Genome-editing: into uncharted territory

by
25 November 2016

This development is hailed by scientists as revolutionary, but it raises some profound ethical issues, says Robin Gill

A BRAND-new technique for altering DNA sequences in plants, animals, and humans has raised exciting possibilities for the future — as well as serious ethical concerns.

Over the past four years, the development of the so-called CRISPR-Cas9 system has shown that it is now possible to make precisely targeted alterations to DNA sequences in living cells, in ways that would not happen spontaneously in nature. The technique, known as “genome-editing” (Comment, 15 September 2015), builds on developments made in genetic engineering over the past four decades, and, more recently, in synthetic biology. But it brings to them considerably more speed, accuracy, and efficiency, as well as lower costs and greater ease of use.

Many scientists are depicting this as a revolutionary breakthrough that may have many beneficial applications in medicine and food production. Of course, inheritable genomes, or their expression, can be altered spontaneously in nature through changes in replication (sometimes causing serious inheritable diseases); through radiation and toxic chemicals; and even, in the strange world of epigenetics, through environmental factors such as poor diet or stress. But now scientists might be able to “edit out” such alterations. Ethicists, however, have been more mixed in their responses to such “editing”.

The Nuffield Council on Bioethics is well aware of this gap between scientific enthusiasm and ethical reserve, and published recently the first part of its review, Genome Editing: An ethical review (available free at: nuffieldbioethics.org/project/genome-editing/). As its subtitle suggests, this is a review: it contains no explicit recommendations for action other than a few hints. These will be contained in a second report at a later date, yet to be announced. For the moment, it concludes that:

Characteristics of many kinds, from the colour or number of blooms in flowering plants, to some disease traits in animals and plants, can be altered, though the extent to which, and ease with which, such alteration can be made is highly variable.

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The Nuffield report recognises that the very term “genome-editing” relies on a homely and somewhat misleading metaphor: namely, that editors work to improve “written” texts. Yet, in reality, rogue editors (just think of some tabloid newspapers) might distort texts, with misguided or even malicious intent. Aware that genome-editing is not a neutral activity, and that DNA is not exactly a text, the report outlines some of the main ethical issues facing genome editing.

 

AMONG the most important of these are concerns about altering the human genome. There are good reasons for wanting to do so in families who carry life-threatening inherited conditions. But the report worries about the possibility of unintended consequences, which it colourfully terms “off-target effects”.

At the moment, too little is known about the complexities of the human genome to be confident about the effects of supposedly targeted alterations. Just think of the many plants or animals that are discarded before much has been achieved in genetic engineering.

Yet it is one thing to discard plants; it is quite another to discard sentient animals, and, especially, human beings. Even with plants, there is the issue of future off-target effects. Altered genomes in plants, animals, or humans alike might, after all, be inherited by generations to come.

A safer (and legal) method for humans to avoid life-threatening inherited conditions is to implant only healthy embryos, where possible, within affected families, using IVF and pre-implantation genetic diagnosis. Another, safer method is to use gene editing only for gene therapy on human beings, not for altering the inheritable genome. Last week, it was announced that scientists at Sichuan University, in China, are already attempting to do this, disabling a single protein (using gene editing) in the blood of a patient with lung cancer.

Another issue concerns animal and environmental welfare. Scientific enthusiasm for genome editing may involve suffering for thousands of animals in advance of any (still illegal) implantation of scientifically edited human embryos. And for edited plants, genetic release remains an important ethical concern, especially about the off-target effects upon the wider environment of releasing edited seeds. An issue that is already present from GM crops might be magnified hugely by low-cost and easily-used plant genome editing.

Some ethicists are also concerned that genome-editing, in all of these areas, is, in principle, “unnatural”. Here, I tend to agree with another Nuffield report, published last year, that looked in depth, but with some scepticism, at the varied meanings of “naturalness”, and their competing implications for public ethics (nuffieldbioethics.org/project/naturalness/the-findings).

More worrying for me is the concern that terrorists, say, might exploit edited malignant germs.

 

WE ARE not going to get any easy answers to these ethical concerns. But the Nuffield Council on Bioethics has done well to alert us so clearly to them. Significantly, the report on genome-editing argues that scientific enthusiasm needs to be tempered by careful ethical consideration:

There is a public interest in research for at least two main reasons. The first is to the extent that a great deal of research in the academic sector is publicly funded. . . The second, more profound, reason is that products and practices, processes and tools produced by the application of knowledge gained through research may have a direct or indirect impact on the well-being and welfare of the public (including their moral and social welfare). . . How technologies like genome-editing are taken up and regulated both reflects and influences the broader moral values on which common social life is based and the social meaning of the practices in question.

 

Canon Robin Gill is the Editor of Theology and Emeritus Professor of Applied Theology at the University of Kent. He is a former member of the Nuffield Council on Bioethics.

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