Letter from Elvin A. Kabat to Michael Heidelberger
Kabat, Heidelberger's first graduate student at Columbia University's College of Physicians and Surgeons and later
his colleague there, went to the University of Upsala in Sweden in 1937 to use the university's newly-developed ultracentrifuge
to type and determine the size of antibody globulins in horse and rabbit antipneumococcal sera, which had been prepared by
Heidelberger. In this letter, written from Cambridge, England, prior to his return to the United States in the summer of
1938, Kabat contemplated the limits of ultracentrifugation in determining the molecular weights of the complex proteins of
antibodies. He also discussed a meeting with the pioneer of X-ray structure analysis of proteins, John Desmond Bernal, who
expressed an interest in subjecting antibody protein to his new techniques of X-ray crystallography.
Item is handwritten.
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22 July 1938
Kabat, Elvin A.
Reproduced with permission of Jon Kabat-Zinn.
Medical Subject Headings (MeSH):
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Letter from Elvin A. Kabat to Michael Heidelberger [23 November 1937]
I certainly seem to be learning things very rapidly on my trip -- especially about the limitations of the centrifuge methods.
Unfortunately there was very little discussion about assumptions etc at Upsala, so I was not at all aware of any uncertainty
in giving the values found as the true molecular weight. Bernal, MacFarlane and Pirie, however, have pointed out the fact
very definitely, that S and D can only be used to calculate M for a rigid aphemical particle, and in these cases f/so should
be 1.0. In all other cases of asymmetric is how -- compart[?] [ . . . ] one cannot assume M = RTs/D(1-PV) to hold since one
gets an oriented sedimentation and hence viscosity effects due to the sliding of one molecule along another -- whether this
is eliminated by running the s concentration curve and extrapolating to zero protein concentration, shouldn't as yet considered
thoroughly. I am convinced, however, that with the horse, cow, and pig having f/fo of 2.0 ie molecule 25 X as lose, as it
[ . . . ] and [ . . . ], monkey and human f/fo = 1.5 ie molecule ca/ox as long as wide, that the actual molecular weights
are meaningless and I think I shall have to be much more cautious in the statements about molecular weight. The bulk of the
data, is of course just as important without a true molecular weight figure. I don't think I mentioned fact in the two
Ea antisera studied
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In the inhibition zone, I found the same ratio of AB mg/EA mg in the compound independent of the moment of excess Ea with
160,000 and 40,000 for the mol. wt., this gives Ea3Ab2. The sedimentation constants of the two compounds formed use ca 8.7,
11.3 and are much too low for such an empirical formula. In view of my talks with the English workers, I am not sure whether
it would not be very rash to assume 160,000 for M and that perhaps the ratio might be 1:1 which would be more reasonable.
In any case opportunity Bernal is the only person able to calculate a true molecular weight for an asymmetric molecule from
X-ray patterns. I have watched his technic [sic] for working dried films to onset the molecules and it would be very easy
for us to send over films of antibody and polysaccharide for him to study. He would be very much interested in doing so.
From my occupations with Adair, I am very much surprised that the osmotic pressure method is not in routine use in every lab
for molecular weight determinations. I think that it would be of very great [ . . . ] to measure the mol. wt. of the two
types of antibody in this warmer[?] for comparison with the centrifuge. It [ . . . ] so little trial and attention, that
perhaps we could do something about it when I get back. A control [ . . . ] the centrifuge to see if we had homogeneous products
would be necessary.
I have been trying to convince Pirie that quantitative precipitins[?] would be of use in his work, but he says that all the
junk in the tobacco juice comes down with the precipitate.
I read Shaffer and Dingle's[?] paper but am not convinced that our degraded antibody explains these results.
I am not going to send away of the three papers off, until you have gone over them. I haven't got all the figures yet,
but if I get them soon, I'll send you the first two. I hope you are having a very pleasant summer. Best wishes to Mrs.
Heidelberger and Chorline.