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From the Lab of Jeremy Knowles

Although he may be an administrator now, the dean of the Faculty of Arts and Sciences has spent most of his 30-year career contributing to the field of chemistry by increasing our understanding of how enzymes function.

By Julian E. Barnes

Dean of the Faculty Jeremy R. Knowles has been very busy these days with his new administrative responsibilities.

Despite all the new duties filling up his schedule, however, the Houghton professor of chemistry and biochemistry still finds time to work in his lab every Friday afternoon, Saturday and Sunday.

But when Knowles moved out of his Mallinckrodt lab to the dean's office in University Hall this summer, he made a decision to give up his research as soon as his graduate students conclude their studies.

Understandably, it is a difficult transition for Knowles, since for the last 30 years, the work he contributed to the understanding of how enzymes operate was one of the most important and most enjoyable parts of his career, he says.

A 'Surgical' Approach

Emery Professor of Organic Chemistry Elias J. Corey, the winner of last year's Nobel Prize for chemistry, calls Knowles the "world's most influential bio-organic chemist."

Corey says that Knowles's approach to research has been "surgical" and characterized by very deliberate experiments and deliberate discoveries.

"He has a rational, logical, mathematical approach to research," Corey says. "It is more than a fishing expedition. Jeremy does not make accidental discoveries."

Knowles's most influential and well known research has dealt with the processes involved in enzyme reactions.

"His most important discoveries add up together to a more in-depth understanding about how enzymes work," Corey says.

Knowles's research has illuminated how enzymes accelerate chemical reactions efficiently. During the early 1970s, Knowles and his group of researchers began to look at the mechanisms involved in enzyme activity.

Knowles's work at that time led to the first complete description of what took place in the enzyme-catalyzed reaction.

In his experiment, Knowles developed a theory of "enzymatic perfection." The biochemist showed that certain enzymes' evolutionary development had reached their most advanced stage.

Knowles was the first person to show that enzymes could reach a maximum possible efficiency and could come to a point where it would be impossible to speed biochemical processes any further.

"This was the first time someone had come up with the concept that enzymes could reach maximum efficiency," says Frank H. Westheimer, Loeb professor of chemistry, emeritus.

Knowles was also able to develop a unique method to enable him to examine the three-dimensional or stereochemical changes in molecular structures that takes place during an enzyme reaction.

His third major contribution to the study of enzymes looked at the resistance of bacteria to penicillin. Bacteria develop a resistance to penicillin by producing an enzyme that makes the antibiotic harmless.

Knowles and his researchers examined the mechanism of how the enzyme blocks penicillin and helped develop a drug to prevent the enzyme from functioning.

Knowles compares his work to that of a bombing mission. "If your bombers are being shot down, you can either develop higher flying bombers or you can knock out the anti-aircraft guns and use the old bombers," says Knowles. By rendering the enzyme inoperable, Knowles effectively knocked out the "anti-aircraft guns."

Will Miss Grad Students

Knowles says the excitement of making new findings is a big part of the joy he finds in his research. But the biochemist says the part of his job he will miss the most is teaching his graduate students.

"Seeing a graduate student come in raw and go out, after four or five years, a fiercely independent thinker is a tremendous pleasure," Knowles says.

As a result of his new position, the biochemist has had to place many of his younger grad students into other programs.

Prior to his appointment as dean there were 20 graduate students and post-doctoral researchers working in his group. Now there are only 13 people working in Knowles's group.

"It is improper for me to supervise new students," Knowles says. "I do not believe in doing two things badly."

Knowles will continue to run his lab until all of his graduate students finish their studies, which will at least be two years.

While Knowles's contributions to bio-organic chemistry were unmatched during his three decades of researching, colleagues say, the biochemist saw a need for his talents elsewhere in the University.

"I think Jeremy was looking for new worlds to conquer," Westheimer says. "I think he will be marvelous. He has a great breadth of knowledge and interests. I think he will be able to do wonderful things for Harvard."

While Corey admits it is for the greater good of the University that Knowles gave up the academic life for the administrative, he is saddened by the biochemist's departure.

"It is certainly a loss for the department," says Corey. "Jeremy is irreplaceable."

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