A Crack in Creation review – Jennifer Doudna, Crispr and a great scientific breakthrough

It began with the kind of research the Trump administration wants to unfund: fiddling about with tiny obscure creatures. And there had been US Republican hostility to science before Trump, of course, when Sarah Palin objected to federal funding of fruit fly research (“Fruit flies – I kid you not,” she said). The fruit fly has been a vital workhorse of genetics for 100 years. Jennifer Doudna’s work began with organisms even further out on the Palin scale: bacteriophages, tiny viruses that prey on bacteria.

Yoghurt manufacturers knew they were important, not least because bacteriophages can destroy yoghurt cultures. Research on the mechanism of this process began in the labs of Danisco (now part of the giant DuPont) in the early 2000s, before spreading through the university biotech labs. In 2012 Doudna and Samuel Sternberg’s team at Berkeley (they are co-authors of the book but it’s written solely in Doudna’s voice) came up with probably the greatest biological breakthrough since that of Francis Crick, James Watson and Rosalind Franklin.

Biologists had become intrigued by a curiosity in the genome of some bacteria: they had repeat patterns interspersed always by 20 bases of DNA, which turned out to match sequences found in the phages (as bacteriophages are always known) that prey on them. They had stumbled on a bacterial immune system, now known as Crispr (Clustered regularly interspaced short palindromic repeats) – a sequence reading the same forwards and backwards.

An astonishing story of molecular countermeasures against phage invasion was revealed; these enable the bacterium to recognise the phage next time it invades. More than that, Crispr guides a killer enzyme to cut the phage’s DNA at the point where the 20‑base sequence is found. Doudna then demonstrated that bacterial Crispr can be reprogrammed to cut any DNA from any organism. This is what has been sought for more than 30 years: an accurate (or almost accurate) way of editing DNA. And there has never been a better example of the unforeseen benefits of pure research because no one guessed that a technique of such power and universality would emerge from what appeared to be a fascinating but arcane corner of biology.

Facebook Twitter Pinterest The ‘Jurassic Park fantasy’ is kept alive by Crispr. Photograph: ILM/Universal Pictures/Amblin En/AP

Crispr is not just a triumph for unfettered scientific curiosity, it’s also a reminder that the secret of life lies in tiny things. The visible world can be beautiful but we are gulled into thinking it must be more important than what we can’t see. People have been making that mistake for a long time. In The Citizen of the World (1762), Oliver Goldsmith mocked the supposed pedantry of all who study the tiny creatures revealed by the microscope: “Their fields of vision are too contracted to take in the whole … Thus they proceed, laborious in trifles, constant in experiment, without one single abstraction, by which alone knowledge may be properly said to increase.” But, of course, it is precisely being able to “see” small things that has unlocked the biological treasure trove.

Very soon after Doudna’s paper on the technique appeared in 2012, labs all over the world tried it and found it was surpassingly easy to use; a gold rush began. It’s always difficult when something like this happens to sort the hope from the hype, but anticipation is now intense. Doudna does, though, sound many notes of caution. Yes, Crispr is the most accurate form of gene editing so far, but it isn’t perfect. There are 3bn bases in the human genome so there is always a chance of a stray 20-base match and a fatal cut in the wrong place. A debate is taking place on whether to allow gene edits only outside the body (with the edited cells reinserted) or to allow editing of eggs and sperm, which changes that germline forever. Doudna comes down cautiously for germline editing, pointing out that mitochondrial replacement therapy, which also leads to permanent genetic alteration, is already a reality in the UK.

Doudna recounts how, soon after her breakthrough, colleagues became rivals, papers were pored over for patent battles

For now the most exciting potential medical application is in single gene diseases, such as cystic fibrosis, sickle-cell anaemia and muscular dystrophy. This is the simplest possible task for Crispr. Just one base has to be corrected out of the 3bn and it’s not a needle in a haystack: Crispr can find and cut and repair it. Sickle-cell anaemia is caused by a faulty haemoglobin gene, so blood can easily be withdrawn from the body, the gene edited and returned to the body. But this approach demands extreme caution. Genes often have multiple effects and the sickle-cell gene is known to protect against malaria. So if you fixed the sickle-cell gene in the African population (where it is prevalent) there would be many new cases of malaria. But then Crispr can probably fix that, too; other researchers, with Gates Foundation funding, are urgently tackling that problem. There is hardly an area of medicine that could not benefit from Crispr, and on the fringe there is the Jurassic Park fantasy, kept tenuously alive by the work of Crispr’s other great name, George Church at Harvard, who is editing the elephant genome to create a creature more like a woolly mammoth.

If medical ethics loom large in debates around Crispr, money and patents loom even larger. Now that this apparently unpromising research has blossomed, the venture capitalists are gathering. Doudna recounts how, so soon after her triumph, “colleagues became rivals; papers were pored over for future patent battles”. The patent battle in question came to fruition after the book was completed. Doudna’s team lost this round, and it’s not clear what the future holds for Crispr’s intellectual property rights. It is unlikely that medical progress will be delayed but there will be some bruised participants and money spent along the way.

It is unusual to have a popular account of a great scientific breakthrough written by the protagonist, so soon after its discovery. Watson’s The Double Helix appeared 15 years after the work. We owe Doudna several times over – for her discovery, for her zeal to take it from the lab into the clinic, for her involvement in the ethical issues raised, for her public engagement work, and now for this book. It’s a fine weapon against the still far too large tribe of those who don’t believe in the power of very small things.

• Peter Forbes’s latest book, written with Tom Grimsey, is Nanoscience: Giants of the Infinitesimal. A Crack in Creation is published by Bodley Head. To order a copy for £16.59 (RRP £20) go to bookshop.theguardian.com or call 0330 333 6846. Free UK p&p over £10, online orders only. Phone orders min p&p of £1.99.