G. V. Bykov The Institute of the History of Natural Science and Technology USSR Academy of Sciences MOSCOW
The Origin of the Theory of Cheinical Structure
Several articles appeared in 1958 and 1959 devoted to the centenary of the theory of chemical structure ( I ) , linking its appearance with works by Kekul6 (2) and Couper (3). However, in works published in recent years in the Soviet Union, the theory is regarded to have originated in 1861, when Butlerov r e d a report on "The Chemical Structure of Substances" (4) at the Congress of German Natural Scientists in Speyer. We have recently explained the basic reason for the divergence in views on the question (6). It is that there are two conceptions of the substance of the classical theory of chemical structure. According to one of them, the theory boils down to the theses of the tetravalency of carbon and the capacity of its atoms to link in chains, and of the use of these theoretical propositions for drawing up formulas for chemical compounds (6). According to the other point of view, both the theses are only premises for the creation of a theory of chemical structure, which combines closely bound propositions, the chief of them being the dependence of the chemical properties of molecules (i.e., their behavior in chemical reactions) on chemical structure. It is thus, beginning with Butlerov's L'Introductionto a Complete Study of Organic Chemistry" (Kasan, 1864-66; Leipsig, 186768), that the theory of chemical strncture has been presented in textbooks. Since the system of propositions mentioned above was first advanced in Butlerov's report in 1861, there is some ground to maintain that 1961 makes the centennial of the foundinc - of structural theory. We shall revieni the history of the theory of structure from this point of view, which may be somewhat new to the reader if he is not acquainted with works in Russian on the history of chemistry. We shall also draw attention to several facts in support of this idea of the origin and development of the theory. The Basic Premises for Developing a Theory of Chemical Structure
The very conception of chemical structure could be formulated only a t a definite stage in the development
We know readers will share our pleasure at being able to present here, in English, a point of view usually found only in Russian language publications. We trust that we are not providing a mere polemic for the historians. Thoughtful reconsideration of ideas previously taken far granted almost always gives an illuminating perspective on concepts presently developing. Dr. Bykov's article and others to which it may lead the inquiring reader can serve this purpose.
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of theoretical chemistry. Butlerov formulated it (4) as follows: Proceeding from the fact that each chemical atom' beam a definite, limited amount of chemical force (a5nity) with which it participates in forming a body, I would call that chemical binding, or manner of the mutual uniting of atoms in a complex body, the chmieal structure.
From this definition, we see that- the concept of chemical strncture could only have been advanced after the concepts of the atom (and consequently of the molecule), of valency (or atomicity as it w& then called), and of interatomic binding were crystallized and accepted. The establishment of a correct conception of chemical atoms and the discarding of the equivalent signs of the elements from formulas was promoted in particular by the International Chemists Congress in Karlsruhe, in 1860. The rejection of the equivalents cleared the way for developing a conception of valency, and consequently, for a theory of strncture. We point out that Couper used the symbol for oxygen as if it had an atomic weight of eight. The artificiality of his arguments was apparent to many and to a certain extent justified the sceptical attitude his contemporaries had toward his work. Just as important was the establishment of the concept of the molecule and of ways to determine the molecular weight of organic compounds. In his "Historical Essay of the Development of Chemistry for the Past Forty Years," in 1879-80, Butlerov wrote (7) that the elaboration of this conception was the most essential achievement in chemistry during the middle of the 19th century: After that, when the conception waa established, and due to an aspiration for a mare exact determination of the chemical nature of substances, a conception. . .of chemical structure developed.
The idea of valency was originated primarily by KekulB. Though Frankland advanced the idea before Kekul6 that "no matter what the character of the uniting a t o m may he, the combining power of the attracting element ... . is always satisfied by the same number of these atoms" (S),his views seem not to have attracted due attention because of his use of equivalent symbols for oxygen, carbon, and certain other elements. Kolbe is an exception; on the basis of similar considerations, he reached the conclusion in 1857 about the 1 By chemical atoms he meant the smallest amounta of the element in the molecule, i.e., chemically indivisible, without predetermining the possibility of further division into still sma.ller particles, physical atoms, which cannot be further divided.
tetraatomicity of "carhonyl," the L'double" atom of carbon, Cp, in which the "C" equals the equivalent, or semi-atom, of carbon (9). At any rate, the theory of valeucy accepted by chemists since the close of the 1850's first appeared in the works of Kekul6 in 1858 (2), though it entailed rejection of the thesis of constant atomicity, or valency, of elements, which he continued stubbornly to support even during the second half of the 1860's. The concept of union between atoms was noted quite clearly by Kekul6 and especially by Couper, who originated the line connecting the symbols of the elements.% We will not dwell in detail on Kekul6's and Couper's views in this matter; i t has been done repeatedly. But we shall attempt to discover whether the theses they examined are sufficient to establish the chemical structure of organic compounds. Couper used both correct and incorrect formulas. His formula for ethylene glycol is correct, for example, while his formula for glycerine is wrong. His only attempt to connect the chemical properties of molecules (in particular the acidic properties) with their structure, by the supplementary hypothesis that molecules have electric poles, led to his formula for oxalic acid:
explained the diverse behavior of chlorine in organic compounds by the fact that in some cases (1.9) the chlorine is located in a place insccessible to the active substance, and to a certain extent within the substance, while in most of the bodies (chlorides), it is easily accessible, can easily be attacked, and thus is subjected to the action of the resgent.
Later, in the third part of the same volume, released in 1861, we also find a correct surmise about the reasons for the definite reaction faculty of acetic acid (14): Out of four hydrogen atom, primarily one moves off in certain reactions, perhaps because it alone is directly joined to the carbon group; moreover, it is especially easily substituted by metals and metal-like radicals, perhaps awing to its position near two oxygen atoms. The other three hydrogen atoms are capable of substitution by chlorine. perhaps because they are directly bound with carbon.. ..
..
Nevertheless, Kekul6 did not prefer the formula for acetic acid showing the bonds between the atoms, but the conventional, typical
For more complex substances, he considered "fully expanded" formulas altogether impossible (16) ;
...
atoms spaced side by side in a molecule cmnat be grouped on the surface of paper in such a way as to show atoms joined in various transformetions side by side in a single formula.
which is also incorrect. It is not surprising that Wurtz (10) found Couper's formulas "too arbitrary and too far removed from experiment," while Butlerov (11) wrote: Of course, they express certain relations for the atkity of the elements when forming bodies resulting from their union, but the question neverthelesa arises why the symbols for oxygen and hydrogen. . .are placed as they are, and not otherwise, among the carbon atoms.
Nevertheless, in his "Historical Essay," Butlerov subsequently expressed a very high opinion of Couper's work for his
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definite conception of chemical structure.. .Together with correct views, Couper presented views not quite correct, and even quite but at any rate, his article is a remarkable incorrect ones, advance in chemical theory.
...
It can he demonstrated that Kekul6 also did not hold his formulas expressing "the relations between mutually linked atoms (Ben'ehungen der sich gegenseitig bindenden Atmne)" (12) superior to typical or even empirical formulas. Kehl6 also used graphic formulas, mainly to illustrate the factors comnlicatine the com~osition of organic compounds. Of course, for his time, this was of enormous value. But according to Kekul6, these formulas of his had the shortcoming of not giving any idea of the relative position of the atmns i n space; it was that, he believed, which primarily determined the chemical properties of the molecule. Thus, Kekul6
-
In all fairness it must be said that in 1789 W. Higgins applied in bis formulas the lines joining "particles" of oxygen, sulfur, and E. R.,J. CEEM.EDUC., "dephlogisticrtted air." See ATKINSON, 17,3 (1940).
Kekul6 continued touse type formulas in the first part of the second volume of his textbook, released in 1863, though he stopped using them in his original works hack in 1861, considering them inadequate and declaring that he would change over to empirical formulas. Re made this declaration a t the Congress in Speyer (16), two days after the report on chemical structure by Butlerov. Butlerov's Report ''On the Chemical Structure of Substances'' (1861)
Butlerov criticized the whole idea of typical formulas, both the mineral types of Gerhardt and the carbon types of Kolhe. He rejected the typical theory just as categorically as Couper did three years before him. Among the arguments against it, Butlerov referred in particular (as did Couper) to the impossibility of expressing addition reactions by typical formulas. Havingrejected typical conceptions, Butlerov pointed to the atomicity of elements as a conception that "could serve as a foundation for a general theory and to allow us to advance rather far in our scientific thinking." Butlerov formulated the concept of chemical stmcture which we have given above. Of course, the "relations between mutually linked atoms" of Kekul6 and the "constitution" of Couper's formulas coincide in their contents with the "chemical structure" of Butlerov. However, his merit consists in the fact that he defined "chemical structure" as a scientific concept, clearly separating it from the concept of "constitution" as used by Gerhardt and his followers in the sense of "mechanical structure of molecules," or the arrangement of atoms in space (17). The error in the view that Butlerov used the term "chemical structure" here for the first time should be noted. Actually, it has been found in Russian works on chemistry as far hack as 1845, but either in the sense of Volume 39, Number 5, May 1962
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the mechanical structure of molecules or for describing the composition of molecules by typical formulas (18). Butlerov adopted the term from them, together with certain others. He put new meaning into them and, making them express new ideas, introduced them into the theory of chemical structure. Butlerov formulated the base thesis of the theory of chemical structure: I would believe it possible meanwhile to change the accepted rule that the nature of a complex molecule is determined by the nature, quantity, and position of its elementary component parts, to the fallowing statement: the chemical nature a j o complez molmule is deternined by the nature of its elernenlary c o m p n a l parts, thew quantity, and chemical structure.
We call this the basic thesis of the theory for two reasons. First, because most other concepts are a more or less direct outcome of it, and second, because it is a substantially new idea, counterposed to the old accepted point of view. In confirmation of the fact that this was the Ruhicon chemists had to cross when accepting the theory of chemical structure, we refer to the following opinion voiced by Kekul6 in 1872 (19): The main trend of contemporary chemistry doubtlessly eonsists in studying the constitution of compounds, but this latter does not refer, as previously, to the position of atoms in space, but rather to their mutual binding in the molecule!'
Of course, Butlerov did not attach absolute infallibility to this thesis, noting that chemical properties depend on chemical structure (and composition) in the first place only. But while posing the question thus, he continued in his report:
...we will deal with problems that can be solved through chemical experiment. . . . further development of the view expressed here
will show how much the chemical properties of substances depend on chemical structure, and how inadequate the rule is."
Butlerov showed ways to determine chemical structure and offered a few rules. He believed that all reactions known to chemists could be applied for this purpose, hut he prefered synthetical reactions to decomposition or double exchange reactions. He said that it was desirable to select conditions so that the residues of the molecules, or radicals formed during the reaction, would preserve their chemical structure. At the same time, Butlerov provided for the possibility of rearrangements during the reaction, and consequently, of extra difficulties in determiring chemical structure. He noted, however, "we may hope that after a detailed study of substances from the point of view of their chemical structure, general laws will he developed for such cases too." He added a few rules to these general theses, "developed from facts, and in part already accepted by most chemists." More than half of them presented the basic theses and conclusions of the current theory of valency, including the possibility of atoms of one and the same element uniting. Among the rules, some gave an elementary explanation of the addition reaction mechanism. It follows from the basic thesis of the theory of chemical structure that the structural formulas must give an idea of chemical properties of molecules. Butlerov wrote in his report that "when the general laws of the dependence of chemical properties of substances on their chemical structure become known, 222 / Journal of Chemicol Educofion
such formulas will express all the properties." However, he did not offer any method for writing them. "Time and experience," he said, "will show just what the formulas for chemical structure should be like." Time and experience have shown that the most suitable formulas are Couper's, with their lines describing bonds; Butlerov in the 1860's preferred formulas using braces, though they might be confused with typical formulas. At the end of his report, Butlerov wrote, "I am far from intending to offer a new theory here." But this must not he regarded as an underestimation of the value for chemistry of his system of views, because he concluded his report with a suggestion to substitute them for the prevalent theory of types in all its forms. Probably Butlerov's words reflect his habitual modesty and also, perhaps, covert contrast to Couper, who had promptly announced a "New Chemical-Theory" he had created. After Butlerov's death, Markovnikov, his closest pupil and the iirst to deal with the history of the theory of chemical structure, said that this report ($0) is of especidy great importance in the history of modem theory. It is a document showing that A. M. (Butlerov) was not only the firat to outline the chief essentials of present doctrine quite clearly and definitely; he also developed them in as much detail es possible in a magazine article. In fact, when we now reread this symbol of faith in the theory of structure, we find no difference in it from the principles guiding contemporary (1887) chemish
Elaboration and Development of the Theory of Chemical Structure
We will outline only the principal stages in the further development of the theory of chemical structure. Isomeric phenomena were among the big problems of theoretical chemistry for decades. True, some were explained by the typical theory, like the isomerism of methyl acetate with ethyl formate. But there was another group of isomers, differing only in the position of their substitutes for the carbon skeleton, and still another, with isomer skeletons. The second group was first explained by Butlerov in 1863, in a big article, "On Different Ways of Explaining Various Cases of Isomerism" ($1). The general explanation of isomerism follows from the basic thesis of the theory of chemical structure; since isomers are substances which (having a similar composition) differ in their chemical properties, they differ also in their chemical structure. I n the same article, Butlerov examined the views of Kekul6 and Kolbe on isomerism critically and in detail. He discovered trimethylcarbinol the next year and pointed for the first time to the possibility of skeletal isomerism in the alcohol series and then of saturated hydrocarbons ($8). He himself confirmed his forecasts of new alcohols and hydrocarbons in experiments during the next three years. The dependence of chemical properties on chemical structure are especially manifested in isomeric molecules. Butlerov explained in his article on isomerism that this is so because though the atoms in isomeric molecules are the same, they are influenced by other atoms, depending on the chemical structure, to acquire differing "chemical signifianee," i.e., differing behavior in chemical reactions. Of course, before the idea of
electrons appeared in chemistry, there could he no correct view of the mechanism of the mutual influence of atoms. Butlerov devoted much attention to this question in his textbook, concluding it with the chapter, "An Essay on the Chemical Significance of Elementary Atoms in the Molecules of Carbon Compounds." His pupil, Popov, made an extensive study of the laws of the oxidation of ketones and other organic compounds (2.9). Markovnikov studied substitution reactions from the same point of view and revised written works, formulating several rules concerning substitution, addition, decomposition, and isomerization reactions, though only one of these rules of his is usually attributed to him. Markovnikov wrote a special monograph, " M e terials on the Question of the Mutual Influence of Atoms in Chemical Compounds" (Kazan, 1869). Part of it was incorporated in his articles in German (24). Subsequently, van't Hoff made a systematic study of this entire field from the theoretical point of view (26). Though other chemists also discovered particular cases of the interdependence between the chemical st.ructure and chemical properties of the molecule in their experiments, the first systematic research was done by Butlerov's school. Butlerov and his pupils studied saturated organic compounds and suggested the formulas for their chemical structure. But in the mid 18601s,the theory also expanded to include unsaturated open chain compounds and aromatic ones. Before this, many chemists, including Kekul6 and Butlerov, had approached the idea of multiple bonds, but it was first voiced definitely following experimental tests (though not very convincing ones) by Erlenmeyer, who gave the familiar formula of ethylene, H2C=CH2, and acetylene, HC=CH (26), while Kekul6 suggested his famous formula for benzene in 1865. Questions of Priority
Most divergencies in the written history of the theory of structure occur in questions of priority, falling into three basic trends. Some authors (1) ascribe the origin of theory of chemical structure to Kekul6 or to Kekul6 and Couper together.= Others, chiefly authors writing in Russian, regard Butlerov as the founder of the theory. The third group regards the theory of chemical structure as a simple development of the theory of valency, and therefore do not draw a line between the two. For example, this view was advanced by Pauling in his Nobel Prize speech ($7). However, the very fact that the terms "structure theory" and "structure chemistry" are used extensively in the literature compels us in the historical aspect, too, to regard the structure theory as something independent of the theory of valency. Actually, as noted above, the thesis that the chemical properties of molecules depend on chemical structure is in no degree a logical conclusion from the theory of valency.
The theory of chemical structure has just as much right to independence as the typical theory of Gerhardt, because the very idea of types, and even types of water and ammonia, had been suggested prior to Gerhardt; and just as much as the stereochemical conceptions of van't Hoff and Le Bel, because the idea of the carbon tetrahedron is found prior to them in Butlerov (1862), Kekul4 (1867), and Patema (1869). The idea of molecular dissymmetry as a cause of optical activity is met in Herschel's work back in 1833, and in Pasteur's in 1860. Finally, the idea that certain isomers ought to he explained by various arrangements of atoms in space given a similar chemical structure was clearly expressed by Wislicenus in 1869 and 1873, and served as the point of departure for the reasoning of van't Hoff. For the same reasons, it is a questionable procedure to identify the theory of chemical structure with the views of Kekul6 and Couper. It can only be done when there is a formal approach to the theory as a simple manipulation with symbols, restricted merely by the rules of element valency. Such an attitude is characteristic, for example, for L. Meyer, who entered into polemics with Butlerov about it in 1868.4 The question remains to be answered: How and why did the tradition arise in the history of chemistry to deny Butlerov's role in originating the theory of chemical structure and to attribute it to Kekul6 or to Kekul6 and Couper together? Only Giua noted in his "History of Chemistry" ($8)that the theory of chemical structure appeared in 1861, and attributed the chief role in originating it to B ~ t l e r o v . ~Delacre (29) sees the beginnings of the structure theory in works by Kolbe, though he highly praises Butlerov's role. Kekul6's famous story that the "stmcture theory" came into his head on the upper deck of a London omnibus in 1856 was taken on good faith. I n 1864 he deemed it necessary to note in an article (SO) that his views on the way atoms unite in the molecule would not change in essence ("wesentlich") if "chemical structure" were to be used to express them. I n that same year, 1864, he even maintained a t the beginning of the second part of the second volume of his textbook that he had presented these ideas in an earlier textbook also. This was not a true statement; Markovnikov spoke out energetically against it (31). Historians of chemistry also apparently have been insufficiently acquainted with utterances by Butlerov himself and by Markovnikov about priority. When he returned from the Congress of German natural scientists in Speyer, Butlerov wrote about a feature of German conventions that had impressed him at that time. He mentioned the "hypertrophied national feeling" of the Germans which "makes them insufficiently appreciate every other nationality" (82). And then, he more than once complained in his published writings lhat his views were often cited without
The episode has been described by H. M. Leicester in the 36,328 (1959). pages of TRIS JOURNAL, The historians of chemistry undervalued a long time the Butlerov's role in the history of classical structural theory profundity snd insight of Couper's conception. I t looks as if d m is very well outlined in Leicester's above-mentioned artiole. his name faded away in the blaze of KekulB's fame. But, as it Complying most willingly with what the author said there, I was recently pointed out by 0. T. Benfey [in ~ a r sJOURNAL, should like to note that his paper aud mine oomplement one 36, 319 (1959)], neglect of Couper eontinuea. another in thia respect. Volume
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any mention of his name, and in a reply to L. Meyer, he wrote plainly that he found his opinions constantly smothered. Butlerov went abroad in 1867-68 to stand up for his priority. The trip was arranged by the University of Kazan in varticular in order to "provide Mr. Butlerov himself the opportunity to make clear to foreign chemists his right to the leading role in developing the trend of contemporary chemistry" (3'3). Jn reply to a letter from Butlerov (from Kazan) which has not been preserved, Markovnikov wrote from Leipzig in October, 1866 (34): "From what you write, I see that the main purpose (of the trip abroad, G. V. B.) is to compel recognition of your priority, historically, in the current views of chemistry. It is not only a delicate business, but difficult too. From Buff's hook (38, you see that anyone who has written anything about it imagmes that he has created the theory. Some people describe it without mentioning nsmes, while still othera, less conceited and less selfish, refer it all to such authorities aa KekulB."
Further, Markovnikov advised Butlerov to come to Germany after the first part of the German translation of his textbook was issued. "Then," he wrote, "when they read i t here, a t least the first part, you can point out that you developed the principle of chemical structure before any Kekulbs or Buffs did." Later, Markovnikov named Butlerov on various occasions as the founder of the theory of chemical structure.@ Trne, he did not develop and did not always support these assertions of his. It has been done by Soviet historians of chemistry, who began a systematic elaboration of the history of the classical theory of chemical structure in the late 1940's. In this article we have attempted to describe the basic conclusionsreached. Acknowledgment
The author is deeply grateful to the editor and reviewers of this paper for valuable comments. Literature Cited (1) STAAB,H. A,, Angm. Chem., 70, 37 (1958); GROHN,H., Chem. Techn. (Berlin), 10, 501 (1958); VERKADE, P. E., Ploe. chem. Sot., 205 (1958); FIRRER, W. V., AND FARRER,K. R., PTOC.Chem. Soc., 285 (1959); BROWN, H. C.. J. CHEM.Eouc., 36, 104 (1959); and "Kekul6J. CHEM.EDUC.,36. Couner Centennial Svm~osium." . 31929 (1959). (2) KEKUL*,A., Ann. Chem. Pharm., 106,129 (1858).
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See Ref. SO, pp. 280, 648,and 684.
(3) COUPER,A. S., Phil. Mag., [4], 16, 104 (1858); Ann. chim. phys., [3],53,467 (1858). (4) BUTLEROV, A., Z. Chem. Pham., 4,541 (1861). (5) Bwov, G. V., PTOC.C h a . Soc., 210 (1960); see also Bwov, G. V., "History of the Classical Theory of Chemical Structure," USSR Acad. of Sci. Publication, Moscow, 1960. (ti) METER,L., Ann. Chem. Pham., 145,124 (1868). (7) BUTLEROV,A. M., "Collected Works," Moscow, 1958, Vol. 3,p. 169. (8) FRANKLAND, E., AND BRODIE,B. C., Phil. Trans., 417 (\----,1 852).
KOLBE,H., Ann. Chem. Pharm., 101,257 (1857). WURTZ,A,, R4p. chim. pure, 1,49 (1858). BUTLEROV, A,, Ann. Chem. Pham., 110, 51 (1859). XEKUL~, A,, "Lehrbuch der organischen Chemie oder der Chemie der Kohlenstoffverbindungen, Bd. 1, Erlangen, 185941,p. 174. (13) Ibid., p. 173. 114) D. 523. ~ - --Ihid.. , (15) Ibid.; 522. (16) K E K U L ~A,, , Z.Chem. Pham., 4, 613 (1861). (17) HIELT, E., "Geschichte der organischen Chemie van 81tester Zeit bis zur Gegenwart," Braunschweig, 1916, p 249-50. (18) BYKOV,G. V., "Problems of the History of Natural Science and Technics," Moscow, 1957, Val. 4, p. 179. (19) KEKUL*, A., Verh. d. naturhista. Vweines d. preussischen Rheinlande u. Westphalas (Bonn), Sitmngsberichte 29, 1.5 - - (1R72) - -.-,. (20) MARKOVNIKOV,V. V., "Selected Works," Moscow, 1955, p. 827. BUTLEROV, -4. M., Z. Chem. Pham., 6,5M) (1863). BUTLEROV, A. M., Z. Chem. Pha~m.,7,385,513 (1864). POPOV,A., Z.Chem., [21, 4, 619 (1868); Z. Chem., 7, 4 (1871); Be?. b u t . chem. Ges., 4, 720 (1871); Ann. Chem. Pharm., 161, 285 (1872); Ann. Chem. Pham., 162, 151 (1872); Popov, A,, AND ZINCKE, T., Ber. deut. chem. Ges., 5,384 (1872). MARKOVNIKOV, V. V. Ann. Chem. Pham., 146,339 (1868); 153,228(1870). TAN'T HOFF,H.J., "Ansichten uber die orgmische Chemie," Braunschweig, Th. 1, 1878; Th. 2, 1881. ERLENMEYER, E., Verh. d . natnrhist.-med. Ve~ereinaru Heidelbe~g,4, 31 (1865); Ann. Chem. Phann., 137, 327 (1866). PAULING, L.,Seiace, 123, 255 (1956). GIUA,M.,"Storia della chimica dall'alchimica aUe dottrine moderne," Torino, 1946, pp. 181, 204. DELACRE, M., "Histoire de chimie," Paris, 1920. KEKULE,A., Ann. C h . Pharm., 130, l(1864). MARKOVNIKOV, V. V., Z. Chem., [ 2 ] , 1,280 (1865). BunERov, A. M., "Collected Works," USSR Acad. of Sci. Pub., Moscow, 1958, Val. 3, p. 78. BUTLEROV. A. M.. "Scientific and Pediteoeical Activitv. A Colle&ion of ~ocuments," USSR A G of~Sci. PUG., Moscow, 1961,p: 84. (34) Letters from Rusa~auChemists to A. M. Butlerov, Nauchnoye nasledstvo, USSR Acad. of Soi. Pub., Moscow, 1961,Val. 4,p. 235. (35) BUFF, H.L., "Grundlehren der theoretischen Chemie und Beziehungen zwiachen den chemischen und physikalischen Eigeoschaften der KGrper," Erlangen, 1866.
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I am sum that everyone feels the pressure for discoveries. We all know they a m coming, but we do not know when. The world of knowledge is so tiny in ~ e l a t i mto the universe of ignorance that the result are still wandering around pretty much is inevitable. In my own field-pharmaceutical wsearch-e in the dark twating the symptoms of disease because we &mu so little about its causes. Our ignorance of both biology and chemistry is so nmumatal that we have to depend much too often on hunch plus plain tvial and error even for s ~ p t o m a t i eresults. How can m e rpestion the productiveness of the years ahead if we sustain our capacityfor discovery? M~LX TISHLER,Pvesidat Merek Sharp & Dohme Research Laboratories (From "The Debt of Dimovery t o Learning," the Industrihl Researah Institute Medal award address. Mar 2 , 1961)
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