CONTINUING METABOLIC STUDIES
THE FFRST BIOMEDICAL STUDIES
In early 1943, there existed about 2 milligrams of plutonium produced at the
Berkeley cyclotron.
This was distributed over the entire research program and
was as Seaborg (1970) said, in retrospect, "a quantity so precious we couldn't
afford to ingest any of it." (3)
The potential external and internal radiation
hazards associated with the production of large quantities of fission products
in the newly developed chain-reacting pile demanded the full attention of the
Plutonium Project's Health Division headed by R. S. Stone, and this miniscule
quantity of plutonium had to be ignored.
However, the situation changed very rapidly.
The Clinton reactor ("Site x,"
i.e., Oak Ridge) began producing milligram quantities of plutonium isotopes
beginning in late 1943.
In early 1944, gram amounts began to be produced with
the start-up of the Hanford reactors ("Site W") and by mid-1945, kilogram
quantities were in existence.
The potential health hazards of plutonium seem to have been first appreciated
by Glenn Seaborg.
As described
in detail
in the Langham and
Healy
(1973)
paper already cited, in January, 1944, Seaborg (19444) expressed his concerns
to Dr. Stone in a letter dated January 5, 1944, and ten days later Seaborg
(1944b) suggested that 10 mg. of plutonium be made available to Joseph G.
Hamilton and his associates at the Crocker Laboratory at Berkeley.
Their
initial job was to determine its metabolism, i.e., its distribution and excretion in contradistinction to its effects.
This was done forthwith using
laboratory mice, and in a remarkably short time, results were reported.
The
plutonium was delivered to Hamilton on February 10, 1944, and the taboratory's
progress report for February (Allison, 1944) contains the following:
"Product studies--oral absorption of all valence states is less
than 0.05%
Lung retention is high
Absorbed material is predominantly in the skeleton
Excretion is very small in urine and feces
How is that for promptness?
begun in one month,
Today, the preliminary paperwork would have only
Thus, it appeared that plutonium acted like radium in that it was a boneseeker
but it was less readily absorbed and more avidly retained, especially in lung.
It was this behavior analogy to radium which became the basis for the first
attempt to set an exposure limit for plutontum.
As more plutonium became available, these first observations were extended in
Hamilton's laboratory and with the organization and development of laboratory
programs, notably at the Chicago "Metallurgical Laboratory" and the project at
the University of Rochester School of Medicine and Dentistry, more detailed
information wag obtained and the several species added.
In late 1946, R. D.
Finkle from Chicago and reports from the group at Rochester confirmed the
basic facts enumerated by Hamilton (Finkle, 1946). But it also began to be
clear that the analogy to radium was only a general one. Many differences
between plutonium and radium became apparent.
Chief among these was the
detailed behavior in bone. Largely from autoradiographic studies in Hamilton's
laboratory, it was clear that plutonium was much less uniformly distributed in
bone than was radium (which is not uniformly distributed itself}.
Particularly,
it appeared chat plutonium was much more likely to collect on surfaces and
interfaces in bone and did not enter the minerak matrix except very slowly and
it did not exchange for calcium as does radium.
The signtficance of this for toxicity was appreciated and added impetus to the
direct measurements of toxicity in animals already begun at Chicago and Rochester,
We will return to this point. But first we must examine what was being done
to learn about the metabolism of plutonium in man.*
STUDIES GCF METABOLISM IN MAN
Whtle the laboratory studies were providing some of the needed information,
the rapid growth in numbers of workers potentially exposed forced quick decisions regarding maximum permissible exposures, As always, the question persisted
as to whether or not man handled plutonium in roughly the same way as the
laboratory animals. This was approached in two ways--directly through the
administration of what were then regarded as tracer quantities of plutonium to
hospitalized patients considered to have short life expectancles and indirectly
by meticulous studies of plutonium excretion by workers.
The study with patients was performed in 1945.
It involved 16 individuals
over 45 years of age who, by the nature of their disease, were considered
unlikely to Live long enough for the plutonium to exert any toxic effect.
The
*Important animal laboratory studies have been conducted in both the United
Kingdom and the Soviet Union,
But both the work and their publication are
much later than the period of primary focus for this review.