Davy (1778–1829)

In April 1799, Humphry Davy reported his initial findings concerning the inhalation of nitrous oxide (N2O) and then embarked upon a series of animal experiments culminating with the publication of, "Researches Chemical and Philosophical: Chiefly Concerning Nitrous Oxide and its Respiration", in 1800. In this, Davy describes guinea pig experiments and the administration of pure nitrous oxide to a "stout and healthy cat".

*"after 5 min the pulse was hardly perceptible; he made no motions and appeared wholly senseless. After 5 min and a quarter he was taken out* ... *in 8 or 9 min he was able to walk* ... *in half an hour he was completely recovered".*

He frequently inhaled the gas himself, once whilst suffering severe pain from a wisdom tooth eruption after which he wrote:

*"As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great e*ff*usion of blood takes place."* [11]

Bentham (1748–1841) and Seturner (1783–1841)

That Davy's findings remained unadopted in medical practice until 1844 is attributed by Cartwright (1950) to the callousness and unprecedented brutality of the 18th-century Englishman [11]. Such callousness may have fuelled a growing philosophical interest in animal suffering, as exemplified by Bentham's proposal that animals be treated according to their capacity to suffer. In 1789, he asked:

*"The question is not, Can they reason? nor, Can they talk? but, Can they su*ff*er?"* [12]

Paradoxically, Bentham's utilitarianism necessitated his support of "justifiable" vivisection. In a letter to the editor of the Morning Chronicle, 4th March 1825, he wrote:

*"Sir—I never have seen, nor ever can see, any objection to the putting of dogs and other inferior animals to pain, in the way of medical experiment, when that experiment has a determinate object, beneficial to mankind, accompanied with a fair prospect of the accomplishment of it. But I have a decided and insuperable objection to the putting of them to pain without any such view".*

While human beings had been capitalising on the analgesic effects of *Papaver somniferum* derivatives since prehistory, the use of opioids in animals remained largely unreported until 1805, following Sertürner's isolation of morphine [13]. He tested an aqueous alcoholic extraction of the salt on four dogs and a mouse "that he found wandering in the laboratory". He gave 6 grains to a dog, followed an hour later by another 6 grains. The dogs vomited, had convulsions, and were sleepy, but did not sleep. One "gentle little dog" died. He reported the results of his animal studies in the *Journalder Pharmacie fuer Aerzte und Apotheker* in 1806, a reading of which would probably not have convinced anyone of the new compound's analgesic potential.
