William S. Knowles dies; Nobel Prize-winning chemist was 95

June 18, 2012

William S. Knowles, a Nobel Prize-winning chemist who helped devise the chemical process used to make a drug for the treatment of Parkinson’s disease, died June 13 at his home in Chesterfield, Mo. He was 95.

He had complications from amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, said his daughter Lesley McIntire.

Dr. Knowles’s work began in the mid-1960s and led to a breakthrough in the technique used to produce L-Dopa, which can help lessen the tremors associated with Parkinson’s. For decades, production of the drug was complex and costly because L-Dopa is almost indistinguishable from a similar molecule, D-Dopa, which is toxic.

Dr. Knowles’s research took account of differences in the shape, form and symmetry of two molecules with the same composition. These differences — often likened to the differences between the right hand and the left — can determine biological and medicinal properties. One form of a molecule may have curative properties, while its mirror image may lack such value, and may even be harmful.

Dr. Knowles, who spent almost his entire career working in St. Louis for Monsanto, was honored with the 2001 Nobel Prize in chemistry for having helped open “a completely new field of research” about chemical catalysts that create only the desired form of a molecule.


William S. Knowles, left, receives the Nobel Prize in Chemistry from King Carl XVI Gustaf of Sweden in Stockholm, Sweden on Dec. 10, 2001. Knowles, from St. Louis, Mo., shared the prize with Ryoji Noyori of Japan and K. Barry Sharpless, of the U.S. (HENRIK MONTGOMERY/ASSOCIATED PRESS)

The prize was divided, with one half given jointly to Dr. Knowles and Ryoji Noyori of Nagoya University in Japan and the other half to K. Barry Sharpless of the Scripps Research Institute in La Jolla, Calif.

“I always thought it would be a neat idea,” Dr. Knowles once said of his work on asymmetric catalysts. “If only I could figure out how to do it.”

The ratios of the desired output to the undesired rose during his several decades of research. The achievement of 88 percent efficiency was regarded as a breakthrough, according to a profile in the Proceedings of the National Academy of Sciences, with the man-made results almost matching those produced in nature.

The milestone came around the time when L-Dopa was being increasingly used to treat Parkinson’s disease. Dr. Knowles was credited with devising the first practical lab technique for making the L form and avoiding the undesired D-Dopa form.

Colleagues lauded him not only for this achievement but also for showing others the most fruitful direction of research. Today, the research by Dr. Knowles and his co-Nobelists is used to make antibiotics, anti-inflammatory drugs and heart medicines.

Dr. Knowles had “broken nature’s monopoly on making asymmetric compounds,” Sharpless said after the Nobel Prize was announced.

William Standish Knowles was born June 1, 1917, in Taunton, Mass. He grew up in New Bedford and attended private boarding schools that gave him a “good lesson in New England thrift,” he wrote in a Nobel biographical sketch.

“To get free ice for our physics experiments,” he wrote, “we had to wait until it snowed.”

Dr. Knowles received a bachelor’s degree in chemistry from Harvard University in 1939. “Competition was fierce and I always got a solid B, but not the straight A’s of many of my class mates,” he wrote in the sketch. He received a doctorate in synthetic organic chemistry from Columbia University in 1942. With World War II raging, Dr. Knowles joined Monsanto to take part in military-related research. He retired from the company in 1986.

Survivors include his wife of 66 years, the former Lesley “Nancy” Cherbonnier of Chesterfield; four children, Lesley McIntire of Kirkwood, Mo., Sarah Knowles and Peter Knowles, both of Seattle, and Elizabeth Knowles of New York; and four grandchildren.

He said the honor of receiving the Nobel Prize so late in life had come “out of the blue,” according to the National Academy of Sciences profile.

“I didn’t really expect it would happen to me,” he said, “but that probably made it doubly sweet.”

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