“The problem of the physical chemistry of the development of form of organisms is a field with a great unknown and immensely existing. To pursue it is like trying to account for the rainbow in the 14th century, to do celestial mechanics before Newton, or to pursue quantum theory in the 1890s.”
See also: Two cultures tensionsIn discussing his Figures 3.2 and 3.3, in his Shaping of Life, which show his five collected data points of calcium concentration vs Acetabularia hair whorl spacing, and how he made entropy and enthalpy determining van’t Hoff plots from this data, Harrison humorously recounts the multi-disciplinary reaction to his work noted at few talks he gave on this data at various meetings: [7]
(1) When I gave a talk on Turing reaction-diffusion theory to my home chemistry department, one of my colleagues remarked:“It’s nice to see that such an apparently difficult problem can be explained by a couple of differential equations.”
I thought ‘Oh, dear. I haven’t got over to him that most biologists reject this theory.’
(2) A biologist said to me:“Wouldn’t it be a pit if the explanation turned out to be just physical chemistry”
wrinkling his nose as if experiencing a bad smell.
(3) After a talk in a chemistry department, one of the audience said to me:“What I like about your [work] is that you go straight from the green stuff to differential equations.”
(4) At a poster show at the developmental biology meeting, my collaborator David Holloway was waylaid by a posse from another modelling group who started their work from molecularly known genetic networks, saying:“Why don’t you guys use real molecules?”
Left: a diagram of the hair whorl pattern formation in so-called life-cycle of Acetabularia acetabulum (Dasycladales), aka the ‘mermaid’s wineglass’, with which Harrison conducts a study in which he varies temperature and calcium concentration [Ca⁺⁺], measuring correlative changes in hair spacing, data from which he, supposedly, makes a van’t Hoff plot, from which he calculates enthalpy and entropy of binding, namely the binding of Ca⁺⁺ to a putative receptor R. [8] Right: an image (Ѻ) of Acetabularia acetabulum. |
“Morphogenesis would be best explained as a process in which the organism’s shape emerges as it achieves minimum free energy (thermodynamic equilibrium) through the disposition of intercellular forces.”
Harrison's circa 1980 cell-as-molecule approach: viewing a cell as a type of large molecule, formed under free energy minimum principles; a model loosely-inspired by the 1970 work of embryonic chick tissue formation experiments of American cellular pathologist Malcolm Steinberg. [1] |
“This picture of cell-as-molecule is a very good start, which needs a lot more attention from physical chemists to establish its scope and limitations. For example, a cell is never, in respect from what is going on inside, at equilibrium so long as it is alive. Sorting-out or engulfment occurs much too rapidly to be attributable to Brownian motion of such large things as cells. Nevertheless, the active movement of cells may in some instances be random, and the use of equilibrium concepts for their behavior in assemblies will then be valid, with appropriate careful redefinitions of the equivalents to some thermodynamic properties of molecular assemblies.”
“It is possible for a structure, essentially heterogeneous, to arise and be maintained by chemical reactions and transport processes, when the equilibrium state would be homogeneous. Kinetics alone then determine the gross morphology of the system. I would like to call such things ‘kinetically maintained structures’. Some thermodynamicists refer to them as ‘dissipative structures’.”The Shaping of Life
Lacking this, Lionel’s approach, best exemplified in his Acetabularia experiments [Chapter 3], was necessarily empirical, and as such, entirely characteristic for a physical chemist: measure patterns and pattern change directly, vary the conditions over which you have control, and analyze the outcome. Here he came closest to putting meaningful numbers on an otherwise mysterious process, deducing such exotic thermodynamic beasties as ΔH and ΔS from measurements requiring only a dissecting microscope, thermometer and micrometer measuring scale. A complete thermodynamics of living systems is clearly some distance in the future, but of various routes to that future, this is certainly one.”
“Harrison’s proximate goal was to discover how patterns of living things are formed or, to use the title form and earlier draft of this book, ‘how life devises its shapes and sizes’. Cautious academics will avoid such fields until the ground rules are better worked out, and until it is clear that a predictable and, hence, grant-worthy rate of progress can be sustained. Coming from the relatively mature discipline of surface chemistry, Harrison, by contrast, was immensely excited by the prospect of doing research on aspects of biology still at the very early stage of their development. It was, to him, like doing ‘celestial mechanics before Newton’.”— Thursont Lacalli (2009), "Foreword" to The Shaping of Life [7]
“Here [Harrison] came closest to putting meaningful numbers on an otherwise mysterious process, deducing such exotic thermodynamic beasties as ΔH and ΔS from measurements requiring only a dissecting microscope, thermometer and measuring scale.”— Thursont Lacalli (2009), "Foreword" to The Shaping of Life [7]
“Of course the first thing to do was to make a grand survey of the country she was going to travel through.”— Lewis Carroll (1871), Through the Looking Glass, quote Harrison intended to use as epigraph to preface of sequel to Kinetic Theory of Living Pattern (1993) [7]