Book review: Walter Isaacson. 2021. The Code Breaker

This book chronicles rather beautifully the complex topic of development of a great scientific advancement with insightful references to a number of dedicated scientists who contributed to realizing it. It details the journey behind Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), a revolutionary gene-editing tool that may forever change the face of humanity. The narrative is told largely with Doudna, a curiosity-driven researcher, as the lead character. It details her personal and research journey to bridge some of the existing gaps in biological sciences. With many trials and tribulations, she along with her collaborators discovers how CRISPR operates and invents a much simpler technique for editing genes. Over a period of time, she becomes one of the world’s leading genetic researchers. By taking a holistic look at what got her onto win the 2020 Nobel Prize, the book tries to highlight, uncover and demystify various facets of high-level scientific research and thinking. It also captures and uncovers few untold instances and stories about this breakthrough scientific discovery and shares with readers the trials and tribulations, as well as the thought processes, personalities and contributions of other scientists in the field of gene-editing. Perhaps, similar untold and unshared stories exist in other scientific discoveries as well. It is quite refreshing to read a story about scientific discovery with two women breaking the proverbial glass ceiling along with relevant details about every significant CRISPR researcher.

In brief, it is a captivating book about the next big thing in science. It describes in an interesting and engrossing manner the greatest advance in biology since the discovery of DNA which can potentially lead to a life sciences revolution wherein we will be able to rewrite the code of life. The author, perhaps rightly so, puts this as the third great revolution of the modern times after the physics revolution at the beginning of the 20th century with Einstein’s papers and the digital revolution following the discovery of the binary bit that led to the Internet and subsequently the cyber-physical systems. Whenever viruses attack a certain bacterium, they do something very interesting: they take a mugshot and put it in their own genetic material. When the virus reattacks, the bacterium remembers it and uses a little guide, RNA (an enzyme that acts as a pair of scissors), and cuts up the invading virus. This allows them to have an adaptive immune system. It is a sophisticated defence mechanism that bacteria evolve to disarm invading viruses, quite similar to the way fungi develop penicillin to protect themselves against bacterial infection. The “scissors” which Doudna and Charpentier discovered are known as CRISPR. These lay the foundation to engineer or reprogramme any sequence of DNA in humans and open a plethora of opportunities towards the diagnosis and treatment of serious illnesses.

This gripping book is divided into nine parts with 56 chapters. The eight chapters in Part one are introductory in nature and take the reader through Doudna’s childhood adventures around her home in Hilo, a Hawaiian island. As a little girl, Doudna would never quite fit-in and would often find solace in reading books that her father would regularly bring for her. One of these detailing the discovery of the structure of DNA in the quest to unravel the molecular structure of DNA was James Watson’s The Double Helix (p. 226) ¹ . This book was an eye-opener that impressed her that “women could be scientists.” These early chapters also introduce many basic concepts such as the gene, DNA, RNA, basic structural biology, and contributions of remarkable scientists such as Darwin, Mendel, Franklin, Watson, and Szostak, among others. Part two comprises 11 chapters and deals mainly with initial struggles of Doudna and her trysts with CRISPR and her collaboration and competition with other scientists until the publication of her seminal paper in Science journal in 2012. Narrative is a bit dull in the beginning but soon the tempo picks up and the reader gets engrossed in various concepts, personalities, journeys, and challenges. The stiff competition about “an idea that has come” has been presented in a charming manner with all scientific as well as real-life concepts, notions, and complex behaviour patterns interwoven seamlessly.

Part three has 11 chapters that broadly cover the technical topic of gene-editing and basic concepts about scientific research, publishing, patents, teamwork, professional rivalry, competition and collaboration, synergy, and complementarity brought in as needed. In this context, many sung and unsung, highly recognized and less-recognized scientists are thrown in the narrative. The race between Doudna and her competitors—most notably Feng Zhang—to develop a versatile gene-editing tool based on RNA technology forms the core of this engaging narrative. The following six parts with remaining 25 chapters extend the book beyond the basic story to the complexities of such wonderful scientific inventions and discoveries. Many applications of CRISPR are inarguably good, such as using it to cure diseases such as sickle cell anaemia, beta thalassaemia, cancer, and blindness, among others. In these cases, scientists alleviate human suffering in a way that does not alter the human germline. In other words, the edits affect only the person who receives them and do not get passed along to subsequent generations. Towards the end, the book makes the readers walk through Doudna’s lab and get a feel of hands-on experience. It also covers the topical coronavirus and related initiatives such as vaccines and clinical trials.

The book sheds light on incremental contributions of many scientists that often go unnoticed, making it clear that nowadays no scientific discovery is possible by a single scientist. The book clearly establishes that nowadays, generally an international network of cooperation, collaboration, and communication of researchers is required for breakthrough scientific inventions and discoveries. It presents deep insights on the inner workings of contemporary global research with an ensemble of international scientists spread across the USA, Europe, China, and other parts of the world and their incremental contributions in the given context. These reflect both merit and manoeuvres, trials and tribulations, rewards and recognitions, and success and failures. Through Doudna and Charpentier’s journey to the 2020 Nobel Prize, the readers are able to learn and appreciate that the line between collaboration and competition could be as thin as a nuclear membrane.

From management perspective, this book covers a host of topics such as innovation, research, leadership, networking, collaboration, entrepreneurship, competition, stakes, co-opetition, group synergy, healthy rivalry as well as associated moral, ethical and legal dilemmas. The author successfully links the struggle to unlock the secrets of RNA with Doudna’s efforts to better understand her own personal journey and relationship with her father, whom she cared for when he was dying of cancer. Along with curiosity, perseverance, restlessness, intensity, and clamour for fame and recognition, the accompanying complexities, dynamics, and uncertainties in her personal and career tours and detours have been captured quite well. It also covers traits, preferences, and personalities of other scientists as well as their PR actions, conflicts, and showdowns during their professional and career journeys. Perhaps, high-level scientific research and thinking needs more structured guidelines, coordination, and control.

Besides providing a navigable history of genetic technology and its development, the book also raises and discusses a host of moral and ethical issues with long- term implications on science, politics, and society. It succeeds fairly well in laying out the parameters of the debate between advocates of individual liberties and of collective welfare; it highlights concomitant issues such as affordability and biohacking and introduces readers to the ideas of philosophers such as John Rawls, Robert Nozick, and Michael Sandel. Although gene-editing could be very useful for diagnosis and treatment of serious illnesses, it could be possibly “dangerous” in contexts such as eliminating diversity from the gene pool or producing “designer babies as was done in China in 2018 when twin girls, Nana and Lulu, were genetically altered to be immune to AIDS.” The book highlights one of the most consequential dilemmas of the 21st century with controversies, debates, and backlashes. The researcher He Jiankui’s intentions were good—helping HIV-positive couples give birth to children who had a gene that would confer resistance to infection with HIV. However, the backlash from the scientific community was ferocious with severe consequences. Two distinct groups clearly emerged: the Utopians and the Conservatives with their own arguments and counterarguments. The author uses a quote from James Watson, “If scientists don’t play God, who will?” in context of the contemporary easily possible gene-editing: However, without taking a clear stand or offering a clear solution to this complex challenging question, the book indirectly suggests that it is the public who should play an engaged and decisive role in drawing and defining the ethical lines.

Overall, the book is really interesting and despite being rather lengthy, keeps the readers engaged. It is a well-researched book that provides a glimpse of how basic science eventually gets turned into applied science. It is succinct, easy to understand, and provides an amazing preview into the complex world of a riveting expedition through chemistry, biochemistry, microbiology, and structural biology. It is able to convincingly put across that “science is a collaborative effort” and “competition drives discovery.” Those familiar with college-level biology will naturally be more comfortable reading it, but others too will not regret the reading experience. More importantly, it takes us through less documented domains of academic politics and captures the rivalry, collaboration, competition, and synergy as well as the raw, magical enthusiasm of living pioneers such as Doudna, Watson, Fang, and others. It also makes an impassioned call to the next generation to appreciate the “wonder, joy, and nobility” of basic science and exhorts them to think about genetic coding along with digital coding as preferred career choices.