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Winter 1959 The Rockefeller Institute Quarterly 1959, vol. 2, no. 4 The Rockefeller University
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VOLUME 2 NUMBER 4 WINTER . 1959 page 1 THE NATURE OF THE NERVE IMPULSE AND ITS CONDUCTION
1 GRADUATE STUDENT RESIDENCE OPENS
7 THE TRUSTEES: GEORGE H. WHIPPLE, M.D.
9 THE FIRST SIGMA XI INITIATION
10 ZIMBLER SINFONIETTA
10 KARL MARAMOROSCH HONORED
10 LEE D. PEACHEY AWARDED LEITZ FELLOWSHIP
10 HOLIDAY FESTIVITIES
11 THOMAS MC ELRATH DEBEVOISE THE NATURE OF THE NERVE profoundly important step in the history of physics and technology. Out of it, too, came techniques in electrophysiological in- IMPULSE AND ITS CONDUCTION vestigations that are being used today. It was a long way from the observation that WHATWE KNOW of the world around us, impulses and much of what we have to electrical stimulation caused a muscle to what we experience within ourselves, and write about concerns the discovery and twitch to the highly refined ideas of today our various physical, emotional and intel- elaboration of this fact. about the why and how of nervous func- lectual manifestations are determined by The Italian physiologist, Galvani, acci- tion. dimly understood processes occurring with- dentally discovered nearly two centuries It is a common fact of our experience in and among some million billion nerve ago that an electrical shock to a frog's that sense impressions may be strong or cells within our bodies. As Wilder Pen- nerve would cause its muscles to twitch. weak, and a muscle may be tensed much or field put it a few years ago: "In them Later he observed (also accidentally) that little. If these stronger or weaker events are throbs the essential energy of life. Through decapitated frogs suspended by brass hooks controlled by sensory and motor nerve im- them the body and the mind alike are con- through their spinal marrow, twitched pulses it is natural to suppose that the im- trolled, and sensorimotor mechanisms are when they were hung over an iron railing pulses must also be stronger or weaker as coordinated and integrated in such a way around his laboratory balcony. He tried the case may be. In a sense this is so, but that conscious thought and direction of other metals with roughly the same result. the strength of the impulse varies in a sur- human activity are possible." Galvani was convinced that the metal prising way. The facts are that although a It is little wonder then that &urobiology, only conducted "animal electricity" already stimulus to a sense organ, ,a nerve, or a the study of the structure and function of present, the flow causing the twitch. Volta, muscle fiber may produce local effects the nervous system, has been an important a contemporary Italian physicist, was which may vary with the strength of the area of research at The Rockefeller Insti- equally convinced that the electricity arose stimulus, the individual nerve impulse, tute for many years. Something of what is from the dissimilar metals and stimulated which travels along the nerve away from known about the nervous system as a result the muscle externally. We now know they the affected region, is not significantly of work carried on by members of the fac- were both right, thoughVoltals purely phys- changed in intensity by making the stimu- ulty of the Institute will be set forth in this ical interpretation was more fruitful at lus stronger or weaker. It is rather like the article-too sketchily, perhaps-but not the time. Out of the storm of controversy progress of burning in a lighted fuse, without interest, we hope, and profit to our that resulted from Galvani's experiments which proceeds at the same speed and with readers. came Volta's development of the electrical the same amount of sputtering as it goes The nervous system is a vastly complex cell composed of two different metals, a (continued on page two) and highly integrated assembly of about i,ooo,ooo,ooo,ooo,oo~neurons,or nerve cells. Nearly all of them are located in the brain and spinal cord, referred to as the GRADUATE STUDENT of the academic life." Three of the four central nervous system, but long fibers floors of the building are devoted to resi- from these cells extend into the remotest RESIDENCE OPENS dences, 50 being single rooms. But in keep- part of the body. These tiny thread-like ing with the modern trend in graduate fibers from individual neurons are gath- A LANDMARK in the Institute's new his- schools, 29 suites for married students are ered together into bundles or cords which tory as a graduate university of science was provided. The suites consist of a living we recognize as nerves. Those extending reached on December 19, 1958 when the room, bedroom, kitchenette, and bath. outside the brain and spinal cord are re- new Graduate Student Residence Hall was Recreational and athletic facilities will ferred to as the peripheral nerves. Early opened for occupancy. As part of the com- be provided on the first floor and base- anatomists misunderstood the function of plex of new buildings and gracious land- ment, where there are squash courts, fenc- nerves, thinking them to be cords, perhaps scaping of the Institute campus, the Resi- ing mats, pool, billiards, and Ping-pong for mechanical purposes. The very word dence Hall will do much to foster the asso- tables with lockers for men and women. "nerve" reflects their confusion, for it is ciation between students and faculty in a There will also be a reading room and so- taken from the Greek word v~vpov,mean- true academic community. Instead of fol- cial hall. ing sinew, tendon, or bow string. lowing the original plan to operate a sepa- The Residence Hall was constructed in Information flows up and down the rate students' commons for breakfast and two stages, and as a result was occupied peripheral nervous system-from sense re- dinner, resident students dine in the fac- while the rest is nearing completion. When ceptors of various kinds into the central ulty refectory of Abby Aldrich Rockefeller final construction and landscaping are ac- nervous system and out again, carrying in- Hall in the morning and evening. complished this Spring the Institute's 13- structions of various sorts. Incoming and No longer need we feel, as was said of acre campus will offer gracious living ac- outgoing fibers are often in the same nerve. the scattered and crowded housing condi- commodations as well as superb scientific The nerve impulses, whether incoming tions at an ancient university in New Eng- and educational facilities in a setting of (sensory), or outgoing (motor), are now land, that our students encounter "a shab- great natural beauty that is unsurpassed in known to be essentially similar electrical by introduction to the much bruited dignity the city of New York. nerve impulses that are transmitted. As we have pointed out, a single nerve may contain hundreds of individual fibers, each carrying an impulse of different char- acter from as many different sense recep- tors. Adrian and Zotterman were able to minimize the confusion from these many sources of impulses, however, by dissect- ing away all but one or two of the sensory origins of a nerve, which then would pre- sumably contain only one or two active fibers. They found that stronger stimuli were reported in two ways: not only did the impulse frequency from any one fiber increase, but more fibers responded by con- ducting impulses, because the sense recep- tors to which they were connected were of differing sensitivity. In no case was it found that the size of the individual impulses changed, only their frequency and the number of conducting fibers. The four oscillograms on this page, made several years later, show the fre- quency effect very clearly. They were made by Dr. Bronk at the Johnson Founda- tion for Medical Physics of the University of Pennsylvania with Dr. Guido Stella, now Professor of Human Physiology at the University of Padua. The impulses from a single pressure-sensitive ending in the ca- rotid sinus nerve (which reports the blood How stronger stimulus increases the frequency of nerve impulses but not their size pressure to the central nervous system) are is shown in these oscillograms of the impulses in the carotid sinus nerve at four dif- shown at four different static pressures. As ferent blood pressures in this large artery. (Bronk and Stella) the pressure increased so did the frequency of the impulses, but their size remained essentially unchanged. THE NERVE IMPULSE continued from page one Adrian was naturally interested to know whether motor impulses to a muscle were regardless of how hot the match was that vidual electrical impulse lasts only about signalled in the same way, and with Dr. lit it in the first place. In nerve, this is re- one-thousandth of a second and after a re- Bronk, then a National Research Council ferred to as the "all-or-nothing" principle, covery period of a few thousandths of a Fellow, began to study motor impulses in and it has been a puzzle of neurophysiology second the nerve is ready for another stim- nerves. Here impulses coming out of the to explain how a nerve which is excited to ulus. As a result trains of closely spaced central nervous system were involved, and the maximum, if excited at all, can trans- impulses at frequencies varying from a it was therefore not possible to eliminate mit impressions of varying intensity. few per second to iooo or more per second all but one source of impulses as was pos- More than 30 years ago, E. D. Adrian are possible, though most fall in the range sible with the sensory nerve. However, (now Baron Adrian of Cambridge, Master of 50 to zoo per second. Adrian and Bronk managed by remarkable of Trinity College and Visiting Professor Adrian and Zotterman (then a Rocke- dexterity and dissection to sever all but two at the Institute), Yngve Zotterman, now feller Foundation Fellow) first studied im- or three individual fibers in a branch of Professor of Physiology at the Royal Vet- pulses in sensory nerves, using the im- the phrenic nerve supplying the diaphragm erinary College of Sweden, and President pulses from the stretch receptors by which and observed the impulses in the remain- Bronk showed at Cambridge how this the degree of stretching in a given muscle ing intact fibers. The trains of impulses happens. The nerve either fires or it does is reported to the central nervous system. they found were very similar to the im- not fire, but a continuing stimulus at a Soon they extended their investigations to pulses in the sensory nerves. A weak con- sense organ or a motor nerve cell produces other sensory systems and finally proposed traction was shown to be the result of a low trains of individual impulses. A strong as was later shown to be true, that all sen- frequency of impulses in comparatively stimulus produces many pulses per second sory nerve impulses indicate varying stim- few nerve fibers. A strong contraction, on and a weak one produces few. Each indi- ulus by varying frequency in the trains of the other hand, was seen to be developed as a result of a high frequency of impulses burst of impulses. The frequency of im- in St. Louis at the Central Institute for the in many fibers. These experiments at Cam- pulses faithfully follows each fluctuation Deaf where he came in 193 1 from Spain, bridge showed the similarity in the trains in pressure. Bronk's associate, Professor H. and in 1936 Lorente joined him at the of all nerve impulses, whether sensory or K. Hartline, long before he came to the Institute. Professor David P. C. Lloyd motor. Institute (where he is still studying the came in 1939 from Oxford where he had Thirty years ago, when the work just de- visual system) showed that intensities of gone as a Rhodes Scholar in 1933. Having scribed was completed, measuring and re- light on the retina also give rise to impulses worked briefly with Sir Charles Sherring- cording techniques were, relatively speak- in the optic nerve that vary in frequency ton during his last days there, Lloyd's in- ing, so primitive that we marvel today at and number of fibers conducting. It has terests have remained largely in the cen- the precision and refinement of the con- been shown that the same principle applies tral nervous system, an aspect of neuro- clusions that were based on them. It was a throughout the nervous system. physiology which space forces us to save time of rapidly advancing techniques, how- for discussion in a later issue of The Rocke- ever, and less than five years later Dr. COMPOSITE IMPULSES feller Institute Quarterly. Bronk at the Johnson Foundation had pro- Neurophysiology became an important By severing all but a single fiber in a duced the beautifully clear oscillograms of area of investigation at The Rockefeller In- nerve Adrian and Bronk had learned a nerve impulses in single fibers, reproduced stitute in 1935 when Dr. Herbert Gasser, great deal about the electrical impulse in on these pages, that show how trains of formerly Professor of Physiology at Cornell single fibers. How the individual impulses impulses carry sensory information into Medical College, succeed'ed Dr. Simon combine to produce the composite action the central nervous system while similar Flexner as Director of the Institute. Gasser potential in the intact nerve was the ob- trains of outgoing impulses control motor and Erlanger had already carried out their ject of studies begun more than 30 years functions. In the upper of the two figures studies of conduction velocity and fiber ago at the Washington University School shown below the carotid sinus nerve im- size in frog nerve at Washington Univer- of Medicine by Dr. H. Gasser who is now pulses are shown under more natural con- sity School of Medicine in St. Louis where Director Emeritus of the Institute, and Dr. ditions as they vary in frequency with the Dr. Gasser began his career as a pharma- Joseph Erlanger, for which they shared corresponding variations in blood pressure cologist. When he came to the Institute he the Nobel Prize in Medicine and Physi- which the nerve reports. It can be seen soon gathered around him a number of ology in 1944. that the individual impulses are wider young men interested in neurophysiology. It is not easy to grasp how difficult such spaced, e.g., of lower frequency, when the Dr. Harry Grundfest came with him from a study could be. More than a hundred pressure is at its lowest; in the lower figure Cornell, but after the diversions of World years ago the German physiologist, Helm- rhythmic bursts of impulses in the phrenic War I1 Grundfest continued his work at holtz, (later turned physicist) ingeniously nerve to the intercostal muscles (by which Columbia University's College of Physi- but nevertheless crudely deduced the ve- chest breathing is effected) are compared cians and Surgeons. Gasser had met Pro- locity at which the composite action poten- with pneumograms that show the corre- fessor Rafael Lorente de N6, a student of tial is conducted in frog nerve. Helmholtz sponding inspirations produced by each the great neuroanatomist Ramon y Cajal, compared the time it took the impulse to
Trains of nerve impulses of varying frequency carry sensory information into the central nervous system and motor stimuli out. In either case the stronger the stimulus the higher the frequency of the impulses. The sensory impulses in the carotid sinus nerve (above) are compared with the corresponding blood pressure variations as the heart beats (upper saw-toothed line). The motor impulses in a fiber of the phrenic nerve to the intercostal muscles (below) are compared with the corresponding pressure fluctuations in the lungs during two successive inspirations (smooth curve). The broken white line in each figure marks intervals of 1/5 second. (Bronk) THE NERVE IMPULSE continued from page 'three indicative of the behavior of the nerve under normal physiological conditions. reach the muscle and make it twitch when first Gasser and Erlanger based their cal- The earlier studies of frog nerve had raised two points on a nerve at different distances culations on the assumption that the speed less question, because the nerves of cold- from the muscle were stimulated. But a of conduction of all the fibers varied only blooded animals are much less sensitive to typical nerve may be a cable of two or according to their physical dimensions. changes in their environment. Gasser and three thousand individual fibers of widely Later, when better amplifiers disclosed Grundfest developed techniques for de- varying size, the smallest of which may be more details in the action potentials, Gasser termining the physiological state of the less than a ten-thousandth of an inch in and Erlanger realized that different groups isolated nerve by comparing its electrical diameter. Each fiber conducts with a char- of fibers exist in nerve, each with a distinct behavior with the same nerve in their acteristic velocity depending on its diam- set of properties. Within each group the animals and this, in turn, enabled them to eter and other factors which will appear relationship of conduction velocity to phys- develop techniques for maintaining the later. Moreover, the character of the elec- ical dimensions was found to hold. normal physiological functioning of iso- trical impulse in the individual fiber is lated mammalian nerve. easily altered by changes in the nerve's A, B, AND C FIBERS When they began their work, Gasser environment-by too little carbon dioxide, Nerve fibers are now classified into and Erlanger worked with systems capable for example, or by dissection to make it three broad types-the fastest, called A of amplifying the weak impulses of nerves accessible. fibers, conduct at velocities from 120 to only a few hundred times. While their When Gasser and Erlanger studied the 15 meters per second; the intermediate, measuring instrument was a great im- total nerve impulse they found the shape called B fibers, which conduct at from 15 provement over the twitching muscle at- of the impulse to be complicated and to to lo meters per second, and the slowest, tached to Helmholtz's frog nerve, it was vary with the distance from the point of C fibers, which conduct at from 2 to less capable of indicating the total quantity of origin of the impulse. This they concluded than 1meter per second. Dr. Gasser's most the electrical impulse but told almost noth- to be the result of the fact that different recent work, which we will later describe, ing of its shape. Yet we have seen how fibers conduct with different velocities. As has disclosed that there are two distinct important the detailed shape of the im- Dr. Gasser has put it, if a race were started types of C fibers. Not all three types of pulse as it passes the recording electrode in which athletes, untrained individuals fibers are found in all nerves. The B fibers, has proved to be. and boys participated, the athletes would for example, are abundant in the frog, but shoot out ahead. At a short distance they do not seem to appear in the mammalian TECHNICAL PROGRESS would be followed by the untrained in- somatic nerves at all. Gasser and Erlanger Early in the igzo's when the oscillo- dividuals and the boys would be far be- very early made a rough correlation of the scope (then called the Braun Tube) was hind, the separation of the groups depend- type of the fibers (and hence their size introduced it must have seemed to Dr. Gas- ing upon the length of the course. and speed of conduction) with their func- ser like giving sight to the blind. Even so, tion. The A fibers, which are the fastest, the difficulties were severe. The earliest THE COMPOSITE IMPULSE control the voluntary muscles. The small- oscillograms were made by repeated im- To show how the individual impulses est, the slow-conducting C fibers, carry pulses superimposed on a single film until separate as the composite action potential impulses to the viscera and from the skin, enough exposure had accumulated to be moves away from the stimulus, Dr. Gasser and, in the skin at least, they appear to be developed. The blurred and distorted re- has very kindly prepared two oscillograms, the most numerous. The larger fibers are sults would be regarded as hopeless mate- shown on the page opposite, of the com- called medullated because they are en- rial for study today, but by patient accumu- posite impulse in the saphenous nerve of cased in a sheath of white fatty material lation and careful analysis of such records a cat at two points along the nerve. somewhat as if insulated. The smaller Gasser and Erlanger found the evidence of It is truly remarkable that in spite of (non-medullated) fibers are bare. Here we varying velocities of conduction described these difficulties and the even greater dif- must pause to admire the economy of Na- above. Today high-gain amplifiers, feeding ficulties imposed by the primitive nature ture, for it appears that the largest fibers cathode ray oscilloscopes, can make the of their electrical recording apparatus, are used only when their high-speed con- slightest electrical activity of a nerve read- Gasser and Erlanger were able 30 years duction is necessary. The more numerous, ily observable with negligible distortion. ago to reconstruct the observed composite but less urgent problems of managing the When, in connection with the award action potential of certain nerves by cal- automatic functions and action of the of the Kober Medal of the Association of culating the velocity and potential contri- senses, are handled by the smaller, slower American Physicians in 1954, Dr. Gasser bution from each fiber in the nerve based fibers. was moved to reflect upon his career, he on microscopic examination. When he came to The Rockefeller In- remarked: "As for myself, I often wonder Over the years and as a result of the stitute in 1935 with Dr. Harry Grundfest, what the story would have been like, if in work of many, a wide range of conduction Dr. Gasser began a series of studies of the 1884 Edison had not observed an electric velocities has been found in nerve fibers, properties of mammalian nerve fibers. One current flowing between the heated fila- varying from a maximum of about 120 question which concerned them was how ment of his lamp and a metal plate which meters per second (nearly 300 miles per to be sure that the impulses observed in he had inserted into the bulb. From these hour) to less than 1 meter per second. At isolated nerves selected for study were strategically important beginnings each of us can trace developments of better ways has now shown that there are two distinct tions of 12,000 diameters. Similarly great for getting answers to our questions, de- types among these extremely fine, slowly sensitivity in the recording techniques is velopments still going forward at an ac- conducting fibers. One carries impulses demanded, for in order to avoid disrup- celerated pace, new means for observing to the viscera; the other carries stimuli tion of the weak C fiber pulses by the events in dimensions progressively smaller, from the skin (presumably sensations of strong A fiber pulses, the measurements new means of observing events in times pain) to the brain and spinal cord. The must be made after the A and C pulses are progressively shorter; in sum methods for success of this work is a further example well separated from each other as they making analyses ever finer and more pene- of the importance of developing refined move along the nerve. Unfortunately this trating." and ever more sensitive techniques of also means that because of the various Recently, Dr. Gasser has pressed his measurement. Tiny variations in the shape speeds among the C fibers their composite studies of fiber types down to the very of the electrical impulse were studied in pulse is blurred when it passes, complicat- finest, the C fibers, and has discovered that bundles of more than 2000 fibers, many ing the analysis. they include at least two distinct types. of which were only one or two ten-thou- More recently still Dr. Gasser has been Just before World War I1 interrupted their sandths of an inch in diameter. The micro- studying C fibers in the olfactory nerve. work Dr. Gasser and Dr. Grundfest, study- scopic inventory of these fibers (necessary In most animals this is a short nerve and ing the C fibers in mammals (notably the in order to calculate the composite action not very accessible. Fortunately, the olfac- cat), found that the C fibers to the viscera potential from them) was done by push- tory nerve of the pike is relatively long and behaved quite differently from those from ing the light microscope to its limit and homogeneous enough as to fiber type and the skin. supplementing it with electron microscope size that electrical measurements are rel- As soon as he could after the war Dr. examinations carried out with the help of atively simple. The number of olfactory Gasser returned to the C fibers, and he Professors Porter and Palade at magnifica- (continued on page six)
The action potential of the saphenous nerve of the cat after conduction for 13 millimeters (upper trace) and 33 millimeters (lower trace). This nerve in- cludes fibers of many sizes, but two groups predomi- nate, a fast group and a slow one, producing the two peaks in the action potential shown in the oscillo- grams. Time of arrival of the peaks is measured from left to right, the first break in the line indicating the start. Thus, the smaller elevation, produced by the slower group, arrives after the higher and faster one in both traces, but it is much later in the lower trace (after 33 millimeters of conduction) than in the upper one (after travelling only 13 millimeters). Careful measurement would show that though the height of the two peaks is less in the lower oscillo- gram their width is greater so that the area under them remains the same. This is exactly what would be expected, since the same amount of energy is pre- sumably being conducted at both points on the nerve, but spread along the nerve more in one case than in the other. Timing pulses at the bottom mark intervals of z/io,oooths of a second. Courtesy of Dr. H. S. Gasser THE NERVE IMPULSE continued frc )rn page five established, are of maximum size. None of this proves that a given impulse nerve fibers is astonishing, however, for and elsewhere found many years ago that is conducted through a nerve fiber without Dr. Gasser estimates 6,000,ooo from one the nervous system does not depend on the losing any of its intensity, however. As a side of the nasal septum of the pig. The size of the nerve impulse to indicate the matter of fact this very question was the properties of the olfactory fibers lead Dr. intensity of excitation. This is done in part subject of considerable controversy thirty Gasser to believe that they could be classi- by exciting fibers of different sensitivity years ago. The question was supposedly fied among the C fibers. and in part by producing in them impulses settled once, but during the past year Pro- As we have pointed out, Adrian and of varying frequency. The all-or-none fessor Rafael Lorente de N6 at the In- Bronk and their co-workers at Cambridge principle holds that the impulses, once stitute discovered evidence to make him believe the controversy was settled in error. What happened is this. Forty years or so ago Keith Lucas and Adrian, studying EDWARD L. TATUM : NOBEL LAUREATE- conduction of nerve impulses through narcotized segments of nerve, found that IN MEDICINE AND PHYSIOLOGY for a given degree of narcosis there was a certain maximum length of nerve through EDWARDL. TATUM,Member and Pro- is a member of the National Academy of which the impulse would pass. The deeper fessor at The Rockefeller Institute, shared Sciences, the American Philosophical So- the narcosis the shorter the length of nerve the 1958 Nobel Prize in Medicine and ciety, and of the National Science Board of through which an impulse would pass. Physiology with George W. Beadle, Pro- the National Science Foundation. That was before today's superbly sensitive fessor of Biology at the California Institute We asked him how he felt when he cathode ray oscillographs or even the only of Technology, and Joshua Lederberg, heard the news of his great honor. "It is relatively delicate techniques of the string Professor of Genetics at the University of quite an overwhelming feeling, naturally," galvanometer were available. It was dif- Wisconsin. Tatum and Beadle were cited he said. "It is always gratifying to a scien- ficult, therefore, to tell exactly what hap- by the Royal Caroline Institute of Medi- tist to have his work recognized and to feel pened when the impulse succeeded in cine, through which the Nobel Awards in that his work has contributed to human crossing the affected segment; for the medicine and physiology are made, for welfare and knowledge. I am sure I express "measuring device" was simply the twitch "their discovery that genes act by regulat- the feelings of my colleagues when I say of the muscle the nerve was attached to. ing specific chemical processes." Lederberg that it makes me proud and humble to rep- was cited for "his discoveries concerning resent America in the field of international genetic recombination and the organiza- research and understanding." Lucas and Adrian interpreted these re- tion of the genetic material of bacteria." More than a hundred of Dr. Taturn's sults to mean that the impulse was con- Beadle and Tatum began their work to- friends and colleagues at The Rockefeller ducted through the affected segment "with gether at Stanford University in the early Institute ,and elsewhere in the vicinity of decrementM-that is to say, the further it 1940's using genetically determined bio- New York gave him a banquet on January went the weaker it got-until it was ex- chemical processes of the mold Neuro- 16 in Welch Hall to pay tribute to the tinguished altogether if the segment were spora as their material for investigation. In honor he had received. too long (or the decrement too steep be- 1945 Tatum joined the faculty at Yale Many Nobel Laureates have been asso- cause of deep narcosis). In the early igzo's University and persuaded Joshua Leder- ciated with The Rockefeller Institute. In a Japanese physiologist, Genichi Kato, at berg, who was then at medical school, to i g i 2 Dr. Alexis Carrel received the Nobel Keio University in Tokyo, reached the con- take a leave of absence to work with him Prize in Medicine and Physiology, and in clusion that Lucas's and Adrian's results on the genetic characteristics of bacteria. 1930 it was awarded to Dr. Karl Land- were wrong because of experimental errors. It was this work which led to their discov- steiner. In 1934, Dr. George H. Whipple, After an incredible number of experiments ery together of the sexual cycle in the bac- who is now Vice Chairman of the Board (to which more than 70,000 hapless giant teria E. coli. The readers of the Quarterly of Trustees of the Institute, shared it with toads were sacrificed) Kato announced will find this work described in consider- Drs. G. R. Minot and W. P. Murphy for his "theory of decrementless conduction." able detail in the article "Biochemical work described elsewhere in this issue. Ten His arguments, backed up by so many Genetics and Inherited Metabolic Disease" years later Dr. Herbert Gasser shared the toads, were compelling, and so it has been that appeared in the Summer 1958 issue, prize with Dr. Joseph Erlanger. In 1946 supposed for twenty-five years that nerve Volume 2. No. 2. Dr. John Northrop shared the Nobel Prize conducts without decrement either in the In 1948 Dr. Tatum returned to Stan- in Chemistry with Drs. James B. Sumner normal state or under narcosis. Kato held ford University, and in 1956 he became and Wendell M. Stanley. Professor Fritz that while narcosis may lower the size of Professor at The Rockefeller Institute. In Lipmann shared the prize in Medicine and the impulse, as long as there is any impulse 1953 he was awarded the Remsen Award Physiology with Sir Hans Krebs in 1953, at all it would travel through any length of the American Chemical Society for his and in 1955 Dr. Vincent du Vigneaud, of narcotized nerve whatever. Dr. Lorente contributions to biochemical genetics and Trustee of the Institute, received the now has demonstrated conduction with for his work with Lederberg. Dr. Tatum Nobel Prize in Chemistry. (continued on page eleven) prevailed upon to undertake a new and' anemia which ultimately led Dr. Whipple larger task at the University of Rochester. to the Nobel Prize began even before he The Trustees A new medical school was being estab- went to Rochester. In San Francisco he lished there, generously endowed by The and Dr. Charles Hooper had undertaken GEORGE H. WHIPPLE, M.D. Rockefeller Foundation and Mr. George studies of liver injuries and bile pigment Eastrnan; further, one million dollars had metabolism which led to interest in hemo- been given by the daughters of Mr. and globin production. It was natural that this GEORGEHOYT WHIPPLE, M.D., Vice Mrs. Henry Strong for construction of the should have led on to anemia studies, and Chairman of the Board of Trustees, is Strong Memorial Hospital of the Univer- the results of some of their studies of the emeritus Professor of the School of Medi- sity. Dr. Whipple was to be Dean of the influence of diet on hemoglobin produc- cine and Dentistry of the University of Medical School. Four busy years later the tion and anemia were published as early Rochester. The Nobel Prize in Medicine first class of medical students started in as 1918. Dr. Whipple credits Dr. Hooper, and Physiology which he shared with Drs. the new facilities, and the hospital was his younger colleague, with having wanted George Minot and W. P. Murphy in 1934 completed a few months later. The school to make clinical tests of liver extracts on was one of his highest scientific honors, and its teaching hospital were under one anemia patients at that time, and his pre- but he has also made noteworthy advances roof, unusual at the time, but the innova- liminary trials were encouraging. But cli- in the field of medical education, and he tion was an important arrangement for the nicians discounted the results of the work is a seasoned and able administrator as vitality of both. and the tests were dropped. Dr. Frieda well. He was dean of the School of Medi- Robbins, a colleague from San Francisco, cine and Dentistry at Rochester from 1921 MEDICINE AND DENTISTRY went to Rochester to continue work there to 195 3, and he has been a member of the Mr. Eastman, whose association with with Dr. Whipple on anemia due to blood Board of Trustees of the Institute since Dr. Whipple in establishing the medical loss. Extensive and methodical experi- 1936. school grew into a close friendship, pro- ments in dogs with various diets soon Born in Ashland in northern New showed that bread, milk, fish and grains Hampshire in 1878, Dr. Whipple congrat- were poor in hemoglobin producing factors ulates himself today on the good fortune while visceral tissue of beef, sheep, pig of having discovered very early the lure of and chicken was quite potent. Liver was the woods, hiking, snowshoeing, canoeing, especially potent. fishing, hunting-the pleasures of the out- In alluding to this work, the official of-doors that remain essential parts of his presentation of the Nobel Prize stated: life today. The portrait that we print here "Whipple's experiments were planned ex- was done by his friend, Ansel Adams, who ceedingly well and carried out very ac- is best known for his beautiful photographs curately, and consequently their results of high places in the mountains of Cal- can lay claim to absolute reliability." The ifornia. prize was awarded to Dr. Whipple jointly Like so many distinguished men in with Dr. George Minot and Dr. William American medicine, George Whipple took Murphy of the Harvard Medical School. his undergraduate and graduate training The relation of the work of these men was at The Johns Hopkins Medical School set forth in the official presentation : "These where he was under the influence of such investigations and results of Whipple's men as Osler and Cushing, and of course gave Minot and Murphy the idea that an Dr. William H. Welch. In 1914 Dr. Whip- experiment could be made to see whether ple married Katharine Waring of Charles- posed that the medical school be combined favourable results might not also be ob- ton, South Carolina, and after a honey- with a school of dentistry that would offer tained in the case of pernicious anemia, moon in the woods of New Hampshire education in dentistry of the highest order. an anemia of quite a different type, by they moved to San Francisco. Dr. Whipple When the medical school opened, applica- making use of foods of the kind that Whip- had been invited by the President of the tions for dentistry were expected but there ple had found to yield favourable results University of California to establish a new were almost none. This led after a few in his experiments regarding anemia from department of research medicine in the years to a decision to offer scholarships loss of blood." medical school and to serve as Director of for graduate instruction in dentistry, and the newly-endowed Hooper Foundation for with the support of The Rockefeller Foun- OTHER HONORS Medical Research. By 1920 Dr. Whipple dation and The Carnegie Foundation an Dr. Whipple has been a member of the had become Dean of the Medical School, experimental program of this sort was es- National Academy of Sciences for thirty and he regarded himself as a settled Cal- tablished. It was eminently successful. years and a member of the American Phil- ifornian. In this way began the School of Medi- osophical Society for twenty. The Univer- Word of his research and administrative cine and Dentistry of the University of sity of Toronto has awarded him its Charles achievements on the West Coast, however, Rochester. Mickle Fellowship and he holds the Kober had reached the East, and in 1921 he was The research on the effects of diet on Medal and the Rochester Civic Medal. He [71 is a past President of the American Asso- THE QUEST FOR MORE SPACE IN THE ciation of Pathology and Bacteriology and was awarded the William Wood Gerhard Gold Medal from the Philadelphia Pathol- ROCKEFELLER INSTITUTE LIBRARY ogy Society. Yet in spite of his many honors for BOOKs AND JOURNAL s are flowing into ture in our collection. Since about three- achievements in research and administra- the Institute's library at an unprecedented quarters of our entire collection consists tion, Dr. Whipple would be remembered rate as the size of the Institute's faculty of bound volumes of journals, the most as a teacher. "Perhaps research may give a increases, the scope of its activities widens, effective solution of the space problem ap- greater sense of accomplishment," he says, and the scale of scientific publication pears to be to arrange them by title and "but teaching carries greater personal hap- throughout the world rises. This accumu- date so that the least-used titles and the piness." lating wealth of information is regarded as oldest issues go to the remotest shelves. a mixed blessing by the Library Committee This is where planning has begun. COLUMBIA UNIVERSITY and the administration who are faced with- As a first approximation a list of journals storing a steadily growing collection in a to be candidates for the basement stacks SCIENCE WRITERS ARE finite volume and in such a way as to make was compiled with the help of nine senior it as convenient and useful for the Insti- faculty members and the Library Com- INSTITUTE GUESTS tute's research as possible: mittee, working with Miss Esther Judkins, Completion of the new laboratory build- the Librarian. This group represents broad- THE INSTITUTEwas host on December ing this Spring will free considerable space ly all of the fields of interest at the Insti- ig to a group of graduate fellows in sci- in the lower part of the library that has tute. Their list of candidates for the base- ence writing who are studying at Columbia been devoted to other uses, thus, tempo- ment (212 out of 636 titles considered) is University under a program sponsored by rarily at least, averting an explosion. But now in the hands of all the faculty as well The Rockefeller Foundation and The this, too, raises problems for the additional as the students to be sure that a key journal Sloan Foundation. After an informal re- free space is not in the reading room of the of daily reference value to someone is not ception and luncheon President Bronk library where we would like it, but in the inadvertently consigned to the lower stacks. welcomed the guests to the Institute and lower stacks. As a result, much thought is It is possible that when the results of spoke of the significant importance that being given to determining the relative use this phase of the survey are at hand it will scientists must attach to those who seek to of the various types and ages of the litera- be found that so many journals are used make the work of science accessible and understandable to the broad public. Dean Edward Barrett of the Columbia Univer- sity Graduate School of Journalism re- sponded, citing the importance that Colum- bia University had attached to the program. He said that the university had made special provisions so that science courses could b.: taken for credit or audited re- gardless of usual prerequisites and require- ments. He commented upon the selectivity which had reduced approximately loo ap- plicants to the six who were our guests. Professor John Foster, who is in charge of the program, then introduced the graduate fellows, each of whom is a mature journal- ist and most of whom are on leave from newspaper offices. Mr. Earl Ubell of the New York Herald Tribune, who was also a guest at the luncheon, presented President Bronk with a certificate of honorary membership in the National Association of Science Writ- ers. Professors Alfred E. Mirsky and Frank L. Horsfall, Jr., then made brief presenta- tions of the work of their laboratories and Physics Physiology Botany Chemistry Mathematics Geology Entomology Zoology its significance to the fields of biochem- PIHLD OF JOURNAL CITED istry and virology. Following a lively dis- ,cussion period the group adjourned. Age of journal collections to contain various percentages of articles cited frequently by someone that other measures For many years the books in the library. been insufficient in the past few years, but will be needed. One such possibility is to have been arranged on the shelves alpha- a part of the rearrangement of the base- place the older issues of the journals in the betically by author, an excellent system ment stacks will include provision of two basement. The problem then would be for those who know precisely what they quiet, air-conditioned rooms overlooking what date to use for the division and want, but frustrating to one who wishes to the East River that will be used as seminar whether to use the same date for all fields browse. It has now been decided to arrange rooms and for study. Moreover, at various of science. the books on the shelves according to Li- places throughout the library small study- Meaningful, quantitative data on the brary of Congress subject classification. carrels will be located. Three experimental useful life of literature in various fields are This task of thousands of trying, intellec- units of this kind have been in heavy use not easily found or compiled, but some tual decisions has been boldly undertaken on the balcony above the main reading interesting information on this subject was by the librarians and is now well under room. published recently by Charles H. Brown, way. In the meantime rearrangement on A number of other plans for improving Librarian Emeritus of Iowa State College the shelves will not be possible until the the library's service are being considered, (Scientific Serials, Association of College entire job is done, perhaps a year or more -but they have not reached a state where and Research Libraries Monograph Num- from now. they could be reported as more than the ber 16, Chicago, 1956). We cannot go Study rooms and working space have bright vision of the future. into the details of this study, but statistics pertaining to the use of back issues have been derived from it and summarized in the accompanying figure. The three pro- THE FIRST SIGMA INITIATION files show the "age" of collections of jour- nals in the various fields that would con- THEROCKEPELLER~NSTITUTE Chap- tific life. Following the formal promotion tain 80 % , go % ,and g 5 % of the articles ter of the Society of the Sigma Xi held its of four Associate Members to full member- cited during the year studied ( 195 3 ). One first initiation ceremony in connection ship, the initiation ceremony was con- limitation in applying these figures to our with a banquet and a lecture by Dr. Peter ducted by Dr. Stoll. Next, President Bronk problem is that they are based on published Debye on Tuesday, November 25, 1958, introduced Mr. Rockefeller who presented citations, not on reading and reference fre- at 6:00 p.m. The initiation was attended the Chapter with a magnificent Initiates quency, distribution of which might be by over a hundred Chapter members and Book containing the Constitution and By- very different. It is evident, however, from initiates and also by Mr. David Rockefel- Laws of the Chapter, with pages for the Dr. Brown's data that no single cut-off ler, the Chairman of the Board of Trus- initiates' signatures for well over fifty years date would serve all fields equally. What tees, Dr. Frank M. Carpenter, President of to come. In his presentation, Mr. Rocke- solution would best suit the needs of those Sigma Xi, and Dr. Peter Debye, Professor feller emphasized his belief in the impor- at The Rockefeller Institute is yet to be Emeritus of Chemistry at Cornell Univer- tance of friendship and easy communica- determined, but it is just possible that with sity. tion among scientists and congratulated good luck the problem may not have to be The initiates numbered forty-three; all Dr. Bronk on the important changes which faced for some years. were members of the faculty of The he has effected at The Rockefeller Insti- Rockefeller Institute or The Rockefeller tute. After a brief word of greeting from OTHER MEASURES Foundation Virus Laboratory. Besides four Dr. Carpenter, the ceremony was ad- While we are on the subject of the li- members emeriti, Dr. P. K. Olitsky, Dr. journed. brary's problems we should mention several W. J. V. Osterhout, Dr. T. M. Rivers and At 8:00 p.m. in Caspary Auditorium measures which have been taken or are Dr. D. D. Van Slyke, nine full Professors Dr. Theodore Shedlovsky introduced Dr. planned to increase its effectiveness. and two Nobel Prize winners were initi- Peter Debye, the Sigma Xi lecturer. Dr. Over a thousand books are being added to ated. As Dr. Carpenter stated, "This is Debye's talk was entitled "Tales of Science the collection each year and the Library probably the most distinguished group of and Scientists" and included several deeply Committee has devised a system for in- initiates in the history of Sigma Xi." penetrating descriptions of the atmosphere creasing this number. Each week as newly- A full list of the new initiates and of the and work patterns of individuals and published scientific books are announced Associate Members who were promoted to groups of individuals that he had known they are secured on approval for display in full membership will be found under In- who were, at the time, making highly sig- the library if they seem to lie within fields stitute Mention on page fourteen. nificant contributions in physics. In con- of interest. Faculty and students are in- The speakers at the dinner, which was clusion, Dr. Debye stressed the importance vited to indicate their interest in having a presided over by Dr. N. R. Stoll, the Presi- of informal conversation in a relaxed at- copy in the library, whereupon either the dent of the Chapter, included Dr. Detlev mosphere for the generation of important book is purchased, or, if no interest is ex- W. Bronk, Mr. Rockefeller and Dr. Car- ideas. pressed, the book is returned. To keep the penter. Dr. Stoll's presidential address The Sigma Xi Chapter plans to have faculty and students abreast of this grow- highlighted the growing realization of the three more meetings this year, each se- ing collection of books, a bimonthly acces- importance of personal communication lected to be of special interest. The Chap- sions list has been initiated by the library among scientists and the significant role ter Initiates Book will be on display shortly for general distribution. that Sigma Xi plays in this phase of scien- in the Commons Room in Welch Hall. MARAMOROSCH GIVEN was based on his work with the corn stunt ZIMBLER SINFONIETTA virus which resulted in showing that one AAAS- CAMPBELL AWARD strain of the virus inhibits the transmission A DOZEN STRING PLAYERS, consisting of a related strain through the insect which of seven violins, two violas, two cellos and DR. KARL MARAMOROSCH,Assistant is one of the vectors transmitting the dis- a double bass, from the Zimbler Sinfoni- Professor at The Rockefeller Institute, was ease. Dr. L. 0. Kunkel, working with etta, presented a concert in Caspary Audi- honored in December by being selected as strains of aster yellows virus which are torium on Sunday, December 14, for the 1 g 58 recipient of the American Asso- also transmitted by leaf-hoppers, had members of The Rockefeller Institute fac- ciation for the Advancement of Science- shown earlier that one strain of this virus ulty, students, and staff and their guests. Campbell Award for Vegetable Research. which multiplies in its insect vector, pro- These artists, all members of the Boston The award, established last year by the tects against infection by a related strain Symphony Orchestra, played works by Campbell Soup Company, consists of a of virus. Dr. Maramorosch's work with Vivaldi, Rossini, Barber, Tansman, Bach bronze medal and $1500. It is given for corn stunt confirms this finding but he and Mozart. The concert was enthusias- "an outstanding single research contribu- has shown that the cross-protection be- tically received by a large and appreciative tion, of either fundamental or practical tween the two strains of corn stunt virus is audience. significance, relative to the production of unilateral, e.g., one will protect the insect Dr. Shedlovsky, who had been instru- vegetables, . ..in the fields of horticulture, against the other, but protection does not mental in arranging the concert, intro- genetics, soil science, plant pathology, occur in the reverse ordkr. This is be- duced the ensemble. One of the violinists, entomology, plant physiology, or other ap- lieved to be the first demonstration of uni- Mr. Harry Dickson, introduced the pro- propriate scientific areas." lateral cross-protection by a plant virus in gram and offered some engaging remarks Award of the medal to Dr. Maramorosch an insect host. about the works played, the instruments of some of the players, and music in general. Mr. Zimbler, leader of the group (which prides itself on being able to play together LEE D. PEACHEY AWARDED LEITZ without a conductor), was joined by others in the ensemble in praise of Caspary Audi- 'ELL OWSHIP FOR GRADUATE STUDY torium as a place for musical perform- ances. Mr. Dickson remarked to the audi- LEE D. PEACHEYhas been selected as last year by the E. Leitz Company in recog- ence: "The acoustics for us were mag- the first recipient of the Leitz Fellowship nition of the contributions The Rockefeller nificent; I hope it sounded well out there." for graduate study at The Rockefeller In- Institute is making through its new pro- In response to the enthusiasm of the audi- stitute. The Leitz Fellowship was created gram of graduate study. Mr. Peachey, who ence, the ensemble played as an encore a is completing his work in preparation for charming excerpt from a suite for strings the degree of Doctor of Philosophy from by Corelli. the Institute. holds a B.S. in engineering - L. FIFTY YEARS AGO AT THE physics from Lehigh University. He came HOLIDAY FESTIVITIES ROCKEFELLER INSTITUTE to The Rockefeller Institute in 1956 after beginning graduate study at The Univer- CONTINUINGA CUSTOM they began Appointment of the First Director of sity of Rochester. several years ago President and Mrs. Bronk The Fellowship is awarded annually to invited the faculty, students, and staff of The Rockefeller Institute Hospital a student in the later years of his graduate the Institute, and their families, to join ONOCTOBER 10,1908, the Board of Sci- program so that he may continue his them in singing Christmas Carols on the entific Directors elected Dr. Rufus I. Cole studies for a longer time than usual. afternoon of December 23rd. More than to be director of the new hospital to be Cytological investigations attempting to six hundred were led in the carols by a built at the Institute, for which Mr. Rocke- correlate structure and function are Mr. group of our best singers, fortified by the feller had provided a special gift of $500,- Peachey's chief research interest. While at return of their former leader, Dr. Smillie, ooo. Dr. Cole, 36 years old, had been the Institute he has concentrated on muscle and our organist, Mr. George Morgan, resident physician of The Johns Hopkins cells, studying impulse conduction and re- Head of the Music Department of the Taft Hospital, where he had done notable work lated structural elements in cells of various School. After singing Christmas classics in clinical bacteriology, especially in devel- species. As is customary for graduate fel- for more than an hour, tea was served and oping a method of cultivating the typhoid lows at the Institute, Peachey has spent Christmas greetings were exchanged. bacillus from the patients' blood. Plans for several months studying abroad. He has As part of their efforts to provide more the organization of the hospital staff, just returned from England where he opportunities for the families of the In- which he began at once to draw up, were studied for 6 months with A. F. Huxley in stitute faculty to meet each other and the very influential in establishing The Rocke- the Physiological Laboratory at Cambridge students, Dr. and Mrs. Bronk were at feller Institute Hospital as a research de- University. Mr. Peachey has carried on home in the President's House on New partment whose members were scientific his work at the Institute under Professor Year's Day to all of the faculty and stu- investigators of disease. Keith R. Porter. dents who reside in New York City. THE NERVE IMPULSE continued fro m page six process. Like the nerve impulse itself, the restoration occurs locally, so that we meas- decrement in frog nerve, and he has also fall, and, more to the point, ions quickly ure a drop in polarity of only very short been able to explain to his own satisfac- diffuse uniformly throughout a solution so duration which spreads along the nerve tion why Kato found contrary results. This that it becomes electrically neutral. The fiber (in both directions, incidentally, un- old controversy will no doubt not be settled living cell is able to oppose this diffusion less the fiber is stimulated at its end). (or re-settled) in a single season, but Dr. and to maintain a difference in concentra- A helpful analogy for visualizing this Lorente is convinced that when others tion of ions between its surface and in- local disturbance which appears to move bring modern measuring techniques to terior. In nerve cells the difference is rec- down the nerve is to consider the nerve this old but significant problem in neuro- ognizable as a rather considerable electri- fiber to be like a long row of dominoes physiology, they will confirm his findings. cal potential, e.g., the nerve is said to be stood on end. If one is pushed down, it will polarized. When a nerve impulse is initi- knock over its neighbors and the disturb- NERVE METABOLISM ated, the mechanism for maintaining the ance will pass along the row. Now if our We have written much about the electri- ion concentrations breaks down locally, imagination will provide each domino with cal behavior of the nerve cell, but have as and we measure the depolarizing effect as a little man to set it upright again as quick- yet said nothing about the source of its a local drop in the electrical potential of ly as possible after it falls, we will see that electrical energy. Study of this question in the surface membrane of the nerve. This the disturbance will flow down the row as recent years has yielded significant results, local breakdown causes adjacent points on a local and temporary tumbling over of thanks to highly refined biophysical and the nerve fiber to be depolarized and the dominoes which spring upright again. Un- biochemical techniques developed at the effect spreads like a wave. But almost at til the first domino is set right again (e.g., Institute and elsewhere. Like all of the the instant the local depolarization occurs, until after the refractory period) no new cells in our bodies, the neurons require the cell sets about to do the work necessary impulse can be sent down the row of food and oxygen which they consume, to sort out the ions again, thus restoring dominoes and hence there is a maximum eliminating carbon dioxide and other waste the original ionic content. Part of the re- frequency at which impulses will pass. .products. These are the processes that en- fractory period of a few thousandths of Moreover, we can see that the impulse able most living cells to maintain them- a second during which the nerve will not would proceed in much the same way, re- selves and to carry out their various highly conduct is accounted for by this re-sorting (continued on page twelve) specialized functions: the growth and di- vision of embryonic cells, the contraction of muscle cells, the secretion of glandular cells, etc. The specialized function of the neuron is conduction of electrical im- pulses,..and study of the relationship be- THOMAS MC ELRATH DEBEVOISE tween the energy-providing processes of metabolism in nerve cells and their energy- consuming electrical activity has provided For understanding of Mr. Thomas M. he encouraged, he mediated, he dissuaded greater understanding of the cellular basis Debevoise it is necessary to understand the -and he found no reason ever to raise his of the nervous control of the body. For old English legal verb "to attorn". At the voice. many years, questions of this kind have feudal law one attorned when he appointed Mr. Debevoise was Counsel to The occupied President Bronk and his col- another to act in his place; and the one Rockefeller Institute for 34 years. He was league, Professor Frank Brink, Jr., who appointed was then called an attorney- moral, grave, and judicious-indeed, he came to the Institute in 1954 from The as he is to this day. was sublime in the poise he brought to a Johns Hopkins University so that he could Gradually, through the centuries, men discussion. Among all those who know continue their collaboration. learned in the law of England came to be what it is "to attorn", Tom Debevoise is The electrical characteristics of nerve divided into two groups : barristers-at-law cherished as a counsellor of unrivalled cells are associated with a difference in who are those who practice as advocates decorum, judgment and taste. This is his the concentration of electrically-charged in the superior courts of justice, and at- best valediction. ions (particularly sodium and potassium torneys-at-law who are the counsellors- He died at the age of 84 on December ions), between the interior of the cell and standing in the place of their principals 20, 1958. Mr. Debevoise is survived by his the exterior body fluids. Such a difference and acting for those principals in all sorts son, Eli Whitney Debevoise, a Trustee is characteristic of many, and perhaps all of matters, both weighty and small. of The Rockefeller Institute; a brother, cells, but in nerve the difference is func- In the oldest and best sense of the word Colonel Paul Debevoise; two sisters, Mrs. tionally of especial importance. -almost in its feudal sense-Mr. Debe- Ronald K. Brown and Mrs. William F. It seems to be one of the properties of voise was an attorney. The flamboyant arts Decker; two grandchildren and 4 great the universe that everything tends more or of the advocate in court were not for him. grandchildren. less quickly toward uniformity-differ- He counselled, he persuaded, he advised, HENRY ALLEN MOE ences in temperature are difficult to main- tain, for example; buildings decay and THE NERVE IMPULSE continued ft.om page eleven ions only facilitate an otherwise impaired but not altogether obliterated ability to gardless of how hard the first domino is the train of impulses, falling back to nor- conduct. struck. mal as the sodium ions quickly diffuse. As Almost incidentally, Dr. Lorente's work Our imaginary little man who sets might be expected, the metabolic rate of with sodium substitutes in nerve function things right after each impulse is obviously the cell is higher during this time. During has led him to discover that sodium is also an important part of the scheme. He, and the past year radioactive potassium has necessary to maintain the filtering ability the ways he uses to restore the system to been used by Paul Hurlbut to study the of the walls of the capillary blood vessels. the conducting state, are essential deter- movement of potassium ions into and out If colloidal albumin or dextran is supplied minants of its behavior. In nerve, they of nerve in the presence of various inhibi- to the hind legs of a bullfrog in a solution correspond to the oxygen metabolism and tors of metabolism. Thus the relation of closely resembling the blood, it is retained the enzymatic processes by which the ion movement to oxygen metabolism is re- inside the blood vessels and does not escape energy of metabolism is converted into the vealed. into the tissues. In sodium-free solution, electrical potential of the cell membrane. however, the colloidal matter quickly dif- Techniques have been developed whereby FIRE-FLY TAILS fuses through the walls of the blood vessels the oxygen consumption of a nerve can be By varying the biophysical and bio- and swells the tissues. None of the sodium measured as the impulse is conducted chemical conditions, many modifications substitutes which restore conduction in so- along its fibers. One such device, capable in nerve cell function and metabolism oc- dium-deficient nerve will prevent this loss of very quick response to changes in the cur that give some clue as to the great of filtering ability in capillaries. nerve's respiration, was developed a few complexity of the detailed processes in the Johns W. Hopkins, 111, Graduate Fellow years ago by Dr. C. M. Connelly, who is nerve. Recent investigations by Dr. Cheng of the Institute who is now working in the now at the Institute. have suggested that though oxygen respira- laboratory of Dr. Mirsky undertook to de- tion is essential to healthy function, nerve termine whether any of the sodium sub- RESPIRATION OF NEURONS cells can call upon energy sources other stitutes that Dr. Lorente found to work in It can be shown that the active nerve than oxygen metabolism. They can main- nerve would also work in the cell nucleus. "breathes harder", so to speak, as it con- tain their electrical function for several They do not, which further complicates ducts pulses at a higher rate. From careful hours when oxygen metabolism is inhib- the question of the precise role of sodium study of exactly how much more oxygen ited by chemicals. Incidentally, readers in the two different cell-functions. it requires as the rate increases, how soon who have wondered all this time what be- it requires it, and for how long after the came of the great quantities of firefly tails CONCLUSIONAND PROLOGUE work ceases, etc., some idea of the nature being sought by our Purchasing Depart- But to pursue such experiments here of the connection between oxygen con- ment (see "Questing for Research, Vol- would lead us far from the nerve impulse, sumption and impulse transmission can be ume 1, No. 3, September 1957) will find for to understand one thing thoroughly we formed. Even more information can be the answer here. One of the enzymes in are often confronted by the necessity to learned from similar experiments in which the firefly's light-producing reactions is understand all. The nerve cell is after all different steps in the metabolic chain are used as a detector for certain components basically like every other cell in our body; interfered with by drugs and various other of the nerve cell's metabolism. all that is being done to understand the cell chemicals. generally, applies, therefore, more or less Hodgkin and Huxley at Cambridge SODIUM SUBSTITUTES directly to the nerve as well. We shall leave have shown during the past ten years or so Precise understanding of the role of these tempting by-ways unexplored, how- that when the nerve impulse passes, so- sodium and potassium ions in nerve func- ever, perhaps to return to them another dium ions seem to move into the nerve and tion has been the object of neurophysiolo- time. potassium ions move outward towards its gists for decades, and for the past several But much remains to be said about the surface. This connection between the ion years this has been a particular interest of nervous system, itself, and the work of movements and nerve processes affords a Dr. Lorente and his colleagues at the In- those at the Institute to understand it- basis for studying the connection between stitute. Recently, he has been able to show studies by Drs. Lloyd, Brooks, and Wilson oxygen consumption and electrical action that sodium can evidently be replaced by of reflex mechanisms; work by Drs. Hart- in nerve. Connelly has shown recently at a number of other chemical substances. line, Ratliff, and Miller on the visual sys- the Institute that the effect of prolonged Nerves that have become non-conductive tems of invertebrates and their implications stimulation at high frequency seems to be because of sodium deficiency are restored for man; and we shall return to Dr. Lorente that the ion re-sorting processes are set in to activity by such ions as ammonium, hy- to mention his work on the brain and spi- motion with such intensity that when the droxylammonium, hydrazinium and guan- nal cord. The intricate but intriguing ques- stimulus ceases an abnormally great extru- idinium ions. In just what way these 'ions tion of the inter-relations among nerves sion of sodium ions from the cell interior act as substitutes for sodium is not clear. and nerve impulses, which they and others occurs. As a result the nerve membrane Dr. Lorente suspects that certain of the are studying, will be the subject of the next becomes electrically polarized more than metabolic processes, even in sodium-defi- article in this series on important fields of normally. This is seen as a momentary cient nerve, must continue to function science as they are pursued at The Rocke- positive potential following termination of with residual sodium while the substitute feller Institute. PAUL A. WEISS Marshall Woods Lecture, Brown University. FA CULTY ACTIVITIES Lowell Lecture, Massachusetts General ~os~ital,Boston. VICTOR H. WITTEN Symposium on A Decade of Anti-Inflammatory Steroids, from Cortisone to Dexamethasone, New York Academy of Sci- ences. Academic Honors DETLEV W. BRONK Society Elections L.H.D., Oberlin College FRANK L. HORSFALL, JR. Affiliate, Royal Society of Medicine, London. Lectures, Conferences and Symposia KARL MARAMOROSCH ALEXANDER G. BEARN Vice Chairman, Section on Insect Vectors, Entomological So- Lowell Lecture, Massachusetts General Hospital, Boston. ciety of America, Salt Lake City. Lecture, Royal Society of Medicine. Chairman, Division of Mycology, New York Academy of Sci- Participant, Symposium on Genetics in Medicine, Harveian ences. Society of London. ALFRED E. MIRSKY LUDWIG BERGMANN Member, Deutsche Akademie der Naturforscher Leopoldina, Participant, Symposium on Viruses in Tissue Culture, New Halle. York Academy of Sciences. DETLEV W. BRONK EDWARD L. TATUM Dedication Address, Millikan and Seaver Science Laboratories, Member the New York Sciences- Pomona College.- Address, International Conference on Scientific Information other ~pp~i~t~~~t~and ~i~ti~~ti~~ Banquet. MERRILL W. CHASE DETLEV W. BRONK Participant, Symposium I1 on the Physicochemical Properties Trustee, Protein Foundation. of Allergic Antibodies, Third International Congress of Honorary President, Tenth Pacific Science Congress. Allergology, Paris. Member, American Committee of the Heart Foundation-Prin- ARPAD I. CSAPO cess Liliane. Participant, Lecture Series on Recent Advances in Endocrin- Member, Electoral College of the Hall of Fame, New York Uni- ology and Intermediary Metabolism, University of Chicago. versity. REN~J. DUBOS Member, National Advisory Council for International Medical Lowell Lecture, Massachusetts General Hospital, Boston. Research. MARILYN G. FARQUHAR VINCENT P. DOLE Participant, Tenth Annual Conference on the Nephrotic Syn- Member, Editorial Board, Circulation Research. drome, Columbia University. REN~J. DUBOS THOMAS D. C. GRACE Member, Panel on Biological and Medical Sciences, Committee Participant, Symposium on Viruses in Tissue Culture, New on Polar Research, National Academy of Sciences-Na- York Academy of Sciences. tional Research Council. MAN-CHIANG NIU The Lilly Research Laboratories Lecture, Indianapolis. D. DZIEWIATKOWSKI Editorial Advisory Board, Archives of Oral Biology. HOWARD A. SCHNEIDER Address before New York Regional Group, Medical Library As- H. KE F F ER HARTLIN E sociation, The Rockefeller Institute. Chairman, Committee on Biological Sciences of the Space Sci- Participant, Arden House Conference on Nutrition. ence Board, National Academy of Sciences-National Re- RICHARD E. SHOPE search Council. Hanau W. Loeb Lecture, St. Louis University School of Medi- FRANK L. HOR s FALL, JR. cine. International Board of Editors, Excerpta Medica Foundation. IRA SINGER ROLLIN D. HOTCHKISS Participant, International Colloquium on Resistant Infections, Trustee, Foundation for Microbiology, New Brunswick. New York, under the auspices of The World Medical Asso- ciation. HENRY G. KUNKEL EDWARD L. TATUM Member, Committee on Blood and Related Problems, National Nobel Lecture, "A Case History in Biological Research", Karo- Academy of Sciences-National Research Council. linska Institute, Stockholm. DAVID P. C. LLOYD A. CECIL TAYLOR Board of Advisory Editors, The Journal of Neurophysiology. Chairman, Conference on Hypothermia, New York Academy of Research Advisory Board, The United Cerebral Palsy Research Sciences. and Educational Foundation. JULES HIRSCH HALSTED REID HOLMAN FACULTY ACTIVITIES FRANK LAPPIN HORSFALL, JR. MARGERIS ADOMAS JESAITIS (continued from page thirteen) SEYMOUR JOSEPH KLEBANOFF RICHARD MICHAEL KRAUSE HENRYGEORGEKUNKEL FRITZ ALBERT LIPMANN DAVID MILLARD LOCKE DUNCAN A. MAC INNES Member of Research Committee, American Philosophical So- ALEXANDER GEDEON MATOLTSY ciety. MACLYN MCCARTY Honorary Editorial Advisory Board for the Collected Works of ALFRED EZRA MIRSKY Irving Langmuir. MARJORIE MARY NEMES PETER KOSCIUSKO OLITSKY KARL MARAMOROSCH WINTHROP fOHN VANLEUVEN OSTERHOUT Campbell Award and Bronze Medal, American Association for GEORGE EMIL PALADE Advancement of Science. GERTRUDE ERIKA PERLMANN CLAYTON RICH JOHN B. NELSON , THOMAS MILTON RIVERS Member, Committee on Gnotobiotics and Specific Pathogen- Free Animals, Institute of Laboratory Animal Resources, ALEXANDREROTHEN National Academy of Sciences-National Research Coun- MARIA ANNA RUDZINSKA cil. RUSSELL WILLIAM SCHAEDLER Griffin Award, Animal Care Panel, Chicago. THEODORE SHEDLOVSKY FABIO SPARATORE RICHARD E. SHOPE JOHN MORROW STEWART Member, Aftosa Technical Advisory Group, Pan American WILHELM STOFFEL Sanitary Bureau, Rio de Janeiro. TOM TED STONIER Member, Technical Advisory Group on Zoijnoses in the Ameri- IGOR TAMM cas, Pan American Sanitary Bureau, Azul. MAX THEILER Member, Panel on Biological and Chemical Warfare, Presi- DONALD DEXTER VAN SLYKE dent's Science Advisory Group. FREDERICK D. VIDAL
EDWARD L. TATUM Nobel Prize in Medicine and Physiology. JAMES GERALD HIRSCH BENJAMIN LOWENHAUPT PAUL A. WEISS Second Annual Honorary Lecture Award, Albany Medical Col- WILLIAM HENRY MILLER lege of Union University. RODES TRAUTMAN JVkw Appointments to the Faculty
DR. LUDWIG BERGMANN, of the Max Planck Institute for Biology, Melchers Division, at Tiibingen, has been ap- pointed a Research Associate in the Laboratory of Dr. Mara- INSTITUTE MENTION morosch.
DR. JOs EPH B. BIRD s E LL, Professor of Anthropology, De- partment of Anthropology and Sociology, University of California at Los Angeles, has been appointed a Visiting Professor of the Institute. New Members of the Society of the Sigma Xi DR. CAR LO B RUNI, who has been an Affiliate of The Rocke- INITIATES feller Institute, has been appointed a Guest Investigator and GEORGE ACS Fellow beginning January 1, 1959, to work in association ALEXANDER GORDON BEARN with Dr. Porter. DIETHELM HARTMUT BOEHME DR. AIDA TRAVERSO CORI, an Assistant in the Department CARL0 BRUNI of Biochemistry, School of Chemistry and Pharmacy at the SONJA MAREID BUCKLEY University of Chile in Santiago, was appointed Guest In- JORDI CASALS-ARIET vestigator on November 25, 1958, and will work with Dr. PURNELL WHITTINGTON CHOPPIN Perlmann in her Laboratory. DELPHINE HARRIET CLARKE ZANVIL ALEXANDER COHN DR. F RA N c I s H . c . c RI c K, of the Medical Research Council ARPAD ISTVAN CSAPO Unit for Molecular Biology in the Cavendish Laboratory, VINCENT PAUL DOLE Cambridge University, has been appointed a Visiting Pro- EARL HOWARD FREIMER fessor of the Institute. DR. FRIEDRICH P. DIECKE, Professor in the Department of DR. ROBERT S. STONE, of the Department of Pathology, the Physiology at the University of Tennessee, has been ap- School of Medicine, University of California at Los pointed a Guest Investigator beginning January 1, 1959, Angeles, has been appointed a Guest Investigator and Fel- and will work in association with Drs. Wilson and Lloyd in low, beginning January l, 1959, and he will work in asso- the Laboratory of Neurophysiology. ciation with Dr. Dan Moore.
DR. SETSURO EBASHI, an Assistant in the Department of Pharmacology of the University of Tokyo, has been ap- Faculty Terminations pointed a Guest Investigator in the laboratory of Dr. Lip- DR. DIETHELM H. BOEHME,a Research Associate in the mann,effective January 1, 1959. Laboratory of Dr. Dubos, left the Institute December 31, DR. MARILYN G. FARQUHAR, a Guest Investigator in Dr. 1958, to work in the Department of Pathology of The New Palade's Laboratory, has been appointed a Research Asso- York Hospital. ciate. DR. LAWRENCE S. FRISHKOPF, formerly a Guest Investiga- DR. ANTONIO GALLEGO,Director of Fundacion Marques de tor in Dr. Hartline's Laboratory, left the Institute on Octo- Urquijo in Madrid, worked for a month during October- ber ist, 1958. November, 1958, as a Guest Investigator in Dr. Lorente's DR. HANS GERD GUNDLACH, Guest Investigator in the Lab- Laboratory. oratory of Drs. Moore and Stein, left on November 21, DR. ERHARD GRO s S, a Visiting Scientist at the National In- , 1958, and is now at the Physiologie-Chemisches Institut, stitutes of Health in Bethesda, was appointed Guest Investi- Universitat Wiirzburg. gator in Dr. Craig's Laboratory, beginning January 19, DR. JEAN-PAULMEYER, appointed as a Guest Investigator 1959. to work with Dr. Weiss, resigned as of December 3, 1958, DR. WILLEM C. HULSMANN,of the Laboratory of Physio- because of illness. logical Chemistry at the university of ~msterdam,has been DR. BE LA =. P. NAGy, in Csapds Laboratory appointed a Guest Investigator to work in association with as a Research Associate, left on October 1, 1958, and is now Dr. Lipmann, beginning January 1, 1959. in the Department of Biochemistry at Columbia University. HAR G' KH ORANA, Head of the Organic Set- DR. MARJORIE M. N E M E S, who was a Research Associate in tion, British Columbia Research Council, University of Dr. Horsfall's Laboratory, left the Institute on November British Columbia, has been appointed a Visiting Professor 30, 1958, and is now a Virologist with Merck, Sharp and of the Institute. Dohme Research Laboratories in West Point, Pennsylvania. DR. in S. PETER MARFE formerly a Guest Investigator Dr. D R . ALFRED R. PRAY, who worked as a Research Associate in Craig's Laboratory, has been appointed a Research Asso- Dr. MacInnes's Laboratory, left the Institute on December ciate. 1, 1958. DR. HIROTO NAORA, formerly an Assistant in Research of the MR. s IDN EY ROS EN,a Guest Investigator in Dr. Dan Moore's Cancer Institute, Tokyo, has been appointed a Research Laboratory, left on December 3 1, 1958, and is now with Associate in Dr. Mirsky's Laboratory. the Psychiatric Department of the College of Physicians DR. THEODORE T. PUCK,of the Department of Biophysics, and Surgeons, Columbia University. University of Colorado Medical Center, has been appointed a Visiting Professor of the Institute. Visiting Profesors in Residence
BETTY the of DR. THEODORE T. PUCK, Professor of Biophysics, University Massachusetts General Hospital, has been appointed a Re- of Colorado Medical Center, October 5-16, 1958. search Associate to work in Dr. Rous's Laboratory. DR. DAVID R. GODDARD,Professor of Botany, University of DR. MURRAY D. ROSENBERG, formerly a Consultant for the Pennsylvania, Philadelphia, October 13-17, 1958. Biophysics and Biophysical Chemistry Study Section of the National Institutes of Health, has been appointed a Re- DR. JOSEPH Be BIRDS ELL, Professor of Anthropology, Uni- search Associate in Dr. Weiss's Laboratory. versity of California, Los Angeles, December 15-19, 1958.
DR. JANUSZ S. SKUPIN,formerly of the Departmentof Agri- culture, Institute of Biochemistry, University of Adan- Guest Speakers nickiewicz, in POsnan, has been a Guest MAGASANIK, Associate Professor of Bacteriology and Investigator to work with Dr. Stein, beginning November Immunology, Harvard Medical School, October 14, 1958. 147 1958. JOHN T. RANDALL, University of London King's College, DR. DAVID S. s M ITH, of the Department of Zoology, Sub- October 21, 1958. Department of Entomology, Cambridge University, has been appointed Guest Investigator and Fellow of the Insti- JACQUES MONOD, Head of the Department of Cellular Bio- tute, beginning November 1, 1958, and will work in Dr. chemistry, Institut Pasteur, Paris, October 28, 1958. Porter's Laboratory. GERHARD SCHRAMM, Max-Planck-Institut fiir Virusfor- schung, Tubingen, Germany, November 4, 1958. DR. WALTHER STOECKENIUS, of the Physiologische Insti- tut, Universitat Hamburg, has been appointed a Research J. D. BOYD, Professor of Anatomy, Cambridge University, Fel- Associate in Dr. Porter's Laboratory. low of Clare College, November 14, 1958.
[ 15 1 For the first year of an 8-year study by Dr. Keith R. Porter on response of cells, in terms of fine structures, to common INSTITUTE MENTION carcinogenic agents $11,270 (continued from page fifteen) From the National Science Foundation for the following work: For studies on the chemical nature and mode of action of a specific inducer of the male sex organ in certain plant species by Dr. Armin C. Braun $30,000 THEODOSIUS DOBZHANSKY,Professor of Zoology, Colum- bia University, November 18, 195 8. For studies by Dr. Lyman C. Craig on the isolation and chem- PETER DEB Y E ,Emeritus Professor of Chemistry, Conell Uni- ical composition of cypridina luciferin $9,000 versity, November 2 5, 1958. For a lecture series on science to young people $24,150 AND R z E J B A J E R , Docent of the Jagellonian University, Cra- cow, Poland, December 2,19 58. For a two-year study on anatomical pathway of various sub- stances across the wall of glomerular capillaries, by Dr. Guest Seminar in Medicine George E. Palade $15,000 M. G. P. s TOKE R, Professor of Virology, University of Glas- From The Rockefeller Foundation towards the cost of scientific gow, November 12, 1958. ' illustrations for a joint research publication on mammalian cytology in the Journal of Biophysical and Biochemistry Cy- New Grants and Contracts tology $200 From the United States Public Health Service for the following From the National Foundation for an 18-months' study by Dr. work : Margeris A. Jesaitis on the manner in which the chemical For studies by Dr. S. William Pelletier on the chemistry of markers of the nucleic acids of the even-numbered T. bac- the aconitum and delphinium alkaloids $21,164 teriophages $527965 THE ROCKEFELLER INSTITUTE
is published for the quarters ending in March, June, September and December of each year.
Inquiries, comments and suggestions should be addressed to Mr. Charles I. Campbell, Editor, .zx 4 THE ROCKEFELLER INSTITUTE QUARTERLY,66th Street and York Avenue, New York,. 21