Commercial Availability of Polio Vaccine Awaits Further Testing

BERKELEY, CALIF.-A report of work which shows great promise of being a major step towards producing an immunizing vaccine for poliomyelitis highlighte...
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T h o m a s M . Rivers ( l e f t ) , Rockefeller Institute for Medical Research, questions Sir F r a n k M . Burnet, W a l t e r a n d Eliza Hall Institute of Research in Pathology and M e d i c i n e , Mel-

b o u r n e , Australia, o n his address describing virus research. Right. H e r a l d R. Cox ( l e f t ) , Lederle L a b s , discusses t h e polio vaccine with W e n d e l l M. Stanley, University of California

C&EN REPORTS: Symposium on Biochemistry a n d Viruses

Commercial A v a i l a b i l i t y of Polio Vaccine A w a i t s Further Testing Chick e m b r y o provides k e y t o mass p r o d u c t i o n of p o l i o vaccine B E R K E L E Y , C A L I F . - A report of work which shows great promise of being a major step towards producing an immunizing vaccine for poliomyelitis highlighted the symposium on biochemistry and viruses which was held in connection with t h e opening ceremonies of the University of California's n e w biochemistry and virus laboratory here, Oct. 9 to 1 1 . Herald R. Cox, director of varus research at Lederle Laboratories, told the 600 persons attending t h e symposium that h e and his coworkers, after many unsuccessful attempts, h a d succeeded in inducing the M E F I strain, Lansing type of poliomyelitis virus to grow in the tissues of the developing chick embryo and that monkeys and chimpanzees given the chick embryo-propagated virus either intracerehrally, orally, or intramuscularly, became immunized against Lansing polio, probably the most deadly of the three major types that afflict mankind. Dr. Cox pointed out that up to this time, polio viruses have been grown only in brain tissues derived from h u m a n s , monkeys, or rodents, that these procedures are most cumbersome and expensive 1 , and that they fail to provide enough virus 4478

for large-scale production of vaccine or diagnostic material. T h e speaker pointed out that t h e logical way to immunize infants a n d children against poliomyelitis is to induce infection by way of the gastro-intestinal tract byfeeding a modified or a t t e n u a t e d live virus. An attenuated Lansing type strain of polio virus produced in mammalian brain tissues has b e e n given recently to 20 h u m a n volunteers with good results, Dr. Cox said, but a d d e d t h a t this method of propagation is far from ideal, inasmuch as there is always t h e d a n g e r t h a t other contaminating viruses can b e picked up in this method of production.

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In contrast, the chick e m b r y o is always readily available, inexpensive, a n d free from potentially d a n g e r o u s microorganisms. D r . Cox said t h a t production of vaccines from chick e m b r y o s is well standardized. T h r o u g h a small o p e n i n g in the e g g shell, a small a m o u n t of living modified virus is injected with a h y p o d e r mic needle. The hole is sealed with collodion a n d t h e eggs i n c u b a t e d for a specific period of time. Before h a t c h i n g , t h e eggs a r e cracked, t h e embryos containing the viruses are h a r v e s t e d a n d processed to produce either killed or living modified virus vaccines. At L e d e r l e , a s many as 14 million eggs are u s e d yearly in t h e production of vaccines for rabies, N e w castle disease, and o t h e r viruses. Mass Production. Of particular interest is the fact that t h e n e w v a c c i n e could b e mass produced a t a cost of only $3.00 or so an innoculation. D r . Cox contrasted this cost with $22.50 for innoculation with immune serum globulin, t h e total output of which would innoculate only 507,000 children or 1.7% of t h o s e u n d e r 10 years. In addition, the speaker said, the "stopgap" u s e of immune s e r u m globulin p r o vides protection for only 21 t o 2 8 days and it is doubtful t h a t its administration would b e beneficial to individuals in whom clinical signs of infection are already a p parent, lie said that w h i l e Lederle could go into* mass production o n t h e n e w vaccine immediately, no plans a r e m a d e to do so until more extensive tests are m a d e with chimpanzees, a n d h u m a n field tests are conducted. Two Faces. N e w w e a p o n s for mass destruction may c o m e o u t of virus r e search, Sir Frank Maefarlane Rurm-t, director of the W a l t e r a n d Eliza Hall In-

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stitute of Research in Pathology and Medicine, Melbourne, Australia, warned the group at a banquet during the dedication ceremonies. Sir Frank said that when biologists pass beyond the point of providing for the needs which all men of good-will can agree are desirable, it is necessary to review progress in the same way that physicists have since 1945, for, he said, biological knowledge can be used just as effectively as physical for the satisfaction of human desires whether these are for security or for power over other human beings. The speaker said that few who have followed developments in the field of virus research could feel confident that within the next decade many new weapons of mass destruction will not appear. He added that it may be an inevitable phase of history that such weapons have to be forged, but urged that we be realists and not claim that the advance of biological knowledge must move invariably toward human well being and the advancement of medicine. Pure Hormones. Isolation of pure forms of the two important hormones, oxytocin and vasopressin, for the first time was reported by Vincent du Vigneaud, Cornell University medical college. Oxytocin, which is used in many clinics to bring on labor in difficult childbirth, and vasopressin, which causes a rise in blood pressure and cuts down kidney secretion, have been especially difficult to separate from each other. Dr. du Vigneaud said almost entirely pure forms of both hormones are the recent result of work begun in 1932 and oxytocin has been obtained completely free of vasopressin. Both of the hormones are polypeptides, made up of eight amino acids, six of which are identical in both compounds. The speaker said that he and his associates have set as their goal the synthesis of the two hormones and the liberation of medicine from the limitations of animal supplies. Inasmuch as the hormones have now been obtained in pure forms and the amino acids identified, he was optimistic that success in synthesizing the compounds would follow. ACTH Studies. Isolation of a form of ACTH nearly 400 times more potest than tile original crude hormone preparation, was announced by George P. Hess and Frederick II. Carpenter, University of California, at a meeting of the Pacific Slope Biochemical Conference held on Saturday of the three day dedication program. Partition columns were used in the isolation of sheep hormone preparations of high biological activities (200 to *00 units per mg.) without prior peptic digestion. When the material of this activity, which was contained in one of three fractions of the original starting material, was rechroinatogramed in the same system, it gave a nearly symmetrical clulioii peak which contained virtually all the material which had been placed on the; column. No gross inhomogenoity was detected in this fraction when it was subjected to further chromatography. VOLUME

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C & E N REPORTS: Symposium o n P o l y h y d r i c A l c o h o l s

industrial Uses W i d e n e d For Polyhydric Alcohols "Polyologisfrs" on polyol applications

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NEW YORK.—Research workers in the fields of resins, pharmaceuticals, tobacco, adhesives, cosmetics, and candy, told of their experiences with the polyhydric alcohols as humectants and industrial chemicals during a symposium arranged here Oct. 15 by the Atlas Powder Co. Atlas has attained continuous catalytic production of sorbitol from corn, but the speakers did not confine themselves exclusively to that product. The symposium, held at the Waldorf Astoria, also heard a general discussion on t h e grain as a chemical raw material by Floyd J. Hosking of the Corn Industries Research Foundation, Washington. More than 600 persons were on hand when the symposium got under way with Sidney Kirkpatrick, McGraw-Hill, acting as chairman. There were no speakers from Atlas Powder. It was a gathering of "polyologists," the chairman remarked; "a clinic in which n o holds would be barred in order to bring us u p to date on the polyols." Research and use of glycerol, pentaerythritol, ethylene glycol, and sorbitol in alkyd resin formulations was explained by Samuel Creselius, chemical division, Naval Research Laboratory, Washington. Ethylene glycol has two hydroxyl groups both of which are primary and hence have the same reaction rate, he said. Only a straight chain polymer can be formed with no cross linking. Glycerol. Glycerol has two primary and one secondary hydroxyl. This allows both cross linking and substitution of monobasic fatty acids without stopping the chain growth, but the esterification rate is slower than for ethylene glycol. Pcntaerythritol has four hydroxyls per molecule, all primary. Eacli methylol group is attached to a central carbon atom, giving the material a symmetrical structure. The probability of cross-linking is greater. Mannitol and sorbitol each have six hydroxyls, two of which are primary and the rest secondary. When csterified in the presence of organic acids and high temperatures these materials lose water and form inner ethers. TI lis uses up two of the hydroxyls and renders them unavailable for esterification. In a series of alkyd resins prepared at the Naval Research Laboratory, 0.5 equivalent sorbitol and 0.5 equivalent glycerol were used with various fatty acids ranging from 28';* phthalic anhydride content upward. It was found that the product gave* a color quite comparable to the pioducts made with straight glycerol, while

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polymerization reactivity during processing fell somewhere between glycerol and pentaerythritol. Pharmaceuticals. Use of the polyols in pharmaceutical manufacture was outlined before the symposium by Henry R. Kreider, aide to the scientific director of William S. Merrell Co. In postwar experience, Dr. Kreider said, it was found that sorbitol possessed certain characteristics which permitted its substitution for highpriced diluents and also introduced other desirable advantages. Sugar, for example, is not wanted by dentists in mouth washes, gargles, and sprays as it is metabolized by certain mouth bacteria to form acids. Sorbitol, lie said, overcame that objection. The stinging sensation of alcohol or glycerol also is absent. In their researches they had not found a commonly occurring organism which will ferment sorbitol, although a conclusive statement as to its stability in this regard could not be made. Tobacco. Tobacco processing, which provides one of the important markets for the polyols as humectants, was detailed by R. C. Ernst, dean of the Speed Scientific School, University of Louisville. The moisture in cigarettes, he said, must he kept at an even, low level, and for this purrpose the industry is using glycerol, diethylene glycol, propylene glycol, and sorbitol. One difficulty with glycerol is its rapid moisture fluctuations. Diethylene glycol has the advantage of good mold control. In tobacco, sorbitol only picks up about three-fifths of the moisture adsorbed by glycerol, but the former alcohol, employed as a 7 0 % aqueous solution, offers more stability. It is also excellent, said Dr. Ernst, for leaf that is exposed to high temperatures, and it is used in combination with other humectants. The speaker supplied an interesting picture of the tobacco industry. When it is first sold by farmers at the auctions, leaf has a moisture content of about 2(Kv. Before it is stored by the manufacturer, this content has to be reduced to 12%. Mending is the most intricate phase of tobacco manufacture and in this moisture control is very important. Printing. Morris Kantrowityz, technical director at the lT. S. Government Printing Office, told the symposium that printing inks and adhesives at the government plant had been vastly improved through the use of the polyols. Diethylene glycol and propylene glycol are employed in combination with sorbitol,, and some of the newer formulas for bindery adhesives employ 4479