Today marks 20 years since Dolly the Sheep was unveiled to the world by British scientists, at BBSRC’s Roslin Institute – which this month welcomed the appointment of a new director. Here ESRC-funded academic Sarah Franklin, who authored the book Dolly Mixtures, looks at where we currently stand on the ethics surrounding cloning.
A designer sheep
On 22 February 1997 the world woke up to a new phenomenon: a cloned Scottish sheep named Dolly. She became a global superstar: famous because she was a completely normal sheep. Dolly embodied a famously misunderstood scientific technique, namely cloning.
‘Clone’ comes from the Greek word for twig, klon. The origins of this reproductive designation lie in viticulture: fruit can’t be reliably propagated from seeds. If you want the same kind of grape you had on the parent vine, you should propagate from the parental body, not a mixture of parental gametes.
Sex is a mess as far as the control of reproduction goes: if you want to breed true take all your sprouts from the same trunk. Dolly wasn’t bred from rootstock, and she wasn’t a true clone. She was a ‘designer sheep’ in the sense that her tailor-made genome was intended to be a template for a new means of transgenic reproduction. But clone or not, Dolly was a shattering proof of principle, marking the dawn of a new age of ‘second creation’. She was the viable offspring of a technique considered to be ‘biologically impossible’ – namely the reprogramming of an entire embryo from a single transferred nucleus. Moreover, in Dolly’s case the nucleus came from an adult cell that had been cultured and frozen: she proved that an entire genome could be regenerated by reprogramming a fertilised egg using microinjection technology.
The extinction of biological impossibility
Dolly also proved the principle we might call the ‘Wilmut Doctrine’ which claims that the expression ‘biologically impossible’ has lost all meaning. Wilmut argued that the extinction of biological impossibility gave rise to a new social condition, which he called ‘the age of biological control’. In the past, biology provided limits, and these were socially useful: it’s not possible, for example, to cross a human with a tomato, or a goat with a fish. Or at least it didn’t used to be possible. In the age of biological control, the challenge is that even if it hasn’t been done already, almost anything might be achieved through the powerful combination of biology and technology that now enables genetic and molecular reprogramming of almost anything.
As a consequence, the Wilmut Doctrine predicts, future human ambition will no longer be bound by the inherent limits of organic life: it will be entirely up to us how we choose to reengineer biology, and so we will need better processes to establish social limits and rules governing what is desirable, permissible and ethical. In short, we will need to become much better at producing good biological governance. And we will need a diverse toolkit of resources, precedents and templates to do this work well.
Governing the ethics behind the biology
Unlike the US, the UK chose not to allocate the lion’s share of the looming biogovernance task to bioethicists. The ESRC Genomics Initiative, launched in 2001, was designed to train a whole new generation of social scientists to deal with questions such as how to regulate GM technology, human embryo research, genetic screening, and so forth.
This strategy expressed a characteristically British faith in a combination of empiricism and pragmatism to deal with questions such as whether or not to allow the patenting of human DNA.
On the whole this strategy has served the UK – which has no national bioethics institute – well enough. The UK is the only country to have successfully introduced comprehensive legislation through an act of parliament governing human fertilisation and embryology, for example. And the philosopher Mary Warnock’s recipe for viable social policy in this area was essentially sociological: she designed a new social contract whereby in exchange for permitting human embryo research up to 14 days, it would be subject to the very strictest regulations. Warnock argued that it was pointless to try to design governance based on the moral status of the human embryo – a topic on which, she argued, agreement was impossible. Instead of determining what was ‘right’ for the embryo, it was better to determine what was ‘alright’ to enough members of society in order for legislation to be passed. At least then there would be some limits, she argued, because the alternative would be none: ‘and this nobody wants’, she wrote.
Warnock’s position was not, as some have claimed, a case of throwing the philosophical principles out with the bathwater. Prioritising the pragmatic goal of viable legislation expressed a clear moral principle, namely that some legal limits were better than none. Reaching this goal, however, required sociological reasoning: in order for viable legislation to be passed, a sufficient consensus would have to be reached based on a carefully negotiated set of compromises.
How well we’re responding to ‘the age of biological control’
We are about to see the carefully negotiated 14-day rule on which the UK’s two Human Fertilisation and Embryology Acts (in 1990 and 2008) are based opened up again, in part because biological limits have been breached. Until recently, it has not been possible to maintain human embryos in culture beyond 14 days. However, Magda Zernicka-Goetz at Cambridge has shown that they can be grown much longer, and the research benefits of studying human embryonic growth for 21 days instead of 14 would be likely to yield many clinical as well as scientific benefits. At this juncture, Dolly’s legacy becomes visible once again. For we will need to ask how well we have responded to Ian Wilmut’s injunction to improve our ability to address the difficult challenges posed by ‘the age of biological control’.
Social scientists in the UK have better answers to these questions than in any other country, and the social study of biomedicine, bioscience and biotechnology is a field of research and research training in which the UK remains a world leader. We need to widen the sociology of translation and social studies of the STEM subjects more generally. Interdisciplinarity is key to this effort, and time is a key factor in developing successful interdisciplinary collaborations between sociologists and their partners in labs, clinics and industry. The social sciences are comparatively inexpensive: but it will be a hugely expensive mistake if vast investments in basic science infrastructure fail to generate broad social benefits because the research priorities they enable are out of synch with the wider society. Better links between the social and human science and basic scientific research need to be further developed, in part by increasing the size of social science departments at places like Cambridge.
Human cloning? The wrong question!
When Dolly was born the first question on every news programme was whether humans should be cloned. In my book Dolly Mixtures I argued this was the wrong question, a distraction, and a missed opportunity. Hers was the much more complicated story of a company, PPL pharmaceuticals, which wanted to produce a new treatment for Cystic Fibrosis, by using transgenic sheep as ‘bioreactors’ to produce alpha-1-antitrypsin (AAP) in their milk – known as ‘pharming’. Ian Wilmut refined the nuclear transfer technique to enable transgenic sheep to be produced more efficiently.
Dolly was thus a template for a more efficient means to reproduce a commercial line of transgenic sheep. Her history, like that of the Roslin Institute, belongs to the post war mammalian turn in developmental biology, and its subsequent human turn after IVF became successful in the 1970s.
Putting Dolly into a broader geopolitical history helps us to understand not only her birth, but the ‘age of biological control’ to which she belongs. This is a skill the social study of biotechnology promotes, and it is one we will need a lot more of in the age of CRISPR-Cas9 gene editing, synthetic biology, personalised medicine, metabolomics and whole genome sequencing.
Dolly was a charming, mediagenic and somewhat mischievous animal. I enjoyed meeting her and playing hide the treat games in her grassy paddock, where she lived a ‘diva sheep’ existence. She was also a fascinating animal model of our times, and one that continues to pose questions for us about how we plan to address the challenges of ‘disruptive’ scientific research in the decades ahead.
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