complex procedures, and real-time reporting of equipment malfunctions and concerns.

Voice recording technology has existed for at least as long as cryonics has, and yet cryonics organizations have rarely made consistent use of it during standby, stabilization, transport and cryopreservation. Instead, cryonics has often relied solely on the services of a “scribe,” whose duty it is to take written notes of all procedures. Voice recording not only provides a more accurate and reliable method of documentation, but also can free up a person to assist with procedures when a clip-on microphone is used. This feature also enables use of voice recorders by multiple team members, including team members performing procedures that are often hard to observe by the scribe, such as surgery. The utility of voice recording can be further strengthened by training team members how to describe specific technical cryonics procedures and to recognize important events.

Brainard points out that the San Diego Fire Department has used voice recording as a standard practice for over two decades to provide objective information about thousands of cases. He writes:

As a best practice, every EMS system should want the truth, good or bad. We should ensure that we’re on the front end of an incident, equipped with all the facts, not just recollections of the facts. If we make a mistake, we must own it; and if we’re being falsely accused, we should want that to come out also.

In addition, voice recording makes case reporting more rigorous and less prone to speculation, which helps to improve quality of care for future patients. Lack of voice recording shrouds cryonics in an aura of secrecy that damages credibility and makes it difficult to factually defend actions of cryonics team members.

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After legal pronouncement of death, cryonics patients benefit from rapid stabilization to protect the brain from injury. The most fundamental intervention is induction of hypothermia. Unlike other interventions such as cardiopulmonary support (CPS) and administration of neuroprotective medications, induction of hypothermia is an intrinsic part of cryonics. Unfortunately, surface cooling with ice is not a very effective way to rapidly drop the core temperature of the patient. There are a number of alternative cooling methods such as peritoneal, colonic, and gastric lavage but these cooling methods can be logistically challenging and require specific (surgical) skills. As a consequence, application of these cooling methods in cryonics is rare. To date, rapid cooling in cryonics is achieved during blood washout, which requires surgical access to the circulatory system of the patient.

Because the neuroprotective effects of hypothermia on the brain are so profound it would be very desirable to be able to induce rapid cooling without the need for surgery and extracorporeal perfusion. In the mid-1990s, cryonics researcher Mike Darwin realized that one might be able to reap some of the benefits of cardiopulmonary bypass-induced cooling by using cold cyclic lung lavage with an inert liquid. Because all of the patient’s blood travels through the lungs, the lungs can be utilized as an endogenous heat exchanger to cool the patient. With his colleagues at 21st Century Medicine and Critical Care Research (CCR), a number of prototypes were built to deliver and remove chilled perfluorocarbons. Initial canine experiments using this technology were successful and in 2001 a paper was published that documented that cooling rates of 0.5 degrees C/min could be achieved. A number of different terms for this technology have been used including liquid ventilation, mixed-mode liquid ventilation (MMLV), and cold cyclic lung lavage, depending on which aspect of the technology needs emphasis, breathing or cooling.

A basic version of cold cyclic lung lavage with perfluorocarbons was used on Alcor patient A-1876 in 2002. This case constitutes the first documented case of cold cyclic lung lavage in cryonics. Although the case summary states that “the combination of external cooling in the ice bath and fluorocarbon cooling via the lungs had reduced her core temperature from around 36 degrees Celsius at the time of death to approximately 9 degrees in just two-and-a-half hours,” no specific details on the equipment or procedure are given. The report does indicate that rapid indication of hypothermia by delivering and removing cold perfluorocarbons from the lungs is technically feasible in cryonics patients. In 2007, the cryonics company Suspended Animation and CCR reported on the development and fabrication of advanced automated prototypes to induce liquid ventilation that can achieve cooling rates superior to the prior art. The recent prototypes are scaled for human lung volumes and could be used in a cryonics case if people are appropriately trained. Although the concept of liquid breathing is not new, the application of such technologies to induce rapid hypothermia to protect the brain is another example of how cryonics research can contribute to mainstream (emergency) medicine.

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Before the scientific conquest of death became a serious topic of conversation, philosophers, writers and poets had to resign themselves to the inevitable demise of the individual in this world. Jeremy Taylor (1613-1667), the “Shakespeare of Divines,” gave poetic expression to the brevity and fragility of life in his The Rule and Exercises of Holy Dying (1651), parts of which later were used by the experimental / folk project Current 93 in the lyrics of The Dream of a Shadow of Smoke:

A man is a bubble, (said the Greek proverb), which Lucian represents with advantages and its proper circumstances, to this purpose; saying, that all the world is a storm, and men rise up in their several generations, like bubbles descending a Jove pluvio, from God and the dew of heaven, from a tear and drop of rain, from nature and Providence; and some of these instantly sink into the deluge of their first parent, and are hidden in a sheet of water, having had no other business in the world, but to be born, that they might be able to die: others float up and down two or three turns, and suddenly disappear, and give their place to others: and they that live longest upon the face of the waters are in perpetual motion, restless and uneasy; and, being crushed with a great drop of a cloud, sink into flatness and a froth; the change not being great, it being hardly possible it should be more a nothing that it was before. So is every man: he is born in vanity and sin; he comes into the world like morning mushrooms, soon thrusting up their heads into the air, and conversing with their kindred of the same production, and as soon they turn into dust and forgetfulness - some of them without any other interest in the affairs of the world, but that they made their parents a little glad and very sorrowful: others ride longer in the storm; it may be until seven years of vanity be expired, and then peradventure the sun shines hot upon their heads, and they fall into the shades below, into the cover of death and darkness of the grave to hide them. But if the bubble stands the shock of a bigger drop, and outlives the chances of a child, of a careless nurse, of drowning in a pail of water, of being overlaid by a sleepy servant, or such little accidents, then the young man dances like a bubble, empty and gay, and shines like a dove’s neck, or the image of a rainbow, which hath no substance, and whose very imagery and colours are fantastical; and so he dances out the gaiety of his youth, and is all the while in a storm, and endures only because he is not knocked on the head by a drop of bigger rain, or crushed by the pressure of a load of indigested meat, or quenched by the disorder of an ill-placed humour: and to preserve a man alive in the midst of so many chances and hostilities is as great a miracle as to create him; to preserve him from rushing into nothing, and at first to draw him up from nothing were equally the issues of an almighty power. And therefore the wise men of the world have contended who shall best fit man’s condition with words signifying his vanity and short abode. Honour calls a man “a leaf,” the smallest, the weakest piece of a short-lived, unsteady plant. Pindar calls him “the dream of a shadow:” another “the dream of the shadow of smoke.” But St. James spake by a more excellent spirit, saying, ‘Our life is but a vapour,’viz, drawn from the earth by a celestial influence; made of smoke, or the lighter parts of water tossed with every wind, moved by the motion of a superior body, without virtue in itself, lifted up on high, or left below, according as it pleased the sun, its foster-father. But it is lighter yet. It is but appearing;a fantastic vapour, an apparition, nothing real; it is not so much as a mist, not the matter of a shower, nor substantial enough to make a cloud; but it is like Cassiopeia’s chair, or Pelop’s shoulder, or the circles of heaven, fainorena, for which you cannot have a word that can signify a vernier nothing. And yet the expression is one degree more made diminutive; a vapour, and fantastical, or a mere appearance, and this but for a little while neither,the very dream, the phantasm, disappears in a small time, “like the shadow that departed; or like a tale that is told, or as a dream when one waketh.” A man is so vain, so unfixed, so perishing a creature, that he cannot long last in the scene of fancy: a man goes off, and is forgotten, like the dream of a distracted person. The sum of all is this: that thou art a man, than whom there is not in the world any greater instance of heights and declinations, of lights and shadows, of misery and folly, of laughter and tears, of groans and death.

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One concern about chemical fixation as a low cost alternative to cryonics is that current fixatives may not be able to permanently fix all biomolecules that are important to preserve the identity of the person. A related concern is that postmortem delays may not permit adequate perfusion of the brain, resulting in pockets of decomposed tissue. On this issue, biostasis at cryogenic temperatures (cryonics) has a distinct advantage because extreme cold will also preserve tissues that were not, or were poorly, penetrated by the cryoprotectant agent.

But even if cryoprotectant toxicity will be overcome to enable reversible vitrification of humans, the procedures of cryoprotectant perfusion, cryogenic cooldown, long term care, rewarming, and resuscitation may often involve (unintended) imperfections that will require advanced cell repair technologies for successful resuscitation.

Perhaps those same advanced technologies could produce a form of biostasis that avoids the crude consequences of contemporary chemical fixation by making precise modifications within and between cells to arrest metabolism and decomposition.

Looking for discussion of this idea, Brian Wowk pointed this writer to Eric Drexler who envisioned such a form of warm biostasis in Engines of Creation. In chapter 7 (section 5) Drexler calls this form of warm biostasis “anesthesia plus:”

To see how one approach would work, imagine that the blood stream carries simple molecular devices to tissues, where they enter the cells. There they block the molecular machinery of metabolism - in the brain and elsewhere - and tie structures together with stabilizing cross-links. Other molecular devices then move in, displacing water and packing themselves solidly around the molecules of the cell. These steps stop metabolism and preserve cell structures.

This procedure would produce a state in which the person will appear to be dead (and warm) for all practical purposes:

If a patient in this condition were turned over to a present-day physician ignorant of the capabilities of cell repair machines, the consequences would likely be grim. Seeing no signs of life, the physician would likely conclude that the patient was dead, and then would make this judgment a reality by “prescribing” an autopsy, followed by burial or burning.

Such a form of warm biostasis would not only produce a true molecular alternative to cryonics, it would also enable long-duration space travel and could be employed as a means to provide trauma care in emergency situations. These kind of applications of molecular nanotechnology are extremely advanced and, as a result, literature, either fiction or non-fiction, about them is virtually non-existent. It seems that the first rigorous treatment of cellular and whole-body warm biostasis will be published in Robert Freitas’ Nanomedicine Volume IIB and Nanomedicine Volume III (personal correspondence).

Perhaps the future of biostasis will be an advanced form of chemical fixation after all.

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H.P. Lovecraft’s Herbert West is a man of science, not superstition. Following Ernst Haeckel, he believes that “all life is a chemical and psychical process,” that the soul is “a myth,” and that “unless actual decomposition has set in, a corpse fully equipped with organs may with suitable measures be set going again in the peculiar fashion known as life.” Not satisfied with conventional medicine, West devotes his life to creating a solution that will restore artificial life after death. Like many biomedical researchers would find out after him, the same solution can have different effects on different species. But what West is really after is reanimation of humans. And reanimation of humans requires experimentation on humans.

West does not only anticipate the future science of resuscitation, but also the phenomenon of selective vulnerability of certain brain cells because we know that West fully realized “that the psychic or intellectual life might be impaired by the slight deterioration of sensitive brain-cells which even a short period of death would be apt to cause.” As a consequence, his corpses cannot be “fresh” enough. Artificial resuscitation turns out to be a step towards bigger things when we learn that West has ventured into the area of “warm” whole body preservation (suspended animation) by creating a “highly unusual embalming compound” that keeps the body fresh for future resuscitation efforts. Still not satisfied, the “materialist” West moves on to prove that there is nothing special about the brain when he attempts to create mental life by pharmacologic modulation of nervous tissue in a decapitated body. One can only guess what direction West’s research would have taken after these bizarre experiments. Science is hard, but for this medical student of Miskatonic University, resuscitation, suspended animation, and stem cell research are all in a days work.

The greatest mystery in Lovecraft’s “Herbert West - Reanimator” is that West succeeds in reanimating anything at all. Injection of West’s solution is not followed by artificial circulation, which makes one wonder how such a solution can confer such profound benefits.

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The blog Practical Ethics reports on pioneering research from a group of scientists in Cambridge who are using fMRI scans to study the brains of people who have been diagnosed as being in a vegetative condition. A Persistent Vegetative State (PVS) is a condition that is characterized by a state of wakefulness without detectable awareness. The researchers found that some patients who have been diagnosed as being in a vegetative state were able to respond to certain stimuli, indicating the possibility of awareness. Although it is encouraging that new medical technologies can assist in preventing misdiagnoses of patients with severe brain injury, the fact remains that few of these patients will ever recover with their former personality and memories intact.

Patients who have been diagnosed with conditions such as Persistent Vegetative State (such as Terri Schiavo) or the Minimally Conscious State (MCS) often suffered serious damage to the brain as a result of severe stroke or cardiac arrest. Although there are rare cases of remarkable recoveries, most patients with such diagnoses have ceased to exist as persons because the parts of their brains that encoded their personalities have ceased to exist.

It is now a well established fact that brain cells do not immediately die after severe hypoxic insults such as stroke or cardiac arrest. Actual necrosis (or apoptosis) takes many hours, or sometimes even days (as a result of a phenomenon called “delayed neuronal death.”). Unfortunately, ischemic insults to the brain exceeding 5 minutes are often sufficient to set parts of the brain on an irreversible path to destruction of the person, even if resuscitation of the patient is possible. Currently, there is no single approved neuroprotective agent that can salvage these brain cells from destruction. Although hyperacute combination therapy may offer hope for people suffering severe hypoxic insults, most of such patients currently would be better served by placing them in a state of biostatis through cryonics before the complete ischemic cascade can run its course.

Although cryonics is often dismissed as speculative, it can be argued that long term preservation of the neuroanatomy of such patients through vitrification offers better hope of recovery as the same person (or any person at all) than immediate resuscitation after the insult. But for acceptance of cryonics as a treatment for patients at great risk of (delayed) severe brain damage to become acceptable, the general public will need more exposure to the technical feasibility of cryonics and perspectives on death that offer a more prominent place to the concept of personhood.

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