Original link: http://www.newsweek.com/2015/03/13/silicon-valley-trying-make-humans-immortal-and-finding-some-success-311402.html
Peter Thiel, the billionaire co-founder of PayPal, plans to live to be 120. Compared with some other tech billionaires, he doesn’t seem particularly ambitious. Dmitry Itskov, the “godfather” of the Russian Internet, says his goal is to live to 10,000; Larry Ellison, co-founder of Oracle, finds the notion of accepting mortality “incomprehensible,” and Sergey Brin, co-founder of Google, hopes to someday “cure death.”
These
titans of tech aren’t being ridiculous, or even vainglorious; their
quests are based on real, emerging science that could fundamentally
change what we know about life and about death. It’s hard to believe,
though, since the human quest for immortality is both ancient and
littered with catastrophic failures. Around 200 B.C., the first emperor
of China, Qin Shi Huang, accidentally killed himself trying to live
forever; he poisoned himself by eating supposedly mortality-preventing
mercury pills.
Centuries later, the search for
eternal life wasn’t much safer: In 1492, Pope Innocent VIII died after
blood transfusions from three healthy boys whose youth he believed he
could absorb. A little closer to modern times, in 1868 America, Kentucky
politician Leonard Jones ran for the U.S. presidency on the platform
that he’d achieved immortality through prayer and fasting—and could give
his secrets for cheating death to the public. Later that year, Jones
died of pneumonia.
But historical precedent hasn’t dissuaded
some of the biggest names in Silicon Valley. Thiel, for example, has
given $3.5 million to the Methuselah Foundation. Aubrey de Grey, Methuselah's co-founder, says the nonprofit’s main research initiative, Strategies for Engineered Negligible Senescence
(SENS), is devoted to finding drugs that cure seven types of
age-related damage: “Loss of cells, excessive cell division, inadequate
cell death, garbage inside the cell, garbage outside the cell, mutations
in the mitochondria, and crosslinking of the extracellular matrix.… The
idea is that the human body, being a machine, has a structure that
determines all aspects of its function, including its chance of falling
apart any time soon, so if we can restore that structure—at the
molecular and cellular level—then we will restore function too, so we
will have comprehensively rejuvenated the body.”
But
SENS, which has an annual operating budget of $5 million, is puny
compared with the Brin-led Project Calico, Google’s attempt to “cure
death,” which is planning to pump billions into a partnership with pharmaceutical giant AbbVie. Google is notoriously secretive, but it’s rumored to be building a drug to mimic foxo3, a gene associated with exceptional life span.
Then there’s the Glenn Foundation for Medical Research,
the granddaddy of modern antiaging initiatives, started by venture
capitalist Paul F. Glenn in 1965. Since 2007, the foundation has
distributed annual “Glenn Awards,”
$60,000 grants to independent researchers doing promising work on
aging. The Glenn Foundation also works to kick-start antiaging
initiatives within large institutions (“It began at Harvard, and then we
sought out MIT and then the Salk Institute and then the Mayo Clinic,”
Mark R. Collins, spokesman for the Glenn Foundation, explains), and it
puts more than $1 million per year toward grants by the American Federation for Aging Research, a charitable foundation dedicated to age-related disease.
The Glenn Foundation also works closely with the Ellison Medical Foundation,
a far younger institution (founded in 1997). Ellison’s passion project
gives out hundreds of thousands of dollars in grants each year to
scholars pursuing research on, and remedies for, aging. Their decision
to fund independent research—as opposed to creating grandiose, in-house
programs—may be paying off. Relatively modest research projects funded
by Ellison and Glenn appear to be developing into a verifiable means to
stave off old age—for lab mice. The tantalizing question: Can those lab
results be replicated in humans?
Aging in Reverse
In
1956, gerontologist Clive M. McCay performed a somewhat ghoulish
experiment on the rural upstate New York campus of Cornell University:
He sewed the flanks of live mice together in order to link their
bloodstreams. In the pairings McCay stitched together, one mouse was
spritely, healthy and young; the other was old and in relatively bad
shape. With their bloodstreams linked, the old mouse seemed to age in
reverse, getting healthier and younger as the experiment continued. The
young mouse, meanwhile, aged prematurely.
At
the time, relatively little was understood about the makeup of blood.
McCay's experiments were fascinating but a bit of a dead end, so he
shifted his focus to calorie restriction, where his experiments eventually made him famous, while his ingenuous blood work was largely left to languish.
Fast-forward
48 years to 2004. Amy Wagers, at Harvard University’s Department of
Stem Cell and Regenerative Biology, repeated McCay's flank-stitching
experiments to see if she could reproduce his results. And it worked. So
Wagers—in part funded by Glenn and Ellison—decided to try to isolate
individual proteins in the mouse blood to see what was causing the
ghoulish effect.
She found that a protein
called GDF11, common in the blood of young mice but sparse in the
systems of the older rodents, caused much of the old mice’s "reverse
aging." In the bloodstream, GDF11 is responsible for keeping stem cells
active; when GDF11 levels drop, as they do with age, stem cells (which
are responsible for tissue renewal) falter, injuries heal more slowly
and aging begins to take hold. But even in very elderly bodies with very
little GDF11 inside them, those stem cells never go away—they merely
become dormant as GDF11 levels drop. Injecting young blood, with its
high levels of GDF11, into old mice seemed to restart those dormant stem
cells, causing the old mice to "age in reverse" as they produced the
healthy, vital tissues associated with youth. The work is “incredibly
promising,” says Collins.
Meanwhile, at the M.D. Anderson Cancer Center in Houston, one of the Ellison Medical Foundation’s Senior Scholars in Aging
had also been experimenting with ways to keep mice from growing old.
Dr. Ronald DePinho was interested in telomeres, structures that cap the
tips of chromosomes like aglets do the end of shoelaces. In young
bodies, an enzyme called telomerase keeps telomeres healthy and stable;
in older bodies, levels of telomerase drop, telomeres shorten, and the
chromosomes begin to fray. It seemed likely these fraying chromosomes
were responsible for some of the physical effects of aging, and DePinho
wanted to find out how.
His team genetically engineered mice
whose telomerase output could be toggled and found that in the “off”
state, where there was no telomerase at all, the mice aged prematurely.
"We took them to the point where they were the equivalent of 90-year-old
humans,” he says, “with shrunken brains, impaired cognition,
infertility, thin bones, hair loss, etc."
Then
DePinho and his colleagues toggled the telomerase back on—and what he
saw was incredible. "The organs started to restore themselves,” he says.
“The brain increased in size, cognition was improved, fertility was
restored, hair returned to a healthy sheen, and all of the other
problems that we saw in the animal were alleviated." Giving telomerase
to a telomerase-deprived animal didn't just halt the aging process—like
GDF11, it seemed to make the animals younger.
Might
either or both of these discoveries be used to create a Ponce de
Leon–style fountain of youth? "We've not done any life span studies on
these animals, so we don't know whether this would have an effect on
their life span. But we think that it would affect one's health
span—meaning the number of years that you live without a significant
illness," says Wagers. Preliminary studies look promising. Wagers says a
colleague has been looking into a protein she describes as the fly
version of GDF11. “When he gives more of it to flies, they live longer.
And if he takes it away, their life span is shortened."
There’s
one (huge) caveat here. Telomerase is linked to both the prevention and
progression of cancer. Aging cells that lack telomerase are more likely
to become cancerous; when older cells replicate, their "fraying"
chromosomes, unprotected by telomeres, often give birth to
cancer-causing mutations. And once cells become cancerous, their
telomerase levels rise, letting the mutant cells spread and multiply
uncontrollably. Doctors treating cancer often work to deprive those
spreading cells of telomerase—and many are worried that flooding the
body with telomerase might help cancer along. In other words, this path
toward making us live longer could kill us.
DePinho and others think telomerase
therapy will likely reduce the incidence of cancer—by making chromosomes
less likely to fray. And though scientists like University of
California, Berkeley's Irina M. Conboy have raised concerns
that GDF11, by promoting cell regrowth, might also increase cancer
incidents, Wagers's cautious optimism mirrors DePinho's: She says there
is no evidence GDF11 causes higher incidence of deadly diseases. Still,
she says, more experiments must be done. Neither she nor DePinho think
their substances of choice will reach human clinical trials for several
years yet.
But with discoveries like
Wagers's and DePinho's prompting an eruption of scientific excitement,
the idea that we could live longer—not a few years more but maybe a
century or even several hundred years longer—suddenly becomes one of the
more stirring and controversial topics of the coming century. "What
this means for longevity must be defined carefully, of course, because
with such dramatic developments there will be a very big difference
between how long people have lived so far and how long people expect to
live," says de Grey. If we start living for an average of 400 years
instead of an average of 80, we may have to rewrite a lot of the stories
we tell ourselves about how life—and death—work.
According
to Wagers, if aging can be reversed, instead of the slow, steady
decline into senescence we are used to, we might just live and live and
keep on living, as healthy and apparently young-seeming humans, right
until some organ or other fails catastrophically. This in stark contrast
to the dystopian future imagined by, for example, Gregg Easterbrook last year in
the article “What Happens When We All Live to 100?” in The Atlantic.
Easterbrook and others posit a future in which life spans keep extending
but "health spans" don't, and the sickly elderly live for decades and
suck all of the money out of the economy. In Wagers’s version, on the
other hand, everybody stays healthy right until they die—so maybe there
doesn't need to be a retirement age, and the economy grows and grows.
Though perhaps that's a recipe for another kind of dystopia: one where
we work and work and work and never stop working for 384 years, until
the day we die.
Print Your New Liver
But
maybe, in the future, we won’t need to worry about organ failure. For
all those times when there isn't an organ to spare, there'll soon be
cloned copies, either grown in the lab or 3-D printed: We've already 3-D printed livers and kidneys, turned skin cells into stem cells and stem cells into organs, and we're redefining the definition of fatality, thanks to a procedure called cold saline resuscitation.
Replacing a dying body's blood with a rush of cold saline can drop the
body's temperature and put a dying patient into a state of suspended
animation. And once a patient is in that state, doctors can fix a whole
lot of things that might otherwise be fatal: gunshot and knife wounds,
hemorrhages and organ failure—especially if there's a handy supply of
spare, cloned organs available in the emergency room.
To
our current tastes, there's something a little ghastly about this
paradigm: living forever, or at least a long time, in an eternal, static
youth, with trips to the emergency room more frequent as we get older,
to periodically replace failing organs. According to a 2012 Pfizer study,
when it comes to aging, our greatest fears are of “being dependent” or
“living in pain.” That might be replaced in our cultural imagination by
fear of eternal youth leading to sudden, stunning death—what if your
heart, 200 years old, suddenly gives out when you're nowhere near a
hospital? The body horror of the future may be very different from
today’s, but it's body horror all the same.
Perhaps
the fix is to replace bodies—these unreliable vessels, plagued with
problems!—altogether. That's the goal of the most ambitious
billionaire-backed immortality investment of them all, Itskov’s 2045
Initiative. Founded in early 2011, the initiative has already collected
an impressive set of experts
in specialties ranging from robotics and neural interfaces to
artificial organ creation. Their goal: replace our current meaty cases
with robotic or holographic avatars by (you guessed it) 2045.
In some ways, the 2045 Initiative’s goal isn't as ridiculous as it sounds. Tele-operated robotic avatars exist,
though so far they're more novelty than lifestyle choice. Itskov thinks
that as tele-operated avatars become more fine-tuned, “the jobs with an
increased risk to human life and health, such as that of a fireman, a
police officer, a first-responder, a miner, etc., will disappear.”
Eventually, says Itskov, these tele-operated avatars will be “superior
to the biological body in terms of its abilities,” thereby ushering in
an era of increased avatar popularity.
But even if such robot avatars
get cheaper and experience a sudden upswing in use, consciousness is
still tied to our meaty, messy brains—and thus far, no one's yet made
headway in transferring it to a more durable medium.
That's
not to say no one's trying. Tech giant Intel is aiming to have an
“exascale” computer—a computer that can operate at the same speed as the
human brain—by 2018. And in August 2013, researchers from Japan and
Germany used Japan's K supercomputer to simulate 1 percent of brain
activity for one second. That may not sound like much to be excited
about, but with exascale machines on the horizon, it’s surely a sign of
what’s to come. Markus Diesmann, one of the scientists involved in the K
supercomputer experiment, told The Daily Telegraph
in 2014, “If petascale computers like the K computer are capable of
representing 1 percent of the network of a human brain today, then we
know that simulating the whole brain at the level of the individual
nerve cell and its synapses will be possible with exascale
computers—hopefully available within the next decade.”
Youth Is Wasted on the Old
But
whether we achieve immortality through robots, injections or protein
packs, one profound and disturbing question remains: Do we really want
to live forever? And if so, why?
Itskov says
he’s driven by frustration. A serial hobbyist, the Russian billionaire’s
taken up judo, weight lifting, diving, practical shooting—“but every
time I achieve certain results in a new type of sport or a hobby, I
realize that if I really want to get serious results, then I need to
make this activity the focus of my entire life and sacrifice something
else for it that is no less interesting.” This dilemma, he says, keeps
him constantly aware of how short life is. “For all the diversity of
opportunities that life gives us, there is so little that we manage to
find out and do.” Hence, Itskov’s incentive for the 2045 Initiative:
“When I am successful in realizing this mega-project, then I will
finally have 10,000 years for numerous hobbies.”
For
other billionaires, a short life doesn’t seem terrible compared with
the calamity aging promises: a slow decline and death that most of us
accept as inevitable. For Ellison, the frustration of the deteriorating
body is personal: “I lost my mother to cancer, and anyone who's watched
anyone suffer from that disease...well, life can't be made much more
dreadful for them,” he told The Guardian in 2001, when his interest in
cures for aging was first piqued. For others, like Thiel, it’s the
mainstream’s refusal to even think to thwart death that’s frustrating.
“The way we psychologically deal with aging is through some combination
of acceptance and denial,” he declared at the Venture Alpha West 2014
conference. “Acceptance is: ‘[It’s] going to happen, there’s nothing we
can do about it.’ Denial is: ‘It’s not going to happen to me.’”
Ask
ethicists about immortality, though, and the quest starts to look a
little less heroic. Paul Root Wolpe, the director of the Center for
Ethics at Emory University, argues that perhaps we ought to pay more
attention to how the elderly are treated today before we think to extend
life spans further. “When you hear people who are pro-life-extension
talk about the greater font of wisdom, experience and perspective you'd
create by extending life, well, we already have a lot of 70- to
90-year-olds in society now, and we do nothing to try to learn from
them,” he says. “So I don't buy that argument.” On the contrary, says
Wolpe, “we already have doubled the average life span of humans, and
what that has created in modern society is a cult of youth.”
The elderly, meanwhile, are
treated like detritus. Between 8 and 10 percent of American seniors were
reportedly abused last year, according to the National Center on Elder Abuse (NCEA), and for every case of abuse on record, the NCEA estimates between 14 and 24 others go unreported. A study conducted by De Montfort University
found that 61 percent of the elderly think society sees them as a
burden, while 57 percent think the media encourages the idea that older
people are a problem for society. Only a third feel their contribution
to society is properly recognized.
Still, even
Wolpe admits the pursuit of happiness may ultimately entail a pursuit of
a lot more time to be happy. The goal, he says, should be to seek out
“healthier living as we age...finding how we slow down the detrimental
aspects of aging. How do we keep people healthier longer and increase
the amount of time that they get to appreciate and enjoy life?” But
should our society be prepared for it, “if in the process of doing that
we also increase life span, that's fine,” he says.
Perhaps
the most worrying question that arises with the prospect of having
millions (and even billions) of multi-centenarians running around on
Earth is whether the planet can support this kind of growth. Current projections
suggest that the world’s population will rise from 7 billion today to
about 9 billion in 2050—at which point it will more or less level out.
And abundant concerns have already been raised about what all these
billions of people will do for work, not to mention where they will get
safe drinking water and the food necessary to live healthily. But those
forecasts don’t consider the possibility that we’ll stop dying. If we
do, the next generation of innovative health-tech entrepreneurs will
face perhaps an even greater challenge: redesigning the planet to
accommodate its massive population of Humans 2.0.
