The big and small of drug discovery

In 1999, a small biotech company called Magainin Pharmaceuticals suffered a near‐fatal blow when its greatest hope, a small antibacterial peptide for the treatment of diabetic foot ulcers, failed to obtain approval by the US Food and Drug Administration (FDA). The agency rejected the compound, first discovered in the skin of the African clawed frog Xenopus laevis , not on the grounds that it was unsafe or inefficient, but solely because it was no more effective than other antibiotics used to treat ulcers. For Michael Zasloff, discoverer of the peptide, and the then president of Magainin Pharmaceuticals, it was the end of an adventure into the ruthless world of biological entrepreneurship; he left the company and returned to an academic position at the University of Georgetown in Washington DC, USA. Speaking from his office as Dean for Research and Translational Science, he remarked “I still have a hole in my chest, and a great deal of sadness about what happened.”This is understandable to any scientist who has made a significant discovery that has fallen on deaf ears. Zasloff's finding, a classic case of curiosity‐driven research producing an exploitable result, goes back to his time carrying out basic research at the US National Institutes of Health (NIH), where he worked with Xenopus oocytes. Noting that the frogs from which he gathered the oocytes did not develop infections despite being operated on with techniques that cause sepsis, Zasloff suspected that they produced a type of antibiotic. In 1987 he identified the substance, a short positively charged peptide with hydrophobic residues, and named it ’magainin‘ from the Hebrew word for ’shield‘. Magainins, he theorized, worked by binding to the negatively charged membranes of bacterial cells, where they assembled to form transmembrane pores that ’bleed' the bacterium to death. Zasloff left the NIH, …