LEAD-POISONING IN FROGS.- 
BY 
JOHN J. MASON, M. D ., 
NEW YORK. 
[REPRINTED FROM THE NEW YORK MEDICAL JOURNAL, JULY, 1877.] 
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I). APPLETON & CO., Publishers, 549 & 551 Broadway, N. I. LEAD-POISONING IN FROGS. 
BY 
JOHN J . MASON, M. I)., 
NEW YORK. 
| REPRINTED FROM THE NEW YORK MEDICAL JOURNAL, JULY, 1877.] 
NEW YORK: 
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1877. LEAD-POISONING IN FROGS? 
The influence which the absorption of lead exerts upon 
the system of a cold-blooded animal seems to have been com- 
monly regarded as requiring no investigation, for I have been 
unable to find so much as an allusion to the subject in any of 
the general treatises on poisons, or in any of the numerous 
monographs on lead-poisoning. 
This appears all the more remarkable when one considers 
the important services which experiments upon the frog have 
rendered, in discovering the mode of action of other toxic 
substances. 
Hermann, in his " Treatise on Experimental Toxicology " 
(Berlin, 1874), when writing (page 24) on the choice of ani- 
mals for experimentation, and naming, in order, man, warm- 
blooded, cold-blooded, and invertebrate animals, says: 
" Among these, cold-blooded animals occupy the highest rank by reason 
of their availableness. The same qualities which have made the frog, after 
a well-known expression, the martyr of physiology, make him also the 
martyr of toxicology. . . . While, in warm-blooded animals, all poisons 
which by paralyzing the heart interrupt the circulation, or which by inter- 
ference with respiration alter the proportions of gases in the blood, cause 
intense functional disturbance in all other organs, in the frog, the toxic 
effects above named have no influence on the condition of other organs, 
like the nervous and muscular apparatus, for example. Disturbance in 
1 Read before the American Neurological Association, June, 1877. 4 
the muscular and nervous systems, observed in the frog after poisoning, 
is surely to be ascribed to the direct effect of the poison upon these 
organs, and not to an indirect effect through a simultaneous disturbance 
of the heart, the breathing-apparatus, etc. . . . Recent toxicology has 
therefore been perfectly right in directing its attention to the frog." 
The following experiments are a few selected from a large 
number which I have made during the past year. The ani- 
mals were carefully examined every day, and the results, as 
noted, are now presented to the Association, in the hope that 
the subject may prove a suggestive and attractive one to other 
observers. 
I. Acute Poisoning.-Orfila {Elements de Toxicologic, 
1843, tome i., p. 633), Dr. Gaspard {Journal de Physiologic 
Experimentale, 1821, tome i., p. 284), and, more recently, Dr. 
Rene Moreau {Recherches Clinigues et Experimentdies sur 
VEmpoisonnement aigu par le Plomb et ses Composes, 1875), 
have given us the results of intra-venous injections of the salts 
of lead in dogs. Little effect was produced by the subcutane- 
ous method of injection, and this failure is ascribed by Mo- 
reau to the slowness of absorption caused by the astringent 
action of the lead salts. 
Experiment 1. March 9, 1876, 3 p. m.-I inject 1| grain 
of the acetate of lead under the skin (dorsal region) of a large 
frog {Pana Tempd). 6 p. m.-The animal remains motionless 
when touched. When turned upon its back it regains the 
normal position without difficulty. 8 p. m.-Voluntary or re- 
flex movements can no longer be excited. 
March VMh, 10 a. m.-Heart exposed, and found to be mo- 
tionless, much enlarged, and filled with blood. Cardiac move- 
ments cannot be excited by pricking or by electricity. Mus- 
cles of the trunk and extremities, with their nerves, respond 
normally to electric irritation. This may be taken as a good 
example of acute poisoning by this salt. 
The action of the poison in thus sparing the motor nerves 
of the extremities, and in being limited to the organs of respi- 
ration and circulation, will be found to correspond quite close- 
ly with the results obtained by Rouget1 and those by Sklarek,2 
1 "Arch, de Physiologie," 1873, p. 336. 
2 "Arch, fiir Anat. u. Phys.," 1866, p. 481. 5 
the former experimenting with the nitrate of silver, and the 
latter with arsenic, both employing the frog. 
This experiment I have often repeated, and, although from 
twelve to twenty-four hours are required for the action of the 
poison to manifest itself, its effects are constant in this species 
{Rana Temp.). 
II. Chronic Poisoning.1-The more gradual absorption of 
lead through that here important organ of respiration, the 
skin, is followed by symptoms which differ widely from those 
noted above. In 1871, E. Heubel2 gave, at short intervals, 
small doses of the acetate of lead to eight dogs, during periods 
varying from two to eight weeks. Wasting and paresis of 
the muscles of the posterior and anterior thoracic regions and 
of the posterior extremities resulted, but no typical lead pa- 
ralysis was observed, nor were the electrical reactions given. 
The above are the latest, and, as far as I can ascertain, the 
only published experiments, made with the object of causing 
the symptoms of chronic lead-intoxication in animals. 
Experiment 2. March 22, 1876.-Four small frogs {Rana 
Temp?) are placed in a glass globe containing: water, 24 fl. 
oz.; acetate of lead, 1 gr. 
25^A.-No change observable. 
28^.-Frogs lively. Solution made stronger by addition 
of seven grains of the lead salt. 
29/A.-No effect observable. 
April Zd.-One frog motionless. Posterior extremities 
paralyzed. Anterior extremities respond to the will. All 
the muscles of the posterior limbs respond far better to the 
action of the voltaic than to that of the faradaic current. 
Division of the spinal cord causes no movement in the lower 
limbs. Direct irritation of the sciatic nerves by electricity 
gives rise to no muscular contraction except in the peroneal 
muscle of one leg, causing slight flexion of the foot. Heart 
normal in size and action. The faradaic current used in these 
11 use the word " chronic " on account of the longer time which elapses 
before the poison affects the system, and of the constancy of the paralytic 
symptoms. 
2 " Pathogenese und Symptome der chronischen Bleivergiftung, Ex- 
perimentelle Untersuchungen." 6 
tests was from the second spiral of Du Bois-Reymond's ap- 
paratus. The voltaic current was supplied by small cells 
containing zinc and copper in pure water. 
5th.-Two more frogs motionless. Motor nerves of lower 
limbs have completely lost their irritability. Muscles respond 
but little to direct faradization, while the voltaic current 
made to act on the same parts causes well-marked contractions 
and movements of the limbs. The hearts of both are normal, 
and beating rhythmically. 
Experiment 3. April 5th.-The remaining specimen, with 
three others of the same species, are placed in : water, 24 fl. 
oz.; acetate of lead, 8 grains. 
Sth.-Frog from experiment 2 motionless. Reaction in 
nerves and muscles to electrical tests is found to be the same 
as that observed in the foregoing cases. 
7th.-Desquamation is very active. This is a constant re- 
sult, and clue to the action of the solution. Microscopic ex- 
amination of the cast-off membranes shows them to consist 
solely of a pavement epithelial layer. 
1OZA.-Since the 7th there has been little to observe. To- 
day all three animals are motionless. Condition of nerves and 
muscles, and their electrical reactions,.are found to be the 
same as in the previous cases. Hearts of normal size, and 
beating. 
I have frequently noticed that some of the frogs always 
croaked as if in pain whenever the spine was pressed gently 
between the thumb and forefinger. The cries were provoked 
with much the same regularity as those caused by stroking 
the back after Goltz's experiment of separating the cerebrum 
from the parts below. 
Experiment 4. April 25th.-A large bull-frog {Pana 
Pipiens) is placed in a solution: water, 48 fl. oz.; acetate of 
lead, 16 grains. 
26/A.-From being very inert, the animal shows signs of 
hypersesthesia. Springs violently when touched lightly with 
the finger. 
May 1<^.-Since the 26th, moderate pressure on one side 
of the abdomen with the smooth end of a glass rod has caused 
violent jumping and loud croaking. 7 
2d.-No signs of hypermstnesia. When placed on the back, 
regains the normal position, but quite slowly. 
9^A.-Quantity of lead increased to 48 grains. 
12th.-Frog is motionless. It cannot turn over when 
placed on the back. Electrical reaction of the sciatic nerves 
is completely lost. That of the muscles is the same as in the 
preceding experiments, viz. : nearly lost to faradization, but 
quite marked with voltaic excitation. Heart of normal size, 
and beating normally. In this species of frog, probably on 
account of their large size and toughness of the skin, much 
stronger solutions of lead are often required than even with 
large specimens of Hana Temporaria. In fact, I have kept one 
two months in a lead solution (one grain to the ounce) without 
being able to note any change in his condition, excepting that 
of active desquamation. Some of this species certainly enjoy 
the same immunity from the usual action of lead when in- 
jected under the skin. I kept alive and active for thirteen 
days a large bull-frog, which was submitted to three sub 
cutaneous injections of four grains each of the acetate of lead 
on three successive days, beginning May 4, 1877. On May 
17th the animal was found motionless. The heart was para- 
lyzed, as in Experiment 1, and distended to twice its natural 
size. No contractions of this organ could be induced by the 
usual mode of irritation. After cutting it so as to allow the 
blood to escape, contractions began, nearly normal in quality. 
This was at 2 p. m. At 9 p. m. the muscles still retained 
their faculty of contracting to faradaic stimulus. At the same 
time (May 4th) one grain of the salt was given in the same 
manner to a vigorous specimen of Ilana Temporaria. and in 
twenty-four hours the heart was motionless. 
From these exceptional cases we have only additional 
proof that the power of resisting the action of this poison, 
which is so noticeable in the systems of painters and others, 
all equally subjected to the same toxic influence, exists also in 
individuals among the lower animals. 
Analysis of a sufficient number of experiments has con- 
vinced me of the truth of the following conclusions: 
I. The rapid absorption of the acetate of lead soon causes 8 
death by stoppage of the heart's action-an effect probably 
common to all the mineral poisons. 
II. The slow absorption of this salt through the skin in- 
duces in the voluntary muscles of the frog a paralytic state, 
identical in its most important features with that which one 
sees so frequently in man. 
In the acute form the motor nerves and muscles are un- 
affected ; in the chronic form the heart is spared. 
The paralysis is developed somewhat rapidly; there is no 
wasting of the muscles; faradization has little or no effect in 
inducing muscular contractions, while the voltaic current acts 
well in this respect;1 cutaneous sensibility is seldom entirely 
lost, and before the complete development of paralysis it often 
seems to be increased.2 
Microscopic examination of the web of the foot, which was 
made in a large proportion of cases, showed marked spasm of 
the arterioles, and dilatation of the venules, with consequent 
slowing of the circulation. The large veins of the extrem- 
ities are generally congested, and sometimes varicose. The 
muscles are paler, and firmer to the touch than when in the 
normal condition, although there is no rigidity of the limbs. 
My attention has been especially directed to the elements 
of the spinal cord. Comparison of sections of this portion of 
the nervous system, taken from frogs which have succumbed 
to the slow action of lead, with a large number made from 
the normal cord, has thus far shown no difference which is 
constant. In some cases the blood-vessels seem much increased 
in number and size, and the nerve-corpuscles of the anterior 
1 The gastrocnemius and sartorius muscles were tested often in Pfliiger's 
myographium. Polar action of electricity is not marked as in healthy 
muscles. Cathode closing is no more effective than anode closing. There 
are no opening contractions with mild currents. Contraction is slow, the 
organ remaining shortened for some little time during the passage of the 
current. The affected muscle never reacts so powerfully to either form of 
current as does a healthy one. 
2 Frogs placed in solutions of arsenious acid, bichloride of mercury, or 
nitrate of silver, die almost as rapidly as they do after subcutaneous in- 
jections of these poisons. With neither of these three salts have I been 
able to produce the same result as that caused by the lead-bath, 9 
horns appear to be less numerous than in the healthy con- 
dition. Nothing like structural or pigmentary degeneration 
has been seen. The sympathetic system has not been ex- 
amined. 
It is almost certain that the poison is capable of acting 
primarily either upon the muscular substance or upon some 
portion of the nervous system. If the alterations are anatom- 
ical, they ought to be found. The spinal cord of batrachians 
is especially adapted to such researches, as the anterior horn- 
cells are very large, and in the lumbar region are closely 
crowded together in a definite, easily-determined space. Thus 
far I have not been very successful with Sokolow's1 method 
in finding even the normal nerve-terminations in the muscles, 
but there is every reason to believe that others may be more 
fortunate. 
In fresh preparations I have as yet found no alteration of 
the muscular or nerve fibres. 
Although the existence of Erb's " entartungs-reaction " is 
strong evidence of a separation of the muscles from their 
spinal nerve-cells, conclusive proof of this is only to be found 
by the discovery of that portion of the nervous system where 
the process of separation begins. The latest authorities favor 
the view that this affection is of neurotic origin, and their 
arguments lack nothing but anatomical support. Westphal 
with characteristic fairness freely admits the doubtful inter- 
pretation to be placed upon the changes observed in his case 
of radial paralysis, and it is certainly unfortunate, from a scien- 
tific point of view, that his researches cannot be more frequent- 
ly made in man.2 The close resemblance, as to symptomatol- 
ogy, of some cases of generalized lead-paralysis with 8 "spinal 
paralysis of the adult," in which there is much reason for 
accepting the coexistence of myelitis of the anterior horns, 
goes far to encourage us in assuming that these portions of 
1 "Sur les transformations des terminaisons des nerfs de la grenouille 
apr&s la section des nerfs." " Arch, de Physiol.," 1874, p. 300. 
2 C. Westphal, " Ueber eine Veranderung der Nerv. radilis bei Blei- 
lahmung." "Arch, fur Psychiatric," etc., Bd. iv., S. 776. 
3 E. C. Seguin, "Myelitis of the Anterior Horns," etc. New York, 
1877. 10 
the spinal cord are first affected by the poison in the higher 
animals. 
May not our knowledge of the pathogeny1 of lead-paraly- 
sis acquire a surer basis than it now possesses by further re- 
searches on lead-poisoning in frogs ? 
1 "Zur Pathogenese der Bleilahmungen." Von Dr. Ernst Remak. 
"Arch, fur Psychiatric," etc., Berlin, 1875, Bd. vi., S. 1. This instructive 
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