Hey Jiankui

Note: This article places the family name before the person's first name. This is the usual order in Chinese. He is the family name here, Jiankui is the first name.

Jiankui He (2018)

He Jiankui (Chinese: 贺建奎; born 1984 ) is a Chinese biophysicist . He taught and researched at the Faculty of Biology of the South University of Science and Technology (Chinese 南方 科技 大学, English Southern University of Science and Technology of China, SUSTec) in Shenzhen , People's Republic of China. As far as publicly known, he is believed to be the first to perform genetic engineering operations in the germ line ( germ line therapy ) of a human embryo, thus sparking a heated debate in 2018 in which the operation was unanimously condemned (Chinese Crisp Crisis).The overwhelming majority of the critics condemned the interference on ethical grounds. In December 2019, he was sentenced to three years in prison.

Career

Jiankui He is the son of rice farmers in Hunan Province. He received his PhD in 2010 from Michael Deem , professor of bioengineering at Rice University , where he had studied physics since 2007. At the time, his research focused on a quick method of predicting which flu strains should be included in the annual vaccinations. According to his doctoral supervisor Deem, the method only took two weeks instead of half a year like the method used by the WHO. The release was on the cover of Protein Engineering Design and Selection in December 2010 . He also published with Deem in Physical Review Letters on the application of statistical methods from evolutionary biology to the question of how the globalization of the world economy increases the susceptibility to recessions. Another work was a mathematical model for predicting the CRISPR mechanism, how bacteria acquire immunity to disease through natural selection. His supervisor Deem described him as a student of high impact ( high impact student ). As a post-doctoral student, he was with Stephen Quake at Stanford University .

Genetic intervention in the human germ line

His attempts to modify the human genome in embryos through genome editing triggered a wave of indignation. Gene therapy with CRISPR was planned by various research groups (for example in beta-thalassemia ), an intervention in the germ line with the result that the gene changes would also be passed on to offspring, but was generally considered premature. It was known that Jiankui He undertook such experiments on animals and human stem cells, and at a conference in Cold Spring Harbor in the summer of 2017, he warned that caution should be taken, as failure could bring the entire research field into disrepute.

In November 2018, he then claimed that he had altered the genome of twin sisters conceived by artificial insemination using the CRISPR / Cas method in order to make them immune to HIV . The father of the children conceived was infected with HIV. The gene for the CCR5 receptor has been genetically modified and deactivated . He also tested for off-target changes and found none. The immunization of one of the twin sisters was also incomplete (mosaic formation), so that some cells could be infected with HIV in the future. More precisely, according to He's records, one girl had 15 deleted base pairs on one of the two copies of the CCR5 gene and one intact gene on the other copy, the other girl had four deleted base pairs on one of the two copies, an additional base pair on the other. The babies were already born at the time of the public announcement and He announced in a YouTube video that the girls were doing well. He said he had thoroughly educated the couple about the risks and method of the procedure. He also stated that he had performed the same procedure on another child. He had selected a total of seven couples, in each of which only the man was HIV positive. Colleagues consider his information to be credible, as the intervention is relatively easy in principle. There are also natural mutations of the CCR5 gene (delta-32 mutation) that immunize against AIDS, but are of a different form, they are missing 32 base pairs in the CCR5 gene.

Jiankui He surprised the international research community when he presented the procedure on November 27, 2018 at the Second International Summit on Humane Genome Editing in Hong Kong. According to his own statements, he proceeded at his own expense and without the knowledge of his university, where he has been released from work since February. He found the volunteers in an AIDS self-help group, but keeps their identity a secret (the twins' aliases are Lulu and Nana). A committee at the clinic in Shenzhen (Har MoniCare Women's and Children's Hospital), where he performed the procedure, was inaugurated. At the conference, He regretted that his approach had become known before a scientific publication (which had already been submitted in 2018 and was in the peer review stage). He considered the operation itself morally justifiable, as there is currently no effective vaccine against AIDS and access to effective drugs is difficult in China.

Chinese authorities confirmed two pregnancies as a result of Jiankui's surgery by mid-January 2019.

Reactions

China's national health authority condemned the procedure and ordered a thorough investigation with possible consequences for He. The government prohibited him from further work in this area. He's nomination for a Chinese National Science Award by the Chinese Society for Science and Technology (CAST) has been withdrawn. His university also convicted him of violating academic ethics and norms. According to Emmanuelle Charpentier , co-discoverer of the CRISPR method , a red line has been crossed. In addition to a lack of transparency, Nobel Prize winner David Baltimore also criticized the lack of medical necessity, since HIV infection can be prevented in a conventional way and the twins may now be more sensitive to other viruses. In particular, there is a suspicion that a defective CCR5 gene leads to a more severe course of influenza. A clear negative effect of the CCR5delta32 mutation is suggested by a population study published on June 3, 2019 by Xinzhu Wei (Univ. Of California) and Rasmus Nielsen (University of Copenhagen), which based on British registry data of over 400,000 people a 21 percent higher probability of death for homozygous carriers of the mutation in the age group 41 to 76 years reported. In October 2019, Wei and Nielsen withdrew their publication in Nature Medicine because of inconsistencies in the UK biobank data on which the study was based.

It was also Baltimore who came forward at the Hong Kong conference immediately after He's lecture and declared He's actions to be irresponsible.

His former PhD supervisor Deem at Rice University was also the subject of an ethical investigation when it was revealed that he knew about the procedure on the twins and was present when the couples gave their consent for the procedure. Deem has minor stakes in two companies He founded and is part of their scientific advisory team. After returning from the USA, he managed to raise $ 35 million for his start-ups. He even commissioned surveys to signal public approval for his plan. As of 2015, He had also received $ 5 million in public research funding.

Many Chinese biotechnology scientists saw the success of their burgeoning biotechnology industry threatened (and particularly the promising CRISPR technology), were particularly strong against He's advance, and published a protest letter with 122 signatures calling his experiment crazy.

An evaluation of the raw data and documents from He for his then still unpublished essay Birth of Twins After Genome Editing for HIV Resistance ( Nature and JAMA, among others, rejected publication) was published in the MIT Technology Review in December 2019 . The essay by He and nine other colleagues (including Michael Deem) made full-bodied claims, among other things, of having achieved a medical breakthrough in controlling the HIV epidemic, without their own data to back it up. Instead of the desired mutation (CCR5 delta32), which causes resistance to HIV, other - albeit similar - mutations were created without it being shown in the article that these also produce resistance to HIV (a test for resistance to HIV would have been available in advance the fertilized cells). In addition, in an embryo only one of the two genes of the cell had a mutation and not the other. It was criticized that the search for off-target mutations was incomplete - in principle, because only a few cells could be removed at a time. It is also believed that the couples who participated in the study were deceived. To protect their babies from their own HIV infection, routine sperm washing would have been enough, but the couples would have expected cheap access to artificial insemination. It was also criticized that the doctors involved were probably not fully informed (which also suggests their lack of authors of the study). The experiments were only entered in the China Clinical Trial Registry after the babies were born. In the study, it is also assumed that the research could indirectly also serve to investigate and treat the HEU syndrome (children with HIV-infected parents are particularly susceptible to childhood diseases). He was in an email exchange with Craig Mello about it . In addition, He's work lacks information about the funding of her study. There is evidence that He wanted to start a medical tourism business for genetically modified babies, seeking help from artificial insemination centers in the United States.

Condemnation

He has not performed publicly since his lecture in Hong Kong on November 27, 2018. On November 29, 2018, he was banned from working and was later dismissed from the university. According to his family, he first lived with her on the campus of the Shenzhen Southern University of Science and Technology in an apartment under house arrest .

After no more information about He's whereabouts, the state news agency Xinhua reported in late December 2019 that he had been sentenced to three years imprisonment and a fine of around 380,000 euros for unethical and unauthorized medical research in a closed trial in Shenzhen be. According to the court ruling, both the parents of the twins were “deceived” about the background of the germline therapy and the approval of ethics committees was obtained under false prerequisites. In order to achieve “fame and profit”, He had “deliberately violated the relevant national regulations for scientific and medical research and exceeded the boundaries of scientific and medical ethics”. Two colleagues, including a veterinarian , were also sentenced to fines and imprisonment.

literature

• Ulrich Bahnsen: Can he do what he can? - The Chinese researcher He Jiankui claims to have created genetically modified twin girls. In: Die Zeit No. 49, November 29, 2018, p. 39 ( zeit.de ).

Individual evidence

1. ↑ Sandee LaMotte: Rice professor under investigation for role in 'world's first gene-edited babies , CNN , November 28, 2018 (English).
2. ↑ Deem, He, Low-dimensional clustering detects incipient dominant influenza strain clusters, Protein Engineering Design and Selection, Volume 21, Issue 12, 2010, pp. 935-946, abstract (English).
3. ^ He, Deem: Structure and Response in the World Trade Network , Phys. Rev. Lett., Volume 105, 2010, p. 198701, abstract (English).
4. ^ He, Deem: Heterogeneous diversity of spacers within CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). In: Phys Rev Lett Volume 105, 2010: 128102, Abstract (English).
5. ↑ Mike Williams, New way of predicting dominant seasonal flu strain , Rice University News, November 17, 2010.
6. ↑ Lena Stallmach: The creator of genetically modified babies has his own value system , Neue Zürcher Zeitung , November 29, 2018.
7. ↑ According to another representation, at least one off-target mutation occurred. The Baby Hobbyist , Der Spiegel, No. 49, 2018, p. 115.
8. ↑ Did he treat her or make her sick? , SRF , December 8, 2018.
9. ↑ The Baby Hobbyist , Der Spiegel , No. 49, 2018, p. 115.
10. ↑ Sonja Kastilan: Dr. Hey - or whether we'll ever learn to love Crispr , Frankfurter Allgemeine Sonntagszeitung , December 2, 2018, p. 64.
11. ↑ Second woman carrying gene-edited baby, Chinese authorities confirm , The Guardian of January 22, 2019 (English).
12. ↑ He Jiankui Must End Research on Babies , Zeit Online , November 29, 2018.
13. ↑ The risk of infection for the twins from their HIV-positive father is negligible if his father is well controlled.
14. ↑ Sonja Kastilan, FAS , December 2, 2018.
15. ↑ Wei X, Nielsen R .: CCR5-∆32 is deleterious in the homozygous state in humans. Nat Med. 2019 Jun 3. doi: 10.1038 / s41591-019-0459-6. [Epub ahead of print] PubMed PMID 31160814 (English).
16. ↑ Wei, Nielsen, Retraction Note: CCR5-∆32 is deleterious in the homozygous state in humans , Nature Medicine, Volume 25, 2019, p. 1796.
17. ↑ Johann Grolle, Julia Koch, Thomas Schulz, Bernhard Zand: The baby handicraftsman , Der Spiegel , NR. 49, December 1, 2018, pp. 114–119, here p. 119.
18. ^ Sandee LaMotte, CNN , Nov. 28, 2018.
19. ↑ Johann Grolle, Julia Koch, Thomas Schulz, Bernhard Zand: The baby handicraftsman , Der Spiegel , NR. 49, December 1, 2018, pp. 114–119, here p. 118.
20. ↑ Lorena Dreusicke: "Chinas Frankenstein" - He Jiankui apparently disappeared , SVZ , December 5, 2018.
21. ↑ Der Baby-Bastler , Der Spiegel , No. 49, 2018, pp. 114, 118.
22. ↑ Antonio Regelado: China's CRISPR babies: Read exclusive excerpts from the unseen original research , MIT Technology Review , December 3, 2019.
23. ↑ Chinese scientist who gene-edited babies fired by university . In: Reuters , January 21, 2019. Retrieved January 23, 2019. 
24. ↑ Chinese genetic engineering researcher could atone for experiments ; Süddeutsche.de of January 14, 2019; accessed on December 30, 2019
25. ↑ Controversial genetic researcher allegedly missing ; Spiegel Online from December 4, 2018; accessed on December 30, 2019.
26. ↑ Researchers sentenced to three years in prison for genetically modified babies , Spiegel Online , December 30, 2019.
27. ↑ Three years imprisonment for germline experiments ; tagesspiegel.de, December 30, 2019.