Will genetic engineering change the world?
Save Log in , register or subscribe to save articles for later. Normal text size Larger text size Very large text size When the twin girls were born, one October night in 2018, they carried a secret: a hidden tweak in their DNA even the hospital in China didnt know about. They were the worlds first genetically engineered humans. The next month, news of their existence broke just as the scientist behind the engineering, Dr He Jiankui, was addressing peers at a global summit. Facing down an uncharacteristically rowdy hall of scientists, he explained: with fertility treatments illegal for prospective parents with HIV in China, he had instead edited the girls as embryos to be resistant to the AIDS virus carried by their father. He said genetic testing showed that Lulu and Nana were as healthy as any babies. Their real identity is now a state secret in China and it is not known how they are doing. But Dr He has been jailed for three years and his research internationally condemned as rogue Frankenstein science. He had faked tests, kept doctors in the dark, and bypassed ethics boards in his quest to be the first to cross the germline and engineer humans. Some even suspected he had targeted the specific gene in question not only because it was linked to HIV infection but because it had been shown to boost brain power, when removed in mice. What had been feared by many in the scientific community, especially since the creation of the breakthrough gene-editing tool CRISPR, had come to pass. In the past 70 years, we have uncovered the structure of DNA, the blueprint of life, built machines to read it and harnessed the power to rewrite it. Gene technologies have helped us track and fight COVID-19 faster than any outbreak in history, with real-time genomic sequencing, and new-generation mRNA vaccines. And scientists believe we are on the cusp of doing a whole lot more: even curing incurable diseases. Credit:Artwork: Matt Davidson For the first time, gene editing saved lives when it was used to help two toddlers with terminal leukemia at Londons Great Ormond Street Hospital in 2015. The girls are still in remission, says Professor Waseem Qasim now. Were starting more trials using [the next generation] of CRISPR tools. Some of this stuff does look like science fiction, at least at first, even to me. But, three years on from the Dr He scandal, experts say regulation is still not keeping pace with the gene-editing evolution. You are made up of trillions of cells, in a constant state of death and rebirth. Almost all of them carry a blueprint, billions of letters long, known as deoxyribonucleic acid or DNA for short with the instructions for making everything from your eye colour to your heart valves. As your cells replicate and replace themselves, this DNA is copied across, re-encoded. But only the parts relevant to that particular cell, known as genes, switch on. So lung cells are built to take in oxygen while red blood cells are programmed to carry that oxygen around the body. This is the impressive, if imperfect, engine of all multicellular life on Earth. Sometimes, DNA makes mistakes when copying itself, mutations. Most dont affect how things run. But some can cause problems, like bugs in computer code. And, occasionally, others will make things better. Over time, these good mutations might build up, and their advantages improve generations. Thats what evolution looks like under a microscope. But now humans have the tools to edit DNA directly, both in living people (known as somatic editing) and embryos not yet born (known as germline editing). This second kind of editing, that so horrified in Dr Hes case, is the easiest way to ensure DNA changes make it to every cell in the body. But any edits will also be permanent; and, critically, pass onto future generations, making the stakes especially high. Right now, researchers agree the technology is not developed enough to do it safely, and so human germline editing is banned in almost every country. Indeed, historian and futurist Yuval Noah Harari writes in his book Sapiens that if we use this technology, humanity will begin to break the laws of natural selection that have shaped life for the past four billion years, and replace them with laws of true intelligent design. Author and geopolitical expert Jamie Metzl, who sits on the World Health Organisations committee on human gene-editing, agrees it is the most powerful technology in history because it can fundamentally change not just individuals, but species. And its [advancing] much faster than most people realise, he says. Advertisement  When the Human Genome Project first mapped all six billion letters of our DNA in 2003, it took $US2.7 billion dollars and 13 years. Today, the price of whole genome sequencing (reading someones entire genetic code) has already plummeted to less than $600. That fall was meant to take six decades, says Harvard Universitys leading geneticist George Church, who has had a hand in everything from the Human Genome Project to CRISPR, and was among the first people on the planet to have their genome sequenced. Many of the technologies were working on now were basically science fiction, only theyve arrived much sooner than anyone expected. Dr He Jiankui consulted with some Western scientists while preparing his gene-editing trial, though many organisations and academics later distanced themselves from the project. Credit:AP One of the key breakthroughs that sped up this clock was CRISPR, a faster, cheaper and more efficient way of editing genes that scientists borrowed from bacteria. Jennifer Doudna and Emmanuelle Charpentier were studying the microbes and their impressive ability to edit their own DNA sequences when the scientists hit upon a Nobel-prize-winning idea: that system could be programmed to work in animal and human cells too. Bacteria live in a constant arms race with viruses, Doudna explains, and so, over millennia, have developed a particularly clever immune system to hunt and destroy viral invaders by searching for their genetic signature. A protein known as CAS9 can cut the viral sequence where it appears in the code. To a virus, this is fatal. But in humans, and other organisms, the double-stranded DNA helix will stitch itself back together again. And so genes can be deleted or even replaced with a new sequence entirely. I generally describe CRISPR as genetic scissors, Doudna says. Dr He was hardly the first to shock at a genetic engineering conference. In 2017, an amateur biohacker famously injected himself with modified DNA mid-talk in the hope it would make him more muscular (it didnt). And today stories of glowing rabbits, malaria-resistant mosquitoes and high-yield crops (GMOs) are increasingly in the headlines. Advertisement  At his University of Sydney lab, Greg Neely has already been using gene-editing to stop pain in mice, block jellyfish venom hurting humans and even extend the lives of fruit flies. I dont want to say how easy it is, or everyone will do it, Neely quips when he talks about CRISPR. But, while the tools might be simpler, editing DNA itself is still complicated. For one thing, just as we are more than our genetics, the parts of us that really are genetics rarely come down to just one gene. They are often the sum of many, all working together in ways we dont quite understand yet. Height, for example, is influenced by more than 700 genes. Eye colour relies on a dozen, and thats before we get into the realm of much less tangible traits such as intelligence (and breakdancing prowess). Even the many, many repeats in our DNA, once called junk DNA, are now known to play a vital function in regulating how different genes interact. That makes analysing a genome less like reading computer code and more like following sheet music, Qasim says, where there are marks for breath and pacing and much more. Metzl himself likens the genome to an ecosystem. Mess with one gene, and you might throw off others in places you dont expect  what scientists call off target effects. Still, while our DNA may be formidably complex, Metzl does not believe it is infinitely so: We dont understand it enough yet. Thats what made [Dr He] leaping ahead so shocking ... but its not indecipherable magic. We will reach a point where we know enough, we know its safe, or worth the risk. Credit: And when it comes to saving lives, sometimes it really is just one gene scientists need to fix. A single mutation causes conditions such as sickle cell anemia, cystic fibrosis and the deadly premature ageing disease progeria, putting them well in reach for safe gene therapies, some of which have already been approved by regulators around the world. When editing the DNA of people already born, Doudna says the hard bit is getting the CRISPR editing molecules where we need them to go in the body. You crack delivery, you open the door to multiple cures. So far, therapies often involve removing blood or bone marrow to edit cells, then putting it back in the patient, where the tweaked DNA will be carried around the body as the cells replenish themselves. Theyre like blood transfusions, Qasim says. Sometimes, nanoparticles released into the blood can even do the gene-editing for doctors inside the body; or a deactivated virus will carry the edits. Its not perfect. CRISPR is designed to cut and whenever you make a break [in DNA], you run the risk of causing damage, mutations, even cancer, Neely says. Its easier to break something than it is to fix it.  Advertisement  The good news is that scientists are already working on CRISPR upgrades. David Liu and his teams at MIT and Harvard have transformed the CAS-9 scissors to instead act as an eraser and pencil  rather than cutting and replacing the DNA sequence, his base editing technique triggers a chemical reaction to actually change the existing letter in the DNA. It can now do this to correct the single gene mutations behind roughly 5000 diseases, and Qasim expects to see many of these therapies go through clinical trials in the next five to 10 years. But both Qasim and Church still see germline editing as something of a distraction, without a clear medical need at present. Embryos can already be screened for disease using existing IVF procedures. Of course, you could argue we should be able to inherit our advances too, Church says. We made smallpox extinct [with vaccines] and now the entire planet is getting that protection for free. Doudna can also imagine a not-too-distant future where germline editing is advanced to the point where its safe and accurate. For families that carry hereditary diseases ... they might want to spare future generations from pain and suffering. The 1997 film Gattaca imagines a future class divide between the enhanced (as played by Uma Thurman) and the unenhanced. Many say here is where we must hold the line: gene-editing should be a rare tool for eliminating serious disease only. But others, including Metzl, see the line between medicine and enhancement as too blurry to last forever. At Harvard, Church has already made a line of pigs resistant to viruses so they can be raised as safe organ donors for humans. And that could be done, we think, in all animals eventually, he says. Advertisement