Jennifer Doudna, inventor of Crispr. Photo / AP
Have you heard the news about sickle cell anaemia and beta thalassemia, the devastating diseases which prevent red blood cells carrying as much oxygen as they should? A new, experimental therapy seems to have reversed the gene errors responsible in two patients.
"Apparently, both patients have been cured," says Jennifer Doudna. "That's an extraordinary thing. Here are diseases of the blood that cause terrible distress and for which there's currently very little that can be done."
Doudna is not responsible for the new therapy. At least not directly. Rather, she is responsible for something with greater implications still – the gene-editing technique, known as Crispr Cas-9, which permitted the correction in the first place.
Crispr's applications are not limited to sickle-cell. Indeed its applications seem barely limited at all, given that it can precisely slice out parts of our DNA and insert customised replacements in their stead. If DNA is the book of life, written into all our cells, Crispr is its word processor, making it one of the most significant, yet least known, scientific advances of the decade.
"It's easy to use," says Doudna, 55, who is Professor in the Department of Molecular and Cell Biology at the University of California, Berkeley. So easy in fact, that scientists can now order Crispr molecules designed to target any part of human DNA as easily as ordering a take-away pizza. "They can just type a gene sequence into their phone and program the Crispr molecules to manipulate DNA in ways that previously would have been impossible," says Doudna. "It has been truly transformative."
In sickle cell, the fault lies with the HBB gene which, fundamentally, is responsible for the production of haemoglobin, the oxygen-carrying molecule in red blood cells.
But HBB is just one of more than 1,000 genes on chromosome 11. And chromosome 11 is just one of the 23 pairs of chromosomes which comprise our DNA. In all, humans are estimated to have between 20-25,000 genes. Any can be edited with Crispr.
Take the DEC2 gene. It influences sleep. And one mutation of the genetic code in DEC2 allows people to thrive, even with very little sleep. You know those annoying people who seem to get by on just a few hours, and to whom we ascribe qualities of hard work and virtue – it turns out they may just have a genetic twist which, with a little editing, we may one day all be able to order for ourselves, or our children.
How about pain? The SCN9A gene contributes to our sensations of it. In Pakistan, a boy with a mutation of SCN9A could not feel pain and earned a living as a street performer, sticking knives through his arm. He died aged 14, after he took his act too far and jumped off a building. But now mice whose DNA has been edited to emulate that mutation also feel no pain. People may not be far behind or, according to one dystopian scenario, battalions of super-soldiers impervious to the agonies that afflict the rest of us.
Alongside the excitement of curing fatal diseases then, Doudna also feels the wariness of one who has unleashed a dramatic new power.
"You can't you can't turn back the clock and can't put the genie back in the bottle," she says, the gravity of her subject matter contrasting with her sunny, upbeat tone. "That's just a reality. You know, you can't undiscover things that you have discovered."
If that seems a self-serving attitude, it does not mean she has been free from agonies of her own since 2012, when she published the pioneering paper (with Emmanuelle Charpentier, usually credited as Crispr's co-inventor, and others) that ushered in the Crispr era.
In Human Nature, a new film which explores Crispr's extraordinary potential, Doudna even tells of panicked visions of the Third Reich. "I ended up having several dreams that were very intense… where I walked into a room, and a colleague said: 'I want to introduce you to someone, they want to know about Crispr." And I realised with horror that it was Adolf Hitler. And he leaned over and said: 'So, tell me all about how it works.' I remember waking up from that dream, and I was shaking. And I thought: 'Oh, my gosh. What have I done?'"
Though gene-editing babies is illegal in the UK and in many places around the world, her eugenics nightmare has already become a reality. Almost exactly a year ago, at a conference in Hong Kong, a Chinese scientist, He Jiankui, stood up and announced that he had created the first gene-edited human babies, their DNA altered with the aim of conferring immunity to HIV.
He had crossed not so much a line in the sand, as a chasm. Not only were the implications of the changes he had made impossible to know fully – given genes' complex interactions with each other and with the environment – but they would also be passed onto future generations. Lulu and Nana, as the twin girls he created are known, will pass on their tweaked DNA, for good or ill, to their own children, with the possibility that problems crop up in the second, third or fourth generation.
Doudna, contacted by He several days before the conference, knew what was coming. But that did not lessen her "horror", which has only grown since. "What was so horrifying was to see what a disaster the whole effort has been, both from a scientific and technical point of view, as well as from an ethical perspective," she says.
"The detailed [gene] changes that were made have never been seen in humans and never even tested in animals. So there's no way to know if those changes are safe or defective. That is a horrifying thing to think about, you know, it reminds you of experiments on humans in the past."
It also turned out that the parents recruited were, as Doudna puts it, "desperate to have children [and] desperate to have their cost of reproductive treatment paid for in the study.
"It was distressing for me to see the use of the technology that I had been involved in developing in the beginning used in this way."
Her particular concern is that experiments like He's, which attract a Dr Frankenstein-stigma, will cause a public backlash against Crispr technology, and its potential benefits. But as she says "it's out of my hands. It was early on."
A Russian scientist, Denis Rebrikov, has already said he aims to follow He and create gene-edited babies. His request was reportedly the subject of a top-level scientific meeting in Russia this summer, attended by Vladimir Putin's daughter, Maria Vorontsova, herself a paediatric doctor. It is easy to imagine Mr Putin inaugurating a genetic arms race, aimed at perfecting, or at least "developing", the human species.
The implications are one reason why the Pentagon has added gene editing to its list of "weapons of mass destruction" and is researching "antidotes" to Crispr, in order to defang genetic arms developed by enemies. Who else should they turn to, but Doudna. Doesn't it feel strange, I ask her, being paid by her government to discover ways of reversing her own discovery. "Yeah, kinda weird," she laughs. "But I'm going with it."
Not that she thinks that gene-editing humans is, ultimately, a reversible trend. Doudna says her own 17 year-old son, Andrew, believes his children will be gene-edited, in order to clip out and correct potentially heritable diseases and conditions. "If you ask him he'll say 'Yes'," she says. "There is an attraction to this that isn't going away."
As the scientist Stephen Hsu puts it in the film: "Fifty years from now, people may say 'I can't believe those barbaric people in the early 21st century were just rolling the [genetic] dice with their kids' lives'.'" The option now exists, he says, to load those dice. Should we use it? Hsu thinks so. "I think the right way to say it is that sex is for recreation, and science is for procreation."
Doudna doesn't put it quite so bluntly, but she doesn't disagree. To be partly responsible for such a landmark development is, she says, "fun, weird, crazy. Thrilling but also unnerving.
"The future is coming," she adds. "It's just a question of how and when."
Crispr-Cas9, abbreviated from 'clustered regularly interspaced short palindromic repeats', is a hybrid of protein and ribonucleic acid (RNA), which works as an efficient hunt-and-cut system in bacteria.
Molecular biologists Jennifer Doudna and Emmanuelle Charpentier realised that it could work well in other cells, including those of humans, to carry out genome editing.
1. An RNA molecule marks a precise point in the genome thread then 'guides' in the Cas9 enzyme, which acts as a pair of scissors to cut both strands of DNA
2. A new DNA segment can then be introduced to repair a faulty gene, or a new gene altogether can be inserted
3. The cut strands of DNA then repair themselves, incorporating the new genetic information. If nothing is inserted, the repair process can silence, or 'turn off', a faulty gene
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