Newswise — The discovery of genetic scissors known as CRISPR-Cas9 has earned two scientists the 2020 Nobel Prize in Chemistry.
Jennifer Doudna, a Howard Hughes Medical Institute (HHMI) Investigator at University of California, Berkeley, and Emmanuelle Charpentier of the Max Planck Unit for the Science of Pathogens are being honored for the development of a method for genome editing, the Royal Swedish Academy of Sciences announced today.
Their work harnessed an ancient mechanism of bacterial immunity and turned it into a powerful and general technology for editing genomes, with wide-ranging implications across biology and medicine. “The ability to cut the DNA where you want has revolutionized the life sciences,” said Pernilla Wittung-Stafshede, a member of the Nobel Committee for Chemistry. “We can now easily edit genomes as desired, something that before was hard or even impossible.” Doudna has been an HHMI Investigator since 1997.
These genetic scissors are now a common tool used in molecular biology labs around the world and have been used in areas as disparate as coronavirus testing, plant breeding, and the treatment of human diseases. Scientists can use this tool to fix genetic damage, the kind that causes sickle cell anemia, said Claes Gustafsson, chairman of the Nobel Committee for Chemistry.
Charpentier and Doudna’s discovery, made only eight years ago, “has already benefited humankind greatly,” Wittung-Stafshede said. “Only imagination sets the limits for what this chemical tool, that’s too small to be visible with our eyes, can be used for in the future.”
In a virtual press conference from UC Berkeley, Doudna said she was in a deep sleep when she heard her phone buzz around 3:00 am. Usually, the Nobel Committee is first to contact winners, but when Doudna picked up the phone, instead she heard a reporter asking for a comment on the 2020 prize. “I said, ‘Who won it’?” Doudna laughed.
“I’m over the moon,” she said about the news that she was one of the winners. “I’m in shock, and I couldn’t be happier.”
A powerful defense mechanism
For bacteria, snipping apart DNA that bears certain signature sequences is a defense mechanism. For scientists working in the lab, the same strategy can be a powerful research tool. Tools that snip apart DNA strands in defined locations are essential for editing genomes in the laboratory to study or alter gene function. To target the specific site in the genome they are interested in, researchers often have to design and produce a protein that will recognize and bind to that particular DNA sequence, a laborious and time-consuming process.
In research published in 2012, Doudna and Charpentier reported the discovery of an RNA-based complex used by bacteria to guide the DNA-cutting enzyme Cas9 to specific sites in the genomes of viruses and other invaders, thus silencing their genes. From this bacterial complex, Doudna and her colleagues crafted a system with which an easily programmable guide RNA can be used in the lab to direct Cas9 to cleave double-stranded DNA at a desired target sequence.
"It’s been a thrill to follow the pioneering work that Jennifer and Emmanuelle have done and continue to do," said HHMI President Erin O'Shea. "I’m also very pleased to see the contributions of women scientists recognized this way.”
Today’s award is the first time two women have shared the Nobel Prize in Chemistry. Doudna said that she’ll continue encouraging her female students to “embrace their passion for their work and to know that their work will be appreciated by broader society.” For many women, she added, there’s a feeling that no matter what they do, their work will never be recognized. “I’d like to see that change, of course. And I think this is a step in the right direction.”
In a typical year, the room where the Royal Swedish Academy of Sciences announces Nobel winners is abuzz with excitement and packed with people. Today, restrictions due to COVID-19 winnowed the number of in-person listeners, many wearing masks, down to a third of the usual – a reminder of the novel coronavirus’s global impact on human health and on science.
Today’s prize-winning work is no exception. In recent months, Doudna’s lab and others have applied the CRISPR system to COVID-19 diagnostic use. She and her colleagues are working on a simple, inexpensive test that would rapidly detect the novel coronavirus in people’s saliva, for example.
An early interest in chemistry
Growing up in Hawaii, Doudna was fascinated by the way things worked. In high school, she was drawn to chemistry because it allowed her to understand science on a fundamental level. A high school chemistry teacher encouraged this interest, and when Doudna graduated, she knew she wanted to go into chemistry.
Later, her desire to understand biochemistry on a molecular level led Doudna to study catalytic RNAs called ribozymes, first as a graduate student in the laboratory of HHMI Investigator Jack W. Szostak at Harvard University, and then as a postdoc in the laboratory of Thomas R. Cech at the University of Colorado Boulder. It was Cech, a former HHMI president and current HHMI Investigator, who discovered in 1982 that RNA can also have enzymatic properties—a finding for which he and Sidney Altman of Yale University shared the 1989 Nobel Prize in Chemistry. Szostak shared the 2009 Nobel Prize in Physiology or Medicine with Elizabeth Blackburn of University of California, San Francisco, and Carol Greider of the Johns Hopkins University School of Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.
In Szostak's laboratory, Doudna worked to create self-replicating ribozymes in a test tube, with the goal of observing how these enzymes may have evolved over time. While working on this project, however, Doudna came to realize that if she wanted to engineer ribozymes and understand how they work, she first needed to know what they looked like. So she headed to Tom Cech's lab to crystallize and determine the three-dimensional structure of a ribozyme, something that had never been accomplished before.
This endeavor took far longer than Doudna could have anticipated. She began the work in Cech's lab in 1991 and completed the project at Yale in 1996, where she had moved to become an assistant professor. But the hard work paid off, and Doudna clearly remembers seeing the structure for the first time. "It was an incredible moment of discovery. My heart was racing, and I had chills down my spine," Doudna said.
She has since crystallized other RNAs, including one from a virus that causes a rare form of hepatitis. Solving these structures is helping scientists answer important questions about how RNA molecules are organized and how they function as enzymes. In separate research, she and her colleagues have discovered that the hepatitis C virus, which causes 10,000 deaths each year in the United States, uses an unusual strategy to synthesize viral proteins—a line of research that could lead to new drugs to block the infection without harming body tissues.
A few years after Doudna’s lab moved from Yale to Berkeley, Doudna remembers having a conversation with UC Berkeley scientist Jillian Banfield about a bacterial immune system called CRISPR. At the time, just a handful of scientists around the world had noticed it, and there was no experimental evidence that it was, in fact, an immunity pathway in bacteria, Doudna said. Years later, in 2011, Doudna met Charpentier at a conference, and the two teamed up to work on one protein in the pathway – CRISPR-Cas9.
The scientists figured out that the protein could cut DNA, and “importantly, that we could control where it cut DNA” – by changing the RNA molecule that guides the protein to a particular DNA sequence. “There really was kind of a Eureka moment for us,” Doudna said.
As she and Martin Jinek, a scientist then in her lab, were discussing the data, they looked at each other, and “realized that this could be an extraordinary tool” because of its ability to trigger genome editing, Doudna said. “I remember that moment very, very clearly.”
Doudna says she is most motivated by the "process of discovery—of having an idea about how something works and setting out to test it. I am intrigued by the many roles of RNA in biology. Understanding the chemical and biochemical basis for this, as well as the ways in which evolution has taken advantage of these properties to involve RNA at every level of gene expression and regulation in cells and viruses is a lifelong pursuit."
Charpentier and Doudna will split the 10 million Swedish kroner (roughly $1 million) for this year’s prize.
In the press conference, UC Berkeley’s chancellor, Carol T. Christ, told Doudna about one other benefit she can expect: a free parking space on Berkeley’s campus, “the most prized of all Berkeley perks,” Christ said.
“I’m really delighted about that,” Doudna replied. “Finally, after 18 years, I can park on campus.”
Doudna is one of more than two dozen HHMI scientists who have won Nobel prizes in Chemistry or Physiology or Medicine since 1978. Last year, HHMI Investigator William Kaelin, Jr. shared the Nobel Prize in Physiology or Medicine with Gregg Semenza and Peter Ratcliffe for discovering how cells sense and adapt to oxygen levels.
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