Explained: Who — and What — Won 2020 Nobel Prize in Chemistry
By Catherine Hsu
Although Emmanuelle Charpentier was surprised to learn that she and her partner Jennifer Doudna had received the 2020 Nobel Prize in Chemistry, she wasn’t surprised that the CRISPR/Cas9 technology had won. Even though the two women had only published the groundbreaking paper on the subject in 2012, it had revolutionized the life science world, and researchers around the world were eager to apply the newly discovered tools to their respective areas of interest. The discovery meant that scientists now had a precise and relatively simple way to cleave very specific sequences of DNA, allowing them to edit the genome at an even smaller level.
CRISPR genes are palindromic, repetitive gene sequences present in many bacteria that work with other sequences called spacers that the bacteria grab from invading viruses. Another type of RNA, trans-activating CRISPR RNA (tracrRNA), helps guide the CRISPR sequences to the Cas9 enzyme, a protein that can cut DNA. When the CRISPR/Cas9 complex meets the specific virus again, it can determine the sequence that it previously grabbed, and the Cas9 enzyme cuts through the double-stranded DNA. The mechanism is a part of the bacteria’s innate system of fighting viruses, and it does so by cleaving the virus’s DNA or RNA to prevent it from replicating and further infecting the bacteria.
Scientists have used the system in a very different way. For a long time, humans have lacked a way to precisely cleave DNA when editing an organism’s genome. The EcoR1 cleaving enzyme, for example, cuts at the palindromic sequence GAATTC. The enzyme has been widely used for inserting human genes into bacterial plasmids, or small rings of DNA within a bacterium. However, since the enzyme cuts at every site where a GAATTC sequence is present, it is unsuitable for cleaving longer genomes, as it would create far more breaks than intended. The CRISPR/Cas9 complex is guided by approximately 20 base pairs of RNA, which guarantees enough accuracy that it would only cut at the specific place scientists intended. The precise breakage would allow scientists to add, delete, or modify genes around the edited area for complex organisms such as plants, mammals, or even humans.
The CRISPR genes and their basic defensive functions had been discovered by the time Charpentier took interest in the early 2000s. At the time, the French microbiologist was studying Streptococcus pyogenes, a type of bacteria that causes many infections and diseases in humans. After asking a fellow microbiologist to sequence the genome of the bacteria, she and her colleagues discovered a type of sequence that seemed closely related to the CRISPR genes. They called it tracrRNA, and Charpentier hypothesized that the RNA guided the CRISPR RNA and Cas9 protein to the correct sites. A student working in her lab, Elitza Deltcheva, conducted the key experiments that showed the hypothesis was correct.
Charpentier first met Doudna in 2011 at a microbiology conference in San Juan. The American biochemist was well-known for her research in RNA, and the two began a partnership that Charpentier has described as “short but intense”. Together, they simplified the mechanism in a way that allowed it to work in a test tube, and modified the genetic scissors so that they would work with any type of genetic material rather than just viral RNA/DNA. This made it an extremely valuable tool in genetic research, and after publishing their paper in the journal Science, it immediately sparked a frenzy. The implications of the research are wide — CRISPR/Cas9 could be used to engineer crops to help them survive in harsher conditions, conduct research on genetic diseases in animals, or search for cures for diseases like cancer or blindness.
But the technology could also be used for other, shadier purposes — editing the human genome to “improve” or “purify” it. For Doudna especially, the worry that their discovery would lead to problematic usage and experiments “kept her up at night”. As a biochemist, she was initially not familiar with this gray area — that is what bioethicists were for. Yet she felt a responsibility to educate both governments and the public on the mechanisms and potential implications of her research. Since 2015, she has given more than 60 talks at a variety of professional settings, including schools, companies, and the US Congress. She and her colleagues also organized a framework that would safeguard the editing of human embryos. Yet despite Doudna’s efforts, a Chinese man named He Jiankui claimed to have edited the genomes of twin baby girls in 2018, creating the first CRISPR babies. Though it is unclear whether the genomes had been successfully edited, or what effects the changes may have on the girls, many researchers worry that He had opened a door to dangerous and murky waters.
Even putting aside their groundbreaking research, Doudna and Charpentier were also drawing attention for being the first all-female team, and the sixth and seventh women to receive the Nobel Prize in Chemistry. They believe that this sends an important message to girls about equality and women in science.
“Among women and girls … sometimes there’s a sense that no matter what they do that their work will not be recognized the way it would be if they were a man…I hope that this prize and this recognition changes that at least a little bit,” Doudna commented in an October 2020 interview.
Charpentier had a similar message, saying that she hoped girls would understand that their achievements would be recognized regardless of their gender. She also believes that though the Nobel Prize and all the other awards that she and Doudna have received were great honors, they were not the reason she pursues research. She continues to research both CRISPR and other microbiology at her lab in Berlin, and also co-founded the company CRISPR Therapeutics, which aims to use CRISPR technology for human gene therapy.
Emmanuelle Charpentier and Jennifer Doudna’s research has greatly impacted the world of genome engineering, and will continue to have implications far into the future. The two women will also no doubt inspire many aspiring female scientists in the years to come.
Sources:
https://www.nobelprize.org/prizes/chemistry/2020/press-release/
https://www.nobelprize.org/prizes/chemistry/2020/doudna/interview/
https://www.nobelprize.org/prizes/chemistry/2020/charpentier/interview/
https://www.nature.com/news/genome-editing-revolution-my-whirlwind-year-with-crispr-1.19063
https://www.britannica.com/biography/Jennifer-Doudna
https://www.britannica.com/biography/Emmanuelle-Charpentier
Catherine Hsu is a sophomore at NYU majoring in Liberal Studies. She is a cat-lover and wants nothing more than to curl up with a cat and a good book.
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