Central Institute for Microbiology and Experimental Therapy

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The Central Institute for Microbiology and Experimental Therapy (ZIMET) was a non-university research institute of the Academy of Sciences of the GDR (AdW). It was based in Jena and emerged in 1970 from the Institute for Microbiology and Experimental Therapy founded by the physician and microbiologist Hans Knöll in the Beutenberg district of Jena, which from 1956 belonged to the research community of the AdW. Several institutes of the Leibniz Association were established as successor institutions in 1992 . ZIMET was involved in the state compulsory doping system in GDR competitive sports .

history

The Institute for Microbiology and Experimental Therapy (IMET) as a forerunner of the later Central Institute emerged from the Schott Zeiss Institute for Microbiology, which existed from 1944. Its director, Hans Knöll succeeded after the end of World War II, the production of the antibiotic penicillin on an industrial scale, commissioned by the SMAD . With few resources, but with an inventive spirit and support, especially from the Jena glassworks Schott & Gen. (Glass culture vessels, bacteria sterile filters). On the one hand, the company Jenapharm or VEB Jenapharm emerged from the institute in 1950 as a production facility for penicillin and other drugs in the German Democratic Republic (GDR). As a research institute, Knöll was then allowed to design and build the IMET. At the beginning (1953) it was subordinate to the Ministry of Health of the GDR and was taken over by the AdW in March 1956. In 1970 the institute was named "Central Institute for Microbiology and Experimental Therapy".

The directors of the institute were Hans Knöll from its founding until 1976, Udo Taubeneck from 1976 to 1984 , Friedrich Bergter from 1984 to 1989 and Michael Oettel from 1989 to 1991 . From 1971 the institute belonged to the Research Center for Molecular Biology and Medicine , the network of bioscientific and medically oriented institutes of the academy. The ZIMET, which also had an art collection , was one of the largest biomedical research institutions in the GDR with around 1000 employees (1985).

Structure and tasks

According to Hans Knöll's intention, the institute's activities focused on broad-based research into anti-tumor and antibacterial agents, from the search for active substances (antibiotics, synthetics, steroids, etc.) to biological tests and investigations into the mechanism of action.

In accordance with this objective, research began in 1953 in the newly built institute building on Beutenberg. From the beginning, in addition to the research laboratories, a chemical and biological technical center was available, as well as institute workshops for the construction and self-construction of special devices as well as animal houses for necessary in vivo tests and the own rearing of laboratory animals.

In its first decade as an academy institute under Hans Knöll, IMET made recognized contributions to basic research in microbiology, in special areas of biophysics and biochemistry, in antibiotic research and in the analysis of steroid hormones. The chemical-synthetic production of potential cytostatics brought initial success. In addition, established production processes for antibiotics have been improved (penicillin, streptomycin, oxytetracycline) (Gumpert, 2012, p. 283).

Since 1967 the state has called for a stronger link between research and industry. This was taken into account through the conclusion of business contracts (among others with the VEB Jenapharm) as well as through cooperation projects, also through cooperation with academy institutes in other countries of the then " Eastern Bloc ". The IMET was divided into four areas:

Antibiotics - Medical Microbiology - Molecular Biology - Experimental Therapy (Gumpert, 2012, p. 284).

Later there were again changes through regrouping or new directions of work. The following overview with eight scientific areas corresponds to the status around 1986 (schicht and Germann, 1987). The areas of work mentioned in extracts are mostly taken from the same ZIMET publication; they span longer periods.

Antibiotic Research:

  • Processing of production processes for known antibiotics (oxytetracycline, erythromycin, paromomycin, turimycin and others)
  • Isolation and characterization of new antibiotic producers and their active ingredients
  • Clarification of the structure and biosynthetic pathway of selected antibiotics
  • Screening models for effects on DNA synthesis (potential cytostatics)
  • Semi-synthetic and biosynthetic modification of active ingredients
  • Continuous expansion of the IMET culture collection founded by Hans Knöll in 1943 in the microbe taxonomy department (gene bank for bacteria, depository for patent strains).

Biotechnology division (division since 1980):

  • Investigation and mathematical description of the growth, metabolism and product formation of microorganisms
  • Optimization of microbial product formers
  • Scale up fermentation for antibiotics
  • Processing of the primary metabolism (lysine), of biologically active proteins and enzymes.

Experimental Therapy:

  • New antineoplastic and antiviral agents
  • Further development of Cytostasan / Bendamustine
  • Processing of known cytostatics (mitoguazone, cis-platinum)
  • Animal models for the necessary studies of pharmacology , endocrinology , toxicology and pathology
  • Laboratory animal science
  • Virology: elucidation of the pathogenesis of model infections.

Medical microbiology:

  • Research on streptococci : morphological, genetic, immunobiological and immunochemical processing
  • Investigation of the infection process: virulence factors
  • Reference laboratory for streptococci
  • Monitoring of the type distribution of A and B streptococci, also internationally
  • Isolation of streptokinase and development to the thrombolytic drug Awelysin

The BCG Institute, which was the first institute unit on Beutenberg to start its work in 1952, was part of the division. The vaccine against tuberculosis for the entire GDR was produced here until the end of 1990.

Methodology and theory (later: biophysics and analytics):

  • Physical and physicochemical properties of DNA when interacting with biologically active compounds: structure, binding kinetics, thermodynamics
  • Interactions of biologically active substances with other biopolymers and membranes
  • Application of spectrophotometric, polarographic and hydrodynamic methods as well as automatic image analysis
  • Use of the department's own large-scale equipment to determine the structure of active substances (mass spectrometry, NMR spectrometry).

Molecular Biology and Microbial Genetics:

  • Representation of the cell nucleus in living fungal and yeast cells during cell division and sporulation
  • Use of phase contrast microscopy; Micro cinematography, research films
  • Work on the cytoskeleton and microtubules of the fungal cell
  • Investigation of bacterial L-forms for statements about the importance of the cell wall
  • Investigations on gene structure and gene expression in microorganisms:
  • Sequence-specific binding of biologically active ligands to DNA
  • Development of microbial expression systems for proteins
  • Production of restriction endonucleases and deoxyoligonucleotides

Environmental microbiology (later: ecology):

Added to ZIMET in 1972 through the inclusion of the previously independent research center for limnology of the AdW.

  • Investigation of the ecosystems of flowing and standing water
  • Microbial decomposition of pollutants through cometabolism
  • Isolation of methanotrophic and methanol-assimilating bacteria and yeasts
  • Investigation of the methane cycle.

Steroid research division (until 1973 part of the experimental therapy division):

  • Steroid hormone metabolism in cancer; Development of microanalytical methods
  • Microbial steroid transformation for comparison with the metabolism in mammals, including pharmaceuticals: Oral-Turinabol (published since 1970, e.g.), and Dienogest
  • Work on the microbial production of steroids from the raw material β-sitosterol
  • Synthesis and testing of new steroids for hormonally effective pharmaceuticals. Active substance classes: soft estrogens, progestins, antigestagens, cardiac active substances, androgens / anabolic steroids
  • Active ingredient class progestins: selection and further processing of dienogest for gynecology
  • Active substance class androgens / anabolic steroids: search for effect dissociation; Pharmacokinetics. This part of the work, used by the FKS Leipzig, justifies the allegation of doping research (see below).

doping

Scientists at the ZIMET goods by the research of doping expert Werner Franke in the research as part of a state plan theme 14:25 designated state-organized doping program in GDR competitive sport involved. The development of new doping preparations was led by the Research Institute for Physical Culture and Sport (FKS) in Leipzig, which worked together with the Jenapharm research department and ZIMET. However, the researchers were only partially informed about the use of the preparations by athletes. After the idea for the use of androstenedione in GDR competitive sport arose at the FKS, Kurt Schubert from ZIMET, Michael Oettel ( Jenapharm ) and Jürgen Hendel ( GERMED ) took part in a colloquium there in June 1981 . A carefully researched description of the doping-related work with anabolic steroids from Jenapharm and from ZIMET can be found in the dissertation by O. Haupt (2017).

Results from the ZIMET

In addition to all research that was published or continued in the successor institutions, at least two active ingredients from the ZIMET should be mentioned, the success of which the institute has outlasted for decades:

  • The cancer drug bendamustine , which is now sold under the brand names Treanda, Levact, Ribamustin and others. a. ranks among the top-selling cancerostatic agents worldwide. It is used for chemotherapy, especially for hematological tumors, mostly in combination with other substances. The compound was first synthesized by Werner Ozegowski and Dietrich Krebs with the institute name IMET 3393, selected by Hans Knöll and then, with the addition of Mannose (Werner et al.), Already used as Cytostasan in the GDR for cancer therapy.
  • The synthetic steroid hormone dienogest , a gestagen with an antiandrogenic component. First synthesized as STS 557 by Michael Hübner and Kurt Ponsold and selected by Michael Oettel, Dienogest was already used in the GDR and later further developed by Jenapharm. It is a component of successful contraceptives, each in combination with an estrogen, for example in the preparations Valette and Lafamme, as well as a monopreparation for endometriosis (Visanne).

Successor institutions

After German reunification , the institute only existed until the end of 1991, in accordance with Article 38 of the Unification Treaty. As one of the successor institutions, the Hans Knöll Institute for Natural Product Research (HKI) emerged from ZIMET at the beginning of 1992, was included in the funding of the so-called Blue List and has been a member of the Leibniz Association since 2003 . Since 2005 it has been called the Leibniz Institute for Natural Product Research and Infection Biology . The Institute for Molecular Biotechnology (IMB) was established as a further successor institution in 1992 and has been on the Blue List since it was founded . The Leibniz Institute for Aging Research emerged from the IMB in 2005 . The limnology division of ZIMET, located in the municipality of Neuglobsow , became part of the Leibniz Institute for Freshwater Ecology and Inland Fisheries, which was founded in Berlin in 1992 .

literature

  • Johannes Gumpert: Hans Knöll - a pioneer in biotechnology. In: Manfred Steinbach (Hrsg.): Jena yearbook on technology and industrial history. Volume 15, Verlag Vopelius Jena 2012, pp. 245-314.
  • Gerald Layer, Dietrich Germann (Red.): Central Institute for Microbiology and Experimental Therapy Jena of the Academy of Sciences of the GDR - 30 years Academy Institute, 1956–1986. Self-published by the institute, Jena 1987

Web links

Individual evidence

  1. ↑ Peer Kösling, Maria Schmid, Gunthard Linde: The art collection of ZIMET - Central Institute for Microbiology and Experimental Therapy of the Academy of Sciences of the GDR: Four decades of art in a research institute in the GDR . Ed .: Städtische Museen Jena. Jena 1995, ISBN 3-930128-20-9 .
  2. ↑ Werner Ozegowski, Dietrich Krebs: ω [bis (chloroethyl) aminobenzimidazolyl (2)] propionic or butyric acids as potential cytostatics . In: J. Prakt. Chemistry . tape 20 , 1963, pp. 178-186 .
  3. ↑ Werner Ozegowski, Dietrich Krebs: IMET 3393, ɤ (1-methyl-5-bis- (β-chloroethyl) -aminobenzimidazolyl- (2) butyric acid hydrochloride, a new cytostatic from the series of benzimidazole mustards . In: Zbl. Pharm. pharmacotherapy, laboratory diagnostics . band 110 , 1971, p 1013-1019 .
  4. ↑ Kurt Schubert, Joseph Schlegel, Helmut Groh, Gunar Rose, Cläre Hörhold: Metabolism of steroid pharmaceuticals . VIII. Structure-metabolic relationships in the microbial hydrogenation of differently substituted testosterone derivatives . In: Endocrinology . tape 59 , 1972, p. 99-114 .
  5. ↑ Michael Hübner, Kurt Ponsold, Michael Oettel, Regina Freund: A new class of highly effective gestagens: 17α-CH2X-substituted gona-4,9 (10) -dienes . In: Arzneimittel-Forsch-Drug Res. Volume 20 , 1980, pp. 401-404 .
  6. ^ Werner Franke: Expert opinion on the type and extent of the involvement of VEB Jenapharm and its scientists in the criminal doping system of the GDR. Heidelberg, December 22, 2004
  7. ^ Federal Doping Commissioner for the Stasi records
  8. ^ Klaus Latzel : State doping - The VEB Jenapharm in the sports system of the GDR. Cologne / Weimar 2009, chapter doping and the pharmaceutical industry of the GDR II, cooperation in the command economy - using the example of androstendione, p. 121ff
  9. ↑ Oliver Haupt: doping agents - history, evidence, developments - with special consideration of the GDR . Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2017, ISBN 978-3-8047-3805-8 , p. 61-152 and 173-184 .
  10. ↑ Johannes Gumpert: The cancer drug bendamustine - a success story of cancer research in Jena . In: Jena yearbook on technology and industrial history . tape 19 . Jena 2016, p. 419-467 .
  11. ↑ Günter Bruns and Hans Knöll: On the problem of the search for cancer-effective substances (IMET 3393 - Cytostasan) . In: Central sheet for pharmacy, pharmacotherapy and laboratory diagnostics . tape 110 , 1971, p 1009-1012 .
  12. ↑ Walter Werner, Michael Herold, Klaus Ruffert, Karlheinz Merkle, Axel Brackhage, Lorenzo Leoni, Bruce D. Cheson: evolution: bendamustine yesterday, today, tomorrow . In: Oncology . 36 (Suppl. 1), 2013, p. 2-10 .
  13. ↑ Michael Oettel, Walter Elger, Michael Ernst, Regina Freund, Anatoli Kurischko, Birgit Schneider, Wolfgang Stölzner: Experimental Endokrinpharmakologie von Dienogest . In: AT Teichmann (ed.): Dienogest: Preclinic and Clinic of a Gestagen . 2nd ed.,. Walter de Gruyter, Berlin; New York 1995, ISBN 3-11-015085-9 , pp. 11-21 .