a. Dr. Saenger submitted ten reports to DASA/DNA from 1961 through 1972 in accordance with the terms of his contract.
b. The reports provide a means to trace the expansion of the research's scope, increased sophistication of techniques, and ambitiousness of future plans. The reports were similar in that they stated the purpose of and criteria for the research, research structure and techniques, how the work was conducted, the results of the experiments, observations and analysis of the data, plans for future study, and individual case histories of patients observed during the reporting period.
2. General information about DoD sponsorship of radiation experiments at the University of Cincinnati 1960-1971.
In September, 1958 Dr. Saenger submitted an unsolicited research application to the Research and Development Division of the Army Surgeon General's Office. The application proposed to research metabolic changes in humans following total body radiation for the purpose of
determining whether the presence of amino-acidura in humans after radiation would provide a reliable biological marker of radiation exposure. Dr. Saenger requested approximately $25,000 for the first year and $21,000 for two subsequent years.
Over the next year the proposal was reviewed within the Defense Department and a contract negotiated. Available documentation reveals that at least four Army Medical Corps and one Medical Service Corps officer reviewed the proposal. They recommended the contract application be approved. In October, 1959 the Defense Atomic Support Agency's (DASA) Deputy Chief of Staff, Weapons Effects and Test requested, thru the Chief, DASA, the Contract Management Branch, Directorate of Logistics negotiate a contract with the University of Cincinnati for the study of the metabolic changes in humans following total body radiation.
In early 1960 a contract (DA-49-146-XZ-029, dated 1 January 1960) was signed between DASA and the University of Cincinnati Board of Directors. The contract provided $25,085 for the study. This contract, with supplements and modifications,
funded the study through February, 1964.
The first contract stated the technical scope of the research was "to study the phenomen of aminoacidura following irradiation, a condition which has been reported in humans and animals, to clarify some of the mechanisms responsible for amino-acidura and to determine whether it is a practical biological test of radiation exposure." The search for a biological marker of radiation exposure was one constant of Dr. Saenger's research effort over the next decade.
On 28 February 1961 the Cincinnati project's
contract was modified for the first time. The
contract was modified to establish a new date for
work completion to provide additional time for
research on amino-aciduria following irradiation;
amended the technical scope of the work to meet
additional objectives of the government; provided
additional funds to meet research requirements
under the amended scope of work; altered portions
of the contract to bring the contract in
accordance with Armed Services Procurement
Regulations that became effective subsequent to
the signing of the original contract.
contract amount increased almost $30,000 from
$25,000 to $54,000 and the length of the project
was extended from February, 1961 to April, 1962.
The scope of the work was expanded by three
requirements: a breakdown of desoxyribonucleic
acid and is derivatives in patients receiving
total body radiation; DNA studies on patients who
received partial irradiation and radiomimetic
chemotherapeutic agents; and preliminary
determination of appropriate psychometric tests.
In June, 1961 the contract was modified for the
second time. An additional $650 was allocated to
use the technical services of a French authority
on radiobiology at a Whole Body Radiation
Conference to be held by DASA at the University of
Cincinnati in October, 1961.
In April, 1962 the project's contract was modified
for the third time. The contract total was
increased approximately $39,000 to $94,400. The
project completion date was extended to April 30,
1963. The scope of work was also further
expanded. Three additional objectives were added.
Additional studies were to be made of--increasing
the upper range of radiation dose to 150-200 rad,
and single doses of nitrogen mustard or other radiomimetic drug using .4mg/kilo. The following tests were to be conducted for 9 days posttreatment--urinary taurine for correlation with leukocyte count, BAIBA in urine, Kynurenic and xanthurenic acids, deoxycytidine, DNA fragments in urine, et al, xanthine and hypoxanthine in urine, urinary phosphate, and glutathione. The test were to be done over a 30 day period--routine electrophresis, immunoelectrophoresis,
quantitative precipitin studies, serum urea nitrogen and/or serum creatine once weekly, urinalysis once weekly and as needed, routine hematology, and completion of the manuscript of the DASA Conference on Total Body Irradiation of October, 1961.
On April 1, 1963 the contract was modified for the
fourth time. The contract was extended through
April 30, 1964. Funding was increased $40,000 to
$134,56. The scope of the work was further
amended. Test to be conducted over a 30 day
period between March 1, 1962 and February 28, 1963
were to be: (1) routine electrophesis, (2)
immunoelectrophesis, (3) quantitative precipitin
studies, (4) serum urea nitrogen and/or serum
creatine once weekly, (5) urinalysis once weekly
or as needed, and (6) routine hematology. During
the same year the following tests were to be
conducted over a 42 day period included 3,4,5,6
and chromosome cultures of peripheral blood.
Contract DA-49-146-XZ-315 came into effect and funded the research from February, 1964 to April, 1969.
Ralph C. Rursiek and Dr. Eugene L. Saenger wrote a
letter, dated May 17, 1965, to Director, Defense
Atomic Support Agency, ATTN: STMD requesting
that NWER No. 03.009 be funded at an estimated
cost of $45,000 for FY65. The overall objective
was to study various phenomena of
desoxyribonucleic acid breakdown and other
abnormalities following whole or partial body
irradiation of human beings. Fifteen patients
were to be studied. The project intended to study
patients for 5-14 days prior to irradiation and
for as long as possible after to evaluate clinical
hematological and psychological changes.
Investigation of the metabolism and urinary
excretion of deoxycytidine was to be continued.
Bone marrow was also to be stored prior to
irradiation. All serum was to be sent to Dr.
Luzzio at Fort Knox.
In 1967 a member of the University of Cincinnati
research team, Dr. James G. Kereiakes, attended an
Atomic Energy Commission sponsored conference at
Oak Ridge, Tennessee. A purpose of the conference
was to refine the dosimetric aspects of whole and
partial body irradiations being used by the
medical community to treat leukemia and widely
disseminated cancers. The aim of the conference
was to standardize the dosimetry being used to
report patient dose. Information developed at the
conference revealed 1,835 patients at about 35
institutions had received whole or partial body
irradiations for the palliation or treatment of
cancers. The use of radiation was widely spread
and acknowledged as an effective modality.
The final contract (DASA-01-69-C-0131), effective May, 1969 funded the research until March, 1972 when the University of Cincinnati refused DASA's offer for additional contract funding.
Dr. Eugene L. Saenger wrote a letter, March 22,
1971, to Dr. Robert Loind, DASA, Attn: STMD. The
cover letter with attachments forwarded the
projects proposal for FY 73. The proposal
requested $70,000 for a study entitled "An
Appraisal of Human Studies In Radiobiological
Aspects of Weapons Effects".
A six page
description of the study's philosophy, the role of
future human research in relation to the remainder
of the radiobiology program, specific areas of
endeavor (eight--clinical evaluation, metabolic
effects, behavioral effects, dose response
studies, partial body studies, prognosis,
therapeutic methods, use of healthy volunteers),
and future plans regarding funding.
Through 1971 DoD ultimately spent over $650,000 on
Dr. Saenger's endeavors which treated 85 adults
whole- or partial-body radiation. Three children
with localized Ewing's tumor were also treated
with whole-body radiation. DOD funds were
provided for laboratory, psychological and
psychiatric tests to assess the effects of varying
doses of whole and partial body irradiation.
funds were paid to the University of Cincinnati
for direct patient care.
The report for the first research period (February
19, 1960 to October 31, 1961) was DASA 1422
Supplement, which was entitled Metabolic Changes
in Humans Following Total Body Irradiation. This
title was used for the reports through 1967. The
report provides a detailed itemization of the
investigations and study projects. The aim of the
studies was "to obtain new information about the
metabolic effects of total body and partial body
irradiation so as to have a better understanding
of the acute and subacute effects of irradiation
in the human." During this period ten patients
received total body irradiation in doses that
ranged from 16 to 150 rads. Patients were selected
for the study were those with "proven metastatic
or far advanced cancer...in relatively good
nutritional status, i.e., able to maintain their
body weight....[and] have normal hematological
values." An explanation of one of the study's
technique stated "the patient is told that he is
to receive treatment to help his sickness. There
is no discussion of subjective reactions resulting
from the treatment. Other physicians, nurses and
ward personnel are instructed not to discuss these
aspects with the patient." The remainder of
report discussed on-going studies, clinical
observations, dosimetry, and other study
techniques supplemented with tables and patient
case histories.
The second report, DASA 1422 reported on the
research from November, 1961 to April, 1963. Ten
patients were treated with total body radiation in
doses that ranged from 150-200 rad during the
report period. The study's statement of aims was
identical to that of the previous report except
that it was expanded. The added aim stated "This
information is necessary to provide knowledge of
combat effectiveness of troops and to develop
additional methods of diagnosis, prognosis,
prophylaxis and treatment of these injuries."
Patient selection criteria was more refined.
addition to those already stated new criteria was
that "patients with lymphoma [were]
excluded... Patients with solid neoplasms not
radiosensitive are sought." The technique
reported previously remained in use. Verbal
consent of the patients was obtained prior to
treatment.
One of the issues the researchers encountered involved complications in trying to determine the
|