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MIT's George Scatchard (right) receives the Richards Medal from Paul D. Bartlett (left), chairman of the ACS Northeastern Section, as Walter H. Stockmayer, MIT, looks on. Scatchard told a meeting of the section of his research on serum albumin
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Behavior of Serum Albumin
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Interaction of albumin with acids probably involves reversible swelling of the molecules
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CAMBRIDGE, MASS.-The interac tion of serum albumin with alkali ions is negligibly small. Interaction with small ions may be explained as a bind ing to specific sites, probably the amino groups, if it is assumed that on the molecule there is one extremely active site, eight very active sites, 18 active sites, and probably 70 less active sites. Interaction of albumin with acids is not merely addition of protons but prob ably involves a reversible swelling of the molecules in acid solutions and an opening u p of new groups. These observations were reported by George Scatchard of MIT in his Theo dore William Richards Medal address before the ACS Northeastern Section. Scatchard went on to say "we have a reasonably clear and precise picture of how serum albumin performs one of its important functions—maintaining the volume of the blood. The secret of how it carries various substances in the blood stream is scarcely clearer now than before. We trust, however, that we have opened u p paths nearer to where the secret lies." Measurements with albumin and acids have actually raised more prob lems than they have solved. Deter minations have been made of binding of protons and anions in mixtures of hydrochloric acid and sodium chloride with total chloride concentrations of CHEMICAL
0.001, 0.01, and 0.05 M in hydrochloric acid, in hydriodic acid, and in thiocyanic acid, Scatchard told a dinner meeting of the section. Carboxyl groups in serum albumin are relatively strong acids. T h e pK is 3.8, while in ovalbumin it is 4.3. In lactoglobulin, it is 4.6. Moreover, the electrostatic hindrance of one proton for another is much less than the hin drance of one anion for another in neutral albumin. T h e anions do not seem to help the binding of protons, Scatchard says. Anion binding can be accounted for qualitatively if it is assumed the al bumin molecule swells in acid so that the electrostatic repulsion is less than that calculated, he says. Very recently, Yang and Foster have shown that both viscosity and optical activity indicate such swelling. To account for proton binding, it can be assumed that there are more basic groups available at low p H than at high, just as has been found for hemoglobin, except that there is as yet no indication that the albumin reaction is measurably slow, according to Scat chard. Questions that need to b e answered about binding of small ions to proteins are: how many, how tightly, where, why, and what of it? Scatchard went on to say that an important function AND
ENGINEERING
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of albumin appears t o be its combina tion w i t h other molecules, particularly with anions, to carry them in the blood stream at moderate activity. Serum al b u m i n combines with small anions more actively than any other protein known. "If we knew enough about this interaction," h e comments, "we could
use it better in medicine a n d perhaps in other ways." In the study of proteins, Scatchard says, the secret never plays with un loaded dice. "This is not dishonesty, only sophistication. An important part of the game is to determine h o w the dice are loaded."
THE COVER
Solutions That Aren't Elementary -pvUFUNG W O R L D W A R I I , a scientist -"^ well known to Pullman porters on night trains between Boston and New York was MIT's George Scatchard. A regular c o m m u t e r on the New Haven & Hiirtford, Scatchard usually spent about half of each week in Boston working with E d w i n J. Cohn of t h e Harvard Medical School on the frac tionation of plasma proteins. The other half, he'd be in New York investigating the gaseous diffusion separation of uranium isotopes with Harold C. Urey a t Columbia. This routine, broken b y frequent trips t o Washington, kept u p for m a n y months, as Scatchard, with his characteristic flair for getting t o t h e heart of technical problems, made im portant contributions to t h e nation's war effort. This m o n t h , at Harvard's Mallinckrodt L a b , Scatchard received a major honor, t h e Theodore William Richards Medal of the ACS Northeastern Sec tion. This award marked a high point in a scientific career that has spanned more than 35 years and has left its imprint both in this country and abroad. Primarily, Scatchard is famed for his work on t h e physical chemistry of solu tions. In research on the equilibrium and kinetic properties of solutions, h e has explored a great range of materials, extending all t h e way from paraffins and alkali halides to ion-exchange resins a n d proteins. Born in Oneonta, Ν. Υ., in 1892, Scatchard got his first taste of chem istry as a teenager while working in his brother's drugstore. When h e en tered Amherst in 1909, h e still h a d n ' t m a d e u p his mind about a future career. " I n those days, w e weren't so rushed into making decisions as young people a r e n o w d a y s , " h e says. Some of h i s teachers, impressed b y his pro ficiency in English and Latin, thought that surely h e ' d major in languages. Young Scatchard disappointed them; he chose chemistry. After graduation in 1913, Scatchard went to Columbia to study organic chemistry u n d e r Marston T. Bogert. Before receiving his P h . D . from ColumV O L U M E
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bia in 1917, h e served for a year under Alexander Smith as a research assistant in physical chemistry. World W a r 1 sent Scatchard off to Europe. Commissioned a first lieuten ant in the Sanitary Corps, he worked with Victor Grignard in Paris on de fensive gas warfare, particularly on methods of counteracting the effects of mustard gas. In 1919, Scatchard returned to teach at Amherst, where he also found time to investigate such problems as speed of reaction in concentrated solutions, hydration of sucrose, a n d mechanism of inversion of sucrose. In 1923, h e ac cepted a National Research Fellowship at M I T , where at the start his work was concerned primarily with proper ties of strong electrolytes. Joining the faculty in 1924, h e has been associated with M I T ever since. On a sabbatical in 1 9 3 1 - 3 2 , Scatchard held a Guggenheim Fellowship that enabled him to study t h e theory of solutions with top-ranking European chemists, particularly Peter Debye at Leipzig. In the latter half of 1946, Scatchard set u p his headquarters in Berlin, where he was scientific adviser to Gen. Lucius D. Clay, then deputy military governor. Recognizing the singular importance
QUOTOONS Î R E G . U. S. P A T E N T
OFFICE)
In industry, people who can fix the blame are a dime a dozen; the ones that get ahead are the ones who can fix the trouble.
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Many chemists enjoy a good game of bridge, especially if they can squeeze it into a lunch hour.
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Λ good scientist never argues with the facts unless he's gone to the trouble of checking them himself.
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—O. A. BATTISTA (Al_L· R I G H T S
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of science, Clay once told him: " D o c , almost everything w e do here is sci ence." While in Germany Scatchard also served as chief of t h e Research Control Branch of the U. S. Military Government. In this capacity, Scatch ard, as successor to Roger Adams, w a s given a prime responsibility for p r e venting revival of German war r e search. As a third job in Berlin, Scatchard was the American representative on t h e Quadripartite Committee on the Liqui dation of German W a r Potential. This committee, composed of representa tives of the U . S., Britain, France, a n d Russia, m a p p e d out plans for destruc tion of German war installations. After Scatchard's trying introduction to t h e work of the committee, Gen. William Draper, quadripartite economics d i rector, attempted to encourage him b y describing in detail the extraordinary delaying tactics used a week before by no less an expert than Molotov a t the ministers 7 meeting in Paris. There upon, one of Scatchard's colleagues, w h o had watched his committee work closely, interjected: "General, D r . Scatchard used all those tricks—and a few more besides." Says Scatchard whimsically: "I never did realize w h a t a scoundrel I could b e . " Active in t h e A M E R I C A N
CHEMICAL
SOCIETY, Scatchard was chairman of its Division of Physical a n d Inorganic Chemistry in 1939. H e served as chair m a n of the chemistry section of AAA S in 1941. In 1 9 5 1 , h e was a national lecturer of Sigma Xi. W h e n it's time for relaxation, Scatch ard delights in listening to music, es pecially chamber music. He's an e n thusiastic supporter of t h e Boston Symphony a n d the local F M radio sta tion that goes heavy on t h e classics. Although during his u n d e r g r a d u a t e days he played guitar in t h e Amherst musical club, he hasn't touched t h e instrument in years. Musical expert i n t h e family is Mrs. Scatchard, who i s associate professor of musical pedagogy at Smith College. W h e n he h a s time to spare, Scatch ard relishes the opportunity to take long brisk walks. He'll even climb a mountain, provided it's w h a t h e calls "just a moderate mountain." Summers, h e spends partly in Montana or N e w Hampshire. In addition, A E C work regularly takes him to Tennessee t o serve as consultant to Oak Ridge N a tional Laboratories. Scatchard reports that, as a scientist, one of t h e prize questions he's usually asked is: W h e n does he get his ideas? "I get them almost anytime," h e says, "on waking u p , shaving in the morning, listening to a concert. Ideas come fairly easily. Then I go to the laboratory a n d find out they're all wrong." 2099
