Science journal retracts article linking CCR5 deletion to reduced life expectancy
Richard Jefferys, TAG
In June 2019, a short paper was published in the journal Nature Medicine reporting that individuals homozygous for the CCR5-∆32 mutation showed a 21% increase in the rate of all-cause mortality compared to those without the mutation (or heterozygotes, who inherit the mutation from one parent). 
The senior author, Rasmus Nielsen, stated to the Wall Street Journal that this would equate to a nearly two-year shortening of lifespan on average. 
The findings were the subject of hundreds of media articles, largely because they came on the heels of a misguided and completely unethical experiment in which the CCR5 gene was edited in two embryos, leading to the birth of genetically altered twins. 
Questions were also raised about possible relevance to HIV cure research studies that attempt to ablate CCR5 expression with gene therapies. 
Yesterday, Nature Medicine published a notice that the paper has been retracted. 
News that the retraction was imminent emerged two weeks ago in an article by Rebecca Robbins for STAT News, after Nielsen tweeted an acknowledgement that a major error had been found. 
The original analysis was based on data from the UK Biobank, and it turned out that a technical artifact meant that individuals homozygous for the CCR5-∆32 mutation were underrepresented in the data (the problem is outlined in a paper available on the bioRxiv preprint server). 
These developments do not necessarily mean that homozygosity for the CCR5-∆32 mutation is entirely benign; a number of published reports have suggested an association with impaired responses to certain infectious diseases (particularly West Nile Virus, and possibly influenza as well). [9, 10]
Also, previously unappreciated roles of the CCR5 receptor continue to be identified, such as the promotion of hematopoietic stem and progenitor cell regeneration after radiation treatment.  But, after this retraction, there is no evidence (at least as yet) that any negative effects of the CCR5-∆32 mutation add up to a reduced life expectancy for homozygous individuals.
Jefferys R. Widely publicised report associating the CCR5-Δ32 mutation with reduced longevity is retracted. TAB Basic Science Blog. (09 Oct 2019).
- Wei X, Nielsen R. CCR5-∆32 is deleterious in the homozygous state in humans. Brief Communication. Nature 2019: 25; 909–910 (03 June 2019).
- Rana P. Study of HIV-related mutation adds to worries about first gene-edited babies (05 June 2019).
- Jeffery R. Treatment Action Group statement on the reported birth of twins with edited CCR5 genes. TAG Blog. (26 November 2018).
- Sax P. Exploiting the CCR5 Receptor: Potential Avenue for HIV Cure?Medscape. Commentary. (19 July 2019).
- Wei X, Nielsen R. Retraction Note: CCR5-∆32 is deleterious in the homozygous state in Nature Medicine (2019).
- Robbins R. STAT News. Major error undermines study suggesting change introduced in the CRISPR babies experiment shortens lives. (27 September 2019).
- Nielsen R. “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. This is an event that will affect you for the rest of your scientific career.” Twitter. (21 September 2019).
- Maier R. No statistical evidence for an effect of CCR5-Δ32 on lifespan in the UK Biobank cohort. ObioRxiv preprint server. (02 Oct 2019).
- Glass WG et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. JEM 203 (1): 35 (17 January 2006)
- Falcon A et al. CCR5 deficiency predisposes to fatal outcome in influenza virus infection. Jour Gen Viro 96 (8). ()1 August 2015).
- Piryani SO et al. CCR5 signaling promotes murine and human hematopoietic regeneration following ionizing radiation. Stem Cell Reports. 13 (1);76-90. (09 July 2019).