The Nobel Prize in Chemistry was jointly awarded Wednesday to Emmanuelle Charpentier and Jennifer A. Doudna for their 2012 work on CRISPR-Cas9, a method to edit DNA. The announcement marks the first time the award has gone to two women.

“This year’s prize is about rewriting the code of life,” Goran K. Hansson, secretary-general of the Royal Swedish Academy of Sciences, said as he announced the names of the laureates.

Charpentier and Doudna, only the sixth and seventh women in history to win a chemistry prize, did much of the pioneering work to turn molecules made by microbes into a tool for customizing genes — whether in microbes, plants, animals or even humans.

The Nobel Prize in Chemistry has been awarded to Emmanuelle Charpentier and Jennifer A. Doudna. Image credit: Twitter

“I’m over the moon; I’m in shock,” Doudna, a professor at the University of California, Berkeley, said at a news conference Wednesday.

It has been only eight years since Doudna and Charpentier — now the director of the Max Planck Unit for the Science of Pathogens in Berlin — co-authored their first paper demonstrating the power of CRISPR-Cas9. Since then, technology has exploded. Doctors are testing it as a cure for genetic disorders such as sickle cell disease and hereditary blindness. Plant scientists are using it to create new crops. Some researchers are even trying to use CRISPR to bring species back from extinction.

Along with these high-profile experiments, other scientists are using CRISPR to ask fundamental questions about life, such as which genes are essential to a cell’s survival. CRISPR “solves problems in every field of biology,” said Angela Zhou, an information scientist at CAS, a division of the American Chemical Society.

“This technology has utterly transformed the way we do research in basic science,” said Dr Francis Collins, director of the National Institutes of Health. “I am thrilled to see CRISPR-Cas getting the recognition we have all been waiting for, and seeing two women being recognized as Nobel Laureates.”

CRISPR has also become one of the most controversial developments in science because of its potential to alter human heredity. In 2018, He Jiankui, a Chinese scientist, announced that he had used the technology to edit the genes of human embryos, which yielded the world’s first genetically modified infants. His experiments were decried by many in the scientific community as irresponsible and dangerous.

“There is enormous power in this genetic tool, which affects us all,” said Claes Gustafsson, chair of the Nobel Committee for Chemistry.

Charpentier and Doudna both stumbled across CRISPR by accident. Charpentier, a microbiologist, spent a number of years studying Streptococcus pyogenes, a species of bacteria that causes scarlet fever and other diseases. Inspecting the microbe’s DNA in 2006, she and her colleagues discovered a puzzling series of repeating segments.

A few scientists had studied these segments since the 1980s, but no one was sure of their function. Francisco Mojica, a microbiologist at the University of Alicante in Spain, gave these DNA stretches a name in 2000: clustered regularly interspaced short palindromic repeats, or CRISPR for short.

Mojica and other researchers spent the 1990s and early 2000s trying to determine why microbes had this mysterious repetitive DNA. It became clear that between these repeats were bits of genetic material derived from viruses that had tried to infect the bacteria. Somehow, the bacteria were grabbing bits of viral genes and storing them away. It was if they were creating an archive of past infections, which they could later use to defend against future attacks.

Charpentier and her colleagues discovered some of the key steps by which the bacteria used this information to attack viruses. The bacteria made molecules of RNA — ribonucleic acid, a cousin of DNA — that recognized the genes of attacking viruses.

After writing a paper on their discovery in 2011, Charpentier recognized she needed to collaborate with an expert on RNA molecules to make more progress. That expert was Doudna.

Doudna (the first syllable rhymes with loud) had never heard of CRISPR until another Berkeley scientist, microbiologist Jill Banfield, brought it to her attention in 2006. Until then, she had studied how bacteria make RNA molecules for other purposes, such as sensing the environment and silencing certain genes.

Charpentier, 51, and Doudna, 56, met at a cafe in Puerto Rico in 2011 while attending a scientific conference and immediately started to collaborate on understanding how CRISPR worked. Soon, they realized that they might be able to harness the RNA molecules to seek out and alter any piece of DNA.

Bacteria defend themselves by using these molecules to recognize the genes of an attacking virus. The weaponry includes an enzyme called Cas9 that slices the viral genetic material.

Charpentier and Doudna realized that they could synthesize a piece of RNA that targeted and chopped up not just a spot on a viral gene — but on any gene. In 2012, the scientists proved this concept could work.

CRISPR was not the first tool scientists invented to alter DNA. But previous methods were relatively crude, involving expensive, cumbersome machines and materials. CRISPR could become a far more precise genetic surgery.

If researchers used CRISPR molecules to make cuts at two neighbouring sites on a piece of DNA, for example, the DNA stretch would heal, sewing itself together without the sliced segment. It became possible to insert a new piece of DNA in the place of the removed one. Subsequent research revealed how to use CRISPR to alter single genetic letters.

What had begun as an ancient system of antiviral defence quickly became one of the most powerful and precise genome-editing tools available to science. In less than a decade, CRISPR has become commonplace in laboratories around the world.

“Other technologies sometimes take a couple of decades before they come into regular practice,” Collins said. CRISPR’s rapid rise to near ubiquity, he added, “is remarkable.”

Jinelle Wint, assistant dean for academic affairs at Stowers Institute for Medical Research in Kansas City, Missouri, described this year’s prize as a “historic win,” both because of its recognition of a revolutionary advancement in biomedical science, as well as its championing of women scientists.

Aspiring female scientists, Wint said, should be empowered to think “that they, too, can be in the next Nobel Prize winners of the future.”

Following her 2011 and 2012 discoveries, Charpentier was told numerous times by colleagues that CRISPR might be Nobel-worthy. But she had trouble internalizing it.

“It’s something you hear, but you don’t completely connect,” she said in a news conference Wednesday. When she received the call, “I was very emotional,” she said.

Still, experts noted, women make up a paltry percentage of science laureates. Scientists of color, especially those who identify as Black, Latino, Native or Indigenous, have been almost entirely left out of the process.

Early on, Charpentier and Doudna recognized the potential dangers of the technology that they helped usher into the world. Doudna left her lab and hit the lecture circuit. In 2017, she co-wrote a book, “A Crack in Creation” to describe both the promise and the peril of CRISPR. Nevertheless, she was taken by surprise a year later when He announced his reckless experiment in China.

“We as a community need to make sure we recognize we are taking charge of a very powerful technology,” Doudna said in an interview Wednesday. “I hope this announcement galvanizes that intention.”

Last month, an international committee concluded CRISPR was not mature enough to use for the alteration of human embryos. But the committee did not rule out the possibility that CRISPR could someday be used on rare occasions to repair life-threatening mutations.

“We don’t know all the effects of tinkering with the human genome,” said Nita Farahany, a bioethics expert at Duke University in Durham, North Carolina. “A major advance can introduce major disruptions, and we need to decide how to embrace it in such a way that responsible science progresses.”

Crispr is also the subject of a long-running patent fight. In 2011, Feng Zhang, a biologist at the Broad Institute in Cambridge, Massachusetts, learned of CRISPR and recognized that it might serve as a gene-editing tool.

As Charpentier and Doudna published research showing how to edit the DNA of bacteria, Zhang and his colleagues forged ahead with experiments on human cells, publishing their research in 2012. Doudna’s team did the same, and both the Broad and Berkeley filed for patents on CRISPR.

Eventually, they ended up in court. While the Broad has won many of the legal battles, the matter remains unresolved.

“It will be interesting to see if the award of the prize changes the parties’ interest in continuing to fight,” said Hank Greely, a professor of law and of genetics at Stanford University. Nothing about the Nobel changes the evidence at hand, he said. But it may “affect the motivations to spend millions of dollars a month.”

In a news conference Wednesday, Doudna looked past that conflict, instead of focusing on the “collaborative spirit” that had driven much of her work with CRISPR and acknowledging the many other scientists that had contributed to driving the field forward.

“In any prize, you know, in any work of science, there are many people who contribute along the way,” she said. “And that’s certainly true in the case of CRISPR.”

After receiving word of the award early Wednesday, Doudna recalled telling her son, “None of us go into science, or at least I didn’t, to win prizes. We went in because we wanted to understand something true about nature.”

Who else won a Nobel Prize this year?

— Harvey J. Alter, Michael Houghton and Charles M. Rice received the Nobel Prize in physiology or medicine Monday for the discovery of the hepatitis C virus, a breakthrough the Nobel committee said had “made possible blood tests and new medicines that have saved millions of lives.”

— Roger Penrose, Reinhard Genzel and Andrea Ghez received the physics prize Tuesday for their discoveries that have improved understanding of the universe, including work on black holes.

When will the other Nobel Prizes be announced?

— The Nobel Prizes in literature will be announced Thursday in Sweden.

— The Nobel Peace Prize will be announced Friday in Norway.

— The Nobel Memorial Prize in Economic Science will be announced next week in Sweden

Katherine J. Wu, Carl Zimmer and Elian Peltier c.2020 The New York Times Company





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