On 7 October 2020, the 2020 Nobel Prize in Chemistry was jointly awarded to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing.” They are the sixth and seventh female chemistry laureates in the history of the prize.
Emmanuelle Charpentier was born in France with a PhD from Institut Pasteur and is currently director of the Max Planck Unit for the Science of Pathogens in Berlin, Germany. Jennifer Doudna was born in the US with a PhD from Harvard Medical School, and is currently professor at the University of California, Berkeley, and investigator at the Howard Hughes Medical Institute. In 2012, they were the first to propose that CRISPR-Cas9 – CRISPR stands for ‘clustered regularly interspaced short palindromic repeats’ – could be used to edit genomes in a precise and efficient manner.
In an interview with Genetic Engineering & Biotechnology News, Dr Charpentier marvelled, “when you see the field of just CRISPR biology, understanding the CRISPR-Cas systems in bacteria and archaea at the physiological level and even more at the mechanistic level, [there] has been an incredible explosion of knowledge and publications … the spectrum of applications is quite incredible. It has created a lot of interest and [also] a lot of jobs in the biotechnology field.”
Today, CRISPR is seen as one of the most transformative and impactful discoveries in the history of science – and in drug development, where CRISPR is widely used. What is striking – and perhaps an important lesson for all healthcare stakeholders today – is the unassuming genesis of this innovative technology platform: in bacteria, and specifically how bacteria use their immune system to protect themselves from viruses.
In an interview conversation with UCLA Executive Vice Chancellor and Provost Emily A. Carter, Dr Doudna revealed, “our research on CRISPR started as a curiosity-driven project to understand how bacteria fight viral infection”. Her long journey towards the Nobel Prize began in graduate school. As she reminisced, “I got interested in RNA because I was fascinated by the question … where did life come from? Why does biology evolve and look the way it does on a molecular level? … I’ve been interested in this question – in different facets of it – for my whole career. How I started working on CRISPR in the first place was to understand how RNA is used as the recording and detecting mechanism in that pathway.”
Charpentier is a microbiologist and she has spent most of her career working in infectious diseases, one of the most underfunded therapeutic areas in the industry today; her PhD thesis looked at the molecular mechanisms involved in antibiotic resistance, another urgent public health concern today. In an interview with CGTN, she lamented, “microbiology is not as fashionable to young scientists who would rather turn to human genetics, neurology or oncology.” But she emphasized the fundamental importance of this work, citing, for example, “microbiology [has been] essential to understand COVID-19 … [microbiology is essential] to understand the evolution of microbes that causes diseases in humans. It’s critical to maintain government organizations to support this research.”
Their fateful collaboration began in 2011, when they met at the sidelines of a conference in Puerto Rico. In her interview with the Nobel Prize organization, Dr Charpentier recalled, “the collaboration was short and intense!” She explained why she approached Dr Doudna: “we were very much in line in the way to do very precise research. Sometimes you work on systems and you know it takes a long time to see what you would like to see. The research is not black and white, it is light grey or dark grey.”
Dr Doudna concurred, contextualizing, “I have been involved in almost countless collaborations now over my 26 years of running a lab. I would say at least half of them fizzle. It really speaks to the fact that Emmanuelle and I shared a vision for what we wanted to do together scientifically.”
Both women have been described as ‘stubborn’ by colleagues but they both see this as a compliment and an essential trait for working in science. Dr Doudna affirmed, “my experience certainly has been that the people I see who are most successful in science tend to be those who are just laser-focused on their passions – they do not let anyone dissuade them from what they want to do,” adding, “I can think of a number of times in my career when … there were questions I had about biological system that I wanted to answer and there were plenty of naysayers saying that is either a silly idea or that will never work. I did it anyway. I was not always right, but at least I satisfied my question and my passion.”
In the same vein, Dr Charpentier advocated, “this is not about a paper published in Nature or in Science … it is really about solid work. You need time to do the work in a proper way, in a deep way. I want to mention this because I would not like to see science having lost this sense.”
Both have also established their own start-ups leveraging the CRISPR technology, Dr Doudna with Mammoth Biosciences and Dr Charpentier with CRISPR Therapeutics. Dr Doudna also had a stint with industry biotech darling Genentech, but she left just two months after because she missed the academic environment and the discovery science she could conduct there.