The impact of directed evolution recognized with Nobel Prize

Sincere congratulations to this year’s Nobel Prize in Chemistry Laureates, Professor Frances H. Arnold, Professor George P. Smith and Sir Gregory P. Winter. The Royal Swedish Academy of Sciences (RSAS) has honored the three researchers for “taking control of evolution and using it for purposes that bring the greatest benefit to humankind.”

Professor Arnold receives half the prize for her ground-breaking work on the directed evolution of enzymes. Professor Smith and Sir Winter share the other half of the prize the development and application of phage display, the directed evolution of antibodies. All three scientists have developed methods that are being used worldwide.

Professor Frances H. Arnold

Professor Frances H. Arnold is the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology. She is rightfully considered a pioneer in directed evolution, having applied the technique for the design of enzymes with novel functions and improved efficacy.

The method involves introducing random mutations in the gene for a given enzyme. The mutated genes are then inserted in bacteria, which produce randomly mutated enzymes. The enzymes can then be tested to discover those that most efficiently catalyze chemical reactions of interest.

Professor Arnold expressed her gratitude to the RSAS and her fellow scientists for the recognition of her work, saying “I love this supportive community. I’m stunned.”

She was the first person to optimize enzymes using directed evolution. She has applied directed evolution to design enzymes now used in more environmentally friendly production of renewable fuels and pharmaceutical compounds.

Research in the Arnold group at the California Institute of Technology continues to focus on evolutionary protein and enzyme design methods.

We generate novel and useful enzymes and organisms for applications in medicine, neurobiology, chemical synthesis and alternative energy. We also construct entire synthetic families of enzymes and other proteins in order to study structure-function relationships free from constraints of natural selection.

— Mission statement for the Arnold group, led by Professor Frances H. Arnold, Nobel Prize in Chemistry Laureate 2018

Here is a selection of Professor Arnold’s impressive work published in Elsevier journals:

Professor George P. Smith

Professor George P. Smith is the Curators’ Distinguished Professor Emeritus of Biological Sciences, University of Missouri, Columbia, United States. He developed the important method now known as phage display. He first worked on the concept in 1985, and it has since become an effective means to generate proteins using viruses and bacteria as the production medium.

The method involves changing the genetic material of bacteriophages (viruses that infect bacteria), causing the peptide produced from the introduced gene to appear on the surface of the phage as part of its capsule protein.

When Professor Smith introduced phage display to the scientific community, it was quickly apparent how it could be used to identify gene function. Researchers could introduce a single gene to see what protein would be produced or even work with multiple genes simultaneously. It has also found important applications in medicine.

Professor Smith is a grateful and humble recipient of the Nobel Prize, reminding interviewers that his work builds on what went before and is part of a longer line of research.

Very few research breakthroughs are novel. Virtually all of them build on what went on before. That was certainly the case with my work. Mine was an idea in a line of research that built very naturally on the lines of research that went before.

— Professor George P. Smith, Nobel Prize in Chemistry Laureate 2018, speaking to the Associated Press

The idea certainly didn’t come to me suddenly. It didn’t just pop into my head. I was trained in immunology and I knew a lot about the phage. My basic training was classic molecular biology. It was an idea from many sources in my background.

— Professor George P. Smith, Nobel Prize in Chemistry Laureate 2018, speaking to Adam Smith of nobelprize.org

Here is a selection of Professor Smith’s impressive work published in Elsevier journals:

Sir Gregory P. Winter

Sir Gregory P. Winter is a Research Leader Emeritus of the MRC Laboratory of Molecular Biology at Cambridge University. He received his knighthood for services to molecular biology in 2004.

He recognized the potential of Professor Smith’s phage display technique for the engineering of phages with particular functionality. His application of phage display has given rise to novel drugs.

The first pharmaceutical based on this directed evolution of antibodies is adalimumab, which was approved for use in 2002. Since then, medicines produced via phage display have been used in therapies that neutralize toxins, counteract autoimmune disorders and treat metastatic cancers.

The method involves introducing genetic information for an antibody’s binding site into a phage’s DNA and generating a library with a huge variety of antibodies. The phages that have strong attachments to the specific pharmaceutical target are selected for further investigation. Successive generations of antibodies with random mutations allow the selection of those with the best specificity for the target protein.

Here is a selection of Sir Gregory Winter’s impressive work published in Elsevier journals:

Congratulations again to the three recipients of this year’s Nobel Prize in Chemistry. As Professor Carol Robinson, President of the Royal Society of Chemistry (RSC) has stated, this year’s award highlights the role of chemistry in contributing to many areas of modern life. Recognizing these achievements recognizes how chemistry solves contemporary problems.