Walter Isaacson

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

Walter Isaacson's The Code Breaker is as interesting as a book — as an object in your hands — as anything in its contents. Conceived long before the arrival of COVID, the story that Isaacson planned to tell, one of competition between molecular biology labs in the development of an amazing new diagnostic tool, was transformed by the global health disaster from a report on the recent past into a dispatch from right now — from the day after tomorrow, almost. For the amazing new diagnostic tool was not only applied to the new virus itself as a diagnostic tool but, more amazingly still, exploited as the basis of vaccines to defeat it.

Or, we might say that Walter Isaacson's reasonable expectations of spending a big part of 2020 on a book tour to promote Code Breaker were completely upset by the urgency of capturing the latest developments in a closely-related sequel. The Code Breaker is a book with an earthquake in the middle of it. This irruption of the virus puts an end to the story that Isaacson was telling; what follows is a miscellany of news flashes and reflections. And yet, in spite of all the excitement, the book's real story, the one narrative aspect that promises something more engaging than a magazine article, can only be sketched from a distance.

That story is about the relationship between Jennifer Doudna, an affable, capable, and competitive American woman who happens to be a scientist, and Emmanuelle Charpentier, a French scientist of equal or superior talent who happens to be a woman. Together, they won last year's Nobel Prize for chemistry. I am not interested in judging one of them to be more remarkable than the other; their fruitful collaboration around the year 2012 owed everything, I think, to the intelligent way in which they harnessed their differences. At one point, Isaacson calls Charpentier "mysterious"; he also describes her as "chic" — one thinks of Glenn Close discussing scarves in Le Divorce. A more important difference between Doudna and Charpentier lies in their relation to institutions, groups, and geography. Once settled at Berkeley in 2002, Doudna and her lab became figures in a metaphysical landscape whose antipode would be Cambridge, Massachusetts. Charpentier, in contrast, has been a maverick, moving about as if she were determined to pollinate every major research institution in the world. Isaacson does not make much of it, but the two women also appear to have strongly different ideas about tooting one's own horn. Their relationship, while it lasted, was productive rather than exciting, but instead of coming to an end in some misunderstanding or other, it simply faded away. Isaacson is not to be faulted for failing to make the most of this working friendship. It is probable that, it they tried to tell their own story, Doudna and Charpentier would do no better. Perhaps only a novelist could do it justice, but that would be fiction and not history.

Isaacson, of course, is a journalist — a former editor of Time Magazine. I have not read any of his other books, four of which are packaged together as "The Genius Biographies" (Leonardo, Franklin, Einstein, and Steve Jobs). The problem with books about geniuses is that they are necessarily addressed to lesser mortals. How do we ordinary folk assess a great mind's achievements and their consequences? How can we be sure that the alleged geniuses are so much smarter than the people around them? And, as the example of Steve Jobs forces us to wonder, what exactly was the achievement? Even without reading any biography, I am fairly certain that Jobs was a brilliant packager/marketer: working backward from potential desires of which the general public was unaware, Jobs sponsored the development of products that would gratify them. As astonishing as the smart phone might be for most of us, its great success was not a surprise to its developer. Far from reminding me of conventional scientists, Jobs appears most to resemble Alfred Hitchcock, "conducting" the audience reaction to Psyscho while standing alone in the theatre lobby. The means by which these men commanded their admirers seems almost beside the point.

We might at this juncture ask, what distinguishes journalism from history? Because Isaacson, too, seems to work backward. He knows his readers. Specifically, he knows how much information about "science" he can ask a lay audience to swallow. He understands that readers must be made to believe that they understand what he is talking about, when the odds are that they can't possibly do anything of the kind, even in the unlikely event that they want to. What they want — and it is the whole purpose of journalism to gratify this desire — is to "know something" about a matter of public, perhaps even of world-historical concern, in this case the manipulation of genetic information in the struggle against disease and birth defect. There can be no doubt that this manipulation has opened an entirely new highway on the terrain of human capability. Many civilians may harbor misgivings about the haste with which the Moderna and Pfizer vaccines were created and made available to the public; it used to take a long time, much longer than a year, to produce a viable vaccine. (A vaccine for HIV has yet to be invented.) Working faster, however, had little to do with the COVID vaccines. It was a matter of working entirely differently, exploiting technologies less than ten years old. This is the story that Isaacson expects, quite reasonably, to grip his readers, and it is a testament to his journalist virtuosity that he can convey the gist of it to readers who would, no matter how smart, be paralyzed by the basics of x-ray crystallography.

The star of The Code Breaker is the code itself: the special bacterial genetic code that we now call CRISPR. Never mind what the acronym stands for; it's more than enough to digest the surprising news that bacteria encode their immunities in their DNA, apparently as a matter of course. A bacterium that has survived attack by a new virus will transcribe a portion of the virus's DNA onto its own DNA, in the form of a CRISPR, thus not only "remembering" it but also conferring immunity on all bacteria descended from it. This fantastic ability appears to be limited to prokaryotic life (bacteria, archaea); eukaryotic organisms — plants, animals, fungi; all the kinds of life that we can see — are not similarly blessed. Undetected, CRISPRs did their work for billions of years. No sooner did humans discover them, however, than they learned how to alter them so as to use them to edit genes of any kind. Just how the CRISPR mechanism works is the discovery for which Doudna and Charpentier were awarded the Nobel Prize. (Hint: Think RNA, not DNA.)

But the work leading up to this discovery was done by many different people, and, in the final stretch, Doudna and Charpentier were racing against competition from the Broad Institute in Cambridge. The story of this competition, and how it led to patent litigation, provided Isaacson with a climax until it was upstaged by COVID. Even by this point, however, I was wondering why Isaacson put Jennifer Doudna's name at the head of his subtitle. It's unlikely that I'd have bought the book otherwise. (The parade of manly change agents constituting Isaacson's earlier work was hardly an attraction.) Doudna was not only a woman but an unknown woman, arguably someone who, like Rosalind Franklin, the notoriously overlooked crystallographer without whose photographs Watson and Crick might never have cracked DNA, deserved wider renown. The reviews unanimously presented her as an attractive human being. I must confess that I fell for the appeal of a nice lady doing major sicence and becoming famous, if only in her own milieu, for doing so.

Although Doudna emerges from Isaacson's handling as just such a woman, she does not hold the spotlight. Yes, she did the work with Charpentier that won the prize, and she had done important work before that. But her role in this book seems more the result of Isaacson's dependence on the luster of isolated geniuses, among whom I doubt Doudna will ever be counted. No one will claim that everyone who has ever won a Nobel Prize in science or math is a thinker on the level of Albert Einstein, and I don't think that in the privacy of his own mind Isaacson inflates Doudna's importance. But his shtick, one fears, requires a singular, outstanding figure. I've already said that it's CRISPR itself that is the star of the book, but Isaacson is too much the journalist to expect his readers to admire, much less to identify with, a string of proteins. His need to put a single human being at the center of this story distorts it. It certainly Disneyfies it. The Disney people would have no reason to edit any of Doudna's quoted remarks, which I found to be disappointingly anodyne.

CRISPR's co-stars, moreover, are institutions, not individuals. It's fashionable to hold that institutions — corporations especially — are made up of actual people, some of whom, perhaps, ought to be held personally accountable for institutional missteps. I wholeheartedly agree. But in a successful institution, individual people deform themselves creatively. They leave their personal problems at home (ideally) and specialize at work in the demonstration of a few highly-developed skills. Successful institutions are vastly more powerful than any individual human being can dream of being — just ask Napoleon or Morgan. Precisely because few if any employees of an institution act professionally as interesting, fully-developed human beings, institutions are hard to write about. (They would probably be absolutely impossible to write about without the hostility of colleagues.) And even when two or more institutions profess to pursue the same ends, they develop, inadvertently or otherwise, differences that are not always insignificant. Another difference between history and journalism is that historians can alter their point of view, looking now closer, now from a greater difference. They can explain, as no mere journalist really can, the difference, say, between Oxford and Cambridge, or the difference between Italy and France — differences that cannot be traced back to specific, photographable individuals. And it is for this, along with other self-inflicted limitations, that journalism is doomed to be a kind of entertainment, and not one of the humanities.

— 23 April 2021

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