The world's first gene-edited human babies have reportedly been born in China. Professor Jiankui He claims that by removing a specific gene from the embryos using the CRISPR-Cas9 technique, the twin girls would have a natural immunity to HIV. But it seems the girls have been born in the eye of an ethical storm, as scientists around the world question the safety, effectiveness and morality of the procedure.

In a video posted to YouTube, the He Lab says the process began with a fairly normal IVF procedure. After the father's sperm fertilized the mother's egg, an embryologist injected the CRISPR-Cas9 proteins into the cell, which performed a "gene surgery" that deleted a gene known as CCR5. This gene encodes for a protein that HIV uses to enter a cell, so by removing it He says the girls should develop a natural immunity to the virus.

But gene-editing is not a clean cut-and-paste – one of the major concerns with the technology is that it may cause unintended mutations elsewhere in the genome. To keep an eye out for that, He and his team say they conducted whole genome and targeted deep sequencing techniques before the embryos were implanted, during the pregnancy and again after birth. The team reports that only the desired genes were altered and there were no off-target mutations. The twin girls, nicknamed Lulu and Nana to protect their privacy, are apparently "as healthy as any other babies" and are now at home with their parents.

After decades of research, the birth of the first gene-edited human babies is a massive milestone – but the achievement may be premature, from a technological and ethical standpoint.

Ethics of editing

If the announcement of CRISPR babies seems like it came out of the blue, that's because it did. The experiment was more or less conducted in secret, and has only now been made public a few weeks after the birth of the genetically-edited children.

That secrecy has raised many a suspicion, with scientists first of all wondering if the results are as groundbreaking as they seem. And if they are, this may be an uneasy first step down a slippery slope towards "designer babies," bypassing the many years of considered debate about how to proceed.

"Important to note that at this stage the reports have not been independently verified so it's hard to say if the claims are real," notes Darren Saunders of the University of New South Wales in Australia. "Scientists everywhere today will be thinking 'show me the evidence' and some of the claims from the scientists involved suggest that the gene editing was only partially successful. If confirmed, this represents a huge technological and ethical leap. It's possible we just saw a huge leap towards editing the human book of life – some might even suggest this is a step towards eugenics."

Scientists also took issue with the chosen disease target. HIV is not a high priority in this area, and isn't worth the other risks introduced by the experimental procedure. On top of that, other teams have already found safer ways to use CRISPR to effectively "cure" the disease in adult cells.

"If true, the recent reports of the first genetically edited human babies are completely irresponsible and for no direct or immediate benefit to the babies edited or human kind," says Greg Neely of the University of Sydney. "In fact, we don't know the full impact of targeting the CCR5 gene in various human genetic backgrounds, and there is no urgent need to discover this at the potential expense of a newborn innocent child. Moreover, we have no idea what side effects the editing process may cause."

Last year, a study found that CRISPR gene-editing may introduce hundreds of unintended genetic mutations, wreaking havoc across the entire genome in a myriad of ways. This study was later retracted by the journal after a review found the data inconclusive, but the concerns remain.

"By disrupting the CCR5 gene in a healthy human, they will likely become more sensitive to a variety of much more common infections, and something relatively benign like the flu may now be lethal," says Neely.

The blowback against the study has been swift and absolute. The Shenzhen Medical Ethics Expert Committee has launched an investigation into the hospital where the study took place. He's former employer, the Southern University of Science and Technology, has released a statement condemning the experiments and distancing the institution from them. And Feng Zhang, co-creator of CRISPR, has called for a moratorium on gene-edited babies until ethical issues can be sorted out.

In Defense

Reckless as it may be, the He Lab could skirt through a loophole. The procedure they performed reproduces a natural genetic variation, present in over 100 million people, that gives them an increased resistance to HIV. The fact that they were mimicking a natural mutation, rather than "creating" a new one, could be an important distinction with some precedent. A few years ago, Swedish researchers successfully argued that their CRISPR-edited cabbage fell outside the definition of a GMO, since they had simply switched off a gene that is sometimes naturally off anyway.

The FDA invoked the same reasoning in 2015, when it declared genetically-modified salmon fit for human consumption. The altered fish didn't need to be labeled as GMOs because they were genetically identical to salmon that naturally had a certain beneficial mutation – the researchers had simply removed the element of chance.

Of course, there's a huge difference here – we're talking about human lives here, not fish or cabbage. The risks are obviously far greater. And besides, the fact that these openly-modified organisms could be legally defined as not GMOs highlights how far behind the regulations are. Experimenting on living humans before these issues are ironed out is hugely unethical.

But in his defense, He compares the team's research to the birth of Louise Brown in 1978, the world's first baby conceived through IVF. Leading up to that breakthrough moment, the technology was widely opposed as ethically questionable. Nowadays it's normalized, with up to six percent of children being conceived using the method. This might not have happened if the researchers hadn't pushed against the scientific consensus.

The future of editing embryos

Genetically editing embryos has huge potential to prevent disease and chronic illnesses, giving people a better quality of life and easing the burden on healthcare systems. The treatment has proven effective before, with recent research completely removing a genetic disease from a human embryo and, as a result, essentially eradicating that disease from the family lineage. But that pre-clinical test was designed to make sure the technique was safe and effective, and the embryo wasn't allowed to be carried to term until the ethics of the matter were resolved.

By conducting the experiment in secret, the He Lab has leapfrogged the issue, apparently for the fame of being the first scientists to genetically edit babies. After all, physiologist Robert Edwards was awarded the Nobel Prize in 2010 for his pioneering efforts in IVF.

"In the end the motivation here seems to be one of personal glory for the scientists involved, and there may be a horrific cost to pay for this hubris," says Neely.

Those effects may be far longer lasting than you might think. The edit doesn't just affect Lulu and Nana but their own future children, continuing indefinitely down the line.

"Historically when we as a society have dealt with disease, we have treated an individual patient or a group of people," says Nobel laureate David Baltimore. "We've developed drugs that can stop the course of disease and return people to health. But we've never done anything that will change the genes of the human race, and we've never done anything that will have effects that will go on through the generations."

Baltimore is the chair of the Second International Summit on Human Genome Editing, which kicks off this week in Hong Kong. The ethics of editing the human genome was one of the main points on the agenda for the meeting, but these discussions are no longer purely hypothetical.

The study has yet to be officially published anywhere, and there's a chance now that no journal will be willing to touch it. Either way, it's both a fascinating and terrifying story.

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