Patients Favor Changing the Genes of the Next Generation with CRISPR

Jeff Carroll inherited the DNA mutation that causes Huntington’s disease. It means that he’ll lose control over his body and slowly go mad. “I have no compunctions about it,” says Carroll, a neuroscientist at Washington University. “I am saying, please, please do mess with our DNA.”
It’s a controversial idea, but now it’s easier than ever to do because of a powerful technology called CRISPR. Many experts at the meeting seem to be leaning toward endorsing an indefinite moratorium on any effort to create gene-modified babies, calling the technology too new, too unsafe, and too limited in medical use, a position that has been endorsed by the Obama administration.
But when MIT Technology Review reached out to several families who’ve dealt with devastating genetic illnesses, all said they approved of using the technology as quickly as possible. That could create a potential clash between desperate families and cautious scientists and politicians.
The debate so far is highly technical and abstract. But that will change once patients get involved. Sharon Terry, CEO of a patient group called the Genetic Alliance, says her in-box has been filled with e-mails from families, with many expressing views like “Hell yes!” Others still haven’t heard about CRISPR, a technology developed only three years ago.
During the three-day meeting of mostly technical presentations, Terry was the only patient advocate invited to speak, and no practicing IVF doctors took the stage. That is an oversight, since it means the deliberations have mostly excluded the people who would actually use the technology. During a question-and-answer session, a woman named Sarah Gray, whose six-day-old child died of a genetic disease, took the microphone and, through sobs, implored scientists to “just frickin’ do it.”
Three broad categories of DNA alterations are seen as possible with gene editing, and society will have to weigh them. One is to correct the DNA of an embryo to eliminate genetic defects like the one that leads to Huntington’s disease. A more speculative further step would be to install gene alterations to protect a person against diseases like Alzheimer’s or HIV infection. A final category, one that is still widely rejected, is enhancement, like trying to change genes to make a person taller or smarter.
Some critics say making genetically modified people for any reason is a “red line” that must never be crossed. Marcy Darnovsky, head of the eugenics watchdog group the Center for Genetics and Society, says there is no medical reason to ever use the technology, in part because people with genetic ailments don’t have to have children. “It should not be considered a medical technology at all. It’s not treating an existing person,” she says.  
Several scientists also argued strongly that germ-line gene editing would solve few, if any, real medical problems not addressed by other approaches. “It’s a vanishingly rare circumstance that presents itself with no alternatives,” says George Daley, a hematologist and stem-cell researcher at Harvard University.
The reason, scientists say, is that it’s already possible to have a child free of genetic disease by testing and choosing embryos created in an IVF clinic. That technology, called pre-implantation genetic diagnosis, or PGD, involves plucking a single cell from an embryo and testing its DNA.
Typically, only half the embryos of a person affected by a genetic disease would also inherit it, a fact that allows doctors to choose and transfer only healthy ones. Approximately 20,000 embryos were tested with PGD in the U.S. last year.
“The truth is, if we really care about avoiding genetic disease, germ-line editing is not the first, second, third, or even fourth thing to worry about. Most people are not even aware they are carriers. Letting them know and allowing them to use PGD would be the best,” says Eric Lander, director of the Broad Institute in Cambridge, Massachusetts.
Carroll says his was among the first Huntington’s families to try PGD when the technology became commercially available in the early 2000s. The procedure was successful, with doctors locating two unaffected embryos out of five. His wife had twins, a boy and a girl. Yet many families haven’t been as lucky, he says. They don’t get any healthy embryos, or the IVF procedure is unsuccessful.
“PGD is a hack, it’s not a fix. And you lose 50 percent of your embryos, which is not trivial,” he says. “It’s intellectually tempting to say PGD can fill the niche. I think gene editing would be a major boon to families.”
Daley says there may be no stopping motivated families. The ardor with which they seek cures could make gene editing hard to control, since parents might go overseas, where there is less regulation, to attempt the process. Some patients see in gene editing a replay of the debate over stem-cell research, a battle that pitted patients against political controls on science. “There is a softly, softly approach of appeasing people who oppose it. My view is that people from a family like mine do not want to delay for one day,” says Charles Sabine, a former NBC News reporter who also has the Huntington’s mutation, calling it “the disease I am going to die from.”
Some companies are trying to turn gene editing into a treatment for adults. One, Sangamo, has been developing a potential gene therapy for Huntington’s that would correct the mutation in adult brains. But neither Sabine nor Carroll expects to be saved by such developments. It’s simply too hard to change the DNA in billions of brain cells. By comparison, fixing a few cells in an embryo looks much easier.
“It’s too late for me,” says Sabine. “But I believe that future generations do not have to be so pessimistic because of the existence of this science.” Carroll says he understands the technology isn’t ready for actual use, but he thinks there is no question it should be used one day. “It’s not ready for prime time, but any immediate revulsion on the part of the scientific community that there needs to be some kind of line in the sand, I can’t agree with that,” he says. “I don’t know where the line is, but I know it’s not Huntington’s.”