Franz Gross (pharmacologist)

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Franz H. Gross-Adomeit (1913–1984) Dr. med., professor, pharmacologist, head of clinical drug testing at Ciba in Basel. Family grave in the Hörnli cemetery, Riehen, Basel-Stadt
Family grave in the Hörnli cemetery , Riehen, Basel-Stadt

Franz Gross (born February 14, 1913 in Leipzig ; † March 26, 1984 in Binningen , Canton of Basel-Landschaft ) was a German-Swiss doctor and pharmacologist and authoritative researcher on high blood pressure and its treatment.

Life

He was a son of the actor Otto Gross (1881–1916) from Basel and his wife, the actress Stella b. David (1883-1950). Both were engaged in Leipzig and Dresden. Franz spent his childhood and youth there. He studied medicine in Leipzig and Berlin. In 1938 he became a doctor of medicine with a work by the internist Karl Matthes (1905–1962) “On the reduction time of blood”. med. PhD. He then worked at the Pathological Institute of the Technical University of Dresden and the Medical Clinic of the University of Leipzig . In 1941 he married Liselotte geb. Adomeit, with whom he had three daughters. During the Second World War he was a medical officer in the Air Force . After the war he first worked with Alexander von Muralt at the Physiological Institute of the University of Bern . In September 1946 he became head of clinical drug testing at Ciba in Basel. In 1958 he qualified as a professor for physiology in Bern. In 1965 he became an honorary professor . In 1967 he received offers to the Max Planck Institute for Experimental Medicine in Göttingen and the Pharmacological Institute of the Ruprecht-Karls-Universität Heidelberg . In 1968 he decided on Heidelberg, where he succeeded Oskar Eichler . It was an unusual step for the time - from an industrial management position to a university chair - and it was the decision to take over the institute in Heidelberg's Friedrichsbau , “a museum institute which, founded in 1890, was structurally largely in its original state ". The authors of a Heidelberg institute history ironic the change: "An important aspect of the handover from O. Eichler to F. Gross was the handover of the key to the director's toilet, which was located in the stairwell of the old institute building." In 1974 the institute moved into a new building Neuenheimer Feld . Retired in 1981, Gross managed it temporarily for another two years. In 1983 Ulrich Schwabe (* 1935), previously professor in Bonn, became his successor.

plant

From his time with Karl Matthes on, Gross was interested in the physiology and pharmacology of the circulatory system. In connection with this, Alexander von Muralt was also interested in the hormones of the adrenal cortex and in the renin-angiotensin system , which among other things regulates the formation of aldosterone in the adrenal cortex. Gross' goal was and remained the understanding and effective therapy of arterial hypertension. He was therefore as much a basic researcher as he was practice-oriented. He also discovered or co-discovered renin , which is named after its origin from the kidney, in Latin ren , outside the kidney, for example in the uterus and placenta as well as the lower salivary gland . In 1958 he summarized the physiological importance of renin and angiotensin, in 1971 their relationship to high blood pressure, and in 1973 the effects of angiotensin and aldosterone on the kidneys in review articles.

In 1950, he and his colleagues from Ciba presented their first new antihypertensive drugs . “The drug therapy of the various forms of hypertension has not yet been solved satisfactorily, since almost all of the substances in question can usually result in a temporary drop in blood pressure, but not a longer-lasting decrease. ... In the pharmacological investigation of phthalazine derivatives we found compounds whose effect on blood pressure is initially characterized by the fact that they cause a peculiar, slow and long-lasting decrease in blood pressure in animals. ... The ... lowering of blood pressure shows ... peculiarities that suggest a special mechanism of action. ”It was the discovery of the phthalazine derivatives and vasodilators hydralazine ( Apresolin ® ; marketed in 1952) and dihydralazine ( Nepresol ® ; 1953). The “special mechanism of action” remained a “special one” even in 1953, after a closer analysis: “Based on the experimental findings, it can be assumed that the pressure-lowering effect of hydrazinophthalazines is based on a particular mechanism of action that is not only due to a direct peripheral vascular effect, but for which influences on central nervous regulation are also responsible. ”In the same year 1953 the description of the pharmacology of reserpin , the main alkaloid of Rauwolfia serpentina , and its introduction as Serpasil ® followed . Indian doctors had described the plant's effects - lowering blood pressure, bradycardia , antipsychotic effects , diarrhea , and parkinsonism - with admirable accuracy since the 1930s . The reserpine had been isolated at Ciba. It became only temporarily important in the treatment of hypertension and mental illness, but has continued to be important as a unique pharmacological tool in the history of catecholamine research . Later antihypertensives from Gross' group were the adrenergic neurone blocking guanethidine ( Ismelin ® ; 1960) and the β-adrenoceptor - antagonist oxprenolol ( Trasicor ® ; 1968).

Substances with a different active character, namely angiotensin II (as Hypertensin ® ) and aldosterone (as Aldocorten ® ), the methadone- related opiate ketobemidone ( Cliradon ® ) and even the much-discussed methylphenidate (as Ritalin ® ) today (2013 ) were under Gross 'Launched into the market with collaboration from Ciba.

In 1977 Gross published the volume “Antihypertensive Agents” in the handbook of experimental pharmacology , with the chapters (from the English; selection) “ Ganglion blockers ”, “Rauwolfia alkaloids”, “Adrenergic neuron blockers ”, “False transmitters as antihypertensive agents”, “ Clonidine and relatives ”,“ vasodilators ”,“ diuretics ”,“ inhibitors of the renin-angiotensin system ”and“ veratrum - alkaloids ”. The ganglion blockers were introduced in the 1940s. When substances with fewer side effects became available with hydralazine, dihydralazine, reserpine and guanethidine, they became obsolete. Thirteen years later, Detlev Ganten and the American internist Patrick J. Mulrow published a new edition under the title “Pharmacology of Antihypertensive Agents”. In the foreword they wrote (from English): “The previous volume on antihypertensive drugs in this handbook, published in 1977, was edited by the late Franz Gross from the Pharmacological Institute in Heidelberg, one of the great old men in high pressure research. Today, more than ten years later, the volume needs to be updated. Since the early days of antihypertensive therapy, which began thirty years ago with substances such as reserpine and guanethidine, cardiovascular treatment has become highly differentiated and effective. "

Gross remained true to his life theme in Heidelberg too. He examined the regulation of the release of renin from the kidneys and took up the question of the mode of action of his vasodilators hydralazine and dihydralazine.

Increasingly, he published general thoughts on medicine, clinical research and the publication of its results. He asked, “Can we develop new antihypertensive drugs?” “The high pressure treatment has gradually improved. ... After the ganglion blockers came hydralazine and reserpine in 1951, five years later the thiazide diuretics , 1961 guanethidine and shortly afterwards methyldopa . The era of β-adrenoceptor antagonists began in the late 1960s, and about ten years later inhibiting the angiotensin-converting enzyme proved surprisingly successful. ”His question, he said, was more correct,“ Can we develop better antihypertensive drugs? ” ; then the answer would be “yes” with the restriction “at least marginally better.” He emphasized the necessity of testing drugs even after their approval , emphasized the need for a discussion of homeopathy in academic teaching and pleaded with the winged word of Shakespeare's Polonius “ brevity is the soul of wit "for keeping it short in scientific language, closing:" Since brevity is the soul of wit, we will be brief "-" Because brevity is the soul of the joke, we want to be short. "

In Heidelberg he founded the Collaborative Research Center 90 “Cardiovascular System” of the German Research Foundation . From 1972 he was a member of the board of the drug commission of the German medical profession . In 1974 he founded the German League for Combating High Blood Pressure , today the German High Pressure League . From 1970 to 1976 he was President of the International Society of Hypertension and Secretary General of the International Union of Pharmacology (IUPHAR).

Students and staff

In Gross' Heidelberg Institute there were several independent groups that cooperated and were supported by him. During his time he completed his habilitation (year of habilitation):

  • Günter Schultz (1970), later professor at the Pharmacological Institute of the Free University of Berlin ;
  • Paul Vecsei (1971), later professor at the Heidelberg Institute, who conducted research on adrenal cortex hormones;
  • Jan Möhring (1973), who worked on the role of vasopressin in blood pressure regulation;
  • Volker Kreye (1974), later professor at the Physiological Institute in Heidelberg;
  • Detlev Ganten (1974), who came from McGill University in Montreal and later became the founding director of the Max Delbrück Center for Molecular Medicine in Berlin-Buch;
  • Harald Frohberg (1975), employee at Merck KGaA in Darmstadt and later head of clinical research there;
  • Karl Hofbauer (1975), who came from Ciba and returned there;
  • Hansjörg Seyberth (1977), later director of the children's clinic at Philipps University in Marburg ;
  • Franz Hofmann (1977), later professor at the Pharmacological Institute of the Technical University of Munich ;
  • Eycke Böhme (1978), who worked in Günter Schultz's group and later became professor at the Pharmacological Institute of the Free University of Berlin;
  • Rainer Dietz (1978), later director of the cardiology department of the Franz-Volhard-Klinik in Berlin-Buch ;
  • Karl Heinrich Jakobs (1979), who worked in Günter Schultz's group and later became a professor at the Pharmacological Institute of the University of Essen ;
  • Ulrich Hilgenfeldt (1980), research area on the renin-angiotensin system, later professor at the Heidelberg Institute;
  • Rudolf Lang (1981), later professor at the Physiological Institute at the University of Marburg;
  • Thomas Unger (1982), who worked in Detlev Ganten's group and later became director of the Pharmacological Institute at the Christian Albrechts University in Kiel ;
  • Klaus Aktories (1983), later professor at the Pharmacological Institute of the Albert Ludwig University of Freiburg ;
  • Wolfgang Rascher (1983), later director of the children's clinic at Erlangen University Clinic .

recognition

In 1970 Gross became an honorary member of the American College of Physicians , and in 1974 a member of the Heidelberg Academy of Sciences . In 1978 he was awarded the Great Cross of Merit of the Federal Republic of Germany . In 1984 the German medical profession awarded him the Paracelsus Medal . In 1995, in its 125th year, the Swiss Medical Weekly reprinted its 1953 article on hydrazonophthalazines as “Scientific Raisin from 125 Years of SMW”.

literature

  • Deutsches Ärzteblatt : Professor Dr. med. Franz Gross The bearers of the Paracelsus Medal of the German Medical Profession 1984. Accessed on July 14, 2013.
  • Dagmar Drüll. Heidelberger Gelehrtenlexikon 1933–1986 , pp. 237–238. Springer-Verlag , Berlin 2009. ISBN 978-3-540-88835-2 .
  • Franz Gross: Inaugural address at the Heidelberg Academy of Sciences. In: Volker Sellin, Sebastian Zwies (eds.): The Heidelberg Academy of Sciences as reflected in its inaugural speeches 1944–2008, pp. 397–401. Universitätsverlag Winter, Heidelberg 2009. ISBN 978-3-8253-5568-5 .
  • Eberhard Hackenthal, Stefan Offermanns, Günter Schultz: Pharmacological Institute, Medical Faculty of the Ruprecht-Karls-Universität Heidelberg. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 329–336. ISBN 3-85093-180-3 .
  • Jürgen Lindner and Heinz Lüllmann: Pharmacological institutes and biographies of their directors. Editio-Cantor-Verlag, Aulendorf 1996. ISBN 3-87193-172-1 .
  • Peter C. Waldmeier: Pharma research at Ciba-Geigy and its predecessor companies Ciba and Geigy. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 858-863. ISBN 3-85093-180-3 .
  • M. Ziegler: In Memoriam Prof. Dr. Franz Gross . In: The cardiologist . 7, 2013, pp. 37-38. doi : 10.1007 / s12181-012-0477-9 . Reprinted in Druckpunkt 1–2, 2013.

Individual evidence

  1. ↑ Eberhard J. Wormer :  Matthes, Karl. In: New German Biography (NDB). Volume 16, Duncker & Humblot, Berlin 1990, ISBN 3-428-00197-4 , p. 400 f. ( Digitized version ).
  2. ↑ Franz Gross: About the reduction time of the blood . In: Journal of All Experimental Medicine, Including Experimental Surgery . 102, 1938, pp. 766-777. doi : 10.1007 / BF02630291 .
  3. ↑ Ziegler 2013.
  4. ↑ Hackenthal and others 2004.
  5. ↑ K. Matthes, F. Gross: Investigations on the effect picture of vascular active pharmaceuticals in humans. Part 2: Sympathomimetica . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 203, 1944, pp. 206-224. doi : 10.1007 / BF01865923 .
  6. ↑ Fr. Gross, K. Matthes: Investigations into the effect of vascular active pharmaceuticals in humans. III. Communication: Periodic breathing according to pervitine and ephedrine . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 204, 1947, pp. 57-66. doi : 10.1007 / BF00738332 .
  7. ↑ Franz Gross: The effect of deoxycorticosterone acetate and table salt on the experimental hypertension of the rat . In: Archives internationales de Pharmacodynamie et de Thérapie . 81, 1950, pp. 211-221.
  8. ^ F. Gross, G. Schaechtelin, M. Ziegler, M. Berger: A renin-like substance in the placenta and uterus of the rabbit . In: The Lancet . 283, 1964, pp. 914-916. doi : 10.1016 / S0140-6736 (64) 91637-X .
  9. ↑ WJ Oliver, F. Gross: Behavior of the renin-like principle in the salivary gland of the white mouse under different conditions . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . 255, 1966, pp. 55-56. doi : 10.1007 / BF00544831 .
  10. ↑ E. Hackenthal, Chr. Koch, Th. Bergemann, F. Gross: Partial purification and characterization of a renin-like enzyme from rat submandibular gland . In: Biochemical Pharmacology . 21, 1972, pp. 2779-2792. doi : 10.1016 / 0006-2952 (72) 90026-3 .
  11. ↑ F. Gross: Renin and Hypertensin, Physiological or Pathological Agents? . In: Clinical weekly . 36, 1958, pp. 693-706. doi : 10.1007 / BF01493136 .
  12. ^ Franz Gross: The renin-angiotensin system and hypertension . In: Annals of Internal Medicine . 75, 1971, pp. 777-787. doi : 10.7326 / 0003-4819-74-5-843_7 .
  13. ^ F. Gross, J. Möhring: Renal pharmacology, with special emphasis on aldosterone and angiotensin . In: Annual Review of Pharmacology and Toxicology . 13, 1973, pp. 57-90. doi : 10.1146 / annurev.pa.13.040173.000421 .
  14. ^ F. Gross, J. Druey, R. Meier: A new group of blood pressure lowering substances with a special effect . In: Experientia . 6, 1950, pp. 19-21. doi : 10.1007 / BF02154049 .
  15. ↑ a b H. J. Bein, F. Gross, J. Tripod, R. Meier: Experimental studies on the circulatory effects of the antihypertensive hydrazinophthalazine derivatives apresolin and nepresol . In: Swiss Medical Weekly . 83, 1953, pp. 336-340.
  16. ↑ HJ Bein, F. Gross, J. Tripod, R. Meier: Experimental studies on "Serpasil" (reserpine), a new, very effective Rauwolfia alkaloid with a novel central effect . In: Swiss Medical Weekly . 83, 1953, pp. 1007-1012.
  17. ↑ K. Starke: Pharmacology of noradrenergic and adrenergic systems. In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke (eds.): General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2010, pp. 198-199, here pp. 187-188. ISBN 978-3-437-42522-6
  18. ^ F. Gross, R. Meier: 1-methyl-4-m-oxyphenyl-piperidine-4-ethyl ketone (Cliradon), a new synthetic analgesic with a morphine-like effect . In: Swiss Medical Weekly . 79, 1949, pp. 1154-1159.
  19. ^ R. Meier, F. Gross, J. Tripod: Ritalin, a new type of synthetic compound with a specific central stimulating component . In: Clinical weekly . 32, 1954, pp. 445-450. doi : 10.1007 / BF01466968 .
  20. ↑ Waldmeier 2004.
  21. ^ Franz Gross (Ed.): Antihypertensive Agents. Handbook of Experimental Pharmacology Volume 39. Springer-Verlag , Berlin 1977. ISBN 3-540-07594-1 .
  22. ^ Detlev Ganten, Patrick J. Mulrow: Pharmacology of Antihypertensive Agents. Handbook of Experimental Pharmacology Volume 93. Springer-Verlag, Berlin 1990. ISBN 3-540-50427-3 .
  23. ↑ KG Hofbauer, H. Zschiedrich, F. Gross: Regulation of renin release and intrarenal formation of angiotensin. Studies in the isolated perfused rat kidney . In: Clinical and Experimental Pharmacology and Physiology . 3, 1976, pp. 73-93. doi : 10.1111 / j.1440-1681.1976.tb00593.x .
  24. ↑ M. Khayyal, F. Gross, VAW Kreyenfeld: Studies on the direct vasodilator effect of hydralazine in the isolated rabbit renal artery . In: Journal of Pharmacology and Experimental Therapeutics . 216, 1981, pp. 390-394. PMID 7463355 .
  25. ↑ G. Bönner, D. Beck, M. Deeg, M. Marin-Grez, F. Gross: Effect of dihydralazine on the renal kallikrein-kinin system of the rat . In: European Journal of Pharmacology . 78, 1982, pp. 219-223. doi : 10.1016 / 0014-2999 (82) 90239-4 .
  26. ↑ M. Khayyal1, F. Gross, VAW Kreye: Differential effects of hydralazine on the biphasic responses of helical strips from rat tail arteries . In: General Pharmacology . 14, 1983, pp. 121-123. doi : 10.1016 / 0306-3623 (83) 90079-4 .
  27. ^ F. Gross: Can we develop new drugs for hypertension? . In: British Journal of Clinical Pharmacology . 13, 1982, pp. 133-136. PMID 6121571 .
  28. ↑ F. Gross: Ongoing examination of drugs . In: Munich Medical Weekly . 126, 1984, pp. 325-329.
  29. ^ Franz Gross: Homeopathy as the perfection of Hippocratic medicine . In: Munich Medical Weekly . 126, No. 14, 1984, p. 18.
  30. ^ HJ Dengler, F. Gross: Brevity is the soul of wit . In: European Journal of Clinical Pharmacology . 24, 1983, p. 571. doi : 10.1007 / BF00542202 .
  31. ↑ Hackenthal and others 2004.
personal data
SURNAME Gross, Franz
BRIEF DESCRIPTION German pharmacologist
DATE OF BIRTH February 14, 1913
PLACE OF BIRTH Leipzig
DATE OF DEATH March 26, 1984
Place of death Binningen