Friedrich Holtz (medical doctor)

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Friedrich Holtz (born October 6, 1889 in Mölln , † June 18, 1967 in Friedrichsdorf ) was a German doctor, biochemist and pharmacologist . Its main merit is the discovery of dihydrotachysterol for the treatment of hypoparathyroidism .

Life

Friedrich Holtz was a son of the businessman Richard Holtz and his wife Hedwig. After graduating from high school in 1917, he studied chemistry and medicine in Göttingen and Würzburg . In 1923 he was promoted to Dr. phil., a year later Dr. med. PhD . From 1926 he worked at the Chemical Institute of the Georg-August University in Göttingen under Adolf Windaus , who received the Nobel Prize for Chemistry in 1928 for his research on sterols . With his double qualification, Holtz was supposed to create the biological-pharmacological department in Göttingen that was necessary for research into the antirachitic sterol vitamins. In 1927 he completed his habilitation in biochemistry.

In 1931 he moved to the Surgical Clinic of the Charité , headed by Ferdinand Sauerbruch , where he headed the chemical laboratory and became an associate professor in 1933 . In 1936 he took over the management of the biological department of the General Institute against Tumor Diseases, founded in 1935, at the Rudolf Virchow Hospital in Berlin . One of his tasks was to set up a central laboratory animal breeding facility . He initially retained his position at the Charité. After personal conflicts , he resigned from his position at the General Institute against Tumor Diseases in 1938. It cannot be clarified whether the disputes had a political background, as he wrote after the Second World War. A position at the Research Association of German Ahnenerbe could not be realized. With the support of the German Research Foundation , Holtz set up a private research laboratory in Berlin-Charlottenburg and from 1939 Berlin-Frohnau . In 1944 he became head of the physiological-biological department of the Central Institute for Cancer Research in Nesselstedt near Posen . He had furniture and equipment from the General Institute against Tumor Diseases transported to Nesselstedt. In October 1944 he reported that the laboratory was running. "The course of the war put an end to these efforts and the central institute, as well as his private institute and house in Berlin-Frohnau, which were completely destroyed by fire."

In 1946, he succeeded Otto Geßner (1895–1968) as the chair of pharmacology at the Martin Luther University in Halle-Wittenberg . After disputes with the authorities, he was deported from the GDR in 1957 and took over the directorate of the Institute for Milk Vitaminization in Frankfurt am Main.

research

Holtz mainly devoted himself to calcium metabolism . Together with his teacher Windaus, he discovered that ultraviolet irradiated ergosterol cured rickets in animal experiments, i.e. it belonged to the vitamin D group . However: "The processes involved in the conversion of the provitamin ergosterol into the vitamin and the physiological mode of action of the vitamin are still unknown," he wrote in 1927.

The search for the actual active ingredient, partly together with the pharmacologist Wolfgang Heubner , led to a product that Holtz and his colleagues called "calcinose factor". "Calcinosefaktor" - in fact a mixture of substances - improved in animal studies the symptoms of after removal of the parathyroid glands resulting hypoparathyroidism , especially the tetany . In 1933 Holtz finally used a further developed preparation, AT 10 , for the treatment of postoperative hypoparathyroidism, which sometimes occurs in humans after removal of the thyroid gland . In the German Journal for Surgery he wrote, main author with six co-authors:

“In January 1927 experimental rat rachitis (avitaminosis D) was cured in Göttingen with tiny doses of ultraviolet irradiated ergosterol; the artificial quartz-mercury sunlamp or the light of a magnesium spark was used to irradiate the ergosterol . <...> I have called the calcium-mobilizing component in the pharmacologically active ergosterine derivatives as the calcinose factor. <...> The effect of the calcinose factor in various ergosterol derivatives was studied qualitatively and quantitatively on numerous test animals. At the same time, attempts were made to therapeutically influence the postoperative tetany of the dog with its calcium salt deficiency in the blood and tissue with calcinose factor, while avoiding symptoms of intoxication . <...> Then I dared to carry out experiments with calcinose factor on myself and my co-workers in order to study the sensitivity and reaction of normal people to the poison. On April 19, I reported to the congress of the German Society for Surgery in Berlin in 1933 about a preparation (designated AT 10) for the treatment of postoperative tetany. The AT 10 contains the calcinose factor dissolved in oil as an effective principle. The phenomena that the supply of the calcinose factor triggers in the body can generally also be produced by AT 10. The beneficial effect of the AT 10 on postoperative tetany could be confirmed by <other>. <...>

Summary.

The antitetanic preparation AT 10 eliminates all symptoms of postoperative tetany. <...> The sick often have to take the preparation for their entire life. The initiation of treatment with AT 10. is dangerous; because storing the preparation can result in a life-threatening overdose. "

The most effective "calcinose factor" was identified as dihydrotachysterol in 1939 and has been the active ingredient of the finished drug AT10, which is still available today (2014) . The vitamin D form calcitriol is mostly used to treat hypoparathyroidism .

In 1937 Holtz summarized the knowledge about the parathyroid glands in the manual of experimental pharmacology . Even after the Second World War, in Halle (Saale) , he remained loyal to calcium, experimentally as well as clinically and health-politically. In 1953 he wrote about his first hypoparathyroidism patient from 1931: "The patient still takes 3 cc AT 10 a week and worked in the laundry of a large hospital until 1953."

"It is thanks to Holtz that he was the first in Germany to campaign sustainably for the treatment of human tetaniums with calcinose factors from irradiated ergosterol." "That a hormone whose protein structure was already known at that time is being replaced by an irradiation product of ergosterol was scientifically an extraordinarily surprising discovery even today and was a rescue from serious illness for many people. "

A second topic for Holtz was oncology . Perhaps it came from vitamin D, because a Göttingen paper from 1931 dealt with the development of skin cancer through ultraviolet radiation. “The experiments have proven the etiological role of ultraviolet rays in human skin cancer.” This topic also extended into the post-war period.

Calcium-Holtz and Adrenalin-Holtz

At about the same time as Friedrich Holtz, Peter Holtz worked as a pharmacologist in Germany , from 1946 to 1951 full professor in Rostock , from 1953 to 1970 full professor in Frankfurt am Main. Its main area was the catecholamines, with adrenaline as the most famous representative. Friedrich Holtz "was considered the 'Calcium-Holtz' within the Ars medica in order to distinguish him from the 'Adrenalin-Holtz' (Peter Holtz, Rostock and Frankfurt / Main). '” Confusion between the two played a role in the discussion of a possible one Involvement of Peter Holtz in the unlawful human experimentation during the Nazi era .

literature

  • Adolf Butenandt: On the 65th birthday of Professor Dr. med. et phil. Friedrich Holtz. . In: drug research . 13, No. 16, 1963, p. 930.
  • Christine Giessler, Jochen Giessler: Institute for Pharmacology and Toxicology, Medical Faculty of the Martin Luther University Halle-Wittenberg. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, ISBN 978-3-85093-281-3 , pp. 287-297.
  • Jürgen Lindner, Heinz Lüllmann: Pharmacological institutes and biographies of their directors. Editio Cantor, Aulendorf 1996, ISBN 3-87193-172-1 .
  • P. Marquardt: On the 60th birthday of Professor Dr. Friedrich Holtz . In: drug research . 8, No. 10, 1958, pp. 676-677.
  • P. Marquardt: In memoriam Friedrich Holtz . In: drug research . 17, No. 7, 1967, pp. 919-920.
  • Ulrike Scheybal: Cancer research in the time of National Socialism with special consideration of the General Institute against Tumor Diseases in Berlin. Dissertation at the Medical Faculty of the University of Leipzig, Leipzig 2000.

Individual evidence

  1. ↑ The date of death 1961 in Lindner and Lüllmann 1996 and Giessler and Giessler 2004 is incorrect. The place of death Friedrichsdorf according to Klee 2007. Lindner and Lüllmann 1996 and Giessler and Giessler 2004 state Frankfurt am Main as the place of death.
  2. ↑ Entry on Dihydrotachysterol. In: Römpp Online . Georg Thieme Verlag, accessed on December 28, 2014.
  3. ↑ Holtz wrote in 1945 that he had to give up his activity at the General Institute "because I dismissed two old party members without notice for fraud". See Scheybal 2000, pp. 56, 57 and 153.
  4. ↑ Klee 2007.
  5. ↑ Scheybal 2000, p. 153.
  6. ^ Giessler and Giessler 2004.
  7. ↑ Friedrich Holtz: The anti-rachitic vitamin . In: Clinical weekly . 6, No. 12, 1927, pp. 535-536. doi : 10.1007 / BF01721633 . Windaus' group published the individual work in the news of the Society of Sciences in Göttingen .
  8. ↑ Wolfgang Heubner, Friedrich Holtz: About the biological inactivity of ergosterol peroxide . In: Clinical weekly . 8, No. 10, 1929, pp. 456-457. doi : 10.1007 / BF01745444 .
  9. ↑ Friedrich Holtz, Emma Schreiber: Some more physiological experiences about the irradiated ergosterol and its conversion products. . In: Hoppe-Seyler's Journal for Physiological Chemistry . 191, No. 1-2, 1930, pp. 1-22. doi : 10.1515 / bchm2.1930.191.1-2.1 .
  10. ↑ Th. V. Brand, F. Holtz, W. Putschar: Comparative pharmacological studies on calcinose factor and parathyroid hormone . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 167, No. 1, 1932, pp. 113-145. doi : 10.1007 / BF01925335 .
  11. ↑ F. Holtz, H. Gissel, E. Roßmann: Experimental and clinical studies on the treatment of postoperative tetany with AT 10 . In: German journal for surgery . 242, No. 7-8, 1934, pp. 521-569. doi : 10.1007 / BF02799296 .
  12. ↑ a b F. v. Werder: About Dihydro-tachysterin . In: Hoppe-Seyler's Journal for Physiological Chemistry . 260, No. 3-4, 1939, pp. 119-134. doi : 10.1515 / bchm2.1939.260.3-4.119 .
  13. ↑ More precisely, the 1939 dihydrotachysterol was dihydrotachysterol 2 , to be distinguished from the cholesterol- derived dihydrotachysterol 3 : Richard B. Hallick, HF DeLuca: 25-hydroxydihydrotachysterol 3 . Biosynthesis in vivo and in vitro . In: Journal of Biological Chemistry . 246, No. 18, 1971, pp. 5733-5738. PMID 4328835 .
  14. ↑ Friedrich Holtz: Active ingredients of the parathyroid glands. In: W. Heubner, J. Schüller (Hrsg.): Handbuch der experimental Pharmakologie , supplementary work, third volume, pp. 151-161. Published by Julius Springer , Berlin 1937.
  15. ↑ Friedrich Holtz, C. Pfennigsdorf, W. Ponsold: The quantitative determination of vitamin D . In: drug research . 5, No. 10, 1955, pp. 557-559.
  16. ↑ F. Holtz, A. Tilgner-Peter: The effect of dihydrotachysterin (AT10) on chickens . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 231, No. 6, 1957, pp. 596-601. doi : 10.1007 / BF00258998 .
  17. ↑ F. Holtz, W. Ponsold: Combating rickets through vitaminization of milk . In: The German health system . 6, No. 33, 1951, pp. 949-952.
  18. ^ F. Holtz: Pathology and Clinic of Parathyroid Tetany (Parathyroid Insufficiency) . In: The German health system . 8, No. 52, 1953, pp. 1581-1584.
  19. ↑ the parathyroid hormone of the parathyroid glands.
  20. ^ Marquardt 1967.
  21. ↑ Walter Putscher, Friedrich Holtz: Generation of skin cancer through long-term ultraviolet radiation . In: Journal of Cancer Research . 33, 1931, pp. 219-260.
  22. ↑ K. Höfer, F. Holtz, M. Koinzer: The survival of deep-frozen vaccine tumors . In: The natural sciences . 27, No. 17, 1939, pp. 275-276. doi : 10.1007 / BF01495540 .
  23. ↑ F. Holtz, H. Frohberg, I. Drebinger: The reactivation of deep-frozen vaccine tumor tissue . In: The natural sciences . 42, No. 3, 1955, p. 75. doi : 10.1007 / BF00589546 .
  24. ^ Giessler and Giessler 2004.
  25. ↑ Christina Witte: “Continue to work scientifically undisturbed…” The pharmacologist Peter Holtz (1902–1970) . Dissertation at the Medical Faculty of the Ernst-Moritz-Arndt University of Greifswald, Greifswald 2006.
personal data
SURNAME Holtz, Friedrich
BRIEF DESCRIPTION German doctor, biochemist and pharmacologist
DATE OF BIRTH October 6, 1889
PLACE OF BIRTH Mölln
DATE OF DEATH June 18, 1967
Place of death Friedrichsdorf