The Development of Penicillin in the Netherlands 1940-1950: the Pivotal Role of Nv Nederlandsche Gist- En Spiritusfabriek, Delft
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THE DEVELOPMENT OF PENICILLIN IN THE NETHERLANDS 1940-1950: THE PIVOTAL ROLE OF NV NEDERLANDSCHE GIST- EN SPIRITUSFABRIEK, DELFT. MARLENE BURNS PhD THESIS DEPARTMENT OF HISTORY UNIVERSITY OF SHEFFIELD SEPTEMBER 2005 The Development of Penicillin in the Netherlands 1940- 1950: The Pivotal Role ofNV Nederlandsche Gist- en Spiritusfabriek, Delft. by Marlene Burns ABSTRACT In November 1945 the recovery of Maria Geene in Delft's Bethel Hospital signaled the success of the secret wartime research on penicillin at NV Nederlandsche Gist- en Spiritusfabriek (NG&SF) in Delft, the Netherlands. Fifty years later, Gist-Brocades, of which NG&SF was the forerunner, had become one of the world's largest producers of bulk penicillin. By the year 2005, Gist- Brocades was part of Dutch State Mines and market forces required that all production of penicillin in Delft stop. While the historiography of the Netherlands during its years of occupation is well documented, little has been recorded of the wartime research with penicillin at NG&SF. Also, little has been documented of NG&SF's determination, at the end of the war, to continue penicillin production, a time when the whole of the Netherlands required reconstruction. By 1950 the continued success ofNG&SF was highlighted by the gift of the predicate Koninklijke (Royal). It is known that it was information on the success of Allied penicillin that stimulated the wartime research ofNG&SF. This thesis, therefore, begins with a general history of penicillin production in Britain, the United States and Canada. This is offset by the unsuccessful experiences of France, Germany and Japan. For the Netherlands, Nazi occupation meant that, from May 1940, the whole country was cut off from the outside world. In fact, this occupation occurred three months before Florey and his associates first published on penicillin in Lancet. Also, from 1943 there was an Allied embargo on publications regarding penicillin. How, therefore, did knowledge of Allied penicillin reach the Netherlands? Was NG&SF the only Dutch company interested in penicillin? Why were they successful? How, at the end of the war, could NG&SF consider financing such a new venture? It is the remit ofthis thesis to bring these questions to the fore. IMAGING SERVICES NORTH Boston Spa, Wetherby West Yorkshire, LS23 7BQ www.bl.uk BEST COpy AVAILABLE. VARIABLE PRINT QUALITY IMAGING SERVICES NORTH Boston Spa, Wetherby West Yorkshire, LS23 7BQ www.bl.uk PAGE MISSING IN ORIGINAL ll1 ACKNOWLEDGEMENTS While it is impossible to thank all of those who, through their openness and willingness to help, aided the research for this thesis, I would, in particular, like to thank the following. Firstly, all those who allowed access to archives, namely Karin van den Tweel and Dr. Huub van der Aa of the Centraalbureau voor Schimmelcultures; Dr. A.J. (Hans) de Neeling of the Rijksinstituut voor Volksgezondheid en Milieu; Dr. Lesley Robertson, Curator of the Kluyver Archive at the Technical University, Delft; and, last but not least, Dr. Hans van Suijdam of DSM (Dutch State Mines) for access to Nederlandsche Gist- en Spiritusfabriek (NG&SF) archives. I am indebted to those who shared their personal experiences and memories with me, specifically Dr. John Hofmyer, Dr. Ant Kaars-Sepijstein, Hens ten Hoopen and, his wife, Truus ten Hoopen-van Hulsentop. I am grateful to those who participated so readily in my interviews, especially the former employees and advisors of NG&SF, members of the 'Delft Team'. Further thanks should also be given to Prof. Ernst Homburg of the University of Maastricht and Prof. Eddy Houwaart of the VU in Amsterdam, both of whom contributed to my knowledge of wartime and post-war Netherlands. Discussion with Dr. Patricia Faase proved very worthwhile, as did my correspondence with Dr. M.E. Nordlohne. Dr. M.A. Verschuyl and Prof. Joan Bennett of Tulane University, New Orleans, have both provided continuous interest in my topic. Special thanks go to Dr. Piet van Dijck of DSM for providing me with assistance and support throughout my research and who, together with Dr. Lesley Robertson, kept me on the microbiological straight-and-narrow. Also to Dr. R. Moore, Bob, my supervisor, for his valuable insight and role as a sounding board. Last but not least, to my husband and sons for their unflagging, enthusiastic, support and encouragement. iv GLOSSARY AND ABBREVIATIONS Aankoopvergunning Permission to buy. Academisch Ziekenhuis, AZ University Hospital. Academische Ziekenhuis Leiden, AZL Leiden University Hospital. Acetone Colourless, flammable liquid with a sweetish smell, used as a solvent. Ammonium salt of penicillin Used to produce long-acting Penicillin G. See: Salt. Amsterdamse Chinine Fabriek, ACF Amsterdam Quinine Factory. Aeratiekolven Aeration flask. Aerobe Bacteria able to utilise (respire) oxygen. Afdeling Antibiotica Antibiotics Department. Agar Gel derived from seaweed and used for growing micro-organisms in the laboratory. Akademische Ziekenhuis, AZ University Hospital. Algemeene toewijzing General allocation. Algemeene vergunning General permit. Amerikaanschen Voorlichtingsdienst American Information Service. Anaerobe Bacteria able to grow in the absence of oxygen. Antibiotic A substance originally produced from a fungus that in small quantities inhibits bacterial growth - originally antibiotics were produced by fungal fermentation although semi- and fully synthetic antibiotics have subsequently been introduced. Apothekers Pharmacists. v Arbeidsfront A workers organisation under the leadership of the NSB modelled on Nazi unions. In 1942 the Nazi occupier disbanded all Dutch Trade Unions and demanded that Trade Unionists become members of the Arbeidsfront, The Arbeidsfront was led by H.J. Woudcnberg. It was disbanded in 1945. Arierverklaring Aryan Declaration. Artsenkamer Medical Association Assessor Examiner. Aspergillus Genus (family) of fungi found, for example, in soil, manure and grains. Bacinol The codename given to the antibacterial substance produced at NG&SF - the name is derived from the Penicillium used to obtain Bacinol, namely Penicillium baculatum. Bvbuizen B-tlasks. Bedrijfs assistenten Company assistants. Beta-lactam The chemical structure central to the penicillin family of molecules. Bibliotheek Library. Binnenlandse Zaken, BZ Ministry of Internal Affairs. Bonnen Vouchers. Brieven Letters. Broad Spectrum Antibiotic An antibiotic effective against many types of bacteria. Brocades, Stheeman en Pharmacia, BS&P Company that developed Expansine. Eventually merged with KNG&SF to create Gist- Brocades. Buffer A solution in which the pH is not altered by the addition of acids or alkali. VI Buisje Small flacon. Butanol A colourless liquid used as a solvent. Also known as butyl alcohol. Caprylic alcohol An anti-foaming agent. Also known as octanoic alcohol. Centraalbureau voor Schimmelcultures, CBS National Collection of Fungal Cultures. Chemisch Technische Dienst, CDT NG&SF's Chemical Technical Service. Chloramphenicol Broad spectrum antibiotic produced by the soil dwelling organism Streptomyces venezuelae and active against a wide range of Gram-positive and -negative bacteria. Usefulness limited by toxic side effects. Clostridium A genus including anaerobic bacteria, some of which are responsible for diseases such as gas gangrene, botulism and tetanus - plural is clostridia and the adjective clostridial. Commissie inzake Antibiotische Geneesmiddelen Commission for Antibiotic Medicines. Commissie Blauw Commission under the leadership Ir. Blauw and Prof. De Boer - charged by the Dutch Government-in-exile with obtaining scientific literature that was not available in occupied Netherlands for distribution in the Netherlands when the war and occupation ended. Com Steep Liquor A by-product of the maize industry that was used to increase yields of penicillin - it was originally applied pragmatically and later discovered to be able to provide building blocks for the penicillin molecule. Corticosterone A steroid hormone secreted by the adrenal gland and involved in stress responses and anti- inflammatory activity. Delfsche Eenheden, DE Delft Units - the arbitrary unit developed by NG&SF in Delft to measure the strength of early penicillin samples. The unit was defined as the amount of bacteriostatic substance, which just completely suppressed the growth of Staphylococcus aureus in 1ml of peptone water at 37°C. One Delft Unit was equivalent to 1110 Oxford Units. Delft University of Technology. TUD. Depocilline A long acting penicillin product introduced by NG&SF originally intended to be called Retarcilline. Depot Scientific term for sustained release preparation. vii Department van Handel en Nijverheid, DHV Department of Trade and Industry. Deutsche Chemische Gesellschaft German Chemical Society. Deutsche-Niederlandische Gesellschaft, DNG German-Dutch Business Association. Deviezen Foreign exchange. Digesta Antibiotica, DA Antibiotics Digest. An NG&SF Company publication on all matters antibiotic, intended as an information source for medical doctors. The DA was published from 1947 until 1966. Distributiewet Distribution Law. Doctor fngenieur, Dr. fr. Doctor Engineer, a Doctorate coupled with a Degree in Chemical Engineering. Dolle Dinsdag Mad Tuesday, 5 September 1944. The day on which reports of an allied breakthrough led to premature celebrations of imminent liberation in the North and West of the Netherlands. Dutch State Mines BV, DSM The company that acquired Gist-Brocades. Economische Zaken, EZ Ministry of Economic Affairs Ensinkketel