By late 1963, Clay had become the top contender for Sonny Liston's title. The fight was set for February 25, 1964, in Miami Beach . Liston was an intimidating personality, a dominating fighter with a criminal past and ties to the mob. Based on Clay's uninspired performance against Jones and Cooper in his previous two fights, and Liston's destruction of former heavyweight champion Floyd Patterson in two first-round knock outs, Clay was a 7–1 underdog. Despite this, Clay taunted Liston during the pre-fight buildup, dubbing him "the big ugly bear". "Liston even smells like a bear", Clay said. "After I beat him I'm going to donate him to the zoo."  Clay turned the pre-fight weigh-in into a circus, shouting at Liston that "someone is going to die at ringside tonight". Clay's pulse rate was measured at 120, more than double his normal 54.  Many of those in attendance thought Clay's behavior stemmed from fear, and some commentators wondered if he would show up for the bout.
Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile .  The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker , at Syntex , discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams . His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception .  In 1952, . Peterson and . Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.  The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $ per gram by 1980. Percy Julian's research also aided progress in the field.  The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.