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Chemistry Nobel for using evolution to create new proteins

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STOCKHOLM -- Three scientists won the Nobel Prize in chemistry Wednesday for using a sped-up version of evolution to create new proteins that have led to a best-selling drug and other products.

The Royal Swedish Academy of Science said their work has led to the development of medications, biofuels and a reduced environmental impact from some industrial processes.

Frances Arnold of the California Institute of Technology in Pasadena was awarded half of the 9-million-kronor ($1.01 million) prize, while the other half was shared by George Smith of the University of Missouri and Gregory Winter of the MRC molecular biology lab in Cambridge, England. Arnold is only the fifth woman to win a chemistry Nobel since the prizes began in 1901.

The winners "have taken control of evolution and used it for purposes that bring the greatest benefit to humankind," the Nobel committee said.

In nature, evolution proceeds slowly as random genetic mutations generate variety in organisms and proteins, and those versions that work best in their environment persist for future generations. The research honored Wednesday mimicked that process by inducing mutations in proteins and selecting those that best met the goals of the research.

Smith, 77, and Winter, 67, worked with viruses called phages that infect bacteria. Smith showed in 1985 that inserting DNA into these viruses would make them display proteins linked to that DNA on their surfaces. It was a way to find an unknown gene for a known protein.

Winter adapted the approach to create useful antibodies, proteins that target and grab onto disease-related targets. Winter introduced mutations to make antibodies progressively better at binding to their targets. In 1994, for example, he developed antibodies that grab onto cancer cells.

The first pharmaceutical based on Winter's work, AbbVie's adalimumab, was approved for sale in 2002. It's used to treat immune-system disorders, including rheumatoid arthritis, psoriasis and inflammatory bowel diseases, the academy said.

Sold as Humira in the U.S. and under other brand names elsewhere, it brought AbbVie $18.4 billion in revenue last year, in part because of its price: about $5,000 a month without insurance coverage in the U.S.

Other antibodies produced by this approach fight cancer, neutralize the anthrax toxin and slow down lupus, the Swedish academy said.

Dr. Wayne Marasco of the Dana-Farber Cancer Institute in Boston said the lab technique developed by Smith and Winter was "revolutionary ... and it's used today, every day."

Arnold, 62, was seeking ways to make improved enzymes, which are proteins that encourage chemical reactions to occur. In 1993, she showed the power of "directed evolution" for doing that.

First she created random mutations in DNA that lets cells produce an enzyme. Then she slipped these mutated genes into bacteria, which pumped out thousands of different variants of the enzyme.

One variant did a particularly good job at a certain task, so she made a new round of mutations in this variant. That produced another variant that worked better. When she made mutant versions of that variant, she got an even better version. It contained a combination of 10 mutations that nobody could have predicted would work so well, the Swedish academy said.

Techniques for directed evolution have improved since then and Arnold has been at the leading edge, the academy said. Her tailored enzymes have become important for making medications and other valuable substances like renewable fuels.

"Her work is incredible," Matt Hartings, an associate chemistry professor at American University, told The Associated Press.

International on 10/04/2018

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