By Helen Wright
7th October granted a single positive headline in a sea of coronavirus updates – the first all-female recipients of the Nobel Prize for Chemistry had been announced, awarded to Emmanuelle Charpentier and Jennifer Doudna ‘for the development of a method of gene editing’. Looking at past Nobel Prize winners, there is a clear lack of female names, with just 56 out of all 916. Furthermore, of these 56 women, only 19 are scientists, which only heightens their achievements given the challenges of working in such a male dominated industry.
Charpentier and Doudnas’ collaboration led to ground-breaking discoveries surrounding the CRISPR/Cas9 system. CRISPR, or clustered regularly interspaced short palindromic repeats, which are sections of a bacterial genome characterised by their distinctive sequence structure. This section is key to a bacteria’s immune system, involved in coding for the Cas9 protein, which works to destroy viruses by cutting their DNA. Interestingly, the bacteria then incorporates the virus’ DNA into the CRISPR section of its own genome, to allow for easier recognition if infected again.
Through Charpentier and Doudnas’ research, they discovered its potential for gene editing outside of bacteria. These ‘genetic scissors’ can and have been used to genetically modify crops to withstand mould, pests and drought. Its other key application is as a medical tool; for example as a cancer treatment or for curing genetic diseases, which has gained significant publicity due to ethical debates surrounding it. A Nobel Prize crediting the research into CRISPR was arguably inevitable, due to its predicted global impact.
Described as a scientific nomad, Emmanuelle Charpentier has worked at nine institutions in five countries. She grew up and studied in Paris, before moving to the Rockefeller University in New York where she focused on bacterial infections. However, after five years she moved to Vienna in favour of a European way of life. She says her aim was ‘to understand how every biochemical pathway in a bacterium was regulated’ and with that passion and determination she received numerous grants to fund her research. This resulted in her discovery of an RNA vital for virulence in the bacteria Streptococcus pyogenes. The coding site for this molecule fell close to a CRISPR region therefore was highly likely to play a key role in the CRISPR system. She further explored the system and identified its three components – tracrRNA, crRNA and the Cas9 protein. This resulted in a surprising hypothesis – the two RNA molecules would guide the Cas9 protein to its target site together, which was unexpected for RNAs.
Despite finding success in Vienna, she never felt at home and so moved to the Umeå Centre for Microbial Research in Northern Sweden in 2009, attracted by the area’s classic Scandinavian architecture and the long dark winters which aided her focus. That summer, she found out that her experiments back in Vienna had worked and her hypotheses on the CRISPR mechanism were true. She was still unknown in the small world of CRISPR however began presenting her findings in conferences around the world. It was at the 2011 American Society for Microbiology conference in Puerto Rico where she met Jennifer Doudna, her future research partner.
Doudna’s involvement in CRISPR research was much briefer before meeting Charpentier, considering it a side project to her other RNA research. Doudna grew up in Hawaii due to her father’s work, however felt out of place there and was happy to leave for Pomona College in California for her undergraduate degree. She then went on to Harvard University to assist Jack Szastok, also a future Nobel Laureate, on his RNA research. Despite no formal training, she used X-ray diffraction to determine some of the first crystal structures of RNA. In 2002, she moved to the University of California, Berkeley where she has since become a Professor. Here she began working with another researcher, Jillian Banfield, who had been identifying CRISPR sequences in unusual bacteria and encouraged Doudna to collaborate with Charpentier.
They were able to form a strong team – Charpentier had extensive experience with the CRISPR/Cas9 system, had a personable nature, as well as strong communication skills, whereas Doudna had an immense knowledge of structural biochemistry and RNA. Together they were able to show how the Cas9 system could be adapted to produce targeted cuts in a genome, creating the possibility for gene editing. They also simplified the system by finding a way to fuse the two RNA components to create a single, synthetic guide for the Cas9 protein.
Since releasing their findings, the two of them have gained quasi-celebrity status. They were named by TIME magazine as among the 100 most influential people in the world and are incredible role models for the next generations of female scientists. They also have both brought up families whilst being dedicated to their job, underpinning how your home life does not limit your career prospects.
Particularly with the current pandemic, there is the need to boost scientific and medical resources to push for a vaccine and better treatment methods. Therefore, there is no better time to inspire young women to be passionate and dedicated to their science, and this incredible collaboration between two strong, successful women has done just that.
Image: Anna Kuptsova