The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

Abstract

Readers of Practical Radiation Oncology will be aware of the concept of gene editing and the plethora of bioethical issues associated with “designer babies.” Less familiar, however, is the fascinating journey that led to a potential cure for sickle cell disease or the world's first genetically modified humans, or even with Jennifer Doudna or CRISPR (clustered regularly interspaced short palindromic repeats) itself. In the nonfiction book The Code Breaker, Walter Isaacson breaks the mold of a traditional biography to tell the intricate story of a monumental scientific discovery that not only resulted in a Nobel Prize but has the potential to change the evolution of humans and other complex organisms (Fig 1).1Isaacson W. The Code Breaker: Jennifer Doudna, Gene Editing and the Future of the Human Race. Simon & Schuster, New York2021Google Scholar Although the book seems to begin traditionally with a glimpse into Doudna's childhood to understand the inspiration for her scientific career, it steadily progresses into a more complex tale about legendary scientific feats with multiple players. Although Doudna's life and career are the cornerstone of the book, these elements serve as a conduit for larger themes. Even her inspiration to pursue science, The Double Helix by the famous, or perhaps infamous, James Watson, is explored through Isaacson's recurring scrutiny of Watson, his sexism, his egoism, and the meaning of legacy. Although we learn how Doudna matures into a world-renowned scientist and celebrated leader, Isaacson also tells the story of CRISPR, its associated innovations, and some of the wreckage left in its wake. CRISPR, a snappy acronym for “clustered regularly interspaced short palindromic repeats,” and Cas (CRISPR-associated) proteins comprise an RNA-mediated immune system found in bacteria to protect from attacking viruses. As Isaacson describes, its discovery, inspired by genuine curiosity, was marked by dedication, diligence, collaboration, and competition, both friendly and acrimonious, and it spurred the international scientific community to establish medical applications for humans. The miraculous—and I do not use the adjective lightly—feature of the CRISPR-Cas9 complex described in Doudna's landmark 2012 paper in Science2Jinek M Chylinski K Fonfara I Hauer M Doudna JA Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.Science. 2012; 337: 816-821Crossref PubMed Scopus (8562) Google Scholar is its ability, if programmed appropriately, to cleave double-stranded DNA at any desired sequence and edit genes. The ensuing race to demonstrate its use in humans has resulted in countless diagnostic and therapeutic tools that are revolutionizing medicine. However, as Isaacson illuminates, these discoveries are mediated by the politics of science, the simultaneous growth of the biotech industry, industry's infiltration into academia, and the unanticipated results of opening Pandora's box. The possibilities seem endless with CRISPR, but the potential dangers are similarly abundant. Isaacson delves into the bioethics of gene editing and how these issues have been handled by the scientific community. He also describes the rise of “biohackers” who threaten, or pledge, depending on your perspective, to make the technology available to everyone from the comfort of one's own home. Throughout the various provocative events he discusses, Isaacson presents both sides and offers his perspective. This simple technique unpacks the complex controversies surrounding CRISPR and provides readers with a signal to consider their own opinions on the issues. As a result, he creates an informative and thought-provoking narrative that amounts to quite the enjoyable read, accessible to those with and without a scientific background. All things considered, The Code Breaker is a must-read, especially for those in the medical field. Radiation oncologists may be especially inspired by the implications of CRISPR for cancer diagnosis and treatment as well as its potential for radiation protection. A world without hereditary disorders that predispose to cancer or cause radiosensitivity that precludes our ability to effectively treat a malignancy may not be far away. This technology may even open the door to inducing differential radiosensitivity among cells to optimize the therapeutic ratio—again, the potential seems limitless. Physician-scientists who have not considered CRISPR as a research avenue may be inspired, and many more may be moved to carefully reflect on the ethical dilemmas created in the process. Even so, Isaacson truly creates a book that is relatable to anyone who loves a complex success story that stems from passion, hard work, and a little bit of luck.