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“The Code Breaker” (Simon & Schuster), the latest book from Walter Isaacson, successful biographer of geniuses from Leonardo da Vinci and Benjamin Franklin to Albert Einstein and Steve Jobs, tells the story of biochemist Jennifer Doudna and the creation of gene-editing technology known as CRISPR.

Read the excerpt below and don’t miss correspondent David Pogue’s interview with Isaacson and Doudna on “CBS Sunday Morning” on March 7th!

Simon and Schuster


Into the breach

Jennifer Doudna couldn’t sleep. Berkeley, the university where she was a superstar for her role in inventing the gene-editing technology known as CRISPR, had just closed its campus due to the rapidly spreading coronavirus pandemic. Against her better judgment, she had driven her son, Andy, a high school student, to the train station so he could make his way to Fresno for a robot building competition. Now, at 2 a.m., she woke her husband up and insisted they pick him up before the game started, as more than twelve hundred children gathered in an indoor convention center. They put on their clothes, got in the car, found an open gas station, and drove the three-hour drive. Andy, an only child, was not happy to see them, but they convinced him to pack his bags and come home. As they exited the parking lot, Andy received a text from the team: “Robotics match canceled! All the kids leave immediately!”

It was then, Doudna recalls, that she realized that her world and the world of science had changed. The government was trying to respond to COVID, so it was time for professors and graduate students, clutching their test tubes and lifting their pipettes, to rush into the breach. The next day – Friday, March 13, 2020 – she led a meeting of her colleagues at Berkeley and other Bay Area scientists to discuss roles they could play.

A dozen of them passed through the abandoned Berkeley campus and converged on the elegant stone and glass building that housed his laboratory. The chairs in the downstairs conference room were grouped together, so the first thing they did was move them six feet apart. Then they turned on a video system so that fifty other researchers from nearby universities could join Zoom. As she stood in front of the room to rally them, Doudna displayed an intensity that she usually kept masked by a calm facade. “It’s not something academics typically do,” she told them. “We have to step up.”

It was only fitting that a virus team would be led by a CRISPR pioneer. The gene editing tool that Doudna and others developed in 2012 is based on a virus-fighting trick used by bacteria, which have been fighting viruses for over a billion years. In their DNA, bacteria develop grouped repeats, called CRISPR, that can memorize and then destroy viruses that attack them. In other words, it’s an immune system that can adapt to fight each new wave of viruses – exactly what we humans need in a time that has been plagued, as if we are still there. in the Middle Ages, by repeated viral epidemics.

Always prepared and methodical, Doudna (pronounced DOWD-nuh) presented slides suggesting ways to tackle the coronavirus. She drove while listening. Although she became a science celebrity, people felt comfortable engaging with her. She had mastered the art of being painstakingly programmed while still finding the time to emotionally connect with people.

The first team Doudna assembled was tasked with setting up a coronavirus testing lab. One of the leaders she approached was a postdoctoral fellow named Jennifer Hamilton who, a few months earlier, had spent a day teaching me how to use CRISPR to modify human genes. I was happy, but also a little pissed off, to see how easy it was. Even I could do it!

Another team has been given the task of developing new types of coronavirus tests based on CRISPR. It helped that Doudna likes business ventures. Three years earlier, she and two of her graduate students had created a company to use CRISPR as a tool for detecting viral diseases.

By launching an effort to find new tests to detect the coronavirus, Doudna was opening another front in his fierce but successful struggle with a cross-country competitor. Feng Zhang, a charming young researcher born in China and raised in Iowa at the Broad Institute of MIT and Harvard, had been her rival in the 2012 race to make CRISPR into a gene-editing tool, and since then, they were locked up. intense competition to make scientific discoveries and create companies based on CRISPR. Now, with the outbreak of the pandemic, they would embark on another race, one spurred not by the search for patents but by the desire to do good.

Doudna has settled on ten projects. She suggested leaders for each and told the others to rank in the teams. They should team up with someone who would perform the same functions, so that there could be a system of promotion on the battlefield: if one of them was affected by the virus, there would be someone. one to intervene and continue his work. It was the last time they had met in person. From then on, the teams will collaborate with Zoom and Slack.

“I wish everyone would start soon,” she said. “Very soon.”

“Don’t worry,” one of the participants assured him. “Nobody has any travel plans.”

What none of the participants discussed was a longer-term perspective: using CRISPR to design hereditary changes in humans that would make our children, and all of our descendants, less vulnerable to viral infections. These genetic improvements could permanently alter the human race. “It’s in the realm of science fiction,” Doudna said with disdain when I brought up the subject after the meeting. Yes, I accepted, it’s a bit like Brave New World or Gattaca. But like all good science fiction, things have already come true. In November 2018, a young Chinese scientist who had attended some of Doudna’s gene editing conferences used CRISPR to edit embryos and delete a gene that produces a receptor for HIV, the virus that causes AIDS. This led to the birth of twins, the world’s first “designer babies”.

There was an immediate explosion of fear and then shock. The guns stirred, committees met. After more than three billion years of life evolution on this planet, a species (us) had developed the talent and recklessness to take control of its own genetic future. There was a feeling that we had crossed the threshold of a whole new age, perhaps a brave new world, like when Adam and Eve bit into the apple or Prometheus wrenched fire from the gods.

Our new ability to modify our genes raises fascinating questions. Should we modify our species to make ourselves less susceptible to deadly viruses? What a wonderful windfall that would be! Law? Should we use gene editing to rule out dreaded disorders, such as Huntington’s disease, sickle cell anemia, and cystic fibrosis? It sounds good too. And what about deafness or blindness? Or be small? Or depressed? Hmmm … how should we think about that? In a few decades, if it becomes possible and safe, should we be enabling parents to improve their children’s IQ and muscles? Should we let them decide on the eye color? Skin color? Height?

Whoa! Let’s stop for a moment before sliding down this slippery slope. What could this have on the diversity of our societies? If we are no longer subject to a random natural lottery when it comes to our endowments, will it weaken our feelings of empathy and acceptance? If these genetic supermarket deals aren’t free (and they won’t), will it dramatically increase inequality – and permanently encode it in the human race? Given these issues, should these decisions be left only to individuals or should society as a whole have a say? Maybe we should make some rules.

By “we” I mean we. All of us, including you and me. Determining if and when to change our genes will be one of the most important questions of the 21st century, so I thought it would be useful to understand how this is done. Likewise, the recurring waves of viral epidemics make it important to understand the life sciences. There is a joy that springs from understanding how something works, especially when that something is ourselves. Doudna savored this joy, and so did we. This is the subject of this book.

The invention of CRISPR and the scourge of COVID will accelerate our transition to the third great revolution of modern times. These revolutions were born from the discovery, a little over a century ago, of the three fundamental nuclei of our existence: the atom, the bit and the gene.

The first half of the 20th century, starting with Albert Einstein’s 1905 articles on relativity and quantum theory, presented a physics-driven revolution. In the five decades since his miracle year, his theories led to atomic bombs and nuclear power, transistors and spacecraft, lasers and radar.

The second half of the 20th century was an era of information technology, based on the idea that all information could be encoded by binary digits – called bits – and that all logical processes could be performed by circuits with switches. On Off. In the 1950s, this led to the development of the microchip, the computer, and the Internet. When these three innovations were combined, the digital revolution was born.

We have now entered an even more momentous third era, a revolution in the life sciences. Children who study digital coding will be joined by those who study genetic code.

Excerpt from “The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race” by Walter Isaacson. Copyright © 2021 by Walter Isaacson. Reproduced with permission from Simon & Schuster, Inc. All rights reserved.

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