Spring Chicken Read online

  Then he tells them about Orville. Long before he ever thought of attending graduate school and becoming a scientist, Austad had chanced into a job as an animal handler for Hollywood movies. His task was to make sure the lions acted their part properly—yawning on cue, for example—and more important, to keep them from biting the actors. You might think that such an occupation would require years of training and experience, but you would be wrong: At the time, his résumé included “semi-employed English major” and “New York City taxi driver.”

  One day, he was out walking Orville on the ranch outside Los Angeles where the animals lived, when into the lion’s path strolled an unfortunate duck. The lion pounced on the duck, and Austad ordered him to drop it, backing up the command by whacking Orville with the metal chain that served as his leash. “One of the things about dealing with big animals like that is they have to do as you say now, the first time,” he says. “It’s not like with my dog, where I’ll say ‘Come! Come! Come?’ ”

  Orville dropped the duck, as ordered, but then he went after Austad instead. In short order, Austad found himself on the ground, with his right leg in Orville’s mouth. When he finally accepted the fact that he couldn’t escape, he managed to calm himself down and assess the situation. The bad news was that he was in the process of being eaten by a lion. The good news, if you can call it that, was that Orville was eating slowly, almost thoughtfully. “The fact that he had my leg meant he wasn’t eating anything else,” he said. On the other hand, he figured Orville would get to the rest of him eventually. Luckily, though, the ranch bordered a road, and just then a carload of tourists happened to pull over to gawk at the animals. The tourists saw a lion on top of a man, and reported the situation to the ranch office.

  Austad spent the next several weeks recovering in the local hospital, where he became a bit of a celebrity because the ranch owner’s wife—actress Tippi Hedren, star of The Birds—would visit him there every day. Miraculously, he ended up keeping his leg, minus a little bit of his femur and a lot of his blood. He even went back to work, but it wasn’t long before Orville charged him again, and it seemed like time to find a new line of work.

  With the exception of Orville, Austad had always loved animals, ever since he was a boy growing up on an Indiana farm, so he headed back to school intending to study lions in the wild. Instead, he got diverted to less glamorous and less toothy critters, like the possums. When he saw Possum #9 stumble off and bash into the tree, he realized that aging was the one big, unsolved problem that affected everything that had ever lived. And we understood almost nothing about it. “It’s the big enchilada in biology,” he says.

  The tale of the two possums seemed to confirm, at least broadly, an intriguing new theory of aging. Dreamed up by a young British scientist named Thomas Kirkwood (who had studied mathematics, not biology), the “disposable soma” theory basically said that our bodies are mere vessels for our reproductive “germ” cells—our DNA—and thus only need to last long enough for us to reproduce. What happens afterward is of no concern. And because the germ cells take priority, our bodies only need to last as long as we’re likely to survive in the wild. So it makes no sense for nature to build a possum that is capable of surviving ten or fifteen years, when it is only likely to live for two or three years.

  “All our genomes need to do is invest enough in the body so that the body is in decent shape for as long as we’re likely to live,” Kirkwood told me. “But in nature it’s a bad strategy to invest more than that, because what is the point? Nature is a dangerous place, so you don’t need a body that can go on indefinitely in tip-top shape.”

  But for possums that are lucky enough to have been born on idyllic, predator-free Sapelo Island, it makes perfect sense to build a longer-lasting body. Over five thousand years, they evolved to live life on a more relaxed timetable, without so much pressure to hurry up and breed. The obvious question, to Austad, was how are they different?

  Most other scientists focused on “model organisms” such as fruit flies, or nematode worms like C. elegans, or mice—“not just mice, but one strain of mouse,” he says. These animals had one trait in common: They did not live very long, which was convenient for obtaining quick study results, but Austad doubted they could teach us much about human aging. “Rodents for the most part are pretty boring, from an aging perspective,” Austad says. So he decided to look outside the usual lab animals, to try to identify other ways in which Nature herself had managed to defeat, delay, or reprogram the aging process in the wild. He started by trying to keep a colony of possums, but they proved difficult to raise under lab conditions. So he began looking for species that already lived longer than one would expect.

  For most animals, lifespan correlates pretty well with size, with bigger animals tending to live longer, in general. (Chihuahuas, and other small but long-lived dogs, are an exception to this rule, thanks to centuries of manipulative breeding.) Using a measure called the longevity quotient, which compares actual with size-predicted longevity, Austad found that humans are actually pretty long-lived, relatively and absolutely: Very few other living things have been observed to live a hundred years or more. So extending human lifespan even further would be quite a difficult trick.

  But a few creatures do manage to outlive us, starting with the famous Galapagos tortoises, some of which had survived the depredations of hungry nineteenth-century whaling crews and lived into the present day—more than 150 years. Lobsters were also well-known longevity champs, at fifty to one hundred years. That’s youthful compared with certain clams that have been known to live hundreds of years. One particular Icelandic clam was recently found to be more than five hundred years old, meaning it had been around nearly since the time of Columbus. The clam, nicknamed Ming, was living happily in captivity until 2013, when researchers had the bright idea of trying to open her up. Lord knows why they did this—maybe to make chowder?—but it resulted in her untimely death at the estimated age of 507.

  There were more surprising cases as well. Ancient handmade harpoon points were found in the carcass of a bowhead whale killed by Inupiat Eskimo hunters in Alaska in the 1990s. Previously, the whales had been thought to live “only” about 50 years, but this specimen turned out to be some 211 years old, based on analysis of changes in its eye lenses. Cold water may be good for longevity: Alaskan fishermen have also hauled in specimens of rockfish, relatives of red snapper and striped bass, in excess of a century old.

  Austad lumps these long-lived species together into what he calls Methuselah’s Zoo, creatures who display little or no evidence of aging—or as scientists say, negligible senescence. And while it’s not easy to conduct aging studies on deep-ocean whales that live for two hundred years, one other very long-lived animal is both easily accessible and very numerous: bats. In the whole mammalian kingdom, Austad found, only nineteen species had a higher longevity quotient than humans, and eighteen of them were bats. In the wild, some bats have been known to live as long as forty-one years, giving them an LQ of 9.8, or double that of humans. (The nineteenth is something called a naked mole rat, a creature so bizarre that I don’t really want to get into it yet.)

  A few years ago, Austad and a colleague collected a bunch of bats from a colony that lived underneath a bridge in Texas, hoping to answer a simple question: How were they different from, say, mice? And how did this help them live longer?

  The most obvious way the bats were different was that they were still alive at ages seven and beyond, when mice would long since have passed on. Another difference was that while mice crank out a litter of five to ten pups every thirty days, bats produce one offspring at a time, once per year. It makes sense: Tucked away in caves, with the ability to fly away from their few predators, bats have the luxury of reproducing slowly—much like the island possums, or humans.

  But what is their “secret”? Is it their high-protein, low cholesterol, bug-based diet? All the exercise from flying around? All that sleep during the daytime? Probably not. Ins
tead, Austad looked deeper, at where aging really resides: in the animals’ cells. In a study, he and colleagues put a bunch of bat cells in a dish and sprinkled toxic chemicals on them, to gauge their powers of stress resistance. Then they did the same to mouse cells and human cells. The bat cells withstood stress much better than mouse or even human cells. Simply put, the longer-lived animals had hardier cells. So they lasted longer.

  It all has to do with cellular maintenance, the internal housecleaning mechanisms in all our cells. In long-lived animals, Austad and others have found, these maintenance programs tend to be far better than in the cells of short-lived critters like mice. So their bodies are better looked-after, and thus last longer. It’s as if you owned two cars, an expensive mint-condition Jaguar that you used on weekends and for special events, and a cheap, well-used Ford Focus for errands around town. You’d take the Jag to an experienced, specialized mechanic, hoping to get as many years as possible out of it, but you would probably take the Focus to Jiffy Lube, because it’s cheap and easily replaceable. The same thing happens on the cellular level. The mice get Jiffy Lube maintenance, while the bats get the Jaguar treatment.

  So now the question becomes: Is it possible, somehow, to make our own cells more like bat cells, and less like mouse cells? More bowhead whale than brook trout? More Jaguar than Ford Focus?

  To answer that, we’ll first have to understand how and why our cells themselves grow old—which we know they do thanks to a scrappy blue-collar kid from row-house Philadelphia, who took on and obliterated a fifty-year-old scientific myth that had been invented and propagated by an old French Nazi.

  Chapter 8

  THE LIVES OF OUR CELLS

  You don’t really believe all this bunkum, do you? This, this holier-than-thou dietary crap, the enema treatments, the mud packs, the sensory deprivation? What’s it going to get us—another six months of eating grape mulch and psyllium seeds? Another year? We die anyway, all of us, even the exalted Dr. Kellogg—isn’t that the truth?

  —T. C. Boyle, The Road to Wellville

  According to Google Maps, it is a mere 104 miles from the Golden Gate Bridge to Leonard Hayflick’s home on the Sonoma coast. So you’d think it would take about two and a half hours to drive there, max. But in the real world, Hayflick himself insisted, the drive takes closer to four hours. “Google Maps will send you the longest way,” he growled in an email, after he agreed to meet with me in March 2013.

  Instead, he snail-mailed me a Xeroxed, hand-drawn, extremely detailed map showing the correct route to his house, covered with scribbled exhortations (“OBEY ALL SPEED LIMITS!!!”). Just the last twenty-seven miles would take a full hour, he said.

  Yet still I doubted him, one of the most important scientists of the twentieth century. So have plenty of other people, apparently; hence the map, which I soon discovered was accurate in all of its particulars. There really were “speed traps everywhere!” and it really did take an hour to drive the last leg, along winding coastal Highway 1. By the time I arrived at Hayflick’s door, exactly four hours after crossing the Golden Gate, I was slightly dizzy from carsickness. Not to mention late.

  “You were right about the drive!” I blurted. He replied with a grunt. By now, he’s used to people not believing him, even when he knows he is right.

  Nearly sixty years ago, young Len Hayflick was working in the lab of Philadelphia’s Wistar Institute, putting his newly minted PhD to use in the trenches of cancer research. His important but unglamorous job was to produce and maintain clumps of living human cells, called cell cultures, for Wistar scientists to use in experiments. This sounds simple enough, but Hayflick kept running into a problem: Every so often, his cell colonies would die out. Either he wasn’t feeding them properly, or the cells were becoming contaminated, or something else was happening that he couldn’t yet diagnose. Whatever was going wrong, it was clearly his fault.

  This he knew thanks to the work of Alexis Carrel, a celebrated French scientist who had essentially invented the discipline of cell culture. In his lab at Rockefeller University in New York City, Carrel had kept a strain of chicken-heart cells alive for decades, beginning in 1912. These were the most celebrated cells in the world; every year, the New York tabloids would celebrate their “birthday,” with reporters and photographers paying visits to them in a dramatic glass-walled amphitheater that Carrel had specifically designed to accommodate the media.

  No one dared question his work; after all, Carrel had won the Nobel Prize in 1912, for developing novel techniques for suturing blood vessels. He was the leading light of Rockefeller University, which was dripping with Standard Oil money (even today, his portrait still hangs in the foyer). In the 1930s, he upped the publicity quotient even farther by working with Charles Lindbergh to design a special pump to help with organ transplants, a stunt that got them both on the cover of Time. The two men also shared a love of eugenics, which Carrel advocated in a notorious 1935 book called Man, The Unknown. Meanwhile, the chicken cells were still living in 1943, when Carrel, a likely Nazi sympathizer, finally left them and returned to collaborationist Vichy France.

  He died the following year, but his dogma lived on: Thanks to Carrel, everyone in the scientific world “knew” that living cells were essentially immortal—that is, they could divide forever. In his lab at Wistar, though, Hayflick began noticing an interesting phenomenon. At the time, he was using cells taken from human embryos, because unlike adult cells, fetal cells had not yet been exposed to contaminating viruses. But since abortion was not legal or common in the United States in the 1950s, fetal cells were difficult to come by. He had to tend them with special care. After a few months, though, they invariably died out. A check of his books showed that the cultures that failed were always the oldest ones.

  He decided to forget about cancer and try to figure out why he couldn’t keep his cells alive. Eventually he came up with what he calls “the dirty old man experiment.” In one dish, he combined a batch of “young” female cells, which had only divided ten times, with an equal number of male cells that had doubled forty times—the dirty old men. A few weeks later, he checked the dishes and found that only female cells remained. The male cells were gone. So either something had killed only the male cells, or there was some other explanation. Like that the older cells were simply dying.

  He knew that his results would upset one of the major apple carts of modern biology, so before he published, he knew he had to try to get buy-in from the established experts in the field—men like George Gey of Johns Hopkins, who a decade earlier had isolated a culture of cells from a young woman who had died from an aggressive form of cancer. Those cells, now known as HeLa from the name of the donor, Henrietta Lacks, had proved incredibly useful in cancer research (and are the subject of Rebecca Skloot’s amazing book, The Immortal Life of Henrietta Lacks).

  Hayflick sent samples of his fetal cells to George Gey and half a dozen other cell-culture poobahs, with instructions to call if and when they stopped dividing. “These guys are the major personalities in the field, using their techniques, which they think are the greatest,” Hayflick recalls. “So when the phone started ringing, telling me that their cultures were gone, I’m thinking, if I’m gonna go down in flames, then I’m gonna go down in flames with some pretty good company.”

  Long story short, he had shown that Carrel had been completely wrong. Cells seemed to have a limited lifespan, after all. But his paper was rejected out of hand. The immortality of cultured cells, insisted one journal editor (employed at Rockefeller U, coincidentally), is “the largest fact to have come from tissue culture in the last fifty years.”

  Hayflick’s paper eventually appeared in a small journal called Experimental Cell Research, in 1965. In it, he showed in painstaking detail how twenty-five different kinds of fetal cells all seemed to crap out at about their fiftieth round of cell division. Far from being immortal, he wrote, normal cells have a finite lifespan. Furthermore, he noted, cells taken from older donors had fewer doublin
gs left in them. Their cells, like their selves, were aged. And the dogma was dead. “There is serious doubt,” he wrote, “that the common interpretation of Carrel’s experiment is valid.”

  Next came what Hayflick calls the “three phases of a new idea”: “First you’re an idiot; second, it’s meaningless; third, it was obvious all along—and nobody gives you credit for it.”

  But Hayflick is nothing if not stubborn. His determination had already taken him from working-class southwest Philadelphia where he had grown up, and had discovered his love of science via the time-honored route of blowing things up in the basement with a Christmas chemistry set, to the nearby University of Pennsylvania, where he earned a BA and a PhD in molecular biology. And it gave him the courage to go into the study of aging, which was considered a scientific “dumping ground,” as he puts it. “To have admitted you were working in the field of aging, in the ’60s, was a recipe for professional suicide,” he says.

  Where others saw suicide, he saw opportunity. By 1975, he was in line to become the first director of the new National Institute on Aging. But then he found himself in the middle of a bizarre scandal, in which another arm of the NIH accused him of essentially stealing one of the cell cultures he had used in the “dirty old man” experiments, a line of cells called WI-38, which he and a colleague had created from lung tissue of a fetus that had been aborted in Sweden in 1962. WI-38 proved to be the most durable and useful cell line ever created: It was versatile, easy to grow, and “clean,” free of viruses and other contaminants. It proved an ideal vehicle for manufacturing vaccines against all manner of diseases, from rabies to polio to hepatitis B. Merck and other major pharmaceutical firms used it to produce vaccines against measles, polio, smallpox, and rabies, among others. Hayflick provided samples of WI-38 to them and anyone else who requested it, in exchange for a small shipping and handling charge.