- "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! But in all probability,
we live in a century too little advanced, and too near the infancy of science,
to see such an art brought in our time to its perfection."
-
- Benjamin Franklin wrote these words in 1773. And what
if the old guy was onto something? What if life had a Skip button, like
the one on your TiVo? Then you could go offline until next year, when your
medication will be approved, or next decade, when your bonds will have
matured, or even next century, when life is scheduled (finally!) to become
perfect.
-
- A company called BioTime shares the dream. BioTime deals
in ultra-profound hypothermia, the body's last stop before freezing. Suspended
animation isn't in the prospectus - yet. For the moment, this 10-person
outfit is helping doctors chill their patients during heart, brain, and
vascular surgery, where lower temperature translates into more available
time on the operating table, less potential for blood loss, and fewer post-op
complications.
-
- Major surgery can be hell on a patient, and procedures
that require interrupting blood flow can be the worst because they starve
the body of oxygen. To prepare for stopping the heart, for instance, doctors
divert the bloodstream through a heart-lung machine that circulates the
entire blood volume 30 to 60 times an hour. The machine can release air
bubbles into the bloodstream, bringing on cognitive loss and personality
change. It also ruptures red blood cells, spilling free hemoglobin into
bodily organs, where it's toxic. Meanwhile, white blood cells, finding
themselves surrounded by plastic tubing, go into a sort of immunological
panic mode. The resulting inflammation can cause capillaries to leak, especially
in the brain.
-
- One way to sidestep these issues is to minimize the body's
oxygen demand, and the simplest way to do that is to cool the affected
tissues. This has spurred a billion-dollar industry in therapeutic hypothermia,
in which a dozen companies jockey for market position. There are blood
coolers and ice-water baths, cold caps and water-circulating pads that
adhere to the skin. Most of these devices are designed to cool a specific
area of the body. Some drop a person's core temperature as low as 90 degrees.
Any lower and blood thickens to sludge while its proteins fold up into
useless shapes, tempting catastrophic circulatory dysfunction.
-
- It's here that BioTime stands out from the pack. The
company has developed a process that cools living bodies much further than
that. Fifty-six degrees further, in fact, right down to the brink of freezing
- a state in which the brain takes hours, not minutes, to wither.
-
- BioTime's secret is dumbfoundingly obvious: antifreeze.
The company's flagship product, Hextend, is an FDA-approved blood-volume
expander designed to maintain blood pressure and chemistry in the wake
of massive blood loss. It's used for this purpose in surgical wards throughout
the US and Canada, but the product has an additional property: It doesn't
coagulate at low temperature. Since 1992, BioTime has been testing Hextend
in baboons, pigs, and dogs, replacing their entire blood supply and then
cooling them to 35 degrees. At that point, vital signs cease. Bleeding
virtually stops. Oxygen-hungry tissues go on a diet. Then technicians raise
the body temperature, reintroduce the blood, and shock the heart to life.
-
- "Right now, we can easily bring animals back from
two hours of absolute clinical death," says Hal Sternberg, BioTime's
VP of research. "No pulse, no respiration, no measurable brain activity."
-
- The astounding thing is that the animals show no sign
of physical or neurological damage. Over a period of weeks, the animal
returns to its cute and cuddly self.
-
- The FDA hasn't approved BioTime's procedure for humans
yet, but with Hextend already on the market as a blood-volume replacement,
Sternberg expects the green light in as little as three years. And when
that happens, it will not only improve surgical safety, but also make way
for longer procedures that no surgeon would dare attempt at room temperature,
such as separating adult conjoined twins fused at the head.
-
- BioTime has other cool stuff in the pipeline, including
HetaFreeze, a solution called a cryoprotectant. This substance makes it
possible to freeze tissue grafts - BioTime has tested it with skin and
hair - without disrupting their cellular structure. It may allow whole
organs, such as hearts, and even intact (but brain-dead) organ donors to
survive partial freezing.
-
- BioTime's story is neat, clinical, and investor-friendly,
with a unique set of medical technologies that have immediate utility.
Clinical death for up to 15 minutes has been reversible since the 1952
invention of the defibrillator; now BioTime is on the brink of extending
that limit to hours. But with the envelope pushing out further and further,
the momentum is carrying the company into stranger territory.
-
- Especially given that Sternberg and his colleagues are
longtime members of the cryonics movement, whose techno-utopian, frozen-head
agenda is well known.
-
- Like many R&D shops, BioTime's headquarters in Berkeley,
California, is strewn with half-finished projects. One involves a pair
of table-mounted pistons capable of generating up to 3,000 atmospheres
of pressure. Ordinarily, ice crystals rupture the cells of a frozen tissue
sample, leaving nothing but freezer-burned goo. But treated with cryoprotectant,
suspended in liquid nitrogen, and pressurized by these pistons, the tissue
enters a glassy, or vitrified, state from which it can be thawed and grafted
onto a living animal. In nature, frogs tolerate partial freezing for weeks
on end, and while Sternberg doesn't hold much hope for reviving such critters
from vitrification, he does talk about vitrifying and restoring their little
hearts.
-
- Meanwhile, the company's cash flow derives mainly from
Hextend, which is manufactured and distributed by Abbott Pharmaceuticals
in Chicago. Like many blood-related products, it comes in clear 500-milliliter
bags covered in tiny blue print. This familiarity is reassuring, because
for nearly 50 years the task of blood-volume expansion has been handled
by balanced electrolyte solutions like ringers lactate - the basic fluid
typically found in an IV bag - or by simple solutions of starch and saline.
But ringers lactate passes through the blood-vessel walls too easily, causing
tissues to swell and blood pressure to drop, and saline throws the body's
electrolytes out of whack. Hextend combines the best qualities of both
products along with a revitalizing shot of glucose.
-
- Sternberg, who invented the solution along with other
BioTime principals, looks a decade younger than his 50 years. Indeed, he
seems dedicated to dodging the grim reaper at any cost. He exercises daily
but avoids sports and stays out of cars, and he eats a diet that can only
be described as eccentric: minimal fat, lots of protein, fiber, and sugar,
and so much hard green fruit that he rubbed his gums right off and had
them surgically replaced with grafts.
-
- "Everyone is focused on molecular biology these
days," he says. "Nobody is thinking about gross physiology. We've
got a worldwide patent and tremendous customer loyalty. When surgeons try
Hextend, they never switch back."
-
- For a solution intended to make up for lost blood, Hextend
is a surprisingly inefficient transporter of oxygen. Blood carries 20 percent
oxygen by weight; BioTime's product holds only 0.3 percent, about the same
as ordinary water. Most people, however, have more red blood cells than
they really need for short-term survival, so diluting the circulatory system
for a few hours of surgery isn't a problem. This is especially true near
the freezing point, where Hextend, supplemented with sodium bicarbonate,
potassium, and magnesium, can safely replace the entire bloodstream.
-
- "Metabolic needs are drastically reduced at these
temperatures," Sternberg notes. "As it turns out, 0.3 percent
is more than enough. And the brain can survive for hours on stored oxygen
alone."
-
- For test animals cooled for more than three hours, BioTime's
success rate drops below 50 percent. If this sounds untenable, keep in
mind that for patients with an inaccessible brain tumors, the alternative
is certain death.
-
- Nonetheless, the idea of popsicle patients horrifies
experts who haven't gotten used to it. "Thirty-five degrees?"
says Jonathon Sullivan, an assistant professor at Detroit Receiving Hospital
who is familiar with hypothermia's effect on the nervous system. "That
sounds like a dead person. The lowest survivable temperature we've seen
from accidental hypothermia is 61 degrees, and that entails prolonged critical
care afterward."
-
- Still, Sullivan cottons to the idea after a few minutes
of mulling. "There's an old axiom of resuscitology," he says:
"You're never dead until you're warm and dead."
-
- That axiom could be the motto of the cryonics movement.
Nonetheless, the medical establishment has shunned advocates of freezing
bodies for eventual revival. And who can blame them? Cryonics is just plain
creepy.
-
- The movement's roots reach back to the 1964 publication
of Robert Ettinger's The Prospect of Immortality, but the current chapter
begins in 1972, with a rift among the founders of Trans Time, a pioneering
cryonics venture. One Trans Time splinter, Alcor Life Extension Foundation,
went on to become supreme tabloid fodder in 2003 when it acquired the remains
of deceased baseball legend Ted Williams after a bizarre custody scuffle
between his children. Things took an even stranger turn when Alcor's former
COO, Larry Johnson, told Sports Illustrated that the company had mishandled
Williams' remains. Alcor insiders, he charged, joked about "throwing
the body away" and "posting it on eBay" to persuade the
sports star's son to pay an outstanding bill in excess of $100,000. Johnson
himself later sold photos on his Web site of Williams' severed head.
-
- This kind of behavior explains why BioTime goes out of
its way to distance itself from cryonics. It's tricky, though, since BioTime
has roots in Trans Time, too. BioTime VP of operations and secretary Judith
Segall insists, "There's no association between the two companies."
However, a 1992 Trans Time newsletter trumpets a "close working relationship"
with BioTime. "Drs. Paul Segall, Hal Sternberg, and Harold Waitz,
BioTime's principal researchers, have a long affiliation with Trans Time,"
the document says. Later, it notes that "Hal Sternberg is currently
our vice president, and BioTime secretary Judy Segall is also Trans Time's
secretary."
-
- BioTime founder Paul Segall - husband of Judith and brother
of Trans Time president John Segall - died in June 2003 from an aneurysm.
Until the firm appoints a new CEO, his business role has been assumed by
his wife and his technical functions by Hal Sternberg and Harold "Frosty"
Waitz, another Trans Time alum.
-
- So it's hard to feel sure you're getting a straight answer
when asking Sternberg about the prospects for long-term suspended animation.
"Oh, jeez, that's a good question," he says. "For the next
few years at least, I expect the limits on a whole person might be two
hours, or maybe slightly longer. However, with a more substantial understanding
of animals in a hibernating state, we may be able to reduce the demand
for food and oxygen dramatically. There may be hormones or other things
that could enable the body to tolerate much longer periods."
-
- How about freezing people altogether, I ask, conjuring
an image of Woody Allen in Sleeper. "Until somebody does it,"
Sternberg says, "we don't know if such people would ever be revived."
-
- Sternberg himself may be among the first to learn, because
Paul Segall is frozen right now, in a liquid nitrogen dewar on Trans Time
premises in San Leandro, California.
-
- Many cryonicists speak of their frozen kin in the present
tense, as if entering suspension were something quite different from dying.
Sternberg doesn't do this. In talking about his departed friend and partner,
he makes liberal use of was and had and even the dreaded d-word itself.
But in a candid moment he affirms his faith.
-
- "It may take a long time," he says, "but
someday we'll wake Paul up."
-
- As far as anyone knows, there's nothing physically impossible
about reviving a frozen head. Still, when you get down to it, Alcor and
Trans Time are taking money for a service that may never exist, and that
even the companies themselves estimate is 150 years down the road. BioTime
is approaching the problem from the other end - the respectable end - by
working to extend established medical procedures. The immediate benefit
will be preventing untimely death in the here and now, which is a completely
different proposition than resurrecting the already dead.
-
- On the other hand, to give the envelope - any envelope
- a meaningful nudge, you have to be a little bit crazy. You need to walk
the knife-edge between the unlikely and the impossible. You need to dream.
NASA has always been keen on hibernation for long space voyages, ¦
la Aliens and 2001: A Space Odyssey. Indeed, several NASA documents cite
a 1995 article in the Journal of Gravitational Physiology called "Low
Temperature Preservation and Space Medicine." The authors? Paul Segall,
Hal Sternberg, and Frosty Waitz.
-
- With a bit of prodding, Sternberg describes the outline
of his daydreams. "You can also freeze small tissues and all kinds
of single cells indefinitely, and it has been shown that bacteria can travel
on a meteorite in a frozen state. How long? With enough research, I think
the answer is indefinitely."
-
- But who would risk their own neural integrity on such
experiments? Ironically, given the need to preserve donor organs for as
long as possible, brain-dead accident victims may lead the way in whole-body
cryobiological research. The day may not be far off when we freeze these
cadavers for transport, then thaw them and place their revived organs into
the bodies of deeply hibernating transplant patients.
-
- When this becomes routine, the next survival boost will
come from freezing prospective organ recipients when death is imminent
and no replacement organ is available. We'll pause their lives for weeks,
months, maybe even years. And once we've done that, can the stars themselves
be far behind?
-
- © Copyright © 1993-2003 The CondÈ Nast
Publications © Copyright 2004, Lycos, Inc. All Rights Reserved. http://www.wired.com/wired/archive/12.05/biotime.html?tw=wn_tophead_6
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