21 August 2017
ByAppeared in BioNews 914
'A crack in creation' is a beautifully dramatic name for this biography of CRISPR/Cas9, the revolutionary genome editing tool of the 21st century. Reading the prologue, I wondered if it would also be an autobiography by Professor Jennifer Doudna at the University of California (UC), Berkeley. Certainly, she begins by describing a rather grandiose, portentous dream - as our narrative heroine and real-life scientist stands on a beautiful beach from her childhood, she spies an approaching tidal wave, which she boldly paddles out to meet and dives through on a surfboard. Everything that CRISPR/Cas9 makes possible is the wave. We - the public, policymakers, and scientists - must be prepared to swim out and engage with it.
But the book is not a scientist's autobiography. I confess, I was a little disappointed. I do like reading autobiographies. By sharing childhood memories, awkward teenage years, and wryly admitted insecurities in adult life, famous scientists reassert themselves as human beings rather than icons. Still, though the book is written in the first person and describes only Professor Doudna's experiences, it is a book about herself in relation to CRISPR/Cas9, from around 2006 to 2016. Dr Samuel Sternberg, co-author of the seminal 2012 CRISPR/Cas9 paper, is listed again as co-author here.
The first half of the book is called 'The Tool'. Professor Doudna begins with an interesting account of 'natural genome editing' - spontaneous genetic rearrangements that have cured patients of genetic diseases through sheer luck - to whet our appetites for CRISPR/Cas9's potential as a tool against genetic disease. Through a brief history of alternative genome editing tools, she brings us to her meeting with Professor Jill Banfield at UC, who introduced her to 'CRISPR' - the sequence of unusual DNA repeats found in some bacteria. Professor Banfield wanted to know more about CRISPR, and based on other studies, had hypothesised that they might play some part in RNAi and bacterial immune systems. Professor Doudna, having spent much of her career studying RNA and with an interest in RNAi as a therapy, was hooked. She integrated CRISPR research into her lab and hired new postdoc researchers to carry out the work.
From here the book describes each step and set of experiments in the eventual characterisation of CRISPR, to the fusing of CRISPR with the enzyme Cas9 to create a customisable genome editing tool. This section of the book is fairly technical and requires attention to understand the significance of each step. Professor Doudna credibly describes the stepwise nature of research, how it is carried out by scientists working as part of a larger institution, occasionally derailed by researchers completing PhDs or needing to seek positions elsewhere, and draws on the published work of other groups around the world. She also emphasises the serendipitous nature of research, from meeting colleagues within the same institution or at conferences abroad, such as when she meets co-author Professor Emmanuelle Charpentier at a conference in Puerto Rico.
On the other hand, this section does describe a very neat narrative of the development of CRISPR/Cas9 - it almost seems inevitable. The inclusion of dates and names of researchers involved certainly creates a strong case for UC's claim (see BioNews 911) to the CRISPR patents.
And if this book does have any autobiographical elements, they are only assertions of Professor Doudna's persona as a scientist first, driven by a passion for research and possibilities. After the section culminates in the publication of the 2012 paper, she describes seeing the publication of other papers on CRISPR/Cas9 editing with 'elation' and 'excitement'. There is just a whisper of the patent dispute when she describes the dissection of the publication dates of these papers as 'a disheartening twist to what had begun as collegial interactions and genuine shared excitement about the implications of this research'. And then it is mentioned no more. There are no chinks in this scientist's armour regarding those matters. No acknowledgement that how scientific research is conducted, and how it is funded, also instigates many of the problems in development and regulation of genome editing technologies. In that sense, the book leaves an impression of forced gloss.
The second half of the book, 'The Task', discusses possible uses of CRISPR/Cas9 in agriculture and healthcare, referencing spots of current and past research. Although interesting and optimistic, I enjoyed the final quarter of the book more when it turned a little personal again. Our narrative heroine and scientist admits eventual caution, and then downright worry that 'public discussion was falling far behind the breakneck pace of [scientific research of CRISPR]'. Her subconscious delivers another helpfully clear and portentous dream where a pig-faced Adolf Hitler wants her to tell him the uses and implications of CRISPR/Cas9. Waking in fright, Professor Doudna draws comparisons between genome editing technology and the development of the nuclear bomb, worries over the transparency of research, and the open availability of genome editing procedures and tools. She arranges a conference to produce an advisory white paper on germline editing in human embryos, admitting such a task intimidated her and that taking a public stand on a scientific issue felt foreign and almost transgressive (see BioNews 795). The rest of the book deals with the public discussion and regulation of CRISPR.
Professor Doudna makes it clear that the book states only her opinions, and it's laudable that she is willing to make them public. She also occasionally discusses the current barriers and regulators of such applications, lifting the book slightly above general pro-science speculation and rhetorical questions. It is perhaps somewhat disappointing that the monetary side of scientific research, the patent disputes, and the distorting influence of commercialisation of technology is not discussed. The book is assiduously devoted to public debate, but the absence of these topics is both a proverbial elephant in the room and a clear message that the author does not want to step into the firing range.
I'm glad to see a scientist engaging so strongly in public debate about the use of technology, rather than speculating on the sidelines. Professor Doudna's perspective as a scientist also adds valuable insight for the public. She closes the book with a powerful call to scientists to be prepared to debate the consequences of their work, but to also communicate the nature of research.
Although the book clearly seeks to state that it was the expertise of her lab and her own specific, lifelong research interests that led to the discovery of the CRISPR/Cas9 genome editing method, she emphasises that open-ended science research was the only way to get there. It took decades of combined research and accumulated studies into the biology and chemistry of bacteria before the prospect of genome editing using CRISPR became apparent.
Professor Doudna's book delivers a positive scientist's view of a future where genome editing can deliver benefits for humankind, provided we strive for a society where everyone's rights are respected regardless of their genes. I gingerly await another author to deliver a more cynical look at whether this is possible.