The Code Breaker

Walter Isaacson, “The Code Breaker: Jennifer Doudna, Gene Editing and the Future of the Human Race,” Simon and Schuster, 2021, 481 pp.

This book is essentially (Cassie would say “basically) a biography of Jennifer Doudna (pronounced DOWD-nuh) and the journey leading to editing of human genes.  Jennifer Doudna and Emmanuelle Charpentier were awarded the 2020 Nobel Prize in Chemistry for their landmark research that has lead to the potential to control future pandemics-- either by outwitting the next viral plague through better screening and treatment or by engineering human beings with better disease resistance programmed into their cells. The technique of gene editing that they patented, which goes by the acronym of CRISPR-Cas9, makes it possible to selectively snip and alter bits of DNA.

The CRISPR history holds obvious appeal for Walter Isaacson, a biographer of Albert Einstein, Benjamin Franklin, Steve Jobs and Leonardo da Vinci. In “The Code Breaker” he reprises several of his previous themes — science, genius, experiment, code, thinking different.

Jennifer Doudna, may be the code breaker of the book’s title, but she is only part of Isaacson’s story. The subtitle promises a wider reach: “Jennifer Doudna, Gene Editing, and the Future of the Human Race.” This may sound like publisher’s hyperbole, but Isaacson devotes much discussion to the ethics of gene editing, especially when it comes to “germline” changes that can be passed on through generations and “enhancements” such as green eyes or high I.Q. that prospective parents could insert into their offspring’s genomes.

 “The Code Breaker” is in some respects a journal of our 2020 plague year. By the final chapter, Isaacson has enrolled in a vaccine trial.  However, there is room in the book to explore Doudna’s childhood, trace her career, meet her competitors and collaborators, fret over the future fallout of the CRISPR revolution and marvel at its positive potential.

Fortunately for Doudna, her early reading of “The Double Helix,” by James Watson, proved formative. She breezed right past Watson’s snarky comments about the structural biologist Rosalind Franklin’s looks and took away an important message: Rosalind Franklin, a female, was a scientist; therefore Jennifer Doudna, a female, could be one, too.

Some of the most interesting sections of “The Code Breaker” detail the way CRISPR researchers rose to the Covid challenge: They developed rapid test procedures and vaccine strategies — and posted them to an open database for the benefit of the entire scientific community, spurring progress to a gallop.

Reflecting on the nature of scientific research, Isaacson lets Emmanuelle Charpentier have the next-to-last words: “At the end of the day,” she tells him, “the discoveries are what endure. We are just passing on this planet for a short time. We do our job, and then we leave and others pick up the work.”

My Notes:

Pg. xiv:  The gene-editing tool that Doudna and others developed in 2012 is based on a virus-fighting trick used by bacteria, which have been battling viruses for more than a billion years.  In their DNA, bacteria develop clustered repeated sequences, known as CRISPRs that can remember and then destroy viruses that attack them. 

Pg. xvii:  The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times.  These revolutions arose from the discovery, beginning just over a century ago, of the three fundamental kernels of our existence: the atom, the bit, and the gene.

The first half of the twentieth century beginning with Einstein’s 1905 papers on relativity and quantum theory, featured a revolution driven by physics.  In the five decades following, his theories led to the atom bomb and nuclear power, transistors and spaceships, lasers and radar. 

The second half of the twentieth century was an information-technology era, based on the idea that all information could be encoded by binary digits—known as bits—and all logical processes could be performed by circuits with on-off switches.  In the 1950s, this led to the development of the microchip, the computer, and the internet.  When these three innovations were combined, the digital revolution was born.

Now we have entered a third and even more momentous era a life-science revolution.  Children who study digital coding will be joined by those who study genetic code.

In the 1990s, Doudna became more interested in DNA's less-celebrated sibling, RNA.  RNA is the molecule that actually does the work in a cell by copying some of the instructions coded by the DNA and using them to build proteins. 

Pg. 28:  Two revolutions coincided in the 1950s.  Mathematicians showed that all information could be encoded by binary digits, known as bits.  This led to a digital revolution powered by circuits with on-off switches that processed information.  Simultaneously, Watson and Crick discovered how instructions for building every cell in every form of life were encoded by the four-letter sequences of DNA.  Thus was born an information age based on digital coding (0100110111001…) and genetic coding (ACTGGTAGATTACA……). The flow of history is accelerated when two rivers converge.

Pg. 43:  Accomplishing the goal of being able to write as well as to read human genes required a shift in focus from DNA to its less famous sibling that actually carries out its coded instructions.  RNA (ribonucleic acid) is a molecule in living cells that is similar to DNA (deoxyribonucleic acid), but it has one more oxygen atom in its sugar-phosphate backbone and a difference in one of its four bases.

Pg. 46:  There are some truly grand questions that our mortal minds may never be able to fully answer: How did the universe begin? Why is there something rather than nothing? What is consciousness? Others may be wrestled into submission by the end of this century: Is the universe deterministic? Do we have free will?  Another of the really big ones may be close to being solved: how life began (on earth). 

Pg. 59:  As RNA is a molecule made up of only four chemicals ( unlike proteins, which have twenty) and, yet, accomplishes complex tasks, Doudna correctly concluded that the different ways RNA is folded must be the key to its ability to solve complex tasks.  

Pg. 66:  RNA interference was discovered in the 1990s, partly by researchers who were trying to make petunias more purple.  RNA interference operates by deploying an enzyme known as ‘Dicer.”  Dicer sips a long piece of RNA into short fragments.  Doudna set about to discover the molecular structure of Dicer.  She hoped that drugs based on RNA interference might someday be a good option for treating severe viral infections, including those from new coronaviruses.

Pg. 113:  For much of the twentieth century, most new drugs were based on chemical advances.  But the launch of Genentech in 1976 shifted the focus of commercialization from chemistry to biotechnology, which involves the manipulation of living cells, often through genetic engineering, to devise new medical treatments. 

Pg. 115ff:  In October, 2011, Doudna and Haurwitz, while at Berkeley, founded a company they named Caribou Biosciences: the name is a cut-and-splice mash-up of “Cas” and “ribonucleotides,” which are the building blocks of RNA and DNA.  Their initial aim was to turn Cas6 into a diagnostic tool that clinics could use to detect the presence of viruses in humans.

Pg. 117:   Note: After WWII Vannevar Bush argued that America’s innovation would require a three-way partnership of government, business, and academia.  He recommended that government should not build big research labs of its own, as it had done with the atomic bomb, but instead should fund research at universities and corporate labs.  This government-business-university partnership produced the great innovations that propelled the US economy in the postwar period, including transistors, microchips, computers, graphical user interfaces, GPS, lasers, the internet, and search engines.  Doudna’s company followed this pattern, adding another philanthropic leg when Bill Gates donated.