X-Message-Number: 4844
Date: 05 Sep 95 17:46:51 EDT
From: "Clifton  G. Clue Jr" <>
Subject: CRYONICS: Free Radicals

Eugen Leitel sent along the following:

>It is =B3known=B2 that free radicals play a large part=20
>in traumatic, vascular and cryo- brain damage.  It=20
>also seems established that cytokineses, etc. in=20
>multiple organ dysfunction syndrome/DIC (MODS) cross=20
>the BBB and open the BBB to allow free radical access=20
>to the brain.

>Question:  is anyone out there studying the above=20
>situation?  I have spent a day or so on MEDLARS and=20
>don=B9t find any articles.  Is there anywhere on the=20
>=8Cnet I should be asking? =20

Keys words are key to doing a meaningful search on any system; especially 
on older ones like the National Library of Medecine's MEDLINE database 
using Grateful Med.  There is no shortage of papers dealing with free 
radical pathology in all of the above areas.  Currently I have TWO deep 
drawer filing cabinets full of reprints on free radical, 
immune/inflammatory cascade mediated injury in ischemia, reperfusion, and 
hypothermic organ preservation.  I may (arguably) be one of the most 
experienced empirical evaluators of radical quenchers: spin trap, OH 
radical quencher, Haber-Weiss radical inhibitors... in the world.  By 
empirical I mean that I have actually tried a lot of these things in 
SURIVAL model animals in various combinations.

You can tell the physician enquiring that there is a HUGE literature on 
this subject with many fine review articles.  You can also tell him that, 
in the case of the brain, due to very special reasons which we here 21st 
are just now teasing out, the choice of individual compounds, their time of 
application, their dosage, and above all the combination is critical.  What 
is happening in our lab with dogs right now is so incredible I can hardly 
believe it myself; the only thing that comes even close is the feeling I 
had when we recovered our first 2 hour asanguineous perfusion dog after 4 
hours at 4C inthe mid-80s. We are, of course, now long past that mark for 
deep hypothermic perfusion (2-4C).  

What we are doing now is simply beyond imagining for ANY of us doing the 
work.  I bring this up because while I believe dealing with free radical 
pathology is critical to success, it is not sufficient.  Cerebral 
ischemia-reperfusion injury is a complex cascade of events some of which 
are not at all directly related to free radicals. As the above quote points 
out, activation of the immune/inflammatory cascade is a major player.  We 
have found that once this ball is rolling -- unless it is STOPPED-- you 
will see remote (i.e., the target organ may well not have been affected by 
the primary insult) and catastrophic injury (the lungs being the a 
principal site).  You are not going to solve this problem simply, either, 
say with leukocyte filters, etc. DIC (diffuse intravasucal clotting) and 
MSOF (multi system organ failure) are merely the end stages of this 
pathology playing out.  I call it sick endothelium syndrome, but it is 
deeper than that.

Other strategies must come into play if survival is the goal.

Sorry to be so vague, but we are in patent process on some stuff, and not 
even ready for patent on other (plus some of this material is covered by 
nondisclosure agreements with our contractors).

I am very pressed for time now, but will be happy to send this physician 
some good references to tutorial articles on free radical and 
immune/inflammatory cascade mediated injury in a wide variety of organ 
systems, including the brain.

Mike Darwin

PS: As to multilevel marketing.  One of the reasons so many cryonicists are 
so down on it  is that many have a get rich quick mentality which has 
robbed them of their hard earned assets, sometimes more than once.  The 
leadership of one cryonics organization (i.e., Board) has at least 4 people 
who wasted a great deal of my or others' time with various MLM schemes.  I 
notice NONE of them has decided to post their PERSONAL experiences :). 
(Probably too embarassing: and believe me, they SHOULD be embarassed!) 

I would also note two other areas where a certain class (mostly activist 
cryonicists) routinely lose their shirts (in some cases having blown a 
lifetime of savings and experienced complete or near complete financial 
ruin).  Here they are:

1) Commodities Market investing (usually highly leveraged): many victims 
here.

2) Stock market investing (always heavily leveraged) plenty of victims here 
too,

3) Giving life savings to various "financial entities" which promise double 
digit rates of return in a year's time or less: fewer victims, but on 
average, more "normal" types.

4) Investment in weird, unlikely start-up companies (great money has also 
been MADE here by a FEW cryonicists).

5) Starting their own TRULY stupid businesses and putting ALL their capital 
into them.

6) Sending large amounts of money to cult-like entities (NeoTech and 
others) which promise quick (weird) easy and rapid solutions to all the 
world's problems.

I will spare the readers more.  I would say this shoyuld be a caution or 
that it might do some good, but it won't.  This is not about rational 
thought processes: IT IS RELIGION or GOLD FEVER.  You cannot argue or 
reason with people in the throes of this kind of thing, anymore than you 
can talk a manic depressive down from a high or up from a low.

I will end on a postive note.  Many cryonicists are RICH, some beyond 
imagining.  Most rank and file cryonicists are increasingly not "marginal" 
or "strange" types.  I believe that one of the reasons the AVERAGE income 
of cryonicists on surveys doesn't turn out to be far higher is that the 
extreme lows (usually due to faulty judgment) offset the extreme highs.  
Sadly (and statistically to be expected) the naieve or wild eyed type are 
attracted to cryonics organizations in leadership positions precisely 
because they have NOT done what they wanted to elsewhere.

One of the most common comments I hear is: "Oh, I'm VERY busy right now 
working on something that will make me a lot of money, then I'm going to 
retire and spend lots of it on cryonics...)  EVERY CEO of EVERY cryonics 
organization is either grinning or shaking their heads (or both) while 
reading this line.

But, as I've so often said, it IS a strange world, and a couple of times 
people have actually gone out, made a lot of money expressly to fund 
cryonics work, and spent a reasonable amount of it on cryonics.

I think we can all agree that's positive.  "And you takes what can gets" :)

Mike Darwin


Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=4844