Panum's studies on "putrid poison" 1856. An early description of endotoxin

In 1855-1856 the Danish physiologist, Peter Ludvig Panum (1820-1885) performed a series of remarkable experiments on "putrid poison", a hypothetical substance claimed to be responsible for the symptoms and signs seen in patients with sepsis. Dogs were given intravenous infusions of putrefying solutions, and symptoms and signs were recorded. Infusion of a suitable amount resulted in characteristic sepsis symptoms and signs, which only started after a delay of half an hour. By modifying his test solutions Panum could show that the toxic principle was a solid substance, soluble in water, but insoluble in alcohol, and with preserved activity after long-term boiling. "Putrid poison" has striking similarities with endotoxin, a cell wall product of Gram-negative bacteria and a powerful inducer of inflammation and septic shock. Thanks to Panum's carefully arranged experiments and meticulous recording of observations it is fair to conclude that "putrid poison" was endotoxin, and as such he deserves credit for being the first to have described endotoxin. Panum published his observations twice, in Danish in 1856, and in German in 1874. At first he rejected the possibility that bacteria could play a causative role in the development of symptoms and signs seen after infusion of "putrid poison". However, in his last publication he hypothesized that "putrid poison" could be a bacterial product, and he envisaged future antibacterial chemotherapy of sepsis and treatment with anti-endotoxin agents.