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Derek Lowe The 2002 Model

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Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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« By Any Other Name | Main | The Last Word on Taste »

May 12, 2004

Beyond the Teeth, Beyond the Pale

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Posted by Derek

The sense of smell is one thing - cast out from its central place in chemistry, it's still an everyday presence. If you want a sense that's really fallen from the sky of the science, try taste.

I'm not old enough to remember the days when people routinely tasted their compounds, but such days there certainly were. If you go back to the early days of organic chemistry (which means, in almost every case, reading German), you find legends like Emil Fischer reporting the appearance, melting point, and taste of all his new carbohydrate derivatives: "Zart", "Suess-Saeure", "Halb-bitter". It gives you the shivers just reading it.

Fine, that was the 1890s. People didn't understand toxicology then, and Fischer didn't know that the phenylhydrazine derivatives he was surrounded by were relentlessly poisoning him. It took a while for people to catch on. Another chiller is the paper (from around 1930) by Alfred Stock where he describes, with detailed examples from his personal experience, the symptoms of chronic mercury poisoning.

But older colleagues of mine fifteen years ago described having tasted the occasional drug candidate earlier in their careers, in very small amounts, just to see if it was bitter enough to be a problem for oral dosing. My guess is that the practice died out in the 1970s, at the latest, but in any case we're talking about compounds that have already been through some rodent toxicity screens, not hydrazones or mercury compounds. The practice of tasting new and unknown organic compounds must belong to the 1940s or before.

Or so I thought. I recently heard a first-hand report from an off-the-beaten track region of Europe that people were tasting compounds there even in the 1980s. I was aghast - the next thing I expected to hear was that the doctors prescribed bleeding for influenza. Who knows what still goes in the backwaters?

Comments (7) + TrackBacks (0) | Category: Life in the Drug Labs


1. Nick Henriquez on May 13, 2004 2:19 AM writes...

Well, many thngs actually. but then many things that used to be normal, but became "out of date" have made a comeback in medicine.

The use of leeches to remove excess blood after reconstructive surgery and the use of fly larveae to prevent gangrene from developing.

So who knows, in a few years maybe you'll be forced to taste some of your compunds as part of a new technology... ;-)

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2. SP on May 13, 2004 11:44 AM writes...

Wasn't the sweetness of aspartame discovered when a researcher making various dipeptides, who hadn't washed his hands or worn gloves, licked his fingers to turn the pages of his notebook? That was in the 60s.

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3. Klug on May 13, 2004 1:40 PM writes...

Yeah, I've heard that. It's my understanding that's how many modern artificial sweeteners were discovered.

I've heard that on occasion, it's been known to happen in various academic labs. (Grad students being curious about structural similarity to sweeteners, for instance.) I gotta say, I was always curious what benzyl-protected glucose derivatives tasted like.

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4. maguzza on May 15, 2004 12:14 PM writes...

1980's in obscure parts of Europe? Try ca. 1995 in the highest echelons of US academic chemistry. When I was in grad school, a well-known chemistry professor who was to win the Nobel prize about 5 years later came to give a seminar in my department. His was a household name in the world of organic chemistry, in part because of an important synthetic name reaction he developed that was taught to introductory organic chemistry students. As a result, a large number of undergrads were encouraged to and did attend the seminar, meaning that seminar attendance approached record levels and had many, many more undergrads than was normal.

The talk was horrendous, ghastly, awful -- totally disorganized and incoherent. I'd hate to have to have a class from this guy. But the highlight was when he mentioned in passing how a number of molecules he mentioned *tasted*. In response to the stunned sucking-in of breath that followed, he said, "Oh yes, I still taste all my small molecules."

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5. Derek Lowe on May 16, 2004 11:00 PM writes...

Well, you certainly give enough clues for me to know who you're talking about. I have a colleague who was a post-doc with this guy, and I'll ask about this and report back.

But I have to say, I certainly can't rule it out, from everything I've heard. . .

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6. Klug on May 17, 2004 12:10 PM writes...

Are we talking about a certain professor in La Jolla? And if so, you would think he'd be far enough removed from his bench. Or is it "bring me that sample -- let me see how it tastes?"

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7. maguzza on May 17, 2004 9:47 PM writes...

Klug -- I wondered exactly the same thing. Does he dictate that his grad students bring him the tastiest of their molecules to sample?

Derek -- Please do let us know if you get some confirmation. When I've met people from that group, I've always asked about his horrific speaking style first and I don't think we've ever made it to the tasting topic (could it be that they are related...?). I know a recent graduate of that group where I am now. If I see him, I'll ask, too.

Or perhaps he just said it for the shock value?

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