Tam on STEAM

Growing up in Hilo on Hawaii’s Big Island, Jennifer Doudna loved to roam the rainforest around the housing tract where her family lived.

In this wild landscape, exotic mosses and fungi caught her eye. She puzzled over one plant with leaves that folded shut when she touched them. ‘‘I’d look at that and think: Now, how does that work?” she told The New York Times Magazine. “There’s some chemical change that responds to touch that allows these leaves to close. But what is it?’’

As she built a career as a top molecular biologist, Doudna never lost that intense curiosity about how things work in the living world. Along the way, a series of remarkable mentors encouraged her to go where her curiosity carried her. 

Now her curiosity has led her to a breakthrough that is revolutionizing biology—the CRISPR gene editing tool. That’s right—an ingenious way to make changes in DNA, the chain of nucleic acid molecules that carries the genetic code in the cells of living things.

DRAWN TO SCIENCE

Doudna was 7 when she moved to Hilo. Her parents taught at local colleges. The tall, blonde Doudna felt like she stood out among her classmates, who were mostly of Asian and Polynesian ancestry. ‘‘I was kind of a nerdy, geeky type,’’ she told the magazine. ‘‘And I loved math. People teased me about it. I felt pretty much like an outcast.’’

She found herself drawn to science. In high school she heard a talk by a young woman scientist on how cells turn cancerous. The subject captivated Doudna, but the scientist herself was even more of a revelation. Doudna realized “that this feminine person was clearly an incredible scientist,” she told California Magazine. “It was an important moment.”

In high school Doudna had a summer job in a biology lab. She relished the messy work of gathering worms and fungus specimens. And she learned to use an electron microscope—a tool that would be crucial in her later discoveries.

TEACHERS AND MENTORS

After high school, Doudna studied biochemistry at Pomona College in California. She worked in the lab of biochemist Sharon Panasenko, an early standout among many teachers who inspired Doudna. “Mentors are critical,” she told California Magazine. “And fortunately for me, I’ve worked with absolutely outstanding scientists at every stage of my career.”

While earning her Ph.D. at Harvard, she worked with Jack Szostak, who later won a Nobel Prize in Medicine. Doudna focused on RNA, a molecule that does a variety of jobs inside cells. Some kinds of RNA carry information from DNA to make proteins, some catalyze chemical reactions, some turn genes on or off, and some block invading microbes.

Dounda did postdoctoral research at the University of Colorado under Tom Cech, a Nobel laureate in Chemistry. In Cech’s lab, Doudna did something researchers had thought was impossible—she used X-ray diffraction to map the structure of a complex RNA molecule.

People who have worked with Doudna say she has a gift for zeroing in on key questions to investigate. “She’s very imaginative and can see possibilities that others don’t,” Cech told California Magazine. “She has an uncanny knack for picking the best experiments to answer a question.”

A POWERFUL TOOL

Doudna joined the faculty at Yale before moving to the University of California at Berkeley in 2002. In 2005 she turned her attention to a new puzzle. She started investigating unusual repeating sequences found in the DNA of some bacteria. These genes—called CRISPR for short—help bacteria fight off invading viruses.

Collaborating with a French geneticist named Emmanuelle Charpentier, Doudna and her team figured out how CRISPR does its job. Then they realized they could put it to work to edit genes. In 2012 they used it to create a tool that can find and snip out any gene in a strand of DNA. It can also insert a new gene between the cut ends.

(See What Is CRISPR? for more on the gene editing tool.)

The discovery is a dream come true for biologists. In her California Magazine interview, Doudna explained why. “We’ve been able to read and write DNA for a long time,” she said. “We have machines to sequence it (read); and to synthesize it (write). What we haven’t been able to do is to rewrite it—to edit it. And now we have a tool that lets you do something about that.”

A STEM ROLE MODEL

Doudna’s discovery has made her a celebrity, at least in the science world. Last year she and Charpentier each received the $3 million Breakthrough Prize from tech industry leaders. Time magazine listed them among the world’s 100 most influential people.

Doudna is married to Dr. Jamie Cate, a biochemistry professor at U.C. Berkeley. They have a teenage son, Andrew. Doudna enjoys gardening and hiking in the Berkeley Hills with her family. Lately, though, it has been harder to find time for those activities amid the whirlwind of CRISPR-related speeches and conferences.

As someone who was inspired by great mentors, Doudna knows that role models are crucial in science. And she realizes that her high profile makes her a powerful example for girls aspiring to STEM careers.

“I think that for a lot of women, there’s a subtle but unfortunately effective discouragement of women pursuing the STEM fields,” she told Huffington Post.

"Women have natural curiosities, as do men,” she added. “And we just want to show women they can pursue these fields and they can be feminine, they can be mothers, they can be wives—they really can do all those things and do it on their own terms.”

Doudna has built her remarkable career on her own terms. And though many now view her as a scientific superstar, she has trouble seeing herself that way.

“I don’t think of myself as a role model, but I can see that I am,” she told The New York Times. “I still think of myself as that person back in Hawaii.”

WHAT IS CRISPR?

The CRISPR gene editing tool has generated a wave of excitement in labs all over the world. Suddenly researchers can carry out experiments they could only dream of before. So what is CRISPR and how is it revolutionizing biology?

CRISPR stands for clustered regularly interspaced short palindromic repeats. It refers to repeating gene sequences found in the DNA of some bacteria.

Jennifer Doudna, a molecular biologist at the University of California at Berkeley, began looking at CRISPR in 2005. Her colleague Jillian Banfield had noticed repeating genes in bacteria that live in harsh acidic environments. Banfield asked for Doudna’s help in investigating the genes.

Other researchers discovered that CRISPR genes are part of a bacterial immune system. They destroy invading viruses by cutting up the viruses’ genetic material.

At a conference in 2011, Doudna met Emmanuelle Charpentier, a French geneticist. Charpentier also was studying CRISPR. The two women hit it off and agreed to work together.

Doudna, Charpentier, and their teams figured out that CRISPR uses two kinds of RNA. One is a “guide” RNA that directs a protein called Cas9 to a certain spot on a DNA strand. The other is a “tracer” RNA that allows the protein to cut the DNA.

It dawned on the researchers that they could put this natural process to work to edit genes. They combined the two kinds of bacterial RNA to create a tool called CRISPR-Cas9. Scientists can use this tool to find and snip out any gene in a strand of DNA. They can also insert a new gene between the cut ends. Doudna and Charpentier described their breakthrough in a paper published in 2012.

GENE EDITING MADE EASY

Before CRISPR, genetic engineering techniques worked slowly—and often they didn’t work at all. Scientists could only change one gene at a time. What’s more, a technique that worked on one species might not work on other organisms.

CRISPR is different. It can make targeted, precise changes in DNA—like a word processor that can delete or insert a letter anywhere in a document. It works quickly, changing genes in weeks instead of years. And it seems to work in just about any living thing. On top of that, it is remarkably easy to use.

Labs around the world raced to put CRISPR to work. Researchers are using it to make new enzymes, create pest-resistant crops, and develop improved medicines. And scientists are starting to explore CRISPR’s huge potential to treat or cure genetic diseases—from muscular dystrophy to cystic fibrosis and from sickle-cell anemia to some kinds of cancer.

ETHICAL QUESTIONS

As excitement over CRISPR grew, Doudna found herself lying awake at night. She worried about the ethical issues raised by the discovery. If CRISPR is used improperly, it could introduce genetic errors. And in theory, it could be used to tinker with evolution—to create “designer” humans.

“Once the discovery is made, it’s out there,” Doudna told NPR. “Anybody with basic molecular biology training can use it for genome editing. That’s a bit scary.”

Doudna began speaking out. She and other researchers called for a voluntary delay in using CRISPR to alter human eggs, sperm, or embryos. Doudna has written articles, organized conferences, given dozens of talks, and even testified before a congressional committee.

It isn’t easy to slow CRISPR’s momentum. Britain recently became the first country to approve research that calls for editing the genes of human embryos. The project is aimed at improving fertility treatments and preventing early miscarriages.

WHO WAS FIRST?

The ethics debate isn’t the only thing keeping Doudna on the go. She is locked in a patent dispute with Dr. Feng Zhang, a scientist at the Broad Institute in Massachusetts.

Researchers at U.C. Berkeley and the Broad Institute were working on CRISPR at the same time. Doudna and Charpentier published the first paper describing CRISPR-Cas9. But Zhang says he developed the tool on his own. He also was the first to describe how to use CRISPR in cells with nuclei, such as human cells.

Both research groups applied for patents. While U.C. Berkeley’s application was under review, the U.S. Patent Office approved Zhang’s application, even though it was submitted later. The University of California appealed the decision. Now the Patent Office is working to determine which team was first with key discoveries.

Billions of dollars could be at stake. Doudna, Zhang, and their colleagues have formed competing companies to look into commercial uses of the tool. The outcome could also help decide who gets the Nobel Prize that is expected to result from the CRISPR breakthrough.

Listen to Jennifer Doudna talk about her discovery.

PBS NewsHour video

https://www.youtube.com/watch?v=m2OwzStEZU4

SOURCES

Doudna, Jennifer. “Genome-editing revolution: My whirlwind year with CRISPR.” Nature, Dec. 22, 2015. http://www.nature.com/news/genome-editing-revolution-my-whirlwind-year-with-crispr-1.19063

Feltman, Rachel. “Britain gives scientists permission to genetically modify human embryos,” The Washington Post, Feb. 1, 2016. https://www.washingtonpost.com/news/speaking-of-science/wp/2016/02/01/britain-gives-scientists-permission-to-genetically-modify-human-embryos/

Kahn, Jennifer. “The Crispr Quandary: A new gene-editing tool might create an ethical morass—or it might make revising nature seem natural.” The New York Times Magazine, Nov. 9, 2015 http://www.nytimes.com/2015/11/15/magazine/the-crispr-quandary.html?_r=0

Lavender, Paige. “Dr. Jennifer Doudna: Women Can Pursue STEM Fields and Still Be Mothers, Wives on Their Own Terms,” Huffington Post, Jan 21, 2015. http://www.huffingtonpost.com/2015/01/21/dr-jennifer-doudna-davos_n_6505830.html

Palca, Joe. “In Hopes Of Fixing Faulty Genes, One Scientist Starts With The Basics.” NPR, Oct. 13, 2014. http://www.npr.org/sections/health-shots/2014/10/13/354934248/in-hopes-of-fixing-faulty-genes-one-scientist-starts-with-the-basics

Pollack, Andrew, “Jennifer Doudna, a Pioneer Who Helped Simplify Genome Editing.” The New York Times, May 11, 2015. http://www.nytimes.com/2015/05/12/science/jennifer-doudna-crispr-cas9-genetic-engineering.html

Russell, Sabin. “Cracking the Code: Jennifer Doudna and Her Amazing Molecular Scissors,” California Magazine, Winter 2014. http://alumni.berkeley.edu/california-magazine/winter-2014-gender-assumptions/cracking-code-jennifer-doudna-and-her-amazing