Vital forces

In many people’s minds, the primary focus of physics is on the very large (black holes, the distant universe and the problems of cosmology) or the very small (the Higgs boson and the other subatomic particles of high-energy physics). But there are some deep, unsolved mysteries of science that appear at scales much closer to our everyday experience. Of these, surely the most profound question is this: what distinguishes living from non-living matter? Ultimately, a naturalistic explanation of life must start with the blind forces of physics, but from these blind forces emerges the apparently purposeful action of living organisms, including ourselves. So what can physics contribute to the solution of this conundrum?

It is this question that physicist Peter Hoffmann attempts to answer in his book Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Earlier generations thought that a so-called “vital force” had a literal and distinct existence, and by the early 19th century this force was beginning to be identified with the newly discovered and still mysterious phenomenon of electricity. But for Hoffmann, the road to understanding the vital force leads through statistical mechanics and his own experimental field: single-molecule biophysics.

Hoffmann covers this ground with an engaging mixture of historical sketches, homely analogies and personal anecdotes from his own experience as someone who trained as a condensed-matter physicist before striking out into new territory at the frontier between physics and molecular biology. The early part of the book contains some reiteration of familiar but important material on the subtleties of entropy. Thought experiments such as Maxwell’s demon get careful discussion, and Hoffmann gives due emphasis to the crucial point that requiring a global increase in entropy does not preclude local ordering, as demonstrated by the many self-assembly processes that occur at equilibrium.

The central image we are left with in this discussion is the “molecular storm” – the maelstrom of Brownian motion in which any biological nanoscale structure or mechanism has to exist, buffeted by the random thermal activity of the molecules around it. This is an unpromising environment, but such are the conditions under which the sophisticated nanoscale machines of cell biology must work. And as Hoffmann’s descriptions of various experiments demonstrate, these marvellously intricate molecular motors do not just work, they work astonishingly effectively and efficiently, and their collective action performs the familiar contraction of our muscles. This discussion brings us right up to date with current experiments and controversies in single-molecule biophysics.

The conceptual breakthrough that allows us to understand how a molecular machine can not only function in a Brownian environment, but even exploit its random motion, takes us back to an image familiar to many physicists from Richard Feynman’s famous lectures. Feynman’s “ratchet and pawl” argument illustrates that one cannot, without further input of energy, extract useful work from Brownian motion – as per the second law of thermodynamics. However, with an input of energy, you can rectify Brownian motion, using the forces generated by the random collisions of solvent molecules to generate directed motion. And it is this directed motion at the molecular level that, integrated to a large scale, leads to the purposeful motion of organisms. This idea is captured in a simple model by the French physicists Armand Ajdari and Jacques Prost: the Brownian ratchet. It is this concept that provides the “life’s ratchet” of the title.

Hoffman explains action but only begins to question purpose

As soon as one gets into the details of how any individual biological motor works, controversy starts, with the key question being “How applicable is this toy model to the particularity of that biological system?” Hoffmann’s coverage of the debate between proponents of “tightly coupled” motors and their opponents who favour “loosely coupled” models gives a flavour of the excitement associated with a field that is very much still developing. But ultimately, as Hoffmann correctly argues, these debates are about the details – fundamentally, all molecular motors are driven by the molecular storm of Brownian motion, whether or not the mapping to simple models is straightforward and easy to see.

In biology, details are important, and Hoffman does give us some of these by describing a variety of biological motors and what organisms use them for. The biology here is very rich, and as they skim past ATP synthase, helicases and RNA polymerase, some physicist readers may get the sense of rather too much biology being packed into too small a space. But we also learn about the physics details, such as what forces these molecules exert, and how these forces are measured through beautiful techniques such as force spectroscopy and optical tweezers.

Many things remain to be worked out, but Hoffmann makes clear that we are getting close to understanding part of what characterizes living matter. Such matter is capable of autonomous motion driven by molecular motors, which use an input of chemical energy to rectify the Brownian motion of the nanoscale environment. Hoffmann summarizes this view with the statement that “the force that drives life is chaos”. But there is still something missing here if we are trying to understand the purposeful action of living things: while Hoffmann explains the action, he only begins to address the question of purpose.

When we talk about the purpose of an organism, we can mean more than one thing. It is tempting to think that there is a purpose to an organism, one that is signalled by its design – but we know from Darwin’s arguments against the argument from design that this is treacherous ground. But organisms themselves have their own purposes. A bacterium swims away from a toxin or towards food because these actions might fulfil its purpose of maximizing its well-being. And Peter Hoffmann writes a book because this might fulfil his purpose of convincing other people that physics might be able explain some fundamental problems in biology. To provide a naturalistic explanation of how purpose, in this sense, arises remains a challenge that Hoffmann’s book only skirts around. Organisms process and integrate information about their environment, and depending on the outcome of that information processing, they act in one way rather than another. Underlying that act of “choice” must surely be the apparatus of signalling networks and gene regulation, and of the coupling of molecular shape change with the catalytic activity of enzymes that leads to chemical computing. And these most profound of scientific problems, too, must surely be susceptible to the insights and experimental techniques of physicists like Hoffmann.