Immortal toil

This past January, while waiting in the Los Angeles International Airport for a flight to Reno, my mother and I got into a memorable conversation with the man sitting next to us. My mother was complaining about the prices at the airport restaurants, and this man chimed in that his bag was full of food he had brought with him. He was tall, with a receding hairline, a graying mustache and goatee, and the thin build of a distance runner. I took him for a health nut, which, as it turned out, was more true than I could have imagined.

We exchanged small talk, but, when I told him I was a science writer, he suddenly shifted from merely friendly to animated, and implied that our meeting was quite a lucky event. And then almost immediately, he launched into his career story, a career that sounded like a mission.

His goal was simple: he wanted to cure aging. He said he had always thought of aging as a disease, and he believed it was possible to stop the process, and, thus, enable people to live for hundreds of years and beyond. He was the head of a biotech company in Reno that was trying to make that happen.

He talked about telomeres, parts of chromosomes that get shorter every time a cell divides, and he said that shortened telomeres are a root cause of aging. If you could make telomeres longer, not only could you prevent aging, you could reverse it—you could turn old people young again. Through a form of gene therapy, that's what he was attempting to do—a biotech version of the fountain of youth.

My impression of him was contradictory in the extreme: He seemed very rational yet, at the same time, what he was saying about making old people young sounded crazy. Seated in the plane, I was wondering who he was, when he came down the aisle and handed us a thin paperback. The book's title was Telomere Lengthening: Curing All Diseases Including Cancer and Aging, and he was one of the authors. His name is Bill Andrews.

Age of innocence

Andrews's company, Sierra Sciences, is located in a nondescript, one-story building just east of the Reno-Tahoe International Airport. The company name, inscribed on a window, is hardly noticeable, and, when I arrived to interview Andrews on a Wednesday afternoon, the parking spaces out front were mostly empty, and the blinds were drawn. It barely looked like a going concern, much less like the potential birthplace of a radical change in the human condition.

The conference room where we talked gave a better impression. On one wall, a row of wooden picture frames held patent certificates (“assays for TERT promoter modulatory agents,” “telomerase expression repressor proteins,” etc.) all with Andrews's name on them. A large whiteboard was almost completely covered with outlines from a recent planning meeting.

Clipped to another whiteboard was a bumper sticker that proclaimed “AGING SUCKS!” That sticker was a gift from Andrews's father, who died a few years ago from Alzheimer's. Andrews, who is 66, said that he was just 10 to 12 years old when his father set him on the career path he is still following.

“I was at a house on Sunnybrae Avenue in Canoga Park,” he said. “On the front lawn with my reflector telescope, looking at stars … when my father walked out, and …he said, ‘Bill, since you're so interested in science and medicine, I think you should grow up and become a doctor and find a cure for aging.'”

The idea of curing aging was Andrews's focus from high school through his Ph.D. program at the University of Georgia, and it carried over into his career in the biotech industry. Early on, he realized that there must be a clock in our bodies, something that ticks constantly and eventually makes us fall apart, makes us age and die. But he had no idea what that clock was or how it might work.

Then, in 1993, he went to an anti-aging conference at Lake Tahoe and heard a talk by Calvin Harley, a scientist at Geron Corporation, a Bay Area biotech company focused on curing aging. Harley's presentation was about telomeres, stretches of DNA that cap the ends of the chromosomes, like the little plastic cylinders stuck on the ends of shoelaces. He talked about how telomeres get shorter each time a cell replicates, and how this shortening is connected to cells growing physiologically old.

Andrews sat in the audience, enthralled. Here was the biological clock he had been looking for, the key to understanding why we age. Almost immediately, he quit his old job and joined Harley to work on telomeres.

That was 25 years ago. Andrews has been focused on telomeres ever since. He and his team made some big breakthroughs at Geron, but he left the company in 1997 when it shifted away from trying to cure aging, and two years later, he founded Sierra Sciences in Reno. Since then, his reputation has grown in the anti-aging community. He has been deeply involved in RAADfest, an annual meeting on reversing aging. (RAAD stands for “Revolution Against Aging and Death.”) He has given talks all over the world, and he was featured in a 2014 documentary, The Immortalists.

He has not yet found an actual cure for human aging. Of course, nobody else has either.

The golden age

At one time, Sierra Sciences seemed to be on the fast track toward finding such a cure. The company was receiving a million dollars a month from two investors, had more than 30 employees, and was doing sophisticated and expensive genetic engineering. But when the 2008 financial crisis hit, that funding dried up, and Andrews had to change strategies. Today, Sierra Sciences is down to a handful of employees, and Andrews's best hope for a cure for aging now lies in a collaboration with a Kansas company called Libella Gene Therapeutics.

The treatment revolves around the gene for telomerase, an enzyme that makes telomeres longer. Andrews knows this gene well; he and his team at Geron discovered the human version of it.

When a cell divides, and the chromosomes replicate, the very outer ends of the telomeres disappear. But the telomerase enzyme builds those ends back up, and the net result is that the telomeres stay the same length.

The rub is that, in humans, the genes that make telomerase are permanently switched off in most cells long before birth. So with every cell division—literally trillions of them in an average lifetime—our telomeres get a bit shorter. And there is some compelling evidence that when telomeres get too short, cells stop working properly. In this view, telomere shortening makes cells age. And as our cells age, so do we.

Suppose, though, that you could produce telomerase genes that were permanently switched on, and deliver them into people's bodies. The genes would crank out telomerase, the telomeres would stop shortening, and these people would stop aging. The telomeres might even get longer, turning back the biological clock, making the subjects physiologically younger. Or, at least, that's the idea.

This sort of telomerase gene therapy is what Andrews has masterminded and Libella plans to carry out. Andrews talks, almost giddily, about a dream patient, the perfect proof of his science. The patient he has in mind is actress Betty White, from the '80s TV show The Golden Girls, and he imagines her walking out onto a stage, looking like she's 30 instead of 90-something.

Coming of age

At Sierra Sciences, Andrews gave me a tour of the lab facilities. It's a labyrinth of rooms, filled with equipment that must have cost millions—powerful microscopes, many machines for amplifying DNA—turning small amounts of it into much larger quantities—ultra-low freezers, incubators, super-fast centrifuges, robotic assaying machines, and much more.

Despite the impressive lab, and despite Andrews's credentials, it is hard to shake the sense that he is operating on the fringes of science and medicine. That thought comes into focus with Libella's plans for the telomerase trials.

The president of Libella, Jeff Mathis, gave me some of the details, and they bear little resemblance to most people's notions of clinical trials. For one thing, the initial trials are to be done on just two or three people. The small number is a result of the outsized cost, some $3 million per patient. One wealthy patient, in a controversial “pay to play” arrangement, is footing the bill for his own treatment.

Also, the trials are to take place, not in the U.S., but in Colombia or Vanuatu. Those localities were chosen partly to avoid regulations; there was no way Libella was going to get FDA approval for the trials. And, although Mathis hopes the first patients will be treated by the end of the year, the logistics still remain to be worked out. For instance, on Libella's website, the use of the clinic in Colombia is given as “Currently in negotiation.”

The whole thing sounds a bit fly-by-night. However, my thoughts about this are only partly negative. Not all breakthroughs come with a stamp of approval from big institutions. Maybe when people are pushing the envelope, the means to the end often look debatable, like what Andrews and Libella are doing.

A more conservative take is that Andrews is on the outside because his assumptions about the influence of telomerase are unrealistic. For instance, Michael Rose, a University of California, Irvine biologist who studies the evolution of aging, believes human lifespans will be greatly extended, but only in small increments, not via the kind of giant leap that Andrews envisions. Rose told me there are single genes in nematode worms and yeast that have huge effects on lifespan, but that such “master longevity” genes do not seem to exist in the fruit flies he studies. And he thinks humans are like fruit flies in this respect, not like nematodes or yeast.

But, on the other hand, in studies of mice and of human skin cells, adding telomerase dramatically reversed the aging process; old mice and old skin cells, by all sorts of measures, became like young mice and young skin cells. Also, among other kinds of evidence, there is a genetic disorder called progeria, in which the afflicted have abnormally short telomeres, and age so quickly that they usually die of age-related diseases in their teens.

In short, despite uncertainties, it isn't hard to see why Andrews and others have become fixated on telomeres and telomerase.

Age of consent

Mike Fossel agrees with Andrews. Fossel, 67, is a well-known player in the community of anti-aging advocates. He is an M.D., and the head of a company called Telocyte, which, like Libella, is developing a telomerase gene therapy treatment.

In his 2015 book, The Telomerase Revolution, Fossel sets forth a radical vision of how telomerase treatments will soon alter the human condition to its core. Many of the issues, he admits, are bound to be alarming. How will we deal with a telomerase-based explosion in the human population? If people remain youthful for hundreds of years, what will happen to family dynamics, to marriage and the relationships between generations?

“A lot of the anchors that you've got, a lot of the foundations that you've got start to shake and lose traction,” Fossel told me, “and you begin to think ‘Wait, what's going on here, what happened?' And that's scary.”

Overall, though, Fossel is extremely hopeful about this impending medical revolution. He envisions a tremendous decline in age-related diseases, from Alzheimer's to arthritis to heart attacks. He foresees people accumulating knowledge like never before, having far more time to fulfill their dreams, and living without the anxiety brought on by deteriorating bodies and minds. In a nutshell, he believes we are on the cusp of enriching human experience and diminishing human suffering to an almost unimaginable degree.

Bill Andrews is certainly aware of such big-picture issues too. For instance, he brought up the notion that making telomeres longer will restore the immune systems of people suffering from AIDS. “So I would like to see us drop pills [that activate telomerase] from airplanes all over Africa … where AIDS is rampant,” he said. “I just want the world to be happier and healthier.”

For the most part, though, one does not get the sense that transforming the world and saving millions of lives is what pushes him. His motivation is much more self-focused than that: He wants to live as long as he can. 150 years would be a good start. Forever would be better. It's an ages-old impulse, the same one that supposedly compelled the early Chinese emperor Qin Shi Huang to drink an elixir of mercury, the same one that had the 19th century physiologist Charles-Édouard Brown-Séquard injecting himself with the ground-up testes of guinea pigs and dogs.

Like a lot of people, Andrews tries to live healthily, but he takes it to extremes. For him, exercise means training for and completing many ultramarathons, including some of the most difficult ones in the world. And he believes that inflammation is a major cause of aging, so he has had himself tested to see what foods give him even a mild inflammatory response, and tailored his diet accordingly. “I'm worse than a vegan,” he says. “I can't eat blueberries, I can't eat tomatoes, I can't eat cucumbers or pickles, 'cause they're inflammatory for me.”

Andrews has no delusion that a healthy lifestyle is going to greatly extend his life. Instead, his goal is to live long enough to develop a treatment that will allow him to live much longer, which in turn might enable him to get an even better treatment, and on and on. In Telomere Lengthening, he quotes another anti-aging advocate, Terry Grossman, who says, “Live long enough to live forever.”

“I just love living too much,” Andrews said.

For the ages

When I went to Sierra Sciences a second time, I found Andrews working on the protocol for the gene therapy trials. There were piles of research papers all over a large conference table, and he had written up a draft protocol that was many pages long.

Before I could even ask a question, he launched into a complicated explanation of how he was going to make sure the viral protein coat used to deliver the telomerase genes would not cause a harmful immune reaction. His formal training is in molecular genetics, not clinical medicine, but that wasn't stopping him. This seemed very much in character—he's a person who doesn't accept normal limitations.

Later I wondered, though, if he is ever crippled by doubts about his chances of success. There are obvious uncertainties at every level of the project. The trials may never even happen. If they do, the treatment may fail to lengthen the telomeres. Or, the telomeres may get longer, but that may not reverse aging after all.

Beyond this, there is a deeper sort of desperation to the enterprise. It's not just about accomplishing some research goal, not just about discovering something new and fascinating. It's about life and death, and, in particular, Andrews's own life and death.

I don't know whether curing aging would be good or bad for humankind and the planet. Still, I cannot help feeling that Andrews deserves some reward for taking so many risks, for thinking outside of the box and standing outside of the system. In spite of my misgivings, I find that I'm pulling for him. I find myself hoping that he at least makes it to 150.