Biographical Memoirs Volume 57 (1987) / Chapter Skim
Currently Skimming:
Otto Krayer
Otto Krayer
Pages 150-225
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 151... ...
It is not acceptable, however, for you to make the practice of your teaching profession dependent upon those feelings. You would in that case not be able in the future to hold any chair in a German university.
|
From page 152... ...
in the flowering of a promising career brought upon him the full retribution of the Nazi hierarchy. Robert Jungk, in his book Brighter Than A Thousand Suns, A Personal History of the Atomic Scientists, writes about those clays in early 1933 in Gottingen: "Only a single one of Gottingen's natural scientists had the courage to protest openly against the dismissal of the Jewish savants.
|
From page 153... ...
Had I not expressed to you the misgivings that made me hesitate to accept your offer immediately, I would have compromised one of these essential human qualities, that of honesty. It seems to me, therefore, that the argument that in the interests of the task at hand I must defer my personal misgivings, is an empty one.
|
From page 154... ...
Most fount! it easiest "not to clecicle." The surgeon Rudolf Nissen, writing of the German university faculties in 1933, has this to say: Another example of rare, almost isolated conduct amidst the crowd of opportunists was given by the Berlin Professor Extraordinarius, Otto
|
From page 155... ...
Trendelenburg: Die Hormone, a task 2 Rudolf Nissen, Helle Blatter dunkle Blatter: Erinnerungen eines Chirurgen (Stuttgart: Deutsche Verlags-Anstalt, 1969)
|
From page 156... ...
Officially representing the American University of Beirut at the Tercentenary Celebration of Harvard University in 1936, he was asked to stay on for a few months as a lecturer in pharmacology at the Harvard Meclical School. Then in 1937 an invitation was extencled for Krayer to join the faculty as associate professor of pharmacology.
|
From page 157... ...
Stock concerning the awarcl of the Nobel peace prize, which are printed on page 121 of the Proceedings of the German Chemical Society of 9 June 1937 oblige me to request that you strike my name from the list of members of the German Chemical Society." Professor Stock, in reply, couIct only imagine that he had been misunderstoocI. "I was only reflecting the feelings of every German scientist," he wrote, "in being upset by such a conscious provocation .
|
From page 158... ...
What made me write my letter of 3 September was the urge to express the view that not every German and- as I am convinced not every German scientist shares your feelings of being upset by the award of the recent Nobel peace prize. The reason for this conviction is what I have read over the last ten years of the writings of Carl van Ossietzky and have learned from other sources about him.
|
From page 159... ...
A final incident is noteworthy, again for the light it sheets on the ethical stanciarcls by which Krayer consistently guiclect all his actions. In 1965 the Academic Council of the Medical Academy of Dusseldorf votect to confer honorary membership on Krayer.
|
From page 160... ...
The reference, in the rector's original letter, to Krayer's maintaining anct furthering contacts with German science will be cryptic to those unfamiliar with an episode that followed shortly on the close of World War Il. With Central Europe literally in ashes, its universities and research institutes in ruins, and its people starving, the Unitarian Service Committee organized a medical mission to Czechoslovakia with Harvard carctiologist Paul DuctIey White as director and Krayer as an active participant.
|
From page 161... ...
Over a period of four decacles, Krayer published seventysix original research articles (not counting abstracts and textbook chapters) , all but one in the field of cardiovascular physiology and pharmacology; the exception was a brief note concerning pumpkin seects as a chemotherapy for tapeworm infestation, a byproduct of his brief stay at the American University of Beirut.
|
From page 162... ...
He was always generous with suggestions, technical assistance, and criticism, but he would not put his own name to research unless he had been a direct participant. ~ consider it more remarkable now than ~ realized at the time that although at the beginning ~ was only a medical student engaged in part-time research in his department, it was taken as a matter of course that ~ would coauthor work for which Krayer had prime responsibility and would be sole author
|
From page 163... ...
, he wrote the following laudatory sentence, which is also an apt clescription of his own attitude: "He felt that any work worth publishing deserves] as much care in the preparation of the manuscript as in the concluct of the experimental work." Krayer held the belief that the aim of pharmacologic investigation is to elucidate mechanisms of drug action, that phenomenologic observations by themselves are only stepping stones to this ultimate goal.
|
From page 164... ...
that increases the heart rate. Does it do so by a direct agonistic effect on receptors mectiating carctioacceleration at the pacemaker?
|
From page 165... ...
Trendelenburg a stanciarcI procedure for using the HEP to stucly drug effects on the failing heart. The competent heart increases its output in response to elevation of the venous reservoir without any significant increase in right atrial pressure that is, the adclitional inflow reacts responsively to an increased stroke volume.
|
From page 166... ...
. This method allowed a clear distinction to be made between ctrugs that primarily affected heart rate anct those (like digitalis)
|
From page 167... ...
being perfused from a clonor dog. Krayer's interest in the Veratrum alkaloids, which dome natecI his research interests from 1942 on, was stimulated, according to his own account ~ ~ 962b)
|
From page 168... ...
Before injection of the cholinesterase inhibitor physostigmine, the blood had no effect on the leech muscle (I)
|
From page 169... ...
OTTO KRAYER 169 FIGURE 2 Veratrum viride, popularly known as Indian pokeweed. This North American wild plant and related species that grow in Central and South America and Europe contain the cardioactive steroidal alkaloids in their roots, stems, and leaves.
|
From page 170... ...
There are two major groups of veratrum alkaloids, the tertiary amine esters and the secondary amines (Figure 3)
|
From page 171... ...
One of the conclusions was that the name of this reflex, hitherto known as the Bezold effect, should more appropriately also bear the name of ~arisch. Krayer's studies with the tertiary amine polyesters, especially protoveratrine A, led him to explore their therapeutic utility in human hypertension.
|
From page 172... ...
The positive inotropic action of veratridine or protoveratrine is of theoretical interest because of its similarity to the effect of the digitalis glycosicles. Inhibition of the sodium pump (soclium-potassium ATPase)
|
From page 173... ...
HEP infused continuously with epinephrine, the steacly-state marked increase in heart rate is promptly abolishect by small doses of veratramine. At the same time the positive inotropic action of epinephrine remains unchanged.
|
From page 174... ...
Within a minute, epinephrine increases the cardiac output (top line) , thus lowering the elevated right atrial pressure and pulmonary pressure; it also increases the systolic arterial pressure all without any increase of heart rate.
|
From page 175... ...
It had aIreacly been shown, first in Brodie's and then in Marthe Vogt's laboratory that reserpine clepletes the brain of its serotonin stores, and this same approach was being extended to brain catecholamines in several laboratories. The immediate stimulus for Krayer's interest was a letter In the New England fournal of Medicine reporting heart failure .
|
From page 176... ...
floes not participate in the carclioaccelerator action. An additional finding of interest, revealing an independent effect of reserpine, was that in the HEP under the rate-increasing effect of a catecholamine infusion, reserpine recluced the heart rate in an atropine-resistant manner reminiscent of veratramine.
|
From page 177... ...
. ~ enjoyed seeing the results with reserpine in the heart-lung preparation." More than a year later, on June 3, 1958, Burn and Rand submitted for publication "The Action of Sympathomimetic Amines in Animals Treated with Reserpine."6 This major contribution establishecl very thoroughly that reserpine clepletes the stores of norepinephrine in arterial walls.
|
From page 178... ...
by an infusion of norepinephrine that repletes the stores. Further significant conclusions were that a continuous slow release of norepinephrine from arteriolar stores probably plays a role In maintaining the normal vascular tone anct also that circulating catecholamines from the adrenal gland probably participate in maintaining the stores at their proper level.
|
From page 179... ...
examined ten Ranwolfia alkaloids and showed that, whereas they all displayed a direct depressant effect on both the heart rate and atrio-ventricular transmission, only half of them were catecholamine depleters. Waud, Kottegoda, and Krayer (1958f)
|
From page 180... ...
to the carcliovascular effects of both catecholamines. Finally, reserpine pretreatment clid not influence the effects of norepinephrine or epinephrine on the heart rate.
|
From page 181... ...
His focus on the HEP tended to limit his "audience." Moreover, his steadfast refusal to draw a conclusion that went beyond his own data meant that the broad significance of the reserpine findings did not "leap off the page." It is true that the field quickly became competitive, whereas Krayer's discovery of catecholamine depletion was probably unique in 1955. Painstaking thoroughness about every aspect of experimentation and the preparation of manuscripts accounted for the passage of two years until the first brief meeting abstracts appeared, and three years until the first full-length papers were published.
|
From page 182... ...
can perhaps understand better than our younger colleagues the significance of kymography practiced as an art. To produce experimental records of the quality evident already in Krayer's Berlin publications of 1929-1933 implied an attention to detail affecting all aspects of an experiment.
|
From page 183... ...
His perfectionism about scientific publication inclucled a strong insistence on the correct use of words. His philosophy about this is expressed, in part, in a publication summarizing many of his studies on drugs affecting the heart rate (1963a)
|
From page 184... ...
A combat wound shortly before the armistice sent him to hospital and then, while still convalescing, he completed the educational requirements for university entrance. Finally, in the autumn of 1919, he enrolled as a medical student at the University of Freiburg.
|
From page 185... ...
dollar—a princely sum in those days of rampant inflation in Germany. And here on the ski slopes near Freiburg he enjoyed the companionship of a classmate, Erna Ruth Philipp, who was (much later)
|
From page 186... ...
These were the students' only opportunities to observe the effects of cirugs on animals; there were no facilities for routine laboratory teaching of medical students. It is interesting, in the light of Krayer's later strong belief in the importance of practical laboratory work in pharmacology for medical students, that in 1927 he embarked on what was then a raclical innovation—a small, elective experimental laboratory course.
|
From page 187... ...
Attendance at the International Physiology Congress at Stockholm in 1926 gave Krayer the opportunity to meet some of the leading cardiovascular physiologists and pharmacologists of the clay Starling himself, J
|
From page 188... ...
One of those who assisted him at this difficult time was Dr. Erna Ruth Philipp, who had been a fellow medical student at Freiburg and eventually was to become Krayer's wife.
|
From page 189... ...
that direct stimulation of the vagus released acety~choline. Within a few months Krayer was approached about the possibility of assuming direction of the Department of Pharmacology at the American University of Beirut.
|
From page 190... ...
190 BIOGRAPHICAL MEMOIRS vigorous outdoor regimen of hiking and climbing and trips on horse-back experiences that lecI to a deep attachment to the scenery of the region. Mount Sannin near Beirut especially captures!
|
From page 191... ...
We do know that Krayer had made the acquaintance of Walter B Cannon at the International Physiology Congress in the summer of 1935 in Moscow.
|
From page 192... ...
Krayer became increasingly disillusioned with the situation and especially with the lack of support from the medical school administration. Six months after his arrival he was offered the chair of pharmacology at Peiping, which had been vacated when van Dyke moved to Columbia.
|
From page 193... ...
At this time, too, he married Erna Ruth Philipp anct moved into the comfortable house in West Newton in which so many students and young colleagues anct their families were to be entertained. Another vignette, from the spring of 1939, epitomizes Krayer's readiness to clo instantly and without weighing consequences—whatever was needed when a worthy person or cause requirec!
|
From page 194... ...
Nevertheless, the war years saw increasing productivity of his own research and the foundations laid for the very strong department that was ultimately to develop. Krayer's first Ph.D.
|
From page 195... ...
laboratory course in pharmacology for all the medical students, on a larger scale than he tract clone in Beirut. With a class of 125 each year, this was a major logistic undertaking, carried out by the capable and loyal Diener Mr.
|
From page 196... ...
. In 1948 Krayer served as chairman of the medical mission to Germany uncler the same auspices.
|
From page 197... ...
Conant himself was a prime mover in this program for integrating research anct teaching in pharmacology and therapy, with the hope of attracting major corporate and inctiviclual donors. Krayer saw in it an opportunity to develop an adequately large single department of pharmacology and pharmacotherapy.
|
From page 198... ...
Although his own research was wholly devotect to unclerstanding drug action at the physiologic level on the functions of organs
|
From page 199... ...
He often ridiculed the reductionism that sometimes led to proposed mechanisms of drug action based on some test tube phenomenon at a concentration vastly higher than could ever be attained in viva. By 1960 the department had moved into new quarters, financed in part with funds provided by the National Insti
|
From page 200... ...
Putting the interests of the meclical school ahead of the long-term needs of his own department, Krayer tract set aside space for a laboratory of neurophysiology "temporarily," as such arrangements are often planned to be at the outset. This statesmanlike action certainly brought glory to the Harvard Mectical School (including, as it turner!
|
From page 201... ...
, was where so many generations of medical students and young scientists had gathered for tea or to ctrink Rhine wine, and to experience Krayer's sincere interest in their welfare and their educational anct scientific progress. Whenever small children were brought to these gatherings, Krayer's stern exterior dissolvect.
|
From page 202... ...
He held a visiting professorship at the University of Arizona School of Medicine anc! a similar appointment at the Technical University of Munchen, where his former associate Melchior Reiter was professor of pharmacology.
|
From page 203... ...
His first major contribution, appropriately, was to serve for five years as associate editor of one of the Society's journals, Pharmacological Rev~ews. This was followed by another five years as editor-inchief.
|
From page 204... ...
The names of these people are just as much Krayer's "bibliography" as the compendium of his own publications, and therefore it is appropriate that they be listed here. Represented are scientists from 26 foreign countries on 5 continents, as well as students, staff, anct visiting scientists from the United States.
|
From page 206... ...
B Pluchino BIOGRAPHICAL MEMOIRS L
|
From page 207... ...
C Barger: "He was one of the few teachers in the medical school that I worshipped—for his superb pedagogic skills, his warm human qualities, and his willingness to fight for principles." B
|
From page 208... ...
Landis graciously allowed me to impose on their time. My own memories were supplemented by those of Rafael Mendez and Douglas S
|
From page 209... ...
1964. "Otto Krayer zum 65.
|
From page 210... ...
1934 Visiting Professor and Head, Department of Pharmacology, American University of Beirut 1936 1937 Lecturer in Pharmacology, Harvard Medical School Associate Professor of Pharmacology, Harvard Medical School 1939 Associate Professor of Comparative Pharmacology and Head, Department of Pharmacology, Harvard Medical School 1951 Professor of Pharmacology, Harvard Medical School 1954 Charles Wilder Professor of Pharmacology, Harvard Medical School 1964 Gustavus Adolphus Pfeiffer Professor of Pharmacology, Harvard Medical School 1966 Gustavus Adolphus Pfeiffer Professor of Pharmacology, Emeritus, Harvard Medical School
|
From page 211... ...
Chairman, Unitarian Medical Mission to Germany (1948) Associate Editor, Pharmacological Reviews ( 1948-1953)
|
From page 212... ...
Honorary Citizen of Kondringen (1957) Torald Sollmann Award of the American Society for Pharmacology and Experimental Therapeutics ~ 1961 ~ Schmiedeberg Plakette of the German Pharmacological Society (1964)
|
From page 213... ...
Visiting Professor, Department of Pharmacology, Technical Un versity of Munchen ~ 1972-1980) Visiting Professor, Department of Pharmacology, College of Medicine, University of Arizona (1972-1980)
|
From page 214... ...
II. Mitteilung: Uber die Ursache der Kreislaufwirkung.
|
From page 215... ...
h. ~ Trendelenburg's Grundlagen der allgemeinen und speziellen Arzneiverordnung, 3d ed.
|
From page 216... ...
I The action of veratrine upon the isolated mammalian heart.
|
From page 217... ...
IV. The sites of the heart rate lowering action of veratridine.
|
From page 218... ...
Krayer. The action of erythrophleum alkaloids upon the isolated mammalian heart.
|
From page 219... ...
Action of epinephrine and veratramine upon heart rate and oxygen consumption in the
|
From page 220... ...
XII. A quantitative comparison of the antiaccelerator cardiac action of veratramine, veratrosine, jervine and pseudojervine.
|
From page 221... ...
Krayer. Clinical studies on veratrum alkaloids.
|
From page 222... ...
Fuentes. Chronotropic cardiac action of reserpine.
|
From page 223... ...
Fuentes. Changes in heart rate caused by direct cardiac action of reserpine.
|
From page 224... ...
Action of guanethidine and reserpine upon the isolated mammalian heart.
|
From page 225... ...
Rate-increasing action of methylguanidine upon the isolated mammalian heart.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.