X-Message-Number: 5119
Date: 06 Nov 95 15:56:52 EST
From: Mike Darwin <>
Subject: CRYONICS: Misc. Responses

Bob Ettinger asks a number of questions:

1) Can he reprint the summary of Greg's recent work in THE IMMORTALIST?

a) It is fine with me if GREG says its OK.  Please copy him on the request.
b) I had sent him a copy of Cryonet containing my post so he could correct 
any factual errors (there will no doubt be some, but I think I did a 
reasonably good job overall). He has had this since yesterday afternoon, 
but may not realize what it is; please advise him that he HAS the text.
c) Numerous details of the work are now flooding out for publication.  Greg 
has been in the same nasty bind we are in;  he has done a lot of REALLY 
good work, but has been unable to publish until patents are issued.  
Worldwide the patent systems differ from that in the US where it is "first 
to invent who gets the patent."  In the rest of the world it is *first to 
patent.*  The GATT agreement will shortly bring the US into line with 
international standards.
d) US patents for medical products are increasingly less important.  Many 
medical products cannot be economically marketed here due to the typical 
quarter billion dollar cost of FDA approval.  Most device manufactuers 
don't even bother with the US market anymore for things like artificial 
hearts, new ventilators, simple screening devices, and new medical products 
with limited market applicability (defined here as "not a major device 
which will come into widespread use ').  
e) The problem here is that many major devices now in widespread use like 
the Swan Ganz catheter did not start out that way; crystal balls are not 
very reliable.
f) The upshot of the above is that we at 21st and others are increasingly 
not even bothering with USA marketing due to prohibitive costs of FDA 
approval (yes, we are sensitive to licensing as an alternative, but this is 
becoming problematic too).  I am negotiating for clinical trials of several 
new things we have on the front burner here overseas.  Marketing them here 
will come later, if at all. US marketing has simply become a factor we 
don't even consider on first pass, and this is rapidly becoming true of the 
big and intermediate sized players as well.

If people are interested, I can do an educational post later documenting 
several products and meds that didn't make it in the US market (and didn't 
make it anywhere because the American companies developing them bet the 
farm on FDA approval).

2) Bob asks about the hyperbaric chamber:

a) Bob, if you have a complete set of CRYOBIOLOGY, go back to the late 60's 
and look for Armand Karow's article on high pressure kidney freezing.  The 
chamber he had is the one we have.  We purchased the whole unit from him, 
but it was shipped uninsured and destroyed in a truck crash.  The chamber 
itself or "bomb" as it is technically known, made it through unscathed.  
The machine did not.  The Haskell pump, the valving and some of the 
controls survived and are in a box.  In my opinion to be made operational 
the unit would need the following:

* Ultra high pressure tubing (Superpressure, Inc. would be a good source).
* A new pressurization system, although the existing Haskell pump may be 
coddled along and gotten to the point where it could work (this would save 
about 5K for a pump).
* Barring use of motor driven pump, you can buy hand operated 
pressurization units, but they will take a LOT of time to use and are very 
inconvenient.  If you want to reach target pressure with minimum exposure 
time and associated barotrauma, you'll want a mechanical pump.
*I picked up a high pressure guage, but it only goes up to 20,000 psi.
*A dewar or well insulated container and a crane would be necessary to 
rapidly cool the bomb by lowering it into LN2 or -190 C pentane. We have 
both.
* A circulating pump for pentane will be necessary to pump coolant through 
the interior cooling channels. This can be easily done; we have the pumps 
and plumbing capability for this: it is low pressure.

If all this sound like a lot, it is.  But, if someone is willing to put in 
the hours, a lot can be done to shave costs.  As Bob well knows, doing it 
yourself can save a lot of money, not just on labor, but on finding 
common-place devices which work as well as very costly ones which are 
special-purpose manufactured.

Right now the bomb is sitting in the wharehouse area of the lab.  It weighs 
a lot, I would guess nearly 1K pounds.  It is intact and looks in good 
shape.  If it is used without being returned for pressure testing, I would 
want to use an enclosure of a lot of sandbags; at least two thick!  Since 
its hydrostatic pressure this will probably suffice for protection.  
Autoclave engineers (the builder) strongly recommends saftey check out.  If 
it were a compressed gas vessel, I'd be inclined to comply.  However, if 
the whole pressurized system is behind sandbags and it is NEVER operated 
with personnel exposed, there should be no significant risk in a 
sprinklered building; and what's more, the work can be done outside here in 
SC.  The big risk is fire/explosion from the pentane being used as the heat 
exchange medium if the bomb blows.

Finally, to put things in perspective, the estimated cost a new bomb of the 
same design (excluding peripherals) today is $45,000. 

>Wistful thought: Maybe Fahy and Ruggera will get the Nobel for the kidney
>work. Seems important enough, in light of the number of kidney transplants
>needed. Probably 10 years or more down the line, even if it happens; but 
it
>would be an enormous boost for cyonics, in several ways.

The problem is that the existing storage time for kidneys is now out to 72 
hours with minimum muss and fuss (UW Solution).  Greg's technology will NOT 
be easy or cheap and is far from application in a clinical setting.  There 
are MANY times more recipients than available kidneys.  Thus, current 
72-hour storage time is more than adequate for logistic purposes.  For most 
kidneys there are many possible recipients.  You will note that Larry 
Hagman is still waiting for a liver.  Mean wait time for livers is about 
4-6 months. The problem is not storage, it is acute shortage.  
Comparatively few grafts are going to waste.

A second problem is how do you want to spend you money?  Rapid progress is 
being made in developing xenografts with recipient specific-antigens.  
Anybody seen the human ear growing out of the nude mouse's back?  Most 
people who need organ transplants have waiting periods available which 
would allow for custom prep or creation of a genetically engineered 
xenograft organ.  This would free up the cadaver harvested supply of organs 
for those with acute need: massive heart attack, trauma, toxic liver 
failure, rapidly developing cardiomyopathy, etc.

My pot bellied pig went from about 10 pounds to 150 pounds in about 4-5 
months. Her kidneys would have supported an adult neonatally (they grow to 
full size quite rapidly upon transplant: you can put a 3 year old's (human) 
kidney in an adult human male and it will be handling his needs in a month 
or two and be full sized!).  Her heart would have supported the average 
woman by 4 months.  Post-partum growth rate can be upregulated with feed 
and hormonal manipulation.  Weight gain on my pet pig would have been far 
more rapid had she been fed ad lib instead of thoughtfully nourished and 
modestly calorie restricted. (This being necessary for her long-term 
health; pigs are, well, pigs!).

If it were my bucks, I'd support continued work towards extending 0-4 C 
hypothermic storage time to 1-2 weeks (already possible in the lab for 
kidneys: 1 week anyway) and spend bucks on genetic engineering of 
xenografts to deal with the fundamental problem of shortage.  Further, as 
cerebral resuscitation progresses, the number of potential donors is going 
to drop since head injury and and brain ischemia secondary to heart attack, 
drowing, and trauma will be increasingly more treatable.  As helmet laws go 
into effect, head injuries plummet and so does graft availability.  Ditto 
better prevention for cardiovascular disease which results in fewer strokes 
and fewer heart attacks (=less SCD=less organs). The same is true with 
better vehicle safety; airbags, side impact reinforcement, etc. The SUPPLY 
is where the problems are.

>On hyperbaric numbers etc.: Mike Darwin says he has a hyperbaric chamber 
and
>accessories maybe large enough for a human brain. Mike, do you have
>experimental numbers on pressures needed for cooling (say) rodent brains,
>without freezing, down to temperatures where freezing will be complete 
when
>the pressure is released? If not, do you or your associates have time and
>interest in finding these numbers? If you need money, how much?  

I have no ideas on numbers re pressures.  This is not a current focus of 
our work, but I remain interested for a variety of reasons I will not go 
into here.

Despite my "terrible" reputation, I am easy to work with on research, and 
very open.  I have no idea what costs would be, but they would be confined 
to materials and specific labor.  Here Mark Connaughton and Paul Wakfer 
would be the men to talk to.  My time for the "biology end" of things would 
be at no charge, within reason.  Simple readily available materials would 
not be charged as long as it is collaboration with equal sharing of results 
and understanding of patenting, etc. (we are very flexible here).

The bomb has been sitting around for at least a decade gathering dust.  I 
would love to see work done in this area, although our primary goal at this 
point is to adapt vitrification to brains, and we have paid for exclusive 
rights to the underlying enabling technology and patents for all brain or 
whole-body applications confined to the area of reversble human/brain 
cryopreservation for future revival (medical time travel) before or after 
legal/clinical death.

Still, work is going on in lots of areas pretty far afield fromour primary 
goal, including and exhaustive and well done series of experiments 
evaluating fixation penetration rates being carried out by Mark Connaughton 
using cattle brains. (Mark is doing about 4-5 brains a week! and gets them 
within minutes of slaughter).


As to the costs of getting the bomb up and running.  I just don't know, but 
suspect they need not be high for a simple system where evaluation of 
principles is more important than speed and conveniece.  I'll ask Greg if 
he has tubing and equipment he can spare, since he is currently (at least 
to my knowledge) not doing hyperbaric work.

Bob, if you are in Phoenix now, you should fly over on a shuttle and go 
through the lab.  We are a couple of exits from Ontario International (ONT) 
airport and shuttles between Phoenix and ONT run frequently and 
inexpensively.  You can leave at 1100 and be back home by 1700 the same 
day.


Mike Darwin


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