Antibodies against organic molecules of low molecular weight by J. Loiseleur, with
the assistance of Mme. Sauvage, Annales de l'Institut Pasteur, 78, 1-64, 151-176 (1950).
Loiseleur reports that he can cause rabbits to manufacture antibodies against simple
organic substances, by several different ways, one of which is to inject amounts of
the order of magnitude of 100 mg, over a period of some days. Massive injections
during a few hours were also used. Two days after the last injection, the serum of
the animal was investigated by measuring its viscosity. The principal test used was
the change in viscosity on adding a solution of the original antigen. The viscosity
of 2.5 ml of the serum,diluted with an equal amount of saline (that is, a 1.25 ml
serum, and 1.25 ml saline) was measured, and then 0.5 ml of saline solution containing
some of the antigen was added, and the viscosity was determined again. With saline
alone the viscosity usually fell by about 5%, but in the presence of the antigen it
might rise, sometimes to 15% above the original value. There seemed to be a zone
phenomenon, in which 2or 3 maxima might be observed, with increasing amounts of added
antigen. Antigens for which this effect were obtained include ethanol, phenol, hydroquinone,
several sugars, sodium acetate and other salts of organic acids, ethyl amine, aniline,
several amino acids, veronal, streptomycin, and other drugs, nicotinic acid, and so
on. Negative results were obtained with benzaldehyde, amylsilicilate, ethyl cinnamate,
testosterone propionate, and bromotriphenylethylene, these fat soluble molecules being
injected in solution in olive oil. The author concludes that a condition for antigenic
action of simple molecules is solubility in water.
A considerable degree of specificity seems to be shown, although there is cross reactivity
between phenol and hydroquinone, glycine, ethylamine, and sodium acetate, and some
other substances. In some cases flocculation is observed to occur on addition of
the antigen, including sodium acetate.
The author also reports that he is able to produce the same effects with normal proteins
by in vitro treatment, at pH approximately 8, provided that some perturbing influence
operates. Higher pH and heat are not satisfactory, whereas ultrasonic radiation or
treatment in the hemogenizer were effective.
He also made some artificial antibodies following our procedure, at pH 11, using arginine,
raffinose, tartaric acid, hydroquinone, antranilic acid, xylose, salicylic acid, and
paraphenylene diamine as antigens, and he obtained, by his viscosity test, some evidence
for specificity.
