For those wondering what the deal with CRISPR is, Michael Specter offers a riveting overview in the New Yorker.
The field has moved quickly. For scientists, ordering genes is almost Amazon-like in its convenience now.
Ordering the genetic parts required to tailor DNA isn’t as easy as buying a pair of shoes from Zappos, but it seems to be headed in that direction. Yan turned on the computer at his lab station and navigated to an order form for a company called Integrated DNA Technologies, which synthesizes biological parts. “It takes orders online, so if I want a particular sequence I can have it here in a day or two,” he said. That is not unusual. Researchers can now order online almost any biological component, including DNA, RNA, and the chemicals necessary to use them. One can buy the parts required to assemble a working version of the polio virus (it’s been done) or genes that, when put together properly, can make feces smell like wintergreen. In Cambridge, I.D.T. often makes same-day deliveries. Another organization, Addgene, was established, more than a decade ago, as a nonprofit repository that houses tens of thousands of ready-made sequences, including nearly every guide used to edit genes with CRISPR. When researchers at the Broad, and at many other institutions, create a new guide, they typically donate a copy to Addgene.
The field has achieved some level of efficiency with the creation of editable mice.
The vivarium at the Broad houses an entirely different kind of mouse, one that carries the protein Cas9 (which stands for CRISPR-associated nuclease) in every cell. Cas9, the part of the CRISPR system that acts like a genetic scalpel, is an enzyme. When scientists originally began editing DNA with CRISPR, they had to inject both the Cas9 enzyme and the probe required to guide it. A year ago, Randall Platt, another member of Zhang’s team, realized that it would be possible to cut the CRISPR system in two. He implanted the surgical enzyme into a mouse embryo, which made it a part of the animal’s permanent genome. Every time a cell divided, the Cas9 enzyme would go with it. In other words, he and his colleagues created a mouse that was easy to edit. Last year, they published a study explaining their methodology, and since then Platt has shared the technique with more than a thousand laboratories around the world.
The “Cas9 mouse” has become the first essential tool in the emerging CRISPR arsenal. With the enzyme that acts as molecular scissors already present in every cell, scientists no longer have to fit it onto an RNA guide. They can dispatch many probes at once and simply make mutations in the genes they want to study.
He stood up and walked across the office toward his desk, then pointed at the wall and described his vision for the future of cancer treatment. “There will be an enormous chart,” he said. “Well, it will be electronic, and it will contain the therapeutic road map of every trick that cancer cells have—how they form, all the ways you can defeat them, and all the ways they can escape and defeat a treatment. And when we have that we win. Because every cancer cell starts naïve. It doesn’t know what we have waiting in the freezer for it. Infectious diseases are a different story; they share their knowledge as they spread. They learn from us as they move from person to person. But every person’s cancer starts naïve. And this is why we will beat it.”
It's a story with all the usual trappings of a technology race. Patent battles and intellectual property lawsuits. Stunning breakthroughs. And of course, the dystopia nightmares that seem to accompany genetics more than any other form of science.
Doudna is a highly regarded biochemist, but she told me that not long ago she considered attending medical school or perhaps going into business. She said that she wanted to have an effect on the world and had begun to fear that the impact of her laboratory research might be limited. The promise of her work on CRISPR, however, has persuaded her to remain in the lab. She told me that she was constantly amazed by its potential, but when I asked if she had ever wondered whether the powerful new tool might do more harm than good she looked uncomfortable. “I lie in bed almost every night and ask myself that question,” she said. “When I’m ninety, will I look back and be glad about what we have accomplished with this technology? Or will I wish I’d never discovered how it works?”
Her eyes narrowed, and she lowered her voice almost to a whisper. “I have never said this in public, but it will show you where my psyche is,” she said. “I had a dream recently, and in my dream”—she mentioned the name of a leading scientific researcher—“had come to see me and said, ‘I have somebody very powerful with me who I want you to meet, and I want you to explain to him how this technology functions.’ So I said, Sure, who is it? It was Adolf Hitler. I was really horrified, but I went into a room and there was Hitler. He had a pig face and I could only see him from behind and he was taking notes and he said, ‘I want to understand the uses and implications of this amazing technology.’ I woke up in a cold sweat. And that dream has haunted me from that day. Because suppose somebody like Hitler had access to this—we can only imagine the kind of horrible uses he could put it to.”