"The Code Breaker" - Summary

Our story begins with Jennifer Doudna's groundbreaking achievement at Yale, where she successfully determined the structure of a self-splicing RNA molecule. This accomplishment propelled her to a faculty position at UC Berkeley in 2002, where she relocated with her husband, Jamie Cate. Cate, a former graduate student of hers at Yale, was now a faculty member at MIT.

Once at Berkeley, Doudna's curiosity led her to explore how the RNA of viruses, such as coronaviruses, can take over cells' protein-making machinery. This early interest hinted at her future work on CRISPR and COVID-19. She also delved into the study of RNA interference, a process where small RNA molecules can mute specific genes. This process was first discovered when scientists tried to enhance flower colors but ended up suppressing some genes instead.

To understand this process better, Doudna used a technique called X-ray crystallography to determine the structure of an enzyme known as Dicer. This enzyme cuts up RNA into fragments that interfere with messenger RNAs, the molecules that carry genetic information from DNA to the rest of the cell. By mapping Dicer's structure, Doudna discovered how its molecular folds enabled it to cut RNAs with precision, targeting specific genes.

This discovery led Doudna to realize that Dicer could potentially be reengineered to silence any gene of interest. This was a significant breakthrough, as it suggested that RNA interference could be used as a tool for both exploring gene functions and regulating genes for therapeutic purposes. Her work also opened up the possibility of using RNA interference to fight viruses, including coronaviruses. Some organisms had naturally evolved to use RNA interference against viruses, and researchers were hopeful that similar therapies could be developed for humans.

Through her foundational work on RNA structure and mechanisms like self-splicing introns and RNA interference, Doudna built a solid reputation in her field. This expertise set the stage for her later realization of the gene-editing potential of CRISPR-Cas, a relatively unknown bacterial immune system discovered in 2006. Doudna's career path underscores the importance of curiosity-driven basic science research. Her early achievements in understanding RNA's inner workings played a pivotal role in the upcoming genomics revolution.