Natural Products Laboratory: History
 |
|
Meeting of the 1960 RTI Executive Committee where the leaders created a vision for a chemical synthesis program |
The Beginning: Drs. Wall and Wani Join RTI
After the second World War, medical research in the U.S. started to gain the upper hand over infectious diseases and the pathogens that cause them, exposing cancer and heart disease as the next great national killers. As a result, and because of lobbying from the then-young American Cancer Society, the United States budget for cancer research blossomed from $1 million in 1940 to over $100 million in 1960.
With this funding, researchers began to examine the world of plants, bacteria, and fungi and their role in cancer-fighting drug discovery. By 1960, the Cancer Chemotherapy National Service Center (CCNSC), a National Cancer Institute (NCI) facility, was screening approximately 30,000 plant- and animal-derived compounds each year.
Early in 1960, the leadership and executive committee of the newly formed Research Triangle Institute (RTI), a nonprofit research institute created by Duke, UNC, and NC State as the research anchor for Research Triangle Park, created a vision for a chemical synthesis program.
Monroe Wall, a medicinal chemist, had worked for almost 20 years in the plant-screening program at a regional U.S. Department of Agriculture office in Philadelphia. By 1960, after establishing a national reputation in plant chemistry, Wall was approached by RTI's Hugh Hunter to form and lead the RTI Natural Products Laboratory (NPL) and secure the promise implicit in natural products research: find cancer-fighting medicines in nature.
 |
| Dr. Monroe E. Wall was recruited in 1960 to lead RTI's newly formed Natural Products Lab |
As writer Frank Stephenson reported in A Tale of Taxol: "One of the dozens of plants Wall's team screened was a large shade tree, Camptotheca acuminata, known as the "happy tree" in its native China. Wall soon became fascinated by the plant -- in lab tests, its extracts showed an ability to kill cancer cells better than anything Wall had ever seen. When it became clear that his agency wasn't interested in much beyond cortisone chemistry -- and even that interest was waning -- Wall took stock of things. Should he ride a moribund program to retirement or gamble on what these crazy people in North Carolina were telling him?"
With a keen eye for opportunity and a determination to unlock nature's medicinal secrets, Monroe Wall decided to move to North Carolina. Once there, he began to build his team by hiring former USDA colleagues Samuel G. Levine and Charles Fenske. Ivy Carroll, highly respected for his work in molecular modeling, and Ed Cook, widely recognized for his work in steroid synthesis and drug metabolism, were hired next.
Wall and his team quickly won two projects (one of which continues to this day) with the NCI's CCNSC program to screen plants for tumor-inhibiting substances. In addition, Wall established what would become a 29-year old research relationship with Walter Reed.
In 1963, Wall hired Mansukh Wani, an organic chemist whose addition to the team would prove invaluable. With a powerful combination of team leadership and scientific expertise, the RTI Natural Products Lab soon established itself as a frontrunner facility in the natural products field.
Process and Discovery at the NPL
 |
| Charles Fenske in 1962 with a large-scale plant extractor in the |
In the world of natural products research, crude plant extracts that show potential for anti-cancer activity become candidates for a special process called fractionation in which the bioactive essence of a substance is isolated. At the time Wall opened his shop at RTI, fractionation was performed at only three laboratories, one of which was the RTI Natural Products Lab.
Wall's experience in isolating small quantities of natural products from plants also helped him pioneer techniques for isolating drug metabolites. He became one of the first individuals to use mass spectroscopy and nuclear magnetic resonance to reveal the structures of drug metabolites. Innovation and persistence became hallmarks of the NPL process and soon yielded astonishing results.
Chief among accomplishments by the Wall and Wani team at the Natural Products Lab were the discoveries of the cancer-fighting drugs Taxol® and camptothecinTM. These discoveries revolutionized both the process and the possibilities of modern cancer research. By isolating and elucidating the structure of these novel, bioactive natural products, Wall and Wani unearthed new mechanisms of action for inhibiting cancer call growth and established new principles for discovering other bioactive compounds from natural sources. More importantly, their discoveries are directly credited with saving the lives of hundreds of thousands of cancer sufferers.
NPL Today and Tomorrow
Although Wall officially left his vice president position in favor of chief scientist in 1983, his steadfast and passionate leadership of the work at RTI's Natural Products Lab was felt throughout his 42-year career. Wall continued his life's work in the lab until his death in 2002.
 |
| RTI senior chemists Mansukh C. Wani, Keith H. Palmer, Monroe E. Wall, and C. Edgar Cook in 1966 |
Today, researchers at RTI examine bioactive compounds in nature such as plants, bacteria, and fungi, focusing on anticancer, antifungal, antibacterial, and central nervous system drug discovery. Each year, more than 2,600 plants, fungi, and bacteria are analyzed. In addition, work has expanded to include herbal supplements and their interactions with cancer and conventional cancer treatments.
The Natural Products Lab continues at the forefront of natural products research in the 21st century because of the early founders at RTI who had the wisdom and foresight to create it, Dr. Wall who had the experience and passion to lead it, and the numerous researchers and scientists today who have the dedication and ingenuity to sustain it.
References
-
Larrabee, Charles X. (1991). Many Missions: Research Triangle Institute's First 31 Years 1959-1990.
-
Stephenson, Frank. (2002). A Tale of Taxol. Research in Review, Florida State University.
NPL in the News
- Journal of Natural Products (Feb 2004): A Tale of Two Tumor Targets
- HerbalGram (2003): Taxol Discovery Commemorated in Washington State
- Chemistry International (Jul-Aug 2003): Camptothecin and Taxol -- The Story Behind the Science
- Research in Review (Fall 2002): The Taxol Story
- Today's Chemist at Work (July 2004): Nature’s Pharmaceuticals
- Chemical Heritage (Winter 2003-2004): Historic Landmarks -- The Discovery of Camptothecin and Taxol
- Chemical & Engineering News (May 2003): Anticancer Research Honored at RTI
rti.org