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Back in 1944, scientists were only just beginning to suspect that DNA was our genetic material.
回到1944年，那时的科学家们才刚开始怀疑DNA是我们的遗传物质。
That's the year Gertrude Elion first started studying nucleotides, the chemical building blocks that form DNA.
那一年，格特鲁德·埃利恩刚开始研究核甘酸基—构成DNA的化学物质。
Over the next five decades, Elion became a leading expert on nucleotides.
在未来的50年里，埃利恩成为了研究核甘酸基的顶尖专家。
And her outside-the-box thinking led to methods that totally transformed the world of drug development
她的创新思维带来了彻底改变药物开发世界的方法
including life-saving therapies we still use today.
包括我们至今仍在使用的救命治疗方法。
Gertrude Elion was born in New York City in 1918, the daughter of Eastern European immigrants.
1918年，格特鲁德·埃利恩出生于纽约市，她是东欧移民的女儿。
The year she finished high school, she watched her grandfather succumb painfully to cancer.
高中毕业那一年，她看着自己的祖父痛苦地死于癌症。
His death inspired her to study chemistry in college, and eventually earn a master's degree.
他的死激励她在大学里学习化学，并最终获得了硕士学位。
There weren't a ton of research jobs available during the Great Depression, particularly for a woman.
在大萧条时期，没有大量的研究工作可做，尤其是对女性来说。
But after World War II broke out, she scored a position in the lab of a guy named George Hitchings.
但二战爆发后，她在乔治·希钦斯的实验室中获得了一个职位。
Hitchings had this idea that if you could understand a biological process,
希钦斯认为如果你能理解一个生物过程
you should be able to use that information to design chemicals to disrupt that process.
那么你应该能够利用这些信息来设计破坏这一过程的化学物质。
This idea might seem obvious now but that's just because it's how we like to develop drugs today.
这个想法现在看起来平淡无奇，但那只是因为这就是我们今天开发药物的方式。
At the time, this rational approach to drug design, as it came to be called, was new and pretty radical.
在那时，这种药物设计的推理研究法是一种全新且相当激进的方法。
See, in the mid-1940s, most of the drugs that were available were either based on plant compounds
在20世纪40年代中期，大部分可用药物要么是基于
that people had been using for millennia, like aspirin or they'd been discovered by accident, like penicillin.
人们使用了数千年的植物化合物，如阿司匹林或他们意外发现的，如盘尼西林。
But Elion and Hitchings wanted to take a more deliberate approach.
但是埃利恩和希钦斯想要采取一种更深思熟虑的方法。
And there were two key reasons why nucleotides seemed like a good place to start.
从核甘酸基开始的关键原因有两点。
One, all cells need them to divide since dividing means doubling your DNA, and DNA needs nucleotides.
其一，所有细胞都需要它们进行分裂，因为分裂意味着DNA加倍，而DNA需要核苷酸。
And two, certain bad cells like cancer, parasites, and bacteria divide way faster than healthy cells.
其二，某些不好的细胞，如癌症、寄生虫以及细菌的分裂比健康细胞快的多。
This makes them especially hungry for nucleotides.
这使得它们特别渴望核苷酸。
If you had a way to exploit this hunger, you might be able to fight all those things.
如果你有办法利用这种饥饿感，那么你可能就能战胜所有这些东西。
The problem was, nobody knew much of anything about how cells make or use nucleotides.
问题是，没人知道细胞是如何制造或利用核苷酸的。
One of Elion's first assignments at her new job was to start figuring all this out.
埃利恩新工作的任务之一就是把这些都弄清楚。
So she synthesized a bunch of chemical analogs that were similar to nucleotides, or things that cells needed for making nucleotides.
所以她合成了一堆类似于核苷酸的化学类似物，或者是细胞制造核苷酸所需要的物质。
The idea was to see what cells would do with these imposter compounds.
这个想法是想看看细胞如何处理这些假冒化合物。
Some of the analogs had key chemical differences that made cells unable to use them like normal nucleotides.
一些类似物存在关键化学差异，这让细胞无法像正常的核苷酸一样使用它们。
They were a biochemical dead end, and they would gum up the works essentially blocking a cell's ability to make DNA or RNA.
它们是生化的死端，它们会把工作搞砸，本质上阻碍了细胞制造DNA或RNA的能力。
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.
这正是埃利恩和希钦斯想在药物中寻找的。但他们必须确保它对人体无害。
The first breakthrough came in 1951, when Elion synthesized 6-mercaptopurine, or 6-MP.
首次突破性进展是在1951年，当时埃利恩合成了6-巯基嘌呤（6-MP）。
It's one of those dead-end molecules, and it's especially good for stopping out-of-control immune cells.
它是那些死端分子之一，对阻止失控的免疫细胞特别有效。
It was a huge step forward in treating childhood leukemia, and it opened the door to new ideas for treating cancer in general.
这是治疗儿童白血病的一大进步，并且它还为治疗癌症的新思路打开了大门。
In testing 6-MP and related molecules, Elion started to piece together that different cell types,
在测试6-MP和相关分子时，埃利恩开始拼凑不同细胞类型
and cells from different species, responded differently to some analogs. And that's the key to making drugs like these work.
以及来自不同种类的细胞，它们对一些类似物的反应也不同。这是制造这些药物的关键。
Once she found a promising lead, she would design slightly different compounds to try to exploit some of those differences.
一旦她发现了有希望的线索，她就会设计出稍微不同的化合物，试图利用其中的一些差异。
Her approach to synthesizing them was novel as well.
她使用的合成方法也很新奇。
On top of that, she was among the first to follow what happened to drugs in the body
最重要的是，她是第一批跟踪药物在人体内变化的人之一
and use that information to design drugs that were more specific, less toxic, and more effective.
还利用此信息设计出了更加明确、毒性更小且更有效的药物。
All of these approaches in combination led to lots of new discoveries about nucleotide metabolism.
所有这些方法的结合引发了大量关于核苷酸代谢的新发现。
And they led Elion to treatments for an incredibly diverse set of problems, including malaria, gout, tissue rejection, and autoimmune diseases.
它们将埃利恩引向了一系列非常复杂问题的治疗方法，包括疟疾、痛风、组织排斥性以及自身免疫病。
Later in her career, she showed that it was possible to develop highly effective drugs for viral diseases.
在她事业后期，她证明了开发治疗病毒性疾病的高效药物是可能的。
In the 1960s, most of the research world, including Hitchings, her partner, believed that since viruses use human cells to replicate,
在20世纪60年代，包括她的搭档希钦斯在内的大部分研究人员都认为由于病毒利用人类细胞进行复制，
it would be impossible to develop a drug that would disrupt viral replication without harming the human host.
所以不可能研制出一种既能中断病毒复制又不伤害人类宿主的药物。
But Elion proved them wrong in a big way.
但埃利恩证明他们是错的。
She connected the dots between several studies — some hers, some from another lab —
她把几项研究的结果联系起来—一些是她的，一些是来自另一个实验室的—
and realized that modified nucleotides could block viral replication. She followed the lead, and developed acyclovir.
她意识到修改核甘酸基可以阻止病毒复制。紧接着，她开发了阿昔洛韦。
It's a compound that interferes specifically with a nucleotide-making enzyme from the herpes virus,
它是一种化合物，专门干扰一种来自疱疹病毒的核苷酸制造酶，
but not the human version of that same enzyme.
但不会干扰人类的这种酶。
And this work paved the way for AZT, the first effective antiretroviral drug in the fight against HIV/AIDS.
这项工作为AZT—抗击HIV/AIDS中的首个有效抗后病毒药物铺平道路。
In fact, it was scientists from Elion's research team who developed AZT, after her official retirement.
事实上，正是埃利恩研究团队的科学家，在她退休后开发出了AZT。
Not only are AZT, 6-MP, and other drugs Elion helped develop still in use today —
埃利恩不仅帮助研发了AZT、6-MP和其他至今仍在使用的药物—
the World Health Organization counts them among the safest, most effective drugs available.
世界卫生组织还认为它们是现在可用的最安全、最有效的药物之一。
But beyond the drugs themselves, it was Elion and Hitchings' contributions to the process of drug discovery that had the greatest impacts.
但除了药物本身，埃利恩和希钦斯对药物发现过程的贡献才是最伟大的影响。
Once they showed that their process worked — that you could rationally build drugs from scratch —
一旦他们证实自己的过程有效—你可以理性地从零开始制造药物—
other drug companies around the world started using it. And that's what earned them a Nobel Prize.
世界其他药物公司就可以开始使用它。他们因而获得了诺贝尔奖。
Elion and Hitchings, along with co-awardee James Black, received the Nobel Prize in Medicine in 1988
埃利恩和希钦斯以及共同受奖者詹姆斯·布莱克获得了1988年药物诺贝尔奖
for their contributions to the field of drug development.
以表彰他们对药物开发领域所做的贡献。
It's rare that a half century of toil earns such recognition but no one can argue it's not well deserved.
半个世纪的辛劳获得如此认可实属罕见，但没有人会说不公平。
And as long as we continue to use the drugs she designed, Elion's contributions will continue to improve the lives of people everywhere.
只要我们继续使用她设计的药物，埃利恩的贡献就将继续改善世界各国人民的生活。
Thanks for watching this episode of SciShow. If you like learning about awesome women in science
感谢收看本期《科学秀》，如果你想对那些科学界令人敬佩的女性有更多了解
and want to help us make more episodes like this one, consider supporting us on Patreon.
并希望帮助我们制作更多类似视频，请在Patreon上支持我们。
You'll earn neat perks, and you'll help us make great free videos for everyone to enjoy. Check it out at patreon.com/scishow.
你将会获得特别优待，还能帮助我们制作人人喜爱的免费视频。点击登录patreon.com/scishow
