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Scientists Open Letter on Cryonics | Evidence-Based Cryonics

To whom it may concern,

Cryonics is a legitimate science-based endeavor that seeks to preserve human beings, especially the human brain, by the best technology available. Future technologies for resuscitation can be envisioned that involve molecular repair by nanomedicine, highly advanced computation, detailed control of cell growth, and tissue regeneration.

With a view toward these developments, there is a credible possibility that cryonics performed under the best conditions achievable today can preserve sufficient neurological information to permit eventual restoration of a person to full health.

The rights of people who choose cryonics are important, and should be respected.

Sincerely (67 Signatories)

Signatories encompass all disciplines relevant to cryonics, including Biology, Cryobiology, Neuroscience, Physical Science, Nanotechnology and Computing, Ethics and Theology.

[Signature datein brackets]

Gregory Benford, Ph.D. (Physics, UC San Diego) Professor of Physics; University of California; Irvine, CA [3/24/04]

Alex Bokov, Ph.D. (Physiology, University of Texas Health Science Center, San Antonio) [6/02/2014]

Alaxander Bolonkin, Ph.D. (Leningrad Politechnic University) Professor, Moscow Aviation Institute; Senior Research Associate NASA Dryden Flight Research Center; Lecturer, New Jersey Institute of Technology, Newark, NJ [3/24/04]

Nick Bostrom, Ph.D. Research Fellow; University of Oxford; Oxford, United Kingdom [3/25/04]

Kevin Q. Brown, Ph.D. (Computer Science, Carnegie-Mellon) Member of Technical Staff; Lucent Bell Laboratories (retired); Stanhope, NJ [3/23/04]

Professor Manfred Clynes, Ph.D. Lombardi Cancer Center; Department of Oncology and Department of Physiology and Biophysics, Georgetown University; Washington, DC [3/28/04]

L. Stephen Coles, M.D., PhD (RPI, Columbia, Carnegie Mellon University) Director, Supercentenarian Research Foundation Inglewood, California [10/7/06]

Daniel Crevier, Ph.D. (MIT) President, Ophthalmos Systems Inc., Longueuil, Qc, Canada; Professor of Electrical Engineering (ret.), McGill University & cole de Technologie Suprieure, Montreal, Canada. [4/7/05]

Antonei B. Csoka, Ph.D. Assistant Professor of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine Pittsburgh Development Center, Magee-Womens Research Institute [9/14/05]

Aubrey D.N.J. de Grey, Ph.D. Research Associate; University of Cambridge;Cambridge, United Kingdom [3/19/04]

Wesley M. Du Charme, Ph.D. (Experimental Psychology, University of Michigan) author of Becoming Immortal, Rathdrum, Idaho [11/23/05]

Joo Pedro de Magalhes, Ph.D. University of Namur; Namur, Belgium [3/22/04]

Thomas Donaldson, Ph.D. Editor, Periastron; Founder, Institute for Neural Cryobiology; Canberra, Australia [3/22/04]

Christopher J. Dougherty, Ph.D. Chief Scientist; Suspended Animation Inc; Boca Raton, FL [3/19/04]

K. Eric Drexler, Ph.D. Chairman of Foresight Institute; Palo Alto, CA [3/19/04]

Llus Estrada, MD., Ph.D.

Ex Head of the Clinical Neurophysiology Section (retired) at the University Hospital Joan XXIII of Tarragona, Spain. [11/21/2015]

Robert A. Freitas Jr., J.D. Author, Nanomedicine Vols. I & II; Research Fellow, Institute for Molecular Manufacturing, Palo Alto, CA [3/27/04]

Mark Galecki, Ph.D. (Mathematics, Univ of Tennessee), M.S. (Computer Science, Rutgers Univ), Senior System Software Engineer, SBS Technologies [11/23/05]

D. B. Ghare, Ph.D. Principal Research Scientist, Indian Institute of Science, Bangalore, India [5/24/04]

Ben Goertzel, Ph.D. (Mathematics, Temple) Chief Scientific Officer, Biomind LLC; Columbia, MD [3/19/04]

Peter Gouras, M.D. Professor of Ophthalmology, Columbia University; New York City, NY [3/19/04]

Rodolfo G. Goya, PhDSenior Scientist, Institute for Biochemical Research (INIBIOLP), School of Medicine,, National University of La Plata, La Plata city, Argentina. [11/22/2015]

Amara L. Graps, Ph.D. Researcher, Astrophysics; Adjunct Professor of Astronomy; Institute of Physics of the Interplanetary Space; American University of Rome (Italy) [3/22/04]

Raphael Haftka, Ph.D. (UC San Diego) Distinguished Prof. U. ofFlorida; Dept. of Mechanical & Aerospace Engineering, Gainesville, FL [3/22/04]

David A. Hall, M.D. Dean of Education, World Health Medical School [11/23/05]

J. Storrs Hall, Ph.D. Research Fellow, Institute for Molecular Manufacturing, Los Altos, CA Fellow, Molecular Engineering Research Institute, Laporte, PA [3/26/04]

Robin Hanson, Ph.D. (Social Science, Caltech) Assistant Professor (of Economics); George Mason University; Fairfax, VA[3/19/04]

Steven B. Harris, M.D. President and Director of Research; Critical Care Research, Inc; Rancho Cucamonga, CA[3/19/04]

Michael D. Hartl, Ph.D.(Physics, Harvard & Caltech) Visitor in Theoretical Astrophysics; California Institute of Technology; Pasadena, CA [3/19/04]

Kenneth J. Hayworth, Ph.D. (Neuroscience, University of Southern California) Research Fellow; Harvard University; Cambridge, MA [10/22/10]

Henry R. Hirsch, Ph. D. (Massachusetts Institute of Technology, 1960) Professor Emeritus, University of Kentucky College of Medicine [11/29/05]

Tad Hogg, Ph.D. (Physics, Caltech and Stanford) research staff, HP Labs, Palo Alto, CA [10/10/05]

James J. Hughes, Ph.D. Public Policy Studies Trinity College; Hartford, CT [3/25/04]

James R. Hughes, M.D., Ph.D. ER Director of Meadows Regoinal Medical Center; Director of Medical Research & Development, Hilton Head Longevity Center, Savanah, GA [4/05/04]

Ravin Jain, M.D. (Medicine, Baylor) Assistant Clinical Professor of Neurology, UCLA School of Medicine, Los Angeles, CA [3/31/04]

Subhash C. Kak, Ph.D. Department of Electrical & Computer Engineering, Louisiana State University, Baton Rouge, LA [3/24/04]

Professor Bart Kosko, Ph.D. Electrical Engineering Department; University of Southern California [3/19/04]

Jaime Lagnez, PhDNGS and Systems biologist for INSP (National Institutes of Health of Mexico) and CONACYT (National Science and Technology Council). [11/21/2015]

James B. Lewis, Ph.D. (Chemistry, Harvard) Senior Research Investigator (retired); Bristol-Myers Squibb Pharmaceutical Research Institute; Seattle, WA [3/19/04]

Marc S. Lewis, Ph.D. Ph.D. from the University of Cincinnati in Clinical Psychology. Associate Professor at the University of Texas at Austin of Clinical Psychology. [6/12/05]

Brad F. Mellon, STM, Ph.D. Chair of the Ethics Committee; Frederick Mennonite Community; Frederick, PA [3/25/04]

Ralph C. Merkle, Ph.D. Distinguished Professor of Computing; Georgia Tech College of Computing; Director, GTISC (GA Tech Information Security Center); VP, Technology Assessment, Foresight Institute [3/19/04]

Marvin Minsky, Ph.D. (Mathematics, Harvard & Princeton) MIT Media Lab and MIT AI Lab; Toshiba Professor of Media Arts and Sciences; Professor of E.E. and C.S., M.I.T [3/19/04]

John Warwick Montgomery, Ph.D. (Chicago) D.Thol. (Strasbourg), LL.D. (Cardiff) Professor Emeritus of Law and Humanities, University of Luton, England [3/28/04]

Max More, Ph.D. Chairman, Extropy Institute,Austin, TX [3/31/04]

Steve Omohundro, Ph.D. (Physics, University of California at Berkeley) Computer science professor at the University of Illinois at Champaign/Urbana [6/08/04]

Mike ONeal, Ph.D. (Computer Science) Assoc. Professor and Computer Science Program Chair; Louisiana Tech Univ.; Ruston, LA [3/19/04]

R. Michael Perry, Ph.D. Computer Science Patient care and technical services, Alcor Life Extension Foundation [9/30/09]

Yuri Pichugin, Ph.D. Former Senior Researcher, Institute for Problems of Cryobiology and Cryomedicine; Kharkov, Ukraine [3/19/04]

Peter H. Proctor, M.D., Ph.D. Independent Physician & Pharmacologist; Houston, Texas [5/02/04]

Martine Rothblatt, Ph.D., J.D., M.B.A. Responsible for launching several satellite communications companies including Sirius and WorldSpace. Founder and CEO of United Therapeutics. [5/02/04]

Klaus H. Sames, M.D. University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine (CEM) Institute of Anatomy II: Experimental Morphology; Hamburg, Germany [3/25/04]

Anders Sandberg, Ph.D. (Computational Neuroscience) Royal Institute of Technology, Stockholm University; Stockholm, Sweden [3/19/04]

Sergey V. Sheleg, M.D., Ph.D. Senior Research Scientist, Alcor Life Extension Foundation; Scottsdale, AZ [8/11/05]

Stanley Shostak, Ph.D. Associate Professor of Biological Sciences; University of Pittsburgh; Pittsburgh, PA [3/19/04]

Rafal Smigrodzki, M.D., Ph.D. Chief Clinical Officer, Gencia Company; Charlottesville VA [3/19/04]

David S. Stodolsky, Ph.D. (Univ. of Cal., Irvine) Senior Scientist, Institute for Social Informatics [11/24/05]

Gregory Stock, Ph.D. Director, Program on Medicine, Technology, and Society UCLA School of Public Health; Los Angeles, CA [3/24/04]

Charles Tandy, Ph.D. Associate Professor of Humanities and Director Center for Interdisciplinary Philosophic Studies Fooyin University (Kaohsiung, Taiwan) [5/25/05]

Peter Toma, Ph.D. President, Cosmolingua, Inc. Sioux Falls, South Dakota. Inventor and Founder of SYSTRAN. Director of International Relations, Alcor Life Extension Foundation. Residences in Argentina, Germany, New Zealand, Switzerland and USA [5/24/05]

Natasha Vita-More, PhD Professor, University of Advancing Technology, Tempe, Arizona, USA. [11/22/2015]

Mark A. Voelker, Ph.D. (Optical Sciences, U. Arizona) Director of Bioengineering; BioTime, Inc.; Berkeley, CA [3/19/04]

Roy L. Walford, M.D. Professor of Pathology, emeritus; UCLA School of Medicine; Los Angeles, CA [3/19/04]

Mark Walker, Ph.D. Research Associate, Philosophy; Trinity College; University of Toronto (Canada) [3/19/04]

Michael D. West, Ph.D. President, Chairman & Chief Executive Office; Advanced Cell Technology, Inc.; Worcester, MA [3/19/04]

Ronald F. White, Ph.D. Professor of Philosophy; College of Mount St. Joseph; Cincinnati, OH [3/19/04]

James Wilsdon, Ph.D. (Oxford University) Head of Strategy for Demos, an independent think-tank; London, England [5/04/04]

Brian Wowk, Ph.D. Senior Scientist 21st Century Medicine, Inc.; Rancho Cucamonga, CA [3/19/04]

Selected Journal Articles Supporting Cryonics:

First paper showing recovery of brain electrical activity after freezing to -20C. Suda I, Kito K, Adachi C, in: Nature (1966, vol. 212), Viability of long term frozen cat brain in vitro, pg. 268-270.

First paper to propose cryonics by neuropreservation: Martin G, in: Perspectives in Biology and Medicine (1971, vol. 14), Brief proposal on immortality: an interim solution, pg. 339.

First paper showing recovery of a mammalian organ after cooling to -196C (liquid nitrogen temperature) and subsequent transplantation: Hamilton R, Holst HI, Lehr HB, in: Journal of Surgical Research (1973, vol 14), Successful preservation of canine small intestine by freezing, pg. 527-531.

First paper showing partial recovery of brain electrical activity after 7 years of frozen storage: Suda I, Kito K, Adachi C, in: Brain Research (1974, vol. 70), Bioelectric discharges of isolated cat brain after revival from years of frozen storage, pg. 527-531.

First paper suggesting that nanotechnology could reverse freezing injury: Drexler KE, in: Proceedings of the National Academy of Sciences (1981, vol. 78), Molecular engineering: An approach to the development of general capabilities for molecular manipulation, pg. 5275-5278.

First paper showing that large organs can be cryopreserved without structural damage from ice: Fahy GM, MacFarlane DR, Angell CA, Meryman HT, in: Cryobiology (1984, vol. 21), Vitrification as an approach to cryopreservation, pg. 407-426.

First paper showing that dogs can be recovered after three hours of total circulatory arrest (clinical death) at 0C (32F). This supports the reversibility of the hypothermic phase of cryonics: Haneda K, Thomas R, Sands MP, Breazeale DG, Dillard DH, in: Cryobiology (1986, vol. 23), Whole body protection during three hours of total circulatory arrest: an experimental study, pg. 483-494.

First detailed discussion of the application of nanotechnology to reverse human cryopreservation: Merkle RC, in: Medical Hypotheses (1992, vol. 39), The technical feasibility of cryonics, pg. 6-16.

First successful application of vitrification to a relatively large tissue of medical interest: Song YC, Khirabadi BS, Lightfoot F, Brockbank KG, Taylor MJ, in: Nature Biotechnology (2000, vol. 18), Vitreous cryopreservation maintains the function of vascular grafts, pg. 296-299.

First report of the consistent survival of transplanted kidneys after cooling to and rewarming from -45C: Fahy GM, Wowk B, Wu J, Phan J, Rasch C, Chang A, Zendejas E, in: Cryobiology (2004 vol. 48),Cryopreservation of organs by vitrification: perspectives and recent advances, pg. 157-78. PDF here.

First paper showing good ultrastructure of vitrified/rewarmed mammalian brains and the reversibility of prolonged warm ischemic injury in dogs without subsequent neurological deficits, and setting forth the present scientific evidence in support of cryonics: Lemler J, Harris SB, Platt C, Huffman T, in: Annals of the New York Academy of Sciences, (2004 vol. 1019), The Arrest of Biological Time as a Bridge to Engineered Negligible Senescence, pg. 559-563. PDF here.

First discussion of cryonics in a major medical journal: Whetstine L, Streat S, Darwin M, Crippen D, in: Critical Care, (2005, vol. 9), Pro/con ethics debate: When is dead really dead?, pg. 538-542. PDF here.

First demonstration that both the viability and structure of complex neural networks can be well preserved by vitrification: Pichugin Y, Fahy GM, Morin R, in: Cryobiology, (2006, vol. 52), Cryopreservation of rat hippocampal slices by vitrification, pg. 228-240.PDF here.

Rigorous demonstration of memory retention following profound hypothermia, confirming theoretical expectation and clinical experience. Alam HB, Bowyer MW, Koustova E, Gushchin V, Anderson D, Stanton K, Kreishman P, Cryer CM, Hancock T, Rhee P, in: Surgery (2002, vol. 132), Learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination, pg. 278-88.

Review of scientific justifications of cryonics: Best BP, in: Rejuvenation Research (2008, vol. 11), Scientific justification of cryonics practice, pg. 493-503. PDF here.

First successful vitrification, transplantation, and long-term survival of a vital mammalian organ: Fahy GM, Wowk B, Pagotan R, Chang A, Phan J, Thomson B, Phan L, in: Organogensis (2009, vol. 5), Physical and biological aspects of renal vitrification pg. 167-175. PDF here.

First demonstration of memory retention in a cryopreserved and revived animal: Vita-More N, Barranco D, in:Rejuvenation Research, (2015, vol. 18), Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans, pg. 458-463.PDF here.

Note: Signing of this letter does not imply endorsement of any particular cryonics organization or its practices. Opinions on how much cerebral ischemic injury (delay after clinical death) and preservation injury may be reversible in the future vary widely among signatories.

Contact: contact@evidencebasedcryonics.org

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Scientists Open Letter on Cryonics | Evidence-Based Cryonics

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cryonics – The Skeptic’s Dictionary – Skepdic.com

Cryonics claims it can store a dead human body at low temperatures in such a way that it will be possible to revitalize that body and restore life at some unspecified future date. One hook the cryonics folks use is to give hope that a cure for a disease one dies of today will be found tomorrow, allowing that cure to be applied to the thawed body before or while bringing the dead person back to life. Cryonics might be called resurrection by technology and believers in it might be classified as suffering from the Moses syndrome. The simple fact is once you are dead, you are dead forever. This fact may seem horrifying, but it is not nearly as horrifying as the thought of living forever.

The technology exists to freeze or preserve people and that technology is improving and will probably get better. The technology to revivify a frozen body exists in the imagination. Nanotechnology, for example, is a technology that supporters of cryonics appeal to. Someday, they say, we'll be able to rebuild anything, including diseased or damaged cells in the body, with nanobots. So, no matter what disease destroyed healthy cells in the living body before preservation and no matter what damage was done to the cells of the frozen body during storage, nanotechnology will allow us to bring the dead back to life. This seems like wishful thinking. Nanotechnology might rebuild a mass of dead tissue into a mass of healthy tissue, but without a complete isomorphic model of the brain it will be impossible to return a mushy brain to the exact state it was in before death occurred. (Of course, since this is an exercise in imagination, one can posit that some day we will be able to preserve the brain without any decomposition or transformation at all.) In any case, some other jolt, probably electricity, will be needed to get the heart beating and the brain working again, assuming, of course, that the mush brain has been reconstructed into a healthy brain.

Some preserved by cryonics have the head severed from the body after death. Then, either the head alone is preserved, or both the head and the body are preserved separately. Maybe some future technology will allow the head to be attached to an artificial body. It can be imagined without contradiction, as the philosophers say, so it is not logically impossible that some day our planet will be inhabited by bodiless heads that are connected to machines that allow either actual or virtual experiences of any kind imaginable without requiring the head to leave the room. Of course, when that times comes medical science will have advanced to the point where the aging process can be reversed or maintained in stasis.

A business based on little more than hope for developments that can be imagined by science is quackery. (Cryonics should not be confused with cryogenics, which is a branch of physics that studies the effects of low temperatures on the structure of objects.) There is little reason to believe that the promises of cryonics will ever be fulfilled. Even if a dead body is somehow preserved for a century or two and then repaired, whatever is animated by whatever process will not be the same person who died. The brain is the key to consciousness and to who a person is. There is no reason to believe that a brain preserved by whatever means and restored to whatever state by nanobots will result in a consciousness that is in any way connected to the consciousness of the person who died two centuries earlier.

For those who want to live forever, cloning might be a more realistic possibility but I wouldn't bank on it. First, there is the aging problem. Even if cloning is successful, you won't be able to clone yourself as younger. Of course, you can hope that future technology will have solved the aging problem. Perhaps your body can be cloned repeatedly until science can assist you to overcome aging. However, there is no reason to believe that your clone would be a continuation of you. Your bodies might have identical looking cells, but the only way your minds could be identical is if you had no experience. (It is logically impossible for your bodies to have identical experiences since they occupy different spatial and temporal coordinates.) In that case, you would be as good as dead.

origin of cryonics

Teacher Robert Ettinger (physics and math) brought cryonics into the intellectual mainstream in 1964 with The Prospect of Immortality. Ettinger founded the Cryonics Institute and the related Immortalist Society. He got the idea for cryonics from a story by Neil R. Jones. "The Jameson Satellite" appeared in the July 1931 issue of Amazing Stories. It told the tale of

one Professor Jameson [who] had his corpse sent into earth orbit where (as the author mistakenly thought) it would remain preserved indefinitely at near absolute zero. And so it did, in the story, until millions of years later, when, with humanity extinct, a race of mechanical men with organic brains chanced upon it. They revived and repaired Jameson's brain, installed it in a mechanical body, and he became one of their company.*

Thus was born the idea that we could freeze our bodies, repair them at a later date, and bring them back to life when technology had advanced sufficiently to do the repairs and the reviving.

ethical & other issues

I will leave to others to discuss most of the ethical, legal, political, and economic issues of cryonics. I'll conclude with some comments about the cryonics case of Ted Williams.

Williams died in 2002 at the age of 83. According to his estranged daughter, Barbara Joyce (Bobby-Jo Ferrell) Williams, he left a will in which he expressed his desire to be cremated and have his ashes spread over his favorite fishing grounds in the Florida Keys. His son (Barbara Joyce's half-brother), John Henry Williams, arranged for Williams's body to be processed by Alcor LIfe Extension Foundation. A story in SportsIllustrated.com (SI) stated:

Hall of Famer Ted Williams' head and body are being stored in separate containers at an Arizona cryonics lab that is still trying to collect a $111,000 bill from Williams' son [he had already paid $25,000], according to a story by Tom Verducci in the latest issue of Sports Illustrated.

Alcor still has Williams's head in a canister and his body in a tank, both filled with liquid nitrogen (to keep the remains at a cool -321 degrees Fahrenheit). According to SI, Alcor representatives met with John Henry Williams, but not Ted Williams, about a year before Ted's death. Furthermore, SI reported that the Consent for Cryonic Suspension form submitted to Alcor after Williams had died had a blank line where his signature should have been.

There was a lawsuit by the estranged daughter that fizzled, allegedly for lack of funds, but no legal action by the authorities was taken against John Henry or Alcor. There is a movement still going to right this ship (see the Free Ted Williams website.) Larry Johnson, who worked briefly at Alcor, is leading the crusade to get Congress and a couple of state legislatures to regulate the cryonics industry and have Ted Williams cremated. A video interview with Johnson on "Good Morning America" discussing the disposition of Ted Williams's body at Alcor can be viewed by clicking here. Johnson's book on the subject, Shiver: A Whistleblower's Chilling Expose of Cryonics and the Truth Behind What Happened to Ted Williams, is scheduled to be published in May 2009.

See also Ralian and my comments on cryonics in Mass Media Funk.

Perfusion & Diffusion in Cryonics Protocol – BEN BEST

by Ben Best CONTENTS: LINKS TO SECTIONS BY TOPIC

Preparing a cryonics patient for cryostorage can involve three distinct stages of alteration of body fluids:

(1) patient cooldown/cardiopulmonary support

(2) blood washout/replacement for patient transport

(3) cryoprotectant perfusion

During patient cooldown/cardiopulmonary support, a cryonics emergency response team or health care personnel may inject a number of medicaments to minimize ischemic injury and facilitate cryopreservation. The first and most important of these medicaments would be heparin, to prevent blood clotting. (For more details on the initial cooldown process, see Emergency Preparedness for a Local Cryonics Group).

Once the patient is cooled, the blood can be washed-out and replaced with a solution intended to keep organs/tissues alive while the patient is being transported to a cryonics facility. At the cryonics facility the organ/tissue preservation solution is replaced with the cryopreservation solution intended to prevent ice formation when the patient is further cooled to temperatures of 120C (glass transition temperature) or 196C (liquid nitrogen temperature) for long-term storage.

For both organ/tissue preservation & cryoprotection it is necessary to replace the fluid contents of blood vessels & tissue cells with other fluids. The process of injecting & circulating fluids through blood vessels is called perfusion. The passive process by which fluids enter & exit both blood vessels & cells is called diffusion.

(return to contents)

Body fluids can be described as solutes dissolved in a solvent, where the solvent is water and the solutes are substances like sodium chloride (NaCl, table salt), glucose or protein. Both water and solute molecules tend to move randomly in fluid with energy and velocity that is directly proportional to temperature. When there is a difference in concentration between water or solute molecules in one area of the fluid compartment compared to the rest of the compartment, random motion of the molecules will eventually result in a uniform distribution of all types of molecules throughout the compartment. In thermodynamics this is termed a decrease in potential energy (Gibbs free energy, not heat energy) due to an increase in entropy at constant temperature leading to equilibrium.

The movement of molecules from an area of high concentration to an area of low concentration is called diffusion. The rate of diffusion (J) can be quantified by Fick's law of diffusion:

dc J = DA---- dx J = rate of diffusion (moles/time) D = Diffusion coefficient A = Area across which diffusion occurs dc/dx = concentration gradient (instantaneous concentration difference divided by instantaneous distance)

Fick's First Law states that the rate of diffusion down a concentration gradient is proportional to the instantaneous magnitude of the concentration gradient (which changes as diffusion proceeds). For movement of molecules from a region of higher concentration to a region of lower concentration dc/dx will be negative, so multiplying by DA gives a positive value to J. Diffusion coefficient is higher for higher temperature and for smaller molecules.

Diffusion can occur not only within a fluid compartment, but across partitions that separate fluid compartments. The relevant partitions for animals are cell membranes and capillary walls. Cell membranes are lipid bilayers that allow for free diffusion of lipid soluble substances like oxygen, nitrogen, carbon dioxide and alcohol, while blocking movement of ions and polar molecules. But cell membranes also contain channels made of protein. Protein channels for water allow for very rapid diffusion of water across the membranes. Protein channels for potassium(K+), sodium(Na+) and other ions allow for more restricted diffusion across cell membranes. There is also facilitated diffusion (active transport) of many types of molecules across membranes.

For a normal 70kilogram (154pound) adult the total body fluid is about 60% of the body weight. Almost all of this fluid can be described as extracellular or intracellular (excluding only cerebrospinal fluid, synovial fluid and a few other small fluid compartments). Extracellular fluid can be further subdivided into plasma (noncellular part of blood) and interstitial fluid (fluid between cells that is not in blood vessels). Cell membranes separate intracellular fluid from extracellular fluid, whereas capillary walls separate plasma from interstitial fluid. The relative percentages of these fluids can be summarized as:

Intracellular fluid 67% Extracellular fluid Interstitial fluid 26% Plasma 7%

Note that blood volume includes both plasma & blood cells such that adding the intracellular fluid volume of blood cells to plasma volume makes blood 12% of total body fluid.

Osmosis refers to diffusion of water (solvent) across a membrane that is semi-permeable, ie, permeable to water, but not to all solutes in the solution. If membrane-impermeable solutes are added to one side of the membrane, but not to the other side, water will be less concentrated on the solute side of the membrane. This concentration gradient will cause water to diffuse across the semi-permeable membrane into the side with the solutes unless pressure is applied to prevent the diffusion of water. The amount of pressure required to prevent any diffusion of water across the semi-permeable membrane is called the osmotic pressure of the solution with respect to the membrane.

Osmotic pressure (like vapor pressure lowering and freezing-point depression) is a colligative property, meaning that the number of particles in solution is more important than the type of particles. One molecule of albumin (molecular weight 70,000) contributes as much to osmotic pressure as one molecule of glucose or one sodium ion. At equilibrium all molecules in a solution have achieved the same average kinetic energy, meaning that molecules with a smaller mass have higher average velocity. Thus, a one molar solution of NaCl will result in twice the osmotic pressure as a one molar solution solution of glucose because Na+ and Cl ions exert osmotic pressure as independent particles.

Solute concentrations are generally expressed in terms of molarity (moles of solute per liter of solution). The osmolarity of a solution is the product of the molarity of the solute and the number of dissolved particles produced by the solute. A one molar (1.0M, one mole per liter) solution of CaCl2 is a three osmolar (three osmoles per liter) solution because of the Ca2+ ion plus the two Cl ions produced when CaCl2 is added to water. Osmolarity, the number of solute particles per liter has been mostly replaced in practice by osmolality, the number of solute particles per kilogram. (For dilute solutions the values of the two are very close.) For describing solute concentrations in body fluids it is more convenient to use thousandths of osmoles, milli-osmoles (mOsm). Total solute osmolality of intracellular fluid, interstitial fluid or plasma is roughly 300mOsm/kgH2O. About half of the osmolality of intracellular fluid is due to potassium ions and associated anions, whereas about 80% of the osmolality of interstitial fluid and plasma is due to sodium and chloride ions.

As stated above, both osmotic pressure and freezing point depresssion are colligative properties. All colligative properties are convertible. One osmole of any solute will lower the freezing point of water by 1.858C. For this reason, a 0.9% NaCl solution is 0.154molar or about 308mOsm/kgH2O, and will lower the freezing point of water by about 0.572C.

The osmolality of a solution is an absolute quantity that can be calculated or measured. The tonicity of a solution is a relative concept that is associated with osmotic pressure and the ability of solutes to cross a semi-permeable membrane. Thus, tonicitiy of a solution is relative to the particular solutes and relative to a particular membrane specifically relative to whether the solutes do or do not cross the membrane. Cell membranes are the membranes of greatest biological significance. Whether a cell shrinks or swells in a solution is determined by the tonicity of the solution, not necessarily the osmolality. Only when all the solutes do not cross the semi-permeable membrane does osmolality provide a quantitative measure of tonicity. It is common to speak as if tonicity and osmolality are equivalent because body fluid solutes are often impermeable. Each mOsm/kgH2O of fluid contributes about 19mmHg to the osmotic pressure.

A solution is said to be isotonic if cells neither shrink nor swell in that solution. Both 0.9%NaCl (physiological saline) and 5%glucose (in the absence of insulin) are isotonic solutions (roughly 300mOsm/kgH2O of impermeable solute). (In the presence of insulin, 5%glucose is a hypotonic solution because insulin causes glucose to cross cell membranes.) Hypertonic solutions cause cells to shrink as water rushes out of cells into the solute, whereas cells placed in hypotonic solutions cause the cells to swell as water from the solution rushes into the cells.

An exact calculation of the osmolality of plasma gives 308mOsm/kgH2O, but the freezing point depression of plasma (0.54C) indicates an osmolality of 286mOsm/kgH2O. Interaction of ions reduces the effective osmolality. Sodium ions (Na+) and accompanying anions (mostly Cl & HCO3) account for all but about 20mOsm/kgH2O of plasma osmolality. Plasma sodium concentration is normally controlled by plasma water content (thirst, etc.)[BMJ; Reynolds,RM; 332:702-705 (2006)]. Normal serum Na+ concentration is in the 135 to 145millimole per liter range, with 135mmol/L being the threshold for hyponatremia. Intracellular sodium concentration is typically about 20mmol/L about one-seventh the extracellular concentration. Glucose and urea account for about 5mOsm/kgH2O. Osmolality of plasma is generally approximated by doubling the sodium ions (to include all associated anions), adding this to glucose & urea molecules, and ignoring all other molecules as being negligible. Protein contributes to less than 1% of the osmolality of plasma. (Cells contain about four times the concentration of proteins as plasma contains.)

Although ethanol increases the osmolality of a solution, it does not increase the tonicity because (like water) ethanol crosses cell membranes. A clinical hyperosmolar state without hypertonicity can occur with an increase in extracellular ethanol (which diffuses into cells)[ MINERVA ANESTESIOLOGICA; Offenstadt,G; 72(6):353-356 (2006)]. Glycerol also readily crosses cell membranes, but it does so thousands of times more slowly than water which means that glycerol is "transiently hypertonic" (only isotonic at equilibrium). Ethylene glycol crosses red blood cell membranes about six times faster than glycerol (and sperm cell membranes four times faster than glycerol). Actually. even for water there is a finite time for hydraulic conductivity across cell membranes.

Cells placed in a "transiently hypertonic" solution (containing solutes that slowly cross a membrane) will initially shrink rapidly as water leaves the cell, and gradually re-swell as the solute slowly enters the cell (the "shrink/swell cycle"). As shown in the diagram for mouse oocytes at 10C, water leaves the cell in the first 100seconds, whereas 1.5Molar ethylene glycol (black squares) or DMSO (DiMethylSulfOxide, white squares) take 1,750seconds to restore the volume to 85% of the original cell volume[CRYOBIOLOGY; Paynter,SJ; 38:169-176 (1999)]. Even if a cell does not burst or collapse due to osmotic imbalance, a sudden change in osmotic balance can injure cells. Nonetheless, cells are somewhat tolerant of hypotonic solutions. Granulocytes are particularly sensitive to osmotic stress, but granulocyte survival is not significantly affected by hypertonic solutions until the osmolality of impermeant solutes approaches twice physiological values (about 600mOsm/kgH2O)[AMERICAN JOURNAL OF PHYSIOLOGY; Armitage WJ; 247(5Pt1):C373-381 (1984)].

PC3 cells show almost no decline of survival upon exposure to 5,000mOsm/kgH2O NaCl for 60minutes at 0C, and show nearly 85% cell survival on rehydration. Nearly 85% survive 9,000mOsm/kgH2O NaCl for 60minutes at 0C, but less than 20% survive rehydration. But although at 23C most cells survive exposure to 5,000mOsm/kgH2O NaCl for 60minutes, only about a third of cells survive rehydration. At 23C and 9,000mOsm/kgH2O NaCl only about half of cells survive 60 minutes and no cells survive rehydration, indicating the protective effect of low temperature against osmotic stress. Water flux at 23C was the same for 9,000mOsm/kgH2O as for 5,000mOsm/kgH2O, and hypertonic cell survival was not affected by the rate of concentration increase[CRYOBIOLOGY; Zawlodzka,S; 50(1):58-70 (2005)].

Hyperosmotic stress damages not only cell membranes, but damages cytoskeleton, inhibits DNA replication & translation, depolarizes mitochondria, and causes damage to DNA & protein. Heat shock proteins and organic osmolytes (like sorbitol & taurine) are synthesized as protection against hyperosmotic stress. Highly proliferative cells (like PC3) suffer from osmotic stress more than less proliferative cells because the latter can mobilize cellular defenses more readily due to fewer cells undergoing mitosis at the time of osmotic stress[PHYSIOLOGICAL REVIEWS; Burg,MB; 87(4):1441-1474 (2007)].

An important distinction to remember in replacing body fluids is the distinction between two kinds of swelling (edema): cell swelling and tissue swelling. Cell swelling occurs when there is a lower concentration of dissolved membrane-impermeable solutes outside cells than inside cells. To prevent either shrinkage or swelling of a cell there must be an osmotic balance of molecules & ions between the liquids outside the cell & inside the cell. Capillary walls are semipermeable membranes that are permeable to most of the small molecules & ions that will not cross cell membranes, but are impermeant to large molecules referred to as colloid (proteins). The colloid osmotic pressure on capillary walls due to proteins is called oncotic pressure. For normal human plasma oncotic pressure is about 28mmHg, 9mmHg of which is due to the Donnan effect which causes small anions to diffuse more readily than small cations because the small cations are attracted-to (but not bound-to) the anionic proteins. About 60% of total plasma protein is albumin (30 to 50 grams per liter), the rest being globulins. But albumin accounts for 75-80% of total intravascular oncotic pressure. Tissue swelling occurs when fluids leak out of blood vessels into the interstitial space (the space between cells in tissues). Injury to blood vessels can result in tissue swelling, but tissue swelling can also result from water leaking out of vessels when there is nothing (like albumin) to prevent the leakage.

Both forms of edema (cell & tissue swelling) can impede perfusion considerably, and is frequently a problem in cryonics patients who have suffered ischemic or other forms of blood vessel damage. Maintaining osmotic balance of the fluids outside & inside cells is as important as maintaining oncotic balance, ie, balance of fluids inside & outside of blood vessels.

Much of the isotonicity of the intracellular and extracellular fluids is maintained by the sodium pump in cell membranes, which exports 3sodium ions for every 2potassium ions imported into cells. Proteins in cells are more osmotically active than interstitial fluid proteins. Because of the Donnan effect the sodium pump is required to prevent cell swelling. When ischemia deprives the sodium pump of energy, cells swell from excessive intracellular sodium (because sodium attracts water more than potassium does) resulting in edema. Inflammation can also cause cell swelling due to increased membrane permeability to sodium and other ions. Interstitial edema can occur when ischemia or inflammation increases capillary permeability leading to leakage of larger plasma solutes into the interstitial space.

[For further details on the sodium pump see MEMBRANE POTENTIAL, K/Na-RATIOS AND VIABILITY]

Near the hypothalamus of the brain are osmoreceptors (outside the blood-brain barrier) that monitor blood osmolality, which is normally in the range of 280-295mOsm/kgH2O. A 2% increase in plasma osmotic pressure can provoke thirst. An increase in plasma osmolality can indicate excessive loss of blood volume. To compensate, the posterior pituitary (neurohypophysis) secretes the hormone 8arginine vasopressin (AVP), which is two hormones in one hence the two names vasopressin and anti-diuretic hormone. AVP action on the V1 receptors on blood vessels causes vasoconstriction (vasopressin). AVP action on the V2 receptors of the kidney causes water retention (anti-diuretic hormone). Deficiency in AVP secretion can lead to diabetes incipidus, so called because the excessively excreted urine is tasteless (incipid), in contrast to the sweet (glucose-laden) urine of diabetes mellitus. Cortisol opposes AVP action on excretion, leading to dehydration and excessive urination of fluid. Reduced blood flow to the kidney stimulates release of renin, which catalyzes the production of angiotensin. Like AVP, angiotensin causes vasoconstriction and kidney fluid retention.

Rats subjected to experimental focal ischemia have shown reduced edema when treated with an AVP antagonist[STROKE; Shuaib,A; 33(12):3033-3037 (2002)]. Hypertonic saline(7.5%) has been shown to halve plasma AVP levels in experimental rats, whereas mannitol(20%) had no effect[JOURNAL OF APPLIED PHYSIOLOGY; Chang,Y; 100(5):1445-1451 (2006)]. Increases in plasma osmolality due to urea or glycerol have no effect on plasma AVP levels[JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; Verbalis,JG; 18(12):3056-3059 (2007)]. The effect of hypertonic saline on osmotic edema due to AVP in a cryonics patient would likely be negligible because of negligible hormone release and transport. So some of the advantage of hypertonic saline over mannitol seen in clinical trials would not occur in cryonics cases.

The net movement of fluid across capillary membranes due to hydrostatic and oncotic forces can be described by the Starling equation. The Starling equation gives net fluid flow across capillary walls as a result of the excess of capillary hydrostatic pressure over interstitial fluid hydrostatic pressure, and capillary oncotic pressure over interstitial fluid oncotic pressure modified by the water permeability of the capillary. For a normal (animate) person, the hydrostatic pressure (blood pressure) at the arterial end of a capillary is about 35mmHg. The hydrostatic pressure drops in a linear fashion across the length of the capillary until it is about 15mmHg at the venule end. The net oncotic pressure within the capillary is about 25mmHg across the entire length of the capillary. Thus, for the first half of the capillary there is a net loss of fluid into the interstitial space until the hydrostatic pressure has dropped to 25mmHg. For the second half of the capillary there is a net gain of fluid into the capillary from the interstitial space. The flow of fluid into the interstitial space in the first half of the capillary is associated with the delivery of oxygen & nutrient to the tissues, whereas the flow of fluid from the interstitial space into the second half of the capillary is associated with the removal of carbon dioxide and other waste products.

Actually, there is a tiny (tiny relative to the total diffusion back and forth across the capillary wall) net flow of fluid from the capillaries to the interstitial fluid which is returned to the blood vessels by the lymphatic system. The lymphatic vessels contain one-way valves and rely on skeletal muscle movement to propel the lymphatic fluid. Infectious blockage of lymph flow can produce edema. A person sitting for long periods (as during a long trip) or standing a long time without moving may experience swollen ankles due to the lack of muscle activity. Swollen ankles is also a frequent symptom of the edema resulting from congestive heart failure. Venous pressure is elevated by the reduced ability of the heart to pull blood from the venous system, whereas vasoconstriction can better compensate to maintain pressure on the arterial side. Reduced albumin production by the liver as a result of cirrhosis or other liver diseases can reduce plasma osmolality such that the reduced oncotic pressure results in edema typically swollen ankles, pulmonary edema and abdomenal edema (ascites).

The Starling forces are different for the blood-brain barrier (BBB) than they are for other capillaries of the body because of the reduced permeability to water (lower hydraulic conductivity) and the greatly reduced permeability to electrolytes. The osmotic pressure of the plasma and interstitial fluid effectively become the oncotic pressures.

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A critical distinction is made in fluid mechanics between laminar flow and turbulent flow in a pipe. For laminar flow elements of a liquid follow straight streamlines, where the velocity of a streamline is highest in the center of the vessel and slowest close to the walls. Turbulent flow is characterized by eddies & chaotic motion which can substantially increase resistance and reduce flow rate. The Reynolds number is an empirically determined dimensionless quantity which is used to predict whether flow will be laminar or turbulent with 2000 being the approximate lower limit for turbulent flow. Transient localized turbulence can be induced at a Reynolds number as low as 1600, but temporally peristant turbulence forms above 2040[SCIENCE; Eckhart,B; 333:165 (2011)].

Turbulent flow could potentially be a problem in cryonics if it reduced perfusion rate or increased the amount of pressure required to maintain a perfusion rate. It is doubtful that turbulent flow ever plays a role in cryonics perfusion, however. Even for a subject at body temperature (37C) Reynolds numbers in excess of 2000 are only seen in the very largest blood vessels: the aorta and the vena cava.

The formula for Reynolds number is: v D Re = ------ = fluid density (rho) v = fluid velocity D = vessel diameter = fluid viscosity

The fact that diameter (D) is in the numerator indicates that only high diameter vessels have high Reynolds number. Velocity (v), also in the numerator, is highest in the aorta & arteries. But the use of cryoprotectants and the increase in viscosity () with declining temperature essentially guarantee that turbulent flow will not occur in a cryonics patient.

More serious for cryonics is the Hagen-Poisseuille Law, which describes the relationship between flow-rate and driving-pressure: pressure X (radius)4 Flow Rate = ---------------------- length X viscosity

Typically in cryonics the flow rate will be one or two liters per minute when the pressure is around 80mmHg. But because flow rate varies inversely with viscosity and varies directly with pressure, pressure must be increased to maintain flow rates when cryoprotectant viscosity increases with lowering temperature. This poses a serious problem because blood vessels become more fragile with lowering temperature. If blood vessels burst the perfusion can fail.

At 20C glycerol is about 25% more dense (=rho, in the numerator) than water. But the role of viscosity is far more dramatic, with high viscosity in the denominator reducing Reynolds number considerably. The viscosity of water approximately doubles from 37C to 10C, but the viscosity of glycerol increases by a factor of ten (roughly 4Poise to 40Poise). At 37C glycerol is nearly 600 times more viscous than water, but at 10C it is about 2,600 times more viscous.

Although turbulence is not a concern in cryonics, the increase in viscosity of cryoprotectant with lowering temperature certainly is. Fortunately, the newer vitrification mixtures are less viscous than glycerol.

The most common strategy in cryonics has been to cool the patient from 37C to 10C as rapidly as possible and to perfuse with cryoprotectant at 10C. Lowering body temperature reduces metabolism considerably, thereby lessening the amount of oxygen & nutrient required to keep tissues alive. Cryoprotectant toxicity drops as temperature declines. But the very dramatic more-than-exponential increase in cryoprotectant viscosity with lowering temperature poses a significant problem for effective perfusion. When open circuit perfusion is used, a higher temperature may be preferable because the opportunity for diffusion time into cells is so limited (about 2hours 1hour for the head, 1hour for the body) although ischemic damage is difficult to quantify.

With closed circuit perfusion, the perfusion times are longer up to 5hours. If a good carrier solution is used for the cryoprotectant the tissues may receive adequate nutrient. This, along with the oxygen carrying-capacity of water at low temperature, may limit ischemic damage while allowing time for cells to become fully loaded with cryoprotectant. If ischemic damage can be safely prevented in perfusion, the only critical issues for temperature selection are the relative benefits of reduced cryoprotectant toxicity at lower temperatures as against increased chilling injury. The fact that the more-than-exponential increase in viscosity with lowering temperature will increase perfusion time will not be problematic if the risk of ischemia is minimized.

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Typically a cryonics patient deanimates at a considerable distance from a cryonics facility and must be transported before cryoprotectants can be perfused. Blood could be washed-out and replaced with an isotonic (ie, osmotically the same as saline) solution, such as Ringer's solution. The patient is then transported to the cryonics facility at water-ice temperature. Freezing must be avoided because ice crystals would damage cells & blood vessels to such an extent as to prevent effective cryoprotectant perfusion. Water-ice temperature will not freeze tissues because tissues are salty (salt lowers the freezing point below 0C).

As body temperature approaches 10C, metabolic rate has slowed greatly and the oxygen-carrying capacity of blood hemoglobin is no longer required. Cool water, in fact, may carry adequate dissolved oxygen at low temperatures. (Water near freezing temperature can hold nearly three times as much dissolved oxygen as water near boiling temperature. Oxygen is about five times more soluble in water than nitrogen.) The tendency of blood to agglutinate and clog blood vessels becomes a serious problem at low temperature so the blood should be replaced if this does not cause other problems (such as delay and reperfusion injury.)

Replacing blood with a saline-like solution for patient transport, however, does not do a good job of maintaining tissue viability or preventing edema and would likely cause reperfusion injury. For this reason an organ preservation solution such as Viaspan, rather than Ringer's solution, has been used for cryopatient transport. Blood is not simply an isotonic solution carrying blood cells. Blood contains albumin, which attracts water and keeps the water from leaving blood vessels and going into tissues (maintains oncotic balance). Tissues which are swollen by water (edematous tissues) resist cryoprotectant perfusion. One of the most important ingredients in Viaspan preventing edema is HydroxyEthyl Starch (HES), which attracts water in much the way albumin attracts water acting as an oncotic agent by keeping water in the blood vessels. Viaspan contains potassium lactobionate to help maintain osmotic balance. Because HES is difficult to obtain and can cause microcirculatory disturbances, PolyEthylene Glycol (PEG) has been used in organ preservation solutions as a replacement for HES with good results[THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS; Faure,J; 302(3):861-870 (2002) and LIVER TRANSPLANTATION; Bessems,M; 11(11):1379-1388 (2005)].

The same benefit might not apply to cryonics patients, however, because of the prevalence of endothelial damage due to ischemia. Larger "holes" in the vasculature can mean that a larger molecular weight molecule is required for oncotic support. HES molecular weight is about 500,000, whereas the molecular weight for PEG used in organ replacement solutions is more like 20,000. Albumin (which has a molecular weight of about 70,000) provides most of the oncotic support in normal physiology. A PEG with molecular weight of 500,000 would be far too viscous and will form a gel. HES has the benefit of being large enough to always provide oncotic support while being much less viscous than PEG of equivalent molecular weight.

Viaspan (DuPont Merck Pharmaceuticals) contains other ingredients to maintain tissue viability, such as glucose, glutathione, etc. (the full formula can be found on the Viaspan website). Viaspan is FDA approved for preservation of liver, kidney & pancreas, but is used off-label for heart & lung transplants. Viaspan is being challenged in the marketplace for all these applications by the Hypothermosol (Cryomedical Sciences, BioLife Technologies) line of preservation solutions.

Rather than use these expensive commercial products, Alcor and Suspended Animation, Inc. use a preservation solution developed by Jerry Leaf & Mike Darwin called MHP-2. MHP-2 is so-called because it is a Perfusate (P) which contains mannitol (M) as an extracellular osmotic agent and HEPES (H), a buffer to prevent acidosis which is effective at low temperature. MHP-2 also contains ingredients to maintain tissue viability and hydroxyethyl starch as an oncotic agent to prevent edema. Lactobionate permeates cells less than mannitol and can thus maintain osmotic balance for longer periods of time, but mannitol is much less expensive. Mannitol also has an additional effect in the brain. Because of the unique tightness of brain capillary endothelial cell junctions ("blood brain barrier"), little mannitol leaves blood vessels to pass into the brain. This means that mannitol can act like an oncotic agent for the brain. If the blood brain barrier is intact, mannitol will suck water out of the extravascular space. The brain is the only place that mannitol can do this, and that is why a mannitol is effective for inhibiting edema of the brain but only if there is not extensive ischemic damage to the blood brain barrier. (Mannitol has yet another benefit in that it scavenges hydroxyl radical [CHEM.-BIOL. INTERACTIONS 72:229-255 (1989)]).

(For the formula of MHP-2 see TableII of CryoMsg4474 or TableVII of CryoMsg2874 which also contains the formula for Viaspan in TableV.)

The initial perfusate can also contain other ingredients to assist in reducing damage to the cryonics patient. Anticoagulants can reduce clotting problems, and antibiotics can reduce bacterial damage. Damaging effects of ischemia can be reduced with antioxidants, antiacidifiers, an iron chelator and a calcium channel blocker.

Both Alcor and Suspended Animation, Inc. use an Air Transportable Perfusion(ATP) system of equipment which allows them to do blood washout in locations remote from any cryonics facilty by using equipment that can easily be carried on an airplane. There is a video demonstration of an ATP on YouTube.

[For further details on organ preservation solution see ORGAN TRANSPLANTATION SOLUTION]

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Cryoprotectants are used in cryonics to reduce freezing damage by prevention of ice formation (see Vitrification in Cryonics ). Cells are much more permeable to water than they are to cryoprotectant. Platelets & granulocytes, for example, are 4,000 times more permeable to water than they are to glycerol[CRYOBIOLOGY; Armitage,WJ; 23(2):116-125 (1986)]. When a cell is exposed to high-strength cryoprotectant, osmosis causes water to rush out of the cells, causing the cells to shrink. Only very gradually does the cryoprotectant cross cell membranes to enter the cell (the "shrink/swell cycle"). For isolated cells, the halftime (time to halve the difference between a given glycerol concentration in a granulocyte and the maximum possible concentration) is 1.3minutes[EXPERIMENTAL HEMATOLOGY; Dooley,DC; 10(5):423-434 (1982)] but tissues & organs would require more time because their cells are less accessible. Even after equilibration, however, the concentration of glycerol inside neutrophilic granulocytes never rises above 78% of the concentration outside the cells.

As shown in the diagram for mature human oocytes placed in a 1.5molar DMSO solution, the shrink/swell cycle is highly temperature dependent, happening with slower speed of recovery and with greater volume change at lower temperatures[HUMAN REPRODUCTION; Paynter,SJ; 14(9):2338-2342 (1999)]. This creates tough choices in cryonics, because cryoprotectants are more toxic at higher temperatures.

Proliferation of cultured kidney cells declines linearly with increasing osmolality due to urea & NaCl above 300mOsm/kgH2O, but the effect of added glycerol on cell growth is much less[AMERICAN JOURNAL OF PHYSIOLOGY; Michea,L; 278(2):F209-F218 (2000)]. Kidney cells which invivo can tolerate osmolalities of around 300mOsm/kgH2O do not survive over 300mOsm/kgH2O invitro, possibly because of more rapid proliferation[PHYSIOLOGICAL REVIEWS; Burg,MB; 87(4):1441-1474 (2007)].

Cells subjected to high levels of cryoprotectants can be damaged by osmotic stress. Quantifying osmotic damage has been a challenge for experimentalists who must distinguish between electrolyte damage, cryoprotectant toxicity, cell volume effects and osmotic stress. Concerning the last two, osmotic damage due to cell shrinkage may be distinguished from osmotic damage as a result of the speed at which the cryoprotectant crosses the cell membrane, ie, by the membrane permeability to the cryoprotectant. Cryoprotectants with lower permeabilities can cause more osmotic stress than cryoprotectants with high permeability.

Membrane permeabilities of a variety of nonelectrolytes (including cryoprotectants) have been studied on a number of cell types, including human blood cells[THE JOURNAL OF GENERAL PHYSIOLOGY; Naccache,P; 62(6):714-736 (1973)]. Critical factors determining membrane permeability are lipid solubility of the substance (which increases permeability) and hydrogen bonding (which decreases permeability). In general, permeability decreases as the molecular size of the substance increases. In contrast to blood cells, human sperm is more than three times more permeable to glycerol than to DMSO[BIOLOGY OF REPRODUCTION; Gilmore,JA; 53(5):985-995 (1995)]. For both blood cells and sperm cells permeability to ethylene glycol is very high compared to the other common cryoprotectants. Yet for mature human oocytes propylene glycol has the highest permeability and ethylene glycol has the lowest permeability of the most commonly used oocyte cryoprotectants[HUMAN REPRODUCTION; Van den Abbeel,E; 22(7):1959-1972 (2007)]. In contrast to human oocytes, however, for mouse oocytes ethylene glycol(EG) permeability is comparable to that of DMSO, propylene glycol(PG), and acetamide(AA), but not glycerol(Gly)[JOURNAL OF REPRODUCTION AND DEVELOPMENT; Pedro,PB; 51(2):235-246 (2005)].

Water and cryoprotectants both cross cell membranes more slowly at lower temperatures. Cryoprotectants slow the passage of water across cell membranes. Glycerol, DMSO and ethylene glycol all reduce the rate at which water crosses human sperm cell membranes by more than half[BIOLOGY OF REPRODUCTION; Gilmore,JA; 53(5):985-995 (1995)].

Aside from the choice of cryoprotectants, a major concern is the way cryoprotectant is administered. For example, glycerol (the standard cryoprotectant used in cryonics for many years) can either be administered full-strength or it can be introduced in gradually increasing concentrations. Under optimum conditions, glycerol results in 80% vitrification and 20% ice formation. Glycerol has been replaced by better cryoprotectants that can vitrify without any ice formation, but I will typically use glycerol as my example cryoprotectant. A patient should probably not be perfused with a 100% solution of glycerol or other cryoprotectant because of the possibility of osmotic damage. It is prudent to begin perfusion with low concentrations of cryoprotectant because water can diffuse out of cells thousands of times more rapidly than cryoprotectant diffuses into cells. Using gradually increasing concentrations of cryoprotectant (ramping) prevents the osmotic damage this differential could cause.

Human granulocytes (which are more vulnerable to osmotic stress or shrinkage than most other cell types) can experience up to 600mOsm/kgH2O hypertonic solution (which shrinks cells to 68% of normal cell volume) for 5minutes at 0C with no more than 10% of the cells losing membrane integrity. But at about 750mOsm/kgH2O (NaCl) or 950mOsm/kgH2O (sucrose) less than half of granulocytes display intact membranes when returned to isotonic solution. Nonetheless, the cells did not display lysis if retained in hyperosmotic medium. In fact, granulocytes could tolerate up to 1400mOsm/kgH2O if not subsequently diluted to less than 600mOsm/kgH2O[AMERICAN JOURNAL OF PHYSIOLOGY; Armitage WJ; 247(5Pt1):C373-381 (1984)]. A subsequent confirming study showed that rehydration of PC3 cells shrunken by NaCl solution creates more osmotic damage than the initial dehydration[CRYOBIOLOGY; Zawlodzka,S; 50(1):58-70 (2005)]. Cell survival after rehydration was higher at 0C than at 23C.

Although toxic effects of 2M (17%w/w) glycerol on granulocytes are quite evident at 22C, almost no toxic effect is seen at 0C[CRYOBIOLOGY; Frim,J; 20(6):657-676 (1983)]. For no mammalian cells other than granulocytes is 2Molar glycerol toxic. Nonetheless, abrupt addition of only 0.5Molar glycerol at 0C resulted in only 40% of granulocytes surviving when slowly diluted to isotonic solution and warmed to 37C. Only 20% of granulocytes survived this treatment when 1Molar or 2Molar glycerol were added (there was no difference in survival between the two concentrations). But if sucrose or NaCl was added to keep the granulocytes shrunken to 60% of normal cell volume, almost all granulocytes survived when incubated to 37C. Insofar as the transient shrinkage of granulocytes due to glycerol is not less than 85% of normal cell volume, it seems unlikely that cell shrinkage can account for the damage[AMERICAN JOURNAL OF PHYSIOLOGY; Armitage WJ; 247(5Pt1):C382-389 (1984)].

Human spermatazoa tolerate much higher osmolality than granulocytes. Sperm cells can experience up to 1000mOsm/kgH2O hypertonic solution for 5minutes at 0C with no more than 10% of the cells losing membrane integrity. At about 1500mOsm/kgH2O (NaCl, white circles) or 2500mOsm/kgH2O (sucrose, black circles) less than half of sperm cells display intact membranes when returned to isotonic conditions. But 80% of sperm cells showed intact cell membrane after exposure to 2500mOsm/kgH2O at 0C if maintained at hypertonicity rather than restored to isotonic solution (NaCl & sucrose, triangles). Sperm cells gradually returned to isotonic solution following exposure to 1.5Molar glycerol at 22C showed only 3% lysis, whereas 20% of sperm cells lysed if the return to isotonic was sudden. No lysis was seen for sperm not returned to isotonic medium. At nearly 5000mOsm/kgH2O glycerol (about 4.5Molar) 17% of sperm cells showed lysis (had loss of membrane integrity) at 0C and 10% had lysis at 8C if not returned to isotonic media[BIOLOGY OF REPRODUCTION; Gao,DY; 49(1):112-123 (1993)]. For cryonics purposes it would be best to maintain cells in a hypertonic condition to maximize potential viability during cryogenic storage.

Cells from mouse kidney (IMCD, Inner Medullary Collecting Duct) can be killed by NaCl or urea that is 700mOsm/kgH2O, but the death is apoptotic and takes up to 24hours. The IMCD cells can tolerate up to 900mOsm/kgH2O of urea and NaCl in combination because of activation of complementary cellular defenses (including heat-shock protein)[ AMERICAN JOURNAL OF PHYSIOLOGY; Santos,BC; 274(6):F1167-F1173 1998)].

Nearly half of mouse fibroblasts displayed cell membrane lysis after restoration to isotonicity following exposure to the equivalent of 3600mOsm/kgH2O of osmotic stress from rapid addition of 4Molar (30%w/w) DMSO at 0C. Few cells were damaged by slow addition of the DMSO[BIOPHYSICAL JOURNAL; Muldrew,K; 57(3):525-532 (1990)].

Human corneal epithelial cells could tolerate 4.3M (37%w/w) glycerol with only 2% cell loss at 4C if the cells were subjected to gradually increasing (ramped) concentration (doubling osmolality in about 13minutes), but for stepped increases of 0.5M every 5minutes above 2M (17%w/w) to 3.5M (30%w/w) glycerol at 0C there was a 27% cell loss. For the same ramped method with DMSO there was a 6% cell loss at 2M (15%w/w) and a 15% cell loss at 3M (23%w/w). The same stepped method for DMSO resulted in a 1.5% cell loss for cells stepped from 2M to 3.5M (27%w/w) and a 22% cell loss for cells stepped from 2M to 4.3M (33%w/w). In all cases cell viability was assessed after washout and three days of incubation at 37C[CRYOBIOLOGY; Bourne,WM; 31(1):1-9 (1994)]. (Conversion of glycerol molarity to %w/w was approximated by multiplying by 8.6 and for DMSO was approximated by multiplying by 7.6)

In the context of cryonics it should be remembered that cells are not being returned to body temperature and need not be returned to isotonicity before cryoopreservation. There would be little time for apoptosis, and most cells would be far better preserved at low temperature and in hyperosmolar solution. Future technologies may be able to prevent apoptosis and have better methods for restoring irreplaceable cells to normal temperatures and osmolalities. For neurons, even abrupt stepped perfusion with cryoprotectant is likely to effectively result in ramped perfusion when allowances are made for the diffusion times required across blood vessels (blood brain barrier) and interstitial space. A more worrisome effect from the point of view of cryonic cryoprotectant perfusion is the effect of the cryoprotectants on vessel endothelial cells notably the effect on edema and vascular compliance.

Cell shrinkage may directly damage the cell (and cell membrane) due to structural resistance from the cell cytoskeleton and high compression of other cell constituents[HUMAN REPRODUCTION; Gao,DY; 10(5):1109-1122 (1995)]. Aside from membrane damage, other forms of cellular damage occur due to hypertonic environments, including cross-linking of intracellular proteins subsequent to cell dehydration. Bull sperm lose motility (often only temporarily) in a less hypertonic medium than one causing membrane damage[JOURNAL OF DAIRY SCIENCE; Liu,Z; 81(7):1868-1873 (1998)]. Osmotic stress can depress mitochondrial membrane potential in a manner that is mostly reversible after restoration to isotonic conditions[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Desai,BN; 99(7):4319-4324 (2002)]. Human oocytes subjected to 600mOsm/kgH2O sucrose showed 44% of metaphaseII spindles having abnormalities[HUMAN REPRODUCTION; Mullen,SF; 19(5):1148-1154 (2004)]. Hypertonic solutions can trigger apoptosis[AMERICAN JOURNAL OF PHYSIOLOGY; Copp,J; 288(2):C403-C415 (2005)].

Despite these other types of damage due to hyperosmolality, the greatest risks in cryoprotectant perfusion in cryonics are those associated with membrane damage and edema due to cell swelling. The evidence that maintaining hypertonicity is more protective of cells than returning to isotonic conditions, and the desire to minimize edema during perfusion seem to make it advisable in cryonics to perfuse in hypertonic conditions.

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Once the patient is at the cryonics facility the transport solution can be replaced with a cryoprotectant solution. A perfusion temperature of 10C gives the best tradeoff of avoiding the high viscosity of lower temperatures and at the same time limiting the ischemic tissue degradation, chilling injury, and cryoprotectant toxicity that would be seen at higher temperatures. (Cryonicists usually worry more about ischemic damage than cryoprotectant toxicity due to a belief that ischemic damage has a greater likelihood of being irreversible irreparable by future molecular-repair technology.)

Cryoprotectants should be sterilized to prevent the growth of bacteria. Sterilization of cryoprotectants by heating can cause the formation of carbon-carbon double-bonds, which are evident by a yellowing of the cryoprotectant. Only a few such double-bonds can produce the yellow appearance, so the fact of yellowing is not evidence that the cryoprotectant is no longer serviceable. But a preferable method of cryoprotectant sterilization is filtration through a 0.2micron filter.

Rapid addition of cryoprotectant causes endothelial cells to shrink thereby breaking the junctions between the cells[CRYOBIOLOGY; Pollock,GA,; 23(6):500-511 (1986)]. On the other hand, endothelial cell shrinkage by hypertonic perfusate can increase capillary volume, thereby increasing blood flow as long as excessive vascular damage does not occur. Blood and clots are often observed to be dislodged during cryoprotectant perfusion in cryonics cases. For cryonics purposes some vascular damage may actually be an advantage insofar as it increases diffusion and vascular repair may be an easy task for future science. In fact, the breakdown of the blood-brain barrier in the 1.8-2.2 molar glycerol range is essential for perfusion of the brain as long as damaging tissue edema (swelling) can be avoided. Aquaporin (water channel) expression in the blood-brain barrier could be a safer means of allowing cryoprotectants into the brain[CRYOBIOLOGY; Yamaji,Y; 53(2):258-267 (2006)].

Closed-circuit perfusion (with perfusion solution following a circuit both inside & outside the patient's body) is contrasted with the open-circuit perfusion used by funeral directors for embalming. In the open-circuit perfusion of embalming, fluid is pumped into a large artery of the corpse and forces-out blood from a large vein and this blood is discarded.

A closed-circuit perfusion, as illustrated in the diagram, can be set up at low cost for gradual introduction of cryoprotectant into cryonics patients. As shown in the diagram, the perfusion circuit bypasses the heart. Perfusate enters the patient through a cannula in the femoral (leg) artery and exits from a cannula in the femoral vein on the same leg. Flowing upwards (opposite from the usual direction) from the femoral artery and up through the descending aorta, the perfusate enters the arch of the aorta (where blood normally exits the heart), but is blocked from entering the heart. Instead, the perfusate flows (in the usual direction) through the distribution arteries of the aorta, notably to the head and brain. Returning in the veins (in the usual direction), the perfusate nontheless again bypasses the heart and flows downward (opposite from the usual direction) to the femoral vein where it exits. A better alternative to the femoral circuit, however, is to surgically open the chest to cannulate the heart aorta (for input) and atrium (for output).

Although it is not shown in the diagram, there will be a pump in the circuit to maintain pressure and fluid movement. A roller pump, rather than an embalmer's pump, should be used. A roller pump achieves pumping action by the use of rollers on the exterior of flexible tubing that forces fluids through the tube without contaminating those fluids. Embalmer's pumps may use pressures much higher than those suitable for cryonics, resulting in blood vessel damage. Embalmer's pumps are also easily contaminated (and hard to clean), unless a filter is used. Contamination doesn't matter much in embalming, but in cryonics contaminants entering the patient through the pump can damage blood vessels, interfering with perfusion. If an embalmer's pump is used for cryonics purposes, ensure that the pressure can be lowered to a suitable level and that it is cleaned and sterilized. The main advantage of roller pumps, however, is the fact that they provide a closed circuit, whereas embalmer's pumps are open-circuit. Roller pumps are generally calibrated in litres per minute. Depending on the viscosity of the solution, a flow rate of 0.5 to 1.5litres per minute will be necessary to achieve the desired perfusion pressure of approximately 80mmHg to 120mmHg (physiological pressures).

Gaseous and particulate microemboli can produce ischemia in capillaries and arterioles. A study of patients having routine cardiopulmonary bypass surgery showed that 16% fewer patients had neuropsychological deficits eight weeks after the surgery when a 40micrometer arterial line filer had been used[STROKE; Pugsley,W; 25(7):1393-1399 (1994)]. Both roller pumps (peristaltic pumps) and centrifugal pumps can generate particles up to 25micrometers in diameter through spallation, although centrifugal pumps generate fewer particles[PERFUSION; Merkle,F; 18(suppl1):81-88 (2003)]. Filtration of perfusate with a 0.2micrometer filter prior to perfusion is a recommended way of removing potential microemboli, including bacteria. At room temperature 20micrometer diameter air bubbles take 1to6seconds to dissolve in water, although high flow rates and turbulence can increase microbubble formation[SEMINARS IN DIALYSIS; Barak,M; 21(3):232-238 (2008)]. De-airing of tubing before perfusion considerably reduces the possibility of microbubbles entering the patient[THE THORACIC AND CARDIOVASCULAR SURGEON; Stock,UA; 54(1):39-41 (2006)].

Mean Arterial Pressure (MAP) for an normal adult is regarded as being in the range of 50 to 150mmHg, and Cerebral Perfusion Pressure (CPP) is in the same range[BRITISH JOURNAL OF ANAETHESIA; Steiner,LA; 91(1):26-38 (2006)]. Vascular pressure normally drops to about 40mmHg in the arterioles, to below 30mmHg entering the capillaries, and is down to 3 to 6mmHg (Central Venous Pressure, CVP) when returning to the right atrium of the heart. Perfusing a cryonics patient at about 120mmHg should open capillaries adequately for good cryoprotectant tissue saturation without damaging fragile blood vessels.

Outside the patient, some of the drainage is discarded, but most is returned to a circulating (stirred) reservoir connected to a concentrated reservoir of cryoprotectant. The circulating reservoir is initially carrier solution which gradually becomes increasingly concentrated with cryoprotectant as the stirring and recirculation proceed. The circulating reservoir can be stirred from the bottom by a magnetic stir bar on a stir table and/or from the top by an eggbeater-type stirring device. The stirring will draw cryoprotectant from the cryoprotectant reservoir, and pumping of the perfusate should also actively draw liquid from the cryoprotectant reservoir. Gradually a higher and higher concentration of cryoprotectant is included in the perfusate and the osmotic shock of full-strength cryoprotectant is avoided.

The carrier solution for the cryoprotectant should perform similar tissue preservation functions as is performed by the transport solution, and should be carefully mixed with the cryoprotectant so as to avoid deviations from isotonicity which could result in dehydration or swelling & bursting of cells. The carrier solution will help keep cells alive during cryoprotectant perfusion.

An excellent carrier solution for cryonics purposes would be RPS-2 (Renal Preservation Solution number2), which was developed by Dr. Gregory Fahy in 1981 as a result of studies on kidney slices. More recently Dr. Fahy used RPS-2 as the carrier solution in cryopreserving hippocampal slices an indication that it is well-suited for brain tissue as well as for kidney. RPS-2 not only helps maintain hippocampal slice viability, it reduces the amount of cryoprotectant needed because it has cryoprotectant (colligative) properties of its own. The formulation of RPS-2 is: K2HPO4, 7.2mM; reduced glutathione, 5mM; adenine HCl, 1mM; dextrose, 180mM; KCl, 28.2mM; NaHCO3, 10mM; plus calcium & magnesium[CRYOBIOLOGY; Fahy,GM; 27(5):492-510 (1990)]. LM5 (Lactose-Mannitol5) is a carrier solution for use in vitrification solutions that include ice blockers. LM5 does not contain dextrose, which is believed to interfere with ice blockers.

The cryoprotectant reservoir will not in general contain pure cryoprotectant (although in principle it could), but rather a "terminal concentration" solution of cryoprotectant that is equal or slightly above the final target concentration. As perfusion proceeds and drainage to discard proceeds, the level of both reservoirs drops in tandem until both reservoirs are nearly empty, at which point the circuit concentration will have reached the cryoprotectant reservoir concentration. Provided that the two reservoirs are the same size and same vertical elevation, the gradient will be linear over time (if the drainage rate to discard was constant).

For cryoprotectant to perfuse into cells there must be constant exposure to cryoprotectant surrounding the cells and there must be pressure to maintain that exposure. In a living animal the heart maintains blood pressure that forces blood through the capillaries and forces nutrients into cells. A dead animal with no blood pressure and which is being perfused with cryoprotectant also requires pressure for the capillaries to remain open and for cryoprotectant to be maintained at high concentrations around cells.

Alcor found that closed-circuit perfusion must be maintained for 5-7 hours for full equilibration of glycerol, because the diffusion rate of water out of cells is thousands of times the rate at which glycerol enters cells. Of course, it would be possible to pump glycerol into a patient for 5-7 hours with open-circuit perfusion, but only by using thousands of dollars worth of glycerol. The newer vitrification cryoprotectants used by Alcor are vastly more expensive than glycerol. When using expensive cryoprotectants it makes far more sense to recirculate in a closed circuit. Closed-circuit perfusion also has the benefit of allowing for ongoing monitoring of physiological changes occurring in the patient's body during the perfusion process. Open-circuit with an inexpensive cryoprotectant has the advantage of avoiding recirculation of toxins.

Cryoprotectants, particularly glycerol, are viscous and cryoprotectants in high concentration are particularly viscous. The introduction of air bubbles into cryoprotectant solutions during pouring and mixing should be avoided because air emboli that enter the cryonics patient can block perfusion. Elimination of air bubbles from viscous cryoprotectant solutions is extremely difficult. Prevention is more effective than cure. Cryonicist Mike Darwin wrote about this problem and possible solutions in a 1994 CryoNet message.

Improper mixing of perfusate containing high levels of cryoprotectant can result in a phenomenon that appears to be high viscosity, but in reality is edema. If, for example, isotonic carrier solution is mixed half-and-half with cryoprotectant solution an open circuit perfusion may have to be halted when no further perfusate will go into the patient. The problem is caused not by viscosity, but by the fact that the isotonic solution became hypotonic due to dilution with cryoprotectant causing the cells to swell and forcing perfusion to end. In closed-circuit perfusion, the cryoprotectant concentrate reservoir contains cryoprotectant at about 125% the terminal concentration in a vehicle of isotonic carrier solution so that when reservoir concentrate is mixed with isotonic carrier there is no change in tonicity.

Newer cryoprotectants are less viscous than glycerol, so perfusions can be done in less time. After 15 minutes of perfusion with carrier solution, cryoprotectant concentration linearly increases at a rate of 50millimolar per minute until full concentration is reached in about two hours (a protocol developed on the basis of minimizing osmotic damage when perfusing kidneys). Perfusion is increased for an additional hour or two until the cryoprotectant has fully diffused into cells (as indicated by similarity of afflux and efflux cryoprotectant concentrations).

Only after a few hours of closed-circuit perfusion is the concentration of cryoprotectant exiting the cryonics patient equal to the concentration of cryoprotectant entering the patient. Only an extended period of sustained pressure will keep capillaries open, and otherwise facilitate diffusion of cryoprotectant into cells. And the exiting cryoprotectant concentration will equal the entering cryoprotectant concentration only when the tissues are fully loaded with cryoprotectant. A refractometer is used to verify that terminal cryoprotectant concentration has been reached in the brain.

(A refractometer measures the index of refraction of a liquid, ie, the ratio of the speed of light in the liquid and the speed of light in a vacuum (or air). Light changes speed when it strikes the boundary of two media, thus causing a change in angle if it strikes the new medium at an angle. Because the refractive index is a ratio of two quantities having the same units, it is unitless. Sodium vapor in an electric arc produces an excitation between the 3s and 3p orbitals resulting in yellow-orange light of 589nm what Joseph Fraunhofer called the "Dline". Insofar as the sodium "Dline" was the first convenient source of monochromatic light, it became the standard for refractometry. The refractive index of a liquid is thus a high-precision 5-digit number between 1.3000 and 1.7000 at a specific temperature, measured at the sodium Dline wavelength. For example, the refractive index of glycerol at 25C nD25 is 1.4730.)

Closed-circuit perfusion may be necessary for removal of water as well as loading of cryoprotectant if it is true that open-circuit perfusion cannot remove water effectively.

One could imagine that the additional time spent doing closed-circuit (rather than open-circuit) perfusion means increased damage due to above-zero temperature. But most cells are still alive and metabolizing very slowly at 10C. Viaspan, RPS-2 and other organ preservation solutions are designed to keep tissues alive for extended periods at near-zero temperatures certainly for the time required for closed-circuit perfusion. Ramping (slowly increasing concentration) of cryoprotectant should be done in such a way that the ion and mannitol or lactobionate concentration remains unchanged in the perfusate. Ramping is not an osmotically neutral process, however, because cryoprotectant is expected to dehydrate tissues.

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Can A Human Be Frozen And Brought Back To Life? – Zidbits

Can A Human Be Frozen And Brought Back To Life?

We see it all the time in movies. A person gets frozen or put in cryosleep and then unfrozen at a later date with no aging taking place, or other ill effects.

Sometimes this happens on purpose, like to someone with an incurable disease hoping a cure exists in the future, or sometimes by accident, like someone getting frozen in a glacier.

The science behind it does exist and the application of the practice is called cryonics. Its a technique used to store a persons body at an extremely low temperature with the hope of one day reviving them. This technique is being performed today, but the technology behind it is still in its infancy.

Someone preserved this way is said to be in cryonic suspension. The hope is that, if someone has died from a disease or condition that is currently incurable, they can be frozen and then revived in the future when a cure has been discovered.

Its currently illegal to perform cryonic suspension on someone who is still alive. Those who wish to be cryogenically frozen must first be pronounced legally dead which means their heart has stopped beating. Though, if theyre dead, how can they ever be revived?

According to companies who perform the procedure, legally dead is not the same as totally dead. Total death, they claim, is the point at which all brain function ceases. They claim that the difference is based on the fact that some cellular brain function remains even after the heart has stopped beating. Cryonics preserves some of that cell function so that, at least theoretically, the person can be brought back to life at a later date.

After your heart stops beating and you are pronounced legally dead, the company you signed with takes over. An emergency response team from the facility immediately gets to work. They stabilize your body by supplying your brain with enough oxygen and blood to preserve minimal function until you can be transported to the suspension facility. Your body is packed in ice and injected with an anticoagulant to prevent your blood from clotting during the trip. A medical team is on standby awaiting the arrival of your body at the cryonics facility.

After you reach the cryonics facility, the actual freezing can begin.

They could, and while youd certainly be frozen, most of the cells in your body would shatter and die.

As water freezes, it expands. Since cells are made up of mostly water, freezing expands the stuff inside which destroys their cell walls and they die. The cryonics companies need to remove and/or replace this water. They replace it with something called a cryoprotectant. Much like the antifreeze in an automobile. This glycerol based mixture protects your organ tissues by hindering the formation of ice crystals. This process is called vitrification and allows cells to live in a sort of suspended animation.

After the vitrification, your body is cooled with dry ice until it reaches -202 Fahrenheit. After this pre-cooling, its finally time to insert your body into the individual container that will be placed into a metal tank filled with liquid nitrogen. This will cool the body down to a temperature of around -320 degrees Fahrenheit.

The procedure isnt cheap. It can cost up to $200,000 to have your whole body preserved. For the more frugal optimist, a mere $60,000 will preserve your brain with an option known as neurosuspension. They hope the technology in the future will allow them to clone or regenerate the rest of the body.

Many critics say the companies that perform cryonics are simply ripping off customers with the dream of immortality and they wont deliver. It doesnt help that the scientists who perform cryonics say they havent successfully revived anyone, and dont expect to be able to do so anytime soon. The largest hurdle is that, if the warming process isnt done at exactly the right speed and temperature, the cells could form ice crystals and shatter.

Despite the fact that no human placed in a cryonic suspension has yet been revived, some living organisms can be, and have been, brought back from a dead or near-dead state. CPR and Defibrillators can bring accident and heart attack victims back from the dead daily.

Neurosurgeons often cool patients bodies so they can operate on aneurysms without damaging or rupturing the nearby blood vessels. Human embryos that are frozen in fertility clinics, defrosted and implanted in a mothers uterus grow into perfectly normal human beings. Some frogs and other amphibians have a protein manufactured by their cells that act as a natural antifreeze which can protect them if theyre frozen completely solid.

Cryobiologists are hopeful that nanotechnology will make revival possible someday. Nanotechnology can use microscopic machines to manipulate single atoms to build or repair virtually anything, including human cells and tissues. They hope one day, nanotechnology will repair not only the cellular damage caused by the freezing process, but also the damage caused by aging and disease.

Some cryobiologists have predicted that the first cryonic revival might occur as early as year 2045.

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Can A Human Be Frozen And Brought Back To Life? - Zidbits

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Rudi Hoffman – Certified Financial Planner, Cryonics …

by Rudi Hoffman, CFP

I expect to have the money to fund my suspension in cash eventually. Mr. Hoffman, why should I take out a life insurance policy to fund my suspension?

This question in some form comes up often in discussions with people with an interest in cryopreservation. The good news is that there may be valid answers that may make sense in individual situations.

The purpose of this article is to answer this question in a clear, concise, understandable manner. Additionally, we will look for an empirical way of determining the optimum funding that can be appealing to many rationally minded cryonicists.

Lets personalize this with a discussion of a hypothetical individual Jack who is a 45 year old software developer.

Okay, Jack, so you want to be cryogenically frozen with the possibility of future re-animation. You have thought about it for some time, but you are of a skeptical and questioning nature, and you have a consituency in the form of a wife and family who are not at all sure if you have not gone off the deep end and do not share your enthusiasm for the possibilities of technology.

You want to create $150,000 to fund the costs of standby, transportation, and cryonic suspension with a cryonics organization. You are excited because your savings investment has been growing well, your career is taking off, and you expect to be seriously wealthy in the future. You want to do the best thing to assure your funding. You have negotiated with your wife, and you and she have decided that you can spend $1200 dollars per year towards cryonics funding.

Here is the key question. Is is better for Jack to spend his 100 dollars per month in a savings investment, or a life insurance policy, to fund his suspension?

Here are the facts. Jack, a healthy nonsmoker, can create an INSTANT $150,000 to fund his suspension in a permanent Universal Life policy. Once he pays 100 bucks and qualifies, there is an IMMEDIATE and SURE payment to his cryonics organization to assure his suspension. The money does not go the cryonics organization at the expense of the survivors. This $150,000 does not have to come out of the estate Jack is leaving for his wife Mary and the children. Nor do they have the opportunity of second guessing Jacks choice and delaying or litigating Jacks wishes.

On the other hand, lets say Jack puts his $100 dollars per month into a savings investment. Even if he averages a great return, it will take decades to generate the required $150,000. What happens if Jack is struck by a truck on the way to work tomorrow? There is no full funding, and Jack will not be suspended.

What if Jack lives long enough to have adequate funding in his account? When Jack dies there is $150,000 which Jack has earmarked for his suspension. But this $150,000 is a much clearer target for any of Jacks potential heirs to contest.

Jacks kids all turned out great. Except for the youngest, Leroy, who felt the world owed him a living. Jack had left each his children $200,000 in his will. But Leroy wanted at least part of the $150,000 Jack had earmarked for suspension! Do you think Leroy could find an attorney who would take this case? Could the money be tied up in a legal battle? Do will and estate contests occur over much less controversial issues than funding cryostasis? Absolutely! And these funding controversies HAVE and WILL CONTINUE to occur.

There are other issues. If Jack is not insurable due to health reasons, he will not be able to obtain life insurance to fund his suspension, and he would be forced to fund his suspension from his estate.

Some people become uninsurable at some point in their lives. It therefore makes sense to find out how affordable it may be to fund your suspension with the financial leverage that life insurance can provide. It the case of cryonicists, the policy may truly become LIFE insurance not DEATH insurance.

Cryonicists tend to be life extensionists who take great care of themselves and thereby can usually qualify for the best possible insurance rates. (Ispend a good deal of time explaining this information to insurance companies!)

In conclusion, for many people it may make sense to use life insurance to fund the exciting possibilities of cryonic suspension.

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Rudi Hoffman - Certified Financial Planner, Cryonics ...

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Cryonics – Merkle

Read the Alcor Membership page and follow the instructions. Most members use life insurance to pay for their cryopreservation. Rudi Hoffman has written most of the life insurance policies in the cryonics community.

If you're interested, but not quite ready to sign up, become an Associate Member.

A common misconception is that cryonics freezes the dead. As the definition of "death" is "a permanent cessation of all vital functions" the future ability to revive a patient preserved with today's technology implies the patient wasn't dead. Cryonics is actually based on the more plausible idea that present medical practice has erred in declaring a patient "dead." A second opinion from a future physician one with access to a fundamentally better medical technology based on a mature nanotechnology lets us avoid the unpleasant risk that we might bury someone alive.

The major reason that cryonics is not more favorably viewed in the medical community is relatively easy to explain. Medicine relies on clinical trials. Put more simply, if someone proposes a technique for saving lives, the response is "Try it and see if it works." Methods that have not been verified by clinical trials are called "experimental," while methods that have been tried and failed are rejected.

In keeping with this tradition, we would like to conduct clinical trials of the effectiveness of cryopreservation to determine whether it does (or does not) work. The appropriate trials can be easily described. Cryonics proposes to cryopreserve people with today's technology in the expectation that medical technology of (say) the year 2115 will be able to cure them. Thus, the appropriate clinical trials would be to:

While this problem is not entirely unique to cryonics (the plight of a dying patient who wishes to know whether or not to take a new experimental treatment is well known), cryonics poses it in a qualitatively more severe fashion: we must wait longer to determine the outcome and we have no preliminary results to provide a clue about what that outcome might be. If a new treatment is being tested we normally have the results of animal trials and perhaps some preliminary results from human patients. Further, we expect to get reliable results within a small number of years. In the case of cryonics, we are quite literally awaiting the development of an entirely new medical technology. Preliminary results, even on experimental animals, are simply not available; and the final results won't be available for several decades.

Thus, while we can begin the clinical trials required to evaluate cryonics today, clinical trials cannot provide a timely answer about the effectiveness of cryonics. It is not possible (utilizing the paradigm of clinical trials) to draw conclusions today about whether physicians tomorrow will (or will not) be able to revive someone who was cryopreserved using today's technology.

The correct scientific answer to the question "Does cryonics work?" is: "The clinical trials are in progress. Come back in a century and we'll give you a reliable answer." The relevant question for those of us who don't expect to live that long is: "Would I rather be in the control group, or the experimental group?" We are forced by circumstances to answer that question without the benefit of knowing the results of the clinical trials.

When we think about this question, it is important to understand that future medical technology will be no mere incremental or evolutionary advance over today's medicine. Think of Hippocrates, the prehistoric Greek physician, watching a modern heart transplant. Advances in medical technology in future decades and centuries will be even more remarkable than the advances we have already seen in centuries past. At some point in the future almost any infirmity that could in principle be treated is likely to be treatable in practice as well. In principle, the coming ability to arrange and rearrange molecular and cellular structure in almost any way consistent with physical law will let us repair or replace almost any tissue in the human body. Whether it's a new liver, a more vital heart, a restored circulatory system, removing some cancerous cells, or some other treatment -- at some point, nanomedicine should let us revitalize the entire human body and even revive someone who was cryopreserved today.

How might we evaluate cryonics? Broadly speaking, there are two available courses of action: (1) sign up or (2) do nothing. And there are two possible outcomes: (1) it works or (2) it doesn't. This leads to the payoff matrix to the right. In using such a payoff matrix to evaluate the possible outcomes, we must decide what value the different outcomes have. What value do we place on a long and healthy life?

When evaluating the possible outcomes, it's important to understand that if you sign up and it works, that "Live" does not mean a long, wretched and miserable life. Many people fear they will wake up, but still suffer from the infirmities and morbidities that the elderly suffer from today. This is implausible for two very good reasons. First, the kinds of medical technologies that are required to restore today's cryonics patients will be able to restore and maintain good health for an indefinite period. The infirmities of old age will go the way of smallpox, black death, consumption, and the other scourges that once plagued humanity. Second, as long as we are unable to restore cryopreserved patients to satisfactory good physical and mental health, we'll keep them cryopreserved until we develop better medical technologies. To put these two points another way, when that future day arrives when we have a medical technology that can revive a patient who was dying of cancer today, and was cryopreserved with today's technology, that same medical technology should be able to cure their senile dementia and restore their musculature; they'll walk out into a future world healthy in mind and body. In the unlikely case it can't, we'll keep our patients in liquid nitrogen until we develop a medical technology that can.

It's also important to understand that technology is moving rapidly, and accelerating. When you wake up, your children and your younger friends and acquaintances are likely to be alive and well, along with most of your awakened friends from the cryonics community. While several decades might have passed, your social network within the cryonics community will still be there and likely many of the younger members of the rest of your social network.

While different people will answer these questions in different ways, this provides a useful framework in which to consider the problem.

At some point in the future we will have direct experimental proof that today's cryopreserved patients either can or cannot be revived by future medical technology. Unfortunately, most of us must decide today if we wish to pursue this option. If we wish to gain some insight today about the chance that cryonics will or will not work we must consider several factors, including most prominently (a) the kinds of damage that are likely to occur during cryopreservation and (b) the kinds of damage that future medical technologies might reasonably be able to repair. Those interested in pursuing this subject should read this web page which discusses the chances of success and The Molecular Repair of the Brain.

Recent coverage of cryonics is available from Google news.

There has been much discussion of cryonics in the blogosphere, notably including discussions at Overcoming Bias and Less Wrong. Ciphergoth has sought articles critical of cryonics.

California Magazine, Summer 2015, "Into the Deep Freeze: What Kind of Person Chooses to Get Cryonically Preserved?" "[Max] More [Alcor's President] comes across as a reasonable man who is acutely aware that most people think his ideas are insane, or repugnant, or both. Like most of the cryonicists I spoke to, he frames his points as appeals to logic, not emotion. His confidence is infectious."

Hopes & Fears, May 11, 2015, "I freeze people's brains for a living" "For me, cryopreservation was an obvious mechanical problem. Youve got molecules; why not lock them in place so that somebody can fix them later?" "I was an ENT physician, but I havent practiced for about five years now. I still have my license. My participation in the cryonics field happened very gradually."

ESPN, May 5, 2015, "The Greatest Hitter Who Ever Lived On" "In her book, Claudia writes what her father told the doctor. ... I'd like to have some more time with my two kids. "

Specter Defied, April 25, 2015, "How to sign up for Alcor cryo" "This article is intended for those who already think cryopreservation is a good idea but are putting it off since they don't know exactly what needs to be done."

The Dr. Oz Show, March 10, 2015, "Why Larry King Wants to Freeze His Body" "I think when you die, that's it. And I don't want it to be it. I want to be around. So I figure the only chance I have is to be frozen. And then, if they cure whatever I died of, I come back."

The List, March 12, 2015, "Live Forever by Freezing Your Body" "First and foremost I look forward to the future, I think it's going to be a great place. I want to live as long as possible." "Many pay for their cryonic treatment by naming the company itself, Alcor, as their life insurance beneficiary."

The Journal of Medical Ethics, February 25, 2015, "The case for cryonics" " insofar as the alternatives to cryonics are burial or cremation, and thus certain, irreversible death, even small chances for success can be sufficient to make opting for cryonics a rational choice."

The Onion, October 15, 2014, "Facebook Offers To Freeze Female EmployeesNewborn Children" "We recognize the many challenges women face starting a family and balancing a career, which is why our company will provide extensive support to female employees who want to preserve their infant in a frozen state of suspended animation until theyre ready for child-rearing, said Facebook spokesperson Mary Copperman, ..."

The Atlantic, August 26, 2014, "For $200,000, This Lab Will Swap Your Body's Blood for Antifreeze" "Cryopreservation is a darling of the futurist community. The general premise is simple: Medicine is continually getting better. Those who die today could be cured tomorrow. Cryonics is a way to bridge the gap between todays medicine and tomorrows."

The Huffington Post, June 23, 2014, "Should Cryonics, Cryothanasia, and Transhumanism Be Part of the Euthanasia Debate?" "Approximately 40 million people around the world have some form of dementia, according to a World Health Organization report. About 70 percent of those suffer from Alzheimer's. With average lifespans increasing due to rapidly improving longevity science, what are people with these maladies to do? Do those with severe cases want to be kept alive for years or even decades in a debilitated mental state just because modern medicine can do it?" "In the 21st Century--the age of transhumanism and brilliant scientific achievement--the question should be asked: Are there other ways to approach this sensitive issue?" "Recently, some transhumanists have advocated for cryothanasia, where a patient undergoes physician or self-administered euthanasia with the intent of being cryonically suspended during the death process or immediately afterward. This creates the optimum environment since all persons involved are on hand and ready to do their part so that an ideal freeze can occur."

Alcor, December 19, 2013, "Dr. Michio Kaku and Cryonics: Why Michio Kaku's Critique of Cryonics is Bogus" "You'd expect that a man of that learning, and knowledge, and experience ... would have done his research and get things right. Unfortunately, just about every single point in that video was incorrect."

BBC, October 31, 2013, "Will we ever bring the dead back to life?" "The woods cool temperature, it turned out, had prevented the womans cells from breaking down as quickly as they would have in a warmer environment, allowing her to lay dead in the forest for around four hours, plus survive an additional six hours between the time the passerby called the ambulance and the time her heart began beating again. Three weeks later, she left the hospital, and today she is happily married and recently delivered a baby."

The Guardian, September 20, 2013, "Cryonics: the people hoping to give death a cold shoulder" "Scores of Brits have also signed up for what the movement has dubbed "a second chance at life""

Singularity Weblog, September 12, 2013, "My Video Tour of Alcor and Interview with CEO Max More" "During our visit CEO Dr. More walked us through the Alcor facilities as well as the process starting after clinical death is proclaimed, through the cooling of the body and its vitrification, and ending in long term storage."

Science Omega, July 1, 2013, "Exploring cryonics: Could science offer new life after death?" "Medical advances have made it possible given favourable circumstances for physicians to bring patients, who are clinically dead, back to life." ... " cryonics has been viewed as somewhat of a fringe science since its inception. However, advances within fields such as regenerative medicine and nanomedicine have caused some experts to acknowledge the fields growing potential. Last month, for example, three academics from the University of Oxford revealed that, once dead, they will be cryogenically preserved until it becomes possible to bring them back to life."

The Independent, June 9, 2013: "Academics at Oxford University pay to be cryogenically preserved and brought back to life in the future"

"Nick Bostrom, professor of philosophy at the Future of Humanity Institute [FHI] and his co researcher Anders Sandberg have agreed to pay an American company to detach and deep freeze their heads in the advent of their deaths.

Colleague Stuart Armstrong is instead opting to have his whole body frozen. Preserving the full body is technically more difficult to achieve and can cost up to 130,000.

Bostrom, Armstrong, Sandberg are lead researchers at the FHI, a part of the prestigious Oxford Martin School where academics complete research into problems affecting the globe, such as a climate change."

"It costs me 25 a month in premiums to cover the cost of getting cryo-preserved, and that seems a good bet, he [Armstrong] said. Its a lot cheaper than joining a gym, which is most peoples way of trying to prolong life."

BuzzFeed, June 6, 2013, "The Immortality Business" "The richest vein of professed cryonicists is, not surprisingly, in the world of technology." Alcors "public-facing members include prolific inventor and Singularity cleric Ray Kurzweil; nanotechnology pioneer Ralph Merkle; and Marvin Minsky, co-founder of MITs artificial intelligence laboratory."

The Observer, April 6th, 2013: "Sam Parnia the man who could bring you back from the dead" '"The longest I know of is a Japanese girl I mention in the book," Parnia says. "She had been dead for more than three hours. ... Afterwards, she returned to life perfectly fine and has, I have been told, recently had a baby."' "One of the stranger things you realise in reading Parnia's book is the idea that we might be in thrall to historical perceptions of life and death and that these ultimate constants have lately become vaguer than most of us would allow."

Discovery Channel, April 16th, 2013: "Maria Entraigues Discovery Channel interview" In Spanish. "Alcor is the place where I will take a little nap so that I can wake up in the future..."

Cryonics, January 2013: "Alcor-40 Conference Review" "From the science of cryopreservation to the implications of neural network research on cryonics to strategies for preserving your assets as well as yourself, no stone was left unturned and no question unasked."

Phoenix New Times, September 17th, 2012: "Best Second Chance - 2012: ALCOR Life Extension Foundation" "ALCOR ... specializes in cryonics, the science of preserving bodies at sub-zero temperatures for eventual reanimation, possibly centuries from now."

CNBC, September 20th, 2012: "William Maris: Google Ventures Managing Partner" "What's the most exciting areas right now?" ... "There are two areas. One, I'm interested in macro trends that are 5 or 10 years out, things like radical life extension, cryogenics, nanotechnology, and then there are trends that are occuring sooner." ... "So go back to cryogenics, how realistic is that idea at this point?"... " we're looking for entrepreneurs that have a healthy disregard for the impossible. If I start from a place by saying that's not realistic, or not possible, we won't make any investments. So I think it's very realistic." ... "I want to know if this is a reality that we could see sometime in my lifetime?" "It's a reality now, there are companies that specialize in cryogenics."

OraTVnetwork, July 17th, 2012: "Seth MacFarlane & Larry King on Cryonics" (41 seconds) Larry King: "How about we get frozen together?" Seth MacFarlane: "Let's do it!"

PBS Newshour, July 10th, 2012: "As Humans and Computers Merge ... Immortality?" Ray Kurzweil, co-founder, Singularity University: "People say, oh, I don't want to live past 100. And I say, OK, I would like to hear you say that when you're 100."

Newsmax Health, December 7th, 2011: "Larry King's Vow to Freeze His Dead Body Is Not Crazy, Experts Say" "the 78-year-old King stated, I wanna be frozen, on the hope that theyll find whatever I died of and theyll bring me back."

SENS5 Conference, September 3rd, 2011: "Cryonic Life Extension" "Cryonics enables the transport of critically ill people through time in an unchanging state to a time when more advanced medical and repair technologies are available" said Max More, President and CEO of Alcor Life Extension Foundation.

Science Channel's Through the Wormhole (Season 2), July 15th 2011: "Cryogenic Preservation" "Cryogenic freezing is a process that could successfully preserve a human body over an extended period of time."

Time, February 10th 2011: "2045: The Year Man Becomes Immortal" "Old age is an illness like any other, and what do you do with illnesses? You cure them."

Rolling Stone, December 2010: "Life on the Rocks: can you bring people back from the dead?" (slow site) "Isn't it a leap of faith to believe in something that hasn't happened yet? 'The comparison's more like talking to someone 150 years ago and saying, "In a little while, humans are going to have flying machines."'"

Lightspeed, October 2010: "Considering Cryonics" Author and Physics Professor Gregory Benford looks at cryonics, and says "...its a rational gamble, especially when you consider that cryonicists buy life insurance policies which pay their organization upon their death..."

Singularity Summit 2010, August 15th, 2010: "Modifying the Boundary between Life and Death" Lance Becker, MD, Director, Center for Resuscitation Science, Emergency Medicine, University of Pennsylvania: "Our initial results are very encouraging. We have taken 6 dead people ... plugged those patients into cardiopulmonary bypass and we have a 50% survival rate out of those 6 patients". On cryonics: "I look forward to seeing that field [cryonics] be synergistic with some of what we're doing."

New York Times, July 5th, 2010: "Until Cryonics Do Us Part" Cryonics can produce hostility from spouses who are not cryonicists.

Colorado Court Order, March 1, 2010: "IN THE MATTER OF THE ESTATE OF: MARY ROBBINS" "The Court finds that the evidence clearly shows Mary's decision in 2006 for Alcor to preserve her last remains by cryonic suspension was an informed and resolute one." "Alcor shall have custody of Mary's last remains..."

Organogenesis, Vol 5 Issue 3, 2009: "Physical and biological aspects of renal vitrification" "We report here the detailed case history of a rabbit kidney that survived vitrification and subsequent transplantation"

The Institution of Engineering and Technology, November 5, 2008: "A Science Without a Deadline" "If sceptics dont want to pursue this area, thats fine, but I ask them not to interfere with my own efforts to save the lives of myself and the people I love"

BBC News,October 20, 2008: "Doctors get death diagnosis tips" "...there is enough ambiguity in diagnosing death that doctors need guidance" "...like low body temperature when it is inappropriate to confirm death." (audio)

Cryonics, 4th Quarter 2008: "A Cryopreservation Revival Scenario using MNT" Molecular nanotechnology is the most compelling approach ever put forward for comprehensive repair of cryopreservation injury with maximum retention of original biological information.

Newsweek, July 23, 2007: "Back From the Dead" "The other is to scan the entire three-dimensional molecular array of the brain into a computer which could hypothetically reconstitute the mind, either as a physical entity or a disembodied intelligence in cyberspace."

Newsweek, May 7, 2007: "To Treat the Dead" ""After one hour," he says, "we couldn't see evidence the cells had died. We thought we'd done something wrong." In fact, cells cut off from their blood supply died only hours later."

Channel 5 (UK), 2006 : "Cryonics Freeze Me" (A.K.A. "Death in the Deep Freeze") "Almost every major advance has met with its critics, who have said that it's impossible, unworkable, uneconomical; and then, of course, when it's demonstrated, they announce that it's obvious and they knew it all along." (If you have a link to the video, please email it to me).

The Wall Street Journal, January 21st 2006: "A Cold Calculus Leads Cryonauts To Put Assets on Ice" "At least a dozen wealthy American and foreign businessmen are testing unfamiliar legal territory by creating so-called personal revival trusts designed to allow them to reclaim their riches hundreds, or even thousands, of years into the future."

This Is London, May 25th 2004: "Sperm 'can be kept for thousands of years'" "...sperm could survive 5,000 or 6,000 years stored in liquid nitrogen."

The Arizona State Legislature is not regulating cryonics.

Reasononline, February 25th 2004: "Regulating the Biggest Chill" "Arizona's state legislature is about to consider one of the silliest pieces of "consumer protection" legislation ever devised."

Guardian Unlimited, January 23rd 2004, "House of the temporarily dead" "Officially, the building is "the world's first comprehensive facility devoted to life extension research and cryopreservation", a six-acre structure that will house research laboratories, animal and plant DNA, and up to 10,000 temporarily dead people."

Science News, December 21st 2002: "Cold Comfort: A futuristic play of cryogenic proportions" an amusing story in which Ted Williams, Carl Sagan and Richard Feynman awake in 2102 and find they are wards of the Martha Stewart Living Foundation. Says Ted: "...the Red Sox should have won a World Series by now."

The Fifth Alcor Conference on Extreme Life Extension resulted in several articles:

Wired News, November 18th 2002: "Ray Kurzweil's Plan: Never Die" "Ray Kurzweil, celebrated author, inventor and geek hero, plans to live forever."

Wired News, November 20th 2002: A Few Ways to Win Mortality War "Discussions among leading researchers in nanotechnology, cloning and artificial intelligence focused on much more than cryonics, the process of freezing the body in liquid nitrogen after death to be later reanimated. Cryonics is basically a backup plan if technology doesn't obliterate mortality first."

Wired News, November 20th 2002: Who Wants to Live Forever? "Gregory Benford, of the University of California at Irvine, believes the public should know that 'cryonicists aren't crazy, they're just really great, sexy optimists.'"

KurzweilAI.net, November 22nd 2002: The Alcor Conference on Extreme Life Extension "Bringing together longevity experts, biotechnology pioneers, and futurists, the conference explored how the emerging technologies of biotechnology, nanotechnology, and cryonics will enable humans to halt and ultimately reverse aging and disease and live indefinitely."

Coverage of cryonics related to the Ted Williams case was voluminous. Wikipedia describes the events succinctly. Here are links to a few contemporaneous articles:

Sports Illustrated, August 2nd 2003: "Splendid Splinter chilling in Scottsdale" Sports Illustrated, June 30th 2003: "Chillin' with the Splinter" The New York Times, September 26th 2002: "Fight Over Williams May End" CNN Sports Illustrated, August 13th 2002: "Williams' eldest daughter asks judge to keep jurisdiction" USA Today, July 28th 2002: "Vitrification could keep tissue safe during the big chill" The New York Times, July 16th 2002: "They've Seen the Future and Intend to Live It" The New York Times, July 9th 2002: "Even for the Last .400 Hitter, Cryonics Is the Longest Shot" (Note that the Boston Globe links and others that have gone dead have been deleted).

Christopher Hitchens quote, February 15, 2011: "If someone is reported dead on Tuesday, and you see them on Friday, the overwhelming, the obvious conclusion is that the initial report was mistaken."

Howard Lovy's blog August 27th 2003: "Unfrozen Cave Men"

Reason Online, August 2002: "Forever Young: The new scientific search for immortality"

New Scientist, September 2nd 2002: "New Scientist offers prize to die for." "When the winner of the New Scientist promotion is pronounced legally dead, he or she will be ... suspended in liquid nitrogen at 196, in a state known as cryonic preservation[sic]."

KRON 4 News, Nightbeat, May 3rd 2001: "Frozen for Life" [medical] advances are giving new credibility to cryonics.

Wired News, July 20th 2001: "Cryonics Over Dead Geeks' Bodies"

Scientific American, September 2001: "Nano nonsense and cryonics"

Search PubMed for published articles on cryonics.

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Cryonics - Merkle

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