In Memoriam: Mansukh Wani

RTI International Principal Scientist (Emeritus) Dr. Mansukh C. Wani passed away from natural causes on Saturday, April 11, 2020, at the age of 95.

Dr. Wani was born and raised in in Nandurbar, Maharashtra, India. He attended the University of Bombay, where he received his bachelor's degree in Chemistry in 1947 and his master's degree in Organic Chemistry in 1950. He came to the United States in 1958 and obtained his Ph.D. in Chemistry from Indiana University at Bloomington in 1962, followed by a postdoctoral fellowship at the University of Wisconsin at Madison. He joined RTI in 1962.

Dr. Wani's first work at RTI was in the field of organic photochemistry, in Dr. Monroe Wall’s newly founded Natural Products Laboratory. His main areas of research included the isolation and characterization of biologically active natural products and synthesis of anticancer and antifertility agents. In the area of natural products research, he was involved in the isolation, purification and characterization of a wide variety of antineoplastic agents including camptothecin and Taxol.

Dr. Wani’s contributions to humanity cannot be understated. Through the Natural Products Laboratory, Dr. Wani and Dr. Monroe Wall changed the landscape of cancer treatment. Together, their findings improved and saved lives and helped advance how researchers around the world approached the disease. Dr. Wani joined RTI in 1962 and until the recent mandatory work-from-home requirements, he continued to come to the office and serve as a mentor, colleague and friend to junior scientists. He embodies RTI’s spirit of innovation and collegiality and is a huge piece of RTI’s impressive, six-decade record of accomplishments. We will miss seeing him on campus and at our events, but we won’t forget his role in helping RTI become who we are today." - RTI President Wayne Holden

Human clinical trials of camptothecin, which Dr. Wani discovered in 1965, began in the early 1970s. Initially, RTI was buoyed by the announcement of the National Cancer Institute that camptothecin stood "front stage center" in the search for drugs inhibiting colon and rectal cancer. Unfortunately, this was a premature assessment. As Dr. Wani remembered, an oncologist at the Mayo Clinic changed his mind about the compound, saying it had "unpredictable toxicity" and "no clinical value at all in the treatment of gastrointestinal cancers." At a 1971 meeting of the American Association for Cancer Research, this researcher went so far as to announce, "I have come here not to praise camptothecin, but to bury it."

Although dismayed by camptothecin's apparent failure, the Natural Products Laboratory pressed on, synthesizing more than 60 analogues of this compound by 1989. That year, Science magazine reported that one of the analogues caused total tumor regression and enhanced the long-term survival of immunodeficient mice carrying human colon cancer cell lines. Unlike previous analogues, this one had low toxicity and produced fewer adverse side effects. "If we had abandoned camptothecin when the initial clinical trials showed it to be toxic, we never would have discovered the more promising camptothecin analogues," Dr. Wani said.

In the 1960s, Dr. Wani, Dr. Wall and colleagues had isolated another groundbreaking compound, paclitaxel (better known by its trade name Taxol), after samples of Taxus brevifolia, a yew tree indigenous to the Pacific Northwest, were mailed to the Natural Products Laboratory. "We tested hundreds of fractions from the tree and isolated one compound in the tree bark that generated anticancer activity," Dr. Wani recalled. Another 12 kilos of yew bark were then shipped to the lab, which used a process called bioassay-directed fractionation to isolate the most active compound.

Dr. Wani, meanwhile, was tasked with determining the structure of this extremely large molecule, pursuing the task for two years, without success, and even working on nights and weekends. In 1970, Taxol finally yielded its structure, and the following year, the lab published a paper asserting that it showed experimental promise as an anticancer agent. Unfortunately, the supply of the chemical was constrained by the endangered status of Taxus brevifolia. "It would have taken all the Pacific yew trees left to treat five patients," former RTI board member William Little said only half-jokingly.

Scientists outside RTI finally built upon the Institute's pioneering research. Interest in Taxol was revived in the 1980s after it was discovered that the compound attacked cancer in an unprecedented way–and after researchers at Florida State University had invented a technique for mass production. By the 1990s, taxol had received an excellent evaluation based on Phase I and Phase II clinical trials, and it emerged successfully from Phase III trials conducted by Bristol-Myers Squibb. In 1992, Taxol was approved for the treatment of ovarian cancer, and it has since been approved for numerous other cancers as well.

These extremely important leads have contributed to the development of four prescription drugs (irinotecan and topotecan from camptothecin, and paclitaxel and docetaxel from Taxol), which together accounted for about one-third of the total cancer chemotherapeutic agent market in 2002. View the timeline for the development of camptothecin and taxol at RTI.

In addition to this work on plant-derived antitumor agents, Dr. Wani also directed efforts towards the synthesis of potent water-soluble camptothecin analogs. He published extensively with over 200 publications and 36 patents to his credit. He was an invited speaker to a number of national and international symposia on taxol and camptothecin.

Dr. Wani is the recipient of many awards, including the Bruce F. Cain Memorial Award given by the American Association for Cancer Research, the City of Medicine Award given by the Greater Durham Chamber of Commerce, and the National Cancer Institute Award of Recognition, the 2000 Charles F. Kettering Prize of the General Motors Cancer Research Foundation, the Ranbaxy Research Award from the Ranbaxy Science Foundation, and the 2003 Distinguished Alumni Award from Indiana University. In August 2002, a plaque commemorating the discovery of Taxol at RTI was unveiled by the Gifford Pinchot National Forest of Washington State, and in April 2003, the American Chemical Society designated the discovery of camptothecin and Taxol at RTI a National Historic Chemical Landmark. In 2005, Dr. Wani received the North Carolina Award in Science from the Governor of North Carolina. In 2008, Dr. Wani received the Paul Ehrlich Magic Bullet Lifetime Achievement Award.