Chapter 3. Human Radiation Experiments Associated With DOE and Its Predecessors

Introduction

This section contains a listing, description, and selected references for documented human radiation experiments sponsored, supported, or performed by the Department of Energy or its predecessors. The list represents work completed by the Office of Human Radiation Experiments through December 1994, and is a work in progress. Additional experiments will be added as they are identified, documented, and confirmed. The experiment list is available on the Internet and will be updated over time.

This list includes experiments released at Secretary O'Leary's June 1994 press conference, as well as additional studies identified during the six months that followed. Cross-references are provided for experiments originally released at the press conference. Some of the 48 experiments released in June 1994 are not listed here, as continuing research is necessary. In the interest of assembling the most comprehensive information possible, a list of experiments described in the 1986 congressional report entitled American Nuclear Guinea Pigs: Three Decades of Radiation Experiments on U.S. Citizens is provided as an appendix. It should be noted that information about some studies in American Nuclear Guinea Pigs has been updated and included in the current DOE list; further update efforts are ongoing.

The experiment list is available on the Internet and will be updated over time.

Basic guidance for identifying experiments is contained in Executive Order 12891 issued January 15, 1994, and in a January 19, 1994 White House memorandum entitled "Retrieval and Inventory of Records of Human Radiation Experiments." These authorities define human radiation experiments as:

Experiments on individuals involving intentional exposure to ionizing radiation. This category does not include common and routine clinical practices, such as established diagnosis and treatment methods, involving incidental exposures to ionizing radiation;

and

Experiments involving intentional environmental releases of radiation that (A) were designed to test human health effects of ionizing radiation; or (B) were designed to test the extent of human exposure to ionizing radiation.

Criteria for Listing Experiments

Several additional criteria were used in compiling the list. First, clear evidence that an experiment took place was required. Given the fragmented and highly disparate nature of the documentation, this was often a challenge. Many documents refer to proposed studies, and in other cases documents provide inconclusive leads that require further research. The experiments listed below have been confirmed through research in primary and secondary sources.

Second, the list is limited to experiments conducted or supported by DOE, its predecessor agencies, or agency contractors. Starting in the late 1940s, hundreds of hospitals and other institutions did work with scores of radionuclides and radioactively labeled compounds. Much of this work involved human radiation experiments. Yet apart from distributing licenses and isotopes, DOE and its predecessors had no active role in most of these experiments. Yet the agency did operate its own cancer hospitals and other research facilities where human subjects were used in radiation research. Moreover, the agency contracted with universities and other institutions for human radiation research. Such experiments are included.

The third consideration for inclusion on the list was evidence that an experiment involved exposure of human subjects to radiation. Studies involving only human tissue samples were not included. Research involving various drugs, hormones, minerals, or other substances also were not included unless radiation was involved.

In judging if a procedure was a "common and routine clinical practice," the following guidelines were used. A human radiation experiment included any of the following situations where radiation was administered

• without realistic expectation of a benefit to the subject;
• to test or determine the potential usefulness of a treatment for other individuals;
• to healthy human subjects;
• to an individual to calibrate radiation detection instruments.

Several types of procedures did not fall within the scope of human radiation experiments. These included procedures where:

• workers occupationally exposed to radiation were measured for potential internal or external radiation exposure by routine dosimetry, bioassay, or whole body counting methods;
• workers were assayed after accidental internal or external radiation exposures;
• individuals were treated with chelating agents for removal of accidental or occupational internal contamination;
• patients were measured for internal radioactivity as part of a legitimate medical, diagnostic or therapeutic process;
• preexisting internal deposition of radionuclides were assessed, measured, or studied in body fluids, excreta, blood, cells, or tissue samples.

Basic Categories of Human Radiation Experiments

There are several common and recurring categories of human radiation experiments. Tracer studies involved use of radioisotopes as tools to learn more about the properties of other biological compounds, transport pathways, and processes in the body. Tracer studies also involved using isotopes as labeling agents where a drug was labeled with a radioactive isotope, including studies conducted to gain knowledge of the effect of radiation upon humans.

Many of the experimental treatment therapies moved from the experimental stage to the routine. The point at which they ceased to be experimental may be difficult to draw with precision.

All radionuclide metabolism studies in human subjects were considered as human radiation experiments. These tests involved the study or analysis of radioisotope uptake, retention, and excretion, and were done to learn more about the specific behavior of elements in the body.

Biological effects of radiation were often determined during dose response studies.

Radionuclides were used in diagnostic studies to research human physiological conditions, or to calibrate radiation detectors or imaging systems.

Finally, experimental treatments for disease, cancer perhaps the most prominent, involved the use of various radiations and radioactive materials. Over time, many of these therapies moved from the experimental stage to the routine. The point at which they ceased to be experimental may be difficult to draw with precision. The reviewers have used their best judgment in listing those treatments that appear to have been experimental at the time they were administered.

The Process of Identifying Experiments

Several steps were involved in locating and reviewing documentary evidence related to human radiation experiments. To start, DOE Office of Human Radiation Experiments (OHRE) staff other personnel searched records with information of potential value. This selective search covered records in work spaces, offices, Federal Records Centers, the U.S. National Archives, and other archival repositories.

References usually contain fragmentary information, and considerable research in primary and secondary sources is often necessary to verify and describe a specific experiment.

When documents were found that might contain information related to human radiation experiments, the documents were copied and provenanced. Provenancing involves noting the location of the original document (site, series, box, and folder). The copies were sent to OHRE through a document processing facility, the Coordination and Information Center (CIC). The CIC numbered and indexed the documents, optically scanned them, and produced copies for distribution to DOE public reading rooms and other interested parties, including the Advisory Committee on Human Radiation Experiments. About 150,000 pages are included in this system. The basic document indexes are now available electronically, including through the Internet. Work is underway to provide enhanced searching capabilities and access to document images through the Internet World Wide Web.

Many varieties of documents reference experiments. These include reports from laboratories or contract correspondence between researchers and agency officials, researcher notes, medical files, experiment protocols and proposals, and research bibliographies. References usually contain fragmentary information, and considerable research in primary and secondary sources is often necessary to verify and describe a specific experiment. This research involved gathering all documents related to a particular experiment and comparing the information with published journal literature. Much of the information on human radiation experiments was published in the open scientific literature.

Summarizing and Listing Experiments

The experiment summaries provide a concise description of what occurred based on the information that could be found. The focus has been on learning when and where the experiment took place; type and dosage of radiation used; how radiation was administered; why the experiment was conducted; numbers and types of subjects involved; experimental results; and funding sources for the experiment. Each experiment summary is followed by a reference section which lists citations to information sources. In addition, case files have been prepared with information concerning each experiment listed.

Challenges

In preparing this list, and in continuing the work to find experiments, a variety of challenges have been encountered. One issue relates to subject populations. With some exceptions, little evidence exists about how researchers chose experimental subjects or what factors went into such decisions. More details are often available about the composition of subject populations, but information in this area is hardly complete.

Another obstacle is dating: references to experiment dates are often incomplete, as some studies were conducted over several years. Occasionally, the date given in the experiment summary is an estimated date based on available information.

The use of informed consent--or any degree of consent at all--is also very difficult to document for many experiments dating before the standard requirements issued by the National Institutes of Health in 1974. Contemporary professional literature typically did not provide much detail about consent issues, nor do contracts, progress reports, or other information sources.

In addition, it can be difficult to determine the role of the Federal government in some experiments. Studies occurring at AEC research hospitals or other agency facilities have an obvious connection to the Government. Yet experiments done in private hospitals often do not. The AEC provided grants, contracts, and other forms of direct support for human radiation experiments, and examples are included in the list. Funding status, however, is not always clear. Where available, funding information is provided.

Finally, this list does not constitute a comprehensive compilation of all human radiation research in which DOE and its predecessors were involved. As indicated above, the work of collecting, assessing, researching, and confirming continues. "

List of Experiments

Plutonium Injection Experiments

PI-1. Plutonium Injection Studies

During 1945 to 1947, 18 persons were injected with amounts of plutonium at the Manhattan Engineer District Hospital in Oak Ridge, TN (1 patient), at Strong Memorial Hospital in Rochester, NY (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; follow-up studies were supported by the U.S. Atomic Energy Commission and the Energy Research and Development Administration. (This experiment was referenced in the Markey report. See Chapter 2 of this Roadmap for further information about this experiment.)

References

Durbin, P.W. Plutonium in Man: A Twenty-Five Year Review. Berkeley: Lawrence Radiation Laboratory, UCRLB20850, 1971.

Durbin, P.W. "Plutonium in Man: A New Look at the Old Data." Chapter 7.2 in Radiobiology of Plutonium, edited by B.J. Stover and W.S. Jee. Salt Lake City: The J.W. Press, 1972. pp. 469B530.

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, LAB1151. 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, p. 350B355. "

Argonne National Laboratory

ANL-1. Radium as an Experimental Therapy for Treating Mental Disorders at Elgin State Hospital in Elgin, IL

Patients in a state 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, IL, between 1931 and 1933. Documents indicate that 70 to 450 micrograms of radium-226 (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. This information was useful for radiation protection guidelines for alpha particle emitters.

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)

References

Rowland, R.E., A.F. Stehney, and H.F. Lucas. "Dose-Response Relationship for Radium-Induced Bone Sarcomas." Health Physics. Vol. 44 (Suppl. 1), 1983, pp.15B31.

Looney, W.B., R.J. Hasterlik, and A.M. Brues. "A 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.

Norris, Speckman, and Gustafson. "Studies of the Metabolism of Radium in Man." American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. Vol. 73, 1955, p. 785.

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. ANLB7531 and ACRHB106. "

ANL-2. Effect of Phosphorous-32 on Hemoglobin Metabolism in Polycythemia Rubra Vera

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 phosphorus-32 (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)

References

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, CHB3760, 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. "

ANL-3. Plutonium Ingestion Study

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 plutonium-239 (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)

References

Memorandum. E.R. Russell to J.J. Nickson. June 20, 1946. U.S. Department of Energy, Chicago Operations, Center for Human Radiobiology, Plutonium Documents. "

ANL-4. Arsenic-76 Biodistribution and Excretion Studies

This study was conducted by the Argonne National Laboratory in 1947 in Chicago. Twelve hospital patients were injected intravenously with arsenic-76 (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. (Previously described in #11 on the original list of 48 experiments released by DOE in June 1994)

References

Neal, W.B., L.O. Jacobson, H. Ducoff, and T. Kelly. Arsenic-76 Preliminary Studies Progress Report. Chicago: Argonne National Laboratory, Biology Division, CH-3830, 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.

ANL-5. Whole Body Counter Calibration With Sodium-24

This study was conducted at Argonne National Laboratory, in the early 1950s, to test and calibrate a sodium iodide scintillation counter. Three individuals ingested a few microcuries of sodium-24 (Na24) and the sodium iodide scintillation counter apparatus was used to determine the gamma-ray activity of Na24 in the subjects. The three subjects were Argonne employees.

References

Marinelli, L.D., C.E. Miller, P.F. Gustafson, and R.E. Rowland. "The Quantitative Determination of Gamma-Ray Emitting Elements in Living Persons." American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. Vol. 73, No. 4, April 1955, p. 661B666. "

ANL-6. Uptake of Thymidine by Human Tumor

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 H3-labeled thymidine prior to their previously scheduled surgery. Samples consisting of tumor and normal abdominal tissues were removed during surgery. 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)

References

Baserga, R., G.C. Henegar, W.E. Kisieleski, and H. Lisco. "Uptake of Tritiated Thymidine by Human Tumors In Vivo." Laboratory Investigation. Vol. 11, No. 5, May 1962, pp. 360B364. "

Brookhaven National Laboratory

BNL-1. Effectiveness of Iodine-131 in Diagnosing and Treating Graves' Disease and Metastatic--arcinoma of the Thyroid

In 1950, Brookhaven National Laboratory conducted a study on the use of iodine-131 (I131) to treat patients with metastatic carcinoma of the thyroid or with Graves' disease. Patients for the study were sent to Brookhaven from Memorial Hospital in New York City. In the study, a therapeutic dose of 4 to 360 millicuries of I131 was given to patients; the exact dose depended in part on the number of metastases and on previous radiation treatment. Graves' disease patients who were unsuitable for surgical therapy were treated with I131 in doses of 6 to 20 millicuries. The patients were monitored for hematological damage. Metabolic studies were also conducted, including study of the effects of radiation dose on renal tubular function. Twelve patients participated in the study, ranging in age from 15 to 63 years old. Of the 12 patients, 8 were females. The study was conducted in conjunction with the Memorial Hospital and was funded by the U.S. Atomic Energy Commission.

References

Memorandum. L.E. Farr to BNL Committee on Use of Radioactive Isotopes in Human Studies. January 20, 1950. Brookhaven National Laboratory Project HB1. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Memorandum. BNL Committee on Use of Radioactive Isotopes in Human Studies. January 20, 1950. Brookhaven National Laboratory Project HB1. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Farr, L.E. "Observations of Renal Function in Patients Receiving Internally Administered Radioactive Isotopes." from Symposium on Radiobiology, A.A.A.S., Cleveland, Ohio. December 30, 1950. "

BNL-2. Boron Neutron Capture Therapy

Brookhaven National Laboratory conducted boron neutron capture therapy (BNCT) on 45 patients from 1951 to 1961. The patients all were suffering from aggressive and otherwise untreatable types of brain tumors, such as glioblastoma multiforme or malignant glioma; all had received conventional radiation treatments. The purpose of BNCT was to attack more precisely the tumors with radiation, destroying the tumor cells. The patients were injected with a discrete amount of boron that was intended to deposit in the tumor. The tumors were then bombarded with a beam of neutrons that was directed to the boron and thus aimed at destroying the tumor. The results of this therapy were unsuccessful. Patients who were treated with BNCT generally lived only as long as those patients, with the same types of brain tumors, who were treated with conventional radiation therapies.

This work was funded by the U.S. Atomic Energy Commission. Currently, advances in technology allowing for greater precision in this technique have brought about the return of BNCT. As a result, Brookhaven is currently performing the therapy. (BNCT was referenced in the Markey report.)

References

Slatkin, D. N. "A History of Boron Neutron Capture Therapy of Brain Tumors." Brain. Vol. 114, 1991, pp. 1,609B1,629.

Lippincott, S.W., Y. L. Yamamoto, and L.E. Farr, "Radiation Effects of Neutron-Capture Therapy on a Malignant Vascular Neoplasm of the Cerebellum." A.M.A. Archives of Pathology. Vol. 69, January 1960, pp. 44B54.

Farr, L.E., S.W. Lippincott, W. Kahle, W.B. Haymaker, and P. Yakovlev. "The Neuropathological and Topographical Study of Whole Brains Following Neutron Capture Therapy for Glioblastoma Multiforme" in Proc. III Congress Int'l de Neuropathologie, Acta Medica Belgica., 1958, pp. 227B228.

Farr, L.E., J.S. Robertson, and E. Stickley. "Use of the Nuclear Reactor for Neutron Capture Therapy of Cancer" fromInternational Conference on the Peaceful Uses of Atomic Energy. June 23, 1955.

Godwin, J. T., L E. Farr, W.H. Sweet, and J.S. Robertson. "Pathological Study of Eight Patients with Glioblastoma Multiforme Treated by Boron Neutron Capture Therapy Using Boron 10." Cancer, Vol. 8. No. 3, May-June 1955, pp. 601B615.

Farr, L.E., W.H. Sweet, L.B. Locksley, and J.S. Robertson. "Neutron Capture Therapy of Gliomas Using Boron." Transactions of the American Neurological Association. 1954, pp. 110B113.

Memorandum. L.E. Farr. February 26, 1951. Brookhaven National Laboratory Project HB15. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Letter. D.L.Sutherland to L.E. Farr. May 23, 1953. Brookhaven National Laboratory Project HB15. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols. "

BNL-3. Iodine-131 Used to Measure Thyroid Function in Young Children with Nephrotic Syndrome

Scientists at Brookhaven National Laboratory conducted a series of experiments using a group of young children suffering from nephrotic syndrome (kidney disease). In 1951, eight of these children, aged 2 to 6 years, with renal functions varying from 14 to 225 percent normal and with varying degrees of edema or lack thereof, were studied after administration of iodine-131 (I131).

A uniform ability by the thyroid gland to extract radioactive iodine from the blood was noted. The maximum uptake by the gland varied from 30 to 60 percent of the administered doses, which ranged from 3 to 5 microcuries. The data was evaluated against comparable data obtained in normal children. The scientists concluded that there is no impairment of the thyroid gland in its ability to take up iodine in young children with the nephrotic syndrome.

References

Farr, L.E., J.L. Gamble, C.G. Foster, and J.S. Robertson. "Thyroid Function in Young Children with Nephrotic Syndrome." Quarterly Progress Report April 1BJune 30, 1951. Upton: Brookhaven National Laboratory, p. 119. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-4. Radioactive Chlorine, Bromine, and Sodium in Extracellular Fluids

From 1952 to 1953, the total volume of extracellular fluids in 15 humans was studied at Brookhaven National Laboratory. Five chronically ill hospital patients were injected with chlorine-38 (Cl38) and sodium-24 (Na24). Ten other patients were injected with Cl38 and bromine-82 (Br82). Total radiation doses were planned so that the weekly dose limit of 0.3 rad would not be exceeded. Blood samples were drawn at various times after injection and the radioactivity measured. During the course of this experiment, urine, red blood cells, pleural fluid, gastrointestinal fluid, and spinal fluid were also measured for Cl38 and Br82. The subjects were considered to be "normal" for purposes of this study. The U.S. Atomic Energy Commission funded this study. (Previously described in #3 on the original list of 48 experiments released by DOE in June 1994)

References

Gamble, J.L., J.S. Robertson, C.A. Hannigan, C.G. Foster, and L.E. Farr. Chloride, Bromide, Sodium, and Sucrose Spaces in Humans. Upton: Brookhaven National Laboratory, BNLB1326, February 3, 1953. U.S. Department of Energy Archives, Record Group 326, U.S. Atomic Energy Commission, Division of Biology and Medicine, Box 3358, Folder 14. "

BNL-5. Measurement of the Turnover Rate of Sodium in Nephrotic Children Using Sodium-24

Brookhaven National Laboratory conducted an experiment in 1954 on nephrotic children to study the rates of exchange of sodium in edema fluid, in ascitic fluid, and in the blood plasma. Sodium-24 (Na24) as sodium chloride was injected intravenously and the plasma Na24 disappearance curve was analyzed and compared to the Na24 appearance curves in the two fluids. It was found that in both fluids the ratio of (a) the rate of change of the Na24 concentration to (b) the difference between the Na24 concentration in the plasma and that in the fluids increased with time during the first few hours after injection.

References

Robertson, J.S. "The Turnover Rate of Sodium in Edema Fluid and "scites." in Federation Proceedings of the American Society for Experimental Pathology. Vol. 13, March 1954, p. 442.

Robertson, J.S. "The Turnover Rate of Sodium in Edema Fluid and "scites." Quarterly Progress Report April 1BJune 30, 1954. Upton, NY: Brookhaven National Laboratory, p. 50. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-6. Degradation Rate of Iodine-131- Labeled Normal Albumin Using the Whole Body Gamma Spectrometer

In 1954, Brookhaven National Laboratory conducted metabolic studies in humans with I131- tagged serum albumin. In prior studies, plasma protein fractions labeled with I131 had been administered to both normal subjects and to patients. A gamma spectrometer was constructed to determine transfer rates of locally injected I131 serum albumin and other substances tagged with gamma-emitting isotopes.

In this study, the biological half-life of I131-labeled human albumin was determined by two methods. The first method was the calculation from serum and urine samples following injection of 59 microcuries of I131. The second method used the whole body gamma spectrometer to measure the amount of label present in the body at stated intervals following injection of 6.6 microcuries of I131. Plasma-specific activity and urinary excretion were followed up to 60 days following injection. The rate of disappearance of the labeled albumin was measured in two patients. The first was a 49-year-old woman with chronic cystic mastitis; the second was a 40-year-old woman who had previously had a mastectomy. This research was supported by the U.S. Atomic Energy Commission.

References

Lippincott, S.W., S.H. Cohn, J.S. Robertson, and L.E Farr, "In Vivo Measurement by the Whole Body Gamma Spectrometer of the Degradation Rate of I131 Labeled Normal Albumin." Laboratory Investigation. Vol. 10, Pt. 1, May-June 1961, pp. 481B491.

Lewallen, C.G. "Studies in Humans with I131 Serum Albumin." Quarterly Progress Report July 1BSeptember 30, 1954. Upton, NY: Brookhaven National Laboratory, p. 51. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports.

Cohn, S.H. "Whole body Counting." Quarterly Progress Report April 1BJune 30, 1959. Upton, NY: Brookhaven National Laboratory, pp. 41B42. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-7. Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome

This study was conducted at Brookhaven National Laboratory from 1955 to 1956. The subjects were six children in various phases of the nephrotic syndrome, including one child who had recovered from the illness, and nine normal subjects, consisting of 8 men and one woman, all between the ages of 21 and 29. These subjects were given intravenous tracer doses of radioiodinated human plasma albumin and radioiodinated human gammaglobulin. Three of the children were then given intravenous injections of radioiodinated human iron-binding globulin. The amount of activity administered was not to exceed 1.5 microcuries per kilogram of body weight.

The disappearance of specific radioiodinated plasma protein from circulation and its cumulative appearance in the urine were studied; the urinary excretion of nonprotein radioiodine was also investigated. This study was supported by grants from the National Institutes of Health, the United States Public Health Service, the Muscular Dystrophy Association of America, the Playtex Park Research Institute, and the U.S. Atomic Energy Commission.

References

Gitlin, D., D.G. Cornwell, D. Nakasato, J.L. Oncley, W.L. Hughes, and C.A. Janeway. "Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome: The Lipoproteins." Journal of Clinical Investigation. Vol. 37, No. 2, February 1958, pp. 172B184.

Gitlin, D., C.A. Janeway, and L.E. Farr. "Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome: Albumin, Gamma-Globulin and Iron-Binding Globulin." Journal of Clinical Investigation. Vol. 35, January-June 1956, pp. 44B56.

Gitlin, D., C.A. Janeway, and L.E. Farr. "Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome. I. Albumin, Gammaglobulin, and Iron-Binding Globulin." Quarterly Progress Report January 1BMarch 31, 1956. Upton, NY: Brookhaven National Laboratory, p. 52. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-8. Metabolism Studies with Acetate Labeled with Carbon-14

In 1957, at Brookhaven National Laboratory, studies were carried out to investigate carbon acetate metabolism. Forty to 100 microcuries of 1-C14Blabeled acetate or 2-C14Blabeled acetate were intravenously injected into human subjects. Diabetics, who had fasted and were denied insulin on the day of the experiment, served as subjects. Both stable and unstable diabetics were used in this experiment, including a 12-year-old girl who had fasted for 15 hours and had received no insulin on the day of the experiment.

After medical staff administered the intravenous trace dose of C14-labeled acetate, metabolism products as triglycerides, cholesterol, ketone bodies, glucose, pyruvic and alpha-ketoglutaric acids, and carbon dioxide were isolated from the blood, urine, and breath, and analyzed by C14 content. The study was supported by the U.S. Atomic Energy Commission.

References

Hennes, A.R. and W.W. Shreeve. "Hormonal Effects on C14 Acetate Metabolism in the Human." in Proceedings of the Society for Experimental Biology and Medicine. Vol. 100, February 1959, pp. 246B250.

Shreeve, W.W. and A.R. Hennes. "Effect of Adrenal Steroid Hormones on the Metabolic Fate of C14-Labeled Acetate in Human Subjects." Quarterly Progress Report July 1BSeptember 30, 1957. Upton, NY: Brookhaven National Laboratory, p. 36. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports.

Shreeve, W.W. and A.R. Hennes. "Effect of Adrenal Steroid Hormones on the Metabolism of 2-C14-Pyruvate in Diabetic Humans." Quarterly Progress Report July 1BSeptember 30, 1957. Upton: Brookhaven National Laboratory, pp. 36B37. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-9. Metabolic Studies with Manganese-54

In 1957, Brookhaven National Laboratory conducted human metabolic studies with the isotope manganese-54 (Mn54). This study was the first to use Mn54 in human subjects. Manganese had been assumed to participate indirectly in hematopoiesis (blood formation). Two or more patients were injected with Mn54 and followed to determine body surface, blood radioactivity, and excretion rates. Blood taken from one of the patients 66 days after injection contained almost the entire radioactivity in the red cell fraction. This research was supported by the U.S. Atomic Energy Commission.

References

Borg, D.C. and G.C. Cotzias. "Incorporation of Manganese into Erythrocytes as Evidence for a Manganese Porphyrin in Man." Nature. Vol. 182, December 13, 1958, pp. 1,677B1,678.

Borg, D.C., G.C. Cotzias, and M. Birnbaum. "Basic Physiology of Manganese." Quarterly Progress Report July 1BSeptember 30, 1957. Upton, NY: Brookhaven National Laboratory, p. 41. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-10. Magnesium Metabolism Studies in Humans with Magnesium-28

In 1959, Brookhaven National Laboratory used magnesium-28 (Mg28) to study the in vivo distribution and retention function of magnesium in man. Ten adultsC3 males and 7 females--were studied at the metabolic wards of the Brookhaven Medical Research Center Hospital. All but one of the male subjects suffered from hypertension. Nine of the subjects received intravenous injections of the isotope; two were studied after oral administration of Mg28. The intravenous dosages, which ranged from 20 to 104 microcuries, were slowly administered to prevent toxic symptoms. Excretion rates were analyzed by measuring Mg28 in urine and stool specimens. This study was conducted with support from the U.S. Atomic Energy Commission.

References

Silver, L.J. Robertson and L.K. Dahl. "Magnesium Turnover in the Human Studied with Mg28." Journal of Clinical Investigation. Vol. 39, February 1960, pp. 420B425. "

BNL-11. Whole Body Counting Technique Used to Study Turnover of Globulins Labeled with Iodine-131

In 1959, Brookhaven National Laboratory conducted studies on the turnover of beta- and gamma-globulins labeled with iodine-131 (I131). The investigators used both the conventional method of blood and urine sampling and a new technique that used the whole body gamma spectrometer. The new device allowed scientists to measure the retention of labeled globulins over long periods of time following administration of low levels of isotopes, particularly internally deposited gamma emitters.

One patient participated in these studies; he was placed in the whole body counter 34 times. The subject was a multiple myeloma patient who was injected with the I131-labeled globulins on three occasions. The amount of iodine activity in the labeled globulins ranged from 17 to 50.16 microcuries. The study was supported by the U.S. Atomic Energy Commission.

References

Lippincott, S.W., S.H. Cohn, H. Hamel, S. Fine, and S. Korman. "Determination of Radioactively Labeled Globulin Turnover by the Direct Whole body Counting Technique." Journal of Clinical Investigation. Vol. 40, January-June 1961, pp. 697B702.

Lippincott, S.W., W.L. Hughes, and S. Korman. "Turnover of Labeled Globulins as Correlated with Serum Electrophoretic Pattern in Multiple Myeloma." Bulletin of the Medical Department July 1, 1959. Upton, NY: Brookhaven National Laboratory, p. 16. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-12. A Study of Metabolic Pathways of Carbohydrate Formation Using Carbon-14

Studies were carried out at Brookhaven National Laboratory to study the metabolic pathways by which human subjects in various metabolic states form glucose. In this study, the subjects were three men with bronchogenic carcinoma, three male diabetics, and one 13-year-old female diabetic.

On the day of the experiment, the subjects were denied food and insulin and then were injected with C14-acetate. Carcinoma patients received 200 microcuries; diabetic patients received from 40 to 100 microcuries as a single 1- to 2-minute injection. Breath samples were collected and analyzed. Some of these patients participated in multiple studies.

In a related study, two moderately diabetic subjects fasted and were given by mouth 0.5B1.0 grams of C14-labeled ethanol per kilogram of body weight. The blood and urinary glucose were isolated. The results indicated that in one patient about 1 percent as much C14 was present in total body glucose as had been excreted as CO2 after 22 hours. In the other patient about 2 percent as much was present. Both patients had excreted about 25 percent of the total administered C14 by the end of 24 hours. This research was partly supported by the U.S. Atomic Energy Commission.

References

Shreeve, W.W., A.R. Hennes, and R. Schwartz. "Production of C14O2 from 1- and 2-C14-Acetate by Human Subjects in Various Metabolic States." Metabolism. Vol. 8, September 1959, pp. 741B756.

Shreeve, W.W. and M. Conovitz. AA Study of Metabolic Pathways of Carbohydrate Formation in Diabetes by Means of Carbon-14." Quarterly Progress Report July 1BSeptember 30, 1955. Upton, NY: Brookhaven National Laboratory, p. 45. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-13. Analysis of Blood Glucose Following Intravenous Injection of Carbon-14

In 1959, at Brookhaven National Laboratory, diabetic and nondiabetic patients were given intravenous injections of 40 to 150 microcuries of lactate or pyruvate labeled with carbon-14 (C14). The injections were followed by serial analysis of blood glucose for C14 content. Subsequently, glycogen was injected in an attempt to estimate relative glycogen labeling. Seven diabetic and three nondiabetic subjects were used in this study. The effects of insulin, tolbutamide, and glucose load were also studied in the same patients. This study was funded by the U.S. Atomic Energy Commission.

References

De Meutter, R.C. and W.W. Shreeve. "Conversion of DL-Lactate-2-C14 or -3-C14 or Pyruvate-2-C14 to Blood Glucose in Humans: Effects of Diabetes, Insulin, Tolbutamide, and Glucose Load." Journal of Clinical Investigation. Vol. 42, No. 4, 1963, pp. 525B533.

Schwartz, R., R.C. DeMuetter, and W.W. Shreeve. "Dynamics of Bicarbonate Movement and Turnover in Humans." Quarterly Progress Report April 1BJune 30, 1959. Upton, NY: Brookhaven National Laboratory, p. 52. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-14. The Metabolism and Fate of Tritiated Thymidine in Man

This study was conducted in 1959, at Brookhaven National Laboratory as part of an investigation of H3-thymidine as a label for DNA of proliferating cells in vivo and in vitro systems. In this study, H3-thymidine metabolism was studied in selected patients following intravenous injection. All patients were beyond reproductive age and were judged to have short life expectancies. In two control patients with normal hematopoiesis (blood-formation), H3-thymidine rapidly cleared the plasma and distributed in a volume as large as total body water within a few minutes after injection. Two of the subjects selected for this initial investigation were patients with brain tumors, judged to have short life expectancies and to be in hemopoietic equilibrium at the time of study. This research was supported by the U.S. Atomic Energy Commission.

References

Rubini J.R., E.P Cronkite, V.P. Bond, and T.M. Fliedner. "The Metabolism and Fate of Tritiated Thymidine in Man." Journal of Clinical Investigation. Vol. 39, June 1960, pp. 909B918.

Cronkite, E.P., J.R. Rubini, S.A. Killmann, V.P. Bond, J. Bateman, L. Feinendegen, E. Adamik, L. Wood, M. Canner, M. Pavelec, and C. Sipe. "Metabolism of H3-Thymidine and H3-Labeled DNA." Quarterly Progress Report April 1BJune 30, 1959. Upton, NY: Brookhaven National Laboratory, pp. 55B56. Brookhaven National Laboratory, BNL Medical Dept., Bldg. 490, Annual Periodic Reports. "

BNL-15. Study of Carbon-14-Labeled Ascorbic Acid Metabolism

A research collaboration in the early 1970s between Brookhaven National Laboratory and Verwoerd Hospital in Pretoria, South Africa, resulted in a study of ascorbic acid (Vitamin C) labeled with carbon-14 (C14) metabolism in Bantu tribesmen with a disease called hemosiderosis. This disease is similar to scurvy and is common among the South African Bantu. It involves excessive iron accumulation and failure to utilize ascorbic acid. This research was conducted to determine the metabolism of ascorbic acid. Four adult Bantu men who had been diagnosed with hemosiderosis and scurvy participated in this study. Ascorbic acid labeled with carbon-14 was given orally, after which blood samples, urine samples, and respiratory CO2 samples were collected and analyzed. The results indicated that most of the C14 was excreted primarily by respiration and secondarily in the urine. This work was jointly supported by the U.S. Atomic Energy Commission and the South African Atomic Energy Board.

References

Hankes, L.V., C.R. Jansen, and M. Schmaeler. "Ascorbic Acid Catabolism in Bantu with Hemosiderosis (Scurvy)." Biochemical Medicine. Vol. 9, 1974, pp. 244B255. "

Hanford Sites

HS-1. Ingestion of Iodine-131 in Milk by Hanford Employees

In 1963, milk from dairy cows fed iodine-131 (I131) was consumed by eight General Electric/Hanford workers either as a single dose or as several daily doses. During the study, the amount of iodine in the cows' diet was increased from 5 milligrams per day to 2 grams per day. The resulting uptake by the human thyroid was determined in Hanford's whole body counter facility. Participants were Hanford scientists who volunteered to drink the milk and be counted over a period of about one month. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #41 on the original list of 48 experiments released by DOE in June 1994)

References

Watson, E.C., I.C. Nelson, D.H. Wood, R.O. McClellan, and L.K. Bustad. "Effect of Varying Stable Iodine in Diets of Cows Fed I131 on Uptake of I131 in Man Drinking the Milk--An Abstract." in Biology of Radioiodine: Proceedings of the Hanford Symposium on the Biology of Radioiodine, Richland, Washington, July 17B19, 1964. Oxford: Pergamon Press, 1964, p. 339.

Handwritten Monthly Report. J.K. Soldat to R.F. Foster. July 1963. Washington State University Tri-Cities Campus, PNL, DOE Richland Public Reading Room, I131, Open Shelving, PNLB9369BDEL. "

HS-2. Intentional Release of Iodine-131 at Hanford in 1963

In July 1963, Hanford Laboratory conducted a study that involved the release of 120 microcuries of iodine-131 (I131) into the environment. These releases were designed to characterize the dispersion of radiation to the environment. The purpose of the experiment was to enable scientists to study how the radioactive iodine spread in turn through the air, soil, and vegetation, and how it affected animals. Two volunteer human subjects (Hanford employees), were stationed in the expected path of the radiation cloud. These subjects intentionally inhaled I131 from the release and were subsequently measured for thyroidal uptake of I131. These experiments were performed under contract with the U.S. Atomic Energy Commission.

References

Gamertsfelder, C.C. "Plans and Hazard Analysis for the First Hanford I131 Field Release Test." Richland, WA: Hanford Atomic Products Operation, Physics and Instruments Laboratory, HWB78312, July 19, 1963. Washington State University Tri-Cities Campus, PNL, DOE Richland Public Reading Room, I131, Open Shelving.

Handwritten Monthly Report. J.K. Soldat to R.F. Foster. July 1963. Washington State University Tri-Cities Campus, PNL, DOE Richland Public Reading Room, I131, Open Shelving, PNLB9369BDEL.

Monthly Report. Senior Engineer to R.F. Foster. August 23, 1963. Washington State University Tri-Cities Campus, PNL, DOE Richland Public Reading Room, I131, Open Shelving, PNLB9370. "

Idaho Sites

IS-1. Administration of Radioactive Material to Volunteers to Test or Calibrate Analytical Equipment

From 1965 to 1972, as many as 18 employees at the U.S. Atomic Energy Commission's Health Services Laboratory at the National Reactor Testing Station in Idaho voluntarily swallowed radioactive material, or inhaled radioactive noble gases, prior to being placed in whole body counters. The following radionuclides were used in the experiments: Ar41, K42, Mn54, Co60, Zn65, Kr85m, Zr95/Nb95, Ru106, Ag110m, I131, Cs132, Xe133, Cs137, and Ce144. In most of the ingestion cases, the radioactive material was encapsulated in plastic so that no radioactive material was absorbed into body tissues. These measurements were performed to develop and evaluate new whole body-counting equipment and to calibrate that equipment. The whole body-counting equipment was used to measure the amount of radioactivity inside the body of occupational radiation workers exposed to radioactive material. Policies for conducting these experiments limited radiation doses to volunteers to levels below the occupational radiation-protection guidelines in effect at the time. (This experiment was referenced in the Markey report.)

References

Anderson, J.I. and D.G. Olson. "A Rotational Technique for Assessing Quantity and Distribution of Body Radioactivity." Health Physics. Vol. 13, 1967, p. 719.

Olson, D.G. AA Direct Calibration Using Gamma Spectrometry for Measuring Radioactivity in Humans." Health Physics. Vol. 14, 1968, p. 438.

Howard, L.E., J.H. Spikard, and M. Wilhelmsen. "A Human Radioactivity Counter and Medical Van." Health Physics. Vol. 21, 1971, p. 417.

Anderson, J.I. and D.G. Olson. "Computerized Helical Scanning to Determine the Location of Specific Nuclides in the Human Body." Health Physics. Vol. 23, 1972, p. 325.

Sill, C.W. Some Guidelines for Studies Involving Internal Administration of Radioactive Materials to Human Volunteers. Idaho Falls: Idaho Operations Office, U.S. Atomic Energy Commission, IDOB12058, October 1966. "

IS-2. Controlled Environmental Radioiodine Tests (CERT)

Atomic Energy Commission scientists and other professionals at the National Reactor Testing Station in Idaho conducted the Controlled Environmental Radioiodine Tests (CERT) to study the transport of radioiodine through the air-vegetation-cow-milk-human food chain from 1963 through 1968. Five of the 24 CERT tests involved exposure of volunteers to iodine-131 to study the transport of radioiodine to and through the human body.

In the first test--CERT No. 1Cseven individuals consumed milk from a cow that had grazed in a pasture where the radioiodine was deposited, and their uptake of radioiodine was determined by thyroid gland monitoring. Average thyroid dose was 0.39 rad; the maximum thyroid dose was 0.63 rad. In CERT Nos. 2, 7, and 10, three individuals, seven individuals, and one individual, respectively, were reportedly exposed during radioiodine releases over the pasture to determine their uptake by inhalation. The number of individuals involved in a similar inhalation experiment during CERT No. 11 was not listed in published reports; however, whole body-counting logs indicate that 10 individuals were apparently involved. Thyroid doses from inhalation during CERT No. 2 were no greater than 0.015 rad, and the reported thyroid activity observed during CERT No. 7 was about the same as that in CERT No. 2. Thyroid doses to volunteers were not reported for CERT Nos. 10 and 11. The volunteers were employees of the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Hawley, C.A., C.W. Sill, G.L. Voelz, and N.F. Islitzer. Controlled Environmental Radioiodine Tests at the National Reactor Testing Station. Idaho Falls: Idaho Operations Office, U.S. Atomic Energy Commission, IDOB12035, June 1964.

Hawley, Jr., C.A., Editor. Controlled Environmental Radioiodine Tests at the National Reactor Testing Station 1965 Progress Report. Idaho Falls: Idaho Operations Office, U.S. Atomic Energy Commission, IDOB12047, February 1966.

Bunch, D.F., Editor. Controlled Environmental Radioiodine Tests Progress Report Number Two. Idaho Falls: Idaho Operations Office, U.S. Atomic Energy Commission, IDOB12053, August 1966.

Bunch, D.F., Editor. Controlled Environmental Radioiodine Tests, Progress Report Number Three. Idaho Falls: Idaho Operations Office, U.S. Atomic Energy Commission, IDOB12063, January 1968. "

Lawrence Berkeley Laboratory

LBL-1. Treatment of Leukemia With Phosphorous-32

Between 1936 and 1947, patients with various types of leukemia were treated with phosphorous-32 (P32) with and without supplemental x-ray treatments. Approximately 129 patients with chronic myelogenous leukemia and 100 patients with chronic lymphatic leukemia were treated at the Radiation Laboratory and the Donner Laboratory of the University of California in Berkeley and San Francisco. Previously it had been demonstrated that radiophosphorous concentrated in the bone marrow and soft tissue of leukemic mice. Therefore, it was expected that P32 would provide a highly localized radiation source for human leukemic patients.

Both studies employed similar average doses of 1 to 2 microcuries per week for 4 to 8 weeks, although higher doses were also included. Approximately half of the patients studied previously received x-ray treatment. It was found that P32 treatment increased the quality of life for chronic myelogenous leukemic patients, but did not prolong the duration of life. In the case of chronic lymphatic leukemia patients, the quality of life was improved and the duration was prolonged. Based on these findings, an unspecified number of chronic lymphatic patients were treated with P32 through 1960. This research was partly supported by grants from the International Cancer Research Foundation.

References

Lawrence, J.H., R. L. Dobson, B.V.A. Low-Beer, and B.R. Brown. "Chronic Myelogenous Leukemia." Journal of the American Medical Association. Vol. 136, 1948, pp. 672B677.

Lawrence, J.H., B.V.A. Low-Beer, and J.W.J. Carpender. "Chronic Lymphatic Leukemia." Journal of the American Medical Association. Vol. 140, 1949, pp. 585B588. "

LBL-2. Metabolic Studies of Bone Tumors Using Strontium-89

An experiment was conducted in 1942 at the Radiation Laboratory of the University of California, Berkeley, on the uptake of radiostrontium by bone tumors. Strontium-89 (Sr89) was administered to six subjects prior to biopsy or amputation. Tissue samples were collected and analyzed to determine the Sr89 uptake. The subjects consisted of five males and one female, ranging in age from 9 to 54 years. Five of the subjects received intravenous injection solutions which ranged from 326 to 1,462 microcuries. The sixth subject was given 1,183 microcuries of Sr89 orally. This experiment showed that Sr89 had therapeutic value in treating certain types of bone cancers. Some of these cancer patients also received therapeutic amounts of Sr89 (a few millicuries), but details are not available. This research was supported by the Rockefeller Foundation and the Columbia Fund for Medical Physics.

References

Treadwell, A. de G., B.V.A. Low-Beer, H. L. Friedell, and J.H. Lawrence. "Metabolic Studies on Neoplasm of Bone with the Aid of Radioactive Strontium." American Journal of the Medical Sciences. Vol. 204, 1942, pp. 521B523. "

LBL-3. Inhalation Studies Using Carbon

From 1944 to 1945, the Aero Medical Laboratory, University of California, Berkeley and the Department of Physiology, Columbia University, conducted a collaborative study using carbon. The radioactive carbon was used as a tracer to determine whether in the human body carbon monoxide (CO) oxidizes to carbon dioxide (CO2). The subjects consisted of four men, including three of the researchers conducting the experiment. The four men inhaled a relatively large dose of CO labeled with carbon, subsequent to which they breathed oxygen. During this time, their expired CO2 was collected and measured for radioactivity, the presence of which would prove that the human body could convert CO to CO2. Geiger counters were placed over various parts of the body (thigh, chest, spleen, and liver) to measure the uptake and elimination of CO2. The CO oxidized to CO2 by the body amounted to less than 0.1 percent of the CO lost from the blood. This work was supported by the U.S. Atomic Energy Commission.

References

Tobias C.A., J.H. Lawrence, F.J.W. Roughton, W.S. Root, and M.I. Gregersen. "The Elimination of Carbon Monoxide from the Human Body with Reference to the Possible Conversion of CO to CO2." American Journal of Physiology. Vol. 145, No. 2, December 1945, pp. 253B263.

Lawrence, J.H. "Positron Emitting Isotopes: Investigative and Diagnostic Studies," pp. 247B262. Lawrence Berkeley Laboratory, John Hundale Lawrence Files, Accession 434B92B0066, File Code 19B14B6, Carton 15, Folder Positron Emitting Isotopes. "

LBL-4. Inhalation of Zirconium-89 on Smoke Particles

Inhalation studies were conducted at Lawrence Berkeley Laboratory in about 1945 using an active smoke containing zirconium-89 (Zr89). One member of the research team was the only human subject. The purpose of this experiment was to determine the degree of retention by the lungs of very finely divided active smoke suspended in air. The results showed that almost 100 percent of the inhaled activity (about 0.5 microcurie of Zr89) was retained within the lungs and upper respiratory tract. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #30 on the original list of 48 experiments released by DOE in June 1994)

References

Scott, K.G., D. Axelrod, J. Crowley, and J.G. Hamilton. "Deposition and Fate of Plutonium, Uranium and Their Fission Products Inhaled as Aerosols by Rats and Man." Archives of Pathology. Vol. 48, No. 1, July-December 1949, pp. 31B54. "

LBL-5. Radioactive Phosphorous as a Possible Diagnostic Procedure for Breast Tumors

In 1946, the University of California Hospital, San Francisco, employed phosphorous-32 (P32) in tracer studies to develop a new diagnostic procedure for distinguishing between malignant and benign breast tumors. Twenty-five female patients with breast tumors were included in the study. All patients had been scheduled for surgery. Each patient was intravenously administered 300 to 500 microcuries of P32 as sodium phosphate 24 or 48 hours prior to surgery. Surface measurements were made over the tumor and over a control area on the opposite normal breast, 2, 4, 6, and 20 hours after the injection of P32. An increase in counts was found over the surface of malignant tumors, whereas counts were not elevated over benign tumors. The malignancy of the tumor was determined by surgery. Results indicated that P32 might be used as a diagnostic procedure for breast cancer, except for very slow-growing or deep-seated cancers.

References

Low-Beer, B.V.A., H.G. Bell, H.J. McCorkle, R.S. Stone, H.L. Steinbach, and W.B. Hill. "Measurement of Radioactive Phosphorus in Breast Tumors in Situ: a Possible Diagnostic Procedure." Radiology. Vol. 47, pp. 429B496. "

LBL-6. Comparison of the Uptake of Zirconium-95 in Tumor and Normal Tissue

In 1946, at the University of California San Francisco and the Crocker Radiation Laboratory, University of California, Berkeley research was carried out to study the deposition of zirconium in a human subject. The subject, a 55-year-old female patient with a reticulo endothelial tumor that had arisen in the spleen and then metastasized to the liver and left leg, was given a test dose of Zr95. This was administered intravenously as an isotonic saline solution 24 hours prior to a midthigh amputation of the left leg. This subject was administered 1.76 millicuries of Zr95 in saline by intravenous injection 24 hours prior to a scheduled midthigh amputation of the left leg. Samples of the tumor, as well as normal tissue, were later obtained from the limb for Zr95 assay. The tumor was found to have greater uptake of Zr95 than the normal tissues of the body. External counting 2 hours after the Zr95 injection showed that the liver contained about 90 percent of the total measurable deposition and the tumor had about 10 percent of the total deposition. This study was supported by the U.S. Atomic Energy Commission.

References

Low-Beer B.V.A., K.G. Scott, J.G. Hamilton, and R.S. Stone. "Comparative Deposition of Zr95 in a Reticulo Endothelial Tumor to Normal Tissues in a Human Patient." Berkeley: University of California Radiation Laboratory, UCRLB68. "

LBL-7. Autoradiographic Studies of the Distribution of Radiolabeled Lewisite and Mustard Gas on Skin

This experiment was conducted in 1947 at the Crocker Radiation Laboratory, University of California, Berkeley and the University of California Medical School in San Francisco. The experiment sought to determine the distribution of mustard and lewisite in skin and eye tissues. These two chemical-warfare gases were labeled with radioactive sulfur (S35) and radioactive arsenic (As74). Small areas of the skin of four normal subjects were exposed to the two labeled gases. Two experiments were performed with mustard gas labeled with S35. The first involved a 10-minute exposure to 475 micrograms of labeled chemical; the second, a 15-minute exposure to 475 micrograms. In both cases, the exposed area was 0.43 square centimeter and biopsy specimens of these areas were taken 24 hours after exposure.

Two experiments were also performed on lewisite labeled with 10 micrograms of As74; the first involved a 10-minute exposure to 475 micrograms of lewisite; the second, a15-minute exposure to 475 micrograms. The new technique of autoradiography was used to determine the skin layer at which the fixation took place on the biopsied human skin samples. Lewisite was found to fix primarily in the epidermis and mustard gas fixed in both the epidermis and dermis.

References

Axelrod, D.J. and J.G. Hamilton. "Radio-Autograph Studies of the Distribution of Lewisite and Mustard Gas in Skin and Eye Tissues." American Journal of Pathology. Vol. XXIII, 1947, pp. 389B411. "

LBL-8. Injection of Americium-241

On June 10, 1947, at the University of California San Francisco, a 16-year-old Chinese male patient of Chinese Hospital in San Francisco, identified as Cal-A, with osteogenic sarcoma of the left femur, and general metastases, received an intramuscular injection of americium-241 (Am241). Estimated dose is around 0.2 microcurie. The same day, two rats were given intramuscular injections of 1 cc of solution made from the same specifications as the Cal-A injection. Readings of the human subject's urine and feces were collected through at least June 24, 1947. On June 12, 1947, the subject was amputated at the left midthigh. Samples of the amputation tissue were dissected the next day. The samples were read for isotope uptake, as the tumor was expected to have higher uptake than normal body tissues. Studies were made of the tumor; the bone tissue in which the tumor was found; the surrounding tissues, both bone and connective; and the muscles. Measurements from the amputated tissues were compared with the rat data; the patient was discharged on July 27, 1947. Rat data showed considerable uptake by the liver; human data appears to show 13 to 20 percent uptake by the bone. The patient died of preexisting ailments on June 15, 1948. The experiment appears to have been done as a comparison to previous human subjects studies involving plutonium, as data sheets for Cal-A show standards for measurements set against Cal-1 (a human injected with plutonium-238).

References

Lawrence Berkeley Laboratory, Joseph G. Hamilton Records, Archives and Records Office, Folder No: Am H (95H).

LBL-9.Uptake of Iodine-131 in Thyroids of Psychiatric Patients

From July 1949 to April 1950 a cooperative research project was conducted by the Departments of Psychiatry, Radiology and Medicine at the University of California Medical School and the Langley Porter Clinic in San Francisco. The objective of this project was to determine whether thyroid function was normal or abnormal in persons with mental illness. Sixty-five subjects were selected from the regular in-patient group at the Langley Porter Clinic. Among the subjects were patients with schizophrenia, manic-depression, mixed psychoneurosis, and anorexia nervosa. A control group was selected of volunteers from the clinics, clerical, and medical staff. Subjects were injected with 150 microcuries of iodine-131 (I131); subsequently, the concentration of I131 in the thyroid was then measured six times over a 72-hour period. The test and control groups underwent medical and psychiatric evaluations , including serum-bound iodine, basal metabolism, plasma cholesterol, and electroencephalogram. No abnormal thyroid function was found in the group with mental illness and no significant differences were detected between the patients and the controls in this study. This study was partly funded by the U.S. Atomic Energy Commission. (Previously described in #2 on the original list of 48 experiments released by DOE in June 1994)

References

Stone, R.S. Biological Effects of Radiations from External and Internal Sources, Progress Report July 1, 1949 to April 15, 1950. San Francisco: University of California Radiation Laboratory, April 1950. U.S. Department of Energy Archives, Record Group 326, U.S. Atomic Energy Commission, Box 3358, Folder 22.

Bowman, K.M., E.R. Miller, M.E. Dailey, A. Simon, B. Frankel, and G.W. Lowe. "Thyroid Function in Mental Disease Measured with Radioactive Iodine, I131." The American Journal of Psychiatry. Vol. 106, No. 7, February 1950. "

LBL-10. Sodium-24 Uptake Studies on Patients with Rheumatoid Arthritis

During the mid 1940s to the early 1950s, the University of California Lawrence Berkeley Laboratory conducted studies on the uptake of sodium-24 (Na24) to evaluate vascular abnormalities in persons with rheumatoid arthritis. Sodium-24 was administered by intravenous injection, usually in 50-microcurie amounts. Systemic transport of Na24 was followed using two gamma Geiger counters: one in the subject's hand, the other placed under a knee. The results showed an impeded blood flow in diseased areas of the body. Uptake of Na24 in the knee joint was also studied after three patients drank a solution of sodium chloride labeled with Na24 in water.

References

Tobias, C. "Sodium Uptake Studies." Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434B89B100, File Code 10B08B063, Carton 25/38, Folder Sodium Uptake Studies. "

LBL-11. Radiation-Related Studies Involving Inmates at San Quentin Prison

From 1949 to the late 1950s, the University of California conducted studies involving radioactive isotopes using inmates at San Quentin Prison as volunteer subjects. Studies included the following: (a) 1949 to 1951: studies on red blood cell production--Blood was drawn from participants, labeled with iron-59 (Fe59), and reinjected into the respective subjects. Four samples were drawn at specific intervals over the next 2 hours. The procedure was repeated for 4 successive days, during which Fe59-labeled red blood cells were counted. (b) 1950: studies on blood volume--At least 13 participants had blood drawn, labeled with phosphorus-32 (P32), and reinjected. Blood volume in the subject was subsequently measured. (c) late 1950s: Studies on red cell volumeCchromium-51 (Cr51) was used as a label to measure red blood cell volume in 201 healthy participants.

References

Letter. J.H. Lawrence to Mr. J.H. Corley. August 17, 1949. Lawrence Berkeley Laboratory. Administrative Files of Administrative Assistants to the Directors of the Biology and Medicine Division and Donner Laboratory, Accession 434B90B0209, File Code 16B5B22, Carton 2, Folder "Historical Donner Laboratory."

Donner Laboratory Clinical Books, 1946B1977. Patient Sheets from February to March 1950, noted "San Quentin" after patient's name. Lawrence Berkeley Laboratory. Donner Laboratory Clinical Logs and Notebooks, Accession 439B89B0151, File Code 8B2B2, Carton 7/10, Binder No. 2.

Wennesland, R., E. Brown, J. Hopper, Jr., J.L. Hodges, Jr., O.E. Guttentag, K.G. Scott, I.N. Tucker, and B. Bradley. "Red Cell, Plasma, and Blood Volume in Healthy Men Measured by Radiochromium (Cr51) Cell Tagging and Hemocrit." The Journal of Clinical Investigation. Vol. 38, No. 7, July 1959, pp. 1,065B1,077. "

LBL-12. Blood and Tissue Studies With Iron-59

This research was conducted at the Donner Laboratory, University of California at Berkeley, in the early 1950s. The purpose of this study was to investigate the rates and pathways of iron transport in the human body, including the differences in iron turnover rates between normal individuals and patients with anemia. The subjects consisted of 22 individuals with anemia and other diseases and 16 normal individuals. From 5 to 30 microcuries of radioactive iron (Fe59) globulin was injected intravenously to label the circulating plasma iron globulin. External radiation measurements were made on the liver, spleen, and bone marrow using a gamma-fluorescence detector. In addition, plasma and whole blood samples were analyzed for Fe59 content. The results showed that iron turnover rates varied, the exact rate depending on the disease state of the patient. This research was partly funded by the U.S. Atomic Energy Commission.

References

Elmlinger P.J., R.L. Huff, C.A. Tobias, and J.H. Lawrence. "Iron Turnover Abnormalities in Patients Having Anemia: Serial Blood and In Vivo Tissue Studies with Fe59." Acta Haematologica. Vol. 9, No. 2, February 1953, pp. 73B96.

Huff, R.L., C.A. Tobias, and J.H. Lawrence. "A Test for Red Cell Production." Acta Haematologica. Vol. 7, No.3, March 1952, pp. 129B143. "

LBL-14. Studies on the Rate of Uptake of Iodine-131 in the Thyroid

In the early 1950s, studies were conducted at the University of California, San Francisco on various aspects of thyroid function in patients with normal and abnormal thyroid glands. At least 427 subjects were studied; of these, at least 25 healthy individuals served as controls, 122 patients had normal thyroid function, and 110 patients had various thyroid problems. After the subjects drank a solution containing approximately 100 microcuries of iodine-131 (I131), an external gamma counter was placed over the thyroid to measure the uptake of radioiodine. A good correlation was found between high rates of uptake and hyperthyroidism and between lower rates and absence of hyperthyroidism.

Further research was also conducted to study aspects of the physiology of the thyroid and other endocrine glands. Studies were conducted on obese patients, and on adult and child hyperthyroid patients requiring thyroid stimulating hormone. This research was funded by the U.S. Atomic Energy Commission.

References

Miller, E.R., M.E. Dailey, A.V. Holmes, G.L. Alexander, and G.E. Sheline. "Studies with Radioiodine: I. Function and Rate of I131 Uptake of Thyroid." Radiology. Vol. 57, No.1, July 1951, pp. 37B47.

Annual Report of Cancer Activities of the Radiological Laboratory. San Francisco: University of California School of Medicine, 1953, pp.1B9. Special Collections, The Library, University of California, San Francisco. "

LBL-15. Measures of Body Fat and Related Factors in Normal Adults Using Potassium-40 and Cesium-137

From 1950 to 1960, the Donner Laboratory at the University of California, Berkeley, in collaboration with the California State Department of Public Health and the Bureau of Public Health Nutrition, conducted a series of experiments using potassium-40 (K40) and cesium-137 (Cs137) to measure body composition. The experiments were designed to accurately determine the human body's total water content, body fat, protein content, and bone mineral content. In all, 2,301 healthy volunteers were used for these experiments. These individuals each received a letter describing the purpose of the study and the parameters to be measured. The laboratory analyses included measurements of total body water after an oral tracer dose of tritium, analysis of specific gravity by the helium dilution technique, and whole body counting of K40. This study was partly supported by a grant from the National Institutes of Health.

References

Steinkamp, R.C., N.L. Cohen, W.R. Gaffey, T. McKey, G. Bron, W.E. Siri, T.W. Sargent, and E. Isaacs. "Measures of Body Fat and Related Factors in Normal Adults-II." Journal of Chronic Diseases. Vol. 18, 1965, pp. 1,279B1,289. "

LBL-16. Study of Ascitic Fluid Using Tritium-Labeled Water and Phosphorus-32

During 1951 and 1952, the University of California Donner Laboratory and the Highland-Alameda County Hospital, Oakland, CA, conducted experiments to determine the total of ascitic fluids in humans. Tritium (H3) was used to trace the flow of water into, and out from, the peritoneal cavity. Six patients with ascites (a condition characterized by fluid buildup in the peritoneal cavity) were injected with 2 microcuries of tritium-labeled water, either intravenously or intraperitoneally. Samples of blood and ascitic fluid were taken over the following 7 to 24 hours. Blood samples were labeled

with phosphorus-32 (P32) and one cc of the labeled blood was injected into the peritoneal cavity. This study showed that the water content of ascitic fluid entered and left the peritoneal cavity at a very rapid rate. It also showed that the peritoneal surfaces of both normal and diseased subjects reabsorbed large volumes of fluid. This work was supported by the U.S. Atomic Energy Commission and the Life Insurance Medical Research Fund.

References

Prentice, T.C., W. Siri, and E.E. Jones. "Quantitative Studies of Ascitic Fluid Circulation with Tritium-Labeled Water." American Journal of Medicine. Vol. 13, No. 6, December 1952, pp. 668B673. "

LBL-17. A Physiological Study in the Peruvian Andes Using Iron-59

The Donner Laboratory of Medical Physics, University of California, Berkeley, used iron-59 (Fe59) in high-altitude studies similar to the previously conducted studies using tritium (H3). The purpose of these experiments was to investigate the physiology of reduced barometric pressure, particularly as seen in high-altitude flights, and the physiology and treatment of various hematopoietic (blood-forming) disorders, especially polycythemia rubra vera, leukemia, and aplastic anemia. In these studies, reported in 1952, healthy subjects (medical students from the University of San Marcos, Lima, Peru) and native Peruvians in the Andes mountains were studied. Four Andean natives suffering from pulmonary silicosis (as well as high-altitude polycythemia rubra vera) were also studied. A few micrograms of Fe59 were incubated for 20 minutes with 10 to 20 milliliters of the subject's plasma and then injected into the subjects. After injection, Fe59 analysis was made on plasma samples taken at hourly intervals for 4 to 5 hours. Acclimatization to high altitude was found to be related to changes in blood volume, plasma volume, and red blood-cell mass. Post-plasma-iron turnover rates and red cell renewal rates increased to roughly twice their normal values in less than 12 hours at high altitude. This study was supported by the U.S. Atomic Energy Commission, United States Navy and the United States Air Force.

References

Lawrence, J.H., R.L. Huff, W. Siri, L.R. Wasserman, and T.G. Hennessy. "A Physiological Study in the Peruvian Andes." Acta Medica Scandinavica. Vol. CXLII (II), 1952, pp.117B133. "

LBL-18. Studies on the Metabolism of Glycine Labeled With Carbon-14

In experiments reported in 1952 and 1953, nine terminally ill patients received intravenous injections of 100 microcuries of glycine labeled with carbon-14 (C14) in an attempt to determine the urinary excretion of C14, the elimination of C14 in the breath, the tissue distribution levels of C14, and the life span of red blood cells in leukemia and polycythemia rubra vera. For four patients, autopsies were carried out within 12 hours after death. Of these patients, the first was autopsied 57 days after administration of the isotope, the second after 105 days, the third after 152 days, and the fourth after 526 days. The study was conducted by the Section on Experimental Medicine, Donner Laboratory of Medical Physics and the Radiation Laboratory, University of California, Berkeley. It was supported by the U.S. Atomic Energy Commission.

References

Berlin, N.I., B.M. Tolbert, and C. Lotz. "Studies in Glycine-2-C14 Metabolism in Man. II. Tissue Distribution." Journal of Clinical Investigation. Vol. 31, 1952, pp. 335B337.

Berlin, N.I., B.M. Tolbert, and HC Lee. "The Metabolism of Glycine-2-C14 in Man. III. The Urinary Excretion of C14 and Cumulative Radiation Dosimetry." Journal of Clinical Investigation. Vol. 32, 1953, pp. 1B4. "

LBL-19. Astatine--211 and the Thyroid

The objective of this experiment was to test the uptake of astatine-211 (At211) and to evaluate its potential benefits in the treatment of thyroid diseases. Eight human subjects were injected with 50 microcuries of the 7-hour half-life alpha emitter At211). These experiments were conducted at the University of California Hospital during early 1954. (Previously described in #37 on the original list of 48 experiments released by DOE in June 1994)

References

Hamilton, J.G., P.W. Durbin, and M.W. Parrott. "Accumulation of Astatine by Thyroid Gland in Man." in Proceedings of the Society for Experimental Biology and Medicine. Vol. 86, 1954, pp. 366B369.

Hamilton, J.G., P.W. Durbin, and M.W. Parrott. "Comparison of Acute and Chronic Changes Produced in Rats by I131 and At211 at Lethal Levels. Preliminary Data on the Uptake of At211 in Patients with Thyroid Disease." Chapter 24 in Proceedings of the 2nd Radioisotope Conference in Oxford, England, July 1954. London: Butterworth Scientific Publications, pp. 219B231. "

LBL-20. Body Water at Sea Level and at High Altitudes by Tritium Analysis

In 1954, scientists from the Donner Laboratory, University of California, Berkeley, and the Instituto de Biologia Andina, Lima, Peru, used tritium (H3) to determine changes in weight and total body water for subjects living in Lima at high altitudes and at sea level. Two groups of subjects were studied. The first group consisted of 15 young male medical students; the second group consisted of 13 normal male Peruvian Indian mine workers. The tritium was administered both orally and intravenously. The mean values of body water for the two groups was normal for their age range and occupations. This research was supported by the Public Health Service, the U.S. Atomic Energy Commission, and the U.S. Air Force.

References

Siri, W.E., C. Reynafarje, N.I. Berlin, and J.H. Lawrence. "Body Water at Sea Level and at Altitude." The Journal of Applied Physiology. Vol. 7, No. 3, November 1954, pp. 333B334. "

LBL-21. High-Energy Beam Irradiation of Breast Cancer Patients

About 1955, the University of California Radiation Laboratory conducted studies on high-energy proton beam irradiation of the human pituitary gland, using breast cancer patients as subjects. The purpose of the studies was to determine whether irradiation of the pituitary gland would cause regression of tumor growth. Twenty-six patients with metastatic breast carcinoma and ranging in age from 27 to 70 participated in the study. Patients came from all parts of the United States, traveling to the Donner Laboratory in Berkeley for treatment. Cumulative doses ranged from 9,000 to 32,000 rads. During the course of the study, patients were irradiated in small doses three times per week. As the study progressed and the effects were observed, individual and cumulative dose levels were increased, and the time required for the entire course or irradiation was decreased. The first patient received 14,000 rads over a 63-day period. Later patients received as much as 30,000 rads in six sessions within 2 weeks. Pituitary function was assessed by measuring thyroid uptake of radioiodine (iodine-131) and by measuring 24-hour pituitary hormone excretion in the urine. The studies demonstrated decreased pituitary function and both gross and microscopic damage to the pituitary gland. A few of the patients studied showed clinical evidence of improvement. At about the same time, four additional cancer patients were similarly irradiated in a separate study, but results were not reported with those of the breast cancer patients. This work was supported by the U.S. Atomic Energy Commission.

References

Tobias, C.A., J.H. Lawrence, J.L. Born, R.K. McCombs, J.E. Roberts, H.O. Anger, B.V.A. Low-Beer, and C.B. Huggins. APituitary Irradiation with High-Energy Proton Beams: A Preliminary Report." Cancer Research. Vol. 18, No. 2, February, 1958, pp. 121B134. "

LBL-22. Iron-59 Metabolism in Patients with Cancer and Anemic Conditions

Studies were conducted in 1959 at the University of California Lawrence Radiation Laboratory, on the metabolism of iron in humans using iron-59 (Fe59) as a tracer. The aim of these studies was to determine the effects of age, gender, and health status on iron metabolism in humans. Approximately 80 cancer patients and subjects with various anemias, hemochromatosis (a disease characterized by an excessive absorption of iron), and iron deficiencies were used in these studies. The rate of hemoglobin synthesis, mean red-blood-cell life span, and mean time required for hemoglobin formation within the total red-cell volume were measured. Gastrointestinal bleeding was correlated with iron and red cell movement in seven human subjects. This work was supported by the U.S. Atomic Energy Commission.

References

Polycove, M. and J.H. Lawrence. "Iron Metabolism." University of California Lawrence Radiation Laboratory Project Description. June 30, 1959. Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434B92B0154, File Code 19B14B43, Carton 21, Folder Program Book. "

LBL-23. Radionuclide Studies to Determine Bone Marrow Distribution in Man

In the early 1960s, at the Donner Laboratory and the Lawrence Radiation Laboratory, University of California, Berkeley, iron-52 (Fe52), iron-59 (Fe59) and technetium-99m (Tc99m)-sulfur colloids were administered to study marrow distribution. The marrow, liver, and spleen were then imaged, using conventional scanners or scintillation cameras. Administered activities ranged from 3 to 100 microcuries. Samples of bone marrow, plasma, red cells, and liver were analyzed to determine tissue activity over time. Subjects included hospital patients and normal volunteers, including children. This work was supported in part by the U.S. Atomic Energy Commission and in part by a grant from the National Cancer Institute of the National Institutes of Health.

References

Van Dyke D.C., H.O. Anger, and Y. Yano. "Progress in Determining Bone Marrow Distribution In Vivo." Progress in Atomic Medicine. Vol. 2, 1968, pp. 65B84.

Lawrence, J.H. "Positron Emitting Isotopes: Investigative and Diagnostic Studies." pp. 247B262. Lawrence Berkeley Laboratory, John Hundale Lawrence Files, Accession 434B92B0066, File Code 19B14B6, Carton 15, Folder Positron Emitting Isotopes. "

LBL-24. Iron Kinetics and Hemoglobin Synthesis in Human Subjects With Iron-59-Bound Plasma

This study was conducted in about 1959 at the University of California, Berkeley, in collaboration with the Veterans Administration in Boston. Its purpose was to develop a suitable mathematical model of hemoglobin synthesis, using sequential measurements of iron-59 present in human blood plasma, red cells, and peripheral blood. Data were obtained from 13 normal, healthy subjects (1 female and 12 male volunteers) between the ages of 24 and 72 years, plus 6 male hospital patients with endogenous hemochromatosis. Five to 20 milliliters of plasma labeled with 10 to 40 microcuries of iron-59 (Fe59) were intravenously injected into the subjects. Plasma and erythrocyte radioactivity were measured with a scintillation counter. This study was supported by the U.S. Atomic Energy Commission with partial support by a grant from the U.S. Public Heath Service.

References

Pollycove, M. and R. Mortimer. "The Quantitative Determination of Iron Kinetics and Hemoglobin Synthesis in Human Subjects." Journal of Clinical Investigation. Vol. 40, 1961, pp. 753B772. "

LBL-25. Intestinal Iron Absorption Studies Using Iron-52, Iron-55, and Iron-59

In a study conducted at the Donner Laboratory, University of California, Berkeley, in 1966, radioactive isotopes of iron were used to measure the rate of iron absorption into the plasma and its distribution in the gastrointestinal tract. Forty microcuries of iron-52 (Fe52) were administered orally to 6 fasting normal subjects. Just prior to the oral dose, iron turnover studies were performed using 2 microcuries of transferrin-bound iron-59 (Fe59) injected intravenously; the subjects were then whole body counted. For the iron turnover studies, 20 to 30 microcuries of iron-55 (Fe55) were injected into the same subjects. Photoscans of the abdomen using the Anger Positron Camera were taken throughout the study. The maximum rate of intestinal iron absorption was found to occur at the time when iron was in the upper gastrointestinal tract. This work was supported by the U.S. Atomic Energy Commission.

References

Fawwaz, R.A., H.S. Winchell, M. Pollycove, T. Sargent, H. Anger, and J.H. Lawrence. "Intestinal Iron Absorption Studies Using Iron-52 and Anger Positron Camera." Journal of Nuclear Medicine. Vol. 7, 1966, pp. 569B576. "

LBL-26. Chromium-51 Metabolism Studies in Patients with Hemochromatosis

Chromium-51 metabolism studies were conducted at Lawrence Berkeley Laboratory on healthy males and on patients with hemochromatosis (a disease characterized by an excessive absorption of iron). Five normal, male subjects were injected with 100 microcuries of chromium-51 to study the retention of chromium. This study was conducted to show that homochromatic diabetes was due to the exclusion of chromium from either the carrying agent or from the liver because of saturation by iron. Eleven subjects were injected with Cr51-chloride. Among the subjects were patients with varying degrees of hemochromatosis, including two hemochromatotic patients depleted of excess iron and two subjects with excess iron but no clinical disease. All of the subjects were followed by whole body counting for up to 6 months. The results showed that the exclusion of chromium occurs principally at binding sites in the liver. Two further studies were conducted on chromium metabolism using plasma analysis, Cr51 clearance rates, the whole body scanner, and the whole body counter. This work was supported by the U.S. Department of Energy.

References

Sargent T. W. and H.H. Stauffer. "Human In Vivo Kinetics of Radionuclide Trace Metals in Health and Disease." University of California Lawrence Berkeley Laboratory Project Description. May 1, 1976. Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434B32B0154, File Code 19B14B43, Carton 22, UCLBL Project Descriptions.

Lim, T.H., T. Sargent, and N. Kusubov. "Kinetics of Trace Element Chromium (III) in the Human Body." American Journal of Physiology. Vol. 244, Vol. 4, April 1983, pp. R445B454. "

LBL-27. Calcium-47 Retention Studies in Juvenile Diabetics

This research was conducted at the Berkeley Donner Laboratory in the early 1970s. This study was undertaken to determine the rate of uptake and retention of calcium-47 (Ca47) in juvenile diabetics. The subjects consisted of eight healthy individuals, of various ages and diets, and three juvenile diabetics (ages 23, 26, and 26). One to 25 microcuries of Ca47 was intravenously administered and the retention of Ca47 in the whole body was determined by direct in vivo counting. The whole body retention of Ca47 did not significantly vary over the wide range of calcium and protein intakes and ages of healthy subjects. Diabetics excreted Ca47 at a higher rate. This work showed a decreased rate of bone mineralization in diabetics. The research was supported by the Energy Research and Development Administration.

References

Sargent, T., J. Linfoot, and H. Stauffer. "Decreased Whole Body Retention of Ca47 in Juvenile Diabetics." IRCS Medical Science Journal. Vol. 4, 1976, p. 58.

Sargent T. W. and H.H. Stauffer. "Human In Vivo Kinetics of Radionuclide Trace Metals in Health and Disease." University of California Lawrence Berkeley Laboratory Project Description. May 1, 1976. Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434B32B0154, File Code 19B14B43, Carton 22, UCLBL Project Descriptions. "

LBL-28. Whole Body Counting Studies on the Retention of Copper-67 and Phosphorus-32

In the mid- to late 1970s, the University of California Lawrence Berkeley Laboratory conducted studies on the retention of radionuclides in humans. The subjects were healthy individuals and patients with a variety of diseases. The protocol for each study with each isotope was separately approved by the Lawrence Berkeley Laboratory for Safeguards in Human Research on Human Subjects. Four subjects were injected with 100 microcuries of copper-67 (Cu67) to determine copper uptake, retention, and excretion rates. Of the four subjects, three were healthy, and one had a copper storage disease. The results showed that there is no abnormality of total body turnover of copper when iron stores are normal. Results also showed that for the subject with the copper storage disease, the excretion of copper was slower than for normal subjects by a factor of two. Six subjects with diseases related to bone marrow production were injected with 1 to 5 millicuries of phosphorus-32 (P32) to determine excretion rates. This was one of the first published studies on human whole body phosphorus turnover. This work was supported by the U.S. Department of Energy.

References

Sargent, T. W. and H. Stauffer. "Whole body Counting of Retention of Cu67, P32, and Cr51 in Man." International Journal of Nuclear Medicine and Biology. Vol. 6, 1979, pp. 17B21. "

LBL-29. Metabolism of Carbon-14-Labeled Methionine in Schizophrenics

This research was conducted in the 1980s at the Lawrence Berkeley Laboratory. Researchers suspected that a defect in the methyl-carbon metabolic pathway was a causative factor in schizophrenia. Methionine labeled with carbon-11 (C11) or carbon-14 (C14) was administered to both schizophrenics and healthy subjects to test this hypothesis. The oxidation of methionine was studied in seven unmedicated schizophrenics, and the effect of high and low methionine in the diet was studied in control subjects. This research was supported by the National Institute of Mental Health, the Donner Laboratory, and the U.S. Department of Energy.

References

Sargent, T.W., N. Kusubov, S. Taylor, and T.F. Budinger. "Tracer Kinetic Evidence for Abnormal Methyl Metabolism in Schizophrenia." Biological Psychiatry. Vol. 32, 1992, pp. 1,078B1,090.

Sargent, T.W. "Metabolism in Brain Disorders." U.S. Department of Energy Field Task Proposal/Agreement. April 1, 1982. Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434B92B0154, File Code 19B14B43, Carton 21, Field Task Proposals/Agreements.

Sargent, T.W. "Metabolism of [14-C-Methy]-Methionine in Schizophrenia and Affective Disorders." Public Health Service, Food and Drug Administration, Radioactive Drug Research Committee, Report on Research Use of Radioactive Drug Study Summary. Lawrence Berkeley Laboratory, Director's Office--LBL Associated Lab, Director for Administration R&D FilesC1981B1987, Accession 434B91B0176, File Code 13B11B14, Carton 58/58, Folder Biology/Medicine General FY87. "

Lawrence Livermore National Laboratory

LLNL-1. In Vivo Calibration Studies Using Humans Administered Niobium-92m, Barium-133, Palladium-103, Chromium-51, and Strontium-85

The purpose of these studies was to develop accurate calibration factors for in vivo counting equipment and to cross-calibrate the various U.S. and European counting centers. Volunteer subjects were administered radionuclides at Harwell Laboratory (United Kingdom) and were whole-body or chest counted at the Lawrence Livermore National Laboratory and at other Department of Energy contractor in vivo counting facilities in the U.S. Two subjects were from Lawrence Livermore Laboratory and the remainder were from the United Kingdom.

This study was broad in scope and spanned several years. From 1972 to 1976, three males inhaled palladium-103 (Pd103) and chromium-51 (Cr51)-labeled microspheres and were counted in 14 labs in Europe and the United States. From 1979 to 1982, 18 men inhaled niobium-92m (Nb92m)-labeled microspheres and were counted at several labs. During the 1988 to 1990 period, five males, who earlier had inhaled Nb92m, were again exposed to Nb92m and counted. Two of these five were injected with barium-133 (Ba133) in March 1986 and one of those two was injected with strontium-85 (Sr85) in June 1987. This research was jointly sponsored by the Atomic Energy Research Establishment--Harwell, British Nuclear Fuels, the General Electricity Generating Board, the International Atomic Energy Agency, and the U.S. Department of Energy (and its predecessor agencies). (Previously described in #15 on the original list of 48 experiments released by DOE in June 1994)

References

Newton, D., F.A. Fry, B.T. Taylor, M.C. Eagle, and R.C. Sharma. "Intralaboratory Comparison of Techniques for Measuring Lung Burdens of Low-Energy Photon Emitters." Health Physics. Vol. 35, 1978, pp. 751B777.

Dean, P.N., R.V. Griffith, and A.L. Anderson. "Design Criteria for Phantoms for Calibration of External Detectors for the In Vivo Assay of Plutonium." Lawrence Livermore National Laboratory, UCRLB76411, November 17, 1975.

Anderson, A.L. and G.W. Campbell. ALLL Plutonium Lung Counter Calibration and Discussion of Errors." Lawrence Livermore National Laboratory, UCRLB78409, June 20, 1976.

Swinth, K.L., W.J. Bair, P.N. Dean, J. Rundo, and F.K. Tomlinson. "Status and Trends in the External Counting of Inhaled Heavy Elements Deposited In Vivo." Lawrence Livermore Laboratory, UCRLB83949, February 5, 1980.

Newton, D., G.W. Campbell, A.L. Anderson, and J.C. Fisher. "Consistent X-Ray Counting Efficiencies for Plutonium In Lungs, Derived by Independent Methods." Lawrence Livermore Laboratory, UCRLB83946, February 4, 1980.

Campbell, G.W., A.L. Anderson, F.A. Fry, D. Newton, and D. Ramsden. "Calibration of Phoswich Detectors for Assessment of Plutonium in Lungs: The Methods of Four Laboratories Compared." Lawrence Livermore Laboratory, UCRLB84516, June 11, 1980. "

LLNL-2. Ozone Effects on Overall and Regional Lung Function

In this collaboration between the University of Washington (Seattle) and Lawrence Livermore Laboratory, the impact of ozone on the human lungs was studied. The objective was to determine the functional changes that might result from low ozone levels in smog. Four healthy, male subjects were exposed to low (0.4 part per million by volume) concentrations of nonradioactive ozone for a total of 2.5 hours. Periods of exercise and rest were alternated during the exposure. The subjects then inhaled small quantities of radioisotope-labeled gas mixtures for the purpose of measuring lung function. The first mixture was a blend of 20 percent oxygen and 80 percent nitrogen-15 (N15), intended to simulate air. The second mix contained 10 percent carbon-15 labeled carbon dioxide (CO2) in air. The results of this test suggested that ozone caused nonuniform mechanical alteration to the central and peripheral airways. The study was performed under a contract from the U.S. Department of Energy from 1977 to 1978 and in part by a grant from the National Heart, Lung, and Blood Institute. (Previously described in #16 on the original list of 48 experiments released by DOE in June 1994)

References

Meyer, P. "Ozone, Respiration, and the Bends." Energy and Technology Review. Lawrence Livermore Laboratory, UCRLB52000B81B12, December 1981, pp. 22B31.

"Ozone Effects on Overall and Regional Lung Function."Lawrence Livermore National Laboratory Review Board File. LLNL B361 Rm. B940A, Institutional Review Board, IRB Protocol File, Active Grants--Collaborative, University of Washington Ozone Effect on Overall Lung Function. "

LLNL-3. Decompression Sickness Studies Using Nitrogen-15 and Argon-41

A joint study between the Lawrence Livermore National Laboratory and the U.S. Navy was conducted during the 1980s, using the radionuclide tracers nitrogen-15 (N15) and argon-41 (Ar41) to determine information on the uptake and clearance of nitrogen gas in man. This research was necessary to better understand decompression sickness of deep-sea divers, which results from excessive accumulation of inert gases (stable nitrogen and argon) in divers' bodies. More than one experiment was conducted during this collaboration. In one such study, nine normal, healthy human subjects (Navy volunteers) breathed air containing N15 and Ar41 and then waited 40 to 100 minutes to allow redistribution and washout. The subjects were then monitored using positron detectors to determine the concentration of N15 and Ar41 remaining in the body.

The amounts of N15 and Ar41 inhaled depended on the amounts breathed by the subjects. This air contained about one microcurie of N13 and 24 microcuries of Ar41 per liter of breathing air. Absorbed doses to subjects were estimated to be about 0.3 to 0.5 rad to the lungs and trachea and 0.01 rad to the whole body. The experiment met the requirements of both the Navy's and Lawrence Livermore National Laboratory's human subjects committees. This work was supported by the Naval Medical Research Institute and the U.S. Department of Energy. (Previously described in #14 on the original list of 48 experiments released by DOE in June 1994)

References

Weathersby, P.K., P. Meyer, E.T. Flynn, L.D. Homer, and S. Survanshi. "Nitrogen Gas Exchange in the Human Knee." Journal of Applied Physiology. Vol. 61, No. 4, October 1986, pp. 1,534B1,545.

Meyer, P. "Ozone, Respiration, and the Bends." Energy and Technology Review. Lawrence Livermore National Laboratory, UCRLB52000B81B12, December 1981, pp. 22B31. "

Los Alamos National Laboratory

LANL-1. Tritium Studies at Los Alamos Scientific Laboratory

During the early 1950s, Los Alamos Scientific Laboratory conducted studies on the human uptake, distribution, and retention of tritium (H3). Three volunteers, all researchers working on the studies, participated as subjects. In one experiment, a male subject immersed his arm up to the elbow in water containing 0.1 millicurie of tritium per cubic centimeter.

This study showed that the rate of absorption through the skin was too slow to pose a hazard. The whole body would have to be immersed for more than an hour before an Atomic Energy Commission recommended exposure limit was reached. In another study, all three subjects inhaled for 4 to 5 minutes oxygen that was saturated with tritium water vapor (HTO) which, when condensed, contained 1.16 millicuries of tritium per milliliter of water. Results showed that 98B99 percent of the tritium was retained in the body after inhalation.

In a third study, the three subjects drank water containing tritium. Water volumes ranged from 100 to 1,000 milliliters (a to 4 cups) and level of activity ranged from 1,640 to 2,920 microcuries. These studies showed that water absorption from the gastrointestinal tract begins 2 to 9 minutes after ingestion, that absorption is a linear function of time, and that it is proportional to the amount ingested. All these studies were used to establish standards for occupational exposure to tritium. This work was supported by the U.S. Atomic Energy Commission. (These experiments were referenced in the Markey report.)

References

Pinson, E.A. The Body Absorption, Distribution, and Excretion of Tritium in Man and Animals. Los Alamos: Los Alamos Scientific Laboratory, LAB1218, March 12, 1951.

Pinson, E.A. Lung Absorption of HTO by Man Upon Inspiration of HTO Water Vapor. Los Alamos: Los Alamos Scientific Laboratory, LAB1465, June 1952.

Pinson, E.A. The Body Absorption of Ingested Tritium Water and the Water Dilution Volume of Man. Los Alamos: Los Alamos Scientific Laboratory, LAB1464, June 1952. "

LANL-2. Metabolism of EDTA in Humans

In 1953, Los Alamos Scientific Laboratory conducted studies on the human metabolism of the chelating agent ethylenediaminetetraacetic acid (EDTA) labeled with carbon-14. The purpose was to gain information that would help establish optimum dosage schedules and identify any harmful effects. Twelve young adult healthy males served as subjects in four groups of three. One group was administered an intravenous injection of 2.2 milligrams of C14-labeled EDTA; the second received an intramuscular injection of 2.2 milligrams; the third received oral administration of 1.5 milligrams; and the fourth group had 2.0 milligrams applied directly to the skin.

The studies showed that EDTA passed through the body essentially unchanged and that it was excreted primarily by the kidney within 1 hour of intravenous injection and 1.5 hours of intramuscular injection. It is poorly absorbed in the gastrointestinal tract and practically not at all through the skin. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #43 on the original list of 48 experiments released by DOE in June 1994)

References

Foreman, H. and T.T. Trujillo. "The Metabolism of C14 Labeled Ethylenediaminetetraacetic Acid in Human Beings." The Journal of Laboratory and Clinical Medicine. Vol. 43, No. 4, pp. 566B571.

Biomedical Research Group of the Health Division Annual Report 1953. Los Alamos: Los Alamos Scientific Laboratory, LAB1690, 1954, p. 17. "

LANL-3. Radiation Exposure of Aircrews in Mushroom Clouds

During the 1955 TEAPOT and the 1956 REDWING nuclear test series, manned aircraft were used to map the amount and distribution of radiation within some of the resulting "Mushroom" clouds. The objective was to obtain information needed to plan for the safe and effective use of military aircraft in cloud areas during combat operations. Studies conducted in 1953 using animal subjects in drone aircraft had previously shown that it would be safe for manned aircraft to enter atomic clouds relatively soon after detonation. Penetrations of clouds from low-yield detonations were made during Operation TEAPOT in 1955. Penetrations of the larger clouds from high-yield detonations were made during Operation REDWING in 1956. Special radiation exposure limits, in excess of the usual 3.9 roentgens Maximum Permissible Exposure, were established for some of these flight crews. During Operation TEAPOT, 4 Air Force officers were permitted to receive up to 15 roentgens, and 2 received this amount. Exposures of up to 25 roentgens were permitted during Operation REDWING, but no one received this amount; the largest doses were approximately 15 roentgens for three officers. Pre- and postmission urine tests and evaluation in whole body counters showed no significant internal deposition of fission products or unfissioned plutonium. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Headquarters Field Command. "The Radiation Hazards to Personnel Within an Atomic Cloud." Report of Operation UPSHOT/KNOTHOLE Project 4.1. Armed Forces Special Weapons Center, WTB743. Reynolds Electrical and Engineering Co., Inc., Coordination and Information Center, Las Vegas, NV, CIC Document 40992.

Headquarters Field Command. "Manned Penetration of Atomic Clouds." Report of Operation TEAPOT Project 2.8a. Armed Forces Special Weapons Center, WTB1156. Reynolds Electrical and Engineering Co., Inc., Coordination and Information Center, Las Vegas, NV, CIC Document 12800.

Headquarters Field Command. "Early Cloud Penetrations." Report of Operation REDWING Project 2.66a. Armed Forces Special Weapons Center, WTB1320. Reynolds Electrical and Engineering Co., Inc., Coordination and Information Center, Las Vegas, NV, CIC Document 68117. "

LANL-4. Determination of the Survival Time of Red Blood Cells by Chromium-51 Labeling

A study was conducted by Los Alamos Scientific Laboratory in 1957 to determine the survival times of circulating blood red blood cells in healthy and diseased subjects. Thirty-two human subjects (7 healthy and 25 diseased) received intravenous injection of samples of their own red blood cells that had been previously removed and tagged with radioactive chromium-51 (Cr51). After tagging, the red cells were injected back into the donor, and the person's uptake and radioactivity was assessed in the whole body counter. Half-times for the survival of the chromium tag were determined. Large volumes of urine were also obtained from the subjects and counted to determine excretion rates. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #26 on the original list of 48 experiments released by DOE in June 1994)

References

"Application of Low Level In Vivo Counting Techniques to Clinical Investigations." H-Division Progress Report August 20, 1948BSeptember 20, 1948. Los Alamos: Los Alamos Scientific Laboratory, LAMSB790, pp. 62B63. "

LANL-5. Studies of the Metabolism and Excretion of Alkali Metal Radionuclides in Man

Scientists at the Los Alamos Scientific Laboratory conducted a series of studies to determine the metabolism and excretion of alkali metals as part of a general research program on the retention, excretion, and absorption of radioactive materials in humans. Sodium-22 (Na22), potassium-42 (K42), and rubidium-86 (Rb86) were administered orally to 10 normal, healthy human subjects and were measured at various times thereafter in the whole body counter. The distribution and retention patterns for these materials were determined periodically for about 1 year. Radiocesium (Cs134 or Cs137) was also administered and measured. These experiments are described separately, under LANLB8. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #25 on the original list of 48 experiments released by DOE in June 1994)

References

Richmond, C.R. "Retention and Excretion of Radionuclides of the Alkali Metals by Five Mammalian Species." Biological and Medical Research Group of the Health Division Semiannual Report July-December 1959. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2445, 1960, pp. 71B79. "

LANL-6. Absorption and Retention of Orally Administered Iron-59 in Humans

This study was conducted at Los Alamos Scientific Laboratory in 1959. The purpose was to determine the absorption and retention of orally administered iron in human subjects. A second objective was to evaluate the whole body counting technique and equipment as a tool for measuring iron in the human body. Sixty-six subjects were part of this test, including 1 pregnant woman and 4 children. Also included in the study were hospital patients with anemia, leukemia, or polycythemia rubra vera. Each of the study participants ingested 0.5 to 0.7 microcuries of iron-59 (Fe59) as ferrous citrate in water. The oral dose was followed with an additional 100 to 200 milliliters of tap water to wash the radioactive iron into the stomach. Body counting and fecal bioassay were used to determine the relationship between ingested, retained, and excreted iron.

The study showed that there was an apparent lack of iron absorption with leukemia and infection. Also, the pregnant woman absorbed larger amounts of iron. This study was supported by the U.S. Atomic Energy Commission. (Previously described in #40 on the original list of 48 experiments released by DOE in June 1994)

References

Lushbaugh, C.C. and D.B. Hale. "Clinical Applications of Whole body Counting: A Clinical Comparison of the Absorbability of Ferrous versus Ferric Salts in Normal Human Subjects." Biological and Medical Research Group of the Health Division Semiannual Report July 1961BJune 1962. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2780, 1962, pp. 337B347. "

LANL-7. Determining Thyroid Uptake and Retention of Iodine-131

In 1959, Los Alamos Scientific Laboratory conducted studies on whole body measurement techniques for determining thyroid uptake of iodine-131 (I131). Seventeen normal or ill male or female patients ranging in age from 10 to 57 drank water solutions containing 1.5 to 3.0 microcuries of I131 as sodium iodide. Study results showed that the whole body liquid scintillometer measurement technique provided a simple, valid means of determining thyroid uptake and thyroid function. Additional studies were conducted to address how thyroid retention changed with disease, chemotherapy, and metabolic status. These studies involved some of the same patients, but added others, as well. Six children whose thyroid gland had been removed were added, as was one patient with an overactive thyroid and one patient with an underactive thyroid. A total of 63 patients were administered I131 either orally or intravenously in these studies. These studies showed that retention rates in diseased patients varied widely from normal rates, and that retention was influenced by therapy. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #45 on the original list of 48 experiments released by DOE in June 1994)

References

Lushbaugh, C.C. and P.S. New. "Clinical Applications of Whole Body Scintillometry. II. A Comparison of Three Different Methods of Determining Retention and Thyroid Uptake of Orally Administered I131." Biological and Medical Research Group of the Health Division Semiannual Report July-December 1959. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2445, 1960, pp. 348B360.

Lushbaugh, C.C. and D.B. Hale. "Clinical Applications of Whole Body Scintillometry. III. Whole Body Retention of Iodine-131 as a Method of Studying Thyroid Function in Man." Biological and Medical Research Group of the Health Division Semiannual Report July-December 1959. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2445, 1960, pp. 361B373. "

LANL-8. Long-Term Retention of Cesium-134 and Cesium-137 in Humans

From about 1959 to 1961, a study was conducted at the Los Alamos Scientific Laboratory on the long-term retention of radioactive cesium (Cs) in humans. Four healthy, adult males participated in this study. Two of subjects received oral doses of 1 and 1.4 microcuries cesium-134 (Cs134) as cesium chloride. The subjects were followed by whole body counting for 106 and 910 days, respectively, to determine the gastrointestinal tract uptake and whole body retention with time. The other two subjects were administered about 1 microcurie Cs137 and were followed by whole body counting for about 500 days. This study showed that the biological retention half-time of cesium in man was about 137 days. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #25 on the original list of 48 experiments released by DOE in June 1994)

References

Richmond, C.R., J.E. Furchner, and W.H. Langham. "Long-Term Retention of Radiocesium by Man." Biological and Medical Research Group of the Health Division Semiannual Report January-June 1961. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2627, 1961, pp. 163B174. "

LANL-9. Study of the Retention and Excretion of Iodine-131

A study was performed at Los Alamos Scientific Laboratory, in 1960 to determine the retention and excretion of iodine-131 (I131) by humans. Twenty-six normal subjects, including 17 women, 3 men, 3 girls, and 3 boys, participated in the study. Each volunteer was given an oral dose of liquid containing 8 microcuries of I131 as sodium iodide, then measured for whole body and thyroid content of I131 within 1 hour. Additional measurements were made on the 1st, 2nd, 3rd, 4th, 7th, 10th, 14th, and 18th days following the ingestion. This study showed that approximately 20 percent of the ingested I131 was taken up by the thyroid gland, and the remaining 80 percent excreted by the kidneys by the urine. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #19 on the original list of 48 experiments released by DOE in June 1994)

References

Lushbaugh, C.C., D.B. Hale, and C.R. Richmond. "Clinical Applications of Whole Body Scintillometry. IV. Turnover Rate of Protein-Bound Iodide." Biological and Medical Research Group of the Health Division Semiannual Report January-June 1960. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2455, 1960, pp. 364B371. "

LANL-10. Absorption and Uptake of Iodine-131 and Sodium-24 in Humans

In 1960, an experiment was conducted at Los Alamos Scientific Laboratory to determine the feasibility of in vivo measurements to study the absorption of radionuclides through the skin. Liquid solutions of sodium-24 (10 microcuries) or iodine-131 (51 microcuries) were placed on the palms of two volunteer subjects employed at the Laboratory. After allowing absorption to occur, the palms were washed and the subjects were counted periodically in the Laboratory's whole body counter to determine the fraction of either radionuclide absorbed through the skin.

In a second experiment, two volunteer subjects ingested 0.18 microcurie of sodium-24 or 0.14 microcurie of iodine-131 to determine the gastrointestinal absorption and whole body retention of these radionuclides. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #27 on the original list of 48 experiments released by DOE in June 1994)

References

Van Dilla, M.A. , C.R. Richmond, and J.E. Furchner. "Cutaneous Absorption by Human Subjects, I. Studies with Sodium-24 and Iodine-131." Biological and Medical Research Group of the Health Division Semiannual Report July-December 1960. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2526, 1961, pp. 164B171. "

LANL-11. Retention of Iodine-131 in Subjects with Inflammatory Liver Disease

In 1960, a study was conducted at Los Alamos Scientific National Laboratory on the use of an iodine-131 (I131) labeled blood dye in determining liver function. Ten normal subjects and 18 persons suffering from inflammatory hepatic disease were injected intravenously with 10 microcuries of I131-labeled dye (rose bengal). The time-activity curves for retention of I131 in the blood stream were determined using the Los Alamos arm counter. The blood retention curve was found to be a better measurement of function than the clearance rate of labeled rose bengal dye measured in urine. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #28 on the original list of 48 experiments released by DOE in June 1994)

References

Lushbaugh, C.C., D.B. Hale, and R. McGill. "The Use of the Arm Counter to Determine the Degree of Hepatic Function."Biological and Medical Research Group of the Health Division, Semiannual Report January-June 1960. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2455, 1960, pp. 223B229. "

LANL-12. Gastrointestinal Passage of Radioactive Particles

In the early 1960s, Los Alamos Scientific Laboratory conducted studies on the passage of radioactive particles through the human gastrointestinal tract. These studies addressed the issue of reentry and destruction of nuclear-powered space vehicles in the earth's atmosphere and subsequent ingestion of the resulting particles by humans. Fifty-seven normal adults participated. Each swallowed a gelatin capsule containing three radioactive particles. One particle was ceramic, about 150 microns in diameter, and contained approximately 150 picocuries of manganese-54. The other two particles were uranium carbide, about 175 microns in diameter, and contained an unspecified amount of uranium-235 activity.

The total calculated radiation dose delivered to the gastrointestinal tract in these studies was extremely low-- well below the maximum permissible level for these materials. Several subjects repeated the ingestion at different times of day to estimate the time-of-day variable in the study. One subject repeated the test 10 different times to estimate the variation within a single individual. The studies showed that particle density did not influence passage rate and that there was no significant holdup of particles in the digestive system. Transit times corresponded more to bowel movement habits than a normal distribution. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Some Biological Aspects of Radioactive Microspheres. Los Alamos: Biological and Medical Research Group, Los Alamos Scientific Laboratory, LAB3365BMS, June 20, 1965. "

LANL-13. Metabolism of Zinc-65 in Human Leukemia

A study was conducted at Los Alamos Scientific Laboratory in early 1961 on the metabolism of zinc-65 (Zn65) in human cancer patients with chronic leukemia. This experiment involved a single subject. A 15-year-old female patient with chronic myelogenous leukemia was given a oral dose of 0.6 microcurie of zinc-65 (Zn65) as zinc chloride 137 days prior to death. One hour after administration and on days 1, 2, 3 ,20, and 137 the subject was studied for whole body Zn65 in the Los Alamos human counter. Also, tissue samples were removed at autopsy and sampled for zinc-65. The findings of this study showed that Zn65 was retained less tenaciously by the leukemia patient than by normal subjects. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #32 on the original list of 48 experiments released by DOE in June 1994)

References

Richmond, C.R., J.E. Furchner, and G.A. Trafton. "Long Term Retention of Zinc-65 by Man." Biological and Medical Research Group of the Health Division Semiannual Report July-December 1960. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2526, 1961, pp. 15B20.

Furchner, J.E., C.R. Richmond, and G.A. Trafton. "Metabolism of Zinc-65 in Humans." Biological and Medical Research Group of the Health Division Annual Report July 1961BJuly 1962. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2780, 1962, pp. 66B77.

Furchner, J.E. and C.R. Richmond. "Effect of Dietary Zinc on the Absorption of Orally Administered Zn65." Health Physics. Vol. 8, 1962, pp. 35B40.

Richmond, C.R., J.E. Furchner, G.A. Trafton, and W.H. Langham. "Comparative Metabolism of Radionuclides in Mammals-I: Uptake and Retention of Orally Administered Zn65 by Four Mammalian Species." Health Physics. Vol. 8, 1962, pp. 481B489.

Richmond, C.R., C.C. Lushbaugh, M.W. Rowe, and M.A. Van Dilla. "Metabolism of Zinc-65 in a Terminal Leukemia Case." Biological and Medical Research Group of the Health Division Semiannual Report January-June 1961. Los Alamos: Los Alamos Scientific Laboratory, LAMSB2627, 1960, pp. 263B269. "

LANL-14. Iodine-131 Used to Determine Thyroid Uptake Measurement Techniques

In 1961, Los Alamos Scientific Laboratory conducted studies intended to improve the accuracy of whole body counting techniques for determining thyroid uptakes. Previous experience had shown that body mass influenced overall absorption and affected the accuracy of thyroid uptake measurements. An unspecified number of subjects received oral administration of 8 microcuries of iodine-131. A "mock iodine" mixture of barium-133 and cesium-134 equal to 2.48 micro