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. . .