DorothfWrlnch and the Structure of Protelns To the Editor: In the article "Dorothy WrinKandaSearch for the Structure of Proteins" by Maureen M. Julian ( I ) there are some statements about me that need to he corrected and amplified. Durine the first semester 1937-1938 I was Georee Fisher Baker ~ l c t u r e rin Chemistry in Cornell ~ n i v e r s z y .I had been working on the oroblem of the structure of oroteins for about threeiears. 1; 1936 Alfred Mirsky and i had published a oaoer (2) about the structure of native and denatured priteins, in which we suggested that in native proteins pol\.peptide rhains are coiled in well-defined ways and are hel-d-idthese native configurations by hydrogen bonds-and other interatomic forces (weaker than those corresuonding to covalent hond formation) acting between polipeptid;! chains, parts of chains, and side chains. During the summer of 1937 I had been trying to determine the structure of the alpha-keratin proteins by analyzing the X-ray diffraction patterns. Warren Weaver of the Rockefeller Foundation knew about mv work. He asked if I would he willine t o talk with ~ o r o t h ; ~ r i n c h about her proposed cyclol &uctures for proteins and make a report to him. I had read the two long papers on this subject that Wrinch had published in Proceedinn of The Royal Society of London in 1937. as well as her other papers, i d I agreed to talk with her. Weaver had Wrinch come to Ithaca, and on 26 and 27 January 1938, I talked with her for about four hours. In addition, she presented her material in aseminar talk, which was followed by some discussion. I formulated eight statements about Wrinch's work, and showed them to her, for her comments. I then sent them to Weaver. I shall quote only one point here. I wrote that Her main cyclal contains 288 amino-acid residues. This corresponds to a molecular weight of ahout 36,M)O. In her lecture she pointed to the agreement between this and Svedherg's similar experimentalvalue for many proteins, giving auditors the impression that this provides strong support for her theory. Zoellner asked if there should not he a correction made for the water entrapped in the globular cyclol. Wrinch seemed unable to understand the question, even after I had repeated it, and she gave the impression that she considered the question silly. The next morning she showed me a 41-page manuscript in which the same cyclol (35,000)is calculated to contain 27 percent water and to have thus an effective molecular weight of ahout 44,000, as ohserved for egg alhumen by Svedberg. It is obvious that she was using two mutually incompatible arguments in support of her theory, and that she was deliberately refusing to discuss Zoellner's question hecause it raised a difficult point. When I asked her about this she said that no protein data (such as Svedherg's on molecular weight, Adair's on hydration) are reliable, and that she had not cited them in her papers or talks as proof of her theory, but only to see if there were some (perhaps accidental) correlation. I reached the conclusion, however, that she did not accept or a t any rate had no interest in a basic principle of research in chemistry and physics, the principle that comparison with nature, through observation and experiment, is essential. There then occurred something that troubled me. This was the publication of papers by Dorothy Wrinch and Irving Langmuir ( 3 , 4 ) in which they claimed that their analysis of the X-ray diffraction data of crystalline insulin published by Dorothy Crowfoot (5) showed that the cyclol theory is correct. I found some serious errors in their analysis, such as to invalidate it. J. D. Bernal also discovered that their analysis
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was incomplete and unreliable (6). Carl Niemann and I decided that we should publish a paper on the structure of proteins in which we made a detailed comoarison of the cyclol theory and the polypeptide-chain theory (7). In this oauer we analyzed the X-rav evidence, the thermochemical evidence, and several other aspects of the problem. In her article about Dorothy Wrinch Maureen M. Julian mentions that a structure somewhat similar to the one aspect of the cyclol structure had been found in the ergot alkaloids. She continues as follows: The structure of the peptide portion of the ergot alkaloid gave Wrinch's theories experimentalverification. The linkage between aminefloupsof neighboring peptrdeehninsronfirmed~ycloltheory. The ergot slkaluidr are, in n s m w . simple versions of proterns, and \\'rind! was at,udutelv deliehred with this rxamole. Fifteen years after Pauling and ~iemannhad "proved" that'the cyclol hond was too unstable to exist, it had been actually found! Alas, the scientific community had moved on to other fronts and it paid little attention. Wrinch once told Marjorie Senechal "First they said my structure couldn't exist. Then when it was found in nature they said it couldn't be synthesized in a laboratory. Then when it was synthesized,they said it wasn't important anyway." These statements do not conform to the facts. In our discussion of thermochemical evidence regarding protein structure (7) Niemann and I showed in several ways that chemical data led to the conclusion that the cyclol structure is less stable than the polypeptide-chain structure by ahout 28 kcallmol per residue. We then said that we could draw the rieorous conclusion that "The cvclol structure cannot he of primary importance for proteins; if i t occurs a t all (which is unlikely because of its great energetic disadvantage relative to polypeptide chains) not more than about 3 percent of the amino-acid residues could oossess this confieuration." Our conclusion that proteins have the polypeptiie-chain structure and not the cyclol structure has, of course, now been verified by complete structure determination of many proteins. We did not say that the sort of chemical structure found in the ergot alkaloids could not exist. We pointed out that it is less stable for proteins than the polypeptide-chain structure. Wrinch's comments quoted by Julian ahove misrepresent the statements made by Niemann and me. Llnus Paullng Linus Paullng lnsliiute of Science and Medlcine 440 Page Mill Road Palo Alto, CA 94306
Literature Cited I .lul na h l a lrrln \I J Chrm E d ~ r19a1.61.nW ? h I ~ m k \ A F .Palllo~,l.lnrrPr 'r . o i A n d .S l'.< 1936.2Y,210 2 Ur nrh.D hl l.ln,~m.llr.I J Am t ' h . ~ 1916.6. 121. % l.auxn.#w I , Wrtnrh 1, hl .Vo&m 1.~28,,4', 5 Cr kmt,D Proc R, 1 . 6 4 , 5 E d ti
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Orm.81..1. I, .Vo,.rr 1939, l 4 7 . 7 4 l'a 11 n?, 1 .Nlernann.l I I , r . . C h m , 3
1939.61, 1960
Rlval Equation Rates To the Editor: In his article "Rival Rate Eauations for Steadv States" (J. Chem. Educ. 1985,62, 490), ~ i l l e shows r diff&ent expressions for k,, the steady state rate constant of the mechanism:
Upon defining R = kll(k-1 k,,, and
-
+ kz), these expressions are
= k,.R
(2)
"..--..
thnm
k,,,, = k, .Rl(1 + R)
(3)
Also, there would be two rates dCldt: (dCldt),= k,.R.A and
-
imation (B 0) leads to k,, and a second (kl 0) makes k., identical with k,,. Since these approximations are consistent with the steady state condition, I see no reason to "disallow" Both novice and expert might be confused or puzzled by a multiplicity . . of published expressions for one steady state rate constant. The purpose of my paper was t o alert readers to an apparent problem and provide its resolution. S. I. Mlller
(dCIdt), = k, .R .(A, - C)/(l+ R)
(5)
Illinois Institute of Technology Chicago. IL 60616
He then states that, hy applying the steady state assumptions R
