- Gertrude Elion developed the drug acyclovir, a potent inhibitor of herpes viruses with remarkably low toxicity, which her team unveiled in 1978.
- Elion and Hitchings invented new medicines for a long list of serious conditions: leukemia, malaria, gout, rheumatoid arthritis, organ rejection, and more.
- Their first drug, 6-mercaptopurine made possible one of the great success stories in cancer treatment.
- The acyclovir compound made it possible to develop highly specific drugs that targeted viruses without causing unwanted side effects.
- Elion continued to inspire other researchers and it’s because of her we got the first HIV antiviral drug AZT, or azidothymidine.
- Scientists also believe that remdesivir can do the same, opening doors to more effective drugs for COVID-19.
With the pandemic bringing us closer to antivirals like Remedisivir, we are reminded of the Nobel Prize winner scientist, Gertrude Elion, who discovered it first, says an article published in National Geographic.
An Important Proof Of Concept
When news broke in April that the drug remdesivir had been shown to speed recovery in patients hospitalized with COVID-19, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, hailed the finding as “an important proof of concept” in the race to bring the pandemic to heel.
For now, results related to remdesivir are mixed, although some studies continue to suggest the drug can improve outcomes for patients with severe forms of COVID-19.
Now, antivirals are used to treat herpes, hepatitis, HIV, Ebola, and more. And arguably, none would exist today were it not for Gertrude “Trudy” Elion.
Early Life
Born in 1918 in Manhattan, Elion overcame early financial hardship and outright sexism to win the 1988 Nobel Prize in Physiology or Medicine, becoming only the fifth woman to do so.
She shared the award with her longtime collaborator George Hitchings, who hired her in 1944 to join his biochemistry lab at the pharmaceutical company Burroughs Wellcome (now part of GlaxoSmithKline).
Rational Approach
Elion was just 19 years old when she graduated summa cum laude from Hunter College in 1937 with a bachelor’s degree in chemistry. Her parents, immigrants from Eastern Europe, were bankrupted by the Great Depression.
They couldn’t pay for their daughter’s graduate education, and none of the programs to which she’d applied would offer her financial aid.
Worse, it seemed no matter how well she’d done in school, research laboratories wouldn’t hire a woman. As she recalled years later, on more than one occasion she was told that, though she was qualified for the position, she would be “a distracting influence” on the laboratory staff.
Nevertheless, Elion worked as a food analyst for a grocery chain, answered phones at a doctor’s office, and taught chemistry in New York City high schools while pursuing her master’s degree at New York University on nights and weekends.
Finally, thanks to labor shortages created by World War II, real opportunities started coming her way, first with Johnson & Johnson and then with Burroughs Wellcome.
Up until the 1970s, most new drugs were found by trial-and-error or stumbled upon serendipitously.
New Proposal
Hitchings proposed another way forward—a rational, scientific approach to drug discovery based on knowledge of a biological target.
He hypothesized that scientists could inhibit pathogen cells from replicating by making defective copies of their genetic building blocks.
Once these copies were integrated into the germ’s metabolic pathways, they would jam up the cellular machinery, interfering with the reactions necessary for DNA synthesis.
Shortly after hiring Elion, Hitchings assigned her to work on purines. Elion didn’t know what they were, but after months of poring over the literature, she began making compounds
“that had never been described before” and “felt the excitement of the inventor who creates a ‘new composition of matter.”
Successful Partnership
Together, Elion and Hitchings pioneered the use of rational drug design, and they were phenomenally successful.
Over a 20-year period, the pair invented new medicines for a long list of serious conditions: leukemia, malaria, gout, rheumatoid arthritis, organ rejection, bacterial infection, and more.
Their first drug, 6-mercaptopurine (6-MP), came about in 1951 through a collaboration with researchers at Memorial Sloan-Kettering Cancer Center in New York.
The 6-MP made possible one of the great success stories in cancer treatment, helping to increase the cure rate of all children from 10 percent in the 1950s to more than 80 percent today.
Several years later, Elion and Hitchings developed the anti-malarial agent pyrimethamine, which is now used primarily to treat a potentially fatal foodborne illness called toxoplasmosis.
Picking Up Where She Left Off
Back in 1948, she had noticed that a compound she’d synthesized for the treatment of cancer—2,6-diaminopurine—had shown impressive antiviral activity.
She was intrigued but became discouraged by the drug’s toxicity, and ultimately shelved it to focus on other work.
In 1968, shortly after Hitchings had left the lab to become vice president of research, Elion came across a report that something similar to 2,6-diaminopurine had recently shown antiviral activity.
The news “rang a bell,” she later said, prompting her and her team of “diligent and devoted scientists” to pick up where she’d left off two decades prior.
The ‘Acyclovir’ Compound
Over the next four years, they secretly studied a remarkable new compound they called acyclovir.
Presented in 1978 at a conference in Atlanta, Georgia, acyclovir was unlike anything the world had ever seen.
“Acyclovir was the drug that changed everything in the effort to develop effective antivirals,”
says Keith Jerome, director of the molecular virology laboratory at the University of Washington medical school.
“It proved it was possible to develop highly specific drugs that targeted viruses without causing unwanted side effects.”
The Final Jewel
Elion called acyclovir her “final jewel,” and indeed, it was the last drug she would develop during her official tenure at Burroughs Wellcome.
She retired in 1983, but those working in her lab almost didn’t realize. “She still came in every day,” recalls St. Clair, who was instrumental in discerning acyclovir’s mechanism of action.
In 1991, Elion was awarded the prestigious National Medal of Science by then-President George Bush, who said she exemplified how one person’s work can help “banish suffering and prolong life for many millions of people.” Elion died in 1999 at age 81.
Inspiration For The First HIV Drug
St. Clair said she and colleagues ended up with AZT, or azidothymidine, the first drug approved for the treatment of HIV.
“That wouldn’t have happened without Trudy,” St. Clair says.
Though only moderately effective, AZT paved the way for later generations of life-saving antiretroviral therapy.
The NIAID’s Fauci has said he believes remdesivir can do the same, opening the door to the discovery and development of new, more effective drugs for COVID-19.
“Trudy showed us we could do this,” St. Clair says. “That things that people thought were impossible are not impossible.”
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Source: National Geographic
