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The Biochemist February 2002 issue; THEME: Pretty poisonous

February 11, 2002

Introduction - The darker end of the spectrum

The 'pretty poisonous' entities that are the subject of this issue of The Biochemist have a much darker side - they might be subject to misuse by those with malevolent intent. Toxins and bioregulators have certainly been considered and developed as weapons by some. In the late 20th Century, third-generation biological warfare programmes, such as in the former Soviet Union, used genetic engineering to modify classical agents. Could the knowledge gained by the genomics revolution be misused? An essential factor in preventing this, says Professor Malcolm Dando (Professor of International Security), is that scientists become much more aware of, and concerned about, the misuse of their work. (p.14)
Contact: Professor Malcolm Dando, Department of Peace Studies, University of Bradford, Bradford BD7 1DP; e-mail: M.R.Dando@Bradford.ac.uk

Warfarin therapy - Rat poison and the prevention of thrombosis

Thrombosis, which has been defined as blood clotting in the wrong place, is among the principal causes of death in the Western world. One of the drugs that is most frequently used to prevent arterial thrombosis is the oral anti-coagulant, warfarin, which was first marketed as rat poison in the 1940s. In 1999, warfarin was the eleventh most prescribed drug in the USA, with annual sales of approximately US$500m. This article describes the history of its discovery, and how it works. (p.15)
Contact: Professor Mike Scully, Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, London SW3 6LR; tel: +44 (0)20 7351 8300; e-mail: mscully@tri-london.ac.uk

Targeting toxins - Drug delivery with poisons

Many organisms produce potently toxic proteins that act on other cells, sometimes with lethal effects. In this way, such proteins help to increase the chance of survival or proliferation of the producing organism. Moreover, a lot of toxins have an exquisitely specific action. For example, proteins studied in the Warwick toxin laboratory - ricin, a toxin from the castor oil seed, and its relatives from the pathogenic Escherichia coli 0157 and the dysentery-causing bacterium (Shigella dysenteriae) - have evolved to target selectively the protein-making machinery within the cells of susceptible organisms. What is very striking, is the clever way these toxins exploit intracellular pathways to travel from the cell surface to the inside of the cell. Research is now aimed at elucidating the molecular details of the cellular uptake of ricin and the Shiga family of toxins, and exploiting their unusual trafficking properties for biotechnological purposes. (p. 18)
Contact: Professor Lynne Roberts, Dept. of Biological Sciences, University of Warwick, Coventry CV4 7AL; tel: +44 (0)24 7652 3558; fax: +44(0) 24 7652 3558; e-mail: lroberts@bio.warwick.ac.uk

The third coming - Thalidomide and a final goodbye

The cyclical rise, fall and resurrection of thalidomide has become one of the most instructive stories in medicine. In the early 1950s, when pathogens were considered to be the primary causative agents of most human diseases, two chemists working for the pharmaceutical company Chemie Grunenthal heated the peptide pthalimidoglutaramide in an attempt to synthesize novel antibiotics. They obtained a compound with a three-ring structure, which they named thalidomide. The medical disaster that ensued has still not been forgotten. But thalidomide is now finding new use in the treatment of cancer, and with the synthesis of derivatives, could the side-effects be conquered? (p. 21)
Contact: Professor Azra Raza, Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3824, USA; tel: +1 (312) 455 8474; fax: +1 (312) 455 8479; e-mail: araza@rush.edu

Policy matters
Reaching the inner ear of EC - How scientists lobby for their interests in the European Commission

In 1999, one American university alone spent US$760,000 on lobbying politicians for funding to improve its science facilities. Boston University was criticized when it contracted a professional lobbying agency, Cassidy & Associates, to do the 'dirty' work - that is how it would be considered in the medieval world of European science politics. Welcome to the arcane, unintuitive and dimly lit labyrinth of the European Commission. While some wander the narrow passageways with no more than a tallow torch to light their way, eventually joining the dusty skeletons, others seem to be friends with its keepers, and know the passwords to the secret rooms. (p. 36)
Contact: Andrew Moore, Project Manager, European Molecular Biology Organization (EMBO), Postfach 1022.40, D-69012 Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany; tel: +49 6221 8891 109; fax: +49 6221 8891 200; e-mail: andrew.moore@embo.org

Other articles
The Biochemical Society has a new Chairman, Peter Downes. Read his thoughts on what lies ahead. (p. 5)
Product focus - Shimadzu-Biotech demonstrate how mass spectrometry interfaced with liquid chromatography is becoming mainstream. (p. 25)
Meeting report - Highlights from the York Meeting in December, including Colworth Medal winner Andrew Sharrocks (award given for outstanding science by a researcher under 35). (p. 29)
Post-genomic partnerships - can biologists and chemists work together? (p. 33)
Day in the life of a Medical Writer. (p. 49)
Cyberbiochemist - What has happened to Bionet? (p. 51)
Neuberger double at Heriot-Watt Meeting - father and son honoured at the same Biochemical Society Meeting in April 2002. (p. 55)

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