Barbara McClintock – Nobel Prize Delayed

Barbara McClintock c. 1983
Barbara McClintock c. 1983

By the 1920s in the United States, many women were going to college. In fact the percentage of women attending universities would decline and not rise to the same level again until the late 1970s. Thirty to forty percent of graduate students in the 1920s were women and 12 to 15 percent of science and engineering PhDs were women, but getting a graduate degree and getting a job were two different things. Most of these women ended up teaching in women’s colleges. Coeducational universities, government, and industry jobs were reserved for men, so for a woman such as Barbara McClintock who wanted to do scientific research the going was difficult.

At the time little was known about genes and their role in heredity. Some scientists didn’t even accept the ideas of Gregor Mendel (remember smooth and wrinkled, green and yellow peas from high school.) By the time McClintock received her PhD in 1927, she had already done ground breaking work in genetics and gathered around her a group of men who wanted to work with her. Most of them already had their degrees, but recognized in her a kind of insight into the cell that others didn’t have. George Beadle once complained to the department chair at Cornell, Rollin A. Emerson, that McClintock interpreted his data more quickly than he did. Emerson responded that he (Beadle) should be glad that someone could explain it. In spite of this recognition, she was an instructor not a professor and would spend years in low paying jobs.

Barbara McClintock was born in 1902, the third daughter of Dr. Thomas Henry McClintock and Sara Handy McClintock. Thomas was a homeopathic physician and Sara had been raised in affluence until she defied her parents to marry Thomas. Barbara’s parents had wanted a boy and her mother seemed to feel that it was somehow her fault that her first three children were girls. This created a distance between her and Barbara that would last a lifetime. Her mother also may have had difficulty understanding a daughter who wasn’t interested in “girly things.” In spite of the fact that the longed for boy was born two years later, Barbara’s father raised her as a boy. She took to it well, loved athletics and nature, and had little patience with the way other girls wanted to play. There must have been early indications of her strong will. When she was four months old, her parents changed her name from Eleanor to Barbara, because Eleanor was too “sweet” a name for their baby girl.

McClintock_family_1907
From left to right: Mignon, Tom, Barbara and Marjorie McClintock (source)

Barbara never felt mistreated by her mother, but she wasn’t supported either. The tension between them and the stress of raising four young children prompted her mother to frequently send Barbara to stay with an aunt and uncle. This uncle sold fish from the back of a wagon and Barbara loved to go with him. He taught her to understand mechanical things and to love nature.

Although Sara gave in to Thomas when he indulged Barbara and told a neighbor to mind her own business when she wanted to teach her “womanly” things, she drew the line at letting her daughters pursue higher education. She had talked Barbara’s oldest sister out of accepting a full scholarship to Vassar, believing that too much education would make her less likely to find a husband. When Barbara graduated from high school, her father was serving in the army in Europe and Sara put her foot down. Unable to go to college, Barbara got a job in an employment agency and studied incessantly at the library in the evenings and on weekends. Fortunately, when Thomas returned from the war, he immediately let Barbara enroll at Cornell in the agriculture department where tuition was free.

McClintock_family
From left to right: Mignon, Tom, Barbara, Marjorie and Sara at the piano (source)

Barbara thrived at Cornell. She was thoroughly modern, bobbing her hair, smoking cigarettes, wearing pants even when she wasn’t in the field, and even playing banjo with a jazz group. She was small and slender with a big laugh and a good sense of humor. Later Barbara would be seen as something of a loner, but many things and relationships just fell by the wayside because of her intense involvement with her work. She always had a few good friends and good relationships with her family. In spite of pressure from her mother and her steady beau, she made a decision not to marry knowing that she had a dominant personality and a drive to work.

After receiving her degree in 1923, Barbara continued as a graduate. For her research Barbara worked with the maize plant and identified its 10 chromosomes and matched them with visible traits. She created a type of map locating the areas that determined whether or not a plant would have purple, waxy kernels for example. Most of her fellow students and colleagues didn’t understand the massive amounts of data, microscope work, and probability analysis she had done. Fortunately, similar work had been done on the fruit fly by Thomas Hunt Morgan at Columbia University and one of his former students, Marcus Rhoades, came to Cornell as a professor. Rhoades took on the task of explaining Barbara’s work. Both Rhoades and Morgan would be supporters of McClintock throughout her career.

After graduating at Cornell, Barbara stayed on as an instructor for a few years at a level far below her colleagues, in order to continue her research. When she was unable to find a job as a professor, Barbara moved from one research grant to another over the next few years developing a reputation as one of the best in the world in maize genetics, but never being welcomed as a professor. At Cal Tech, she was not allowed in the faculty club and only Linus Pauling welcomed her into his lab. In spite of this, Barbara loved the work and was thrilled to finally be offered a job at the University of Missouri as an assistant professor working with Lewis Stadler in 1936.

Barbara McClintock with George P. Redei in 1978 (source)
Barbara McClintock with George P. Redei in 1978 (source)

The environment at Missouri was very conventional and the culture shock went both ways. Eventually, the administration came to see Barbara as a troublemaker. In 1941, she asked the dean if she would ever be promoted to a permanent position. He told her that if Stadler ever left, she would probably be fired. It was the last straw and Barbara took a “leave of absence” and told him she wouldn’t be back. After so many years of trying to get a job commensurate with her experience and expertise, she gave up. But she still cared about her corn and her research.

In desperation, Barbara contacted Marcus Rhoades and asked where he planted his corn. He told her Cold Spring Harbor, a research center established in 1890 for evolution research. She managed to get an invitation to plant her corn for the summer, then a temporary position, then finally support through the Carnegie Foundation for a permanent position. It was perfect. She could focus solely on her research without worrying about teaching or the politics of the administration.

Although Barbara’s work had already been incorporated into textbooks and would appear in books such as Great Experiments in Biology (Gabriel and Fogel) and Classic Papers in Genetics (ed. James A. Peters), Cold Spring Harbor is where she did the work that finally earned her the Nobel Prize. In 1929, working with a graduate student, Harriet Creighton, they had proved that genes were carried on chromosomes and that the exchange of chromosomal parts created variety in the species. Barbara also had seen evidence that genes could move on a chromosome and between chromosomes, but she needed proof. After six years of research at Cold Spring Harbor, she had her proof. Genes didn’t have to have a fixed position. She also discovered an activator gene, one that could turn another gene on and off, and a gene that could cause the activator gene to move, causing another gene to turn off. Today this is called genetic transposition and the moving gene is sometimes called a “jumping” gene.

McClintock in Mexico in 1959
McClintock in Mexico in 1959

Barbara’s research was unfortunately 15 – 20 year before its time. Many in the scientific community ignored her or thought she was crazy. In the genetics community, no one thought she was crazy, but her research was hard to follow and understand. Many scientists still held to the belief that the structure of chromosomes was stable and fixed. Frustrated she finally quit publishing in 1953. She never quit collecting date and began to see evidence of transposition in other species. Barbara even took a couple of years to go to Latin America to train cytologists and to study indigenous maize varieties and the geographic distribution of specific chromosomes.

Finally in the 1960s and 70s the scientific community began to catch up with McClintock. James Shapiro and others found transposable elements in bacteria and other species. People began flocking to Barbara’s door to learn from her and the awards began to come. Then in 1983, she heard the announcement on the radio that she had been awarded the Nobel Prize in Physiology or Medicine and that the Nobel committee called her discovery “one of two great discoveries of our time in genetics.” (The other was the discovery of the structure of DNA.) The Prize was unshared and praised throughout the scientific community. The recognition was long awaited.

Barbara continued her work schedule, reading voraciously in many different areas, and continuing her exercise routine. As she approached 90 years old, she even slowed down to an 8-9 hour work day. After finally being recognized for her great contributions, Barbara McClintock died of natural causes at her home on Sept. 2, 1992.

Resources
Nobel Prize Women in Science by Sharon Bertsch McGrayne

Read about other Famous Women in Math and Science

Gertrude Belle Elion – Nobel Prize Winner in Medicine

Gertrude Belle Elion, unknown date, courtesy of the National Cancer Institute (source)
Gertrude Belle Elion, unknown date, courtesy of the National Cancer Institute (source)

“Acyclovir turned out to be different from any other compound Elion had ever seen. It is so similar to a compound needed by the herpes virus for reproduction that the virus is fooled. The virus enters normal cells and starts to make an enzyme that helps it reproduce. This enzyme activates Acyclovir and turns into something that is toxic to the virus. In short, Acyclovir makes the virus commit suicide.”

This is a quote from Sharon Bertsch McGrayne’s excellent book Nobel Prize Women in Science, which explains not only how one of the many compounds developed by Gertrude Belle Elion works, but also exemplifies her approach to research. She wanted to understand how the compounds were metabolized in the body and how they fought disease. Together with Dr. George Hitchings and a team of researchers at Burroughs Wellcome, she developed drugs that would change the lives of many people for the better, reducing suffering and extending lives.

Gertrude Belle Elion was born in New York City on January 23, 1918 to a Jewish immigrant family. Her father, Robert Elion, immigrated to the US from Lithuania when he was 12 and worked hard to graduate from New York University School of Dentistry in 1914. He was very successful, opening several dental offices, and investing in stocks and real estate. Her mother, Bertha Cohen, immigrated alone at the age of 14 to come live with older sisters who were already established. Bertha was 19 when she and Robert married, and although she never pursued higher education, she was a voracious reader who frequently read the books her children brought home from school. She came from an intellectual Russian Jewish family that valued education and knew how important it would be to her children’s futures.

When Gertrude, Trudy to the family, was six years old her brother Herbert was born. Shortly afterward, the family moved to the Bronx where they had a happy childhood. Before the move another person joined the family, her grandfather from Russia. His failing eyesight prevented him from continuing his profession as watchmaker, so after Herbert was born, he spent a great deal of time with Trudy forming a close bond. He was a Biblical scholar and spoke several languages; together they spoke Yiddish, and shared time in the park, the Bronx zoo, and music.

Trudy’s father was also a music lover, specifically the opera. He and Trudy often went to the Metropolitan Opera, a habit that Trudy would maintain for the rest of her life, flying to New York on weekends from North Carolina. Robert influenced her in another way. He was always planning imaginary trips using maps, train and bus schedules. After Trudy became successful, she began to travel, visiting many places in the world before her death in 1999.

Trudy was a successful student in high school, and when she graduated she entered Hunter College in 1933. She was a sponge for knowledge and enjoyed learning just about anything, but her decision to study science was made when she was 15 and watched her grandfather die painfully from stomach cancer. Trudy decided that no one should have to suffer as her grandfather had, so she wanted, if possible, to do something about it. Inspired as a girl by the life of Marie Curie and the book The Microbe Hunters by Paul DeKruif, she knew that she needed to study biology or chemistry, so she chose chemistry and graduated summa cum laude in 1937.

Robert Elion had lost most of his wealth in the crash of 1929, and although he still had his dental practice and loyal customers, there wasn’t much money for college. Hunter College, the women’s section of City College of New York, was free for those who could beat the fierce competition, but graduate school was a different story. Hunter was also an all-girl’s school, and Trudy had never really faced discrimination because of her gender. She placed many applications for fellowships and assistantships, but nothing came through. It was the Depression and there weren’t many jobs available, but there were none for women in fields that were dominated by men. In one eye-opening interview, she was told that she was qualified, but that they had never had a woman in the lab and they thought she would be a distraction!

Trudy’s mother had always encouraged her to have a career of some type, so she finally enrolled in secretarial school, but when she got the opportunity to teach biochemistry at the New York Hospital School of Nursing, she dropped out and took the job, even though it only lasted for 3 months. Finally, she met a chemist at a party and asked him if she could work in his lab as an assistant. He agreed, but couldn’t pay her anything to start. She was willing because it allowed her to continue learning and after a year and a half, she was making $20 a week and had saved enough living at home for one year of graduate school.

In the fall of 1939, Trudy entered New York University with money for one year’s tuition. She worked part-time as a receptionist and took education classes that allowed her to substitute teach in the public schools. In 1941, Trudy completed her Master’s Degree in Chemistry and began the task of looking for the perfect job. Her focus was always to look for jobs that would allow her to learn and get closer to her goal of working in medical research.

When WWII began, the demand for women increased in laboratories across the country. Trudy got a job in a laboratory doing quality control work for the A&P grocery chain. Always concerned with learning new things, when she felt she had learned as much as she could, she applied to an employment agency for research jobs. For about six months, she worked for a Johnson & Johnson lab until it was disbanded. Having gained the experience she needed, she then had a number of jobs to choose from, but was most intrigued by a job as an assistant to George Hitchings working for Burroughs Wellcome.

She found out about the job when her father asked her what she knew about the company after they sent some sample painkillers to his dental office. She decided to call and ask if they had a research lab and a job opening. She and Hitchings were a good match. He explained that he didn’t like the traditional trial and error method of drug research. He was also content to let her learn at her own pace and move from one area to another to satisfy her thirst for knowledge. While she had moved on from other jobs because she felt she had learned all she could, she never moved on from Burroughs Wellcome (now GlaxoSmithKline.) There was always something new to learn and she had the freedom to do it there. But more importantly, they began to make a difference in people’s lives.

Although Trudy started as Dr. Hitchings assistant, within two years she was publishing her own papers under his guidance and by the mid 1960s she had developed a reputation apart from Hitchings. This was in spite of not having a Ph.D. For two years, she worked on a Ph.D. at Brooklyn Polytechnic Institute until the dean told her that she would have to quit her job and work full time on her degree. She wasn’t willing to quit her job, so she quit school. It was an agonizing choice to make, but she knew that she had the potential to make a difference where she was, so she stayed.

Her faith in the job paid off. In 1950, Elion synthesized two cancer treatments for leukemia. Both of these drugs are still used today and when combined with other drugs result in close to an 80% cure rate. One of these drugs, referred to as 6-MP, was found to suppress the immune system in rabbits. Reading about the rabbits, a British surgeon tried 6-MP in dogs with kidney transplants and found that it extended their lives. He contacted Elion and asked if they had similar compounds that he could try which might be more effective. One of these, later marketed as Imuran, proved to be very effective in suppressing the immune system and since 1962 has been given to most of the kidney transplant patients in the US.

But what Elion called her “final jewel” was Acyclovir. Prior to its unveiling in 1978, there hadn’t been much research done on viruses. It was assumed that any compound toxic enough to kill a virus would also be extremely toxic to normal cells. Because Acyclovir was so selective to the herpes virus, it was very nontoxic to normal cells. Not only was it a break through in treating herpes, but it was a break through in virus research, opening the doors to many new possibilities including treatments for AIDS.

The intervening years had brought life changes for Trudy as well. In 1941, she had been planning to get married to a brilliant young statistician named Leonard. He fell ill with a strep infection, bacterial endocarditis, and died, just a few years before penicillin became available. Her mother also died of cervical cancer in 1956. Both of these losses served to intensify Trudy’s drive to continue in her research.

In 1970, the company moved its research facility to the Research Triangle Park in North Carolina. For a life long NYC resident this was quite a change. She adjusted well however, and it was here that she received the call in 1988 from a reporter telling her she had received the Nobel Prize together with Dr. Hitchings, and Sir James W. Black. She had already retired in 1983, but had remained in a consulting position. Winning the prize gave her a visibility that she had not had along with opportunities to contribute in many other ways.

In spite of the accolades that eventually came her way, what always meant the most to Trudy were the letters and handshakes she got from people who wanted to tell her how her discoveries had changed their lives. Although she never met anyone that could take Leonard’s place and never married, she loved her work, opera, traveling, and had loving relationships with her brother and his family. Gertrude Belle Elion lived a full and rewarding life and died in her sleep at her home in North Carolina on February 21, 1999, with a folder full of letters from people whose lives she had touched and whose lives she had helped save.

Resources
Nobel Prize Women in Science by Sharon Bertsch McGrayne
Academy of Achievement – A Museum of Living History
First Woman elected to the national inventor’s hall of fame 1991 (New York Times)

Read about other Famous Women in Math and Science

Gerty Radnitz Cori – Nobel Prize Winning Biochemist

Gerty Radnitz Cori
Gerty Radnitz Cori

In the late 19th century after universities began admitting women, there were still challenges to overcome. Most secondary schools for girls focused on social graces and being a good conversationalist but didn’t prepare them for entrance to the university. When Gerty Radnitz at 16 decided that she wanted to go to medical school, she was completely unprepared. She overcame this disadvantage to become the first woman to win a Nobel Prize in Physiology and Medicine and the first American woman to win a Nobel Prize.

Gerty Theresa Radnitz was born August 15, 1896, in Prague which was then part of the Austro-Hungarian Empire. Her family was Jewish and moderately well off. Her father, Otto Radnitz, was a chemist who invented a method for refining sugar and managed several beet sugar refineries. The oldest of three girls, Gerty was tutored at home until the age of ten when she went to finishing school. Recognizing her talent, her uncle who was a physician encouraged her to go to medical school. With the help of family and tutors, over the next two years she accumulated the equivalent of 5 – 6 years study in Latin, mathematics, physics, and chemistry in preparation to take her entrance exams. She passed and at 18 enrolled at the German branch of the Charles Ferdinand University at Prague.

During her first year of university, Gerty discovered two things that changed her life: biochemistry and Carl Cori. Carl was the son of Carl Cori, a physician, and Martha Lippich. His father went on to get a doctorate in zoology and do research at the Marine Biological Station in Trieste where he was the director. He often took the younger Carl with him on field expeditions to do research and gather specimens. Trieste, in what is now northern Italy, was a diverse area where Carl was exposed to people of different backgrounds and developed what he called “immunity to racial propaganda.” The fact that Gerty was Jewish and he was Catholic didn’t bother him at all, but it would play a role later in their lives.

For two years they studied together and enjoyed taking trips for hiking or skiing, until in 1916, Carl was drafted into the Austrian army. In 1918, assigned to a field hospital for infectious disease, he saw first hand the effect of disease on the troops, as well as the impact of the Influenza pandemic sweeping the world. The Cori family had a history of scholarship, with a number of professors on both sides of the family. This combined with his sense of helplessness in the face of disease contributed to his desire to do research. Once the war was over, Carl and Gerty were reunited and received their medical degrees in 1920. They also published their first joint paper, beginning a collaboration that would last for their entire careers.

After receiving their degrees, they traveled to Vienna where they were married, and Carl and Gerty were both able to obtain positions doing post-doctoral research. The post war years were difficult. Research was a low priority and supplies were hard to obtain. Carl was one of the few able to do research, because his father sent him a bag of frogs. Gerty worked in pediatrics doing research on thyroid and blood disorders. The conditions were poor, however. She worked only for meals which were not very nutritious, causing her to develop a vitamin A deficiency. The fact that Gerty was a woman and Jewish, even though she had converted to Catholicism when she married made finding a position very difficult. Carl became even more uneasy about the situation in Europe when he was required to prove his Aryan ancestry for a position at Graz. They began considering moving to the United States.

Photo from the Smithsonian Institution Archives via Wikimedia Commons

After working in different cities, Carl in Graz and Gerty in Vienna, any position would only be acceptable to Carl if he could obtain a position for Gerty as well. Carl and Gerty Cori were ideally suited as research partners. William Daughaday of Washington University School of Medicine said “Carl was the visionary. Gerty was the lab genius.” In personality, they were the reverse of Irene and Frederic Joliot-Curie. Carl was somewhat shy, relaxed, and a slower more contemplative thinker. Gerty was outgoing, vivacious, and a brilliant quick thinker. She was also more ambitious than Carl and more demanding in the lab.

Finally, in 1922, Carl obtained a position at the Institute for the Study of Malignant Disease (later renamed the Roswell Park Memorial Institute), in Buffalo, New York. Gerty was given a position as an assistant pathologist. Although they worked in different labs, they continued the practice of publishing papers together, even though Gerty was told more than once to stay out of Carl’s lab. Eventually, the benefit of allowing them to work together was acknowledged and the breach in protocol was overlooked. During their time in Buffalo from 1922 to 1931, Carl and Gerty established their reputations and became US citizens.

Gerty and Carl were primarily interested in studying insulin and the production of energy in the body. If you remember your high school biology, the Cori cycle explains how the body breaks down glycogen into glucose for use in muscles and converts lactic acid back into glycogen for storage in the liver. The discovery and explanation of this process in 1929 would be the basis for their Nobel Prize in 1947. This research, however, wasn’t a good fit for the work being done at the Institute, which was primarily focused on cancer research, so together the Cori’s began looking for other positions.

In spite of the fact that Gerty had published frequently, individually in addition to jointly with Carl, he began to receive job offers, not Gerty. Most of these offers, including those from Cornell and the University of Toronto, did not include a possibility for positions for her. At the University of Rochester, Carl was offered a position under the condition that he stop collaborating with his wife. Gerty was even taken aside and told that she was hindering his career because it was “un-American” for a husband and wife to work together. In fact it was very common for women to work in conjunction with their husbands during this time, although it was usually as low or unpaid “assistants” meaning that the wife rarely received recognition for her contribution. This was unacceptable to both Carl and Gerty.

Finally in 1931, they received job offers from the Washington University medical school in St. Louis. Even though Carl became the chairman of the pharmacology department, Gerty was only offered a position as a research associate at one-fifth the pay. Still they were able to collaborate and would remain at Washington University for the remainder of their careers doing groundbreaking research in glycogen utilization and with enzymes. During World War II, the demand for women scientists increased due to the reduced work force and Gerty finally became a full professor.

From left to right Dr. Carl F. Cori, Dr. Joseph Erlanger, Dr. Gerty T. Cori, and Chancellor Arthur H. Compton. Photo taken in 1947.
Copyright © Becker Medical Library, Washington University School of Medicine

Gerty and Carl were supportive of other scientists as well, hiring women and Jews when other universities and even other departments at Washington refused to do so. Eventually, the work done in their lab resulted in eight Nobel Prizes, including a joint prize for Carl and Gerty in Physiology and Medicine. Over time, Carl became more involved in writing, directing research of students, and administration, and running the lab became exclusively Gerty’s domain. As with many passionate people, she was not always liked or easy to work for. She demanded precision. The work and the results demanded it.

Both of the Coris impressed others with their depth of knowledge about a wide range of topics. For most of her time at Washington, Gerty had 5 – 7 books delivered weekly to her from a local lending library. Every Friday she would prepare her list for the next week. She loved history and biography, while Carl was a poet and read archeology and art. She was the one who constantly read journal articles and kept people in the lab up-to-date on new findings in biology and related fields.

The Coris worked hard, but also tried to leave work at the lab. They entertained, kept a garden, and continued enjoying the outdoors. It was on a mountain climbing trip in 1947 that Gerty first fell ill and they discovered she had a disease that would eventually take her life. Her bone marrow was no longer producing red blood cells. She worked almost to the end. Her only concessions to the disease were taking time out for the blood transfusions that were necessary, and setting up a cot in her office where she would lie down to do her reading. Gerty Cori died at her home on October 26, 1957.

Resources
Nobel Prize Women in Science by Sharon Bertsch McGrayne
American Chemical Society National Historic Chemical Landmark

Read about other Famous Women in Math and Science