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Date: Wed, 15 Jun 1994 20:57:57 -0700
Subject: CRYONICS Trans Time newsletter
THE TRANS TIMES
Life Extension through Cryonic Suspension
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Volume 3 Number 3 June 1994
Research Achievements Presented at
'Experimental Biology 94'
Improving cryonic suspension procedures requires research, and
research costs *money*. Our colleagues at BioTime have already
raised more than $10,000,000 for cryonics-related research. They
also raised over $7,000,000 while they were involved with
Cryomedical Sciences. You read ongoing reports of their research
in THE TRANS TIMES.
Recently Dr. Hal Sternberg and Dr. Paul Segall gave formal
presentations at the Federation of American Societies for
Experimental Biology conference in Anaheim, California. The
BioTime group also submitted five abstracts for publication in
the conference proceedings. Here are reports on some of the work
they presented, derived from the abstracts.
HAMSTERS REVIVE FOLLOWING SIX HOURS OF CARDIAC ARREST
H. Sternberg, P.E. Segall, and H.D. Waitz.
They anesthetize female hamsters and surround them with crushed
ice. Each animal is placed on a temperature-regulated surgical
platform and body temperature is lowered to about 12-15 degrees
C. They expose the right carotid artery and jugular vein, and a
micro-cannula is inserted into the artery. Temperature is further
lowered to below 5 degrees C. They ventilate each animal with
100% oxygen and begin arterial infusion of blood-substitute
solution by puncturing the vein to allow outflow.
Cardiac activity (EKG) is monitored using a Grass polygraph.
During the infusion of blood substitute, cardiac activity ceases.
The infusion is stopped after about 3 blood volumes of solution
are delivered. They keep the ice-cold animal in circulatory
arrest for 5 hours.
Next infusion with blood-substitute is again initiated followed
by infusion of whole blood. When the hematocrit reaches about
20%, the animal is gradually warmed. When cardiac activity
resumes, they ventilate the animal. When the hematocrit reaches
40%, the vein is tied off and perfusion is discontinued. The
cannula is pulled and incisions are sutured.
After about 6 hours of cardiac arrest, 2 animals have revived to
complete consciousness, responsiveness and upright posture. They
use this model to develop and improve blood-substitute solutions
for low-temperature surgical procedures.
THE TRANS TIMES first reported on the above research in our
October, 1993 issue.
HAMSTER CARDIAC FUNCTION OBSERVED FOLLOWING IN-SITU SUB-ZERO
OVERNIGHT STORAGE
H.D. Waitz, H. Sternberg, and P.E. Segall.
These experiments proceed just like the previous one through
cooling and perfusion with the blood-substitute solution. After
replacing the blood with substitute, they infuse a second
solution containing cryoprotectants. The animal is then placed in
a plastic bag and immersed in a cooling bath set at -2.0 to -4.0
degrees C. Probes placed rectally indicate that the hamster's
temperature reaches the bath temperature within one hour.
Following overnight storage at these temperatures they thaw the
animal by intermittent microwave pulses. The cold animal is
perfused with blood substitute to remove cryoprotectants,
followed by perfusion with whole blood, and then warmed. They
monitor cardiac activity using a Grass polygraph and by visual
observation.
Heartbeat was restored in 2 hamsters cooled to -4 degrees C and
in other animals cooled to between -3 and -3.5 degrees C.
ARTIFICIAL PLASMA KEEPS ICE-COLD ANIMALS ALIVE
P.E. Segall, H. Sternberg, H.D. Waitz, E.M. Breznock, J.M.
Zabramski, and G.V. Letsou.
(BioTime Inc., U.C. Davis, Barrow Neurological Institute of St.
Joseph's Hospital, and Yale-New Haven Medical Center)
Artificial plasma solutions containing starch, electrolytes,
sugar and buffer, have been used in hypothermic total body
washout procedures in the hamster, rat, sheep, dog and baboon.
Members of each of these species have been revived after total
blood replacement at ice-cold temperatures, and members of all of
the above species, except sheep, were successfully maintained
long term.
Hamsters appear to survive these procedures more easily, as they
are hibernators, and thus adapted to function at low
temperatures. Rats can also be revived after ice-cold blood
substitution, but seem to be more susceptible to lung damage.
Sheep, which have large rumens that fill with gas, can be
difficult to cool or heat, and may be prone to gaseous embolisms.
Baboons have revived after periods exceeding 2 hours, and dogs
have revived after periods exceeding 4 hours, of blood
substitution at deep body temperatures below 10 degrees C, and as
low as 1-4 degrees C. Some of these dogs and baboons have lived
long term, and have recovered with no measurable gross deficit.
Those survivors that fully recovered and were subsequently
autopsied showed no evidence of histological or neurological
pathology.
Research Plans
by Hal Sternberg, Ph.D.
Just recently I attended the Experimental Biology 94 Conference
in Anaheim. There were many presentations relevant to low
temperature medicine. In particular, Drs. Wang and Layne's group
from the Univer-sity of Rochester reported their work on rat
heart preservation. Perhaps the most interesting suggestions made
were:
1) With respect to cardiac preservation in an isolated
preparation, it appears advantageous to perfuse the organ with
the appropriate storage solution intermittently (for example, for
5 minutes every 6-8 hours).
2) Heartbeats could be recovered after sub-zero storage, using a
cryoprotective protocol that involved gradually increasing (and
later gradually decreasing) the cryoprotectant concentration.
We are in the process of expanding the model systems that we use
to evaluate and improve cryoprotective solutions and protocols.
Following our recent successful liquid nitrogen storage and
transplantation of full thickness rat skin, we are studying the
outcome of nitrogen stored knee joints. This tissue is
histologically evaluated 7 days post-transplant into recipient
rats.
Cryoprotected tissues frozen to liquid nitrogen temperature are
damaged to varying degrees. This damage may be repairable by
natural repair mechanisms post-transplant. Currently, we suspect
there is damage to the circulatory system of tissues and organs
after freezing and thawing. We are concentrating our efforts on
preservation of the circulatory system.
We are also considering the most appropriate environment in which
to transplant post-frozen tissues that could help support the
tissue while it repairs and builds back its circulatory system.
One reason our laboratory has successfully stored skin is that it
can be supported by neighboring tissue while it restores its
circulatory system. Skin is relatively thin and nutrients will
diffuse throughout the tissue supporting it. In addition, its
metabolic demands may be low.
Other thicker tissues cannot be similarly supported. If we could
place tissues and/or organs in an environment that could deliver
sufficient nutrients via diffusion to prevent irreversible
ischemic injury, the tissue might repair itself to become
functional.
Job Opening
Trans Time does its accounting on computer, using the Peachtree
Complete Accounting system. For many years we have been hiring
part-time workers to run the system under Art Quaife's
supervision. These employees have typically lasted six months to
a year before moving on. We would prefer to hire a fellow
cryonicist for the job, who we might expect to stick with the job
for a long time.
The employee spends about half the time doing accounting, and
half giving general office assistance (preparing literature,
getting out mailings, running errands, etc.).
There is a great deal more work here that needs to get done, for
anyone that gets very involved in our operation, and can shoulder
responsibility and write well. This means that the position could
evolve into full-time, and at higher pay.
If you are interested, please give Art Quaife a call. Interviews
start immediately.
TITLE: Accounting Clerk
DUTIES: Run our Peachtree accounting system on an IBM PC-
compatible computer. Modules include general ledger and accounts
receivable. Also, provide general office assistance. Applicant
should have a car.
EXPERIENCE: Applicant should have job experience in computerized
bookkeeping/ accounting, or have taken college courses in
accounting. Knowledge of WordPerfect is very useful.
SALARY: $12.00/hour.
HOURS: 20 hours/week. Prefer 1:00 - 5:00 p.m. weekdays.
CONTACT: Art Quaife, 510-639-1955.
Investing for the Centuries
by Art Quaife, Ph.D.
Our clients establish trust funds to pay the ongoing costs of
keeping them in suspension. It is crucial that the trust fund
never runs out of money, else the patient may wind up thawed. In
a previous article [2], I used a plausible model to determine the
probability that trust funds of various sizes would survive for
200 or 400 years.
My estimates of future stock market returns were based upon the
historical results for the period 1926-1990, as reported in [3].
There is excellent data available for this period. But since we
are preparing for very long-term suspension, we are interested in
the longest periods with known investing results.
Ibbotson and Brinson [1] show the total return on the U.S. Stock
Market from 1790 through 1990 (201 years). Their results from
1790 to 1871 are somewhat sketchy, obtained by linking together
various New York Stock Exchange indices of "undocumented
characteristics". From 1871 until the present, the results are
based upon purchasing all stocks on the NYSE, weighted by market
value. It is remarkable how consistent the results are over the
years, as shown in the Table below.
In [2] I assumed the real returns were 8.8% q 21.0%. The results
for the whole 201-year period are 8.5% q 19.9%. The respective
one year Kelly growth rates are 6.6% and 6.5%, so my results
would change very little using the longer-term figures.
Most cryonicists know of our favorite quote from Benjamin
Franklin:
I wish it were possible, [reference to experiments in
which he revived flies drowned in Madeira wine], to
invent a method of embalming drowned persons, in such a
manner that they might be recalled to life at any period,
however distant; for having a very ardent desire to see
and observe the state of America a hundred years hence, I
should prefer to an ordinary death, being immersed with a
few friends in a cask of Madeira, until that time, then
to be recalled to life by the solar warmth of my dear
country!
It is less well known that when Franklin died in 1791, he left a
trust of about $5,000 to be invested for 200 years, to benefit
medical students and fund scientific research [1]. When the fund
was liquidated in 1991, it had grown 400-fold to $2,000,000, even
after the spending. (The Table results predict over
$4,000,000,000 with no taxes or spending). Thus Franklin's trust
provided proof-of-principle that cryonic suspension funding *can
work*. If only Franklin had instructed his executors to preserve
him in a cask of Madeira, his trust could surely have paid the
maintenance, and Ben would still be around today--pleasantly
pickled!
Survivorship Bias
The two-centuries results of investing in U.S. equities have been
excellent. Britain is another country that has provided excellent
returns to investors over centuries.
But social upheaval, or the loss of a war, may wipe out equity
values--especially to foreign investors, whose assets may be
expropriated. The 1917 advent of communism in Russia, World War I
in Germany, and World War II in Japan, wiped out equity values in
those countries. Thus U.S. returns for the last two centuries are
much better than would have been obtained by investing in a
diversified international portfolio.
We who expect to be suspended in America are betting on the long-
term stability of the American government and economy. But the
history of the collapse of other economies suggests that, over
the long term, it is prudent to hedge one's bets by investing
trust funds in a diversified international portfolio. (This is
somewhat mitigated by the presumption that we are less likely to
have our investments expropriated by the U.S. government than by
a foreign government.)
Recent Returns
The Graph shows returns over the 21 year period 1970-1990. The
curves are the loci of points that have the same Kelly growth
rate, assuming that the returns are lognormally distributed. That
is,
G = log((1+return) / (1 + (std/(1+return))^2)^.5).
Over this period, the Kelly growth rate of stocks was only a
little better than that of government obligations. Over the
longer period 1926-1993, stocks outperformed bonds by a much
larger margin, and small company stocks beat large company
stocks.
The EAFE index of 1000 foreign stocks did even better. I show
just two of the foreign stock markets that outperformed U.S.
stocks.
U.S. Equity Total Returns for 1790-1990 by Subperiod
(From [1], Table 8-4)
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Geometric Arithmetic
mean mean Standard Serial
return return deviation correlation
Period (%) (%) (%) (%)
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Whole period
1790-1990
Nominal 8.3 10.1 19.6 -1
Real 6.6 8.5 19.9 -1
Half-centuries
1790-1839
Nominal 7.5 9.4 19.8 -11
Real 7.6 9.7 20.9 -6
1840-1889
Nominal 7.9 9.4 19.0 12
Real 7.5 9.1 19.1 9
1890-1939
Nominal 6.3 8.6 21.6 -1
Real 4.8 7.2 22.0 -2
1940-1990
Nominal 11.5 12.8 16.6 -8
Real 6.7 8.1 17.4 -2
In the Table, the arithmetic mean of the past performances is a
few percent higher than the geometric mean. Which mean should we
use for forecasting into the future?
Suppose we find that at the end of each of the last n+1 years,
the index we are tracking had values V[0], . . . V[n]. Let m[i]
= V[i] / V[i-1] = (1 + return for the ith year). Let
m_bar_g = (PRODUCT m[i])^(1/n)
i
be the geometric sample mean.
Suppose we wish to estimate the mean and variance of the
distribution k years from now. I have shown that the minimum
variance, unbiased estimators are:
m_bar_best(k) = m_bar_g^k Q((n-k)sigma_bar_a^2, n, k) ,
s_bar_best^2(k) = m_bar_g^2k (Q(4(n- k)sigma_bar_a^2, n, 1) -
Q(2(n-2k)sigma_bar_a^2, n, 1)),
where sigma_bar_a^2 is the sample variance of {log(m[i])}, and
Q(t, n, k) = 1 +
oo 1 ((n-1) k t) j
SUM ----------------------- |---------| .
j=1 j! (n-1) . . . (n+2j-3) ( 2n )
Although complicated, these formulas are easily programmed on a
computer. For quick-and-dirty hand approximations, we can look at
two special cases:
When you are trying to predict the mean only a few years into the
future, compound the *arithmetic* mean.
When you are trying to predict the mean about n years into the
future, compound the *geometric* mean.
[Graph of Total Returns (1970-1990) omitted]
References
[1] Ibbotson, R., and Brinson, G. Global Investing. New York:
McGraw-Hill (1993).
[2] Quaife, Art. Staying Cold: Providing Sufficient Maintenance
Funding. The Trans Times 1:3, 1-8 (1992).
[3] Stocks, Bonds, Bills, and Inflation 1991 Yearbook. Chicago:
Ibbotson Associates (1991).
Annual Meeting
TRANS TIME held its Annual Meeting of Shareholders on April 17.
The current Board of Directors was reelected for the upcoming
year. At the following meeting of the Board of Directors, the
current officers were reelected for the upcoming year. So the
current Board is:
Art Quaife, Ph.D., President
Hal Sternberg, Ph.D., Vice-President
Judy Segall, Secretary
Norm Lewis, Treasurer
Carmen Brewer
Stephen Kehrer
Have Something to Say?
We invite our readers to submit cryonics-related articles for
possible publication in this newsletter. The best way to submit
is to send us the article in a WordPerfect file, on an MS-DOS
diskette. Call us about other electronic formats you may use. We
will also consider typed or handwritten submissions.
Upcoming Meetings
TRANS TIME holds bimonthly business meetings at which visitors
are welcome. The next meeting will be held Sunday, June 19, 1:00
p.m. at:
The Home of Stephen Kehrer
2909B Newbury Street
Berkeley, CA 94703
(510) 549-3208
The following meeting is planned for Sunday, August 21, 1:00 p.m.
at:
The Home of Judy and Paul Segall
1003 Middlefield Road
Berkeley, CA 94708
(510) 644-3153
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