When you hear “gene editing,” do you think cancer cures? Designer babies? What about new fuel sources or drought-tolerant crops? Gene editing with a technique known as CRISPR/Cas9, hailed as a scientific breakthrough, could mean all those things.
There’s a possibility, of course, that CRISPR/Cas9 may not live up to expectations. That’s happened before. Twenty-five years ago, recombinant DNA was supposed to transform society in a way that, well, didn’t happen. But any past biotech disappointments are not stopping a slew of Bay Area CRISPR startups from taking the leap into the new world of DNA tinkering and synthetic biology. They are, in fact, everywhere, from biotech labs in Emeryville to kitchen counters in Burlingame.
“It’s something that people read about, it’s something people see that’s cutting edge,” says Josiah Zayner, a former synthetic biologist at NASA. “Yet it’s so accessible, it’s something that you can do in your home, on your kitchen table.”
Zayner has considered himself a “biohacker” for a long time. Now it’s his full-time job.
He’s started a company called The Open Discovery Institute, or The ODIN (not coincidentally, the name of the Norse god connected with healing, knowledge and … death). The point, he says, is to make science more accessible by providing low-cost supplies for people to practice gene editing at home. The first shipments from his Indiegogo crowdfunding campaign are expected this spring.
“You can learn about cutting-edge science by actually doing it,” Zayner says. “When I started experimenting with CRISPR I thought, ‘That’s pretty crazy!’ I would definitely want that opportunity.”
In Zayner’s kitchen I get a crash course in how this new kind of gene editing works. Zayner’s kits have three major parts: the Cas9 protein (other forms can use other proteins), the “guide” RNA and the donor DNA. The Cas9 protein makes precise cuts in the sections of the DNA to which it’s led by the guide RNA. Sensing the cut, the cell’s own repair mechanisms will try to repair it, by inserting a new piece of DNA. If all goes well, it will add a section of the donated DNA containing the desired gene or genes.
“So you kind of trick the cell into using your new piece of DNA instead of some other piece of DNA it finds, or the original piece of DNA,” says Zayner.
To see the process in action, we insert a yeast mutation that will change its color from milky white to rusty red. We mix a chemical solution called a buffer (which helps the cell accept the DNA into its wall), the Cas9 protein, the guide RNA and the donor DNA together in a small plastic test tube.
“So we’re going to try to get this inside the yeast cells,” Zayner says, holding up the clear fluid.
Zayner has some yeast growing on an agar-filled culture plate in his fridge. We transfer the yeast with a thin plastic loop. We heat up the cells by putting the test tube in a warm bowl of water, then let them cool again and rest before spreading them on a plate to let them grow. The yeast only needs to grow a day or two to see if the experiment was successful. A few days later, Zayner says it was.
This is fairly simple stuff. Zayner’s editing kits are more about fostering an interest in science than creating a new breed of super-humans — not that he necessarily would have a problem with that.
“Gene editing is the next step for humanity,” Zayner says. “Why should we limit ourselves to what evolution has told us we should have based on natural selection? When we can decide what works best for humanity?”
Gene editing technology has made great strides in the three years since CRISPR/Cas9 burst onto the scientific scene. Despite the rapid pace of advances, many scientists are urging caution as the technology becomes easier to use and the experiments become more ambitious.
“We haven’t really had the conversation about humans and what’s ethically appropriate or inappropriate,” says Mildred Cho, a bioethicist at Stanford University. She sees a huge potential for breakthroughs in gene editing, but also the possibility of misuse. “And we haven’t really had the conversation about widespread release of organisms that we won’t be able to get back once they’re released into the environment.” Cho, however, says it’s not up to scientists to decide such things. “So far, those discussions have not been very widespread outside of the expert communities.”
Yet Silicon Valley and the local biotech community are forging ahead. In San Francisco’s Mission Bay neighborhood, Twist Bioscience is making the components of DNA and RNA that companies and academic researchers can use in their synthetic biology experiments.
“We started Twist to disrupt the DNA-writing market,” says Emily Leproust, one of the co-founders. “There is a massive demand. A huge demand.”
Leproust says many drugs, antibiotics and vaccines begin from DNA, with engineered microbes used to make them. And in the area of industrial chemicals, many researchers and companies are modifying algae, yeast and E. coli to turn them into bio-factories that make specialty chemicals.
Twist doesn’t disclose the names of its clients. And in the interest of safety, Twist executives say, they restrict what sequences of DNA they’ll sell, and to whom. But there are lots of local labs and companies using DNA in this way, and they’re raising boatloads of money.
According to CrunchBase.com, Zymergen in Emeryville has raised $44 million, Caribou Bioscience in Berkeley $14 million, Sangamo BioSciences in Richmond about $74 million, and Twist itself more than $130 million.
That’s why, Leproust says, it’s good, today, to be in bio.
“If you were in the ’50s, you wanted to be in space and aeronautics and in the ’90s you wanted to be in computers. And nowadays you want to be in biology because that’s where the next big economic growth is going to come from.”
Time will tell. But local startups are betting and betting big on the new generation of gene editing.