276 KOPIN
schizophrenic patients because their 24-hour urine volumes were about
three-fold greater than those of the normal control subjects.
Another hypothesis about a biochemical abnormality in schizophrenia
involved adrenochrome. Abram Hoffer, Humphrey Osmond, and John
Smithies had published a monograph^1 based on an anecdote that dur
ing World War II, when supplies of adrenaline were running out, vials
containing outdated adrenaline that had turned pink had to be used. It
was rumored that when pink adrenaline was injected, some of the patients
developed hallucinations. Since pink adrenaline is the result of auto-
oxidation of the adrenaline to form adrenochrome, this anecdote was the
basis for the hypothesis that schizophrenia resulted from adrenochrome
formed by abnormal metabolism of adrenaline. Stephen Szara and Axelrod
showed that adrenochrome could not be demonstrated in the blood of
normal or schizophrenic patients.
Thus, some of the earliest efforts of the scientists in Kety’s laboratory
were directed at critically examining several hypotheses regarding bio
chemical abnormalities in schizophrenic patients.
At that time, studies of catecholamines were an exciting research area.
Ulf von Euler had proven that norepinephrine was the transmitter re
leased from sympathetic nerve endings and many grant applications
were coming into the NIH study sections requesting funding to support
research on the role of catecholamines in various diseases. However, little
was known about sensitive and specific methods for measurement of
catecholamines in plasma or about catecholamine metabolism. To inform
the scientific community better, a symposium was held in October 1958
at the NIH Clinical Center to review what was known about catecho
lamines: how they could be measured, how they were formed in the
body, how they produced their effects, how their actions were termi
nated, and what their role in brain function is. I do not think that any
of the organizers anticipated that five Nobel Prizes would be awarded
to the participants of this symposium on catecholamines. The sym
posium was published in Pharmacological Reviews.^2 Between the time
that this symposium was originally proposed and when it was actually
held, there had been a number of striking advances in the field.
Marvin D. Armstrong, Armand MacMillan and Kenneth N. F. Shaw
had found that the major urinary metabolite of epinephrine and norepi