The Best American Science and Nature Writing 2013

by Siddhartha Mukherjee

  But the most frustrating explanation for our dearth of knowledge about the immortal jellyfish is of a more technical nature. The genus, it turns out, is extraordinarily difficult to culture in a laboratory. It requires close attention and an enormous amount of repetitive, tedious labor; even then, it is under only certain favorable conditions, most of which are still unknown to biologists, that a Turritopsis will produce offspring.

  In fact there is just one scientist who has been culturing Turritopsis polyps in his lab consistently. He works alone, without major financing or a staff, in a cramped office in Shirahama, a sleepy beach town in Wakayama Prefecture, Japan, four hours south of Kyoto. The scientist’s name is Shin Kubota, and he is, for the time being, our best chance for understanding this unique strand of biological immortality.

  Many marine biologists are reluctant to make such grand claims about Turritopsis’s promise for human medicine. “That’s a question for journalists,” Boero said (to a journalist) in 2009. “I prefer to focus on a slightly more rational form of science.”

  Kubota, however, has no such compunction. “Turritopsis application for human beings is the most wonderful dream of mankind,” he told me the first time I called him. “Once we determine how the jellyfish rejuvenates itself, we should achieve very great things. My opinion is that we will evolve and become immortal ourselves.”

  I decided I’d better book a ticket to Japan.

  One of Shirahama’s main attractions is its crescent-shaped white-sand beach; the name Shirahama means “white beach.” But in recent decades, the beach has been disappearing. In the 1960s, when Shirahama was connected by rail to Osaka, the city became a popular tourist destination, and blocky white hotel towers were erected along the coastal road. The increased development accelerated erosion, and the famous sand began to wash into the sea. Worried that the town of White Beach would lose its white beach, according to a city official, Wakayama Prefecture began in 1989 to import sand from Perth, Australia, 4,700 miles away. Over fifteen years, Shirahama dumped 745,000 cubic meters of Aussie sand on its beach, preserving its eternal whiteness—at least for now.

  Shirahama is full of timeless natural wonders that are failing the test of time. Visible just off the coast is Engetsu island, a sublime arched sandstone formation that looks like a doughnut dunked halfway into a glass of milk. At dusk, tourists gather at a point on the coastal road where, on certain days, the arch perfectly frames the setting sun. Arches are temporary geological phenomena; they are created by erosion, and erosion ultimately causes them to collapse. Fearing the loss of Engetsu, the local government is trying to restrain it from deteriorating any further by reinforcing the arch with a harness of mortar and grout. A large scaffold now extends beneath the arch, and from the shore construction workers can be seen, tiny flyspecks against the sparkling sea, paving the rock.

  Engetsu is nearly matched in beauty by Sandanbeki, a series of striated cliffs farther down the coast that drop 165 feet into turbulent surf. Beneath Sandanbeki lies a cavern that local pirates used as a secret lair more than a thousand years ago. Today the cliffs are one of the world’s most famous suicide spots. A sign on the edge serves as a warning to those contemplating their own mortality: “Wait a minute. A dead flower will never bloom.”

  But Shirahama is best known for its onsen, saltwater hot springs that are believed to increase longevity. There are larger, well-appointed ones inside resort hotels, smaller tubs that are free to the public, and ancient bathhouses in cramped huts along the curving coastal road. You can tell from a block away that you are approaching an onsen because you can smell the sulfur.

  Each morning, Shin Kubota, who is sixty, visits Muronoyu, a simple onsen popular with the city’s oldest citizens that traces its history back 1,350 years. “Onsen activates your metabolism and cleans away the dead skin,” Kubota says. “It strongly contributes to longevity.” At 8:30 A.M., he drives fifteen minutes up the coast, past the white beach, where the land narrows to a promontory that extends like a pointing, arthritic finger, separating Kanayama Bay from the larger Tanabe Bay. At the end of this promontory stands Kyoto University’s Seto Marine Biological Laboratory, a damp, two-story concrete block. Though it has several classrooms, dozens of offices, and long hallways, the building often has the appearance of being completely empty. The few scientists on staff spend much of their time diving in the bay, collecting samples. Kubota, however, visits his office every single day. He must, or his immortal jellyfish will starve.

  The world’s only captive population of immortal jellyfish lives in petri dishes arrayed haphazardly on several shelves of a small refrigerator in Kubota’s office. Like most hydrozoans, Turritopsis passes through two main stages of life, polyp and medusa. A polyp resembles a sprig of dill, with spindly stalks that branch and fork and terminate in buds. When these buds swell, they sprout not flowers but medusas. A medusa has a bell-shaped dome and dangling tentacles. Any layperson would identify it as a jellyfish, though it is not the kind you see at the beach. Those belong to a different taxonomic group, Scyphozoa, and tend to spend most of their lives as jellyfish; hydrozoans have briefer medusa phases. An adult medusa produces eggs or sperm, which combine to create larvae that form new polyps. In other hydroid species, the medusa dies after it spawns. A Turritopsis medusa, however, sinks to the bottom of the ocean floor, where its body folds in on itself—assuming the jellyfish equivalent of the fetal position. The bell reabsorbs the tentacles, and then it degenerates further until it becomes a gelatinous blob. Over the course of several days, this blob forms an outer shell. Next it shoots out stolons, which resemble roots. The stolons lengthen and become a polyp. The new polyp produces new medusas, and the process begins again.

  Kubota estimates that his menagerie contains at least 100 specimens, about three to a petri dish. “They are very tiny,” Kubota, the proud papa, said. “Very cute.” It is cute, the immortal jellyfish. An adult medusa is about the size of a trimmed pinkie fingernail. It trails scores of hairlike tentacles. Medusas found in cooler waters have a bright scarlet bell, but more commonly the medusa is translucent white, its contours so fine that under a microscope it looks like a line drawing. It spends most of its time floating languidly in the water. It’s in no rush.

  For the last fifteen years, Kubota has spent at least three hours a day caring for his brood. Having observed him over the course of a week, I can confirm that it is grueling, tedious work. When he arrives at his office, he removes each petri dish from the refrigerator, one at a time, and changes the water. Then he examines his specimens under a microscope. He wants to make sure that the medusas look healthy: that they are swimming gracefully; that their bells are unclouded; and that they are digesting their food. He feeds them artemia cysts—dried brine shrimp eggs harvested from the Great Salt Lake in Utah. Though the cysts are tiny, barely visible to the naked eye, they are often too large for a medusa to digest. In these cases Kubota, squinting through the microscope, must slice the egg into pieces with two fine-point needles, the way a father might slice his toddler’s hamburger into bite-size chunks. The work causes Kubota to growl and cluck his tongue.

  “Eat by yourself!” he yells at one medusa. “You are not a baby!” Then he laughs heartily. It’s an infectious, ratcheting laugh that makes his round face even rounder, the wrinkles describing circles around his eyes and mouth.

  It is a full-time job, caring for the immortal jellyfish. When traveling abroad for academic conferences, Kubota has had to carry the medusas with him in a portable cooler. (In recent years he has been invited to deliver lectures in Cape Town; Xiamen, China; Lawrence, Kansas; and Plymouth, England.) He also travels to Kyoto when he is obligated to attend administrative meetings at the university, but he returns the same night, an eight-hour round trip, in order not to miss a feeding.

  Turritopsis is not the only focus of his research. He is a prolific author of scientific papers and articles, having published fifty-two in 2011 alone, many based on observations he makes on a private beach f
ronting the Seto Lab and in a small harbor on the coastal road. Every afternoon, after Kubota has finished caring for his jellyfish, he walks down the beach with a notebook, noting every organism that has washed ashore. It is a remarkable sight, the solitary figure in flip-flops, tramping pigeon-toed across the 400-yard length of the beach, hunched over, his floppy hair jogging in the breeze, as he intently scrutinizes the sand. He collates his data and publishes it in papers with titles like “Stranding Records of Fishes on Kitahama Beach” and “The First Occurrence of Bythotiara Species in Tanabe Bay.” He is an active member of a dozen scientific societies and writes a jellyfish-of-the-week column in the local newspaper. Kubota says he has introduced his readers to more than 100 jellyfish so far.

  Given Kubota’s obsessive focus on his work, it is not surprising that he has been forced to neglect other areas of his life. He never cooks and tends to bring takeout to his office. At the lab, he wears T-shirts—bearing images of jellyfish—and sweatpants. He is overdue for a haircut. And his office is a mess. It does not appear to have been organized since he began nurturing his Turritopsis. The door opens just wide enough to admit a man of Kubota’s stature. It is blocked from opening farther by a chest-high cabinet, on the surface of which are balanced several hundred objects Kubota has retrieved from beaches—seashells, bird feathers, crab claws, and desiccated coral. The desk is invisible beneath a stack of opened books. Fifty toothbrushes are crammed into a cup on the rusting aluminum sink. There are framed pictures on the wall, most of them depicting jellyfish, including one childish drawing done in crayons. I asked Kubota, who has two adult sons, whether one of his children had made it. He laughed, shaking his head.

  “I’m not a very good artist,” he said. I followed his glance to his desk, where there was a box of crayons.

  The bookshelves that line the walls are jammed to overflowing with textbooks, journals, and science books, as well as a number of titles in English: Frank Herbert’s Dune, The Works of Aristotle, The Life and Death of Charles Darwin. Kubota first read Darwin’s On the Origin of Species in high school. It was one of the formative experiences of his life; before that, he thought he would grow up to be an archaeologist. He was then already fascinated with what he calls the “mystery of human life”—where did we come from and why?—and hoped that in the ancient civilizations he might discover the answers he sought. But after reading Darwin, he realized that he would have to look deeper into the past, beyond the dawn of human existence.

  Kubota grew up in Matsuyama, on the southern island of Shikoku. Though his father was a teacher, Kubota didn’t get excellent marks at his high school, where he was a generation behind Kenzaburo Oe. “I didn’t study,” he said. “I only read science fiction.” But when he was admitted to college, his grandfather bought him a biological encyclopedia. It sits on one of his office shelves, beside a sepia-toned portrait of his grandfather.

  “I learned a lot from that book,” Kubota said. “I read every page.” He was especially impressed by the phylogenetic tree, the taxonomic diagram that Darwin called the Tree of Life. Darwin included one of the earliest examples of a Tree of Life in On the Origin of Species—it is the book’s only illustration. Today the outermost twigs and buds of the Tree of Life are occupied by mammals and birds, while at the base of the trunk lie the most primitive phyla—Porifera (sponges), Platyhelminthes (flatworms), Cnidaria (jellyfish).

  “The mystery of life is not concealed in the higher animals,” Kubota told me. “It is concealed in the root. And at the root of the Tree of Life is the jellyfish.”

  Until recently, the notion that human beings might have anything of value to learn from a jellyfish would have been considered absurd. Your typical cnidarian does not, after all, appear to have much in common with a human being. It has no brain, for instance, and no heart. It has a single orifice through which its food and waste pass—it eats, in other words, out of its own anus. But the Human Genome Project, completed in 2003, suggested otherwise. Though it had been estimated that our genome contained more than 100,000 protein-coding genes, it turned out that the number was closer to 21,000. This meant we had about the same number of genes as chickens, roundworms, and fruit flies. In a separate study, published in 2005, cnidarians were found to have a much more complex genome than previously imagined.

  “There’s a shocking amount of genetic similarity between jellyfish and human beings,” said Kevin J. Peterson, a molecular paleobiologist who contributed to that study, when I visited him at his Dartmouth office. From a genetic perspective, apart from the fact that we have two genome duplications, “we look like a damn jellyfish.”

  This may have implications for medicine, particularly the fields of cancer research and longevity. Peterson is now studying micro-­ RNAs (commonly denoted as miRNA), tiny strands of genetic material that regulate gene expression. MiRNA act as an on-off switch for genes. When the switch is off, the cell remains in its primitive, undifferentiated state. When the switch turns on, a cell assumes its mature form: it can become a skin cell, for instance, or a tentacle cell. MiRNA also serve a crucial role in stem-cell research—they are the mechanism by which stem cells differentiate. Most cancers, we have recently learned, are marked by alterations in miRNA. Researchers even suspect that alterations in miRNA may be a cause of cancer. If you turn a cell’s miRNA “off,” the cell loses its identity and begins acting chaotically—it becomes, in other words, cancerous.

  Hydrozoans provide an ideal opportunity to study the behavior of miRNA for two reasons. They are extremely simple organisms, and miRNA are crucial to their biological development. But because there are so few hydroid experts, our understanding of these species is staggeringly incomplete.

  “Immortality might be much more common than we think,” Peterson said. “There are sponges out there that we know have been there for decades. Sea-urchin larvae are able to regenerate and continuously give rise to new adults.” He continued: “This might be a general feature of these animals. They never really die.”

  Peterson is closely following the work of Daniel Martinez, a biologist at Pomona College and one of the world’s leading hydroid scholars. The National Institutes of Health has awarded Martínez a five-year, $1.26 million research grant to study the hydra—a species that resembles a polyp but never yields medusas. Its body is almost entirely composed of stem cells that allow it to regenerate itself continuously. As a PhD candidate, Martinez set out to prove that hydra were mortal. But his research of the last fifteen years has convinced him that hydra can, in fact, survive forever and are “truly immortal.”

  “It’s important to keep in mind that we’re not dealing with something that’s completely different from us,” Martínez told me. “Genetically hydra are the same as human beings. We’re variations of the same theme.”

  As Peterson told me: “If I studied cancer, the last thing I would study is cancer, if you take my point. I would not be studying thyroid tumors in mice. I’d be working on hydra.”

  Hydrozoans, he suggests, may have made a devil’s bargain. In exchange for simplicity—no head or tail, no vision, eating out of their own anus—they gained immortality. These peculiar, simple species may represent an opportunity to learn how to fight cancer, old age, and death.

  But most hydroid experts find it nearly impossible to secure financing. “Who’s going to take a chance on a scientist who doesn’t work on mammals, let alone a jellyfish?” Peterson said. “The granting agencies are always talking about trying to be imaginative and reinvigorate themselves, but of course you’re stuck in a lot of bureaucracy . . . The pie is only so big.”

  Even some of Kubota’s peers are cautious when speaking about potential medical applications in Turritopsis research. “It is difficult to foresee how much and how fast . . . Turritopsis dohrnii can be useful to fight diseases,” Stefano Piraino, a colleague of Ferdinando Boero’s, told me in an e-mail. “Increasing human longevity has no meaning, it is ecological nonsense. What we may expect and work on is to improve the quality
of life in our final stages.”

  Martínez says that hydra, the species he studies, is more promising. “Turritopsis is cool,” he told me. “Don’t get me wrong. It’s interesting that it does this weird, peculiar thing, and I support researching it further, but I don’t think it’s going to teach us a lot about human beings.”

  Kubota sees it differently. “The immortal medusa is the most miraculous species in the entire animal kingdom,” he said. “I believe it will be easy to solve the mystery of immortality and apply ultimate life to human beings.”

  Kubota can be encouraged by the fact that many of the greatest advancements in human medicine came from observations made about animals that, at the time, seemed to have little or no resemblance to man. In eighteenth-century England, observation of dairymaids exposed to cowpox helped establish that the disease inoculated them against smallpox; the bacteriologist Alexander Fleming accidentally discovered penicillin when one of his petri dishes grew a mold; and, most recently, scientists in Wyoming studying nematode worms found genes similar to those inactivated by cancer in humans, leading them to believe that they could be a target for new cancer drugs. One of the Wyoming researchers said in a news release that they hoped those genes could “contribute to the arsenal of diverse therapeutic approaches used to treat and cure many types of cancer.”