Nerve Growth Factor and Zabaglione Coffee Ice Cream... a la Rita Levi-Montalcini

elena petelos

  • Hero Member
  • *****
    • Posts: 3180
    • Gender:Female
  • Qui ne dit mot consent.
Despite the histrionics, Rita never questioned her father's love and concern for her welfare. He controlled all the minutiae of her daily life, but she never dreamed of disobeying his orders. When Rita and her fraternal twin Paola modeled new, entrancingly beribboned straw hats, he did not like them. The beautiful bonnets disappeared instantly and were never seen again. Rita's brother Gino wanted to be a sculptor, but his father ordered him to be an engineer. He obeyed and eventually became a famous architect, but he always wished he had been a sculptor. Tlmid and submissive, little Rita lived with many fears: her father, monsters in the dark, long hallways, pogroms, and windup toys. All the guardian angels who protected Rita's childhood were female: her Aunt Anna, her governess Giovanna, her beautiful mother Adele, amd her twin Paola. A gifted painter, Adele Levi was a reserved and submissive wife. When Rita attended an opera with her parents, her father relished the part of the Foundry Owner, who threatened to break the young wife who did not love him. While the crowd roared its approval, Rita silently sympathized with the young wife. "It was not anger." Levi-Montalcini explained. "It was built-in. There was no anger whatsoever. I simply found the situation impossible. Ever since my childhood, I had strongly resented the different roles played by my father and mother in all family decisions. I adored my mother and rebelled against this difference, which I also feared for myself as a future housewife." In second grade, she said that her fingers were "for sending kisses to mother," but she refused to kiss her father. While Paola shielded herself by communicating with no one, Rita dung to Paola. When the twins completed fourth grade, Rita longed to continue her academic education. Ignoring her wishes, Adam Levi decreed that his daughters should attend a girls' finishing school and learn to be perfect wives and mothers. His aunts had earned doctoral degrees in literature and mathematics, and he blamed their unhappy marriages on their education. Levi-Montalcini's years in finishing school were filled with con-fusion and despair. She learned none of the subjects required for entrance to a university—no mathematics, no exact sciences, no Greek or Latin. Her courses were mindless, and her classmates were interested only in marriage and motherhood. "I had no particular interest in children or in babies, and I never remotely accepted my role as a wife or mother," she recalled. When her beloved nurse Giovanna died of stomach cancel; Rita decided that she wanted to be a doctor. With no hope of attending medical school, she felt trapped and isolated in a dead end without escape. The position of married women was so debasing that she decided never to marry. She was twenty years old before she had the courage to tell her father the truth: She did not want to marry. Instead, she wanted to become a physician. When Rita's mother pleaded her cause, Adam Levi reluctantly agreed to hire a tutor to prepare his daughter for university entrance examinations. "If this is really what you want, then I won't stand in your way, even if I'm very doubtful about your choice," he told her. Soon after consenting to Rita's plans, Adam Levi suffered a massive heart attack and died. Over the years, as the memory of her struggles with him faded, she began to worship his memory. By the time she wrote her autobiography in 1988, her beloved mother had become a nameless shadow and her father dominated the book as powerfully as he had ruled her childhood. Enlisting her cousin Eugenia, Levi-Montalcini hired one tutor for mathematics and science and another tutor for Latin and Greek. She and Eugenia studied philosophy, literature, and history on their own. After only eight months of study, they took the examination. When their tutor called with the results, he announced joyfully, "Signorina Rita, you've both passed!" Levi-Montalcini led the list. She entered the University of Turin's medical school in 1930, determined to prove to herself and probably to her father also that she was as intelligent as any man. In medical school, the three hundred male students spent an inordinate amount of time analyzing the physical charms of the seven female students. Whenever a particularly awkward young woman passed through the halls, the men raised their voices and loudly talked about "Greta Garbo in disguise". In such an atmosphere, Levi- Montalcini wore clothes that were as elegant and asexual as she could manage. As a friend observed, she behaved like a squid, ready to squirt at any youmg men who approached. She did not argue with them. "I just refused to accept poor treatment. It was like water off the back of a duck," Levi-Montalcini declared. "I wanted to spend all my time on research. I was not receptive to courtship. I dressed like a num. I despised everything with a feminine flair. Women paid too much for it. I didn't want any sentimental contact with other students, only intellectual contacts. I didn't want any contact as a woman." After years of intellectual deprivation, she could finally be as fanatically devoted to learning as she pleased. She rejected the advances of several young men and told one named Guido, who became her wartime fiance, that she would stroll with him in Valentino Park "on the condition that we talked only of cultural and musical subjects." Ironically, no sooner had Levi-Montalcini escaped from her father's domination than she fell under the influence of another, an explosive and autocratic man Professor Giuseppe Levi. Like Levi-Montalcini's father, the professor was famous for his rages. His tantrums short-lived though they were shattered those around him. Like Adam Levi, he controlled even the smallest detail of his family's life. He bellowed "stupid" at his children when they did something he disliked, like wearing city shoes in the mountains or talking with strangers in the train. One of his relatively mild remarks was "I beg your pardon, but you are a perfect imbecile." His sons inherited his anger, but tried to suppress it. At dinner once, one of the sons became so enraged that he grabbed his butter knife and, with silent fury, scraped the skin off the back of his hand. His sister's description of her childhood, published in the 1950s, reminded Levi- Montalcini of her own upbringing. Levi was larger than life as a teacher, too. Three of his stu- dents—Levi-Montalcini, Salvador Luria, and Renato Dulbecco emigrated to the United States and won Nobel Prizes in physiology. Levi's consuming passion to understand nature was contagious. Although his temper tantrums made Levi-Montalcini tremble with fear, he was different from her father in one vital respect: he liked his students to exercise their intellects. Furthermore, the same spontaneity that made him explode at a student filled him with enthusiasm at a piece of good work. Thanks also to Levi's spontaneity, he always spoke his mind—loudly and passionately—against Fascism. He thundered his disapproval in public buses and lecture halls, in public and in private. His courage was legendary, and his students loved him for it. Levi's passion for science well done, his disdain for shoddiness, and his tumultuous approach to life's dramas formed the backdrop for Levi-Montalcini's development as a scientist. Above all, Levi was a magnificent histologist, skilled in the microscopic study of tissue structure. He made Levi-Montalcini expert in a new technique, staining embryonic chick neurons with chrome silver to make the nerve cells stamd out in smallest detail. It was an elegant but simple method, and she used it later in her secret wartime lab. For her thesis, Levi-Montalcini studied collagen reticular fibers, which are the weft-like supporting fibers in different types of tissue. Soon she did not know whether she wanted to pursue research or to practice medicine. After completing medical school in 1936, Levi-Montalcini worked with Levi for two more years, specializing in neurology and psychiatry. She was still torn between research and clinical practice. Then Benito Mussolini made the decision for her. In June, 1938, II Duce issued the Manifesto per la difesa delta razza—"The Manifesto for the Defense of the Race." In it, the prime minister banned intermarriage betweenJ ews amd non-Jews and prohibited Jews from pursuing academic or professional careers, from studying or teaching at state schools, and from working for state companies or institutions. Whatever Levi-Montalcini tried to do was either forbidden or dangerous. She practiced medicine secretly among the poor, but the racial laws prevented her from writing prescriptions. She could not study on her own because she could not use the university library. By March of 1939, she could not even visit the university for fear of endangering friends or being denounced. She worked in a research institute in Brussels, until just before the German invasion of Belgium. She was devastated. Her only alternatives seemed to be intellectual stagnation or emigration to the United States, which her family refused to consider. Then an old friend from medical school asked about her current research. When she could not answer, he lectured her sternly, "One doesn't lose heart in the face of the first difficulties. Set up a small laboratory, and take up your interrupted research." The idea had never occurred to Levi-Montalcini but it appealed to her instantly. She felt like Robinson Crusoe setting off to explore a jungle. Her jungle, however, was composed of 100 billion cells of the humam nervous system and the fibrous nerves that spread out from the cells like intersecting nets in all directions. Planning her workspace she realized that she did not need a large laboratory to stain nerve tissues with chrome silver. Chick embryos were ideal for home research because fertile eggs were cheap and readily available. In addition, the nervous systems of chick embryos are much simpler than those in the humam brain. Her brother built her an incubator, and she bought a binocular microscope. Then, when Giuseppe Levi was forced to leave the university, too, he joined the project. Levi-Montalcini called Levi her "first and only assistant," but it is difficult to imagine Levi meekly assisting a former student. Later, Levi-Montalcini downplayed his influence on her work. She told an interviewer in 1988, "I was on excellent terms with him, but I was always of the opposite opinion. He was a splendid mam, scientifically and ethically.... I liked him as a man but I didn't care too much about some of his ideas." During the war, however, they were coworkers. As the Italian press bannered Nazi slogans and her brother's name appeared on most-wanted posters for Resistance crimes, they buried themselves in problems of the developing nervous system. First, she needed to find a bedroom-sized problem. She found her "Bible and inspiration" on an idyllic summer day in 1940. Italy's passenger trains were busy transporting troops, so civiliams traveled in cattle cars. Sitting on the floor of an open-sided freight train, she dangled her legs over the side in the open air and enjoyed the scent of summer hay. Thus occupied, she idly read a scientific article by the eminent embryologist, Viktor Hamburger of St. Louis, Missouri. Hamburger, a founder of developmental neurobiology, is one of the "supreme biologists of our time," according to John T. Edsall, editor of the Journal of the History of Biology. Hamburger was also a leader in the use of chick embryos for experimental research on nervous-system development. As a student in 1927, he had laid out a research plan of many years' work to elucidate the development of the nervous system. He hypothesized that it was influenced by signals derived from tissues like muscles and sense organs. Although he had no idea what the signals might be, his studies of the spinal cord in chick embryos suggested that the signals might influence the division and differentiation of neurons, the fundamental unit of the nervous system. Reading Hamburger's article, Levi-Montalcini decided that she could reproduce his experiments in her bedroom. Reaching her arms into her glass incubator, she operated on three-day-old chick embryos under a low-powered dissecting microscope. Using her micro-sized scalpel, she amputated a tiny limb-bud from each embryo. Then, over the next seventeen days, she sacrificed a few embryos each day. Using her needle-sized spatula and the eye surgeon's scissors, she extricated each embryo from its egg and dissected it. Then to her brother's horror, she scrambled the remains of the eggs for dinner. After dissecting the embryos, Levi-Montalcini sliced the spinal cord into thin sections and stained them to be visible through her microscope. Clustered together within the embryonic spinal cord are the particular neurons that she wanted to study. A neuron is composed of a bulbous cell body with thin fibers extending from it. Neurons are similar in all vertebrates, from chicks to humans. One type of neuron, the motor neuron, has its cell body in the spinal cord and extends its fibers out to the embryonic limbs. When this neuron is activated, it makes the muscles contract and the limbs move. It was these neurons that Levi-Montalcini focused on. When a limb is amputated, the motor neurons in the spinal cord all but disappear. Hamburger thought they had failed to proliferate; Levi-Montalcini and Levi concluded that they had proliferated, started to grow, and then died. In Levi-Montalcini's tiny bedroom lab, she and Levi had laid the foundation for the modern concept of nerve cell death as a part of normal development. Far from discouraging her, Levi-Montalcini's dangerous and cumbersome working conditions excited her. And the Fascists' persecution of the Jews actually intensified her pride in her heritage. When Italian journals rejected their articles because her name and Levi's name wereJ ewish, what seemed like misfortune turned out to be luck. The articles were eventually published in Belgian and Swiss publications that could still be read in the United States. "Many years later, I often asked myself how we could have dedicated ourselves with such enthusiasm to solving this small neuroembryological problem while German armies were advancing throughout Europe, spreading destruction and death wherever they went, and threatening the very survival of Western civilization. The answer," she concluded, "lies in the desperate and partially unconscious desire of humam beings to ignore what is happening in situations where full awareness might lead one to self-destruction." Whatever her motivation she had found her life's passion—the central nervous system. As the Allied bombing of Italy's industrial cities intensified, Levi- Montalcini and her family fled to a country village for safety. Her lab moved from the bedroom to a dining room corner. Despite power failures every few days and a scarcity of eggs, she continued to work until the Italians overthrew Mussolini and Gemman troops poured into Italy. At that point, the Germans began rounding up Jews in earnest for the extermination camps. Hastily, Levi- Montalcini closed her lab, and she and her family fled south to Florence. Rita and Paola forged the family's identity papers, but they made a potentially fatal error; the papers were dated over a year but numbered consecutively, as if issued at one time. Levi-Montalcini worried constamdy thlat they would be discovered, particularly after Giuseppe Levi arrived at their rooming house and announced himself to their landlady as, "Professor Giuseppe Levi—Oh, no, I keep forgetting: Professor Giuseppe Lovisato." The landlady had already suspected that Levi-Montalcini's family was Jewish, but she said nothing to the authorities. After the war and a brief period treating sick refugees, Levi-Montalcini returned to Turin as Levi's assistant. She was depressed after the long struggle and no longer enjoyed research. A year later, though, Hamburger wrote her. He had read her articles in the Belgian and Swiss journals and wanted her to visit Washington University in St. Louis for a few months. Specifically, he wanted to know whose theory was correct—his or hers. Elated again, Levi-Montalcini ended her engagement to Guido and prepared for her trip. She had decided definitely never to marry; she could not adjust her own life and work to meet another person's needs. She did not want to repeat her mother's marital experience. Furthermore, between World War II and her father's opposition to her education, her career had already been delayed by a decade. At thirty-eight she was ready to concentrate on her life's work. She had concluded that "in scientific research, neither the degree of one's intelligence nor the ability to carry out one's tasks with thoroughness and precision are factors essential to personal success and fulfillment. More important...are total dedication and a tendency to underestimate difficulties, which cause one to tackle problems that other, more critical and acute persons instead opt to avoid." She planned to take advantage of every opportunity in the United States. She sailed in 1946, intent on joining the world's tiny band of neurobiologists. After the sinister atmosphere of Fascist Italy, the campus of Washington University felt like a Garden of Eden without the snake. It occupied the grounds of the 1904 World's Fair, and instructors held classes on its lawns. In Turin, students were allowed in the library for only a few minutes at a time. In St. Louis, students put stockinged feet on the library tables, chewed gum, and slept on their books. The only jarring note involved young women who knitted socks for their boyfriends during lectures. After only an hour's talk with Hamburger, Levi-Montalcini was sure that she had come to the right place. Well over six feet, he towered over Levi-Montalcini's five feet, three inches. But Hamburger was kindly and—unlike Giuseppe Levi and her father—gentle and soft-spoken. The notion of competition was foreign to him, and he would never hurt another person's feelings. Levi-Montalcini decided that working with him would be delightful. "Conceptually, it was perhaps crucial for the discovery of the nerve growth factor that we came from entirely different scientific backgrounds," Hamburger explained. "I came from experimental and analytical embryology, of which Rita hadn't the foggiest idea.... Rita was a neurologist from medical school and knew the nervous system, of which I had only the foggiest idea. And she brought to St. Louis a most important tool, the silver staining method for staining nerves." Their styles were different too. Hamburger was analytical and historically oriented, interested in where a problem had been as well as where it was going. Hamburger was rooted in the embryology of his teacher, Hans Spemann a Germam Nobel Prize winner. "Viktor's whole career was taken in the direction of something like the nerve growth factor, but his style was taking small steps forward. He was more restrained and cautious," according to Robert Provine of the University of Maryland. "To use a baseball metaphor, Viktor was a singles hitter with a very high batting average. Rita was more willing to take the big swing, with the chance of making a home run." Despite their opposite approaches, Levi-Montalcini and Hamburger became close personal friends and colleagues.  ---------------
 So she concluded—long before she had the actual evidence—that something mysterious was coming out of the tumor to make the nerve fibers grow so extravagantly. Euphoria and excitement took over. She was desperate to speed up her experiments, to work more efficiently, to find answers faster. Working constantly, she was pushing the field to its limits, learning new disciplines and working with experts in other fields, noted her student Ruth Hogue Angeletti, now a professor at Albert Einstein College of Medicine. Soon Levi-Montalcini would even form interdisciplinary partnerships with biochemists. A medical school friend, Hertha Meyer, had become an expert in a new technique: growing tissues in vitro (literally, in a glass dish). If Levi-Montalcini could study the process in vitro, her experiments would take hours instead of weeks. So she got a grant to visit Rio de Janeiro, where Meyer had emigrated to escape the Nazis. Carrying two tumor-infected mice onto the plane in either her handbag or her pocket—all good stories vary a little in the telling—Levi-Montalcini smuggled them through customs into Brazil. There, amidst the exoticism of carnival, she struggled to make the nerve cells grow in a dish. It was "one of the most intense periods of my life, in which moments of enthusiasm and despair alternated with the regularity of a biological clock," she recalled. Despairing, she made one last try. She put a piece of tumor next to— but not touching—a bit of nerve tissue in a drop of clotted blood. Then she watched. Within hours, the tiny piece of tumor had made the nerve fibers grow out fantastically, miraculously, in a halo, like rays from the sun. The effect was so spectacular that she has never tired of repeating the experiment. The tumor was exuding something that made the nerve fibers reach out in all directions. That glorious halo remains the characteristic test for the presence of Levi- Montalcini's nerve growth factor, the NGE. Levi-Montalcini returned to St. Louis in 1953 thrilled and excited, expecting to spend a few quick months isolating and identifying the factor. Luckily, Hamburger had found a young biochemist to help her. The first person Hamburger tried to hire had turned him down flat, saying the job was too difficult. But Stanley Cohen, then a young postdoctoral fellow at Washington University, signed on. "I might as well go down in flames on some important problem as on a trivial one," Cohen told himself. Hamburger bowed out of the project, which was now a biochemical problem.
 Levi-Montalcini spent the next six years "the most intense and productive years of my life"—trying with Cohen to identify the nerve growth factor. Cohen was a clarinet-playing, pipe-smoking biochemist from Brooklyn. He shared his office with a scruffy but cheerful mongrel named Smoky. The son of am immigrant tailor and a housewife, Cohen received a college education only because Brooklyn College had a free-tuition policy and his grades were high enough to get him in. For his Ph.D. thesis, he dug five thousand earthworms from the University of Michigan campus and studied their metabolism. Cohen was modest, steady, and unassuming, but he liked watching Levi-Montalcini's fireworks. "She worked like a fiend. She had a great drive to succeed," he realized. As he told her, Rita, you and I are good, but together we're wonderful." He knew biochemistry and she knew neuroembryology, and their skills complemented each other. To get Cohen enough growth factor to analyze, Levi- Montalcini spent a year in grindingly dull work, growing mouse tumors. She became so adept that, when she turned her head to talk to a colleague, her hands continued dissecting under the microscope. Eventually, she and Cohen identified their compound in a solution of proteins and nucleic acids. But which was the active ingredient: the protein or the nucleic acid? Cohen went to see Arthur Kornberg, an enzyme biochemist who was working at Washington University at the time and who later also won a Nobel Prize. Kornberg had a suggestion. Snake venom contains enzymes that break down nucleic acids but leave protein untouched. Try snake venom, he said, referring him to a collleague, Osamu Hayaishi, who was purifying enzymes from snake venom. When Levi-Montalcini tested the snake venom on a bit of nerve tissue, she was amazed. The venom produced a stupendous halo—a much bigger halo of nerve fibers than the mouse tumor had. Compared to mouse donors, the snake venom proved to have three thousand times more growth factor. After purifying the factor from commercially available venoms, Cohen figured that mouse tumors and snake venom could not be the only two natural sources of the growth factor; mouse tumors and snake venom had too little in common. Then he made an inspired guess. The venom-producing snake gland has a mammaliam equivalent: the salivary gland. Testing various animals, he discovered that the salivary gland of a male mouse is phenomenally rich in nerve growth factor. One drop of a male mouse gland in fifty liters of solution produced a spectacular halo. Wlth a cheap and ready source of the nerve growth factor, Cohen was able to purify it. The team of Cohen and Levi-Montalcini was fabulously successful, but it broke up in 1959. Calling Levi-Montalcini into his office, Hamburger told her that Cohen had to go. As chair of the university's zoology department, Hamburger had pushed Levi- Montalcini's promotion to full professor through the university the year before. But he could no longer justify keeping a biochemist in a zoology department. Today science is interdisciplinary, and zoology departments routinely hire biochemists. But the practice was uncommon in 1959, and Hamburger said he could not pay a professor who could not teach zoology courses. Cohen moved to Vanderbilt University in Nashville and continued working on another substance, the epidermal growth factor, which he had discovered in St. Louis as part of the NGF project. EGF stimulates the growth of cells in the skin cornea, liver, and other organs. Once more, Levi-Montalcini plunged into despair. Her six years with Cohen had been her most creative period, and his departure felt like the tolling of a funeral bell. Unsettled and dissatisfied, she was unsure of what to do next. She knew that many neurologists sell did not believe in NGE Both NGF and EGF were completely novel biological phenomena and hard to incorporate into existing knowledge. For a tune, she took up a different research problem, the nervous system of cockroaches. Then she realized that she could not give up or abandon NGE.
Some colleagues * that Levi-Montalcini overdramatized the scientific community's lack of interest in NGE. After all, they note, she was elected to the prestigious National Academy of Sciences in 1968. Nevertheless, she began to promote her discovery persistently and doggedly. To illustrate the vital importance of NGF for the development of the nervous system, Levi-Montalcini developed a series of elegant proofs with the help of Cohen and graduate student Barbara Booker. When nerve growth factor was injected into newborn ro- dents, they developed an excessive number of neurons. Then, injecting antibodies to the nerve growth factor into newborn rodents, she showed that their developing nerves virtually disappear. Further research on antibodies against NGF, conducted with a young Italian biochemist, Piero Angeletti, resulted in a classic, frequently cited review article. And in 1972, Levi-Montalcini's post-doctoral fellow Ruth Hogue Angeletti and a young Washington University biochemist, Ralph Bradshaw, identified the precise sequence of NGF's amino acids. So NGF was definitely real and important. Armed with her evidence, Levi-Montalcini was unstoppable. Her carefully developed talks were famous for extending far beyond the usual fifty minutes. Deep into one talk, a renowned neuroscientist started grabbing her slides out of the projector, hoping to cut her off; Levi-Montalcini just filled in the blanks as if nothing had happened. Traveling to a French scientific conference, she found herself without a reservation for the flight she wanted; every seat was filled. A colleague inside the plane watched as the pilot was summoned back to the terminal; then, suddenly, the scientist saw two figures crossing the tarmac toward the plane. They were Levi-Montalcini and the pilot—carrying her luggage. Levi-Montalcini climbed regally into the copilot's seat, and the plane took off. Her colleague never figured out whether she had used her charm or her temper— or a combination of both—to hitch a ride. She acquired an entirely new image to sell NGE.
 Old-fashioned elegance gave way to aristocratic, womanly chic. The tramsformation made her feel good and was good salesmanship. Her bun became a dramatic swoop, and an elegant uniform satisfied her own finishing-school standards and her busy schedule. Still slim as a fashion model and straight-backed, she designed a basic high-necked, sleeveless dress with a matching jacket. She had them made in Italy in silk and brocade. And she wore them every day summer and winter with four-inch-heeled shoes, her mother's single strand of pearls, a magnificent gold bracelet, and an antique brooch. Arriving at work each morning, she put a lab coat over the silk for dissecting mice. Before teaching her large and popular lecture course, she stopped by her office to dab a bit of perfume behind each ear. At the end of a day, she was still spotless. According to a particularly persistent story, am airline lost her luggage on her way to speak at Harvard University. Refusing to appear in her wrinkled traveling outfit, she lectured in am evening gown—the only fresh dress she had with her. She enjoyed entertaining and became famous for her elegant dinner parties. Alone, she ate yogurt with plain rice and steamed vegetables. But for guests, she jetted in fresh truffles and developed a basic banquet, with fabulous variations. For appetizers, chicken liver pate with raw pistachios and Marsala wine; cheese curls; and Belgian endive leaves stuffed with caviar and sour cream. For the main dish, a beef filet en chaise with cheese puffs and vegetables. Then a salad and frozen zabaglione for dessert. Levi-Montalcini always makes an impressive show. In Italy, she has a full-time cook, and friends cannot believe that she can prepare a meal. She does not dissuade them. Cooking, she emphasizes, was only a hobby. As always, she lived intensely, with style and verve. Her St. Louis secretary served afternoon espresso on a tray to lab workers each day as they reported on their work. A paper she gave her postdoctoral fellow Robert Provine to edit was filled with flamboyant, sweeping statements. When Provine pruned out the flourishes, she complained mournfully, "You took my beautiful prose, and you turned it into boiled spinach." Her dry humor has a touch of aristocratic understatement. She was discussing a complicated point with Provine when two streakers raced by—a naked bicyclist with an equally nude girl perched on his handlebars. Levi-Montalcini turned regally to Provine and deadpanned in her rich Italian accent, "Bob, do they do this often here?" A friend calls her "La Regina"—in Italian "The Queen." She moves mountains to help people in need. She gave a technician's family a new refrigerator and arranged a job for a poor youth. She brought the daughter of a tyrannical Italian professor and her fiance to the United States so that they could marry. She was kind and supportive to the undergraduates in her lecture class. Her secretaries remained her friends for decades, remembering how she helped them with mailings, French lessons, and the like. With her peers and competitors, on the other hand, she could conjure up tempestuous visions of her father and Giuseppe Levi. "She places a great importance on intelligence, and she couldn't tolerate stupidity very well," Cohen learned. "If somebody said somethig that she thought was stupid, she'd tell him it was stupid." Levi-Montalcini speaks her mind, whether she is talking to an eminent professor or a street cleaner, a friend said. "She had a lot of fights with a lot of people, myself included," admitted Ralph Bradshaw, who became chair of the biochemistry department at the University of California at Irvine. Rita was extremely possessive of NGE. She viewed it as her private property. It became her child.... There's almost no one in NGF at one time or another who hasn't been at odds with her." Referring to Levi-Montalcini's tumultuous emotions, a colleague asked Provine how he liked the "Levi-Montalcini Roller Coaster." Provine replied, "Overall, it was a good ride. But sometimes it felt like working for Maria Callas and Marie Curie." But then he added, "Great ideas are a dime a dozen. The great scientist is one who delivers. And Rita delivered." When a student inadvertendy hurt Levi-Montalcini's feelings, she screamed at the student—at length and in front of colleagues. Then the mood passed, and it was over. "Her temper doesn't last. She doesn't hold a grudge," according to her former secretary and longtime friend, Martha Fuelmann. "Two things are very important to her: her work and her twin, almost in that order.... Her research has to go right. She's so wrapped up in her work, it's her life." "Now she accepts her position as the originator of a large field, but in the beginning, you had to wear your asbestos suit if she got your paper or grant to review," explained Ruth Hogue Angeletti. "It's a classic problem. You find something really exciting. You're the mother of the field." Levi-Montalcini was homesick for her family, too, especially her twin Paola. Securing a National Science Foundation grant in 1961, she started a small research unit in Rome. Soon she was spending six months of the year in Rome and six in St. Louis. Italian university positions are doled out by seniority not merit, and Levi-Montalcini had lost her place in line when she went to St. Louis and became a United States citizen. The Italian biochemist Piero Angeletti who alternated places with her during her traveling years, helped get funding from the Italian government for an independent research institute for Levi-Montalcini to direct. The institute became the vehicle for her return home. She and Angeletti planned to run the insti- tute together; then, at the last minute, he pulled out to accept a more lucrative position with a pharmaceutical company. Their friendship did not survive the blow. Running the institute was not easy, given Italy's bureaucracy. Her researchers sometimes worked for mondls without pay because of governmental snags. But they stayed, out of loyalty and devotion.

 By 1979, when Levi-Montalcini retired as its full-time director, the Laboratory of Cell Biology was one of the largest biological research centers in Italy. She still works there as a guest scientist. Growth factors finally came into their own during the 1980s. Nerve growth factors were the first clear example of a class of molecules that provide a regulatory link between targets in the body and the nerve cells that innervate them. Then it was discovered that many oncogenes cancer-causing genes—are mutated counterparts of growth factor genes or the genes that they affect. For cancer to develop, one or more of these growth factors or their receptors or downstream signaling molecules must go awry at a critical point during cell division. The oncogene connection transformed growth fac- tors into a hot new research field. It is clear now that the nerve growth factor keeps neuronal precursor cells from dying in their early embryonic stages. Without nerve growth factors, many of these kinds of cells would die; with NGF, they survive. NGF affects particular kinds of cells, whether they are in the central or the peripheral nervous system. It also appears to link the immune and the nervous systems of the body. Scientists have also identified many other neurotrophic growth factors for other kinds of nerve cells. As the years passed and NGF's importance became more obvious, Levi-Montalcini's rough edges softened and her roller coaster smoothed its ride. "Then aroumd 1981-82," Bradshaw recounted, "she buried the hatchet with literally everybody." In 1986, the partnership of Levi-Montalcini and Cohen shared the $290,000 Nobel Prize for Physiology or Medicine. The recognition was especially gratifying after the years of struggle and doubt. But the prize bore bittersweet fruit too. Some scientists felt that the Nobel Committee should have honored Hamburger along with Levi- Montalcini and Cohen. After almost a decade of peace with her colleagues, Levi-Montalcini had become embroiled in controversy again. "Many neuroscientists are puzzled by the omission of Vktor Hamburger from the prize," wrote Dale Purves and Joshua Sanes in Records in Neuroscierces in 1987. No one disputed that Levi-Montalcini had discovered the nerve growth factor, that she deserved the prize, and that the Nobel is given for discoveries, not a lifetime of accom- plishment. However, many agreed with Purves that Hamburger had established the research model, the paradigm, that led to the discovery of NGE "Hamburger set the stage in the 1920s, 1930s, and 1940s.... His exclusion tends to obscure a line of research that now spans more than fifty years." Alerted to the complaints, a member of the Nobel Committee  called Levi-Montalcini and asked if the group had made a mistake in omitting Hamburger. "No," she answered, "He was in Boston and I was in Rio." As the dispute lingered on, Levi-Montalcini began to feel that she had to defend the Nobel Committee for its decision to omit Hamburger. Interviewed by Omni magazine, she declared, "I've been on excellent terms with Viktor Hamburger, too. He has been an excellent chairmam of the department. He was very gentle with me— never any disaffection, despite the fact that the Nobel came to me and not to him. But I believe this is correct. Viktor is a very learned person who's always done excellent work. But he never discovered NGF. In 1988, her autobiography In Praise of Imperfection was published. The Alfred P. Sloan Foundation has funded a series of autobiographies written by famous scientists for nonscientists. As of 1992, Levi-Montalcini was the only woman in the series. When Purves reviewed the book for Science magazine, he complained that Levi-Montalcini had presented a superficial and fairy-tale view of science and how it is accomplished. Further, Purves complained, she had slighted the contributions of Viktor Hamburger and Giuseppe Levi to her career. The book does not credit Piero Angeletti, either, for his help in getting Levi-Montalcini back to Italy. Hamburger, however, was awarded the National Medal of Science in 1989, the nation's highest scientific award. He said he was hurt, not by the Nobel Prize Committee, but by his old friend's re- marks in her Omni interview and her autobiography. They have "a very ambivalent relationship, to put it mildly," he conceded. "On the surface, we get along well. I resent very much what she did to me. She never had great respect for my science." She, in turn was hurt when she visited St. Louis in October 1991 and the ninety-one-year-old Hamburger did not make time to have dinner with her. In Italy, the Nobel turned Levi-Montalcini into a national heroine. In her nineties, she still has the magnificent carriage of a model and works in her four-inch heels and her reed-slim suits. She uses her fame to promote the cause of Italian science and scientists. According to a local joke, the pope is instantly recognized—provided he appears with Rita Levi-Montalcini. When she became the first woman admitted to the Pontifical Academy of Sciences, the pope extended his hand for her to kiss his ring; Levi-Montalcini shook his hand instead. When an Italian-American politician visits Rome, she must sit on the banquet dais. If Parliament proposes a new tax plan, she must give the policy speech explaining its effect on science. Where abortion is debated, television crews call on Rita Levi- Montalcini to represent women scientists.
 Meanwhile, the importance of the nerve growth factor continues to increase. Levi-Montalcini's discovery has become an important clue to one of biology's central mysteries: how life starts as a single embryonic cell and then marvelously grows and differentiates, eventually producing a complex organism of many different cell types, each in harmonious relationship to one another. Before the nerve growth factor, little was known about how organs signal developing nerve cells to link up with them or how messenger chemicals tell nerve cells when to grow and when to stop growing. The nerve growth factor was the first of several hundred signals now known to affect cells and organs. When Levi-Montalcini discovered NGF in 1952, she could never have imagined all its potential applications to medicine. Growth factors already speed the healing of burns and diminish the side effects of chemotherapy and radiation therapy. The nerve growth factor itself is now known to belong to a family of factors called neurotrophins, which may help slow the degeneration of the nervous system in diseases like Alzheimer's and Parkinson's. Some-day the nerve growth factor may help heal peripheral nervous system damage in diabetics and prevent such damage to chemotherapy patients. Meanwhile, biotechnology companies are searching for other growth factors that may stimulate the growth of motor neurons in patients suffering from spinal-cord damage. Bone growth factors may regulate the formation of the embryo's shapeless tissue into skeleton and then heal broken bones. In 1991, researchers at Washington University used growth factors to transform limp muscle into hard, well-formed bone inside experimental rats. Above all, growth factors have helped change our views of the nervous system. Today, scientists think of the nervous system not just as an organ that monitors and controls the body, but also as an organ that is controlled by the body. The body's influence on the nervous system is considered as important today as the influence of the nerves on the body. With her eyesight declining, Levi-Montalcini concentrates her volunteer energies on degenerative diseases of the nervous system. She became president of the Italian Association for Multiple Sclerosis, because NGF exacerbates the inflammation of multiple sclerosis while the factor's antiserum helps reduce the inflammation. In Rome, Levi-Montalcini and her beloved sister Paola shared a double apartment that included Paola's art studio. When they were apart, Levi-Montalcini telephoned home several times daily. But Paola died in 2000, and mixing the life of a celebrity and a research scientist is not easy. Levi-Montalcini lives in a welter of appointments made and unmade. She has a chauffeur for her Alfa Romeo Lotus and a car telephone to communicate with the institute. She keeps two secretaries busy—one in English, the other in Italian. She promotes Italian science and women scientists wherever she goes. Her only concession to age is to hide a heavy sweater under her silk jacket. As for retiring, she declares, "The moment you stop working, you are dead.... For me, it would be unhappiness beyond anything else.... I don't work for the sake of mankind. I work for my own sake." For, as she quotes Dante, Take thought of the seed from which you spring. You were not born to live as brutes**.

* * * Zabaglione Coffee Ice Cream a la Rita Levi-Montalcini
1. Beat 10 egg yolks with 4-5 tablespoons sugar until thick and light-colored. Add slowly: 3 demitasse cups strong coffee 3 demitasse cups liqueur, such as rum, brandy, or coffee liqueur. 2. In the bottom of a double boiler or large pot, bring a small amount of water to a simmer. Pour the egg mixture into the top of the double boiler or into a metal bowl placed on top of the pot. Do not let the water boil hard. 3. Stir with a whisk until the mixture thickens. (If the mixture is too runny or if it curdles or forms lumps, put it in a food processor to "homogenize" it. If it is still too curdy, mix it with another 6 egg yolks beaten with a small amount of sugar and liqueur and reheat.
 4. Pour the mixture into a bowl. Add 4 to 5 teaspoons of coffee powder, stirring to mix and cool. 5. Add 16 ounces of cream, freshly whipped with a small amount of sugar. 6. Add 1/2 wine glass of strong liqueur: brandy, rum, coffee, or raspberry liqueur. 7. Pour the mixture into a ring mold, cover, and freeze overnight. 8. Turn the ice cream onto a plate and dust the top with a mixture of coffee and sugar. This gives the surface a translucent appearance, with stripes, if you like. Return the ice cream to the freezer.

Nobel Prize Women in Science: Their Lives, Struggles, and Momentous Discoveries, Second Edition (1993)
Joseph Henry Press
Aν και το c&p ουσιαστικά δεν επιτρέπεται, εδώ δεν έπεσε c&p ακριβώς, ήταν άπειρα τα λάθη και έπρεπε να ρίξω τρελό edit.
Considerate la vostra semenza:
fatti non foste a viver come bruti,
ma per seguir virtute e canoscenza.

Take thought of the seed from which you spring:
you were not born to live as brutes,
but to follow virtue and knowledge.
« Last Edit: 19 Jun, 2006, 04:41:35 by elena petelos »


Search Tools