Remarks at Dr. Frances Arnold Lecture
I must begin by thanking Dr. Marlene Belfort, Distinguished Professor in the Departments of Biological Sciences and Biomedical Sciences at the University at Albany; and Dr. Georges Belfort, Institute Professor in our Howard P. Isermann Department of Chemical and Biological Engineering, for their great generosity in endowing this lecture series, “Life at the Interface of Science and Engineering.”
They are helping us to realize our vision for Rensselaer Polytechnic Institute as The New Polytechnic—as a great crossroads for talented people, across disciplines, institutions, sectors and geographies, using the most advanced tools and technologies to tackle global challenges.
We are honored to have the third guest in this series with us today, Dr. Frances Arnold, the Linus Pauling Professor of Chemical Engineering, Bioengineering, and Biochemistry, and Director of the Donna and Benjamin N. Rosen Bioengineering Center at the California Institute of Technology, or Caltech. For her pioneering work on the directed evolution of enzymes, Dr. Arnold was just awarded the 2018 Nobel Prize in Chemistry. We are so honored to have her here today.
Today, she will tell us about “Innovation by Evolution: Expanding the Enzyme Universe.” And I will note how fortunate we are! Rensselaer apparently has achieved a triumph of scheduling—because just twelve days ago, Dr. Arnold was forced to cancel a lecture at the University of Texas Southwestern, when the Nobel Prizes in Chemistry were announced, in order to return for a press conference and celebration at Caltech.
Dr. Arnold grew up in Pittsburgh, Pennsylvania, the child, I am pleased to say, of a distinguished nuclear physicist, Dr. William Howard Arnold. After a high school career in which she failed to learn chemistry, she has said, because she was too busy cutting classes, she then attended Princeton University, and earned a degree in Mechanical and Aerospace Engineering in 1979. After Princeton, an interest in clean energy drew her briefly to the Solar Energy Research Institute, which was created by President Jimmy Carter during the oil crises of the 1970s.
She then decided to earn a doctorate in Chemical Engineering at the University of California, Berkeley, with the goal of researching biofuels—and became fascinated with the possibilities in a new field known as biotechnology.
After moving to Caltech, and being named assistant professor in 1987, she explored the possibilities of engineering enzymes, the catalysts designed by nature to produce reactions in living things, as the basis for a new, greener form of chemistry.
However, given the daunting complexity of these proteins and the shapes they assume—with relatively little known about them—it often is not feasible to rationally design enzymes for desired properties—even today, with our tremendous capabilities in computational simulation and modeling.
So Dr. Arnold began using nature’s own method for generating useful molecules—evolution—or rather, directed evolution—akin to the breeding used by farmers, who, throughout history have created better crops and livestock by selective breeding for desirable traits through the generations.
Dr. Arnold practiced the same breeding on molecules, although her methods were many times faster. By creating random mutations in the genetic code that yields a particular enzyme, and introducing those mutations into bacteria, she was able to produce variants of the enzyme she wanted.
Screening for and choosing the few variants that worked best, she introduced a new round of random mutations that helped her to screen for and choose the few variants that worked even better, and so on. After a few such cycles, an enzyme might become thousands of times more effective.
Of course, I have underestimated the complexities here. New chemistries and methodologies had to be developed to detect the mutations with the functional properties that were sought, particularly under the conditions that would be valuable for synthesis and production.
Today, Dr. Arnold’s methods are used by both academia and industry, and the enzymes created through directed evolution have many practical applications in pharmaceuticals, detergents, agricultural chemicals, and biofuels.
Recently, Dr. Arnold and her laboratory have used directed evolution to create new structures not seen in nature, including molecules containing silicon-carbon bonds.
This work is, of course, extremely interesting to us at Rensselaer, where many members of our Center for Biotechnology and Interdisciplinary Studies also are working on the problems and possibilities of biomanufacturing—particularly in our distinguished Biocatalysis and Metabolic Engineering Constellation.
For example, a collaboration led by our Broadbent Senior Constellation Professor Robert Linhardt, and our Howard P. Isermann Professor of Chemical and Biological Engineering Jon Dordick—seeking a safer alternative to the animal-derived blood thinner heparin that killed 80 people in 2008—has successfully created a synthetic version of this essential drug using enzymatic synthesis.
In addition to the Nobel Prize, Dr. Arnold has received many accolades for her work, including, in 2011, the National Medal of Technology and Innovation and the Charles Stark Draper Prize awarded by the National Academy of Engineering. In 2017, she received the Sackler Prize in Convergence Research from the National Academy of Sciences, and in 2016, the Millennium Technology Prize granted by the Technology Academy Finland.
Dr. Arnold is the first woman to be elected to all three branches of the National Academies: the National Academy of Engineering, the National Academy of Medicine, and the National Academy of Sciences.
Again, we are so delighted to have her with us today.