Pharmacist and natural-products chemist, who devised widely used treatments for cancer.
Pierre Potier, who died on 3 February 2006 at the age of 71, was at the forefront of the French school of natural-products chemistry during the second half of the twentieth century. He was a leading light in the development of anticancer drugs from natural sources, and also in encouraging communication between the public and private sectors. In France, these circles tend not to mix. Potier showed that cooperation between the CNRS, the main agency of publicly funded research, and industry could be highly fruitful if the two communities shared their knowledge and experience.
The son of a watchmaker, Potier was born in Bois-Colombes, a northern suburb of Paris. He first trained as a pharmacist, graduating in 1957 from the Faculty of Pharmacy at the University of Paris. He then completed his PhD in chemistry as a student of Maurice-Marie Janot and Jean le Men, taking his first steps in the field of drug synthesis from natural products under the tutelage of Janot at the CNRS's new Institute of Natural Products Chemistry in Gif-sur-Yvette. Following Janot's death, Potier took up the baton in collaborating with the likes of Edgar Lederer, Derek Barton and Guy Ourisson on various projects. Potier himself first co-headed, then headed the institute from 1974 to 2000, and so was responsible for guiding the research of several hundred investigators in learning from, and imitating, nature.
Potier was himself a highly innovative scientist. In 1965, he devised a modification of the Polonovski reaction, which is used to obtain the N-demethylation (or N-deacylation) of various plant alkaloid derivatives. The modification consisted of replacing one reagent (acetic anhydride) with another (trifluoroacetic anhydride), which facilitated the biomimetic synthesis of many indolic natural products that could not otherwise be made. This reaction was central to the later work involving the ‘vinca’ alkaloids.
In 1976, Potier and colleagues created a new tool for drug development: the tubulin test for identifying anticancer treatments. Tubulin is the main component of microtubules, which have a central role in cell division. The test was devised by Potier and Daniel Guénard. It does not require sophisticated lab conditions, and allows the swift and cheap evaluation of a drug's capacity to inhibit cell division — and thus of its potential anticancer activity.
The tubulin test led Potier's team to identify the anticancer activity of vinorelbine (Navelbine), a semi-synthetic derivative of the vinca alkaloids vincristine and vinblastine found in periwinkles. All three drugs inhibit cell division, and have been part of anticancer treatments since the mid-1970s. The production of vinorelbine was taken up by the Pierre Fabre Laboratories for use in treating lung cancer and breast cancer in particular. (Poignantly, Potier's first wife Marie-France, herself a pharmacist, had died of breast cancer in 1968. Potier remarried, and is survived by his second wife Odette and three children.)
But perhaps Potier's greatest contributions came between 1979 and 1994 from a succession of discoveries involving the chemistry of the yew tree. With Guénard and Françoise Guéritte, he first synthesized docetaxel (Taxotere) using a semi-synthetic pathway based on a reaction with 10-deacetylbaccatin III extracted from the needles of the European yew. Taxotere, which was developed with the Rhône-Poulenc Rorer laboratories, is a highly potent antineoplastic drug used mainly against breast, prostate and lung cancer. With Andrew Greene, and using the same chemical steps, the same team then found a way to produce large amounts of paclitaxel (Taxol). The drug had previously been made from the bark of Pacific yew, so that entire trees had to be sacrificed.
More recently, Potier became involved in studying the origin of the degenerative effects of diabetes. He identified a role for glyoxal and methylglyoxal (end-products of carbohydrate metabolism) in causing the enhanced protein degradation seen in diabetic patients. These molecules damage proteins unless they are detoxified by mechanisms involving glyoxalases. Potier patented several drug candidates for treating diabetes in 2005, but at the time of his death was still carrying out experimental investigations on them.
Potier was an author on more than 400 publications and several dozen patents. Ever keen to encourage international cooperation, he created the Franco-Japanese Society of Fine and Medicinal Chemistry, and the Franco-American Chemistry Society. Both nationally and on the global stage, he was especially effective in fostering the collaboration between chemists, biologists and clinicians that is so necessary for successful drug development, and in encouraging links across the academic–industrial divide. It was this background that perhaps led to Potier's appointment by the French government as director-general for research and technology at the Ministry of Research. He held this position from 1994 to 1996, giving priority to promoting publicly funded research and the status of science in France.
He retired from the Institute of Natural Products Chemistry five years ago, but remained emeritus director. On his retirement, he noted with justifiable pride that the royalties paid by pharmaceutical companies marketing the drugs he discovered were able to fund the entire institute.
Pierre Potier became an eminent man, with connections among top politicians and scientists in France and internationally. He received many prizes, among them the CNRS gold medal and the Ernest Guenther Award in the chemistry of natural products; he was also a member of the French Academy of Sciences and the National Academy of Pharmacy, as well as of five foreign academies. Yet he didn't take himself too seriously, retaining the gifts of whimsy and a readiness to laugh. Claude Bernard, a towering figure in physiology during the nineteenth century, was among the first Frenchmen to dream of reconciling the aims and methods of chemists and biologists. With his acute scientific brain and cross-cultural awareness, allied with his sense of humour, generosity and deep appreciation of literature and history, Potier holds a prominent place among Bernard's successors.
About this article
Cite this article
Chast, F. Pierre Potier (1934–2006). Nature 440, 291 (2006). https://doi.org/10.1038/440291a