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Radio Review: HIV protective gene paper retraction

21 October 2019
Appeared in BioNews 1020

There are numerous reasons why the story of two baby girls, who had been genetically engineered as embryos and consequently equipped with an HIV protective gene variant, startled researchers and the public around the world (see BioNews 977). Within the scientific niche, one major surprise was the breach of the scientific process, or the scientific etiquette, by the former Professor He Jiankui.

Dr Adam Rutherford, the presenter of the BBC Inside Science programme, decided to revisit the saga of the genome-edited babies, and the scientific work that followed, in order to give the listeners an insight into the traditional scientific process and the instrumental role of social media in addressing its flaws.  

Dr Rutherford discusses with Dr Helen O'Neill from University College London, UK, who was at the International Human Editing Summit in Hong Kong in November 2018, when He Jiankui revealed his experiment. Dr O’Neill emphasised that 'There was nothing normal about the process that he [Jiankui] went through; be it in terms of getting patients, or having scientific approval, or ethical approval, or regulatory approval.' Consequently, this work would not have passed a scientific peer-review, a key step in the scientific process that forms a prerequisite for publication in a scientific journal, and hence the birth of the genome-edited babies was announced on YouTube. Dr O’Neill went on to explain that: 'He [Jiankui] released these nice videos, justifying his actions and research, with the grounds to doing good.'

In response to Jiankui’s experiment, two researchers from the University of California, Berkely, USA, Dr Xinzhu Wei and Professor Rasmus Nielsen, published an article in Nature Medicine, which claimed that the CCR5 gene edit, which Jiankui introduced, may result in shortened lifespan, or increased mortality (see BioNews 1001). However, this conclusion was contested by Dr Sean Harrison from the University of Bristol, UK, who re-did the analysis the evening that the publication came out, and did not find any evidence for this association.

Prior to the podcast, Dr Harrison told the BBC: 'The methodology was not as strict (…) at the University of Bristol we have much more stringent measures in place, so that when we do the analysis, there is much less chance of bias coming into the results.' He published his re-analysis on Twitter and his blog, which engaged the wider scientific community, including Professor Nielsen. As a result of this 'post-publication peer-review', as Dr Rutherford described it, Professor Nielsen decided to withdraw and retract his original publication, thus preserving his scientific integrity. He has released a new article this month explaining why his former analysis was flawed.

This saga of the genome-edited babies and the CCR5 gene, so well-known to the general public, was used on BBC’s Inside Science to illustrate how the scientific process works. Drs Rutherford and O’Neill clarify that the expected elements of scientific work include: study design, gaining the necessary approvals prior to conducting the study, writing it up in a scientific research article and submitting for publication to a journal. Once submitted, scientific work is normally subjected to a peer-review, which Dr O’Neill elegantly likened to doing a spell check prior to printing. As the presenter and his guest agreed, this was the weak link, which failed Professor Nielsen and Dr Wei, and which should have revealed the analysis flaws demonstrated by Dr Harrison.

There was also no clarification of the fact that there is little incentive for scientists to act as peer-reviewers, because they usually have to do it in their own time outside of work hours and are bound by confidentiality agreements so it is very hard, if not impossible, for them to be acknowledged or credited for this work. Also, except for occasional discounts on future own publications, there is no financial incentive to conducting a peer-review. Hence, this step is a major flaw in the scientific process, which the podcast did not emphasise strongly enough, especially in context of such a high-ranking journal as Nature Medicine.

Nonetheless, Dr O’Neill did stress that: 'Every scientist is under pressure to publish, publish, publish.' This pressure, together with the lack of formal recognition for the peer-review work, will likely have led to many more similarly flawed scientific publications, which would not have been identified and subsequently retracted, because they were not describing a controversial subject, or at least a trending topic. 

If someone set off alarm bells in the pre-social media era, the discussion would usually only include the authors and the publisher. In this context, the podcast certainly emphasised the positive effect of the availability and use of social media for real-time scientific discussions. Dr Rutherford applauded: 'This is in fact a good way for science to transpire, if pursuit of the truth is our ultimate goal.' 

This BBC Inside Science podcast was first broadcasted on 3rd October 2019 and is available on the BBC website.
 

SOURCES & REFERENCES
No statistical evidence for an effect of CCR5-Δ32 on lifespan in the UK Biobank cohort
bioRxiv |  2 October 2019
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