Jennifer Doudna

2.1. Childhood and background

Jennifer Doudna was born on February 19, 1964, in Washington, D.C., to Dorothy Jane (Williams) and Martin Kirk Doudna. Her father earned his PhD in English literature from the University of Michigan, and her mother held a master's degree in education. When Doudna was seven years old, her family relocated to Hawaii so her father could accept a teaching position in American literature at the University of Hawaii at Hilo. Her mother further pursued her education, earning a second master's degree in Asian history from the university and teaching history at a local community college.

Growing up in Hilo, Hawaii, Doudna was captivated by the island's natural beauty, its diverse flora and fauna, and its unique environment. This fascination nurtured her sense of curiosity and her desire to understand the fundamental biological mechanisms of life. This natural inclination was complemented by the intellectually stimulating environment fostered by her parents at home. Her father, an avid reader of science, filled their home with numerous books on popular science. A pivotal moment occurred when Doudna was in the sixth grade: her father gifted her a copy of James Watson's 1968 book, The Double Helix, which detailed the discovery of the structure of DNA. This book served as a major inspiration for her future scientific pursuits. Doudna's interest in science and mathematics also flourished during her school years. Despite being told that "Women don't go into science," she remained resolute in her ambition to become a scientist. She later reflected that such discouragement only strengthened her determination.

While attending Hilo High School, Doudna's scientific curiosity was further cultivated by her 10th-grade chemistry teacher, Jeanette Wong, whom Doudna has consistently cited as a significant influence. A visiting lecturer on cancer cells also encouraged her to pursue science as a career. She spent a summer working in the University of Hawaii at Hilo lab of the noted mycologist Don Hemmes and graduated from Hilo High School in 1981.

2.2. Education

Doudna pursued her undergraduate studies at Pomona College in Claremont, California, where she specialized in biochemistry. During her freshman year, while taking a general chemistry course, she experienced self-doubt about her ability to succeed in science and considered changing her major to French as a sophomore. However, her French teacher encouraged her to persist in science. Chemistry professors Fred Grieman and Corwin Hansch at Pomona College significantly influenced her. She began her first scientific research in the laboratory of Professor Sharon Panasenko. She earned her Bachelor of Arts degree in biochemistry in 1985.

For her doctoral studies, Doudna chose Harvard Medical School, where she earned a PhD in Biological Chemistry and Molecular Pharmacology in 1989. Her PhD dissertation focused on a system that enhanced the efficiency of a self-replicating catalytic RNA, and her research was supervised by Jack W. Szostak. After completing her PhD, she held research fellowships in molecular biology at the Massachusetts General Hospital and in genetics at Harvard Medical School. From 1991 to 1994, she served as a Lucille P. Markey Postdoctoral Scholar in Biomedical Science at the University of Colorado Boulder, where she worked under the mentorship of Thomas Cech.

3.1. Research on ribozyme structure and function

Early in her scientific career, Doudna dedicated her efforts to unraveling the intricate structure and biological function of RNA enzymes, also known as ribozymes. While working in the Szostak lab, Doudna successfully re-engineered the self-splicing Tetrahymena Group I catalytic intron into a true catalytic ribozyme capable of copying RNA templates. Her initial focus was on engineering ribozymes and understanding their underlying mechanisms. However, she soon recognized that the inability to visually observe the molecular mechanisms of ribozymes presented a significant challenge.

To overcome this, Doudna moved to the laboratory of Thomas Cech at the University of Colorado Boulder in 1991. Her goal was to crystallize and determine the three-dimensional structure of a ribozyme for the first time, which would allow for a direct comparison between ribozyme structure and that of enzymes, the catalytic proteins. She completed this pioneering project at Yale University in 1996, having joined Yale's Department of Molecular Biophysics and Biochemistry as an assistant professor in 1994.

At Yale, Doudna's research group achieved a significant breakthrough by successfully crystallizing and solving the three-dimensional structure of the catalytic core of the Tetrahymena Group I ribozyme. Their findings revealed that a cluster of five magnesium ions formed a hydrophobic core within one region of the ribozyme's P4-P6 domain, around which the rest of the structure could fold. This arrangement was analogous to, yet chemically distinct from, the way proteins typically form a core of hydrophobic amino acids. Her group went on to crystallize other ribozymes, including the Hepatitis Delta Virus ribozyme. This foundational work in solving large RNA structures paved the way for further structural studies on an internal ribosome entry site (IRES) and various protein-RNA complexes, such as the signal recognition particle.

Doudna was promoted to the prestigious position of Henry Ford II Professor of Molecular Biophysics and Biochemistry at Yale in 2000. In 2000-2001, she held the distinguished title of Robert Burns Woodward Visiting Professor of Chemistry at Harvard University.

3.2. Academic positions and leadership

In 2002, Jennifer Doudna relocated to Berkeley, California, to join her husband, Jamie Cate, accepting a professorship in biochemistry and molecular biology at the University of California, Berkeley. This move also granted her access to the Advanced Light Source synchrotron at Lawrence Berkeley National Laboratory, which was crucial for her experiments involving high-powered X-ray diffraction.

In 2009, Doudna took a leave of absence from Berkeley to work at Genentech, where she was tasked with leading discovery research. However, after just two months, she returned to Berkeley, aided by her colleague Michael Marletta, canceling her other obligations to dedicate herself to the study of CRISPR. This experience reinforced her understanding that the academic environment was a better fit for her research focus.

As of 2023, Doudna remains a prominent figure at the University of California, Berkeley, where she directs the Innovative Genomics Institute (IGI). The IGI, which she co-founded in 2014, is a collaborative effort between Berkeley and the University of California, San Francisco (UCSF), dedicated to developing genome editing technology and applying it to address some of society's most pressing challenges in human health, agriculture, and climate change. Doudna holds the Li Ka-shing Chancellor's Professorship in Biomedicine and Health and chairs the Chancellor's Advisor Committee on Biology. Her laboratory's current research focuses on the structure and function of CRISPR-Cas systems, the development of new genome editing technologies, novel delivery mechanisms for CRISPR therapeutics, and innovative techniques for precisely editing microbiomes.

Beyond her roles at Berkeley, Doudna is also a faculty scientist at the Lawrence Berkeley National Laboratory, a senior investigator at the Gladstone Institutes, and an adjunct professor of cellular and molecular pharmacology at UCSF.

3.3. CRISPR-Cas9 genome editing discovery

Doudna's groundbreaking work on CRISPR began in 2006 when she was introduced to the system by Jillian Banfield, who had found Doudna through a Google search for "RNAi and UC Berkeley." In 2012, Doudna and her colleagues made a pivotal discovery that significantly reduced the time and effort required to edit genomic DNA. Their breakthrough centered on a protein called Cas9, found in the Streptococcus bacterial "CRISPR" immune system. This Cas9 protein, in cooperation with guide RNA, functions like molecular scissors: it targets and slices the DNA of invading viruses, thereby preventing bacterial infection.

While the CRISPR system was initially discovered by Yoshizumi Ishino and his colleagues in 1987 and later characterized by Francisco Mojica, it was Doudna and Emmanuelle Charpentier who, for the first time, demonstrated that it could be programmed using different RNAs to precisely cut and edit various DNA sequences. This discovery has since been extensively developed by numerous research groups for a wide array of applications, ranging from fundamental cell biology and plant and animal research to potential treatments for debilitating diseases such as sickle cell anemia, cystic fibrosis, Huntington's disease, and HIV.

As CRISPR technology became increasingly adopted for editing multicellular organisms, Doudna emerged as a leading voice on the ethical implications of using CRISPR to alter an organism's function. She, along with several other prominent biologists, called for a worldwide moratorium on any clinical application of gene editing in humans using CRISPR. Doudna explicitly supports the use of CRISPR for somatic gene editing, which involves gene alterations that are not passed on to future generations. However, she advocates against germline gene editing, which would result in heritable changes. She expresses optimism about CRISPR's potential to cure currently untreatable genetic diseases and improve sustainable agriculture, but also voices concern that the benefits of the technology might not reach those who need it most if its development is not approached thoughtfully and deliberately.

The development of the CRISPR system provided a new, straightforward method for editing DNA, which led to a rapid pursuit of patents for the technique. Doudna and her collaborators at UC Berkeley applied for a patent, as did a group at the Broad Institute affiliated with the Massachusetts Institute of Technology and Harvard. Feng Zhang at the Broad Institute had demonstrated that CRISPR-Cas9 could edit genes in cultured human cells just a few months after Doudna and Charpentier published their method. Before the UC Berkeley patent application was decided, a patent was granted to the Broad Institute investigators. UC Berkeley subsequently filed a lawsuit challenging this decision. In 2017, the court ruled in favor of the Broad Institute, which had argued that their research began earlier and they were the first to demonstrate its application in human cell engineering, while the UC Berkeley group had only suggested this application. UC Berkeley appealed, contending that their initial publication clearly described and detailed how to perform the application that the Broad Institute had pursued. In September 2018, the appeals court again decided in favor of the Broad Institute's patent in the United States. Meanwhile, UC Berkeley and its co-applicants were also granted a patent covering the general technique. Further complicating the issue, in Europe, the Broad Institute's claim of having initiated the research first was disallowed due to a procedural flaw in their application, involving a discrepancy in the personnel listed in the lawsuit versus the patent application. This led to speculation that the UC Berkeley group might prevail in Europe.

3.4. Company founding and commercialization

To facilitate the commercialization of CRISPR technology, Jennifer Doudna co-founded Caribou Biosciences in 2011. In September 2013, despite ongoing legal battles, Doudna co-founded Editas Medicine with Zhang and others. However, she departed from Editas in June 2014. Subsequently, Emmanuelle Charpentier invited Doudna to join CRISPR Therapeutics, but Doudna declined, citing the experience at Editas as akin to a "divorce." Doudna is also a co-founder of Intellia Therapeutics, a spin-off company from Caribou, and Scribe Therapeutics, which has pioneered CasX, a more compact, next-generation Cas9 enzyme capable of efficiently cutting DNA.

In 2017, Doudna co-founded Mammoth Biosciences, a San Francisco-based bioengineering technology startup. The company initially raised 23.00 M USD in funding, followed by a Series B funding round in 2020 that raised 45.00 M USD. Mammoth Biosciences is dedicated to improving access to biosensing tests that address critical challenges across various sectors, including healthcare, agriculture, environmental monitoring, and biodefense.

In 2017, Doudna co-authored A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution with Samuel H. Sternberg. This book is notable as a rare first-person account of a major scientific breakthrough, specifically aimed at educating the general public about gene editing.

Beyond her work on CRISPR, Doudna has also made other significant discoveries, such as revealing that the hepatitis C virus employs an unusual strategy to synthesize viral proteins. This research has the potential to lead to the development of new drugs that can effectively stop infections without causing harm to the body's tissues.

3.5. COVID-19 response

Beginning in March 2020, Jennifer Doudna spearheaded an initiative to leverage CRISPR-based technologies in response to the COVID-19 pandemic. Working alongside Dave Savage, Robert Tjian, and other colleagues at the Innovative Genomics Institute (IGI), she helped establish a dedicated COVID-19 testing center. This center processed over 500,000 patient samples, serving not only UC Berkeley students, staff, and faculty but also members of the surrounding community and farm workers in the Salinas area.

Concurrently, Mammoth Biosciences, a company co-founded by Doudna, announced the peer-reviewed validation of a rapid, CRISPR-based point-of-need COVID-19 diagnostic test. This new diagnostic offers advantages by being faster and less expensive than traditional qRT-PCR-based tests.

3.6. Other activities

Jennifer Doudna is a founder and the chair of the governance board of the Innovative Genomics Institute, which she co-founded in 2014. She also holds positions as a faculty scientist at the Lawrence Berkeley National Laboratory, a senior investigator at the Gladstone Institutes, and an adjunct professor of cellular and molecular pharmacology at the University of California, San Francisco (UCSF).

Doudna serves on the scientific advisory boards of the companies she co-founded, including Caribou Biosciences, Intellia Therapeutics, Mammoth Biosciences, and Scribe Therapeutics. Additionally, she holds advisory roles for other prominent organizations such as Altos Labs, Isomorphic Labs, Johnson & Johnson, Synthego, Tempus AI, and the Welch Foundation. In 2022, she joined Sixth Street Partners as their chief science advisor, where she guides investment decisions related to CRISPR technology.