ALBERT HOFMANN'S 'PROBLEM CHILD'

The Swiss chemist Albert Hofmann, who died on Tuesday at the age of
102, assembled a remarkable track record as an investigator -- one
that stretched back to the wild west days of chemistry and pharmacy,
when ventilated fume hoods were considered an expensive affectation,
occasional self-experimentation was not only permitted but expected
and a lone individual was involved in every stage of drug discovery
from conceptualization to fabricating the pills.

As a graduate student, Hofmann revealed the structure of insect
chitin; later he would master the complex chemical world found within
ergot, a cereal fungus with a fantastical range of effects on the
human nervous system. His ergot-derived "children," as he called
them, would include drugs that remain in the pharmacopoeia to this
day: methergine to prevent obstetrical bleeding, the anti-dementia
vasodilator hydergine, dihydergot for migraines.

But Hofmann, as often happens, reserved the greatest affection for
what he referred to in a remarkable 1980 memoir as his "problem
child": lysergic acid diethylamide.

LSD-25, as it was known when Hofmann first synthesized it in 1938,
was originally just one in a long series of ergot-derived compounds
that he considered promising. He hoped it would turn out to be an
effective "circulatory and respiratory stimulant." In animal tests, a
modest clinical effect was noted, but mostly the subjects just became
"restless." The batch was discarded. Ergot was expensive, war was
approaching and Hofmann's employer, Sandoz, was tight-fisted. No one
could have imagined that humans would ever again synthesize LSD-25.

But Hofmann had felt a "peculiar presentiment," and five years later,
on April 16, 1943, he made more, hardly knowing what he would do with
it. The new batch amounted to a speck of a few centigrams. As he was
finishing up, he was, in the words of the lab report he later
scribbled, "interrupted" by a feeling of dizziness that obliged him
to abandon his desk and go home, where he lay down and was regaled
with "an uninterrupted stream of fantastic pictures, extraordinary
shapes with intense, kaleidoscopic play of colors."

On recovery, it seemed clear to him that he had accidentally ingested
a microscopic amount of something toxic -- something with a
hallucinatory strength per gram far transcending that of any known
substance. He had been working with LSD, so it was the obvious
candidate. Clearly, a further experiment, carefully documented as it
happened, was in order.

On April 19, he deliberately took a quarter-milligram of LSD.
Generations of acid-heads have gotten a belly laugh out of Hofmann's
expectation that he could take coherent notes after absorbing such a
massive hit. The part of his "trip report" written under the
influence is 13 words long: "Beginning dizziness, feeling of anxiety,
visual distortions, symptoms of paralysis, desire to laugh." Even
this much was scrawled, he later said, "only with great effort."
Nursed through a three-hour trip by a bemused neighbour and a country
doctor, Hofmann was surprised to find that he felt well, even
refreshed, and that he could remember his experience in fine detail.

From that day forward, the sober, reserved scientist began to live a
double life. The psychiatric profession embraced LSD, and in the '50s
its power to impose the cosmic perspective and distort the ego showed
promise in treating psychosis. While acting as chief consultant to
this research program, Hofmann became a confidant and friend to
non-academic experimenters like Aldous Huxley (whose last words on
Earth were a request for an intramuscular jab of LSD). In later
years, he also had to calm freaked-out youths who occasionally turned
up at his office or his home, explaining to one young American girl
that her plan to secretly dose president Johnson probably wasn't very
practical.

Before long, the genie escaped the bottle. This was largely owing to
Harvard lecturer Timothy Leary, whose experiments with psychedelics
gradually strayed further and further outside the lab. By
1963,Hofmann reflected ruefully, "The experiments had turned into LSD
parties," and Leary had become a messiah of LSD. Meanwhile, amateur
chemists had mastered the intricacies of its production, and its
influence outside the controlled setting was proving ambivalent,
though surely never quite so evil as hysterical newspaper critics made out.

Hofmann and Leary had only one genuine conversation, sharing lunch at
a train station in Lausanne in 1971 after Leary's escape from a
California prison. Hofmann lectured the American about his
publicity-seeking and his dangerous habit of giving LSD to the young.
Leary replied, with customary asininity, that doing so was perfectly
safe "because teenagers in the United States, with regard to
information and life experience, were comparable to adult Europeans."
Hofmann left the station more confident than ever that Leary was a
menace -- the man who had led his "problem child" astray. He was to
die awaiting the day that proper research into its healing potential
could resume.