Franklin honorees include a pioneer in fighting "superbugs"

Christopher T. Walsh "has shown elegantly how microorganisms are the best chemists on the planet," a fellow scientist said.
Christopher T. Walsh "has shown elegantly how microorganisms are the best chemists on the planet," a fellow scientist said.
Posted: November 04, 2013

When Christopher T. Walsh was president of the Dana-Farber Cancer Institute, cancer patients everywhere were increasingly battling an additional foe.

Their weakened immune systems were falling prey to "superbugs" that resisted the best weapons in the arsenal of modern medicine.

Walsh, also on the faculty at Harvard Medical School, set out to find what made the bugs tick.

Because of his success over the last two decades, which is helping scientists to find new drugs, Walsh is among the nine newest winners of annual awards given by the Franklin Institute.

The 2014 class of laureates is to be announced Monday. The winners, who are to receive their awards at a black-tie ceremony in April, include scientists with a wide array of accomplishments.

Among them are Mark Kryder of Carnegie Mellon University and Shunichi Iwasaki of Japan's Tohoku Institute of Technology, for their work on increasing the storage capacity of computer hard drives; Columbia University's Joachim Frank, for his use of cryo-electron microscopy to capture images of how proteins are made; and Lisa Tauxe of the Scripps Institution of Oceanography, for deciphering changes in the Earth's magnetic field.

One business executive is among the nine honorees: William W. George, former chief executive officer of the medical-device maker Medtronic Inc. and now an author and professor at Harvard Business School. He is to receive the Bower Award for Business Leadership.

Walsh, who left Dana-Farber in 1995 and remains at Harvard, is considered a pioneer in biological chemistry.

But he would be the first to admit that his chemistry skills are dwarfed by what is found in nature, where millions of years of evolution have allowed microbes to develop a host of chemical weapons and defenses.

One such weapon is vancomycin, which is produced by bacteria that live in the soil as a weapon against other bacteria and has been co-opted by humans as a potent antibiotic.

Walsh became increasingly concerned that vancomycin was unable to defeat certain "gram-positive" enterococcal infections, especially in cancer patients who had undergone chemotherapy. More recently, hospitals also have encountered cases of the drug-resistant bug MRSA that have developed resistance to vancomycin.

Walsh and colleagues found out how bugs thwart the antibiotic's attack. Vancomycin works by attacking the cell wall of bacteria, and certain bugs can evade that attack by producing enzymes that change the very chemical structure of their cell wall.

Walsh then proceeded to play a big role in determining how bacteria make vancomycin, so scientists could design alternatives.

He and colleagues found that bacteria use a series of enzymes to make vancomycin, in an elaborate assembly-line process with three dozen steps.

"Chris has shown elegantly how microorganisms are the best chemists on the planet," said Michael A. Fischbach, a former student of Walsh's who is now an assistant professor at the University of California, San Francisco.

This detective work involved using chemistry to break the assembly line into its component parts, studying one piece at a time, said Rahul Kohli, another former student of Walsh's who is now at the University of Pennsylvania's Perelman School of Medicine.

Walsh's findings have led science to discover that other potent natural compounds are made in a similar assembly-line fashion, among them the antibiotic penicillin and cyclosporine, which suppresses the immune system so transplant patients do not reject donor organs.

Researchers are starting to make alternatives by tweaking the existing drugs, and by looking throughout bacterial genomes to find the recipes for other weapons.

"Microbes in nature still have new molecular scaffolds of antibiotics yet to be revealed," Walsh said.

Though Walsh is best known for his work on bacteria and antibiotics, he has gained notice for other research on nature's chemists, even as a Harvard undergraduate. Working with the ecologist Edward O. Wilson, he studied a chemical secreted by fire ants that highlights the trail between food and the insects' nest. Their work was published in Nature in 1965.