THE THYROID STUDIES A Follow-up Report on the Use of Radioactive Materials in Human Subject Research that Involved Residents of State-Operated Facilities within the Commonwealth of Massachusetts from 1943 through 1973 Submitted by THE WORKING GROUP ON HUMAN SUBJECT RESEARCH to Phillip Campbell, Commission Commonwealth of Massachusetts Executive Office of Health & Human Services Department of Mental Retardation June 1994 TABLE OF CONTENTS Introduction Metabolic Thyroid Studies STUDY 1: Thyroid Function in Persons with Myotonia Dystrophica STUDY 2 & 3: Thyroid Function in Persons with Down Syndrome-Fernald Thyroid Function in Persons with Down Syndrome-Wrentham Nuclear Fallout Thyroid Study STUDY 4: Minimal Dosage of Iodide Required to Suppress Uptake of Iodine 131 by Normal Thyroid - Wrentham Radiation Experts Opinions on Dosages & Risks How Was Consent Sought? Including Copies of Archival Records Found Findings & Recommendations ACKNOWLEDGEMENTS Special thanks and recognition goes to: The Follow-up Working Group - members of the original Task Force on Human Subject Research that agreed to stay on as advisors to the final stage of research and reporting: Dr. Mary-Lou Buyse Dr. Allen Crocker, Program Director Medical Director Developmental Evaluation Center Fernald State School Boston Children's Hospital Dr. Anne Hoard Rev. Dr. Richard Robison Professor Director of Community Relations Fitchburg State College Department of Mental Retardation Peter O'Meara - Facility Director at Fernald and Project Manager for the Task Force on Human Subject Research Nick D'Alusia - Facility Director at Wrentham & Linda McCarthy, Director of Client Services at Wrentham Members of the Social Work Departments at Fernald and Wrentham Schools Peter Brand Joseph Foley Karen Liazos Linda Gershman Paula Potvin Joan Ricketts Those persons who were willing to serve as advisors on a frequent or infrequent basis to the Follow-up Working Group and offer their time, skills and technical assistance to the completion of this work: Margaret Dale Dr. Louis Lasagna Associate Dean for Bioethics Faculty Affairs TUFTS University Harvard University Medical School Ellen Anderson Johannah Dwyer Research Specialist Director, Francis Stern Nutrition Massachusetts General Center Hospital Thyroid Center Tufts University School of Medicine Grant Carrow Dr. Phillip Reilly Deputy Director Director Bureau of Environmental The Shriver Center Monitoring Massachusetts Department of Public Health MaryEllen Collins, RD Kristy Hendrick Director, Department of Nutrition Center Nutrition TUFTS University Brigham & Women's Hospital Some extraordinary individuals who offered extraordinary support Jim McInnis Bonnie Stecher Paul Proccocino Helen Samuels Susan Ford & Penny Ford Carlton Helen Hickery Bruce Gale Heartfelt gratitude goes out to you all. Doe West Project Coordinator THE TASK FORCE ON HUMAN SUBJECT RESEARCH Frederick M. Misilo Jr., Esq. Chairperson Dr. Mary Louise Buyse Doris Manson Medical Director, Fernald School Parent & Advocate Dr. Allen Crocker Rep. Edward J. Markey Governor's Commission on MR U.S. House of Representatives Dr. Gunnar Dybwad George Mavridis Professor Emeritus, Brandeis Family Member & Advocate Charles Dyer The Rev. Richard Robison Former member, The Science Club Parent & Advocate Dr. Anne Howard Virginia Tisei, Esq. DMR Statewide Advisory Committee Family Members & Advocate Richard Krant The Rev. Doe West Parent & Advocate Advocate & Project Coordinator Austin LaRocque David White-Lief, Esq. Former member, The Science Club Chair, Human Rights Committee 1 INTRODUCTION Please Note: This report is a follow-up study to the Task Force on Human Subject Research's original study entitled "A Report on the Use of Radioactive Materials in Human Subject Research that Involved Residents of State-Operated Facilities within the Commonwealth of Massachusetts from 1943 through 1973." This introduction will only briefly touch on the steps taken in that investigation. For an in-depth look at this process and those findings please see the original report. Copies are on file at the State Archives in Massachusetts, the Library of Congress in Washington, DC, the Boston Public Library, the Newton Free Library and the Howe Library at Fernald School. In the spring of 1993, President Bill Clinton directed federal agencies to implement a post-Cold War declassification process that would allow citizens to gain access to archival records that had previously been denied to them. The Department of Energy (DOE) initiated a massive release of documents for public inspection beginning in the summer of 1993. Subsequently private citizens, advocacy groups, and the press began to review these declassified records and make public many previously unknown, or little-know, experiments and research studies that had used radioactive materials throughout the United States. In November 1993, the Albuquerque Tribune of New Mexico printed a series of articles by Eileen Welsome that detailed research dating back to the 1940s which involved the injection of plutonium into human subjects. The reporting of these events was a catalyst for the establishment, by President Clinton, of the President's Advisory Committee on Human Radiation Studies and its Human Radiation Interagency Working Group. In December 1993, the Boston Globe published an article written by Scott Allen in which he identified the Walter E. Fernald School as one of the institutions in Massachusetts where radioactive material was administered to residents by researchers from the Massachusetts Institute of Technology (MIT). It was reported that young male residents of Fernald, who were members of a "Science Club", were used as subjects in nutritional studies using radioactive materials in the 1940s and 1950s. Out of concern for the nature of the facts revealed in the Globe article, the identified institutions stated publicly that their current staff was unaware of these studies. The institutions also pledge their commitment to work cooperatively and openly to respond to the need for full and accurate public reporting. 2 Following the initial meetings to plan a course of action for an objective and immediate review, Philip Campbell, Commissioner of the Department of Mental Retardation (DMR), created the Task Force on Human Subject Research to design and conduct this comprehensive study. Their charge was to secure all available facts on such studies within the facilities operated by the Commonwealth of Massachusetts. In April 1994 a final report was published that outlined all of the findings of the study. The report included an appendix that reproduced some of the archival records so as to allow the public an opportunity to view relevant correspondence and file records relating to the studies. In this tangible manner, the Task Force sought to fulfill its mission of a full and accurate disclosure of all of the facts found. While doing the research on the nutritional Calcium and Iron studies (which involved the unearthing of literally thousands of pages of archival records) for the original report, information was discovered concerning a set Thyroid studies that were not originally known to exist. These Thyroid studies became a point of focus and potential concern due to the use of 131I (iodine-131; a radioactive isotope) used as a tracer in these biomedical studies. This report focuses exclusively on the Thyroid studies. The chart below outlines the studies by name, number and years of research and publication. The asterisk by the subject numbers and identities signifies that each chapter holds details on identification issues. THYROID STUDIES Year of Year of Study Research Publication 1952 1954 Thyroid Function in Persons with Myotonia Dystrophica 6 Subjects: identities found* (STUDY NO. 1) 1952 1957 Thyroid Function in Persons with Down Syndrome: Fernald 28 Subjects: identities found* (STUDY NO. 2) 1961 1965 Thyroid Function in Persons with Down Syndrome: Wrentham 104-167 Subjects: 42 identified* (STUDY NO. 3) 1961 1962 Nuclear Fallout Study: Wrentham 70 Subjects: ?identities overlap* (Study No. 4) * Please see these chapters for clarifying information on the identification of subjects process and relevant issues. 3 STUDY #1: THYROID FUNCTION IN PERSONS WITH DOWN SYNDROME FERNALD (1957) The following definitions are offered to address the issues in all of the studies in this report. The Thyroid Gland: Many of the activities of our body are control and regulated through a set of chemicals (hormones) carried by the blood and lymph systems. The term hormone was coined in 1902 in connection with the discovery of secretin - a substance secreted by the duodenum to stimulate pancreatic secretions. The formal study of these hormones (endocrinology) did not begin until the 1920s. These hormones (defined as a chemical substance produced by an organ or tissue which has a specific effect on tissues that are relatively remote from the tissue of origin) are secreted by the endocrine glands; these include the pituitary, adrenal glands, pancreas, duodenum, testes or ovaries, placenta, parathyroids and the thyroid gland. The thyroid gland is a highly vascular organ with two lobes joined by an isthmus (bridge of tissue). It is normally found in the front of the neck with two lobes (halves) that lie on either side of the "windpipe", just below the "Adam's apple". Iodine is found in foods such as seafood, salt, bread and milk. The thyroid gland takes this iodine out of the blood stream and uses it to make the full level of hormones needed to guide such bodily functions as the rate of metabolism; body temperature regulation; protein, fat and carbohydrate catabolism in all of the cells in the body; skeletal (bone) maturation; heart rate; central nervous system development; muscle tone and strength, and other fine tuning of our bodily functions. The two most important of the thyroid hormones are thyroxine (T4) and triiodothyronine (T3) - (the subscript numbers refer to the number of iodine atoms contained in each hormone molecule). The hormones are stored in the gland until needed. Once released, they ride carrier protein molecules throughout the body. The level of hormone is maintained constantly by the pituitary gland. It sends out TSH (thyroid stimulating hormone) to maintain thyroid cell function. If the thyroid gland puts out too much hormone it causes hyperthyroidism. The reverse state, too little hormone, causes hypothyroidism. The thyroid can become infected and inflamed or develop cysts or tumors. Problems with thyroid levels can run in families (often skipping generations before the next manifestation); thyroid dysfunction tends to be found in women more than men; and, there are a set of related inherited tendencies toward other conditions such as premature gary hair, patchy hair loss, white patches on the skin (vitiligo), anemia (pernicious anemia), rheumatoid arthritis, and diabetes mellitus ("sugar diabetes"). Testing of the thyroid was done in the 1930s through the 1970s via tests such as basal metabolic rate, protein-bound iodine (PBI) and radioactive iodine uptake tests. Today highly sensitive and specific methods allow blood levels of T4 and T3 and TSH to be measured much more reliably. "Your Thyroid: A Home Reference", Wood, Cooper & Rigway (1982) A special definition text box will appear in each chapter for disorders, system functions or associated scientific information as each associated area appears in the chronological order of the studies and research findings. 4 In 1952, Dr. Clemens Benda (Medical director at Fernald School) wrote an introduction to the study proposal which outlined the medical understanding of the disorder Myotonia Dystrophica at that time: "Myotonia Dystrophica is a genetic neuro-endocrine disorder n which a specific myotonic reaction of striated muscle is associated with a progressive muscular dystrophy and complex endocrine disorders in which gonadal atrophy, both in males and females, is most characteristic. Extensive clinical and endocrine studies which will be reported elsewhere (noted as "to be published in Medicine") indicate that in addition to the gonadal atrophy changes in the pituitary of the type of basophilism, anomalies in the adrenal and thyroid pathology are observed. four autopsies which were available to us, and a survey of the literature, indicate that myotonia dystrophica is usually associated with a resting colloid goiter. The thyroids of our cases weighed 37, 75, 22 1/2, and 30 grams respectively, in contrast to a control material of over 300 cases of other types of neuropathological conditions excepting goiter, in which hardly a single thyroid weighed more than 25 grams. These observations suggest that it might be desirable to study the thyroid function in myotonic patients with the use of radioactive iodide and determinations of protein-bound iodine." PROTEIN BOUND IODINE (PBI) TEST A PBI test did not involve the use of radioactive isotopes. It involved the taking of a fasting blood test for laboratory studies. However, it was often used in conjunction with a tracer amount of radioactive isotope which was then signified as a PB131I test. It determined the fraction of the administered dose of radioactive iodine present as a protein-bound iodine 72 hours later. If more than 0.27 percent had been taken up into hormones and released int to the blood by the thyroid, hyperthyroidism may be present. These tests are now rarely used as clinical tests of the thyroid. They measured the iodine rather than the actual thyroid hormone level, so any iodine in the blood could elevate the results. this level of insufficient reliability had to be accepted until the more refined nd specific measurements of the concentrations of blood levels (serum) thyroxine (T4) and triiodothyronine (T3) were developed. They are the tests which are now routinely used. Benda went on to state: "there are two forms of muscular dystrophy combined with myotonic reactions, the so-called "myotonia dystrophica" or "dystrophica myotonica" and "Thomsen's Disease" or "myotonia congenital". While the two genetic entities overlap each other, there is considerable argument whether the two conditions represent different model entities or only different manifestations of the same genetic disorder." Note: All persons with myotonia dystrophica in this study did succumb to complications of this disorder at relatively young ages. All were identified and death certificates examined. In this study1 {1 C.E. Benda, D.J. Maletskos, J.C. Hutchinson & E.B. Thomas, "Studies of Thyroid Function in Myotonia Dystrophica", AmJ. of Med.Sciences, 228, 668-672 (1954)}, six males who had myotonia dystrophica were studied. Three of the subjects were brothers. Each subject was administered a tracer dose of 54 microcuries of 131I in 100 milliliters (approximately 3 ounces) of water with 100 micrograms of 127I as a carrier. An additional 100 milliliters of water was used to wash the glass and drunk by the subjects. 5 IODINE-131 (131I) In 1986, the scientist Baumann showed that there was a high concentration of iodine in the thyroid which marine and Feiss (1915) and Marine and Rogoff (1916) followed up with further studies that proved the thyroid has a selective affinity for iodine. Based on these test, many researchers (such as Perkin, Brown and Lang (1934); Watson (1936, 1938); and Elmer (1938) created iodine tolerance tests to measure the level of thyroid function. In 1934, fermi and his staff prepared a radioactive isotope of iodine (128I, with a half life of only 25 minutes). Hertz, Roberts and Evans (1938) created the first test technique using a radioactive isotope of iodine for studying thyroid function. this included the demonstration that if one administered an increased amount of iodine it would create a lowered uptake of any of the radioactive iodine administered. After that, radioactive iodine was widely employed as the primary tool to study the physiology and function of the thyroid gland. It was not until the 1970s that researchers began to discontinue the use of 131I in children, and over the next decade, in adults as well. today, in the United States, 131I is used for treatment of thyroid disease, but diagnostic thyroid uptake tests now primarily use 123I (which was not readily available until the 1970s) with 131I less frequently being used for this purpose. However, other countries are still extensively using 131I for diagnostic thyroid uptake tests. 127I is the stable common form of non-radioactive iodine (isotope) that was used as a carrier substance. Carriers were added from time to time to make sure all of the substance being studied was actually delivered. It may be, in fact, that a carrier was used in other studies but was simply not mentioned due to their non- radioactive nature. Earlier it was noted that extra iodine given to a subject could actually inhibit the uptake of the radioactive tracer, however, in this case, the amount was not sufficient to block the thyroid uptake but only acted as a carrier to assure that all of the 131I in the container was actually ingested. PBI measurements (without the additional use of any radioactive isotopes) were made on 4 of the 6 subjects one week prior to and 3 days after the study administration of the radioiodine tracer: The "in vivo" (in the live subject) measurement of the thyroid uptake was determined on the 1st, 2nd, 3rd, 6th and 8th days after administration b use of a "four channel scintillation counter" (Geiger counter) located at the Thyroid Laboratory of the Beth Israel Hospital in Boston, MA. A small thin rubber container than contained a reference standard 6 source of 131I equal in activity to the dose given internally to the subjects was held against their neck by the thyroid gland to correct for the absorption and scattering of the 131I gamma rays. The conclusions of this study showed that the 131I uptake and excretin, s well as the PBI values, were normal for all of the subjects. As pathology reports indicated that the thyroid gland was found to be larger than normal in most patients with myotonia dystrophica, the authors concluded that in persons who have this disorder the thyroid gland operates at a lower than normal capacity, but the capacity is sufficient to maintain an output of hormone levels that is clinically and biochemically within normal range. An article describing this study (see footnote 1) was found while working on the study for the original report. The article contained the initials of the 6 subjects with no further identification. By reviewing some of Dr. Benda's private records, which had previously been donated to Harvard University's libraries, the subjects in the Calcium studies had been positively identified. Further, they also supplemented records from MIT which allowed positive identification of the subjects in the Iron studies. It was hoped that Benda's records might again serve as a primary source for subject identification. Additional Benda records, secured outside the previous sites, were identified and reviewed. Within this batch of records, extensive writings on myotonia dystrophica were found. Within these records, the original drafts of the manuscript for the article were found along with the positive identifications of all six subjects. The letters sent out seeking permission and the responses were also found (see Appendix for copies of the archival records). The researchers involved in this study were from MIT, the Harvard Medical School, and Fernald. The research was supported by the Atomic Energy Commission and other unidentified sources. 7 THYROID FUNCTION IN PERSONS WITH DOWN SYNDROME; 2 ARTICLES Study No. 2 - Fernald (1957) & Study No. 2 - Wrentham (1961) DOWN SYNDROME Down syndrome (formerly referred to as "Down's Syndrome") is a congenital disorder, caused by trisomy (retention of a third copy) of the 21st Chromosome with a birth incidence of 1 in every 1,000 births. "There are hints in the historical records that an awareness of the condition of Down syndrome existed hundreds, perhaps even thousands of year ago. Images in old paintings and ancient stone carvings suggest that this might be so (Milton & Gonzalo, 1974; Zellweger, 1968). But there can be no doubt that a paper by J. Langdon Down in 1866 stands as a landmark document in the written history of Down syndrome. Down, in attempting to classify the various forms of "feeblemindedness" that he observed, probably influenced by Charles Darwin's thoughts on evolution, concluded that individuals with mental disabilities belonged to various ethnic classifications, including the "Ethiopian and Malay varieties." (..his description of persons he felt belonged to the "Mongolian family"..in light of the era or racial elitism in which he lived)[1] Since Down syndrome was first described more than a century ago, many theories have been postulated about is cause..such untenable hypotheses that alcoholism, syphilis, or tuberculosis (were the cause)..by the end of the early 1930s, some investigators suspected that Down syndrome might be due to a chromosomal problem. However, at that time the technology of examining chromosomes was not advanced enough so that this theory could be proven." In 1956 new laboratory techniques were developed that allowed scientists to visualize and better study chromosomes, (tiny rod-like structures carrying the genes inside the nucleus of each cell) and it was found that the previous theory that there were 48 chromosomes was in error, and that the actual number was 46. In 1959, Lejeune reported that persons with down syndrome had one extra, small chromosome lending to this observation of 47 chromosomes in this disorder. Instead of the ordinary et of #21 chromosomes, there were three. This led to the term "trisomy 21". since that time, geneticists have found that this trisomy is most often preesent, but that there can also be other chromosomal problems such as translocation (attachment to a different group, such as the D or G group) or mosicism (an error in one of the initial cell divisions so that some cells have 47 chromosomes but other have 46). The National Down Syndrome Congress (a parent advocacy organization) refers to it as "the leading clinical cause of mental retardation." There have been a number of archaic medical terms used for this syndrome such as "mongolism", or the more insulting term "mongolian idiot". The use of such terms as "idiots", morons", "fools", "feebleminded", and "mentally deficient" was addressed and apologized for in the first report. It is important to bear in mind that Down syndrome has an associated mild to moderate level, i.e.,: rarely a severe level, of mental retardation. + most of above derived from writings by Siegfried M. Pueschel & Jeanette K. Pueschell, 1992; but was supplemented wit discussions with Working Group Members and Advisors At the time of this study, the accepted medical terminology was "mongolism". 8 STUDY NO. 2 - FERNALD During this earlier time period, it was Dr. Benda's belief2 {2 Benda, C.E. Mongolism and Cretinism, ed. 2. New York, Grune and Stratton, (1949) Benda, C.E. What is Mongolism? Internat. Rec. Med. 165:75, (1952) Benda, C.E. Dayton, NA and Prouty, RA: On the etiology and Prevention of Mongolism, Am.J.Psychiat.99: 822, (1943) Benda, C.E. Prenatal Factors in Mongolism, IAMA.139:979 (1949)} that the thyroid function abnormalities found in a large number of persons with Down syndrome were actually the casual factor in the development of this disorder. To quote from his article, he believed this syndrome was "(the) result of deceleration of normal growth during the fetal period." Persons who have Down syndrome ultimately have a significantly higher rate of thyroid malfunction. By the 3rd to 4th decade of life, over 25% of persons with down syndrome will develop hypothyroidism. This is also a unique phenomena found in persons have Down syndrome: a higher finding of an autoimmune antibody relating to the thyroid can be found in the parents of children having this disorder than in the total population. This phenomenon is not fully understood by endocrinologists. Benda's earlier articles (as footnoted below) had shown "a possible relationship between abnormalities in development and function of the thyroid gland and the fetal growth process in mongolism is suggested by anatomic evidence of pathologic alterations in the thyroids of mongoloid children and the reported frequency of abnormal thyroid function in their mothers". Benda shared the belief of a number of his contemporaries that his would be found to be the major causal factor that could lead to the discovery of a "cure" or a definitive "treatment for" mental retardation as stated in this permission letter for this study (see section on Consent). It is stated further in this article that "although data are available concerning isolated phases of thyroid function in mongolism, a detailed investigation of the various aspects had not, at that time of our studies, been carried out. This report presents the results of an investigation of the thyroid gland in mongolism, utilizing a variety of recently available techniques." The study reported in this article included a total of 28 subject: 21 were persons with Down syndrome (stated as residents of the Fernald School) and 7 parents. Their ages were stated as ranging from 5 to 26 years. The identities of the residents of Fernald and the parents were both discovered in the archival records.3 {3 [Note: In the Benda papers, we were able to positively identify 22 residents of Fernald whose test results were submitted to the authors for inclusion in this article. Five sets of initials in the report do not match any of the names on the Benda lists. There are gages mission on three of them and the only child below the age of 16 (in this case a girl of 5 years of age) are in that set of five unidentified subjects. Every other record kept Benda, for all studies, had the inclusion of ages. It may be that these last 5 were persons in the Beth Israel lab files (as were the control subjects whose data was used). However, in the dosimetry and risk evaluations, we will address the 5 year old maximum dosage and risk levels as stated int eh article. It does not appear, however, that the 5 year old was one of the residents tested for this article.]} 9 The article4 {4 G.S. Kurland, J.S. Fishman, M.W. Hamolsky, & A.S. Freedberg, "Radioisotope Study of Thyroid Function in 23 Mongoloid Subjects, including Observations in 7 Parents", J.Clin.Endoc.&Metab., 17, 552-60 (1957)}also notes that "64 euthyroid (normal functioning thyroid) subjects ranging in age from 10 to 65 years served as controls". It was later determined, by conversation with one of the researchers, that his set of control data was from studies done at the Thyroid Lab at the Beth Israel Hospital and did not include other residents from the Fernald School. The persons with Down syndrome, of all ages, received a standard dose of 70 microcuries of carrier-free radioactive iodine (131I) as a tracer. This was administered orally. The parents, like the control subjects from the other studies at the Beth Israel Hospital, received 100 microcuries. The measurement of the thyroid uptake of the racer was done with a four-tube G-M method, modified by a correction factor for scatter and absorption by holding a container of any equivalent dose of 131I against the neck of the subjects. Measurements were taken at three separate intervals over a five day period. On page 553 of the article, it is stated that "thyroxine metabolism was studied in 2 mongoloids (sic) by following the rate of disappearance from the plasma of intravenously insured 131I labelled thyroxine and by measuring the appearance of radioactivity in the tyroid after the infusion." this shows that tow subjects were administered 55 microcuries of 131I thyroxine in addition to the 131I iodide thyroid tracer. Since the two tracers differ in their biological behavior, a simple addition of radioactivity is not a scientifically proper calculation. However, their total radiation dose would be increased. This total dose is discussed in the section of this report that outlines the outside experts' opinions. Following the finds, a second set of 23 control subjects was compared. Record review has determined that they were subjects from the Beth Israel Thyroid Lab and not residents of the Fernald School. The conclusion of the study was that the 131I uptake and excretion levels were within normal range for the subjects with Down syndrome, as was the runover rate of labelled thyroxine. Nor was any significant abnormality found in the 7 parents. The subjects with Down syndrome did demonstrate higher turnover rates of iodine, which suggested that a smaller effective portion of the thyroid gland was working at an intense rate in order to maintain normal levels of thyroid hormones. The researchers were from Harvard Medical School and the Beth Israel Hospital in cooperation with fernald staff. The research was supported by the National Institute of Arthritis and Metabolic Diseases and the Atomic Energy Commission. 10 STUDY NO. 3 - WRENTHAM The second study on thyroid function as it relates to persons with Down syndrome was conducted at eh Wrentham School in 1961-2 and published in 1965 5. {5 K.M. Saxena and C.V. Pryles, "Thyroid Function in Mongolism" J.Pediatrics 67, 363-70 (1965)}. The two authors of this article were also involved with the earlier Nuclear Fallout study at Wrentham in 1961 (see next chapter). From conversations with the researchers, it appears that some of the data from that earlier research were used in a pooling of subjects for this second work. The article noted that the subjects had normal PBX and thyroid uptake studies, but that there was an elevated uptake of T3 by erythrocytes and a higher than normal circulating thyroid antibody level that bore further investigation. "The mechanism and significance of these anomalies" were the basis for this study and discussion. The subjects included 53 persons with Down syndrome and 51 persons wit mental retardation associated with other disorders. Identities were noted only by sex and age groupings for those with down syndrome. 23 sets of initials were also given for this group. Using these factors, those 23 identities have been established with a good statistical basis for positive identification. An additional 19 identities are also considered sound. The lack of actual archival records deters us from making that claim as "positive" at this time. The conclusion from the research was that iodine uptake and plasma levels of thyroid hormones were within the normal range for all subjects. The researchers also concluded that red blood cell uptake of the thyroid hormone triiodothyronine (T4) labelled with 131I could be used as test of thyroid function. This was done using a standard venous blood draw and did not require giving radioactive iodine to the children. As was the case when the original Calcium and Iron studies were investigated, a major problem was the lack of any standardized and required record keeping or notations of any studies in the actual records of the residents. The researcher's records were kept separately and researchers kept their own personal records in a location away from the research site. The two surviving authors, who were interviewed for this report, did not themselves keep any of the records from these studies. What records may have existed at the Thyroid lab at Beth Israel were either discarded or lost in a flood that occurred in that storage area a number of years ago. Therefore, the take of identifying any potential subjects feel to the time-consuming and frustrating effort of sorting through a pool of over 2,000 records of former and present clients. By defining boundaries in the search that included the age of the resident, date of admission and discharge, sex and disability, we have bene able to reduce the number potential subjects to just under 300 as of the writing of this report. The researchers were from the Harvard Medical School, Massachusetts General Hospital, and the Boston University School of Medicine. The research was supported by the Division of Radiological Health, Research Branch, of the U.S. Public Health Service. 11 STUDY 4: MINIMAL DOSAGE OF IODIDE REQUIRED TO SUPPRESS UPTAKE OF IODINE-131 BY NORMAL THYROID WRENTHAM (1961) "Chapman and Saxena from the Unite [The Thyroid Clinic & Laboratory, Mass. General Hospital] measured the uptake of radioiodine in human subjects when administration was accompanied by varying doses of carrier iodine. The importance of this was that information was needed on the amount of iodine that would be needed to inhibit the retention of radioiodine in the event of fallout from an atomic accident or explosion. 131I is the predominant isotope resulting from an accident in a nuclear power plant or explosion of an atomic weapon. they were the first to define the necessary dose in normal human subjects, although there was information on this point from the Mendoza study on iodine- deficient subjects. This problem was the subject of a recent (1989) conference called by the European Community [note: Chernobyl occurred in 1986]. The Saxena-Chapman paper had been forgotten, but it was brought to the attention of the attendees." John B. Stanbury, M.D.* "A Constant Ferment", Ipswich Press, 1991 *on page 90 of this book, the author states that he was a consultant on nuclear accidents to the Atomic Energy Commission (AEC). A press release was issued by the Task Force on February 8, 1994, to inform the public that a study which fell under what society has come to call "Cold War experiments" (ones that focus on the medical effects a civilian population will suffer from fallout following a nuclear attack or accident) had been discovered in the archival record review. The body requires iodine as a nutrient, and uptake of the small amounts normally present in the diet is high. The purpose of this study was to determine how much normal iodine was needed to be added to the diet of children to block the uptake of radioactive iodine they might be exposed to from nuclear fallout. 12 IODIDE VS. IODINE Iodine is a chemical element, in the same group on the periodic table as fluorine, chlorine and bromine (called halogens by chemists). It is rarely found alone for it usually combines with another element to form a compound, called iodide. Iodine combines readily with alkali metals, such as sodium or potassium. Most often, we take in iodine in the form of sodium iodide salt. In this study, the 131I was administered orally as both potassium and sodium iodide salt. This study5 {5K.M. Saxena and C.V. Pryles, "Minimal Dosage of Iodide Required to Suppress Uptake of Iodine-131 by Normal Thyroid" Science 138, 430-31 (1962)} involved 70 subjects, ranging in age from 1 to 11 who were residents of the Wrentham School. The identities of the subjects have not been fully determined at the time of thiswriting, as discussed in Study No. 3. Benda, whose personal papers had allowed the positive identification of all subjects of the thyroid studies at the Fernald School had not been involved in this study. None of the researchers involved in this study had kept their records. Using a set of criteria (age, sex, date of admission, status in relation to Down syndrome, etc) we have reduced the pool of potential subjects to 300 persons and a careful records review is underway to try to find identifying information. The 63 primary subjects were given daily dietary supplements of stable (nonradioactive) sodium iodide, ranging from 100 micrograms to 1,000 micrograms, for a period of 12 weeks. An additional 7 subjects were given a single dose of 1,500 micrograms per square meter of body surface of stable iodide. The Task Force has been informed by outside nutritional biochemistry experts that the stable iodine should have posed no risk in and of itself as it is a normal dietary requirement. Literature cited in the journal article arising from this study sated that even unusually high levels of ordinary iodine would only pose problems if administered for several years. With enriched flour and other foods, the modern diet can easily include about 1,000 micrograms per day of iodide. Radioactive iodine, 131I, was given as a tracer to measure the rate of uptake of the stable dietary iodine. It appears from Figure 1 of the article6 { 6Ibid.} that 1 microcurie of 131I was given to 5 2-year-old subjects every 2 weeks for 14 weeks. Thus, each subject received a total of 8 microcuries of 131I. The researchers were from the Harvard Medical School, Massachusetts General Hospital, and the Boston University School of Medicine. The research was supported by the Division of Radiological Health, Research Branch, of the U.S. Public Health Service. 13 Radiation Expertsþ Opinions on Dosage and Risk In the first report by the Task Force, concern was expressed about the ages of the subject who received these doses of the radioactive iodine tracers and the potential for the subjects to have developed thyroid cancers. Opinions were sought from a total of 8 persons who currently function as nationally noted experts in the fields of radiation, thyroid studies and epidemiology. One of the experts, Dr. Joseph Lyon, who (while calculating his epidemiological risk factors for the Calcium and Iron studies) brought this potential for concern to the attention of the Task Force and this special detailed follow-up study was called for. In addition, 7 other experts were called together to serve as a Dosimetry and Risk Assessment Subcommittee for the Follow-up Working Group. Their reports are contained in the following pages of this chapter. In summary, there was a consensus that, as Dr. Lyon stated in his report, þin neither group of children would the radiation dose have been sufficient to increase the risk by as much as a single caseþ. Even in the study conducted at Fernald (Study No.2), where the original review of the article and potential dosages had created the basis for the concern and call for this follow up review, the formal dosimetry revealed that it was again a fraction of a single case for increased risk of thyroid cancer being discussed and that, according to Lyon, þ..if a single case (of thyroid cancer) was found (within the group of subjects) it would be impossible to attribute this to the 131iodine exposureþ. These findings are consistent with a large epidemiological study of 35,074 patients in Sweden8 {8 L.E. Horn, K.E. Wiklund, G.E. Lundel, N.A. Bergman, G. Bjelkengren, U.S. Ericsson, E.S. Cederquist, M.E. Lidbert, H.V. Wicklund, and J.D. Boice, Jr., þCancer Risk in Population Examined with Doses of I-131,þ Nat. Cancer Inst. 81, 302-306 (1989).} who were given 131I for diagnostic purposes. The patients did not show an increase from the normal risk of cancer found nationally after periods of 10 to 20 years. The average dose to the thyroid gland in the Swedish studies was 50 rads, about the same as the maximum dose to any subject in the Wrentham study. The following pages hold the text of the opinions offered by the 8 outside experts who were gathered to do an independent and comprehensive dosage and epidemiological review. Special attention is called to the report by Dr. Lyon and the Summary & Discussion pages of the Dosimetry and Risk Assessment Subcommittee report. Additionally, a graph is shown below which demonstrates the level of full body dosage received from the studies vs. an annual background dose for a resident of Denver. This allows a comparable reference to that used in the graphs for the Calcium and Iron studies in the original Task Force report. 14 However, with the administration of 131I, there is a unique characteristic that impacted this charting. The isotope is taken up almost exclusively by the thyroid. Therefore, a second chart was need that shows the dosage to the thyroid gland in isolation. However, the standard for this dose should not be an annual background dosage for accurate comparison of dose and risk. Therefore, the standard it is measured against is a medical scan done in the 1960s using 131I for an average patient entering the thyroid lab for a diagnostic evaluation in that era. Thyroid Studies with Iodine-131 Effective Dose Equivalent (millirems, thyroid excluded) Thyroid Studies with Iodine-131 Dose to Thyroid Gland (rads) FOR REFERENCE SEE (6bb72) 15 Report on Thyroid Cancer Joseph L. Lyon, M.D., M.P.H. I have reviewed the data prepared by Drs. Litster and Shore concerning the possible increases in thyroid cancer that might have followed the radioactive iodine studies at Wrentham and Fernald Schools. I think that their estimates of radiation doses are reasonable and have used them to estimates the risk of thyroid cancer among the children exposed at each school. I have used the risk estimates for thyroid cancer published by the National council on Radiation Protection and Measurements Report Number 80 (National council on Radiation Protection and Measurement, 7910 Woodmont Avenue, Bethesda, Maryland 20813, 1985 pp. 56).. The annual estimate of thyroid cases attributable to 131iodine ingestion is 0.00000084 case/years-rad. This estimate is the average of the risk for men and women, since women had a risk coefficient twice that of men. I also assumed the populations of the two institution were equally divided between men and women. Because the number is the annual risk I estimated the excess number of cases that would occur is a person survived to ages 50, 60, 70 and 75. The following table contains these estimates. Table Excess number of thyroid cancers to the stated age Age at Death 50 60 70 75 Wrentham School 0.36 0.44 0.51 0.55 N=116 Fernald School 0.13 0.17 0.19 0.20 N=21 The risk of developing a thyroid cancer for an individual who lives to age 75 is 0.04 or 4 cases per 1000 individual living to age 75. For the Wrentham School exposed population we would have expected 0.464 cases of thyroid cancer if all the children survived to age 74, and 0.084 cases among the children at the Fernald School. The radiation would have added 0.55 extra cases to the 0.464 cases expected. The children at the Fernald School would have an extra 0.20 cases over the 0.084 cases expected to occur naturally. In neither group of children would the radiation dose have been sufficient to increase the risk by as much as a single case. Another way to think about is as follows. If all the children who were exposed at the Wrentham School lived to age 74, and if they had all received the maximum dose before age 1, then there might have been one case of thyroid cancer by the time they reached age 74. The extra radiation would have contributed to this 16 since it would be expected to produce half (0.55) extra cases of thyroid cancer. If one case were seen it would be impossible to determine if the case was the result of the radiation received from 131iodine. The children exposed to radioactive 131iodine at the Fernald School also had Downþs syndrome, and those with Downþs syndrome rarely survive past their middle fifties. We would expect only 0.084 cases of thyroid cancer if they all lived to age 74. The radiation received from the radioactive 131iodine would increase the number of thyroid cancers seen if this group lived to age 74 from 0.084 to 0.284. Again the number expected is small, and even if a single case was found it would be impossible to attribute this to the 131iodine exposure.