Designer Babies Are Here. What’s the Next Edit?

Scientists have identified a number of genes that could be targets for upgrading the human genome. Illustration by Aart-Jan Venema

A Chinese scientist engineered kids to resist HIV. Here are other changes that could be on the feature list for Humanity 2.0.

He Jiankui stunned the world this week when a report revealed he had edited genes in human embryos aiming to make people resistant to HIV infection. So far, two children, twin girls named Lulu and Nana, have been born with altered genomes.

The Chinese scientist’s work crossed a line that many have feared and some have dreamed of: the creation of designer babies engineered for certain enhancements.

Editing genes in embryos is hugely controversial because the changes can be passed along to future generations. You can imagine, for instance, using gene editing to wipe out a genetic disease in an entire family tree. This is what makes altering DNA in sperm, eggs, or embryos — known as germline editing — so powerful. But if something were to go wrong, like cutting an unintended place in the genome, the resulting child could have health problems or introduce new, potentially harmful mutations into the gene pool, where they could be difficult to eradicate. That risk has made the scientific community wary of using gene editing in this way.

The floodgates are open, and further efforts to edit DNA in germline cells are already being discussed.

But He didn’t edit embryos afflicted with a disease-causing gene. Instead, he edited healthy embryos with the aim of imparting a genetic advantage: resistance to HIV. His experiment involved using the gene-editing technology known as CRISPR-Cas9 to disable a gene called CCR5. A subset of Europeans have a mutation in this gene that makes them resistant to HIV.

Crossing the line

The scientific community has widely condemned He’s work. After all, safe and effective ways to prevent and treat HIV already exist. Moreover, there’s evidence that knocking out CCR5 could increase susceptibility to West Nile virus and aneurysms in the aorta.

But the floodgates are open, and further efforts to edit DNA in germline cells are already being discussed. Beyond preventing diseases, enhancing the human genome suddenly is on the table.

Speaking at the Second International Genome Editing Summit in Hong Kong on Nov. 28, Harvard Medical School Dean George Daley made the case for ethical uses of germline editing. Daley said He’s recklessness should not derail other scientists.

“Just because the first steps were missteps doesn’t mean that we shouldn’t step back, restart, and think about a plausible and responsible path for clinical translation,” Daley said.

Photo of He Jiankui in front of a microphone
He Jiankui, who claims to have created designer babies, presenting his work at the Human Genome Editing Conference in Hong Kong, Wednesday, Nov. 28, 2018. (AP Photo/Kin Cheung)

Potential upgrades

Geneticists studying human DNA tend to focus on harmful mutations, but some appear to have beneficial effects.

“There are plenty of people walking around with apparent normal function who are lacking CCR5,” says David Nelson, president of the American Society of Human Genetics and professor of molecular and human genetics at Baylor College of Medicine.

It’s possible that recreating other helpful genetic mutations could effectively upgrade the human genome, yielding healthier individuals and eventually, whole populations.

One is PCSK9. Scientists have been interested in this gene as a drug target because some people with mutations have low cholesterol. The idea is, if a drug were to interfere with PCSK9 and reduce the amount of protein it makes, it would cut cholesterol. Mimicking the naturally-occurring PCSK9 mutation before birth using CRISPR hypothetically could protect individuals from high cholesterol throughout their lives, reducing the risk of heart disease.

Another beneficial genetic variant that might be copied with genome editing occurs in the APP gene. This gene carries instructions to make amyloid, the protein that builds up in the brains of people with Alzheimer’s disease. A mutation found in Icelandic and Scandinavian populations protects against Alzheimer’s. This variant, A673T, is rare: Only about 0.5 percent of Icelanders and 0.2 to 0.5 percent of Finns, Swedes, and Norwegians have it. Editing it into the germline could potentially cut the risk of Alzheimer’s among a broader population.

People with a mutation in the FUT2 gene are much less likely to get norovirus, a highly contagious virus that’s notorious for causing bouts of vomiting and diarrhea on holiday cruises. About 30 percent of people of European ancestry and 20 percent of those of African ancestry carry this variant. The mutation doesn’t appear to be completely protective, and norovirus isn’t life-threatening. Would humanity be better off with fewer cases of the cruise-ship virus?

Features or bugs?

Other mutations are known to bestow health benefits but also bring their own problems. For example, mutations in the NPC1 gene confer resistance to Ebola but cause a subtype of Niemann-Pick disease, a serious metabolic disorder. And mutations in the G6PD gene seem to protect against malaria but also cause anemia. So, while these genetic variants might have nominal benefits, the side effects — in some cases, lifelong diseases — almost certainly outweigh the potential advantages.

“Even if you think you’re making a very simple mutation, there could be effects that we didn’t intend,” Nelson says.

He Jiankui is the first to set foot in this messy landscape. It’s not yet clear that his experiment worked well — or at all. The protective mutation in the CCR5gene involves a change in 32 base pairs of DNA, and whether He created that exact mutation is unknown. It’s not certain that either of the engineered twins is actually HIV-resistant, and one reportedly carries both altered and unaltered cells, a condition known as mosaicism.

A larger question is whether germline editing of certain genes can improve on natural selection. Time spans measured in thousands of years may be necessary to fully evaluate the tradeoffs.

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