★★★☆☆ I am not the target market for this book.
The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race
Walter Isaacson
The first thing that struck me as I began reading The Code Breaker was "I know these people!" Note 6 in chapter 4 ("The education of a biochemist") especially brought this home to me:
6. Sharon Panasenko, “Methylation of Macromolecules during Development in Myxococcus xanthus,” Journal of Bacteriology, Nov. 1985
I knew Sharon Panasenko. She and I overlapped in the close-knit Stanford Biochemistry Department, and after she left we were both members of the small community of myxobacteria researchers. It is even possible that I met Jennifer Doudna around this time, when I was a Stanford grad student and she a Pomona College chemistry undergrad in Sharon's lab. The book is full of names familiar to me, known to me by reputation or in a few cases personally. The only major player in the CRISPR story I know personally is Eric Lander. (By "know personally" I mean we worked in the same lab and had multiple conversations.) But I also know several of the minor players and have met and spoken with many of the older participants.
Doudna (whom I have never met) seems a quite familiar type of scientist to me. Although she is clearly an extraordinary biologist, there are hundreds of extraordinary biologists, and Doudna is extraordinary in an ordinary way -- that is, she is extraordinary in the same way that most extraordinary biologists are extraordinary. The best short description of her comes from her PhD mentor Jack Szostak, “Jennifer was fantastically good at the bench, because she was fast and sharp and could seemingly get anything to work,” Szostak says. “But we talked quite a bit about why the really big questions are the important questions.”
Let's dispose of the "big questions" cliche. Isaacson recounts the following:
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.
"Ask big questions" is a cliche among scientists. I have heard versions of it hundreds of times. It is like a Disney Princess saying "True Love conquers all" or a coach in a Hollywood sports movie saying "You can do anything if you put your mind to it." It is not evidence of deep thought, but rather the opposite.
What's more, it is, like the Hollywood examples, problematic. The injunction to "ask big questions" mistakes the goal for the path. Clearly you want to ANSWER big questions. (And, to give credit where it's due, Szostak is one who has done that.) It is natural to think that the way to answer big question is to ask big questions. Natural but wrong. The way to answer big questions is to ask little questions. Isaacson gives several examples, from Darwin asking "What birds live on the Galapagos Islands?" to Mendel's pea-breeding hobby. And the CRISPR story is a prime example of asking little questions. Who could forget the yogurt microbiologists? I could easily give dozens of examples from the history of science and mathematics, but you're already bored.
What Doudna is is "fantastically good at the bench, ... fast and sharp and [able] seemingly [to] get anything to work". She's a top-notch bench scientist. That is the ordinary way for an extraordinary biologist to be extraordinary.
It seems obvious to me that Isaacson chose to present Doudna this way. As he tells us early in the book, he wants to reveal some truths about how science is really done. Among these truths is that the myth of the hero-scientist is wrong and pernicious. (He doesn't say that in so many words -- this is my surmise.) Could Isaacson have written Doudna as a hero scientist? Well, what do you think? Isaacson is an accomplished biographer, who has written biographies of Einstein, Da Vinci, and Franklin. Could he have written a hero story for Doudna?
Of course he could. Hero-scientist stories persist not because they are true, but because they are entertaining. Isaacson wants us to know that biological research is a collective endeavor, and that you grossly misunderstand it if you make the players solitary heroes. In fact, as he writes later of a conversation at a CRISPR conference.
“Is there any field that is more cutthroat and competitive than biological research?” one of the participants asks me after Zhang and Sternberg give their dueling talks. Well, yes, I think, almost every field can be, from business to journalism. What distinguishes biological research is the collaboration that is woven in. The camaraderie of being rival warriors in a common quest suffuses the Quebec conference.
He is right!
The first quarter of the book describes how Charpentier and Doudna figured out CRISPR, culminating in the June 2012 paper. This is the best part of the book. After that we get into tedious wrangling when competitors leapt onto the discovery to develop methods for gene editing in humans. (For what it's worth, I personally am convinced that the Nobel Committee was right in giving credit to Doudna and Charpentier. After their work the applications were obvious and required no extraordinary tricks.) Doudna has a problem with private-sector work -- as recounted in the book, she twice had to give up participation in commercial research because it literally made her sick.
After the silly wrangling about credit for applications, we have two major sections of the book left: ethics and Covid. The ethics of gene editing is not a new question. I appreciated that Isaacson made an effort to present the question thoughtfully, without the performative appeal to rhetorical hysteria that contaminates so much of this discourse. On the other hand, if you have been following the question over the years there is nothing new in his discussion.
Covid doesn't really make sense as a part of the story Isaacson set out to tell. I have the feeling that when the pandemic struck Isaacson's journalistic instincts kicked in. Finding himself with extraordinary access (because of his work on the biography) to two labs that were mounting responses to Covid, he couldn't resist the temptation to report on it. But I have followed the technical side of the Covid story very closely since January 2020 and I'm bored with it.
So, that explains my headline. There were large parts of the book I didn't much appreciate because of who I am and what I already know. Others might enjoy it more.
I will say one thing for Isaacson: he gets stuff right. Although he necessarily simplifies the science at times, I never caught him doing it in a way that would cause serious misunderstanding. That is a rare thing in science popularization.