The Big Question: Is the Promise of Gene Editing Worth the Risks?
(Bloomberg Opinion) -- This is one of a series of interviews by Bloomberg Opinion columnists on how to solve today’s most pressing policy challenges. It has been condensed and edited.
Timothy Lavin: Clustered regularly interspaced short palindromic, or CRISPR, may prove to be one of the most significant discoveries of the century. By allowing scientists to “edit” the human genome, CRISPR is already helping to treat certain heritable diseases and may one day cure them entirely. But it might also allow parents to select genetic traits for their children, from hair color to intelligence, or prove to be a powerful weapon in the wrong hands.
You’ve written several biographies of great innovators, from Leonardo da Vinci to Steve Jobs. Your latest book, “The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race” tells the story of the scientists and researchers rushing to understand this system — most notably Jennifer Doudna, a biochemist and Nobel Prize winner, who was among the first to recognize that CRISPR could be used as a tool to easily edit an organism’s DNA. What drew you to writing about this subject?
Walter Isaacson, author, “The Code Breaker”: I’ve always been interested in innovation revolutions, starting with Albert Einstein and the physics revolution, and then the digital revolution, which I examined through “Steve Jobs” and “The Innovators.” And I realized that the driver of innovation for the first half of this century was going to be the life-sciences revolution.
So I started hanging out with the people who were involved in genetic editing and other biotech fields. And the more I got to know Jennifer Doudna, the more I realized she would be a great central character because she touched on every aspect of the revolution. She figures out the structures of RNA, and RNA turns out to be this miracle molecule that not only serves as a guide for gene-editing tools, such as CRISPR, but also as a messenger that allows us to make vaccines against things like the coronavirus. And it struck me that all these things can be recoded now, and that molecules have become the new microchip.
TL: You write that “figuring out if and when to edit our genes will be one of the most consequential questions of the 21st century.” Do you think that the full significance of this tool has started to dawn on policy makers?
WI: When the Chinese scientist He Jiankui created twin girls by editing their embryos in 2018, that was a wake-up call that this technology could be used not simply to treat diseases in patients, but to create designer children, or “CRISPR babies.” There were some congressional hearings on it, but I don’t think society as a whole has begun to discuss the question of when it would be right to edit our genes and when it goes too far. That’s one of the reasons I wrote the book. I also wrote it because I think this is an exciting prospect and not just a scary one, and I wanted people to understand how useful these tools will be.
TL: You mention the potential, for instance, to treat sickle-cell disease. Are there other uses for it that seem especially promising to you?
WI: Actually a woman was treated for sickle cell just recently by editing her genes using CRISPR. And there are dozens of simple genetic flaws that are already being fixed in clinical trials. I think the next wave of diseases will be things like Tay-Sachs or muscular dystrophy or cystic fibrosis, things that are simple genetic flaws. CRISPR is also being applied to the fight against cancer by helping to edit our immunotherapy systems. So, in the next five years, I think you’ll see many more applications of these treatments.
TL: A formative experience for Doudna was reading James Watson’s “The Double Helix,” about discovering the structure of DNA. I was struck by a line in his book, in which he says: “science seldom proceeds in the straightforward logical manner imagined by outsiders. Instead, its steps forward (and sometimes backward) are often very human events in which personalities and cultural traditions play major roles.” It seems to me like that was very much the story of CRISPR.
WI: Yes. CRISPR began as a pursuit of pure curiosity. Why do bacteria have these clustered repeated sequences in their genome? And eventually it was discovered that this is a way they fight viruses, by remembering which viruses have attacked them, and then being able to cut them up if they attack again. That becomes a useful tool when people like Doudna figure out how to repurpose the system to cut our own genes in any place we target. So sometimes the pursuit of basic science leads to unexpected places and produces unforeseen technologies. Science moves in starts and fits but there are certain people that push the frontiers forward. And Doudna, along with 20 or so other people in my book, are the colorful characters who have been doing that.
TL: Steve Jobs makes a few appearances in the book as well, including his famous ode to troublemakers and misfits. I was struck by the number of characters in the story who seemed to be outsiders in some sense, including Doudna herself. Why do you think that is?
WI: I’ve always noticed that there’s some correlation between curiosity and feeling like an outsider. That was true of Leonardo da Vinci, who was born out of wedlock and gay and left-handed, and always asking, Well, how do I fit in? And of course, it was true of Albert Einstein and Steve Jobs. Doudna grew up in Hawaii, as a lanky girl from the mainland, in a small town where all the other students were of Polynesian descent. She told me she always felt like an outsider and kept asking, How do I fit into things? And I think all of us feel like outsiders at times. We should use that feeling to spark our curiosity about the world around us and to ask how we fit in.
TL: At one point, you chronicle some slightly unseemly efforts to patent and commercialize these discoveries. And you quote one of Doudna’s colleagues, who says: “We see with CRISPR the toxic effects of turning academic institutions into money hungry hawkers of intellectual property.” Do you agree with that sentiment?
WI: I think that the patent wars over CRISPR were too bitter. And in some ways, fighting over intellectual property has harmed the collegial and collaborative nature of science. But to some extent, that balance was restored when the pandemic hit. In the book, I show how Doudna’s team and their rivals both turned their attention a year ago to fighting Covid-19. And in doing so, they were very open about sharing the discoveries they were making in real time and not asserting patent protection for any of them, so that others could build on their work. I think it was a reminder that science can and should be a noble pursuit, in which helping humanity is the main goal.
TL: Much of the book wrestles with the ethical implications of using CRISPR to edit human genes. You draw a distinction between fixing abnormalities (like eliminating a disease) and making enhancements (like improving your child’s IQ). Why do you think that distinction is so important?
WI: I think that before we mess with Mother Nature, we need to have a good reason to do so. And if something is medically necessary, in order to prevent someone from leading a challenging life or facing an early death, then we want to go down that road. But if it’s simply to make our children have the hair color we want or the height we want or have more muscles, that’s not medically necessary. Plus, it carries the danger of allowing rich people to buy better genes for their children, which would mean that the inequalities in our society would not only be widening, but they’d be encoded into the species — the way you read about in “Brave New World” or you see in the movie “Gattaca.” That’s a dystopian future.
TL: At one point, Doudna has a nightmare in which Adolf Hitler, appearing with a pig’s face, says to her: “I want to understand the uses and implications of this amazing technology.” What do you think caused her to be more concerned about the ethical implications of her own work?
WI: Her thinking evolves as the book progresses, and so does my mine. Initially, like most people, we recoiled at some uses of gene editing. But Jennifer found in many of her talks about CRISPR that people would come up to her at the end and show her a picture of their daughter, and say, “They tell me she’s gonna die in three years from this genetic condition she has, can you save her?” Even since I’ve published this book, I’ve gotten emails from people telling me about some horrifying problem that their family faces because of a genetic condition, and asking me to put them in touch with Doudna. So you can’t simply ask if it would be immoral to use this technology. You also have to ask: Would it be immoral not to use it?
TL: At one point in the book you wonder what Van Gogh would’ve been like without bipolar disorder, or Miles Davis without sickle cell disease. Do you buy the argument that something ineffable might be lost when we start eliminating or reducing certain human difficulties?
WI: Yes. As we eliminate human difficulties, things are lost in terms of forging character. Franklin Roosevelt was forged by polio. He probably would’ve been a less-than-successful playboy had he not gained the empathy and humility that came from having polio. That said, we don’t get rid of polio vaccines in the hopes that our children will become Franklin Roosevelt. Likewise, sickle cell anemia drove Miles Davis to drugs and drink and maybe to his death. But it also drove him to produce “Bitches Brew” and “Kind of Blue,” the greatest jazz albums you can imagine. So there will probably be something lost. However, we’ll also lose the horrible suffering and pain that the diseases cause. It’s a trade-off that we should be discussing. But personally, I think it’s a trade-off worth making.
TL: Do you think that there are aspects of this technology that should be regulated?
WI: Yes, and I think they will be. With an international consensus on what type of gene editing should be allowed, we should be able to control, to a large extent, how this technology progresses. And I’d start by saying that we should approve gene editing when there’s a medical need and pause on approving it when it’s simply for pure enhancement purposes. I also think it’s easier to approve it when you’re talking about a living patient who can give consent rather than in reproductive cells and embryos that will produce children who will pass on the edits to all of their descendants. So those are the kinds of guidelines we should start looking at.
TL: You note that, in 2016, the director of national intelligence for the first time categorized genome editing as a potential weapon of mass destruction. The report cites the technology’s “broad distribution, low cost and accelerated pace of development.” Do you worry that CRISPR makes gene editing too easy?
WI: CRISPR makes it very easy to gene edit, and to quickly reengineer the tool to make different edits. And that’s why the Defense Department has been providing funding to Doudna’s lab and others to produce what’s called anti-CRISPR — or ways to reverse the effects of CRISPR if some malevolent actor or enemy country decides to create, say, super mosquitoes that can spread pathogens or super-infectious agents of some kind. It’s a good idea.
TL: You profile the so-called biohacker Josiah Zayner at one point. And you say: “his dream is that millions of people around the world will take up amateur bioengineering.” I found the idea kind of horrifying, but you also thought that there might be benefits to spreading this technology a bit more broadly.
WI: The digital revolution came to be largely because of things like the Homebrew Computer Club: Bill Gates and Steve Jobs and Steve Wozniak and others who took the power of microprocessors into their own hands and made personal computers and other things. And so I like the notion that science can be pushed forward by ordinary citizens on the cyber frontier or the biotech frontier. Zayner in my book pops up often in the narrative, the way Puck does in “A Midsummer Night’s Dream,” sort of smiling and saying, “What fools these mortals be.” And as Jobs would say, people like him push the human race forward. The people who are crazy enough to think they can change the world are the ones who do. So I’m hopeful that more people will feel more connected to biology in the future. At the same time, we certainly need safeguards against people performing biotech procedures in their garage.
TL: Toward the end of the book, you try gene editing yourself. Did you have the sense that you were engaged in something momentous or profound while you were doing it?
WI: No, actually. I was working with two graduate students, using a pipette, putting solutions in test tubes and then looking at the imaging of what resulted and noticing that cells had been edited. It wasn’t like some cauldron where all of a sudden, life is bubbling forth. It was rather undramatic. And afterward, we carefully mixed whatever I did with a lot of chlorine and washed it down the drain to make sure none of my edited cells became part of life on this planet.
This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.
Timothy Lavin writes editorials on technology and politics and has been stationed in Hong Kong, London and New York. He was a senior editor at the Atlantic.
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