Posted by on February 18, 2021 12:36 am
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The Code Breaker and Crispr People — the ethics of editing humanity – Financial Times

In November 2018, the Chinese scientist He Jiankui revealed the results of a groundbreaking experiment: the birth of the first gene-edited babies. The arrival of twins Lulu and Nana, who had been edited as embryos to supposedly reduce their likelihood of being infected with HIV, sparked immediate outrage and condemnation from other scientists. The Chinese government later sentenced He to three years in prison.

For many observers, He had set the world on an uncertain path to reshaping humanity. It was as world-changing as a moon landing, or a death of a US president. Yet, do you remember where you were when you heard?

For all the headlines generated by the experiment in Shenzhen, it did not spark a global ethical debate about Crispr, the gene-editing technology that will almost certainly be used to change the course of life. While the world clashed over how to regulate the digital revolution, decades after those technologies had been unleashed, debates over building guardrails for the genetic revolution also risk being left until it is too late.

Crispr is a surprisingly simple-to-use tool with a clunky name: Clustered Regularly Interspaced Short Palindromic Repeats. It was developed by bacteria billions of years ago to fight viruses. But the breakthrough came in 2012, when scientists Jennifer Doudna and Emmanuelle Charpentier showed how snippets of Crispr could be used to identify stretches of DNA, guiding an enzyme known as Cas9 to snip out or change their function.

The technology could transform medicine: it is being used to treat genetic diseases, such as the blood condition sickle cell anaemia, in small human trials. It has been adapted to work as a diagnostic in new Covid-19 tests and, in the future, it could be used by humans to defeat viruses.

But some fear it could also enable humans to play God. They see a clear line between editing a living person with a disease, and editing an embryo with changes — such as removing genes responsible for inherited diseases such as Huntington’s — or, eventually, enhancing children into so-called “designer babies”. These changes, known as human germ line genome editing, are passed down forever.

With one of the biggest questions of our time so poorly understood by the general public, two new books try to shine light into the ethical labyrinth for the lay reader. In The Code Breaker, Walter Isaacson recounts the drama of the discovery in a digestible narrative that tackles the promise and the peril of Crispr. In Crispr People, law professor and bioethicist Henry Greely provides a more detailed framework for how to think about regulating to get the best out of Crispr, while avoiding a repeat of He’s experiment with life.

Jennifer Doudna, co-inventor of the revolutionary gene-editing tool Crispr © Getty Images

For Isaacson, an accomplished storyteller of innovation with past biographies of Leonardo da Vinci and Steve Jobs, it is something of a case of after the atom, then the bit, now the gene. The next great scientific revolution lies in biology and in Doudna, the co-discoverer of Crispr, Isaacson has found a new hero.

Growing up in Hawaii, Doudna got a taste for the scientific hunt when she picked up a copy of The Double Helix by James Watson, who helped discover the structure of DNA. She initially thought it was a mystery novel — and, while she soon realised her mistake, the book set her off on a career following clues.

A major staging post on that quest was reached last October when the Berkeley scientist and her collaborator, Charpentier, won the Nobel Prize for their world-changing work. “The men who had sequenced DNA taught us how to read the code of life, but the more important step would be learning how to write that code,” declares Isaacson.

Recounting complex scientific tales as if he were a storyteller around a fire, Isaacson helps the reader with signposts — “remember this tiny molecule” — and playful translations. Ribonucleic acid, or RNA, which Doudna devoted her life to studying, becomes a “middle manager” for its role in translating DNA into proteins.

Doudna, the liberal arts college graduate whose wide interests bridge the sciences and humanities, herself comes across as a far more amiable figure than Isaacson’s earlier subject, the mercurial Jobs. She says she prefers people in her team to get along, even if that means losing out on the talent of a wonderful misfit. Yet, when it comes to rivals, she is comfortable with cut-throat competition.

But, by focusing on Doudna, Isaacson has also picked a side in a stormy battle over who gets credit for Crispr. Perhaps inevitably, the discovery of Crispr has been accompanied by conflicting claims and legal wrangles over patents. Many of these ultimately boil down to determining how obvious it was that a tool proven in a test tube could be used in human cells. Doudna and Charpentier argue it was obvious. Rivals such as Feng Zhang of MIT, who pipped them to the post in publishing a paper that showed how he used Crispr successfully in human cells, argue it was a leap forward in its own right.

Isaacson does travel to Berlin to interview Charpentier. He also spends time — and apportions acclaim — to Feng. But there is no doubting who he sees as the driving force behind Crispr. Doudna is an obvious choice of main character because she has been driven into the public arena by a sense of responsibility for her creation. Her excitement about its potential is paired with a recognition of its perils: she once dreamt of inadvertently meeting Hitler, who had a pig’s face and was asking to understand the uses and implications of her technology.

So she was horrified when, on Thanksgiving 2018, she received an email with the cheery subject line “Babies Born”. He, whom she barely knew, told her he had done what scientists had called for a moratorium on: edited not just the cells of a human but an embryo, making a change in the CCR5 gene that could be passed down for generations.

Doudna was shocked and rushed to a conference in Hong Kong, where she persuaded He to take the stage and explain his experiment.

He Jiankui shocked the world by announcing the first gene-edited babies © Bloomberg

The Chinese babies experiment marks the start of Greely’s book. The Stanford law professor, who attended the first conference on the ethics of Crispr organised by Doudna, condemns it as “reckless, irresponsible, immoral, illegal, and probably fattening” (a possible unintended consequence of messing with genes we don’t understand).

Greely set out to discover exactly what He did — but, sadly for the reader, failed. Instead, the author pieces the story together from press cuttings from 2018. The trail quickly goes quiet. The Chinese government swiftly placed He under surveillance and later prosecuted him in private.

But what the first half of Crispr People lacks in gory details, Greely makes up for in the second half, where he tackles the substance of the ethical issues raised by He’s actions. Several countries, mainly in Europe, have banned human germ line editing. In the US, it is curtailed by regulations governing how the Food and Drug Administration can spend its money. Yet Crispr is fairly easy to use — and to hide. Many scientists, including Doudna, think it is already too late for a moratorium.

Greely condemns He so thoroughly because he believes the risks were sky high, and there were no real benefits. He edited CCR5, a gene that has made some populations less vulnerable to HIV, but we do not know enough about what else it does. We also do not know how to ensure every cell gets an edit. The supposed benefits are also suspect: the twins’ father was HIV positive but the risk of him passing on the condition is very minimal with a much safer procedure called sperm washing. Greely is also unconvinced that the parents were informed well enough to give proper consent.

While Isaacson is breathless in how momentous he thinks Crispr is, Greely breaks down what looks like an impossibly large problem — how to decide if we should edit the human race and in what circumstances — to the point where it almost looks like a regulatory framework for an existing drug.

Refusing to buy the argument that any human germ line genome editing is a slippery slope into science fiction, Greely argues that most of the edits we make are likely to already be in some of the world’s near eight billion people’s genome. In other words, it is unlikely we will create a genome that has never appeared in nature. Nor, Greely adds, do we really know enough about our genes to be able to make the enhancements that many fear: there is no single gene for smart or tall.

To tackle the scientific problems, Greely suggests starting with a cautious trial on a small group of parents with clear genetic problems they do not want to pass to their children. These offspring should be monitored for years to understand any untoward effects.

On a broader scale, both authors call for the public debate that has so far been lacking. Greely argues that the real dilemmas will be ones we already grapple with: safety and equity of access. Isaacson ranges more widely, examining how far we are from agreeing what “disadvantages” should be corrected — with many communities, such as deaf people, not considering themselves disabled — to fears that editing could breed conformity, as people could try to protect their children from discrimination by, for example, changing their skin colour. “Will we lose our diversity? Our humility and empathy? Will we become less flavourful, like our tomatoes?”

On a more immediate note, Isaacson has added an 80-page final section on how Crispr is being used to fight the coronavirus pandemic. The genetic revolution has helped us tackle Covid-19 with a new generation of vaccines that were quicker to make because they relied on Doudna’s favourite middle manager, RNA. But Crispr’s starring role is likely to come in a later public crisis, once it can be used to destroy viruses directly.

Emmanuelle Charpentier and Jennifer Doudna received the Nobel Prize for their work on Crispr © Getty Images

There is, however, another key aspect of the pandemic that, I fear, may be pertinent to the future of Crispr. Covid-19 has shown that we struggle to hold a scientific conversation in a polarised public square, where experts are often pilloried, not prized. If we cannot agree on the wisdom of wearing masks, how will we reach a consensus on how to rewrite our genetic future?

The Code Breaker’s confident, cinematic style makes Crispr accessible like never before, taking readers on a journey that is exciting, as well as ethically treacherous. Crispr People provides a more academic map for how to think about the regulation we need. But, sadly, neither can offer us the wisdom we need to come together, as Isaacson entreats at the end of his book, and feel our way into this “new room” together “step by step, preferably hand in hand”.

The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, by Walter Isaacson, Simon & Schuster, RRP£30, 560 pages

Crispr People: The Science and Ethics of Editing the Human Genome, by Henry T. Greely, MIT, RRP£22.50, 288 pages

Hannah Kuchler is the FT’s Pharmaceuticals Correspondent

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Published at Thu, 18 Feb 2021 05:30:57 +0000