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Nobel Prize in Chemistry Is Awarded to 3 Scientists for Work ‘Snapping Molecules Together’ Nobel Prize in Chemistry Is Awarded to 3 Scientists for Work ‘Snapping Molecules Together’
(about 4 hours later)
The Nobel Prize in Chemistry was awarded to Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless on Wednesday for the development of click chemistry and bio-orthogonal chemistry — work that has “led to a revolution in how chemists think about linking molecules together,” the Nobel committee said. The 2022 Nobel Prize in Chemistry has been awarded to three scientists whose work harnessed the power of molecular interaction and introduced new, unobtrusive ways of studying the natural world.
Dr. Bertozzi is the eighth woman to be awarded the prize, and Dr. Sharpless is the fifth scientist to be honored with two Nobels, the committee noted. Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen and K. Barry Sharpless of Scripps Research will share the prize, which honors the scientists’ independent research that resulted in the development of what is known as click chemistry and bio-orthogonal chemistry. The three researchers will also split a prize of 10 million Swedish kronor, around $900,000. Their works have “led to a revolution in how chemists think about linking molecules together,” said Johan Aqvist, the chair of the Nobel Committee for Chemistry.
Johan Aqvist, the chair of the chemistry committee, said that this year’s prize dealt with “not overcomplicating matters, instead working with what is easy and simple.” In winning the award on Wednesday, Dr. Sharpless became only the fifth person to win two Nobels, having received the chemistry prize in 2001 for his work on chirally catalyzed oxidation reactions. The other two-time winners were Marie Curie, John Bardeen, Linus Pauling and Frederick Sanger. Dr. Bertozzi also became the eighth woman to be awarded the chemistry prize, the latest since Emmanuelle Charpentier and Jennifer A. Doudna in 2020.
“Click chemistry is almost like it sounds,” he said of a field whose name Dr. Sharpless coined in 2000. “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.” Molecules are reacting all around us, constantly, in our drinks, on the tips of our fingers, in our phones. These reactions create new molecules, break down old ones, allow energy swaps — they shape the variegated dynamics of the universe. For scientists looking to understand these forces, combining molecules in a controlled way can be difficult, especially in a delicate environment like a living cell, because everything is so closely connected. Often the surrounding molecules are disturbed in the process, changing the very thing a researcher wants to study.
Shortly after Dr. Sharpless coined the concept, both he and Dr. Meldal independently discovered a chemical reaction called copper-catalyzed azide-alkyne cycloaddition, known today as the crown jewel of click chemistry. In 2001, Dr. Sharpless and some of his colleagues published a paper introducing something he called click chemistry, a new way of approaching this kind of molecular control when applied to the creation of new drug compounds. The method would be based around one rule, he wrote: “All searches must be restricted to molecules that are easy to make.” Instead of trying to synthesize, or chemically create, molecules by forcing a difficult organic bond, Dr. Sharpless, said, focus instead on bonds that form fast and produce stable byproducts. If done in the right way, the tougher bonds will form automatically, clicking into place. Think of them “as gifts of nature,” Dr. Sharpless wrote.
“When this reaction was discovered, it was like opening the floodgates,” Olof Ramström, a member of the Nobel Committee for Chemistry, said in a briefing after the laureates were announced. “We were using it everywhere, to build everything.” “What’s unique about click chemistry is that the two reagents, in the presence of hundreds of thousands of different types of molecules, they will only seek out each other and only give one product,” said Jiong Yang, a program director at the National Institute of General Medical Science who oversees Dr. Sharpless’s work. “That’s the basis of all this technical development.”
Dr. Bertozzi, a chemist and professor at Stanford, was able to apply this reaction to biomolecules, often found on cell surfaces, in living organisms without affecting the chemistry of the cells she was observing. Before her extensive research with glycans, or sugar chains, scientists’ understanding of this subfield of glycobiology had been hampered by an inability to see molecules in action in living cells. This shift in approach was soon followed by the discovery of a reaction called copper-catalyzed azide-alkyne cycloaddition, which put the theory into practice. Azides and alkynes are two types of molecules, and Dr. Meldal and Dr. Sharpless independently found that when they were combined, using copper as a catalyst, the reaction was fast and efficient and the product was stable. Now known as the “crown jewel of click chemistry,” the discovery was “like opening the floodgates,” said Olof Ramström, a member of the Nobel Committee for Chemistry in a briefing after the laureates were announced. “We were using it everywhere, to build everything.”
Her work “revolutionized the way we can analyze or see molecules in the living body,” Dr. Ramström said. Molecules could now be combined quickly, efficiently and without much fuss, and the applications immediately extended “beyond chemists,” said Angela Wilson, the president of the American Chemical Society. Material science, pharmaceutical development, tissue regeneration, brightening agents — “this just opens up a world of possibilities in terms of materials and polymers,” Dr. Wilson said. “It’s like putting Lego pieces together — you do it much more easily and are able to build bigger molecules.”
By pioneering a method for mapping biomolecules on the surface of cells, Dr. Bertozzi later devised a way to build click reactions, or complex molecules, inside living organisms. These so-called bio-orthogonal reactions have since been applied widely to pharmaceutical developments in cancer, DNA sequencing and material sciences. Jon Lorsch, the director of the National Institute of General Medical Science, also used the Lego analogy. “It allows you to assemble molecules in a fairly defined way, such that you can direct what’s attached to what easily.” Dr. Lorsch added, “Almost anything you look at these days, you can find an example of where this chemistry has been applied.”
“The field of click chemistry is still in its early phases,” Dr. Bertozzi said in a call after the announcement, adding that there were “many new reactions to be discovered and invented,” as well as new applications to be found in industries like biotech, and in treating and diagnosing illnesses. What may have been the most pivotal application of click chemistry began to take shape before the term was even coined. In the 1990s, Dr. Bertozzi was studying glycans, carbohydrates that sit on the surfaces of proteins and cells, the functions of which were not wholly understood. While much attention was being paid to genomes and proteins, glycans were relatively overlooked, in part because they were really difficult to track inside living organisms.
She emphasized the importance of click therapy in medicine and “drug delivery,” which involves “doing chemistry inside living patients to make sure drugs go to the right place and not to the wrong place.” Dr. Bertozzi began looking for ways to attach fluorescent molecules to glycans so she could map them as they moved. But the molecules used to track the glycans couldn’t interfere with the rest of the cell’s functioning. So the method had to be, as Dr. Bertozzi put it, bio-orthogonal. It had to stay out of the cell’s way.
“These are areas that will be very strongly impacted by click chemistry, and they already have been,” said Dr. Bertozzi, who earned her Ph.D. in organic chemistry at the University of California, Berkeley, in 1993. Around the same time that click chemistry emerged, Dr. Bertozzi was able to develop bio-orthogonal tracking methods, and she realized that she could apply the new paradigm to her work, attaching fluorescent alkynes to glycans to be tracked. The reaction, as it stood after Dr. Sharpless’s and Dr. Meldal’s contributions, required a copper catalyst, which would be toxic to living organisms. But Dr. Bertozzi came up with a different way of getting the two molecules to click together, modifying the alkyne’s structure to fill the catalyst’s role.
The Nobel committee said in a statement that “click chemistry and bio-orthogonal reactions have taken chemistry into the era of functionalism,” adding that “this is bringing the greatest benefit to humankind.” “This was a known concept,” said Laura Kiessling, a chemist at the Massachusetts Institute of Technology, about Dr. Bertozzi’s insight. “What she did was recognize and apply that concept to a reaction that we could use in biological systems.”
The key was to find “good chemical buckles,” Dr. Aqvist said. “They have to react with each other, easily and specifically. Morten Meldal and Barry Sharpless independently found the first perfect candidates that will easily snap together, and importantly they won’t snap with anything else.” Like many scientists, Dr. Kiessling, a friend and colleague of Dr. Bertozzi’s, uses bio-orthogonal click chemistry to map the internal structures of organisms, and the movements of their cells. For instance Dr. Kiessling does research on tuberculosis, and said that, with the method, she was able to “visualize classes of carbohydrates that we couldn’t see before.” Other applications include tracking tumors, sequencing DNA and studying viruses. Dr. Kiessling added, “We use this chemistry all the time — as do others.”
Dr. Aqvist noted that click chemistry “can now be used for building drug molecules, polymers, new materials and many other things.” “This has really opened up an immense amount of new space for scientists to study how different living processes work and to watch those processes in action, even in real time,” said Dr. Lorsch, whose organization has funded both Dr. Bertozzi’s and Dr. Sharpless’s research.
Before the award was announced on Wednesday, the committee hinted that the prize could again be given to a woman, with a pair of Twitter posts highlighting Marie Curie and the 2020 winners, Emmanuelle Charpentier and Jennifer Doudna. During the award announcement, Dr. Bertozzi, who joined remotely, acknowledged the potential of her and her fellow laureates’ work. “The field of click chemistry is still in its early phases,” she said, adding that there were “many new reactions to be discovered and invented,” as well as new ways to integrate the science in industries like biotechnology. One such application is in “drug delivery,” which involves “doing chemistry inside living patients to make sure drugs go to the right place and not to the wrong place.”
“I’m absolutely stunned. I’m sitting here and can hardly breathe,” Dr. Bertozzi said after the announcement. “I’m still not entirely positive that it’s real, but it’s getting realer by the minute.” But all those plans for the future came after her surprise, which registered when she first called into the committee. “I’m absolutely stunned. I’m sitting here and can hardly breathe,” she said. “I’m still not entirely positive that it’s real — but it’s getting realer by the minute.”
While she said that she had not yet had time to consider how to use the award money, Dr. Bertozzi noted that “to the extent that the prize casts a light on chemical biology, that’s a wonderful thing.”
The committee also telegraphed how rare it is for scientists to win two Nobels, noting that Curie was one of the few to have done so. Dr. Sharpless, the committee noted afterward, becomes the fifth member of that club, having received the chemistry prize in 2001 for his work on “chirally catalyzed oxidation reactions.”
As well as Curie, the other double Nobel laureates are John Bardeen, Linus Pauling and Frederick Sanger, the committee noted.
After the announcement, video on social media showed Dr. Meldal, who is Danish, being met with applause and cheers at the University of Copenhagen, where he is a professor.
The chemistry prize is the third Nobel given this week, after the awards in physiology or medicine on Monday and in physics on Tuesday. The prizes are among the highest honors in science.
The prize was awarded to Benjamin List and David W.C. MacMillan for their development of a tool that spurred research into new drugs and reduced chemistry’s effect on the environment.The prize was awarded to Benjamin List and David W.C. MacMillan for their development of a tool that spurred research into new drugs and reduced chemistry’s effect on the environment.
The Physiology or Medicine prize was awarded on Monday to Svante Pääbo, a Swedish scientist who peered back into human history by retrieving genetic material from 40,000-year-old bones, producing a complete Neanderthal genome and initiating the field of ancient DNA studies.The Physiology or Medicine prize was awarded on Monday to Svante Pääbo, a Swedish scientist who peered back into human history by retrieving genetic material from 40,000-year-old bones, producing a complete Neanderthal genome and initiating the field of ancient DNA studies.
The physics prize went to Alain Aspect, John F. Clauser and Anton Zeilinger on Tuesday for their experiments that pioneered developments in the field of quantum mechanics.The physics prize went to Alain Aspect, John F. Clauser and Anton Zeilinger on Tuesday for their experiments that pioneered developments in the field of quantum mechanics.
The Nobel Prize in Literature will be awarded on Thursday by the Royal Swedish Academy of Sciences in Stockholm. Last year, Abdulrazak Gurnah won for “his uncompromising and compassionate penetration of the effects of colonialism and the fate of the refugee in the gulf between cultures and continents.”The Nobel Prize in Literature will be awarded on Thursday by the Royal Swedish Academy of Sciences in Stockholm. Last year, Abdulrazak Gurnah won for “his uncompromising and compassionate penetration of the effects of colonialism and the fate of the refugee in the gulf between cultures and continents.”
The Nobel Peace Prize will be awarded on Friday by the Norwegian Nobel Institute in Oslo. Last year, Maria Ressa and Dmitri A. Muratov, both journalists, won for their efforts to protect press freedoms.The Nobel Peace Prize will be awarded on Friday by the Norwegian Nobel Institute in Oslo. Last year, Maria Ressa and Dmitri A. Muratov, both journalists, won for their efforts to protect press freedoms.
Next week, the Nobel Memorial Prize in Economic Sciences will be awarded on Monday by the Swedish Academy in Stockholm. Last year, the prize went to David Card, Joshua D. Angrist and Guido W. Imbens.Next week, the Nobel Memorial Prize in Economic Sciences will be awarded on Monday by the Swedish Academy in Stockholm. Last year, the prize went to David Card, Joshua D. Angrist and Guido W. Imbens.
All of the prize announcements will also be streamed live by the Nobel Prize institution. Prize winners will receive their awards at a ceremony in Stockholm in December.All of the prize announcements will also be streamed live by the Nobel Prize institution. Prize winners will receive their awards at a ceremony in Stockholm in December.