Are chemists designers?

Not according to a provocative article by Martin Jansen and Christian Schön in Angewandte Chemie. They argue that 'design' in the strict sense doesn't come into the process of making molecules, because the freedom of chemists is so severely constrained by the laws of physics and chemistry. Whereas a true designer shapes and combines materials plastically to make forms and structures that would never have otherwise existed, chemists are simply exploring predefined minima in the energy landscape that determines the stable configurations of atoms. Admittedly, they say, this is a big space (the notion of 'chemical space' has recently become a hot topic in drug discovery) – but nonetheless all possible molecules are in principle predetermined, and their structures cannot be varied arbitrarily. This discreteness and topological fixity of chemical space means (they say) that "the possibility for 'design' is available only if the desired function can be realized by a structure with essentially macroscopic dimensions." You can design a teapot, but not a molecule.

Chemists won't like this, because they (rightly) pride themselves in their creativity and often liken their crafting of molecules to a kind of art form. Having spoken in two books and many articles about molecular and materials design, I might be expected to share that response. And in fact I do, though I think that Jansen and Schön's article is extremely and usefully stimulating and makes some very pertinent points. I suppose that the most immediate and, I think, telling objection to their thesis is that the permutations of chemical space are so vast that it really doesn't matter much that they are preordained and discrete. One estimate gives the number of small organic molecules alone as 10^60, which is more than we could hope to explore (at today's rate of discovery/synthesis) in a billion years.

Given this immense choice, chemists must necessarily use their knowledge, intuition and personal preferences to guide them towards molecules worth making – whether that is just for the fun of it or because the products will fulfil a specific function. Designers do the same – they generally look for function and try to achieve it with a certain degree of elegance. The art of making a functional molecule is generally not a matter of looking for a complete molecular structure that does the job; it usually employs a kind of modular reasoning, considering how each different part of the structure must be shaped to play its respective role. We need a binding group here, a spacer group there, a hydrophilic substituent for solubility, and so on. That seems a lot like design to me.

Moreover, while it's true that one can't in general alter the length or angle of a bond arbitrarily, one can certainly establish principles that enable a more or less systematic variation of such quantities. For example, Roald Hoffmann and his colleagues have recently considered how one might compress carbon-carbon bonds in cage structures, and have demonstrated (in theory) an ability to do this over a wide range of lengths (see the article here). The intellectual process here surely resembles that of 'design' rather than merely 'searching' for stable states.

Jansen and Schön imply that true design must include an aesthetic element. That is certainly a dimension open to chemists, who regularly make molecules simply because they consider them beautiful. Now, this is a slippery concept – Joachim Schummer has pointed out that chemists have an archaic notion of beauty, defined along Platonic lines and thus based on issues of symmetry and regularity. (In fact, Platonists did not regard symmetry as aesthetically beautiful – rather, they felt that order and symmetry defined what beauty meant.) I have sometimes been frustrated myself that chemists' view of what 'art' entails so often falls back on this equating of 'artistic' with 'beautiful' and 'symmetric', thus isolating themselves from any real engagement with contemporary ideas about art. Nonetheless, chemists clearly do possess a kind of aesthetic in making molecules – and they make real choices accordingly, which can hardly be stripped of any sense of design just because they are discrete.

Jansen and Schön suggest that it would be unwise to regard this as merely a semantic matter, allowing chemists their own definition of 'design' even if technically it is not the same as what designers do. I'd agree with that in principle – it does matter what words mean, and all too often scientists co-opt and then distort them for their own purposes (and are obviously not alone in that). But I don't see that the meaning of 'design' actually has such rigid boundaries that it will be deformed beyond recognition if we apply it to the business of making molecules. Keep designing, chemists.