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Saturday, 21.07.2018

Carl Lange

1834 – 1900
A Founding FatherofNeurology,Psychophysiology and Lithium Therapy
A Biographical Portrait*
Johan Schioldann



            Carl Georg Langewas born December 4, 1834, at Vordingborg, into the Danish artistic and scientific elite. His father, Frederik Lange (1798-1862), was a theologian, classical scholar and educationalist. His mother, Louise (1803-1862), was a memberof the highly intelligent Paludan-Müller family. Her father, Jens Paludan-Müller (1771-1845), was a prominent bishop and one of her brothers was the famous poet, Frederik Paludan-Müller (1809-1876). Another brother, Caspar Paludan-Müller (1805-1882), was an outstanding professor of history. Carl Lange’s brother, Julius Lange (1838-1896), became a renowned art historian and another brother, Frederik Fritz Lange (1842-1907), an eminent psychiatrist, who was,like Carl, to play an important role in the history of lithium therapy.

            Already by adolescence, according to Georg Brandes, a famous literary critic who was close to the Langebrothers, Carl Lange struck others with his brilliance, amazing erudition within natural sciences, history and literature and his knowledge of foreign languages, Roman and German. “When a young man,”Brandes said, “(Lange) in full earnest would take a bet that he, extempore, could obtain a Master’s Degree in any subject. He could not comprehend which questions one could not answer if given six weeks and the Royal Library (of Copenhagen) at one’s disposal. (Therefore, he had not much respect for Master’s Degrees)… better brains than his, I have not known.” In 1859, Lange graduated in medicine from the University of Copenhagen.

            From 1859 to 1863 he was Naval Medical Officer and Intern at Royal Frederiks Hospital in Copenhagen. From 1863 to 1866 he was Medical Registrar at this hospital and from 1866 to 1867 Assisting Doctor at Almindelig Hospital (General Hospital), also in Copenhagen.

            During this period, Lange published several excellent works within the fields of the history of medicine, epidemiology, nosography and public health. Among them were descriptions of the “black death” in the 14th century, the symptomatology and incidence of rheumatic fever based on 1,900 cases, and the incidence of tuberculosis in Greenland, where he had been sent in 1863. In 1866 he became Co-Editor of Hospitals-Tidende, a weekly medical bulletin.

            The main fields of Lange’s expertise became physiology ˗ possibly inspired by his countryman, the outstanding physiologist P. L. Panum˗ neurology and neuropathology, inspired during his appointment to Almindelig Hospital, Denmark’s “la Salpêtrière.” In 1867-68, he studied histology under C. J. Eberth and H. Freyin Zurich and neurophysiology under Moritz Schiff in Florence. Schiffaroused his interest in vasomotor reactions, seminal for many of his later scientific contributions.

            Lange’s first neurological work, in 1866,Bemærkninger om Aphasien(Comments on aphasia), is considered to be on par with Hughling Jackson’s classic aphasia study. M. Lund opined that he could not have known this work. In 1868 Lange coined the term “acute bulbar paralysis.” Subsequently, in 1875, E. von Leyden used this term, after which it became generally accepted and known. In 1872 followed: “On the conduction in the posterior spinal cord columns and some remarks on the pathology of tabes dorsalis” where, 22 years before Jean Nageotte, Lange was the first to describe the pathogenesis of tabes dorsalis, the “root-theory” - an anticipation of the later neuron doctrine. This paper was translated into German the same year and, subsequently,was referred to by several authorities on neuropathology, whereas Nageotte had not seen fit to mention it in his own work in 1894. Eventually, Lange’s landmark-description disappeared from the international literature. In his “On chronic spinal myelitis,” from 1873-74, he subdivided chronic myelitis into three syndromes:anterior horn atrophy; lateral tract paraplegia; and posterior tracts ataxia and root pain. His “Lectures on the pathology of the spinal cord,” 1871-76, with many references to Schiff, contain original neuropathological and neurophysiological contributions on paralysis; sensibility disturbances; reflex pain and projected pain; and - years before the description by C. S. Sherrington in 1893 of the “stretch reflex”–“latent innervation” or “resting tone.” The next major work by Lange was his 1883 “General pathological anatomy.”

            Subsequently, with his1885“On emotions. A psycho-physiological study,”Lange became one of the founders of psychophysiology. This study, he wrote, “owes its genesis primarily to an urge, for practical medical purposes essentially, to elucidate for myself the relation of the emotions to bodily, partly pathological phenomena, and if possible to shed light on this relation in a more precise and, furthermore, more physiological way than has been applied heretofore.” In his opinion emotions were not primary psychological experiences but secondary emotions, indirectly aroused by physiological vasomotor reflexes. The work also described conditioned reflexes, two decades before Pavlov.

            Lange is likely to have been to some degree influenced by a work by his countryman, August Sell in 1883, but not by William James’ classic study on emotions from 1884. In 1890 Jameswrote, though: “Now the general causes of the emotions are indubitably physiological. Prof. C. Lange, of Copenhagen… published in 1885 a physiological theory of their constitution and conditioning, which I had already broached the previous year in an article in Mind,” and in 1894 he wrote: “Professor Lange of Copenhagen and the present writer published, independently of each other, the same theory of emotional consciousness.”

            The respective emotion theories by James and Lange became known as the “James-Lange theory of emotion,” which was to have a major impact on the development of psychophysiology, experimental psychology and on philosophy, e.g.,the classical mind-body problem, until the early 1930s, by which time it had become obsolete and psychoanalysis dominated.

            It is interesting to note that Freud, in his “General theory of the neuroses,” 1916-17, had this to say: “What you may gather about affects from psychology - the James-Lange theory, for example - is quite beyond understanding or discussion to us psychoanalysts,” although he was emphatic that “psycho-analysts never forget that the mental is based on the organic.”

            Furthermore, Lange in this treatise came close to formulating alternating periodsof mania and depression as a nosological entity, years before Kraepelin’s1899concept das manisch-depressive Irresein. After having stated that “it is our vasomotor system which we can thank for all of the emotional side of our psychic life, our happy and unhappy hours,”Lange proceeded to say:

“Every psychiatrist knows the strongly developed forms which occur as ‘melancholia’ or ‘mania.’ Every doctor, who occupies himself with nervous illnesses, has abundant opportunity to observe the even more instructive mild cases which lie on the border between the insanities proper and such ‘indispositions,’ which could be subsumed under concepts such as oddity, morosity, despondency and so on and so forth. Most frequently sadness is encountered, the picture of sorrow, at times even despair, which often enough results in suicide in spite of the clear awareness that there is complete lack of any psychic motive for the sorrow. Almost as common is the morbid anxiety, which is often linked with its close relative, sorrow, but often it also occurs alone. It is a more rare occurrence, of course, that joy is manifested in a morbid way as such; the mere fact that joy appears in an unmotivated way, without cause, as can be easily understood, will usually not be sufficient, not for the layman at any rate, to characterise it as something morbid, and even less to seek the condition changed by medical treatment; (for this) would usually require either the happy mood to vent itself in an absolutely careless and uncontrollable manner, in the form of a more or less pronounced mania, or that it in a striking manner alternates with periods of depression and thus leaps to the eye as something abnormal.”


            In accordance with these views by Lange, it becomes understandable that he, in his emotion treatise, would stress that “the study of ‘the emotional illnesses’ becomes particularly important from a psychological viewpoint, or at any rate, this will be the case once it (the study) has become more systematised than hitherto has been the case.”

            Lange would have been well-acquainted with the psychiatric literature not only from his own studies but also from his psychiatrist brother, Frederik Lange, who in 1894 published the first collected textbook of psychiatry in the Danish language. He made reference to both Falret’s1851foliecirculaire, and Baillarger’s1854 folie à double forme. He also mentioned L. Kirn, who in his 1878work on “periodical psychoses” operated with concepts such as periodical mania, periodical melancholia and circular insanity. Finally, he made reference to Th. Meynert, who in his “Psychiatry” in 1884, explained both mania and melancholia as manifestations of functional disturbances of the cerebral blood circulation, the former due to cortical hyperaemia, and the latter to cortical anaemia.

            In fact, in 1886 Carl Lange presented to the Medical Society of Copenhagen a study of “the emotional illnesses,” entitled “On periodical depression and their pathogenesis”(i.e., the so-called uric acid diathesis), although he felt that it was “lacking in no small degree the scientific exactitude and precision that nowadays are mandatory even within the clinical field.” Moreover, he was of the opinion that this “serious form of illness,” which he thought could be caused by uric acid diathesis, the Lange theory of depression, had “strangely enough… almost completely escaped any notice in the literature,” and for which he had coined the term “periodical depression.”

            In 1899, Lange published a continuation of his studies on emotions, namely “Contributions to a physiology of enjoyment as the basis for a rational aesthetic.” It was reviewed in the Journal of Mental Science the following year by A. Friis, who wrote that “this work of the well-known Danish specialist in nervous diseases attempts to found conditions and phenomena, which hitherto have been regarded as purely intellectual, completely mental, on the basis of natural science, and to explain them in a complete physiological manner, following the common laws of physiology.” The reviewer concluded that “it is so full of original thoughts and views, its remarks are so appropriate, and the whole style is so brilliant, that the mere reading is an intellectual pleasure.” However, from aesthetes and philosophers, it gained him more criticism and indignation than praise.

            Among Lange’s “Private Papers,” held at the Royal Library in Copenhagen, is an unfinished manuscript: “A draft for a psychology,” which he had written in 1899. This “draft” was an attempt at providing a materialistic psychology without metaphysical speculations. It was published in 1927.

            In the 1897second edition of his “General pathological anatomy,”Lange distinguished between “pseudoheredity” and “blastogenic” or true heredity. It was in accordance with this view that his countryman, the botanist and geneticist, W. L. Johannsen, later distinguished between false and true heredity, concepts that are fundamental to the biological laws of heredity.

            In 1873, the position of Physician-in-Chief at the Royal Frederiks Hospital in Copenhagen, had become vacant. It was decided that it should become an academic post. Knud Faber, Lange’s biographer, stressed that Lange was the only doctor who had sufficient physiological scientific experience and talent to further Danish medicine. Lange had been grooming himself for this position. He had published prolifically and had been a reader at the Copenhagen University from 1869 to 1871. In his application he placed emphasis on the fact that hardly any applicant would be able to compete with him as regards scientific production, which he had published “in our various (Danish) and a couple of foreign medical journals,” and he thought, therefore, that this might render him suitable for the position – “the aim of my life,” on which “vital matter” he had “staked so much in psychological and material regard.”

            However, there were two other applicants for the position, one of whom was the incumbent of the chair of pathological anatomy, C. M Reisz, and the other Fr. Trier. They had both written a doctoral dissertation, which Lange had never taken the trouble to do, as he apparently, according to Brandes, did not attach much importance to dissertations. Furthermore, he was regarded as a relatively poor teacher. The medical faculty, placing emphasis on teaching skills, recommended Reisz be appointed to the position. In their recommendation, which had been conceived by Panum, the faculty made no mention of scientific talents or experience. Lange was passed over.

            In 1870, Lange opened a private neurology practice with an institute for “Medical Electricity,” and he became widely known as “Nerve-Lange.” In 1874, in partnership with a colleague, F. V. Rasmussen, he had also taken over a medico-pneumatic clinic for diseases of the chest. From 1868 to 1876, he was City and District Medical Officer in Copenhagen, and also, for a number of years, surgical prosector.

            In 1875, Lange became reader in pathological anatomy at the University of Copenhagen; in 1877 lecturer; and finally, somewhat belatedly, in 1885, he was appointed to a professorial chair, that of Pathological Anatomy and General Pathology. A chair of neurology was not established until 50years later, in 1935.

            Lange also became a leading figure in Danish public health, poor relief, medical jurisprudence and medical education, for the furtherance of which he had visited various hospitals and medical research institutes in Europe in 1887. He was Vice-President of the International Congress of Physicians in Philadelphia in 1876. He was Secretary-General of the Eighth International Medical Congress that was hosted by Copenhagen in 1884, under the auspices of Panum -it was hailed as a great success, not least thanks to Lange. Several of the “heroes of medicine” were among the almost 1,250 delegates. Lange was also the untiring editor of the Congress Transactions, published with some delay in 1886.

            The Copenhagen Congress helped Danish medicine out of its isolation from European medicine and thus restored its self-respect after the country’s humiliating defeat in the Danish-German War in 1864, when Denmark lost two fifths of her territory, Schleswig-Holstein and Lauenburg, and one third of her population. It was Lange’s hope that Denmark, henceforth, would become “more international in scientific regards.”

            Later, in 1889, Lange was the Danish member of the international Comitée d’honneur at the Congress for Physiological Psychology in Paris, arranged under the auspices of Charcot, who, according to A. Friedenreich, had wished to attend the Copenhagen Congress, but had been prevented from doing so because his son had “fallen seriously ill.”

            In 1896, Lange founded the Danish Biological Society, a section of the Medical Society of Copenhagen, of which he was President, 1890-92. From 1883 to 1897, he was Member of Copenhagen City Council. He had strongly supported the finding of suitable premises for the Copenhagen Medical Society. Moreover, he had been in the forefront of advocating the vacation of the old-fashioned Royal Frederiks Hospital. Eventually, in 1903, the government agreed to this. The new Copenhagen University Hospital, Rigshospitalet, was opened in 1910.

            Lange’s expertise also spanned anthropology, cultural history, geography and philosophy. Brandesrelates that he was a true “encyclopaedia,” and emphasised his special knowledge on Africa and Napoleon.

            It has been much speculated why the brilliant Lange did not ensure that his neurological works, in general, some of them pioneering or original contributions, were translated into foreign languages. It was certainly not due to lack of international contacts. In 1878, he had become Editor-in-Chief of Hospitals-Tidende. Renowned are the annus medicus with which he, from 1880 to 1885, introduced each annual volume of this journal concerning current events in medicine, national and international, topics of the day, etc., and obituaries, including those of foreign doctors. It was also in this local journal that he chose to publish most of his works.

            Faber, the leading physician in Denmark in this time and, in 1916-17, Chancellor of the University of Copenhagen, had worked under Lange for a period of three years, from 1891, and became personally very close to him - full of admiration. His view was that thelack of publishing in foreign languages was possibly caused by his “idealistic defiance” and his “anti-German sentiments” that he had developed due to Denmark’s humiliating defeat in the Danish-German War. Yet, in 1890 he had become Co-Editor of the prestigious Zentralblatt für Nervenheilkunde und Psychiatrie.

            A German edition of his “Lectures on the pathology of the spinal cord” had been planned at some stage but Lange, according to Faber, did not appear to be interested, not only for “national” reasons but also “possibly due to a mixture of increased self-esteem and depression (‘Blanding af Selvfølelse og Depression’).” Furthermore, Faber related that “there was no continuation of [Lange’s] earlier neurological works; he was apparently at a low ebb”(‘i en Bølgedal i sit Liv’), and, moreover, the “Special Part” of the afore-mentioned work “never appeared… and as the first part was not translated into foreign languages, it quickly fell into oblivion.”Faberfinally concludedthat “it did not fall to Lange, but to von Leyden, Charcot and Westphal to edify, in Europe, the pathology of the spinal cord.”

            Consistent with this view, another of Lange’s contemporaries, H. Munch-Petersen, emphasised that these lectures would have become “one of the cornerstones in the development of neurology, had they been translated into a major foreign language,” and Lange’s name would have been included “among the other great names” in neurology. Viggo Christiansen expressed a similar view in his Éloge at the Centenaire de Charchot in Paris in 1925.

            Thus, Lange, “Denmark’s first neurologist,” forfeited a ranking among the great pioneers of neurology. His colleague, C. J. Salomonsen, an eminent pathologist, had compared him with no less a person than Charcot.

            In his centenary speech, Christiansenadded that Lange was “un élève et un admirateur ardent de Charcot.”

            Lange shunned public recognition and it caused great consternation when he refused to accept and wear the Order of Dannebrog bestowed on him by the Danish king on the occasion of the Copenhagen Congress. He was required to provide an explanation to the Ministry of Education for what was deemed almost irreverent behaviour towards the king. Subsequently, the decoration was annulled, which was exceptional. As mentioned previously, he did not seek recognition by writing a doctoral thesis. In 1893, however, he accepted an honorary doctorate from the University of Lund, Sweden, and he became Honorary Member of several foreign medical societies.

            Lange’s assistant from 1897 to 1900, Johannes Fibiger, relates that “the general opinion among colleagues” was that Lange was “an unamiable and repulsively arrogant man.”Fibiger, however, vigorously disputed this view, emphasising that “behind the shell of reserve, which kept most people away from him, there was a rarely fine and pleasant nature.” Like others, Fibigerwas also struck by his “wonderful” intelligence. Lange’s criticism, though, “was always strongly shattering, extremely superior and apt, not seldom so shattering that one lost courage,” but when he realised that his criticism could be devastating, he would “change course at once,” seeking to “console” his victim, and he would then become an “excellent adviser.”

            Fibigerremembered his time under him “as one of the happiest periods” of his life, and it had been “one of the proudest moments I have experienced, when he told me that I ought to become his successor and sometime later learnt that he had expressed the same view to the university.” In fact, Fibiger succeeded him at his death, in 1900, after customary competition.

            Apparently, Lange had judged him rightly for in 1927 Fibiger was awarded the Nobel Prize in Medicine for achieving the first controlled induction of cancer in laboratory animals (Spiroptera-cancer), ground-breaking in cancer research.

            Lange had also been a strong supporter (along with J. H. Chievitz) of Niels Finsen in establishing him with a “light institute” in 1896, enabling him to continue his epoch-making research on the application of light in the treatment of skin diseases, for which he was awarded the Nobel Prize in Medicine, in 1903.

            Brandes relates that Lange’s “self-confidence was probably not small, but it was not shown as arrogance, even less as vanity.” He also mentions that Lange was claimed to be “greedy for power, even to a high degree, and that he was keen to extend his influence as far as possible.” An example of this has been more than suspected in connection with the establishment of the chair of General Pathology at Copenhagen University, to which Salomonsen was appointed in 1893.Brandes, however, had not himself witnessed that side to him.

            Faber characterised him as a fine, unselfish and warm person. Moreover, and significantly, he emphasised his “many personal disappointments” and the “shipwreck” that his great scientific mind had suffered during “the ups and downs of life,” and that many of his colleagues had been ‘oblivious’ of his contributions.Faber finally concludedthat “it took an European yard stick to measure his scientific works!”

            Judging by Lange’s bibliography, which Faber included in his biography, it is difficult to assess whether from some time in the mid-1870s to sometime in the early 1880s, there had been a real decline in his literary output, yetthe amount of neurological works dropped. Faberquoted him as having stated that nowhere did he see the slightest sign that his lectures on the pathology of the spinal cord had had any impact. His disappointment at having been passed over as Physician-in-Chief must probably also be given some weight. However, further biographical sources are required to draw a more detailed psycho-biographical profile of him. The question can be asked, though, whether he was given to mood swings, as was, for instance, his famous uncle, the poet Fr. Paludan-Müller, according to his psycho-biography, by Fr. Lange. This work also contains information to the effect that there was a tendency to “melancholy and insanity,” which was “not rare” in this line of the family.

            In the brilliant career of Carl Lange, it is less generally known that he was also a founding father of lithium therapy.

            His previously mentioned lecture on depression, in 1886, is not only a fascinating early description of endogenous depression, especially its mild to moderate manifestations, including its masked forms, but also the first account of the systematic use of lithium in the acute treatment and prophylaxis of periodical depression.

            This classic speech, which was presented in the most beautiful and eloquent Danish, was printed the same year, and, subsequently in 1895, reprinted with a postscript by himself. It appeared in German translation by H. Kurella in 1896, but never in English. The first edition was reprinted by Amdi Amdisen in 1982, but in Danish, and the German edition by W. Felber, in 1996. An English edition by the author appeared in 2001 (and reprinted in 2009 and 2011).

            For the last 10years of his life, the disappointed Lange suffered ill health, severe angina pectoris and failing eyesight. He died from a heart attack, on May 4, 1900.

            In his commemorative speech on Lange in 1927, Kn. Fabercharacterized him, “this peculiar sympathetic demigod” as “the greatest scientific mind” of Danish medicine in the 19th century. Brandesopined that he was “one of the brightest and strongest minds” of his time.

            Now that Carl Lange is recognized as a founding father of neurology, psychophysiology and lithium therapy, he must be counted among the 19thcentury’s great medical minds.




*From the author’s “Carl Lange: A Biographical Portrait.” In: Commemoration of the Centenary of the Death of Carl Lange. The Lange Theory of “Periodical Depressions.” A Landmark in the History of Lithium Therapy.Adelaide Academic Press, 2001, pp. 11-22. Modified March 2018. “References and Notes” have not been included from the original book version where they appear as footnotes but are available from the author at    j.



July 12, 2018