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

by Walter Isaacson

The first half of the twentieth century, beginning with Albert Einstein’s 1905 papers on relativity and quantum theory, featured a revolution driven by physics. In the five decades following his miracle year, his theories led to atom bombs 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.

The paths that led Watson and Crick to the discovery of DNA’s structure were pioneered a century earlier, in the 1850s, when the English naturalist Charles Darwin published On the Origin of Species and Gregor Mendel, an underemployed priest in Brno (now part of the Czech Republic), began breeding peas in the garden of his abbey. The beaks of Darwin’s finches and the traits of Mendel’s peas gave birth to the idea of the gene, an entity inside of living organisms that carries the code of heredity.

Darwin was hesitant to publish his theory because it was so heretical, but competition acted as a spur, as often happens in the history of science. In 1858, Alfred Russel Wallace, a younger naturalist, sent Darwin a draft of a paper that proposed a similar theory. Darwin rushed to get a paper of his own ready for publication, and they agreed that they would present their work on the same day at an upcoming meeting of a prominent scientific society.

As a middle-class Chicago boy breezing through public school, James Watson was wickedly smart and cheeky. This ingrained in him a tendency to be intellectually provocative, which would later serve him well as a scientist but less so as a public figure. Throughout his life, his rapid-fire mumbling of unfinished sentences would convey his impatience and inability to filter his impulsive notions. He later said that one of the most important lessons his parents taught him was “Hypocrisy in search of social acceptance erodes your self-respect.” He learned it too well. From his childhood into his nineties, he was brutally outspoken in his assertions, both right and wrong, which made him sometimes socially unacceptable but never lacking in self-respect.

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.

Szostak had a guiding principle: Never do something that a thousand other people are doing.

Szostak’s excitement about discovering how life began taught Doudna a second big lesson, in addition to taking risks by moving into new fields: Ask big questions. Even though Szostak liked diving into the details of experiments, he was a grand thinker, someone who was constantly pursuing truly profound inquiries. “Why else would you do science?” he asked Doudna. It was an injunction that became one of her own guiding principles.

An essential quality of living things is that they have a method for creating more organisms akin to themselves: they can reproduce. Therefore, if you want to make the argument that RNA might be the precursor molecule leading to the origin of life, it would help to show how it can replicate itself. This was the project that Szostak and Doudna embarked upon.7

Their choice of Berkeley is a testament to America’s investment in public higher education. Its roots stretch back to when Abraham Lincoln, in the middle of the Civil War, thought public education was important enough that he pushed through the Morrill Land-Grant Act of 1862, which used funds from federal land sales to establish new agriculture and mechanical colleges. Among those was the College of Agricultural, Mining, and Mechanical Arts near Oakland, California, founded in 1866, which two years later merged with the nearby private College of California. It became the University of California, Berkeley, and grew into one of the world’s greatest research and learning institutions. In the 1980s, more than half of Berkeley’s funding came from the state. However, since then Berkeley, like most other public universities, has faced reductions. When Doudna arrived, state funding accounted for only 30 percent of Berkeley’s budget. In 2018, state funding was cut again, and it amounted to less than 14 percent. As a result, Berkeley’s undergraduate tuition for a California resident in 2020 was $14,250 per year, more than triple what it was in 2000. Room, board, and other fees raised the total cost to around $36,264. For an out-of-state student, total costs were around $66,000 a year.

Mojica had been corresponding with Ruud Jansen of Utrecht University in the Netherlands, who was studying these sequences in tuberculosis bacteria. He had been calling them “direct repeats,” but he agreed that they needed to come up with a better name. Mojica was driving home from his lab one evening when he came up with the name CRISPR, for “clustered regularly interspaced short palindromic repeats.” Although the clunky phrase was almost impossible to remember, the acronym CRISPR was, indeed, crisp and crispy. It sounded friendly rather than intimidating, though the dropped “e” gave it a futurist sheen. When he got home, he asked his wife what she thought of the name. “It sounds like a great name for a dog,” she said. “Crispr, Crispr, come here, pup!” He laughed and decided it would work.

Enzymes are a type of protein. Their main function is to act as a catalyst that sparks chemical reactions in the cells of living organisms, from bacteria to humans. There are more than five thousand biochemical reactions that are catalyzed by enzymes. These include breaking down starches and proteins in the digestive system, causing muscles to contract, sending signals between cells, regulating metabolism, and (most important for this discussion) cutting and splicing DNA and RNA.

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. Genentech became the model for commercializing biotech discoveries: scientists and venture capitalists raised capital by divvying up equity stakes, then they entered into agreements with major pharmaceutical companies to license, manufacture, and market some of their discoveries. Thus did biotech follow the path of digital technology in blurring the lines between academic research and business. This fusion in the digital realm began right after World War II, mainly around Stanford. With prodding from its provost Frederick Terman, Stanford professors were encouraged to turn their discoveries into startups. The companies that sprang out of Stanford included Litton Industries, Varian Associates, and Hewlett-Packard, followed by Sun Microsystems and Google. The process helped turn a valley of apricot orchards into Silicon Valley.

Competition gets a bad rap.2 It’s blamed for discouraging collaboration, constricting the sharing of data, and encouraging people to keep intellectual property proprietary rather than allowing it to be free and open for common use. But the benefits of competition are great. If it hastens the discovery of a way to fix muscular dystrophy, prevent AIDS, or detect cancer, fewer people will die early deaths.

Opposing this biotech utopianism was a group of theologians, technoskeptics, and bioconservatives who became influential in the 1970s. Princeton professor of Christian ethics Paul Ramsey, a prominent Protestant theologian, published Fabricated Man: The Ethics of Genetic Control. It is a turgid book with one vivid sentence: “Men ought not to play God before they learn to be men.”

The modern foundations for each of these perspectives was expressed in two influential books written fifty years ago: John Rawls’s A Theory of Justice, which comes down on the side of favoring the good of the community, and Robert Nozick’s Anarchy, State, and Utopia, which emphasizes the moral foundation for individual liberty. Rawls seeks to define the rules that we would agree to if we had gathered to make a compact. In order to make sure things are “fair,” he said that we should imagine what rules we would make if we didn’t know what place we would each end up occupying in society and what natural abilities we would have. He argues that, from behind this “veil of ignorance,” people would decide that inequalities should be permitted only to the extent that they result in benefits for all of society, and specifically for the least advantaged. In his book, this leads Rawls to justify genetic engineering only if it does not increase inequality.3 Nozick, whose book was a response to that of his Harvard colleague Rawls, likewise imagined how we might emerge from the anarchy of a state of nature. Instead of a complex social contract, he argues that social rules should arise through the voluntary choices of individuals. His guiding principle is that individuals should not be used to promote a social or moral goal devised by others. This leads him to favor a minimalist state that is limited to functions of public safety and enforcement of contracts but avoids most regulations or...

The reluctance to play God can also be understood in a more secular way. As one Catholic theologian said at a National Academy of Medicine panel, “When I hear someone say that we shouldn’t play God, I’d guess that ninety percent of the time they are atheists.” The argument can simply mean that we should not have the hubris to believe that we should fiddle with the awesome, mysterious, delicately interwoven, and beautiful forces of nature. “Evolution has been working toward optimizing the human genome for 3.85 billion years,” says NIH director Francis Collins, who is not an atheist. “Do we really think that some small group of human genome tinkerers could do better without all sorts of unintended consequences?”

I have no idea what’s awaiting me, or what will happen when this all ends. For the moment I know this: there are sick people and they need curing. —Albert Camus, The Plague, 1947