They Harnessed the Power of Evolution

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2018 with one half to Frances H. Arnold “for the directed evolution of enzymes” and the other half jointly to George P. Smith and The Nobel Prize 2018 in Chemistry Sir Gregory P. Winter “for the phage display of peptides and antibodies”. the Nobel Foundation. Nobel the Nobel Prize® and the Nobel Prize® medal design markdesign registered are trademarks of

They harnessed the power of evolution

The power of evolution is revealed through the diversity of life. The Nobel Prize in Chemistry 2018 is awarded to Frances H. Arnold, George P. Smith and Sir Gregory P. Winter because they have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture biofuels and pharmaceuticals, amongst a great deal else. Antibodies Binding evolved using a method called phage display combat autoimmune site on antibody Cancer cell diseases and can, in some cases, cure metastatic cancer.

Since the first seeds of life arose around Because proteins are masters of chemistry, 3.7 billion years ago, almost every crevice researchers have used rational approaches Renewable Greener on Earth has filled with different organisms. to try to change them to solve humankind’s fuels industry Life has spread to hot springs, deep oceans chemical problems, but proteins are and dry deserts, all because evolution complex and human intelligence is limited. has solved numerous chemical problems. Success was first achieved when the 2018 Life’s chemical tools – proteins – have Laureates in Chemistry started imitiating Randomly Antibody/ been optimised, changed and renewed. evolution. By using the principles of evolution mutated genes Pharmaceutical Contrast medium pharmaceutical Chemistry has become increasingly advanced, – random genetic mutations and selection – production for brain imaging producing new organisms and resulting in they have revolutionised chemistry and the fantastic diversity of life that now exists. the development of pharmaceuticals. The most effective Phage display enzymes are selected Binding site on antibody Gradually Enzyme with the improved desired properties specificity Generation 3

Part of gene Generation 2 for antibody Frances H. Arnold George P. Smith Sir Gregory P. Winter Randomly Target for mutated pharmaceuticals Born 1956 in Born 1941 in Norwalk, Born 1951 in Leicester, enzymes Pittsburgh, USA. Linus USA. Curators’ UK. Research Bacteriophage Pauling Professor Distinguished Leader Emeritus at library of Chemical Professor Emeritus MRC Laboratory of Generation 1 Engineering, of Biological Sciences Molecular Biology, Bioengineering and at University of Cambridge, UK. Biochemistry at Missouri, Columbia, California Institute USA. Arnold starts playing with evolution Smith uses a bacteria virus Winter develops targeted pharmaceuticals of Technology, In 1993, Frances Arnold conducted the first In 1985, George Smith developed an elegant In the early 1990s, Gregory Winter started to Pasadena, USA. directed evolution of enzymes (proteins that method that is called phage display, in which use phage display for the directed evolution catalyse chemical reactions). She mutated bacteriophages – viruses that infect bacteria – of antibodies. He created a library of phages genes and produced a library of randomly can be used to produce new proteins. that carried millions of different types of mutated enzymes. From this, she chose the A bacteriophage has a protein capsule that antibodies on their surface. Then he used enzymes that were most effective at catalysing surrounds the genetic material that codes for a protein as a kind of fishing hook to catch a chemical reaction. Then she repeated the the capsule. Smith put the gene for a foreign phages with antibodies that attached to process, so the enzyme gradually improved. protein into the gene for a phage capsule the protein. Using random mutations and Using directed evolution, Frances Arnold protein, so the foreign protein ended up on numerous cycles of directed evolution, he has produced enzymes that can, among the surface of the phage. The strength of then improved the accuracy of the antibodies. other things: work as a contrast medium phage display is that it provides a physical Using phage display, Gregory Winter started during brain imaging; produce renewable link between a protein and its gene. to develop antibodies that can work as fuels for a greener transport sector; replace pharmaceuticals. The first one, adalimumab, corrosive acids and toxic heavy metals in was approved in 2002 and is used to the production of pharmaceuticals and treat rheumatoid arthritis, psoriasis and in other chemical manufacturing. inflammatory bowel diseases. Since then, phage display has produced antibodies that can neutralise toxins, combat autoimmune diseases and even cure metastatic cancer. Photo: portrait of Frances Arnold: Caltech; portrait of George Smith: Michael Cali/MU ASC Photo; portrait of Sir Gregory Winter: Graham CopeKoga.

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