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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

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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May 1, 2008

O Pioneers!

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Posted by Derek

Drug Discovery Today has the first part of an article on the history of the molecular modeling field, this one covering about 1960 to 1990. It’s a for-the-record document, since as time goes on it’ll be increasingly hard to unscramble all the early approaches and players. I think this is true for almost any technology; the early years are tangled indeed.

As you would imagine, the work from the 1960s and 1970s has an otherwordly feel to it, considering the hardware that was available. And that brings up another thing common to the early years of new technologies: when you look back on them from their later years, you wonder how these people could possibly have even tried to do these things.

I mean, you read about, say, Richard Cramer establishing the computer-aided drug design program at Smith, Kline and French in nineteen-flipping-seventy-one, and on one level you feel like congratulating his group for their farsightedness. But mainly you just feeling like saying “Oh, you poor people. I am so sorry.” Because from today's perspective, there is just no way that anyone could have done any meaningful molecular modeling for drug design in 1971. I mean, we have enough trouble doing it for a lot of projects in 2008.

Think about it: big ol’ IBM mainframe, with those tape drives that for many years were visual shorthand for Computer System but now look closer to steam engines and water wheels. Punch cards: riffling stacks of them, and whole mechanical devices with arrays of rods to make and troubleshoot stiff pieces of paper with holes in them. And the software – written in what, FORTRAN? If they were lucky. And written in a time when people were just starting to say, well, yes, I suppose that you could, in fact, represent attractive and repulsive molecular forces in terms that could be used by a computer program. . .hmm, let’s see about hydrogen bonds, then. . .

It gives a person the shudders. But that must be inevitable – you get the same feeling when you see an early TV set and wonder how anyone could have derived entertainment from a fuzzy four-inch-wide grey screen. Or see the earliest automobiles, which look to have been quite a bit more trouble than a horse. How do people persevere?

Well, for one thing, by knowing that they’re the first. Even if technology isn’t what you might dream of it being some day, you’re still the one out on the cutting edge, with what could be the best in the world as it is. They also do it by not being able to know just what the limits to their capabilities are, not having the benefit of decades of hindsight. The molecular modelers of the early 1970s did not, I’m sure, see themselves as tentatively exploring something that would probably be of no use for years to come. They must have thought that there was something good just waiting right there to be done with the technology they had (which was, as just mentioned, the best ever seen). They may well have been wrong about that, but who was to know until it was tried?

And all of this – the realizations that there’s something new in the world, that there are new things that can be done with it, and (later) that there’s more to it (both its possibilities and difficulties) than was first apparent – all of this comes on gradually. If it were to hit you all at once, you’d be paralyzed with indecision. But the gap in the trees turns into a trail, and then into a dirt path before you feel the gravel under your feet, speeding up before you realize that you’re driving down a huge highway that branches off to destinations you didn’t even know existed.

People are seeing their way through to some of those narrow footpaths right now, no doubt. With any luck, in another thirty years people will look back and pity them for what they didn’t and couldn’t know. But the people doing it today don’t feel worthy of pity at all – some of them probably feel as if they’re the luckiest people alive. . .

Comments (8) + TrackBacks (0) | Category: Drug Industry History | In Silico | Who Discovers and Why


1. Jose on May 1, 2008 11:50 AM writes...

Yup, considering how crude (even humorous at times) modelling is today, trying fancy stuff with the equivalent of a Vic20 and a tape drive just seems quaint.

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2. Sigivald on May 1, 2008 12:15 PM writes...

Naw, they would've had big, expensive IBM hard disk packs, not tape or cards, at least for storage.

Depending on the budget, they might well have had interactive programming and data entry, completely bypassing paper.

And definitely FORTRAN; it was bone-standard for scientific computing well before 1971.

(But yes, by modern standards, stone-knives-and-bearskins territory. Shoulders, giants, etc.)

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3. Aspirin on May 1, 2008 12:26 PM writes...

Those were truly the intrepid pioneers. Their perseverance is to be admired. And like you said, that's true for leaders in any field.

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4. SRC on May 1, 2008 12:49 PM writes...

FORTRAN! Sigh. Takes me back...

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5. MolecModeler on May 1, 2008 1:04 PM writes...

FORTRAN always gets a bad rap, but many of the most commonly used numerical libraries in molecular modelling are highly optimized in FORTRAN. You would not get faster performance from re-coding in a modern language like C/C++/C#.

Obviously you wouldn't want to do any GUI development with it, however.

As a synthetic chemist, why even care what our software is written in? :) Hell it could be written in pig latin, as long as it "worked". And as I'm sure you know it depends on the defenition of "work".

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6. Kay on May 2, 2008 7:37 AM writes...

We are indeed standing on the shoulders of giants. For example, the rule of 5 has saved our bacon to date. It could be improved, however. The next iteration might be 'rule of 5 plus stock price.' (the next iteration will still be known as rule of 5 around Pfizer)

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7. John Spevacek on May 2, 2008 7:48 AM writes...

"Punch cards: riffling stacks of them, and whole mechanical devices with arrays of rods to make and troubleshoot stiff pieces of paper with holes in them."

Thank goodness that ALL of this technology has gone bye-bye and isn't used for political elections or such.

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8. Jonadab the Unsightly One on May 26, 2008 1:01 PM writes...

> why even care what our software is written in?
> :) Hell it could be written in pig latin,

I think there's a source filter module for that on the CPAN...

Fortran isn't too bad for number cruching, provided that's all you want to do. It's pretty terrible for creating user interfaces of any kind, though. One would be tempted to write the core of the application in Fortran and then throw a wrapper around it that's written in something else, which calls the Fortran program to do the grunt work, so that the user never has to deal with the Fortran program directly.

Of course, these days you probably want to run any serious number crunching in a distributed fashion (assuming it's parallelizable), so you want a language with good networking libraries, thus, not Fortran. But that wasn't so much of a consideration in the seventies.

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