Name: The Woman Who Changed Drug Development
Uploaded: 2020-03-30T04:33:17.000Z
Duration: 5 min 20 s
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Back in 1944, scientists were only just beginning to suspect that DNA was our genetic material.

That's the year Gertrude Elion first started studying nucleotides, the chemical building

Over the next five decades, Elion became a leading expert on nucleotides.

And her outside-the-box thinking led to methods that totally transformed the world of drug

development — including life-saving therapies we still use today.

Gertrude Elion was born in New York City in 1918, the daughter of Eastern European immigrants.

The year she finished high school, she watched her grandfather succumb painfully to cancer.

His death inspired her to study chemistry in college, and eventually earn a master's

There weren't a ton of research jobs available during the Great Depression, particularly

But after World War II broke out, she scored a position in the lab of a guy named George

Hitchings had this idea that if you could understand a biological process, you should

be able to use that information to design chemicals to disrupt that process.

This idea might seem obvious now — but that's just because it's how we like to develop

At the time, this rational approach to drug design, as it came to be called, was new and

See, in the mid-1940s, most of the drugs that were available were either based on plant

compounds that people had been using for millennia, like aspirin — or they'd been discovered

But Elion and Hitchings wanted to take a more deliberate approach.

And there were two key reasons why nucleotides seemed like a good place to start.

One, all cells need them to divide — since dividing means doubling your DNA, and DNA

And two, certain bad cells like cancer, parasites, and bacteria divide way faster than healthy

This makes them especially hungry for nucleotides.

If you had a way to exploit this hunger, you might be able to fight all those things.

The problem was, nobody knew much of anything about how cells make or use nucleotides.

One of Elion's first assignments at her new job was to start figuring all this out.

So she synthesized a bunch of chemical analogs that were similar to nucleotides, or things

that cells needed for making nucleotides.

The idea was to see what cells would do with these imposter compounds.

Some of the analogs had key chemical differences that made cells unable to use them like normal

They were a biochemical dead end, and they would gum up the works — essentially blocking

Which is exactly what Elion and Hitchings were looking for in a drug.

But they had to make sure it wasn't too toxic to people.

The first breakthrough came in 1951, when Elion synthesized 6-mercaptopurine, or 6-MP.

It's one of those dead-end molecules, and it's especially good for stopping out-of-control

It was a huge step forward in treating childhood leukemia, and it opened the door to new ideas

In testing 6-MP and related molecules, Elion started to piece together that different cell

types, and cells from different species, responded differently to some analogs.

And that's the key to making drugs like these work.

Once she found a promising lead, she would design slightly different compounds to try

Her approach to synthesizing them was novel as well.

On top of that, she was among the first to follow what happened to drugs in the body

— and use that information to design drugs that were more specific, less toxic, and more effective.

All of these approaches in combination led to lots of new discoveries about nucleotide metabolism.

And they led Elion to treatments for an incredibly diverse set of problems, including malaria,

gout, tissue rejection, and autoimmune diseases.

Later in her career, she showed that it was possible to develop highly effective drugs for viral diseases.

In the 1960s, most of the research world — including Hitchings, her partner — believed that since

viruses use human cells to replicate, it would be impossible to develop a drug that would

disrupt viral replication without harming the human host.

But Elion proved them wrong in a big way.

She connected the dots between several studies — some hers, some from another lab — and

realized that modified nucleotides could block viral replication.

She followed the lead, and developed acyclovir.

It's a compound that interferes specifically with a nucleotide-making enzyme from the herpes

virus, but not the human version of that same enzyme.

And this work paved the way for AZT, the first effective antiretroviral drug in the fight

In fact, it was scientists from Elion's research team who developed AZT, after her official retirement.

Not only are AZT, 6-MP, and other drugs Elion helped develop still in use today — the

World Health Organization counts them among the safest, most effective drugs available.

But beyond the drugs themselves, it was Elion and Hitchings' contributions to the process

of drug discovery that had the greatest impacts.

Once they showed that their process worked — that you could rationally build drugs

from scratch — other drug companies around the world started using it.

And that's what earned them a Nobel Prize.

Elion and Hitchings, along with co-awardee James Black, received the Nobel Prize in Medicine

in 1988 for their contributions to the field of drug development.

It's rare that a half century of toil earns such recognition — but no one can argue

And as long as we continue to use the drugs she designed, Elion's contributions will

continue to improve the lives of people everywhere.

Thanks for watching this episode of SciShow.

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The Woman Who Changed Drug Development

approach

process

depression

deliberate