October 2020 – In a history-making announcement, the Noble Prize in Chemistry was jointly awarded to French scientist Dr. Emmanuelle Charpentier, director of the Max Planck Unit for the Science of Pathogens in Berlin, and Dr. Jennifer Doudna, an American professor at the University of California, Berkeley, for their discovery of the gene-editing method CRISPR/Cas9, generally known as “genetic scissors.”
In a ground-breaking experiment, scientists Charpentier and Doudna were able for the first time to cut DNA at sites of their choosing. Since it was made public, CRISPR/ Cas9 has been considered, both by the scientific community and media, to be one of the biggest biotech discoveries of the century. And not surprisingly, it has also raised ethical concerns – particularly related to the potential modifications of the human germline, and launched costly patent rights battles.
“This … is about rewriting the code of life,” said Göran Hansson, secretary general of the Royal Swedish Academy of Sciences, of the pioneering discovery.
What few know is that the first steps in discovering CRISPR/Cas9 were taken by Charpentier at the Max Perutz Labs in Vienna, where from 2002 to 2009, she led a group including her PhD student Krzysztof Chylinski as part of an international network focused on RNA (ribonucleic acid) research, initiated by renowned Austrian biochemist Professor Renée Schröder. This strong community of researchers included a large number of women working on the biological macromolecule considered to be the “source of life.” Charpentier focused on the research of bacterial RNA.
It was in 2006 when Charpentier first became interested in the CRISPR system, which she had read about in scientific journals. In the years that followed, Charpentier and her teams in Vienna and later in Umeå, Sweden, studied tracrRNA, a molecule abundant in bacteria, that is located in the vicinity of the CRISPR system and is crucial for its function. Even though Charpentier moved to Sweden in 2009, she continued her collaboration with her PhD student Chylinski, based in Vienna.
In a research paper published in Nature in 2011, Charpentier and her collaborators were the first to describe a unique defense mechanism of bacteria, observed in the CRISPR system. That it involved the tracrRNA molecule was clear, but a mysterious protein that neutralized the attacks of viruses by cutting portions of the DNA was still to be identified.
In 2012, Charpentier started an international collaboration with Doudna focused on the Cas9 protein. Following an intense trial-and-error process, the team that also included Chylinski and Martin Jinek, a postdoctoral fellow at the Doudna Lab, discovered that tracrRNA was required in the process of cutting DNA that was performed by the Cas9 protein, and that the system could be programmed to target any DNA sequence selected.
This success led to the invention of the CRISPR/Cas9 gene-editing tool that is based on the natural defense mechanism of bacteria.
At the time of their first breakthroughs, the team was not yet fully aware of the impact of their pioneering discovery. As is often the case in basic science research, “you don’t realize at first how important the discovery is,” remarks Schröder, who followed the CRISPR/Cas9 research closely. Almost a decade later, she sees CRISPR/Cas9 as an “elegant system” that “totally changes how science is done.”
At the heart, says Chylinski, is “curiosity-driven research.” It was an “openness to ideas and people” in the collaboration that led to the discovery of CRISPR/Cas9. In basic scientific research, what matters is “having open eyes when you are getting lucky,” says Chylinski. He is often in awe seeing “how people are coming up with ideas [of how] to use an imperfect tool.” Applications range from modifying agricultural crops to medical treatment, in particular of rare and genetic diseases such as sickle cell anemia.
The Fight Over CRISPR/CAS9
Into the early 2010s, there were several teams working on the CRISPR system, then still a niche topic, but about to take off with the progress in genomic engineering. Notably in the US, several leading institutes were conducting research on CRISPR.
After the publication of the research results on CRISPR/Cas9 in the scientific journal Science in 2012, interest grew. Soon, the number of research papers on the topic exploded.
With several labs claiming the discovery, CRISPR/Cas9 suddenly became an “apple of discord.” Bitter and expensive legal fights over patent rights followed along with a race to commercialize the tool with applications in bioengineering and medical research. Some are ongoing.
That the 2020 Nobel Prize for Chemistry was awarded to Charpentier and Doudna, did not come as a surprise. For many years, colleagues had expected their pioneering scientific discovery to be rewarded with the prestigious prize; it was just a question of time. “Well deserved,” say both Schröder and Chylinski who met to celebrate the event at the Café Korb in the 1st district soon after the announcement.
This was the first time in the more than a century-long history of the Nobel Foundation that a science Nobel Prize went to two women. Charpentier and Doudna entered the hall of fame of the “women who changed science,” joining the ranks of pioneering researchers Marie Curie (1911), Irène Joliot-Curie (1935), Dorothy Crowfoot Hodgkin (1964), Ada E. Yonath (2009), Frances H. Arnold (2018), awarded the Nobel Prize in Chemistry.
Charpentier hopes her and Doudna’s win of the highest distinction in science “can provide a really strong message for young girls,” – that everyone can make a contribution that matters, regardless of their gender.
In science as in many other fields “women are often overlooked,” Schröder said. Scientific research is highly competitive, and it is becoming increasingly difficult to thrive in the field, especially for women. In a scientific world obsessed with high mobility, getting tenure often involves having to move countries, which makes combining family and science even harder.
For Charpentier herself, the path to winning the Nobel Prize was difficult. In 2009, after not getting a tenure-track position in Vienna, she moved to Sweden. Schröder remembers how hard it was to see her talented colleague “Manue” leave Vienna and the strong team she had built here.
In 2014, Charpentier moved again, this time to Germany, where she was finally offered a permanent position. By that time, she had already achieved a high-level of recognition in the scientific community.
Charpentier’s extraordinary resilience, dedication and passion for science has brought her the recognition and most prestigious awards science has to offer. And like her role model Marie Curie, she too has left a mark on her field that will be an inspiration to the next generation.