Wellcome Laboratories

Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Department of Clinical Science at South Bristol, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BSl 3NY, UK Astrid.Linthorst bristol.ac.uk... 

The origins of antiviral therapies can be traced to the early 1950s, when sulfonamide antibiotics were tested for activity against poxviruses using mice infected with vaccinia (1). A decade of work at the Wellcome laboratories culminated in the development of methisazone, which was introduced in 1960 for the prophylaxis of smallpox (see Scheme 1). Notable success in the smallpox epidemic in Madras in 1963 demonstrated the value of this compound, but vaccines introduced soon after led to eradication of the disease and made the compound redundant. However, the principle that chemotherapy was effective for treating antiviral diseases had been demonstrated. 

This work was supported by grants from the Burroughs Wellcome Laboratory (USA) and the CONICET (Argentina). 

Based on work carried out at Burroughs Wellcome Laboratories, London, it would appear that pure polymyxin B HCl should assay approximately 10,000 units per milligram. 

In the oxathiolane area, a paper from Wellcome Laboratories describes work done there on the preparation of 3-thiacytosine and related compounds, whilst a synthesis of 3TC involving an enantioselective enzymic hydrolysis has been reported. The difluorophosphonate analogue 200 of FTC has been made as a racemate with other diastereomers, and 1,2,6-thiadiazine dioxide analogues of 3TC have been reported. A full account has appeared concerning the synthesis of regioisomeric systems such as 201 (see Vol.28, p.297). ... 

It is likely that ara-HxMP similarly exerts its antiviral activity in the form of the triphosphate, ara-HxTP, since ara-HxTP inhibits HSV-1 DNA polymerase (49). Another possible explanation of the antiviral activity of ara-HxTP is that it is metaboHcaHy converted to ara-AMP. In fact, it has been shown at Wellcome Research Laboratories that ara-HxMP is a substrate for adenylosuccinate synthetase, and that the resulting arabinofuranosyladenylosuccinate is cleaved to ara-AMP by adenylosuccinate lyase (1). The selective action of ara-A against HSV appears to be a consequence of the preferential inhibition of ara-ATP against HSV-1 and HSV-2 polymerases. Ara-ATP also inhibits normal cellular DNA polymerases, which may be the reason for its cellular toxicity. Also, it has been observed that ara-A is incorporated uniformly throughout the HSV-1 genome, which may result in defective viral DNA (50). 

Research in the author s laboratory is supported by the SERC, the MRC and the Wellcome Trust. The author is indebted to Dr. M.T. Cairns, Dr. A. Davies, Dr. A.F. Davies and Dr. P.J.F. Henderson for many helpful discussions and access to unpublished information. Mr. R.A.J. Preston and Mrs. J. Baldwin provided invaluable help in the preparation of the figures. 

Department of Pharmacolo, Wellcome Research Laboratories, Langley Court,... 

We would like to thank all our colleagues in Manchester for allowing us to discuss their unpublished work. Research in this laboratory has received funding from the BBSRC, the British Medical Research Council, and The Wellcome Trust. 

The work described was supported by grants from The Wellcome Trust (UK) to G. D. P. We thank members of the Pavitt laboratory for critical comments on the manuscript. 

Work in the authors laboratory is supported by grants form the Medical Research Council (UK), the Wellcome Trust and the UK Multiple Sclerosis Society. S.M.A. is a MRC Senior Research Fellow and holds a RCUK Fellowship in Translational Medicine. 

Harmonization of pharmacopeial standards as a practical matter began at the International Congresses of Pharmacy between 1865 and 1910 [2], but the first formal attempt can be traced to 1902. Both USP President Horatio C. Wood, M.D., and Frederick M. Power, Ph.D., an American chemist of the Wellcome Chemical Research Laboratories of London, were appointed by the U.S. Secretary of State as delegates to represent the United States government at the International Conference for the Unification of the Formulae for Heroic Medicines, a conference of 19 countries from Europe and North America [3]. The second conference occurred in 1918. The 3rd in 1925 was attended by 31 countries from all continents except Asia and Australia. They drafted a new International Convention, which came in force in 1929. It revised the 1902 agreements on 77 heroic medicines and introduced the concept of maximum dose. It also requested that the League of Nations create a permanent secretariat of pharmacopeias [4]. Andrew G. DuMez, Ph.D., represented the USP, and was officially appointed by the U.S. Public Health Service to represent the United States at this conference [4,5]. An expert committee of the League of Nations planned a third conference for 1938, but it was never convened because of World War II [2]. 

Formerly Head of Clinical Pharmacology at Wellcome Research Laboratories, then Medical Director Rhone-Poulenc and Visiting Professor at the University of Cape Town, South Africa. He was later a Director of Imperial Cancer Research Technology Ltd, Visiting Professor of Clinical Pharmacology and Therapeutics at the University of Vienna, Austria, the University of Cape Town, South Africa and a member of the British Pharmacopoeia Commission. 

Brand Name/ Company Septra /Glaxo Wellcome Inc. Bactrim /Roche Laboratories ... 

Edmund M. Wise, Jr The Wellcome Research Laboratories. Research Triangle Park. NC, Antibiotics Peptides Donald T. Witlak, University of Wisconsin-Madison. Madison. Wl. 

David A. Johnston, Wolfson-Wellcome Biomedical Laboratory, Department of Zoology, The Natural History Museum, Cromwell Road, London SW7 5BD, UK. Email, daj nhm.ac.uk Matty Knight, Biomedical Research Institute, 12111 Parklawn Drive, Rockville, MD 20852, USA. Email, mknight afbr-bri.com... 

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