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

By Walter Isaacson

Simon & Schuster/March 2021

Reviewed by Bartha Maria Knoppers

March 22, 2021

Considering its length at 480 pages, biographic nature (not usually my bag), and intimidating, heraldic title: The Code Breaker: Jennifer Doudna, Gene Editing and the Future of the Human Race by Walter Isaacson, it was with some trepidation that I accepted to review this tome. Little did I know that it would be an enjoyable journey down memory lane.

While I am an international biotech policy wonk and not a basic scientist, the credo of “know your subject matter” before pronouncing (or denouncing) scientific breakthroughs, has meant that the last 43 years of my academic life have been spent in the exciting, competitive and somewhat terrifying world of “rocket science” – the very trajectory of Jennifer Doudna. As described and interpreted so vividly and engagingly by Walter Isaacson, the high-octane world of academia, its pleasures (students/research teams), perils (funding) and prizes/patents (rare), sounds more intoxicating than the reality of non-stop slogging, publishing and conferencing. Fuelled by the gene for curiosity, which has yet to be mapped and sequenced, its multiple expressions are found in this brilliant book.

In 2012, Doudna and her UC Berkeley colleagues made a breakthrough that revolutionized the process of editing genomic DNA based on the discovery and development of CRISPR (acronym for “clustered regularly interspaced short palindromic repeats”). In 2020, Doudna and French researcher Emmanuelle Charpentier were awarded the Nobel Prize in chemistry for their work on the CRISPR gene editing technology.

One of Doudna’s first mentors and a Nobel prize winner himself, Jack Szostak (Harvard University), was in my homeroom class in Riverdale High School in Montreal, Quebec. The enriched program we were enrolled in was as unconventional and fun as our respective careers turned out to be. Yet, already then, the Crick-Watson discovery of DNA’s double helix was reverberating in the world of science. As remarked by Isaacson, few were aware of the pivotal role of Rosalind Franklin in its discovery. While Doudna may have been building the novel world of RNA science and while feminism was beginning to make its mark in socio-political discourse, structural and systemic barriers faced even brilliant and fearless women such as Doudna, as described by Isaacson.

The book is divided into nine parts: The Origins of Life; CRISPR; Gene Editing; CRISPR in Action; Public Scientist; CRISPR Babies; The Moral Questions; Dispatches from the Front, and finally, Part 9: Coronavirus, Isaacson mixes personal interviews (with the world-renowned scientists that were part of Doudna’s path), with an understanding of the actual complexities of basic genetic science. The tensions of publishing struggles, the politics of laboratories and academic departments, the competitiveness of colleagues, the battles of private versus public funding, to say nothing of the ensuing CRISPR patent wars are all ably addressed with both insight and an appreciation of the dynamic nature of basic science. It bears noting that Doudna and Charpentier’s knowledge and discoveries also contributed to the world’s first RNA vaccines against COVID. Indeed, the impact of RNA vaccines — a world first — on the global battle against COVID-19 has yet to be measured.

In 2015, I published, with Doudna and others, the research paper CRISPR germline editing-the community speaks (NatBiotech) but did not meet her personally until the 2019 CRISPR annual meeting, held that year in Quebec City. It is rare to meet a more accessible and ELSI-savvy basic scientist.

The mapping of the human genome was ending as Doudna began her foray into basic science but her pioneering work on RNA-mapping efforts rewrote the code of life. Along the way, the actors and protagonists are accurately (and quite astutely) portrayed by Isaacson. Irascible characters and large egos abound in the upper echelons of international science alongside the more gentle and collaborative leaders. To take but one example, while Watson admirably set aside a percentage of the human genome sequencing budget for the study of the ethical, legal and social implications (ELSI) of the mapping effort in the 1990s, I also witnessed his public remarks about individuals with genetic “defects”. Isaacson’s character portrayals of Doudna’s colleagues are right on point.

In addition to the scientific and personal frustrations and joys portrayed throughout all nine parts, Isaacson pays particular attention to the ELSI aspects. He notes how researchers themselves are well aware that science is not neutral. Whether at Asilomar (1975), Napa Valley (2015), Washington (2017) or Hong Kong (2018), their summits and meetings have consistently questioned the perils and promises of gene editing. Yet, provided the safety and efficacy risks could be addressed, the adage of “Proceed with Caution” became their ultimate calling card. They could not totally dismiss the therapeutic promise of gene editing.

In 2015, I contributed, along with with Doudna and others, to the series CRISPR germline editing-the community speaks (NatBiotech) but did not meet her personally until the 2019 CRISPR annual meeting, held that year in Quebec City. It is rare to meet a more accessible and ELSI-savvy basic scientist. Isaacson’s accurate assessment of her “humanist” qualities was certainly validated as I witnessed her respectful and open discussion with young researchers and students. One would have thought that her international stature would preclude such generosity of time and effort.

The Code Breaker is a brilliant and engaging book. There are many quotable gems but I have chosen one sentence from the epilogue that epitomizes not only Doudna but also Isaacson himself, whose book title ends with a hortatory claim that CRISPR affects “the future of the human race”:

“To guide us, we will need not only scientists, but humanists. And most important, we will need people who feel comfortable in both words, like Jennifer Doudna.”

Need I add, like Walter Isaacson?

Professor Bartha Maria Knoppers is the Canada Research Chair in Law and Medicine and the Director, Centre of Genomics and Policy of McGill University. She was a member of the International Commission on Heritable Human Genome Editing (2019-20).