1650 words, on Bill Andrews, the medical illustrator

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POPSCI.COM POPULAR SCIENCE 51

Bill Andrews has spent

two decades unlocking the

molecular mechanisms

of aging. His mission: to

extend the human life span

to 150 years, or die trying

THE Obsessives

Bill Andrews’s feet are so large, he tells me, that back when he was 20 he was able to break the Southern California barefoot-waterskiing distance record the fi rst time he put skin to water. Then he got ambi- tious and went for the world speed record. When the towrope broke at 80 mph, he says, “they pulled me out of the water on a stretcher.”

The soles of the size-15 New Balances that today shelter those impressive feet strike a steady clap-clap on the macadam as Andrews and I lope down a path along the Truckee River that takes us away from the clutter of cut-rate casino hotels, strip malls and highway exit ramps that is downtown Reno, Nevada. Andrews, 59, is a lean 6-foot-3 and wears a close-cropped salt-and- pepper Vandyke and, for today’s outing, a silver run- ning jacket, nicely completing a package that suggests a Right Stuff–era astronaut. He is in fact one of the better ultramarathoners in America. I am an out-of-shape former occasional runner, so it gives me pause to listen as Andrews describes his racing exploits. “I can run 100 miles, fi nish, turn around, and meet friends of mine on the course who are still coming in,” he says. “I’ve been in many races where I’m stepping over bodies of people who have collapsed, and I’m feeling great.”

His return to running after a middle-aged break was, he says, inspired by a revelation he had at a time when he and a small team of scientists at his biotech start-up, Sierra Sciences, had been working 14 to 18 hours a day

in the lab for fi ve years, rather obsessively pursuing a particular breakthrough. Finally, his doctor told him he was headed for an early grave. “I thought, god, I don’t want to cure aging and then drop dead,” Andrews says.

That would indeed be ironic. Because Andrews does intend to cure aging. This stated ambition induces in some listeners the suspicion that Andrews might suffer from delusions of grandeur, but he has a scientifi c pedi- gree that insists he be taken seriously. Unlike his friend Aubrey de Grey, the University of Cambridge longevity theorist who relentlessly generates media attention with speculations that straddle the border between science and science fi ction, Andrews is an actual research scien- tist, a top-drawer molecular biologist.

In the 1990s, as the director of molecular biology at the Bay Area biotech fi rm Geron, Andrews helped lead a team of researchers that, in alliance with a lab at the Uni- versity of Colorado, just barely beat out the Massachu- setts Institute of Technology in a furious, near-decade- long race to identify the human telomerase gene. That this basic science took on the trappings of a frenzied Great Race is a testament to the biological preciousness of telomerase, an enzyme that maintains the ends of our cells’ chromosomes, called telomeres. Telomeres get shorter each time a cell divides, and when they get too short the cell can no longer make fresh copies of itself. If we live long enough, the tissues and organ systems that depend on continued cell replication begin to falter: The

The Man Who Would Stop

Time photographs by john b. carnett ILLUSTRATIOn BY ALBERTO SEVESO

By Joseph Hooper

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one attractive enough to bring in a billionaire or a Big Pharma partner with pockets deep enough to take a drug candidate through the FDA’s time-consuming and fabulously expensive approval process.

“I want to cure my aging,” Andrews tells me, “my friends’ and family’s aging, my investors’ aging, their friends’ and families’ aging, and make a ton of money. And I want to cure everybody else’s aging too—I put that probably equal to making a ton of money.”

Doctors tend to look at bodily decline through the prism of so-called diseases of aging, our increasing sus- ceptibility over time to killers like cancer and heart dis- ease. But in the 1950s, research biologists began to view aging itself as the disease. When free radicals scavenge electrons from their neighbors, they set in motion some ugly chain reactions. Cholesterol molecules become oxi- dized and begin to interact with the artery walls to form atherosclerosis-causing plaque, for instance, or the DNA in the cell nucleus suffers mutations, laying the ground- work for cancer. Later refi nements of this theory em- phasize the role of the mitochondria, the cellular power plants that help convert glucose into energy. As the mi- tochondria age, they spew out increasing amounts of the free radicals that hamper energy production and dam- age the entire cell, accelerating our all-systems decline.

Among cell biologists, these mechanisms remain to this day the most accepted ways of explaining what’s happening to that face refl ecting back at us in our bath- room mirror. But telomere science has opened up the possibility of drilling even deeper into the molecular bedrock of aging. The fl edgling fi eld was energized in 1984, when biochemist Elizabeth Blackburn of the University of California at Berkeley and her then-grad student Carol Greider discovered the telomerase enzyme in a pond-scum protozoan, an achievement that won them a Nobel Prize. Since then, our picture of human telomeres and telomerase has sharpened consider- ably. Telomeres are made of repeating sequences of six

52 POPULAR SCIENCE AUGUST 2011

skin sags, the internal organs grow slack, the immune- system response weakens such that the next chest cold could be our last. But what if we could induce our bodies to express more telomerase? We’ll see, because that is what Andrews intends to do.

Andrews had scheduled this afternoon’s run as an 18-miler, but he graciously downscaled those ambitions on my behalf long before we set out from the parking lot of the Grand Sierra Resort Hotel. Four miles in, he’s hardly winded—and I’m out of gas. As we make our way back to his car, he consults his training watch and informs me that our pace was an almost respectable 8:40, excepting the latter stretches when I walked, push- ing our average up to 10 minutes a mile.

The embrace of fi tness has for Andrews a telomeric logic. Make poor lifestyle choices, and you’re likely to die of heart disease or cancer or something well before your telomeres would otherwise become life-threateningly short. But for the aerobicized Andrews, for anyone who takes reasonable care of himself, a drug that activates telomerase might slow down the baseline rate at which the body falls apart. Andrews likens the underlying causes of aging, free radicals and the rest, to sticks of dynamite, with truncated telomeres being the stick with the shortest fuse. “I believe there’s a really good chance that if we defuse that stick,” he says, “and the person doesn’t smoke and doesn’t get obese, it wouldn’t be surprising if they lived to be 150 years old. That means they’re going to have 50 more years to be around when somebody solves the other aging problems.”

But in his race to cure aging, Andrews may himself be running out of time. The stock-market crash of 2008 nearly wiped out two investors who had until then been his primary funders. Without the money to continue refi ning the nearly 40 telomerase-activating chemicals he and his team had already discovered, Andrews made the decision last September to cut a deal with John W. Anderson, the founder of Isagenix, an Arizona-based “network marketing” supplement company. This month, Isagenix will launch an anti-aging product containing several natural compounds that Sierra Sciences has veri- fi ed to have “telomere-supporting” properties. It’s not the powerful drug Andrews originally envisioned, but he says he believes it will promote “health and well-being” and just possibly generate enough cash to underwrite the expensive “medicinal chemistry” required to come up with a more fully developed anti-aging compound—

A BRIEF HISTORY OF IMMORTALITY

Antiquity

According to Greek mythology, the goddess Eos asked Zeus to

confer immortality on her Trojan lover Tithonus so she could

enjoy his favors eternally. In one of the early “be careful what you

wish for” tales, Eos forgot to specify eternal youth and Tithonus

eventually passed into never-ending decrepitude. Eos shut him

in a room where he babbled to himself for the rest of time.

THE Obsessives

“I WANT TO CURE MY AGING, MY FRIENDS’ AND

FAMILY’S AGING, MY INVESTORS’ AGING, AND I

WANT TO MAKE A TON OF MONEY,” ANDREWS SAYS.

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POPSCI.COM POPULAR SCIENCE 53

YOUTH ELIXIR

Bill Andrews

examines one of

tens of thousands

of compounds

he has screened

for anti-aging

properties.

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teens, usually at a rate of 50 base pairs a year. By the time some of our telomeres drop below about 5,000 base pairs, typically well into our “golden” years, our cells may have lost the ability to divide. They become senescent, bad at doing the work they were designed to do but good at doing things like releasing infl ammatory chemicals that harm their neighbors. Or they may be targeted for cell death.

Andrews sounds almost giddy when he describes the “aha” moment 20 years ago when he fi rst heard his soon-to-be boss at Geron, pioneering telomere biolo- gist Calvin Harley, lecture about telomeres as a “mitotic clock,” in which the steady shortening of the telomeres serves as the tick-tock of the aging cell. “I was fl oored,” Andrews says. He found the lockstep precision sug- gested by the metaphor irresistible.

Cultured in the lab, cells can divide just 50 to 70 times before packing it in (this is known as the Hayfl ick Limit, after longevity-research eminence Leonard Hay-

13th century

The English philosopher Roger Bacon writes

that aging is caused by the progressive

loss of vital spirit, or “innate moisture.” To

extend their life span, he advised old men to

spend time in the company of young women,

thereby absorbing their sweet, moist breath.

1513

Juan Ponce de León, the fi rst governor of Puerto Rico, discovers what

is now Florida while supposedly searching for the Fountain of Youth.

Legend has it that the 55-year-old Spanish explorer, who was mar-

ried to a much younger woman, was looking for a semitropical Viagra.

Though no documentary evidence exists, the story of the failed quest

was widely promoted by subsequent biographers and historians.

DNA bases—two thymine, one adenine, three guanine (TTAGGG)—that serve to “cap” chromosomes, prevent- ing potentially cancerous breaks; the analogy usually trotted out is the plastic aglet that prevents a shoelace from fraying at the ends. Telomeres also assist cell division. Every time a cell splits, the ends of its chromo- somes fail to get fully copied in the two new daughter cells, and a bit of telomeric DNA gets lost. No harm is done to the rest of the chromosome, but in cells that divide frequently, the telomeres shorten with each repli- cation. Telomerase’s job is to synthesize new DNA to add to the shrinking telomeres, slowing down the decline.

Human life, it turns out, is a losing effort to hang on to our telomeres. At conception, telomeres have roughly 15,000 DNA base pairs. Because telomerase can’t keep up with rapid cell division in utero, they shrink to about 10,000 base pairs at birth. At that point, the telomerase gene is mostly turned off. Without the enzyme, we continue to lose telomeric DNA—once we’re out of our

PSC0811_WL Longevity R1.indd 53 6/14/11 11:33 AM

54 POPULAR SCIENCE AUGUST 2011

fl ick, who discovered the phenomenon). The human body is signifi cantly more complex than a petri dish, but some similar limit must be enforced there, Andrews says, to account for the fact that the maximum human life span is so tightly regulated, with the longest-lived humans making it to 100 and, to the best of our knowl- edge, nobody surviving past 125. If free-radical damage were really the primary driver of aging, he says, people’s rate of bodily decline would vary widely based on the amount of environmental damage they had absorbed, a major contributor to the free-radical load, and therefore so would their maximum life span. “But you can look at a person and have a 95 percent chance of guessing their age within fi ve years,” he says. “There has to be some kind of internal clock ticking inside of us.”

Biologists continue to debate the extent to which aging at the cell level determines the aging of the whole organism. Most have argued that short or damaged

1726

Jonathan Swift publishes Gulliver’s Travels, especially memorable for its depiction of the Struldbruggs, who are born immortal with red dots on their forehead. Gulliver is delighted with his discovery of the Struld- bruggs until he learns that they’re doomed to eternal old age. Their hair and teeth fall out, and they gradually lose the ability to speak with their fellow Luggnaggians, unable to keep up with changes in the language.

1889

French physician Charles-Édouard Brown- Séquard recommends the dried and ground sex glands of guinea pigs and dogs as a tonic to extend youthfulness and virility. He sets off a craze for rejuvenation injections and even human-testes transplants.

telomeres aren’t as big a deal as Andrews, or even the more measured Harley, make them out to be. Tissues and organ systems that depend on cell division have a fair amount of reserve capacity, and the cells that seem to play the biggest role in our decline, neurons and heart- muscle cells, hardly replicate at all.

But over the past few years, the case for telomeres as a major player in aging, possibly even the prime mover, has grown stronger. Heart health, telomere biolo- gists point out, depends heavily on the endothelial cells that line the blood vessels, and brain health on the glial and schwann cells that make the myelin that protects neurons, all of which are cell types that hear the ticking of the mitotic clock. And last year, Harvard University researcher Ron DePinho published two studies in the journal Nature that have reframed the debate about telomerase activation. DePinho created an ingenious model whereby he could turn telomerase off in a mouse

Cancer Mutations in nuclear DNA can lead to out-of-control cell growth.

Cells stop replicating P53 fl ags cells for apoptosis, programmed cell death.

Atherosclerosis Free radicals oxidize cholesterol, which then sticks to artery walls.

Lower cell energy Decreased energy output has an eff ect on the entire cell.

Fewer new mitochondria Telomere dysfunctional cells lose the ability to produce new mitochondria.

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A UNIFIED THEORY OF AGING In February, Ron DePinho, a researcher at Harvard, connected telomeres, mito- chondria and free radicals into a single cycle of cellular aging. He calls it the “death spiral.”

PCG-1ALPHA, PCG-1BETA These proteins responsible for mitochon- drial function are repressed by P53.DECREASED CELL FUNCTION

Mutations can lead to damaged telomeres, more free radicals, and impaired function.

MITOCHONDRIA FAILURE With the PCGs repressed, mitochondria decrease in mass and energy.

MORE FREE RADICALS Compromised mitochondria can produce an increas- ing amount of free radicals.

NUCLEAR DNA MUTATES Free radicals scavenge electrons from nuclear DNA, creating mutations.

SHORTENED TELOMERES Telomeric DNA is lost after every cell replication.

P53 ACTIVATION The gene is activated in response to criti- cally shortened or damaged telomeres.

PSC0811_WL Longevity R1.indd 54 6/14/11 11:34 AM

and then restore it, simply by administering, or with- holding, a synthetic estrogen drug. In the fi rst study, the mice with turned-off telomerase exhibited signs and symptoms of decrepitude akin to what we might endure at the age of 80 or 90: wrinkled skin, sluggish intestines, shrunken brain. When telomerase production was turned back on, the tissues rejuvenated within a month. “We treated these animals that were the equivalent of your grandmother,” DePinho says, “and they became like young adults.” He says he had expected to be able to stop or slow down the rate of aging. What he found was the proof-of-concept that living tissue could actually go back in time. (When Andrews talks about the possibility of running a seven-minute mile at the age of 130, he’s got the Harvard mice for backup.)

The second Nature paper was DePinho’s attempt at developing a unifi ed theory of late-life aging, “the death spiral,” as he calls it, that can transform a spry, alert 80-year-old into a shell of herself at 90 or 100 even in the absence of diagnosable disease. His mice data suggest that the major aging pro- cesses—free-radical damage, mitochondrial dysfunc- tion, and short or damaged telomeres—interrelate and that the telomeres can instigate decline, acting as the fi rst domino that sets in motion the rest. If the telomeres can be preserved, the entire system may be granted at least a temporary reprieve.

DePinho says he envisions more animal-model re- search leading to human clinical trials leading—years or, more likely, decades down the road—to FDA- approved drugs. The high-speed, low-rent workaround of a telomerase-activating supplement beyond the reach of the FDA doesn’t please him. “Even if you did get telomerase activity,” he says, “you sure as hell would want to know where and when to turn it on. Telome- rase can be deleterious as well.” Elizabeth Blackburn, now at the University of California at San Francisco, has reservations about a good-for-what-ails-you supplement. “A magic pill?” she says. “I think we’ve been there about a million times before in human history.”

POPSCI.COM POPULAR SCIENCE 55

1964

Physics teacher Robert Ettinger publishes The Prospect of Immortality,

introducing the idea of “cryonics,” the preservation of the human body by

freezing until the time when advanced technologies can revivify it. In 1972

the company Alcor, now in Scottsdale, Arizona, was born, and in 1976 it

performed the fi rst “cryopreservation.” You can preserve your entire body

or just your head, and the price varies accordingly.

1996

William Regelson publishes The Melatonin

Miracle, which inspires a Newsweek cover

story and ignites a fad for “Nature’s Age-

Reversing, Disease-Fighting, Sex-Enhancing

Hormone.” The original studies behind the

book have since been somewhat discredited.

Sierra Sciences operates out of a small, dun- colored offi ce park near downtown Reno. From the outside, it could be mistaken for a Sun Belt Staples, but inside are touches that speak to Andrews’s specifi c his- tory and sense of mission. He walks me into a confer- ence room decorated with plaques commemorating U.S. patents issued, and a whiteboard with an “Aging Sucks” bumper sticker plastered on it. “Dad sent that,” Andrews says, identifying the handiwork of Ralph Andrews, a retired Los Angeles game-show producer (his biggest hit was You Don’t Say!, which ruled the daytime airwaves in the 1960s). For reasons Andrews can’t adequately explain, his father, still hale at 84, has always been dead set against aging, and once suggested to his preteen son that he might want to take a shot at solving the problem. “My dad probably told me to do a lot of things, but this just struck a chord,” he says. “I never thought aging was inevitable. I just thought nobody had fi gured it out yet.”

In the late ’90s, Andrews came to feel that Geron had lost the true telomerase-activating religion, having redirected most of its resources into stem-cell therapies. He left Geron, crossed the Sierras, and in 1999 gathered around him in the Nevada desert a small circle of re- searchers who believed almost as ardently as he that it might be possible to engineer a “small molecule” drug that would fl ip the telomerase gene’s “on” switch inside a living human body. Since then, the company has gone through two distinct phases, pre-crash and post-crash. In the fi rst era, two especially benefi cent investors unques- tioningly underwrote his efforts to crack the telomerase code. (Start-ups working on an actual product in devel- opment attract venture capitalists. More-speculative ven- tures like Sierra Sciences typically draw individual “an- gels”—in the anti-aging fi eld, often older, wealthy men willing to risk losing money in the hopes that somebody will come up with a way to extend their fruitful lives.)

During this fi rst phase, Andrews and his team deployed an elegant recombinant DNA approach, arguably better suited to an academic lab than a start-up that needed marketable results. They would painstakingly alter one or two DNA bases out of the thousands that make up the telomerase gene, cycling through thousands of slight variations in an effort to fi nd one that the regulatory molecule that normally keeps the gene turned off, the “repressor,” would no longer recognize. This would reveal the molecular identity of the repressor, and the team could then create a drug to neutralize it—repressing the repres-

MISSION CONTROL

At Sierra Sciences,

an eight-person lab

staff works to dis-

cern the molecular

mechanisms of the

enzyme telomerase.

“A MAGIC PILL?” SAYS NOBEL PRIZE WINNER

ELIZABETH BLACKBURN. “I THINK WE’VE BEEN

THERE ABOUT A MILLION TIMES BEFORE.”

THE Obsessives P

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56 POPULAR SCIENCE AUGUST 2011

BEAT THE CLOCK

Bill Andrews has

run more than

100 races of 50

miles or more.

His longest ever

was 135 miles

through Death

Valley, California.

PSC0811_WL Longevity R1.indd 56 6/14/11 11:34 AM

THE Obsessives

sor and switching the telomerase gene back on. By 2006, after seven years of effort and one excru-

ciatingly close miss (they found “a” repressor but ap- parently not “the” repressor), Andrews fi nally shifted strategies. If developing a telomerase-activating drug with recombinant-DNA methods was a bit like trying to fi nd a needle in the haystack by analyzing the haystack molecule by molecule, the new approach was brute force: Grab a pitchfork and start digging. The company bought libraries of several hundred thousand chemical compounds and tested each one to see if it would acti- vate telomerase in cultured human cells.

The cells Andrews chose were fi broblasts, which are found in skin and connective tissue and which are relatively cheap and easy to culture. They also have little ability to express telomerase in a lab setting. When An- drews fi rst started the company, he ran into skepticism from some of his high-profi le scientifi c advisers, who doubted his overall strategy of trying to turn on telom- erase. “They were even laughing at it,” he says. Now at this later stage of the game, a few of his paid consultants questioned his decision to use fi broblasts. “Bill is the most persistent guy I’ve ever met,” says Bryant Villepoin- teau, a Geron alum and a former Sierra Sciences consul- tant. “Sometimes if he’s committed to something, he will go beyond the point where it’s wise.”

But Andrews had his reasons—the fi broblasts behave themselves in the lab and don’t change into other cell types, unlike stem cells, which can be moving targets. And after a year and a half of testing for telom- erase activation, running compound after compound through a screening assay, he fi nally caught a break. On the 57,684th run, the team got a chemical hit. C0057684 was too toxic to be easily transformed into a drug pros- pect, but it gave the company a positive control. In other words, they could use it to tune their detection tests to recognize fainter and fainter levels of telomerase ac- tivation, which is essential when you’re working with stodgy, underperforming fi broblasts.

By then, however, the market crash of 2008 had

POPSCI.COM POPULAR SCIENCE 57

2008

British pharmaceutical giant GlaxoSmithKline pays $720 million to

buy Sirtis, the start-up that discovered that resveratrol, a compound

found in red grape skins, extended the life span of obese lab rats. Sirtis

co-founder David Sinclair devised potent resveratrol “analogues,” but

since then, two major labs have failed to reproduce his results. Glaxo

has announced that it has stopped work on the original compound.

2005

Futurist and inventor Ray Kurzweil publishes

his best-selling The Singularity Is Near. In it,

he writes that in the not-so-distant future, the

human brain may be uploaded to a computer,

creating functional immortality, although

our bodies won’t be around to enjoy it.

clipped the wings of the company’s two angels, radi- cally altering Andrews’s job description. Rather than spending his days and nights in the lab, he became a telomerase-activation evangelist, crisscrossing the country in search of funding. “Where’s Bill?” became a regular link on the company’s website. His doleful SOS bounced around the life-extension blogosphere: “The bottom line is that Sierra Sciences needs $200,000 per month as soon as possible.”

The worst part for Andrews was leaving the day-to- day responsibilities of the lab and retreating to his offi ce, where he works the phones and e-mail trying to pilot the company out of fi nancial peril. The long hours and per- sonal austerity required by the new mission are by now second nature and, this afternoon, become grist for an enthusiastic show-and-tell. The offi ce fridge: “For break- fast, I have a protein shake, and every two weeks I go to Trader Joe’s or Whole Foods and buy a whole bunch of frozen foods that I heat up for dinners.” The low- slung chest of drawers with the cushion on top where he spends many of his nights, cutting down on the commute in from his ranch 25 miles outside of town: “My legs overhang the edge, but that’s OK. If I bend my knees, my legs are on the cushion.” (The last bed I saw with such awkward dimensions belonged to Father Ju- nipero Serra, the 18th-century founder of the California Franciscan missions—his attempt to mortify the fl esh presented a resonant contrast to Andrews’s efforts to make it something closer to immortal.)

For all the monastic devotion he brings to the cause, Andrews is a pure gene jock. It’s a sign of our nutraceutical-besotted times that such a scientist has made a marriage of convenience with a supplement in- dustry often equated with hippie herb lovers and cynical marketers looking to exploit the next pseudoscience fad. Gone are the bulk shipments of synthetic chemicals to be assayed, replaced by a small weekly delivery of ingredi- ents derived mostly from traditional Chinese and Indian medicinal herbs that John W. Anderson prepares in his fi ve-man Arizona lab. To Andrews’s surprise (and con- siderable relief), at least three of these compounds have tested positive for telomerase activation in the lab, even though many of the source materials are readily available in health-food stores. Have longtime devotees of tradi- tional Chinese and Indian medicinal

“UNEQUIVOCALLY, HE’S PAID A PRICE WITH HIS SCIENTIFIC PEERS,” FEDERICO GAETA SAYS.

“HOW BIG, I DON’T KNOW. BUT BILL’S

NOT GOING TO BREAK.”

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herbs been activating their telomerase with- out knowing it? Anderson, a self-described nutraceutical research scientist and medi- cine hunter, demurs, saying only that his nonchemical extraction and refi ning pro- cess concentrates and enhances any heal- ing properties they may have previously exhibited. As Jon Cornell, Andrews’s admin- istrative lieutenant at Sierra Sciences, says, if herbs and roots naturally had the level of telomerase-inducing activity that Andrews and his team are really looking for, “we’d probably already have immortal people.”

Andrews leads me through a succes- sion of compact lab rooms, each of which contains more equipment than people to run it. (Since 2008, he has cut the number of staff scientists from 34 to eight.) The center of the complex is a single cramped room where a couple of cell biologists and lab techs tend to plastic fl asks holding millions of human fi broblast cells. The cells will be transferred to tiny plastic vi- als, frozen in liquid nitrogen, and then, when their number is called, thawed and bathed for 24 hours in one of Anderson’s natural ingredients. Then they’re whisked across the hall, where another small group of scientists and techs run a production line that sends plates of the treated cells through a LightCycler analyzer, which amplifi es what’s going on at the molecular level using PCR (polymerase chain reac- tion, better known as the perp-catching technology on CSI). Telomerase is made up of two components—the RNA, which serves as a template to be used by the second part, a catalytic protein that synthesizes the DNA added back to telo- meres. The LightCycler scans for RNA activity suggestive of telomerase expres- sion. Promising compounds are then run through a slower, by-hand assay to look for hard evidence of the protein at work. “It’s cherry picking,” Andrews says. “The machine selects the reddest cherries.”

The analogy sounds so delightful that it’s jarring to remember that the measuring rod, the “standard control” the lab uses to evaluate telomerase activity in test com- pounds, is cancer—specifi cally the HeLa cancer cells that were the fi rst cell line to achieve immortality. Back when Andrews

THE MAN WHO WOULD STOP TIME

[Continued from page 57]

THE Obsessives

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was working with the more potent synthetic chemicals that he says were, in theory, capable of putting the brakes on aging, his team was able to get one compound up to a 16. That would be 16 percent of the telomerase required to make the HeLa cells live forever. “What we really want to do is to get it to 100 percent and above,” he says.

Telomerase, as Blackburn once noted, is a Dr. Jekyll and Mr. Hyde proposition. Though it will not cause a cell to turn cancerous by itself, telo- merase in its uncivilized Mr. Hyde mode does fuel the unregulated growth of most cancers. By activating the en- zyme, Calvin Harley says, “there is a risk, a small probability, that it could cause a premalignant cell to divide enough times to become malignant.” But both Harley and Andrews say they believe that any increased cancer risk is outweighed by the potential rewards. Telomerase can also be a benign Dr. Jekyll that protects against the chromo- somal breakage and re-fusion that can lead to cancer, and it can help drive the proliferation of immune-system cells whose job it is to fi ght cancer. A study in the July 7, 2010, Journal of the Ameri- can Medical Association highlighted the correlation between cancer and short telomeres: People with shorter- than-average telomeres had three times the risk of developing cancer and 11 times the risk of dying from it. Andrews is not shy about talking with cancer patients—seemingly the group most vulnerable to the Mr. Hyde risks of runaway telomerase—about the po- tential health advantages of telomerase activation. “I’m always careful to qual- ify that I’m not an M.D., I’m not able to provide medical advice,” he says. “I do say that if I had cancer, I’d be taking as much telomerase activator as I could get my hands on.”

As it happens, he already is. In 2002, a New York City entrepreneur and former appliance manufacturer, Noel Thomas Patton, licensed the rights to Geron’s research on a telomer-

ase-activating compound found in the Chinese medicinal herb astragalus, for supplement use only. (Geron is fi nal- izing a plan to send an astragalus-based telomerase-activating drug candidate through clinical trials.) Three years ago, Patton’s TA Sciences test-launched its TA-65 supplement with 100 clients, each willing to pay $25,000 a year to be anti-aging guinea pigs. Paying patient number one: Bill Andrews.

TA Sciences has this year ramped up production and dropped the strato- spheric price tag, although so far the most impressive effects remain anec- dotal—more energy, greater mental clarity, a sexual boost, even improved vision. Andrews says his ultramarathon times dropped when he started taking TA-65. An observational study co-au- thored by Harley, who helped discover the original molecule at Geron, found improvements in the immune system of those fi rst 100 clients. Andrews was hoping for a more pronounced effect. As he describes what it was like to take that fi rst dose of the supplement in 2008, I can hear the voice of a kid who hasn’t entirely grown up, anti-aging as a never-ending Hardy Boys adventure: “I remember Noel and I sitting having dinner, and we were wondering, What are we going to look like two weeks from now? We talked on the phone practically every day, and we were both disappointed that we didn’t look any younger right away.”

Andrews’s tendency to let his enthusiasms take him out on a limb, especially when he’s trying to attract investors, makes him a polarizing fi gure in the research community. To some academics, his standard pitch- cum-sound-bite, “We age because our telomeres shorten,” is a crude oversim- plifi cation. Even Andrews seems to suspect that Sierra Sciences’s company motto, “Cure Aging or Die Trying,” isn’t winning him many friends among people who possess advanced biology degrees. “Some people like it and other people say it’s embarrassing,” he says. “So I don’t know what to do.”

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I later ask Federico Gaeta, Geron’s for- mer head of chemistry and a current Sierra Sciences consultant, whether Andrews’s reputation has suffered for his damn-the- nuance pursuit of longevity. “Unequivo- cally, he’s paid a price with his scientifi c peers,” he says. “How big a price, I don’t know, but there is an excellent chance that he will ultimately be vindicated.” Now, Gaeta says, “he’s in a position where he has to show that he’s done something.” The years of angels with blank checks are over, and the pressure to produce—and to raise the money to buy the time to produce—is tremendous. “He’s not going to break,” Gaeta says. “I know that about him. Bill’s not going to break.”

By 5 P.M., midwinter darkness is be- ginning to fall, and the skeleton crew at Sierra Sciences is mostly gone, though Andrews is looking at another long night that will probably end on his makeshift bed. The last employee to leave is Randy

Lee, the IT guy, an old Southern California prep-school buddy of Andrews’s. He’s been hanging around because he has some bad news to deliver. Lee has the unenviable job of reconfi guring the lab’s now inadequate computer system. Today he lost a cache of valuable data when the system crashed. When he delivers the news, Andrews visibly compresses, as if another 10 pounds has been added to the weight already on his shoulders. Then he collects himself. “I told people we’re either going to never move forward with our system or we’re going to take the chance of losing things,” he says. “Well, try to get a good night’s sleep. I’m sorry for your sake that it happened.”

After Lee heads for home, I ask An- drews to consider a hypothetical. If I wrote him a check for $10 million, would that be enough to send him back to the lab to fi nd that home-run telomerase-activating chemi- cal? “No,” he says, “but that would increase our chances of getting a really good natural

product that nobody could compete with. To do the pharmaceutical, we’d need $30 million.” I toss out a fl ip rejoinder—“Sorry, Bill, I can only do the $10 million”—and Andrews freezes for a half-second, then slumps back in his chair. “I’ve got business plans that have all that budgeted,” he says. “What the money would be used for.”

I ask Andrews what the worst-case sce- nario would be for Sierra Sciences. “The worst-case scenario,” he says, “is that we put out a telomerase activator and every- body who takes it dies right away.”

“No,” I clarify, “the worst-case fi nancial scenario?”

Andrews, his voice phlegmy with fa- tigue, tries again. “The company folds. I fi nd another job, but I still work on trying to fi nd more investors to resurrect it. I can’t be happy unless I’m working on this. The mission won’t die unless I die.”

Joseph Hooper is a contributing editor

at POPULAR SCIENCE.

OULD STOP TIME

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