Hoffman was working for the Sandoz laboratories in Zurich, under Professor Stroll, trying to isolate the active components of plants deemed too unstable to use in pharmaceutical preparations.

Ergot of Rye was one of them, but Hoffman didn't work on it until later in his career.

The reason was that Pr. Stroll had in 1918 discovered an Ergot alkaloid, which he called ergotamine, and further research was stopped until the 1930's for the Sandoz labs. Research around the world started to take place again, giving the scientific world at the time a discovery which will revolutionise research in Ergot; the isolation and characterisation of the nucleus common to all Ergot alkaloids - Lysergic Acid.

Hoffman wanted to resume research on ergot, and was given the go ahead by Pr. Stroll.

Ergot was used in medicine in obstetrics (childbirth) first to induce childbirth, but then to stop afterbirth bleeding due to its effect on the uterus, and the treatment of migraine.

However, after many successes with the synthesis of ergot alkaloids, Hoffman set off to create new Lysergic acid compounds in the hope that they could bring other benefits in medicine, by adding amino acids to Lysergic acid.

In creating LSD 25 – (lysergic acid diethylamide abbreviated LSD-25 (Lyserg-saure-diathylamid for laboratory usage) – Hoffman intended on creating a circulatory and respiratory stimulant, but the lab tests proved pretty disappointing and apart from the expected uterotonic activity, and restlessness in the lab rats, there were none of the effects Hoffman anticipated and LSD-25 was shelved.

Hoffman carried on his researches on ergot, but it's not until 5 years later that Hoffman started to look at LSD-25 once again.
Now this is an extremely unusual practice as once a substance has been found to be lacking in pharmacological interest, it is stricken from the research programs.

Hoffman describes: A peculiar presentiment - the feeling that this substance could possess properties other than those established in the first investigations , which spurred him on to start researching LSD-25.

And it is in synthesizing it, in the spring of 1943, that Hoffman made his discovery.
He had to stop his work, and go home as he got disturbed by strange feelings, a sort of dizziness, and while lying down, his imagination was racing...

He later decided that he had somehow got in contact to LSD-25, and had been poisoned by its effects. He thought that since he took a lot of precaution when working the contact could have been only extremely minimal, and concluded that this must be an extremely powerful substance.
To be sure, he decided to conduct a self-experiment the next day and with the aide of his assistant, self administered the dose of 0.25mg.
He had the most intense experience, and asked his assistant, in one of his lucid moment to take him home, which they did on bicycles.
The details of his experience and the rest of his discoveries with LSD and other hallucinogens are described in his book, and I would highly recommend anyone interested to read it, as not only does he defend LSD with all his might, he also recognises the powerfulness of this substance, and his worries should it be used recklessly.

It upset him that it was taken over by the “Hippy generation” as his intentions were for it to be used in medicine, and he believed that it has potentials with dealing with mental illnesses.  I am grateful they did, even though I treat and regard it with the utmost respect.

It is hard still to see why he went back to LSD-25, it had no interests in the field of research he had intended it for. Was there something bigger than we can comprehend that would push this scientist to have “feelings” in his type of work, a man of substance and logic?

Links to the facts

http://www.flashback.se/archive/my_problem_child/

http://www.psychedelic-library.org/child.htm