The Code Breaker by Walter Isaacson review – a science page-turner
One of the most striking passages in Walter Isaacson’s new book comes towards the end. It is 2019 and a scientific meeting is under way at the famous Cold Spring Harbour Laboratory in New York State, but James Watson, the codiscoverer of the structure of DNA, is banned from it because of the racist and scientifically unfounded views he has expressed on intelligence. Isaacson, who is to interview Watson, therefore has to make his way to the house on the nearby campus that the scientist has been allowed to keep. When the conversation sails dangerously close to the race issue, someone shouts from the kitchen: “If you are going to let him say these things, then I am going to have to ask you to leave.” The 91-yearold Watson shrugs and changes tack.
The voice from the kitchen belonged to Rufus, Watson’s middle-aged son who suffers from schizophrenia. “My dad’s statements might make him out to be a bigot and discriminatory,” he once said. “They just represent his rather narrow interpretation of genetic destiny.” In many ways, Isaacson observes, Rufus is wiser than his father.
Genetic destiny is a central theme of The Code Breaker, Isaacson’s portrait of the gene-editing pioneer Jennifer Doudna, who, with a small army of other scientists, handed humanity the first really effective tools to shape it. Rufus Watson’s reflections encapsulate the ambivalence that many people feel about this. If we had the power to rid future generations of diseases such as schizophrenia, would we? The immoral choice would be not to, surely? What if we could enhance healthy human beings, by editing out imperfections? The nagging worry – which might one day seem laughably luddite, even cruel – is that we would lose something along with those diseases and imperfections, in terms of wisdom, compassion and, in some way that is harder to define, humanity.
Doudna contributed to the identification of Crispr, a system that evolved in bacteria over billions of years to fend off invading viruses. Crispr-Cas9, to give it its proper name, disarms viruses by slicing up their DNA. Bacteria invented it, but the insight that won Doudna – a biochemist at the University of California, Berkeley – the Nobel prize in chemistry last year, along with French microbiologist Emmanuelle Charpentier, was that it could be adapted to edit genes in other organisms, including humans. The paper that sealed the duo’s fame was published in 2012, when Charpentier was working at Umeå University in Sweden. By the beginning of 2020, two dozen human trials were under way for medical applications of the technique – for conditions from cancers to atherosclerosis to a congenital form of blindness.
The Crispr story is made for the movies. It features a nail-biting race, more than its fair share of renegades, the highest prize in chemistry, a gigantic battle over patents, designer babies and acres of ethical quicksand. It presents a challenge to a biographer, however, who has to pick one character from a cast of many to carry that story. Isaacson chose Doudna, and you can understand why. Having helped to elucidate the basic science of Crispr, she remains implicated in its clinical applications and in the ethical debate it stimulated – unlike Charpentier, who has said that she doesn’t want to be defined by Crispr and is now pursuing other science questions. Doudna is the thread that holds the story together.
Still, you can’t help wondering how that story might have read if it had been told from the point of view of Francisco Mojica, the Spanish scientist who first spotted Crispr in bacteria inhabiting salt ponds in the 1990s. He intuited that it did something important, then doggedly pursued this line of research despite a lack of funding and the fact that everyone told him he was wasting his time. A different story again might have been told via the two French food scientists who realised in 2007 that Crispr could be harnessed to vaccinate bacteria against viruses, thus securing the future of the global yoghurt industry, or the Lithuanian biochemist Virginijus Šikšnys, who moved the story on again, but whose work was rejected by top journals.
Each one made an essential contribution, and it’s difficult to say whose, if any, was the most important. A similar dilemma preoccupied Carl Djerassi and Roald Hoffmann in their 2001 play Oxygen, which asked who should receive a “Retro-Nobel” for the discovery of the eponymous gas. Should it go to the scientist who discovered oxygen but didn’t publish his discovery, the one who published but failed to understand the discovery’s significance, or the one who grasped its significance but only thanks to the insights of the other two?
Focusing on Doudna also paints the Crispr story as more American than it was. Doudna herself acknowledged its international dimension, in her own account, A Crack in Creation (2017). “All told, we would be quite the international group,” she wrote of the team that produced the seminal 2012 paper, “a French professor in Sweden, a Polish student in Austria, a German student, a Czech postdoc, and an American professor in Berkeley”. The fact that her Czech postdoc and Charpentier’s Polish student had grown up close to each other – either side of a border – and that both spoke Polish, reinforced the group’s synergy and sped the writing of the paper.
It was precisely because so many people contributed, and because they disagree about the significance and primacy of their contributions, that they remain entangled in a row over ownership. The Crispr revolution owes a great deal to America and the premium it places on creativity and innovation, but as with so many scientific breakthroughs, there was an element of convergence – of people independently and more-or-less simultaneously arriving at the same insight. (Isaacson suggests radar and the atomic bomb were American inventions too, but radar was developed in many countries in the run-up to the second world war, while European refugees from that war helped build the bomb.)
It’s not only the discovery process that is collective. As soon as a discovery is made public an even wider circle of people will apply it, and they may not have the same priorities. It’s easy and right to condemn Chinese maverick He Jiankui for editing the genes of twins Lulu and Nana, supposedly to protect them from HIV infection, but in his impassioned reply to Doudna’s criticism of his act there seems buried a grain of truth. “You don’t understand China,” he told her. “There’s an incredible stigma about being HIV positive, and I wanted to give these people a chance at a normal life ...” Genetic destiny means different things to different people, as Rufus Watson understands.
Isaacson, who is best known for his lives of Steve Jobs and Leonardo da Vinci, remains a consummate portraitist. He captures the frontier spirit of Harvard geneticist George Church in an anecdote about how, when Church was a child, his physician stepfather let him administer hormone injections to his female patients (Church has been testing experimental Covid-19 vaccines on himself lately). Isaacson also has a privileged vantage point, knowing the Crispr backstory and the personalities that shaped it. In 2000, as editor of Time, he put the two men leading competing efforts to sequence the human genome – Francis Collins and Craig Venter – on the cover. He understands the tensions that drive discovery and how flawed brilliant people can be. This story was always guaranteed to be a page-turner in his hands. It’s just that science has outgrown biography as a medium. His subject should have been Crispr, not Doudna.
Isaacson understands the tensions that drive discovery and how flawed brilliant people can be