BEIJING – Chinese scientist He Jiankui has been sentenced to three years in prison and fined ¥3 million (US$429,421) for illegally carrying out the human embryo gene editing that led to the birth of twin girls and another baby with heritable changes to their genomes.  

He was convicted at Nanshan District People’s Court of Shenzhen on Monday along with two other researchers, Zhang Yinli and Qin Jinzhou.

According to the Xinhua official Chinese news agency, the three, who are not qualified to work as doctors, “deliberately violated the relevant national regulations on scientific research and medical management” and knowingly acted against scientific and medical ethical principles, in carrying out gene editing as part of in vitro fertilization procedures.

The court found He, who was an associate professor at the Southern University of Science and Technology in Shenzhen, had fabricated the ethical review certificate. He and his team then recruited eight couples in which the male partners were positive for HIV, intending to use CRISPR/Cas9 to edit the CCR5 chemokine receptor gene, with the aim of making the babies immune to HIV infections.

The verdict held the researchers acted “in the pursuit of personal gain” and have “seriously disrupted medical order.”

The case was heard in private to protect the privacy of the families concerned. The three men are said to have pleaded guilty. Zhang was sentenced to two years in prison and fined ¥1 million; Qin received an 18-month sentence, suspended for two years, and was fined ¥500,000.

In November 2018, He announced to the second International Summit on Human Gene Editing in Hong Kong that twin girls, known as Lulu and Nana, with edited CCR5 genes had been born in China. He claimed to have used CRISPR to disable the CCR5 gene, which makes a protein that allows HIV to enter blood cells. The experiment, a first in humans, sent shock waves through the medical community domestically and abroad.

He also revealed that another pregnancy of a gene-edited embryo was in its early stages. The court verdict is the first time that the birth of this third baby has been confirmed.

Before Chinese state media broke the news of He’s trial, the scientist had not made any public appearances since the summit and was believed to be under investigation or possibly house arrest.

There also had been no details of the progress of any investigations being conducted by Chinese authorities

He’s research was brought back into the spotlight earlier this month, when MIT Technology Review released manuscripts from the experiment, which experts said seemed flawed in many ways.  The main criticism was that the medical benefits of the procedure were “dubious at best.”

Gene editing experts now warn the babies born as a result of He’s experiments and their offspring are at risk for serious medical issues such as cancer.

The safety of CRISPR is widely questioned, as the gene editing tool may induce mutations elsewhere in the genome beyond the target gene, creating off-target edits that could lead to cancers.

Kiran Musunuru, a gene editing specialist at the University of Pennsylvania, said it would not be surprising if some or all of the cells ended up with an off-target edit.

“If the mutation occurs in a tumor suppressor gene or oncogene, it could potentially drive cells towards cancer. This would be true even if only some of the cells in the body had the mutation. Other diseases like heart disease could also result from off-target edits,” Musunuru told BioWorld Asia.

In addition, the edit may not be present in all the babies’ cells. He used CRISPR to edit the embryos at the single cell stage, immediately after fertilization. However, it can take time for CRISPR to make edits and the embryos could have started dividing before the edit was complete, leading to mosaicism.

“So, some cells in the embryo can get the desired edits, while others might not,” Musunuru explained. “Since the embryo becomes the live-born child, there might be some cells […..]  that don't have the desired edits and might allow HIV to get a foothold in the body.”

Musunuru warned of potentially serious health problems, and said it will take years before CRISPR is honed into a truly precise gene editing tool.

Life sciences experts also have condemned He’s work on the grounds it was not necessary because there is already technology to help HIV-positive men have healthy babies.

More disturbingly, no further details or data have been made public in more than a year.

“We could not get the information,” Hui Yang, a gene editing scientist from the Institute of Neuroscience of the Chinese Academy of Sciences, told BioWorld Asia.

In a paper he published with another Chinese researcher, Haoyi Wang, this year, Yang pointed to “unpredictable consequences” for the twins. In particular, mosaicism remains a major concern that cannot be addressed by preimplantation genetic diagnosis, since scientists cannot sequence all cells in an embryo.

“This means that even if the tested cells are correctly edited, there is still a non-negligible risk that other cells in the embryo remain unedited or carry unwanted mutations that may have unpredictable consequences,” he wrote.

 On the basis of the data He made available in his presentation last November, experts have said the embryos generated are likely to have mosaicism.

Yang’s paper also raised the likelihood that on-target mutagenesis effects could result from double-strand breaks generated by CRISPR.

“On-target effects include large chromosome deletions, chromosome truncations, and homozygosis of the genome by inter-homology repair. Currently, no single method could detect all these types of off-target mutations,” Yang said.

Yang stressed that the lack of details of sample collection and data analysis of He’s experiment has made it impossible to draw a robust conclusion. Yang called for a thorough examination of all the original data.

Robin Lovell Badge, of the Francis Crick Institute in London, who moderated the Hong Kong summit session at which He presented his data, agreed. “There are still many details of the case that have yet to be released, such as confirmation of the edits made to the CCR5 gene, whether or not there were also off-target events, if there is indeed mosaicism where not all cells have the same edit, or any at all, as suggested in the data presented by He,” Lovell Badge said.

Mending the ethics gap

He’s experiment also raised questions about scientific ethics and regulation in China.

Musunuru said the case highlighted the lack of oversight of the scientists’ activity, which might point to regulatory deficiencies.

“The scientists involved had no medical qualifications whatsoever, or ethics training, and were entirely unqualified to run this medical experiment. Somehow, they were able to get an ethics committee to rubber-stamp the experiment, something that wouldn't happen in a country like the U.S.,” he said.

According to the Xinhua report of the trial, the health department in Guangdong Province has told the IVF clinic and hospital involved to improve oversight and supervision. All staff involved in He’s work have been barred from working on IVF procedures for life, while academic scientists who were part of He’s team have been barred from carrying out human genetics research.

Often doubted for its ethical stance, China has been rolling out various regulations this year to improve the reputation of its scientific research.

In March, the health authorities proposed to increase scrutiny over the use of new high-risk biomedical technologies, such as gene editing, stem cell technology, cloning and assisted reproduction, in a move that aimed to "ensure medical safety and uphold human dignity and wellbeing."

The rules stress the role of ethical reviews and make government approval a requirement for clinical research and translational work involving those technologies.

Then in July, China approved a plan to set up a national committee for ethics in science and technology. The committee is tasked with promoting a coordinated governance system to oversee scientific integrity and professional ethics.

Three months later, the country drafted regulations on handling scientific misconduct. Researchers will face a penalty for unethical research that endangers people’s health.

Yang told BioWorld Asia in a previous interview that regulations surrounding gene editing are still taking shape in China, and work is being done.

“[The authorities] invited me to give them a lecture on gene editing and discuss how to regulate the technology, like what kind of quality control should be done before going to clinical application,” he said.

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