Select Page
The WIRED Guide to Crispr

The WIRED Guide to Crispr

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.

Perhaps predictably, a patent battle ensued—one that is still going on today. Crispr’s early pioneers founded three companies with exclusive licenses to exploit Crispr/Cas9 to cure human diseases; one of them began its first human trials in early 2019. Uncertainty over who will ultimately own the technology has done little to slow the appetite for all things Crispr. If anything, it unleashed a flood of interest in developing competing and adjacent tools that promise to further refine and expand Crispr’s already ample potential.

Many of the field’s founding luminaries have also formed, or are currently advising, companies working to lower the cost and labor associated with gene editing, to make it accessible to everyone. But in November 2018, at least some of them got a lesson in what democratization of Crispr really looks like.

On the eve of the Second International Summit on Human Gene Editing, news broke that a Chinese scientist named He Jiankui, who was scheduled to speak at the meeting, had been recruiting couples in an effort to create the first Crispr’d babies. Hours later, He Jiankui himself posted five slickly produced promotional videos to YouTube claiming to have already done so: “Two beautiful little Chinese girls, Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago.” The only difference was that the twins had been injected with Crispr when they were still embryos, in an effort to eliminate a gene called CCR5 and make them resistant to HIV. In a presentation to the summit a few days later, He provided further evidence of his experiment, which he appears to have conducted largely in secret, and revealed that a second pregnancy was underway. Buried in the pages of his clinical paperwork were notes that indicated He had ordered his Crispr components from US biotech companies, in violation of their “research use only” policies.

These firms joined the scientific community’s chorus of disgust, outrage, and near-unanimous condemnation of He’s work. Jennifer Doudna said she was “horrified,” Feng Zhang called for an immediate moratorium on the implantation of gene-edited embryos, and more than 100 Chinese scientists signed a letter decrying the study as “crazy.” Within days, He had been fired from his university post and all his research activities were suspended. A subsequent investigation by government authorities found that He violated Chinese law, and he is now serving a three-year prison sentence.

And as new revelations keep trickling in, policymakers are scrambling to lay down some ground rules for this new Crispr-baby world. In the aftermath of the He debacle, China formed a new national ethics committee with broad authority over all high-risk medical biotechnologies. It will be tasked with enforcing the country’s new clinical research guidelines, released in February. The World Health Organization has assembled a panel to develop global standards for governments to follow. Late last year, the Russian government cited the advice of this panel when it barred a Russian scientist from creating Crispr babies.

What is Crispr Gene Editing? The Complete WIRED Guide

What is Crispr Gene Editing? The Complete WIRED Guide

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.

What is Crispr Gene Editing The Complete WIRED Guide

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.

The WIRED Guide to Net Neutrality

The WIRED Guide to Net Neutrality

The Bush-era FCC took a first pass at anti-discrimination rules for the internet in a policy statement in 2005. It prohibited internet service providers from blocking legal content or preventing customers from connecting the devices of their choosing to their internet connections. Under this policy, the FCC ordered Comcast in 2008 to stop slowing connections that used the peer-to-peer file-sharing software BitTorrent, which was often used for digital piracy but also had legitimate uses. Comcast sued the FCC, arguing the agency had overstepped its bounds. A federal court agreed, ruling that the FCC had failed to make the legal case that it had the authority to enforce the 2005 policy statement.

In 2010, the Obama-era FCC passed a more detailed net neutrality order that it hoped would stand up to legal scrutiny. But the agency was sued again, this time by Verizon, and in 2014 the same court ruled the agency didn’t have the authority to impose net neutrality regulations on services that weren’t considered common carriers under Title II of the Communications Act, like traditional telephone services.

Later that year, the FCC floated a new proposal that net neutrality proponents worried would allow internet “fast lanes.” The idea drew the ire of comedian John Oliver, who encouraged viewers of his show Last Week Tonight to file comments to express their support for net neutrality. The flood of comments crashed the FCC’s website. The agency eventually received 21.9 million comments on the issue, shattering the record previously held by Janet Jackson’s 2004 Super Bowl “wardrobe malfunction.”

Then-FCC chair Wheeler eventually changed tack and decided to reclassify broadband providers as Title II carriers, though with fewer obligations than landline telephone operators. The FCC passed its sweeping net neutrality order in 2015, and was again sued by telecommunications firms. The same federal court that shot down the FCC’s previous attempts at net neutrality rules finally sided with the agency, ruling that the 2015 rules were legal. An industry group appealed that decision to the Supreme Court, which has yet to hear the case.

Meanwhile, control of the FCC changed as a result of the 2016 election. In January 2017, President Trump appointed Republican FCC Commissioner Ajit Pai as the agency’s new chair. In April, he announced a plan to reverse the 2015 net neutrality order. The FCC website was once again flooded with comments. But this time, observers noticed that a huge number of comments, many of which opposed net neutrality, were filed not by people but by bots.

The December 2017 FCC vote effectively threw out the 2015 rules in their entirety. The FCC’s new rules drop the common-carrier status for broadband providers, as well as any restrictions on blocking or throttling content. In place of those restrictions, the new rules only require that internet service providers disclose information about their network-management practices. It will now be up to the Federal Trade Commission to protect consumers from alleged net neutrality violations. But the FTC is only an enforcement agency: It can’t create new rules. That means that unless a net neutrality violation is also illegal under existing fair-competition laws, there’s not much the agency can do about it. Outright blocking a competitor may well be an antitrust violation, but creating fast lanes for companies that pay extra for special treatment might not be.

What Is Net Neutrality The Complete WIRED Guide

The Future of Net Neutrality

The future of net neutrality is now in the hands of Congress, the courts, and the states. Twenty-one state attorneys general sued the FCC in January 2018 to block the new rules and restore the old ones; so did several consumer-advocacy groups. A federal court decided mostly in the FCC’s favor in 2019 but ruled that the agency couldn’t override state-level net neutrality laws.

Several states have already passed such laws. Washington became the first in March 2018, and Oregon followed soon after. California passed one of the most comprehensive net neutrality laws of all, but the rules are currently on hold amidst a legal challenge from the federal government. Governors of Hawaii, Montana, New Jersey, New York, and Vermont have passed executive orders banning state agencies from doing business with broadband providers that don’t uphold the principles of net neutrality.

In the meantime, you can expect broadband providers to slowly take advantage of their new freedom. They probably won’t take big overt steps to slow down or block competing services, especially not while courts are still deliberating the FCC’s latest decision. But you can expect to see more of the practices that carriers already employ, like letting their own content bypass data limits. For example, AT&T lets you watch its DirecTV Now video service without having it count against your data plan, but watching Netflix or Hulu still chews through your limit.

What Is Net Neutrality The Complete WIRED Guide

Learn More

  • Here’s How the End of Net Neutrality Will Change the Internet
    If you want to know more about what broadband providers are most likely to do once the net neutrality rules go away, start here. We take a deeper look at the ways companies already use data caps to shape your internet experience, and what clues these practices provide about what the future holds.

  • The Covid-19 Pandemic Shows the Virtues of Net Neutrality
    It might seem quaint to worry about net neutrality during the coronavirus pandemic. But the crisis has made the internet more important than ever, highlights why people need unfettered access content, and illustrates why key arguments against net neutrality just don’t hold up.

  • California Net Neutrality Bill Would Go Beyond Original Protections
    Several states have passed executive orders to protect net neutrality, and both Oregon and Washington have passed their own rules as well. But so far no state’s protections are quite as robust as the Obama-era FCC rules. California could change that. The state passsed the toughest net neutrality bill yet.It’s on hold pending the resolution of a challenge from the Department of Justice, but it sets an example for other states.

  • Why Trump Supporters Should Love Net Neutrality
    Net neutrality is a partisan issue in Washington, but it shouldn’t be. Here’s why conservatives should fight big cable and embrace net neutrality.

  • The FCC Says Net Neutrality Cripples Investment. That’s Not True
    We took a hard look at earnings reports from the broadband industry, and found that one of the biggest claims made by net neutrality opponents is false. In fact, some broadband providers actually invested more on infrastructure after the 2015 net neutrality rules passed.

  • How Bots Broke the FCC’s Public Comment SystemThe FCC received an unprecedented number of comments on its plan to reverse its net neutrality protections. But researchers think the vast majority of those comments came from bots. We took a look at the evidence and what it means for the future of online debate.

  • FCC Plan to Kill Net Neutrality Rules Could Hurt Students
    Broadband plays a crucial role in education, from grade school to career retraining. Here’s how the end of net neutrality could set students back.

  • This Is Ajit Pai, Nemesis of Net NeutralityFCC chair Ajit Pai might be the most hated man on the internet. WIRED tracks his progression from nerdy high school student to policy wonk to head of the country’s top telecom regulator.

  • Plus! Local legislation and more WIRED net neutrality coverage.


This guide was last updated on May 4, 2020.

Enjoyed this deep dive? Check out more WIRED Guides.

What Is Net Neutrality? The Complete WIRED Guide

What Is Net Neutrality? The Complete WIRED Guide

Net neutrality is the idea that internet service providers like Comcast and Verizon should treat all content flowing through their cables and cell towers equally. That means they shouldn’t be able to slide some data into “fast lanes” while blocking or otherwise discriminating against other material. In other words, these companies shouldn’t be able to block you from accessing a service like Skype, or slow down Netflix or Hulu, in order to encourage you to keep your cable package or buy a different video-streaming service.

The Federal Communications Commission spent years, under both the Bush and Obama administrations, trying to enforce net neutrality protections. After a series of legal defeats at the hands of broadband providers, the FCC passed a sweeping net neutrality order in 2015. But in December 2017, the now Republican-controlled FCC voted to jettison that order, freeing broadband providers to block or throttle content as they see fit unless Congress or the courts block the agency’s decision.

Net neutrality advocates have long argued that keeping the internet an open playing field is crucial for innovation. If broadband providers pick favorites online, new companies and technologies might never have the chance to grow. For example, had internet providers blocked or severely limited video streaming in the mid-2000s, we might not have Netflix or YouTube today. Other advocates highlight the importance of net neutrality to free expression: a handful of large telecommunications companies dominate the broadband market, which puts an enormous amount of power into their hands to suppress particular views or limit online speech to those who can pay the most.

Most large broadband providers promised not to block or throttle content ahead of the ruling, but all four major mobile carriers began slowing down at least some video content before the FCC had fully repealed the rules. Net neutrality advocates worry things could get worse. A broadband provider might, for example, allow some companies to pay for priority treatment on broadband networks. The fear is that, over time, companies and organizations that either can’t afford priority treatment, or simply aren’t offered access to it, will fall by the wayside.

What Is Net Neutrality The Complete WIRED Guide

The History of Net Neutrality

Columbia University law professor Tim Wu coined the term “network neutrality” in a 2003 paper about online discrimination. At the time, some broadband providers, including Comcast, banned home internet users from accessing virtual private networks (VPNs), while others, like AT&T, banned users from using Wi-Fi routers. Wu worried that broadband providers’ tendency to restrict new technologies would hurt innovation in the long term, and called for anti-discrimination rules.

The Bush-era FCC took a first pass at anti-discrimination rules for the internet in a policy statement in 2005. It prohibited internet service providers from blocking legal content or preventing customers from connecting the devices of their choosing to their internet connections. Under this policy, the FCC ordered Comcast in 2008 to stop slowing connections that used the peer-to-peer file-sharing software BitTorrent, which was often used for digital piracy but also had legitimate uses. Comcast sued the FCC, arguing the agency had overstepped its bounds. A federal court agreed, ruling that the FCC had failed to make the legal case that it had the authority to enforce the 2005 policy statement.

In 2010, the Obama-era FCC passed a more detailed net neutrality order that it hoped would stand up to legal scrutiny. But the agency was sued again, this time by Verizon, and in 2014 the same court ruled the agency didn’t have the authority to impose net neutrality regulations on services that weren’t considered common carriers under Title II of the Communications Act, like traditional telephone services.

Later that year, the FCC floated a new proposal that net neutrality proponents worried would allow internet “fast lanes.” The idea drew the ire of comedian John Oliver, who encouraged viewers of his show Last Week Tonight to file comments to express their support for net neutrality. The flood of comments crashed the FCC’s website. The agency eventually received 21.9 million comments on the issue, shattering the record previously held by Janet Jackson’s 2004 Super Bowl “wardrobe malfunction.”

Then-FCC chair Wheeler eventually changed tack and decided to reclassify broadband providers as Title II carriers, though with fewer obligations than landline telephone operators. The FCC passed its sweeping net neutrality order in 2015, and was again sued by telecommunications firms. The same federal court that shot down the FCC’s previous attempts at net neutrality rules finally sided with the agency, ruling that the 2015 rules were legal. An industry group appealed that decision to the Supreme Court, which has yet to hear the case.