Wayne Woolley Named Eli Lilly Award Winner
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ΎΗν Caver · , Wayne ΗΙΜΙΙΙΠ \;ΙΙΙΙΙΜΙ Eli Lilly Award Winner A STAFF RHPOHT f^4HKMiCAii sets were comparâtivcly un- known in my country," explained Oil- worth Wayne Woolley as ho reflected on his boyhood in Alberta, where he was born of American parentage. The 33-year-old biochemist of the Rockefeller Institute for Medical Research, however, found this lack of the usual starting apparatus of many young scientists no serious setback to his early career. Mute testimony to this fact is borne by a record of 84 publica- tions in 13 years and an impressive list of honors which became one longer when it was announced at the national meet- ing of the AMERICAN CHEMICAL SOCIETY in Chicago on Monday evening that he ΛΉΙ receive the Eli Lilly Award in Biochemis- try. The award will be presented at the fall mooting of the Society. Canadian liackarffurul Wayne Woolley, as he prefers to be called, began his scientific pursuits at the Raymond, Alta., high school where chem- istry quickly captured his major interest. The biochemical bent became pronounced at the University of Alberta, from which he received his bachelor of science degree in 1935. This tack into biochemistry he attributes in part to his own inclinai ions plus that major factor of chance which at times seems to open doors and mark paths with a compulsion that leaves the indi- vidual no choice but to follow. The year 1936 found Woolley receiving a master of science degree from the University of Wisconsin. Two years later a Ph.D. degree followed from the same source, where W. Η. Peterson had been his major professor. A trip to England in the summer of 1938 on a traveling fellowship of the 16th International Physiological Congress punctuated a postdoctoral so- journ at Wisconsin which ended in 1939 when he joined the Rockefeller Institute as a fellow. Scientific interest and accomplishment are not the exclusive property of the male half of the Woolley household. The distaff side has its claims too in the form of Janet McCarter Woolley, a bacteriologist, and one of his earlier coauthors, who also re- ceived her master's and doctor's degrees at Wisconsin. They met, worked together, and published their joint paper at that university, where the future Mrs. Woolley stayed until 1944. Then a Guggenheim Fellowship brought her to the College of Physicians and Surgeons of Columbia University. In 1945, at the completion of the fellowship, Columbia lost a bacteriolo- gist and Woolloy, gained a wife who still, in Woollt>y's words, "shoots a guinea pig now and then" between her household duties. Perhaps it is a peculiar coincidence that it was "the husband of a bacteriologist who has de* ne so much to investigate and ex- ploit, tiie use of bacteria as organisms for the biological assaying of vitamins. When concluding his address in 1940 before the meeting of the Society of American Bac- teriologists, at which, incidentally, he re- ceived another Eli Lilly Award, this time for work in immunology and bacteriology, Woolley said, " I believe that studies on the nutritive requirements of bacteria will elxicidate many facts concerning bac- terial physiolugv which have not before been discussed. It is becoming apparent that tiie same compounds are concerned in the growth of all living eells. Many facts concerning the mechanism of biochemi- cal processes may he discovered as a result of the application of the knowledge of growth factors. In addition, the use of bacteria, rather than ra.ts and other ani- mals, for assays of the vitamins will materially reduce the cost and labor in- volved in analyzing for these interesting materials." The above paragraph brought to a close a paper that was devoted to a review of the results of several studies that had been made on the nutritive requirements of bacteria. At the outset of this paper, WooLley had explained some of the facts regarding growth factor and amino acid re- quirements of certain bacteria and how studies in bacterial nutrition have ad- vanced the whole field of nutrition and bio- chemistry. In 1938, h e revealed, a study had been inaugurated by his co-workers and him to determine the nutritive re- quirements of hemolytic streptococci. It was found that treatment of a try ρ tone and Liver extract medium with alkali made it incapable of supporting growth. When riboflavin, pantothenic acid, and a re- ducing compound such as reduced iron were added this alka.li-trea.tcd medium was restored to effectivity. The observa- tion "was made that the addition of any two of tliese substances did not accomplish the restoration; all three together were necessary. Subsequent investigations showed thatsixlfhydryl compounds such as glutathione, tbiioglycollie acid, and ascor- bic acid were also effective. Finely divided reduced iron, however, remained as tiie best reducing agent. This work immediately gave rise to the question of the definition of an anaerobic organism. It was long known that hemo- lytic streptococci can be grown on the surface of agar plat.es and are generally not considered to be anaerobic. These studies, however, showed that the medium must, contain a substance which lowers the oxidat ion-reduction potential to the proper value. The question of definition was further compounded by the fact that, al- though Clostridia are usually considered to be strict, anaerobes, growth can be accom- plished on a synthetic medium or one con- taining peptone, if a suitable reducing agent is added, without resorting to use of anaerobic jars. For these reasons, Woolley explains, it would seem that the need for an anaerobic atmosphere cannot be used as a criterion for determining the classification of organisms as anaerobic or aerobic. Λ more suitable definition, he asserts, would be that an anaerobic organism is one which cannot by itself create an oxidat ion-reduc- tion potential suitable for the initiation of growth. This definition is not the final answer, according to Woolley, because all peptones and extracts of organs unless treated with alkali contain sulfhydryl compounds which bring about a favorable reducing atmosphere. It is possible, how- ever, to apply this definition to those organisms which can be grown on purified media. Experimenting with Hem aty I ic S t rep Lacocci The next logical step in the development of this work was to attempt the growth of the hemolytic streptococci on a synthetic medium containing only the above men- tioned growth factors. Strain II 69 D 5 failed to grow in this medium until liver extract was added. Fractionation of the extract isolated the active ingredient which proved to be a* basic substance similar to vitamin B fi , which had just been isolated at that time. Subsequent tests showed that this vitamin was indeed the active ingredient. Amino acids remained as the only un- known constituents of the basal medium. The good growth resulting from the sub- stitution of a mixture of 19 pure amino acids showed that the hydrolyzate con- tained no essential unrecognized sub- stance. To find which of these 19 acids were indispensable, experiments were run in which one acid at a time was eliminated and the growth or omission of growth noted. Glutamic acid and tryptophane proved to be the indispensables. Ad- ditional work added isolcucinc, lysine, arginine, cystine, and tyrosine to the list of needed acids. The Harvey Lectures (1945-46) of the New York Academy of Medicine gave Woolley the opportunity to present the results of his studies on ''Biological An- tagonism between Metabolically Im- portant Compounds and Their Structural Analogs." In essence, the theme of this presentation reduces to two major observa- tions: that materials very similar to vita- 1148 CHEMICAL AND ENGINEERING NEWS
Transcript of Wayne Woolley Named Eli Lilly Award Winner
ΎΗν Caver · ,
Wayne ΗΙΜΙΙΙΠ \;ΙΙΙΙΙΜΙ Eli Lilly Award Winner
A S T A F F R H P O H T
f̂ 4HKMiCAii sets were comparâtivcly unknown in my country," explained Oil-worth Wayne Woolley as ho reflected on his boyhood in Alberta, where he was born of American parentage. The 33-year-old biochemist of the Rockefeller Institute for Medical Research, however, found th is lack of the usual starting apparatus of many young scientists no serious setback to his early career. Mute testimony to this fact is borne by a record of 84 publications in 13 years and an impressive list of honors which became one longer when it was announced at the national meeting of the AMERICAN CHEMICAL SOCIETY in
Chicago on Monday evening that he ΛΉΙ receive the Eli Lilly Award in Biochemistry. The award will be presented at the fall mooting of the Society.
Canadian liackarffurul
Wayne Woolley, as he prefers to be called, began his scientific pursuits at the Raymond, Alta., high school where chemistry quickly captured his major interest. The biochemical bent became pronounced a t the University of Alberta, from which he received his bachelor of science degree in 1935. This tack into biochemistry he attributes in par t to his own inclinai ions plus that major factor of chance which at times seems to open doors and mark paths with a compulsion that leaves the individual no choice but to follow.
The year 1936 found Woolley receiving a master of science degree from the University of Wisconsin. Two years later a Ph.D. degree followed from the same source, where W. Η. Peterson had been his major professor. A trip to England in the summer of 1938 on a traveling fellowship of the 16th International Physiological Congress punctuated a postdoctoral sojourn at Wisconsin which ended in 1939 when he joined the Rockefeller Institute as a fellow.
Scientific interest and accomplishment are not the exclusive property of the male half of the Woolley household. The distaff side has its claims too in the form of Janet McCarter Woolley, a bacteriologist, and one of his earlier coauthors, who also received her master 's and doctor's degrees at Wisconsin. They met, worked together, and published their joint paper at that university, where the future Mrs. Woolley stayed until 1944. Then a Guggenheim Fellowship brought her to the College of Physicians and Surgeons of Columbia University. In 1945, at the completion of the fellowship, Columbia lost a bacteriolo
gist a n d Woolloy, gained a wife who still, in Woollt>y's words, "shoots a guinea pig now and then" between her household duties.
Perhaps i t is a peculiar coincidence tha t it was "the husband of a bacteriologist who has de* ne so much to investigate and exploit, t i ie use of bacter ia as organisms for the biological assaying of vitamins. When concluding his address i n 1940 before the meeting of the Society of American Bacteriologists, at which, incidentally, he received another E l i Lilly Award, this time for work in immunology and bacteriology, Woolley said, " I believe that studies on the nutritive requirements of bacteria will elxicidate many fac t s concerning bacterial physiolugv which have not before been discussed. It is becoming apparent that t i ie same compounds are concerned in the growth of all living eells. Many facts concerning the mechanism of biochemical processes may he discovered as a result of t h e application of t h e knowledge of growth factors. In addition, the use of bacteria, rather than ra.ts and other animals, for assays of t h e v i tamins will materially reduce the cost a n d labor involved in analyzing for these interesting materials."
T h e above paragraph brought to a close a paper tha t was devoted to a review of the results of several s tudies t h a t had been made on the nu t r i t i ve requirements of bacteria. At t h e ou t se t of this paper, WooLley had explained some of the facts regarding growth factor and amino acid requirements of certain bacteria and how studies in bacterial nutrit ion have advanced the whole field of nutrition and bio-chemistry. In 1938, h e revealed, a s tudy had been inaugurated by h i s co-workers and him to de te rmine the nutri t ive requirements of hemoly t i c streptococci. I t was found that treatment of a t ry ρ tone and Liver extract medium with alkali made it incapable of supporting growth. When riboflavin, pantothenic acid, and a reducing compound s u c h as reduced iron were added t h i s alka.li-trea.tcd medium was restored t o effectivity. The observation "was made t h a t the addition of a n y two of tliese substances d id no t accomplish the restoration; all three together were necessary. Subsequent investigations showed thatsixlfhydryl compounds such as glutathione, tbiioglycollie acid, and ascorbic acid were also effective. Finely divided reduced iron, however, remained as t i ie best reducing agent.
Th i s work immediately gave rise to the question of the definition of an anaerobic
organism. I t was long known tha t hemolytic streptococci can be grown on the surface of agar plat.es and are generally not considered to be anaerobic. These studies, however, showed that the medium must, contain a substance which lowers the oxidat ion-reduction potential to the proper value. The question of definition was further compounded by the fact that , although Clostridia are usually considered to be strict, anaerobes, growth can be accomplished on a synthetic medium or one containing peptone, if a suitable reducing agent is added, without resorting to use of anaerobic jars. For these reasons, Woolley explains, it would seem t h a t the need for an anaerobic atmosphere cannot be used as a criterion for determining the classification of organisms as anaerobic or aerobic. Λ more suitable definition, he asserts, would be tha t an anaerobic organism is one which cannot by itself create an oxidat ion-reduction potential suitable for the initiation of growth. This definition is not the final answer, according to Woolley, because all peptones and extracts of organs unless treated with alkali contain sulfhydryl compounds which bring about a favorable reducing atmosphere. It is possible, however, to apply this definition to those organisms which can be grown on purified media.
Experimenting with Hem aty I ic S t rep Lacocci
The next logical s tep in the development of this work was to a t t empt the growth of the hemolytic streptococci on a synthetic medium containing only the above mentioned growth factors. Strain II 69 D 5 failed to grow in this medium until liver extract was added. Fractionation of the extract isolated the active ingredient which proved to be a* basic substance similar to vitamin Bfi, which had just been isolated at t ha t t ime. Subsequent tests showed that this vi tamin was indeed the active ingredient.
Amino acids remained as the only unknown constituents of the basal medium. The good growth resulting from the substitution of a mixture of 19 pure amino acids showed tha t the hydrolyzate contained no essential unrecognized substance. To find which of these 19 acids were indispensable, experiments were run in which one acid a t a t ime was eliminated and the growth or omission of growth noted. Glutamic acid and t ryptophane proved to be the indispensables. Additional work added isolcucinc, lysine, arginine, cystine, and tyrosine to t he list of needed acids.
The Harvey Lectures (1945-46) of the New York Academy of Medicine gave Woolley the opportunity to present the results of his studies on ''Biological Antagonism between Metabolically Important Compounds and Their Structural Analogs." In essence, the theme of this presentation reduces to two major observations: tha t materials very similar t o vita-
1148 C H E M I C A L A N D E N G I N E E R I N G N E W S
mins, hormones, and other metaholically impor tant substances have been synthesized or found to exist in na tu re and t h a t these s tructural analogs have the property of calling forth in living organisms some or all signs associated with deficiency of t h e metabolite to which they are related. Fur the r reduced, th is amounts to the concept of the vi tamin versus the antivitamin with which Woolley is associated. The concept is diagrammatically represented on the cover of this magazine by the proper meshing of the vi tamin gear with the central wheel of life. T h e ant i -vi tamin "gear" though similar to t h a t of the vitamin cannot mesh properly and life figuratively and li terally grinds to a halt .
An excellent illustration of this mechanism is seen in the work done by Woolley and his co-workers in which they replaced the sulfur a tom of thiamine with a vinyl group forming the pyridine analog of the vi tamin, pyrithiarnine. This substance when fed to mice resulted in the animals ' becoming unable t o stand, the dwindling of their appetites, and their subsequent
JL H E thirty-sixth annual meeting of the Western Petroleum Refiners' Association was held at the Hotel Galvez, Galveston, Tex. , April 5 to 7, and almost 600 had registered b\T the t ime tha t the technical sessions were well under way.
Opening t h e technical sessions was a discussion of t rends in motor gasoline refining and utilization by W. M. Holaday, director of the Socony-Vacuum Laboratories. He began by s ta t ing tha t "barring political upsets, we should anticipate no long-term shortage of crude oil and we certainly should not see ourselves running out of liquid hydrocarbon products. Even with unprecedented demands for crude, our known reserves are larger than a t any t ime in the past ." He developed in some detail comparisons between various refining processes and then devoted the remainder of his discussion to fuel economy and efficient utilization of antiknock quality. D u e to the fact that over S4 billion must be spent by the petroleum industry in the next several years to meet quant i ty demands alone, he predicted only moderate increase in antiknock quality until the quant i t y demand begins to be satisfied.
In discussing antiknock qual i ty he pointed out data showing tha t significant improvements in fuel economy can be affected by going to high compression rat io engines and high octane number
death, all symptoms of thiamine deficiency. The administration of thiamine in the later stages of the disease, however, restored act ivi ty.
Inhibition Index
The action of the pyrithiarnine, Woolley points out, does not depend on the absolute amoun t of the substance present b u t rather on the ratio of amount of pyrithiarnine to thiamine. For this reason, a n tagonism between a metaboli te such as a v i tamin or hormone and i t s structural analog is usually of a competitive nature, each vying for the a t tent ion of the organism. This ratio between the concentration of the analog necessary to cause a biological response and t h a t of t h e metabolite needed to reverse or negate it exactly is called the inhibition index. With few exceptions, this index is greater than uni ty, showing tha t much more inhibitory analog must be added to a n organism than there is of metabolite present.
Another general observation that can be
A STAFF REPORT
fuels—the latter a point which has been under considerable discussion in some quar ters of the petroleum industry. Assuming tha t high compression engines a re developed, he predicted as an over-all effect a demand for higher research number octane gasoline (as contrasted with the motor octane number), since high compression engines favor "sensitive" fuels of high research octane number and the research number thus becomes a much more significant criterion of fuel antiknock qual i ty than the motor octane number. This , then, points to advantageous use of catalytic cracking plus concurrent installation of catalytic polymerization equipment.
W. A. Howe of the Gulf Oil Corp. presented a paper on the subject of additives to improve engine lubricating oils, and t h e developments in oil from oil shale problem were covered in a paper by Boyd Guthrie and D a n Lankford of the Bureau of Mines Rifle, Colo., installation.
Hydrocarbon Synthesis
Considerable attention was paid to hy drocarbon synthesis. R. W. Krebs, associate director of the Esso Laboratories, gave a general presentation of the applications of the fluid catalyst technique t o catalytic cracking and hydrocarbon synthesis, and R. C. Alden, director of r e search for the Phillips Petroleum Co., gave
made i s tha t in many instances the only organisms which are affected by the analog are those for which the metabolite is a nut r i t ive essential. T h e structurally similar analog, as expected, is ineffectual if the an imal or bacter ium is able to syn thesize the metabol i te .
AVoolley, now an associate member of t h e Rockefeller Inst i tute , belongs to severa l scientific societies, including the AMERICAN C H E M I C A L SOCIETY, the Society
of Biological Chemistry, the New York Academy of Medicine, the New York Academy of Science, t h e Society of American Bacteriologists, t he American Ins t i tu te of Nut r i t ion of which he is a councilor, and the Society for Experimental Biology and Medicine. His awards include the Mead Johnson Award of the American Inst i tute of Nutrit ion, the t w o E l i Lilly awards previously mentioned, and the Research Award of the American Pharmaceut ical Manufacturers Association which he received last week at t h e meeting of t h a t group in Havana . Busy man this Woolley!
a report entitled "Appraisal of Gas Synthesis Operat ions ." Dr. Alden emphasized a number of interesting points . He s ta ted t ha t the steel requirement (six tons pe r B/ID) is so great as to t ake up to 5 % of t h e 1945 steel production i n this country in order t o build installations producing 650,000 B / D . Against t h i s a corresponding production of synthet ic l iquid fuels from coal would take abou t twice a s much investment and nearly twice as much steel a n d the coal required would equa l 2 8 % of the 1945 production. Point ing ou t t h a t t h e natural gas reserves have been increasing at a faster ra te than the marketed production of natura l gas, he nevertheless limited hydrocarbon synthesis operations to those states (10 in number) which have sufficient reserves, since a producible natural gas reserve of 0.5 trillion cubic feet is required to sustain a 7,000 B / D gas synthesis operation for 20 years. Pu t t ing together various figures from recent sources he showed tha t even a comparatively small synthesis gas development will have a profound effect on the markets for the chemical by-products, acetic acid a n d e thyl alcohol being the two commodit ies probably most affected.
New officers elected by the association were H . T. Ashton, president, and J. C. Day , secretary-treasurer; all other officers were re-elected.
No Long Term Shortage of Crude Oil Anticipated
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