Arthur C Clarke famously noted that ‘any sufficiently advanced technology is indistinguishable from magic’. Over the years, I think that many of us have had a chance to feel some of the truth behind that statement. I myself would not have believed that the long-feared ‘protein folding problem’ would (largely but certainly not completely) evaporate by this time, to pick one example. And I would also not have believed that this was accomplished without our learning much more about the physics of protein folding, but rather by a computational onslaught of pattern-matching and machine learning algorithms.
As for hardware, back when I was a PhD student I might well have flatly refused to believe the sorts of things that mass spectrometry equipment can get up to these days, or the way that huge protein structures could be solved by cryo-electron microscopy without ever bothering about crystallising them. Both those are, of course, also driven by those computational-onslaught techniques, which realisation would have caused me to wonder exactly what sorts of computers we were working with in this future era. That would have been a good time to show 1980s Derek the phone that 2020s Derek carries around in his pocket, I think.
But what technologies would one put on a wish list for the coming decades for chemistry and biology? I for one would like some way of finding where our molecules go on a subcellular level. As it stands, when a drug candidate enters a cell (or, realistically, if it enters the cell at all) we lose track of it almost completely. We have to infer things from the behaviour it sets off downstream. Knowing how our compounds distribute and what the time courses might be – and having some way to observe our all-important ‘target engagement’ directly, instead of looking for clues that it happened – that would be very worthwhile indeed.
It’s worth thinking about how some of our own abilities would have looked almost as impossible to chemists and biologists of earlier generations
I would also (in a similar vein) like to have some protein structure method that works on native samples with very high time resolution. In short, what I want is real-time, x-ray-resolution movie footage of proteins in action: every wiggle, every allosteric shift, every newly exposed binding site, the works. Molecular protein dynamics is a hot topic, and deservedly so, but we mostly have to rely on calculated simulations, which makes me a bit nervous about the buildup of possible errors across useful timescales. But real data? Yes, please!
To aid the hard-working bench chemist, I would also like what an old colleague of mine referred to as a ‘Molecular Weight Grabber’. That, he explained, would be a device whose business end you stuck into your reaction mixture, after turning a dial on the top to the desired range of molecular weights you were interested in. Only those species would adhere to the Grabber as you swished it around; then you would pull it out, dip it into another vial or flask, and hit a button to make it release its catch into the new solution. Doesn’t that sound more relaxing than the purification techniques you’re stuck with now?
I will not be offering tips on how to realise these nanotechnological visions – well, not this month, anyway. But it’s worth thinking about how some of our own abilities would have looked almost as impossible to chemists and biologists of earlier generations. Metal-catalysed coupling reactions seemed rather eerie as they began to work their way into the repertoire, I can tell you. My graduate-school self would have been struck by the thought of chemists having completely dropped the habit of running thin-layer chromatography plates of all their reactions, wondering what might have replaced them. Biologically, the idea of sequencing a single cell’s DNA (or getting a vast profile of its RNA content) would have seemed science-fictional. The speed of sequencing in general (and how routine it has become) would have been hard to believe as well.
It’s a new world. But that’s the great thing about science – it’s always a new world. Magic happens, becomes mundane, and is eventually replaced by … even more magic. The whole process shows no signs of running out, which means that if it ever does, the fault will surely be ours. Let’s keep going!
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