Daniel Nicholson

ABSTRACT

In 1926, Haldane published an essay titled ‘On Being the Right Size’, in which he argued that the size of an organism fundamentally shapes its way of life. Size constrains the kind of physical structure an organism can have, as well as its mode of behavior. Many of Haldane’s examples were based on the square-cube law, which states that the volume of a physical body increases much faster than its surface area. The shape of warm-blooded animals, the form of the leaves and roots of higher plants, and the intricate structure of the pulmonary alveoli and gastrointestinal tract of mammals can all be explained by appealing to this remarkably simple geometric relation. Haldane also showed that the functional capacities of organisms are conditioned by the physical forces that exert the greatest effect at the scale at which they exist. For example, gravity poses no danger to small animals, yet the surface tension of water can be a very serious threat to them. The exact opposite is true for large animals. In this talk I shall revive Haldane’s ninety-year-old argument and put it to work in the context of contemporary molecular biology. Owing to their minuscule size, molecules and cells are subject to very different forces than macroscopic organisms. In a sense, macroscopic and microscopic entities inhabit different ‘worlds’: the former is ruled by gravity and inertia, whereas the latter is governed by Brownian motion. One implication is that we should be extremely skeptical of models and analogies that seek to explain properties of microscopic entities by appealing to properties of macroscopic ones. Unfortunately, this is precisely what the appeal to engineering metaphors in molecular biology attempts to do. Molecular biologists routinely resort to such metaphors because they are familiar and intuitively intelligible. But if our machines were the size of molecules, it would be impossible for them to function the way they do. It follows that we should avoid distorting biological reality by construing it in engineering terms. This talk will examine four key metaphors of molecular biology—‘genetic program’, ‘cellular circuitry’, ‘molecular machine’, and ‘molecular motor’—and show how that their deficiencies derive from their neglect of scale. Time permitting, I will also try to explain why many biologists appear to have forgotten the importance of scale that Haldane drew attention to in his essay. The reason, I will suggest, has to do with the influence of Schrödinger’s argument in What Is Life? regarding the stability of the gene.