Sat. Oct 1st, 2022
3d render of DNA spirals.

3d render of DNA spirals.

According to Walter Isaacson, three great technological revolutions have shaped the modern world, based on three fundamental nuclei of human existence: the atom, the bit and the gene. After exploring the physics revolution through the eyes of Einstein and the digital revolution through Apple’s supreme leader, Steve Jobs, the best-selling biographer thought it was time to turn to DNA. It’s no surprise, then, that he chose Jennifer Doudna, the co-discoverer of CRISPR’s gene-editing technology, to tell the story of how the human species seized control of its own evolutionary destiny.

Isaacson’s latest book, the code breaker, Breathlessly follows Doudna from a childhood trekking through the wilderness of Hawaii, to her pioneering work using a bacterial defense system to rewrite the code of life – and the bitter patent battle that followed – and finally winning the ultimate honor, the Nobel Prize. Based on more than five years of reporting from the front lines of the DNA hacking wars, the book is a compelling deep dive into the fascinating science of gene editing and the personal dramas that unfold behind the discoveries. Even if you think you know the story of CRISPR, you don’t know it like Isaacson does.

He spoke to WIRED from his home in New Orleans, where he is now a professor of history at Tulane University. This interview has been edited for length and clarity.

WIRED: The biotech revolution didn’t start with CRISPR or with Doudna. So why her?

Walter Isaacson: Jennifer Doudna’s journey begins in sixth grade, when her father leaves The double helix, by James Watson, on her bed and she realizes it’s actually a detective story. That’s why she wants to become a scientist. And even after her counselor told her girls don’t do science, she persisted. She then helped to figure out the structure of a type of RNA that helps answer one of the biggest questions: How did life on this planet begin? And then her RNA research led her to CRISPR and the discovery that it could be a gene-editing tool, the magnitude of which leads her to gather scientists to understand the moral issues of how to use such a discovery.

My father gave me The double helix when I was in high school too. And while I’ve always been interested in biochemistry, I’ve always regretted not taking it beyond a few courses in college. There is joy in understanding how something works, especially when that something is ourselves. So while there are all kinds of wonderful characters that could have been the focus of this book, Doudna’s life journey just seemed like a compelling storyline through this longer history of scientists striving to understand what makes us human.

You don’t shy away from setting up Doudna’s conflict with the Broad Institute on CRISPRr credit as a contemporary parallel to Rosalind Franklin’s own struggle to be recognized for her contributions to discovering the structure of DNA. Was that intentional?

What Doudna has done is unravel the mysteries of life with the same mindset as Rosalind Franklin, namely that the structure of a molecule is the clue you need as a detective to figure out how it really works. When Doudna and Charpentier won the Nobel Prize, a vision flashed into my mind of Franklin with a tight but contented smile on her face.

So you start writing about Jennifer Doudna, and before you know it she wins the Nobel Prize. Chance?

Despite what people think about rigged election systems, I don’t have the ability to hack the Swedish Academy’s voting process. I thought it was too early for CRISPR. I mean, it’s only been eight years since Doudna and Charpentier’s landmark paper. But on the morning the Nobel Prize in Chemistry was due to be announced, I still set my alarm for 4 a.m. so I could listen to the live feed. And when I heard the announcement, I let out a scream. The funny thing is that Doudna actually slept through the phone calls from Stockholm. When I spoke to her a few hours later, she told me that she had only learned about her victory afterwards, from a reporter who called to get her comments.

That moment was in many ways the culmination of a years-long battle over who deserves credit for turning CRISPR from a biological curiosity into one of the most powerful technologies ever invented. What was it like capturing that?

Everyone I spoke to was very generous. Feng Zhang, the main competitor for patents and awards, is one of the most charming, open and interesting people you will ever meet. I was a little concerned when I met him because I wrote about people who had been his rivals, but he couldn’t have been nicer.

And so I think that access has helped me show that science is a truly human endeavor that often comes with a lot of competition – for patents, for awards and for recognition. Competition is a good thing. It urges us on. So did the competition between Intel and Texas Instruments in the development of the microchip. And it was true with CRISPR. But what’s also true is that when COVID hit, all of these scientists put aside the race for patents and turned their attention to fighting the coronavirus and quickly made their discoveries public for everyone involved in that battle to use.

So my hope for the book is that it shows the mix of competition and collaboration that is at the heart of science. And the fact that while these are real people with egos and ambitions, they – more than most people rightly – realize that they are part of a noble pursuit with a higher purpose. I hope everyone in the book comes across as a hero in their own way, because they are.

You were reporting this book when something seismic happened in the world of CRISPR. In 2018, a Chinese scientist named He Jiankui revealed not only had he edited human embryos, but started pregnancies with them, which led to the birth of twin girls. How did that affect the course of the story you were trying to tell?

That really became a pivotal turning point in the story. For now all these scientists were forced to grapple with the moral implications of what they had helped create. But then things changed again when the coronavirus hit. I ended up working on the book for another year to see the players as they battled this pandemic. And that actually made my own thinking about CRISPR evolve.

How’s that?

I think at times I felt a visceral resistance to the idea that we could edit the human genome, especially in ways that would be heritable. But that changed for both me and Doudna as we met more and more people who themselves suffer from terrible genetic problems or who have children who suffer from them. And when our species was struck by a deadly virus, I was more open to the idea that we should use all the talents we have to thrive and be healthy. So I’m now even more open to genetic engineering for medical purposes, whether that’s sickle cell anemia, or Huntington’s disease, or Tay-Sachs, or even to increase our resistance to viruses and other pathogens and to cancer.

SIMON AND SCHUSTER

I still have concerns. One is that I don’t want gene editing to be something only the rich can afford and lead to the encoding of inequalities in our societies. And second, I want to make sure we don’t diminish the wonderful diversity within the human species.

Do you have ideas for doing that?

I struggle with that question in the last few chapters of my book. And I hope not to preach, but to enable the reader to go hand in hand with me and Jennifer Doudna and find out for themselves what their hopes and fears are about this so-called brave new world that we are all stepping into together. I once had a mentor who said that there are two kinds of people from Louisiana: preachers and storytellers. He said, “For God’s sake, be a storyteller, ’cause the world has too many preachers.”

So by telling the story of CRISPR in all its scientific triumphs, rivalries, and excitement, I hope to push people into science. But I also want to make them more qualified to grapple with one of the most important questions that we as a society will face in the coming decades: if we can program molecules the way we program microchips, what do we want? to do with this fire we snatched from the gods?

This story first appeared on wired.com.

List image by SIMON AND SCHUSTER

By akfire1

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