Easy to Understand What Jennier Doudna Discovered

The path to Walter Isaacson's latest book began when he was 16 years old.

That was when his father gave him a copy of "The Double Helix," James Watson's account of his team's discovery of the structure of DNA, a molecule containing the instructions an organism needs to develop, live and reproduce.

"Ever since then, I've been fascinated by biochemistry," Isaacson, 68, said in an interview, even though the New Orleanian majored in history and literature at Harvard.

The same life-changing event — receiving a copy of "The Double Helix" — happened early on to Jennifer Doudna, the subject of "The Code Breaker: Jennifer Doudna, Gene Editing and the Future of the Human Race" (Simon & Schuster, $35), which will be published Tuesday.

"Unlike me," Isaacson said, "she decided to pursue her passion and do biology."

Did she ever. Last October, when Doudna was 56, she shared the Nobel Prize in chemistry for creating a gene-editing tool called CRISPR (for Cluster of Related Sequences) to fight viruses by altering DNA sequences and thereby modifying gene function. Doudna shared the accolade with the French researcher Emmanuelle Charpentier, who also had been studying CRISPR.

Their investigation of the basic structure of life was nothing less than revolutionary, Isaacson wrote. The Swedish Academy acknowledged that fact by honoring the two women for work that was eight years old, compared with the decades that often can elapse before Nobels bless scientists' work.

That was the theme of the Swedish Academy's announcement of the prize: "This year's prize is about rewriting the code of life. These genetic scissors have taken the life sciences into a new epoch."

The achievement turned out to be timely because Doudna had worked with ribonucleic acid, commonly known as RNA, whose primary role is to carry instructions for synthesizing proteins.

In viruses, RNA also can carry genetic information, and here's where Doudna's story becomes up-to-the-minute. In some viruses, RNA can hijack cells' protein-making machinery to reproduce in a process called RNA interference.

Among these biochemical culprits are viruses known as coronaviruses. Within the past year, the coronavirus known as COVID-19 — short for coronavirus disease 2019, the year in which it was discovered — has morphed into a pandemic that has spread around the globe, killing more than 500,000 people in the United States alone.

The work that Doudna and her colleagues had done at the University of California, Berkeley, to enhance the understanding of RNA was key in helping other scientists develop vaccines to fight the pandemic, Isaacson said.

"RNA is the strand that runs throughout Doudna's career and this book," he wrote.

"I never ever got over my fascination about how RNA can do so many things," Doudna told Isaacson in the book. "It's the genetic material of the coronavirus and, in a very interesting way, could be the basis for vaccines and cures."

The Nobel Prize has had a noticeable impact on her field, Doudna said in an email.

"The biggest change is how firmly mainstream the topic of CRISPR technology has become," she wrote. The award has increased interest in CRISPR's potential, and scientists are seeing huge investment in companies applying it in unique ways, such as developing new rapid diagnostics and genetic medicines, she said.

And, Doudna and the Innovative Genomics Institute team receive more requests than ever regarding genome engineering projects and collaborations, she said.

Based on his fascination with the structure of RNA and the work Doudna and her colleagues were doing, Isaacson signed up last year to join the clinical trial at Ochsner Medical Center of the coronavirus vaccine that Pfizer Inc. and BioNTech had developed.

In what is standard procedure for such tests, half the participants at Ochsner and other sites received the vaccine, and the other half received a harmless placebo — in this case, saline solution. In clinical trials, the placebo group's data serve as a baseline to gauge the effect of the vaccine on the other volunteers.

Isaacson didn't know during the trial what was being injected into his arm — that's also standard procedure — but once the experiment was complete, he learned he had received the placebo. Because Isaacson had been in the trial, he received the Pfizer-BioNTech vaccine once the federal Food and Drug Administration approved it.

He wrote about his experience for The Times-Picayune | The New Orleans Advocate: "There is something sweet about being a small part of a process that seems to have gotten us closer to a vaccine. And it's made me a lot more comfortable about recommending the vaccine once it finally gets approved."

Isaacson, who first became interested in this topic six years ago, met Doudna and worked with her in her Berkeley laboratory. She even let him edit human cells.

"It was easy," Isaacson said. "It was like being in Mrs. Dyer's biology class at Newman, using pipettes and mixing stuff in a test tube. It wasn't that high-tech. You put it in a centrifuge, and you spin it.

"The good thing about Jennifer Doudna's journey is that what she discovered is easy to understand. It's just a guided pair of scissors that can change any gene in our body."

In discussing the vaccine trial and his work with Doudna in her lab, Isaacson inserted himself into the narrative.

That, he said, was part of his plan for approaching a subject that can seem forbiddingly abstruse.

"I really come at this as somebody who is a curious outsider. I hope that makes the book more accessible," Isaacson said. "I wanted this book to be about you and me wrestling with all of this because this will be the most interesting and important technology of our lifetime, and we're all going to have to figure out how we could use it.

"I wanted to make it very personal, so the reader and I could walk through this hand in hand, not only reading about it but also understanding it."

Part of understanding Doudna's work involves coming to grips with moral issues, including the limit to which scientists can — and should — take this powerful technology. Doudna and her Innovative Genomics Institute team are often asked about how to responsibly apply CRISPR in a way that is affordable and accessible to all, she said.

It's a topic Isaacson tackles in his book.

"Once we start fiddling with our genes and designing our babies, you get perilously close to playing God," he said, "and we have to have some caution so we make sure we use these things to make ourselves healthier and stronger and more resistant to viruses but don't misuse it to try to create artificial designer babies.

"We have to make these decisions and not leave them to the scientists. That's why we have to go on these journeys of discovery to understand the beauty and challenges of the new technology. I don't want people to be intimidated or bedazzled. Like any technology, it's only as good or as bad as we decide to use it."

Isaacson, who was a reporter for The States-Item before taking on leadership positions at Time, CNN and the Aspen Institute, has written biographies of such notable individuals as Henry Kissinger, Leonardo da Vinci, Albert Einstein and Steve Jobs.

This is Isaacson's first book in which the major character is a woman — and a woman scientist, no less — and it comes at a time when women are being urged to consider scientific careers.

Doudna didn't get that pep talk — she said her high-school guidance counselor told her women didn't become scientists — and women have been overlooked when Nobels are awarded.

"I hope Walter's book increases the public's understanding and value of curiosity-driven, basic fundamental science and how it can positively impact our society," she wrote in an email. "For all young scientists, especially women, I want them to know that they belong and their work can make a lasting difference."

Before last year, Isaacson said, only five women, starting with Marie Curie in 1911, had won Nobels out of 184 chemistry honorees.

While Isaacson acknowledged the importance of female role models, he said that wasn't the reason he took on this topic.

"I wrote about her not because she's a woman but because her discovery was worth the most important Nobel Prize of our time for rewriting the code of life," he said. "It brings science into a new epoch. This isn't just a simple discovery. It changed everything."

BOOK DISCUSSIONS

WHAT: Walter Isaacson will discuss and sign "The Code Breaker," in a COVID-19-safe, in-person event at a private home, presented by the Garden District Book Shop

WHEN: 5 p.m. Saturday, March 13

WHERE: Go to gardendistrictbookshop.com for tickets, reservations and info

WHAT: Zoom discussion hosted by Tulane University

WHEN: 6 p.m. Monday, March 15

WHERE: Go to news.tulane.edu for the Zoom link.

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Source: https://www.nola.com/entertainment_life/books/article_28dc2600-7a45-11eb-89c6-fb7d808df3b3.html

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