Initial Medical Applications

Niels Bohr was arguably the most important linking figure in the development of nuclear and related sciences throughout the 1900s. When he first learned of Rutherford’s work characterizing alpha, beta and gamma radiations, he went and visited his lab. Their discussions led him to conceptualize the model of the atom that led to rapid  increasing knowledge of the atom, its constituents, and their properties.  Throughout his career, Bohr identified, mentored, and stimulated young people and senior scientists. He worked with the world’s top physicists and biologists in their labs, and many visited and worked with him at his Copenhagen Institute. Among them was the Hungarian chemist George de Hevesy (a future Nobel laureate, later known as the father of nuclear medicine Hevesy Father, see: Hevesy The Father of NM JNM 1979). It was when Bohr visited Rutherford’s lab in 1911 that he and Hevesy first met.  Hevesy worked for many years thereafter in the Copenhagen Institute. In the late 1930s, he performed many important animal studies using 32P and  24Na produced using mixed neutron sources, and material obtained from the Berkeley cyclotron.

Blumgart realizes that the external measurement of radioactivity will allow him to measure pulmonary transit time non-invasively.
Blumgart realizes that the external measurement of radioactivity will allow him to measure pulmonary transit time non-invasively.

Radioactive elements were first used by Hevesy as tracers in 1923 to study biological processes while working in Rutherford’s lab. He used naturally-occurring radioisotopes of lead and bismuth to define their distribution in plants and small animals.

The first use of radioactive tracer in man were conducted by Herman Blumgart, a Boston clinician, who performed the first radiotracer test on himself in 1925 using radon, the radioactive gas,  222Rn in solution. Blumgart collaborated with Yens and Weiss in clinical investigations in which they measured the time it took for the Rn gas containing fluid to pass through the lungs and heart in healthy and diseased patients. Initially tracers were a main stay in experimental biology, biochemistry and medical research, and 30+ years later  they were used widely in the practice of medicine .

The discovery of isotopes by Soddy occurred in 1923.  In 1932, Urey discovered the stable isotope Deuterium, (heavy hydrogen, an atom the nu8cleus of which contained one neutron, and one proton), and the kinetics of many deuterium and 15N labelled stable tracer substances were used as markers to elucidate metabolic pathways. Many famous physician/biochemists worked in Denmark in the Carlsberg laboratories. Fritz Lipmann, and Konrad Block were joined by Rudolpf Schoenheimer in the use of novel biosynthetic methods  in metabolic research.  Schoenheimer took de Hevesy’s tracer work to a higher level by labeling molecules on different constituent atoms and thereby tracing the metabolic fate of the different parts of the molecule. This type of chemistry had been used with stable tracers (mostly deuterium) , but the work was much more easily accomplished with radioactive tracers.  Deuterium labeled studies  were relatively easy as deuterium is not normally present in tissue, thus  background levels were negligible). Studies with  13C and 15N , naturally occurring stable isotopes of the more abundant 12C and 14N, are more challenging as they require more difficult separation and analytic techniques to cope with non zero natural background levels. High efficiency chemical separations were used to unravel the complexities of hemoglobin metabolism using stable tracers (Shemin and Rittenberg), while investigations of photosynthesis and glucose metabolism used the simpler  methods employing radioactive14C, and 13N. Schoenheimer died young, but many consider him the Father of biochemical tracer methodology, having added important chemical speciation precision to Hevesy’s simpler isotope dilution methodology. It is noteworthy that Hevesy considered the indicator dilution method as his major contribution to science.

The discovery of radioactive elements attached to biologically important molecules  led to new understandings of biochemical and physiological processes in plants and animals. Scientists and physicians went further used these tools to study normal and abnormal processes in healthy and diseased human subjects.  Nuclear tracer studies provided a versatile tool that rapidly  evolved into medical practice based on collaborations between medical and biological scientists, physicists, engineers, and chemists. Bohr continued throughout his life to explore how to predict chemical reactions based on fundamental atomic, and molecular properties . See March 2013 Physics Today for more on this subject by Bohr.

 

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