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The Case for CRISPR Babies
Some families with genetic diseases are finding hope in the controversial technology
In November 2018, a Rubicon was crossed in biomedical science. Chinese researcher He Jiankui announced he had created the first “CRISPR babies” — infants whose genomes were edited before they were born. The outcry was swift and scathing. Scientists condemned the experiments as unethical, unsafe, and perhaps worst of all, unnecessary. On Monday, it was announced that a Chinese government investigation determined He “seriously violated” state laws, and that he would likely face criminal charges.
But for some families with severe genetic disorders, the experiment offered something else: hope.
The gene-editing technology CRISPR emerged in 2013 as a sort of “cut-and-paste” tool for DNA.
One of its greatest promises is the ability to treat and potentially eliminate genetic disorders in humans. Clinical trials that use other forms of gene-editing therapy on blood or immune cells are already underway to treat patients with genetic conditions like sickle cell disease and certain types of cancer.
But editing the genome of an embryo adds a whole extra layer of complexity. Germline editing, as it’s called, is like playing with evolution. A single mistake could cause devastating consequences. Not only will that person’s genome be affected, but so will their children’s and their grandchildren’s and their great-grandchildren’s. This is because editing an embryo at the earliest stage changes the genes not only in those few preliminary cells, but in all the cells that develop after, including the eggs or sperm.
Scientists have called for a moratorium on editing the genome of human embryos until the methods are perfected and the moral implications — including the fear of “designer babies” — are hashed out.
That’s why He’s announcement in November was such a shock. It blew past all the ethical dilemmas and “what ifs” scientists had been discussing for years. He claims to have edited the embryos of twin girls to add in a genetic mutation that protects against HIV. The girls’ father is HIV positive, and he and his wife wanted to make sure he wouldn’t pass the virus on to his children. However, safe and effective ways to prevent parent-to-child HIV transmission already exist that don’t involve the risk — and controversy — of genome editing.
But there are plenty of genetic diseases with limited treatment options and no means of prevention. And now that Pandora’s box is opened, where do families faced with the risk of passing on severe genetic illness stand on the issue?
A recent poll by the Associated Press-NORC Center for Public Affairs Research showed that 71 percent of people are in favor of germline editing to prevent a fatal disease, and 65 percent support editing an embryo to prevent nonfatal conditions.
Ann Bryan is one of them. A mother of four, Bryan’s two youngest sons, ages three years and 17 months, both have hemophilia. It means they don’t produce enough of a critical blood clotting factor. Without it, blood clots don’t form; so if a child starts bleeding, they won’t stop.
Bryan describes a day when one of her sons woke up with blood covering his pillow. The cause was a new tooth coming in. Bryan had to give her son an intravenous transfusion of the missing blood clotting factor to make him stop bleeding. “I became my own nurse,” she says. “I know how to infuse, I know how to hit the vein. That’s just the life of a hemo mom.”
Hemophilia is caused by a genetic mutation on the X chromosome, so it is almost exclusively found in boys. Women, who have two X chromosomes, have two copies of the gene, so they typically aren’t affected by the disorder because the healthy gene compensates for the mutated one. However, women can pass the faulty gene on to their children.
Bryan’s brother also has hemophilia, so she knew from an early age that she could be a carrier. She took a genetic test before getting pregnant, but the results came back negative, and her first two children were born without complications. The test results must have been wrong, she says, because her third child, AJ, was diagnosed with hemophilia after he was born.
“When I found out AJ had hemophilia, it was a complete surprise,” says Bryan. “Knowing the life you live with it [from my brother], it was very hurtful.”
When she found out she was unexpectedly pregnant again less than a year later, Bryan and her husband considered having an abortion. Ultimately, they decided to go through with the pregnancy, even though the baby boy also had the mutation.
Knowing what she does now, Bryan says that if embryonic gene therapy — like the kind performed by He — was available, she definitely would’ve considered it.
“I’m never going to have any more kids, but if it was around when I had my boys, if I knew I was a carrier, I would definitely do it,” she says. “I would not want to bring a child into this world to suffer or to go through the pain these kids go through.” She’s quick to add that she would want to make sure that it’s safe and that she knows all the potential side effects first.
Clinical trials using genome editing to fix the mutation in the blood cells of adults with hemophilia are currently underway. These kinds of techniques aren’t perfect yet, and there are concerns about potential off-target effects in which other parts of the genome are accidentally changed. But Bryan hopes that the treatment is an option for her sons someday soon. “Anything that’s going to enhance the quality of my kids’ life, I’m willing to try it,” she says.
“I think it’s unfair to pass something like that on to a child who has no choice in it.”
Duchenne muscular dystrophy is another condition caused by a single genetic mutation on the X chromosome that scientists are hoping to correct with genome editing. Several gene therapy clinical trials are underway to treat the disease, which can cause weakness, paralysis, and even death.
Ben Dupree, a 26-year-old with Duchenne, is too old to enroll in the current clinical trials; scientists ideally want to correct the gene before the disease progresses too far. But if he was eligible, he would partake. “In general, people with Duchenne are willing to tolerate a greater amount of risk for potential benefit than most people,” he says.
Despite being in a wheelchair, Dupree hasn’t let the disease slow him down. He earned a degree in biochemistry and is now applying to master’s programs for social work. But he says Duchenne has impacted his decision to have a family. “I really don’t think I would ever want to have children just because of the chance of passing on muscular dystrophy to a child,” he says. “I think it’s unfair to pass something like that on to a child who has no choice in it.”
However, if germline editing was an option and he could guarantee his child wouldn’t inherit the condition, Dupree says he would reconsider having a family. “If CRISPR was possible, approved, legal, and could treat Duchenne muscular dystrophy in an embryo, that might be something I’d think about.”
Daniel Whiston, the father of a son with myotubular myopathy, takes a more cautious stance. Myotubular myopathy is a rare genetic disorder that is similar to Duchenne, but more severe. Half of the children diagnosed with the condition don’t make it to their second birthday.
Whiston’s son, William, is seven and can move his fingers and play on an iPad, but he can’t walk, crawl, or roll over. The family’s biggest concern is respiratory issues. The diaphragm is one of the muscles affected by myotubular myopathy, making it difficult for children to breathe and cough. William has been on a ventilator since he was one.
The family launched a foundation in William’s name to support research into myotubular myopathy, which helped fund an animal study that used gene therapy to correct the disease-causing mutation. Based on that research, the first clinical trial is now ongoing.
Although he’s excited by the trial, Whiston says doing gene therapy in an embryo is a step too far. “Germline editing is something that, those boundaries have not yet been set, and there’s reasons why people are very skeptical of it and it’s a well-regulated area,” he says.
One of his biggest concerns is pushing the science too far, too fast — as many argue He has already done — and causing a major setback for the rest of the field. In 1999, an early genome editing trial for a rare liver disease resulted in the death of an 18-year-old boy. The tragedy halted gene therapy research for over a decade.
“Being somewhat selfish, had better precautions been taken in the 1990s, would [gene] therapy have been developed for my son?” Whiston says. “Would it have been available when he was born?”
“I think it will be great to get rid of these genetic diseases. But that doesn’t mean we should all run around expecting it to happen tomorrow morning.”
Arthur Caplan, a professor of bioethics at New York University School of Medicine, also advises a cautious approach to germline editing. “I’m for it,” he says. “I think it will happen. I think it will be great to get rid of these genetic diseases. But that doesn’t mean we should all run around expecting it to happen tomorrow morning.”
“Families need to know that it’s just not ready yet,” Caplan adds. “These techniques for repairing disease’s germlines are just not studied enough or understood enough.”
In the meantime, there is another option for would-be parents who carry a genetic mutation: preimplantation genetic diagnosis. The procedure requires in vitro fertilization (as would germline editing), after which scientists can test five-day-old embryos for any number of genetic conditions, such as Tay-Sachs, cystic fibrosis, and even cancer predisposing mutations like BRCA1. Only the healthy embryos are transferred into the mother’s womb, ensuring the baby is disease-free.
“The problem of these genetic diseases is very serious, and what’s exciting and important for patients, and even clinicians, to know is that we have the ability to help them have healthy children,” says Zev Williams, director of Columbia University Fertility Center who specializes in preimplantation genetic diagnosis. “CRISPR has gotten tons of attention, but it’s sort of like a more cumbersome high-risk way of doing what’s already being done safely.”
Even so, experts and families alike believe that sooner or later, CRISPR babies will be here.
“The potential for eliminating a lot of diseases… I think that’s just too beneficial to pass up,” Dupree says. “We’ve opened the box, and even if we find it morally objectionable, it’s going to keep progressing. I think refusing to use gene editing at all for fear of those bad things happening would cost a lot.”