A scientist teases The Codebreaker

On October 7, 2020 the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to Dr. Emmanuelle Charpentier of the Max Planck Unit for the Science of Pathogens, and to Dr. Jennifer Doudna of UC Berkeley, “for the development of a method for genome editing.” 

In their words, Doudna and Charpentier “have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.”

Indeed, a little over a decade ago, the CRISPR revolution began. Leveraging a bacterial system for immunity against viral infection, Doudna and Charpentier created a CRISPR-based biohack for changing a DNA sequence. Due to its scalable nature and practical accessibility to a wide range of scientists, CRISPR-based genome editing accelerated the pace of discovery in biomedical science, as well as the development of potential gene editing applications to cure human disease. Given CRISPR’s impact on scientific advances and clinical translational opportunities, Walter Isaacson authored this year’s NephJC Book Club selection, The Code Breaker, on Doudna’s journey as a scientist and the triumphs and controversies emerging from CRISPR technology.

A comprehensive explanation of how CRISPR works is beyond the scope of this brief summary, but a simplified explanation can be found here. Perhaps more germane to a NephJC Book Club discussion are some themes and threads that run throughout Isaacon’s work. 

For example, Doudna was inspired by reading James Watson’s The Double Helix, which captured the elegance of how chemistry intersects life in molecular biology, while also exemplifying how scientific collaboration and curiosity can be sullied by unassigned credit (e.g., Rosalind Franklin) fueled by competition. Isaacson devotes quite a bit of his work to outlining how competition drove both discovery in the CRISPR field and the drama and legal battles that hampered collaboration. Doudna described competition as “the fire that stokes the engine,” but can the promise of scientific glory that inspires competition also be dangerous? 

This issue was raised by the bioethics controversies emerging from the scientific arms race to be the first to apply CRISPR in clinical applications. Although CRISPR holds great clinical promise in Phase I/II trials for sickle cell disease and cancer, in this race, an ethical line was crossed when a rogue scientist from China applied CRISPR technology to edit the genomes of embryos that were successfully implanted, leading to the birth of the world’s first CRISPR babies whose gene edits were not related to life-threatening genetic diseases. Is this a gateway to eugenics (which was, as Isaacson described, horrifically embraced by Watson)? 

Thus, Isaacson raises the question: when scientific discoveries outpace ethics discussions and guidelines, how do we determine what is acceptable without hindering important work that could improve the health of many people? And who should determine it? After all, CRISPR has already facilitated promising medical advances described in the book and has the potential to wipe out devastating genetic diseases.

Although there may not be a clear answer, Isaacson does offer the following potentially controversial statement: “All creatures large and small use whatever tricks they can to survive, and so should we. It’s natural . . . . After millions of centuries during which the evolution of organisms happened ‘naturally,’ we humans now have the ability to hack the code of life and engineer our own genetic future. . . . Nature and nature’s God, in their infinite wisdom, have evolved a species that is able to modify its own genome, and that species happens to be ours.”

See you Tuesday, August 22 at 9 pm EDT for more discussion!

Jennie Lin