Elion, Gertrude Belle WORLD OF MICROBIOLOGY AND IMMUNOLOGY184•
able that women were invited into the lab,” Elion told the
Washington Post.
For Elion, the war created an opening in the research lab
of biochemist George Herbert Hitchings at Wellcome
Research Laboratories in Tuckahoe, New York, a subsidiary of
Burroughs Wellcome Company, a British firm. When they
met, Elion was 26 years old and Hitchings was 39. Their
working relationship began on June 14, 1944, and lasted for
the rest of their careers. Each time Hitchings was promoted,
Elion filled the spot he had just vacated, until she became head
of the Department of Experimental Therapy in 1967, where
she was to remain until her retirement 16 years later. Hitchings
became vice president for research. During that period, they
wrote many scientific papers together.
Settled in her job and encouraged by the breakthroughs
occurring in the field of biochemistry, Elion took steps to earn
a Ph.D., the degree that all serious scientists are expected to
attain as evidence that they are capable of doing independent
research. Only one school offered night classes in chemistry,
the Brooklyn Polytechnic Institute (now Polytechnic
University), and that is where Elion enrolled. Attending
classes meant taking the train from Tuckahoe into Grand
Central Station and transferring to the subway to Brooklyn.
Although the hour-and-a-half commute each way was
exhausting, Elion persevered for two years, until the school
accused her of not being a serious student and pressed her to
attend full-time. Forced to choose between school and her job,
Elion had no choice but to continue working. Her relinquish-
ment of the Ph.D. haunted her, until her lab developed its first
successful drug, 6-mercaptopurine (6MP).
In the 1940s, Elion and Hitchings employed a novel
approach in fighting the agents of disease. By studying the
biochemistry of cancer cells, and of harmful bacteriaand
viruses, they hoped to understand the differences between the
metabolism of those cells and normal cells. In particular, they
wondered whether there were differences in how the disease-
causing cells used nucleic acids, the chemicals involved in the
replication of DNA, to stay alive and to grow. Any dissimilar-
ity discovered might serve as a target point for a drug that
could destroy the abnormal cells without harming healthy,
normal cells. By disrupting one crucial link in a cell’s bio-
chemistry, the cell itself would be damaged. In this manner,
cancers and harmful bacteria might be eradicated.
Elion’s work focused on purines, one of two main cate-
gories of nucleic acids. Their strategy, for which Elion and
Hitchings would be honored by the Nobel Prize forty years
later, steered a radical middle course between chemists who
randomly screened compounds to find effective drugs and sci-
entists who engaged in basic cellular research without a
thought of drug therapy. The difficulties of such an approach
were immense. Very little was known about nucleic acid
biosynthesis. Discovery of the double helical structure of
DNA still lay ahead, and many of the instruments and meth-
ods that make molecular biologypossible had not yet been
invented. But Elion and her colleagues persisted with the tools
at hand and their own ingenuity. By observing the microbio-
logical results of various experiments, they could make
knowledgeable deductions about the biochemistry involved.To the same ends, they worked with various species of lab ani-
mals and examined varying responses. Still, the lack of
advanced instrumentation and computerization made for slow
and tedious work. Elion told Scientific American,“if we were
starting now, we would probably do what we did in ten years.”
By 1951, as a senior research chemist, Elion discovered
the first effective compound against childhood leukemia. The
compound, 6-mercaptopurine (6MP; trade name Purinethol),
interfered with the synthesis of leukemia cells. In clinical trials
run by the Sloan-Kettering Institute (now the Memorial Sloan-
Kettering Cancer Center), it increased life expectancy from a
few months to a year. The compound was approved by the
Food and Drug Administration (FDA) in 1953. Eventually
6MP, used in combination with other drugs and radiation treat-
ment, made leukemia one of the most curable of cancers.
In the following two decades, the potency of 6MP
prompted Elion and other scientists to look for more uses for
the drug. Robert Schwartz, at Tufts Medical School in Boston,
and Roy Calne, at Harvard Medical School, successfully used
6MP to suppress the immune systems in dogs with trans-
planted kidneys. Motivated by Schwartz and Calne’s work,
Elion and Hitchings began searching for other immunosup-
pressants. They carefully studied the drug’s course of action in
the body, an endeavor known as pharmacokinetics. This addi-
tional work with 6MP led to the discovery of the derivative
azathioprine (Imuran), which prevents rejection of trans-
planted human organs and treats rheumatoid arthritis. Other
experiments in Elion’s lab intended to improve 6MP’s effec-
tiveness led to the discovery of allopurinol (Zyloprim) for
gout, a disease in which excess uric acid builds up in the
joints. Allopurinol was approved by the FDA in 1966. In the
1950s, Elion and Hitchings’s lab also discovered
pyrimethamine (Daraprim and Fansidar) a treatment for
malaria, and trimethoprim, for urinary and respiratory tract
infections. Trimethoprim is also used to treat Pneumocystis
carinii pneumonia, the leading killer of people with AIDS.
In 1968, Elion heard that a compound called adenine
arabinoside appeared to have an effect against DNA viruses.
This compound was similar in structure to a chemical in her
lab, 2,6-diaminopurine. Although her own lab was not
equipped to screen antiviral compounds, she immediately
began synthesizing new compounds to send to a Wellcome
Research lab in Britain for testing. In 1969, she received
notice by telegram that one of the compounds was effective
against herpes simplex viruses. Further derivatives of that
compound yielded acyclovir (Zovirax), an effective drug
against herpes, shingles, and chickenpox. An exhibit of the
success of acyclovir, presented in 1978 at the Interscience
Conference on Microbial Agents and Chemotherapy, demon-
strated to other scientists that it was possible to find drugs that
exploited the differences between viral and cellular enzymes.
Acyclovir (Zovirax), approved by the FDA in 1982, became
one of Burroughs Wellcome’s most profitable drugs. In 1984,
at Wellcome Research Laboratories, researchers trained by
Elion and Hitchings developed azidothymidine (AZT), the
first drug used to treat AIDS.
Although Elion retired in 1983, she continued at
Wellcome Research Laboratories as scientist emeritus andwomi_E 5/6/03 2:12 PM Page 184