A Matter of Life & Death — Gertrude Elion and Her Remarkable Life In Science
You might expect to know the name of a Nobel Prize winner whose work directly resulted in effective treatment for leukaemia, AIDS and Covid, who was prominent in the World Health Organisation and who 70 years ago co-pioneered an approach to drug research and design that remains the basis of such work even today. However, how many of us recognise Gertrude Elion?
Elion’s achievements are all the more remarkable when considered alongside the many obstacles she faced. Born in the US in 1918 to Jewish immigrant parents (her mother had arrived from Russian ruled Poland at the age of 14 and her father from Lithuania aged 12), Gertrude’s exceptional intelligence was recognised early on when she jumped two years ahead of her class at the age of 12. Things were going well at home too, her father having qualified as a dentist enabling the family (now including Gertrude’s brother) to move to a bigger place in the Bronx. This progress however ended abruptly when the 1929 Stock Market crash wiped out the Elions.
Her parents had a drive for their children’s education that Elion attributed to a view “among Jewish immigrants” that it was the one way to success. The Stock Market crash would have put an end to such dreams were it not for the fact that Hunter College provided Gertrude with a free place. Her work there culminated in her emerging aged 19 with a bachelor’s degree (with the highest distinction) in chemistry. The chances of landing a career in her chosen area were slim though so she earned a living from teaching and secretarial work.
This was also not the only call on her time. The day jobs funded her evening and weekend studies for a master’s degree in chemistry from New York University which she successfully completed in 1941 (the only woman in her class.) If she’d hoped that this would be a step into a chemistry career she was disappointed but not deterred, talking unpaid (and uninspiring — she described it as repetitive) lab work simply to be closer to the research that she so passionately wanted to pursue. It did little to advance her prospects in a sector that saw the presence of women in the lab as a ‘distracting influence.’
That was about to change — forced by expediency rather than enlightenment. The war meant that there were fewer men available and so the path for women became slightly more open. Even then, the most important development in her career came about via a slightly tangential route. Her father bought dentistry drugs from Burroughs Welcome in Tuckahoe New York and he suggested his daughter visit them to enquire about work. It paid off. In 1944, she was recruited as an assistant to 38 year old Dr George Hitchings and there began a 40 year collaboration that has been described as “one of the greatest drug discovery partnerships in the history of medicine.”
Hitchings had joined Burroughs Wellcome two years earlier and his focus was on the differences in metabolism between normal and tumour cells. His idea was that, by preventing organic compounds called purines from DNA synthesis, the growth of poisonous organisms including cancer cells could be blocked.
The work was ground-breaking but tough — the structure of DNA was unknown at the time and so, to a degree, they were working in the dark. It was also far from glamourous. The lab was above a manufacturing unit making infant formula in dryers which meant that the lab floor could reach 140 degrees and staff had to wear protective footwear. Her working day also didn’t stop when others’ did — she regularly took work home for evenings and weekends. She was driven. She had found her place.
Within 6 years, Hitchings and Elion had developed drugs to disrupt the formation of leukaemia cells. Their positive impact was temporary however and their toxicity caused vomiting side effects. Elion’s next iteration — developed by testing over 100 purines — led to a treatment which, even today, treats 80% of children with leukaemia. It was a stunning achievement but it was only the start.
Hitchings encouraged Elion and his other assistant Elvira Falco, to pursue their ideas through increasing autonomy which resulted in Elion leading progressively bigger teams.
Hitchings was rather more than a mentor. Elion was acutely aware of the academic requirements necessary for her chosen career and had therefore enrolled part time to study for a Ph D however she was told that this could only continue if she studied full time. She was at a crossroads. It was Hitchings’ promise that the lack of a qualification would not hinder her that persuaded her to pit aside her studies in favour of working full time at Burroughs Wellcome. She chose an unconventional path but she was proven unequivocally right.
Hitchings’ and Elion’s discoveries in the 1950s impacted the treatment of gout and malaria as well as enabling organ transplants for people with compromised immune systems that would otherwise have rejected them — a path towards the often routine nature of transplants today. Their work in the 1960s on bacterial and viral DNA resulted in treatments for urinary and respiratory bacterial infections, meningitis and septicaemia.
Elion’s achievements were supported by Hitchings’ atypical approach to scientific recognition. He was not interested in keeping the research papers and associated academic acknowledgement for himself and so encouraged Elion to publish her own findings — which she did no less than 225 times. As Hitchings rose in the organisation, so too did Elion, developing her own teams of assistants along the way. She was well and truly out of her mentor’s shadow.
The results of the pair’s work were ground-breaking. So too was the method which would change the shape of drug discovery. Its basis was very different to the traditional trial and error approach in which a scientific finding then went in search of a use in treatment (think Penicillin.) In contrast, their starting point had a hypothesis, a target — that the introduction of defective copies of genetic building blocks could potentially disrupt specific cells’ ability to grow thereby destroying bad cells and leaving good cells untouched. This would become known as Rational Drug Design. It was a quiet revolution at the time and is standard now.
When Hitchings retired in 1967, Elion was promoted to Head of the Department of Experimental Therapy — the first woman to lead a major research group at Burroughs Wellcome (GSK today.) She relished the chance to “show what I can do on my own” by further developing the principles and achievements from the previous 23 years. Within a year she and her team had started work on what she would later call her “final jewel.” Unveiled in 1978, the drug Acyclovir inhibited herpes and fought chickenpox and shingles without side effects. Its success disproved the long held view that viral diseases simply couldn’t be treated. Effective antivirals had arrived; their ability to slow down and block infections continues to this day as a critical second line of defence where vaccines have not prevented infection.
Virologist Marty St Clair who worked for Elion from 1976 was part of a team that then took many of the procedures used to develop Acylovir and applied them to AIDS research, leading in 1987 to AZT becoming the first drug to be approved for AIDS treatment.
By then Elion had been retired for four years but still went into the lab every day (she described herself as being “about as unretired as anyone can be”) as Scientist Emeritus and Consultant. She certainly deserved a rest but she didn’t want one. As Research Professor at Duke University, she mentored medical students who recognised her as both inspirational and approachable. Her choice of company too was always students over dignitaries although, as advisor to the World Health Organisation, there were plenty of those seeking her opinion.
Her achievements were deservedly recognised. In 1988, Elion, Hitchings and James Whyte-Black (the Scottish professor responsible for critical discoveries leading to treatments for angina and duodenal and stomach ulcers) were awarded the Nobel Prize for Physiology and Medicine for discovering ‘important principles of drug treatment.’ That the award came some three decades after the work appears somewhat baffling from this distance but the Nobel committee generally didn’t award pharmaceutical company employees which may account for it. Elion’s gender, her lack of a PhD and the fact that some of the key work took place around the depression all make a very strong case for the award to have been made much earlier. By 1991 however, the recognition was underlined when Elion became the first woman to be inducted into the National Inventors Hall of Fame and was awarded the National Medal of Science.
This recognition was a long time ago and, being academically focused, maybe it was never sufficiently mainstream to have made Elion’s name as publicly recognised as it deserves to be. Not that it mattered to her. What did matter was the impact of her work — how what happened in the lab made its way into people’s lives. “What we were aiming at” she said, “was getting people well and the satisfaction of that is much greater than any prize.”
This focus can be explained by one overriding factor in Elion’s momentous career. Behind her academic brilliance and indefatigable drive was the loss of two people very dear to her. In 1933 — just four years after the family had been wiped out by the Great Depression — Elion’s much loved Grandfather died of stomach cancer. Nine years later, with her life on the verge of big changes, her fiancé Leonard Canter died of a heart infection. The shattering losses and the brutality of both diseases awakened in Elion a fierce advocacy of scientific discovery — “it really was”, she said at the time, “a matter of life and death” — alongside a fierce determination to play her part. At this stage she was just starting out on her career but by 1956 when her mother died from cervical cancer, that single minded resolution would only be intensified.
Measured against these events, academic acknowledgement and awards would seem rather trite. There was however one element of recognition that had a particular satisfaction for Elion — and the beneficiary wasn’t so much her as others impacted by her. At a time when twentieth century women in science faced absurd obstacles, Elion became a trailblazer. Like many inspirational people, she was not deterred by the realisation of the difficulties she would face (“I hadn’t been aware that any doors were closed to me until I started knocking on them” she said); instead, she negotiated them with drive and a focussed single mindedness (“in my day I was told that women didn’t go into chemistry” she said “but I saw no reason why we couldn’t.”) Exceptional people prevail when the rest of us likely walk away.
Her success would mean the removal of some of those obstacles for those that followed. Sometimes this was in very direct ways such as the scholarship — funded by Burroughs Welcome — at her old college, Hunter, for female graduate chemistry students and her continued mentoring and encouragement. Sometimes it was in broader cultural changes as her example shone through.
The commitment following her Grandfather’s death to dedicate herself to scientific research, didn’t waver — “I never really stopped to think about anything else” she said of that moment. She didn’t marry and, although she had a range of passions including photography, opera, travel and ballet, they existed alongside (or more likely behind) work. When she died aged 81 in 1999, that drive and commitment left a huge mark.
That was however far from the end of her impact. Elion’s role in the development of anitivirals was underlined in the starkest possible global terms when in April 2020 trials of the drug remdesivir delivered early positive results in hastening the recovery of Covid patients. It was a stark reminder of the extraordinary long term impact of a woman who, almost 90 years ago, decided to make a difference.
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