Giants in genomics: Jennifer Doudna

Jennifer Anne Doudna is a Nobel Prize-winning biochemist who led the development of a revolutionary technology that can precisely edit tiny sections of our DNA. This technology, called CRISPR-Cas9, is in use in hundreds of laboratories around the world and could potentially have a huge impact on multiple areas of science, including medicine and the food industry.

Early life

Jennifer was born in Washington, D.C., USA, in 1964. As a young girl she moved to Hawaii with her family after her father accepted a teaching position there. Her parents were both academics in the field of humanities but Jennifer found herself drawn towards science. She spent summer holidays in the laboratories of family friends, read science books (including James Watson’s account of the discovery of the DNA double helix) and visited museums.

Jennifer was inspired by having a strong female role model in a world still dominated by men.

She started her scientific career in 1981 as an undergraduate at Pomona College in Claremont, California, USA. Her undergraduate supervisor was Sharon Panasenko, and Jennifer was inspired by having a strong female role model in a world still dominated by men. She earned her degree in chemistry from Pomona in 1985. She then went on to study for her PhD at Harvard, under the supervision of Jack Szostak.

Understanding RNA

It was while she was at Harvard that Jennifer gained a fascination with RNA, which was known to have an important role in making proteins within a cell. However, investigations by Jennifer and others were indicating a new function of RNA – it could function like an enzyme. This form of RNA – called a ribozyme – could catalyse processes in the cell, notably RNA splicing.

She honed this area of her knowledge while in the laboratory of Thomas Cech, who won the 1989 Nobel Prize in Chemistry for discovering that RNA can act like an enzyme. During this time, Jennifer worked on creating crystal structures of RNA to understand what they look like at a molecular level and discover more about their function.

Discovery of CRISPR-Cas9

In 2002 she moved to University of California, Berkeley, as a Professor of Biochemistry and Molecular Biology. During her time at UC Berkeley, Jennifer has been studying the structure and function of RNA, including understanding the process of RNA interference – where RNA molecules stop certain genes from being expressed.

She was introduced to CRISPR by Jillian Banfield, a colleague at UC Berkeley. Jillian had discovered CRISPR in the course of her work and wondered whether it was a bacterial version of RNA interference. Intrigued by the prospect, Jennifer agreed to investigate CRISPR further in her lab, little knowing that this decision would eventually lead her to the discovery that led to her Nobel Prize.

As her lab became more interested in CRISPR, Jennifer met Emmanuelle Charpentier, who was a specialist in how CRISPR works in bacteria. Together they began to investigate whether CRISPR could be used to edit DNA. They discovered that pairing CRISPR RNA with an enzyme called Cas9 created a system that could be guided to very specific areas of DNA and act like a pair of scissors, cutting out the desired piece of DNA.

While gene editing technologies existed before the discovery of CRISPR-Cas9, what made this technology special was that it could be targeted to a very specific location in the genome. This means that any DNA in a plant, animal or human has the potential to easily be modified with great accuracy, reducing the risk of ‘off-target’ effects, where the gene-editing technology edits the wrong gene or accidentally edits surrounding DNA, which could have devastating consequences.

One of the reasons that there is such excitement about CRISPR-Cas9 is that it could be used to cut out a gene that causes disease and replace it with one that doesn’t lead to illness, without having side-effects caused by off-target gene editing.

Genome Editing Controversy

The discovery of something as powerful as CRISPR-Cas9 has of course caused some controversy.

The discovery of something as powerful as CRISPR-Cas9 has of course caused some controversy. The ability to edit genes has the potential to treat or eliminate certain conditions, but this brings up several moral and ethical issues. Jennifer continues to be an important voice in the ethics of using CRISPR and believes that it shouldn’t be used for medical purposes or for editing genes which can be passed on to the next generation.

There have also been some legal battles about who owns the patent for developing the CRISPR-Cas9 technology, with Jennfier and her team” at UC Berkeley claiming that they developed the technology first. This is disputed by Feng Zhang and colleagues at the Broad Institute of MIT, who claim that they were the first to use the technology in eukaryotic systems. The patent dispute is still ongoing.

Nobel Prize and Beyond

This is the first time two women have been awarded the Prize together.

Jennifer and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for their discovery of CRISPR-Cas9 in 2020. This is the first time two women have been awarded the Prize together.

In recent years, Jennifer has been investigating how CRISPR technologies could help in the ongoing Covid-19 pandemic. She remains active at UC Berkeley, with her lab focusing on genome editing and further investigating RNAi structure and function.

Article written by Louise Walker, Public Engagement Development Coordinator at Wellcome Connecting Science