He Jiankui


He Jiankui is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology in Shenzhen, China. Earning his Ph.D. from Rice University in Texas on protein evolution, including that of CRISPR, He learned gene-editing technique as a postdoctoral researcher at Stanford University in California.
He Jiankui became widely known in November 2018 after he had claimed that he had created the first human genetically-edited babies, twin girls known by their pseudonyms, Lulu and Nana. The announcement in November 2018 of Lulu and Nana, who were born by mid-October 2018, was initially praised in the press as a major scientific advancement. But following scrutiny on how the experiment was executed, He received widespread condemnation, and on 29 November 2018, Chinese authorities suspended all He's research activities. On January 21, 2019, He was fired by SUSTech, according to the university's announcement.
In May 2019, lawyers in China reported, in light of the purported creation by He Jiankui of the first gene-edited humans, the drafting of regulations that anyone manipulating the human genome by gene-editing techniques, like CRISPR/Cas9, would be held responsible for any related adverse consequences. In December 2019, MIT Technology Review reported an overview of the controversy to date, including excerpts of the unpublished research manuscript. On 30 December 2019, the Shenzhen Nanshan District People's Court sentenced He to three years imprisonment and RMB 3 million fine.
He was listed in TIME magazine's 100 most influential people of 2019.

Education and career

Born in Xinhua County, Loudi, Hunan in 1984, He Jiankui was educated at the University of Science and Technology of China as an undergraduate student from 2002 to 2006. He entered Rice University in 2007 and received his Ph.D. degree from the Department of Physics and Astronomy under the supervision of Michael W. Deem in 2010. After his Ph.D., Deem arranged for He to work on CRISPR/Cas9 gene-editing technique as a postdoc fellow with Stephen Quake at Stanford University. He returned to China in 2012 under the Thousand Talents Program of the Government of China and opened a lab at the Southern University of Science and Technology. As part of the program, he was given 1 million yuan in angel funding, which he used to start biotech and investment companies. He founded Direct Genomics in 2012 in Shenzhen, to develop single-molecule sequencing devices based on patents invented by Quake that had formerly been licensed by Helicos Biosciences. Direct Genomics received 40 million yuan in subsidies from Shenzhen, and raised hundreds of millions yuan more in private investment, but He sold his stake in 2019. He also founded Vienomics Biotech, which offers genome sequencing services for people with cancer.
He Jiankui's achievements were widely revered in Chinese media, including China Central Television which covered his research and described him as "the founding father of third-generation genome editing" during a program celebrating the 19th National Congress of the Communist Party of China. He took an unpaid leave from the university starting in February 2018, and began conducting the genome-editing clinical experiment. On 26 November 2018, he announced the birth of gene-edited human babies, Lulu and Nana. Three days later, on 29 November 2018, Chinese authorities suspended all of his research activities, saying that his work was "extremely abominable in nature" and a violation of Chinese law. In December 2018, following public outcry regarding his work, He appeared to have gone missing. China's Southern University of Science and Technology denied the widespread rumors that he had been detained.

Research

In 2010, at Rice University, He Jiankui and Michael W. Deem published a paper describing some details of the CRISPR protein; this paper was part of the early work on the CRISPR/Cas9 system, before it had been adopted as a gene editing tool.
In 2017, He gave a presentation at Cold Spring Harbor Laboratory describing work he did at Southern University of Science and Technology, in which he used CRISPR/Cas9 on mice, monkeys, and around 300 human embryos.
In August 2018, He met with Chinese-American doctor John Zhang to discuss plans to launch a company focused on "genetic medical tourism." The business was to target elite customers, operating out of China or Thailand. The business plans were shelved with He's detainment in November 2018.
In January 2019, scientists in China reported the creation of five identical cloned gene-edited monkeys, using the same cloning technique that was used with Zhong Zhong and Hua Hua – the first ever cloned monkeys - and Dolly the sheep, and the same gene-editing CRISPR/Cas9 technique allegedly used by He in creating the first ever gene-modified human babies Lulu and Nana. The monkey clones were made in order to study several medical diseases.

Human gene-editing experiment

On 25 November 2018, He Jiankui first announced on YouTube that his team successfully created the world's first genome-edited babies, Lulu and Nana. Formally presenting the story at the Second International Summit on Human Genome Editing at the University of Hong Kong three days later, he said that the twins were born from genetically modified embryos that were made resistant to HIV. His team recruited 8 couples consisting each of HIV-positive father and HIV-negative mother through Beijing-based HIV volunteer group called Baihualin China League. During in vitro fertilization, the sperms were cleansed of HIV. Using CRISPR/Cas9 gene-editing, they mutated the gene called CCR5, which would confer resistance to HIV infection. The People's Daily announced the result as "a historical breakthrough in the application of gene editing technology for disease prevention".
The experiment had recruited couples who wanted to have children; in order to participate, the man had to be HIV-positive and the woman uninfected. At the time, it was not disclosed whether the clinical experiment had received appropriate ethical review from an institutional review board before it started, and it was unclear if the participants had given truly informed consent.
He Jiankui said that he edited the genomes of the embryos using CRISPR/Cas9, specifically targeting a gene, CCR5, that codes for a protein that HIV-1 uses to enter cells. He was trying to create a specific mutation in the gene,, that few people naturally have and that possibly confers innate resistance to HIV-1, as seen in the case of the Berlin Patient. He said that the girls still carried functional copies of CCR5 along with disabled CCR5 given mosaicism inherent in the present state of the art in germ-line editing. There are forms of HIV that use a different receptor instead of CCR5, and the work that He did could not protect resulting children from those forms of HIV.
He Jiankui said that he used a preimplantation genetic diagnosis process on the embryos that were edited, where three to five single cells were removed and the editing was checked. He said that parents were offered the choice of using edited or unedited embryos.
The twin girls were born by mid-October 2018, according to emails from He to an adviser. According to He, they appeared to be healthy in all respects. When they were born, it was unclear if there might be long-term effects from the gene-editing; He was asked about his plans to monitor the children, and pay for their care should any problems arise, and how their confidentiality and that of their parents could remain protected. The names of the children used in reports, "Lulu" and "Nana", along with the names of their parents, "Mark" and "Grace", are pseudonyms. In February 2019, He's claims were reported to have been confirmed by Chinese investigators, according to NPR News.
He Jiankui also said at the Hong Kong meeting that a second mother in his clinical experiment was in the early stages of pregnancy. Although there are no official reports, the baby was expected around August 2019, and the birth was confirmed from the court verdict on 30 December which mentioned that there were three genetically-edited babies.

Gene-editing controversy

He Jiankui's human gene-editing clinical experiment was conducted without public discussion in the scientific community. It was first made public on 25 November 2018 when Antonio Regalado published a story about the work in MIT Technology Review, based on documents that had been posted earlier that month on the Chinese clinical trials registry. He Jiankui refused to give any comment on whether the pregnancies were aborted or carried on. It was only after the story was posted that the experiment was revealed in a promotional video on YouTube by He Jiankui and the next day in the Associated Press report. He Jiankui had engaged a public relations firm as well.
Once the existence of the clinical experiment was made public, He Jiankui's conduct was widely condemned. On 26 November, 122 Chinese scientists issued a joint statement that He's works were unethical, crazy and "a huge blow to the global reputation and development of Chinese science". Other Chinese scientists and institutions harshly criticized He; an article in Nature stated that concerns about He's conduct were "particularly acute in China, where scientists are sensitive to the country's reputation as the Wild West of biomedical research". An eminent bioethicist, Ren-zong Qiu, speaking at the Second International Summit on Human Genome Editing, commented on He's research as "a practice with the least degree of ethical justifiability and acceptability".
Geneticist Eric Topol stated, "This is far too premature... We're dealing with the operating instructions of a human being. It's a big deal." Nobel prize-winning biologist David Baltimore considered the work "irresponsible". Developmental biologist Kathy Niakan of the Francis Crick Institute said, "If true...this would be a highly irresponsible, unethical and dangerous use of genome editing technology." Medical ethicist Julian Savulescu of the University of Oxford noted, "If true, this experiment is monstrous." Bioethicist Henry T. Greely of Stanford Law School declared, "I unequivocally condemn the experiment," and later, "He Jiankui’s experiment was, amazingly, even worse than I first thought." Biochemist Jennifer Doudna, of the University of California, Berkeley, a pioneer of the CRISPR/Cas9 technology, condemned the research. George Church, a geneticist at Harvard University, defended some aspects of the experiment and said gene editing for HIV resistance was "justifiable" since HIV is "a major and growing public health threat", but questioned the decision of this project to allow one of the embryos to be used in a pregnancy attempt, since the use of that embryo suggests that the researchers’ "main emphasis was on testing editing rather than avoiding this disease".
Arthur Caplan, bioethicist at the New York University School of Medicine, said that engineering human genes is inevitable and, although there are concerns of creating "designer babies", medical researchers are more interested in using the technology to prevent and treat diseases, much like the type of experiments performed by He.
Carl Zimmer compared the reaction to He's human gene editing experiment to the initial reactions and subsequent debate over mitochondrial replacement therapy, and the eventual regulatory approval of MRT in the United Kingdom.
The National Institutes of Health of United States announced a statement on 28 November 2018 signed by its Director Francis S. Collins, condemning He and his team for intentionally flouting international ethical norms by doing such irresponsible work, and criticizing that He's "project was largely carried out in secret, the medical necessity for inactivation of CCR5 in these infants is utterly unconvincing, the informed consent process appears highly questionable, and the possibility of damaging off-target effects has not been satisfactorily explored". NIH claims no support for the use of gene-editing technologies in human embryos.
The Chinese Academy of Medical Sciences published an announcement in the journal Lancet, stating that they "are opposed to any clinical operation of human embryo genome editing for reproductive purposes in violation of laws, regulations, and ethical norms in the absence of full scientific evaluation", and condemning He for violating relevant ethical regulations and guidelines that have been clearly documented by the Chinese government. They emphasized that the "genome editing of germ cells or early embryos is still in the stage of basic research,... scientific research institutions and researchers should not undertake clinical operations of genome editing of human germ cells for reproductive purposes, nor should they fund such research", and they will "develop and issue further operational technical and ethical guidelines as soon as possible to guide and standardise relevant research and applications according to the highest scientific and ethical standards."
In February 2019, scientists reported that the twin babies Lulu and Nana may have inadvertently had their brains enhanced.
In 2019, the World Health Organization has launched a global registry to track research on human genome editing, after a call to halt all work on genome editing.
In April 2019, genetics experts from the Chinese Academy of Science noted, “ believe there is no sound scientific reason to perform this type of gene editing on the human germline, and that the behavior of He and his team represents a gross violation of both the Chinese regulations and the consensus reached by the international science community. We strongly condemn their actions as extremely irresponsible, both scientifically and ethically.”

Investigations

The Southern University of Science and Technology stated that He Jiankui had been on unpaid leave since February 2018, and his research was conducted outside of their campus; the university and his department said they were unaware of the research project and said it was inviting international experts to form an independent committee to investigate the incident, and would release the results to the public. Local authorities and the Chinese government also opened investigations.
Michael W. Deem, He's doctoral advisor at Rice University, was involved in the clinical project, and was present when people involved in his study gave consent. Deem came under investigation by Rice after news of the work was made public.
As of news reported on 28 December 2018, He was sequestered in a university apartment and under guard. According to news reported on 7 January 2019, he could face severe consequences. William Hurlbut, Stanford University neuroscientist and bioethicist, reported that he was in contact with He who was staying in a university apartment in Shenzhen “by mutual agreement” and was free to leave; often visiting the gym and taking walks with his wife. Nonetheless, He may have been under some form of surveillance.
On 25 February 2019, news was reported that suggested the Chinese government may have helped fund the CRISPR babies experiment, at least in part, based on newly uncovered documents.

Preliminary authoritative report

An investigating task force set up by the Health Commission of China in Guangdong Province released a preliminary report on January 21, 2019, stated that He Jiankui had defied government bans and conducted the research in the pursuit of personal fame and gain. The report confirmed that He had recruited eight couples to participate in his experiment, resulting in two pregnancies, one of which gave birth to the gene edited twin girls in November 2018. The babies are now under medical supervision. The report further said He had made forged ethical review papers in order to enlist volunteers for the procedure, and had raised his own funds deliberately evading oversight, and organized a team that included some overseas members to carry out the illegal project. Officials from the investigation said that He, as well as other relevant personnel and organizations, will receive punishment per relevant laws and regulations, and those who are suspected of committing crimes will be charged.

Outcome

The SUSTech announced a statement on its website on 21 January 2019 that He Jiankui had been fired.
On 30 December 2019, the Shenzhen Nanshan District People's Court sentenced He Jiankui to three years in prison and fined him 3 million RMB. His collaborators received less penalty – Zhang Renli of the Guangdong Academy of Medical Sciences and Guangdong General Hospital, a two-year prison sentence and a 1-million RMB fine, and Qin Jinzhou of the Southern University of Science and Technology, an 18-month prison sentence and a 500,000 RMB fine. The three were found guilty of having "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos into two women."