ATTACHMENT 6

			RESEARCH REPORT-MEDICAL DIVISION

			Oak Ridge Associated Universities





		      FOR THE YEAR ENDING DECEMBER 31, 1966




	  	         Operating Under Contract With

		    The United States Atomic Energy Commission

NASA Study on Radiation Effects

Retrospective Study on Deleterious Radiation Effects in Man

The great need for more precise knowledge about the radiosensitivity
of man gave rise to a retrospective search for human radiation-
exposure data that could be analyzed by rigidly imposed 
statistical methods. This study, supported jointly by the National 
Aeronautics and Space Administration and the U. S. Atomic Energy 
Commission is now in its third year. The commencement of the Apollo 
program for human exploration of the moon's surface has created 
deadline pressures for completion of the part of the study focused 
on the effects of single and repeated exposures within an eight-day 
period.


Previously we reported two such studies in which first we used only 
data obtained from the hospital records of 100 patients treated at 
the Medical Division of Oak Ridge Associated Universities, and then 
combined that study with similar data obtained from the University 
of Cincinnati and the City of Hope Hospital, Duarte, Calif. We are 
now in process of expanding the study to include a total of about 
1000 such hospital observations. We anticipate that this large 
amount of data will increase the accuracy of our statistical 
analysis so that greater reliance can be placed upon the correctness 
of the estimates now underlying shielding requirements of space 
vehicles. We also expect that correlation of medical and nursing 
observations of untoward changes in this large group of patients 
after the various levels of radiation exposure will enable 
predictions to be made of the kinds and severity of physiologic 
responses to be expected in normal man in certain radiation fields. 
We hope that such knowledge will supply on-ground monitors a basis 
for deciding whether or not an astronaut showing symptoms of 
distress in space is suffering from radiation exposure rather than 
from some other stress.

In the interest of giving our results to date the widest and 
earliest dissemination, the dose-response relations developed for 
symptoms of the human prodromal response were incorporated in 
Chapter 5.2.2 "Prodromal Response" and Chapter 6.0 "Lethality" in 
Space Radiation Hazards, a book to be published soon (March 1967) 
by the National Research Council. National Academy of Sciences under 
the editorship of W. H. Langham and Douglas Grahn (C. C. Lushbaugh 
and G. A. Andrews).

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The responsibility for data storage, retrieval and programming 
analysis has been transferred from the Mathematics Division of Oak 
Ridge National Laboratory to personnel of the Data Processing Center 
of Oak Ridge Associated Universities. The computer facilities of 
ORNL are still required to handle the large volume of data and 
perform the required analyses and statistics evaluations 
(A. S. Gloster and Donna Bibler).

The data under study are from 27 participating institutions that 
have provided 1226 usable patient charts out of 1274 
obtained (Evalyn Reppiinger and Dorothy Voian). At present, 
approximately one-half million dose-correlated reservations are 
in the study, although not all information from all charts has been 
completely encoded. This volume of data required development of an 
efficient data management system to obtain analytic results in 
reasonable time periods. This development has paralleled a search 
for more appropriate statistical methods of data analysis for this 
kind of study. Probit analysis, the method used so far, was neither 
designed nor intended to be used in retrospect so that deviations 
from implied assumptions are not ascertainable with it. Even so, our 
use of probit analysis appears justified by its widespread use in 
experimental radiobiology so that relative comparisons can be made 
between sick and well persons and various species of small and large 
animals. We are also applying methods used in testing of inanimate 
engineering components for reliability and durability. The Weibuil 
density function that describes wear-out failure rather than chance 
failure, predicting the time that any rate of failure will be evident, 
seems most promising, since most symptoms and signs of biological 
distress can be considered as evidence for "wear-out" of a homeostatic 
physiologic system (E. Frome).

The following abstract of one of our studies is included because it 
illustrates one of the many complex problems that must be solved as 
a basis for this program.

During the year, further refinement has been achieved in the 
estimates of doses required for production of specific prodromal 
effects. These new estimates will not be reported in detail here 
because they will be refined still further in the future as larger 
numbers of patients are analyzed.

Dosimetry Used in Equating Various Radiation Exposures for 
Determining Dose-Response Relationships

W. Beck, R. Cloutier and F. V. Comas

The factor that can affect most the validity of our retrospective 
determination of human dose-response relations is the accuracy of 
each dose estimate. The statistical analysis commonly used in such 
studies contains the assumption that the independent variable, dose, 
is known precisely while the biological response may not be accurately 
measured.

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The retrospective study was divided into four phases. Phase I was a 
pilot study of only 100 single exposures of less than 24 hr in 
patients at the Medical Division.1 Phase II was an extension of this 
study to test the feasibility of using data from other hospitals, and 
also included only single radiation exposures.2 Phase III, now being 
completed, includes single and fractionated exposures (greater than 
one day and less than eight days). Phase IV is planned to study 
protracted exposures where exposure time was greater than eight days.

Phase I. Phase I was composed of 93 single-exposure cases of 
therapeutically administered total-body irradiation (TBI) and seven 
cases of accidental TBI. Eighty-four of these were treated with the 
Division's medium-exposure-rate total-body irradiator,3 and the other 
nine were treated with the Division's cobalt-60 temporary irradiator.4

The dose estimates for the 93 patients were based on a dosimetric 
study by Hayes, et al.4 The dosimetric system consisted of an aqueous 
ferrous sulfate solution (Fricke dosimeter) within a plexiglass 
phantom. The absorbed dose to the solution was taken as the patient's 
dose when he was exposed to the same amount of radiation.

Using this technique we determined the whole-body average dose (WBAD), 
and the midepigastric dose for all 93 patients. The WBAD is an estimate 
of the average energy absorbed per gram of tissue, where the average is 
taken for every gram of tissue in the body. The midepigastric dose is 
an estimate of the average energy absorbed per gram in the upper 
abdominal compartment.

The dose estimates for the seven accident cases were determined by a 
mock-up of the accident at its site.5

Phase II. Phase II extended the pilot study by the addition of 11 new 
ORAU cases, 29 from Cincinnati General Hospital, Cincinnati, Ohio, 
and 23 from the City of Hope Medical Center, Duarte, Calif., bringing 
the total number of patients in the study to 163.

The dose estimates for the new ORAU cases were made with the same 
technique described in Phase I. However, all the ORAU dose estimates 
were modified for patient size. The size-correction factors were 
determined from the experimental measurements of the absorbed doses 
in three phantoms representative of an adult, an adolescent and a 
child.

The dose estimates for the Cincinnati and the City of Hope cases were 
based on a comparison of phantom depth-dose measurements made at 
each facility.


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