WPI research may advance cancer drug

Worcester Polytechnic Institute professor Susan Roberts, head of the chemical engineering department, has developed a genetic engineering technique that could speed up manufacturing of a widely used cancer drug and lower its production costs.

The process involves collecting and growing cells from the Pacific yew (Taxus) tree, making it possible to multiply production of paclitaxel, better known by the brand name Taxol, which is used to treat ovarian, lung, cervical, and pancreatic cancers.

Included on the World Health Organization’s Model List of Essential Medicines, paclitaxel or PTX has a market value of more than $2 billion annually. First identified as an anti-cancer agent in the 1970s and given FDA approval in 1992 for treating ovarian cancer, it is now used to treat a wide range of tumors, as well as AIDS-related Kaposi sarcoma, and may have other medical uses, including treatment for Alzheimer’s disease.

PTX is nature’s defense system for the Pacific yew tree, helping it resist fungal infections and other stressors in nature, Ms. Roberts said. Unlike humans, “trees can’t run away from mice or insects,” she said.

For many years, PTX was obtained by harvesting and processing the bark of the tree, a process with a low yield. It takes three 1-year-old trees to produce enough PTX to treat a single patient. In addition, the process is environmentally unfriendly, as trees are cut down and harsh solvents are used to obtain PTX.

“Essentially, we are manipulating the tree’s own defense system in the laboratory to create more PTX and related compounds. We start new cultures every year in late summer," Ms. Roberts said.

In recent years, techniques have been developed for chemically synthesizing the compound, though the complex processes cannot be easily scaled for mass production. Most of the world’s production now is achieved by culturing cells taken from the needles of yew trees. In fact, PTX is one of the few commercial products in the world manufactured through plant cell culture technology, Ms. Roberts noted.

While using cell culture is a greener method than extracting the chemical and related compounds from yew bark, the yields are still low and variable and the production process is not optimal. Scientists have sought to enhance production by applying genetic engineering methods to manipulate metabolism through the addition or removal of genes to or from Taxus cells. However, finding reliable and stable gene transfer methods has proven difficult.

In a recent paper in the journal In Vitro Cellular & Developmental Biology, Ms. Roberts and her research team described a reliable way to stably genetically engineer Taxus cells, a process that could make production of PTX faster, easier, and greener, and make the medications and products produced less expensive. The process involves the use of a bacterium known as Agrobacterium, which transforms the cell’s genome, ultimately resulting in metabolic changes that increase the yield of PTX.

By way of example, Ms. Roberts said altering Agrobacterium can take a week. “The plant cells that we alter can take months.”

In her current research, funded by a $600,000 grant from the National Science Foundation, Roberts is taking a new approach that aims to eliminate cells in culture that do not produce high amounts of PTX. Part of that work involves using genetic engineering to control the metabolic pathways that Taxus cells use to both replicate and manufacture hundreds of compounds, including the precursor molecules for PTX.

Putting it in layman’s terms, Ms. Roberts said, “We kill off the cells that don’t produce the PTX and keep alive the ones that do.”

“What we’ve already accomplished could easily double production of Taxol consistently. Research has really evolved over the years,” said Ms. Roberts, who has been working on this project for 25 years.

She explained that in the early days researchers weren’t able to look inside the cells, but now with new technology that is possible.

“By combining different strategies, especially using the genetic engineering tool we just developed, we could expect multifold increases in production,” Ms. Roberts said, adding that many of the techniques the WPI team is developing in the laboratory can accelerate the production of other plant-based medications.

Ted Wells to receive honorary degree

The College of the Holy Cross will award an honorary degree to prominent litigation attorney and alumnus Theodore V. "Ted" Wells Jr. during a campus celebration of the 50-year anniversary of Holy Cross' Black Student Union.

Mr. Wells, who graduated from Holy Cross in 1972 and was a co-founder and former president of the BSU, will be the keynote speaker at an event Nov. 9 celebrating the heritage of the BSU and the people who have played a role in shaping it. Founded in 1968 after the assassination of the Rev. Martin Luther King Jr., the BSU was created in an effort to provide a support system for African-American students and all members of the Holy Cross community by creating an environment promoting leadership, embracing identity and encouraging diversity.

After graduating from Holy Cross, Mr. Wells went on to serve as the college’s first African-American trustee from 1977 to 1994 and again from 2002 to 2008. He now serves on the Holy Cross board of advisors.

He holds a master’s degree from Harvard Business School and a law degree from Harvard Law School.