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Journal of Anaesthesiology Clinical Pharmacology | April-June 2015 | Vol 31 | Issue 2 149
Animal testing in the history
of anesthesia: Now and then,
some stories, some facts
Arthur Guedel called him “Airway”
Dr. Hasnain calls her “Morphine”
I call mine “Magic”
The dog is man’s best friend. There are many interesting
anecdotes, serendipitous stories and mesmerizing details
about how dogs have been loved, named and tested by
many anesthesiologists, in the past and present. However,
the contribution of experiments on animals such as rabbit,
monkey, mice, guinea pigs etc., also played a significant role
in the evolution of both general and regional anesthesia. Some
facts and intriguing stories from the history of anesthesia have
been put together though not chronologically, in this report to
make an interesting subject of reading.
Arthur Guedel first successfully demonstrated the safety of a
cuffed tracheal tube in 1926 on his dog that he affectionately
called “airway.”[1] In his famous “dunked dog” demonstration
at a medical convention, Guedel submerged his dog in an
aquarium after anesthetizing him with an ethylene-oxygen
mixture via a cuffed tracheal tube. A to-and-fro circuit with
soda lime absorption system was used to provide positive
pressure ventilation underwater by his fellow anesthesiologist
and friend, Ralph Waters. Guedel wanted to show that if his
cuffed tube could prevent the dog from drowning in water,
it could also effectively protect the trachea from aspiration
of water. The dog was crowned “airway” and since then,
airway and anesthesia are almost synonymous.
Andreas Vesalius used bellows to resuscitate an asphyxiated
dog in the 16th century. Robert Hook also performed the
demonstration of artificial respiration in 1678 on a dog that
had an open chest, but was kept alive by attaching rhythmically
contracting bellows to its trachea. By exposing fresh air with
oxygen to the circulating blood, he proved that the chest
movements are not the fundamentals of respiration.[2]
In 1884, Carl Koller applied a suspension of cocaine crystals
to the eyes of a dog in his laboratory and noticed that it made
the corneas totally numb, even to pin prick. Koller was so
convinced that he tried the same on his own eyes and finally
used the local anesthetic properties of the drug for superficial
ophthalmic surgery.[3]
In 1885, Corning injected cocaine to a dog and noticed that he
fell down because of the weakness of his hind legs.[4] He was
actually experimenting on some neurological problem when
he accidently punctured the dog’s dura mater. He witnessed
a motor block in the hind legs and noticed that it reversed in
some time on its own. Theodore Tuffier in 1900 and later
in 1915, Smith and Porter demonstrated sympatholysis
associated with spinal anesthesia on dogs and cats.[5]
During World War II, it is said that the Jews mysteriously
sneaked out of Germany in boats after duping the Nazi dogs.[6]
The captains dipped handkerchiefs in rabbit’s blood and
sprinkled cocaine on them. The ferocious search dogs came
for the smell of blood and sniffed the cocaine. This numbed
their strong sense of smell and gave them a high so that they
lost their focus for some time.
An interesting anecdote is related to the introduction of
halothane into clinical practice. In 1955, Bull, an eminent
anesthesiologist, who was then working in the Nuffield
Department of Anesthetics at the University of Oxford,
received a sample of a secret new anesthetic agent for trial
in dogs.[7] The agent had not been named then even by its
inventor, Raventos, and the “nondescript little bottle” was
labeled nonexplosive agent (NEA). A number of nylon
bags were filled with 1-5% concentrations of this NEA and
several dogs were anesthetized using a low resistance one-
way valve. Dr. Bull noted that NEA had superb handling
characteristics and provided both a smooth induction and
a steady maintenance in dogs. These trials of NEA on
dogs significantly led to the clinical use of the most popular
inhaled anesthetic in the history of anesthesia-halothane.
As Professor Bull mentions “compared with the elaborate
protocols that surround the acceptance of any new drug
today, the introduction of what was for years the most popular
inhalational anesthetic was unbelievably simple.”
Nearly 500 years ago in South America, an arrow poison,
later called curare was used to kill the game by progressive
paralysis of the motor nerves from peripher y to the center.
However, in 1814, Brodie and Waterton injected curare
to a donkey and demonstrated that it could only be kept
alive if artificial respiration was given along with (the lungs
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Goyal: Animal testing
150 Journal of Anaesthesiology Clinical Pharmacology | April-June 2015 | Vol 31 | Issue 2
were inflated with a pair of bellows). The drug was called
woorara and the donkey, Wouralia. He nurtured the donkey
for 25 years on his estate and used the drug to treat tetanus
and rabies.[4]
January 1976, Farber’s investigation published in “The
Times” about the suspicious deaths of 40 patients at River
dell Hospital in Oradell Bergen County, New Jersey by an
unidentified surgeon “Dr. X” created a media stir in the
country.[8] Eighteen empty vials of curare were found in the
locker of Dr. X, each of which had the potency to kill a man
if not supported with artificial respiration. Dr. X was Mario
Enrique Jascalevich, the chief surgeon at that hospital who
in his statement declared that he used curare for experiments
on dying dogs. Though there was no evidence of any dogs
been supplied to him for this purpose, jurors acquitted Dr.
X in 1978.
Pal discovered the drug to reverse the effects of curare in
Vienna in 1900, decades before it came into clinical practice
as a muscle relaxant during surgical anesthesia in 1942. While
studying the physiology of the gut, Pal injected physostigmine
to a dog that was already paralyzed with curare. To his
surprise, the dog started breathing spontaneously, and the
idea of reversal of the effects of neuromuscular drugs was
conceived.[9]
Liver is not only the most important organ for drug metabolism
(pharmacokinetics) but also gets affected by various drugs
or their metabolites. Thus, the prediction of the human
pharmacokinetics is an important tool when new drugs are
developed so that their adverse reactions and toxicity may be
known and/or avoided. Animal data have suggested certain
significant paths in this direction, but its extrapolation may
not be accurate and, therefore, chimeric mice with humanized
liver have been used to predict human drug metabolism and
drug-drug interaction.[10]
Several researchers studied anesthesia induced neuronal
cell death or apoptosis on neonatal rodents and nonhuman
primates. Following convincing evidence in animals, multi-
centric human studies are now underway to test long-term
neurocognitive outcomes in children after exposure to
anesthesia.[11,12] Animal contribution is boundless, but the
scope of this article is too small to acknowledge them all.
Some considered it as a contribution to scientific discoveries
while the others accused it as cruelty to animals. Animal
experiments have contributed immensely towards scientific
progression, but it cannot be denied that they have not been
totally either judicious or legal every time. Overzealous
and irrational animal testing was not unknown until 1822,
when the first law for animal protection was passed in the
British Parliament, followed by the 1876 Cruelty to Animals
Act. American Society for the Prevention of Cruelty to
Animals (PCA) was formed in 1860s, and the boundaries
between acceptable and illegal animal experiments began to be
examined. A lot of arguments were exchanged between the pro
(vivisectionists) and anti-animal testing (antivivisectionists)
lobbies for many years. However, the fast development of
medical science as well as the pharmaceutical industry did
not stop on the grounds of misinterpreted and exaggerated
accusations of animal exploitation. Claude Bernard, the prince
of vivisectors and the father of physiology, finally established
animal experimentation as part of the standard scientific
methods.[13]
In 1966, the Laboratory Animal Welfare Act finally had
a more focused approach towards animal protection and
judicious use of animals for medical testing. At present, the
Office of Laboratory Animal Welfare enforces the standards of
the “Guide for the Care and Use of Laboratory Animals” in
USA. Since 2010, the European Union follows the “directive
2010/63/EU” on the protection of animals.[14,15]
In India, the PCA Act, 1960 (amended in 1982), was
made to prevent the infliction of unnecessary pain or suffering
on animals. A Committee for the Purpose of Control and
Supervision of Experiments on Animals (CPCSEA) was
formed by the Central Government to ensure the same. Ever y
individual/institution is required to seek prior permission
from CPCSEA for carrying out every animal experiment
according to a notification published in Extraordinary
Gazette of India (September 8, 1998). The government
has further made “Breeding of and Experiments on Animals
(Control and Supervision) rules, 1998” (amended during
2001 and 2006) to regulate the experimentation on animals.
These rules prevent the indiscriminate use of animals for
teaching, acquiring the surgical skills or for repeating a
known fact.[16,17]
Modern scientific research sans animal testing would probably
be incomplete and unthinkable. However, it is pertinent
not to forget that all efforts should always be thoughtful,
well-judged and lawful. The immeasurable contribution
of animal research to the science of anesthesiology must be
truly acknowledged.
Acknowledgments
I extend my sincere thanks to Dr. Mukul Kapoor and all my
colleagues who helped me in collecting data for this manuscript.
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Goyal: Animal testing
Journal of Anaesthesiology Clinical Pharmacology | April-June 2015 | Vol 31 | Issue 2 151
Rakhee Goyal
Department of Anesthesia and Critical Care,
Armed Forces Medical College and Command Hospital (SC),
Pune, Maharashtra, India
Address for correspondence: Dr. Rakhee Goyal,
NP-5 MH, CTC, Pune - 410 040, Maharashtra, India.
E-mail: rakheegoyalkumar@icloud.com
References
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2. Liss HP. A history of resuscitation. Ann Emerg Med 1986;15:65-72.
3. Rushman GB, Davies NJ, Atkinson RS. A Short History of
Anaesthesia. The First 150 Years. Oxford: Butterworth Heinemann;
1966.
4. Corning JL. Spinal anesthesia and local medication of the cord. N
Y Med J 1885;42:483.
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9. Nickalls RW, Nickalls EA. The first reversal of curare. A translation
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11. Ramage TM, Chang FL, Shih J, Alvi RS, Quitoriano GR, Rau V,
et al. Distinct long-term neurocognitive outcomes after equipotent
sevoflurane or isoflurane anaesthesia in immature rats. Br J
Anaesth 2013;110 Suppl 1:i39-46.
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13. LaFollette H, Shanks N. Animal experimentation: The legacy of
Claude Bernard. Int Stud Philos Sci 1994;8:195-210.
14. Statement of the Royal Society’s Position on the Use of Animals in
Research; 2006; September, Ref 16/06. ISBN-13: 978 0 85403 628
8. Available at www.royalsoc.ac.uk. [Last accessed on 2015 Jan 15].
15. History of Animal Testing. Av ailable from : http://www.
en.wikipedia.org/w/index.php?title=History_of_animal_
testing&oldid=491072378. [Last accessed on 2013 May 24].
16. CPCSEA (Committee for the Purpose of Control and Supervision
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17. Krishna SC. Animal testing in India. Lancet 2001;357:885-6.
How to cite this article: Goyal R. Animal testing in the history of
anesthesia: Now and then, some stories, some facts. J Anaesthesiol
Clin Pharmacol 2015;31:149-51.
Source of Support: Nil, Confl ict of Interest: None declared.
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