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Nobel prize won by biochemical engineer

24 October 2018

Comment by Professor Paul Dalby on Nobel prize for chemistry award to biochemical engineer Frances Arnold, and pioneers of phage display and antibody engineering, George Smith and Sir Greg Winter

glass flask in laboratory

Those working in the field of protein engineering have been wondering if it was ever going to get the recognition it deserved. Now these three pioneers of the field have been recognised with the Nobel Prize in Chemistry. What makes these three special is the sheer impact they have had on our lives whether we know it or not.

Most of us know someone who has been prescribed an antibody therapy for rheumatoid arthritis, breast cancer, Crohn’s disease or Leukemia, and most of us have benefited from enzymes that have been evolved to work better in everything from biological washing powders to the synthesis of pharmaceuticals, and biofuel production.

In 1994 I joined the MRC centre for protein engineering in Cambridge to work with Sir Alan Fersht who Co-directed the “CPE” with Greg Winter. It was co-located with the MRC LMB to form a crucible of Nobel prize winners including Sydney Brenner, John Walker, Aaron Klug, Cesar Milstein, Fred Sanger, Max Perutz, and of course Crick and Watson.  There was a common room downstairs where everyone descended like clockwork at 10am and the groups would mingle. Discussions were almost always scientific and there I learnt about phage display and of course Cambridge Antibody Technology that had just been founded by Greg Winter.  Photocopies of the laboratory phage display protocols of George Smith has been passed around the world like a highly coveted secret document.

In 1998 I attended a “retreat” in West Virginia organised by my funders. Bill DeGrado had sent me as postdoc in his place, and I found myself surrounded by some of the world’s leading scientists, including a highly impassioned Frances Arnold discussing directed evolution of enzymes. It was already clear then that this was developing into something with real potential, and modified enzymes were set to reinvigorate the biocatalysis industry. Feeling massively out of place, I nervously asked Frances some question I immediately realised was not a very good one, but she took it graciously and replied without hesitation with an answer that was far better than the question merited.

Some years later I returned to Cambridge for a celebration of Alan Fersht’s 60th birthday. Greg Winter gave a lecture in the history of Antibody engineering. One issue with previous antibodies was their reliance on mouse sequences. They pushed phage display as a route to human antibodies that would cause fewer adverse immune responses. Greg candidly admitted that there was little actual evidence for this at the time, but it was enough to win financial backing, and of course some years later it turned out to be absolutely correct.

Paul Dalby