The Song of the Cell: An Exploration of Medicine and the New Human

by Siddhartha Mukherjee

In 2020, a group of Dutch researchers, looking for genes that might increase susceptibility to severe Covid, found the glimpse of an answer. The group identified two sibling pairs from different families, four young men, who had suffered unusually aggressive forms of the disease. Genetic sequencing revealed that one pair had inherited an inactivating mutation in a gene, TLR7 (fraternal siblings, on average, will have half their genes in common). Astonishingly, the second pair of brothers had also inherited a mutation in that very gene that appeared to decrease its activity (the exact mutation was different—but it was in the same gene). What about the TLR7 gene might explain its involvement with such severe consequences of SARS-COV2 infection? Recall the innate immune system, which responds to patterns or signals of danger sent out by cells during the very first phases of an infection. Well, before the innate system can be activated, the cell first has to detect the invasion. TLR7—or Toll Like Receptor 7—it turns out, is one of the key detectors of viral invasion. It’s a molecular sensor, built into cells, that is turned “on” when the cell is infected by a virus. The activation of TLR7, in turn, galvanizes a cell’s danger signals—among them, a molecule called type 1 interferon, to alert other cells to amplify their antiviral defenses, and to jump-start the immune response. The theory is that mutations in TLR7 in both sibling pairs had somehow inactivated the protein, or dec...

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