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The exact cause of the Flesh Change, and what triggered its onset, was not known. Malcador The Sigilite initially believed it was due to an error in the XVth's "gene encoding", a belief he clung to for many years before he and the Emperor ultimately realised they could not cure the Thousand Sons.{{Fn|63}} There may be a link with sustained, heavy, use of psychic powers, as the Thousand Sons fell en mass to the Flesh Change during the burning of Prospero, when the Thousand Sons desperately unleashed ever more powerful "sorceries" at the Space Wolves and Custodes of the Censure Host to try and defeat them.{{Fn|3p}} Another victim who fell under similar circumstances was [[Revuel Arvida]], who continuously used his powers to assist the White Scars, during their campaigns against the [[Death Guard]] and other Traitor forces.{{Fn|64}} However, this may simply be correlation and not causation, as Thousand Sons legionaries who completely lacked psychic ability were just as susceptible to the Flesh Change.{{Fn|3q}}
Before the discovery of Prospero, and the Legion's reunification with Magnus, the Thousand Sons had attempted to hold the Flesh Change at bay with retro-virals, alchemy, meditative techniques, and sheer willpower, but all of these techniques eventually failed in time. Legionaries who became aware of the onset of the condition - or condition—or who had to be subdued by their brother legionaries when the change was sudden and overwhelming - were put into stasis, in the hopes a future cure could be found.{{Fn|3r}}
When the Flesh Change was a gradual onset, afflicted Legionaries could feel their flesh rebelling beneath their skin, and their appearance often took on a pallid, waxy, look. When the change took over suddenly, the results were immediate and spectacular: the flesh and blood of the legionary was in complete flux, with power armour shattering and mutating flesh spewing out as the former Space Marine grew larger and monstrous. [[Phosis T'Kar]]'s changing form at the Burning of Prospero grew to such proportions he dwarfed [[Constantin Valdor]].{{Fn|3x}}{{Fn|38x}} In addition to the riot of change that wreaked havoc with their flesh when the condtion took over, in the overwhelming majority of cases when a legionary was lost to the Flesh Change, he devolved into a mindless monstrosity—an especially horrific fate for the Thousand Sons, who took pride in their learning and culture. When the Flesh Change struck the ranks of the Thousand Sons during the final stages of the Burning of Prospero, legionaries who succumbed to the Flesh Change attacked anything within reach, regardless of whether they were Space Wolves or Thousand Sons.{{Fn|3r}}{{{Fn|38n}}