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The dark side of DNA editing

Genetic engineering can lead to great medical advances but, as Matthew Cobb’s new book shows, it also brings alarming ethical dilemmas.

By Henry Marsh

Genetic engineering is the artificial alteration of DNA – the self-replicating molecule from which genes for all living organisms are formed. The advent of this new technology has often been compared to the development of the atomic bomb. But rather than destroy life with bioweapons, genetic engineering can alter life, or even synthesise it. And rather than simply modifying the genome – the genetic make-up – of a single organism, it can change the genomes of the organism’s descendants for generations to come.

The consequences of this are almost impossible to predict, as genes are so complex. Although there are only 20,000 human genes, they all interact. Eye colour in humans, for instance, is determined by seven genes, and, even when those genes are known, you can only predict eye colour with 70 per cent certainty. Schizophrenia is thought to involve at least 100 genes acting in concert. Altering an organism’s genome is not to be undertaken lightly.

There are serious questions about the safety of genetic engineering, but also profound social and ethical questions about its use. Matthew Cobb, in his detailed and deeply researched book The Genetic Age, is concerned as much about these questions as he is about the technical details of the engineering. Genetics and genetic engineering are fiendishly complicated. Cobb provides an overview as he recounts the history of the science, but the book is not a primer for understanding the field; it is much more than that. Cobb, it is worth noting, is a historian (of France during the Second World War) as well as a scientist and professor of zoology at the University of Manchester.

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Genetic engineering, he tells us, began in 1972 (although only the scientific magazine Nature noticed it at the time). Researchers at Stanford University led by Paul Berg published a paper showing that they could combine DNA from the bacterium E coli, which lives in the human gut, with the DNA of a mammalian virus known as SV40. This technique of creating “recombinant DNA” – that is, DNA formed from the DNA of more than one species – was rapidly developed and it became possible to fuse together DNA from almost any organisms. From this, Cobb writes, came “the explosion of the biotechnology industry, the development of GM [genetically modified] crops and gene therapy, massive advances in our scientific understanding of the whole of biology and, ultimately, the current excitement over CRISPR gene editing”. Recombining DNA is like cutting and pasting text from one document to another, while CRISPR editing is like rewriting the original text. These are clearly tools of enormous potential power.

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To help us understand the risks (and benefits) of genetic engineering, Cobb gives us a chronological account of how it developed, and describes the times when worried geneticists – most unusually for scientists – agreed (temporarily) to suspend research to assess its risks. Such pauses occurred four times, in 1971, 1974, 2012 and 2019. The researchers’ concerns were mainly about how to make genetic research safer, and how it might be regulated. There was little, if any, discussion of the moral question of whether the work should be carried out in the first place. There was decreasing unanimity over the years as to whether research should be regulated or not. Some (such as Jim Watson, who had established the structure of DNA with Francis Crick in 1953) argued that regulation was inherently wrong, as it was impossible to know what the risks of research might be without carrying it out in the first place.

At first research was almost exclusively carried out in the US, but it is now taking place all over the world, making any attempts at regulation even more difficult. Cobb mentions with approval examples of regulatory bodies, such as the International Civil Aviation Organisation and the UN Convention on Biological Diversity, but gives us few grounds for optimism that similar agreement might be possible with genetic engineering. As it is, the US has not signed up to the latter convention. Moreover, federal regulation can only apply to federally funded research – and much of the research is going on in commercial organisations in the US.

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The commercial use of genetic engineering is worth billions of dollars and the profits involved have had an enormous impact on academic research. Some scientists have become millionaires and universities scramble to put patents on discoveries made in their laboratories. Biotech has become hugely profitable for patent lawyers in the US and intense commercial rivalry has contaminated the pure science of academia. Spin-off biotech companies are created on a cloud of hype that attracts venture capital; they then must struggle to achieve what has been promised.

The founders of Genentech, one of the first biotech firms, raised millions of dollars and committed themselves to manufacturing insulin from bacteria without a clear idea as to how it could be done. They were successful, but many other start-ups were not. The scandal of Elizabeth Holmes’s company Theranos, where a start-up raised hundreds of millions of dollars on an entirely false hope of producing multiple analyses of a pinprick drop of blood, is an example of the risks of this way of doing business.

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The story of genetic engineering is one of tremendous achievement, with many Nobel Prizes being won, but, as Cobb observes, that “scientific discovery is… overdetermined… In the long term the impact of any given individual is generally of little significance.” The science advances with its own momentum, discoveries often being made simultaneously in different laboratories, followed by a slightly farcical race to be first to publication, so as to win a Nobel. Besides, I would suggest, science now is so much a question of teamwork that the Nobel Prizes for individual scientists verge on rather silly theatre.

Cobb fears the misuse of genetic manipulation in three main areas. First, the editing of the human germ line, as occurred both egregiously and incompetently in 2018 in China when researchers used CRISPR to produce a pair of twins with significantly altered genomes. Second, the creation of “gene drives”, which involve inserting genes into an organism that will kill it after it has reproduced, and are irreversibly passed on to every succeeding generation, resulting in the eventual extermination of that organism. Third, the creation of lethal pathogens, either for research or as bioweapons, that could escape from the laboratory and cause untold harm. Covid is a reminder of just how vulnerable we remain to pathogens.

One of the striking conclusions to this complex book is that the practical achievements of the genetic engineering revolution, despite the profound advances in scientific understanding and all the hype and excitement, have often been more modest than you might suppose. The dangers, however, remain. The application of gene therapy to single-gene diseases has been fraught, although there have been some wonderful successes, such as in treating children with severe combined immunodeficiency or spinal muscular atrophy, and in CAR T therapy for leukaemia. But the number of patients who have benefited is vanishingly small and such treatments cost millions of dollars per case.

GM crops are now grown all over the world and yet the early claims that they would transform agriculture in developing regions, as in Africa, have not been borne out, just as the hysterical fears over “Frankenfoods” have not been realised. CRISPR editing is not completely precise, in that editing one gene might damage other genes “off target”. Cloning remains highly inefficient. One successful clone comes at the cost of hundreds of embryos that fail to develop. Attempts to clone successful racehorses, for instance, have been abandoned.

Cobb writes that he remains “enthusiastic” but “deeply concerned” about the possibilities of genetic engineering. There cannot be any simple conclusions other than that the technology has scarcely started to realise its full potential for both good and bad.

Henry Marsh is a former neurosurgeon. His most recent book is “And Finally: Matters of Life and Death” (Jonathan Cape)

The Genetic Age: Our Perilous Quest to Edit Life
Matthew Cobb
Profile, 448pp, £25

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This article appears in the 02 Nov 2022 issue of the New Statesman, The Meaning of Rishi Sunak