Will gene-edited babies be healthy? Probably, but nobody knows

History was made last November when the MIT Technology Review published an astonishing article revealing that a Chinese physicist had secretly edited the genes of two embryos and implanted them into a woman’s uterus. That woman gave birth to the first gene-edited babies that month: two baby girls, Lulu and Nana.

In the videos published by the physicist Jiankui He’s lab on the same day as the MIT Technology Review story surfaced, He explains that the father of the twins is HIV-positive and could potentially have passed the virus on to his children. To make the embryos resistant to the HIV infection, He decided to use gene editing, despite the fact that other effective solutions already existed.

According to He, the girls are healthy so far.

Gene editing in embryos is allowed in many countries such as the U.K. and China, but the embryo must be discarded after 14 days — and absolutely not implanted into a human uterus. In China, researchers violating these guidelines could lose their research licenses, while in countries like Australia the punishment could be a jail sentence.

The shocking news came just three days before scientists from all over the world were due, ironically, to gather in Hong Kong for the Second Summit on Human Gene Editing.

“At first I didn’t believe it. I assumed that the news was fake and that the experiment hadn’t been done,” says Nicole Paulk, an assistant professor of biochemistry and biophysics at the University of California, San Francisco. “Then I saw the presentation and realized that it had been done.”

Lulu and Nana’s origins raised a thunderstorm of ethical dilemmas, ranging from whether the parents were in a position to give consent to the procedure to whether HIV resistance should be edited in an embryo’s DNA considering that there are reliable ways of preventing the infection from passing from father to child, says Fyodor Urnov, the deputy director at the Altius Institute of Biomedical Sciences in Seattle, Wash.

But it is imperative to understand the deeper biological concerns surrounding the situation: The CRISPR-Cas9 technology used to edit the embryos is not precise enough yet for work in humans, experts say. The mutations achieved by He do not match known therapeutic mutations, or mutations that are known to have health benefits, says Sean Ryder, a professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School.

The big idea

He, who has been working without permission and supervision from his university — the Southern University of Science and Technology in Shenzen — has yet to release a paper detailing his entire methodology, though parts of it are now known,  AP reported. 

The sequence He edited was the CCR5 gene, which controls whether HIV can enter cells. Previous research has demonstrated that mutating this gene in certain ways causes HIV resistance. The best-known mutation is called delta 32, which means that 32 bases (building blocks of DNA) were removed from the gene.

But this is not the mutation that He achieved.

The devil is in the details

CRISPR-Cas9, often compared to genetic scissors, is a tool used by scientists to cut out specific DNA segments, like parts of the CCR5 gene. But while the cuts are much more precise than any technique that’s existed before, the technology can still make unwanted cuts in DNA.

“I think most of the labs, if not all of the labs, would agree that the technology is too error-prone,” Ryder says. “These are not precise mutations that change the DNA to a predicted DNA.”  

After a cut in the DNA is made and an unwanted gene is removed, the cut must be repaired. Animal studies have shown that in some cases these repairs can be controlled and directed to produce a specific result. In other instances, however, the gene is repaired with a random mutation by the cell, Ryder says.

In Lulu and Nana’s case, the cell was left to repair itself after the cut in the CRR5 gene, according to He’s presentation. This produced two different results in the girls — each one of the genes from each parent were changed in a different way. None of the mutations were delta 32.

This is where Ryder became interested. After looking carefully at the mutations, he noticed none were the ones shown to protect against HIV. Moreover, only one copy of the gene was mutated in Lulu, instead of two.

It is possible that the mutations may be effective in preventing HIV; still, the difference in mutations introduces a level of uncertainty.

“Imagine that we have a car and we stopped it by puncturing a left front tire,” Urnov explains. “Somebody else punctured the right front tire and claims that it will stop the car. Do we believe them? Of course.”

But in the world of gene editing, different edits don’t necessarily produce the same results. Nana will likely be HIV resistant as the CCR5 gene will still be disrupted by the mutations. But only one of Lulu’s CCR5 genes was changed, which means the other can still function normally, so she will most likely remain susceptible to the virus, Paulk says.

So are Lulu and Nana healthy, or in danger? Nobody knows for sure.

It could be that the mutations act like delta 32 and protect Nana. Or the gene edits could simply not work, and the girls could be just as susceptible to HIV as beforehand, Ryder says.

An admittedly rare but scary possibility for both girls would be the so-called “gain of function” mutation, in which a gene starts producing abnormal proteins. But this isn’t a common occurrence and the mutations will probably be harmless, Ryder says.

Many scientists agree that the girls will probably be healthy.

But just hoping that the mutations are benign is not a good enough strategy for Urnov, he says. He argues that there are already gene-editing studies occuring in the adult HIV-positive community, such as an experiment in which researchers attempted to extract a patient’s white blood cells, alter them and infuse them back into the patients. Prior to the study, patients had hours-long discussions with their doctor, weighing the benefits and risks of the genetic treatment. In the end, the choice was their own — a choice that Lulu and Nana were not given.