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TRAYECTORIA PROFESIONAL
La llegada de la II Guerra Mundial cambió las reglas del juego que hasta entonces había.
Muchos hombres que se dedicaban a la ciencia tuvieron que irse al frente, así que por primera
vez, las mujeres podían optar a puestos de trabajo antes inaccesibles. Elion estuvo trabajando
como química analítica en una empresa de alimentación un año y medio hasta que lo cambió
por un puesto de investigadora en la farmacéutica Johnson & Johnson.
En 1944 la joven pudo acceder a un trabajo como ayudante de George H. Hitchings en la
compañía farmacéutica Burroughs-Wellcome (actualmente GlaxoSmithKline). En su
laboratorio, la científica pasó de ser experta en química orgánica a adentrarse en los campos
de la bioquímica, la inmunología, la farmacología…
Era una época en la que aún no se conocían bien los ácidos nucleicos (la estructura de
la doble hélice se descubrió en 1953), pero Elion y Hitchings plantearon una hipótesis: si las
células de los seres vivos necesitaban sintetizar ácidos nucleicos, podían bloquear de algún
modo el crecimiento de bacterias, parásitos o células cancerosas (cuyo metabolismo es más
rápido que el de las células sanas) introduciendo piezas erróneas en el organismo. Esta teoría
conocida como la teoría de los antimetabolitosnecesitaba de complejos estudios de síntesis
química. La clave era fabricar moléculas muy similares a las bases pirimidínicas y púricas de
los ácidos nucleicos, pero que tuvieran algún error estructural que consiguiera detener su
metabolismo. Es decir, Elion y Hitchings utilizaron las diferencias bioquímicas entre células
humanas normales y patógenas (agentes causantes de enfermedades) para diseñar fármacos
que pudieran eliminar o inhibir la reproducción de patógenos particulares sin dañar las
células huéspedes. Pasaban así de la 'prueba de ensayo y error' a una estrategia mucho más
racional, directa y a la larga, eficaz para diseñar fármacos que pudieran eliminar o inhibir la
reproducción de patógenos particulares sin dañar las células huéspedes.
A los dos años de trabajar en el laboratorio de Burroughs Wellcome, Elion se vio obligada a
elegir entre el doctorado y su trabajo en la compañía farmacéutica. Por presiones del decano
del Brooklyn Polytechnic Institute, donde realizaba la tesis a tiempo parcial, la joven
científica abandonó sus estudios para dedicarse a la ingeniosa labor de sintetizar
antimetabolitos. Y paradójicamente años después se convirtió en Premio Nobel sin haber
obtenido el doctorado. Nunca llegó a obtener el título oficial de doctora, pero posteriormente
fue reconocida con tres doctorados honoris causa por la Universidad George Washington,
la Universidad de Brown y la Universidad de Michigan.
El trabajo con Hitchings dio sus primeros frutos a finales de la década de los 40. Lograron
demostrar que "la inhibición de la síntesis del ADN en las células tumorales, las bacterias y
los virus, podía conseguirse utilizando análogos de los ácidos nucleicos", cuentan Rosich y
Bosch. En 1948, Elion sintetizó por primera vez la diaminopurina. Este compuesto inhibía el
crecimiento de Lactobacillus Casei mediante su incorporación a las cadenas de ADN. Los
estudios clínicos de este compuesto mostraron resultados esperanzadores en el tratamiento de
la leucemia. Sin embargo, también se observaron efectos secundarios relacionados con
náuseas y vómitos. A pesar del revés, Hitchings y Elion no dejaron de trabajar en ello. Tres
años después, sintetizaban dos derivados que inhibían la biosíntesis purínica: la 6-tioguanina
y la 6-mercaptopurina. "Especialmente importante fue la mercaptopurina", explica Baños.
Considerado el primer anticanceroso eficaz en la lucha contra la leucemia infantil, permitió
aumentar la supervivencia de los niños de 3 a 12 meses.
Sus resultados conllevaron a la rápida aprobación del fármaco por parte de la Administración
de Alimentos y Medicamentos de EE.UU. (FDA por sus siglas en inglés). La síntesis de la
mercaptopurina marcó, sin duda, un antes y un después en la historia de la medicina:
actualmente el compuesto se usa en combinación con otros fármacos en pacientes
con leucemia linfoblástica aguda. Con ello, el pronóstico de esta enfermedad es mucho más
favorable, pues remite en torno al 80% de los casos y los niños que la superan alcanzan la
vida adulta.
El trabajo de Gertrude B. Elion, el cual desembocó en terapias curativas. Así fue como en
1950 llegaría la pirimetamina, un medicamento exitoso en el tratamiento de la malaria. La
lista de fármacos pronto comenzó a crecer con la trimetoprima o la azatioprina. En este
segundo caso, pudieron demostrar su eficacia como inmunosupresor en pacientes receptores
de trasplantes. Otros trastornos, como la gota, la artritis reumatoide o la leishmaniasis, fueron
por fin combatidos gracias a la labor de estos investigadores.
Cuando Hitchings se jubiló en 1967, Gertrude B. Elion siguió trabajando al frente del grupo
como Jefa del Departamento de Terapia Experimental de Borroughs Wellcome. Meses
después llegó el aciclovir, considerado como el primer fármaco antiviral que bloqueaba la
replicación del virus del herpes. Elion se retiró en 1983, pero no dejó de lado su pasión por la
ciencia. Continuó como investigadora emérita, ayudando en el desarrollo del primer
medicamento contra el SIDA: la zidovudina (AZT).1
También trabajó para el Instituto Nacional del Cáncer, la American Association for Cancer
Research y la Organización Mundial de la Salud.
Aunque su mayor investigación, y por la que le otorgaron el Premio Nobel en Fisiología o
Medicina 1988 junto a George Hitchings y James W. Black, es el estudio de las diferencias
bioquímicas entre células humanas normales y patógenas para diseñar fármacos que pudieran
eliminar o inhibir la reproducción de patógenos particulares sin dañar las células huéspedes.
Otros premios que recibió son la Medalla Nacional a la Ciencia (1991) y el Premio
Lemelson-MIT al logro de toda una vida (1997). En 1991 se convirtió en la primera mujer
perteneciente al National Inventors Hall of Fame.
DESCUBRIMIENTOS
RECONOCIMIENTOS
Born in New York City, the daughter of Jewish emigrants, she graduated from Hunter
College in 1937 and New York University in 1941. She died of natural causes in North
Carolina in 1999, aged 81. She remained single and never had children.
When deciding on a specialization in her studies, she was greatly influenced by the illness
suffered by her grandfather, with whom she was very close, and who died of cancer when she
was 15 years old. This fact motivated her to delve deeper into that illness and how to cure it.
Therefore, it was decided by the scientific branch: chemistry.
As reported by Laia Rosich and Felix Bosch of the Dr. Antoni Esteve Foundation, Elion
always showed interest in acquiring new knowledge. Both affirm that she was a person with
great determination and perseverance, which allowed her to face the prejudices against her
condition as a woman.
He studied Chemistry at Hunter College when he was only 15 years old, two less than he
should. Elion managed to complete the degree free of charge thanks to his good academic
record. The financial crash of 1929 had affected considerably the economic situation of the
family, who could not afford to pay for their daughter's studies at the University.
The difficulties also continued when leaving the University. As in any economic crisis, there
was not much work. In addition, women scientists had more difficult access to the workplace
at the time. "In a job interview, she was rejected for fear of distracting the attention of
workers who, of course, were all men," say Rosich and Bosch. Elion combined teaching with
a small job as a laboratory assistant to pay for postgraduate studies.
In 1939 he began a master's degree in Chemistry at the University of New York. She was the
only woman there was. I worked in the morning as a receptionist in a doctor's office and in
the afternoon as a chemistry and physics teacher. He spent the nights and weekends studying
the master's degree, which ended in 1941.
The same year that Elion finished the master's degree, the highest academic degree she got,
her fiancé died due to bacterial endocarditis. A disease that was curable only a few years later
with the arrival of penicillin. The loss of both loved ones was the trigger to try harder to find
a treatment to the diseases they suffered.
CAREER PATH
The arrival of World War II changed the rules of the game that had existed until then. Many
men who were dedicated to science had to go to the front, so for the first time, women could
opt for previously inaccessible jobs. Elion was working as analytical chemistry at a food
company for a year and a half until she changed it to a position as a researcher at Johnson &
Johnson Pharmaceuticals.
In 1944 the young woman was able to access a job as an assistant to George H. Hitchings at
the pharmaceutical company Burroughs-Wellcome (now GlaxoSmithKline). In her
laboratory, the scientist went from being an expert in organic chemistry to entering the fields
of biochemistry, immunology, pharmacology ...
It was a time when nucleic acids were not yet well known (the structure of the double helix
was discovered in 1953), but Elion and Hitchings proposed a hypothesis: if the cells of living
beings needed to synthesize nucleic acids, they could block Somehow the growth of bacteria,
parasites or cancer cells (whose metabolism is faster than that of healthy cells) by introducing
wrong parts in the body. This theory known as the antimetabolite theory needed complex
chemical synthesis studies. The key was to make molecules very similar to the pyrimidine
and purine bases of the nucleic acids, but that had some structural error that could stop their
metabolism. That is, Elion and Hitchings used the biochemical differences between normal
and pathogenic human cells (disease-causing agents) to design drugs that could eliminate or
inhibit the reproduction of particular pathogens without damaging host cells. They thus
passed from the 'trial and error test' to a much more rational strategy, direct and in the long
run, effective in designing drugs that could eliminate or inhibit the reproduction of particular
pathogens without damaging the host cells.
After two years of working in Burroughs Wellcome's laboratory, Elion was forced to choose
between a doctorate and her work in the pharmaceutical company. Under pressure from the
dean of the Brooklyn Polytechnic Institute, where she was working part-time, the young
scientist abandoned her studies to devote herself to the ingenious task of synthesizing
antimetabolites. And paradoxically years later he became a Nobel Prize winner without
having obtained a PhD. She never obtained the official title of doctor, but later she was
recognized with three honorary doctorates by George Washington University, Brown
University and the University of Michigan.
Working with Hitchings bore fruit by late 40's were able to show that "the inhibition of DNA
synthesis in tumor cells, bacteria and viruses, could be achieved using nucleic acid
analogues" include Rosich and Bosch. In 1948, Elion synthesized diaminopurine for the first
time. This compound inhibited the growth of Lactobacillus Casei by incorporating it into the
DNA strands. Clinical studies of this compound showed encouraging results in the treatment
of leukemia. However, side effects related to nausea and vomiting were also observed.
Despite the setback, Hitchings and Elion did not stop working on it. Three years later, they
synthesized two derivatives that inhibited the purine biosynthesis: 6-thioguanine and 6-
mercaptopurine. "Mercaptopurine was especially important," explains Baños. Considered the
first anticancer effective in the fight against childhood leukemia, it allowed to increase the
survival of children from 3 to 12 months.
Their results led to the rapid approval of the drug by the US Food and Drug Administration.
(FDA for its acronym in English). The synthesis of mercaptopurine marked, without doubt, a
before and after in the history of medicine: currently the compound is used in combination
with other drugs in patients with acute lymphoblastic leukemia. With this, the prognosis of
this disease is much more favorable, since it remits in around 80% of the cases and the
children that overcome it reach the adult life.
The work of Gertrude B. Elion, which led to curative therapies. Thus, in 1950,
pyrimethamine, a successful drug in the treatment of malaria, would arrive. The list of drugs
soon began to grow with trimethoprim or azathioprine. In this second case, they could
demonstrate its efficacy as an immunosuppressant in patients receiving transplants. Other
disorders, such as gout, rheumatoid arthritis or leishmaniasis, were finally combated thanks to
the work of these researchers.
When Hitchings retired in 1967, Gertrude B. Elion continued to lead the group as Head of the
Experimental Therapy Department at Borroughs Wellcome. Months later came acyclovir,
considered the first antiviral drug that blocked the replication of the herpes virus. Elion
retired in 1983, but he did not put aside his passion for science. She continued as a researcher
emeritus, helping in the development of the first medicine against AIDS: zidovudine (AZT)
.1
He also worked for the National Cancer Institute, the American Association for Cancer
Research and the World Health Organization.
Although his major research, and for which he was awarded the Nobel Prize in Physiology or
Medicine 1988 along with George Hitchings and James W. Black, is the study of the
biochemical differences between normal and pathogenic human cells to design drugs that
could eliminate or inhibit the reproduction of particular pathogens without damaging the host
cells. Other awards he received are the National Medal for Science (1991) and the Lemelson-
MIT Award for Lifetime Achievement (1997). In 1991 she became the first woman
belonging to the National Inventors Hall of Fame.
DISCOVERIES
• Trimethoprim (Septra), effective against bacterial meningitis and some types of septicemia,
and bacterial infections of the urinary and respiratory tract.
• Three honorary doctorates from George Washington University, Brown University and the
University of Michigan
• Nobel Prize in Physiology or Medicine with George Hitchings and James W. Black (1988)