'26 
The toxone is one of the primary metabolic products of the diphthe- 
ria bacillus. It possesses the same haptophore group as the toxin ^ but 
has far less avidity for antitoxin. When the diphtheria poison and 
antitoxin are brought together the toxone is the last to enter into com- i 
Ihnation with the antitoxin, as both the toxin and toxoid have greater 
affinities for the antibodies than the toxone. The toxone.^ as before ^ 
mentioned, has the same haptophore group as the toxin but has a 
different toxophore group, as it is incapable of producing acute effects, 
cutaneous necroses and death, but is responsible for the local edema 
and the diphtheritic paralysis. ' 
The diphtheria poison is first investigated biologicall}" b}- adding 
varying quantities of the poison to the immunity unit and inoculating 
the mixtures into a series of guinea pigs. In this way it is veiw evi- ; 
dent, as Ehrlich has shown, that two limits, boundaries, or zones are 
alwa}’S shown, which are of the greatest importance in determining the 
nature and composition of the poison. Each of these limits is desig- 
nated the letter L, from limes^ a boundaiw or zone. ! 
These limits are known, respectively, as L® C^==nil) and L+ (-[- = 
death). | 
By is meant that quantity of poison which just neutralizes or 
saturates one immunity unit as shown at the necropsy done forty-eight 
hours after the subcutaneous injection of the mixture into the guinea 
pig. The reaction at the site of the inoculation at this examination 
must he hardly noticeable. 
Theoretically the L*’ dose of tctxine must unite with and neutralize 
just 200 ‘‘combining units’' of antitoxin. The L” dose, therefore, ; 
contains just 200 minimal lethal doses of a theoretical!}’ pure poison. 
By L+ is meant the smallest quantity of toxine that will neutralize | 
one immunity unit, plus a quantity necessary to kill the animal on 
the fourth day. As defined by Ehrlich, the L+ dose is that quantity ! 
of poison which, despite the antibodies contained in one immunity 
unit of serum, contains a sufficient excess of the poison to cause the 
death of the guinea pig within the course of four days. 
In studying the constitution of the diphtheria poison it is also nec- 
essary to determine its absolute toxicity with the greatest ])ossible I 
precision. The absolute toxicity of the diphtheria poison is usually 
spoken of as the minimal lethal dose (MED), sometimes as the mini- 
mal fatal dose (MFD), and occasionally as the simple lethal dose. The ; 
determination of the minimal lethal dose is often an exceedingly 
tedious problem, and in some cases requires as many as 100 animals. 
This is due in part to the fact that the determination of the exact limits 
is largely inffuenced by the individuality of the guinea pigs, so that it ! 
is necessary to repeat the work on a series of animals in order to reach i 
an average. 
