Rudolf Magnus

Rudolf and Gertraud Helene Magnus around 1905

Rudolf Magnus (born September 2, 1873 in Braunschweig , † July 25, 1927 in Pontresina ) was a German doctor, pharmacologist and physiologist . His most significant contribution to biology was the study of the reflexes that contribute to posture . The pharmacologists Wolfgang Heubner and Göran Liljestrand (1886–1968) and Rudolf's son Otto Magnus (* 1913) have presented his life and work .

Life

Rudolf Magnus came from a Braunschweig Jewish family. His parents were the lawyer Otto Magnus (1836–1920) and his wife Sophie geb. Isler (1840-1920). Paternal grandfather and great-grandfather were doctors. The maternal grandfather, Meyer Isler (1807–1888), was the director of the city library, now the State and University Library , Hamburg. After graduating from high school in 1892 at the Martino-Katharineum in Braunschweig, Rudolf decided to study medicine despite his love for poetic literature. He completed it in Heidelberg, briefly also in Berlin and Munich. In Heidelberg he was particularly impressed by the physiologist Wilhelm Kühne . With him he completed his dissertation “About measuring blood pressure with the sphygmograph ”, which he reported on in 1895 at the Third International Physiological Congress in Bern. With him he also met the later physiologist Otto Cohnheim-Kestner of the same age and the somewhat older zoologist and philosopher Jakob Johann von Uexküll , who became his friends. In 1898 he passed the state examination and was awarded a Dr. med. PhD.

After a trip to England, where he gave a lecture on “Contributions to the pupillary reaction of the eel-eye” at the Fourth International Physiological Congress in Cambridge , he began to work as an assistant at the Heidelberg pharmacologist Rudolf Gottlieb . In 1900 he completed his habilitation with a thesis “About Diuresis . II. Communication: Comparison of the diuretic effectiveness of isotonic salt solutions ”and became a private lecturer . During the semester break he often worked in laboratories abroad, for example in 1901 with the physiologist Edward Albert Sharpey-Schafer in Edinburgh and in 1902 and 1903 with Jakob Johann von Uexküll at the Naples Zoological Station . In 1902 he married Gertraud Helene Rau (1875–1947) in Munich, also from a Jewish family. Both of them had been baptized before they were married. The couple had five children, among them the youngest Otto, who later wrote Rudolf's detailed biography. Further trips to England led in 1905 to the physiologist John Newport Langley in Cambridge and in 1908 to the physiologist Charles Scott Sherrington in Liverpool . Here at the end of April he received a letter from Gottlieb that he could no longer give him the position of first assistant. Hardly back in Heidelberg, at the beginning of May, he received a call from Queen Wilhelmina of the Netherlands to the newly created chair for pharmacology in Utrecht , the first pharmacology chair in the Netherlands .

Magnus accepted and moved into a church-like building, "Leeuwenbergh", in Utrecht, built as a hospital in 1567 as his institute. There were several German or Austrian professors in Utrecht, and Magnus initially gave his lectures in German with the approval of the students. According to an anecdote at the beginning of a lecture, around 1918 it was restless in the lecture hall; Magnus made sure his clothing was correct and only realized after twenty minutes that he was speaking Dutch; from then on he taught in the local language.

The First World War did not change anything until Magnus was called to a military hospital in Speyer in October 1915 and to the Kaiser Wilhelms Academy for military medical education in Berlin in June 1916 . He turned down a call to the pharmacology chair at the United Friedrichs University in Halle-Wittenberg in 1915. In 1917, because he was no longer available there, he was able to return to Utrecht. “The Utrecht student body caught up with him at the train station like a prince and cheered him back to his place of work.” He also declined calls to Groningen in 1924 and (as Gottlieb's successor) to Heidelberg. With the help of the Rockefeller Foundation , he planned the construction of a new institute building. The foundation stone was laid in 1926. Magnus died before completion. At the cremation in Zurich, Otto Cohnheim-Kestner, the Zurich physiologist Walter Rudolf Hess , Wolfgang Heubner and Magnus' closest colleague Adriaan PHA de Kleijn (1883–1949) spoke . The new institute "Nieuw Leeuwenbergh" was opened in 1928 by Magnus' successor Ulbe Gerrit Bijlsma (1892–1977).

plant

Heidelberg

General

Magnus' habilitation thesis was published not only as a separate print but also in Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology , there as one of five communications entitled "About diuresis". All of them were about the function of the kidneys and the development of edema . What role did fluid filtration in the glomerula on the one hand, and secretion and reabsorpotion in the renal tubules on the other hand play in urine production ? What role did the kidneys play in edema on the one hand, and the permeability of the blood capillaries on the other? According to the habilitation thesis, sodium sulfate had a more diuretic effect than sodium chloride , probably because of “a different effect in the secreting elements of the kidney itself”. It is difficult to classify it in today's knowledge of kidney physiology.

During his time in Heidelberg, Magnus worked on several other topics, such as cardiac glycosides , the pharmacology of respiration and - three articles with this title - "The constipating effect of morphine "; he examined the latter with the help of the X-rays he had just discovered .

Physiology and pharmacology of the intestine

Contraction measurement on the intestine and recording on a kymograph .

The most lasting were his “Experiments on the surviving small intestine of mammals” - seven articles with this title in Pflüger's archive for the entire physiology of humans and animals . In the first essay, he presents his method:

"In researching the movement phenomena of individual organs, it has so far always proven to be advantageous, in addition to the experiments on the whole animal with its complex innervation relationships and changing influences of the circulatory system , to carry out the examination of the surviving organ in order to determine the performance of this organ by itself , unaffected by those external factors, be capable. ... The following is a simple method to be described, by which one can easily study the phenomena of motion of the surviving small intestine of mammals, and which in my view is suitable for the intestine the same to make as the known Langendorff ' specific method for the heart. ... I started from the findings of Otto Cohnheim , who found in his resorption experiments that the cat's intestine in blood, through which oxygen bubbles, moves vigorously for hours. "

Magnus then shows that bowel loops can also be kept alive in saline solutions instead of blood. "Indeed, under these circumstances the intestine continues its more or less lively movements unchanged for hours, and the entire intestine as well as individual smaller pieces of it can be made accessible to the experiment under these conditions." He describes the consequences of temperature changes, Changes in internal pressure and oxygen deprivation and includes:

“In the foregoing I believe that I have shown that the method described, of observing and registering the movements of the isolated intestine, accomplishes everything that can be expected of such a procedure. Hopefully it will be possible with your help to penetrate deeper into the mechanism of bowel movement, which is still dark in many points, and also to promote the understanding of poisonous effects on the bowel. "

The hope was fulfilled, for example, in Paul Trendelenburg's initiation of the discovery of the opioid receptors in 1917. “Magnus was called ... to give pharmacology a very versatile process and a huge impetus. ... That the method for studying the isolated intestine ... has also become the model for all investigations that have dealt with the study of any smooth muscle organs, the uterus , the retracted penis , the bronchi, the ureters , the arterial strips, Bladder stripes, pupil stripes, even the heart stripes and other objects, that is common property of pharmacologists today. ” Leopold Ther included a detailed description in his“ Pharmacological Methods ”. Probably few who use the method, says Otto Magnus, know about the fundamental observations of their inventor.

Goethe as a natural scientist

In addition to research and pharmacological teaching, Magnus found time for ten lectures on “Goethe as a natural scientist” in the 1906 summer semester. In addition to his literary inclination, there was a suggestion from Uexkülls. He dedicated the book to his "wife and loyal colleague". It is the first work that could be based on the thirteen volumes of the “Weimar Edition”, which have just been completed, with Goethe's scientific writings. In addition, it became Magnus “through the kind courtesy of Mr. Geh. Councilor Dr. Ruland in Weimar made it possible to repeat his experiments in the Goethe house with the poet's own well-preserved apparatus ”.

The lectures are framed by two poems: “Wide world and wide life ...” from 1817 and “Eins und Alles” from 1821. Magnus finds the final verse of the first poem “Well! you have come a long way ”. “Because in Goethe we actually see one of the outstanding natural scientists at the turn of the 18th and 19th centuries, who pursued his studies with the greatest energy in all the numerous areas that he worked on and was never content with amateurish activity, but rather did not rest until he had acquired the knowledge and independence of the specialist. ”In two lectures the botanical work, in two the osteological and comparative anatomical, in two the work on the theory of colors and in one lecture the work on mineralogy, geology and Meteorology dealt with. The description of Goethe's “most careful and laborious detailed studies” and their classification in the science of the time excludes an assessment of the knowledge of the beginning of the twentieth century. One example is Magnus' judgment on Goethe's relationship to the theory of descent . “One has often wanted to see a forerunner of Darwin in Goethe . Häckel especially tried to justify this view. In any case, it is correct that Goethe, as one of the founders of comparative anatomy, laid the foundations on which Darwin continued to work. On the other hand, in Goethe's main morphological works ... there are no views that can be described as Darwinist in the narrower sense. "In his 1822 treatise" Fossil Bull "Goethe wrote:" In any case, the old bull can be seen as a widespread one consider lost parent races, of which the common and Indian bulls should be considered descendants. ”According to Magnus, this is almost the only unambiguous affirmation of a descent hypothesis. Again and again he emphasizes that even where Goethe's conclusions were wrong, as with Isaac Newton in physical optics, his observations were correct.

The frontispiece of the book is Bertel Thorvaldsen's drawing , with which Alexander von Humboldt in 1807 appropriated Goethe's "Ideas for a geography of plants along with a nature painting of the tropical countries": "The genius of Posie, Apollo , lifts the veil of the goddess of nature." Goethe's title “Metamor <phose> of Plants” is carved on a stone at the feet of the goddess . For Magnus, drawing and appropriation represent the recognition that Goethe as a natural scientist gradually received a lot of criticism and that came from Arthur Schopenhauer and Johannes Peter Müller , for example, in terms of physiological - as opposed to physical - optics .

In 1949 an English translation of the "still best generally understandable treatment of the topic, even more than a generation after the first publication" appeared.

Utrecht

General

Contraction of an isolated heart before (lower curve) and after (upper curve) addition of a cardiac glycoside

On the one hand, Magnus continued his Heidelberg themes in Utrecht. An essay was written on cardiac glycosides “On the elementary effects of digital bodies”. It rightly bears the title, not in the sense of the elementary effect on the molecular level, but on the level of the organ “heart”: namely, amplification and acceleration of the contraction. The picture for this was reprinted several times later. His experience in the pharmacology of respiration led to Magnus' work in combat gas research at the Kaiser-Wilhelms-Akademie for military medical education in Berlin. The results were published in 1921 in nine articles "About war gas poisoning" of the journal for the whole of experimental medicine . Magnus and pharmacologist Ernst Laqueur were the main authors in two of the nine publications.

Posture

On the other hand, the move to Utrecht meant a thematic turning point: Posture control became a new and dominant topic. The suggestion came from von Uexkull, who had observed that the movements of the arms of brittle stars , triggered by irritation of their nervous system, were more pronounced when the muscles of the arms were stretched at the time of the irritation. Was there such a dependency in vertebrates? Magnus turned to Sherrington in Liverpool, who had just published "The Integrative Action of the Nervous System". With “Liverpool” as the location, the first of four communications “On the regulation of movements by the central nervous system” appeared in 1909: “I would like to take the opportunity to say thank you very much to Professor Sherrington at this point too. ... The following observations were made for the most part during the Easter break in 1908 in Liverpool. Some additional findings and the cinematographic recordings were obtained later in the Utrecht Pharmacological Institute. "

Vertebrates reacted like brittle stars. Magnus and Sherrington tested the hamstring reflex in dogs whose spinal cord had been severed a few months earlier to eliminate the effects of the brain, and they also observed the reaction of the other leg, the "crossed reflex". “It has now been found that the movements of the crossed leg in this reflex depend in a completely regular way on the position and position that this leg assumes when the reflex is triggered. If the leg is bent at the hips, knees and ankles, extension takes place. ... Exactly the opposite result occurs if the leg is held straight beforehand. ... As you can see, there is a very different reaction to one and the same stimulus, depending on the position that the limb previously occupied. "

Response of the right leg to the hamstring reflex on the left leg

The findings are of fundamental importance for our conception of the function of the central nervous system. The spinal cord is “different in every moment, as it were” and reflects the position and position of the various parts of the body and the whole body in every moment. Each posture corresponds to a certain distribution of excitability in the central nervous system. The body adjusts its central organ in the right way.

In his book "Body Position" in 1924 Magnus summarized the research in Utrecht - 84 articles from his institute. The book shows how different receptors (sensory cells), different areas of the central nervous system and different reflexes, “standing or posture reflexes” for the body at rest and “righting reflexes” contribute to posture from an abnormal position. An extensive chapter is devoted to the “effects of poisons”, pharmacology. The book brings, judged contemporaries, a "sum of knowledge ... that 20 years ago nobody knew anything". It stands next to Sherringont's work "as the most important contribution to the physiology of the nervous system of the last decades". These judgments have stood. “The Utrecht School (Magnus and de Kleijn) began with Sherrington's observations of 'reflex figures' in decerebral animals and then described the patterns of orientation and posture that are familiar today. Sir erred at times, but these errors mean little in view of the abundance of careful observation. The fact that the Dutch researchers did not resort to stereotactic methods may have something to do with Magnus' untimely death in 1927. ”A Russian translation appeared in 1962 and an English translation in 1987.

The " tonic neck reflexes", which are standing reflexes when the position of the head in relation to the trunk changes, are particularly well known because they are also used clinically . They are triggered by deep sensitivity receptors in the neck area. Turning the head leads to the asymmetrical tonic neck reflex : arms and legs on the side to which the chin is turned are stretched, arms and legs on the opposite side are bent. According to the discoverers, one speaks of the "Magnus de Kleijn reflex". It is found in the motor skills of healthy people or animals, but only becomes apparent when the forebrain is switched off due to brain damage. In healthy babies, it disappears at around six months of age. Later onset can be a symptom of a brain disease.

recognition

Magnus was an honorary member of several medical scientific societies. In 1919 he was elected a member of the Royal Dutch Academy of Sciences and received with de Kleijn the "Guyot Prize" of the Senate of the University of Groningen . In 1925 he was elected a member of the Leopoldina . In the same year he received the "Bailey Medal" of the London Royal College of Physicians and in 1928 posthumously the " Hans Horst Meyer Medal" of the Austrian Academy of Sciences . In 1927 he and de Kleijn were nominated for the Nobel Prize in Physiology or Medicine , and the Nobel Committee found their work worthy of the award; but Magnus died before the final decision. In 1968, sixty years after its founding, the Utrecht Pharmacological Institute was named "Rudolf Magnus Institute of Pharmacology". Today it is rededicated as the “Rudolf Magnus Institute” for research in clinical and experimental neurosciences.

literature

• Reinhard Bein : Rudolf Magnus. In: Life stories of Braunschweig Jews. döringDruck, Braunschweig 2016, ISBN 978-3-925268-54-0 , pp. 198–205.
• Wolfgang Heubner: Rudolf Magnus. In: Naunyn-Schmiedebergs Archive for Experimental Pathology and Pharmacology . 128, 1928, pp. 17-23, doi : 10.1007 / BF02130142 .
• G. Liljestrand: Obituary for Rudolf Magnus. In: Results of Physiology 29, pp. 646-654, 1929.
• Otto Magnus: Rudolf Magnus. Physiologist and Pharmacologist 1873-1927. Koninklijke Nederlandse Akademie van Wetenschappen, Amsterdam 2002. ISBN 90-6984-327-7 .

Individual evidence

1. ^ Printed by JB Hirschfeld in Leipzig. Heidelberg University Archives UAH H-III-111/132 fol. 108r – 117v.
2. ↑ Otto Magnus p. 79.
3. ↑ Otto Magnus p. 193.
4. ↑ Otto Magnus p. 198.
5. ↑ Heubner p. 21, analogously also Otto Magnus p. 200.
6. ↑ R. Magnus: About diuresis. II. Communication: Comparison of the diuretic effectiveness of isotonic salt solutions. In: Archives for Experimental Pathology and Pharmacology. 44, 1900, pp. 396-433, doi : 10.1007 / BF01966877 .
7. ↑ Otto Magnus p. 88.
8. ^ R. Magnus: Experiments on the surviving small intestine of mammals. I. Notification. In: Pflüger's archive for the total physiology of humans and animals. 102, 1904, pp. 123-151, doi : 10.1007 / BF01681793 .
9. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 358, 1998, pp. 1-109, here pp. 40-41. doi : 10.1007 / PL00005229 .
10. ↑ Heubner p. 19.
11. ^ Leopold Ther: Pharmacological methods. Wissenschaftliche Verlagsgesellschaft, Stuttgart 1949, pp. 289–294.
12. ↑ Otto Magnus p. 129.
13. ↑ Rudolf Magnus: Goethe as a natural scientist. Lectures held in the summer semester of 1906 at Heidelberg University. Published by Johann Ambrosius Barth, Leipzig 1906.
14. ^ Quote from Magnus. In Goethe's original it says instead of “the old bull” “the old creature”.
15. ^ But see Hermann Bräuning-Oktavio : From the intermaxillary bone to the idea of ​​the type. Goethe as a natural scientist in the years 1780–1786. In: Nova Acta Leopoldina Volume 18, Number 126. Johann Ambrosius Barth, Leipzig 1956. Bräuning-Oktavio quotes Goethe on pp. 51–53: “And yet a series of beings can be placed <between turtle and elephant> that connects the two. “Furthermore:“ Herder's new writing makes it probable that we were first plants and animals. What nature will continue to stamp out of us will probably remain unknown to us. "
16. ↑ Otto Magnus p. 145.
17. ↑ R. Magnus, SCM Sowton: On the elementary effect of the digital body. In: Archives for Experimental Pathology and Pharmacology. 63, 1910, pp. 255-262, doi : 10.1007 / BF01840952 .
18. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 358, 1998, pp. 1–109, here p. 38. doi : 10.1007 / PL00005229 .
19. ↑ E. Laqueur, R. Magnus (12 employees named by name): About war gas poisoning. III. Experimental pathology of phosgene poisoning. In: Journal for all of experimental medicine, including experimental surgery. 13, 1921, pp. 31-179, doi : 10.1007 / BF02998609
20. ↑ E. Laqueur, R. Magnus: About war gas poisoning. V. Experimental and theoretical principles for the therapy of phosgene disease. In: Journal for all of experimental medicine, including experimental surgery. 13, 1921, pp. 200-290, doi : 10.1007 / BF02998611 .
21. ↑ R. Magnus: For the regulation of the movements through the central nervous system. I. Communication. In: Pflüger's archive for the total physiology of humans and animals. 130-130, 1909, pp. 219-252, doi : 10.1007 / BF01677965 .
22. ^ R. Magnus: body position. Published by Julius Springer , Berlin 1924.
23. ↑ Heubner p. 20.
24. ↑ Liljestrand p. 653.
25. ↑ Translated from the English. Ragnar Grant: Comments on history of motor control. In: Vernon B. Brooks (Ed.): Handbook of Physiology, Section 1: The Nervous System, Volume II. Motor Control, Part 1, pp. 1-16. American Physiological Society, Bethesda 1981.
26. ↑ Otto Magnus p. 252.
27. ↑ R. Magnus, A. de Kleijn: The dependence of the tone of the limb muscles on the head position. In: Pflüger's archive for the total physiology of humans and animals. 145, 1912, pp. 455-548, doi : 10.1007 / BF01681127
28. ↑ Magnus and de Kleijn neck reflexes in: Farlex Free Medical Dictionary .
29. ^ University of Groningen: The Guyot Prize.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.  
30. ^ H. Schück and others: Nobel - The Man and his Prizes, pp. 145 and 311. Published by the Nobel Foundation. Elsevier Publishing Company, Amsterdam, London, New York 1962.
31. ^ Website of the Rudolf Magnus Institute .