X-Message-Number: 16537
From: Brent Thomas <>
Subject: interesting example of mainstream convergence
Date: Thu, 14 Jun 2001 10:00:55 -0400
Here's an interesting example of mainstream research and inquiry yielding
fruits that may be highly
applicable to our interests in cryonic suspension. The more mainstream
dollars applied to this sort of research
the more likely we are to see some interesting results.
from http://www.sciencedaily.com/releases/2001/06/010614063420.htm
Source:
Fred Hutchinson Cancer Research Center (http://www.fhcrc.org/)
Date:
Posted 6/14/2001
Hutchinson Center Researchers First
To Induce State Of Suspended
Animation In Model Vertebrate
Organism
Last February, a toddler in Alberta, Canada, made headlines
worldwide after she wandered outside and nearly froze to death.
Although her heart stopped beating for two hours and her body
temperature was 61 degrees when she was found lying face
down in the snow, 14-month-old Erika Nordby made a
complete, stunning recovery.
While such recovery from biological limbo seemingly defies
scientific or medical explanation, researchers at Seattle's Fred
Hutchinson Cancer Research Center have developed a method to
induce a similar state of so-called suspended animation in the
zebrafish, a relatively new model of vertebrate developmental
biology.
Their work, the first demonstration of this phenomenon in a
vertebrate model organism highly suitable to laboratory analysis,
will be described tomorrow in the June 12 issue of the
Proceedings of the National Academy of Sciences (Early Edition
No. 24).
This discovery, by Mark Roth, Ph.D., a member of the
Hutchinson Center's Basic Sciences Division, promises to open
new paths of research into understanding the phenomenon of
suspended animation. The achievement ultimately could lead to
new ways to treat cancer and prevent ischemic injury from
insufficient blood supply to organs and tissues.
Roth, in collaboration with postdoctoral research fellow Pam
Padilla, Ph.D., discovered that after 24 hours of oxygen
deprivation - resulting in cessation of all observable metabolic
activity, including heartbeat - zebrafish embryos can resume a
normal course of development with no harmful effects on their
health or growth.
Roth's studies on biological limbo may shed light on two
problems that perplex cancer biologists: the control of stem-cell
division and how oxygen deprivation affects tumor growth.
"We typically think of cancer cells as growing out of control,"
said Roth, also an affiliate associate professor of biochemistry at
the University of Washington School of Medicine. "But actually,
within a tumor there are many types of abnormal cells, and only
a subset are multiplying at any one time. The vast majority of
cells in a tumor are in a state of low oxygen tension and are
non-proliferating - which is the reason that some tumors don't
respond to certain forms of radiation and chemotherapy." Most
chemotherapeutic agents work by selectively killing actively
dividing cells, meaning that many quiescent, or non-dividing,
tumor cells are immune to treatment.
Suspended animation also has a role in the growth of normal
cells, Roth said.
"Stem cells - like those that give rise to your skin - are
self-renewing and have the capacity to reproduce at certain times
in your life," he said. "Some of those cells might be dividing
right
now, while others withhold their proliferation potential until a
later time. Lots of scientists are interested in how cells maintain
this state of quiescence and then resume cell division." The
phenomenon also is critical for the normal development of many
animals.
"Numerous organisms have naturally occurring states of
suspended animation," Roth said. "About 70 species of mammals
alone do this as a way to increase reproductive fitness. For
example, mice delay implantation of their embryos in the uterus
while they are lactating. The embryos halt implantation - and any
further development - until lactation stops."
Zebrafish in the wild haven't yet been observed to undergo
suspended animation, but the metabolic shutdown that Roth
induces in his laboratory resembles the reversible state of limbo
that has been observed in nature in other organisms.
Roth and Padilla, the paper's co-author, compared the
developmental capability of zebrafish embryos that had been
exposed to normal atmospheric conditions to those grown in
anoxic (oxygen-free) chambers. Absence of oxygen caused
development to arrest and all observable metabolic activity to
cease - including a shutdown of the heart, which normally beats
100 times per minute. The researchers found that embryos 25
hours post-fertilization or younger could survive without oxygen
for 24 hours and resume normal development after re-exposure
to standard levels of oxygen.
"We can't detect any abnormalities in these fish after they
recover," Roth said. "They have grown to adulthood, mated and
produced normal offspring."
Roth's next goal is to figure out the molecular pathways that
permit this recovery and why some vertebrates can survive a
lack of oxygen - or other forms of extreme stress - and why
others can't. "In the case of heart disease, humans typically die
of a failure to get enough oxygen to cells," he said. "Cells
deprived of oxygen for too long, particularly brain cells,
typically
undergo apoptosis - a form of cell suicide. If that happens and
you live, you suffer from brain damage."
Some humans, for unexplained reasons, do manage to survive
extreme forms of stress, such as brutally cold temperatures for
an extended amount of time, and manage to recover from a
metabolic shutdown. "What makes some animals - and even
some people, like the case of the frozen little girl in Canada -
able
to survive extreme stress? Wouldn't it be great to have some
control over this process?"
While it may seem in the realm of science fiction right now, a
potential application of this control would include helping people
survive life-threatening injuries while in transit to a hospital
emergency room. Bodies or organs held in a state of suspended
animation could be repaired and suffer no long-term
consequences from extreme stress such as oxygen deprivation.
Roth admits that it is hard to predict whether such strategies will
work, but for now, he is caught up with trying to explain the
mechanisms controlling this puzzling phenomenon.
"Understanding the mechanisms that control biological
quiescence could have dramatic implications for medical care, as
it could give us an ability to control life processes at the most
basic, fundamental level," Roth said.
This work was supported in part by funding from the National
Institutes of Health and the National Science Foundation. The
Hutchinson Center has filed a patent application to cover this
technology, which is available for licensing.
The Fred Hutchinson Cancer Research Center is an independent,
nonprofit research institution dedicated to the development and
advancement of biomedical technology to eliminate cancer and
other potentially fatal diseases. Recognized internationally for
its
pioneering work in bone-marrow transplantation, the Center's
four scientific divisions collaborate to form a unique environment
for conducting basic and applied science. The Hutchinson Center
is the only National Cancer Institute-designated comprehensive
cancer center in the Pacific Northwest and is one of 37
nationwide. For more information, visit the Center's Web site at
http://www.fhcrc.org.
Brent Thomas
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