This book is not for the faint of mind. Walter Isaacson is a great storyteller who has devoted his justly acclaimed career as a biographer to such history-changing individuals as Albert Einstein, Steve Jobs, Henry Kissinger, and Leonardo da Vinci. Now, in his new book The Code-Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, he tries to do the same with Jennifer Doudna, the engaging and brilliant University of California, Berkeley scientist who shared the 2020 Nobel Prize in chemistry with her French collaborator Emmanuelle Charpentier for discovering the inner workings of gene editing. Supported by a cast of eager and intensely competitive scientists who spanned the globe from Spain to China, Doudna and Charpentier figured out how to not only make human gene editing relatively simple but also turn it into what is, simultaneously, a hope-giving and terrifying technology.
As is typical for his work, Isaacson has done prodigious research—even learning to gene-edit himself. But perhaps his biggest challenge was that it may be easier to explain the achievements of da Vinci or even Einstein to the public than to describe the deep science that Doudna and her colleagues devoted their lives to.
The first half of the book is essentially a genetic detective story about the generations-long search to discover how genes and DNA work. But despite Isaacson’s best efforts to explain it in layman’s terms, the science is so complex it is often difficult to follow his narrative as international teams of scientists compete vigorously—yet just as often cooperate with one another—to discover the secrets behind a mysterious but naturally occurring genetic process known as CRISPR. This is the now-famous acronym for a term that explains how genes behave, but it is all but incomprehensible to anyone not schooled in genetic science: “Clustered Regularly Interspaced Short Palindromic Repeats.”
In a historic 2012 paper in Science, Doudna and Charpentier showed for the first time that thanks to CRISPR, a form of RNA processing known as the Cas9 protein can be deployed as a kind of molecular scalpel to edit DNA in an in vitro system. Using the CRISPR/Cas9 “genetic scissors,” researchers can now change the DNA of animals, plants, and microorganisms with high precision and even, if they choose, have these organisms pass it on to future generations.
Scientists can, in other words, very swiftly improve on current species or even create new ones, including new kinds of humans. And this is not science fiction; it’s what we are becoming capable of right now. In just the last few years, scores of new CRISPR start-ups have come on the scene, many started by the very scientists (Doudna among them) who helped create the technology.
As Isaacson writes, the fascinating backstory to what Doudna and her multinational colleagues accomplished began, prosaically enough, with a company selling yogurt cultures. Building on the work of predecessors like Spanish scientist Francisco Mojica—who first gave CRISPR its name—Rodolphe Barrangou and Philippe Horvath of the Danish food conglomerate Danisco sought to discover why so many yogurt cultures died, costing Danisco business. In the process, they discovered the mechanism bacteria had been using to deploy CRISPR naturally for millions, perhaps billions, of years to fight off viruses. Viruses attack cells, destroying their DNA, but a small subset of bacteria at some point began mounting defenses through processes called tracrRNA and crRNA. In other words some bacteria, through natural selection, began creating DNA sequences that duplicated the virus’s invasive DNA sequences and thereby fought them off. The bacteria genomes, on their own, had discovered a way to develop an immune response to the viruses by copying the appropriate DNA strand of the invading virus and then simply snipping away the harmful DNA with naturally occurring CRISPR/Cas9. In 2005, Danisco started using CRISPR to protect the bacterial strains that were its product.
But it was Doudna and Charpentier who, less than a decade later, figured out how the process worked and broke it down into its mechanical parts, along with other scientists such as Feng Zhang of the Massachusetts Institute of Technology, who competed with them intensely for patents on the work.
Now, with CRISPR/Cas9 nearly perfected as a practical tool, humans can do deliberately what bacteria once did naturally—and we can apply gene editing almost anywhere and to almost any living thing, including ourselves. We can deploy it for all the right reasons—to cure deadly diseases like Alzheimer’s and Huntington’s; to develop crops that resist mold, pests, and drought; and even to develop new species of mosquitoes that won’t carry malaria. As the Nobel Committee noted, “In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true.” Isaacson does a commendable job of narrating the personal struggles behind these efforts, vividly describing the rivalries and patent fights that ensued over the CRISPR tool and even, poignantly, the growing coolness between the two Nobel winners, Doudna and Charpentier, apparently over what the Frenchwoman considered to be the crass competitiveness of her U.S. partner.
Yet in the end, The Code Breaker proves somewhat disappointing in that Isaacson, a longtime science and tech geek, tends to gloss over the truly existential hazards of CRISPR. He also largely sidesteps the sociopolitical forces that are already pressing us to abuse it in scary ways.
True, Isaacson asks many of the right questions—questions that go to the fundamental issue of what it means to be human. If we seek to rid humanity of its worst diseases, will we be less interesting or accomplished as a species? Say you get rid of bipolar disorder and schizophrenia—another moving sub-theme in the book involves the struggle that DNA’s co-discoverer, James Watson, had in reckoning with his son’s schizophrenia—what might be the loss in human endeavor and accomplishment?
“To what extent does dealing with mood swings, fantasies, delusions, compulsion, mania, and deep depression help spur, in some people, creativity?” Isaacson asks. “Would you cure your child from being a schizophrenic if you knew that, if you didn’t, he would become a Vincent van Gogh and transform the world of art?” Like many other scientists, the controversial and outspoken Watson had no doubts: Of course, we have to cure it, rid ourselves of it for all time. It is far worse to inflict such agony on ordinary people than to sacrifice future van Goghs.
And what of grieving parents who have lost children because of hereditary diseases? Doudna herself explains this was the key factor in her gradual acceptance of “germline” or inheritable editing (by which male sperm and female eggs are modified to pass on traits forever to future generations). In the beginning, Doudna was frightened by the implications of what she had created, waking from a nightmare at one point in which she dreamt she had met Adolf Hitler, who pressed her for answers about her technology, no doubt to create his master race. “Have we created a toolbox for future Frankensteins?” Doudna thought to herself. But she became increasingly moved by the stories of families who had lost young children to inherited genetic diseases. As a parent herself, Doudna said, “My heart broke. … I feel that I would want to have that choice to make about my own health or own family’s health as these technologies came along.”
These may be the hardest ethical questions of our time, but they require a book more profound than Isaacson’s to address them. In his eagerness to get back to the scientific narrative, Isaacson glides rather too glibly over existential issues that are already emerging.
It’s not that Isaacson doesn’t understand many of the implications. “One odd result of allowing super-enhancements could be that children will become like iPhones: a new version will come out every year with better features and apps. Will children as they age feel that they are becoming obsolete?” Isaacson writes. “Fortunately, these are questions we can ask for amusement but not for an answer. It will be up to our grandchildren to figure these out.”
Uh, not quite. We are already figuring them out, and the answers aren’t always amusing. Already we can see two big trends: a gathering impulse toward the self-eugenization of the species and a global trend of inequality that may already be pointing the way to an unsettling, possibly dystopian, future. As Isaacson points out, this is not the future of Brave New World and other dystopian science fiction where the government takes control, nor is it a new kind of Nazi-controlled eugenics in which the weak and unintelligent are weeded out per the regime’s orders.
No, what we face is far more challenging. Evil governments like the Nazis can be overthrown; individual human ambition cannot. And in a supreme irony, the worst threat may come not from genocidal monsters like Hitler but from those who embrace the highest human virtues: love and compassion of the kind that Doudna expresses as she gradually drops her opposition to germline gene editing. Such techniques should be used only to cure inheritable diseases, Doudna insists in one of her many interviews with Isaacson. But realistically, who is going to stop there? If you can locate the chromosome for Alzheimer’s disease to halt memory loss, then why not seek to enhance memory? If you discover what causes physical deficiencies, then why not edit in stronger physical capacity? Similar attempts to permanently fix genetic dispositions to diseases like breast cancer and cystic fibrosis could lead to important discoveries about the reversal of aging.
Indeed, CRISPR comes along at a time when we may be witnessing a titanic convergence of trends that could forever change human destiny. At the very moment technology is becoming capable of creating better human beings, the same markets that produced this technology are creating their own demand—in the hands of the elites, the much-despised “one percent,” who have come to own most of the world’s wealth. And once they accumulate their fill of pleasure domes and hot cars and private jets and yachts—not to mention self-improvement through cosmetic surgery—what is left for these elites to covet but a better brand of humanity? In an era when well-advantaged parents are already desperately buying college acceptances and fake entrance exam results for their children, what might happen with such new technologies available? If one believes one’s future children might be competitively disadvantaged by genetic enhancements in their peers, would such a parent burden their progeny with the drawbacks of being “natural,” a mere random product of evolution’s genetic lottery? Is it even ethical for a parent to do so? In the end it may be much more parentally responsible to purchase a handy cerebral augmentation for one’s baby—if one can afford it. And the one percent, well, they can afford anything.
Oh, sure, no one will be happy about it. As they do now with influence peddling, bribes, and huge donations to the schools they want their children to get into—if you haven’t already, be sure to read The Price of Admission: How America’s Ruling Class Buys Its Way into Elite Colleges, the 2006 book by the Pulitzer Prize-winning reporter Daniel Golden—the super-rich will say, “Yeah, we know it’s not right, but if everyone else does it, you have to play the game.” And what sorts of human beings exactly will they be creating? After all, scientists are likely to locate the genes that contribute to human intelligence far sooner than they discover the ones for virtue and humility.
In the end, just what Doudna and her colleagues have let out of the lab remains to be seen, and the answers to all these questions might, as Isaacson says, await another generation or two. They certainly will require another book than this one, as impressive an accomplishment as it is.
