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CRISPR Wizard Feng Zhang: The Making Of A Sunny Science Superstar07:32
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Feng Zhang, in a 2015 file photo (Susan Walsh/AP)MoreCloseclosemore
Feng Zhang, in a 2015 file photo (Susan Walsh/AP)

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Possibly the most famous Boston-area scientist you've never heard of is named Feng Zhang.

By any measure — papers, prizes, impact — Zhang is a science superstar, one of the most inventive life scientists in the world. And he’s only 36.

"Feng is a one-in-a-generation scientist who sees connections that the rest of us have overlooked," says Robert Desimone, director of the McGovern Institute for Brain Research at MIT. "And by seeing those new connections, he’s able to make these gigantic new discoveries."

Those discoveries include work on two major advances: one in brain science, and CRISPR, the breakthrough method for editing genes.

MIT's Zhang, who is based at the Broad Institute in Cambridge and the McGovern, is a scientist who says he wants to change the world. And he already has.

The Making Of A Science Star

When Feng Zhang — pronounced Fuhng Jahng — was 11 years old, his parents, both computer scientists, decided the American style of education would work better for him than the schools in China. Less rote learning. More hands-on.

"Because I like to take things apart and break things," Zhang says, "and it would be better for me to be in a system where I'm not so confined to a specific type of learning."

Zhang didn't speak any English when his mother first brought him to Des Moines, Iowa, in 1993. But he quickly impressed Ed Pilkington, a former science teacher who coordinated the high school gifted and talented program.

Zhang wasn't just highly intelligent, Pilkington says; he had unstoppable drive, "and that's unique. I've seen students that test better than him. Not everybody is able to fail 20 experiments and then get up and then come up with something brilliant."

Zhang was soon ready for more than just classroom science. So with Pilkington's help, he volunteered at age 16 at a local gene therapy lab. Biology was no longer about memorization and smelly dissection frogs. It was about controlling the molecules of life itself.

"Not everybody is able to fail 20 experiments and then get up and then come up with something brilliant."

Former science teacher Ed Pilkington, Zhang's mentor in Iowa

"One of the very first experiments I did was to put a green fluorescent protein into a cell, and then the cell glowed green," he recalls. "And I thought that was magical."

That green-glowing cell was part of the gene therapy lab's effort to find new treatments for cancer.

Zhang realized "that you can actually build biological things that can help people," he says. Science shifted for him.

"It became not just new learning for him," Pilkington says. "It became discovery, and he had a real passion for that. He would spend late hours in the lab, and just the light in his eyes when he would make a new discovery."

Zhang went to Harvard on full scholarship and then to Stanford for grad school. There, he helped develop a game-changing brain science tool — optogenetics, which lets researchers control neurons with light to figure out more about how the brain works.

MIT professor Ed Boyden recalls that the method was working in neurons in a dish. Zhang set out to make viruses that could deliver optogenetics into the brains of living mice, so that by using light to turn their neural circuits on and off, scientists could see how it affected their behavior: They could see what those circuits do.

Zhang "knew a lot about viruses and knew molecular biology," Boyden says, "and pretty soon he was putting these molecules into viral vectors, and we were putting them into the living brain, and sure enough, it worked!"

'That's So Neat! How Can I Make Use Of That?' 

Zhang "is so amazingly creative because he's infinitely curious," says Eric Lander, director of the Broad Institute in Cambridge. "Feng looks around the natural world in a way that you might call almost childlike. He has kept the ability to be fascinated by everything.

"So when he looks at a new bacteria or some biological process, he says, 'Wow, that's so neat! How can I make use of that? How does it work? How might I deploy it?' "

That's what Zhang did with CRISPR. He and others found a way to take a sort of a molecular scissors that existed in nature and engineer it into something incredibly useful to humans: a way to edit genes that's so much easier, it's like going from pen and paper to word processing.

Other scientists worked on CRISPR as well, but Zhang was first to develop CRISPR to edit genes in animal and plant cells. He published a pivotal paper in the journal Science, alongside another seminal article led by Harvard's George Church, in early 2013.

Since then, CRISPR has swept thousands of labs around the world. It's turbo-charging research on cancer and malaria and genetic diseases; it's yielding a whole new field of gene-edited food. Clinical trials that use CRISPR to correct genetic diseases — including sickle-cell anemia — are expected to begin as early as this calendar year.

On a recent afternoon, among the spinners and Petri dishes and flasks of bacterial broth in his Broad Institute lab, a humming space with a team of about 20, Zhang describes a current experiment: trying to "design a new piece of DNA so that we can introduce them into cells to be able to modify RNA."

Using CRISPR to edit RNA, a chemical cousin of DNA, opens up a huge new realm of possible uses in medicine. Editing DNA is permanent; editing RNA could be more like turning the dial on the dosage of a drug.

"One of the things that we really want to do, and I'm really passionate about, is trying to develop ways to be able to treat neurological diseases," Zhang says.

Tackling brain disease has been his goal ever since he saw friends in college suffering from severe mental illness.

"It turns out that to correct the DNA in brain cells is fairly challenging," Zhang says. "And so some of the recent work that we have been doing has been shifting away from DNA and moving into the RNA space."

Biotech Battle, But 'Share The Toy'

With CRISPR expected to be worth billions to for-profit companies, Zhang has been embroiled in a patent fight that's been called the "Biotech Battle of the Century," an East Coast-West Coast conflict between the Broad and the University of California Berkeley.

Berkeley biologist Michael Eisen is outspokenly in the West Coast camp, but he gives Zhang kudos — if perhaps with a slight edge: "He's incredibly good at scouring the literature, often the obscure literature in the field," Eisen says, "and finding little pieces of things that can help, and then pouncing on them, and he's sort of brutally efficient, almost."

Feng Zhang of the Broad Institute and MIT's McGovern Institute for Brain Research (Carey Goldberg/WBUR)
Feng Zhang of the Broad Institute and MIT's McGovern Institute for Brain Research (Carey Goldberg/WBUR)

Zhang's work on CRISPR is a story of sharing as well as conflict, though. When he won MIT's half-million-dollar Lemelson prize last fall, the award cited not just his science but his generosity.

Through a local nonprofit, Addgene, he has sent out the bits of DNA that other academic researchers need to work on CRISPR to more than 2,000 labs in more than 60 countries.

Zhang is a hero at Addgene for working so hard to spread CRISPR components to others, says Melina Fan, its chief scientific officer. Years ago, he was even known to stuff some envelopes himself — which may not have been the best use of his time, she allows, "because he's such a brilliant scientist. However, I give him a lot of credit for being willing to do that. It really shows how much he cares about sharing."

Zhang, for his part, credits his mother: "When I was growing up, my mother would always tell me you should try to do something that's useful and good for the world, and sharing is a way to be able to do good for the world."

That's also a lesson Zhang and his wife, Yufen Shi, who was a biomedical engineering grad student back at Stanford when they met, teach their two young children: Share the toy, Zhang says, "and playing together, you can mutually enjoy the experience, and that really amplifies happiness everywhere."

Where's The Ego?

Now, you may be thinking at this point: This world-class scientist sounds like such a sunny guy. Where's the stereotypical genius ego?

Not here, says Zhang's grad student, Omar Abudayyeh. He objects when people assume Zhang must be hard to work for to accomplish so much. Zhang has been an incredible mentor, he says — and very forgiving.

One time, Abudayyeh really messed up, he says: He wasted hours of Zhang's time because he accidentally gave him the wrong tube to work with. The experiment just didn't work.

"Oh, that's because I was supposed to give you this tube," Abudayyeh recalls telling Zhang sheepishly. "And he just looks at me, and he's like, 'Omar... Omar... Omar... All right, I'll do it again tomorrow.' "

"He's just really patient," Abudayyeh says, "willing to — I guess — see you grow."

And he encourages his students to just "go tinker," says grad student Jonathan Gootenberg, leading them to advances like SHERLOCK, a new CRISPR-based test on a strip of paper — something like a pregnancy test -- that can diagnose diseases.

Growing Young Scientists

Zhang wants to help more young scientists grow: He's been donating chunks of his science prize money to groups that support science education. He's been awarded about a million and half dollars just over the last couple of years — more than a Nobel prize would typically bring — and he's on many a short-list for the Nobel as well.

Eisen of Berkeley says the world needs more scientists like Zhang, and that as his story shows, that takes support — at an early age.

"I think all of us who are successful scientists owe our success to things that happened when we were kids," Eisen says. "If we value scientists like Feng, then we should put more emphasis on the idea that every potential budding scientist out there gets a chance — and we clearly don't."

Broad Institute director Lander points to one more element of Zhang's success: He doesn't mind the risk of failing, because he is having fun — deep fun.

"The joy that comes from learning something about nature — it's addictive, it's wonderful, there's nothing that can match it," Lander says. "And that's why scientists do science, and Feng does that so obviously — you can see that joy in his face."

In the future, Lander says, he expects Zhang to find and develop more surprising systems — like CRISPR — that were created by nature, but hold great promise for humankind.

This segment aired on April 26, 2018.

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Carey Goldberg Twitter Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth blog.

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