Directed Evolution – Caltech Professor

Scientists’ dreams of constructing new forms of life—either to enhance human well-being or just to prove that we can do it—are somewhat grander than the reality, because we are profoundly ignorant of the mapping from DNA sequence to biological function. Details of molecular interactions rule function, and we don’t understand the details. For forward engineering of biological systems, I argue that we should look to the design algorithm that has produced the entire biological world: evolution. This simple algorithm works at all scales of complexity, from single proteins to ecosystems, and can be ‘directed’ by controlling the molecular diversity (mutations) and applying artificial selection. By emulating evolution in the laboratory, we are able to create new, finely-tuned enzymes that exhibit desired properties, including functions not observed in the natural world. I will show how we use these enzymes to construct and optimize organisms that produce fuels and chemicals from renewable resources.

Evolving new enzymes in the laboratory has also allowed us to explore fundamental processes of protein evolution. Proteins can readily adapt to new functions or environments via simple adaptive walks involving small numbers of mutations. With the entire ‘fossil record’ available for detailed study, these experiments have provided new insight into adaptive mechanisms and the effects of mutation and recombination.

Prof. Frances H. Arnold was elected to the National Academy of Engineering in 2000, the Institute of Medicine of the National Academies in 2004, and the National Academy of Sciences in 2008. She is one of only 8 persons elected to all three branches of the National Academies, and the only woman awarded this distinction.

B.S., Mechanical and Aerospace Engineering, Princeton University, 1979; Ph.D., Chemical Engineering, University of California, Berkeley, 1985