Podcast Review: The Life Scientific - Jennifer Doudna

The new era of gene technology presents an exciting approach to treat deleterious, inherited genetic conditions. In the podcast series of The Life Scientific, presenter Professor Jim Al-Khalili of the University of Surrey talks to Professor Jennifer Doudna of the University of California, Berkeley, from her early life to her research into molecular biology, to the development of the CRISPR/Cas9 genome editing system.

'We're at a point where technologies are converging to allow scientists to do experiments and research that hasn’t been possible before,' said Professor Doudna.

As a seven-year-old growing up in Hawaii, Professor Doudna was motivated by books and ideas. In the podcast opening, she refers to reading 'The Double Helix' by Dr James Watson at the age of 13, which piqued her interest and curiosity into how the molecular structure of DNA could be uncovered experimentally. Describing science as 'fun', she explained how she focused her scientific career on understanding the fundamentals of biology, with an emphasis on revealing the basic mechanisms and functions of RNA.

Professor Doudna recalls the discovery of the bacterial defence system, CRISPR, by Spanish scientist Professor Francisco Mojica of the University of Alicante, Spain in 2000. Fascinatingly, Professor Mojica's research uncovered how bacterial cells store and save fragments of viral DNA within the CRISPR system, serving as a genetic memory bank if the same virus attacks the cell again. This led to the beginning of a new age of genome editing.

It was only when a food company, DuPont, released a 2007 publication that the potential of CRISPR technology was realised. Professor Doudna describes this as a time that changed her line of research to focus on this new and obscure technology. She describes the collaboration with Professor Emmanuelle Charpentier of the Max Planck Institute, Germany, a medical microbiologist, which led to the discovery of two crucial RNAs (crRNA and tracrRNA) found within the bacterium Streptococcus pyogenes, which guides the Cas9 protein – a molecular scissor - to cleave the DNA target.

Towards the end of the podcast, it is interesting to hear Professor Doudna's opinion about the ethical implications of the technology that her team pioneered. She shares a sense of 'growing unease' as many laboratories adopted the genome editing tool, using various types of cells from different species including mice and monkeys.

The technology could also be used in human embryo and germline cells in countries that lack stringent regulation. She describes the latter as a 'horrifying thought', as it could lead to heritable changes being passed onto future generations and paves the way to control human evolution. So far, in the UK the HFEA (Human Fertilisation and Embryology Authority) have only approved the use of CRISPR/Cas9 in embryos that are donated for research purposes (BioNews 837) within IVF clinics. While more recently, Chinese scientists have edited the cells of a normal human embryo (BioNews 892); which poses concerns around 'designer babies'.

The topic of eugenics was very briefly touched upon during the podcast. 'One of the beauties of human life is variety,' said Professor Doudna, and takes a stand against the technology being used in this way. She has currently called for a global pause on the use of the CRISPR/Cas9 system until it is deemed safe for clinical application.

In my opinion, although the system has revolutionised the way in which incurable diseases (such as cystic fibrosis) could be eradicated in the future, it certainly raises many ethical, social and regulatory challenges.

The risks of off-target DNA mutations that could lead to unwanted genetic complications (BioNews 837) must be considered, and possibly the creation of new inheritable conditions. Here, healthcare professionals including genetic counsellors would play a vital role in helping couples make an informed choice about the benefits but also risks of genome editing. However, how will informed consent be implemented when the biological changes and safety risks are transmitted to future generations?

Further, who will be able to access treatment? Will it be available for only those who can afford to pay for the technology? If so, could this potentially result in less support offered to newborns and adults with disabilities and lead to stigmatisation towards affected individuals and their families? Many questions remain unclear.

As a clinical research associate, who works to stringent global, country and site level regulations to get safe drugs to market, I have been surprised by the minimal guidelines or regulation in some countries for powerful technology. At times, the most rigorous regulations stem from tragic events, as seen in the drug industry, and hence precautions with CRISPR/Cas9 should start now and be embedded in a global regulatory framework. However, this will be challenging.

The short podcast is an interesting insight into the development of the CRISPR/Cas9 system through a joint collaboration. It is interesting to not only hear what motivated Professor Doudna at an early age to a career uncovering the basic biology of RNA, and what eventually led her to the CRISPR/Cas9 system, but also her ethical views on the new technology.

The tone of the interview set by Professor Al-Khalili is formal and the questions posed allow Professor Doudna to meander through her scientific career. Towards the last few minutes of the podcast, listeners also learn about her personal feelings on how CRISPR/Cas9 has 'profoundly' changed her life, and how it is unlikely to change back in the near future.

Verdict: a recommended podcast for those curious about the scientific life and the pioneer of CRISPR/Cas9.