Reports out of China suggest first human gene-edited babies have been born

On Sunday, news reports indicated that the first gene-edited human babies had been born in China. As of right now, the information on what, exactly, has been accomplished is confusing. The scientist behind the announcement has made a variety of claims but has not submitted his data to the community in order for his claims to be verified. But even in its current state, the announcement has set off a firestorm of criticism within the scientific and ethics communities. Most scientists feel that the technology isn't ready for use in humans and that there are better ways to deal with the problem the work was addressing: HIV infection.

Editing genes

The most complete report we currently have comes from the Associated Press. Its reporters talked to the researcher behind the announcement, He Jiankui of Shenzhen, China, in advance of his public announcement. That public announcement came at the start of the Second International Summit on Human Genome Editing, taking place this week in Hong Kong. The summit is intended to help work out the "science, application, ethics, and governance of human genome editing," but He apparently chose to go ahead in advance of those being settled.

He is expected to present more details of his work on Wednesday, but it's clear that he used biotechnology called CRISPR to perform the gene editing. CRISPR is a system that evolved in bacteria to protect them from viruses by allowing them to recognize and cut viral DNA. By changing part of the CRISPR system, it's possible to direct it to cut an arbitrary DNA sequence. That can include sequences within the human genome.

Cells interpret the resulting break in their DNA as damage and attempt to repair it. In many cases, this repair is inexact and results in the deletion of a handful of individual base pairs within the targeted sequence. Depending on the precise details of this deletion, this can disable a targeted gene. (There are also means of replacing the targeted sequence, but those weren't needed for the work described here.)

This is where the first ethical issue of the work comes in. The frequency of successful editing in early work on human cells was only about five percent. And just this year, a study involving human cells showed that CRISPR editing can also make arbitrarily large deletions that affect neighboring genes or trigger complex rearrangements of the genome that can be difficult to detect if they aren't specifically looked for. All of this suggests that accurate editing of a single targeted gene isn't guaranteed, and we're still working out how to screen for it.

Is this really necessary?

That should be a large enough ethical problem to block the work. But there were more, including the reason for doing the editing in the first place. The researchers targeted a gene called CCR5, which encodes an immune system protein that the HIV virus latches onto in order to enter cells. People with mutations in CCR5 are notable because they have low rates of HIV infection and tend to have the disease progress extremely slowly (or not at all) if infected.

He Jiankui claims to have used volunteer couples in which the male partner has an HIV infection. He then targeted CCR5 for editing in an embryo generated through IVF.

There are a huge number of issues with this. To begin with, offspring of HIV-positive male parents are not considered to be at risk of picking up the infection during fertilization. And, once born, it's relatively easy for them to avoid infection, even when sharing a home with an infected individual. Thus, the editing being done here doesn't seem to address a significant risk. If infection does occur, we now have viable, long-term treatments, making this approach even less necessary.

Compounding matters are indications that the loss of CCR5 leaves individuals at heightened risk of infection from other viruses, including West Nile. So, rather than simply eliminating a risk, the work here seems to involve exchanging risks.

Or that would be the case if He had limited his work to instances in which the editing was successful. He claims that a pair of twins were born following the editing procedure (other couples tried but have not yet brought a baby to term). But the AP showed data obtained from He to a number of scientists, who indicated at least one of the twins born was a mosaic—editing took place after the embryo started cell divisions, making that individual a patchwork of edited and unedited cells.

"In that child, there really was almost nothing to be gained in terms of protection against HIV, and yet you're exposing that child to all the unknown safety risks," Kiran Musunuru of the University of Pennsylvania told the AP. Harvard's George Church suggested that the "main emphasis was on testing editing rather than avoiding this disease." That's consistent with He's video, linked above, in which he describes the need for this editing for treating incurable genetic diseases—something that doesn't describe this work.

An ethical train wreck

So how did this get past the ethics authorities at the institutions where He worked? It's not clear that it has. Tech Review indicated that the Shenzhen City Medical Ethics Expert Board was beginning an investigation, saying that the hospital that supposedly granted approval for the research did not do a full reporting of its approval process. And the university that employs He has suspended him without pay, saying his work "seriously violates ethical and academic standards and regulations."

Meanwhile, scientific and ethical communities have nearly universally come out against He's work. One hundred Chinese scientists quickly organized an open letter in which they say, "We can only use the word 'crazy' to describe the experiment conducted directly on human beings."

Meanwhile, two of the people who helped pioneer development of CRISPR technology have also come out against He's work. The Broad Institute's Feng Zhang is calling for a moratorium on gene editing in embryos, while UC Berkeley's Jennifer Doudna released a statement saying "this work reinforces the urgent need to confine the use of gene editing in human embryos to settings where a clear unmet medical need exists and where no other medical approach is a viable option."

More details will likely become available after He's talk on Wednesday in Hong Kong or as they leak out through various channels in the meantime. We will continue providing updates as appropriate.