CRISPR pioneer muses about long journey from China to pinnacle of American science


That’s because of CRISPR, the gene-editing technique that lets scientists manipulate the genetic code of organisms almost like revising a sentence with a word processor. Zhang was one of its pioneers, and on Wednesday he emerged victorious after a bitter patent dispute.The ruling, by judges with the U.S. Patent Office, declared that Zhang’s work on living plant and animal cells was sufficiently original to deserve its own protection. It was a decisive outcome that will surely prove lucrative for Zhang and the Broad Institute, but he did not do anything special to celebrate. He made no immediate public comment. He did not even read the news coverage, he said.

“The patent stuff is not so interesting, and it can be distracting,” the soft-spoken scientist offered a day later, finally addressing the case as he sat down with a Washington Post reporter for a previously scheduled interview. “Now we can get back to work.”

The patent dispute was closely followed in the triangle of geography marked by the institute, Harvard University and the Massachusetts Institute of Technology. Here, in what has become the Silicon Valley of the life sciences, Zhang and his colleagues have spun off ventures that can commercialize their inventions.

CRISPR is an all-purpose tool that promises great advances in the prevention of diseases caused by genetic mutations. In China, Zhang’s birth country, it is already being used in human clinical trials.

Yet the technique has also raised unsettling possibilities for cosmetic human enhancements and “designer babies.” Earlier this week, the National Academy of Sciences and National Academy of Medicine produced a long report on the ethics of gene editing, arguing for extreme caution when dealing with heritable human traits but leaving open the possibility of use to remove disease-causing genes.

Some critics worry about a slippery slope, but Zhang thinks the bioethics committee got it just right.

“I think these are important issues, but I don’t think right at this second we should be overly concerned about it. It’s too far off,” he said.

The politics of science

Even with the patent case behind him, however, there is another significant distraction these days. It arises not through the courts but from the White House.

Science is inherently an international enterprise, built around a universal language of discovery and methodology. Zhang’s lab, like similar facilities across the country, has a large percentage of foreign-born scientists drawn to research opportunities in the United States.

President Trump’s executive order banning entry from seven Muslim-majority countries has alarmed this global community. The Broad, as it is commonly called, put out a statement of opposition, saying the order “turns its back on one of America’s greatest sources of strength: the flow of visitors, immigrants and refugees who have enriched our nation with their ideas, dreams, drive, energy, and entrepreneurship.”

 Zhang talks of his own life story when asked about Trump’s action.

“From my own experience, America has been an amazing place,” he said. “And it sort of gives opportunities for immigrants to realize what they want to do, to reach for their potential, and also, by doing that, make the world a better place. I’m very fortunate to have had the opportunity to move here.”

He was 11 when he first came to the United States in 1993. He spoke almost no English, arriving with his father to at last rejoin his mother. The teeming city of Shijiazhuang, in the north of China, was replaced by the alien landscape of Des Moines.

His mother had not intended to stay following her studies here, but Iowans embraced her. She got a good job with a company called the Paper Corp. She decided to start a new life and bring her son and husband to the United States. They each received a series of visas and green cards. She eventually became a citizen, as did her son. Her husband remains a Chinese citizen.

“I never felt I was discriminated against. I never felt we weren’t welcome there,” Zhang said of his youth in the heartland. And there were other immigrants, too, many of them Vietnamese refugees from war zones. He spent half the day learning English and then playing word bingo to hone his vocabulary.

He hung out with other kids interested in science. “We were all nerds,” he said. As a teenager, he got a position working after school at the Human Gene Therapy Research Institute. He could call himself a bench scientist, often working late into the evening while his mother waited for him in the parking lot.

Elite institutions soon recognized his brilliance. His résumé includes a degree from Harvard, then a doctorate from Stanford. He learned about the natural bacterial immune system, CRISPR, an acronym for clustered regularly interspaced short palindromic repeats.

Bacteria evolved a defense mechanism against viral invaders that would insert genetic material into bacterial DNA. The system functions like molecular scissors, snipping away the invasive material.

Two other researchers, who would become rivals in the patent case, published the first paper describing the gene-editing technique and applied for patents. Jennifer Doudna and Emmanuelle Charpentier showed how to turn the natural bacterial system into a laboratory tool, but initially they did not apply it to plant and animal cells. That was Zhang’s breakthrough, published in 2013 at the same time as a similar paper by Harvard geneticist George Church.

“Feng was very early in recognizing the importance of reducing it to practice in mammalian cells,” Church said this week.

Doudna and Charpentier can still receive patents on their original discovery. In an email Friday to The Post, Doudna wrote, “Obviously the Broad Institute is happy that their patent didn’t get thrown out, but we are pleased that our patent can now proceed to be issued.”

But she raised another concern. The judges’ decision was based in part on public comments she made, expressing uncertainty about whether CRISPR would work in cells with nuclei. Because of that, she fears the ruling could have a chilling effect on scientific communication.

“Must every scientist now factor in a potential patenting strategy and alter how transparent they are about their work?” Doudna wrote.

Doudna and Charpentier have already received the $3 million Breakthrough Prize funded by Silicon Valley tech tycoons. Then earlier this year they won the Japan Prize, each receiving the equivalent of about $420,000.

And lurking out there somewhere is the Nobel.

‘Why do we age?’

On Thursday, the morning after the ruling, Zhang drove his 2004 BMW to work as always, arriving at 7:30 to meet with a student and help him prepare for a class presentation. Then he had a call with an oil executive in the United Arab Emirates who is funding research on a genetic disease that affects the executive’s daughter.

He still has a spot in his lab for experiments, though he does those during the summer since right now he’s busy teaching two classes. The lab work is in the hands of about 20 researchers, some already with doctorates and medical degrees.

CRISPR gets all the publicity these days, but it is not the only game in town. Life is a complex chemical system that over billions of years has developed all sorts of tricks and mechanisms. Most of the microbes in the human gut have never been cultured or characterized. Basic questions remain unanswered.

“Why do we age?” Zhang asked.

The CRISPR system is itself a work in progress. It’s an inexact editor still.

“It cuts very well,” he said. “To insert something, it doesn’t work very well at all.”

But he’s working on that. Everyone stand by.

Source:www.washingtonpost.com

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