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

by Siddhartha Mukherjee

Toghrul, Jia, Dan, and I sent our data for publication in the winter of 2021. We proposed a radically new hypothesis about osteoarthritis. It isn’t merely a degeneration of cartilage cells, caused by grind and tear. It is, first, an imbalance caused by the death of Gremlin-marked cartilage progenitor cells that cannot generate adequate bone and cartilage to keep up with the demands of the joint. And so we have a theory to answer the fourth age-old mystery: Why doesn’t cartilage in joints get repaired, just as a bone fracture does, in adults? Because the repairing cells die during the injury. Injury and repair share a border—except, as we age, injury, and the weariness of regenerative capacity, keeps infiltrating, creeping over the hedge. Osteoarthritis is a degenerative disease that arises from a regenerative disease. It is a flaw in rejuvenative homeostasis.