if cryonics interests you read this...

john grigg (starman125@hotmail.com)
Wed, 29 Sep 1999 15:14:38 PDT

Hello everyone,

If cryonics interest you at all then read these posts, especially those by Mike Darwin. His posts make for very interesting reading. It appears 21st Century Medicine has made very important leaps forward in the methods used for cryonic suspension. I have reproduced here posts from the Cryonet showing the comments and queries of Robert Ettinger, myself and Thomas Donaldson.

Mike Darwin later responds with very detailed posts explaining not only about the technical advances but also on where credit should be given for these breakthroughs. This is a very exciting time for cryonics even though much still needs to be done in relation to both research and application. Mike Darwin is without doubt a brilliant and extremely dedicated individual who though blunt says it how he sees it.

sincerely,

John Grigg

Message #12443
From: Ettinger@aol.com
Date: Mon, 20 Sep 1999 14:08:22 EDT
Subject: 21CM patent

Go to www.uspto.gov to access the full text of the patent (Sep.14) assigned to 21st Century Medicine Inc. Oddly enough, the inventors listed do not include Greg Fahy; they are Brian G. Wowk, Michael G. Federowicz ["Darwin"], Sandra R. Russell, and Steven B. Harris. It runs about 18 printed pages.

Naturally, we will investigate the procedures and substances mentioned.

There are many interesting features in the patent, not least the structure of
claims. The claims start broadly, including any alkoxylated organic compound in a concentration sufficient to permit vitrification and cooling until vitrified; and the application of this to any organ, tissue, or animal. More specific claims relate to use of 2-methoxyethanol and 3-methoxy-1,2-propanediol.

The inventors acknowledge that glycol ethers have been used before to preserve embryos and cell suspensions, but believe they have priority in application to tissues, organs, and animals. Obviously, there are potentially
interesting questions in patent law--both as to the relation between these inventors and prior users of glycol ethers, and between these inventors and later users of new variations and applications.

"Summary" of the invention mentions perfusing an inert fluid through the vascular system and controlling the temperature of the fluid; and a class of new glycol ether CPAs. Oddly enough, the Claims do not (to my legally untutored mind) appear to make any direct or specific reference to cooling methods, even though in the "Summary" that seems important.

"Glycol ethers" are understood to include compounds containing alkoxy--and particularly methoxy--functional groups. Included are alkoxylated alkanes and
alkoxylated alcohols and polyols, with several sub-groups given.

For some organs, cooling and rewarming rates can exceed 100 degC per minute. [This seems to suggest possible use with other CPAs, such as amides.]

"Large animals can be perfused wit high concentrations of glycol ethers near
0 C with rapid equilibration, no dehydration, no edema or other visible evidence of toxic effects. Histologic preservation is excellent at microscopic and ultrasturctural levels."

References include Skrecky's proposal in Cryonet #5174, 1995; CRYONICS: REACHING FOR TOMORROW (Wowk & Darwin, 1991; and THE PROSPECT OF IMMORTALITY, 1964; and a Darwin/Hixon piece in CRYONICS July 1984, as well as various patents and publications in recognized journals.

I have not found any patent entries under "ice blockers," although the instant patent says that suppression of ice formation is an important feature. I believe 21CM has a different class of substances it calls ice blockers, acting through a different mechanism.

The "Conclusion" mentions unprecedentedly high rates of cooling and rewarming,;and the advantages of the new CPAs, including penetration and low viscosity, rapid equilibration, ice inhibition, minimization of toxicity, and
glass forming properties.

Congratulations to all the inventors involved. Lots of work ahead.

Robert Ettinger
Cryonics Institute
Immortalist Society
http://www.cryonics.org

Message #12452
From: "john grigg" <starman125@hotmail.com> Subject: Congratulations to 21st Century Medicine!! Date: Thu, 23 Sep 1999 12:56:52 PDT

Hello everyone,

I looked over the patent for 21st Century Medicine's research developments and must say I am VERY IMPRESSED!!! I congratulate those who made it possible!!

>From the patent document:


            INITIAL COOLING RATE
                             FINAL COOLING RATE
    ORGAN   (AT 0.degree. C.)
                             (AT -90.degree. C.)
    ______________________________________
    Kidney  360.degree. C./min.
                             36.degree. C./min.
    Liver    95.degree. C./min.
                             10.degree. C./min.
    Brain    50.degree. C./min.
                              5.degree. C./min.
    Body     9.degree. C./min.
                              1.degree. C./min.
    ______________________________________



The cooling rates shown in Table III are more than ten times greater than can be achieved by previous external cooling methods. Such rapid cooling will allow significant decreases in the concentration of cryoprotectants needed to vitrify, enhancing the prospects for successful cryopreservation of organs with non-toxic CPA mixtures. These cooling rates also for the first time open the possibility of vitrifying whole humans.

(Later at the conclusion)
CONCLUSION

The method of the present invention allows cooling and subsequent rewarming from temperatures lower than -100.degree. C. at rates exceeding 100.degree. C. per minute for some organs. These rates are much higher than can be achieved by external heat transfer methods, and will allow significant reduction of the concentration of cryoprotective agents needed to achieve reversible vitrification of organs for long-term banking. Heat transfer by inert fluid perfusion is also beneficial for reducing ice crystal damage and cryoprotectant toxicity during ordinary freezing and thawing.

The present invention also provides a class of new cryoprotective agent (glycol ethers) for reduction and prevention of ice formation during cooling of vascular tissues and organs. Glycol ethers generally, and methoxylated compounds in particular, are highly penetrating agents that equilibrate rapidly upon perfusion, and exhibit strong ice inhibition and glass forming properties. The low viscosity and freezing point of these compounds also make them well-suited for sub-zero perfusion to minimize toxic effects. Toxicities are compatible with the potential use of glycol ethers in perfusate solutions for reversible cryopreservation of organs and large organisms by freezing or vitrification.

(End of patent document reproduction)

That cooling rates using these techniques are TEN times faster then in the past is incredible. And that glycol ethers are far superior penetrating agents compared to what was used in the past is a major step forward.

"These cooling rates also for the first time open the possibility of vitrifying whole humans" is a statement in the patent document that made me wonder when will these new methods in their entirety be used to TRULY vitrify a human??

And with such a combination of major advances what still needs to be done?? How could things still be improved? What are the possibilities down the road? What is next for 21st Century Medicine? And how is the Prometheus Project doing?

I hope the major cryonics providers will all adopt these methods for their clients. Is 21st Century Medicine working with the various organizations to bring them up to speed? Just how expensive will it be to offer these techniques??

I remember reading in the Cryocare archives a paper by Mike Darwin where he admitted the major damage suspension did on the cellular level and how so much still had to be done. Reading his paper took away much of my early hope in cryonics and a desire that breakthroughs would be made.

But having read through the patent I feel new hope!! Again my congratulations and thanks to all those who made it possible!! I want to hug you all!!

I look forward to hearing from you all regarding this patent and my views and questions about it.

Sincerely,

John GriggMessage #12453
From: Thomas Donaldson <tdonald@hubble.dialix.com.au> Subject: about 21st Century Medicine's advances Date: Fri, 24 Sep 1999 23:28:10 +1000 (EST)

Hi everyone!

I too look forward to wider application of the cryoprotectants and perfusion technology created by 21st Century Medicine. Yes, it may not be immediate; the first thing to do is to try these methods on brains. (There was a time lapse between the first Wright brothers flight and the use of 747's, after all).

There is also some question in my own mind about whether or not some of the perfusion methods described will prove to be patentable ... but even the cryoprotectants alone make a big advance.

As for congratulations, it seems to me that the most congratulations are due to Saul Kent and Bill Faloon, who funded 21st Century Medicine in the first place. Yes, such advances do require redoubtable technical and scientific knowledge, too, but they could not have occurred without funding ... and in my own personal estimation, they might have occurred as long as 10 years ago, if only the funding had then existed.

                        Best and long long life to all,

From: Thomas Donaldson <tdonald@hubble.dialix.com.au> Subject: I was using two standards, one for knowledge and another for action Date: Tue, 28 Sep 1999 23:42:03 +1000 (EST)

Hi Mike!

Perhaps I put the matter too strongly. I've frequently found, however, that things which first look simple turn out to be much harder than we think, and it was general thoughts of this kind which made me comment that working out how to vitrify brains may take longer than expected.

In terms of the problem we're setting ourselves, we want to know that we can vitrify the brains of primates (ideally chimpanzees, the closest to us, though that starts to become morally questionable... and there are plenty of other primates not so bright). Without actually doing that, we don't KNOW that a treatment we've applied to a quite different animal will still work. Yes, it's very likely, but not certain. And if it DID turn out not to work so easily, we'd have to do extra experiments to fix that problem.

So maybe I'm just setting higher standards for certainty.

I will point out, though, that if I find that I am dying (or those who are caring for me find that) then I'd want to be suspended by a method which is the best available within my budget. What you say increases my conviction that vitrification with one of the solutions 21st Century Medicine has found is likely to be best available, NOW. I'm using two different standards here: the evidence needed to assure me that something is true, and the evidence needed to tell me that something is likely.

In any case, it's still good work and deserves praise, and even some money.

                        Best and long long life,

                                Thomas Donaldson



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