Gene editing takes the spotlight with Chemistry Nobel for Charpentier and Doudna

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Emmanuelle Charpentier and Jennifer Doudna, two biochemists who are known for their part in developing the powerful gene editing technique called CRISPR, have been awarded the 2020 Nobel Prize in Chemistry.

Both women have previously been recognized for their work, and in 2016 were among those awarded the Canada Gairdner International Award for a discovery that is widely regarded as having transformed the life sciences.

“CRISPR is a revolutionary technology,” said Janet Rossant, a senior scientist at Toronto’s Hospital for Sick Children and scientific director of the Gairdner Foundation. “These two were the ones who really took a system identified in bacteria … and used biochemistry to turn it into a tool that could be used to modify DNA in cells from plants, animals and humans.”

Armed with CRISPR (pronounced “crisper”), scientists have been able to seek, repair and replace sections of DNA in living organisms with unprecedented specificity. Since the method was introduced less than a decade ago, it has become an indispensable tool for identifying the functions of different genes and is currently being tested as a therapy for cancer and various inherited ailments, including sickle cell anemia.

More controversially, the technique has made it relatively easy to alter “germ line” cells that pass on the human genetic code to future generations. In 2018, the use of CRISPR to alter the DNA of a set of twins born in China raised alarm among scientists and ethicists, and led to a wave of media reports about a future shaped by “designer babies.”

The two winners will share equally in their prize, worth approximately $1.2-million – the highest recognition to date for any of the several researchers associated with the development of CRISPR and its broad applications to medicine, agriculture and other areas of biotechnology.

They are just the sixth and seventh female scientists to be awarded a chemistry Nobel in the 120-year history of the prize.

During a call with reporters after Wednesday’s announcement of the prize by the Royal Swedish Academy of Sciences, Dr. Charpentier said despite having often been told that her discovery would one day lead to a Nobel, “When it happens you’re very surprised and you feel that it’s not real.”

Dr. Charpentier, 51, was born in Juvisy-sur-Orge, France, and received her PhD at the Pasteur Institute in 1995. Since 2015, she has been the director of the Max Planck Institute for Infection Biology in Berlin.

Dr. Doudna, 56, was born in Washington, D.C., and earned her PhD at Harvard Medical School in 1989. She is a professor at the University of California, Berkeley, where she has been based since 2002 and where she began working on CRISPR in 2009.

That same year, Dr. Charpentier moved from a position in Vienna to lead the Laboratory for Molecular Infection Medicine in Umea, Sweden, where she, too, would find her research interests intersecting with CRISPR.

CRISPR is an acronym that stands for “clustered regularly interspaced short palindromic repeats.” The term refers to a collection of mirror-image genetic sequences that were noticed in the DNA of certain bacteria as early as the 1980s.

By 2005, scientists knew the CRISPR sequences were separated by other regions of bacterial DNA, which seemed to consist of genetic sequences copied from viruses. A teaming up of researchers connected with the dairy industry led to the next realization – that the viral sequences embedded in the bacterial DNA are a form of molecular memory that allow bacterial cells to identify and protect themselves from harmful viruses.

The team’s goal was simply to understand how some strains of bacteria that are used to make yogurt are able to dodge viral infections. To answer the question, the group enlisted the help of Sylvain Moineau, a University of Laval microbiologist and expert in the study of viruses that attack bacteria. Starting in 2007, work in Dr. Moineau’s lab led to a series of papers that identified some of the key components of an elaborate defence system designed to thwart those attacks.

Dr. Charpentier and Dr. Doudna played the pivotal role of discovering precisely how that system works. Both were leading separate teams when they met at a conference in 2011 and decided to join forces. The partnership was to have far-reaching consequences.

Working jointly, their teams showed how the CRISPR sequences, along with additional genes, were used by bacteria to build a structure that could zip along any strand of DNA it encountered and look for a match with a viral sequence from its memory. When such a match turned up, the structure closed like a pair of scissors to cut the DNA strand, thereby disabling an invading virus.

Next, the researchers took a bolder step by replacing the viral sequence that guided the scissors with a tailor-made genetic sequence. In doing so, they showed that CRISPR could now be used not just to cut the DNA of a particular virus, but the DNA of any organism at precisely the desired spot. Their landmark 2012 paper that describes the process forms the basis for this year’s Nobel.

Other researchers were working in the same direction. Both Feng Zhang, a neuroscientist at MIT, and geneticist George Church at Harvard University found ways to refine the system for precision editing of mammalian DNA, setting the course for future biomedical applications of CRISPR – as well as a long-running patent dispute between California and Massachusetts-based companies over ownership of the technology.

Since then and despite occasional setbacks, CRISPR has been applied by teams around the world toward the development of a plethora of future therapies.

“Professors Doudna and Charpentier have paved the way for clinician scientists to harness the power of their CRISPR technology,” said Sheila Singh, a McMaster University researcher who is using CRISPR-based methods to study glioblastoma, a form of brain cancer.

She said the technology also has allowed her and her colleagues to understand, for the first time, exactly what genes drive the recurrence of cancer after therapy fails.

Meanwhile, the apparent ease with which CRISPR can also be used by scientists to alter an organism’s DNA has led to a series of recommendations about how and when the technology should be applied to the human germ line.

Last month, the U.S. National Academies of Science and Britain’s Royal Society jointly published the report of an international working group on the regulation and application of germ line editing. The report states that the technology is neither safe nor efficient enough to even consider such applications at present.

In future, said Toronto’s Dr. Rossant, who was on the report’s oversight committee, the use of the technology “should be restricted to cases of severe genetic disease where there is no alternative possibility for a couple to have normal children.”

A second group, formed by the World Health Organization, is looking at international oversight mechanisms for gene therapy. It is expected to report later this year.

In a statement following her Nobel win, Dr. Doudna reiterated her call for researchers and the public to engage in a continuing dialogue about the ethical uses and responsible regulation of CRISPR.

Editor’s note: An earlier version incorrectly said the winners also shared the Canada Gairdner International Award in 2015. The correct year was 2016.

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