LAUSR

There has perhaps been a perception that the field of chemical biology, as for chemistry, has a future as a ‘service technology’ rather than an independent science. In addressing this then one must perhaps think about the role of chemistry in biology, as well as Chemistry in Biology. Without wishing to seem arrogant, chemistry is a longstanding and hence, in part through historical accrual, a sophisticated science. It certainly creates uniquely powerful molecular technologies that can be transformative but perhaps more importantly sets up its own aesthetic, philosophy and approach. Its power in society is undeniable and, aside from arguments about what is chemistry and what is not, the list of fundamental discoveries that have merited the Nobel prize (as a gauge of “the most important chemical discovery or improvement”) reads as a list of societal evolution. It is therefore not only an intellectual imperative that this power is as accessible as possible, it is an ethical one too. This raises the prospect of ‘service’. Full exploitation of the depth and subtlety of knowledge necessarily requires expertise, sometimes at a level that may frustrate those who wish to gain access. Yet, maintaining rigour is also a prime ethical imperative (see below). We must therefore find moral solutions and philosophies in a space where the ethical tension arises between rigour and accessibility. There is no doubt, for example, that attachment of fluorophores (proteinaceous or otherwise) to biomolecules has been transformative, yet it is the hypothesis-testing that they enable that is the scientific joy – it is easy therefore to see why some might say, as a now ex-collaborator of mine once said several years ago, “Bolt me on a fluor and I can take it from there.”. It might be said that we have more than enough ways of ‘bolting on fluors’ or similar – instead, it is the molecular precision in the chemical understanding of biology that is the rich seam that I think modern chemical biology is now tapping. What then is chemistry’s distinction or position (for example in the chemical understanding of biological questions)? Phrases such as ‘the central science’ give comfort but sometimes deepen a sense of service. One core centrality, as I would see it, is one of access to and control of informational content in biology. The molecular level is the cutoff at which the units of information (genes in their original sense) become discernible and usable. Those units may be found in all parts of biology (not simply nucleic acids) and, without wishing to open a debate that is not strictly relevant to this essay, one might argue that information transfer is an imperative thread in what we consider to be life. Analysing such informational constructs is at least one centrality that we should take on board. This should be done in a suitably clear manner, lest we create issues that faced even Kant: ‘I am often accused of obscurity, perhaps even deliberate vagueness in my philosophical discourse, to give it the air of deep insight’ – some current analyses draw on notions of ‘systems’ as similarly intractable, ‘vague’ blackboxes; these too will become accessible in time to precise chemical thought in the areas of, for example, the origin of life, epigenetics, and even the molecular basis of thought or memory – all of which remain very much open questions. These perhaps seem hard to understand using current modes of nucleic acid-derived linearity but may be more readily understood in beautiful, thermodynamically-precarious systems maintained at farfrom-equilibrium hotspots with great functional value: in biology’the instructions are ready made but their fulfilment is epigenetic’. These ideas are perhaps, to the chemically-minded, no more than simply notions of kinetic control of informational content. Therefore the initial programming of information, largely covalently, has been a central goal. An example that I often return to, is that of what is loosely described as mutagenesis. Transformative manipulations in nucleic acids lead directly from a connection between structure and ‘gene’, yet the more complex question of information closer to functional output (e.g. in proteins) has barely been touched on, despite profound insights set down over 50 years ago. This brief essay will explore a few illustrative areas with the goal of capturing the distinctive nature of chemical analysis of biology, which to me lies in great part in the precision that it might bring to bear.