Path B: Bob Heyssel

Heyssel boyBob Heyssel came to Vanderbilt after finishing a fellowship in Hematology under Carl Moore at Washington University and immediately took on the role of Co-Investigator on ongoing projects. He added new hematology studies dealing with red cell physiology and platelet labeling extending prior work at Washington University. Heyssel was quick to recognize the potential clinical uses of Meneely’s WBC, which was then just becoming operational. Carl Moore’s group had pioneered in studies of iron metabolism, as had Paul Hahn and the Vanderbilt group. Heyssel using the WBC extended the iron absorption and turnover studies. This provided accurate quantitative data on the amount of 59Fe in the total body, and activity in plasma and red cells was measured out to 140 days following 10 uCi injections (the usual activity then used). The studies were later extended to include imaging of organ uptake and turnover, when the WBC was modified to allow regional mapping of 59Fe kinetics in different organs. Iron metabolism studies were done in normal subjects, and patients with different diseases, including paroxysmal nocturnal hemoglobinuria, a rare disorder studied in collaboration with Bob Hartmann, Head of Hematology. (Much of this work was expanded later using scanning detectors in the Whole Body Counter to collect data on levels and turnover of 59Feactivity in marrow sites, liver, spleen uptake along with RBC uptake and clearance from plasma. This provided the reference data published in the Medical Internal Radiation Dose (MIRD) Committee with data provided by Ron Price). The whole body counter allowed one to do clinical studies while administering very small amounts of radioactivity. This was ideal for metabolic research studies as one could assess body losses by urine collections without the need to collect and assay radioactivity in daily 24-hour stool samples.

In 1963 Heyssel was joined by Cliff McKee, an Internist/Hematologist who completed a fellowship in Hematology in 1964 at Vanderbilt having completed his residency in 1960, prior to two years in the Navy. Cliff participated in and coordinated many of the hematology studies working with postdoctoral fellows from many countries. Marie Wasson was Bob’s Head Technician responsible for the conduct of animal research studies. Glenda Barnes was the clinical technician who worked under Bob’s direction in the Radioisotope Center, where she performed the in vitro diagnostic studies, thyroid uptakes, blood volume, and other in vitro studies. Graduate student wives provided the best secretaries and technical assistants that staffed the program.

→ Visiting Scientists: The initial whole body counting studies measured  40K from which lean body mass was estimated. These were done in collaboration with visiting scientists from Athens, Greece ( Constantinides Takis) and Scotland (Ross Lorimer) who carried out long-term studies on hypertensive patients receiving diuretic therapy. Many of the earlier tracer turnover studies based on blood sampling, and measurements of the whole body space of distribution of different administered radiotracers were now done with low doses and whole body counting.

There are many methods of measuring body composition. The vaious methods currently in use are reviewed in a recent publication entitled “Measuring body composition” by Wells and Fewtrell (2006).

The earliest methods used involved the measurement of the amount of water displacement when the whole body is immersed in water, and skin fold measurements. Francis Moore and then Meneely and others took advantage of the fact that the rare radioisotope,  40K is in equilibrium in the body with stable potassium. The measurement of  40K emissions from the body requires the use of sensitive radiation detectors to record the amount of its 1.46 MeV gamma rays coming from the body parenchymal cells. Given the low level of potassium in fat cells, and bone one can measure Lean Body Mass (LBM) based on whole body counting (WBC) of 40K , knowing its naturally occurring ratio with total potassium. It was ro accomodate this that Meneely built the Vanderbilt WBC, described on the main page. Alternatively, if one injects radioactive 42K , one can make a good estimate of the LBM based on a measurement of its space of distribution in the body. The main obstacles to this are that it requires the administration of a radioactive substance, whereas with 40K no added radiation dose is needed and furthermore  42K has a short half-life, and is no longer commonly available.

For more information of the subject of body composition, see Francis Moore’s classic book entitled: The body cell mass and its supporting environment: Body composition in health and disease. Further, the ICRP entitled “Basic Anatomical and Physicological Data for Use in Radiological Protection Reference Values” (2002), contains much valuable information, as did the earlier publication entitled “Report on the Task Group of Reference Man” (1975).


STUDIES
→ Platelet Studies: Heyssel’s interest in platelet kinetics started in his St. Louis days when Bill Harrington and Tom Brittingham (later of Vanderbilt fame) did landmark studies on autoimmune thrombocytopenia (AITP). They self-administered plasma from patients with AITP, which demonstrated the immune process underlying the disease, and its potency as it almost killed them, his early clinical mentors. Bob’s first NIH grant was to improve means of labeling platelets for platelet survival studies. Over the years, he tested a series of agents starting with 14C labeled 5 hydroxy tryptamine (serotonin).

→ Vitamin B12 And Pernicious Anemia: The location of a WBC in a Medical School provided an opportunity to study biochemistry and physiology in patients with different diseases and to test different diagnostic, and therapeutic hypotheses. The study of the absorptive defect in patients with Pernicious Anemia (PA) was an early illustration. The group studied 24 patients, some with PA, others with diabetes, and some healthy subjects. They fed subjects 1 uCi of 60 Co labeled B12 for the absorption studies, and the results of whole body counts clearly showed a quantitative measure of the absorptive defect (little 60 Co retained by PA patients). In the same study they demonstrated normal clearance half time of IV injected material in PA patient, i.e. the material had been “absorbed” and was therapeutically effective.

→ A number of other important studies on B12 metabolism were done in the WBC: One study of the turnover of endogenously labeled 57Co B12 was done in collaboration with veteranarian colleague (MC Bell) at the animal research center at ORNL (KARL). This demonstrated that endogenously and chemically labeled B12 behaved in the same way. To do so, they fed a lamb 57Co at KARL, which the lamb synthesized into B12 that was stored in its liver. The animal was euthanized, its liver removed, and the radioactive liver delivered to Vanderbilt where it was frozen and stored. The liver was cooked and fed to patients. From these data, the minimal dietary requirements were established based on the fraction of the amount fed that remained in the body. The study was done in a collaboration with Dick Bozian, from Cincinnati and Bill Darby. The fact that the freezer subsequently failed, presented an expected disposal problem.

The second WBC Symposium organized by Meneely was held in Nashville in 1963, after Meneely had left for a job at the American Medical Association in Chicago. The Vanderbilt WBC was intended to be used for biomedical and environmental measurements and  directed towards detection and quantitation of contamination from industrial/environmental sources, the latter including fallout from nuclear weapons testing.

The most inclusive record of what was done in and with the WBC facility is given in two publications that came from the 1960, and 1963 Whole Body Counting Symposia. Maria Heyssel, Heyssel’s wife, assisted by Con Ball made all the arrangements for the hosting of speakers, running the meetings and arranging publications of the results of these well-attended important meetings.

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