Major contributions of physics to biology (1950 – now)

Those of us who work at the interface of physics and biology appreciate that the history of both disciplines is highly intertwined; neither discipline would exist in its current shape without significant contributions from the other. Yet, many biologists are not aware of the role physics has played in their discipline, and similarly, physicists are not aware that biological physics is not just biology.

To address this, we - the Biological Physics committee - have collected together a set of brief statements that could be quoted by those who face the question “What can physics contribute/has already contributed to biology?”. This question is rarely asked explicitly, but it can be implicitly asked during job interviews, discussions with our non-interdisciplinary colleagues, reviews of our papers and grant applications. This list comprises what we consider to be major contributions of physics to biology. Each item contains a brief description of a specific achievement and a reference to the original paper(s).

While such a list can never be fully objective, we have tried to cover a very broad range of contributions. The current version has been obtained by members of the BP committee proposing about 50 contributions that they considered particularly important in their sub-field. We then narrowed the list down to (currently) 13 achievements that were mostly highly voted for by the committee members (often with different expertise).

We have limited achievements in the list to discoveries that took place after 1950. Earlier contributions are relatively known and do not need further endorsement. The physics of microscopes (Ernst Abbe), brownian motion (explained by Albert Einstein in his seminal paper), the electron microscope (Ernst Ruska and Max Knoll, 1930’s), DNA as “aperiodic crystal” (E. Schroedinger, “What is life”, 1940’), Luria and Delbrueck experiment (1940’), as well as many others have not been included. We have also not included examples of biologically-motivated physics, unless such works have already (in our opinion) become relevant for biology. The focus is thus on contributions that have advanced our understanding of biological processes or provided new tools enabling such advancements.

We intend this short list to serve as a starting point in the discussion about “major achievements” in our discipline. We are also keen to have the whole biological physics community involved in improving our initial attempt at defining such major contributions, and preparing an extended version (50 contributions) of this list in the future.

Please let us know what you think about this list by emailing us on iop-biological-physics-group-committee@googlegroups.com. We look forward to your feedback!

Timeline of major contributions (1950s – now):

The Chemical Basis of Morphogenesis (1952)

Alan Turing (of Enigma fame) developed a theoretical framework for understanding how biological patterns, such as zebra stripes and jaguar spots, can emerge. This pioneering work introduces the concept of a “morphogen” - which was experimentally validated 30 years later with the discovery of Bicoid in Drosophila.

Structure of the DNA (1953)

Explained by Watson and Crick in their paper (Nobel prize in Physiology or Medicine for them as well as Maurice Wilkins in 1962). Notably, Rosalind Franklin, despite obtaining critical evidence (with Raymond Gosling) that helped to develop the model of the DNA, had neither been included in the original paper nor acknowledged in any way until the 1960’s, long after her death. The model helped to establish the central dogma of molecular biology, and led to the development of structural and molecular biology, genetic engineering, genomics, and other areas of biology and biological physics/chemistry.

Hodgkin–Huxley model (1952)

A non-linear mathematical model describing the mechanisms at membrane channel and ionic pump level for how action potentials in neurons are created and how they propagate [1]. Nobel prize in 1963. Notably, Andrew Huxley went on to describe the theoretical basis of muscle contraction (sliding filament theory: reviewed here) shortly afterwards.

Molecular Dynamics (1950s)

Following the earlier success of the Monte Carlo methods, numerical methods were devised to solve Newton’s equations of motion for atoms and molecules [1]. Molecular dynamics (MD) simulations can provide information on, e.g., energy, temperature, pressure, and diffusion coefficients. They can also capture the dynamics of complex processes such as protein folding, chemical reactions, and phase transitions. The MD field has grown enormously; nowadays, simulations of biomolecules and solvents employ MD to extract details of both structure and dynamics [2], [3], [4], and the recent spectacular successes of AI-driven protein folding predictions are grounded in MD tools [5].

Soft matter theory – the physics of polymers, liquid crystals and membranes (1950 - now)

Nearly all biological matter is soft, i.e., made of structured liquids with non-covalent interactions that lead to self-assembly of large structures such as DNA, proteins, and lipid membranes [1]. The fundamental understanding of mechanisms underpinning such biological structures and processes was developed, among others, by Paul Flory (polymer thermodynamics), Lars Onsager (electrolytic solutions, liquid crystals, and the now-famous reciprocal relations [2]), and Pierre-Gilles de Gennes (nearly every topic in soft matter physics [3]).

The cell membrane (~1970-1980)

The cell lipid bilayer had been known since the late 19th century, but the late 70’s and 1980s were the decade when theories of membrane fluctuation (Helfrich and others [1], [2], [3], [4]) and flow were developed fully, and matched to experiments on in-vitro systems. These were the foundations for contemporary work which continues on understanding membrane induced interactions, membrane heterogeneity and phase separation.

Self-assembly of viruses (1971)

The process of self-assembly of viruses investigated for the tobacco mosaic virus using electron microscopy [1]. Aaron Klug and Don Caspar explained how a highly-symmetric polyhedra-like shapes of viruses arise from interactions of protein subunits making the virus capsid. A. Klug was awarded the 1982 Nobel Prize in Chemistry for this and other works.

Super-resolution and single-molecule fluorescence microscopy (1978 - now)

There are fundamental limits (Abbe limit) on the resolution of a microscope due to the shape of the system point-spread function (PSF). Nobel prize winners (2014): Stefan Hell, Eric Betzig and W. E. Moerner developed new methods that can either reshape the PSF, or use analytical methods to localise the intensity centroid of fluorescent point source emitters (SMLM approaches), to generate a spatial resolution better than the Abbe limit. The initial demonstration of SMLM (PALM) relied of photoactivatable GFP from Jennifer Lippincott Schwartz. Xiaowei Zhuang invented the related technique of STORM (stochastic optical reconstruction microscopy) that is widely used.

Invention of the atomic force microscope (AFM) (1985)

Following from the development of STM by G. Binnig and H. Rohrer, G. Binnig, C. F. Quate, and Ch. Gerber developed the technology further to use detection of atomic forcefields to map out surface topologies [1]. The development of AFM that can achieve nanoscale resolution under liquid environments and with low forces allows the observation of soft, native-like biological structures. AFM has led to pivotal insights in molecular and mesoscale biological structures.

Optical tweezers used in biology (1987)

Arthur Ashkin and J.M. Dziedzic demonstrated optical trapping of viruses and bacteria [1]. Arthur Ashkin, Gerard Mourou and Donna Strickland all received the Nobel prize for this investigation and their application to optical systems. Donna is one of a small number of women to have received the Nobel prize in Physics for her development of the laser that is critical for this technique. The technique has been used ever since to manipulate and study single cells.

Active matter (1995 to now)

Understanding how the complex behaviour of bird flocks, fish schools, insect swarms, bacterial suspensions, cytoskeleton, epithelial tissues, and others arise through the interplay of individual “agents” that consume energy to move or exert forces. The Vicsek model is the prototype of many such systems.

Quantitative synthetic biology (2000)

Development of genetic circuits that act as a toggle switch [1] and an oscillator [2]. Besides shedding light on the function of more complex gene regulatory networks having similar motifs, similar circuits have subsequently been applied to many problems in biology (cell labelling, logical circuits). Petra Schwille has driven this field through her work in trying to build a cell division system from the bottom up (reviewed here).

Noise in gene expression (2002)

The amount of a protein produced from a specific gene fluctuates in time and across cells/organisms due to the inherently random nature of chemical reactions. Early works focused on prokaryotes [1], [2]; further research has demonstrated the presence of noise in eukaryotic cells, the role of network motifs in noise amplification/suppression, the role of noise in survival strategies such as bet hedging, and many others.