From: Randy Smith (email@example.com)
Date: Fri Feb 08 2002 - 09:41:34 MST
excellent article; thanks for posting it...I take it you are back with
>From: Eugene Leitl <Eugene.Leitl@lrz.uni-muenchen.de>
>CC: extropy <firstname.lastname@example.org>
>Subject: New Prospects for Putting Organs on Ice
>Date: Fri, 8 Feb 2002 15:51:58 +0100 (MET)
>-- Eugen* Leitl leitl
>ICBMTO: N48 04'14.8'' E11 36'41.2'' http://www.leitl.org
>57F9CFD3: ED90 0433 EB74 E4A9 537F CFF5 86E7 629B 57F9 CFD3
>New Prospects for Putting Organs on Ice
>After a lull, scientists are again exploring vitrification and other
>techniques for deep-freezing tissues and organs
>In the movie Vanilla Sky, Tom Cruise has his broken body frozen in the
>hope that he'll someday be revived and healed. In reality, cryonics, as
>this practice is known, remains the most speculative science fiction.
>Researchers have failed for decades to deep-freeze and thaw most
>tissues--let alone organs or animals--without damaging them, often
>seriously. But recently, a few cryobiologists have celebrated successes
>with ovaries and complex tissues like vascular grafts.
>The work has sparked hope that donated organs can eventually be banked for
>longer than the current few days, which would buy time for distributing
>them and finding recipients who are good immunological matches. And as
>progress is made engineering artificial livers, bladders, and other
>tissues containing living cells, the need for better preservation
>techniques is expected to grow (see Viewpoint on p. 1009). "Each company
>at some point will need to store and transport their product," says Mike
>Taylor of Organ Recovery Systems in Charleston, South Carolina.
>Currently, transplant surgeons perfuse whole organs with a special
>solution that enables them to be banked just above 0șC for up to a few
>days. Ideally, they would like to preserve organs at -196șC, the boiling
>point of liquid nitrogen--so cold that molecular motion virtually stops
>and tissues cease to decay. Half a century ago, that seemed within easy
>reach. Scientists found that blood and sperm could survive such deep
>freezing if mixed with glycerol. The glycerol lowers the cells' freezing
>point and keeps them from getting lethally salty when they do freeze and
>water diffuses out. And since 1972, embryos have been frozen with liquid
>nitrogen and later successfully implanted.
>Organs, however, don't hold up so well below the freezing point. Water
>leaked from cells during freezing forms ice crystals in the space between
>cells, and this ice destroys fragile structures such as ducts and blood
>vessels. Sometimes pieces of organs, such as pancreatic islet cells, work
>adequately after freezing. But larger, more complex organs such as kidneys
>don't function properly when sufficiently ravaged.
>As a way around this problem, some researchers turned to vitrification, or
>"ice-free" cryopreservation. The idea is to fill the organ with a viscous
>fluid that turns into a glassy (not crystalline) solid at low
>temperatures. This reduces the problems of ice, but toxicity of the
>cryopreservant can still damage organs. And ice crystals tend to form as
>vitrified tissue--especially large pieces--is warmed. Partial success came
>in the 1980s, when Red Cross scientist Greg Fahy showed that rabbit
>kidneys could withstand the high concentrations of cryoprotectants needed
>to vitrify these organs. They worked when reimplanted, but Fahy had only
>cooled them to -3șC. Many experiments later, it's clear that
>"vitrification is very, very complicated," says cryobiologist David Pegg
>of the University of York, U.K., and in most labs vitrification of large
>organs has been on hold.
>Recently, cryobiologists have had better luck studying vitrification on a
>smaller scale. For example, fine-tuning the solutions that are injected
>into the organs, as well as heating and cooling rates, minimized injury to
>2- to 3-centimeter-long pieces of rabbit veins, Taylor's team at Organ
>Recovery Systems reported in the 18 March 2000 issue of Nature
>Biotechnology. The vessels retained 80% of their function when dosed with
>drugs that cause them to contract, compared to 20% following simple
>freezing. When implanted in rabbits, the grafts appeared to work normally.
>"We're the first to demonstrate [that vitrification works better than
>freezing] in reasonably complex tissue," Taylor says. Two other groups
>have recently shown that they can vitrify corneas, getting much less
>damage than from freezing. But the scientists have yet to show whether
>these corneas function in vivo.
>Roger Gosden and colleagues at McGill University in Montreal have had
>success even with conventional freezing with a small organ, they reported
>last month in Nature. They froze rat ovaries, fallopian tubes, and
>attached blood vessels in liquid nitrogen and transplanted them into
>genetically identical rats whose ovaries had been removed. The animals
>ovulated. Some ice damage occurred, so vitrification might be even more
>successful, suggests Gosden, now at the Jones Institute for Reproductive
>Medicine in Norfolk, Virginia.
>Several groups are tackling problems that thwart both vitrification and
>conventional freezing. Pegg's group at York, for instance, is working on
>how to thaw tissues and avoid ice crystal formation. The team has
>developed a technique that Pegg says can evenly and quickly heat pingpong
>ball-sized clumps of cells embedded in gelatin to simulate large tissue.
>Taylor's group, meanwhile, is collaborating with Carnegie Mellon
>scientists on dosing tissues with iron compounds that are then excited
>with magnets to generate heat.
>Taking a cue from nature, researchers are also using natural antifreeze
>proteins to help mop up crystals formed during freezing and thawing. Many
>organisms, from carrots to fish to beetles, produce proteins that latch
>onto and isolate growing ice crystals. The one drawback is that at
>temperatures well below 0șC, this system can backfire by causing ice
>crystals to form spikes that disrupt cells. Several companies are
>developing improved synthetic versions of these "ice blockers"; for
>example, Taylor's company hopes to produce smaller molecules that attach
>to ice crystals at the base as well as the face, which could prevent spike
>Fahy, meanwhile, has never given up trying to vitrify large organs. "He
>has soldiered the way on this for years and years," Pegg says. Now at a
>company called 21st Century Medicine in Rancho Cucamonga, California, Fahy
>has tested hundreds of vitrification solutions and patented the most
>promising ones. "Greg has always been tantalizingly close to getting it to
>work," says cryobiologist William Rall of the National Institutes of
>Health. The company Fahy works for receives funding from the Life
>Extension Foundation, which supports cryonics. Fahy says his work is
>strictly limited to cryopreserving organs. But he adds, "If I'm
>successful, perhaps it will remove some of the [cryonics] controversy."
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