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Martin Rodbell and Alfred Gilman filled in the gap, “an intermediate set of elements”, that was left open by Norbert Wiener when he wrote: “In such a theory, we deal with automata (machines in the metal or in the flesh) effectively coupled to the external world, not merely by their energy flow, their metabolism, but also by a flow of impressions, of incoming messages, and of the actions of outgoing messages. The organs by which impressions are received are the equivalents of the human and animal sense organs. They comprise photoelectric cells and other receptors for light; radar systems, receiving their own short Hertzian waves; hydrogen-ion potential recorders, which may be said to taste; thermometers; pressure gauges of various sorts; microphones; and so on. The effectors may be electrical motors or solenoids or heating coils or other instruments of diverse sorts. Between the receptor or sense organ and the effector stands an intermediate set of elements, whose function is to recombine the incoming impressions into such form as to produce a desired type of response in the effectors”. (Wiener N. Cybernetics: or control and communication in the animal and the machine. MIT press, paperback 2nd edition, 1965; p. 42)
Indeed, in his book on Cybernetics, Wiener never describes in detail the connection between receptors and effectors but, in a different chapter, he does elaborate on transducers. He defines them as apparatuses which have as an input a single function of time (example sound wave detection) and which as their outputs another function of time (example generation of an electric current). The output is completely determined by the past of the input; but in general, the adding of inputs does not add the corresponding outputs. Such pieces of apparatus are known as transducers. One property of all transducers, linear or non-linear, is an invariance with respect to the translation in time. If a machine performs a certain function, then, if the input is shifted back in time, the output is shifted back by the same amount. (Wiener N. Cybergenitics: or control and communication in the animal and the machine. MIT press, paperback 2nd edition, 1965; p. 178).
Martin Rodbell and Alfred Gilman were interested in how receptors communicate with effectors, and in particularly with adenylyl cyclase. Rodbell, of a more philosophical nature, had concocted a conceptual scheme in which he placed a “transducer” in between the two (see image above and below). The transducer should be understood here as the translator in time. As for the choice of the term, in his Nobel speech he pays tribute to Oscar Hechter (Chicago) ((Rodbell M. Nobel lecture, December 8, 1994). Not only had Hechter found good evidence that different hormones must act on a common pool of adenylyl cyclases, because maximal doses of each failed to show additive responses in rat adipose membrane fractions (Bär, HP, Hechter O. (1969). Adenyl cyclase and hormone action. 1. Effects of adrenocorticotropic hormone, glucagon, and epinephrine on the plasma membrane of rat fat cells. Proc. Natl. Acad. Sci. USA 63, 350-356), he apparently was familiar with Wiener’s cyber-speak and shared his knowledge with Rodbell on several occasions. Their first discussion, held in a Washington hotel bar on the eve of an NIH colloquium (November 1969, in honour of the discoveries of Earl Sutherland) is thought to be at the origin of the transducer concept (published for the first time in Rodbell M, Birnbaumer L, Pohl SL, Krans HMJ. Hormone receptors and adenyl cyclase activity in mammalian cells. In: Rodbell M, Condliffe P, editors. Colloquium on the Role of Adenyl Cyclase and Cyclic AMP in Biology. Fogarty International Center, U.S. Government Printing Office; Washington, D.C.: 1970b. pp. 59–76). Note that initially GTP was not yet present in the scheme and that membrane lipid was the suspected transducer (because of the sensitivity of the assay system to detergent).
With the discovery of GTP-binding proteins as “transducers”, Rodbell and Gilman not only had defined the “intermediate set of elements” that connect receptors with effectors, they also revealed a mechanism that Earl Sutherland had not yet substantiated, namely how different hormones stimulate (or inhibit) the same pool of membrane-bound adenylyl cyclase. Scientific theory at that time was strongly influenced by the model of allosteric regulation as proposed by Monod, Wyman and Changeux (Monod J, Wyman J, Changeux JP. 1965. On the nature of allosteric transitions: a plausible model. J.Mol. Biol. 12:88–118) and Sutherland had suggested that different hormones control catalytic activity by combining with a common regulatory subunit of adenylyl cyclase.
The late Martin Rodbell could not claim the term transducer or transduction as his intellectual property. As for many discoveries there is never one person that deserves all the credit. The term transduction was initially (starting in the fifties) used to describe the process of bacterial DNA transfer by bacteriophages, and then progressively (in the early seventies) it entered into the vocabulary of scientists working in the field of sensory organs, such as vision, olfaction, gustation and hearing. Whether these were also inspired by Wiener’s book is unknown to me. Indeed, the GTP-binding protein that was shown to act downstream of rhodopsin was named “transducin” precisely in the same year as Rodbell published his much cited review on “The role of hormone receptors and GTP-regulatory proteins in membrane transduction” (Fung, BKK, Hurley JB, Styer L. Flow of information in the light-triggered cyclic nucleotide cascade of vision. PNAS USA 1981, 78:152-156; Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 1980; 284:17-22). Robell’s article, however, exposed the term to a very wide public and the word was carried by a future Nobel laureate.
Dr Kramer’s 3rd edition of Signal Transduction is a reference on cellular signaling processes that provides a historical overview of how the concept of stimulus-response coupling arose in the early twentieth century and shaped our current understanding of the action of hormones, cytokines, neurotransmitters, growth factors and adhesion molecules.
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About the Author
IJsbrand Kramer (principal author) is a Professor at the University of Bordeaux, working in the European Institute of Chemistry and Biology (IECB). He holds a Bachelors and Masters degree in BioMedicine from the University of Utrecht, The Netherlands, with a one year research-excursion in the Department of Cell Biology at the University of Liverpool, UK. Most of his research centers on the theme of inflammation, starting with neutrophils and the NADPH oxidase, synovial fibroblasts and destruction of the joint and more recently podosomes formation and extracellular matrix destruction in vascular endothelium. He has been co-director of two European Programmes (Interbio and Transbio) that aimed at enhancing industrial innovation in the biomedical sector in the South West European Region (SUDOE).
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