Overton, Charles Ernest
OVERTON, CHARLES ERNEST
(b. Stretton, Cheshire, England, 25 February 1865; d. Lund, Sweden, 27 January 1933), cell physiology, pharmacology.
Overton was the son of the Reverend Samuel Charlesworth Overton and Harriet Jane Fox, daughter of the Reverend W. Darwin Fox, a second cousin of Charles Darwin. He was educated at Newport Grammar School until 1882, when his mother, for health reasons, moved with her children to Switzerland. He studied biology, especially botany, at the University of Zurich, where in 1889 he obtained the Ph.D. and, in 1890, was appointed Dozent in biology. From Zurich, Overton moved to the University of Würzburg in 1901 as assistant to Max von Frey in the physiology department. In 1907 he accepted the chair of pharmacology at the University of Lund, where he remained until his retirement in 1930. In 1912 he married Dr. Louise Petrén. Overton published his most important papers between about 1893 and 1902. His productivity subsequently decreased considerably, owing to impaired health.
As early as 1890–1893, before finding his final field of research, Overton had done pioneering work in plant cytology, in which he showed that the haploid chromosome number is characteristic not only of the sex cells themselves but also of the whole gametophyte.
At about this time Overton became interested in the fundamental problem of how living cells, isolated from their surroundings so that the solutes in the sap are prevented from diffusing out, are nevertheless able to take up nutrients from without and to throw off the waste products of their metabolism. In the 1890’s living cells were commonly thought to be virtually impermeable to the great majority of solutes but readily permeable to water. Overton, however, observed that there is a whole series of intermediate cases between substances totally unable to penetrate living protoplasts and those that do so as rapidly as water. Moreover, he found that all the widely different kinds of plant and animal cells are surprisingly similar in their permeability properties. In 1899 Overton pointed out a striking parallel between the permeating powers of different substances and their relative fat solubility—that is, their partition coefficient in a system composed of fat and water. The smaller this coefficient, the more difficult the passage of the substance through the protoplast. This was at first sight a very surprising result, but Overton explained it by assuming that the invisible plasma membranes, already theoretically postulated by Pfeffer, are “impregnated” with fatlike substances, such as cholesterol or phosphatides.
This hypothesis, now universally known as Overton’s lipoid (or lipide) theory of plasma permeability, was first published in a preliminary form, his intention being to present the detailed basis for it in a later extensive publication. The larger work containing definite proof of the theory was, however, never finished. Thus, it is understandable that, although the theory aroused a great deal of interest, it also met with doubt and even violent opposition, especially since Overton never replied to the attacks on his views. Apart from minor modifications, however, later experiments have confirmed his results.
In 1896 Overton pointed out that both plant and animal cells can transport solutes against the concentration gradient. Such an active transport carried out at the expense of energy set free by metabolic processes is a phenomenon quite different from the simple diffusion of substances through the protoplasts. Active transport, as Overton anticipated, has proved to be of fundamental importance to living cells.
In carrying out permeability experiments with muscle cells, Overton found that their irritability is reversibly lost when the sodium ions that are normally present between them diffuse out from the muscles. To explain this and other related observations, he tentatively proposed the hypothesis that for an extremely short interval the surface of the contracting muscle fibers becomes permeable to sodium and potassium ions. This fundamental idea in the theory of propagation of impulses in nerves and muscles was worked out almost fifty years later by A. L. Hodgkin and A. F. Huxley, for which they were awarded the Nobel Prize in physiology or medicine in 1963.
In studying the permeability properties of plant and animal cells, Overton observed that those substances which, owing to their great lipide solubility, penetrate the protoplasts most rapidly also have the ability to produce narcosis. It was only natural that he assumed their narcotizing effect to be in some way dependent on their lipide solubility. Almost simultaneously with Overton but independently of him, the pharmacologist Hans Horst Meyer reached much the same conclusion. Although the Meyer-Overton theory does not offer a complete explanation of the mechanism of narcosis, it remains an important starting point for newer, more elaborate theories of this phenomenon.
A gentle and placid man, Overton had a striking intuitive ability to recognize the great, fundamental problems and to envision a means of solving them without recourse to complicated apparatus. He never founded a school in the proper sense of the word, and his publications, almost all of which were written in German, do not seem to have been widely read in the original, especially in English-speaking countries. Nevertheless, his influence on the development of cell physiology and pharmacology has been strong and long-lasting. He was one of those scientists whose stature is more obvious after their death than it was during their lifetime.
Overton’s most important publications are “On the Reduction of the Chromosomes in the Nuclei of Plants,” in Annals of Botany, 7 (1893), 139–143; “über die allgemeinen osmotischen Eigenschaften der Zelle, ihre vermutlichen Ursachen und ihre Bedeutung für die Physiologie,” in Vierteljahrsschrift der Naturforschenden Gesellschaft in Zurich, 44 (1899), 88–135; Studien über die Narkose (Jena, 1901); “Beiträge zur allgemeinen Muskelund Nervenphysiologie,” in Pflügers Archiv für die gesamte Physiologic, 92 (1902), 346–386; and “über den Mechanismus der Resorption und Skretion,” in W. Nagel, ed., Handbuch der Physiologie des Menschen, II (Brunswick, 1907), 744–898.
For a more complete biography and bibliography, see P. R. Collander, “Ernest Overton (1865–1933), a Pioneer to Remember,” in Leopoldina, 3rd ser., 8–9 (1962–1963), 242–254.