This year’s Nobel Prize in Chemistry has been awarded to two scientists who transformed an obscure bacterial immune mechanism, commonly called CRISPR, into a tool that can simply and cheaply edit the genomes of everything from wheat to mosquitoes to humans.
The award went jointly to Emmanuelle Charpentier of the Max Planck Unit for the Science of Pathogens and Jennifer Doudna of the University of California, Berkeley, “for the development of a method for genome editing.” They first showed that CRISPR—which stands for clustered regularly interspaced short palindromic repeats—could edit DNA in an in vitro system in a paper published in the 28 June 2012 issue of Science. Their discovery was rapidly expanded on by many others and soon made CRISPR a common tool in labs around the world. The genome editor spawned industries working on making new medicines, agricultural products, and ways to control pests.
Many scientists anticipated that Feng Zhang of the Broad Institute, who showed 6 months later that CRISPR worked in mammalian cells, would share the prize. The institutions of the three scientists are locked in a fierce patent battle over who deserves the intellectual property rights to CRISPR’s discovery, which some estimate could be worth billions of dollars.
“The ability to cut DNA where you want has revolutionized the life sciences. The genetic scissors were discovered 8 years ago, but have already benefited humankind greatly,” Pernilla Wittung Stafshede, a chemical biologist at the Chalmers University of Technology, said at the prize briefing.
CRISPR was also used in one of the most controversial biomedical experiments of the past decade, when a Chinese scientist edited the genomes of human embryos, resulting in the birth of three babies with altered genes. He was widely condemned and eventually sentenced to jail in China, a country that has become a leader in other areas of CRISPR research.
Although scientists were not surprised Doudna and Charpentier won the prize, Charpentier was stunned. “As much as I have been awarded a number of prizes, it’s something you hear, but you don’t completely connect,” she said in a phone call with the Nobel Prize officials. “I was told a number of times that when it happens, you’re very surprised and feel that it’s not real.”
At a press briefing today, Doudna noted she was asleep and missed the initial calls from Sweden, only waking up to answer the phone finally when a Nature reporter called. "She wanted to know if I could comment on the Nobel and I said, Well, who won it? And she was shocked that she was the person to tell me."
No previous science Nobel has been given to two women only. "It’s great for especially younger women to see this and to see that women’s work can be can be recognized, as much as men’s," Doudna said. "I think for many women, there’s a feeling that no matter what they do, their work will never be recognized as it might be if they were a man. And I’d like to see that change, of course, and I think this is a step in the right direction."
Doudna added that she used to get puzzled looks when she said she worked on a bacterial immune system. Bacteria use the original form of CRISPR to fend off viruses, slicing up their DNA. “I am so pleased that the [Nobel] award description led off with the bacterial adaptive immune response, which is a truly amazing system, thus highlighting how basic research is absolutely critical for medical applications,” says CRISPR researcher Maria Jasin of the Sloan Kettering Institute.
Doudna and Charpentier—who is originally from France and at the time of the discovery worked at Umeå University—showed they could program a small strip of what they called “guide RNA” to carry a bacterial CRISPR-associated (Cas) enzyme to exact DNA sequences, allowing them to target specific genes. Cas then cuts the double-stranded DNA. In many cases, the DNA repair mechanism of the cell makes errors, which can cripple a gene—knocking out a gene in this fashion is an effective way to study its normal role. CRISPR also allows researchers to insert a new stretch of DNA at the cut site.
The ability to cut DNA where you want has revolutionized the life sciences.
Harvard University chemist George Church says the Nobel Committee made “a really great choice.” Church published a study showing CRISPR could edit mammalian cells at the same time as Zhang, who previously was a postdoc in his lab. But Church doesn’t think either of them were slighted by not being included in the prize. As he sees it, Charpentier and Doudna made a discovery, which is what the committee prefers to reward, and he and Zhang were inventors. “If anyone wants any tips on how not win a Nobel Prize, it’s pretty easy,” Church says. “I’ve carefully avoided all this kind of brouhaha by focusing on inventions.” And, he says, Zhang is young. “Feng Zhang is so full of creative ideas that I have no doubt that he will get one or two in the future.”
Erik Sontheimer, a CRISPR researcher at the University of Massachusetts Medical School, also endorses the Nobel committee decision. “The prize is not based on anything related to patent law,” he says. He called Zhang being excluded “appropriate,” noting that several other researchers, including Zhang’s main collaborators and Church, helped show CRISPR could edit mammalian cells at roughly the same time. “I don’t see that it would have been legitimate to single him out. It’s always the case that there will be pieces [of a scientific advance] that cannot be recognized.”
Tom Welton, president of the Royal Society of Chemistry, said he was “hugely pleased to see that the Nobel committee has chosen to honor two leading women in active research.” This year’s prize is the first time any science Nobel has gone to an all-female team.
Many genome editors existed before CRISPR, but using them was time consuming, cumbersome, and expensive. CRISPR not only works with remarkable ease and speed, it is also the first editor that allows researchers to alter several genes in a single experiment. Rudolf Jaenisch of the Massachusetts Institute of Technology, whose group published one of the first studies of CRISPR-edited mice, said “any idiot can do it.” (Watch this story’s reporter fail at CRISPR, however.)
Rodolphe Barrangou, a researcher at North Carolina State University who began to use bacteria’s CRISPR mechanism in 2007 to make yogurt cultures that were resistant to infection, says the prize is “a great opportunity to celebrate pioneers in the field.” Doudna and Charpentier, he says, “developed an amazing technology that enabled the scientific community and democratized genome editing.” He says before their work, “relatively few people cared about CRISPR.”
Fyodor Urnov, a CRISPR researcher who works with Doudna, calls it “the most deserved Nobel Prize of the past 20 years.” Doudna’s and Charpentier’s discovery “changed everything for the better,” says Urnov, who previously worked on a more cumbersome gene editor called zinc fingers. “We can improve the world around us in extraordinary ways,” he says, noting that a CRISPR application has already cured a person of sickle cell disease. “The 21st century will be the age of CRISPR—thanks to Jennifer and Emmanuelle.”