Aernoud Fiolet

34 Chapter 1 Conventionally, this is guaranteed for the sponsor by the ability to register as the market authorisation holder and by patents that protect intellectual property. Patents have a limited time span, to allow for widespread production after a predefined period of time. The last step in drug development should be, when patent protection ends, the generic pharmaceutical company begins large-scale production. This should decrease costs and, finally, the burden to the health care system. Drug repurposing From a clinical and biological perspective, it is highly likely that compounds can servemultiple therapeutic purposes. In fact,medical historyhas taught us that some chemical compounds or drugs are even more effective in their second than their first life. 121 (Table 1) Often such discoveries are impressive cases of serendipity: an eponym derived from the Persian tale “The Three Princes of Serendip” (Serindip, being an old name for Sri Lanka), where the main characters stumble upon all sorts of unplanned fortunate discoveries. 122,123 An example par excellence of serendipity in medicine is our introduction to antibiotics. Alexander Fleming failed to disinfect the cultures of bacteria he was investigating. When he returned from his vacation he realised that the cultures that were contaminated with Penicillium moulds all had perished; by accident he discovered the Gram-positive bacteria growth inhibiting properties of the fungus, introding Penicillin as the worlds first antibiotic. 121 Another example is the observation of the strong leukopenic effects of mustard gas, used as chemical warfare agent in World War I and II. This particular characteristic of nitrogen mustard led to the invention of the first chemotherapeutic drug. The cytotoxic effects of nitrogen mustard were used to its advantage in the treatment of excesses of leukocytes such as seen in lymphoma and leukemia. 124 This also gave rise to the first alkylating agents (mechloretamine) and later to studies on interacting with folic acid, leading to the development of methotrexate. Lastly, highly appealing to the imagination as an example of serendipity, are the anecdotal records on trials of sildenafil, which was originally designed as an anti-anginal drug. Trial participants reportedly did not return study medication due to unexpected "desirable side effects” of the drug. It now has widespread use in erectile dysfunction, and is well- known by its brand name Viagra. 123