LONDON – There has been widespread condemnation following the claim by a Chinese scientist that he has used CRISPR/Cas9 technology to create the world's first genetically edited babies.

The two girls, born a few weeks ago, are said to be healthy. Their genomes have been edited to express a modified version CCR5, a chemokine receptor that is the route by which the HIV virus infects white blood cells.

In a video on YouTube, He Jiankui, of the Southern University of Science and Technology of China, Shenzhen, acknowledges his work will be controversial, but said the "gene surgery" is "another in vitro fertilization enhancement" in the long line of improvements to the technique since the birth 40 years ago of Louise Brown, the first test tube baby.

After adding the CRISPR editing instructions at the single cell stage immediately after fertilization, He said the gene edit was checked by whole genome sequencing. Following implantation, the pregnancy was normal. Deep sequencing of the genomes of the girls, given the pseudonyms of Lulu and Nana, showed that one of the twins has only one copy of the modified CCR5 gene.

Outrage has been expressed at many levels – that the procedure is unethical being the chief complaint, but also that the research has not been published in a peer review journal, that more work is necessary to understand the mechanisms of CRISPR editing in human embryos before any are implanted, and that CCR5 knockout is a bad exemplar, given the low risk of transmission from the girls' HIV-positive father.

He's timing also is being seen as a huge affront to scientists and ethicists assembling in Hong Kong this week at the second International Summit on Human Gene Editing. The summit was established in December 2015 to ensure proper international oversight of human germline editing. (See BioWorld Today, Dec. 8, 2015.)

In China, 122 top-level scientists published a statement on the social media platform Weibo expressing opposition and condemnation of He's announcement. Direct human experimentation with CRISPR/Cas9 "can only be described as crazy," they said. He's work "is a huge blow to the global reputation of Chinese science, especially in the field of biomedical research," according to the statement.

The signatories called for regulators and the Southern University to conduct a comprehensive investigation.

He will be facing his scientific peers on Wednesday, when he is due to speak at the summit in Hong Kong, sharing a platform with Kathy Niakan, group leader at the Crick Institute in London, who was the first researcher in the U.K. to be given a license to use CRISPR/Cas9 for research in human embryos.

If true, the report of the first gene edited babies is very concerning, Niakan said. "This would be a highly irresponsible, unethical and dangerous use of gene editing technology."

There are significant doubts about safety, including the potential for harmful side effects. Much more research is needed to understand the fundamental biology, before germline gene editing is applied clinically.

He's report "highlights the urgent need for public consultation and international regulation," said Niakan. In addition to the very real risks posed to the individuals involved, this threatens to undermine support for ethical, well-regulated basic research, such as her own.

Yalda Jamshidi, senior lecturer in human genetics at the University of London, questioned the choice of CCR5. "We do not need gene editing to ensure [HIV] is not passed onto offspring. Most people would argue that experimentation on humans for an avoidable condition, just to improve our knowledge, is morally and ethically unacceptable," Jamshidi said.

Peter Braude, professor of obstetrics and gynecology at King's College London, agreed, saying, "If gene editing is to be used after appropriate safety testing, then surely it would be prudent to use it first for serious genetic diseases for which no safe alternative exists."

Putting future research at risk

Following on from the first summit on gene editing in Washington in 2015, the Nuffield Council on bioethics in the U.K. spent 20 months examining all aspects of genome editing. Its conclusion, published in July, was that germline gene editing to prevent transmission of serious inherited diseases could be morally permissible but that a public debate is needed because – contrary to He's view that it is just another technical refinement of IVF – CRISPR/Cas9 would take reproduction to a different level. (See BioWorld, July 18, 2018.)

"We need legislation," said Joyce Harper, professor of genetics and human embryology at University College London, who sat on the Nuffield working group. "But before this procedure comes anywhere near clinical practice, we need years of work to show that meddling with the genome of the embryo is not going to cause harm to the future person."

Another scientist due to speak at the summit in Hong Kong, Sarah Chan, fellow at the institute for population health sciences at Edinburgh University, was highly critical of the way news of Lulu and Nana's birth was announced, without peer review publication.

"The covert application of human genome editing, followed by this cavalier announcement of the work as a fait accompli, puts at risk the entire future of this crucial technology," she said.

For Julian Savulescu, director of Oxford University's center for practical ethics, editing healthy embryos with no known diseases is "monstrous." There are many effective ways of preventing HIV infection, while gene editing is not only "experimental" and "associated with off-target mutations" but also "capable of causing genetic problems early and later in life, including cancer," he said.

Defending his choice of editing CCR5, He said HIV infection is a big problem in China, with people who are HIV-positive subject to social stigma and discrimination. The parents of Lulu and Nana did not want them to face that. "Their parents didn't want a designer baby, just one[s] without risk of getting a serious disease," He said in the YouTube video.

After completing a PhD at Rice University, Houston in 2010, He went on to do postdoctoral research at Stanford University in California before returning to China. In addition to clinical research, He is president and CEO of Direct Genomics, a company he set up to develop and market a low-cost sequencer specifically designed for clinical applications.

He claims he has full ethical approval for the research, and the patient consent forms and other relevant documents are posted on his lab's website. But concerns about informed consent will be heightened by the fact that couples taking part were offered IVF treatment and prenatal care up to the value of $40,300.

Since the report of Lulu and Nana's birth, the Southern University of Science and Technology has put out a statement saying the academic committee of its department of biology believes the research seriously violates academic ethics and academic norms.

The university said He has been on leave since Feb. 1 and is not due back until January 2021. It is now setting up an independent panel to investigate the case.

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