Gertrude Elion, DNA Hacker

Some people become scientists because they have an insatiable sense of curiosity. For others, the interest is born of tragedy—they lose a loved one to disease and are driven to find a cure. In the case of Gertrude Elion, both are true. Gertrude was a brilliant and curious student who could have done anything given her aptitude. But when she lost her grandfather to cancer, her path became clear.

As a biochemist and pharmacologist for what is now GlaxoSmithKline, Gertrude and Dr. George Hitchings created many different types of drugs by synthesizing natural nucleic compounds in order to bait pathogens and kill them. Their unorthodox, designer drug method led them to create the first successful anti-cancer drugs and won them a Nobel Prize in 1988.

Gertrude in high school. Image via JWA

Inspiration and Perspiration

Gertrude Belle Elion was born on January 23, 1918 in New York City to hard-working immigrant parents. Her father was a dentist and he ran his practice out of a large apartment that doubled as the family’s living quarters. He did well and invested much of his earnings in the stock market, but lost it all in the crash of 1929.

In spite of this, Gertrude and her younger brother had a happy childhood. She had an insatiable desire to learn and found every subject equally interesting. When she graduated high school at age fifteen after skipping two grades, she couldn’t decide what to specialize in. Unfortunately, the answer came as she watched her beloved grandfather succumb to stomach cancer over the course of several agonizing months. From then on, she was determined to develop a cure for cancer.

Gertrude graduated in 1937 with a chemistry degree from Hunter College, a tuition-free women’s university. If not for Hunter, she may have never had the chance at higher education. There was no money for her to go to graduate school, so she applied for fellowships. But none in the field took her seriously in spite of her spotless GPA. All fifteen of the applications she sent out were rejected.

For the next few years, she worked odd jobs and volunteered at a chemistry lab just to get her foot in the door. After a couple of months, the chemist she was assisting started paying her. Soon, she was able to save enough tuition to apply to the master’s program at NYU, and put herself through graduate school with teaching jobs. At NYU she met the love of her life, Leonard Canter, and the two became engaged. Leonard spent a semester studying abroad and developed a bacterial infection in his heart valves. He died shortly after returning home. Gertrude was left heartbroken and all the more driven to fight disease. She never did marry.

In the lab with George Hitchings and Sir James Black. Image via JWA

From Food Scientist to DNA Hacker

By the time Gertrude finished her master’s degree in 1941, World War II was in motion. The resulting labor shortage in industrial laboratories gave her the opportunity to prove her scientific abilities. She got a job as a food chemist doing mundane things like checking the acidity of pickles and making sure the mayonnaise was the right color. It wasn’t cancer research, but it was a start.

After a while she wasn’t learning anything and became restless. She tried using an agency to find lab positions and was eventually offered a research job at Burroughs Wellcome in Tuckahoe, New York.

She was hired as an assistant to a medical doctor named George Hitchings. Hitchings had studied purines during his time at Harvard and was intent on unlocking their mysteries. Purines are a class of organic compounds that includes adenine and guanine, two of the building blocks of DNA and RNA. Gertrude studied purine compounds of all kinds to look for differences in the metabolization process between healthy cells and pathogens like cancer cells, viruses, and bacteria.

Until this point, pharmacology was largely a process of trial and error. Hitchings wanted to use purines to develop drugs that would selectively block the growth of disease microbes without interrupting healthy cell growth. He based this idea on the recent development of sulfa drugs. Sulfates had been shown to interfere with microbial metabolism, so Hitchings reasoned that other drugs could do it, too.

They soon discovered that bacteria relied on certain purines in order to metabolize and flourish. Within a few years, they had synthesized two anti-metabolites that were structurally the same as adenine and guanine. By doing this, they essentially created decoy purines that attract pathogens but don’t support their growth. Since they can’t metabolize, the diseased cells die off.

Gertrude and Hitchings show off their favorite molecules. Image via JWA

Towards a Cure for Leukemia

Soon, Gertrude created a new molecule by substituting one of the oxygen atoms of a purine with a sulfur atom. The resulting drug, 6-mercaptopurine (6-MP), held a lot of promise in the fight against childhood leukemia. It flew through the hoops of FDA acceptance and was approved a mere ten months after the clinical trials began.

Unfortunately, 6-MP wasn’t quite the wonder drug they had anticipated. Half of the children with leukemia who took it went into remission, but later relapsed and died. Gertrude spent the next six years focused on the drug and eventually found that 6-MP did in fact cure acute lymphoblastic leukemia when taken with other anti-cancer drugs.

Gertrude and Hitchings went on to create many more drugs both together and separately using the synthetic purine method. They developed drugs to combat gout, rheumatoid arthritis, herpes, malaria, and bacterial infections. One derivative of 6-MP was found to suppress the immune system. This led to the development of azathioprine, an immunosuppressant that makes the body less likely to reject donor organs after transplant surgery.

Gertrude was made head of the Department of Experimental Therapy in 1967 and kept that post until she retired in 1983. When Glaxo Wellcome moved to Research Triangle Park in 1970, Gertrude went with them and remained there until her death in 1999. After retiring, she continued to work as a consultant to her old colleagues and helped them develop AZT, the first successful drug used against HIV. She and Hitchings received the 1988 Nobel Prize for Physiology or Medicine along with Scottish pharmacologist Sir James Black.

Gertrude examines a molecular model. Image via JWA

A Selfless Scientist

In spite of all the obstacles she faced, Gertrude never got discouraged. She found her work immensely rewarding and to her, winning the Nobel Prize was just icing on the cake. The real happiness was in the work itself—saving lives and healing others.

Gertrude received numerous awards including a National Medal of Science and 23 honorary degrees. She sat on dozens of boards and served several committees, tirelessly giving of herself to science and its students until the end.

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