W.S. McCulloch
On June ninth death by coronary occlusion ended the fifty-fifth and, despite repeated heart attacks, the most productive year of Dusser de Barenne's productive life. Born at Brielle, Holland, June 6, 1885, to Dorothea Vogelzang and Elize M. Dusser de Barenne, and the last of the name, he had finished his medical training and begun research in Amsterdam University by 1909. His first paper published the following year earned for him the nickname he enjoyed—“strychnine,” for in compelling recognition of his scientific ability it indicated that fruitful course which he never relinquished. Freely translated, the title reads “The Working of Strychnine on the Central Nervous System, an Inquiry as to the Physiological Differentiation of Various Mechanisms of the Central Nervous System.” In presentation that paper is dramatic; in substance it reveals the man. An unknown man, with purely negative findings, he annihilated the then accepted theory as to how and where strychnine acts by laying his head on the block for the validity of his observations. In the thirty years that followed his head was on that same block one hundred and twenty-five times and no one struck it off. Typically, he advanced no alternative theory nor would he consider one except as accumulating facts compelled him to it. From the beginning he lived by Ludwig's precept,—never to think if it is possible to experiment.
He experimented from 1909 to 1911 while teaching in Amsterdam. The findings constitute nine papers of which seven record how in his hands strychnine locally applied had become a most apposite probe for exploring functionally many mechanisms of the central nervous system which without it had remained unknown. He had found his way into the devious and complex paths mediating sensibility. He experimented from 1911 to August 1914, although busy as a psychiatrist at the Meerenberg Lunatic Asylum, and from 1914 until the end of the war, although serving as a medical officer with the colors. Then he returned to the laboratory as Lecturer and Privat-Docent in the Departments of Pharmacology and Physiology at Utrecht University where he continued to experiment. Papers published throughout this time are sufficiently varied to indicate the breadth of his physiological interests and significant enough to have made for him a name second to none in Holland. It is not surprising that, working intimately with Magnus and collaborating with de Kleyn, much of his attention was devoted to problems of postural mechanism, to tonic and labyrinthine reflexes. It would be impossible to pick up all the threads of that busy and productive period. In 1915, by minute local applications of strychnine to various areas of the cortex of the cat, combined with clinical observation of the animal's exaggerated responses to stimulation, he had delimited that portion of the cortex which is indubitably concerned in bodily sensations and had indicated to what parts of the animal particular parts of the cortex correspond. In 1924 he visited Sherrington's laboratory where he made similar experiments upon the monkey. Within five years the paper embodying those observations had become a classic of Neurophysiology. In 1926, in collaboration with Sager, he used the same combination of methods on the cat to explore the last relay of sensation, the thalamus opticus. Thus, by 1927, he had, by local strychninization, delineated the entire central system subserving bodily sensation. Even this achievement fails to reveal the caliber of the man.
To understand that, one must know how those accidents and peculiarities which would have been the catastrophies and vices of a little man became the opportunities and virtues of Dusser de Barenne. Within a year the three chairs of Physiology in Holland, any one of which he could have filled with distinction, fell vacant and were, for extraneous reasons, occupied again by others. Holland's loss was our gain, for by 1930, established here as Sterling Professor of Physiology, he was building the Laboratory of Neurophysiology, free of those obligations to teach which would have burdened him in Holland, and provided with facilities for experimentation which he would have lacked in his native land. The solidity of his untrammeled work soon made itself felt.
But shortly thereafter his wife, Kate Snellen, who had borne him three daughters, Charlotte, Dorothea, and Elizabeth, and to whom he was devoted, suddenly died. Characteristically, even then, depressed so much he wondered whether he could continue science, he lay awake night after night thinking only that there was no way forward, no method to determine which layers of the cortex were requisite for sensation, until, in the middle of one long lonely night he began to imagine breakfast. “Then,” to quote him, “I saw an egg cooking slowly. I jumped from bed and rushed to the laboratory, heated a brass rod in boiling water and applied it to the cortex. In twenty minutes there was the method of laminar thermocoagulation!” It is equally characteristic of the man that he used that insomnia which never left him as an opportunity to become most erudite. As referee editor of the American Journal of Physiology and co-founder and co-editor of the Journal of Neurophysiology he made that erudition as serviceable to the publications of others as it was to his own work.
It was not until 1935 that he married again, this time Emily Greene by whom he had another daughter, Marion. He had desired a son to carry on the name but lacking one he became the increasingly tolerant pater familias of what he called his “official family.” To succeed at all any man so heartily kind and trusting must carry a shield. To the outsider he appeared suspicious and as blunt as only those can afford to be who are completely humble to the fact. But once past that guard all were compelled, by his very openness, to give him their best. Here his peculiarities appeared.
He was quick tempered, but the explosion, like a thunderstorm, served to clear the air. He was impatient of all delay but his inability to wait was responsible for discoveries, notably that extinction of response which is seen when a second period of stimulation follows too soon after a first. Yet, once a fact came to light he would relentlessly continue the experiment until it was proved past per adventure. We have had, as he would say, “to go doggishly on” for 55 hours repeating an observation every three minutes on a single point on a single hemisphere before he was satisfied. He was slow and uncertain of his own reasoning powers when the argument became abstract or mathematical and would insist that the question was either just words or could be reduced to a question of fact and settled by experiment at once. Thus, theory was compelled to be subservient to experiment at every step, and the step was taken then and there. It would be useless to catalog the technical difficulties which such a course entailed—and he was no technician—but he first saw the requirement and had some idea as to the method. From this sprang work with Marshall, Wendt, Lane, Prescott, Nims, and Goodwin on systems for altering, stimulating, measuring, and recording many hitherto uncontrolled variables affecting the experiment. These have opened up two profitable lines of investigation. The first of these was an analysis of the way in which antecedent activity of the central nervous system altered the response to subsequent stimulation. The studies ranged from electric recording of hitherto unsuspected after-discharges persisting sometimes for minutes even when they led to no overt act, through slow voltage changes and concomitant threshold variations, to alteration of the acidity of the brain resulting from its activity and in turn affecting that activity. It was in these experiments that he blazed the trail for the physiologically controlled study of the chemistry of the brain in situ, a study which he lived long enough to see well started in collaboration with Nims, Marshall, and Stone. No matter whether he had formulated these problems, supervised every procedure and assisted in recording the results he always signed under protest, saying, “No one thinks I am in chemistry except in strychnine.”
In 1935 Sager came from Bucharest to Dusser de Barenne's laboratory to map with him the thalamus opticus of the monkey, as they had that of the cat. This done, the groundwork was then laid for the second line of investigation. We had been working for some time on the effects of various procedures,—stimulation, thermocoagulation, etc.,—on the electrical activity of the cortex, when he finally gave permission to put on strychnine and watch the oscillograph. His face when he saw the first record is as unforgettable as the strychnine spike itself. Thenceforth local strychninization and recording of electrical activity became his method for investigation of the functional organization of the sensory cortex; first, of any given area of the cortex, next, of larger regions like the arm-subdivision of the sensory cortex, then, of the entire sensory cortex and, finally, of the relation of the sensory cortex to thalamus opticus, to striatum, even to nucleus gracilis and cuneatus. As soon as these were mapped in the monkey he turned to the chimpanzee to discover finer differentiations and a better indication of what might be expected in man. Experiments on the chimpanzee were well underway when Dusser de Barenne died, but only a preliminary note and a short abstract have as yet been published. Several manuscripts which he had almost completed and others for which his notes and conclusions exist are still to be published. The projected experiments which he had tentatively outlined will be performed and the findings published as nearly as possible as he would have had them.
Those who have collaborated in the strychnine experiments—Brody, Ogawa, Bailey, and Garol—have sensed the increasing pressure under which he worked as he sensed the coming end of his labors. Both in the laboratory and as editor of the Journal of Neurophysiology he brought the weight of his accumulated wisdom to bear efficiently in a matter of minutes rather than of hours or days. His lectures and demonstrations, always delightful, became more energetically pointed. Each day fewer words served him for more sense. So the life devoted to functional analysis of the central nervous system culminated in five years of work as intense as it was productive. In Neurophysiology it will be hard to find his like, and we who were with him daily will miss most the light that was forever dancing in his eyes.
—W. S. McC.
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Keywords: Truth, System, Paper, Year, Findings, Occlusion, Strychnine, Theory, Knowledge
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