1964) and camptothecins (in 1966). Both classes of drug were isolated and characterized by the laboratory of Monroe Wall at the Research Triangle Institute. Taxanes Paclitaxel (Taxol) was a novel antimitotic agent that promoted microtubule assembly. This agent proved difficult to synthesize and could only be obtained from the bark of the Pacific Yew tree, which forced the NCI into the costly business of harvesting substantial quantities of yew trees from public lands. After 4 years of clinical testing in solid tumours, it was found in 1987 (23 years after its initial discovery) to be effective in ovarian cancer therapy. Notably, this agent, although developed by the NCI in partnership with Bristol-Myers Squibb, was exclusively marketed by BMS (who had utilized the synthetic methodology developed by Robert Holton at Florida State University) who went on to make over a billion dollars profit from Taxol. Camptothecins Another drug class originating from the NCI was the camptothecins. Camptothecin, derived from a Chinese ornamental tree, inhibits topoisomerase I, an enzyme that allows DNA unwinding. Despite showing promise in preclinical studies, the agent had little antitumour activity in early clinical trials, and dosing was limited by kidney toxicity: its lactone ring is unstable at neutral pH, so while in the acidic environment of the kidneys it becomes active, damaging the renal tubules. In 1996 a more stable analogue, irinotecan, won Food and Drug Administration (FDA) approval for the treatment of colon cancer. Later, this agent would also be used to treat lung and ovarian cancers. Platinum-based agents Cisplatin, a platinum-based compound, was discovered by a Michigan State University researcher, Barnett Rosenberg, working under an NCI contract. This was yet another serendipitous discovery: Rosenberg had initially wanted to explore the possible effects of an electric field on the growth of bacteria. He observed that the bacteria unexpectedly ceased to divide when placed in an electric field. Excited, he spent months of testing to try to explain this phenomenon. He was disappointed to find that the cause was an experimental artifact — the inhibition of bacterial division was pinpointed to an electrolysis product of the platinum electrode rather than the electrical field. This accidental discovery, however, soon initiated a series of investigations and studies into the effects of platinum compounds on cell division, culminating in the synthesis of cisplatin. This drug was pivotal in the cure of testicular cancer. Subsequently, Eve Wiltshaw and others at the