The Nuffield Council on Bioethics discusses genome editing

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Image by the Nuffield Council on Bioethics, http://nuffieldbioethics.org/

The Nuffield Council on Bioethics has just released the first part of an important two-part discussion of genetic modification: “Genome editing: an ethical review” (128 pages, Sept. 2016). The contribution is very broad in scope, carefully thought-through, and aims at a comprehensive, balanced evaluation of genome modification. For that reason the review has the potential to shape the public discussion on genome editing and may have an influence on policies.

The first part describes the genetic procedures involved and surveys issues in wider society such as moral and religious points of view, the role of science in society, and the current political framework. The second part, which is going to be more clearly evaluative than the current descriptive one, will follow in 2017. While the Nuffield Council has also made a condensed, more accessible version of the report available, this post discusses the original, long version. Although the report discusses genome modification in humans, animals, plants, and ecosystems as well as technology and safety questions in an even wider sense, my analysis here will mostly be restricted to genome modification in humans. Indeed, this is where the review sees the greatest need for ethical evaluation as well.

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Image by the Nuffield Council on Bioethics, http://nuffieldbioethics.org/

The Nuffield Council on Bioethics itself is an interdisciplinary scholarly body, based in the UK, that advises on public and political questions raised by developments in the biomedical realm. The current working group consists of eight experts in the life sciences as well as professors of sociology, science, bioethics, and law (chair: geneticist Andy Greenfield). Through additional fact-finding meetings and a more widely disseminated call for evidence, the Council has also drawn on the expertise of numerous other experts, especially in the life sciences, but also in fields like sociology, philosophy, theology, and political science. The result is a detailed overview of many aspects involved in a wide field of scientific and technological research.

But if the evaluation is only to follow in a year, why go through the trouble of reading now if you’ve got the facts of genome editing right? The answer is, of course, that the way you describe a problem and lay out the issues can already set the course for a particular evaluation. So it is worth looking at the first part of the Nuffield Report to see what we can learn and where there may be further need for discussion.

The report is well aware that the importance of new technological developments is often blown out of proportion in early news reporting (112 note 511). Oneinnovation might add that efforts to find third-party funding and to highlight the prestige of the science-technology sector in wider society may also influence early evaluations of new technologies. This critique should not blind us, however, to
the possibility of truly groundbreaking developments. The report calls genome editing “transformative” in that it may change cultural practices and modify concepts.

Other posts of this blog have drawn attention to therapeutic and potential “enhancing” uses of genome editing. Here, the report adds a new dimension: genome editing might bring about new human physical abilities that could become critical in a changing environment: “As a species facing a number of potential environmental catastrophes, [humans will find that] Darwinian evolution may just be too slow” (51). At the same time I think it is debatable if the Council’s first example – equipping humans physiologically for “long distance space travel” (50) – should indeed be taken as seriously as many other issues surrounding genome editing.

Climate change may be a more important catalyst for genome modification when the report describes how scientists make plants resistant against pests and extreme environmental conditions. naturalis_biodiversity_transgenic_pigYields may perhaps be increased by genetic tweaking as the population on this planet keeps growing. In addition, animals can be rendered less susceptible to disease, and they may be adapted to large-scale farming (as in designing cows without horns). Many of these projects would not be possible with traditional breeding practices. Finally, micro-organisms may be modified to produce materials that are new or difficult to obtain, although this has already been achieved with methods that predate CRISPR and related gene editing techniques. [1]

The authors of the report also contend that we should not think of the relation of ethics, on the one hand, and science and technology, on the other, as inherently antagonistic (113f). Ethicists may, for example, push for a liberalisation of certain technological uses. This may certainly be true. For me personally, reports on vitamin-enriched rice and GM cotton that requires far fewer pesticides due to inherent pest resistance (again two examples developed with methods predating CRISPR and similar genome editing techniques) have shown that GM critics at least need to factor in the human cost of rejecting certain new technologies. But the report also identifies another dimension in the relation between ethics and science. It is to be commended for paying remarkable attention, on the sociological side, to which factors drive scientific innovation and applications, apart from strictly scientific exploration. The report rightly notes that science does not simply function as a repository of objective knowledge that is gained in a “value-free zone” in which other social concerns do not play a role.

Of course this does not mean at all that societies ‘make up’ science. But while scientists strive for testable explanations that enrich our knowledge of the natural world, other factors are always at play as well. Ethicists may also ask which criteria scientists use to pick out particular projects. Kathy Niakan, for example, whose current research modifies human embryos genetically in order to gain a better understanding of human fertility problems, argues: “It is up to society to decide what is acceptable: science will merely inform what may be possible.” Certainly there is some truth in this, but who makes the choices of what’s on society’s menu of options, and why in this way rather than that? In the words of the Council review:

“A commonplace but now largely discredited perspective viewed science as a resource from which innovators draw, leading to new technological innovations that provide social or commercial benefits, such as increased wellbeing and productivity. The flaws in this ‘linear model’ are generally thought to stem from its failure to give due attention to the complexity of innovation processes, the importance of feedbacks, the role of markets and other actors, and the effects of uncertainty and serendipity.” (15)

This is also a helpful reminder in the context of those genetic modifications, mentioned by the report, that might ease long-distance space travel: why precisely is this on a researcher’s agenda? As for the review, it is not clear to what degree such insight about the impact of non-scientific factors on science is still on the radar when the review mentions ideas to use genome modification to enhance human “night vision or olfactory sensation” (51).

So how exactly do scientists choose which applications to explore?

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Francis Bacon (1561-1626), a protagonist of the Scientific Revolution who argued that science must be beneficial to humankind

The Nuffield Council notes that scientists share a commitment not to do harm (25). This is a more modest approach than seeking to benefit society. Indeed, the review argues that the effects of discoveries are often unknown or depend, for good or ill, on the uses to which society will put them later on (25). However, according to a survey conducted by the Nuffield Council, a large number of scientists holds on to the creed that science is about ‘making scientific discoveries for the benefit of society’. This is the typically ‘modern’ creed of the scientific revolution, and this is remarkable. Certainly there is no reason to doubt the sincerity of the sentiment, and who would argue against the idea that among the achievements of science, there have been great improvements to the human lot? Yet again, the surveyed scientists would presumably not wish to be held accountable to the standard of a benefit to society. For it is not always clear what exactly a benefit to society is. The idea that a benefit and progress are a very straightforward affair is typical of the optimistic spirit of modernity, especially of the Scientific Revolution. This ‘benefit’ sentiment expresses the widespread, but doubtful idea that science is simply the objective pursuit of unambiguous progress. Apart from unknown effects and the varying application of new technologies (think of nuclear fission), we will still be concerned with another question about potentially beneficial uses of science.

To what extent do scientific associations reflect on the nature of society and what would constitute a benefit? Presumably, a factor that also drives many scientists is the pure fascination of ‘looking under the bonnet’ of nature, perhaps even of making discoveries that no human being has ever made. This is fully legitimate, as is, to a good extent, the simple wish to advance one’s own career by employing one’s talents. But given the far-reaching consequences that genome editing can very well have, it seems to me that at least the wider debate in society should aim at greater specificity than a simple assertion that ‘people’ would ‘wish to have’ certain medical and technical abilities.

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According to John Gast’s painting “Spirit of the Frontier”, progress does not “march” on, but floats.

For example, the review mentions efforts to revitalise extinct species, including even the woolly mammoth. What to make of that? The media reverberations of this project have been strong, driven both by fascination and bewilderment. What is the point of coming up with a project like this in particular? For the technical part, researchers would recover ancient DNA of an extinct species (say, a mammoth), modify the DNA of a related living species (an elephant) accordingly, produce a fertilised egg, implant it in the existing relative, and hope the new-boivf_smallerrn baby resembles the extinct species. The Council describes the hypothetical revitalisation of a mammoth as “more speculative” and “fanciful, if headline-grabbing”.

If the goals of the extinct species project included drawing public attention to new genetic applications, the project hit its target. But isn’t the creation of a mammoth a project perhaps at least as woolly as the mammoth itself? Letting a mammoth – if indeed it turns out to be one – roam free in Siberia is in one way very similar to abandoning a child’s pet when it’s no longer wanted. Surely our bunny will manage on its own in the wild!

Further, the Council speaks of the idea of creating a living Neandertal, a member of the human species that went extinct in the Stone Age, as a “more technically plausible possibility, however, although one that is far more ethically complex” (79). This phrasing gestures with some nuance and subtlety at a wider critique. Perhaps with too much nuance and subtlety?

When evaluating the ethical implications of scientific research, we certainly need to be careful to preserve academic freedom. That is why scientists should be held accountable not to the standard of benefitting society but to that of not inflicting harm – which also allows for neutral results. And indeed the review reminds us that any particular stance on genome editing, negative ones as well as a positive, can “contribute to or detract from a just society, one that, for example, fosters respect and fair treatment for women and people with disabilities” (49). In that respect, we do need to get a clearer picture of the potential risks of various genome editing applications – not just the medical risks of unwanted side effects, but potential social risks.

The larger point that I am pursuing here relates to what the report calls “‘technological momentum’, whereby the speed and impact of advancing technology pressurise normative structures” (39). Political regulation may perhaps be “ridden over by innovation” with insufficient deliberation. Pressure on political decision makers may come from various sources, such as public opinion, worries about scientific competitiveness, and economic factors. Technological momentum may also influence the moral discourse. New technological procedures may change what becomes the “new normal”, what we think of as acceptable and desirable. On a technical level, the review distinguishes technological momentum from a slippery slope effect, which is often cited in bioethical discussions but may be difficult to evaluate precisely.

The review certainly does not wave any banners inscribed “slow down technological momentum”. Nonetheless, I wonder if the playful fascination with potentially outlandish science projects might crowd out societal debates about potentially harmful effects of the methods employed. The slightly playful fascination with genome editing projects such as improved biological night vision and olfactory sensation, enhancements for long distance space travel, woolly mammoths, and Neandertals – I’ve been fascinated with those myself – contributes to and shapes public discourse in subtle but significant ways. But from a scientific point of view, why not focus on goals that arouse less short-term excitement, while still contributing to less outlandish goals such as therapeutic ones?

This is relevant given how, for example, a widely circulating popular science magazine like National Geographic – otherwise rightly noted for outstanding reporting – can uncritically lionise geneticist George Church, the protagonist of the woolly mammoth project, as spearheading the inexorable advance of science into a golden future (in an article entitled, “The Future Without Limit”). Not to speak of other prominent, more clearly one-sided public figures peddling a strictly gene-centred view of life in general. On the other hand, bioethics is sometimes viewed critically for a supposedly knee-jerk anti-science reflex [2]. Yet my point does not feed on any animosity against science per se. It is about how the public debate is conducted. Can public debate maintain a fair and balanced perspective in this dynamic play of powerful forces? Certainly, popular science should be commended for efforts in public education. But do conflicting concerns of similar importance have a similar representation in public discourse? Some people with disabilities who argue for disability rights advocate for the maxim, “Nothing about us, without us!” So to what extent are people with disability themselves involved and heard in public debates on genetic modification?

Indeed, the report raises the possibility that “genome editing combined with social liberalism may facilitate the ‘consumerisation’ of human biology” (52), mentioning a potential “commodification and manipulation of life under neoliberal capitalism” (100). Manipulations of the “biological conditions of human existence … allegedly interfere with [the] identity of the person in morally significant ways” (52). This is especially relevant for the question of a modification of the genome of an embryo. Technically, this procedure is still fraught with great difficulties, but it also raises particular ethical questions apart from the technical risk. In other words, is it reasonable to suppose that a person who was genetically modified, perhaps at the embryonic stage, perhaps for therapeutic purposes but also perhaps for cosmetic ones, would feel uneasy about having been ‘tinkered’ with, about not being unconditionally accepted in his or her very identity?

The point in raising this question is not to suggest, at least at this stage in the discussion, that the answer is simply ‘yes.’ In addition to the life stage at which the intervention would be done (an embryo? a born baby? a child, juvenile, or an adult?) and the therapy/cosmetics distinction, much depends on individual circumstances, and last but not least the success or failure of the intervention. The more general presentation of the question can also take on greater urgency with the possibility that a potential ‘normalisation’ of genome editing gives common currency to “‘eugenic’ views”, i.e. the “particularly toxic concept” (49) of discrimination against genetic outliers. Does the modification of the human genome bring us closer to a “‘selection society'”? (49) Clearly, the review does not shy away from addressing vexing questions.

“Disability justice and rights scholars have made a range of moral arguments against selective technologies, from individual rights based arguments such as the right to life of people with disabilities, to arguments for the social and emotional value (e.g. vulnerability to contingency) of biological difference, to the value to humankind of conserving disability cultures, and the importance of the visibility of disability in establishing social attitudes, behaviour, and structures.” (28)

The committee highlights the notion of human dignity as a point around which public no_shacklesdebate can meaningfully crystallise (28). Not many implications are drawn out, however, and it is not clear how the notion of human dignity might play out. In what sense and to what degree are people with disability included in the number of people whose dignity is at the centre of debate? How does their dignity relate to that of parents who wish to make free choices about an embryo, and how does it relate to that of geneticists whose work is of high quality from a strictly scientific point of view? How does the overall moral climate of a society that is more or less welcoming of people with disability enter the picture?

Not all passages in the review are equally sensitive, however. On the one hand, one definition of eugenics offered in the report struck me as conspicuously aseptic in not mentioning discrimination against people with disability: “the control of reproduction to increase the occurrence of desired heritable characteristics in a population”. Dicey, too, is a statement that treats “disability” primarily as a defect to be prevented rather than a personality trait. Here the report weighs the potentially therapeutic and preventative dimensions of genome modification, and as part of these deliberations then asserts that genome modification “is therapeutic … and it is preventative” in that it may prevent a child from “being born with a serious or life-limiting disability.” [3] There is no doubt that certain disabilities can be seriously life-limiting – but is that the whole story?

On the other hand, the report clearly highlights the critical possibility that societal preferences might change at the expense of people with disability:

“So, for example, the claim that the use of technologies that have the effect of reducing the incidence of disability (say, Down’s syndrome screening or preimplantation genetic diagnosis) expresses and compounds negative attitudes towards people with disabilities has been asserted, by some, as a reason to prohibit their use; others would see such a measure as an inadequately justified intrusion into private life and liberty.” (30)

In presenting the issues involved in a moral evaluation of genome modification, the review is walking a fine line, navigating issues such as free exploration on the part of science, the project of medical therapy, free individual choice, the manipulation and commodification of life, and discrimination against people with disability.

There are two further ways in which the committee wishes to evaluate genome modification, both fair enough to me. For one, the Council rejects a “precautionary

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Titian’s allegory of prudence

principle” in favour of a “precautionary approach” (69). A precautionary principle could lead to societal paralysis, critics argue, for the abstract fear that many things might go wrong so nothing should be attempted. Indeed, certain things can go wrong, but certain things that go wrong already could also be improved. Accordingly, using a “precautionary approach” instead would factor in the social cost of not acting. While the decision for a “precautionary approach” hardly prejudges the outcome of the second part of the report, it is clear that the Council rejects a simplistic, far-reaching prohibition of genetic modification.

With a rising world population and a mounting climate crisis, the implications of this may be clearer in the area of GM plants than in human genome modification, however. Further, the report indicates that the Council will orientate the ethical evaluation that is still to be published less based on the intrinsic qualities of genome modification than based on its consequences (72). This means that the evaluation will not be a purely scientific one taking place in the realm of genetics exclusively. Not all questions can be treated as “‘ELSI’ questions (questions about the ethical, legal and social implications of genome editing)” (115). For example, whether a disability is to be conceived of as a medical shortcoming, as a factor that may increase societal diversity, or both, is not a purely scientific question.

With these convictions in place, the second part of the report is highly anticipated. The concluding section of the first part highlights the question whether the genetic modification of human embryos before implantation – i.e., in the case of artificial fertilisation – should be allowed. If so, regulations would have to be changed, which involves a political process taking several years. To have a debate about this sooner rather than later is indeed advisable. As the committee argues, this can help avoid a situation in which putative research results are haphazardly carried over into far-reaching legal arrangements that might end up harming embryos and parents as well as public trust in science, technology, and the political process. Should it turn out that such a debate needs to be decided in favour of genetic modification, then it is indeed better to make such procedures available sooner rather than later.

So while the report makes a point of not restricting the ethical evaluation of genome editing to purely scientific aspects, the concluding section focuses very narrowly on specific practical questions. This is not necessarily a conflict. But at the same time it could indicate that the authors orientate the scope of the debate more narrowly towards very specific applications at the expense of the wider social and ethical concerns. That would indeed be unhelpful.

Above I have indicated slight tensions in the report that could perhaps have an important impact on the eventual conclusions. This would be unfortunate, as this current first part of the report presents a trove of helpful observations about the role of science and technology in society and its impact on how we see human life. I for one am hoping that the ensuing final part of the review will keep these factors firmly in view.

[1]

John Parrington mentions in his book that insulin was first produced by modified bacteria in 1982, so that diabetics no longer had to rely on the extraction of insulin from slaughtered pigs. This highlights important possibilities that genetic modification has had from early on, as well as an important humanitarian potential. CRISPR, however, makes possible endeavours more complex than the modification of bacteria.

[2]

Ted Peters, “CRISPR, the precautionary principle, and bioethics“, Theology and Science 13 (2015), pp. 267-270.

John Harris, “The Accidental Professor“, Cambridge Quarterly of Heathcare Ethics 25 (2016), pp. 574-582, p. 581.

The luddite charge presumably contributes just as little to a better ethical orientation as the blanket charge of bioethics “selling out” to biotech companies.

[3]

The passage in question (49) makes a distinction between genome editing, on the one hand, and gene therapy, on the other, which in the early 1990s and then again in 2000 was used to treat patients suffering from disease. While these two attempts seemed highly promising at first, they resulted in the death of one patient treated in one of the efforts and cases of leukaemia in the other. There has also been a notable gene therapy project in Germany about which there has been an explosive debate. A journalist accused the lead researcher of grave errors that left eight out of ten patients dead. The researcher, in turn, took the reporter to court for this conclusion, in part successfully. See also Carl Zimmer, “Gene therapy emerges from disgrace to be the next big thing, again“. Some journalists also conflate the terms gene editing and gene therapy. One of the reasons we might hesitate to call genome editing therapeutic is that it may (or may not, in fact) be used to modify the genome of a fertilised egg cell, which does not appear to treat evident symptoms. In addition, there certainly are uses of genome editing that are not therapeutic. But other uses of genome editing might even be described as gene therapy with more effective instruments. As the passage in the report also notes, the therapeutic uses of genome editing are not at all limited to embryos.

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