03 July 2017
ByAppeared in BioNews 907
'This technology really gets the imagination going. It's almost anything that you could imagine wanting to control at the level of genetics, is now in principle within reach.'
And the power to control evolution raises important questions of responsibility. This is the message of Professor Jennifer Doudna at the University of California (UC) and pioneer of CRISPR. It's a message that was repeated throughout her book launch conversation with science writer Dr Adam Rutherford, held as part of the 2017 Hay Festival.
It was Friday, a pleasant summer evening in London, and I was one of a small audience who had chosen to spend it in a dark auditorium at the Royal Institution listening to Professor Doudna. Here at BioNews, we have been closely following the latest developments in genome editing through CRISPR: covering updates about trials, regulatory debates, and patent disputes. I was keen to hear what Professor Doudna really thought...
But a conversation cannot be rushed. Dr Rutherford and Professor Doudna first skimmed through the history of genetic engineering until 2012 when she and Professor Emmanuelle Charpentier of the Max Planck Institute, Germany, published their landmark CRISPR paper.
CRISPR, said Professor Doudna, came at a time when there was a hunger to manipulate genomes with greater specificity. She explained how CRISPR is derived from the bacteria's adaptive immune system. Although it was being studied by 'a few labs around the world', she said, her work came about when a geobiologist at UC, Professor Jill Banfield, brought Doudna's attention to CRISPR DNA sequences found in bacterial species.
Professor Doudna acknowledges papers existed which suggested the purpose of these bacterial sequences, but no one had done an experiment yet. 'I was just fortunate that I had smart people who were thinking of me, and reaching out,' she said.
Professor Doudna frequently championed the importance of collaboration in science and Rutherford praised her book, for giving 'a very accurate account of academic life' and its constant stream of communication and conferences. This idea felt at odds with the current patent dispute – essentially, who worked out how to use CRISPR in animals first and who deserves that commercial credit. Professor Doudna's next response addressed my silent query.
'When [the 2012 paper] was published, I knew people would immediately understand,' she said, meaning that scientists would understand that the technology could be applied to different systems, allowing precise editing. And they did – in human cells, yeast, plants...
But it was a 'mindblowing' paper describing the editing and implantation of a monkey embryo in China, brought to her attention by a reporter, which stirred her into action. Her initial thought – that these debates should be left to bioethicists, not scientists –seemed odd to me. Now, she felt the technology was rushing ahead too fast: she had to get involved in influencing its regulation and educating the public about CRISPR, even if doing so would ostracise her in the science world.
Dr Rutherford and Professor Doudna discussed the legacy of gene therapy: a technology which like CRISPR had presented huge possibilities, but had been derailed by difficulties in developing safe clinical applications and even deaths in clinical trials (see BioNews 028). Although she has called for a moratorium on germline editing (see BioNews 795), she believes there will be a point in the future where it will be unethical not to use CRISPR to remove diseases from embryos.
Halfway through the event, Dr Rutherford opened the floor to questions. Professor Doudna delivered polished and confident answers, and indeed I found the structure and topics of the conversation closely followed the introductory chapter of her book.
How accurate would CRISPR need to be for clinical applications? We’re not there yet, said Professor Doudna. An audience member with a recent diagnosis of incurable spinocerebellar ataxia asked, quietly, how long a cure for such conditions might take, with CRISPR in the scientific arsenal. 'People send me pictures of their kids and ask me questions like that,' she responded sympathetically, and again emphasised that while she thought the speed of genome editing technology was great, the flipside was that it could generate negative consequences without the proper guidelines.
Someone brought up the recent paper which suggested CRISPR's legendary accuracy was overestimated (see BioNews 905). Professor Doudna dismissed it as a poorly done and flawed study. Those scientists, she said, just wanted attention, and they got it.
Who owns CRISPR? For the first time in the evening, Professor Doudna mentioned the patent dispute, casually, as 'something the audience may have noticed if they follow media'. But can you describe how you feel about it, she was asked.
'Honestly, it's hard,' she admitted. I for one appreciated these touches of personal honesty, which elevated the event beyond a rehearsed set of speeches to a genuine conversation. She believes she gave a scientist's answers to earlier questions about CRISPR but now, Professor Doudna says, when she talks about CRISPR she is aware that 'somebody's lawyers somewhere' are taking notes.
'But I'm not going to not be who I am. I can't not be a scientist," she said.
When I asked if she was frustrated by the focus on ownership and commercialisation, she responded that as an academic she was 'fascinated' by it, rather, to learn about the business side of science. And she wondered if the patent process could be improved for technology such as CRISPR - wouldn't it be great if UC and MIT did not waste tens of millions of dollars and instead invested it into research? 'I guess I just try and be philosophical about it, I can't do anything about it anyway, so I just try to learn from it.'
A convincing answer, confident and clear, yet human, emphasising her scientific background, and perhaps slightly humble. Really, this summed up the speaker. Though the event was short at less than ninety minutes and the auditorium only a third full, a lot had been packed in and I felt we had many more questions to ask, and Professor Doudna would have been willing to keep delivering answers. I enjoyed the event, and in effect I suspect the conversation can be continued by reading her book.