Long for This World

by Jonathan Weiner

  Somewhere in the gunk on the wall of the tank she found a rare, single-celled pond creature called Tokophrya, and she fell in love with it. The adult Tokophrya looks like a miniature hydra. It’s another stick figure of life. Its body is a stalk. At the base it has a sort of suction cup called a holdfast. At the top it has sixty or seventy tentacles. The tentacles stand out from it in long straight lines like rays around a child’s drawing of the sun, waving in the water. If a paramecium swims too close, it gets stuck and impaled. Then Tokophrya sucks its victim’s innards through the tentacles, as if it were drinking its prey (still alive and struggling) through a dozen straws.

  In all that, it is like the hydra. But the way Tokophrya gives birth is more like us. A tiny bud, a baby, grows in the cell inside a miniature womb called a brood pouch. When the baby is ready to be born, it whirls and struggles in the pouch for ten or twenty minutes, and then bursts out. The parent looks pretty tired. But it recovers quickly and gives birth again in a couple of hours. A healthy Tokophrya can perform this miracle as many as twelve times in twenty-four hours. Its name means, in Greek, “the well of birth.”

  Each newborn Tokophrya swims away. Within a few hours it metamorphoses into a young adult, growing a sturdy holdfast, with which it grips the floor of the test tube or the petri dish. It stays put in that one spot for the rest of its life, giving birth to more Tokophrya.

  This vaguely mammalian style of labor and delivery fascinated Rudzinska. When a paramecium or an amoeba is ready to reproduce, it just splits in two. After each of the halves is full-grown, those split also. Biologists thought of cells like that as virtually immortal. There is never a moment when you can say that one has died. It just goes on and on.

  By contrast, Tokophrya endures the labor of birth, like us. And day by day, while standing on its holdfast and trawling with its tentacles for food, Tokophrya grows old—just like us. So Tokophrya makes a good subject for a study of mortality, and because of its holdfast, it is a convenient one; unlike the amoeba or the paramecium, or the yeast cells that swirl around in a pint of beer, each Tokophrya stays put. Each mortal poses for the camera all its life. Through the microscope, Rudzinska could watch a single cell on its ride from birth to old age and death and try to figure out what goes wrong inside the cell. It was as if she had the whole problem of life and death on the head of a pin.

  When Rudzinska came to New York as an émigré after the war, she worked on other things, including the longevity of the amoeba. She was one of the first biologists to use the new high-powered electron microscope to study the intricate machinery inside cells, those tiny bubbles that keep themselves alive and intact so much longer than a mere bubble of water drifting on a pond. Her microscope back in Poland could make things look one hundred, two hundred, five hundred times larger than life. The electron microscope made them more than fifty thousand times larger than life.

  That was useful research, she told me, but as a scientist her heart still belonged to Tokophrya and the way it seemed to diagram the mystery of aging. She was convinced that Tokophrya would be ideal for the study of length of days. Only a few people in the world were working with Tokophrya. She’d lost her own stocks of the creature as an exile and émigré the stocks that a biologist in Brooklyn shared with her were not ideal for her purposes. She must have told me why, but I’ve forgotten. What I remember is the tale of her search. She looked everywhere, in ponds, lakes, ditches, and puddles in several states, but she could not find Tokophrya, and she could not quite find her way back into the thrill and romance of scientific research that she had felt in Poland during the war. Eventually she fell sick with a high fever, and spent weeks lying in a bed in Rockefeller’s research hospital. She thought, Can this be where my story ends?

  Then, one day in the hospital, while looking out her window, she thought of the fountain pool near her laboratory in Theobald Smith Hall. The pool was not far from York Avenue, but like the rest of the Rockefeller campus it seemed a world apart. It was surrounded by slate walks and marble love seats and ivy-covered sycamores.

  From her hospital bed, she asked one of her young laboratory assistants to go down to the pool and collect some water there. She told her assistant to take the water and put a drop under the microscope. And there at last, just as she had hoped, was Tokophrya.

  That was how Maria Rudzinska recovered her life’s work.

  After our lunch, she led me to her laboratory. When successful scientists are in the prime of their careers they can command whole floors of prime research space, as Alex Carrel did in his heyday in Founder’s Hall. But when they are old and retired, they have to make room for the next generation, Rudzinska explained, ruefully. She worked in the basement of Theobald Smith Hall. Rockefeller’s buildings are linked by a system of underground tunnels, and because it was a cold winter day, she led me from the cafeteria through a few of these twisting tunnels until we came to her small, windowless laboratory. She walked slowly and it took us a while to get there.

  In her recent experiment, she’d been assisted by two younger scientists, although she usually preferred to work and publish alone. She’d invited both of them to be there when I arrived. They were older than I was, but they looked very young when they stood next to her. They each wore an extra-bright, extra-wide smile that was somewhere between the beaming of reverence for the old master and the beaming of indulgence for the ancient.

  Rudzinska explained her latest experiment. With the help of her two young collaborators, she’d collected a few more jars of water from the fountain pool. In her laboratory, they had grown—or, in the jargon of cell biologists, they had isolated and cultured—more Tokophrya infusionum in screw-capped tubes. Through the microscope they could see a field of Tokophrya waving their tentacles in the water, each one standing on its holdfast. The researchers would search for a single healthy specimen. Using a very fine platinum wire with a tiny loop at the end, like a shepherd’s crook, they’d pick out that specimen. They transferred it to a glass slide that had a little shallow depression, called a well. The well was filled with sterilized water.

  At the end of each day of the experiment, Rudzinska had inspected the Tokophrya in the well through a microscope. It gave birth again and again. She counted the new arrivals, removed the parent with the shepherd’s crook, and put it in a fresh drop of water. On Monday, Tuesday, and Wednesday the cell gave birth all day long. But it was growing older: only one birth on Thursday and one on Friday. None on Saturday.

  The aging cell’s tentacles weakened, too. Rudzinska was feeding the cell with Tetrahymena, which is another protozoan that lives in pond scum. (Through the microscope, it looks something like a hairy mango.) She made sure her Tokophrya specimen got just enough Tetrahymena every day, not too many and not too few, by directing a stream of them with a fine pipette right at the Tokophrya. When it had caught enough food, she would remove the Tokophrya, with its prey still in its arms, and transfer it to a fresh well, filled with two drops of sterile pool water.

  The healthy cell’s cytoplasm was bright and clear. The old cell was dark and shabby, full of dirt and age spots. One of the most famous researchers at Rockefeller, Christian de Duve, had won the Nobel Prize in 1974 for his discovery of a key way the cell cleans up its garbage. He spotted a sort of floating garbage disposal inside the cell, which he called the lysosome, from the Greek: literally “splitting body.” Lysosomes swallow cellular trash and digest it. That is one of the cell’s great secrets of rejuvenation. The process by which the cell consumes itself in the lysosome is known as autophagy, which means, literally, “self-eating.” It is as vital to the life of the cell as eating; but in Rudzinska’s aging Tokophrya cell, the garbage-disposal system seemed to be failing, too. Everything was failing. When Tetrahymena brushed against the elderly cell, they just pulled away and swam on. The cell got darker and weaker, and on Sunday it died.

  Rudzinska was looking at a relatively simple life through the transparent walls of its body using one of the most powerful microsc
opes in the world, and she still could not figure out what was going wrong inside it. The cell died and she did not know why. There were so many possible explanations. At about that time a biologist tried to list them all and counted three hundred theories of aging: genetic theories, evolutionary theories, mathematical and physicomathematical models of aging. Which one was right? This is what Rudzinska was trying to understand, quietly and patiently. Where was the fatal damage? Was it in the clear jelly of the cytoplasm or inside the dark coiled ball of the nucleus? And why did it happen? Did it have to happen at all?

  In retrospect, I was lucky to have met a gerontologist in 1984. I was just in time to catch a glimpse of the slightly depressive backwater that the field had been for generations. “Research on aging, like its subject matter, does not move very fast,” as the British immunologist Peter Medawar put it in 1981, when that science was still in the doldrums. “In almost any other important biological field than that of senescence,” wrote Alex Comfort, another British gerontologist, in 1979, “it is possible to present the main theories historically and to show a steady progression from a large number of speculative ideas to one or two highly probable, main hypotheses. In the case of senescence this cannot be profitably done.”

  Comfort was a familiar name to me. Yes, Rudzinska said, Alex Comfort was not only a gerontologist; he was also the author of the worldwide bestseller The Joy of Sex.

  “We were so angry with him for writing that,” she added.

  Such a hard and unappetizing problem, aging. The aging of a living thing is not like the aging of a fine cheese or a fine wine. There the chemistry alters, the molecules change around, and the cheese and wine improve. Nor is aging like the deterioration of a car or a can-opener or any other manmade machine. When gadgets break down they can’t fix themselves, and neither can they make more of themselves—whereas a living body, even a microscopic bubble of life like Tokophrya, can accomplish both those miracles as long as it lives. Even when Tokophrya is ancient, too frail to reproduce, it is still repairing and remaking its own working parts, which is also a kind of reproduction, in a sense; the cell performs the hard work of passing its own body along from one moment to the next, creative work that never stops till death.

  So what is aging? Why does the cell stop repairing itself? This is the question that Bacon was asking at the start of the scientific adventure. He knew nothing about single cells but he understood this question. Again, we are so very good at growing and staying in shape when we are young. The mortal body of that single coddled Tokophrya would have a chance to last and last if it could only keep up the repairs on Friday the way it did on Monday, when it was young.

  Through the microscope, Rudzinska could see so many signs of trouble. Tokophrya wears a few coats, or membranes, one on top of the other. Its outermost membrane, called the pellicle, is made of two separate layers that are linked by fine mortise-and-tenon joints. Those joints were popping loose, and the layers were separating. The cell was literally coming apart at the seams.

  Of the many studies of aging that she had on her mind in 1984, the most interesting was already fifty years old. In 1934, a biologist at Cornell University named Clive McCay had reported a remarkable breakthrough with laboratory rats. McCay found that if he fed the rats all the nutrients they needed but cut their daily allowance of calories in half, the rats would live about twice as long. Since that time, McCay’s discovery had survived test after test. Back when I visited Rudzinska, experimenters were still raising thousands of rats and mice on calorie-restriction diets. The rats and mice got thin and scrawny, but they did live a long time. Nobody knew why.

  So Rudzinska investigated the clue of caloric restriction with her Tokophrya. Was there something about the reduction of calories that slowed down the metabolic rates of the cells of those mice? Did slowing down their metabolisms make them live longer? She found that when she kept the cells chilly and half-starved, they did live longer.

  Rudzinska tried that experiment again and again. She put a single Tokophrya in a hanging drop of water on the glass lid of a chamber. Then she fed it, say, three Tetrahymena. The next day when she checked on it, it was still healthy and it had produced about that same number of babies. But if she gave a Tokophrya forty Tetrahymena, it would produce only one baby. If she gave it a hundred Tetrahymena, swamped it with fish food, the Tokophrya just ate and ate, gorged without stopping. It ballooned out into a giant—dark, opaque, with short, stunted tentacles. It stopped giving birth. It lost its tentacles. And after a few hours, the cell fell apart—cut short in its prime. On the other hand, if she kept a Tokophrya on a restricted diet, half-starved for Tetrahymena, fed them only one day every two weeks, her Tokophrya would live about twice as long.

  So calorie restriction worked for species as far apart on the tree of life as mice and Tokophrya, which seemed to argue that it might also work for us.

  Rereading her papers now, I can see that for all her pains she was a bit isolated, cut off from the news. Most of the names she cites in her papers were already half-forgotten then, biologists who had studied aging in the paramecium and in the amoeba when she was a young scientist in Poland. All around her, biologists at Rockefeller were helping to establish molecular reality; but she did not work with genes and molecules. What you can see inside a cell at 500 or even 100,000 times life size is still coarse compared to what you can see if you get down to the molecular level. The brave new world of molecules was passing her by. And of course she could not begin to explain why multicellular animals like us age, and why unicellular animals seem to escape from aging, or why some multicellular animals do not seem to age at all, like the hydra; while some unicellular animals do age, like Tokophrya, even though these two creatures have such a strong family resemblance in body plan and lifestyle that each is like a crude sketch of the other. This kind of confusion is discouraging to scientists, to people who like to figure things out.

  Down in the basement of Theobald Smith Hall, Rudzinska and her two young assistants had set up a little demonstration for me. I looked through a microscope on the laboratory bench and saw a whole field of Tokophrya standing close together, swaying gently on their holdfasts like a field of alien corn. I turned the knob of the microscope slowly and surveyed the field. There were hundreds and hundreds of cells. It was something to see them, after hearing so much about them, and I looked up to thank the old biologist. Then I put my eye back to the lens. Just when I was about to take my eye away for the last time, I spotted a cell that was shaking back and forth on its holdfast. There was a baby trembling inside it. After a moment, the baby popped out and swam away.

  I left the basement laboratory and swung out of Theobald Smith Hall into the pale winter day. Before I walked down the main path to the stone gate on York Avenue, I made a detour through the campus and found Rudzinska’s fountain. It had been drained for the winter. A few wet dark leaves from the ivy and the sycamores, the last of the wreckage of the year before, lay plastered to the concrete basin like tea leaves in the bottom of a cup. Somewhere in there, Tokophrya lay dormant and encysted, waiting out the winter.

  At the time, I found it romantic that science could not answer these elemental and universal questions, questions that must have struck every thoughtful mortal again and again from more or less the beginning of their lives and from more or less the beginning of time. How did we come to be mortal? Do we have to be mortal? What can the science of life do about our mortality? What is aging? The image of that microscopic birth in the laboratory still floated before my eyes. I felt as if I had just been granted a glimpse into the fundamentals of birth and death—as if I’d seen as much as anybody could see, looked down to the bottom of the well. No one understood the problem of mortality.

  It was clear that Maria Rudzinska loved her work. She loved the questions. She used to sign her letters Doctor Tokophrya. But it was also clear to me that she would not be the one to find the answers. And I found that beautiful. I loved the mystery—or else I’d persuaded myself t
o love it. Everyone knows that we have to grow old and die, just as surely as everyone hopes for long life. If you drink your cup to the bottom, you reach dregs. If you blunder, if you mess up, if you fumble as you reach for the cup, it spills and it shatters. That is our portion on this planet. The lines of an inscription in Osmington Church, Dorset, carved in 1609, take the shape of the cup:

  Man is a Glas: Life is

  a water that’s weakly

  walled about: sinne bring

  es death: death breakes

  the Glass: so runnes

  the water out

  finis.

  Finis! End of all mortal explanations—whether you think of the problem as spiritual or physical, sacred or secular. We are glass, and we break. We are water, and we spill. We are dust, and to dust we shall return.

  That was the problem of mortality as I’d grown up with it. That was the problem of aging with which my generation came of age. Rockets might take us to Mars someday, or out beyond the asteroid belt, but wherever we baby boomers went we would go on bearing the same mortal weight. Rockets might take us to the stars, but only myths could take us to Mount Olympus. We were mortals—and yet the Eagle had landed on the Moon.

  So we believed in limits, and we didn’t—just like the readers of Mandeville’s travels when he described a wonderful bird the size of an eagle in the Egyptian city of Heliopolis, the City of the Sun. The bird is called the Phoenix. “And he hath a crest of feathers upon his head more great than the peacock hath,” and his neck is iridescent like “a stone well shining.” And the Phoenix lives forever.

  Chapter 4