by John Rennie
With genetic engineering techniques and antibodies,
researchers can use a process of directed evolution
create useful proteins.
Developers of that technique have now been
with a Nobel Prize in Chemistry.
the power of evolution
researchers opened new avenues
Nobel Prize in Chemistry went
to three scientists who harnessed the power of evolution and
accelerated it in the laboratory to produce novel, beneficial
enzymes used in pharmaceuticals, renewable energy, industrial
chemistry and many other fields.
Frances H. Arnold, a
professor of chemical engineering at the California
Institute of Technology, received half of this year's prize
for being the first to artificially direct the evolution of
enzymes; in the process, she became only the fifth woman to
receive the chemistry Nobel.
George P. Smith, a
professor emeritus of biological sciences at the University
Gregory P. Winter, a
research leader emeritus at MRC Laboratory of Molecular
...shared the other half
of the prize for developing a technique called phage display,
directed evolution to produce
pharmaceutically useful enzymes.
"For thousands of
years, we humans have used selective breeding to create animals
and plants with properties that have been useful for us.
This year's Nobel
laureates have taken the next step," said Claes Gustafsson,
chair of the Nobel chemistry selection committee and a
biochemist at the University of Gothenburg, in his remarks at
"In doing so, they
have been able to make evolution many thousand times faster, and
they have also been able to direct evolution to create proteins
with new and useful properties."
Vitor Pinheiro, a synthetic
biologist at the Rega Institute for Medical Research in
"The laureates laid
out some of the early principles of directed evolution of
proteins and inspired many, like me, to look at biology as a
flexible canvas that can be shaped to a desired function."
sparked a revolution because it allowed researchers to mimic the
same process that nature used to 'create' the endless
diversity of species that fills the world.
With his theory of
evolution through natural selection,
Charles Darwin identified
how an iterative process of genetic mutation, selection by the
environment, and proliferation by the winners could, over
generations, allow organisms to become better at solving complex
problems of survival.
In the same way, protein
chemists can use artificial processes of mutation and selection to
coax living cells to find biochemical solutions to problems that
would be intractably hard for humans to solve through planning or
trial and error.
exploited the concept of Darwinian evolution for thousands of
years with selective breeding," said Stefan Lutz, the chairman
of the chemistry department at Emory University.
takes this same principle and applies it to the lab."
By the 1970s, many
scientists were dreaming that new genetic engineering technologies
might someday be used to create novel proteins with exceptional
abilities, such as enzymes that could speed up drug manufacturing.
But the hurdle to doing
so was huge.
"Protein design was
an academic exercise. Our computational methods weren't
sophisticated enough to make it practical for designing
proteins," according to Lutz.
Frances H. Arnold, George P. Smith and Gregory P. Winter (from left)
been named the winners of the 2018 Nobel Prize in Chemistry
their milestone contributions to the development
process called directed evolution.
Caltech (Arnold); Marjorie R. Sable (Smith);
Cambridge/Nick Saffell (Winter)
During the 1980s, Frances H. Arnold tried and failed to
subtilisin, a bacterial enzyme with
diverse commercial applications, so that it could work in solvents
other than water.
She eventually abandoned
that approach in favor of a more evolutionary approach in which she
repeatedly induced mutations in bacteria, screened them for the
desired traits, and then bred more of them.
By 1993, she had
succeeded in making the enzyme 256 times more effective than it had
was to recognize that the most amazing molecules in the world
weren't created by chemists, but rather by the biological
world," said Jesse Bloom, a computational biologist at the Fred
Hutchinson Cancer Research Center and a former student of
"Most scientists were
accustomed to thinking of 'evolution' in terms of fossils of
long-dead creatures, while chemical engineering was something
that involved 'synthetic chemicals' in the lab."
The idea of applying
evolutionary biology to problems in
chemistry and biotechnology, he said,
"was a real leap."
Much of the success of
directed evolution in chemistry depended on finding more efficient
ways to create and screen for useful forms of new proteins.
The foundations of that
were laid in 1985, when George P. Smith demonstrated a way to
use bacteria and simple viruses called
phages to isolate the genes for
targeted proteins. He linked genes of interest to the phage virus's
own gene for its protein capsule.
With antibodies, he could
then isolate any phages that made the protein target.
Graphic illustrating the work flow
directed evolution of enzymes
Gregory P. Winter was one of the researchers who subsequently
adapted Smith's techniques to screen for biomolecules with useful
In the 1990s he used them
to screen for variant forms of antibody proteins that would attach
to various biochemical targets.
In 2002 a therapeutic
antibody based on Winter's method was approved to treat rheumatoid
arthritis and other inflammatory conditions; many other such evolved
antibody drugs have followed.
Many more methods for directed evolution have been developed
in recent years, but the pioneering contributions of Arnold, Smith
and Winter, along with those of many other scientists who helped to
develop the field, are still held in esteem.
Arnold still works to
further apply directed evolution to pharmaceutical research
and renewable energy.
work has enabled and inspired researchers all over the world to
harness the power of 'natural selection' for protein
Jennifer R. Cochran, a
biochemist at Stanford University, via email.
Their techniques have
"backbone of the
further highlighting their societal and commercial impact."
This article includes
contributions from Jordana Cepelewicz and Jonathan Lambert...