NEW YORK — William S. Knowles, who was 84 and in retirement when he shared the Nobel Prize in Chemistry in 2001 for improving ways to manufacture drugs, including L-dopa for the treatment of Parkinson’s disease, died June 13 at his home in Chesterfield, Mo., a suburb of St. Louis. He was 95.
His death was confirmed by his daughter Elizabeth Knowles. His daughter Lesley McIntire told the Associated Press that Dr. Knowles died of complications from amyotrophic lateral sclerosis.
Dr. Knowles, a native of Taunton, Mass. who grew up in nearby New Bedford, worked for the Monsanto Co. from 1942 to 1986. He had been retired for 15 years when he was woken up by an early-morning phone call from Stockholm in October 2001, telling him that he had been awarded the Nobel Prize.
‘’I’ve been retired and out of the running for some time,’’ he told his local newspaper in Chesterfield, The Webster-Kirkwood Times.
The prize, for work in a field known as chiral chemistry, was also awarded to Ryoji Noyori of Nagoya University in Japan and K. Barry Sharpless of the Scripps Research Institute in San Diego.
At boarding school in the Berkshires, I ‘got a good lesson in New England thrift. To get free ice for our physics experiments we had to wait until it snowed.’
Just as the left hand is a mirror image of the right, many molecules come in two forms, identical in chemical composition but mirror images of each other.
The two forms can have very different properties and sharply different effects on the body. For example, one version of the molecule limonene smells of oranges; its mirror image has a lemony, turpentinelike odor.
The drug L-dopa is another example. In one form, called L, it reduces Parkinson’s symptoms like tremors and rigidity. But it also comes in another form, D-dopa, which is toxic. In the 1960s, the standard process to make L-dopa yielded equal amounts of the two forms. Separating them after they were made was time-consuming and expensive.
Dr. Knowles figured out a way to tweak the manufacturing process to produce more of the most desirable form of certain molecules, including L-dopa. His tool was a catalyst, a substance often used to speed up a chemical reaction.
He developed a process called asymmetric hydrogenation, which uses a catalyst not just to speed the reaction but also to skew it to produce 97.5 percent L-dopa and only 2.5 percent of the unwanted D form. Monsanto then began large-scale production of the drug, which is still a mainstay in treating Parkinson’s, especially in the disease’s early stages.
William Standish Knowles was born June 1, 1917. He graduated a year early from the Berkshire School, a boarding school in Western Massachusetts, and was admitted to Harvard. But after being strongly advised that he was not socially mature enough for college, he did a second senior year of high school at another boarding school, Phillips Academy in Andover, Mass.
In an autobiographical essay he wrote for the Nobel committee, Dr. Knowles called Western Massachusetts “definitely the most beautiful part of the state. I’ll never forget the fall colors on the Berkshires. In those days I was terrible at athletics and never made a team, but quite easily led my class in academics. I was particularly good at math and science. I also got a good lesson in New England thrift. To get free ice for our physics experiments we had to wait until it snowed.’’
At Andover, Dr. Knowles wrote, “I took my first chemistry course from a teacher named Bushy Graham and was fascinated by the subject. I remember . . . his discussion of the dangers of hydrogen and oxygen. At the end of the year, I took a competitive exam and won my first prize, the $50 Boylston prize in chemistry.’’
Dr. Knowles graduated from Harvard with a bachelor’s degree in chemistry in 1939 and completed his doctorate at Columbia in 1942.
At Harvard, he wrote, “I took the minimum of humanities. I was told I’d be a natural for physical chemistry but taking organic with Louis Fieser changed my mind. It was there I got my introduction to optical isomerism and the tetrahedral carbon atom. At Harvard competition was fierce and I always got a solid B, but not the straight A’s of many of my classmates. These were the days when most got a gentleman’s C.’’
Dr. Knowles started work for Monsanto in Dayton, Ohio, before transferring to the company’s home base, St. Louis, in 1944, where he worked until retiring in 1986.
In 2004, he was admitted to the National Academy of Sciences.
Besides his daughters Lesley McIntire and Elizabeth Knowles, Dr. Knowles leaves his wife of 66 years, Nancy; a son, Peter; another daughter, Sarah Knowles; and four grandchildren.
Elizabeth Knowles said her father did not keep any of the Nobel Prize money — more than $200,000. He gave some to two Monsanto colleagues who had collaborated on his L-dopa research and donated the rest to Harvard and Columbia.