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November 2009

Gertrude B. Elion (1918-1999)

Credit for this page goes to the wonderful Jewish Women's Archive

Overview

"It's amazing how much you can accomplish when you don't care who gets the credit."

Gertrude Elion's accomplishments over the course of her long career as a chemist were tremendous. Among the many drugs she developed were the first chemotherapy for childhood leukemia, the immunosuppressant that made organ transplantation possible, the first effective anti-viral medication, and treatments for lupus, hepatitis, arthritis, gout, and other diseases. With her research partner, George Hitchings, she revolutionized the way drugs were developed, and her efforts have saved or improved the lives of countless individuals.

 


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 Although Elion herself cared far more about the practical outcome of her lab's collective work than about her own reputation, her achievements earned her one of the highest honors a scientist can receive: the Nobel Prize in Medicine. She overcame enormous obstacles to reach this pinnacle. Battling longstanding prejudices against women in science, she initially had trouble even getting a job, but a combination of brilliance, determination, and stubbornness brought her to the top of her profession. She was the fifth female Nobel laureate in Medicine, the ninth in science in general, and she reached this height without earning a Ph.D.

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Elion worked tirelessly to convey the fun and excitement of science to students of all ages and to encourage children—especially girls—to pursue scientific careers. A warm, animated woman with a great love of life, she was also an avid photographer, an eager traveler, and a true opera enthusiast. Her achievements, her curiosity about the world around her, her generosity, and her concern for humanity make her not only a valuable role model for budding scientists but also an inspiration for all who wish to better the world.

"Thirst for Knowledge"

Gertrude ("Trudy") Elion was born in New York City on January 23, 1918. Her father, Robert Elion, a dentist, had immigrated to the United States from Lithuania at the age of 12. Her mother, Bertha Cohen, came to America alone at the age of 14 from the part of Russia that is now Poland; studying English at night school, she worked in the needle trades before marrying Robert at 19.

 


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From a very young age, Trudy displayed the qualities that would lead her to a Nobel Prize. Even before she started school, she wished to learn about the world around her. A voracious reader with "an insatiable thirst for knowledge," she was interested in everything around her. "It didn't matter if it was history, languages, or science," she later recalled. "I was just like a sponge."


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As a student at the all-girls Walton High School in the Bronx, Elion was not yet focused on science. Exploring history, writing, and performing, she received the school's Cooperation in Government Award and a prize in American history; belonged to the History Dramatic Club, the Electron Science Club, and the Glee Club; and published an essay and a poem in the yearbook. Propelled by her quick intelligence, she skipped two grades and graduated from high school in 1933, at the age of 15.

 

The Turning Point

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Soon after graduating from high school, Elion found a focus for her widespread intellectual curiosity. Watching her beloved grandfather die painfully of stomach cancer and deciding "nobody should suffer that much," she dedicated herself to finding a cure for cancer. "That was the turning point," she later recalled. "It was as though the signal was there: 'This is the disease you're going to have to work against.' I never really stopped to think about anything else."

That fall, Elion entered Hunter College. Unlike many people of their era, the Elions never thought twice about sending their daughter to college. Trudy attributed her parents' emphasis on education to their Jewish background. "Among immigrant Jews," she said, "their one way to success was education, and they wanted all their children to be educated.... [I]t's a Jewish tradition. The person you admired most was the person with the most education. And particularly because I was the firstborn, and I loved school, and I was good in school, it was obvious that I should go on with my education. No one ever dreamt of not going to college. That never came up." Luckily for the Elions, who had suffered financially from the stock market crash of 1929, Hunter was free to those with good enough grades to get in.


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In preparation for working on cancer, Elion majored in chemistry rather than biology because, as she said later, she wished to avoid dissecting animals. The all-female Hunter provided a supportive environment for studying science, and Elion commented later that it did not occur to her that there was anything unusual about her choice of a subject. "There were seventy-five chemistry majors in that class," she remembered. "[W]omen in chemistry and physics? There's nothing strange about that."

 

The Job Hunt

In 1937, at the age of 19, Elion graduated from Hunter College summa cum laude and Phi Beta Kappa. Wanting to pursue a career in chemistry research, she applied to fifteen graduate schools. Despite her impressive academic record, however, not one would grant her the financial aid she needed to begin work on her Ph.D.

 

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After being turned down for several laboratory jobs for which she was more than qualified, Elion began to realize the true source of her difficulties. Major obstacles lay in the path of women in science; with much of society believing that science was a man's business, hiring and admissions committees were unable to look beyond the fact that Elion was a woman to recognize her brilliance. "I hadn't been aware that any doors were closed to me until I started knocking on them," Elion later commented wryly. "Of course,...it was a very bad time to graduate. It was the Depression, and nobody was getting jobs. But I had taken that to mean that nobody was getting jobs."

Discouraged, Elion enrolled in secretarial school but lasted only six weeks, quitting to take a one-semester job as a lab assistant in a nursing school. Three months later, again out of a job, she began volunteering in a chemistry lab, enduring daily anti-Semitic jokes from the company president but gaining valuable experience. By the end of a year and a half, she was paid $20 a week, out of which she saved enough to enroll at New York University. The only woman in her graduate chemistry classes, she wrote her thesis at night and on weekends while working first as a doctor's receptionist and then as a substitute teacher of high-school chemistry and physics. In 1941, she received her Master's degree.

 

Personal Tragedy

After graduating from college, Elion met and fell in love with Leonard Canter, a handsome young statistics major at City College. After he graduated, Canter received a fellowship to study abroad, and through the letters they exchanged, he and Elion fell even more in love. After he returned, they planned to get married.

 


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In 1941, the young couple's dreams were shattered when Canter fell ill with acute bacterial endocarditis, an infection of the heart. A few years later, his illness would have been easily cured by penicillin, but at the time, little could be done. Six months later, Canter died.


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Canter's death, like her grandfather's, spurred Elion's scientific drive. "It reinforced in my mind the importance of scientific discovery, that it really was a matter of life and death to find treatments for diseases that hadn't been cured before," she said. A decade and a half later, that message was again intensified in a very personal manner when Elion's mother died of cervical cancer in 1956.

Following her fiancé's death, Elion threw herself even more into her work. None of her subsequent suitors could ever live up to Leonard, and she never married. Her brother's children and grandchildren took the place of the children she never had; indeed, she called her niece and nephews "our children," occasionally even "my children." Her great-nieces and -nephews adored her, and one even referred to her as "my goddess."

 

Burroughs Wellcome

By the time Elion earned her Master's degree, World War II was in full swing. With many male scientists now involved in the war effort, chemical laboratories were finally willing to look to women to fill jobs. Elion began working as a food chemistry analyst for the Quaker Maid Company, measuring the acidity of pickles, the color of mayonnaise, and the mold levels on fruit. After a year and a half, however, she was eager to find a research job. She found a promising position at Johnson & Johnson, only to see the lab close six months later.


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In June 1944, as Elion was weighing several job offers with which she was not quite satisfied, her father received a sample of painkiller at his dental office. Noticing that Burroughs Wellcome, the pharmaceutical company that made the drug, was located in nearby Tuckahoe, New York, he suggested Trudy inquire about a job. That Saturday, she was interviewed by Dr. George Hitchings. Elion was intrigued by Hitchings' research project; he was impressed by the young woman's intelligence and energy. Over the next decades, the Hitchings-Elion partnership proved immensely fruitful.


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For the first time, Elion had a job she truly found intellectually stimulating, and she adored it. She voluntarily brought work home every weekend, and when once she came home empty-handed, her mother assumed she was sick. Conditions were often difficult; with the lab located directly above the dryers for an infant formula, Elion had to wear thick, rubber-soled shoes to withstand the floor's 140° heat. But the staff had water fights to break the heat, and Elion was thrilled that Hitchings encouraged her and his other assistant, Elvira Falco, to pursue their research independently. As she said in 1990, "I originally set out thinking, 'I'm going to stay here as long as I continue to learn.' Here I am, 46 years later and I'm still learning."

 

Early Research


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Hitchings' and Elion's approach to their work was highly innovative. Contrary to most previous drug developers, who had depended largely on trial-and-error methods, they actively designed drugs based on knowledge of how cells worked. Although Watson and Crick had yet to discover the double-helix structure of DNA, scientists did know that cells need nucleic acids to reproduce. Hitchings theorized that by interfering with the DNA of cancer cells, bacteria, and viruses—which, because they need very large amounts of DNA to reproduce, should be particularly vulnerable to disruptions of their lifecycles - they could prevent the unwanted cells from replicating and thus stop the spread of disease. The goal was a drug that would disable the disease cells without harming normal cells.

Hitchings assigned Elion to work on the purines, two of the four bases that make up DNA. Elion created slightly altered versions of the purines, hoping to make one that would be similar enough to the real base that the disease cell would be fooled into incorporating it but different enough that it would be unable to use it to reproduce. "We used to call it a rubber donut," she said. "It looked like the real thing, but it wouldn't work."


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Even as Elion became immersed in her research, she continued to aspire to the Ph.D. she had as yet been unable to earn. Enrolling at the Brooklyn Polytechnic Institute, she commuted three nights a week from her job in Westchester County, to Brooklyn, and home to the Bronx. After two years, however, the dean demanded that she either work full-time on her doctorate or leave school. Unwilling to give up the exciting job that had been so difficult to get, Elion reluctantly gave up her dreams of a Ph.D.

 

The First Breakthroughs


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After several years of painstaking research, Elion finally developed a compound that interfered with the replication of leukemia cells. Although it was too toxic to be truly effective, it showed that she was on the right track. She continued to experiment, eventually formulating and testing over 100 purine compounds.

Finally, in 1950, Elion synthesized 6-Mercaptopurine, or 6-MP. 6-MP caused complete remissions in children with leukemia, but a relapse invariably followed. The excruciating highs and lows of watching children improve and then die drove Elion to work even harder to refine the drug. As she studied the metabolism of 6-MP over the next years, she discovered that much of it was destroyed in the body, and she was able to use that knowledge to improve the workings of the drug. When 6-MP was combined with later medications, approximately 80% of child leukemia patients would be cured; prior to 6-MP, half of all children with acute leukemia died within a few months.


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Elion was elated. "What greater joy can you have than to know what an impact your work has had on people's lives?" she asks. "We get letters from people all the time, from children who are living with leukemia. And you can't beat the feeling that you get from those children."

 

Transplants and Antivirals

As Elion modified 6-MP, other researchers discovered that the drug suppressed the immune response in rabbits. Scientists had already experimented with organ transplantation, but the body's natural rejection of foreign substances had prevented success in all but identical twins, who have the same genetic structure.


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In 1958, a young British surgeon used 6-MP to prevent temporarily the rejection of a transplanted kidney in a dog. Excited, Elion gave him several similar compounds, in the hopes that one would be even more effective. The following year, he used Elion's drug azathioprine (known as Imuran), to transplant a kidney successfully into a dog named Lollipop. In 1961, doctors used Imuran to perform the first successful kidney transplant between two unrelated humans. Thanks to Elion's work, organ transplantation has become routine today.


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In 1968, Elion returned to an area she had first studied in the 1940s: antiviral medications. Scientists had long believed that any drug able to harm the DNA of a virus would be toxic to the surrounding healthy cells, too. Indeed, one of Elion's early compounds had shown some effectiveness against viruses but was so highly toxic that Elion put it aside in favor of her work on leukemia, transplantation, and gout. But when she heard that a similar compound had shown some antiviral properties, she returned to the subject.


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After several years of work, the Burroughs Wellcome team triumphantly unveiled acyclovir (Zovirax), the first medication effective against viruses. Elion later referred to acyclovir as her "final jewel.... That such a thing was possible wasn't even imagined up until then." In 1984, the year after Elion retired, her lab developed AZT, the only drug licensed to treat AIDS in the United States until 1991. Although Elion claimed to have had little to do with AZT, her methodology had laid the groundwork for its discovery.

 

Growing Recognition

Over the years, Elion's career prospered. Despite some tensions in their relationship, George Hitchings proved not only an invaluable research partner but also a helpful mentor. Unlike many prominent scientists, he encouraged his assistants to write their own papers, and within two years, Elion began to publish the findings of her research; over the course of her career, she published over 225 papers. Hitchings also promoted her behind him up the ladder at Burroughs Wellcome. Eventually, Elion had a large department of assistants working for her.

Notwithstanding her achievements, Hitchings knew that Elion was still sensitive about her lack of official academic qualifications, and he hoped that membership in the distinguished American Society of Biological Chemists would be some compensation. With three strikes against her—she was a woman, had no doctorate, and was employed in industry rather than academia—her nomination appeared unlikely, but Hitchings pushed hard and was able to secure it in the early 1950s, after the publication of her twentieth article.


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Elion's prestige continued to grow. In 1962, she won the American Chemical Society's Garvan Medal; in 1967, when she was named Head of Experimental Therapy, she became the first woman to lead a major research group at Burroughs Wellcome. Two years later, she received a call from George Mandell of George Washington University, who said, "[T]he kind of work you're doing, you've long since passed what a doctorate would have meant. But we've got to make an honest woman of you. We'll give you a doctorate, so we can call you 'doctor' legitimately." As she grasped her honorary degree—the first of 25 honorary doctorates, including one from Brooklyn Polytechnic —her only thought was "I wish my mother were here."

 

Retirement

In 1970, needing more space and better facilities, Burroughs Wellcome moved from New York to Research Triangle Park, North Carolina. Although Elion was sad to leave the area in which she had lived her entire life, she never considered not moving with the company. She returned regularly to New York to attend her beloved Metropolitan Opera, where she retained her season subscription, but she quickly grew to love North Carolina.


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In 1983, after almost four decades at Burroughs Wellcome, Elion retired from active research. She remained "about as unretired as anyone can be," however, serving as Emerita Scientist and consultant to the company, sitting on committees and editorial boards for organizations from the World Health Organization to the National Cancer Advisory Board, lecturing across the United States and abroad, and serving as research professor at Duke University. Not wanting to stop learning, she continued to attend professional meetings.


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Elion also traveled widely; an adventurous globetrotter throughout her life, she had already seen most of the world, and she extended almost every professional trip she took with personal travel. A few years before she died, a relative joked that she had been everywhere except Antarctica. The following year, Elion signed up for a cruise to Antarctica.

The Nobel Prize

 


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At 6:30 am on October 17, 1988, Elion was getting dressed when a reporter called to congratulate her on winning the Nobel Prize. Startled, she retorted, "Quit your kidding. I don't think it's funny. Whoever put you up to it, I think it's a sick joke." When reporters continued to call, reality finally sank in: Elion, Hitchings, and Sir James W. Black of the University of London had indeed been awarded the Prize in Physiology or Medicine, "for their discoveries of important principles for drug treatment."

With the main body of their work having been done decades earlier, the prize came as a complete surprise. Elion knew that Hitchings had been nominated in the past, but she had no idea she herself had ever been nominated. In fact, when Hitchings and Elion were nominated as a pair, a Nobel Committee member asked why Elion was included, wondering if she had really contributed. Only when a professional friend of Elion's pointed out that Elion had been first author on many of the early papers, and that her antiviral discoveries had occurred after Hitchings retired, was the committee finally convinced.

 


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Elion's receipt of the Nobel Prize was particularly significant, given the hurdles she had had to overcome. Few Nobels have gone to scientists working in the drug industry or those without Ph.Ds, even fewer to women; Elion was only the fifth female Nobel laureate in Medicine, the ninth in science in general.

 


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Following the Nobel Prize, additional honors and recognitions poured in. Elion was elected to the National Academy of Science in 1990 and received the National Medal of Science, the United States' highest scientific honor, in 1991. Also in 1991, she became the first woman inducted into the National Inventors Hall of Fame and was elected to the National Women's Hall of Fame. The Nobel Prize made Elion even more in demand as a speaker and a spokeswoman, and her busy schedule quickly became even busier.

A Mentor and a Role Model

 


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Never very comfortable with scientific luminaries, Elion preferred to spend time with students. Speaking often to young people from elementary through medical school, she communicated the fun and excitement of science. "It's a wonderful life," she said. "I don't think I could have chosen anything that would have made me happier. I don't think people emphasize that enough—they think about the scientist as someone stuck away in the laboratory and oblivious to the rest of the world. That's the farthest thing from the truth. I feel as though I've made a contribution with my life." Urging her listeners not to be deterred from following their dreams, she often quoted Admiral Farragut: "Damn the torpedoes! Full speed ahead!"

 


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Elion acquired a widespread reputation as an inspiring, approachable, down-to-earth mentor to students, assistants, and colleagues. She encouraged her staff to explore their own ideas and made it a point never to take credit for her assistants' work; unlike most scientists, she did not put her name on papers simply because the research had been done in her lab. Always a team player, she cared far more about the outcome of the lab's collective work than about her own reputation.

 


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Elion never felt she needed female role models and preferred to be known simply as a "scientist" rather than as a "female scientist." She was acutely aware, however, of the difficulties she had encountered because of her sex, and she recognized that the Nobel Prize put her in a unique position to smooth the way for other women. Encouraging girls to pursue scientific careers was a cause dear to her heart; she was a leader of a Glaxo Wellcome (successor to Burroughs Wellcome) program that provided mentoring and scholarships for women studying science, and when Burroughs Wellcome gave her $250,000 to contribute to a charity of her choice, she created a scholarship at Hunter College for female graduate students in chemistry.

A True Humanitarian

 


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Elion was a true humanitarian as well as an outstanding scientist. Although she respected those who did science for science's own sake, she always kept in mind the patients whose diseases she aimed to cure and focused on the practical applications of her research. The personal tragedies she had experienced and the contact she had with patients kept the goal of curing people squarely in front of her.

Far more than she did the Nobel Prize, Elion treasured the knowledge that her work had directly benefited the lives of countless individuals. "[Y]ou can't beat the feeling that you get from those children," she said. "[W]hen the Nobel Prize came in, everybody said, 'How does it feel to get the Nobel Prize?' And I said, 'It's very nice but that's not what it's all about.' I'm not belittling the prize. The prize has done a lot for me, but if it hadn't happened, it wouldn't have made that much difference.... When you meet someone who has lived for twenty-five years with a kidney graft, there's your reward."

 


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Elion had a great love of life and a warm personality that infected everyone around her. Those who knew her unanimously emphasize—even more than her scientific achievements—how much she cared about people, from her family and friends, to those who took her drugs, to the nameless masses who might someday benefit from her research. When it was discovered that one of her drugs was an effective treatment for Leshmaniasis disease, a serious problem in South America, she pushed hard for Burroughs Wellcome to follow up on the matter, regardless of the money involved. As a former colleague remarked, "She has a real social conscience.... In fifty years, Trudy Elion will have done more cumulatively for the human condition than Mother Theresa."

 

To see our video on Dr. Elion, click here.

Jewish Women's Archive. "JWA- Gertrude Elion."