Radioisotopes in Biology Reviewed at Madison A STAFF REPORT X HE extremely rapid growth of a t t e n tion given to the use of radioisotopes in research in t h e biological and related sci ences was strongly emphasized last m o n t h in a symposium on " T h e Use of Isotopes in Biology a n d Medicine," sponsored b y the University of Wisconsin. N o t only was the chemistry of this field reviewed but detection, applications, and research techniques were examined in individual papers and panel discussions b y experts. T h e meeting opened with a group of review papers, in the first of which H a n s T. Clarke of Columbia University talked on the historical background of this field, describing experimental work and ad vances made before the era of the atomic pile. A review of the preparation of radio active isotopes was presented by Glenn Τ Seaborg, University of California. Harold Urey, University of Chicago, talked on the preparation of stable isotopes. Dr. Ure}' pointed out the fact t h a t the chemi cal properties of isotopes are not identical as was supposed for a long time but are actually found to be slightly different. This, he stated, makes this separation problem one of the most difficult in chem istry. However, he declared, it is now possible to separate t h e isotopes of a n y element if it is worthwhile. Dr. Urey cited chemical preparation methods as the most valuable from t h e standpoint of cost of a p p a r a t u s and opera tion for the separation of isotopes of inter est in biochemical problems, even though its application requires special s t u d y for each element. Production
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Paul Aebersold of t h e Atomic Energy Commission spoke optimistically of t h e isotope distribution program. Almost every isotope found in nature or produced b y man is now available, he stated. D r . Aebersold expressed the hope that tritium will soon be available and said t h a t ex tensive studies are now being made on pro duction, measurement, a n d packaging. H e reported that since distribution began Aug. 2, 1946, 1,100 shipments of pile-pro duced radioisotopes have gone to about 160 organizations. He noted particularly t h a t there is an increasing use by industrial organizations. I t was stated t h a t 60 differ e n t radioisotopes have been shipped and t h a t t h e largest number of shipments of chemically separated isotopes were P 3 2 and I 131 , largely for medical diagnosis and ther apy, accounting for total activities greater t h a n 10,000 mc. each. One hundred ship ments of C 1 4 with a total activity of over 150 mc. h a v e been made. Enriched forms of three stable isotopes
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have been made available, according to Dr. Aebersold. These include heavy hydro gen as deuterium gas and heavy water containing 99.8 parts of deuterium to 0.2 part of protium; boron in calcium fluo ride-boron trifluoride containing B 10 con centrated to 9 6 % of the boron content— fivefold enrichment of B 10 ; and O 18 con centrated to seven times the» concentration in nature, available in water in which deu terium is not enriched. Improved meth ods for the preparation of C 14 , he stated, have permitted a reduction in its price from $367 to $50 per mc. The issue of a revised catalog and price list was a n nounced and copies were made available at the meeting. In addition to radiosotopes, said D r . Aebersold, investigators m a y secure serv ice irradiation when necessary, t h u s mak ing possible the use of the effect of irradia tion on crystals, organic chemicals, seeds, intact metal parts, and numerous other materials of special interest. Also available are S 35 of high specific activity in sulfuric acid and sodium sulfide, small quantities of Ca 35 , and other radioisotopes such as iron, calcium, and chlorine, with a higher specific activity t h a n that of earlier sam ples. Dr. Aebersold listed three types of products which are available: (1) regular products or stock items, a s extracted or separated forms of C 14 , P 3 2 , a n d I 131 , as well as S 35 and, in t h e near future, Ca 4 5 ; (2) materials produced irregularly in batches—fission products, Ca 45 , and C 1 4 labeled compounds; (3) units irradiated upon completion of orders.
Detection Alfred Nier, University of Minnesota, in speaking of the detection of stable isotopes pointed out t h a t for some elements, not a b l y oxygen and nitrogen, radioactive iso t o p e s having suitable half-lives do not exist, and, hence, stable separated isotopes m u s t be employed in tracer experiments a n d some m e a n s m u s t be found for de t e c t i n g their presence. " W e i g h i n g " the e l e m e n t under investigation t o see how m a n y atoms of abnormal weight it con t a i n s is t h e most effective m e a n s of ac complishing this. Such weighing, he said, m a y be accomplished t h r o u g h atomic weight determinations, density determina t i o n s , or observations of the optical spec t r u m or mass spectrum, the l a t t e r being by far the best. This, it was explained, is accomplished by ionization of a gaseous form of t h e substance in t h e mass spec t r o m e t e r t u b e by electron b o m b a r d m e n t , t h e ions then being separated according to t h e i r mass b y means of a suitable combina t i o n of electric and magnetic fields. A null m e t h o d for measuring isotope abundance r a t i o s directly has been developed, he said, which not only gives results in a s h o r t e r time b u t also achieves greater ul t i m a t e accurac\>\ T h e analysis of hydrogen is complicated b y t h e production of t r i a t o m i c ions which a r e measured simultaneously with the molecular ion containing the heavy iso t o p e , as well as a " m e m o r y effect" in the i n s t r u m e n t , said D r . Nier, b u t suitable precautions can prevent serious interfer ence.
Conrad Eivehjetn and Edgar Condon, chairman of ments for the symposium, both of University of
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Martin Kamen, Washington University, and Charles Coryell, Massachusetts Institute of Technology, dealt with the detection of radioactive isotopes. Dr. Kamen stated that the tritium assay' problem is still not solved by commercially available equipment, but that such equipment will be released soon. He indicated that the vibrating reed electrometer will prove a most satisfactory instrument for this work. He declared that tritium will be very valuable in tracer studies particularly because of its high dilution measurement. What can be done with deuterium, he stated, can be done with tritium, but the latter has greater sensitivity and, eventually, easier measurement. The big dilution factor which is disadvantageous in the use of carbon 14 or deuterium for work with such molecules as cholesterol will not prove such a hindrance with tritium. Tritium, he said, will be an important tracer for carbon. In dealing with C11, Dr. Kamen emphasized its particular usefulness for rough exploratory experiments. The hard quality of its radiations makes its assay relatively simple, he declared, but it must be used near a cyclotron because of its short half-life. The most important of the radioactive tracers for biological use at present is C14, according to Dr. Kamen; its assay problem is now simplified to a place where most problems can be handled with commercially available equipment. The time is rapidly approaching, he averred, when there will be no excuse for spending a large fraction of time on assay rather than experimentation, as good equipment will soon be available commercially in quantity and at reasonable price. He considered the simplest assay method available at present to be the use of solid samples, counting with an end window counter. General Use of Radioactivity Dr. Coryell covered the use of radioactivity throughout the periodic system without specific reference to biochemical or medicinal uses. He gave the phenomenology and methodology of radioactivity in general with reference to beta, gamma, and x-rays and cited recently declassified Manhattan Project material not widely known but widely useful. In speaking of operational philosophy, Dr. Coryell emphasized that it is less important to worry about expensive equipment than about the measurements being made. Ho opined that a cheap instrument well understood and properly applied is better than an expensive unit loosely used. In another admonition he warned against absolute trust in present conclusions from observations in nuclear physics or chemistry because of the extreme complexity of the field. For example, he stated, I 131 was widely used and thought to be one of the best understood radioisotopes. Recent work, however [Reid, A. F., and Keston, A. S., Phys. Rev., 70, 987 (1946)], uncovV O L U M E
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ered significant contamination with 56-day iodine. This was corroborated [Glendenin, L. E., and Edwards, R. R., Phys. Rev., 71, 742 (1947)1 and it was shown that the contaminant was I 125 emitting x-rays. This, stated Dr. Coryell, may be useful in opening trie possibility of double iodine tracing (watching two atoms in the same molecule), as in thyroxine in metabolism. Dr. Coryell also stated that the fact has been established (Deutch, M.f Meaker, C , and Miller, A. C , private communication, MIT) that 15% of the gamma rays from I 131 have an energy of 0.6 m.c.v., whereas it was previously thought to be entirely 0.397 m.e.v.
Chemical Reactions A panel discussion on chemical reactions was presented by J. E. Willard and Farrington Daniels, University of Wisconsin, and Drs. Seaborg and Coryell. I t was pointed out at the opening of the discussion by Norris F . Hall, University* of Wisconsin, who presided, t h a t in his estimation too few chemists are applying tracer methods to their problems. This point was reiterated by each of the speakers. Dr. Seaborg spoke principally of the radiochemical studies t h a t led to the identification of the missing chemical elements: element 43 now called technetium (Tc) by Perrier and Segrè of the University of
Types of Radioactive Decay in his talk on the fundamental aspects of the detection and measurement of radioactivity at the Madison symposium, C. D. Coryell described six types of spontaneous nuclear reactions that are of interest to chemists and biologists. (Not discussed were forced nuclear reactions and delayed neutron emission.) The six types, illustrated below, are: 1. Alpha emission. Occurs only for "nuclides" (a term proposed by T. P. Kohman to describe an atomic species of given structure and composition; more specific than the overworked term, isotope) of mass greater than 208 except for one "Sin isotope which is a natural alpha emitter. 2. Beta emission. Is very common. Part of the energy is carried off by the neutrino, v, which does not give detectable ionization. Often the final state of the nucleus is me tas table, resulting in 3. Beta decay with gamma emission. A similar readjustment may follow the other five types of decay. 4. Isomeric transition. Energy may b e released by gamma emission (a) or by internal conversion (b and c)
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