New study shows that researchers probably won't create 'designer babies' anytime soon

Creating “designer babies” with a revolutionary new genome-editing technique would be extremely difficult, according to the first U.S. experiment that tried to replace a disease-causing gene in a viable human embryo.

Partial results of the study had leaked out last week, ahead of its publication in Nature on Wednesday, stirring critics’ fears that genes for desired traits — from HIV resistance to strong muscles — might soon be easily slipped into embryos. In fact, the researchers found the opposite: They were unable to insert a lab-made gene.

Biologist Shoukhrat Mitalipov of Oregon Health and Science University, who led the first-of-its-kind experiment, described the key result as “very surprising” and “dramatic.”

The “external DNA” provided to fertilized human eggs developing in a lab dish “was never used,” he told STAT. The scientists excised a mutated, heart-disease-causing gene from the embryos—a gene that came from sperm used to create them through in vitro fertilization—and supplied them with a healthy replacement. But every single one of the 112 embryos ignored it. Instead, they copied the healthy gene from their mother and incorporated that into their genome to replace the father’s.

Via Giphy

“This is the main finding from our study,” Mitalipov said: Embryos’ natural preference for a parent’s gene “is very strong, and they won’t use anything else.”

The discovery suggests that opportunities for disease prevention are more limited than scientists assumed and that enhancement—giving a days-old embryo “better” genes—is unlikely to succeed, at least with current methods. Genetic tinkering can, however, eliminate a “bad” gene that an embryo got from one parent and replace it with a “good” gene from the other parent. And the experiment showed for the first time in a large number of embryos that this can be done efficiently and without harming other genes.

That offers the prospect of preventing inherited diseases such as cystic fibrosis, Huntington’s disease, and some cancers, as long as one parent carries a healthy gene to replace the disease-causing one. (The age-old desire of many couples to choose which parent’s traits their child inherits could also become a reality, though probably not for years.)

Polls show greater public support for using “germline editing” — changing the DNA of very early embryos — to prevent disease than for giving embryos souped-up genes for, say, extraordinary memories or unbreakable bones. Such traits would be passed on to all subsequent generations. Although some studies have identified genes associated with those enhanced traits, they are extraordinarily rare. To bestow the traits on an embryo would require creating the genes in a lab and injecting them — the exact thing that failed completely in the new study.

The surprise finding showed that “to introduce a novel gene is [an] issue,” said Fredrik Lanner, of Karolinska University Hospital in Sweden, who was not involved in the Oregon study. (Lanner received permission last year to conduct similar experiments editing the genome of human embryos). “More research would be needed to really know how efficiently a new gene version can be introduced.”

The discovery that human embryos might have natural barriers to accepting introduced DNA — something other kinds of human cells, and other animal embryos, have no problem doing — offers some assurance that designer babies are not in the offing anytime soon. But critics of editing the human germline were not mollified.

Marcy Darnovsky, executive director of the Center for Genetics and Society, argued that there are other ways for couples to have a biological child free of the known genetic defects carried by one parent or both: Screening the DNA of IVF embryos through a technique called preimplantation genetic diagnosis (PGD) lets parents choose only healthy embryos to implant.

“We have to weigh the medical benefit to a few” from correcting an embryo’s mutation “against the social risks for all of us,” she said, adding that “enhancement-type alterations” might in fact be possible. “I don’t see any reason to doubt that Mitalipov or others will pursue other new wrinkles in these procedures, to enable more extensive genetic alterations.”

The research hit other hot buttons. Mitalipov (a skilled reproductive biologist known for pushing boundaries) and his colleagues created human embryos. Doing that for research is legal in Oregon and some other states but illegal in others and ardently opposed by many religious groups. And the scientists destroyed them after a few days, which some critics regard as murder. (The researchers had no intention of implanting the altered embryos in a uterus.)

A 1995 law prohibits the use of U.S. funds to create human embryos for research or to destroy them, and the National Institutes of Health bans use of its grants to edit the genome of human embryos, but this study was funded by private foundations and university funds.

At first glance, the experiment ran according to script. The scientists created embryos by fertilizing (in lab dishes) eggs from a dozen healthy donors with sperm from a man with the mutation that causes the rare heart disorder called hypertrophic cardiomyopathy. At the same time, the scientists injected CRISPR-Cas9.

This revolutionary genome-editing technology typically has three components. A targeting molecule carries the CRISPR complex to the target gene within a cell. A molecular scissors snips out the target gene. A healthy gene is supposed to replace the excised one. In experiment after experiment in regular human cells (not embryos), this now-classic use of CRISPR-Cas9 shreds the targeted DNA and the double helix stitches in a replacement like a seamstress darning a sock.