It’s been up for a while, but I found this essay on the future of X-ray crystallography at Chemical and Engineering News to be interesting. It was part of their “100 years of crystallography” section from August 2014, and those sort of have to end with a “Where do we go from here?” piece. Even if you’re not into X-ray, though, it’s worth a read, because the issues it raises are experienced by many other fields.
That is to say, they get easier, and as they do, they work on harder problems. Back when the first inorganic salts were being obtained, getting any x-ray structure at all was an invitation to lots of hard work. Just gathering the reflection data was (by modern standards) a terrible slog, and then you had the fun of doing all the calculations by hand. It gives a person the shakes just thinking about it. Under those conditions, working out the crystal structure of copper sulfate was a real accomplishment. (And just think of the nerve of pioneers like Bernal and Hodgkin, going after protein crystals at such early dates).
It got better. And it got better from many directions at once – better computational methods, wildly better computational hardware to run them, far brighter and higher-quality X-ray sources than anyone could have imagined in the old days, and hugely more sensitive detectors. All those processes are still going on, by the way. What that’s meant, as it has in any other field (think DNA sequencing for one example) is that what was first worth a Nobel then became worth a PhD dissertation, then became just some of that grunt work that had to be done on the way to something else, and then eventually became a routine method that involved turning a couple of knobs and hitting a few keys. All kinds of small-molecule X-ray structures are routinely obtained by people who can barely begin to explain any of the math or physics behind them, in the same way that you wouldn’t want to sit a thousand walk-up NMR users down, give them blank pieces of paper, and ask them to consider the Hamiltonian (shiver).
The people who actually lived through the heroic era of any technology can react to all this in several ways. Some get bitter – there were, I’m reliably told, organic chemists who had a terrible time getting used to what NMR spectra could reveal about natural product structures, because they were so heavily invested in the old methods of structure determination. Others follow Elvis Costello’s advice, and thus used to be disgusted, but now try to be amused. And others just look at the way things used to be, are deeply happy that neither they nor anyone else has to go through that any more, and turn their attention to the sorts of problems that are on the current edge of feasibility. There’s always hard stuff out there if you want it.
For crystallography, some of that hard stuff is to be found with bigger molecules, smaller samples, and shorter collection times, and the end result of that would be atomic-level resolution of huge protein complexes, in situ, on a femtosecond time scale. Can that be done? Got me – I’m glad to don’t have to deliver it. But if you push all the sliders over all the way, that’s what you come up with, and no one can say that it’s completely impossible, either.The sorts of things being done now would have been thought pretty unlikely not all that long ago. Doesn’t have to be done with just X-rays – you can diffract electrons, neutrons, what have you, and maybe you’ll want all of the above in the eventual wonder machine.
What that means, though, is the same as in any other field as it evolves: it’ll move away from you if you’re not careful. You have to keep a close eye on things as what used to be special gradually becomes routine, and make sure that you’re not just offering your services to the diminished number of people who haven’t caught on yet. That, actually, is what I was getting at in those posts about the “synthesis machine“. As they exist now, no one’s automated organic synthesis device is much of a threat to the field’s practitioners. But it doesn’t have to stay that way, and a lot of people are trying to make sure that it doesn’t (and I think that they have the right idea). In the sciences (and in most other situations, too) work that can be done by machines probably should be done by machines, and free the rest of us up to do something else.