Metamorphosis, p.22
Metamorphosis, page 22
Fabre was a god-fearing man, and to him this seemed a miracle. Later in life, he would write to Darwin that he’d have no truck with evolution, judging its tenets a secular inanity. “I am sorry that you are so strongly opposed to the descent theory,” Darwin replied in 1880, “I have found the searching for the history of each structure or instinct an excellent aid to observation.”
To the shy Wigglesworth, Fabre’s miracle was a mystery to be solved: How does the meltdown occur? How does the creature reassemble? What are the factors controlling molting and metamorphosis?
When he turned eighteen, Wigglesworth enrolled to read biochemistry and physiology at Cambridge (the émigré Vladimir Nabokov would arrive the following year). Taking a medical degree, he moved to the London School of Hygiene and Tropical Diseases and began to spread his wings as a medical entomologist. First to Nigeria, the Gold Coast, and Sierra Leone, armed with a self-contained laboratory complete with a bed and bath (and microscope), and a determination to combat a disease spread by the bite of the tsetse fly. Then it was to India, Java, Burma, Malaysia, and Ceylon, where he was present in 1934 during the lethal malaria epidemic that killed more than one hundred thousand. All the while, Wigglesworth was learning the secrets of the insects, a million-times-a-million-times-a-million in number, four-fifths of the living species on Earth.
It was already clear to him that combatting pests to mitigate disease depended first on understanding the insects themselves. And physiology was where the answers were to be found. So he used his position to conduct truly “useful” as opposed to “futile” research, a distinction he thought more meaningful than the usual “pure” versus “applied.” The result was a book that got him elected to the Royal Society. A book that dealt, in part, with the birth of a butterfly.
He thought he knew what the problem was. A butterfly has wings that can only be powered by an elaborate musculature. The muscles, in turn, demand a respiratory system to bring them oxygen. Respiration is useless unless the air-filled tubes called tracheae can deliver oxygen to the muscles. Without hemolymph, the insect equivalent of blood, nutrients can’t reach their destination, either. But when the caterpillar melts down in the pupa, neither its muscles nor its breathing organs nor its heart or brain remain as they were. And since a butterfly looks nothing like a caterpillar, and lives in a different environment, new kinds of organs suited to new functions need to be constructed from a gooey mush. After all, the butterfly will eat different foods as an imago, so will need entirely new mouthparts, and a new gut. It will fly and land and take off again, so it will need elongated legs besides a pair of hardy wings. It will mate, so will need a set of compound eyes, antennae, and genitals. To orchestrate its new behaviors a new brain will be necessary. Somehow, through a process of massive destruction and reconstruction, a new nervous system will have to be built.
In Principles of Insect Physiology Wigglesworth put his nose to the ground. He knew that many insects, like mayflies and cicadas, undergo only an incomplete metamorphosis. Never becoming a pupa like beetles, moths, or butterflies, nor changing their shape dramatically, they grow from nymph to nymph, until their wings and new eyes and sex organs appear in the final molt. Molting allows for growth in size, metamorphosis for change of form; clearly the two were not synonymous. But Wigglesworth began to think of them as homologous. After all, butterflies and moths may seem a world apart from mayflies or cicadas, but, however they went about developing, evolution had already placed in both the recipe for becoming true adults.
Wigglesworth now saw that his childhood hero Fabre had been wrong: The pupa was not, in fact, a bunch of goo and mush. Instead, everything inside had its place, but it was extremely delicate; treat it with anything less than utter gentleness and it would burst. If you did treat it delicately, you’d see that what were termed “imaginal discs” were cells that had been born early in development from the ectoderm, only didn’t decide what they would be when they grew up. Instead, they remained apart, undifferentiated in a kind of sac, until the caterpillar was ready to pupate. That’s when they’d wake up to form new eyes and wings and legs and genitals. It was as if the insect had two separate developmental programs that lived side by side but marched to a different clock.
But how could Wigglesworth figure out what was really happening in metamorphosis? In The Voyage of the Beagle, Darwin had reported being bitten by a kissing bug near the river Luxan in Argentina: “It is most disgusting to feel soft wingless insects, about an inch long, crawling over one’s body,” he wrote. “Before sucking they are quite thin, but afterward they become round and bloated with blood, and in this state are easily crushed.” One hundred twenty years later, scholars would suggest that the kissing bug (Rhodnius prolixus) gave Darwin a horrible disease of the heart and intestines called Chagas, which eventually turned him into an invalid.i But it also gave Wigglesworth an idea.
Soon he was turning the blood-sucking, incompletely metamorphosing kissing bug into his own loyal guinea pig. Rhodnius could be kept on a shelf like a reagent, and survive without eating for months. It was also known for its fifth quick, and final, molt: the wings appearing suddenly, the larger chest, and compound eyes, the full-blown genitalia. There had to be some signal that brought about such dramatic changes so rapidly, a message arriving to its cells, telling them: “Begin, differentiate, there’s no time to lose!” Wigglesworth already knew from the pioneering work of a biologist named Stefan Kopeć in Warsaw that it couldn’t be the nervous system that delivered the crucial missive. And so he went searching in the bloodstream for a “hormone.”
Hormones had recently become household names, following the discovery of the human gonad-stimulating and other pituitary and thyroid hormones and their role in fashioning breasts and genitalia and muscle mass and voice pitch suddenly at puberty, transforming girls to women and boys to men. Why, Wigglesworth wondered, couldn’t the same be true of insects? Day in and day out he’d travel from his home in Beaconsfield to his lab in London, break at a quarter to one for lunch, then return until evening. Everyone from his children to his students would remember Wigglesworth as a cold, reserved man, without emotion. But in reality Wigglesworth’s heart was about to burst.
Wigglesworth knew that the kissing bug went through five molts. He knew that the first four of these molts produced slightly bigger nymphs, and that only the fifth turned into a true adult, with wings and compound eyes and genitalia. He knew that the kissing bug drank blood and that its molts were perfectly timed to its meals, beginning at some critical period after the nutrients in the blood had enough time to be digested. Knowing all this, Wigglesworth devised a plan: a careful series of decapitations. Using scissors and thread, he took a kissing bug in its third molt and cut off its head, just after the critical period. Sure enough, it continued to digest its blood meal, to excrete waste, and it went on to molt. But when he decapitated another nymph before the critical period, although it survived for nearly a year, it never molted again.
This was important. To Wigglesworth it signaled a clear and stark conclusion: A hormone released in or near the head was being carried through the hemolymph to the rest of the body, somehow triggering it to molt. When the head was removed before the body got the message, molting failed; but if enough time had passed, even without a head the bug would molt. If this was true, hemolymph from an insect that had passed the critical period should induce molting even in an insect that had been decapitated too soon. And so he beheaded two nymphs, one before and one after the critical period. By joining their decapitated bodies with the help of paraffin wax, he let the juices flow freely between them. The more recent decapitee molted, unsurprisingly, but lo and behold, so did its neck-to-neck mate. Clearly the mixed hemolymphs had delivered the hormone! But where, exactly, was the hormone coming from?
It had to be in the bug’s head, Wigglesworth thought, like the pituitary gland in humans, or somewhere close by at least, innervated by nerves coming from the head. Dissecting with great care, he found an organ in the kissing bug’s head called the corpus allatum. No one understood its function before him, but now Wigglesworth saw that during the fourth molt its cells divided with great flair. Curiously, during the fifth and crucial molt, when the nymph becomes an adult, the activity in the corpus allatum ceased entirely.
Another peculiarity arose when Wigglesworth decapitated fourth-stage nymphs, which had passed the critical period, and conjoined them to fifth-stagers that had not: The fifth-stage nymphs did not turn into adults. They just molted into larger nymphs. On the other hand, if he glued a first-stage decapitee to a fifth-stager that was in the process of molting, the headless nymph turned into a tiny precocious adult. If only a molting hormone were involved, it should have turned into a second-stage nymph.
Suddenly Wigglesworth got it: This was a game of activation and inhibition! There must be two factors in action: a molting hormone and an inhibiting one. Cutting up butterflies and dragonflies, grasshoppers and locusts, mayflies and moths, helped strengthen his line of reasoning. Gory amalgams Wigglesworth made with two bodies of separate creatures conjoined to a single head of a third proved the point. The corpus allatum was inhibiting the change to adult—that’s why it shut down at the fifth stage. Wigglesworth christened its product: “juvenile hormone.”
The reserved man from Lancashire had invented a field, and become famous. A poem about him by John Updike appeared in The New Yorker in 1955, and he’d be knighted in later years. And yet Lynn Riddiford and Jim Truman’s department chair, the one with whom they deposited their special secret, would pretty much take it from there. Working at Harvard on the giant silkworm moth, Carroll Williams figured out the details of the system: that bead-like strings of cells around the trachea are what secrete the molting hormone, named ecdysone.ii That the production of this hormone is controlled by a master hormone—which he called “the brain hormone”—emanating from organs in the brain called corpora cardiaca. That the brain hormone is carried in the hemolymph to the prothoracic gland, where it gives the order to start producing ecdysone. That each of the nymphal molts is due to a pulse or more of that hormone, jump-started in special neurosecretory cells in the brain, which send their signal to the corpora cardiaca, which sends its signal to the prothoracic. That the neurosecretory cells, cleverly, take their cues from the environment: a stretched stomach full of blood in the satiated kissing bug, for example, or warmer temperature as seasons change in the silkworm moth. That’s how the life cycle of insects connects to the world around them.
Wigglesworth had been right about the corpus allatum: It was truly the source of the third hormone—his juvenile one—the absence of which allows for the final, dramatic metamorphosis. But it was the American with the Tidewater accent, Williams, who beat him to it, leaving him feeling a bit like a kissing bug without a head.
Like so many discoveries, this one involved a lucky break. A Czech collaborator of Williams’s, Karel Sláma, arrived at Harvard with several jars of fire bug larvae. But for some reason, when they were left in their jars, the larvae never turned into adults, the way they had in Sláma’s lab in Europe, and the two men were stumped. Then they noticed that the same was true when the larvae were placed on copies of The New York Times, Boston Globe, and Scientific American, and the penny dropped. Unlike European paper mills, American mills used balsam fir to make their pulp, and balsam had developed natural anti-insect defenses that kept the larvae from maturing into an adult. The trees were emitting an analogue of the juvenile hormone.
Soon he and his collaborators had extracted and purified the juvenile hormone, and the media went wild. The “elixir of youth,” they called it, and wondered whether, to become Peter Pan, humans should spray it into their nose, massage it into their skin, or simply chug it. In his affable manner, Williams took the hype with a smile. This was all harmful nonsense, good for getting young students excited at a Radcliffe PreMed and Science Society meeting, maybe, but nothing more. And yet juvenile hormone might be used to develop insect-killers much hardier than DDT, even if it was useless for retarding development in humans; after all, insects would find it hard evolving resistance to their own hormones. In time, juvenile hormone–based insecticides would become extremely specific: able to kill just one sort of pest by stunting their cycle, while sparing all the rest.
Jim and Lynn walked down Mount Monadnock sheepishly on that Sunday in the fall of 1969. With their secret discovered, life on campus wouldn’t be quite the same anymore. Still, however much Wigglesworth and Williams had pried open metamorphosis, there were many more mysteries to uncover. On Monday, their work would be waiting for them in the lab.
Footnotes
i Members of the Reduviidae family are sometimes called “vampire” or “assassin” bugs, and in the Latin Americas are known by the further names barbeiros, vinchucas, pitos, chipos, and chinches. The kissing bug spreads its pathogen, a wormlike protozoa called Trypanosoma cruzi, by defecating near the site of the bite. Unsuspecting humans scratch the area, unwittingly assisting the pathogen to swim into the bloodstream.
ii A Japanese researcher had christened them the prothoracic gland, and two Germans would later call the steroid hormone ecdysone, from the Greek for “shedding,” a name that stuck.
6.
THE MOLECULAR TRINITY
I embark on the 8:55 a.m. from Anacortes to Friday Harbor island. Snowy Mount Baker looks upon the scene from the distance, and the sun is peeping from behind a morning mist. The cold Northwest Pacific waters are silky, almost ominously still. When I walk off the ferry an hour later, two small figures holding hands are waiting for me at the end of the wharf. She’s a little stiff-kneed and, wearing large white sneakers, a crimson, three-quarter-length coat, gray wool hat, and bulky dark sunglasses, looks a bit like someone from a witness protection program. He’s wearing a green baseball cap and a gray beard, his blue jeans are folded above worn-out walking shoes, and he’s missing a few bottom teeth. They smile and shake my hand warmly. At long last, after months of corresponding, we finally meet: Lynn Riddiford and Jim Truman have been married for nearly fifty-five years, and at eighty-eight and seventy-nine, respectively, are known as the world’s greatest experts on metamorphosis.
We drive in their small hatchback past giant Douglas firs. A deer jumps into the woods to get out of the way and we stop to watch it; for us they’re pests, Jim says, pointing at a double fence he’s constructed around a vegetable garden on their three-and-a-half-acre plot. And then, through the trees, barely noticeable until we’re right in front of it, a wooden house appears, on a bluff overlooking the waters. The San Juan archipelago lies below us, home of harbor seals and orcas. For millennia before white people arrived, Sooke, Saanich, Songhees, Lummi, Samish, and Semiahmoo American Indians fished these waters in canoes, returning with their catch to dome-shaped willow-reed and grass huts sprinkled on the islands. Inside the Riddiford-Truman home, figurines of walruses and giraffes and owls adorn the living room cabinets, rock and wood and clay mementos from years of international travel. On the walls are photographs of zebras and paintings of alligators; in the kitchen are bowls depicting butterflies, on the chair a pillow sporting horses, on a low, dark-mahogany table neatly stacked National Geographic and Science magazines. A large, beautifully groomed black cat, Spook, shies away from me, as does Shadow, a mackerel tabby. Light floods through large, wooden, rectangular windows, as if invited to bring with it clarity.
Lynn and Jim’s secret became even more public when they announced, immediately after Jim received his doctorate, that they were getting married; unsurprisingly, half of the department already knew. The wedding took place at Lynn’s parents’ farm in Illinois. That fall of 1970, Jim had become a junior fellow at Harvard, an honor bestowed upon young scholars judged to have extraordinary potential. Already he’d chosen his future path: the biology of insect behavior. Back at Notre Dame, he’d witnessed how powerful biological control could be over behavior: Grinding up the gland that makes sperm in a male mosquito and injecting the contents into a virgin female, his mentor George Craig Jr. had shown that the virgin now acted as if she’d already mated. No longer interested in the males, she rejected their incessant advances, and went about searching for a “blood drive” to supply the meal that would allow her to make a batch of eggs. Jim was flabbergasted: A little injection had turned a flighty virgin into a calculating materfamilias. How incredible.
When he arrived as Lynn’s grad student at Harvard, he tried replicating the mosquito experiments on giant silk moths—a difficult task since silk moths have scales, and Jim was violently allergic to them. Wearing a mask would reduce inhalation, but it was tough to peer down a microscope with one. Eventually the lab bought a reverse flow laminar hood in which dissections could be made with the scales carried in the other direction. But Jim’s result was a bust.
In the library one day, Jim read a new article claiming that just below the esophagus inside a cockroach’s head there was a bundle of nerve cells, called a ganglion, that stored a biological clock. A clock could order behavior, he told Williams excitedly when he bumped into him in the hall. “That’s all wrong,” Williams brushed by him, which left Jim rather crushed. That evening he decided that he had to find out why Williams thought it was all wrong, but rather than using cockroaches, he’d stick to the giant silk moth. Lynn raised these beautiful creatures on wild cherry trees in rural areas surrounding Concord. Each spring, she’d bring pupae out of diapause and let them emerge, mate, and lay eggs in large shopping bags. Lab members would gather in the early mornings and travel to the tree sites, guided by Lynn, who never needed a map to return to her favorite places. They’d pull huge nets over entire trees, place egg papers within the nets, and at the end of the season the cocoons would be harvested and separated for experiments. And they’d stop for ice cream on the way back to Cambridge.
