The 2018 Nobel Prize in chemistry was awarded Wednesday to Frances H. Arnold, George P. Smith and Gregory P. Winter for using evolutionary principles to create new proteins.
Arnold, a professor of chemical engineering at California Institute of Technology, won half of the prize “for the directed evolution of enzymes.” Smith, at the University of Missouri, and Winter, at the MRC Laboratory of Molecular Biology in Cambridge in Britain, shared the other half of the prize “for the phage display of peptides and antibodies.”
“This year’s prize is about harnessing the power of evolution,” Göran K. Hansson, secretary general of the Royal Swedish Academy of Sciences, told reporters in Sweden. These scientists used evolutionary techniques in the laboratory to create antibodies, biofuels, drugs and other important biological molecules. In 1993, Arnold was the first person to create new enzymes — molecules that speed up chemical reactions — with a technique called “directed evolution.”
The award was for chemistry, but the research also has wide applications throughout biology and engineering. Arnold is one of the few people to be a member of the exclusive National Academy of Sciences, National Academy of Medicine and the National Academy of Engineering.
Organisms evolve through a process called natural selection. The most successful living things pass their traits to their offspring. The most successful of those offspring reproduce and pass their traits along. But the advantageous traits didn’t appear by design — they’re random variations. Mutations, the result of jumbling genetic information, can lead to new chemicals, new features and ultimately new species.
Humans have used evolution’s mechanisms for our benefit for millennia. We’ve bred puny fingers of maize into thick corn cobs and bred wolves to be sheepdogs, retrievers and bichons frises. The laureates used chemistry "to accelerate the evolution of natural biological molecules,” thousands of times faster than would happen in the wild, said Peter Dorhout, president of the American Chemical Society and a Kansas State University chemistry professor.
Just as humans bred animals and plants with the most useful traits, Arnold selectively bred bacteria. She introduced random point mutations in bacteria, which changed the potency of their proteins. This, said Claes Gustafsson, chair of the Nobel Chemistry Committee, was applying the “principles of Darwin in the test tube.”
After repeatedly screening and mutating those microbes, she could use them to build a more powerful version of a desired protein. The resulting molecule could be hundreds of times more potent than the original version.
These improved molecules have a wide range of applications, including brain imaging, environmentally friendly detergents and pharmaceuticals, said biochemist Sara Snogerup Linse, a member of the chemistry committee.
Other academics scoffed at the engineering bent of Arnold’s early research — until she demonstrated the power of directed evolution.
“Some people looked down their noses at it,” she told Slate in a 2013 profile. “They might say ‘It’s not science’ or that ‘Gentlemen don’t do random muto-genesis.’ But I’m not a scientist, and I’m not a gentleman, so it didn’t bother me at all. I laughed all the way to the bank, because it works.” In 2011, for instance, Arnold and her colleagues evolved Escherichia coli into organisms capable of producing biofuels. Her work at Caltech has also led to synthetic pheromones — chemical signals — that, when smelled by pests, scare harmful bugs away from crops.
In 1985, Smith developed a method called phage display, based on a kind of virus known as a bacteriophage that infects bacteria. Those viruses are little more than loops of genetic material shrouded in a protein capsule. By introducing a gene into the phage, Smith could evolve new types of proteins on that virus capsule. Because the phages produce, or display, proteins on the outside of their shells, scientists can easily screen and harvest the molecules called peptides.
Smith predicted that phage display of peptides could help develop new vaccines. His 1997 review paper on the phage display method has been cited more than 1,000 times and has influenced at least 10 times that many papers, according to Matthew Toussant, senior vice president of the American Chemical Society’s CAS database division.
The big pharmaceutical breakthrough with phage display came in 1990, when Winter and his colleagues reported they had developed a fully functional antibody on a bacteriophage.
Antibodies are the molecules that our immune cells use to recognize other cells. Winter applied the phage display technique to create antibodies that could be used to treat disease. These antibodies have been used to neutralize toxins, treat metastatic cancer and fight inflammatory bowel disease and other autoimmune diseases, the academy said. In 2002, the Food and Drug Administration approved the first human-antibody-based drug, adalimumab, sold as a rheumatoid arthritis treatment called Humira by pharmaceutical company AbbVie.
Winter, in an interview Wednesday with the Associated Press, said that few breakthroughs are truly novel — his work expanded upon the research of many other scientists. “It’s happenstance. That was certainly the case with my work,” he said.
This was the 110th Nobel Prize awarded for chemistry since 1901, and this year was the first that women have been included in both the chemistry and physics Nobel Prizes. Arnold is the fifth woman to win a chemistry Nobel.
Arnold was "first, stunned. Then thrilled. Then eager to share a celebration with my students, friends, and family. I’m on a plane home to LA at this very minute,” she wrote in an email to The Post on Wednesday afternoon. “I hope that science and technology capture the imaginations of your readers and their children. It’s so important for the well being of our planet and all its inhabitants. And it’s a wonderful expression of our human creativity and curiosity.”
She will get half of the award of 9 million kronor (that’s about $1 million). Winter and Smith will split the remainder of the money. The next Nobel, the Peace Prize, will be announced Friday.
This post has been updated.