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K. Barry Sharpless of La Jolla’s Scripps Research wins second Nobel Prize in chemistry

K. Barry Sharpless of Scripps Research is pictured in 2011.
(K.C. Alfred / The San Diego Union-Tribune )

He shares the prize for pioneering ‘click chemistry’ that builds molecules.

K. Barry Sharpless of La Jolla’s Scripps Research won a second Nobel Prize in chemistry Oct. 5, this time for helping create a swift, Lego-like method for building molecules that is revolutionizing the development of pharmaceutical drugs.

The Royal Swedish Academy of Sciences announced that Sharpless, 81, will share this year’s Nobel with Carolyn Bertozzi of Stanford University and Morten Meldal of the University of Copenhagen, Denmark.

Sharpless is only the fifth person in history to win a Nobel twice. He shared the prize in 2001 for related work that has proved useful in everything from creating medications to new materials. Only one other person — late British scientist Frederick Sanger — has won the Nobel in chemistry twice.

This also is the second time in as many years that a scientist at Scripps Research — which has helped create key drugs such as Surfaxin and Zeposia — has won a Nobel. Last year, Ardem Patapoutian won the Nobel in physiology or medicine for helping discover cell receptors that enable people to sense heat, cold, pain, touch and sound.

The Nobel in chemistry comes with a roughly $900,000 prize that will be split among Sharpless, Bertozzi and Meldal.

Sharpless received the news from Stockholm, Sweden, at his home in La Jolla long before the sun peeked above the horizon.

“I’m pretty cheeky about thinking my ideas are good ideas,” Sharpless said in a statement. “It’s how I keep myself motivated when everyone thinks I’m crazy.”

His latest Nobel win reflects California’s continuing dominance in the chemistry field. Over the past 20 years, 13 Californians have shared the Nobel in chemistry. Sharpless’ achievements burnish San Diego’s standing as a world leader in life sciences and biotech.

The Nobel Committee said Sharpless, Bertozzi and Meldal “laid the foundation for a functional form of chemistry — ‘click chemistry’ — in which molecular building blocks snap together quickly and efficiently.”

The committee added that “Bertozzi has taken click chemistry to a new dimension” and started using it in living organisms.

Bertozzi is only the eighth woman to win a Nobel since the prizes were first awarded in 1901. She is being honored for expanding on the work of Sharpless and Meldal by creating bioorthogonal chemistry, which enables scientists to change and map molecules inside cells. The technique could prove useful in fighting cancer, the second-leading cause of death in the United States.

Sharpless said in his statement that “I thought click chemistry was a good idea, and probably good enough to be worthy of a Nobel Prize. But winning for a second time is absolutely thrilling, and it’s so gratifying that it’s happening in my lifetime. I’ve always been lucky, but right now I think I’m the luckiest person.”

Sharpless’ share of the Nobel arose from his efforts to simplify the process of creating molecules. He wanted to move away from the traditional method, which is tied to replicating the behavior of natural molecules.

The older method led to generations of pharmaceutical drugs, but it can be a very expensive, difficult and time-consuming process that often creates unwanted products that have to be carefully removed.

In 2001, Sharpless published a landmark journal article that pointed to a possible way to do things better and more quickly. It involved a comparatively inexpensive, streamlined process for snapping simple molecules together to create other types of molecules, particularly those meant to prevent and treat disease.

K. Barry Sharpless (left) receives the 2001 Nobel Prize in chemistry from Swedish King Carl XVI Gustaf.
(AP)

Sharpless “frequently contemplated his science during long walks or runs along the Torrey Pines Mesa, the Pacific Ocean horizon by his side,” Scripps Research said in company magazine in 2019.

“In his mind ... he would turn over the three-dimensional shapes of various molecules, pondering how the molecules of life assembled and behaved. In the same way, he had once gazed at interesting sea creatures during childhood fishing outings.”

Sharpless dubbed the method click chemistry and joined Bertozzi, Meldal and other scientists around the world in turning the idea into reality.

Johan Aqvist, chairman of the Nobel’s chemistry committee, told journalists Oct. 5 that “click chemistry is almost like it sounds. It’s all about snapping molecules together. Imagine that you could attach small chemical buckles to different types of building blocks. Then you could link these buckles together and produce molecules of greater complexity and variation.”

Sharpless marveled at the process that led to the advance, telling journalists Oct. 5, “One of the things that is most dramatic about humans is that we’re so impressed by ourselves and we have so many things we think we can do.”

“It’s a miracle we can do anything in [the] chemistry world,” given the minuscule size of the molecules scientists need to manipulate, he said. “We’re trying to do something that doesn’t make any sense.”

The breakthrough built on Sharpless’ earlier advances in synthesizing chemicals. He shared the 2001 Nobel in chemistry with William Knowles, who had worked at the agricultural corporation Monsanto, and Ryoji Noyori of Nagoya University in Japan.

“Winning for a second time is absolutely thrilling, and it’s so gratifying that it’s happening in my lifetime. I’ve always been lucky, but right now I think I’m the luckiest person.”

— K. Barry Sharpless

"[Sharpless] has had a tremendous impact on chemistry, first with his development of asymmetric synthesis and now with his elegant click chemistry,” Scripps Research President Peter Schultz told The San Diego Union-Tribune.

“His work opened whole new scientific frontiers that have had a major impact on the fields of chemistry, biology and medicine,” he added. “Barry has a remarkable combination of chemical insight, uncanny intuition and real-world practicality — he is a chemist’s chemist and a wonderful colleague.”

Sharpless was born April 28, 1941, in Philadelphia, where his early years were devoted to his two great loves, fishing and boating.

“While I had an overwhelming passion for fishing, school I merely enjoyed and I never planned to be a scientist,” he told the Nobel Committee for an official biography. “In fact, passion, not planning, is the engine driving all my thought and action. The almost unimaginably good fortune of my youth was that other people made such very, very good plans and choices for me ...

“I was a pre-medical student solely because my parents always hoped that I’d become an MD like my father. Pre-meds majored in chemistry or biology, and between the two I leaned toward chemistry. I didn’t get really interested, however, until I had two semesters of organic my sophomore year from a young chemistry professor who chose me to do research in his lab.”

Sharpless went on to earn a bachelor’s degree at Dartmouth College, then a doctorate in organic chemistry from Stanford. He later spent many years on the faculty at the Massachusetts Institute of Technology and, for a shorter period, at Stanford.

In 1990, he moved to the Scripps Research Institute, which today is known simply as Scripps Research. Over the years, the private biomedical research center has been home to figures such as Kurt Wuthrich, Bruce Beutler and Gerald Edelman, all of whom won a Nobel Prize.

“Prizes don’t change me at all,” Sharpless told journalists Oct. 5. “Prizes aren’t what I’m doing science for. I have to do it. It is kind of a compulsion.”

Following tradition, this year’s Nobels in physics, chemistry, literature and physiology or medicine will be awarded Saturday, Dec. 10, in Stockholm. The Nobel Peace Prize will be conferred on the same date in Oslo, Norway. ◆

Updates

8:45 a.m. Oct. 6, 2022: This article was updated with new comments from K. Barry Sharpless.