The Code Breaker

by Walter Isaacson

The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery, beginning just over a century ago, of the three fundamental kernels of our existence: the atom, the bit, and the gene.

Discoveries

the key to innovation is connecting a curiosity about basic science to the practical work of devising tools that can be applied to our lives—moving discoveries from lab bench to bedside.

Practical application

We all see nature’s wonders every day, whether it be a plant that moves or a sunset that reaches with pink fingers into a sky of deep blue. The key to true curiosity is pausing to ponder the causes.

Curiosity

Darwin and Wallace had a key trait that is a catalyst for creativity: they had wide-ranging interests and were able to make connections between different disciplines.

Creativity

Franklin was a focused scientist, sensibly dressed. As a result she ran afoul of English academia’s fondness for eccentrics and its tendency to look at women through a sexual lens, attitudes apparent in Watson’s descriptions of her. “Though her features were strong, she was not unattractive and might have been quite stunning had she taken even a mild interest in clothes,” he wrote. “This she did not. There was never lipstick to contrast with her straight black hair, while at the age of thirty-one her dresses showed all the imagination of English bluestocking adolescents.” Franklin

Sexism in science - all that mattered was whether she was attractive, wore makeup and nice clothes!!

In the weirdness engendered by red-baiting and McCarthyism, Pauling was stopped at the airport in New York and had his passport confiscated because he had been spouting enough pacifist opinions that the FBI thought he might be a threat to the country if allowed to travel. So he never got the chance to discuss the crystallography work done in England, thus helping the U.S. lose the race to figure out DNA.

The US loses out

As Watson later admitted in a feeble attempt at graciousness, “Her past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist.”

A scientist not a mere woman! Rather grudging, though...

In Watson’s memorable and only slightly hyperbolic phrase in The Double Helix, “Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life.”

Discovery

Thus was born an information age based on digital coding (0100110111001…) and genetic coding (ACTGGTAGATTACA…). The flow of history is accelerated when two rivers converge.

Love this

“I thought, ‘I don’t want to become a chemist if I’m not going to have a shot at being at the top.’ ”

Doudna's ambition.

Watson’s science had intersected with real life. The massive international project to map the human genome would no longer be for him an abstract, academic pursuit. It was personal, and it would ingrain in him a belief, bordering on obsession, in the power of genetics to explain human life. Nature, not nurture, made Rufus the way he was, and it also made different groups of people the way they were.

It's personal - which makes it more interesting of course.

“Today we are learning the language in which God created life,” President Clinton proclaimed at the White House ceremony

Szostak had a guiding principle: Never do something that a thousand other people are doing. That appealed to Doudna. “It was like when I was on the soccer field and wanted to play a position that the other kids didn’t,” she says. “I learned from Jack that there was more of a risk but also more of a reward if you ventured into a new area.”

Don't follow the crowd

Ask big questions. Even though Szostak liked diving into the details of experiments, he was a grand thinker, someone who was constantly pursuing truly profound inquiries. “Why else would you do science?” he asked Doudna.

Big questions

Their encounter was an example of the mix of competition and collegiality that marks scientific research (and many other endeavors).

Scientists' dynamics

“I’m someone who’s thinking about science all the time,” she says. “I’m always focused on what’s cooking in the lab, the next experiment, or the bigger question to pursue.”

Singleminded

the enduring power of being in the same location as other smart people.

Feeding off energies.

Bonds can take different forms, both in chemistry and in life. Sometimes an intellectual bond is the strongest.

Doudna and her father

Their choice of Berkeley is a testament to America’s investment in public higher education. Its roots stretch back to when Abraham Lincoln, in the middle of the Civil War, thought public education was important enough that he pushed through the Morrill Land-Grant Act of 1862, which used funds from federal land sales to establish new agriculture and mechanical colleges.

Historical Note

What Mojica had stumbled upon was a battlefront in the longest-running, most massive and vicious war on this planet: that between bacteria and the viruses, known as “bacteriophages” or “phages,” that attack them.

War

When new viruses came along, the bacteria that survived were able to incorporate some of that virus’s DNA and thus create, in its progeny, an acquired immunity to that new virus. Mojica recalls being so overcome by emotion at this realization that he got tears in his eyes.8 The beauty of nature can sometimes do that to you.

The emotion

From this misstep, she became more aware of her passions and skills—and also her weaknesses. She liked being a research scientist in a lab. She was good at brainstorming with people she trusted. She was not good at navigating a corporate environment where the competition was for power and promotions rather than discoveries. “I didn’t have the right skill set or passions

Doudna

This transition from player to coach happens in many fields. Writers become editors, engineers become managers. When bench scientists become lab heads their new managerial duties include hiring the right young researchers, mentoring them, going over their results, suggesting new experiments, and offering up the insights that come from having been there.

Changing roles

Why else do we do science? We do it to go after big questions and take on risks. If you don’t try things, you’re never going to have a breakthrough.”

Always asking the big questions.

They were designed to get her researchers to look up from the details and see the big picture. Why are you doing this? she will ask. What’s the point?

The big picture

That is when Doudna’s competitive juices kick in. She doesn’t want another lab to beat hers to a discovery. “She might storm into the lab unexpectedly,” Harrington says, “and without raising her voice make it clear what things need to be done and be done quickly.”

Competition

Women in science tend to be shy about promoting themselves, and that has serious costs. A study in 2019 of more than six million articles with women as the principal author showed that they are less likely to use self-promotional terms, such as “novel” and “unique” and “unprecedented,” to describe their findings.

Women in science

Thus did biotech follow the path of digital technology in blurring the lines between academic research and business.

Science and business

None of the venture capitalists they met with was a woman, and this was in 2012. So instead of continuing to seek venture money, they decided to raise what they could from friends and family. Both Doudna and Haurwitz put in their own money.

Investing in women

As with so many other observant and creative people, she found that a sense of detachment or slight alienation made her better at figuring out the forces at play. That helped her honor the maxim often preached by Louis Pasteur himself: Be prepared for the unexpected.

Charpentier

That’s because science is most often advanced not by great leaps of discovery but by small steps. And disputes in science are often about who made each one of these steps—and how important each really was.

Baby steps

The other enticement was that it was just the sort of detective tale that gave Doudna a sense of purpose: the hunt for the key to one of life’s basic mysteries.

Detectives

“It was a double joy,” she recalled, “a moment of fundamental discovery of something that is so cool, and being able to share it with my son and explaining it in a manner where he can get it.” Curiosity can be beautiful that way.

Explaining to a child

They paused for a moment and looked at each other, then Doudna said, “Wow.” As she recalls, “It was one of those moments in science that just comes to you. I had this chill and these little hairs on my neck standing up. In that moment, the two of us realized that this curiosity-driven, fun project had this powerful implication that could change the direction of the project profoundly.”

Wow

afternoon sun setting over San Francisco Bay, Doudna spoke of how pleasant it had been collaborating with her. “It was a glorious moment when we finally got to share in person the joy of discovery and also some personal confidences,” Doudna recalled. “We got to take a breath and talk about how hard we’d worked together across thousands of miles.”

The joys of collaboration and sisterhood.

This is how science is accelerated, when you know that it’s a competitive situation. It gives you an impetus to push the process.”

Competition

In explaining the amazing mechanisms of life, little things matter. And very little things matter a lot.

Yes

Competition drives discovery. Doudna calls it “the fire that stokes the engine,”

Competition

This may seem like a small thing. But it’s over such small discoveries, or lack of them, that battles for historic credit are waged.

Little Things mean a lot