Mansukh C. Wani, PhD, died from natural causes on April 11, 2020, at age 95. To the natural products community, he is most well-known for discovering the natural compound paclitaxel (Taxol®; Bristol-Myers Squibb; New York, NY) with his colleague of nearly 40 years, Monroe E. Wall, PhD (1916-2002). Taxol, one of the best-selling cancer drugs ever manufactured, was first isolated from the bark of the Pacific yew tree (Taxus brevifolia, Taxaceae). If that singular achievement were not enough, he and Wall also discovered camptothecin, a compound from the Chinese happy tree (Camptotheca acuminata, Nyssaceae). That discovery led to two chemotherapeutic agents: topotecan and irinotecan, which are analogues that circumvent the solubility problems of isolated camptothecin.
It is difficult to fully quantify either of those discoveries. They led to the development of multibillion-dollar drugs that have been used to treat millions of patients with cancer. Wani’s original publications on paclitaxel and camptothecin have prompted thousands of research projects. They are evidence of the value of nature to help mitigate human disease. In fact, Taxol is also used to coat stents, mitigating heart disease by preventing restenosis (the recurrence of abnormal narrowing) in arteries.
I had the distinct honor of working with Wani for more than two decades, often traveling with him to meetings and conferences. While he was always proud of those discoveries, he was also extremely humble. He loved to talk about the many challenges associated with the research that ultimately led to those compounds being advanced into drugs. Yet he was quick to point out the numerous players along the way, from botanists, to bench scientists, to pharmacologists, to leading oncologists, all of whom played critical parts.
Wani was born in Nandurbar, Maharashtra, India, on February 20, 1925, and received his bachelor’s and master’s degrees from the University of Bombay. He came to the United States in the late 1950s to pursue his PhD at Indiana University. He was an older student, in his 30s, with a previous career in India as a chemistry lecturer. He was drawn to the pursuit of knowledge, which was evident until his death, as he still had an office, traveling there by Uber when he could no longer drive, just so he could read up on the literature and correspondence.
He completed his PhD in about two and a half years and moved to the University of Wisconsin for a short postdoctoral stay. Then, he began working at the newly formed Research Triangle Institute (RTI), which is now called RTI International, in North Carolina in 1962.
At first, Wani did not work directly with Wall, who led the chemistry efforts at RTI. After Wani had worked there for about two years, Wall developed a notion that Wani had almost “magic” hands when it came to generating crystals suitable for x-ray crystallography — and even when I joined their team in 1998, Wall still held that belief. Wani was moved to a project to help develop a crystal for their work on camptothecin, which he achieved in about six months and led to their first seminal paper. From that point forward, he always worked with Wall, both on the isolation and structure elucidation of natural compounds and on the development of analogues thereof, mostly to improve solubility and potency. In fact, at the time of Wall’s death, they were still working on camptothecin analogues, having registered more than 20 patents in that regard over the years.
Wani loved to tell the story of the discovery of Taxol. The structural work on Taxol took much longer than camptothecin, and on more than one occasion, Wall told Wani to stop working on that project, because they had many other priorities, including ongoing studies on camptothecin. Wani instead received permission to do the work on a low-priority basis, which, he would smile and say, meant working on evenings and weekends. Even when he had determined what he believed was the correct structure of Taxol, Wani continued experimenting, trying to enhance the compound’s potency. However, the chemical reactions were not working as planned, and that flummoxed him for several weeks until he realized that his initial structural hypothesis was wrong. If it were not for those extra experiments, he said, Wall and Wani would not be famous for the structure of Taxol, but rather would be infamous, or perhaps even a footnote, for publishing it incorrectly. Wani once confided in me that he breathed a great sigh of relief when the total synthesis of Taxol was reported in the early 1990s, independently confirming that the structure was correct.
Wani, in his humble way, would emphatically point out that determining the structure of Taxol was only the beginning of the story: Susan Horwitz, PhD, performed critical pharmacology experiments to determine the mode of action, followed by the development efforts of the US National Cancer Institute, followed by the circumvention of supply issue problems by Robert Holton, PhD, etc. The abbreviation “etc.” does not do it justice, however, as thousands of people were involved, leading to US Food and Drug Administration approval to treat ovarian cancer (1992) and then breast cancer (1994). Clinicians who are old enough can point to the days before Taxol and after Taxol, as it had that large of an impact on cancer chemotherapy.
The medicinal plant world has lost a pioneer, scientist, mentor, and inspiration. Wani is survived by his wife Ramila, son Bankim, daughter-in-law Darshana, and grandson Nilesh.