Senior Physiologists' News
Letter to Donald C. Marsh

Paul Bach-y-Rita writes: “I am responding to your letter of June 5. For many years I have enjoyed reading letters from Senior Physiologists, and now I have become one! I am pleased to state that I am still a full-time Professor of Orthopedics and Rehabilitation, and of Biomedical Engineering at the University of Wisconsin, Madison. Your letter came at an interesting moment. This April I celebrated my 70th birthday, shortly after I was diagnosed with stage 4 lung cancer. Both of these events are inducements to reviewing my life’s work.
“Within the last few years, my federal funding has increased dramatically. Within the last year my group has received approximately 4 million dollars, including my five year NEI RO1 for 2.1 million that will begin this Summer, and we are expecting another 2 million within the next few weeks. Our results have been extraordinary (e.g., http://www.wicab.com), and particularly satisfying is that my work in nosnsynaptic diffusin neurotransmission, late brain plasticity and sensory substitution for losses such as blindness and vestibular loss, all of which were first published approximately 40 years ago, are now becoming accepted. In particular, tactile vision substitution, which we first absolutely proved in a Nature paper in 1969, is now getting a lot of support, not only in this country, but in several European countries, as well as Canada and Mexico.
     “Several years ago, with NIH sponsorship, a major advance in the human-machine interface (HMI) technology was developed and patented by the University of Wisconsin (WARF), which assisted me in developing a company to commercialize devices based on our tongue HMI, and much of the new federal funds have been to the company (including two NIH phase 2 SBIRs) for this purpose.
     “So in summary I am continuing both my theoretical and practical research and development activities, while trying to overcome a major illness. The web page mentioned above has many of my publications.”


Letter to G. Edgar Folk, Jr.

Howard Jacobson writes: “I apologize in advance for taking so long to get back to you to thank you for your kind invitation. As you may have guessed, I have been alarmed at your health care system for a long time. Maybe the time has come for some beginning steps. Physiology is so crucial that it needs to be involved. I hope I gave it a little shove.” 

Letter to Alan Hofmann

Sid Ochs writes: “Thank you for your letter asking ‘what are you doing now?’ Since my retirement in 1994 I have continued working on problems relating to nerve functions, in particular on axoplasmic transport, though increasingly writing on the history of nerve. This has resulted in a book titled, A History of Nerve Functions: From Animal Spirits to Molecular Mechanisms published by Cambridge University Press this July. When the Cambridge University Press asked for a book on nerve back in 1983, I thought that one dealing mainly with the history of transport in the last half of the century would suffice. It would show how the mechanistic theory of transport advanced by Paul Weiss in mid-20th century, the dominant view at the time, holding that the axoplasm
produced in the cell body was the force for its movement down within the fibers, much as lead is propelled in an automatic pencil, at a rate estimated at several mm per day, a continual ‘axonal flow,’ was replaced by the recognition of an energy driven fast transport mechanism moving materials down at a rate of more than 400 mm per day. Its nature was revealed when the necessary research tools were made available in the last half of the 20th century; isotopes to trace the path of transport of newly synthesized materials in the fibers, biochemical processes and micro-assay techniques to show the flow of energy needed for transport, the revelation of protein structure, the role of DNA and RNA in protein synthesis in the cell body, electron microscopy revealing the molecular structures in the nerve fiber underlying transport, etc. The story shows how transport underlies other basic nerve functions; by the supply of ion channels and pumps to the membrane underlying conduction of the action potential, metabolic components to supply energy locally to the transport mechanism, turnover of structural elements, and neurotransmitters and transmitter-associated components carried down to the terminals. Further, in the brain transport in the dendrites of neurons appears to underlie learning and memory. The story of such a protean process could well be of interest not only to the neuroscientist but as well to those in other sciences and medicine. 
“In the course of writing, I soon saw that for a full appreciation of transport a more extended examination of its history, the concepts of transport given by Gerard, Young and in the earlier decades of the century Goldscheider and Ramon y Cajal. Their concepts in turn were based on fundamental advances made in the 19th century, in particular the work of Waller in the middle of the 19th century which pointed to the influence of the cell body on the viability of the nerve fiber, an influence that he inferred from the degeneration of fibers amputated from their cell bodies and the recognition of the neuron. Though considered to be a concept recognized toward the end of the19th century, it made an early appearance in the 1830’s when Remak showed nerve fibers emerging from cell bodies. Of interest were theories of transport in nerve that were advanced before then, theories that had their beginning in the belief of animal spirits, a concept that arose in ancient Greece when science itself first originated. This then resulted in my book A History of Nerve Functions: From Animal Spirits to Molecular Mechanisms. I am now in the course of extending studies described in the book which relate transport in neurons in the cortex and brain centers to higher cognitive functions.
     “In your letter you ask ‘which of your contributions do you think most important?’ These would be the recognition and the characterization of fast
axoplasmic transport with a fast rate of 410 mm per day, the process present in all types of nerve fibers, in a wide range of mammalian species. We showed that transport is dependent on oxidative metabolism supplying ~P in ATP to its mechanism. Other contributions were the recognition and the analysis of the form change of fibers seen as beading, studies of the direct cortical responses and spreading depression of Leão in the cerebral cortex. I hope that my text, The Element of Neurophysiology published in 1965 by Wiley, my monograph “Axoplasmic Transport and its Relation to Other Nerve Functions” published by Wiley in 1982, the founding and editing of the Journal of Neurobiology, and my new book on History of Nerve Functions will also be considered useful contributions. 
     “You ask ‘do you have a choice anecdote involving your career or an eminent physiologist?’ While I was a PhD graduate student of Ralph Gerard at the University of Chicago in the late 1940’s and early 1950’s, the dominant theory of neural activity in the central nervous system at the time was that the electrical discharge in presynaptic nerve fibers was the agent exciting neurons they end on, the concept advanced by John Eccles that was widely accepted at the time. Eccles, using fine microelectrodes based on those originally developed by Gilbert Ling in Gerard’s laboratory, found that the electrical impulse invading the presynaptic nerve terminals ending on spinal cord motoneurons was followed by a response in the motoneurons only after a delay of a millisecond or two. This finding decisively falsified the concept of electrical transmission. When Eccles visited Gerard at the University, Gerard asked me to come into the office where Eccles recounted his new discovery in that my doctoral studies were on the effect of current flow in the spinal cord of cats based on Eccles’ electrical theory. Gerard, who had theorized that electrical fields in the brain integrated neuron activity on the basis of Eccles’ theory was visibly discomfitted and attempted to protect the electrical theory. This impressed me with how emotional the supposed unperturbedly analytic mind of the scientist can be where fundamental beliefs were at issue, something I saw repeated many times over the years.”
     “Eccles’ finding using microelectrodes showed the value of a new technique to answer a basic problem. However, too great an attachment to a new technique could also be a hindrance. When I later was a postgraduate student with van Harreveld at the California Institute of Technology, we worked on the problem of the profound shut down of brain activity seen as a slow spreading wave of depression of the cortex, the phenomenon discovered by Leão. We found the spreading depression to be due to the movement of ions and water from the intercellular space of the cortex into neurons and glia, from an intercellular space of some 20-25%, one much larger than the 5% determined from electron micrographs. The smaller space was shown due to the shift of ions and water into the cells that incurred in the preparation of cortical tissue for electron microscopy. This was indicated by an increase in the electrical impedance of brain tissue and by freeze-substitution. Such a larger space in the normal cortex was violently opposed by the electron microscopists at the time who felt that because of the superior view of fine structure afforded by the new electron microscope and their indication of the smaller space was therefore inherently better. 
     “You ask ‘do you have any words of wisdom to pass on to your younger colleagues?’ I would like to say to work on some important fundamental problem that really interests you. But this is not as easy to do today as it was in the earlier decades after WWII when grants were easier to get. Hopefully, the present tendency to award grants for ‘safe’ research projects with the lure of commercial drug products in the offing, may change and more grants given to projects where taking a chance on a possible fundamental advance is encouraged.” 

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