2018 NOBEL PRIZE IN CHEMISTRY: A MODERN, MOLECULAR-SCALE PROMETHEUS

By: Tyler Reagle; October 8^th, 2018

James Whale © Universal Pictures

Tryptophan synthase from RCSD PDB file 1kfk.pdb

A week ago, on October 3^rd, the 2018 Nobel Prize in Chemistry was awarded to Frances H. Arnold (USA), George P. Smith (USA), and Sir Gregory P. Winter (UK) for their use of accelerated, directed evolution of biomolecules. While the Nobel Prize in Chemistry has long presented the deep-rooted relationship between the fields of biology and chemistry, the recipients of the 2018 award illustrate a triumph for the relatively new field of chemical biology. Chemical biology applies the tools of chemistry to better enable biological research for pharmaceutical development, disease fighting, or other topics of pressing biological importance. The work of the 2018 Nobel laureates certainly upholds this description. Arnold- who was awarded half the award- alongside Smith and Winter- who each hold a fourth of the prize- have demonstrated methodology for bioengineering and rapid chemical screening towards novel biochemical functionality. As surrogates for natural selective pressures and/or intelligent creator, chemical researchers can emulate these scientists in their goals of addressing humanity’s problems related to biology AND chemistry.

Left to Right: Frances H. Arnold, George P. Smith, Sir Gregory P. Winter

Ill. Niklas Elmehed. © Nobel Media

The career of Frances H. Arnold of the California Institute of Technology has outlined protocol regarding the accelerated evolution of enzymes and their capacity for bioorganic catalysis in the field of organic synthesis. Thus, for a field preoccupied with derivation of novel synthetic routes requiring large amounts of time, solvents, and potentially dangerous compounds, organic chemistry research has much to learn from Arnold’s development of synthetically-valuable enzymes for reliable chemical conversion in a refreshing, aqueous environment. Indeed, a glance at Arnold’s publication history outlines a series of tools instrumental in extension of “Green” chemistry for environmentally-sustainable chemical research. Notably, according to the intense chemical-screening processes of Arnold that have succeeded in design of enzymes with 200-fold activity over just three generations, it is obvious that sustainability does not have to sacrifice operability. As a result, it is speculated that enzymatic catalysis possesses the power to revolutionize fuel and pharmaceutical industries at multiple levels.

Likewise, the combined careers of George P. Smith and Sir Gregory P. Winter offer an alternative application of test-tube evolution. The two laureates share half of the award for their research in bacteriophages- bacterial viruses. Ironically, as Smith stated in a New York Times article, his original research goal was simply the correlation between small peptides and their corresponding genes; “I was not smart enough to anticipate what would come out of this research,” Smith modestly explained. Through genetic recombination, he inserted a targeted protein-sequence into phage coat-proteins for chemical-screening via complementary antibody-binding for connecting a protein product with its gene.

 

A bacteriophage is composed of a small genome, viral envelope, and several other protein structures upon which genetic recombination can be performed. The ‘head’ of this virus is coated in the proteins targeted by Smith’s method.

Ill. Stephen T. Abedon. © Biology as Poetry

The assay is now commercially-available under the name ‘phage display’ owed to the simplicity of phage anatomy and its capacity for large-scale screening. As a result, the method has proven invaluable for accelerated, directed evolution.

The technique was used to its fullest potential by the work of Sir Gregory P. Winter who employed Smith’s approach to screen numerous antibodies for pharmaceutical development in the treatment of several human diseases. The antibodies evolved through this process have been integral in the antibody-mediated treatment of cancer and multiple autoimmune disorders.

From the perspective of a biochemistry student, these developments are exciting, and it is my hope that the positive presentation of this subdiscipline of chemical research aids in minimizing popularized “Chemophobia” against genetic recombination. Certainly, the capacity of good for the methods illustrated by the 2018 Nobel laureates ensures that the divine flame of directed evolution will not soon be extinguished and that any parallels to a molecular-scale Frankenstein are unwarranted for these scientists.

References:

“Arnold Research Group.” Arnold Group, CalTech, fhalab.caltech.edu/.

Chang, Kenneth. “Use of Evolution to Design Molecules Nets Nobel Prize in Chemistry for 3 Scientists.” New York Times, 3 Oct. 2018.

“Phage Display FAQs.” New England BioLabs.