DOE Openness: Human Radiation Experiments: Roadmap to the Project
DURING 1945 TO 1947, 18 persons were injected with amounts of plutonium at the Manhattan Engineer District Hospital in Oak Ridge, Tennessee, (1 patient), at Strong Memorial Hospital in Rochester, New York (11 patients), at Billings Hospital of the University of Chicago (3 patients), and at the University Hospital of the University of California in San Francisco (3 patients). Excreta were obtained from patients and sent to Los Alamos for plutonium analysis. These data were used to establish mathematical equations describing plutonium excretion rates.
This research was funded by the Manhattan Engineer District; followup studies were supported by the U.S. Atomic Energy Commission and the U.S. Energy Research and Development Administration. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)
Durbin, P.W. Plutonium in Man: A TwentyFive Year Review. Berkeley: Lawrence Radiation Laboratory, UCRL20850, 1971.
Durbin, P.W. APlutonium in Man: A New Look at the Old Data.@Section 7, Chapter 2 in Radiobiology of Plutonium, edited by B.J. Stover and W.S. Jee, pp. 469B530. Salt Lake City: The J.W. Press, 1972.
Langham, W.H., H. Bassett, P.S. Harris, and R.E. Carter. Distribution and Excretion of Plutonium Administered Intravenously to Man. Los Alamos: Los Alamos Scientific Laboratory, LA1151. Republished in Health Physics. Vol. 38, 1980, pp. 1,031B1,060.
Stannard, J.N. Radioactivity and Health: A History. Office of Scientific and Technical Information. 1988, pp. 350B355. "
PATIENTS IN Astate mental hospital were injected with radium as an experimental therapy for mental disorders. The experiment appears to have been conducted at the Elgin State Hospital, in Elgin, Illinois, between 1931 and 1933. Documents indicate that 70 to 450 micrograms of radium226 (Ra226) were injected. This experiment occurred prior to the establishment of the Argonne National Laboratory and the U.S. Atomic Energy Commission. Argonne National Laboratory later collected records and attempted to locate the subjects. Researchers believed that if the patients could be located and body content measurements made in the 1950s, a valid retention curve for radium in humans over several decades could be constructed. Argonne National Laboratory made all later measurements.
The records contain information regarding radium content of the located subjects, medical information relating to the subjects=admission to the hospital, periodic medical examination results, and causes of death and death certificates for deceased subjects. (Previously described in #31 on the original list of 48 experiments released by DOE in June 1994; included in The DOE Roadmap of February 1995, and since revised)
Looney, W.B., R.J. Hasterlik, and A.M. Brues. AA Clinical Investigation of the Chronic Effects of Radium Salt Administered Therapeutically.@American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. Vol. 73, 1955, pp. 1,006B1,037.
Miller, C.E., R.J. Hasterlik, and A.J. Finkel. The Argonne Radium Studies: Summary of Fundamental Data. Chicago: Argonne National Laboratory and Argonne Cancer Research Hospital. ANL7531 and ACRH106.
Norris, Speckman, and Gustafson. AStudies of the Metabolism of Radium in Man.@American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. Vol. 73, 1955, p. 785.
Rowland, R.E., A.F. Stehney, and H.F. Lucas. ADoseResponse Relationship for RadiumInduced Bone Sarcomas.@Health Physics. Vol. 44 (Suppl. 1), 1983, pp. 15B31.
Schlundt, H., J.T. Nerancy, and J.P. Morris, ADetection and Estimation of Radium in Living Persons. IV. Retention of Soluble Radium Salts Administered Intravenously,@American Journal of Roentgenology and Radium Therapy. Vol. 30, 1933, pp. 515B522. "
THIS STUDY was conducted by the Health Division of the Metallurgical Laboratory at the University of Chicago at the University Hospital=s Hematology Clinic (six patients) and at the University of Minnesota (one patient). Five patients were administered 15 to 40 microcuries of phosphorus32 (P32), and two patients were injected with undetermined amounts of P32 in a study of the metabolism of hemoglobin in man. These experiments took place between October 1944 and June 1945. (Previously described in #10 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)
Schwartz, S., E.J. Katz, L.M. Porter, L.O. Jacobson, and C.J. Watson. Studies of the Hemolytic Effect of Radiation. Chicago: Metallurgical Laboratory, CH-3760, July 10, 1946. National Archives and Records Administration, Record Group 326, U.S. Atomic Energy Commission, MED/AEC, Metallurgical Laboratory/Argonne National Laboratory, Classified Correspondence Files, Box 23X, 2 of 4, Folder 651. "
IN MAY 1946, six male employees of the Metallurgical Laboratory of the Manhattan Engineer District in Chicago drank a water solution containing about 0.18 nanocurie of plutonium239 (Pu239). The purpose of this study was to investigate the gastrointestinal absorption and fecal excretion rate of ingested plutonium. Researchers also hoped to use the results to improve the interpretation of previously collected data on persons occupationally exposed to plutonium. Participation in this experiment was voluntary, and the amounts of plutonium ingested were sufficiently low to be barely detectable in urine and feces with instrumentation available in 1946. At least two of the subjects were still alive in 1994. (Previously described in #7 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)
Russell, E.R. Monthly Summary for Biochemical Survey Section. U.S. Department of Energy: Chicago Operations Office, Center for Human Radiobiology, Plutonium Documents, June 20, 1946. "
THIS STUDY WAS CONDUCTED by the Argonne National Laboratory in 1947 in Chicago. Twelve hospital patients were injected intravenously with arsenic76 (As76), administered as potassium arsenite, to study the uptake, retention, distribution, and excretion of arsenic. The subjects included five males and seven females, all between the ages of 18 and 67 years and hospitalized with leukemia, Hodgkin=s disease, polycythemia rubra vera, melanocarcinoma, and carcinoma of the parotid. Amounts of As76 administered were 0.5 to 15.4 millicuries.
This study showed that As76 rapidly distributed throughout the body, failed to localize in tumors or lymphatic tissue, and was rapidly excreted in urine and via the intestinal tract. The study was supported by the U.S. Atomic Energy Commission. The therapeutic administration of As76 trioxide was attempted in 1948 on 19 patients with tumors of the hematopoietic system. This therapy resulted in no significant remission of disease. (Previously described in #11 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)
Jacob, L.O., M.H. Block, E.K. Marks, E. Skirmont, and E. Simmons. Clinical Studies on the Treatment of Leukemia, Hodgkin=s Disease, and Related Diseases with Various Doses of Radioarsenic. Chicago: Argonne National Laboratory, Biology and Medical Divisions, ANL-4227, November 1, 1948, pp. 14B15.
Neal, W.B., L.O. Jacobson, H. Ducoff, and T. Kelly. Arsenic76 Preliminary Studies Progress Report. Chicago: Argonne National Laboratory, Biology Division, CH3830, June 1, 1947, pp. 1B16. National Archives and Records Administration, Record Group 326, U.S. Atomic Energy Commission, MED/AEC, Metallurgical Laboratory/Argonne National Laboratory, Classified Correspondence Files, Box 23, Box 3 of 5, Folder 699. "
THIS STUDY WAS CONDUCTEDat Argonne National Laboratory, in the early 1950s, to test and calibrate a sodium iodide scintillation counter. Three individuals ingested a few microcuries of sodium24 (Na24) and the sodium iodide scintillation counter apparatus was used to determine the gammaray activity of Na24 in the subjects. The three subjects were Argonne employees. (Included in The DOE Roadmap of February 1995)
Marinelli, L.D., C.E. Miller, P.F. Gustafson, and R.E. Rowland. AThe Quantitative Determination of GammaRay Emitting Elements in Living Persons.@American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. Vol. 73, No. 4, April 1955, pp. 661B666. "
IN 1962, A STUDY was conducted on the uptake of thymidine labeled with tritium (H3) by human tumors. This study was a cooperative effort between the Departments of Pathology and Surgery, Northwestern University Medical Hospital, Chicago, and Argonne National Laboratory. Four male patients between the ages of 54 and 69 years old were included in the study. Three were in the terminal stages of various forms of cancer.
All subjects were injected with 10 microcuries of H3labeled thymidine prior to their previously scheduled surgery. Samples consisting of tumor and normal abdominal tissues were removed during surgery and later were analyzed for H3. Samples were also collected during the autopsies of the terminal subjects.
The results showed similar growth in both cancerous and noncancerous cells, a finding that was in agreement with previous animal studies. This project was partly funded by the U.S. Atomic Energy Commission. (Previously described in #9 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)
Baserga, R., G.C. Henegar, W.E. Kisieleski, and H. Lisco. AUptake of Tritiated Thymidine by Human Tumors In Vivo.@Laboratory Investigation. Vol. 11, No. 5, May 1962, pp. 360B364. "
DURING 1943 AND 1944, researchers at the Manhattan Engineer District=s (MED) Metallurgical Laboratory, at the University of Chicago conducted studies of blood changes in patients after total-body irradiation (TBI) at Billings Hospital, University of Chicago, and in volunteer laboratory staff members. A total of 14 subjects ranging in age from 23 to 75 years participated, and were divided into three groups as follows: (Group I) 8 patients (both male and female) with incurable neoplasms; (Group II) 3 male and female patients with generalized, chronic illnesses; and (Group III) 3 normal male volunteers. Subjects were exposed to fields of x-ray radiation at various levels.
Group I subjects each received a single exposure of 27, 60, or 120 roentgens. Group II subjects each received multiple exposures up to a total of 100, 300, or 500 roentgens. Group III subjects each were exposed to a total of 21 roentgens over a period of 3 days. Study subjects were exposed to total-body radiation at various exposure levels specifically to better measure radiation-induced changes in circulating blood at different dose levels and intervals post-exposure. This information was needed to improve the scientific basis for radiation protection of MED workers.
These studies showed that the most consistent effect of total-body irradiation in Groups I and II was the reduction of white blood cells that are formed in lymphoid tissue. No effect was observed in Group III. This latter finding suggested that the existing radiation protection limit for occupational exposure of 0.1 roentgen per working day was protective against directly detectable radiation injury, and that routine monitoring of the blood components would not be a practical method for assessing usual occupational radiation exposures. This work was supported by the Manhattan Engineer District. (This experiment was referenced in the Markey report.)
Nickson, J.J. ABlood Changes in Human Beings Following Total-Body Irradiation.@Chapter in Industrial Medicine on the Plutonium Project, edited by R.S. Stone, New York: McGraw-Hill, 1951, pp. 308B337. "
STUDIES WERE CONDUCTED between 1943 and 1946 at the Manhattan Engineer District=s (MED) Metallurgical Laboratory at the University of Chicago on the effects of radiation, process chemicals, and toxic metals in man. The purpose of these studies was to identify biochemical indicators of tissue damage after excessive exposures. Some of the data used in these studies were obtained by observing the effects of radiation in patients treated for cancer (solid tumors) with external x-rays or with internally administered phosphorus-32 (for polycythemia vera). These were standard procedures for cancer therapy at the time. However, a separate group of four healthy, volunteer Metallurgical Laboratory employees was administered total-body x-rays (30 roentgens at the skin surface) to evaluate various blood changes and other observable biochemical responses.
One of the four subjects received 15 daily exposures of 2 roentgens of radiation from x-rays, while the three others each received 3 daily exposures of 10 roentgens. Adenosine triphosphate (a normal compound in the body that is active in glucose metabolism and energy production) levels were then evaluated in samples of white cells from each subject.
Inconsistent changes in white blood-cell phosphorus were observed among the four subjects after total-body x-ray radiation. The study also included review of various biochemical and tissue-function changes in Manhattan Project workers exposed to different types of radiation and toxic metals during the course of their employment at sites including: Los Alamos, the Metallurgical Laboratory, Iowa State University, Ames, Oak Ridge, and Washington University in St. Louis.
It was concluded that white blood-cell chemistry was an important factor in assessing the radiation sensitivity of workers to radiation, and that a test for urinary excretion of uranium was the best method for determining worker exposures to uranium. This work was supported by the Manhattan Engineer District.
Schwartz, S. ABiochemical Studies Relating to the Effects of Radiation and Metals.@U.S. Atomic Energy Commission Report AECD-2198, Technical Information Division, Oak Ridge, Tennessee, July 1, 1947, p. 18. "
STUDIES WERE CONDUCTED between 1946 and 1948 at Argonne National Laboratory on the tissue localization, metabolism, and excretion of arsenic-76 (As76) in animal and human subjects. The purpose of these studies was to provide a basis for calculating the radiation dose to a particular tissue or organ in preparation for the clinical use of As76.
Two hospital patients (one with Hodgkin=s disease and one with lymphatic leukemia) were administered 2.7 or 3.0 millicuries of As76 as sodium arsenite by intravenous injection. Measurements were then made of the amounts of As76 excreted in urine and feces for 7 days post-injection.
Large differences were observed in the rates of excretion of As76 by human subjects when compared to rates in laboratory animals, suggesting a species-dependent biological retention. Arsenic levels in circulating blood were also determined. A third human subject (a moribund 65-year-old female with carcinoma of the parotid) was given 500 microcuries As76 by intravenous injection 20 hours before death in anticipation of post-mortem tissue studies. The distribution of As76 in liver, kidneys, spleen, and 17 other organs and tissues was determined at time of death. This work was supported by the U.S. Atomic Energy Commission.
Ducoff, H.S., W.B. Neal, R.L. Straube, L.O. Jacobson, and A.M. Brues. ABiological Studies with Arsenic-76. II. Excretion and Tissue Localization.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 69, OctoberBDecember 1948, pp. 548B554.
Straube, R.L., W.B. Neal, Jr., T. Kelly, and H.S. Ducoff. ABiological Studies with Arsenic-76 I. Preparation of Arsenic-76 by Pile Irradiation of Cacodylic Acid.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 69, OctoberBDecember 1948, pp. 270B272. "
IN 1947, RESEARCHERS in the Health Division of the University of Chicago exposed hands of subjects to x-rays in order to identify and examine changes that may occur in the skin of people occupationally exposed to radiation. Fifteen subjects participated in this study. Fourteen subjects were hospitalized cancer patients who were receiving x-ray therapy to parts of their body other than their hands. The other subject was a member of the hospital staff who occasionally prepared radiation materials for patient treatment.
The 14 patients received between 200 and 600 rads of radiation from x-rays to the cuticle of the left fourth finger. The staff member was exposed to radiation from a radium plaque placed on the skin. Skin biopsies were obtained before the treatment and for up to 2 weeks after, and were examined microscopically for radiation-induced changes.
The results indicated that some patients showed temporary reddening of the skin and enlarged or broken blood vessels. No permanent changes to the skin occurred at or below the 600-rad dose level. This study was funded by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)
Nickson, M. Effects of Single Dose X-Ray to the Nail Fold Area of Human Subjects. (Preliminary Report), Chicago: Metallurgical Laboratory, CH-3833, June 20, 1947. "
BETWEEN 1948 AND 1953, studies were conducted at the Departments of Medicine and Surgery at the University of Chicago and Argonne National Laboratory on the value of arsenic-76 (As76) as an internally administered radiotherapeutic agent. The purpose of these studies was to determine the effects of As76 on the hematopoietic (blood-forming) tissues of 24 hospital patients with leukemia, and on the potential effectiveness of As76 as a treatment for several different malignant tumors in an additional 19 patients.
Arsenic-76 (17 to 90 millicuries) was administered intravenously to 24 patients with tumors of the hematopoietic tissues, 2 with polycythemia vera, and 1 with a metastatic carcinoma of the stomach. Arsenic-76 was found to be about as effective as any of the commonly used therapy agents; remissions were induced in some cases of leukemia, multiple myeloma, and metastatic carcinoma.
In a follow-up study, the researchers studied the biological effects of As76 on normal hematopoietic tissues, such as the liver, spleen, and bone marrow. Tissue biopsies were obtained before and after administration of As76 from 19 patients with leukemia, polycythemia vera, and multiple myeloma. The amounts of As76 administered ranged from 12 to 88 millicuries. Patients received one to four As76 injections. Normal tissue biopsies were evaluated for signs of cellular destruction after As76 injection.
Results of these studies showed that As76 occasionally produced cellular damage and decreased cellularity, but there was little evidence of cytolysis or inhibition of cellular proliferation. Results were similar to those observed earlier with nitrogen mustard chemotherapy. This work was supported by the American Cancer Society, the U.S. Public Health Service, and the U.S. Atomic Energy Commission.
Block, M., L.O. Jacobson, and W. Neal. ABiologic Studies with Arsenic-76. III. The Effect of Arsenic-76 Upon the Clinical Course of Patients with Tumors of the Hematopoietic Tissues.@The Journal of Laboratory and Clinical Medicine. Vol. 34, 1949, pp. 1,366B1,375.
Block, M., L.O. Jacobson, and W. Neal. ABiological Studies with Arsenic-76. IV. The Histopathologic Effect of Arsenic-76 Upon the Hematopoietic Tissues of Patients with Leukemia.@The Journal of Laboratory and Clinical Medicine. Vol. 41, No. 4, 1953, pp. 499B515. "
IN THE EARLY 1950S, conducted in the Division of Biological and Medical Research, Argonne National Laboratory compared human excretion rates of injected carbon-14 (C14)Blabeled sodium bicarbonate to rates observed in animals. The purpose was to provide a basis for computation of permissible human doses of this isotopic compound.
Ten microcuries of C14-bicarbonate in isotonic solution were injected into an unspecified number of healthy volunteers. Expired CO2 was collected during the following 3 hours with the subjects at rest, and measured for C14 activity. Ninety-five percent of the radioactivity exhaled as CO2 was eliminated during this period. These results were then compared with isotope excretion data from other species.
It was concluded that a hypothetical intravenous injection of 20 to 40 millicuries of C14-bicarbonate or the inhalation of a comparable amount of C14O2 would be required to give a 70-kilogram man a total radiation dose of 1 roentgen equivalent over his entire life span. The research was supported by the U.S. Atomic Energy Commission.
Buchanan, D.L. AElimination of Intravenous C14 Bicarbonate by Man.@Division of Biological and Medical Research Quarterly Report. Chicago: Argonne National Laboratory, ANL-4571, NovemberBJanuary, 1950B1951, p. 101. "
IN THE EARLY 1950s, scientists at Argonne National Laboratory administered carbon-14 (C14)Blabeled dextran to an unreported number of subjects to determine its metabolic fate. After administration, the patients=urine, feces, and exhaled breath were monitored for tracer C14 and C14O2. The available literature suggested that an isotonic solution containing 6 microcuries per gram was used. The amounts administered are unknown.
The results indicated that human dextran metabolism was similar to dextran metabolism measured in rats and dogs. About 50 percent of the administered dextran was excreted unchanged during the first 3 days, while a large part of that remaining in the animals oxidized into CO2 over a longer period of time. After administration, neither dextran nor any of its metabolic products was excreted by way of the intestinal tract. This work was supported by the U.S. Atomic Energy Commission.
Lathrop, K.A. and J.G. Allen. AProgress Report: Metabolism of Dextran.@Argonne National Laboratory Monthly Progress Report, April 1952. Chicago: Argonne National Laboratory, Biological and Medical Research, Radiological Physics and Health Services Divisions, ANL-4791, items 6400-13 and -20, p. 7.
Lathrop, K.A., and J.G. Allen. AProgress Report: Metabolism of Dextran.@Division of Biological and Medical Research Quarterly Report, NovemberBDecember, 1951. Chicago: Argonne National Laboratory, January 1957, ANL-4745, pp. 60B65. "
A SERIES OF STUDIES was conducted at the Argonne National Laboratory in the 1950s and 1960s to calibrate a whole-body counting apparatus, and to evaluate whole-body counting techniques. In 1955, potassium-42 (K42) was administered orally (or possibly by intravenous injection) to as many as 75 subjects, and whole-body radioactivity measurements were made. Urine samples were also collected and analyzed for K42 content at various times after administration. The amounts administered varied for each group of subjects, but some are known to have received 0.54, 2.0, or 5.0 microcuries. Some of the subjects received multiple doses. Twelve of the subjects have been identified as Argonne employees. Other employees also participated in similar but unreported experiments.
In the mid-1960s, Argonne scientists collaborated with workers at the Department of Medicine of Loyola University Stritch School of Medicine in Hines, Illinois, and with others at the Bionucleonics Department of Purdue University in Lafayette, Indiana, in investigations of the precision of whole-body potassium assays made at Argonne and Purdue University. In this study, 44 healthy subjects participated in whole-body counting studies before and after oral or intravenous administrations of an unreported amounts of K42. Because measurements of the latter were not made until 2 to 5 days (4 to 10 half-lives) after administration and Arelatively high count rates@were reported, the amounts administered may have been very substantial. In other collaborative studies with researchers at Loyola University, 250 microcuries were administered. These investigations were supported by the U.S. Public Health Service and by the U.S. Atomic Energy Commission.
Hukkoo, R.K., and C.E. Miller. ASome Problems of Accurate Measurement of Potassium in Man.@Gamma-Ray Spectroscopy Group Semiannual Report. Chicago: Argonne National Laboratory, Health Division, ANL-6839, JanuaryBJune 1964, pp. 63B78.
Miller, C.E., and L.D. Marinelli. APreliminary Observations on the Potassium Content of the Human Body.@Report on Biological, Medical and Biophysics Programs, Part II, Semiannual Report of the Radiological Physics Division. Chicago: Argonne National Laboratory, ANL5456, July 1955, pp. 120B122.
Miller, C.E., A.P. Remenchik, and W.V. Kessler. APrecision of Assay of Whole-Body Potassium in Man.@Gamma-Ray Spectroscopy Group Research Report. Chicago: Argonne National Laboratory, Health Division, ANL-7461, July 1965BJune 1968, pp. 50B72.
Remenchik, A.P., and C.E. Miller. AThe Measurement of Total-Body Potassium in Man and its Relation to Gross Body Composition.@In Whole-Body Counting, Proceedings, 1961 Symposium. International Atomic Energy Agency, Vienna, 1962, pp. 331B339. "
BETWEEN 1955 AND 1964, measurements of radionuclides in subjects from natural sources and from fallout from atmospheric weapons testing were made at Argonne National Laboratory using the whole-body counter. The whole-body counter was calibrated for potassium measurements by administering known amounts of potassium-42 (K42) to subjects, both Laboratory employees and hospital patients. The whole-body counter was also calibrated for cesium by administering known amounts of cesium-132 (Cs132) to a separate group of hospital patients. The number of subjects and the amounts administered for calibration purposes were not stated. These subjects showered, dressed in activity-free garments, and were then counted for 50-minute measurements. The calibration factors were used over a period of several years to determine trends in fallout uptake. This work was supported by the U.S. Atomic Energy Commission.
Miller, C.E. ACs137 Trends in Humans From 1955 to 1964.@Gamma Ray Spectroscopy Group Semiannual Report. Chicago: Argonne National Laboratory, Health Division, ANL-6839, JanuaryBJune 1964, pp. 79B86. "
IN 1956, nine Argonne National Laboratory employees participated in experiments to study the natural levels of radium in subjects by measuring radon gas exhalation. In order to improve the accuracy of radium estimates, scientists at Argonne National Laboratory sought ways to distinguish between radon produced in the body and radon absorbed by the body from the environment. This required two new experiments: one to measure the amount of atmospheric radon absorbed through the skin, the other to estimate the amount of atmospheric radon that is dissolved in the body.
In the first experiment, two subjects were immersed for several hours in an atmosphere containing elevated levels of radon gas. During the period of exposure, they breathed from a radon-free air supply. The purpose of this experiment was to measure the amount of exhaled radon that might result from the absorption of environmental radon through the skin. One subject was exposed for several hours in a room in which the radon concentration was in the range of 120 to 144 picocuries of radon per liter of air. The same subject was later exposed for several hours while enclosed to the neck in a bag containing 180 picocuries of radon per liter of air. A second subject was exposed for several hours while enclosed to the neck in a bag containing 310 to 340 picocuries of radon per liter air.
In a second experiment, eight subjects, including one who participated in the first experiment, were exposed for either 8 or 72 hours in a room where the radon gas was maintained at elevated levels in the range of 48 to 107 picocuries of radon per liter of air. The subjects=radon exhalation rates were measured at the end of the exposure period in order to provide baseline information for the interpretation of radon exhalation data from subjects exposed to environmental radon.
The goal of both experiments was to provide a measure of the natural radium content of subjects based on the exhalation of radon internally generated from the decay of natural radium. These experiments were funded by the U.S. Atomic Energy Commission.
Lucas, H.F., and A.F. Stehney. ARadon Contamination in the Measurement of Low Levels of Expired Radon. Part II.@Radiological Physics Division Semiannual Report. Chicago: Argonne National Laboratory, ANL-5596, JanuaryBJune 1956, pp. 6B11. "
IN THE EARLY 1970s, investigators at Argonne National Laboratory participated in experiments to study the role of bile acids in gallstone formation. These experiments were conducted through various phases at the Mayo Clinic, in Rochester, Minnesota. The work was part of an effort to determine whether bile acids labeled with tritium (H3) were useful in human metabolic studies and also to determine whether compounds labeled with stable isotopes could be used in the place of radioactively labeled compounds.
Two healthy subjects were injected intravenously with 46 microcuries of chenodeoxycholic acid (a bile acid) labeled with H3 and 10 microcuries of chenodeoxycholic acid labeled with carbon-14 (C14). This series of experiments was conducted to determine the metabolic fate and excretion routes of various labeled bile acids. In another series, bile acids labeled with carbon-13 (C13) and C14 were administered orally to an unknown number of fasting patients. Bile and serum samples were obtained for the evaluation of bile acid content. The purpose was to validate the use of C13labeled bile acids in the measurement against conventional methods based on C14-labeled acids; to validate bile acid kinetic measurements based on serum sampling; and to establish procedures for the simultaneous measurement of all bile acids. The estimated radiation doses to subjects were 2.8 millirems from H3 and 21.0 millirems from C14-committed effective dose equivalent to the whole body.
Both experiments indicated that radioactively labeled as well as stable isotope-labeled bile acids are suitable for kinetic studies of bile acids in humans. Methods using stable isotope labels were intended to increase patient comfort, eliminate the need for hospitalization, and eliminate the use of radioactive tracers for the measurement of bile acid kinetics. The U.S. Atomic Energy Commission, U.S. Energy Research Development Administration, the National Institutes of Health, and the U.S. Public Health Service funded these experiments in conjunction with the Eli Lilly Research Foundation, Eli Lilly and Co., and Mead Johnson and Co.
Cowen, A.E., A.F. Hofmann, D.L. Hachey, P.J. Thomas, D.T.E. Belobaba, P.D. Klein, and L. Tokes. ASynthesis and Biologic Stability in Man of 11,12-H2 and 11,12-H3BLabeled Chenodeoxycholic and Lithocholic Acids.@Division of Biological and Medical Research Annual Report, 1974. Chicago: Argonne National Laboratory, ANL-75-30, 1974, p.186.
Cowen, A.E., A.F. Hofmann, D.L. Hachey, P.J. Thomas, D.T.E. Belobaba, P.D. Klein, and L. Tokes. ASynthesis of 11,12-H2 and 11,12-H3BLabeled Chenodeoxycholic and Lithocholic Acids.@Journal of Lipid Research. Vol. 17, 1976, pp. 231B238.
Cowen, A.E., A.F. Hofmann, D.L. Hachey, P.J. Thomas, D.T.E. Belobaba, P.D. Klein, and L. Tokes. ASynthesis of 11,12-H2 and 11,12-H3BLabeled Chenodeoxycholic and Lithocholic Acids.@Division of Biological and Medical Research Annual Report, 1976. Chicago: Argonne National Laboratory, ANL-77-55, 1976, p. 125.
Klein, P.D., P.A. Szczepanik, K.Y. Tserng, A.F. Hofmann, and P.Y. Ng. AStable Isotope Studies: Measurement of Bile Acid Kinetics in Human Subjects Without Duodenal Intubation; Kinetic Studies of Serum Bile Acids Following Administration of C13-Labeled Bile Acids.@Division of Biological and Medical Research Annual Report, 1975. Argonne National Laboratory, ANL-76-99, 1975, pp. 161B163. "