Monday morning, September 13, 1999, a team of physicians led by Steven Raper and James Wilson at the University of Pennsylvania threaded a thin tube through an incision in the groin of human subject OTC.019 to administer thirty milliliters of a modified adenovirus to his liver. The subject, like the seventeen who had preceded him, suffered from a rare hereditary disorder, ornithine transcarbamylase deficiency (OTCD), in which patients accumulate toxic levels of ammonia. Half of all infants born with severe forms of the disorder die within seventy-two hours of birth. However, participants in this study suffered from a mild form – one that could be controlled with medication and a restricted protein diet.
Like the previous subjects, OTC.019 developed the usual symptoms of viral infection: achiness, fevers, and a headache. Eighteen hours after the infusion, however, the response of OTC.019 headed into unfamiliar territory. He began showing signs of jaundice, a troubling sign for someone with a liver disorder. He became disoriented and agitated. Tests indicated dangerous levels of ammonia in the volunteer's blood, and soon thereafter he slipped into a coma.
Thirty or so hours after receiving the vector, OTC.019 began hyperventilating. Elevated oxygen threatened to increase the rate at which his body broke down the proteins released by his deteriorating blood cells; this, in turn, would drive his ammonia levels higher, portending brain damage. To control his breathing and reduce his blood oxygen, physicians placed OTC.019 on a ventilator. But OTC.019 continued to hyperventilate.