One of biology’s wilder facts is that we’re all family. You and me, sure, but also me and a mushroom. Triceratops shared genes with you. So does the virus that makes you cough, and a rosebush. Bacteria left us on the tree of life around 2.7 billion years ago, but the wet world they came from is still ours: One code runs all of life. The same proteins that imprint memories in your neurons, for example, do so in octopi, ravens, and sea slugs. This genetic conservation means tricks from one species can be hijacked. If you stick a jellyfish gene in a monkey, it’ll glow green.
What’s important to understand is that CRISPR is a strip of bacterial genome, a rudimentary immune system that evolved some 4 billion years ago.
Now, scientists have hacked a trick from bacteria that is about to change the world. The trick is called CRISPR, and it lets people do surgery on genes more quickly and easily than ever before. The discovery, first made by Berkeley biochemist Jennifer Doudna, is transforming biology from cancer to cornfields to mental illness. “CRISPR provides the ability to have ‘write’ privileges in DNA, in addition to ‘read’ privileges,” explains Alex Marson, an immunologist at the Innovative Genomics Institute of Berkeley and UCSF. “So we suddenly have the power to go in and change the code of life.”
CRISPR is intimidating, in part because of its unwieldy name: clustered regularly interspaced short palindromic repeats. Yeesh. What’s important to understand is that CRISPR is a strip of bacterial genome, a rudimentary immune system that evolved some 4 billion years ago. Long before the first primates stood up and plodded toward tools, Hamlet, and atom bombs, CRISPR was fighting off invaders.
As it’s commonly used, CRISPR is a catchall for CRISPR-Cas9. Cas9 is essentially a cutting tool, shaped like a clam shell, that CRISPR uses to sever a strand of viral DNA. What tells it where to cut is a strip of code, called guide RNA, that pairs with a matching strand in a target gene. Like an X marking the spot, the target DNA signals to Cas9: “Cut here!”
Scientists first found this ancient weapon in Streptococcus bacteria. Most of us are used to thinking of strep as something we have to fend off with our immune systems or antibiotics. But strep and other bacteria have immune systems, too, for fighting off viruses. In 2005, Berkeley microbiologist Jillian Banfield was studying the self-defense mechanisms of strep when she noticed lots of repeated DNA segments: CRISPR sequences. Intrigued, Banfield asked if Doudna, who had spent years investigating the “secret life of RNA,” would be interested in having a deeper look.
Doudna soon partnered with French scientist Emmanuelle Charpentier. The duo identified Cas proteins as the tools that sliced the viral DNA. The true breakthrough, however, came when they realized that, not only could the same mechanism be used by humans, but it could also be programmed. Suddenly, they had the technology to insert genes more precisely than ever before, or cut a single gene, the way you might cut a word from this sentence. The potential was huge: Doctors might be able to replace the defective genes with healthy ones to cure or prevent disease.
Bioethicists largely agree that editing reproductive cells should be banned for now, that this is the ethical line that we dare not cross. Except we already have.
When Doudna and Charpentier’s paper on CRISPR came out in the journal Science in 2012, it went off like a bomb. Biologists still remember where they were when they first heard about it. Not only did it promise huge advances in science and medicine, it also raised a slew of ethical questions, starting with: Should we edit our offspring?
Just imagine: Your baby has a bad gene, and you know it. In utero, the doctors see the signs—a gene for early Alzheimer’s, meaning memory loss by midlife, chased by early death. Your baby’s fate is written in a code that doctors know: One error on chromosome 21 makes a plaque that will clog her brain. What are you going to do? Using the new gene-editing technique (snip-snip), your baby could be spared a ruined mind midlife. But why stop there? Genes for a dark disposition? No problem. Snip-snip: no more mood swings, just happy, well-adjusted, standardized kids. But gone may be the quirks that brought us Newton, now thought to have possibly been autistic. Or the legions of manic-depressive writers and artists. No more Emily Dickinson or Edgar Allen Poe. No more melancholic Charles Darwin. And without him, no Theory of Evolution. No CRISPR.
“Germline editing” is the name for this baby-sculpting in a dish. What’s scary about it—changing the chromosomes that make a person—is that you aren’t only changing one baby, you’re changing their future kids. Bioethicists largely agree that editing reproductive cells should be banned for now, that this is the ethical line that we dare not cross. Except we already have. Just last November, a geneticist in China took the initiative. Like the man who pioneered ice-pick lobotomies, he pushed fast to discover something new, breezing past ethical boundaries on his way.
Chinese scientist He Jiankui announced that he had made the world’s first “designer babies”: altered human embryos. Dr. He used CRISPR-Cas9, he claimed, to make babies resistant to HIV. The move was roundly denounced by the international scientific community as both unethical and scientifically dubious.
“I think it’s very disturbing,” Jennifer Doudna told CNN of He’s renegade experiment. “I think there’s no way to defend it.”
“CRISPR is the workhorse in the drug industry and any molecular biology lab anywhere in the world today,” said UCSF’s Bruce Conklin.
Among the concerns are the usual questions of mystery consequences and social inequity: Who will reap the benefits? Who will get left behind? Also, who gets to decide which traits should be permanently written into human DNA? After all, imagine what the Nazis might have done with CRISPR; this is the “gene editing” that elicits nightmares. In her 2017 book, A Crack in Creation, Doudna describes a dream in which a fellow researcher asks her to explain the technology to “someone very powerful,” then ushers her into a room to meet Hitler, who is wearing a pig mask and taking notes.
“I woke up in a cold sweat,” Doudna wrote. “And that dream has haunted me from that day.”
But for all the potential perils, the promise of CRISPR is simply too great to ignore: farm crops resistant to drought and disease, biofuels made with CRISPR-edited algae, a cure for cancers and heart disease—the leading cause of death worldwide.
If you’re worried about a heart attack, gene editing may help. CRISPR might soon allow scientists to tailor new drugs to your heart specifically.
Bruce Conklin is a professor at UCSF’s Institute for Human Genetics, where he collaborates with Doudna and another giant in the field, Shinya Yamanaka, to expand the frontiers of “therapeutic editing” in humans. In 2012, Yamanaka won a Nobel Prize for a game-changing technique called “cellular reprogramming,” which gives scientists the power to “rewind” cells of a living person into an embryonic state, then nudge them into whatever type of mature cell they choose: liver, heart, blood, brain.
These cells, note, are different than the ones that He Jiankui meddled with. They are not sperm, eggs, or embryos, containing DNA passed down for generations. The body’s somatic, or non-reproductive, cells can be tweaked by CRISPR to help a single patient overcome a disease or to help doctors design new drugs in a dish. They are a driving force in personalized medicine, not a tool for eugenics.
“You can see the beating areas,” Conklin said, describing cells in a petri dish developing into living heart tissue. Using CRISPR on these reprogrammed cells, Conklin and colleagues can test new drug targets and develop screening tools for rare diseases—without making people the guinea pigs.
Scientists are using CRISPR now to kill mosquitoes that carry malaria. But what happens when you wipe out an insect that’s always been part of our world?
“CRISPR is the workhorse in the drug industry and any molecular biology lab anywhere in the world today,” Conklin said. And not just at the university level. Even high schools are experimenting with it. In the future, Conklin imagines CRISPR will be injected into people’s bodies, programmed to detect and delete key genes in certain cells. While drugs will remain important treatment, Conklin said, he thinks that therapeutic gene editing will eventually be “a standard of care, like heart transplants or kidney transplants.”
That may be a ways off, but already CRISPR is being used in human patients. Victoria Gray, a 34-year-old mother from Mississippi, recently became the first American patient to be treated with CRISPR. Gray has sickle cell disease, a painful and life-threatening genetic disorder that affects mostly people of African origin. In an experimental treatment that spanned months, Gray was injected with billions of her own bone marrow cells. The cells had been programmed to express hemoglobin, a protein that helps carry oxygen in the blood. If the treatment works as planned, Gray will have healthier red blood cells and a longer life. “I’m just genetically modified now,” Gray told NPR. “I’m a GMO. Isn’t that what they call it?”
What makes CRISPR thrilling but scary is the unknown. Sickle cell disease evolved because one copy of the mutation makes you partially immune to malaria, an illness that kills 1,200 children daily. Conceivably, sickle cell could be treated on a population level with germline edits. We could eradicate the disease entirely, in other words, not just in individuals. But in doing so, what else might we be affecting? How would we know? Scientists are using CRISPR now to kill mosquitoes that carry malaria. But what happens when you wipe out an insect that’s always been part of our world? We can’t know: We just have to try, or not.
In the absence of answers, fears fill the mind. Yet this alien weapon brings tremendous hope as well. Gene editing somatic cells is safe: The cells injected into patients today, from blood or bone marrow, are new weapons for old battles—against cancer, heart disease, brain disorders, sickle cell disease. But for the victims of cystic fibrosis, or the rare form of heritable Alzheimer’s, the only possible solution may be to edit the germline. The journal Nature published an editorial in March by 18 scientists from seven countries. It argued for a moratorium on germline editing until safety and ethics standards emerge. This will be hard to regulate, as always, but if precautions are taken, CRISPR’s benefits should far outweigh the risks. Humanity has built itself yet another set of wings. Now we’ll try, once again, not to fly too close to the sun.
Taylor Beck is a writer and a teacher who used to study the brain. His writing has appeared in The Atlantic, The Washington Post, Nautilus, and other publications.