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October 4, 2018

Nobel in Chemistry Awarded for Directed Evolution of Enzymes and Antibodies

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    The underlying principle for the directed evolution of enzymes. After a few cycles of directed evolution, an enzyme may be several thousand times more effective. [Johan Jarnestad/The Royal Swedish Academy of Sciences]

    This year, the Nobel Prize in Chemistry recognizes that when scientists need to improve enzymes and antibodies, scientists sometimes find that the most rational thing they can do is abandon rational design. Instead, they may resort to directed evolution, that is, a human-directed version of the biology’s most powerful process.

    The pioneers of directed evolution recognized by the Nobel committee include Frances H. Arnold, Ph.D., the Linus Pauling Professor of chemical engineering, bioengineering and biochemistry at the California Institute of Technology, George P. Smith, Ph.D., Curators Distinguished Professor Emeritus of biological science at the University of Missouri, and Sir Gregory P. Winter, Ph.D., of the MRC Laboratory of Molecular Biology. Dr. Arnold received half the Nobel “for the directed evolution of enzymes,” and Drs. Smith and Winter shared the other half “for the phage display of peptides and antibodies.”

    Like natural evolution, directed evolution involve mating and selection. In directed evolution, however, these processes are managed. For example, in directed evolution, mating may be accomplished by DNA shuffling, and selection is a matter of imposing selection pressures that have been chosen to accomplish desirable ends, such as generating a high-performing enzyme, a convenient biofuel, or a cancer-killing drug.

    The inspiration for the Nobel winners comes from life’s chemical tools—proteins. Since the first seeds of life arose around 3.7 billion years ago, proteins have been optimized, changed, and renewed, creating incredible diversity, solving untold numbers of chemical problems.

    Taking cues from nature Arnold conducted the first directed evolution of enzymes in 1993. Since then, she has refined the methods that are now routinely used to develop new catalysts. The uses of Dr. Arnold’s enzymes include more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels for a greener transport sector.

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    The principle for the directed evolution of antibodies using phage display. This method is used to produce new pharmaceuticals. [Johan Jarnestad/The Royal Swedish Academy of Sciences]

    In 1985, Dr. Smith developed an elegant method known as phage display, where a bacteriophage—a virus that infects bacteria—can be used to evolve new proteins. Dr. Winter used phage display for the directed evolution of antibodies, with the aim of producing new pharmaceuticals. The first one based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis, and inflammatory bowel diseases. Since then, phage display has produced antibodies that can neutralize toxins, counteract autoimmune diseases, and cure metastatic cancer.

    In recognizing the contributions of Drs. Arnold, Smith, and Winter, the Nobel committee noted, “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.”

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