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Biomedicine

How to (Really) Engineer a Human Baby

A global meeting in Washington, D.C., isn’t just about whether or not we should alter our species with CRISPR. It’s about how we can pull it off.

How would you engineer a baby? I mean really, actually do it.

Last April, Chinese researchers reported that they had tried genetically editing human embryos for the first time to correct a disease gene. Out of more than 80 embryos, however, only a handful came out correctly. In the rest, the gene didn’t get fixed properly, or they ended up with unintended alterations to their DNA (see “Chinese Team Reports Gene-Editing Human Embryos”).

The scientific community pounced on the problems with a collective phew. Don’t worry, they said, it’s not even practical. Not yet.

Next week, in Washington, D.C., the world’s experts on a powerful new genetic-engineering technology called CRISPR will convene at the National Academy of Sciences for a historic meeting at which they’ll consider calling for a global moratorium on anyone trying to use the technique to make genetically modified babies.

The worry is that changing the DNA of the next generation is unsafe and a slippery slope toward eugenics. Yet many of the scientists attending the Washington meeting won’t be there to ban the technology, but to trade tips about how, exactly, they might be able to do it right.

One scientist who thinks he knows is Jinsong Li, a biologist at the Shanghai Institutes for Biological Sciences. Earlier this year, Li managed to use CRISPR to edit a gene that causes eye cataracts in mice, creating healthy newborn animals with “100 percent” success.

The way Li’s team did it was to avoid embryos, and instead edit “spermatogonial” stem cells growing in his lab. These are the factory cells that make sperm. By gene editing mouse sperm cells first, and then using corrected sperm to make embryos, Li’s mice came out perfect every time.

A scanning electron micrograph of mature sperm.

Li, who is part of the large Chinese delegation travelling to Washington, says he is convinced that embryo editing “is unacceptable” and that correcting reproductive cells is “the only possible strategy.”

Of course, edited sperm would only help prevent genetic diseases passed along by the father. Yet some scientists agree that sperm may be the most practical avenue for making designer people. “It could turn out to be a very good option,” says George Church, a professor at Harvard University and one of the inventors of the CRISPR technology.

Any gene-edited baby would likely start life in an IVF clinic where doctors could oversee its creation. The problem is that rewriting a gene with CRISPR is still hit or miss—the edits only work about 20 percent of the time, and occasionally it introduces unwanted mistakes. That’s no obstacle for engineering flies or worms. Just try again. But it’s a huge problem for anyone who wants to repair an embryo in an IVF clinic and then make a baby.

Editing sperm stem cells overcomes this problem, says Li. He says his team simply first identified stem cells that had been correctly edited and used those to produce swimming sperm, and after that healthy mice. He was also able to check that no accidental edits, or “off target” effects, had occurred.

There are still obstacles to making Li’s sperm technique work in humans. The biggest: no one has figured out how to very successfully cultivate human sperm cells in the lab. “That’s the bottleneck,” says Kyle Orwig, a scientist at the University of Pittsburgh who specializes in male reproduction. “We have to learn how to culture them.”

Li thinks there is still a “long way to go” before any GM babies are born. But he does hope to eventually try making human embryos using gene-edited sperm. One type of DNA error he hopes to correct is the kind that results in male infertility.

Scientists say working with eggs will be harder. Men produce millions of new sperm a day—clear proof of stem cells at work. But women’s bodies work differently. Women appear to be born with all the eggs they’ll ever have, and biologically, it seems unlikely there is such a thing as an egg stem cell in adults.

Yet other scientists are already developing a work-around. They predict it will eventually be possible to take a skin cell from a woman and use a technology called “reprogramming” to convert it into an artificial egg in the laboratory. And they could make sperm the same way.

That means IVF clinics in the future might take a skin punch from a customer and return either gene-edited eggs or sperm a few weeks later. “There is no reason to think it can’t be done,” says George Daley, a noted stem cell researcher at Harvard University’s medical school. From what he’s seen, he says, the prospect of installing custom DNA edits into lab-grown reproductive cells is “very real.”

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