focus of the Goldwater group's antimalarial research
was on American Atabrine, a synthetic antimalarial
first developed in Germany in the 1930s. Though
scientists in the United States had synthesized
the drug within a few years, troops did not usually
take their medicine. The Atabrine turned them
yellow, made them sick, and seemed to take forever
to work. What was the problem?
Army doctors dispensed the Atabrine at the same
dose levels they had used for quinine. In the 1940s,
however, a new method of dose-setting was coming
into vogue, and one of the biggest proponents of
what was called the "New Pharmacology"
was Dr. James Shannon. At Goldwater, he put Drs.
Brodie and Udenfriend on the problem of re-setting
the dosage for Atabrine, using this new approach.
the scientists had to find a way to measure the
concentration of the drug in the blood. Second,
they had to figure out what blood concentration
would yield the desired result. And third, they
had to set a dosage schedule to maintain that
desired blood level.
Brodie and Udenfriend figured out how to measure
Atabrine levels in the blood using fluorescence.
Since Atabrine fluoresced at a certain wavelength,
all they had to do was take a sample of blood
from a malarial patient who had taken Atabrine.
When seen through a fluorometer, the plasma would
"glow" at a level proportional to the
amount of Atabrine in the sample.
scientists found that, at the current dosage,
the Atabrine was soaked up in muscle fiber and
the liver, causing uncomfortable side effects
before it was able to build up in the blood. By
changing the dosage-to a first-day big dose to
saturate the tissues followed by small daily doses
that would then go right to the blood-the Goldwater
group was able to save Atabrine, as well as millions
of American troops abroad.
Shannon's so-called "gospel of blood levels"
revealed the central importance to pharmacology
of being able to measure the concentrations of
drugs in the blood. This central issue led the
Goldwater team to be interested in a more sensitive
instrument than the fluorometer they had used
during the war, and therefore led to the development
of the SPF.