Michel Eichelbaum

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Michel Eichelbaum

Michel Eichelbaum (born May 19, 1941 in Leipzig ) is a German internist and clinical pharmacologist . He is best known for his work on the influence of gene mutations on the pharmacokinetics of drugs.

Life

His parents were the businessman Gustav Eichelbaum and his wife Emma, ​​nee. Michel. The son Michel passed the Abitur examination at the Leibniz Oberschule in Leipzig in 1959. In the same year he fled with his mother and two younger brothers via Berlin (West) to West Germany. In 1960 he passed the West German supplementary examination for the GDR high school diploma in Stuttgart. He then studied medicine in Heidelberg until the state examination in 1966. In 1968 he was awarded a PhD with a dissertation “Uptake, Distribution, Excretion and Metabolism of 14 C-Prenylamine” written by Hans J. Dengler (1925–1997) in Heidelberg. med. PhD . When Dengler became director of the Medical Polyclinic at the University of Giessen in 1968 , Eichelbaum followed him, as did when Dengler took over the chair for internal medicine at the University of Bonn in 1973 . There he completed his habilitation in 1976 with a thesis "A newly discovered defect in human drug metabolism: The lack of N-oxidation of sparteine"

In 1970 and 1971 he worked with Bernard Beryl Brodie (1907-1989) and James R. Gillette (1928-2001) in the Laboratory of Chemical Pharmacology of the National Heart, Lung and Blood Institute of the National Institutes of Health in Bethesda, 1973 and 1974 with Folke Fritz Gustaf Sjöqvist (1933–2020) at the Department of Clinical Pharmacology at the Karolinska Institute in Solna near Stockholm .

In 1985 he succeeded Jürgen C. Fröhlich (* 1939) as director of the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology at the Robert Bosch Hospital Stuttgart. In 1996 he also took over the then newly created chair for clinical pharmacology at the University of Tübingen . He spent the winter semester 1995–1996 as Visiting Professor at the Department of Clinical and Experimental Pharmacology at the University of Adelaide with Felix Bochner (* 1939) and Andrew Somogyi.

Retired in 2007, Eichelbaum continues to work at his former institute at the Robert Bosch Hospital, which has been headed by his student Matthias Schwab (* 1963) since 2007. He has a son and a daughter.

research

Clinical pharmacology

His further research was already indicated in Eichelbaum's Heidelberg dissertation. It was about the fate of the prenylamine (Segontins ® ) used in coronary heart disease in the body, that is to say about the pharmacokinetics of this substance. He examined them for the dissertation in animal experiments, later, in Gießen, in humans. Pharmacokinetics, especially in humans, became his main topic. In doing so, he always kept an eye on pharmacodynamics , that is, the effect of drugs; it is determined by the pharmacokinetics, for example the elimination . Eichelbaum became - like his first and most important academic teacher Dengler - an internist and clinical pharmacologist. As such, he examined a wide range of topics, including the anti- epileptic carbamazepine and the antiarrhythmic propafenone. The results on the genetics of the cytochrome P450 enzymes, on the role of chirality in pharmacology and on foreign substance transporters should be emphasized .

Sparteine-Debrisoquine Polymorphism

Even in casting began work on the broom - alkaloid sparteine , which was then tested as antiarrhythmic agents for inducing labor. They led to a momentous discovery that Eichelbaum and his co-authors first reported on at a meeting of the German Pharmacological Society in 1975: “When analyzing the pharmacokinetics of Sparteine, we found a small number of apparently healthy people who were practically incapable To metabolize sparteine . ... These 'non-metabolisers' did not convert sparteine ​​into the corresponding ... oxidation products . 4 of more than 100 test persons showed the deviation. In these 4 more than 90% of a sparteine ​​dose was excreted unchanged as sparteine, in all the others only 15–30% of the dose. The sparteine plasma levels were two to four times higher in the non-metabolisers than in the 'metabolisers'. ... Only the non-metabolisers, not the metabolisers, experienced undesirable effects such as visual disturbances, headache and dizziness. "

Two years later, a London working group reported another interindividual difference in drug oxidation: the antihypertensive agent debrisoquine was extensively oxidized in 91 out of 94 people, but hardly in the 3 others. The difference was genetic. Another three years later, in 1980, Eichelbaum and his colleagues brought the two anomalies together: the defect in the sparteine ​​metabolism and the defect in the debrisoquine metabolism were genetically caused defects in the same enzyme system, a sparteine-debrisoquine polymorphism .

Genetic variations in drug metabolizing enzymes had already been found in the 1950s. However, these were relatively special enzymes, for example pseudocholinesterase , which splits two muscle relaxants . However, as Eichelbaum had already shown in his habilitation thesis, the enzyme responsible for oxidation of sparteine ​​and debrisoquine belonged to the cytochrome P450 system, the most important enzyme system that breaks down most foreign substances (through oxidation).

As a result, the effect of the defect on the metabolism of other drugs and its frequency in different ethnic groups were investigated. The gene for the responsible P450 enzyme was located on the long arm of chromosome 22 and cloned by a US-Swiss research group . The enzyme was named cytochrome P450 2D6 (CYP 2D6). Numerous mutations that lead to a decrease (or increase) in enzyme activity have also been identified, to date (2011) more than 100. According to this, there are normal metabolizers ( extensive metabolizers ), deficient metabolizers ( poor metabolizers ) or extremely fast metabolizers ( ultrarapid metabolizers ). The importance arises on the one hand from the large number of people affected, around 15% of Europeans deficient metabolisers, on the other hand from the large number of drugs that are exclusively or partially metabolized by CYP 2D6, more than 50 - including propafenone. For example, one of many examples, CYP 2D6 - and thus its polymorphism - contributes to the metabolism of tamoxifen and thereby influences its effectiveness in breast cancer .

Verapamil: stereoselective pharmacokinetics

Verapamil was recognized as a calcium antagonist by Albrecht Fleckenstein at the end of the 1960s and is still widely used today for cardiovascular diseases. It soon became apparent that the usual dose for intravenous administration, 5–10 mg, was ineffective when administered orally, and even a five to ten-fold higher oral dose was only unreliable. To find the reason, Eichelbaum's group developed a gas chromatographic-mass spectrometric method to measure the substance and its metabolites. It turned out that although verapamil was completely absorbed from the intestine, it was then largely broken down in the intestinal wall and liver, i.e. that it did not reach the heart due to this first-pass effect , the breakdown during the first passage through the intestinal wall and liver. That answered a question.

The next posed the paradox that a certain concentration of verapamil in the blood obtained by oral administration affected the heart less than the same concentration obtained by intravenous administration. "We then realized that verapamil had a chiral center and was administered as a racemate - we remembered that verapamil was a chiral molecule and was used as a racemate ." The Bonn researchers only had the total concentration of, as was not possible at the time "(R) - + (S) -Verapamil" measured. Also, since it was known that the (S) - enantiomer was the actual active ingredient, at least at heart much more strongly acted as the (R) enantiomer, they hypothesized that liver build the first pass effect mainly the (S ) Enantiomer. Then the blood should contain less of the effective (S) -verapamil at a certain total concentration of "(R) - + (S) -Verapamil" achieved by oral administration than at the same total concentration achieved by intravenous administration.

At that time the enantiomers could not be separated. The way to test the hypothesis had to be rethought. It consisted of labeling one of the two isomers with the stable hydrogen isotope, deuterium . The deuterated enantiomer could then be separated from the non-deuterated one thanks to its greater mass in the mass spectrometer. The results were available in 1984. Indeed, (S) -verapamil was subject to a greater first pass effect than (R) -verapamil, and after the same oral dose, the concentration of (S) -verapamil in the blood was much lower than the concentration of (R) -verapamil, one stereoselective metabolism with considerable consequences for the effect of the substance. (R) - and (S) -Verapamil also differ in their binding to plasma proteins . Stereoselective pharmacokinetics became a separate area of ​​research. Sparteine ​​is also metabolized stereoselectively, and the enantiomers of propafenone differ in metabolism and effect. The 1984 publication was reprinted in 2004 in a special Citation Classics in the British Journal of Clinical Pharmacology 1974-2003 , with Eichelbaum commenting that he considered it one of his best.

Effect of rifampicin on the absorption of digoxin from the intestine. By inducing P-glycoprotein ( b ), rifampicin increases the return transport of digoxin into the intestinal lumen.
Pharmacogenetics of the antiemetic ondansetron . Dependence of the blood level on the cytochrome P450 2D6 , the entry into the brain on the P-glycoprotein , the effect on the 5-HT 3 receptor on its genetics.

Digoxin and Rifampicin: Transporters

The pharmacokinetics is also determined by transporters that transport foreign substances through cell membranes. An important transporter is the P-glycoprotein . Using adenosine triphosphate, it removes foreign matter from cells. For example, cytostatics are channeled out of cancer cells and the cells are thus cytostatics-resistant - this effect led to the discovery in 1976 and also led to the alternative name Multidrug-Resistance-Protein 1 (MDR1; also ABCB1). Verapamil racemate, it was known since 1981, inhibited outward transport. Its use in tumors was opposed to the (in this case undesirable) cardiovascular effects. Eichelbaum, with his experience in stereoselective pharmacology, therefore initiated a comparison of the effects of (R) - and (S -) - verapamil on cancer cells: Both increased the effect of cytostatics, and to the same extent. In contrast to the racemate, the conclusion is drawn, the (R) -enantiomer, which has little effect on the cardiovascular system, could become a useful aid in cancer chemotherapy - a hope that was ultimately not fulfilled.

P-glycoprotein is also found in healthy cells and has several pharmacokinetic functions. For example, it restricts the absorption of some drugs, such as the cardiac glycoside digoxin, from the intestine by pumping them back into the intestinal lumen. This resulted, as the Stuttgart researchers discovered in 1999, a new type of drug interaction: taking the antibiotic rifampicin in addition to digoxin reduced its concentration in the blood by increasing the content of P-glycoprotein in the intestinal mucosa and thus further increasing the return transport of digoxin. The mechanism of P-glycoprotein replication - increase in its transcription of the gene - was clarified, other substances, for example from St. John's wort , acted like rifampicin, and similarities were observed in other transporters. The induction of drug metabolizing enzymes had found a counterpart in the induction of transporters.

In collaboration with a group at the Charité in Berlin and a biotechnological company, Eichelbaum Gruppe systematically searched for mutations in the P-glycoprotein gene at the end of the 1990s. Fifteen were found, and one of them (C3435T) had pharmacokinetic consequences: in homozygous carriers of the mutation, the amount of P-glycoprotein in the intestine was reduced and, after ingestion of digoxin, the concentration of the glycoside in the blood was increased. 25 years after the discovery of the CYP 2D6 polymorphism, this was the first clinically relevant polymorphism of a transporter. The publication has stimulated much further research, and the general medical meaning of the mutation is not clear. It seems to increase the risk of developing kidney tumors, ulcerative colitis and Parkinson's disease and influences the success of treatment in ulcerative colitis.

Knowledge transfer

Eichelbaum tried to convey his results and knowledge to the health professions and the general public in writing and organizing. From 1987 to 1990 he was President of the German Society for Clinical Pharmacology and from 2000 to 2003 Vice President of the German Society for Experimental and Clinical Pharmacology and Toxicology . He is a member of the drug commission of the German medical profession and is working on their drug prescriptions, which are now in their 22nd edition - recommendations for rational pharmacotherapy .

He (co) publishes clinical pharmacological journals such as the European Journal of Clinical Pharmacology and Pharmacogenetics and Genomics . In review articles for doctors he has emphasized the importance of pharmacogenetics for individualized medicine . With Matthias Schwab he presented his subject in textbook articles.

In 2007 he worked in an international group of scientists for a network for the avoidance of serious drug side effects (SADR): “When good drugs go bad. ... It is unthinkable that selecting drugs for individual patients remains an empirical exercise. ... A global SADR network will not be cheap, but it will be a fraction of the current cost of SADRs to the healthcare system. - When good medicines become bad. ... It would be irresponsible to leave the choice of drugs for individual patients to unchecked opinion. ... A global SADR network would not be cheap, but would only be a fraction of the current costs for SADR. "

recognition

In 1976 Eichelbaum received the Paul Martini Prize from the foundation of the same name and in 1983 the medal of the same name. In 1988 he was awarded the Robert Pfleger Research Prize together with Konrad Beyreuther . In 1991 the German Society for Pharmacology and Toxicology honored him with the Rudolf Buchheim lecture. In 2001 he became a member of the German Academy of Sciences Leopoldina , in 2003 of the Academy of Sciences and Literature in Mainz. In 2008 the German Society for Experimental and Clinical Pharmacology and Toxicology awarded him its highest scientific award, the Schmiedeberg plaque .

Individual evidence

  1. ↑ M. Eichelbaum and K. von Bergmann: Prof. Dr.med. Hans J. Dengler. In: DGPT-Forum Heft 23, 1998, pp. 9-10.
  2. ^ Wilhelm Kirch: Oswald Schmiedeberg Medal of the DGPT for Prof. Eichelbaum . In: Biospektrum 14, 2008, p. 309. Retrieved on January 17, 2013.
  3. ↑ Eichelbaum on the website of the drug commission of the German medical profession. ( Memento of the original from July 25, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved January 17, 2013. @1@ 2Template: Webachiv / IABot / www.akdae.de
  4. ↑ HJ Dengler and M. Eichelbaum: Investigations into the behavior of C 14 -D, L-prenylamine in the organism . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . 260, 1968, pp. 105-106. doi : 10.1007 / BF00537915 .
  5. ↑ M. Eichelbaum, N. Spannbrucker, HJ Dengler: N-oxidation of sparteine ​​in man and its interindividual differences . In: Naunyn-Schmiedebergs Archives of Pharmacology . 287, 1975, p. R 94.
  6. ^ A. Mahgoub, JR Idle, LG Dring, R. Lancaster, RL Smith: Polymorphic hydroxylation of debrisoquine in man . In: The Lancet . 310, 1977, pp. 584-586. doi : 10.1016 / S0140-6736 (77) 91430-1 .
  7. ↑ L. Bertilsson, HJ Dengler, M. Eichelbaum, HU Schulz: Pharmacogenetic covariation of defective N-Oxidation of sparteine ​​and 4-hydroxylation of debrisoquine . In: European Journal of Clinical Pharmacology . 17, 1980, pp. 153-155. doi : 10.1007 / BF00562624 .
  8. ↑ M. Eichelbaum, L. Bertilsson, J. Säwe, C. Zekorn: Polymorphic oxidation of sparteine ​​and debrisoquine: related pharmacogenetic entities . In: Clinical Pharmacology and Therapeutics . 31, 1982, pp. 184-186. doi : 10.1038 / clpt.1982.29 .
  9. ↑ M. Eichelbaum, MP Baur, HJ Dengler, BO Osikowska-Evers, G. Tieves, C. Zekorn and C. Rittner: Chromosomal assignment of human cytochrome P-450 (debrisoquin / sparteine ​​type) to chromosome 22 . In: British Journal of Clinical Pharmacology . 23, 1987, pp. 455-458. PMC 1386095 (free full text).
  10. ↑ Frank J. Gonzalez, Radek C. Skodat, Shioko Kimura, Morio Umeno, Ulrich M. Zanger, Daniel W. Nebert, Harry V. Gelboin, James P. Hardwick and Urs A. Meyer: Characterization of the common genetic defect in humans deficient in debrisoquine metabolism . In: Nature . 331, 1988, pp. 442-446. doi : 10.1038 / 331442a0 .
  11. ^ Alan C Gough, John S. Miles, Nigel K. Spurr, Julie E. Moss, Andrea Gaedigk, Michel Eichelbaum and C. Roland Wolf: Identification of the primary gene defect at the cytochrome P 450 CYP2D locus . In: Nature . 347, 1990, pp. 773-776. doi : 10.1038 / 347773a0 .
  12. ↑ Ulrich M. Zanger, Sebastian Raimundo, Michel Eichelbaum: Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 369, 2004, pp. 23-37. doi : 10.1007 / s00210-003-0832-2 .
  13. ↑ M. Eichelbaum, M. Schwab: Effects of the organism on pharmaceuticals: general pharmacokinetics. In: K. Aktories, U. Förstermann, F. Hofmann, K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pages 36-64, here page 63. ISBN 978-3-437-42522-6
  14. ↑ Werner Schroth, Matthew P. Goetz, Ute Hamann, Peter A. Fasching, Marcus Schmidt, Stefan Winter, Peter Fritz, Wolfgang Simon, Vera J. Suman, Matthew M. Ames, Stephanie L. Safgren, Mary J. Kuffel, Hans Ulrich Ulmer, Julia Boländer, Reiner Strick, Matthias W. Beckmann, Heinz Koelbl, Richard M. Weinshilboum, James N. Ingle, Michel Eichelbaum, Matthias Schwab, Hiltrud Brauch: Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen . In: Journal of the American Medical Association . 302, 2009, pp. 1429-1436. doi : 10.1001 / jama.2009.1420 .
  15. ^ TE Mürdter, W. Schroth, L. Bacchus-Gerybadze, S. Winter, G. Heinkele, W. Simon, PA Fasching, T. Fehm, M. Eichelbaum, M. Schwab, H. Brauch: Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and phase II enzymes on their concentration levels in plasma . In: Clinical Pharmacology and Therapeutics . 89, 2011, pp. 708-717. doi : 10.1038 / clpt.2011.27 .
  16. ↑ Michael Schomerus, Berthold Spiegelhalder, Barbara Stieren, Michel Eichelbaum: Physiological disposition of verapamil in man . In: Cardiovascular Research . 10, 1976, pp. 605-612. doi : 10.1093 / cvr / 10.5.605 .
  17. ↑ M. Eichelbaum, P. Birkel, E. Grube, U. Gütgemann, A. Somogyi: Effects of verapamil on PR-intervals in relation to verapamil plasma levels following single iv and oral administration and during chronic treatment . In: Clinical weekly . 58, 1980, pp. 919-925. doi : 10.1007 / BF01477049 .
  18. ↑ a b Michel Eichelbaum: Author's commentary . In: British Journal of Clinical Pharmacology . 58, 2004, pp. S804-S805. doi : 10.1111 / j.1365-2125.2004.02300.x .
  19. ↑ B. Vogelgesang, H. Echizen, S. Schmidt, M. Eichelbaum: Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of L- and D-verapamil examined with a stable isotope technique . In: British Journal of Clinical Pharmacology . 18, 1984, pp. 733-740. PMC 1463564 (free full text). , accessed October 18, 2011.
  20. ^ Annette S. Gross, Barbara Heuer, Michel Eichelbaum: Stereoselective protein binding of verapamil enantiomers . In: Biochemical Pharmacology . 24, 1988, pp. 4623-4627. doi : 10.1016 / 0006-2952 (88) 90330-9 .
  21. ^ AS Gross, A. Somogyi, M. Eichelbaum: Stereoselective drug metabolism and drug interactions. In: Michel Eichelbaum, Bernard Testa, Andrew Somogyi: Stereochemical Aspects of Drug Action and Disposition. Handbook of Experimental Pharmacology 153, pp. 313-339. Berlin, Heidelberg, Springer-Verlag 2003. ISBN 3-540-41593-9
  22. ↑ T. Ebner, CO Meese, M. Eichelbaum: Regioselectivity and stereoselectivity of the metabolism of the chiral quinolizidine alkaloids sparteine ​​and pachycarpine in the rat . In: Xenobiotica . 21, 1991, pp. 847-857. doi : 10.3109 / 00498259109039524 .
  23. ↑ Heyo K. Kroemer, Christian Funck-Brentano, David J. Silberstein, Alastair JJ Wood, Michel Eichelbaum, Raymond L. Woosley, Dan M. Roden: Stereoselective disposition and pharmacologic activity of propafenone enantiomers . In: Circulation . 79, 1989, pp. 1068-1076. doi : 10.1161 / 01.CIR.79.5.1068 .
  24. ↑ K. Häußermann, B. Benz, V. Gekeler, K. Schumacher, M. Eichelbaum: Effects of verapamil enantiomers and major metabolites on the cytotoxicity of vincristine and daunomycin in human lymphoma cell lines . In: European Journal of Clinical Pharmacology . 40, 1991, pp. 53-59. doi : 10.1007 / BF00315139 .
  25. ↑ Bernd Greiner, Michel Eichelbaum, Peter Fritz, Hans-Peter Kreichgauer, Oliver von Richter, Johannes Zundler, Heyo K. Kroemer: The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin . In: The Journal of Clinical Investigation . 104, 1999, pp. 147-153. doi : 10.1172 / JCI6663 .
  26. ↑ Anke Geick, Michel Eichelbaum, Oliver Burk: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin . In: The Journal of Biological Chemistry . 276, 2001, pp. 14581-14587. doi : 10.1074 / jbc.M010173200 .
  27. ↑ D. Rosskopf, HK Kroemer, W. Siegmund: Pharmacokinetic problems in practice - role of drug transporters . In: German Medical Weekly . 134, 2009, pp. 345-356. doi : 10.1055 / s-0028-1124005 .
  28. ^ S. Hoffmeyer, O. Burk, O. von Richter, HP Arnold, J. Brockmöller, A. Johne, I. Cascorbi, T. Gerloff, I. Roots, M. Eichelbaum, U. Brinkmann: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo . In: Proceedings of the National Academy of Sciences . 97, 2000, pp. 3473-3478. doi : 10.1055 / s-0028-1124005 .
  29. ↑ Ann K. Daly: Pharmacogenetics and human genetic polymorphisms . In: Biochemical Journal . 429, 2010, pp. 435-449. doi : 10.1042 / BJ20100522 .
  30. ^ Matthias Schwab, Michel Eichelbaum and Martin F. Fromm: Genetic polymorphisms of the human MDR1 drug transporter . In: Annual Review of Pharmacology and Toxicology . 43, 2003, pp. 285-307. doi : 10.1146 / annurev.pharmtox.43.100901.140233 .
  31. ^ KR Herrlinger, H. Koc, S. Winter, A. Teml, EF Stange, K. Fellermann, P. Fritz, M. Schwab, E. Schaeffeler: ABCB1 single-nucleotide polymorphisms determine tacrolimus response in patients with ulcerative colitis . In: Clinical Pharmacology and Therapeutics . 89, 2011, pp. 422-428. doi : 10.1038 / clpt.2010.348 .
  32. ↑ M. Eichelbaum, M. Schwab: Pharmakogenetik . In: Monthly Pediatrics . 153, 2005, pp. 741-750. doi : 10.1007 / s00112-005-1199-x .
  33. ↑ Michel Eichelbaum, Magnus Ingelman-Sundberg and William E. Evans: Pharmacogenomics and individualized drug therapy . In: Annual Review of Medicine . 57, 2011, pp. 119-137. doi : 10.1146 / annurev.med.56.082103.104724 .
  34. ↑ M. Eichelbaum, M. Schwab: Effects of the organism on pharmaceuticals: general pharmacokinetics and drug concentration in the organism as a function of time: pharmacokinetics in the narrower sense. In: K. Aktories, U. Förstermann, F. Hofmann, K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pages 36-79. ISBN 978-3-437-42522-6
  35. ↑ Kathleen M. Giacomini, Ronald M. Krauss, Dan M. Roden, Michel Eichelbaum, Michael R. Hayden, Yusuke Nakamura: When good drugs go bad . In: Nature . 446, 2007, pp. 975-977. doi : 10.1038 / 446975a .
  36. ↑ Member entry of Michel Eichelbaum at the German Academy of Natural Scientists Leopoldina , accessed on July 5, 2016.
  37. ↑ Member entry by Michel Eichelbaum at the Academy of Sciences and Literature Mainz , accessed on October 11, 2017


personal data
SURNAME Eichelbaum, Michel
BRIEF DESCRIPTION German internist and clinical pharmacologist
DATE OF BIRTH May 19, 1941
PLACE OF BIRTH Leipzig