hen Rachel Haurwitz started her biology Ph.D. at the University of California, Berkeley, the award-winning biochemist Jennifer Doudna suggested Haurwitz investigate part of a bacterial immune system. She studied how microbes store genetic mementos of attacking viruses and recognize them to fight off future assaults. “It was an esoteric project,” Haurwitz says.
It’s esoteric no more. This system, called Crispr, has become one of the hottest technologies in biology, with the potential to give scientists control of the building blocks of life and give investors rich rewards. Crispr had no obvious relevance to human health when it was first described in 1987, but Doudna, who won the Breakthrough Prize in Life Sciences for her Crispr work, and other pioneers have discovered ways to turn it into a gene-editing tool. Haurwitz and Doudna helped found Caribou Biosciences in 2011 to get in on the action. Haurwitz, still in her 20s, became CEO the next year.
Haurwitz is not the only young entrepreneur who sees opportunity in gene editing. Doudna cofounded Mammoth Biosciences with some of her other doctoral students and two Stanford Ph.D.s. Trevor Martin, the company’s 30-year-old CEO, has raised $23 million from such investors as Apple CEO Tim Cook. In 2015, in Cambridge, Massachusetts, 29-year-old Luhan Yang founded eGenesis with her mentor, Harvard geneticist George Church, to use Crispr to help transplant pig organs into people. Omar Abudayyeh and Jonathan Gootenberg, also in their 20s, cofounded Sherlock Biosciences with another Crispr pioneer, 37-year-old Feng Zhang of the Broad Institute of MIT and Harvard.
“They may be young, but in both cases these are people at the top of their game scientifically,” Doudna says of her cofounders. “They’re fearless in all the right ways and very aware of the ethical challenges.”
Given that no one had built a Crispr company until a few years ago, “there’s maybe more of an opportunity for people with nontraditional backgrounds,” Haurwitz says.
Crispr is an acronym for “clustered regularly interspaced short palindromic repeats.” It refers to the way bacteria store, in their genomes, snippets of viral DNA, like mug shots. Those markers are used to identify invaders that return, much as a human immune system uses telltale elements of a polio virus remembered from a vaccine.
If an invading virus matches a stored mug shot, enzymes associated with Crispr break the virus’ lethal DNA into harmless pieces. Doudna and others figured out how to use those enzymes to snip DNA at precise points in order to insert or modify genes. Thus does Crispr promise to make the expensive and buggy process of rewriting DNA easier, opening up new ways to treat diseases caused by genetic mutations, create cheaper diagnostic tests and engineer cells that kill cancer.
Eight years after its start in Berkeley, Caribou has raised $41 million and cut licensing deals—potentially worth hundreds of millions of dollars—with DuPont Pioneer, Novartis and others. It’s starting to develop medical therapies.
Haurwitz grew up in Austin, Texas, and earned a bachelor’s degree in biology at Harvard. She didn’t have a clear plan when she went on to UC Berkeley, but she thought she might later become a patent attorney.
That thinking changed as her Ph.D. work got more exciting. Haurwitz and Doudna spent a lot of time talking about how they could repurpose Crispr for modifying genomes to cure disease. Program the naturally occurring Crispr system to cut the gene you want to modify, and it’s theoretically possible to use it to change the genetic code to either fix “misspellings” that cause illness or disrupt the production of an unwanted protein.
Caribou started out with the notion of making Crispr technology available for DNA editing in applications such as drug development, agriculture and basic biological research. Haurwitz’s cofounders didn’t want to leave academia and were “crazy enough to let a 26-year-old who had never worked for a company in her life take on the role of president and CEO,” she says.
Haurwitz took a few business classes before getting her Ph.D., then pitched venture capitalists on funding a technology they didn’t really understand. Caribou was securing an exclusive license to some Crispr patents held by the University of California system and the University of Vienna. Still, “pretty much every VC we talked to kind of said, ‘Meh,’ ” Haurwitz remembers. This was 2012, and they thought she was overestimating Crispr’s potential.
The papers that propelled Crispr into the limelight came the next year, and investor dollars and a wave of new companies quickly followed. Editas Medicine, cofounded by Sherlock’s Feng Zhang, raised $43 million to apply the technology to medical therapies. Next was Intellia Therapeutics, cofounded by Caribou, which raised $15 million in its 2014 launch. And Crispr Therapeutics, founded by Crispr pioneer Emmanuelle Charpentier, raised $89 million. The three went public in 2016 and now have a combined market capitalization of $3.8 billion.
Meanwhile, Haurwitz was being cold-called by plant-breeding and drug companies. DuPont led an $11 million investment in 2015. Caribou raised another $30 million the next year and has been able to sustain itself on that funding and payments from licensing and partnership deals.
Caribou licensed to Integrated DNA Technologies the right to sell biology researchers what they’d need for gene-editing experiments. Genus, an animal genetics firm, paid Caribou an undisclosed amount for the exclusive right to use its proprietary Crispr technology to engineer the genes of pigs and other livestock. Similarly, the Jackson Laboratory is paying Caribou to use Crispr to engineer new populations of research mice that model human diseases.
Haurwitz will soon have to seek venture capital again, as Caribou has pivoted to drug development, which is expensive but potentially more lucrative. Her first focus: improve on existing cancer therapies that take patients’ immune cells and train them to attack cancer. Crispr, she says, could be used to edit the DNA of immune cells from healthy donors so that these cells could be given to any cancer patient. The company plans to start trials in humans next year. There’s competition, from Allogene Therapeutics and its partner Cellectis, which have a combined market cap of $3.9 billion.
Caribou is also developing a program in another buzzy area: the microbiome, or the many bacteria that inhabit all parts of the human body, particularly the gut. This time, investors know what Crispr is, and Haurwitz has already won some over. “She’s one of the few people that I’ve met in my life that is able to toggle between business talk and scientific talk in a heartbeat,” says Ambar Bhattacharyya, a Caribou investor at Maverick Ventures.
Beyond the competition, there is an intellectual property conflict. Overlapping patent claims from the University of California and the Broad Institute emerged for the foundational technology, which involves an enzyme called Cas9, used to cut DNA. A lawsuit between the institutions was decided in favor of the Broad, but the U.S. Patent Office has granted patents to both. UC’s patents claim broader rights than were demonstrated in its application, says Lisa Ouellette, a Stanford Law School professor, and could make them vulnerable to a legal challenge. (UC disagrees.)
Whoever owns the technology will command fat fees. Caribou might run trials related to a particular gene, but if other companies want to run trials related to other genes, they may have to approach Caribou, says Jacob Sherkow, a professor at New York Law School. “They’re going to have to pay handsomely.”
Legal battles aside, the new field risks public backlash. In November, Chinese scientist He Jiankui announced he’d used Crispr to tinker with the genomes of human embryos born as twin girls, thereby heightening pressure on Crispr scientists to consider the ethics of how they’re using the life-altering tech. Caribou’s license agreements include language to prevent its use on human embryos, Haurwitz says.
Doudna says researchers need to vet the science of editing the genes of embryos, and then people need to discuss how to use it responsibly. “Are there real unmet medical needs that would require this kind of editing or not? I think that’s one question.”
Debate over the answer will shape Crispr’s path to commercialization, one that holds immense potential for its youthful founders—and the likelihood of yet more controversy and conflict.
-Michela Tindera;Forbes Staff
-Ellie Kincaid;Forbes Staff