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 to see Professor Doudna in person. 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, and I was keen to hear what Professor Doudna really thought about all this...
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', her role began when a geobiologist at UC, Professor Jill Banfield, brought Doudna's attention to the CRISPR DNA sequences found in bacterial species.
Professor Doudna acknowledged 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 modestly.
Throughout the talk she frequently championed the importance of collaboration in science. Rutherford also 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, which essentially boils down to 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.' 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 – sounded odd to me. Would an expert in a new scientific technology really be so happy to step aside from debates on its use? But as Professor Doudna began to perceive the technology as rushing ahead too fast: she felt she had to get involved in the matter of its regulation, and the education of 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. Saying she gave a scientist's answers to earlier questions about CRISPR, Professor Doudna is now aware that when she talks about CRISPR 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.
It was time for my question. I wanted to know if she was frustrated by the focus on ownership and commercialisation of CRISPR, rather than on the science. Professor Doudna 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, emphasising her scientific background, and yet slightly humble. Really, this summed up my perception of 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 all had many more questions to ask, and Professor Doudna would have been willing to keep delivering answers. I enjoyed the event, and I suspect the conversation can be continued by reading her book.