News in focus CRISPR, short for clustered regularly interspaced short palindromic repeats, is a microbial ‘immune system’ that prokaryotes — bacteria and archaea — use to prevent infec- tion by viruses called phages. At its core, the CRISPR system gives prokaryotes the ability to recognize precise genetic sequences that match those of a phage or other invader, and to target these sequences for destruction using specialized enzymes. Previous work had identified these enzymes, known as CRISPR-associated proteins (Cas), including one called Cas9. But Charpentier, working first at the University of Vienna and later at the Umeå Centre for Microbial Research in Sweden, identified another key component of the CRISPR system — an RNA molecule that is involved in recognizing phage sequences — in the bacterium Streptococcus pyogenes, which can cause disease in humans. Charpentier reported the discovery in 2011 and that year struck up a collaboration with ALEXANDER HEINEL/PICTURE ALLIANCE/DPA Jennifer Doudna and Emmanuelle Charpentier share the 2020 Nobel chemistry prize. Doudna. In a landmark 2012 paper (M. Jinek et al. Science 337, 816–821; 2012), the duo and their teams isolated the components of the CRISPR–Cas9 system, adapted them to func- PIONEERS OF CRISPR tion in the test tube and showed that the system could be programmed to cut specific sites in GENE EDITING WIN isolated DNA. The programmable gene-editing system has inspired a gold rush of applications CHEMISTRY NOBEL in medicine, agriculture and basic science — and work continues to tweak and improve CRISPR Emmanuelle Charpentier and Jennifer Doudna and to identify other gene-editing tools. “We were hoping that we could really trans- share award for developing the precise technology. late this into a technology for rewriting the genetic code of cells and organisms,” says By Heidi Ledford & Ewen Callaway the system, but several other researchers have Martin Jinek, a biochemist at the University of been cited — and recognized in other high-pro- Zurich who was a postdoc in Doudna’s lab and t’s CRISPR. Two scientists who pioneered file awards — as key contributors in the develop- a co-author of the pivotal Science paper. “What the revolutionary gene-editing technology ment of CRISPR. They include Feng Zhang at we didn’t quite appreciate was how quickly the are the winners of this year’s Nobel Prize the Broad Institute of MIT and Harvard in technology would be adopted by others in the in Chemistry. Cambridge, Massachusetts, George Church field and then pushed forward.” The Nobel committee’s selection of at Harvard Medical School in Boston, Massa- IEmmanuelle Charpentier, now at the Max chusetts, and biochemist Virginijus Siksnys at Race to commercialize Planck Unit for the Science of Pathogens in Vilnius University in Lithuania. In less than a decade, researchers have used Berlin, and Jennifer Doudna, at the University CRISPR–Cas9 to develop genome-edited of California, Berkeley, puts an end to years of “The ability to cut crops, insects, genetic models and experimen- speculation about who would be recognized tal human therapies. Clinical trials are under for their work developing the CRISPR–Cas9 DNA where you want way to use the technique to treat sickle-cell gene-editing tools. The technology allows has revolutionized anaemia, hereditary blindness and cancer. precise edits to the genome and has swept the life sciences.” Doudna, Charpentier and others in the field through laboratories worldwide since its incep- have launched a generation of biotechnology tion in the 2010s. It has countless applications: companies aimed at developing the technique researchers hope to use it to alter human genes Doudna was “really sound asleep” when her to achieve these goals. to eliminate diseases; create hardier plants; buzzing phone woke her and she took a call But the technology has also generated con- wipe out pathogens; and more. from a Nature reporter, who broke the news. troversy — in particular for its nascent appli- “The ability to cut DNA where you want has “I grew up in a small town in Hawaii and I never cations in human cells. In November 2018, revolutionized the life sciences,” said Pernilla in 100 million years would have imagined this Chinese biophysicist He Jiankui announced Wittung Stafshede, a biophysical chemist and happening,” says Doudna. “I’m really stunned, that twin girls had been born from embryos member of the Nobel chemistry committee, at I’m just completely in shock.” that he and his colleagues had edited using the prize announcement. “The ‘genetic scissors’ “I know so many wonderful scientists who CRISPR–Cas9. The news sparked an outcry: were discovered just eight years ago, but have will never receive this, for reasons that have editing embryos raises a host of ethical, social already benefited humankind greatly.” nothing to do with the fact that they are won- and safety concerns, and many researchers Doudna and Charpentier and their col- derful scientists,” Doudna says. “I am really kind worldwide quickly condemned He’s work. leagues did crucial early work characterizing of humbled.” In September, an international panel 346 | Nature | Vol 586 | 15 October 2020 ©2020 Spri nger Nature Li mited. All rights reserved. ©2020 Spri nger Nature Li mited. All rights reserved. convened by leading US and UK scientific soci- the door to modelling and potentially treating the Milky Way, said the Royal Swedish Academy eties concluded again that the technology is human diseases — Church says that this work of Sciences, which awards the prize. not ready for use in human embryos that are could be classified as engineering and inven- Astrophysicist Monica Colpi at the Univer- destined for implantation. tion, rather than scientific discovery. “I think sity of Milan Bicocca in Italy says the prizes are The work also sparked a fierce patent bat- it’s a great choice,” he says. highly deserved. “The observational data by tle — mainly between the Broad Institute and It is always difficult to single out a discov- Genzel and Ghez are splendid and truly unique Berkeley — that rumbles on to this day over who ery for a prize, says geneticist Francis Collins, in their ability to monitor star motions around owns the lucrative intellectual-property rights head of the US National Institutes of Health in this object.” to CRISPR–Cas9 genome editing. Bethesda, Maryland. But one unique aspect of Penrose, meanwhile, is “a giant in theoreti- Still, Church agrees with how the award was CRISPR–Cas9 genome editing has been the ease cal physics”, who has influenced generations divvied up. Although he is proud of the work and versatility of the technique, he adds. “There of scientists, says Carole Mundell, an astro- in his lab and in Zhang’s — which adapted the is no molecular-biology laboratory that I know physicist at the University of Bath, UK. He is system to work in mammalian cells, opening of that hasn’t started to work with CRISPR–Cas.” “a genuinely creative thinker with immense imagination, sense of fun and a passion for curiosity in everything he does”, she adds. General relativity to geometry In a seminal 1965 paper, Penrose demon- PHYSICISTS WIN NOBEL strated how, according to general relativity, black holes could form given the right condi- PRIZE FOR BLACK-HOLE tions — the formation of a surface that traps light (R. Penrose Phys. Rev. Lett. 14, 57; 1965). DISCOVERIES Inside this surface, mass enters an irreversible gravitational collapse, producing a region of Mathematical physicist Roger Penrose shares award infinitely dense energy called a singularity. Previous researchers had demonstrated this with astronomers Andrea Ghez and Reinhard Genzel. inevitability only under conditions that were considered physically unrealistic. By Elizabeth Gibney & US astronomer Andrea Ghez and German Penrose’s contributions span many areas of Davide Castelvecchi astronomer Reinhard Genzel, share the mathematics and physics. He communicated other half of the 10-million-Swedish-kronor with the graphic artist M. C. Escher and inspired mathematical physicist and two (US$1.1-million) award for discovering the Uni- some of his drawings of impossible geometrical astronomers have won the 2020 verse’s most famous black hole — the super- objects. In the 1970s, he developed a geomet- Nobel Prize in Physics for discover- massive object at the centre of the Milky Way. rical theory: a non-repeating 2D pattern now ies relating to the most massive and Since the 1990s, Ghez and Genzel have each called Penrose tilings. These patterns occur in mysterious objects in the Universe led groups that have mapped the orbits of stars nature in ‘quasicrystals’, which were the subject A— black holes. close to the Galactic Centre. These studies led of the 2011 Nobel Prize in Chemistry. British mathematical physicist Roger them to conclude that an extremely massive, Penrose introduced sophisticated math- Penrose receives half the prize for theoret- invisible object must be dictating the stars’ ematical techniques into several branches of ical work that showed how Albert Einstein’s frantic movements. The object, known as physics, says Matilde Marcolli, a mathematical general theory of relativity should result in Sagittarius A*, is the most convincing evidence physicist at the California Institute of Technol- black holes. yet of a supermassive black hole at the centre of ogy in Pasadena. “It was a completely new way of thinking,” she says. Whereas Penrose laid the theoretical founda- tions for the existence of black holes, Ghez and Genzel’s teams produced powerful evidence that such a void sits at our Galaxy’s heart. Since the 1960s, astronomers had suspected that a supermassive black hole — with a mass more than one million times that of the Sun — might lie at the centre of most galaxies. The Milky Way was a prime candidate: radio obser- vations had revealed energetic emissions from its centre. But peering closely was a challenge, because gas and dust obscured emissions from the stars.