Podcast Review: The Joy of Why – What's the future of gene editing?

Fourteen years ago, Professors Jennifer Doudna and Emmanuel Charpentier published the first demonstration of CRISPR-based genome editing (see BioNews 730). It would not be an understatement to say that this has completely changed the landscape of experimental biology. It has led to advanced therapies that were previously confined to the realm of scientific speculation, sparked one of the largest patent disputes in modern history (see BioNews 1292, 1031, 967 and 954) and made it remarkably accessible to manipulate an organism's DNA.

In an interview with astrophysicist and author Professor Janna Levin for the podcast The Joy of Why, which features discussions with leading researchers about their work, Professor Doudna explains how this breakthrough came about. Unsurprisingly, like many of the most important scientific discoveries, it involved a great deal of serendipity and was anything but a direct path.

Reflecting on her career, Professor Doudna concedes that, despite the fame and successes she has achieved, 'I certainly did not know that I was a natural match for my subject area.' She attributes her love of science to a high school chemistry teacher and later to reading the classic The Double Helix by James Watson.

I found her description of how her understanding of science was shaped during her high school years particularly relatable: 'It was the realisation that science is a process of discovery. It's not about memorising a bunch of facts. It's about figuring things out. I remember thinking clearly when I was in high school that it would be a really fun career to be paid to figure things out, and that's what I've always pursued.'

I think that this realisation – that science is actually creative rather than prescriptive, as it is often taught in earlier years at school – is a common turning point for many people who go into research.

It was also fascinating hearing about Professor Doudna's academic career and the story leading up to the work that won her the Nobel Prize (see BioNews 1070). Originally, her work focused on RNA, a molecule that is a key component of CRISPR but is also ubiquitous throughout biology, and has more well-known roles in regulating gene expression.

Originally, Professor Doudna was interested in studying the structure adopted by a specific type of RNA molecule and how this enables it to catalyse chemical reactions. It was not until 2002, when she moved to the University of California, Berkeley, that she met a colleague who had discovered the first evidence of an RNA-guided immune system in bacteria that would later be recognised as CRISPR.

The explanation of how CRISPR was discovered and exactly what it is was extremely clear and accessible. I think it can be confusing for a lay audience that CRISPR refers both to a naturally occurring bacterial immune system and to the genome-editing technology derived from it. However, here, Professor Doudna clearly explains how the system works in nature and why this made it an ideal tool for making genetic changes, even though this 'certainly wasn't the motivation for the project in the beginning.'

There were some topics that I would have liked to see her reflect more on. When asked whether some people might choose not to have a gene therapy due to potential side effects or other ethical reasons, Professor Doudna focuses more on the inherent risk of advanced therapies and the need to proceed carefully. 'With any technology of course there's always risk, right?' she says. 'So, I think, gene editing, we have to employ it cautiously because it does require a lot of knowledge about what effect a genetic change is going to have.'

While this is undoubtedly true, I would have liked to hear her engage more directly with the questions around ethics and patient choice that I felt Professor Levin was raising. One of my colleagues recently organised a roundtable bringing together families, researchers and clinicians affected by an inherited form of autism and intellectual impairment. When one parent was asked whether they would have wanted the opportunity for their child to receive a gene therapy, they said no, simply because they felt it might have altered who their child was. As advanced therapies become available for an increasing number of conditions, this debate will only intensify.

Still, the interview covers so many aspects of the wider implications of CRISPR in medicine and science. From the now infamous 'CRISPR babies' (see BioNews 977, 991 and 1029), to applications in agriculture and climate change, the discussion of the technology's potential benefits and consequences is comprehensive and serves as an excellent introduction to the field. I was particularly pleased to hear discussion of a challenge that receives less attention outside academia: the need to create improved delivery systems to transport CRISPR and other gene therapies into human cells.

I would highly recommend this interview as a commute listen to anyone curious about CRISPR, the scientific process, or the story behind one of the most important scientific discoveries in recent years.