‘They Will Be Studied for the Rest of Their Lives.’ How China’s Gene-Edited Twins Could Be Forever Changed By Controversial CRISPR Work

For now, they’re known as Lulu and Nana, pseudonyms that are meant to give them some amount of anonymity amid the international uproar over their birth. As the first babies born after their genomes were edited (while they were embryos, by the genetics tool CRISPR) the twin girls, born in Shenzhen, China, are the subject of scientific and public scrutiny that will only escalate as they get older.

He Jiankui, a professor at the Southern University of Science and Technology, stunned the world when he claimed, both in a video posted by his lab and in an interview with a journalist, that he used CRISPR to disable a gene involved in helping HIV to enter healthy cells. By doing so, he gave the resulting edited embryos, including the twin girls, resistance to the virus. Doing so means He violated current guidelines prohibiting using CRISPR on human embryos for pregnancy. For now, He’s claims are only claims, since he has not published his work in a scientific journal for others to review and validate. While he did present his findings at a conference a few days after his YouTube announcement, researchers can only take the data at face value. He says he plans to publish the data, but now that the report has been released to the public, it’s difficult to predict which journals would accept the manuscript.

The Chinese researcher’s university denied knowledge of his experiment and said that He has been on leave since last February. Chinese authorities have now suspended He’s work, and Xu Nanping, vice minister of China’s Ministry of Science and Technology, said He’s study was “abominable in nature” and “violated Chinese laws and regulations,” according to the government’s Xinhua news.

The reason for the scientific censure boils down to the fact that He preempted a continuing debate over how and when CRISPR should be used in people. The technology, discovered in 2012, provides unprecedented precision and power to edit any genome, including the DNA of people, by snipping out portions of mutated genes and either allowing the genome to repair itself or by providing healthy versions of the gene. But because the approach is relatively new, scientists are still learning about exactly how precise their edits can be, and what some of the potential negative and long term consequences of altering human DNA could be.

Nearly all international genetics groups have guidelines prohibiting using CRISPR to edit human embryos and implanting them for pregnancy, as the Chinese researcher did. Experts fully support using CRISPR in cells that can’t be passed down from generation to generation, like skin cells or blood cells.

But what He did will forever change the twins’ DNA. Because he altered their genomes when they were embryos, those changes were picked up by every new cell that the embryos made as they continued to divide and develop, eventually forming the twins. So when the girls are ready to have children, their eggs may contain the CRISPR edits that He gave them, and they could pass on their altered genes to their children and all future generations of children in their lineage.

Having the gene itself is not necessarily a bad thing — the edit He made is meant to protect people from getting infected with HIV — but the problem is that scientists aren’t convinced yet that the HIV protection will be the only thing the CRISPR edit did to the twins’ genomes.

It’s not clear, for example, that CRISPR is as precise as researchers would like it to be. It makes mistakes. In some cases, CRISPR may make unintended changes in random parts of the genome, like an autocorrect feature that mistakenly corrects typos to produce an entirely different word. In other cases, it may not make the edits as consistently as needed, so some cells may be edited while others are not, and some cells may even be partially edited, leaving a patchwork result scientists call mosaicism.

According to experts who reviewed some of the data He presented at a conference days after his stunning announcement, they say there is evidence that both girls born with the CRISPR edits showed such signs of mosaicism when they were embryos, meaning they are now likely to have the same mishmash of CRISPR’d and unCRISPR’d cells in their bodies. That means that they may not even benefit from the resistance to HIV that He’s grand experiment was meant to provide.

There’s also evidence that compromising the HIV gene may have other consequences — for example, making people more susceptible to West Nile Virus and possibly the flu.

It’s because of these unanswered questions — and potential risks — that scientists have favored a moratorium on using CRISPR in human embryos meant for pregnancy, at least until they have a better grasp on how CRISPR works and what some of the long term effects of editing might be. While the U.S. National Academy of Sciences in 2017 allowed for the eventual possibility of human babies whose genomes have been edited by CRISPR, it provided strict criteria for how that should happen: under strict monitoring and only in cases where there is no other medical option.

Neither of those criteria were met in the controversial CRISPR study. The university and the hospital where the births took place denied knowledge of He’s work, and the scientific community was blindsided that he had been proceeding with transferring human embryos for pregnancy. The gene he altered also does not represent an unmet medical need — among the couples he worked with, only the fathers were HIV positive, meaning they were unlikely to pass on their infection to their children. What’s more, the fathers were on anti-HIV medications, which controlled their infection and make it even less likely they would infect their partners or their children.

In the twins’ case, what happens when they want to have children? Will they be allowed to have children naturally, and pass on their edited genes and whatever potential side effects might arise from their altered DNA? Or will regulatory or scientific authorities step in and attempt to control whether their genes continue into future generations by requiring the twins to have IVF and only implanting the embryos that do not show signs of the edited gene? Would those regulatory and scientific bodies even have the right to make such a request?

“The implications go beyond just these twins,” says Dr. Kiran Musunuru, professor of cardiovascular medicine and genetics at University of Pennsylvania Perelman School of Medicine. “If we talk about the sanctity of human life, and the inherent dignity of human life, not much has been gained here. These babies were treated as subjects in a grand medical experiment, and we have to believe that they will be studied for the rest of their lives; it’s sad actually.”

In his presentation and in his video, He justified his unorthodox actions by focusing on the personal. He said the father of the twins now feels motivated to find work and care for his family, and that altering the gene will protect future generations from HIV. But HIV experts say that judicious use and distribution of currently available drugs can effectively stop transmission of the virus, without taking such drastic steps of trying an unproven genetic procedure and exposing people to its unknown risks.

While their identities are still protected for now, it’s unlikely the twins will remain anonymous for long. In bypassing ethical guidelines prohibiting the experiment that he conducted, He not only violated basic tenets of responsible scientific inquiry, he also forever changed how the girls will be viewed by society, and ultimately the decisions they make as a result of their involuntary status as the world’s first CRISPR babies.