Chemistry Reference
In-Depth Information
His later experiments using washed erythrocytes and then studies by S. Flexner
and H. Noguchi, which S. W. Mitchell himself inspired, revealed that the noted
'coagulation' did not result from procoagulants (clotting factors) in blood. As stated
by these authors, 'the value of the use of washed corpuscles comes especially from
the fact that the suspension of lytic phenomena is eliminated. Agglutination,
therefore, may be studied purely' [2] . The ' venom - agglutination ' was especially
strong with rabbit erythrocytes, with swine and ox cells being less susceptible, and
akin to the reaction with ' intermediary bodies ' (today known as immunoglobulins)
[2]. Its biochemical nature was defi ned in 1984 after purifying the agglutinin of
Crotalus durissus
venom, a C-type lectin [3]. This feat underscored the pioneering
character of S.W. Mitchell's research for lectinology. Groundbreaking as it was,
the spirit and attitude with which he carried out his work, as captured on p. 1 of
his report [1], also continue to set a commendable example: 'for the researches
which form the novel part of the following essay, I claim only exactness of detail
and honesty of statement. Where the results have appeared to me inconclusive,
and where further experimental questioning has not resolved the doubt, I have
fairly confessed my inability to settle the matter. This course I have adhered to in
every such instance, thinking it better to state the known uncertainty thus created
than to run the risk of strewing my path with errors in the garb of seeming truths'.
The range of study was extended to plants as sources for agglutinins by a medical
thesis in 1888 (Table 15.1 ).
Using the same technique of hemagglutination, extracts of plant seeds, initially
from the toxic castor beans (
Ricinus communis
), were also shown to be active.
H. Stillmark described a toxin with agglutinating activity, termed ricin, in his MD
thesis in 1888. This thesis was prepared under the guidance of R. Kobert at the
University of Dorpat (now Tartu) in Estonia, then belonging to the Russian empire
[4] . He defi ned ' ricin ' as a protein ( ' Eiweissk ö rper, sog. Phytalbumose ' ), conglom-
erating (or agglutinating) the red blood corpuscles in defi brinated serum - contain-
ing blood (' Zusammenballung der rothen Blutk ö rperchen ' ) [4] . Such an activity
was also found in
Abrus precatorius
seeds ('abrin'), the respective protein fractions
from these extracts were produced and tested in R. Kobert's pharmacological
institute. Preparations of ricin and abrin, made commercially available by the
Merck Company in Darmstadt on Kobert's initiative, found immediate use beyond
that of lectinology. They substituted for bacterial toxins in P. Ehrlich' s fundamen-
tal studies on the immune response [5]. Once that activity was measured and the
degree of purity increased, the need for a name became obvious.
15.2
Early Defi nitions
On the initiative of R. Kobert, who left Dorpat for Germany in January 1897 due
to the russifi cation of the Baltics unleashed by an attempted assassination on Czar
Alexander III, the issue of determining a name was addressed in 1898. M. Elf-
strand introduced the term ' Haemagglutinin (Blutk ö rperchenagglutinin) ' into the
literature [6]. He also noted the ' striking similarity ' between agglutinating proteins
