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Jennifer Doudna, a Pioneer Who Helped Simplify Genome Editing


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Cool profile of the Berkeley biochemist Jennifer Doudna, who helped develop the Crispr-Cas9 technique -- which is currently embroiled in a major IP dispute as well as a potentially earthshaking ethics issue.

She's not only a great scientist, but she fights for ethics too.

Three years ago, Dr. Doudna, a biochemist at the University of California, Berkeley, helped make one of the most monumental discoveries in biology: a relatively easy way to alter any organism’s DNA, just as a computer user can edit a word in a document.

The discovery has turned Dr. Doudna (the first syllable rhymes with loud) into a celebrity of sorts, the recipient of numerous accolades and prizes. The so-called Crispr-Cas9 genome editing technique is already widely used in laboratory studies, and scientists hope it may one day help rewrite flawed genes in people, opening tremendous new possibilities for treating, even curing, diseases.

But now Dr. Doudna, 51, is battling on two fronts to control what she helped create.

While everyone welcomes Crispr-Cas9 as a strategy to treat disease, many scientists are worried that it could also be used to alter genes in human embryos, sperm or eggs in ways that can be passed from generation to generation. The prospect raises fears of a dystopian future in which scientists create an elite population of designer babies with enhanced intelligence, beauty or other traits.

Scientists in China reported last month that they had already used the technique in an attempt to change genes in human embryos, though on defective embryos and without real success.

Dr. Doudna has been organizing the scientific community to prevent this ethical line from being crossed. “The idea that you would affect evolution is a very profound thing,” she said.

Development of CRISPR techniques started with basic research:

In 2005, Dr. Doudna was approached by Jillian Banfield, an environmental researcher at Berkeley who had been sequencing the DNA of unusual microbes that lived in a highly acidic abandoned mine. In the genomes of many of these microbes were unusual repeating sequences called “clustered regularly interspaced short palindromic repeats,” or Crispr.

No one was quite sure what they did, though over the next few years scientists elsewhere established that these sequences were part of a bacterial immune system. Between the repeated sequences were stretches of DNA taken from viruses that had previously infected the bacteria — genetic most-wanted posters, so to speak.

If the same virus invaded again, these stretches of DNA would permit the bacteria to recognize it and destroy it by slicing up its genetic material. Dr. Doudna was trying to figure out exactly how this happened.

“I remember thinking this is probably the most obscure thing I ever worked on,” she said.

It would prove to have wide use. At a conference in early 2011, she met Emmanuelle Charpentier, a French microbiologist at Umea University in Sweden, who had already made some fundamental discoveries about the relatively simple Crispr system in one bacterial species.

The bacterial expert and the structural biologist decided to work together.

“It was very enjoyable, because we were complementary,” said Dr. Charpentier, who recalled sitting in her office near the North Pole while Dr. Doudna regaled her with stories about Hawaii.

Along with postdoctoral researchers Martin Jinek and Krzysztof Chylinski, the two scientists eventually figured out how two pieces of RNA join up with a protein made by the bacteria called Cas9 to cut DNA at a specific spot. The researchers also found that the two RNA pieces could be combined into one and still function.

In a eureka moment, the scientists realized that this cellular defense system might be used to edit genomes, not just kill viruses.

A specific sequence of guide RNA could be made to attach to a spot virtually anywhere on the genome, and the Cas9 protein would cleave the DNA at that spot. Then pieces of the DNA could be deleted or added, just as a film editor might cut a film and splice in new frames.

The researchers demonstrated this using DNA in a test tube. While there were other genome editing techniques, they found that Crispr-Cas9 was much simpler.

The paper describing the technique, published by the journal Science in June 2012, set off a race to see if it would work in human, plant and animal cells.

Dr. Doudna, whose expertise was in working with molecules, not cells, reported such a demonstration in human cells in January 2013. But her report came four weeks after two papers were published simultaneously, one by George Church at Harvard and the other by the Broad Institute’s Dr. Zhang.

Jennifer Doudna is learning to live with her newfound quasi-celebrity status.

She has been invited to hobnob with entrepreneurs in Silicon Valley, to speak to science fiction writers, to advise Hollywood on science-themed movies. The garden, her hobby, has had to wait.

In November, Dr. Doudna and Dr. Charpentier were each awarded $3 million Breakthrough Prizes, endowed by leading Internet entrepreneurs. They accepted their awards at an Oscars-like black-tie affair attended by movie stars like Cameron Diaz and Benedict Cumberbatch. Recently Time magazine listed the two scientists among the 100 most influential people in the world.

Dr. Doudna, who has a 12-year-old son, Andrew, also finds herself a role model for women in science. Her secret: “I have a great partner,” with whom she shares the chores.

Her husband, Dr. Cate, is also a professor at Cal-Berkeley. The couple have adjacent offices, with views of the Golden Gate Bridge in the distance. Dr. Cate also studies RNA; there is some overlap, but mostly they do their own research. Andrew walks to their office from his middle school each afternoon and hangs out until his parents are ready to go home.

“I don’t think of myself as a role model, but I can see that I am,” Dr. Doudna said. “I still think of myself as that person back in Hawaii.”

She's a great role model for all people, not just strong women.  More scientists and professionals should be so circumspect and ethical.  

Hope she wins the patent fight.  Sigh.

She really has had an extraordinary career, and her thoughtfulness comes through with every article I read about her.

As for the patent fight, yeah. I'm with you.

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