Errors in CRISPR-Baby Study Geneticists Retract Paper That Suggested First Gene-Edited Babies Might Die Early

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common than previously thought, she says. which are very closely related to very, very Virologist Ayato Takada at Hokkaido Three in the same family were discovered in dangerous pathogens,” she says. University in Sapporo, Japan, is also excited animals in the past year: the Mengla virus in It remains unknown whether these viruses about being able to study BSL-4 pathogens in Chinese bats and two Ebola-like viruses found can infect or harm humans, says Mühlberger. animals in Japan. Until now, researchers had to in fish in the East China Sea. “It is amazing But their diversity is “pretty scary”, she says. apply for access to BSL-4 labs overseas, which how many animals are infected with viruses “These viruses are everywhere.” are in high demand. ■

GENOME EDITING Errors in CRISPR-baby study Geneticists retract paper that suggested first gene-edited babies might die early.

BY EWEN CALLAWAY University of China in Shenzhen, said he predicted it should — a sign that individuals with targeted CCR5 because people with a 32-DNA- two copies were dying earlier, on average, than study that raised questions over the letter deletion known as delta-32 in the gene the population at large, Wei and Nielsen argued. future health of the world’s first gene- are resistant to HIV but seem not to experience Questions over the conclusion emerged as soon edited babies has been retracted because significant related health problems. as the paper was published. Sean Harrison, an Aof key errors that undermined its conclusion. He has not published data supporting his epidemiologist at the University of Bristol, UK, The research, published in June in Nature work, but his announcement — presented attempted to replicate the findings that night. Medicine1, had suggested that people with two at a scientific meeting — indicated that, for He did not have UK Biobank data on the gene copies of a natural genetic mutation that confers one twin, both copies of CCR5 were altered, variant that Wei and Nielsen used to identify HIV resistance are at an increased risk of dying whereas the other twin carried edits in just one carriers of delta-32, so he analysed genetic earlier than other people. It was conducted of her two copies. None of the changes exactly variants near it on the genome that should have in the wake of controversial experiments by matched the delta-32 variation. given the same result (adjacent parts of the the Chinese scientist He Jiankui, who had genome tend to be inherited together, allow- attempted to recreate the effects of this muta- RESULTS NOT REPLICATED ing scientists to infer the presence or absence tion in the gene CCR5 by using the CRISPR Research has hinted that the delta-32 of a DNA sequence by analysing neighbouring gene-editing technique in human embryos. The mutation, which is relatively common in peo- variants). When they didn’t, he described his twin girls born last year as a result of the work ple of European ancestry, might carry down- findings in tweets and a blogpost. did not end up carrying this exact The discrepancy piqued the mutation, but the research attracted interest of David Reich, a popula-

GETTY attention because of its potential tion geneticist at Harvard Medical relevance to such experiments. School in Boston, Massachusetts, However, studies2–4 that looked whose lab is studying CCR5. Work- anew at the Nature Medicine research ing with Nielsen, his team discovered2 find no evidence that people with the that Nielsen and Wei’s method had mutation die early. The erroneous caused them to undercount the num- conclusion about CCR5 was caused ber of people in the UK Biobank with by errors in how the mutation was two copies of the delta-32 mutation, identified in a population-health because the probe that measured the database. variant they were tracking did not “I feel I have a responsibility to always identify its target sequence. put the record straight,” says Rasmus This — and not the supposed harmful Nielsen, a population geneticist at the effects of the mutation — explained University of California, Berkeley, the apparent absence of carriers who led the study, which the authors from the UK Biobank database, says retracted on 8 October. Nielsen A 32-letter deletion in the gene CCR5 confers resistance to HIV. Nielsen. also co-authored one of the papers Researchers emphasize that the rebutting its findings. sides — one small study5 found that carriers unravelling of Wei and Nielsen’s results does not Some researchers stress that because the twins were more likely than other people to die from mean it is a sound idea to target CCR5 for gene did not receive exactly the same mutation that influenza. To tackle the question in larger editing. “It’s very reasonable to expect that it occurs naturally, the original research and its data sets, Nielsen and his Berkeley colleague might have a valuable function that we just don’t retraction would not necessarily offer insights Xinzhu Wei looked at the UK Biobank data- know how to measure. It seems very unwise to into their health anyway. But the episode raises base, which contains genome and health data edit it out,” says Reich. ■ questions about how best to assess the safety of from 500,000 people. 1 1. Wei, X. & Nielsen, R. Nature Med. 25, 909–910 (2019). future attempts to edit genes in human embryos. Their paper reported that people with two 2. Maier, R. et al. Preprint at bioRxiv https://doi. He Jiankui shocked the scientific world copies of the delta-32 mutation were slightly org/10.1101/787986 (2019). when he announced, in November 2018, that more likely to die by the age of 76 than were 3. Gudbjartsson, D. et al. Preprint at bioRxiv https://doi.org/10.1101/788117 (2019). his team had used CRISPR to disable the CCR5 those with one or no copies. They also found that 4. Karczewski, K. J., Gauthier, L. D. & Daly, M. J. Preprint gene in two babies born that month. He, who the database harboured fewer people with two at bioRxiv https://doi.org/10.1101/784157 (2019). was at the time a biophysicist at the Southern copies of the mutation than evolutionary theory 5. Falcon, A. et al. J. Gen. Virol. 96, 2074–2078 (2015).