Recent opportunities for an increasing role for physical explanations in biology
Introduction
The relations between physics and biology have always been difficult, and sometimes tempestuous. One should recall that the rise of biology as an independent science and the adoption of the word “biology” at the beginning of the 19th century were late consequences of the vitalistic movement so active in medicine and the biological sciences in the second part of the 18th century. This movement was itself a reaction to the research programme initiated by Galileo Galilei and Descartes to explain the properties of organisms by the existence of internal mechanical devices.
The opposition I am referring to was between 17th century physics, with its emphasis on mechanism, and the life sciences of the same time. Physics and biology have been deeply transformed since these early times, and it might seem absurd to oppose physics and biology today in the same way. Physics—as well as biology—is a historical object in permanent evolution. There are different forms of physics, in the same way as evolutionary and molecular biology have little in common. Is it reasonable to oppose physical and biological explanations, as if the specific form of these explanations was not simply the result of a historical, contingent process? My conviction is that, even if it is obviously impossible to provide absolute criteria to distinguish a physical explanation from a biological one, history has nevertheless moulded and stabilized forms of explanations, ways to address questions that can be unambiguously called “physical” or “biological”.
One difficulty for those who want to favour the encounter between the two disciplines is that physical explanations are in fact already everywhere in biology. The three-dimensional structures of macromolecules—proteins and nucleic acids—that are the basis of the mechanistic explanations of molecular biology are determined by physicists, using physical devices, and physical theory to interpret the data. Metabolism, the whole set of reactions necessary for the synthesis and degradation of the different constituents of the organism, cannot be understood without thermodynamics. The same is true for protein structure. Physics is everywhere, in cell and molecular biology, but also in other fields of biology: in neurophysiology and neurobiology since the 19th century, and obviously in many parts of medicine. And this presence of physics, physical descriptions and models is unproblematic and well accepted. I want to illustrate this point by one example: the present explanation of the nerve influx, the process by which neurons can communicate, or stimulate the activity of other tissues such as muscles. One important step in the scientific understanding of this phenomenon—not the first—was the physical model proposed by Hodgkin and Huxley in 1952 (Hodgkin & Huxley, 1952). This model hypothesized that the propagation of the nerve influx was due to the generation of transient currents across the cell membrane, resulting from its selective opening to ions such as sodium and potassium. From 1952 to the end of the 20th century, the description of the molecules involved in this process, and of their behaviours, progressed dramatically. The transient movement of the ions across the membranes was explained by the existence of pores or channels within the membrane, identified with proteins. The three-dimensional structure of these proteins was determined (Jiang, Lee, Chen, & Cadene, 2003), and from their structures explanations were provided to account for the three major characteristics of these channels: their transient opening when the propagation of the nerve influx alters the transmembrane voltage, their closure after a short delay, and their selectivity for particular ions, sodium or potassium. A physical model—the Hodgkin-Huxley model—was progressively replaced by a mechanistic description at the molecular level. Most biologists would consider that the molecular explanations, in terms of weak bond formation, conformational changes and relative displacement of different parts of the proteins, are biological explanations, which have positively replaced the abstract physical models. But as we have seen, these molecular descriptions were made possible by the work and concepts of physicists. When one looks more closely at the explanations that are provided for the behaviour of these channels, they are in fact a complex mixture of intertwined physical and biological explanations. Consider for instance the question of the specificity of one of the channels, the potassium channel. Why does this channel allow the passage of the potassium ion, and not of the sodium ion, which is of very similar size? The explanation which is provided today is a thermodynamic one: in solution, the ions are associated with molecules of water. The pore is narrow and the ion must drop these water molecules when it enters the channel. The loss of energy resulting from the loss of the water molecules is compensated by the formation of bonds between the ion and the charged amino acids forming the wall of the pore. The slight difference in size between the potassium and sodium ions is sufficient to allow the first to form stronger bonds with the amino acids present in the pore wall, sufficient to compensate for the loss of energy due to the departure of the water molecules; the gain of energy is less for the sodium ion and is unable to compensate for the loss of energy associated with the release of the water molecules. This already sophisticated model has been complemented by a dynamic view of the interactions between ions and the protein channel (Noskov, Bernéche, & Roux, 2004).
Many other examples of this narrow intertwining of physical and molecular (biological) explanations can be provided. Consider for instance the interactions between repressors and their DNA targets. Precise molecular structures permitted a description of the different bonds that stabilize the interaction. But this precise description failed to explain how the repressor binds to its specific target (von Hippel, 2004). Kinetic models show that a chance encounter cannot account for the rate at which the repressor binds to its target, one short sequence of DNA among a million different ones. In fact, the repressor finds its target by sliding along the DNA molecule, thanks to the non-specific interactions that the repressor has with any DNA molecule. Later, a precise molecular description of these unspecific interactions was obtained (Kalodimos, Biris, Bonvin, & Levandoski, 2004).
In this case as in the previous one, there was a back-and-forth movement between explanations that will be felt by biologists as “biological”—the molecular explanations—and those that will be felt as “physical”.
So physical and biological explanations coexist in biology, and they are tightly interwoven. This movement of balance between these two forms of explanation may originate, as in the previous cases, in the limits of the molecular descriptions, unable to explain some of the characteristics of the objects under study. These limits of molecular explanations create opportunities for future encounters between biology and physics as we will demonstrate in the third part. But before that, we must go deeper into our understanding of the difficulties that these encounters face and which make the introduction of physical explanations into biology frequently so problematic.
Section snippets
Why is the introduction of physical explanations into biology so problematic?
The history of science can be of some help in understanding the origin of these difficulties. We will successively consider two eminent physicists who tried to introduce physical explanations of biological phenomena, but had limited success and encountered strong opposition, and two fields of research in which physicists claimed to have afforded explanations when biologists did not.
The main work of D’Arcy Thompson On Growth and Form sought to demonstrate that complex biological forms could be
Opportunities created by the recent developments in molecular and cell biology
Nevertheless, I am convinced that the recent developments in molecular and cell biology have created huge opportunities for a renewed interaction between physicists and biologists, for two different reasons. The first is that the accumulation of molecular data has provided the material on which to elaborate physical models and/or to test them. The second is that by pushing molecular descriptions as far as was possible, molecular biologists were able to reveal the limits of these explanations. I
Conclusion
I have shown that there are many opportunities for physical explanations in present-day biology that have emerged from recent precise molecular descriptions. I have described a panel of opportunities without placing them into well-defined categories. From the examples that I have selected, it emerges that physical studies can enrich the description of the systems under study, improve predictability and verifiability, complement and overcome the limits of molecular and evolutionary explanations,
Acknowledgments
I am indebted to David Marsh for critical reading of the manuscript, and to Darrell Rowbottom for his continuous help, and huge patience.
References (26)
Mechanical indiction of Twist in the Drosophila Foregut/Stomodeal primordium
Current Biology
(2003)- et al.
Structural features of the GroEL-GroES nano-cage required for rapid folding of encapsulated protein
Cell
(2006) - et al.
A synthetic multicellular system for programmed pattern formation
Nature
(2005) - et al.
Frequency-modulated nuclear localization bursts coordinate gene regulation
Nature
(2008) - et al.
Tissue deformation modulates Twist expression to determine anterior midgut differentiation in Drosophila embryos
Developmental Cell
(2006) - et al.
Phyllotaxis as a physical self-organized growth process
Physical Review Letters
(1992) - et al.
A synthetic oscillatory network of transcriptional regulators
Nature
(2000) - et al.
The evolution of hierarchical gene regulatory networks
Nature reviews/genetics
(2009) - et al.
Control of phyllotaxy by the cytokinin-inducible response regulator homologue ABPHYL1
Nature
(2004) The chemical kinetics of the bacterial cell
(1946)
A quantitative description of membrane current and its application to conduction and excitation in nerve
Journal of Physiology
X-ray structure of a voltage-dependent K+ channel
Nature
Structure and flexibility adaptation in nonspecific and specific protein-DNA complexes
Science
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