Walter Isaacson

Review: The Code Breaker

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The Code Breaker, Walter Isaacson. New York: Simon & Schuster, 2021.

Summary: The story of the 2020 Nobel Prize winner in Chemistry, Jennifer Doudna, and the discovery of ways to use CRISPR enzymes to edit genomes, and her subsequent efforts to establish ethical standards for the use of this breakthrough discovery.

Benjamin Franklin. Henry Kissinger, Steve Jobs, Leonardo da Vinci. And Jennifer Doudna? Why has Walter Isaacson chosen to include her among the seminal figures who have been the objects of his books. It just may be that her work as a biochemist is as game-changing for humanity as any of the efforts of these others. James Watson, co-discoverer of the structure of DNA rated her discovery the most significant after his own. Apparently the Nobel Prize committee agreed. In October 2020, she was awarded, along with Emmanuelle Charpentier, the Nobel Prize in Chemistry for a landmark paper in 2012 that described how to use an enzyme found in bacteria, nicknamed CRISPR, in this case CAS9, to edit genomes, removing and inserting genetic material. In 2018, twins, and another child were born in China with the gene for the receptor that makes one susceptible to HIV edited out, an important protection for a child that has an HIV positive parent. CRISPR has been used for a therapy to cure sickle cell anemia, and in the fight against COVID-19. It’s possible that someday a gene could be edited into our genome at conception to make us immune to COVID-19 and other diseases.

Walter Isaacson does several things simultaneously in this book. One is that he profiles Doudna, the lanky blonde growing up in Hilo, Hawaii, and thus a bit of an outcast, who compensated with books. Her father, a professor, left a copy of The Double Helix by James Watson on her bed. She thought it a mystery, and in a way it was as she raced through the book to understand how Watson and Crick unraveled the mystery of the genetic code. That set her on the path to become a scientist, despite the high school counselor who told her girls didn’t become scientists. Isaacson traces her academic journey, including the crucial mentoring of her doctoral advisor at Harvard, Jack W. Szostak, who turned her research interests toward the study of RNA. She researched the structural biology of RNA, first at Yale, and then at UC Berkeley, where much of the book is focused. A 2011 meeting with Emmanuelle Charpentier, who had been studying the CRISPR enzyme, and needed the help of a structural biologist to understand how it worked, brought the two of them together to understand how CRISPR worked in editing genes in bacteria. Their collaboration led to the discoveries described in their 2012 paper.

This set off a frenzied competition of patent applications, the creation of companies, much with a researcher at MIT’s Broad Institute Feng Zhang. This reveals another side of science, the heated competition to capitalize entrepreneurially on such breakthrough research. Isaacson, though focused on Doudna, offers an even-handed profile of Zhang and those who worked with him and the sometime collaboration and sometime cut-throat competition to create applications of the CRISPR technology.

Yet what seems to drive all these scientists is the love of the science. Isaacson takes us to the lab bench in his own attempts to use CRISPR to do gene edits, and to profile Doudna at the bench as well as her leadership of her research group. This aspect of Isaacson’s work is a great account of what the daily life of research scientists looks like, and many of the photos in this book are taken in labs.

The love of science also emerged in the rallying of rival lab groups to collaborate in the fight against COVID-!9. Isaacson shares how they overcame barriers of traditional science research publishing in the new world of online pre-print publishing to share research findings in an open-source, real-time fashion in an effort for the public good in developing new testing and treatment approaches. Although not directly tied to Doudna’s efforts, Isaacson talks about the use of messenger RNA molecules in the vaccines that have been most effective against COVID.

The most interesting and perhaps most important part of the book is the emerging discussion around the use of CRISPR technology in germline gene editing. This involves pre-implantation genetic testing and editing of embryos, which may remove lethal or problematic genes (think Huntington’s disease and especially other single-gene defects) or to enhance the embryo (think height, eye color, etc.). It appears that Doudna only gradually comprehended the ethical questions her research would raise, but then took the lead to draw up ethical frameworks to govern the use of the technology–frameworks which didn’t prevent the Chinese scientist from using the technology in human embryos that were implanted resulting in live births. At publication, this is very much a live question. Most consider this may be acceptable in some circumstances but where is the line to be drawn? Then there are more chilling possibilities. Could CRISPR be used to breed super-soldiers for example? And what of equity, when one considers the cost of these therapies?

The choice of Doudna as Isaacson’s focus is interesting. He shows us the rise of women in science. He also shows us the arc of a career from a junior researcher to one who is shaping the conversation in her discipline and considering how science serves the common good. One can imagine young women reading this story and becoming convinced that this could be their story. And why not? lt happened that way for a lanky sixth grader finding a copy of The Double Helix on her bed.

Review: Leonardo da Vinci

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Leonardo

Leonardo da Vinci, Walter Isaacson. New York: Simon and Schuster, 2018.

Summary: A biography of da Vinci, from his illegitimate birth, his life long quest for patrons, his insatiable curiosity, his various artworks, and the notebooks, in which are revealed so much of the genius of da Vinci.

This is a magnificent biography in every way. Isaacson delves deeply into the life, the notebooks, the travels, and the works of art of da Vinci and renders an account of the peculiar, dazzling, and flawed genius of Leonardo. This is a book you need to read in print. It is a heavy book because it is printed on high quality paper with ample, full-color Figures rendering the notebooks and artworks of Leonardo. A full-color timeline at the front of the book highlights the works of Leonardo, and the key events of and during his life.

A theme that runs through this book is the insatiable and child-like curiosity of Leonardo, who wonders why the sky is blue (and arrived at a basically accurate explanation of this phenomenon) and wanted to describe the tongue of the woodpecker. He was fascinated with optics, from how the eye works to how light was refracted, and why distant objects appear different in color and distinctness from those closer up. He was an innovator in applying these insights in his use of perspective of his paintings. He did pioneering studies of human anatomy that, if published, would have advanced the understanding of anatomy a hundred years earlier. His fascination with hydraulics resulted in an accurate explanation of the closure of the heart’s aortic valve. His notebooks contain speculations questioning a geocentric universe in advance of Copernicus.

Leonardo was an observer. He not only was curious about everything, but he closely studied the objects of his interest, whether it was the play of light on his subjects, the proportions of the human body, consummately illustrated in his Vitruvian Man, the movements of the wings of a dragonfly, the contractions of the leg muscles of a horse, or the way water flowed in a river. Isaacson notes: “Here’s a test. All of us have looked at birds in flight, but have you ever stopped to look closely enough to see whether a bird moves its wing upward at the same speed as it flaps it down? Leonardo did….”

Leonardo had the ability to draw upon everything he knew with anything he did. This was one of the things that made him such a fascinating subject for Isaacson, who writes, “I embarked on this book because Leonardo da Vinci is the ultimate example of the main theme of my previous biographies: how the ability to make connections across disciplines-arts and sciences, humanities and technology-is a key to innovation, imagination, and genius.” His study of light and optics shows up in his use of sfumato in painting, where objects are not defined by hard lines, but gradual shadings of tones into one another. He sees analogs between root and branch systems in plants and the human circulatory system. His anatomical studies culminate in the mysterious smile of Mona Lisa and his anatomical drawings are themselves works of art.

Isaacson also traces the peculiar genius of Leonardo, who conceives of giant cross bows, flying machines, and engineering projects, all of which are never executed. He was a path-breaking scientist who never published the results of his studies. Thankfully, even after 500 years, we still have 7200 pages of his notebooks. A number of his paintings were never “finished” and even Mona Lisa was still in his studio when he died. He abandoned commissions that he never finished. He experimented with techniques of mural painting that were spectacular failures and have challenged preservation efforts ever since.

Isaacson candidly discusses Leonardo’s personal life without becoming lurid. He covers his illegitimacy, his ambivalent relationship with his father, and his homosexuality, including his relationship with his apprentice, Salai. He traces his lifelong quest for patrons, courting the various powerful families of Florence and Milan, and ending with King Francis I of France, who, legend has it, cradled the head of Leonardo in his death throes (a legend that has been questioned).

The author concludes with lessons from Leonardo’s life, some that run through this review. Even if you don’t buy this book, I would encourage you to peruse these. The front cover jacket copy refers to Leonardo as “history’s most creative genius.” Isaacson’s biography makes that case, and does so with exquisite writing, typography and graphic design. This one’s a keeper!