March 24, 2015, by Brigitte Nerlich

From recombinant DNA to genome editing: A history of responsible innovation?

In this post I shall report on a recent call for ethical and regulatory reflection by scientists engaged in a new genomic technology. I’ll then put this into a historical context of previous initiatives of that kind, and finally ask whether this can be called ‘Responsible Research and Innovation’.

CRISPR

Recently, a new controversy has emerged within genetics and genomics, fields that have had their fair share of controversy. This one is centred around a new technology to cut and splice DNA that would allow scientists to edit genomes. This technology has been applied to bacterial, plant and animal genomes but could also be applied to the human genome. This could lead to eliminating heritable diseases (similar to promises made around gene therapy), but could also enable the creation of ‘designer babies’ or ‘perfect babies‘. And, of course, the technique could also be used to resurrect the woolly mammoth, as reported in newspapers on 23^rd March. The real issue is perhaps that mistakes can be made in this cutting and splicing and that these mistakes could lead to unintended changes to the human genome. As New Scientist reported: Editing human embryos is genetics new battleground. Questions around interfering in evolution and around human enhancement are being asked again.

The controversial cutting and splicing technique is called CRISPR, which stands for: Clustered Regularly Interspaced Short Palindromic Repeats. (And as a social scientist, not biologist, I find it quite difficult to get my head round it) The acronym was first used in 2002 and CRISPR was first shown to work as a genome engineering/editing tool in human cell culture in 2012 (wiki). Two scientists in particular have been involved in developing a particular variant of this technique: CRISPR-Cas9 (and here on YouTube). They are Emmanuelle Charpentier, an immune biologist who works at the Helmholtz Centre for Infection Research at the University of Braunschweig and Jennifer Doudna, a specialist in molecular and cell biology at UC Berkeley (see their article in Science, 2014). Both have expressed worries about the potential misuse of this technique and Doudna organised a meeting in Napa, California in January this year to talk about ethical challenges ahead.

On 20^th March the American science magazine Science published a special section on the ‘CRISPR revolution’ (online 19^th March). This contained a ‘policy focus’ piece by 18 scientists and ethicists, entitled “A prudent path forward for genomic engineering and germline gene modification” (corresponding author: Doudna). The paper advocates a moratorium on “any attempts at germline genome modification for clinical application in humans”and calls for a “framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome”.

One of the authors of the article, the Nobel laureate David Baltimore, spoke to the New York Times. Interestingly, Baltimore was involved in the famous 1975 Asilomar conference on recombinant DNA in which a “group of about 140 professionals (primarily biologists, but also including lawyers and physicians)” came together to “to draw up voluntary guidelines to ensure the safety of recombinant DNA technology” (wiki). In the NYT interview Baltimore said: “’In 1975, scientists worldwide were asked to refrain from using a method for manipulating genes, the recombinant DNA technique, until rules had been established. We asked at that time that nobody do certain experiments, and in fact nobody did, to my knowledge,’ said Dr. Baltimore, who was a member of the 1975 group. ‘So there is a moral authority you can assert from the U.S., and that is what we hope to do’” in the case of genome editing.

The warnings expressed by the scientists writing in the journal Science echo those by scientists involved in a complementary enterprise using a slightly different approach who published their views in an article for the UK science journal Nature a week earlier under the title “Don’t edit the human germ-line”. Similarly, the International Society for Stem Cell Research (ISSCR) urges scientists “to stop the tampering and editing of the human germline genome in order to get involved with a larger discussion among scientists along with the public that will tackle ethical issues.”

Are these warnings exceptional or part of a pattern of scientists reflecting on their impacts on society? In the following I’ll show how they are part of a pattern that began, at least, in 1975 with the Asilomar conference. The conference happened in the context of the responsible science movement and early calls for what later became bioethics (see also this article by Alice Bell).

Asilomar, synbio and beyond

The Asilomar conference was organized by Paul Berg who had created the first recombinant DNA molecules in 1972 to review scientific progress in research on recombinant DNA molecules and to discuss appropriate ways to deal with the potential biohazards of this work. Scientists were worried about the dangers posed by this new technology, as it allowed the combination of genetic information from very different species. The statement they issued became a landmark which reverberated through the ages, not only in biotechnology, but also nanotechnology and, more recently, also in the context of geoengineering.

Synthetic biology, which makes use of recombinant techniques and in some instances may also involve the use of the CRISPR system, began to emerge in the early 2000s. “Like conventional biological engineering, synthetic biology rests on revolutionary advances in DNA sequencing and synthesis technologies. Unlike most recombinant DNA work, synthetic biology seeks to do biological engineering with standardized biological parts, modularized design, and routinized methods of assembly.” (Oye, 2012) From the very beginning, scientists and science educators involved in synthetic biology, especially those organising  the famous iGEM competitions, have not shied away from discussing ethical and regulatory issues around synthetic biology. Now, movements are afoot to implement more stringent regulations.

As early as 2004 a news item in Science entitled “Should there be a synthetic biology Asilomar?” reported on key scientists and ethicists talking together about “responsibilities to society,” and a desire to hold a meeting “modeled on the 1975 Asilomar Conference, at which biologists defined safeguards needed to contain genetically engineered microbes.” In 2006 risks and ethical issues surrounding synthetic biology were discussed at a Synthetic Biology 2.0 conference, which again was framed as a synthetic biology version of Asilomar, and in 2007 a synbio governance report was published. In 2014 a policy group within the seminal synthetic biology Institute led by Craig Venter published a Report on Challenges and Options for Oversight of Organisms Engineered Using Synthetic Biology Technologies. In the same year, George Church, one of the leaders in the field and contributor to the Science article led by Doudna, spoke about the risks and benefits of genome editing at the Harvard Museum of Natural History. (He is also the one talking about using CRISPR for exploring cold resistant genes in the woolly mammoth)…

Responsible innovation

Can all these long-standing ethical, social and regulatory reflections initiated by scientists collaborating with ethicists in the context of biotechnology and synthetic biology be entitled ‘Responsible Research and Innovation’ (RRI), a new approach to ethics, regulation etc. advocated for the democratic governance of emerging technologies? The article in Science calling for a moratorium on CRISPR says that “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations”. Supporters of RRI would surely applaud all the ethical work and reflection scientists have already been carrying out for so many years together with ethicists and governmental organisations. However, they would also urge them to engage more and earlier with members of the public. As the UK’s Synthetic Biology Roadmap famously said: ‘engagement’ “means genuinely giving power to a wide range of diverse social groups, including those who will be the end users or presumed beneficiaries of the technologies, taking their concerns seriously, and enabling them to participate throughout the whole pathway of technological development”. How to implement this aspiration is another matter.

[This Making Science Public post also contributes to my social science work on the BBSRC/EPSRC funded Synthetic Biology Research Centre.]

——

Articles etc. published AFTER the publication of this post:

A new YouTube video on CRISPR by Jennifer Doudna

A ‘dinner table’ explanation/video by Carl Zimmer

Fascinating history of recombinant DNA controversy in the 1970s  (thanks to @nccomfort for tweeting this); and more on ethics in The Conversation:  (HT @SynFutures)

On the Napa meeting and its (legal) implications

Silvia Camporesi in the Huffington Post

On intellectual property and CRISPR

Claims are emerging that Chinese scientists have edited the genomes of human embryos (22 April, 2015)

The paper itself – An editorial in Protein & Cell explaining why it was published and urging caution (28 April, 2015)

A great article by Carl Zimmer on these developments (23 April) with the best explanation of CRISPR etc I have seen so far!!

Interesting ethical reflections calling for reason not emotion, and a defence of the Chinese experiment

Nuffield Council on Bioethics inquiry

Blog post by Peter Mills (including discussion of Pinker) (2 September)

Blog post by Peter Mills (27 November)

Philip Ball arguing that this is not a slippery slope (7 May, 2015)

More on the issue in Nature – article by Sara Reardon – and another Nature article from 3 June, 2015

And, of course, an article in io9 by George Dvorsky

Expert reactions gathered by the Science Media Centre

An article asking whether the discussion has been nuanced enough by Arvind Suresh  Genetic Literacy Project

ICYMI: Fascinating discussion about #CRISPR w/ @carlzimmer, Marcy Darnovsky of @C_G_S, & Nobel laureate Craig Mello HT @nccomfort

A philosophical comment by Christian Munthe – with apt Jackson Pollock metaphor (25 April)

A long article in Scientific American on ethical debate (29 April)

Ronald Bailey argues in Reason.com that the Chinese experiment was ethical (1 May)

Article in New Scientist with good info on various gene editing techniques (2 May)

A round-up of the controversy on Vox (4 May)

An article in the New Statesman (5 May)

Editorial in Nature (6 May)

Article in The Observer (6 May)

A radio programme from the CBC (8 May)

Is embryo engineering a moral duty, asks Tony Perry (13 May)

An article combining discussion of revolution and responsibility (14 May)

The scientific community speaks – compilation of voices in Nature (14 May)

And now US science leaders are convening a science/ethics summit! (18 May) RRI in action?

Interview with Francis Collins (18 May)

And an appeal to take social justice into account (19 May)

A PNAS article – Core Concept: CRISPR gene editing

BMJ: UK scientists reject call for moratorium on gene editing

Invoking the spectre of Eugenics

VERY interesting reflections on what a public debate about gene editing might mean by Gregor Wolbring, 2 June, 2015

Dan Sarewitz on genome editing and democratic deliberation (25 June, 2015)

Bioethics and accountability

Francis Collins writes about CRISPR and the microbiome (14 July, 2015) (thx Brett Johnson for alerting me to this!)

Eric Lander writes about CRISPR (12 July)

An insightful paper by Nathaniel Comfort on CRISPR and the threat of a eugenics of personal choice (16 July, 2015) – nicely written up in biopoliticaltimes

And now with added Pinker – overview of ensuing debate in Popular Science and a blog by Richard Ashcroft (11 August) and more by Pinker! And more by Hastings Centre (12 August), and more by Nathaniel Comfort (13 August)

A very good and balanced article in the Economist (22 August)

An article by @Fausto_Sterling – very good summary and some realism!

Initial joint statement on genome editing in human cells – by UK funding bodies (2 September)

Hinxton group say genome editing is essential (10 September) – and a reply by Peter Mills from Nuffield (15 September)

A wonderful overview of the whole technology by the Wellcome Trust (11 September)

Royal Society convenes deliberations (15 September)

Application to use CRISPR on viable human embryos in UK – response by Centre for Genetics and Society (19 September)

Insightful response from Philip Ball (21 September)

George Church says: ‘bring it on’ (19 September)

The question posed in the title of my post seems to have been answered and the answer is no and again here and here (but no real advice on HOW to involve the public!) (If a new Asilomar is not the answer what is?)

And here Sarah Zhang tells the real, messy story behind CRISPR (if somebody can tell me how, when and where to fit in ‘public deliberation’ into this roller-coaster, I’d be very grateful; just a few pointers and practical tips would be great!)

Not quite a debate yet but at least a survey! http://www.whatisbiotechnology.org/survey/index/670a773b/ (4 October) and https://theconversation.com/the-public-must-speak-up-about-gene-editing-beyond-embryo-modification-48623 and http://www.bionews.org.uk/page_575076.asp

Michael Brook talks sense in this New Statesman article on gene editing (or should it be ‘curating’, he asks) (5 October)

Good post by RRI tools on synbio, CRISPR, opening up science and patenting (I just wondered in how far synbio is discussed more in public than CRISPR) (8 July)

Gene editing record smashed in pigs (George Church) – article in Nature (6 October) (would one still call this xenotransplantation?)

Another (slightly panicky) call for more deliberation from a UNESCO bioethics committee (6 October)

CRISPR and industrialisation http://www.technologyreview.com/news/542311/dupont-predicts-crispr-plants-on-dinner-plates-in-five-years/ (11 October)

Nature looks at the regulatory map – very important!

And results from another SURVEY (30 October)

Nice summary of gene editing by John Parrington for Aeon Magazine (1 November)

Speculations about designer babies – and a a good comment from somebody actually using CRISPR in the lab

Gene editing to be tested on people by 2017? Editas (5 November)

article on Gene hackers in the New Yorker (9 November 2015)

CRISPR, a path through the thicket, Nature, Debra J. H. Mathews, Robin Lovell-Badge and colleagues (10 November)

Editing children, Eric Parens, Hastings Centre, Aeon (11 November)

LOTS of stories about Layla Richards and the use of gene editing (Talens) to treat her cancer: https://www.sciencenews.org/article/gene-editing-helps-baby-battle-cancer

Experts debate: Are we playing with fire when we edit human genes? I like Pinker’s metaphor: “A droplet in the maelstrom of churning genomes” (17 November)

BBC World Service Video with Robin Lovell-Badge explaining (and slightly hyping?) gene editing (27 November)

CRISPR and public engagement and initial survey results (26 November)

Interesting debate between Francis Collins and George Church! (30 November)

Gene editing summit to canvass GLOBAL ATTITUDES ! (30 November)

A very powerful pro gene editing statement by John Harris (2 December)

Thoughtful article by Sir Mark Walport on gene editing of embryos (9 December)

Summary of human gene editing summit in Washington, 1-3 December, Nature (10 December)

Good overview of the summit from Nuffield’s Andy Greenfield (17 December)

Report on a PET conference on ’embryo engineering’ (21 December)

Jennifer Doudna on her whirlwind year with CRISPR (21 December)

Crispr in action (16 January, 2016)

Plus: Eight Guardian articles, by Sheila Jasanoff, The Editor and Jonathan Montgomery (Nuffield Council on Bioethics) and one on the Chinese experiment by Ian Sample with “nuanced and interesting comments from the public on the whole” (@hilarysutcliffe); and a call for global public engagement by @FilippaLentzos and others. And a defence of germline engineering. Article by Ian Sample: GM embryos: time for ethics debate, say scientists and and Editorial. (and more)

and an article by Ian Sample on the forthcoming summit (30 November)

Flckr image labelled for reuse

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