Trio wins Nobel Prize by using chemistry to ‘evolve’ the building blocks of life

Frances H. Arnold, George P. Smith and Sir Gregory P. Winter won the 2018 Nobel Prize in Chemistry for using biochemistry to force the evolution of proteins — one of building blocks of life.

Arnold, who became the first woman to earn the chemistry Nobel since 2009 and the fifth in history, will receive half of the prize for her work on enzymes — proteins that accelerate biochemical reactions within cells. Smith and Winter will split the second half for their experiments with bacteriophages — a special class of viruses made for attacks on bacteria.

But this year’s chemistry Nobel also comes with some political controversy, as one of the winners — Smith — has been accused of promoting anti-Israel views.

Who are the winners?

Arnold, 62, was born in Pittsburgh. She works as a protein engineer at the California Institute of Technology, where she tweaks DNA code to adapt new functions for enzymes.

Smith, 79, hails from Norwalk, Connecticut, but now serves as a professor emeritus of biological sciences at University of Missouri, Columbia. Smith has also penned multiple editorials in favor of Palestine, and once described the creation of Israel and its aftermath as “a shameful chapter in Jewish history.” In 2015, 36 campus organizations at the university protested Smith’s views on Israel. That same year, he was slated to teach a class — perspectives on Zionism — that was cancelled due to no enrollment.

Winter, 67, was born in Leicester, UK. He conducts his research on genetics and protein engineering at Cambridge University, where he also earned his doctorate.

What they did

All three winners used biochemistry to pressure proteins into working for us. While this concept — known as directed evolution — was originally theorized in 1984, Arnold would become the first to employ the practice about a decade later.

Arnold accomplished this task by growing bacteria and their internal enzymes in a hostile environment filled with a solvent — a chemical that erodes other objects. She and her lab were trying to develop enzymes that could resist the corrosive powers of the solvent.

So along with the solvent, they exposed the bacteria to a mutagenic compound — a chemical that creates random mutations in DNA. (Reminder: DNA provides the blueprint for proteins like enzymes. Mutate the DNA, and you change the enzymes.)

The underlying principle for the directed evolution of enzymes. After a few cycles of directed evolution, an enzyme may be several thousand times more effective. Diagram by Johan Jarnestad/The Royal Swedish Academy of Sciences. Caption by Nobel Foundation

This combination — solvent and mutagenic agent — creates a scenario in which the bacteria and its enzymes can adapt in real time. Over multiple rounds of this process, the bacteria’s enzymes become tougher.

In a landmark study from 1993, Arnold showed her method could produce a modified enzyme that is 256 times better at accelerating biochemical reactions than its original form.

Smith and Winter’s research plays on evolutionary principles, too, but in a very different way.

Their work involves bacteriophages — viruses that coat their exteriors with proteins. Some of these exterior proteins can behave like anchors.

In 1985, Smith reasoned that you could take protein anchors from organisms and use genetics to embed them onto bacteriophages. Bacteriophages have simple DNA genomes can be easily manipulated. Though at the time, Smith’s procedure — known as phage display — was state-of-the-art.

Phage display – George Smith developed this method for finding unknowns genes for a known protein. Diagram by Johan Jarnestad/The Royal Swedish Academy of Sciences. Caption by Nobel Foundation

These modified viruses were used, in turn, to infect E. coli bacteria. Inside the bacteria, the viruses multiplied until millions burst forth, covered in these protein anchors.

What did Smith do with this pool of anchors? He used it to find the best hooks. In the early 1990s, his lab developed a way to screen for materials — other proteins — that could stick to the anchors on these bacteriophages. This tactic is called biopanning, because it is similar to panning for gold.

Around the same time, Winter applied Arnold and Smith’s techniques to pan for antibodies — Y-shaped proteins involved with our immune systems.

He threw a bunch of antibodies into bacteriophages, mutated them and then biopanned for an antibody that could bind to and neutralize TNF-alpha, a compound made naturally by our bodies. Too much TNF-alpha can cause runaway inflammation and perpetuate autoimmune diseases. Winter’s technique helps prevent that.

Why it matters

In 2002, Winter’s biopanned antibody — adalimumab — was approved for the treatment of rheumatoid arthritis. Adalimumab is now also used for tackling various types of psoriasis and inflammatory bowel diseases.

Meanwhile, Arnold applied directed evolution to turn bacteria and their modified enzymes into chemical factories. Her lab’s evolved bacteria can produce biofuels, and other scientists have employed her methods to make detergents, taste enhancers and diabetes drugs.