In this letter, Dr. Simon Flexner reported to Osler on tissue samples taken from leprous patients at Johns Hopkins Hospital.
He gave a detailed analysis of the relation of the disease bacteria and the lesions, and commented on likely routes of transmission.
Flexner (1863-1946), a pathologist and bacteriologist, became the first director of the Rockefeller Institute for Medical
Research in 1901.
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1897-04-13 (April 13, 1897)
Original Repository: Alan Mason Chesney Medical Archives. William Osler Collection
This item is in the public domain. It may be used without permission.
"Father of Modern Medicine": The Johns Hopkins School of Medicine, 1889-1905
The Johns Hopkins Hospital
Baltimore, April 13/97
Dear Dr. Osler,
The following is, in brief, a description of the leprous nodules in the skin and subcutaneous tissue of the patients at present
in Ward I. You already know that cover-slip preparations made by smearing the excised tissue from the area on cover slips
and stained by Gram and Ziehl-Neelson's methods showed many bacilli having the characters of the B. leprae.
The sections of the skin and subcutaneous tissue containing the tubercles were stained in haemotoxelin and eosine and in carbol-fuchsin
and methylene blue. As regards the first: the tubercle are situated chiefly in the subcutaneous areolar and adipose tissue;
they are usually discrete and always well-preserved.
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Evidences of necrosis were not met with. The tubercles are made up of cells of the epithelioid type, usually with single nuclei,
but a rather unusual number of multi-nucleated cells are found in certain tubercles. The great majority of these cells --
whether single or multi-nucleated -- show the vacuolization described by Virchow. Often the cell protoplasm is enormously
swollen and crowded with vacuoles. Now and then a smaller cell will have suffered partial colloid degeneration of the protoplasm.
The nodules are sharply circumscribed by the connective tissue in which they lie altho [sic] in the younger and forming nodules
elongated outgrowths appear to be going on. These are however separated by more or less tissue from the original and older
tubercles. Blood vessels are numerous in the tubercles.
The behavior of certain of the skin structures is interesting. Sections of sudoriparous glands are included in the tubercles
and these are
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at one time quite normal in appearance and at another rapidly filling up with cells resembling the leprous cells until finally
the contours are lost and they become a part of the tubercle. Some of the giant (multinucleated) cells of the tubercles are
derived by confluence from the epithelial lining of these glands. They may also be seen to undergo the typical vacuolization.
The arrectores pilorum are hypertrophied, a fact already pointed out by Virchow. Sebaceous glands were very scanty in the
sections studied so that nothing especial was made out of their relation to the tubercle formation.
The relation of the bacteria to the lesions are as follows: In the tubercles they are present in the usual great numbers.
There seems to be no reasonable doubt that they exist in the epithelial and giant cells, surrounding the nuclei of these cells.
Whether they are also exist at times within the nuclei themselves could not be determined. This case agrees with those studied
by a host of others (Neisser, Corrick(?), Unna, etc.) inasmuch as the organisms are found not to invade the epithelial cells
of the sudoriparous glands and epidermis. Now others in a [ . . . ] appearance are obtained suggesting a few bacilli in sweat
glands; but it is not excluded that the organisms are not in the interstitial tissue between sections the sections of the
coils. On the other hand, the outer sheath (Haarkelg[?]) of the hairs often contains bacilli in considerable numbers. There
can be no doubt that Unna is correct in his statement that the bacilli exist in lymph spaces independently of cells. But this
condition is found not within the tubercle as he supposed but in the corium [dermis]. Small masses of bacteria may be easily
discerned in the tissue spaces. They grow fewer in numbers and the sizes of the masses diminish as the epidermis is approached.
The bacilli may however be followed by the epithelium on the rete [reticular] layer. Just below this bacilli are found in
structures which much resemble in outline, altho [sic] pigment was wanting, chromatophores. I think this fact important when
it is considered that the bacilli are found in this case in fair numbers in the horny layer of the surface of the epidermis.
There are two ways in which they may gain entrance though the unbroken skin to the surface. One is demonstrable in this case,
namely from the sheath of the hairs. The other is by the action of chromatophores, which it is well known emigrate between
the epithelial cells.
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and are capable of reaching the surface. On the skin surface the number of bacilli is greatest in the place where the horny
scales are thickest. The bacilli are found in the smaller blood vessels in the tubercles. They infiltrate all the coats but
exist in greatest numbers in the endothelial cells of the intima which often are crowded with them. The vessels are pervious[?].
I have not seen in my reading a reference to the occurrence of the bacilli on the surface of the intact skin. I should like
to study further the epidermal scales from various parts of the body in order to follow their distribution, or, if you prefer
it, I shall be glad to assist in the house officer in charge of the case in this study. In any event I shall study more carefully
the behavior of the chromatophores or what I take to be these structures. Perhaps it may be possible to trace them thro [sic]