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Friday, September 27, 2019

Change introduced in the CRISPR babies experiment may shorten lives

A scientific study published this past spring came with damning implications for Chinese scientist He Jiankui, who created the world’s first gene-edited babies: People with the rare genetic variants that He tried to engineer into embryos, the study asserted, had an increased death rate.
On Friday, the paper’s senior author said his study was wrong.
“The one thing that all scientists fear the most is to find out that a major result they have published was based on erroneous data,” Rasmus Nielsen, of the University of California, Berkeley, wrote on Twitter. He said that he had been notified of an error in the data from the massive genetic database that Nielsen and his collaborator, Xinzhu Wei, had analyzed to reach their conclusion.
The error “likely explains most or all of our results” regarding the genetic variant that He tried to alter, he said.
Nielsen said he and Wei would work with the editors of the journal that published their study, Nature Medicine, to correct the publication.
Nielsen, Wei, and Nature Medicine could not immediately be reached for comment on Friday afternoon.
The apparent error centers around the effects of a variant of the gene known as CCR5, called Δ32, which is best known for protecting against infection with HIV, the virus that causes AIDS. In explaining his choice to target CCR5 in his controversial experiment last year, He said he aimed to prevent the pair of twin babies he experimented on from inheriting the virus from their HIV-positive father. HIV infection is extremely stigmatized in China.
When news of his experiment stunned the world last fall, He acknowledged that the CCR5 variant had been associated with a higher risk of serious complications and flu death from influenza as well as infection with West Nile virus.
In their study, Nielsen and Wei sought to better understand the health effects of the CCR5 variant. They probed data from 409,693 people of British ancestry in the U.K. Biobank, an ambitious initiative to study the effects of DNA on health and other characteristics. The dataset is widely used by genetic researchers.
Nielsen wrote on Twitter that Harvard scientist David Reich, who has previously studied the CCR5 variant, had identified the error in their U.K. Biobank data that casts doubt on their findings.
Reached by email on Friday, Reich told STAT: “I think it’s best just to have a scientific discussion and not to comment to the press while this discussion is going on.”
When the paper was published in June, it generated some pushback online from scientists who took issue with Nielsen and Wei’s approach.
One of those critics was Sean Harrison, a University of Bristol epidemiologist and statistician who has worked with data from the U.K. Biobank.
Shortly after the paper’s publication, Harrison put out a series of tweets and, later, a blog post mapping out his concerns with the study’s methodology. Harrison criticized the authors for neglecting to account for related people in their sample, failing to take certain quality control measures, and conducting a type of statistical analysis that seemed inappropriate for the study design, among other issues. Harrison wrote that he tried to replicate the analyses using U.K. Biobank data. When he did so, “I found… Nothing,” Harrison wrote in his blog post.
Nielsen said on Twitter that it was Harrison who inspired Reich to probe the results of the CCR5 study.

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