Edith Graef McGeer - Society for Neuroscience

338 Patrick L. McGeer and Edith GraefMcGeer
A few memories remain from those days about the odd new field we were
embracing. Bill Gibson sent Edie in early 1956 to a meeting of psychiatrists
in Chicago. It was much smaller than an American Chemical Society
meeting and much different in tone. Edie still remembers listening for
what seemed like hours to a hot debate as to whether monkeys could have
an Oedipus complex. We both remember driving back with Bill Gibson
from our first meeting with psychiatrists at the mental hospital. We were
giving polite responses to Bill's questions about our impressions when he
remarked in a meditative tone, 'Oh well, there's no reason why a person
with a diseased hip can't be an orthopedic surgeon.'
Hoffer, Osmond, and Smythies introduced the term 'hallucinogen' to
describe compounds with opposite effects to the tranquilizing agents.
These were compounds such as LSD and mescaline that would induce
bizarre mental changes while, like the tranquilizing agents, having little
effect on the periphery of the body. In those days, hallucinogens were not
street drugs but scientific curiosities. Hoffer, Osmond, and Smythies
developed the theory that schizophrenia was caused by abnormal metabolism
of adrenaline, forming a compound they called adrenochrome, which
mimicked the hallucinogen mescaline. John Smj^hies moved from Hoffer's
laboratory in Saskatoon to work with Dr. Gibson on silver staining of
boutons. He introduced Dr. Gibson to the hallucinogenic theory of schizophrenia.
Dr. Gibson wanted a chemist to measure the levels of
adrenochrome in schizophrenic and normal urine. Edie synthesized
some adrenochrome and found it so unstable in urine that it disappeared
within a few seconds, which ended that approach. Nevertheless, it seemed
at the time that the answer to schizophrenia was just around the corner.
That corner is yet to be turned, and a metabolic abnormality remains an
attractive hypothesis almost half a century later.
The introduction of tranquilizing agents immediately began to focus
attention on the overlap between mental disorders and extrapyramidal
function. Although chlorpromazine and reserpine relieved psychotic symptoms,
they induced prominent parkinsonian side effects. What sort of
chemistry produced this overlap?
The answers were to emerge from investigations of a group of aromatic
compounds that became known as the biogenic amines. Martha Vogt
reported in 1954 that 'sympathin' (noradrenaline) existed in relatively
high concentrations in the midbrain and hypothalamus, which could not
be explained on the basis of vascularity. The previous year, Twarog and
Page found an unusually high concentration of serotonin in brain. Shortly
after, Amin, Crawford, and Gaddum reported the highest concentration to
be in the h3rpothalamus and limbic system. WooUey and Shaw proposed
that either an excess or deficiency was responsible for mental illness.
Fletcher, Shaw, and Brodie began to provide closure by noting that
reserpine depleted serotonin from the gut, which was followed by reports