Jennifer Doudna: Rewriting the Code of Life
When she was in the sixth grade in Hilo, Hawaii, her father left a paperback of James Watson's *The Double Helix* on her bed. She read it expecting a detective story and got one, but the detail that stayed with her was Rosalind Franklin. "It struck me then for the first time," she wrote later, "that a woman could be a great scientist." Her high school guidance counsellor subsequently advised her that girls did not do chemistry. In October 2020 she and Emmanuelle Charpentier became the first two women to share a Nobel Prize in the sciences.
An Outsider on the Big Island
Jennifer Anne Doudna was born on 19 February 1964 in Washington, D.C., the eldest of three daughters. Her father Martin was a speechwriter at the Department of Defense; her mother Dorothy taught at a community college. In 1971, when Jennifer was seven, the family moved to Hilo on Hawaii's Big Island.
She was a haole, a non-native, and school was lonely. She responded by reading and by walking into the landscape, hiking and exploring caves on an island she describes as offering "a rich palette of biological diversity." The isolation and the surroundings did what neither alone might have: they made a naturalist out of a solitary child.
Pomona, Harvard, and the RNA World
Ignoring the guidance counsellor, she entered Pomona College in 1981 and graduated in 1985 as its top chemistry student. A summer in Don Hemmes's laboratory studying fungal infection of papayas gave her, she says, "my first taste of the thrill of scientific discovery."
She took her doctorate at Harvard Medical School under Jack Szostak, working on self-replicating RNA molecules, a line of research aimed at the origin of life itself. Their 1989 *Nature* paper demonstrated RNA-catalysed synthesis of complementary-strand RNA. In 1991 she moved to the University of Colorado to work with Tom Cech, who had won a Nobel Prize for showing that RNA could act as an enzyme, and learned X-ray crystallography, the technique Franklin had used on DNA.
Yale, and the Shape of an Enzyme
Doudna became an assistant professor at Yale in 1994. There, with her graduate student Jamie Cate, whom she later married, she determined the first detailed atomic structure of a self-splicing RNA enzyme. Their 1996 *Science* paper is regarded as a landmark: it showed that RNA folds into intricate three-dimensional machines in the way proteins do, and it established Doudna as one of the field's leading structural biologists a decade and a half before CRISPR.
In 2002 she and Cate both moved to UC Berkeley as professors in the College of Chemistry and faculty scientists at Lawrence Berkeley National Laboratory. They had married in 2000; their son Andrew was born in 2002.
A Cup of Tea in Berkeley
The SARS outbreak of 2002 pushed her toward RNA interference, the mechanism by which small RNA molecules silence genes. The consequential move, though, came from a stranger. The microbiologist Jillian Banfield found Doudna's work through a Google search and proposed they talk. Over tea at a Berkeley café, Banfield described strange repeating sequences in bacterial genomes, interspersed with fragments of viral DNA, that had been named CRISPR. Nobody knew what they did. Banfield wondered whether they worked through RNA interference.
Doudna started pulling on the thread. By 2008 her group had organised the first international CRISPR conference in Berkeley, at a point when the field was small enough to fit in a room.
June 2012
At a microbiology conference in Puerto Rico in 2011 she met Emmanuelle Charpentier, who had been working on the same system from the bacterial side and had identified a second RNA molecule, tracrRNA, essential to its function. They agreed to collaborate. Working with Martin Jinek in Doudna's lab and Krzysztof Chylinski in Charpentier's, the two groups worked out that the Cas9 protein was guided to a specific DNA sequence by RNA, and then cut both strands. More importantly, they showed the two natural RNAs could be fused into one engineered single guide RNA, and that changing its sequence would send Cas9 to any target the experimenter chose.
The paper, "A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity," appeared online in *Science* on 28 June 2012. What had been an obscure bacterial immune system was now, in the Innovative Genomics Institute's phrase, a tool that "allows scientists to rewrite DNA, the code of life, in any organism, including human cells, with unprecedented efficiency and precision." Doudna has described the period as one of "pure joy."
The Ethics Problem She Made Her Own
Almost immediately she began worrying about what she had helped release. In 2015 she called publicly for a moratorium on editing the human germline and convened twenty researchers in Napa Valley to draft guidelines, then co-organised the International Summit on Human Gene Editing that December. She co-wrote *A Crack in Creation* with Samuel Sternberg in 2017 to put the argument to a general readership. When a Chinese scientist announced gene-edited babies in 2018, Doudna pressed for international regulation and took the case to US senators.
She founded the Innovative Genomics Institute in 2014 with Jonathan Weissman and helped launch Editas Medicine and Caribou Biosciences to move the technology into clinics. In March 2020 the IGI converted itself in a matter of weeks into an automated coronavirus testing laboratory and released its COVID-19 intellectual property as open source. The institute went on to run the first FDA-approved CRISPR clinical trial for sickle cell disease.
Why Jennifer Is Called a Genius
Doudna's distinctive ability is recognising that a curiosity is actually a tool. CRISPR had been observed by others; its function as a bacterial immune system was being worked out by microbiologists; Charpentier had the crucial piece from her side. What Doudna brought was two decades of thinking about RNA as a three-dimensional machine rather than a passive message, which is precisely the training that let her see a programmable cutting device where a microbiologist saw an interesting defence mechanism. The single guide RNA, collapsing two natural molecules into one engineered component, is an engineer's simplification, and it is what turned a phenomenon into a technology anyone could use.
The honest counter-case is substantial and she does not dodge it. The Nobel was shared with Charpentier, and neither would claim sole authorship; Jinek and Chylinski did much of the decisive bench work; Banfield supplied the question; Feng Zhang and George Church demonstrated CRISPR editing in human cells shortly afterward, and a long patent dispute followed over who is entitled to what. CRISPR was, more than most Nobel-winning discoveries, a convergence, and Doudna's own statement on the day of the award said as much: the honour "recognizes the history of CRISPR and the collaborative story of harnessing it into a profoundly powerful engineering technology." What is uniquely hers is the structural insight, the decision to keep pulling on an obscure bacterial oddity for four years before anyone thought it mattered, and then the unusual choice to spend her fame arguing for restraints on her own invention.
Legacy
Doudna holds the Li Ka Shing Chancellor's Chair in Biomedical and Health Sciences at Berkeley, is a Howard Hughes Medical Institute investigator, a faculty scientist at Berkeley Lab, a senior investigator at the Gladstone Institutes, and president and chair of the board of the IGI. Before Stockholm she had won the Breakthrough Prize in Life Sciences in 2014, the Gruber Prize in Genetics and the Princess of Asturias Award in 2015, the L'Oréal-UNESCO Award and the Gairdner in 2016, the Japan Prize in 2017 and the Kavli Prize in Nanoscience in 2018. Walter Isaacson's *The Code Breaker* made her a public figure in 2021. CRISPR is now used to model human disease, breed disease-resistant crops, drive genes through mosquito populations and treat sickle cell disease in human patients. On the morning of the Nobel announcement, asked what it meant that two women had won it, Doudna's answer was two words: "Women rock."
Achievements
- Nobel Prize in Chemistry — 2020
- Foreign Member of the Royal Society — 2016
- Wolf Prize in Medicine — 2020
- Notable work: Jennifer Doudna: We can now edit our DNA. But let's do it wisely
- Held posts at Howard Hughes Medical Institute, University of California, Berkeley and University of California, San Francisco
- Educated at Harvard University, Hilo High School and Pomona College
- Fields of research: Hepatitis C virus, RNA interference, X-ray crystallography and biochemistry
