鈥淚t was one of those moments of pure joy,鈥� says Jennifer Doudna. 鈥淭he joy of suddenly understanding something.鈥�
In 2012, Doudna鈥檚 team made one of the biggest discoveries in the history of biology: how to edit the DNA in living cells with relative ease. In essence, it gives humans the power to direct evolution.
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It wasn鈥檛 what the team had set out to do, but they realised immediately that CRISPR gene editing had immense potential. So did the rest of the world. Just six years on, it has already been used to help treat cancer and to alter the DNA of many plants and animals 鈥� including that of human embryos.
Doudna, who until then had worked on relatively obscure biochemical mysteries, suddenly found herself in a prominent position, with reporters phoning up asking for her opinion on the latest developments. 鈥淚t makes me feel very humble,鈥� she says. 鈥淚鈥檓 this girl from rural Hawaii who took on this role. It鈥檚 kind of bizarre.鈥�
Doudna鈥檚 upbringing in Hawaii sparked her interest in biology. She was fascinated by the way plants and animals had evolved in an island setting. Her father, meanwhile, passed on a liking for puzzles. 鈥淚 loved the idea of being able to have one鈥檚 career be focused around figuring out how things work.鈥�
The discovery of CRISPR gene editing was the culmination of a working life spent uncovering the secrets of RNA. At Yale, her group worked out the three-dimensional structure of a key RNA enzyme, cracking a major scientific puzzle. Her group at the University of California, Berkeley, was interested in the CRISPR Cas9 protein because it is guided by RNA. No one understood how it worked until her team solved the mystery in 2012. Over the next few years, CRISPR took the scientific world by storm. By 2015, the first gene-edited monkeys had been born.
It was around then that Doudna began to have tsunami dreams. Tsunamis mean more to Doudna than most: the small town where she grew up, Hilo, was hit by a massive one in her parents鈥� lifetime, so she was aware of the threat from an early age.
In the dreams, the tsunami was CRISPR, spreading beyond control. 鈥淚 began to feel a bit like Doctor Frankenstein. Had I created a monster?鈥� she wrote in her 2017 book on the subject. That was when she decided she needed to be part of the debate.
No longer incurable
Since then, Doudna has arranged conferences, given talks around the world, advised policy-makers and answered every kind of query from the public to raise awareness of CRISPR鈥檚 potential.
And that potential is huge. CRISPR is being turned into an extremely powerful toolset for disabling genes, repairing faulty genes or turning genes on or off. As Doudna points out, that means every genetic disease could be transformed into a potentially treatable condition.
But there are dangers, too. Take gene drives 鈥� bits of DNA that copy themselves to ensure they get passed to all offspring, not just half as with ordinary gene variants. There are many natural gene drives, but until CRISPR, no one had created an effective artificial one. Now several teams are testing them in fruit flies, mosquitoes and mice. The risks are great. For instance, if a gene drive designed to wipe out an invasive species 鈥� rabbits in New Zealand, say 鈥� escaped, it could drive that species to extinction.
The rewards could be great, too. 鈥淚 think it is worth taking that risk,鈥� says Doudna. 鈥淚magine if you really could use that method to remove a strain of mosquito that spreads malaria.鈥�
The ethical issue that has attracted by far the most headlines, though, is whether CRISPR should be used to permanently alter the DNA of our children, and by extension all our descendants. That idea horrifies some, including one of the co-discoverers of CRISPR, Emmanuelle Charpentier. But not Doudna. 鈥淚f the technology was shown to be safe and effective for doing things like correcting the cystic fibrosis mutation, I personally think that that鈥檚 OK,鈥� she says.
We can already prevent almost all genetic diseases by screening the embryos of couples undergoing IVF, but this involves throwing away any with mutations. 鈥淢any people have shared with me that it鈥檚 a very uncomfortable feeling to throw away embryos,鈥� Doudna says. 鈥淪o for some it might feel like a better decision to instead correct a mutation.鈥�
What if we want to enhance children, rather than just prevent disease? 鈥淚 have a problem with that,鈥� says Doudna. 鈥淢aybe I鈥檓 a fuddy-duddy.鈥� But her issue is a practical one. There are actually very few, if any, gene variants that we are 100 per cent certain would provide significant benefits. Take intelligence 鈥� it seems to be determined by hundreds of genes, each with a tiny effect. What鈥檚 more, the same variant can have different effects in different people.
鈥淚 began to feel a bit like Doctor Frankenstein. Had I created a monster?鈥�
So there is no guarantee that children would be better off. 鈥淚鈥檓 not sure I鈥檇 be comfortable taking a risk with my child鈥檚 life in that way.鈥� But we don鈥檛 need an absolute ban on genetic enhancement, she says. We might get to the stage where we can be sure modification is beneficial.
One fear is that it could make society even more unequal. This is already a problem with access to healthcare in general, Doudna thinks, and the same will apply to genetic enhancement. 鈥淚n principle one wants to be working towards using any technology to benefit the largest number of people,鈥� she says.
That might be the case if CRISPR can enhance the animals and plants we depend on. 鈥淚 think the biggest impact is going to be in agriculture,鈥� says Doudna. Indeed, biologists have already used CRISPR to create everything from gluten-free wheat to and goats that produce more cashmere wool.
Will we all soon be eating gene-edited food? This depends partly on public perceptions 鈥� and many people haven鈥檛 even heard of CRISPR or gene editing yet. 鈥淢any won鈥檛 until it actually impacts them personally,鈥� Doudna says. And perception depends partly on where people get their information from. 鈥淲e definitely have challenges with Hollywood and the way they portray gene editing.鈥� Doudna was talking to me before the trailers aired for , a movie in which 鈥済ene editing鈥� turns ordinary animals into uncontrollable monsters, including a giant flying wolf.
Yet we really will be able to create extraordinary animals one day, says Doudna, including unicorns and winged lizards. Perhaps not flying wolves, though: animals will still have to obey the laws of physics.
By solving the puzzle of CRISPR, Doudna has created a far greater conundrum: how to use its immense power. It is something humanity is likely to wrestle with for centuries to come. But Doudna is upbeat. 鈥淚鈥檓 not worried. I feel excited,鈥� she says.
Jennifer Doudna is professor of chemistry, and of biochemistry and molecular biology at the University of California, Berkeley. Her 2017 book A Crack in Creation: The new power to control evolution, is published by The Bodley Head
This article appeared in print under the headline 鈥淒irector of evolution鈥�
