DNA Wars in Cambridge

Last December, the world’s most accomplished CRISPR researchers gathered at the National Academies of Sciences, Engineering, and Medicine, in Washington, DC, for a summit on the science and ethics of human gene editing. / Pam Risdon/Risdon Photography via National Academies of Sciences, Engineering, and Medicine

Like many game-changing moments in human discovery, gene editing can be compared to putting a man on the moon. “Kennedy knew that you could get to the moon if you could just strap five Saturn rockets together,” says Bill Lundberg, chief scientific officer of CRISPR Therapeutics. “It was no longer a scientific discovery problem. It was an engineering problem. That’s where it feels like we are with CRISPR technology. The fundamental discovery of correcting DNA is there. We just have to figure out the engineering applications of how to get it.”

CRISPR Therapeutics has set up its research and development lab in Cambridgeport, just west of MIT. “[Cambridge has] a tremendous density of really smart, creative, interesting people,” Lundberg says. “It’s a vibrant, dynamic ecosystem for new companies like ours.” In April 2014, CRISPR Therapeutics announced its first $25 million of funding, and in no time, the company began staffing up: It hired its first 25 full-time scientists in the second half of 2015, and it’s aiming to hire about 35 more in 2016.

Despite the ongoing battle over intellectual property, scientists and pharma companies are racing ahead at full speed. And the money is rolling in: Last fall, CRISPR Therapeutics forged a $105 million partnership with Boston-based Vertex Pharmaceuticals to invent treatments for sickle cell anemia and cystic fibrosis, followed by a $335 million collaboration with Bayer to treat congenital heart disease and a form of blindness.

Less than 2 miles away, Zhang and Church’s competing outfit, Editas, has set up shop near Kendall Square. It’s also working on sickle cell treatments, and its ceo, Katrine Bosley, boldly predicts that a drug to treat a rare form of blindness will likely start in clinical trials by 2017. In August, Editas announced $120 million in new funding, on top of the $43 million it launched with, and in January the company announced plans to go public—a sign of how fast the CRISPR field is moving.

Meanwhile, Intellia, with its headquarters four blocks from Cambridgeport’s CRISPR Therapeutics, has raised $85 million in funding. The company, run by ceo Nessan Bermingham, announced a partnership with Novartis in January 2015 that appears to be focusing on cancers, especially blood cancers, and is taking its own shot at sickle cell anemia. Intellia has also announced its expansion into autoimmune and inflammatory diseases. It’s not hard to imagine that heart disease could be right around the corner. “What if I told you that you could come into the doctor’s office for a one-time injection,” Cowan asks, “and it would delete a gene in your liver that would give you a lifetime of low cholesterol and a low risk of heart attack? It’s a vaccine for heart attack!”

As the three Cambridge CRISPR companies try to invent new drugs, editing human genes has turned out to be the easy part. Researchers have already used the CRISPR technique to correct the single gene that causes sickle cell anemia; now the challenge is finding a way to deliver those edited genes to a patient’s body. Cowan, who spends his Tuesdays off from Harvard working as one of CRISPR Therapeutics’ scientific advisers, predicts that the biotech industry will start slowly, first using CRISPR to combat simpler single-gene diseases for which inserting modified genes into some areas of the body—such as the blood and the liver—will be relatively simple. Next, it’ll tackle single-gene diseases with tougher delivery challenges: in the kidneys, lungs, muscles, and nervous system. The futures of Cambridge’s CRISPR companies depend on whether they can master the delivery of CRISPR-based therapies. If CRISPR proves to be the game-changing biotechnology it appears to be, the patent war will ultimately become more about who holds the financial upper hand in future licensing negotiations.

Cowan wishes the two sides of the patent war would make peace. “Why not take the legal money, put it into research, and agree to cross licensing?” he asks, before answering his own question. “But there’s money involved, enough [so that] there’s a benefit to being a clear winner.”

While CRISPR holds great potential to cure diseases (and generate profit), it also raises the terrifying specter of eugenics and other fears about the dangers of humans playing God. Its critics, and even some of its inventors, warn that the technology could also be used to permanently change the human gene pool and create so-called designer babies. That’s why, this past December, the world’s most accomplished CRISPR researchers, including many familiar faces from Boston and Cambridge, gathered at the National Academies of Sciences, Engineering, and Medicine, in Washington, dc, for a summit on the science and ethics of human gene editing. As CRISPR technology continues to spread, local scientists are leading the national debate, asking, How much should we really mess with nature?

The summit began with somber warnings about dystopian futures. Caltech president emeritus David Baltimore, the conference’s chief organizer, invoked Aldous Huxley’s Brave New World to caution against “a society built on selection of people to fill particular roles.” It’s a warning scientists should take to heart, Baltimore argued, as they debate “when and whether to proceed with conscious modification of the human genome…changes that can be passed on to future generations.” Yale University historian Daniel Kevles gave conference-goers a primer on the eugenics movement in Nazi Germany and 20th-century America. He warned that the pre–World War II movement, focused on “getting rid of the undesirables and multiplying the desirables,” isn’t as far in the past as we might like to think. “One might ask how couples will respond if CRISPR enables them to select for, or even to engineer, advantageous traits into their children,” Kevles said. “Their right to reproductive freedom would assist them,” he added, “and so would enticements from the biotechnology industry.”

No one at the meeting of distinguished scientists went so far as to argue that CRISPR should be used to make superior babies. Instead, they debated whether there’s any compelling medical reason to edit genes in human reproductive cells, or whether the conference should call for a moratorium or a ban on such experiments.

Eric Lander, the president and founding director of the Broad Institute, tamped down some of the hype about CRISPR, mocking the idea that CRISPR could wipe out humanity’s worst genetic diseases and give everyone the best possible genes. To accomplish that, he pointed out in his conference speech, the entire human race would have to conceive kids in test tubes: “It would require everybody’s efforts to stop reproducing naturally…. I don’t think that’s so likely to happen.”

In fact, Lander argued, reproductive gene editing may not have many medical uses at all. Many parents with a rare genetic disease can already avoid passing it down to their children by using in vitro fertilization and having doctors screen the embryos for disease before implanting them in the mother’s womb. The most common genetic diseases involve a lot of genes, Lander said, so editing one won’t make much difference. “All those genes that have been found for common disease have exceedingly modest effects,” Lander said. “Evolution beats down the frequency of [high-risk genes].”

Church and another local researcher, George Daley, of Boston Children’s Hospital and the Dana-Farber Cancer Institute, spoke on the conference’s key panel about reproductive gene editing. “I’m skeptical about the Brave New World scenario of designer babies,” Daley said. Traits that parents might really want for their children, such as intelligence and courage, “involve small contributions from many, many genes,” Daley argued, and are greatly affected by the environment a child is raised in—nurture as well as nature. In other words, it would be incredibly difficult for scientists to gene-edit their way to super girls or super boys.

Still, scientists have not ruled out the notion of editing humans. Lander, Church, and Daley all mentioned rare hypothetical cases in which there could be a compelling argument for editing reproductive cells. If two prospective parents have the same rare genetic disease, such as congenital deafness, DNA editing could help them conceive a child who could hear, Lander noted. Daley also brought up the scenario of “savior children,” who could be donors for siblings in need of a bone-marrow transplant.

At the conference, some dissenters spoke up: An ethicist warned of the danger of “market-based eugenics”; a British researcher expressed concern that “unscrupulous clinics” could someday offer unproven, unsafe gene editing, as some do now with stem-cell treatments. But in the end, few scientists at the summit wanted to impose a strict moratorium on reproductive gene editing. The consensus seemed to be: Keep regulators at bay and let the scientists develop a peer standard—with ostracism the penalty for disobedience, rather than financial or criminal punishment. All three companies—CRISPR Therapeutics, Intellia, and Editas—issued statements explaining that they refrain from editing any human reproductive cells. “I hope that we will be able to find a way that we can resist the temptation to go where we should not,” Daley said, “and yet not limit our ability to use this for great medical need.”

Instead of a moratorium, summit organizers carefully worded a statement supporting “intensive basic and preclinical research,” but added that if any human embryos or reproductive cells undergo gene editing, “the modified cells should not be used to establish a pregnancy.” It would be “irresponsible,” the scientists said, to proceed with any clinical use of reproductive gene editing until safety issues such as mistaken edits are resolved and society reaches a consensus that such a therapy is appropriate. The careful stance went over well with Boston researchers, including Church and Zhang. “The technologies are exciting, so it’s good that people can continue to develop it,” Zhang says. “But of course, because the technology is so powerful, we have to be thoughtful and be careful.”