IN THE EARLY days of gene editing, biologists had a molecular tool kit that was somewhat akin to a printing press. Which is to say, altering DNA was a messy, labor-intensive process of loading genes onto viruses bound for target cells. It involved more than a fair amount of finger-crossing. Today, scientists have the genetic equivalent of Microsoft Word, and they are beginning to edit DNA almost as easily as software engineers modify code. The precipitating event? Call it the Great Crispr Quake of 2012.
If you’re asking “What’s Crispr?” the short answer is that it’s a revolutionary new class of molecular tool that scientists can use to precisely target and cut any kind of genetic material. Crispr systems are the fastest, easiest, and cheapest methods scientists have ever had to manipulate the code of life in any organism on Earth, humans included. It is, simply, the first technology truly capable of changing the fundamental chemistry of who we are.
The long answer is that Crispr stands for Clustered Regularly Interspaced Palindromic Repeats. A Crispr system consists of a protein with sequence-snipping capabilities and a genetic GPS guide. Such systems naturally evolved across the bacterial kingdom as a way to remember and defend against invading viruses. But researchers recently discovered they could repurpose that primordial immune system to precisely alter genomes, setting off a billion-dollar boom in DNA hacking.
Every industry is throwing mad money at Crispr—pharma, agriculture, energy, materials manufacturing, you name it. Even the weed guys want in. Companies are using it to make climate-change-fighting crops, biofuel-oozing algae, self-terminating mosquitoes—and, yes, potential Covid-19 treatments. Academic researchers have almost universally adopted Crispr to more deeply understand the biology of their model organisms. Supporting this biohacking bonanza is an increasingly crowded Crispr backend supply chain: businesses building gene-editor design tools and shipping synthetic guide RNAs or pre-Crispr’d cell lines to these companies’ doors. So far, though, very few Crispr-enhanced products have made it into the hands of actual consumers. In their place, hyperbolic headlines have bugled society’s greatest hopes and fears for the technology, from saving near-extinct species to igniting a superbaby arms race.
In November 2018, a Chinese scientist named He Jiankui stunned the world with claims that he had Crispr’d the first humans in an experiment fraught with ethical violations. The fast-unfolding scandal roused the world’s scientists and government officials to address the now-urgent need to figure out how to regulate such a powerful technology. Crispr may have delivered designer children faster than anyone thought possible. But it’s still a long way from ending disease or hunger or climate change. Maybe it never will. Crispr is, however, already beginning to reshape the physical world around us in much less radical ways, one base pair at a time.
The History of Crispr
It all started with yogurt. To make it, dairy producers have long employed the help of Streptococcus thermophilus, bacteria that gobble up the lactose in milk and poop out lactic acid. It wasn’t until 2005, though, that a young microbiologist named Rodolphe Barrangou discovered that S. thermophilus contained odd chunks of repeating DNA sequences—Crisprs—and that those sequences were keeping it safe from the viruses that can attack it and result in spoilage. (If the thermophilus is gone, nastier bacteria can move in and feed off the lactose, ruining the product.)
Before long, DuPont bought the Danish company that Barrangou worked for and began using strains carrying this naturally occurring Crispr to protect all of its yogurt and cheese cultures. Since DuPont owns about 50 percent of the global dairy culture market, you’ve probably already eaten Crispr-optimized cheese on your pizza.
All the while, gene sequencing costs were plummeting and research scientists around the world were assembling the genomes of bacteria. As they did, they found Crisprs everywhere—more than half of the bacterial kingdom turned out to have them. Oftentimes those sequences were flanked by a set of genes coding for a class of strand-cutting enzymes called endonucleases. Scientists suspected they were involved in this primitive immune system, but how, exactly?
The key insight came from a particularly nasty bug—the one that causes strep throat. Its Crispr system made two RNA sequences that attached to a clam-shaped endonuclease called Cas9. Like a genetic GPS, those sequences directed the enzyme to a strand of DNA complementary to the RNA sequences. When it got there, Cas9 changed shape, grabbing the DNA and slicing it in two. The molecular biologists who made this discovery—Jennifer Doudna and Emmanuelle Charpentier—demonstrated Crispr’s programmable cutting on circular stretches of DNA floating in test tubes. They published their work in Science in 2012, but not before patenting the technology as a tool for genetic engineering. If you just switch out the RNA guide, you can send Cas9 anywhere—to the gene that causes Huntington’s disease, say, and snip it out. Crispr, they realized, would be a molecular biologist’s warp drive.
Six months later, a molecular biologist at the Broad Institute of MIT and Harvard named Feng Zhang published a paper in Science showing that Crispr-Cas9 could edit human cells, too. In fact, with the right genetic guides, you can Crispr pretty much anything. That meant it might be put to work on next-generation medicines that could do things like erase genetic defects and supercharge the body’s natural defenses against cancer. And that meant big money.
