Three researchers won the 2018 Nobel Prize in Chemistry for applying the principles of evolution to create new molecules that have been the building blocks for developments in pharmaceuticals and biofuels.
Frances Arnold, an elected fellow of the American Association for the Advancement of Science, was awarded half of the $1.01 million prize for conducting the first directed evolution of enzymes in 1993. George Smith – also a AAAS fellow – and Sir Gregory Winter shared the other half of the award for Smith’s method for evolving new proteins and Winter’s work using that technique to develop antibody-based drugs, according to the Royal Swedish Academy of Sciences, which announced the awards Oct. 3 in Stockholm.
“This year’s prize in chemistry rewards a revolution based on evolution,” said Claes Gustafsson, chairman of the Nobel Committee for Chemistry. “Our laureates have applied principles of Darwin in the test tubes and used this approach to develop new types of chemicals for the greater benefit of humankind.”
Arnold is the fifth woman to receive the Nobel Prize in Chemistry in the 117-year history of the award. She was elected a fellow of AAAS’ Section on Engineering in 2009. A member of AAAS, Arnold has also served as a member of the AAAS Committee on Nominations from 2015 to 2017 and as a Member at Large from the Section on Engineering.
Like many of her fellow researchers, Arnold initially took a logical approach to rebuilding enzymes – the catalysts for chemical reactions in organisms – to give them new properties. Arnold soon decided to abandon this approach in recognition of the infinite complexity of enzymes. Instead she sought inspiration from evolution by introducing random changes to an enzyme. She was able to produce thousands of new varieties. Into one that worked best in a particular solvent, Arnold introduced another set of random mutations, yielding a variant that worked 256 times better than the original enzyme. In contrast with natural selection, directed evolution allows the scientist to select the fittest enzyme from random mutations.
Arnold, a professor of chemical engineering, bioengineering and biochemistry at the California Institute of Technology, is now working to develop enzymes that can be used to produce biofuels and greener plastics. She has created enzymes that have led to more environmentally friendly pharmaceuticals because chemical processes are sped up and produce fewer byproducts.
The other half of the award honored Smith and Winter for their work that has led to new pharmaceuticals. Smith, now professor emeritus in biological sciences at the University of Missouri, developed a technique in 1985 called phage display, which uses a virus that infects bacteria, known as a bacteriophage, to evolve new proteins. Smith was elected a AAAS fellow in the Section on Biological Sciences in 1999.
Winter, research leader emeritus at the MRC Laboratory of Molecular Biology in Cambridge, U.K., used this technique to evolve new antibodies that form the basis for new medicines. He and his colleagues developed the first pharmaceutical drawn from a human antibody, adalimumab, which is sold under the name Humira to treat rheumatoid arthritis, psoriasis and inflammatory bowel disease. Its success has inspired new research – currently in various stages – on other pharmaceuticals made from antibodies to treat metastatic cancer, autoimmune diseases and Alzheimer’s disease.
“Directed evolution and phage display have become powerful and widely used methods for identifying molecules with sought after properties. They rely on the creation of a large and diverse set of possibilities and selecting the ones with the most desirable properties,” said Jeremy Berg, editor-in-chief of the Science family of journals, said. “Many research reagents, drug candidates, and catalysts have been discovered through these approaches.”
Said the Nobel Committee, “We are in the early days of directed evolution’s revolution which, in many different ways, is bringing and will bring the greatest benefit to humankind.”