Poisons ol ancienl Pem
A climbing plant, a fish, a frog-these natural sources of toxins
long known to the early peoples of Peru have already contributed
significantly to neurophysiology and the study of nerve impulses
E
ven before the structure of the
tissues of the nervous system was
discovered, many of the poisons
present in nature were known to have a
neurotoxic action. Sorne of these toxins
were discovered and put to use by the
ancient civilisations of Peru; they were
used mainly on the arrows and spears
used for hunting, fishing and warfare.
Their continuous use down to the pre-
sent day, references to them in the 16th
century chronicles of the Spanish Con-
quest, and their appearance in pre-
Columbian art are not just a remarkable
historical and archaeological curiosity;
they also represent an interesting cul-
tural link between students of the past
and present-day neurophysiologists.
Claude Bernard, the French scientist
who is regarded as the creator of mod-
ern physiology, deduced that there must
be some connecting organ between
nerve and muscle: a myoneurallink. He
arrived at this conclusion through his
investigations into curare, a hunting
poison used by the natives of Amazonia.
In Bernard's experiments, both the
nerve fibre and the muscle fibre were
stimulated at two points, A or B, by an
electrical current. Normally, stimulation
at A produces a muscular response al-
most identical to that obtained by stimu-
lation at B. Over a century ago, in one of
the earliest attempts to use poisons for
the study of physiology, Bernard proved
that under the effect of curare the
stimulus at A could not reach the mus-
cle, even though the muscle remained
excitable; thus the discovery was made
that the toxin does not cause muscular
problems.
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by Fernando Cabieses
Theo in 1907, using curare in inner-
vated or denervated muscles, J. Langley
established the basis for the physiology
of the · motor end-plate, or myoneural
junction. lt was not until 1936 that H.
Dale demonstrated that the production
of acetylcholine, which had already been
identified as the chemical intermediary
in the end-plate, is not inhibited by
The puffer fish-Spheroides spengleri
-origin of the lethal poison tetrodo-
toxin.
Photo WHO/F. Cabieses
curare unless the latter acts after the
myoneural junction, that is, in the mus-
cle receptors themselves.
Three years la ter, A. Hodgkin and
A.F. Huxley took a tremendous step
forward by studying electrical potentials
and ion exchange in the isolated axon of
the squid. From that time onward,
natural neurotoxins of different origins
have been essential for advanced re-
search on neurophysiology.
A great deal has been written about
curare, and a hundred legends have
been woven around the mystery of its
ongm. Even today, when the patient
research of Dermot Taylor and the emi-
nent botanist Ramon Ferreyra has pro-
duced detailed information on its source
and preparation, people still daim it is
an unknown mixture of various sub-
stances of obscure and unexplained ori-
gin. This is simply not true. Basically,
curare is an extract from a climbing
plant of the Amazonian region, with
the scientific name Chondodendron
tomentosum.
The indigenous collectors of this
plant, whose daily efforts are unfortu-
nately contributing to its extinction,
fetch from the forest small bundles of
stems of varying thickness, which they
boil in large pans. This extraction by
boiling is not a simple process ; it lasts
several days, until a smooth, sticky paste
is obtained. The paste undergoes a
number of tests that have been in use
since time immemorial, and suggest the
existence of sophisticated biological
knowledge among the ancient peoples.
Quality, for example, is determined by
the ability of a specified dosage of the
paste to paralyse a toad in a given time.
From the two main types obtainable in
the forest, "calabash curare" ( curare C)
and "pipe curare", modern scientists
have managed to purify C-curarine and
tubocurarine, whose use in ' modern
medicine as a muscle relaxant is well
known.
A hundred legends have been woven around
curare-the poison used on the spears and
arrows of native hunters and fishermen
throughout the Amazonian region.
Photo WHO
 Anyone who eats the offal of the
puffer fish, especially the liver or roe,
feels a numbness and tingling of the lips,
tangue and cheeks after a few minutes.
This presently becomes complicated by
debility and progressive paralysis of all
the muscles, vomiting, low blood
pressure, tachycardia and respiratory
paralysis ; death ensues within half an
hour.
If a fraction of a milligram of the toxin
is administered intravenously to a dog,
within seconds it causes cardio-respirat-
Above : The coi-coi, a brightly coloured frog ory death and incapacity of all the
used in preparing the most patent non-
proteinic poison existing in nature. muscles to respond to electrical stimuli.
An extensive series of neuro-phy-
Below : The same frog figures on the pottery
of the Nazcas, who knew its useful properties siological experiments initiated by
many centuries ago. Fusao Ishihara in 1918 and recently
Photo WHO/F. Cabieses
completed by Toshio Narahashi, showed
that tetrodotoxin mainly and initially
affects the axon of the motor nerve ;
only at a later stage does it directly
affect the muscle.
Today tetrodotoxin, the poison of the
puffer fish which terrorised the Con-
quistadors of Peru, has become a tool
for the electro-chemical study of the
conduction of nerve impulses. lt has
made possible, for instance, the discov-
ery that the channels for sodium inter-
change in the nerve axon are selective
and different from the channels for
potassium.
Poisonous fish
Poison from a frog
From the earliest days of their explo-
rations in Peru, as comments in contem- lt has been claimed that the ancient
porary chronicles show, the Spaniards Peruvians so often depicted batrachians
knew of the existence of an extremely on their finest pottery because, -accord-
poisonous fish which, on account of its ing to their primitive polytheism, they
ability to inflate itself rapidly to a much looked upon the toad as the rain-god.
larger size, became known as the "puf- There is room for speculation here, but
fer fish". Various eighteenth-century the truth is that little or no evidence of
sources tell us that people in Japan and this was uncovered by the early Spanish
European sailors exploring the South missionaries bent on destroying pagan
Pacifie suffered from the highly taxie forms of worship. On the other hand, a
effects of this fish. The species most number of records mention that the
common in Peru, Spheroides spengleri, magicians and medicine men of the
is found in the mangrove swamps of the subjugated culture used frogs and toads
Tumbes area. They are fish of the family for preparing various hallucinogenic or
Tetraodontidae, so called because they poisonous potions.
have four teeth. The family has given A frog painted in different colours
its name to the toxin which is the ac- appears very frequently on Nazca pot-
tive principle for its lethal action: tery. A study of the poisonous frogs still
tetrodotoxin. valued by Peruvian and Colombian In-
As long ago as 1883, Yoshizumi , dians in modern times has led to the
Tahara in Tokyo attempted to isolate identification of two genera of small
the pure toxin from this fish, but it was brightly-coloured frogs, which are used
not until 1950 that Akira Y okoo and for preparing very powerful hunting
Kyosuke Tsuda, working independently poisons by various tribal groups, par-
of each other, managed to obtain it in ticularly in Colombia and the northern
pure crystal form. · part of Peruvian Amazonia. These frogs
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are the same as th ose shown on N azca
pottery.
The genera Dendrobates and Phylo-
bates contain a number of species whose
skin produces a secretion regarded as
the most patent non-proteinic poison
existing in nature. A small frog two
centimetres long can provide enough
poison to kill 50' adults .
Of all the non-proteinic natural
poisons, therefore, the two most effec-
tive are those that were already used
as arrow poisons by the ancient Peru-
vians : one from the puffer fish and one
from the frog popularly known as the
coi-coi-tetrodotoxin and batracotoxin.
They are fatal in a dosage of one-
millionth of a gram per kilo gram of body
weight.
Batracotoxin is a steroid which has
been exhaustively studied by Bernard
Witkop and others. Unlike tetrodotoxin
which is hydrophilic (moisture-absorb-
ing), batracotoxin is lipophilic (having
an affinity for body fats) and acts in the
opposite way to the former within the
sodium ion pathway in the axonal mem-
brane. Whereas tetrodotoxin blacks the
movement of the sodium ion, batracoto-
xin selectively increases the membrane's
permeability for sodium. The contrast-
ing action of these two ancient Peruvian
poisons has led to extremely important
discoveries concerning the · molecular
physiology of nerves and muscles.
Another small frog which also seems
to have been familiar to the N azcas,
Dendrobates histrionicus, also pro-
duces highly taxie poison used on
arrows by the Amazonian Indians :
histrionicotoxin.
lt would be asking too much to take
the reader into the arid wastes of mol-
ecular biochemistry, and to describe all
· the neurophysiological conclusions to
which we are being led by the experi-
mental use of these poisons as we study
the generation and transmission of
nerve impulses. To the alkaloids of cu-
rare, tetr-0dotoxin, batracotoxin and his-
trionicotoxin, we can add other natural
poisons from elsewhere in the world
such as bungarotoxin ( derived from the
krait snake), saxitoxin (from mussels),
and holothurin (from sea cucumber).
Perhaps the most appropriate place for
the motta displayed by the great
Rudolf Virchow at the entrance to his
dissecting room would be the neuro-
physiology laboratory: Hic mors gaudet
succurrere vitae-" Here death is pleased
to assist life. " •