Turning a bacterial defense mechanism into one of the most powerful tools in genetics has earned Jennifer Doudna and Emmanuelle Charpentier the Nobel Prize in Chemistry.
The award for these genetic scissors, called CRISPR / Cas 9, is “a fantastic award,” said Pernilla Wittung-Stafshede, a member of the Nobel Committee on Chemistry, at a Oct. 7 press conference in Stockholm by the Royal Swedish Academy. of Science to announce the award. "The ability to cut DNA wherever you want has revolutionized the life sciences. We can now easily edit genomes as we wish, something that was previously difficult or even impossible."
“Genetic scissors were discovered just eight years ago, but they have already benefited humanity a lot,” he said. "Only imagination sets the limits for what this chemical tool can be used for in the future. Perhaps the dream of curing genetic diseases will come true." He later modified the statement to say that ethics and law are also important in determining what can and should be done with the tool, as human gene editing is extremely controversial.
Only five other women have won the Nobel Prize in Chemistry. "I would like this to provide a positive message specifically for girls … girls who would like to follow the path of science and I think to show them that women in science can also receive awards, but more importantly women in science they may also have an impact through the research they are conducting, ”Charpentier said in response to a question during the press conference.
The two will share 10 million Swedish kronor, about $ 1.1 million.
From left: © Helmholtz / Hallbauer & Fioretti; Sam Willard / Sam Willard Photography, Berkeley
The tool, a programmable molecular scissors known as CRISPR / Cas9, has been used by bacteria and archaea for millions to billions of years to fight viruses (SN: 4/5/17).
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. In essence, these brief, repetitive snippets of the DNA sandwich bacteria version of the FBI's most wanted list: invasive viruses. Every time the bacteria find a virus, they take a cup of DNA and file it between repetitions. The next time the bacteria find that virus, they make RNA copies of the cup shots. These RNA photocopies are combined with another bit of RNA known as CRISPR RNA or tracrRNA trans activator, to form an all-point bulletin known as guide RNA. Guide RNAs guide the virus to the Cas9 DNA cleavage enzyme, where the enzyme cleaves and eliminates the threat.
Doudna of the University of California, Berkeley and Charpentier, now director of the Max Planck Institute for Infection Biology in Berlin, met in 2011 at a conference in Puerto Rico. “We walked through Old San Juan and talked about CRISPR / Cas9,” Doudna recalled during a virtual press conference on October 7th. The scientists decided to team up to study the bacterial defense system and ended up turning it into a gene editor. His innovation was to fuse the cup-shooting RNA with the tracrRNA, creating a single guide RNA. And the researchers realized that the cups should not be molecular images of viruses. Instead, by replacing the mug shot with RNA that matches a gene, scientists could direct Cas9 to cut that gene or any gene.
“The key article they published together has been cited more than 9,500 times, approximately once every eight hours since its publication in 2012,” says David Liu, a chemical biologist and researcher at the Howard Hughes Medical Institute at Harvard University. Liu and others modified the original CRISPR system so that researchers could use it in various ways.
The victory was "highly anticipated. I think everyone has been talking about CRISPR (as a Nobel nominee) for a long time," says Luis Echegoyen, a chemist at the University of Texas at El Paso and president of the American Chemical Society. Although the gestation period from the discovery to the Nobel Prize is usually much longer, the CRISPR award “is overdue,” says Echegoyen.
The promise of CRISPR was immediately evident, says Stanley Qi, a bioengineer and biotechnologist at Stanford University. As a student in Doudna’s lab, Qi had a seat to discovery and knew then that CRISPR would do great things. "In these eight years there have been so many advances and advances," he says, "it's far beyond my expectations."
Doudna and Charpentier "kept looking at the broad category of CRISPR enzymes," says Qi. His ongoing work has provided new perspectives on the evolution and mechanisms behind the functioning of the bacterial system. Doudna’s work to define the structure and function of the Cas9 enzyme laid the groundwork for improving the accuracy and efficiency of gene editing, he said.
Many researchers have taken these genetic scissors to the next step, using CRISPR / Cas9 to cut and edit genes in human cells. Scientists rejoice at how cheap, versatile and easy to use CRISPR is. The researchers used it to edit genes in a wide variety of animals, including dogs (SN: 30/08/18), mice (SN: 26/01/17), butterflies (SN: 24/08/16), cows (SN: 2/3/17), pigs (SN: 8/10/17), snails (SN: 14/05/19) and mosquitoes.
The tool was also used to encode data and store films in bacterial DNA (SN: 7/12/17). Plants and mushrooms also received CRISPR treatment. And the gene editor was used to reprogram human immune cells to fight cancer (SN: 16/11/16) and to turn cancer cells against each other (SN: 7/11/18).
With the great power of CRISPR a great controversy arises, Doudna warned in her 2017 book A Crack in Creation with co-author Samuel Sternberg. While the gene editor can be used to eliminate invasive species and prevent mosquitoes from carrying disease, it can also extinguish entire species or create ecological disasters. Scientists have already removed small populations of mosquitoes in the laboratory using a CRISPR-based molecular copying machine known as the genetic unit (SN: 24/09/18).
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The most controversial was that a scientist in China edited genes in human embryos, producing twin girls in 2018 (SN: 11/28/18). The reaction against his actions was quick and vocal. But many people fear that the door is already open to “designer babies,” health inequalities, and other abuses (SN: 17/12/18).
“This enormous power of this technology means we need to use it very carefully,” Claes Gustafsson, chairman of the Nobel Committee on Chemistry, said at the press conference. "But it's equally clear that this is a technology … that will provide humanity with great opportunities."
More hopefully, clinical trials testing the ability of CRISPR / Cas9 to treat cancer, sickle cell disease, beta-thalassemia, and inherited blindness began in 2019 (SN: 14/08/19). If successful, CRISPR / Cas9 can provide therapies, or even cures, for genetic conditions that previously could not be treated.
CRISPR also played a role in the coronavirus pandemic, with CRISPR-based diagnostic testing for COVID-19 (SN: 31/08/20) and developmental therapies.
When Charpentier received the news that she was a newly minted Nobel laureate, “I was very emotional,” she said at a news conference in Berlin after the announcement. "It's one thing to be told several times that maybe one day you'll be awarded the Nobel Prize, but another thing when it happens."
Charpentier hopes the award will send a message to the public "that fundamental research is key." CRISPR / Cas9 is a “perfect example of a discovery that has a huge impact on the life sciences, research and development, but also on biotechnology and food production, in medicine,” he said. "That really stems from pure, fundamental research, delving into the mechanisms of life."
His work, "denies the notion that basic and applied research occupies different areas of knowledge," Douglas Clark, dean of Berkeley & # 39; s College of Chemistry, told Doudna's press conference. "They're woven together, as is DNA."
Doudna said she learned of his victory when a reporter called to ask for comments. She is the first female professor to win the Nobel Prize in UC Berkeley's 150-year history, said Carol Christ, the university's chancellor. (Christ also awarded the long-awaited Berkeley Prize, a free parking space on campus.) Doudna and Charpentier are the only women to share the chemistry prize. “I’m proud of my gender,” Doudna stated when asked about the importance of the former. "I think for many women there is a feeling that their work will never be recognized as it could be if they were a man. I want to see that change and I certainly hope this is a step in the right direction."
Almost all the science awards for CRISPR / Cas9 honored Doudna and Charpentier. Some awards also included Feng Zhang of the Broad Institute of MIT and Harvard, which holds the patent on the use of the gene editor to make changes in eukaryotic cells, including human and animal cells. Patent rights were disputed by the institutions of Doudna and Charpentier. Many people thought that the award would not honor work at CRISPR until the patent dispute was resolved. (Zhang is a board member of the Society for Science & the Public, an educational nonprofit in Washington, D.C., which also publishes Science News. He is also a former student of the Society's Regeneron Science Talent Search.)
Two other scientists, Rodolphe Barrangou of North Carolina State University in Raleigh and Philippe Horvath of DuPont Nutrition & Biosciences in Dangé-Saint-Romain, France, were also honored for the CRISPR-related discoveries. The duo discovered the natural role of CRISPR as a bacterial immune system while working with yogurt bacteria in the food ingredient company Danisco.
And two grand prizes – the Warren Alpert Foundation Prize and the Kavli Prize in Neuroscience – honored Virginijus Šikšnys, a biochemist at Vilnius University in Lithuania. Šikšnys was the author of an independent article describing the same innovation made by Doudna and Charpentier that remained in the publishing process and did not reach the press until three months after the UC Berkeley team report.
When asked if other scientists had been considered for the award, Gustaffson said, "This is a question we never answer. We are very happy for this year's laureates. It's a big field and a lot of good science is being done."
Staff writer Maria Temming contributed to this story.