Capla comments on Even better cryonics – because who needs nanites anyway? - Less Wrong

49 Post author: maxikov 07 April 2015 08:10PM

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Comment author: mikedarwin 09 April 2015 06:54:23AM *  49 points [-]

I was asked by several people to comment on this post/proposal. Clearly, Maxikov put a lot of time and effort into this post and, at least in part, there's the pity. When you find you have an idea which seems at once compelling and obvious (in tems of the science) in an already well explored field, the odds are very good that you weren't the first to reach that conjecture. And that almost always means that there is someting wrong with your premises. Very smart and capable people have been trying to achieve cryopreservation of cells, tissues, organs and organisms for over 50 years now and the physical chemistry of water under very high pressures and very low temperatures has been understood for far longer. This should be a hint that some careful searching of the literature is in order before going public with a proposal to "fix cryonics," and especially before spending a lot of time/energy on proposal like this.

Attempts to use extreme hydrostatic pressure to mitigate or eliminate freezing injury go back at least 60 years, and probably longer. As your phase diagram above shows, when the pressure is sufficiently high during cooling the expansiuon of water is prevented, but ice formation is not. What happens is that other allotropes of ice form which do not require expansion. However, this turns out to be a bad thing, since, as opposed to any of these ices being formed first in the interstitial spaces, as happens with Ice I, freezing occurs both intracellularly and extracellularly at the same time in the presence of other ice allotropes. Crystal formation inside cells results in devastating ultrastructural disruption - far worse than would occur if ice formed outside cells first, grew slowly and dehydrated the cells, and finally resulted in a vitrified cellular interior (providing that cryoprotectant is present).

However, the problem with this approach doesn't stop there. Extreme hyperbaria itself is directly damaging by at least two mechanisms: denaturation of cellular proteins (including critical enzymes and membrane proteins) and damage to cell membrane lipid leaflets resulting in permeabilization of the membrane to ions (Onuchic LF, Lacaz-Vieira F., Glycerol-induced baroprotection in erythrocyte membranes. Cryobiology. 1985 Oct;22(5):438-45.) Irreversible membrane damage occurs in mammalian red cells exposed to a pressure of 8000 atm (~117,600 psi) applied for ~10 minutes. Exposure of more comnplex mammamalian cells to far lower pressures~20,000 psi, results in loss of viability due to protein denaturation, and perhaphs due to alterations in the molecular structure of membrane lipids,as well. Interestingly, the same compounds that provide protection cellular (molecular) protection against freezing damage also confer substantial protection against baroinjury. Fahy, et al., have extensively explored the use of hyperbaria to augment vitrification in the rabbit kidney (http://www.freepatentsonline.com/4559298.pdf) and have further extended work from the 1980s demonstrating that cryoprotectives are also substatntially baroprotective.

The first work that I'm aware of to attempt to achieve organ cryopreservation using hyperbaria was that of the late Armand Karow, in the late 1960s - early 1970s (Karow AM Jr, Liu WP, Humphries AL Jr. Survival of dog kidneys subjected to high pressures: necrosis of kidneys after freezing.Cryobiology. 1970 Sep-Oct;7(2):122-8. PMID: 5498348). Karow was able to demonstrate the brief tolerance of dog kidneys to pressures of about ~18,000 psi, however, kidneys subjected to isothermal hyperbaric freezing, even in the presence of of moderate cryoprotection, did not survive.

When I started research and experimentation in cryobiology nearly 40 years ago, there was no Internet, no (affordable) photocopiers and the only way to do a "literature search" was with something called the Index Medicus (http://en.wikipedia.org/wiki/Index_Medicus) which was a veritable wall of bound volumes. I used 3" x 5" index cards to write down possible cites to look up - which then required a trip(s) to the "stacks" to look for the journals. Today, I have the Internet, Pubmed, the international patent database and on line library for 30 million books available. I currently have a digitial library of 12,000 mostly scientific and technical books which, at its current rate of growth, should double in size within a few months. My computer is almost constantly reading a book to me with software that cost me just under $5.00. One of the books I "read" recently was The Shallows: What the Internet Is Doing to Our Brains by Nicholas Carr. Carr argues that the Internet is fundamentally altering the way most people today process information - and not for the better. I don't use the Internet the way most people seem to, today. I rely heavily on books, especially textbooks, to educate me about areas with which I have little or no familiarity, and my approach is pretty much what it has been since I started my intellectual life; namely to study intensively and deeply until I achieve basic mastery of an area, and only then use skimming and browsing over large amounts of material to advance my knowledge. The tools of the information-digitial age have thus been a nearly unblemished advantage to me. If you want to reads Carr's book, click on this link:

http://www.mediafire.com/download/5s4wdr554ia4axn/Nicholas_Carr-The_Shallows__What_the_Internet_Is_Doing_to_Our_Brains_(2010).epub and then click on the green Download button.

I'm also posting links to a number of full text books on cryobioolgy which you can download, as per above:

ADVANCES IN BIOPRESERVATION: https://www.mediafire.com/?raccqhv0rrqfhmh

ADVANCES IN LOW TEMPERATURE BIOLOGY: https://www.mediafire.com/?4i6v9qublf3l8q2

FUNDAMENTALS OF CRYOBIOLOGY: https://www.mediafire.com/?pxq6mxbxvfib41j

CURRENT TRENDS IN CRYOBIOLOGY: https://www.mediafire.com/?pxq6mxbxvfib41j

CRYOPRESERVATION... https://www.mediafire.com/?pxq6mxbxvfib41j

LIFE IN THE FROZEN STATE: https://www.mediafire.com/?ydx3a89m2f47r7y

THE FROZEN CELL: https://www.mediafire.com/?ydx3a89m2f47r7y

Cheers, Mike Darwin

Comment author: Capla 09 April 2015 03:50:58PM 4 points [-]

With which of those books should I start?

Comment author: mikedarwin 09 April 2015 08:36:27PM 7 points [-]

I'd say FUNDAMENTALS OF CRYOBIOLOGY, followed by Baust's ADVANCES in BIOPRESERVATION. However, you may find another starting point better. I recently felt the need (out of self defense) to learn about dentistry. That's a bit like saying I decided to learn about neurosurgery:that covers a lot of ground. However, mostly what I was interested in was plain old restorative dentistry and the much more exotic implant dentistry. There are easily half a dosen textbooks on basic, restorative dentistry... After perusing a number, I settled on one as a proper "read through" introduction. All were adequate, but only that one really communicated in my style. The good thing about most modern textbooks is that there are now study and review guides and, of course, mock-up Board exams. This kind of learning allows me to get a good basic grasp of what is being done to me and to overcome the "condescension" factor when speaking with the dental professionals treating me. Please note, it does NOT make me a dentist! I wish I could recommend the same thing vis a vis cryobiology or cryonics. But I can't. I've tried to get support to start a formal training college for cryonics professionals (I actually have some funding), but have been laughed at, or dismissed out of hand - perhaps justifiably so. Nevertheless, that is what needs to be done and textbooks, study guides, testing and certification do not occur until a discipline is professionalized and formally taught.