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A risk-taker in the laboratory

A biography of biochemist Jennifer Doudna raises hard questions about where genetic research is heading

Janna Thompson Books 14 May 2021 1911 words

Slippery slope? Jennifer Doudna at the Royal Society in London in March 2018. Jeff Gilbert/Alamy

The Codebreaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race
By Walter Isaacson | Simon and Schuster | $49.99 | 560 pages

When news emerged in 2018 that the first-ever “designer babies” had been born in a Chinese hospital, the international furore was immediate. Scientist He Jiankui had used gene editing technology to modify the embryos to make them immune to HIV, the disease suffered by their father, defying an international agreement among scientists to limit the technology’s use.

He Jiankui was convicted by a Chinese court for violating scientific and medical ethics. But the scientists who had developed the technology already knew the risk that this line could be crossed; and they also knew that the potential benefits of gene editing were too great to ignore.

Gene editing is at the centre of a new book by American journalist Walter Isaacson, well known for his biographies of Steve Jobs, Leonardo da Vinci and others. In The Codebreaker, Isaacson focuses on one of the scientists who developed the technology, Jennifer Doudna, who went on to win the 2020 Nobel Prize in Chemistry with Emmanuelle Charpentier for “rewriting the code of life.” Doudna is an ideal protagonist for Isaacson, having played a leading role both in the revolution in biological science and in the public debate about its ethical implications.

But the story Isaacson tells in this excellent book is about scientific discovery itself and the scientists who made important contributions to breaking the code of life. Their breakthroughs, interactions, rivalries, and growing concern about the implications of their work are his larger subject.

Isaacson describes Doudna’s girlhood curiosity about why a type of swamp grass in her native Hawaii curled up when she touched it. “Nature is beautiful,” Doudna says, and its beauty is one of the themes of the book. But Isaacson also makes it clear that success in science requires more than curiosity and aptitude. Doudna was successful because of her willingness to take risks, and her ability to collaborate and coordinate the work of a team, and also because of her “competitive streak.”

Risk-taking was a feature of her early career. After Francis Crick and James Watson discovered the structure of DNA — the molecule that carries the genetic code of all living things — most research focused on how its sequences were put together in humans and other forms of life. Doudna had a hunch that RNA, the molecule responsible for expressing genes and manufacturing proteins in human cells, plays a more fundamental role in the origin of life than most others thought. She and her team at the University of California in Berkeley discovered that strands of RNA in a bacterium would cut up invading viruses and paste copies into its DNA, thus making it immune to future virus attacks.

Working together across national borders, Doudna and Charpentier discovered how this cut-and-paste operation works and how it can be manipulated. In their prize-winning publication they predicted that it could be used to edit genes in humans as well as in other complex forms of life.

By using a system similar to that employed by bacteria, teams of scientists soon learned how to take a gene out of a human cell and put another in its place. With a bit of help from postdoctoral researchers, Isaacson was even able to do it himself. The practical implications of gene editing are obvious. If genes can be replaced, then those that cause undesirable effects can be edited out.

Isaacson describes a successful experimental use of gene therapy to treat a woman suffering from sickle cell anaemia. Stem cells extracted from her blood were edited and reinserted into her body. The treatment affected the cells in her body only, but gene editing also makes it possible to replace genes in germline cells, which alters the genetic code of future generations. This was the problematic step taken by the Chinese scientist.

Isaacson’s book has two main themes. First, he provides an account of the development of genetic technology through the eyes of the scientists concerned. To achieve this, he immersed himself in their world. As well as conducting many interviews with those involved in the discovery process, he attended their conferences, spent time in their labs and joined them in their informal conversations over dinner. Second, he explores the implications of gene editing for humanity’s future and how scientists have grappled with the ethical issues it has raised.

Although Doudna’s career takes us into the world of twenty-first-century science, not all the pressures and ethical challenges are new. The tension between science as a collaborative enterprise and the rivalry of scientists seeking credit for a discovery has always existed. Which competitive behaviour is fair and which is unethical is adjudicated by the scientific community itself. It was all right, most of her colleagues agree, for Doudna to beat her competitors by putting pressure on a journal to fast-track the publication of a paper. “I would have done it myself,” admitted one of these rivals. It was not all right for James Watson to take Rosalind Franklin’s data from her lab without her permission in order to be the first to construct a model of DNA.

When scientists are encouraged to work with industry, form their own companies and take out patents on their discoveries, and when universities hire lawyers to ensure that they profit from the work of their scientists, collaboration can become the victim of market incentives, confidentiality agreements and legal proceedings. Isaacson describes how Doudna and her team became embroiled in a long, costly dispute with another group over a patent on gene editing. Agreeing to share patent rights, Isaacson concludes, would have been more sensible and better for the progress of science. Many of the scientists he interviewed agreed.

Though his account shows that the close relationship between industry and science can have detrimental effects, Isaacson is convinced that, overall, it works out for the best. Scientific innovation is costly and risky, he says, and without collaboration with industry and the incentives provided by intellectual property law, progress in genetic technology would have been much slower. Even if he is right, there is reason to doubt whether the public good, or the good of science, is best promoted by the incentives of the market. Could public trust in scientists be one of the casualties? Some think so. “Financial interests undermine the ‘white coat’ image of the scientist,” a bioethicist complained to Isaacson.

Doudna dreamed one night that Hitler visited her, wanting to learn about genetic engineering. Disturbed by this nightmare she decided that bioscientists had to confront the ethical implications of gene editing technology. At a conference in California in 2015 all agreed that using the technology to cure disease by editing non-inheritable genes was a good thing provided it could be made safe. But most of the attendees also agreed that using it to alter heritable genes is more ethically problematic and has to be controlled.

The consequences of altering heritable genes, intended or not, will be visited on our descendants. If mistakes are made, it is they who will suffer. This is one reason why bioscientists were alarmed by news of the Chinese babies. But the ability to alter the human genetic code has the potential to bring great benefits. The technology could some day be used to eliminate Huntington’s disease, sickle cell anaemia and other genetically carried diseases. It could be used to make humans immune to viruses like Covid-19. Those who attended the Napa meeting had good reason for not wanting a total or permanent ban on its development and use.

The problem with germline editing is not merely that a future Hitler might be able to use the technology to construct what he regards as a master race. The ability to edit our genes could propel us down what ethicists call a slippery slope. Genetic engineering to eliminate disease seems obviously desirable. Why not also eliminate congenital deafness and blindness? Why not prevent the birth of children with low intelligence or ugly features? Why not use the technology to increase intelligence, to make humans taller or more muscular, or to give future people new capabilities like night vision or resistance to harm from radiation?

Isaacson worries that unrestrained use of the technology will decrease human variety and the good that comes from diversity. He points out that it could also have bad consequences for social harmony and liberal institutions. Wealthy parents will be able to afford genetic enhancements for their children, poor parents will not. Economic inequality will turn into genetic inequality, widening with each generation. He also takes seriously the warning of the philosopher Michael Sandel, who thinks that the ability of people to sympathise with the plight of others will be lessened when our characteristics are no longer given to us by nature.

One of the most serious objections to allowing parents to choose their children’s characteristics is that they will no longer be so ready to love whatever child they get. Their regard will be conditional on whether their children meet their expectations. They will insist on value for money. The German philosopher Jürgen Habermas fears that a loss of autonomy — a denial of the right of individuals to choose their own goals and way of life — will be the inevitable consequence of making children into goods manufactured according to the specifications of parents or the state.

One suggested way to arrest the slide down the slippery slope is to draw a line between genetic therapy — using gene editing to cure disease and disability — and genetic enhancement — using it to make better babies. The first, according to this view, should be permitted; the second should not.

But the distinction is fuzzy, and many ethicists are not convinced of its importance. Parents enhance their children’s opportunities by giving them a good education, bioethicist John Harris points out. Why shouldn’t they be able to improve their opportunities by means of genetic technology? The Australian bioethicist Julian Savulescu argues that parents have a duty to bring into the world children who will have the best possible lives. If genetic technology makes a better outcome possible, then they ought to use it.

Doudna and most of her fellow scientists think that governments shouldn’t permit the market-driven development and use of genetic technology — at least until the implications are thoroughly discussed. “If we are wise,” concludes Isaacson, “we can pause and decide to proceed with more caution. Slopes are less slippery that way.” But one of the thoughts likely to trouble readers of his book is that ethical qualms, however wise, and restrictions, however judicious, are likely to prove a weak bulwark against the desire of many parents to use whatever means are available to give their children advantages. If some parents are prepared to use unethical and illegal means to get their children into top universities, they will probably also be prepared to use unethical and illegal means to give their children what they regard as the best genes.

One of Doudna’s colleagues told her that he had been consulted by an entrepreneur who proposed starting a business called Happy Healthy Baby that would enable parents to choose some of the genetic characteristics of their children. The scientist told the entrepreneur that the technology was not likely to be approved by the American government in the foreseeable future. Not a problem, the entrepreneur replied. She would set up her clinic in a country that was more permissive. Parents who could afford the treatments would be willing to travel. •

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