Reengineering Life

The Next Gene-Edited Babies Could Be Free of Sickle Cell or Muscular Dystrophy

But the technology isn’t reliable enough yet, says a global committee

Reengineering Life is a series from OneZero about the astonishing ways genetic technology is changing humanity and the world around us.

The advent of CRISPR in recent years has introduced the prospect of using gene editing not only to treat disease but to prevent it altogether. By tweaking the genes of a human embryo, it would be possible to make the resulting baby — and generations to come — free of certain inherited diseases.

For now though, the technology is not yet mature enough to do so safely, according to an international commission of scientists and ethicists in a much-anticipated new report. They conclude that edited human embryos should not be used to create a pregnancy until scientists can establish that precise genetic edits can be made reliably without introducing unintended changes.

Even then, the authors say gene editing in embryos should only happen in very specific and limited circumstances. If a nation does allow “heritable human genome editing,” its initial uses should be limited to the prevention of serious diseases caused by a mutation in a single gene — such as cystic fibrosis, sickle cell anemia, muscular dystrophy, or Tay-Sachs disease. For these cases, the report suggests, embryo editing should be used to help couples with little to no chance of having a healthy, biologically related child. These situations, in which both parents harbor the same disease-causing mutation, are rare.

The authors say gene editing in embryos should only happen in very specific and limited circumstances.

The recommendations come from a panel organized by the U.S. National Academy of Medicine, U.S. National Academy of Science, and the U.K.’s academy of sciences, the Royal Society. The panel was formed in 2019 after Chinese researcher He Jiankui revealed that he used the gene-editing tool to create human embryos with a genetic mutation known to protect against HIV and establish pregnancies. The world’s first gene-edited babies were born as a result.

The revelation caused an uproar in the scientific community. Researchers widely condemned He’s experiment, calling it irresponsible and an attempt to “enhance” humans. Some called for a complete ban on making more gene-edited babies. Meanwhile, the National Academies organized a commission, and the World Health Organization convened a separate expert committee to suggest some ground rules. In December 2019, a year after the debacle, a Chinese court sentenced He to three years in prison, according to China’s Xinhua news agency.

CRISPR is already being tried in clinical trials in an attempt to treat genetic blood disorders, inherited blindness, and certain cancers. But in those trials, doctors are treating adult patients with gene editing. Editing embryos, by contrast, would not only result in changes made to the resulting baby’s DNA but to future offspring as well. That’s what makes gene-editing embryos so alluring, but also risky and ethically fraught. If the editing goes as it should, it could wipe out a heritable disease for generations to come. But if something went wrong, those genetic changes could be passed down indefinitely.

“In the case of heritable genome editing, those edits can be passed on to subsequent generations,” said commission co-chair Richard Lifton, MD, PhD, president of the Rockefeller University, during a public webcast on September 3. “This gives this technology an unusual reach that goes beyond the individual who has received the editing.”

No country has formally decided to allow heritable gene editing. In fact, making gene-edited babies is either directly or indirectly prohibited in dozens of countries, including in the United States. But the new 225-page report, as well as forthcoming recommendations from the WHO committee, could influence how governments decide to eventually move forward with heritable genome editing.

Other than serious single-gene diseases, the report acknowledged that countries may consider embryo editing for other conditions, like inherited deafness, that affect a person’s quality of life but aren’t life-threatening. In the September 3 webcast, panelist Michèle Ramsay, PhD, a professor of human genetics at the National Health Laboratory Service and University of the Witwatersrand in South Africa, pointed out that disease perception and treatment varies across countries and cultures.

“Severity might mean different things to different people,” she said. A genetic condition may be manageable in another country but not in another.

Before the technique can be tried to prevent any condition though, scientists will need to demonstrate that heritable genome editing is safe, the report authors say. A major hurdle is that CRISPR could cause accidental edits resulting in harmful mutations. Newer types of genome editing, including a technique called base editing, could be more precise than the original version of CRISPR. But these technologies are still early in their development, Lifton noted.

Wang Haoyi, PhD, a member of the Chinese Academy of Sciences who sat on the panel, said during the public webcast that for edited embryos to be used in pregnancies in the future, embryos will need to be tested to make sure the editing didn’t cause any undesired changes. Such changes are difficult to detect with current technology. Another issue that can arise with embryo editing is called mosaicism, where some cells are successfully edited and others aren’t. Some cells would still harbor the disease-causing mutation, meaning the resulting baby could end up with symptoms of the condition that the gene editing was meant to prevent. Wang said it will likely take several more years of research until scientists can show that editing embryos is safe and effective.

The report advises against editing embryos for so-called “polygenic diseases,” which are those caused by multiple genes, because the technology isn’t advanced enough to safely edit more than one gene at once.

For couples that do qualify for heritable genome editing, Wang said it will also be important to get informed consent. It’s unclear if the parents who consented to He’s experiment understood the procedure and the unproven nature of the technology.

Scientists should also be required to conduct long-term studies to track the health of any babies born from heritable gene editing, as well as their children, according to the report authors.

The authors of the new report call “extensive societal dialogue” before a country makes a decision on whether to permit heritable genome editing.

The report also calls for an “international mechanism” to field concerns from whistleblowers about heritable genome editing work that “deviates from established guidelines.” Several scientists around the world knew about He’s plans to make gene-edited babies, but they say they didn’t sound the alarm because they didn’t know how or where to report it.

A survey published in the Journal of Human Genetics in July suggests that the public supports the use of gene editing in embryos to prevent serious diseases. But the responses came overwhelmingly from well-educated white people from Western countries.

The authors of the new report call for “extensive societal dialogue” before a country makes a decision on whether to permit heritable genome editing. Other researchers, like CRISPR inventor Jennifer Doudna, PhD, have also called for widespread public engagement on the topic. But it’s unclear how that will play out. No country has yet to put the issue to a vote.

“One of the major concerns that our commission had was that this technology could be used by rogue scientists who just say, ‘I’m going to go ahead and do this,’” Lifton said. “So it’s important that there be strong regulatory authority that oversees this technology.”

Former staff writer at Medium, where I covered biotech, genetics, and Covid-19 for OneZero, Future Human, Elemental, and the Coronavirus Blog.

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