Image: Ben Edwards/Getty Images

US Scientists Just Confirmed They’ve Genetically Modified Human Embryos

The researchers want to move onto clinical trials in humans and “monitor the birth of children."

Aug 2 2017, 5:06pm

Image: Ben Edwards/Getty Images

On Wednesday, scientists confirmed widely circulating reports that they'd genetically modified human embryos in a US lab—and said that, after more research and ethical debate, they hope to begin clinical trials. That would mean "transplanting some of these embryos with the goal of establishing pregnancy and monitoring the birth of children," lead author Shoukhrat Mitalipov of Oregon Health and Science University told reporters.

A clinical trial like this wouldn't be possible right now in the US, where there are rules in place restricting embryo editing. But that doesn't mean it couldn't be done elsewhere. If the US won't allow trials to proceed, "we would be supportive of moving this technology to different countries," said Mitalipov.

Although Mitalipov was careful to talk about this work in terms of genetic "correction," not "enhancement," we are on the road towards a time where it'll be possible to make genetically engineered humans, giving us the ability to stamp out specific inheritable diseases and wield incredible power over our genome. Ethicists are concerned we are racing towards a future we aren't prepared for, with risks we don't understand.

In the experiment, first reported last week in MIT Technology Review and described in detail on Wednesday in the journal Nature, Mitalipov and colleagues took sperm from a man who carried a mutation of the MYBPC3 gene. Inheriting a single copy can cause hypertrophic cardiomyopathy, a heart disease that can cause sudden cardiac arrest in young people.

They fertilized eggs from female donors with the sperm, and then used CRISPR, the powerful gene editing tool, to "cut" the mutant sequence. Breaks were fixed using the non-mutated copy from the egg donor as a "template," the researchers explained. About two-thirds of the embryos ended up with two mutation-free copies of the targeted gene.

Representative images showing normal morphology of CRISPR–Cas9-injected pronuclear stage zygotes, eight-cell embryos and blastocysts. Image: Mitalipov et al/Nature

Maybe even more impressively, researchers saw no evidence of "off-target effects" (in other words, CRISPR didn't edit the genes it was supposed to leave alone). They also managed to eliminate mosaicism (when embryos are made up a mix of two or more genetically different kinds of cells). Both problems have been seen with CRISPR experiments in the past.

The human embryos, though viable, were never intended to be implanted into a woman to start a pregnancy, these researchers stressed. After five days, they were destroyed.

Although three Chinese teams have reported using CRISPR to genetically modify human embryos already, one of those experiments was done with abnormal embryos, while the other used embryos derived from immature eggs, said co-author Paula Amato. "We think this is the first, largest study from which you could draw reasonable conclusions," she said.

If this method is proven safe after more research, not only does it hold the potential to fix damaging genetic mutations in a child born of the edited embryo—because this type of genetic engineering is inheritable, it should also protect that child's kids, grandkids, and so on. This method "can potentially be used to prevent transmission of genetic disease to future generations," said Amato, who is a reproductive endocrinologist.

Read More: We Risk Programming Inequality into Our DNA

And it could theoretically be applied to other mutations affecting only one allele (or variant form of the gene). According to Amato, that would include the mutations responsible for cystic fibrosis, and BRCA, known as the breast cancer gene. Finding a method to fix mutations impacting both the maternal and paternal allele would require a different strategy.

Even so, there's already a way to avoid transmitting dangerous mutations to one's kids, and right now, it's far less risky than tinkering with the human genome. Preimplantation genetic diagnosis (PGD) screens embryos for mutations before they're implanted into a woman, which is usually done through in vitro fertilization.

Amato said that genetic editing could be used when PGD isn't an option, or together with it, to increase "the number of normal embryos available for transfer."

I phoned Françoise Baylis, a bioethicist at Dalhousie University who has been deeply involved in the CRISPR debate. While she hadn't read Mitalipov's latest paper, she expressed concerns. "We need to stop reframing this as a positive potential future therapeutic intervention," Baylis told me. "We don't have humans we're offering a treatment to." These are embryos, she noted, not people. "We need to have more than excitement to justify the kinds of moves that people are wanting to make."

Baylis was a member of the 12-person committee behind the first International Summit on Human Gene Editing in 2015, where many of these issues were debated by scientists and other stakeholders from around the world. That meeting ended with a statement supporting basic, pre-clinical research with human embryos, but also said it would be "irresponsible" to go ahead with clinical use of germline editing until safety and efficacy issues are resolved—and until there's broad societal consensus around it.

Still, perspectives are evolving. In 2017, the US National Academy of Sciences (NAS) said editing the DNA of a human embryo could be ethically allowable to prevent disease. Mitalipov and co-authors cited these NAS recommendations, as well as approval from their university ethics board, as giving the go-ahead to their research.

Mitalipov was careful to avoid the term "designer baby," and whether this technique could be used to select for traits like intelligence or hair colour in the future. "The title of our paper says 'correction,'" he noted. "We don't like the word 'editing' because really we didn't edit or modify anything. All we did is unmodify an already mutant gene." Because of this, he said, it is "unlikely" this method could be used to select for specific genetic traits.

"We the people have a right to say what should happen to the human germline"

Mitalipov was also a pioneer of mitochondrial replacement therapy—so-called "three parent babies." Although that technique is effectively banned in the US, the UK has greenlighted it. In a similar way, if the US bars clinical trials of this new gene editing method, he would consider moving the technology elsewhere. "These mutations are pretty common," he said. "If other countries decided they want to proceed, we would be very supportive in moving forward, just like we did with mitochondrial replacement therapy."

But what if people take up this technology in places where there aren't strict regulations, like in the US and the UK? "There is of course [that] concern," Mitalipov said, adding that unregulated clinics likely wouldn't have the expertise to do this today.

Baylis stressed that it isn't up to "individual governments" to decide what happens with CRISPR and with the human genome. "We the people have a right to say what should happen to the human germline," she stressed. As governments and scientists debate, the genie may slip from the bottle. The US can bar clinical trials, but that doesn't mean they won't happen elsewhere—nor will it stop the technology from being taken up in other places including, eventually, for-profit fertility clinics attracting medical tourists from abroad.

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