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He Jiankui affair

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The Lulu and Nana controversy revolves around twin Chinese girls born in October 2018, who have been given the pseudonyms Lulu (Chinese: 露露) and Nana (Chinese: 娜娜).[1] According to the researcher, He Jiankui, the twins are the world's first germline genetically edited babies.[2][3][4] He Jiankui has reported that the girls were born healthy.[5] The girls' parents were participants in a clinical project run by He, in which he offered standard in vitro fertilization services and in addition, used CRISPR-Cas9, a technology that can modify DNA, to modify the CCR5 gene in the embryos that were generated, to attempt to confer genetic resistance to HIV.[6] The clinical project was conducted secretly until November 2018.[2]

The reaction to He's actions was widespread criticism[7][8] and included concern for the well-being of the girls.[6][9][10] Near the end of November, Chinese authorities suspended all his research activities.[11] As of 28 December 2018, He is sequestered in a university apartment, under some sort of surveillance,[12][13] and may face serious consequences.[14] In 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.[15][16][17]

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.[18][19][20]

In May 2019, lawyers in China reported, in light of the purported creation by Chinese scientist He Jiankui of the first gene-edited humans, the drafting of regulations that anyone manipulating the human genome by gene-editing techniques, like CRISPR, would be held responsible for any related adverse consequences.[21] In December 2019, MIT Technology Review reported a substantial overview of the controversy to date.[22][23] Later in December 2019, Chinese authorities announced that He Jiankui had been sentenced to three years in prison and fined 3 million yuan (US$430,000) for his genetic research efforts.[24][25]

Announcement

He Jiankui's announcment

Chinese scientist He Jiankui announced his experiment involving editing the genes of twin babies 'Lulu and Nana' in an interview with the news agency Associated Press on 19 November 2018, the eve of the Second International Summit on Human Genome Editing at the University of Hong Kong. On 25 November 2018, He posted the announcement of his experiment and the successful birth of the twins on Youtube.[26] Dr. He's experiment had received no independent confirmation, and had not been peer reviewed or published in a scientific journal.[27][28][29][30] Soon after He Jiankui's revelation, the university at which He was previously employed, the Southern University of Science and Technology (SUSTech), stated He's research was conducted outside of their campus, and they were unaware of the research project and its nature.[31] China’s National Health Commission also ordered provincial health officials to investigate his case soon after the experiment was revealed.[27]

Origins

The embryos that became Lulu and Nana were generated during a clinical experiment run by He Jiankui, a Chinese scientist of the Southern University of Science and Technology in Shenzhen, while he was on leave from the university and working through Shenzhen Harmonicare Women’s and Children’s Hospital.[32] The project had recruited couples who wanted to have children. In order to participate in the experiment, the man chosen had to be HIV-positive and the woman, uninfected.[32] The couples were recruited through a Beijing-based AIDS advocacy group called Baihualin.[32] Dr. He kept the clinical project secret from the scientific community until the experiment's announcement, and as of 28 November 2018, it was unclear whether the participants had given truly informed consent.[33][34]

Experiment and birth

He Jiankui, the researcher, took sperm and eggs from the couples, performed in vitro fertilization with the eggs and sperm, and then edited the genomes of the embryos using CRISPR/Cas9.[32] The editing targeted a gene, CCR5, that codes for a protein that HIV uses to enter cells.[34][35] He was trying to create a specific mutation in the gene, (CCR5 Δ32), that few people naturally have — that possibly confers innate resistance to HIV,[34] as seen in the case of the Berlin Patient.[36] Dr. He said that Lulu and Nana still carried functional copies of CCR5 along with disabled CCR5 given mosaicism inherent in the present state of the art in germ-line editing.[citation needed] There are forms of HIV that use a different receptor gene instead of CCR5; therefore, the work of Dr. He did not theoretically protect Lulu and Nana from those forms of HIV.[34] He used a preimplantation genetic diagnosis process on the embryos that were edited, where three to five single cells were removed, and fully sequenced them to identify chimerism and off-target errors. Dr. He says that during the pregnancy, cell-free fetal DNA was fully sequenced to check for off-target errors, and an amniocentesis was offered to check for problems with the pregnancy, but the mother declined.[34] Lulu and Nana were born in secrecy in October 2018.[37] Dr. He said that they appeared to be healthy.[33]

Reactions and aftermath

He did not disclose the parents' names and they did not make themselves available to be interviewed, so their reaction to this experiment and the following controversy is not known.[32] There was widespread criticism in the media and scientific community over the conduct of the clinical project and its secrecy,[38] and concerns raised for the long term well being of Lulu and Nana.[33][30] Bioethicist Henry T. Greely of Stanford Law School declared, "I unequivocally condemn the experiment,"[39] and later, "He Jiankui’s experiment was, amazingly, even worse than I first thought."[40]

Michael W. Deem, an American bioengineering professor at Rice University and Dr. He's doctoral advisor, was involved in the research, and was present when people involved in He's study gave consent.[32] Deem came under investigation by Rice after news of the work was made public.[41] A series of investigations were opened by He's university, local authorities, and the Chinese government. On 25 November 2018, MIT Technology Review published a story about the work, based on documents that had been posted earlier that month on the Chinese clinical trials registry.[29] After that story was posted, Dr. He released a promotional video on YouTube and the next day the Associated Press published an interview with him.[29][32] He had engaged a public relations firm as well.[42] He eventually presented the work that led to the birth of the girls on 28 November at the International Human Genome Editing Summit.[33] On 29 November 2018, Chinese authorities suspended all of He's research activities, saying his work was "extremely abominable in nature" and a violation of Chinese law.[43] As of 28 December 2018, He Jiankui is sequestered in a university apartment under some sort of surveillance,[44][45] and may face serious consequences.[46]

On 29 January 2019, it was learned that a U.S. Nobel laureate Craig Mello interviewed He about his experiment with gene-edited babies.[47] In February 2019, He's claims were reported to have been confirmed by Chinese investigators, according to NPR News.[48] Later in 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.[49][50][51]

Related research

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 Jiankui in creating the first ever gene-modified human babies Lulu and Nana. The monkey clones were made in order to study several medical diseases.[52][53]

In February 2019, scientists reported that Lulu and Nana may have inadvertently (or perhaps, intentionally[17]) had their brains altered,[54] since CCR5 is linked to improved memory function in mice,[55] as well as enhanced recovery from strokes in humans.[56] Although He Jiankui stated during the Second International Summit on Human Genome Editing, that he was against using genome editing for enhancement,[57] he also acknowledged, that he was aware of the studies linking CCR5 to enhanced memory function.

In April 2019, for the first time, use of the CRISPR technology to edit human genes to treat cancer patients, with whom standard treatments were not successful, has been reported.[58][59]

In June 2019, researchers suggest that the purportedly genetically edited humans may have been mutated in a way that shortens life expectancy.[60][61][62] However, this study was later retracted.[63]

See also

References

  1. ^ Cohen, Jon (1 August 2019). "The untold story of the 'circle of trust' behind the world's first gene-edited babies". Science. Retrieved 1 August 2019.
  2. ^ a b Bulluck, Pam (14 April 2019). "Gene-Edited Babies: What a Chinese Scientist Told an American Mentor". The New York Times. Retrieved 14 April 2019.
  3. ^ Begley, Sharon; Joseph, Andrew (17 December 2018). "The CRISPR shocker: How genome-editing scientist He Jiankui rose from obscurity to stun the world". Stat News. Retrieved 17 December 2018.
  4. ^ Begley, Sharon (26 November 2018). "Claim of CRISPR'd baby girls stuns genome editing summit". Stat News. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  5. ^ Begley, Sharon (28 November 2018). "Amid uproar, Chinese scientist defends creating gene-edited babies - STAT". STAT.
  6. ^ a b Reuters (26 November 2018). "China Orders Investigation After Scientist Claims First Gene-Edited Babies". The New York Times. Archived from the original on 27 November 2018. Retrieved 26 November 2018. {{cite news}}: |author= has generic name (help)
  7. ^ Kolata, Gina; Belluck, Pam (5 December 2018). "Why Are Scientists So Upset About the First Crispr Babies? - Only because a rogue researcher defied myriad scientific and ethical norms and guidelines. We break it down". The New York Times. Retrieved 5 December 2018.
  8. ^ The Editorial Board (28 January 2019). "Should Scientists Toy With the Secret to Life? - The gene-editing technology Crispr has the power to remake life as we know it. Questions about how to use it concern everyone". The New York Times. Retrieved 29 January 2019.
  9. ^ Regalado, Antonio (25 November 2018). "Exclusive: Chinese scientists are creating CRISPR babies - A daring effort is under way to create the first children whose DNA has been tailored using gene editing". MIT Technology Review. Archived from the original on 27 November 2018. Retrieved 26 November 2018.
  10. ^ Cyranoski, David (27 November 2018). "How the genome-edited babies revelation will affect research - Some scientists worry the startling claim will lead to knee-jerk regulations and damage the public's trust in gene editing". Nature. doi:10.1038/d41586-018-07559-8. Archived from the original on 27 November 2018. Retrieved 27 November 2018.
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  27. ^ a b Reuters (26 November 2018). "China Orders Investigation After Scientist Claims First Gene-Edited Babies". The New York Times. Archived from the original on 27 November 2018. Retrieved 26 November 2018. {{cite news}}: |author= has generic name (help) [verification needed]
  28. ^ Begley, Sharon (26 November 2018). "Claim of CRISPR'd baby girls stuns genome editing summit". Stat News. Archived from the original on 27 November 2018. Retrieved 26 November 2018. [verification needed]
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  30. ^ a b Cyranoski, David (27 November 2018). "How the genome-edited babies revelation will affect research - Some scientists worry the startling claim will lead to knee-jerk regulations and damage the public's trust in gene editing". Nature. doi:10.1038/d41586-018-07559-8. Archived from the original on 27 November 2018. Retrieved 27 November 2018. [verification needed]
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  35. ^ de Silva E, Stumpf MP (December 2004). "HIV and the CCR5-Delta32 resistance allele". FEMS Microbiology Letters. 241 (1): 1–12. doi:10.1016/j.femsle.2004.09.040. PMID 15556703. [verification needed]
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  37. ^ Bulluck, Pam (14 April 2019). "Gene-Edited Babies: What a Chinese Scientist Told an American Mentor". The New York Times. Retrieved 14 April 2019. [verification needed]
  38. ^ Kolata, Gina; Belluck, Pam (5 December 2018). "Why Are Scientists So Upset About the First Crispr Babies? - Only because a rogue researcher defied myriad scientific and ethical norms and guidelines. We break it down". The New York Times. Retrieved 5 December 2018. [verification needed]
  39. ^ Farr, Cristina (26 November 2018). "Experiments to gene-edit babies are 'criminally reckless,' says Stanford bio-ethicist". CNBC. Archived from the original on 27 November 2018. [verification needed]
  40. ^ Greely, Henry T. (15 April 2019). "He Jiankui, embryo editing, CCR5, the London patient, and jumping to conclusions". Stat News. Retrieved 15 April 2019. [verification needed]
  41. ^ LaMotte, Sandee (27 November 2018). "Rice professor under investigation for role in 'world's first gene-edited babies'". CNN News. Archived from the original on 27 November 2018. Retrieved 27 November 2018. [verification needed]
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  44. ^ Chen, Elsi; Mozur, Paul (28 December 2018). "Chinese Scientist Who Claimed to Make Genetically Edited Babies Is Kept Under Guard". The New York Times. Retrieved 29 December 2018. [verification needed]
  45. ^ Senthilingam, Meera (7 January 2019). "Chinese scientist was told not to create world's first gene-edited babies". CNN News. Retrieved 21 January 2019. [verification needed]
  46. ^ Ramzy, Austin; Wee, Sui-Lee (21 January 2019). "Scientist Who Edited Babies' Genes Is Likely to Face Charges in China". The New York Times. Retrieved 21 January 2019. [verification needed]
  47. ^ C; Choi, Ice; Marchione, Marilynn (28 January 2019). "AP Exclusive: US Nobelist was told of gene-edited babies". AP NEWS. Retrieved 29 January 2019. [verification needed]
  48. ^ Schmitz, Rob (5 February 2019). "Gene-Editing Scientist's 'Actions Are A Product Of Modern China'". NPR News. Retrieved 5 February 2019. [verification needed]
  49. ^ Qiu, Jane (25 February 2019). "Chinese government funding may have been used for 'CRISPR babies' project, documents suggest". STAT News. Retrieved 1 March 2019. [verification needed]
  50. ^ Chen, Angela (26 February 2019). "New documents suggest Chinese government helped fund the CRISPR babies experiment". The Verge. Retrieved 1 March 2019. [verification needed]
  51. ^ Belluz, Julia (4 March 2019). "CRISPR babies: the Chinese government may have known more than it let on - The latest developments in the gene-editing saga raise more questions than answers". Vox. Retrieved 4 March 2019. [verification needed]
  52. ^ Science China Press (23 January 2019). "Gene-edited disease monkeys cloned in China". EurekAlert!. Retrieved 24 January 2019.
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  54. ^ Regalado, Antonio (21 February 2019). "China's CRISPR twins might have had their brains inadvertently enhanced - New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories". MIT Technology Review. Retrieved 21 February 2019.
  55. ^ Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K.; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha (20 December 2016). "CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory". eLife. 5. doi:10.7554/eLife.20985. ISSN 2050-084X. PMC 5213777. PMID 27996938.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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  60. ^ Gallagher, James (3 June 2019). "He Jiankui: Baby gene experiment 'foolish and dangerous'". BBC News. Retrieved 3 June 2019.
  61. ^ Stein, Rob (3 June 2019). "2 Chinese Babies With Edited Genes May Face Higher Risk Of Premature Death". NPR News. Retrieved 3 June 2019.
  62. ^ Wei, Xinzhu; Nielsen, Rasmus (3 June 2019). "CCR5-∆32 is deleterious in the homozygous state in humans". Nature Medicine. 25 (6): 909–910. doi:10.1038/s41591-019-0459-6. PMID 31160814.
  63. ^ https://www.nature.com/articles/d41586-019-03032-2

External links

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