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saqarTvelos mecnierebaTa erovnuli akademiis macne
Известия Национальной Академии Наук Грузии
Proceedings of the Georgian National Academy of Sciences
biomedicinis seria
БИОМЕДИЦИНСКАЯ СЕРИЯ
BIOMEDICAL SERIES
2018 № 3-4 44
Jurnali daarsebulia 1975 wels
Журнал основан в 1975 году
Founded in 1975
Tbilisi Тбилиси Tbilisi
2018
tomi
ТОМ
VOL.
281
saq. mecn. erovn. akad. macne, biomed. seria, 2018, t. 44, # 3-4 ISSN-0321-1665
Известия нац. АН Грузии, биомед. серия, 2018, т. 44, № 3-4
Proc. Georgian Nat. Acad. Sci., Biomed. Series, 2018, vol. 44, No 3-4
IVAN TARCHANOFF (TARKHNISHVILI) AND MARIA
MANASSEINA: TWO PIONEERS OF SLEEP RESEARCH
M. Tsagareli
I. Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia
This article is dedicated to two outstanding scientists of the nineteenth century, Ivan
Tarchanoff (Ivane Tarkhnishvili) and Maria Manasseina, Russian physiologists worked at
the St. Petersburg Medico-Surgical Academy. Among the numerous contributions of
Tarchanoff was the discovery of the skin galvanic reflex and of the influence of X-rays on
physiological systems and functions, among them the central nervous system and animal
behavior, the heart and circulation, and embryonic development. Maria Manasseina, one of
the first Russian women-doctors greatly contributed in biochemistry and both scientists are
founders of experimental sleep research by their original discoveries. Tarchanoff and
Manasseina presented their interesting findings in experimental studies on sleep at the
International Congress of Medicine in Rome in 1894 and published their papers in Archives
Italiennes de Biologie in the same year.
Key words: sleep deprivation, somnology, history of sleep research
INTRODUCTION
Maria Manasseina (1843-1903) joined and began to work with Professor Ivan Tarchanoff
(1846-1908) at the Department of physiology of the St. Petersburg Medico-Surgical
Academy (since 1881 Military Medical Academy) in the 1870s. Here she performed
pioneering studies in puppies with prolonged deprivation of sleep. For this time, Maria
returned from Germany and Austria where she worked in famous laboratories of
physiological chemistry and studied the process of alcoholic fermentation.
Ivane Tarkhnishvili (Tarkhan-Mouravi; Cyrillic: Ivan Ramazovich [Romanovich]
Tarkhanov or Tarchanoff, depending upon the Russian or western European publications
and sources, respectively) was an outstanding Russian physiologist of Georgian origin.
He worked under the supervision and was follower of the founder of Russian physiology –
Ivan Sechenov (1829-1905). After less than 40 years of research activity, Tarchanoff was
considered one of the leading scientists in the Russian Empire and in Europe (Fig.1).
Following his initial research on muscle, blood, and visceral physiology, Tarchanoff
discovered the galvanic skin reflex, which had still not lost its importance in human
282
psycho-physiology [14-16]. But his most significant contribution was the discovery of the
influence of X-rays on the central nervous system (CNS), on animal behavior, on the
heart and blood circulation, and on embryonic development [10,14]. Indeed, these pioneer
works gave rise to a new research area that of radiobiology. In the study of higher brain
functions, Tarchanoff tried to bridge the gap between psychology and physiology, which
was described in his books On the Psychomotor Centers and their Development in
Humans and Animals (1879) and Spirit and Body (1904).
Fig. 1. Ivan Tarchanoff as a head of Department
of Physiology at Military Medical Academy
(1894).
Shortly on Ivan Tarchanoff’s legacy
Tarchanoff was interested in different fields of physiology. His greatest interest was in
electrophysiology, which was a direct continuation of the work of I. M. Sechenov, of
whom Tarchanoff was one of the first disciples [12]. Tarchanoff engaged in experimental
studies on the phenomena of summation in the nervous system (1869). He also studied
the influence of compressed air, oxygen, and carbonic acid on nervous irritability (1876).
He described the formation of bile pigments in animals and humans (1874) and was one
of the first to show the restoration of fading functions in anemic animals by infusing
saline in the body (1871). He dominated work in the field of the physiology of aging [14].
In 1894, Tarchanoff gave several lectures at the World Congress of Physicians in Rome.
In 1895, he reported “On the mechanism of luminous apparatus of Italian fireflies” at the
World Congress of Physiologists in Bern. Tarchanoff’s work “Psychic phenomena and
bodily processes in animals and man,” is an expression of his thinking that runs through
the whole of his scientific creativity. His thoughts ended with the monograph, Spirit and
283
Body (1904), in which he spoke of the unity of spirit and body, and the relationship
between body and environment. In 2010, this book was republished in Moscow [3].
I.R. Tarchanoff was one of the first to investigate hypnotic suggestion. In 1881, he
published his observations on autosuggestion. Tarchanoff’s Hypnotism, Suggestion and
Mind-reading (1886; translated into French in 1891) and Suggestion and Hypnotism
(1905) aroused wide public interest [14].
Among distinguished scientists contributing to research on the electrodermal response
were the Georgian (Russian) Tarchanoff, the French Marie Gabriel Vigouroux (1831-
1911) and Charles Samson Féré (1852-1907), the German Georg Sticker (1860-1960),
and the Swiss Otto Veraguth (1870-1944). The electrical activity of the skin maybe
measured in one of the two following ways: the Féré method or the Tarchanoff method.
The French neurologist, Féré, used an “exosomatic” method, often called the Féré
effect/phenomenon, in which a small current was passed through the skin from an
external source, after which the resistance to the passage of the current was measured
(1888). Tarchanoff used an “endosomatic” method, often referred today as the Tarchanoff
effect/phenomenon, in which electrical activity is measured at the surface of the skin with
no externally imposed current (1889). The Féré method has been modified today for the
measurement of skin conductance, which is the reciprocal of skin resistance, and
Tarchanoff’s method is still used today to measure skin potential. Féré’s measure records
changes in the resistance of skin to the passage of a weak electric current, while
Tarchanoff’s measure records weak current actually produced by the body [14].
Tarchanoff also demonstrated that not only physical stimuli, but also mental activity and
emotions resulted in skin potential changes [5, 11].
The skin galvanic reflex is still used in applied psychophysiology as part of the polygraph
in lie detection in which the changes are recorded in several physiological variables while
the subject is asked a series of questions pertaining to a specific issue under investigation [15].
Tarchanoff and sleep research
Ivan Tarchanoff was extremely interested in sleep. His articles published in 1876 include
“Experiments on animals’ natural sleep” and “Some observations on normal sleep”. In
these papers he asks, does the spinal cord sleep? And why would a man sleep if the brain
continued to work even more intensively than in the waking state?
On these questions he answered and considered that in a dream, the brain centers of
respiration, circulation, and speech did not sleep; in a dream human subjects spoke, and
the centers of attention, hearing, and smell did not sleep.
Finally, the cerebellum, as evidenced by the acrobatics displayed by lunatics, does not
sleep. So what then sleep is? Only centers that focus our minds sleep. Everything else
works and even more intensely than during the day. In fact, consciousness is present
during sleeping and waking. If it were not so, man could not remember dreams [14].
284
It should be noted here that Tarchanoff in experiments on puppies found a decrease in
blood pressure during sleep (1894). In this article, he concluded that during sleep, firstly,
the spinal cord does not sleep; secondly, not all parts of the brain are inactive, that is, on
the contrary, is a source of inhibition that extends to parts of the spinal cord. In this point
of view, a normal dream cannot be considered as a consequence of the complete loss of
all the function of the brain, as suggested by the most common hypothesis in that time. It
is quite possible that the weakening during a normal sleep of a number of functions is due
to depressing effects of the brain on the activity of automatic or reflex centers regulating
these movements [13]. It was truly progressive view on the brain activity in sleep.
Being in Florence in 1894 in May for 4 weeks, Tarchanoff was carried away by the
mechanism of luminosity of Italian fireflies (Luciola Italica). In December, he presented
the results of his observation at the meeting of the St. Petersburg Society of Russian
Doctors under the chairmanship of Ivan Pavlov (1849-1936). In his speech, he raised the
issue of excitatory and inhibitory processes in the neural plexus (brain) of fireflies and
connected them with the mechanism of the inducing sleep. He found that insect with cut
off head shines all day and night without a pulsation until it loses all signs of life.
Consequently, the neuronal chain, in the sense of the center, exerts a great influence on
the periodicity of the peripheral luminous apparatus. Hence, from the "brain" there are
impulses, amplifying and oppressing light. Obviously, the extinction impulses come from
the brain centers, since the decapitated firefly loses its ability to go out of tune [2].
Tarchanoff related his observations with the mechanisms of sleep and came to the
conclusion that during "sleep" in fireflies, the absence of luminescence of the apparatus
indicates the excitation of those centers of the brain that suppress the flickering of light.
Tarchanoff concluded his report with the words: "... a dream is incomparably more
complex than it is ordinary to think" [2, p. 208].
Presenting at the report, Ivan Pavlov expressed a doubt that the existence of special
depressing circumstances in relation to the lantern is not convincing in choosing the
theory of sleep. To this Tarchanoff clearly signified that the indicator of the brain's
activity in a firefly is a lantern; this lantern can go out, and if it blows out, then the brain
is active, because if it is inactive, then the lantern shines all the time. During sleep
Luciola has a function extremely suitable for it. This firefly developed an instinct that the
lantern is necessary for certain occasions, and in other it is necessary to extinguish, but
extinguish can only the brain, so it is excited. If we allow the existence of a sleep center,
then its purpose should be to get excited and to put out the extinguishing impulses.
Pavlov recalled that the late S.P. Botkin was just pointing out the substance of this center,
to which Tarchanoff politely replied that "... you strengthen my opinion with your words
in my assumptions" [2, p. 210].
Manasseina contribution to physiological chemistry
Maria Manasseina (also known as Marie von Manassein and Marie de Manacéine,
depending upon the German or French publications and sources, respectively) was one of
285
the first women in Russia (and probably in Europe) to obtain a higher medical education
in 1860s. She graduated from female medical courses, receiving the special degree of
“woman-doctor,” and later the degree of Doctor of Medicine (Fig. 2). She spent six
months training in the laboratory of Julius Wiesner (1838-1916) at the Polytechnical
Institute in Vienna where she studied the process of alcoholic fermentation. While being
there, she made a discovery of paramount importance thus becoming a founder of the new
science of physiological chemistry, as now biochemistry. She demonstrated that the
process of fermentation is due to specific substances (so-called “unorganized enzymes”,
using the terminology of that time) that could be isolated from yeast cells, but not the
living yeasts per se. These experiments ruled out Louis Pasteur’s “physiological” theory
of fermentation and confirmed the “chemical” hypothesis proposed by such outstanding
scientists as Claude Bernard, Justus von Liebig, and Marcelle Berthelot [6, 7].
Fig. 2. Maria Manasseina at her young age.
More than a quarter of a century had passed before these results were completely
confirmed by a German chemist, Eduard Buchner (1860-1917), who in spite of being
aware of Manasseina’s work, purposely failed to make any reference to it. Unfortunately,
the name of Manasseina as a pioneer of the chemical nature of fermentation was
forgotten, while Buchner received the Nobel Prize in 1907, four years after her death, for
the discovery of the extracellular (chemical) nature of fermentation [6].
At the time of its publication, Manasseina’s paper on fermentation was evidently noticed
with interest by the great German chemist Justus Liebig (1803-1873), who invited her to
join his laboratory in Giessen [7]. For the problems in her family she could not accept
Liebig’s invitation because had to return to St. Petersburg. Soon she started work in the
laboratory of Ivan Tarchanoff, a friend of her husband Vyacheslav A. Manassein (1841-
1901), a Professor of the Military Medical Academy, a publisher of the first Russian
286
medical magazine ‘Vrach’ (Physician), and a rather well-known person in the history of
Russian medicine [6].
In the late of 1870s marital problems arose in the family of the Manasseins, and in 1879
Maria left her husband (by the rumors of contemporaries for Ivan Tarchanoff, who was
already married at that time to a widow, a certain S.G. Loris-Melikova), but refused to
divorce. Thus, she did not give any possibility to her former husband to marry again but
also doomed herself to the similar fate. Maria had no children and she lived alone the rest
of her life.
Maria Manasseina and the first experimental study of sleep deprivation
As stated above, Ivan Tarchanoff was extremely interested in sleep problems and
published works include “Towards the physiology of normal sleep in animals” and “Does
the spinal cord sleep?” Manasseina’s interest in sleep research was stimulated by her
collaboration with I.R. Tarchanoff, as she was his assistant and disciple. Under his
influence, Maria Manasseina performed pioneering studies in puppies with prolonged
deprivation of sleep.
Likewise as Tarchanoff, the first experimental study on sleep deprivation Manasseina
presented at the International Congress of Medicine in Rome in 1894, where both
scientists traveled together to discuss their data on sleep research. She performed her
investigation on 10 puppies (2, 3, or 4 months old), fed by their mothers, by keeping the
animals in constant activity [4, 6].
The experiment came to the straightforward conclusion that the total absence of sleep is
more fatal for the animals than the total absence of food, since the dogs could be rescued
after 20-25 days of starvation, but they were irreparably lost after a sleep deprivation of
96-120 hours. Manasseina also noted that older dogs were more resistant to insomnia that
younger ones and that body temperature decreased from the second day of sleep
deprivation on and was 4, 5, or even 5.8ºC lower than normal before the animal’s death.
After the initial decrease of body temperature (0.5-0.9 ºC), locomotor activity had started
becoming “slower and weaker”, and red blood cells counts had decreased. The weight
loss of the animals before death was relatively mild (5-13%). The histological study of
body organs clearly demonstrated that the brain was the site of predilection of the most
severe and most irreparable changes, fat degeneration in many brain ganglia,
abnormalities of blood vessels, and small hemorrhages. These changes were very
different from those Manasseina had observed in animals that died of starvation, in which
the brain was remarkably spared. She concluded that findings provided a proof of the
great importance of sleep for the organic life of animals equipped with a cerebral system,
and also entitles to consider a bad paradox the strange opinion regarding sleep as a
useless, stupid and even noxious habit [8].
The works of Manasseina had a tremendous impact upon sleep studies. In 1898 three
Italian investigators, L. Daddi and G. Tarozzi from Pisa, and C. Agostini from Perugia,
287
inspired by her studies, performed more detailed investigation of sleep deprivation in
dogs. They also found that prolong and continuous insomnia could affect brain histology.
The investigators generally supported Manasseina’s data on the relation of sleep with
cerebral activity and suggested that the function of sleep – yet unknown – is vital [4]. In
1896 two American psychologists, G.T.V. Patrick and J.A. Gilbert, clearly inspired by
Manasseina’s pioneer work, performed the first study of sleep deprivation in humans [6].
In 1889 M. Manasseina published a large book entitled Sleep as One Third of Human
Life, or Physiology, Pathology, Hygiene and Psychology of Sleep (the 2nd Russian
edition, 1892) [1]. Its revised and significantly expanded version was later published in
English (de Manacéïne, 1897) [9]. Several important additions were made, including the
results of Manasseina’s experiments with sleep-deprived pups, experimentally induced
confusional episodes associated with awakening from an apparently “deep” sleep in
humans, the study of dreams, etc. This book was the sleep encyclopedia of its time, where
for the first time all knowledge on the sleep problem was presented in a popular
statement. The book had tremendous success that it was translated into Swedish [6].
CONCLUSION
The pioneering studies of Ivan Tarchanoff and Maria Manasseina on experimental
insomnia represent the first attempts to relate sleep with brain neural centers. These
studies suggested a vital role of sleep for body and drew attention to the cerebrum as the
site of damage induced by sleep deprivation. Therefore the hypothesis of Tarchanoff and
Manasseina that cerebral “substrate of unconsciousness” retains its activity during sleep
was well before her time. Apparently, Tarchanoff and Manasseina had taken the first step
to building a new scientific paradigm that received the definitive completion in the works
of the great somnologists of the twentieth century, Nathaniel Kleitman (1895-1999),
Allan Rechtschaffen and Michel Jouvet.
REFERENCES
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[Sleep as One Third of Human Life, or Physiology, Pathology, Hygiene and Psychology of
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289
ИВАН ТАРХАНОВ (ТАРХНИШВИЛИ) И МАРИЯ МАНАСЕИНА:
ДВА ПИОНЕРА ИССЛЕДОВАНИЯ СНА
М. Цагарели
Центр экспериментальной биомедицины им. И. С. Бериташвили, Тбилиси, Грузия
РЕЗЮМЕ
Cтатья посвящена двум выдающимся ученым девятнадцатого века Ивану Тарханову (Иване
Тархнишвили) и Марии Манассииной, российским физиологам, работавшим в Санкт-
Петербургской медико-хирургической академии. Среди многочисленных исследований
Тарханова было открытие кожно-гальванического рефлекса и влияние рентгеновских лучей
на физиологические системы и функции организма. Мария Манассиина, одна из первых
российских женщин-врачей, внесла большой вклад в биохимию, и оба ученых стали
основателями экспериментального исследования сна своими первоначальными открытиями.
Тарханов и Манассиина представили свои интересные результаты экспериментального
исследования сна на Международном конгрессе медицины в Риме в 1894 году и опублико-
вали свои работы в Итальянском Архиве Биологии в том же году.
