by David Livermore, Daily Sceptic:
Sometimes a paper on a new method delivers a side punch to current understanding. Nothing in the title hints at this, and the authors deliver the critical blow en passant.
Over a 40-year career in microbiology I’ve met several cases. For example, the scientist who found a problematic type of antibiotic resistance to be extremely prevalent in Pakistan. This exercised him not one jot, despite obvious implications for treatment and for import into the U.K. What motivated Joe, whose name I’ve changed, was perfecting a test to detect bacteria with this resistance. One of his collaborators (a former colleague, I think) just happened to be in Pakistan, which proved – owing to the high prevalence of the resistance – to be the ideal testing ground.
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Some scientists don’t want the trouble that comes from a disturbing result, especially when they have a new method to publicise. They fear the opprobrium reserved for heretics and disruptors. At best, controversial observations delay your paper’s publication. At worst, they lead to it being rejected. Why court trouble, especially if you have patents or intellectual property claims? More simply, some, like Joe, just have a ‘techno’ mindset. If they discovered a Roman mosaic whilst digging the garden they’d fixate on how it’d affect the roses.
Now, consider this paper, published a few days ago: ‘Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning’ by Luo, J., Molbay, M., Chen, Y. et al in Biotechnol (2025).
The title suggests that it’s a paper for imagers and radiographers. The abstract – where you summarise the main points – outlines how ‘Single Cell Precision Nanocarrier Identification’ visualises the tissue distribution of encapsulated drug formulations, notably including those using lipid nanoparticles (LNPs). Even when dosages are tiny the method can reveal individual cells that the particles reached. The LNPs’ distribution is very wide, and the resolution very impressive. The end of the Discussion – where you reiterate key discoveries – stresses how the method may help pharmaceutical developers identify carriers that distribute only to the desired tissues. Examples are presented.
This is high-quality work, nicely described. Nothing I write here should be construed as a criticism. But, mid-Abstract, there’s the by-the-bye killer punch, describing a step used to validate the method. With my additions in brackets, it reads:
We demonstrate that intramuscularly-injected LNPs (lipid nanoparticles) carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to proteome (i.e., protein expression) changes, suggesting immune activation and blood vessel damage.
The Results tell the detail. Luo et al confirm the wide tissue distribution of LNPs following intramuscular injection of mice. On the positive side, they concentrate in lymph nodes, which should promote an immune response. More concerningly, they also reach the heart. And, once the LNPs were loaded with the relevant mRNA, this prompted production of the SARS-CoV-2 spike protein, principally by the endothelial cells of the heart capillaries.
When mice were given intramuscular LNPs with no mRNA, 240 capillary endothelial cell proteins were up-regulated and 135 down-regulated. These numbers swelled to 578 and 201, respectively, once the LNPs were loaded with mRNA for SARS-CoV-2 spike protein.
Proteins that were up-regulated or down-regulated only with the spike mRNA present included those involved with protein and RNA metabolism and the immune response. And – more concerningly – those involved in the formation and maintenance of the blood vessels. Some correspond to those which, in humans, are associated with the Vascular Function Score, a predictor of stroke and heart attack risk. More generally, dysfunction of capillary endothelial cells is a marker for cardiac disease and a European Society of Cardiology Working Group describes them as “Sentinels of cardiac health”.
