In search of principles: when biology met physics

This is an excerpt from the introduction of Bill Bialek's book on biophysics. Bialek was a professor at Berkeley when I was a graduate student, but has since moved to Princeton. See also For the historians and the ladies, As flies to wanton boys are we to the gods and Prometheus in the basement.

... In one view of history, there is a direct path from Bohr, Delbruck and Schrodinger to the emergence of molecular biology. Certainly Delbruck did play a central role, not least because of his insistence that the community should focus (as the physics tradition teaches us) on the simplest examples of crucial biological phenomena, reproduction and the transmission of genetic information. The goal of molecular biology to reduce these phenomena to interactions among a countable set of molecules surely echoed the physicists’ search for the fundamental constituents of matter, and perhaps the greatest success of molecular biology is the discovery that many of these basic molecules of life are universal, shared across organisms separated by hundreds of millions of years of evolutionary history. Where classical biology emphasized the complexity and diversity of life, the first generation of molecular biologists emphasized the simplicity and universality of life’s basic mechanisms, and it is not hard to see this as an influence of the physicists who came into the field at its start.

Another important idea at the start of molecular biology was that the structure of biological molecules matters. Although modern biology students, even in many high schools, can recite ‘structure determines function,’ this was not always obvious. To imagine, in the years immediately after World War II, that all of classical biochemistry and genetics would be reconceptualized once we could see the actual structures of proteins and DNA, was a revolutionary vision—a vision shared only by a handful of physicists and the most physical of chemists. Every physicist who visits the grand old Cavendish Laboratory in Cambridge should pause in the courtyard and realize that on that ground stood the ‘MRC hut,’ where Bragg nurtured a small group of young scientists who were trying to determine the structure of biological molecules through a combination of X–ray diffraction experiments and pure theory. To make a long and glorious story short, they succeeded, perhaps even beyond Bragg’s wildest dreams, and some of the most important papers of twentieth century biology thus were written in a physics department.

Perhaps inspired by the successes of their intellectual ancestors, each subsequent generation of physicists offered a few converts. The idea, for example, that the flow of information through the nervous system might be reducible to the behavior of ion channels and receptors inspired one group, armed with low noise amplifiers, intuition about the interactions of charges with protein structure, and the theoretical tools to translate this intuition into testable, quantitative predictions. The possibility of isolating a single complex of molecules that carried out the basic functions of photosynthesis brought another group, armed with the full battery of modern spectroscopic methods that had emerged in solid state physics. Understanding that the mechanical forces generated by a focused laser beam are on the same scale as the forces generated by individual biological molecules as they go about their business brought another generation of physicists to our subject. The sequencing of whole genomes, including our own, generated the sense that the phenomena of life could, at last, be explored comprehensively, and this inspired yet another group. These examples are far from complete, but give some sense for the diversity of challenges that drew physicists toward problems that traditionally had been purely in the domain of biologists. ...

... we proceed to explore three candidate principles: the importance of noise, the need for living systems to function without fine tuning of parameters, and the possibility that many of the different problems solved by living organisms are just different aspects of one big problem about the representation of information. Each of these ideas is something which many people have explored, and I hope to make clear that these ideas have generated real successes. The greatest successes, however, have been when these theoretical discussions are grounded in experiments on particular biological systems. As a result, the literature is fragmented along lines defined by the historical subfields of biology. The goal here is to present the discussion in the physics style, organized around principles from which we can derive predictions for particular examples. ...