The Little-Known Nonprofit Behind the CRISPR Boom

When Feng Zhang was a graduate student in the early 2000s, he helped make a groundbreaking discovery: Light-sensitive proteins from pond scum can actually be inserted into brain cells, giving scientists the ability to control parts of the brain with nothing much more than light. This idea spread like wildfire through neuroscience labs. It attracted Nobel buzz. It also made Zhang an expert on FedEx shipping.

So many labs clamored to use the technique that sharing vials of DNA that encode these light-sensitive proteins became a regular lab chore. Every few weeks, Zhang sat down to help print shipping labels and stuff a batch of envelopes. “I’m probably the most experienced FedEx label maker at MIT,” jokes Zhang, who now runs his own lab at MIT and the Broad Institute.

Later, in 2013, Zhang published a paper on the gene-editing tool CRISPR, which again became a game-changing idea—this time not just in neuroscience, but in all of biology. CRISPR involves taking proteins from bacteria—like ones that cause strep infections—and repurposing them to edit DNA. The editable DNA could be in human embryos, microbes, mice, dogs, monkeys, corn, fish, pigs, mosquitoes, elephants, mushrooms—virtually any species on the planet. Such is the transformative potential of CRISPR.

Once again, labs all over the world clamored to use the tool. But this time Zhang deposited the DNA coding for CRISPR at a small nonprofit called Addgene, located a mile down the road from MIT. Now, he no longer had to personally FedEx CRISPR tools. Scientists could order them straight from Addgene’s website for $65 a pop.

Addgene’s whole purpose is to share bits of useful DNA. As a graduate student in biology, its co-founder Melina Fan found herself on the opposite end of Zhang’s sharing problem: She waited months for other labs to send DNA, only to sometimes get the wrong one. A central DNA repository would be much more efficient than emailing individual labs and deciphering hand-labeled vials. So in 2004, she and two others—her brother, Kenneth Fan, and her husband, Benjie Chen—launched Addgene as a nonprofit sharing service. The company collects, manufactures, stores, and sends out DNA parts to academic labs and other nonprofits.

Addgene grew steadily at first, reaching more and more scientists every year. Then came CRISPR. “The year of CRISPR we took a very large increase,” says Joanne Kamens, Addgene’s executive director. The company has shared CRISPR components from Zhang’s lab more than 42,000 times, with more than 2,000 institutions in 62 countries. They account for four of the top 10 all-time most popular items available on Addgene’s site.

“If Addgene didn’t exist, our entire lab would be fulfilling these orders,” says Zhang. The nonprofit has also helped CRISPR become one of the fastest-spreading biotechnologies ever. (Other labs have also deposited versions of CRISPR with Addgene. That notably includes Jennifer Doudna’s lab at the University of California, Berkeley, which is locked in a patent dispute with Zhang and the Broad Institute over CRISPR. CRISPR components from Zhang’s lab have been shared much more widely, at least through Addgene.)

Today, CRISPR accounts for about 20 percent of Addgene’s orders. But the company, whose full catalogue contains more than 60,000 DNA parts, is about more than the spread of CRISPR alone. The remixing of DNA from different species is now a routine part of molecular-biology research—whether that’s using algae proteins to study mouse brains or jellyfish proteins to make cancer cells glow in the dark. Addgene has made it easier to get all of these parts.

Jason Ikpatt, a graduate student at the University of Texas at Austin, who also moonlights as a hip-hop producer, told me, “I can’t help but notice the similarities between an Addgene repository and a downloadable sample pack of pre-recorded sounds.” In his own research, Ikpatt has ordered DNA from Addgene to insert genetic material from prairie voles into mice, in hopes of understanding what makes some voles monogamous.

The two single most popular DNA components of all time on Addgene are isolated parts of an HIV virus that could, in turn, be used to insert, say, human genes into a mouse to study their function in disease. How’s that for remixing? “At the time, many people thought it quite strange that one would use a lethal pathogen for something like that,” says Didier Trono, the virologist who created the manipulated virus. “But it turns out be a marvel.” The underlying technology has since been widely used to manipulate the genes inside of cells as well as living animals like mice and rats. The DNA that Addgene distributes contains only a few components of HIV, so it cannot infect anyone.

Addgene now ships its DNA parts, as well as live viruses for DNA manipulation, to more than 80 countries. This requires a grasp of the baroque customs and import laws all over the world. Most of Addgene’s users are located in the U.S.; China comes second. Three-hundred-and-fifty boxes leave its Cambridge office everyday at 4 p.m. (UPS knows them so well that their deliveryman’s son ended up interning at Addgene.) The only countries where Addgene cannot ship are Cuba, Iran, North Korea, Sudan, and Syria.

For scientists in many developing countries, Addgene’s relatively cheap DNA parts are a godsend. At $65 plus shipping, a typical order costs far less than the hundreds of dollars for commercial products used in similar DNA work. Rebah Al-Gafari, a microbiologist at Al-Nahrain University in Baghdad, says that in Iraq graduate students and supervisors have to pay for their research out of pocket. They couldn’t afford anything more expensive. “The salvation came through Addgene and their principle of nonprofit,” he told me in an email.

In 2014, Al-Gafari and a Ph.D. student ordered DNA from Addgene because they wanted to insert a gene into probiotic bacteria for livestock feed. Around the same time, ISIS militants were closing in on major cities in Iraq. Nothing could get through amid the fighting. “Trust me, it was a dark time for all of us, and my student was in despair,” Al-Gafari wrote. Addgene saw the shipment was delayed, and offered to resend the DNA for free when the roads reopened.

“I do not know what to say, this email made me speechless,” Al-Gafari wrote in reply to Addgene at the time. “It is like a light shed on me in the middle of the darkness that we live in this country.”

Five months later, when the roads finally reopened, they got the DNA and resumed their research.