THE CHEMICAL WORLD THIS WEEK beef adrenals. In addition, it has been found that by using different enzymes, it is possible to effect definitive changes at chosen points on the basic molecular framework of the adrenocorticotropic steroids. There are, for example, seven different positions on the basic 21-carbon structure where oxygen theoretically can be introduced (o form adrenocorticotropic hormones. Perfusion studies have shown four of these reactions to progress. In studying the changes which different compounds undergo in the adrenals, perfusion techniques, with the addition of recycling fluids through the adrenal glands, have shown that the conversion of pregnenolone to compound F is a stepwise reaction. The most recent phase of work in this field, said Dr. Dorfman, involves the use of carbon 14 tracers to follow the chemical reactions leading to the formation of the various steroids. Concentration Through Ion Exchange Ion exchange has proved a valuable Members of the APMA audience were "put to work" by J. C. Spickler (standing), of A. T. Kearney & Co., in demonstrating how work simplification could speed up production means of concentrating corticotropin. In a process described by Maurice S. Raben of New England Center Hospital, corticoC & E N REPORTS: A m e r i c a n P h a r m a c e u t i c a l M a n u f a c t u r e r s ' A s s o c i a t i o n . C e n t r a l tropin can be increased in activity from Scientific Section 20 units per milligram to about 100 units per milligram through selective adsorption of the hormone on powdered cellulose. The active component is adsorbed from a 0.1 N acetic acid solution, and is subsequently washed from the cellulose adsorbent with 0.1 N hydrochloric acid. There is strong evidence that the adsorpBiosynthesis and purification techniques improve tion is effected through ion exchange, Dr. Raben said. Support for the postulaoutlook for adrenal and pituitary hormones tion of an ion exchange mechanism is CHICAGO - I n the three years that have est techniques for the biosynthesis of the supplied by the fact that the adsorption is vastly increased by using oxidized celpassed since it was found that the adrenal steroids. gland could be removed from the body Perfusion techniques, in which removed lulose (oxycellulose) instead of plain and artificially stimulated to produce glands are stimulated by treatment with Edward F. Rosenberg, Michael Reese adrenocorticotropic hormones, biochemists ACTH or other chemicals, have shown Hospital, and Ralph I. Dorfman, Worcesand biologists have made highly significant that a large number of reactions occur ter Foundation for Experimental Biology, progress toward improving production within the glands; studies have indicated discuss work in hormone biosynthesis techniques for the biosynthesis of adrenal that the adrenals may produce 30 or more steroids—widely acclaimed for their use- separate steroids. Of these, at least six fulness in the treatment of arthritis and have exhibited high biologic activity in related disorders. Until about three years metabolic processes, Dr. Dorfman said. It ago, according to Ralph I. Dorfman of has also been shown that human adrenals the Worcester Foundation for Experimen- perfused with ACTH yield an array of tal Biology, it only had been shown pos- steroids different from those produced by sible to isolate adrenocorticotropic steroids with the power of simulating the action The W e e k ' s Events of the adrenal gland in situ. Upon this basic discovery, however, has Radiation Energy Soon t o Be Used since been built a sizable structure of For Chemical Processes by Industry 647 knowledge concerning the glands, the UNESCO Told to Tackle More Basic chemicals which affect their performance, Problems b y Scientists 650 and the chemicals which they produce unVolwiler Receives Honorary A I C der varying conditions. Speaking before Membership 652 the central scientific section of the AmeriChemical Combination Effect on can Pharmaceutical Manufacturers' AssoRadioactivity Confirmed a t APS Meeting 654 ciation, which met here Feb. 4 to 6, Dr. Mellon t o Receive Fisher A w a r d in Dorfman described, in a symposium on Analytical Chemistry 664 adrenal and pituitary hormones, the lat-
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powdered cellulose as adsorbent. Oxycellulose containing 1 1 % of carboxyl radicals has b e e n s h o w n to pick u p 6 2 5 times as much corticotropin as plain cellulose, and t h e adsorbed product in this case is four times as potent biologically as that recovered from cellulose. Slow R a t e of Reaching Equilibrium The principal drawback with the u s e of oxycellulose is its extremely slow rate of reaching equilibrium. T h e l o w rate makes continuous adsorption in ion exchange columns impractical; batch methods, 'which involve agitating t h e solution with t h e resin for 2 4 hours, have b e e n found desirable. It has b e e n determined experimentally, Dr. Raben said, that t h e weight ratio o f oxycellulose t o corticotropin must be' h e l d a t 0.08 or lower to assure complete adsorption of only t h e active component. The significance of this work, Dr. Raben indicated, lies in proving that the active principle of corticotropin can b e isolated -without t h e hydrolytic procedures previously considered essential. There are w i d e differences in structure b e t w e e n the adsorbed and t h e nonadsorbed fractions, as shown b y spectrophotometric inspection. E v e n d i e product adsorbed on oxycellulose, however, is not absolutely pure in the biological sense. One disappointing finding in the study, Dr. Raben said, was that t h e active principle is virtually identical i n chemical composition to the inactive portion from which it is removed. Paper chromatograms of the t w o fractions are almost indistinguishable. Clinical Corticotropin Should B e Upgraded Since t h e material adsorbed o n oxycellulose is more stable in storage, and particularly since it has been found in clinical studies to help patients w h o no longer respond to commercial grades of corticotropin, Dr. Raben recommended that all corticotropin intended for clinical use should b e upgraded b y the oxycellulose purification method. About 2.4 grams of the highly active principle can b e isolated from each 1000 grams of anterior pituitary powder. After more than t w o years of clinical study w i t h cortisone and corticotropin, said E d w a r d F . Rosenberg of Chicago's Michael Reese Hospital, the optimism first expressed i n connection, with the materials, seems Justified to a large degree. W h i l e t h e hormones have in no case effected a cure, t h e y have given a large measure o f relief to numerous patients, and have enabled many to resume a fairly normal life. Side reactions have proved serious complications in only a very f e w isolated cases; i n virtually every case, Dr. Rosenberg said, it appears that benefits in relief from suffering afforded b y hormone treatment offset b y a w i d e margin the discomforts of secondary reactions. In D r . Rosenberg's experience, there has been n o case of death clearly attributable t o cortisone or corticotropin treatments. V O L U M E
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C&EN REPORTS: ACS New York Section Meeting-in-Miniature
Industry Will Soon Use Radiation Energy for Chemical Processes Techniques for sterilization, reaction acceleration a r e r e a d y when price is right N E W Y O R K . - " I n t h e near future radiation chemistry will b e out of t h e laboratory a n d into t h e plant," t w o Columbia University investigators promised the N e w York Section of the A M E R I C A N C H E M I C A L
SOCIETY at their fourth meeting-in-miniatufe on F e b . 8. Although as a gross energy source radiation energy can never b e competitive with heat energy and there is still no general theory which will predict the chemical effects of radiation, E . L. Caden and E. J. H e n l e y told the group that the h i g h level of interest in industry coupled w i t h AEC's desire to dispose of accumulating fission products will ensure t h e utilization of radiation energy b y industry within the next f e w years. T h e development of this application, however, is b e i n g hampered at t h e present because no fission wastes are available even for laboratory experiments and all techniques must b e investigated by extrapolation of the effects of pure isotope irradiation. Radiation effects, they-said, can only b e used profitably i n systems that will "help." Unless t h e reaction is between thermodynamically unstable compounds, or is autocatalytic, or proceeds b y chain induction t h e amounts of radiation required would b e prohibitive. I n a C—H compound where the bond energies are about 2 5 electron volts, about 2 5 billion roentgens would b e required to break 1% of t h e bonds in o n e gram of t h e material. Certain empirical ^generalities about t h e probabilities of radiation-induced reactions w e r e submitted b y the authors. T h e yield of polymerization reactions under radiation will increase with the degree of unsaturation of the monomer, they said. Of t h e sample data submitted the acrylonitrile polymerization gave the best yield b y several orders of magnitude. Condensation reactions, they said, also are favored b y unsaturated compounds and are about t h e only radiochemical reactions possible with the extremely radioresistant aromatics. Saturated hydrocarbons in general dehydrogenate under radiation. Yields in this case are increased by high hydrogen-carbon ratios, increased saturation, l o w molecular weight, and molecular simplicity. Fatty acids under radiation, it was reported, hydrogenate to a small extent but their primary reaction is decarboxylation. T h e destruction of polar groups seems to b e a general characteristic of radiation. Alcohols and aldehydes undergo similar radiation-induced reactions. Some cracking occurs i n all irradiation, the authors stated. Resonating ring compounds and conjugated chains usually resist this process but introduction of a side
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chain on a ring compound increases t h e fragmentation. Oxidation is also a general effect of radiation whenever free or combined oxygen is available t o t h e system. At present, the authors reported, t h e industrial reactions receiving t h e greatest attention from radiochemists are gas phase reactions, w i t h and without conventional catalysts. T h e production o f ammonia from nitrogen and hydrogen, a n d t h e oxidation of sulfur dioxide t o t h e trioxide seem t h e most promising. Irradiation Sterilization Sterilization by particle irradiation is probably the most advanced o f the radiochemical techniques for industry, t h e y reported. It will probably b e applied first to drugs a n d other n o n f o o d products. Further studies of t h e effects of radiation on nutritional qualities will h a v e t o prec e d e t h e use of this t e c h n i q u e o n food products. In an informal discussion after t h e presentation of his paper C a d e n admitted that present lines of development i n radiation chemistry would indicate that radiation from particle accelerators w i l l probably come into industrial. use b e f o r e t h e techniques of utilizing fission -waste products are perfected. One such accelerator, d e v e l o p e d expressly for industrial use, w a s described in a contribution presented b y W . Huber of the Electronized Chemicals Corp. This device, called the capacitron, uses a combination of an impulse generator and a laminated discharge tube to produce bursts of high intensity, fast electrons lasting for periods of a f e w microseconds. Although standard counting devices cannot b e used to measure radiation concentrations for such short periods, Huber described a calorimetric technique w h i c h indicated that each of the bursts carried energy equal to "hundreds of millions o f rep-grams [roent gen-equivalent-physical-grams ] / ' Since the capacitron is intended specifically for sterilization, it u s e s t w o electron beams originating on opposite sides of the radiation zone. Huber s h o w e d that this arrangement permits t h e t w o beams to overlap in t h e center of t h e b o d y being irradiated. Although both b e a m s are weakened b y absorption w h e n they reach this point, t h e sum of their intensities is nearly equal t o that of the original beam. This technique is particularly important in sterilization, since t o destroy all bacteria it is necessary that t h e most lightly irradiated zone must receive a lethal irradiation regardless of the intensity of t h e energy received b y t h e rest of the mass. 647
