Freud's Irma Dream and the Possibility of Biochemical Pathways from Diseases to Dreams

A later version of this paper was published in Dreaming: Journal of the Association for the Study of Dreams, Volume 5, Number 4. December, 1995 (267-287)

In the time of sleep ... small impulses seem to be great ... Since the beginnings of all things are small, obviously the beginnings of diseases ... must also be small. These then must be more evident in the sleeping than in the waking state. (Aristotle On Prophecy in Sleep)

I would like to thank Dr. Dietrich Hoffmann for discussing tobacco chemistry with me and for editing the sections on tobacco chemistry in a rough draft of this paper. I have included his suggestions, but I may have missed some, and so I take responsibility for errors.

Introduction

INTRODUCTION

There are over forty writings on Freud's Irma dream, the first dream he ever "submitted to a detailed interpretation" (Freud, 1900, p. 106). Freud used it as "a specimen dream" in The Interpretation of Dreams (pp. 106ff), the book he praised as containing "the most valuable of all the discoveries it has been my good fortune to make" (Freud, 1900, p. xxxii). In the early 1900's, both Karl Abraham and C. G. Jung discussed the dream in letters to Freud, and Freud responded to both (Freud & Abraham, 1965; Freud & Jung, 1974). As far as I can tell, the first article on the dream was written in 1954 by Erikson, and this has been followed by one after another book chapters and journal articles (and letters to editors). Well over five hundred pages have been written about the dream so far, and many of the analyses represent independent thinking. (I include the dream as Appendix 1 below).

The analyses have produced much interesting information about Freud (a lot can be inferred from a dream, just as a lot can be inferred from a letter, and there is no single correct deduction). In this paper I present connections between the dream and Freud's smoking and cancer. It appears that there is a congruence between the image of Irma’s mouth (in the dream) and the reality of Freud’s mouth in 1923 when he developed his cancer. The most obvious explanation of this is that Freud was smoking at the time of the Irma dream in 1895 and that there was irritation at the place in his mouth where he later developed his tumor. Examination of his own analysis of the Irma dream (in ...) suggests that he was conscious of nasal irritation but not of its possible connection to a tumorus growth.

Four other possibile explanations of this congruence will be mentioned, the most interesting of which is that the tumor had already begun in 1895 and that the dream marked its initiation. Though this may seem unlikely, it serves to underscoref the possibility of a connection between physical processes like tumor biogenesis, and dreams. This in turn leads to the question of the possibility of using dreams as diagnostic tools in physical illnesses. This is virgin territory, and I will sketch out a research proposal in this area with which I am involved.

There is a vast difference between saying that a dream may “capture” sensations that are currently pre-conscious or unconscious but that could become conscious if attention is focused on them and the view that a biological process might provoke a dream where there is absolutely no sensation even with focused attention. 

Freud thought that the bodily state of a dreamer can provoke dreams. He even examined some of his own dreams in this light (for example, his dream of riding a horse [1900, pp. 229-32]). He took it as obvious that "internal organic somatic stimuli" can provoke and be the sources of dreams (Freud, 1900, Chapter 1, Section C3 , a section also containing a review of the literature from Aristotle to the late 1890's).

With respect to dreams as prodromes or "symptoms" of diseases, Freud wrote that "pronounced disorders of the internal organs obviously act as instigators of dreams in a whole number of cases" (1900, p. 34). Without admitting for a moment that dreams may be prophetic, he accepted the possibility of dreams having some diagnostic powers.

Parallels between the Irma Dream and Freud's Cancer

PARALLELS BETWEEN THE IRMA DREAM AND FREUD'S CANCER

In the Irma dream, Freud was confronted by a female patient who had, on the inside of her mouth, on the right, "a big white patch [Ger.:Fleck]."1 While this patch reminded Freud of diphtheria (1900, p. 111), it fits the definition of leukoplakia as "a lesion of the mucous membrane characterized by white patches" (Churchill's Medical Dictionary).

Pichler's now almost legendary notes (Pichler, n.d.), written during his sixteen years as Freud's oral surgeon, described many leukoplakia in Freud's mouth.  An example is in his first note where he described Freud's first surgery of April 20, 1923.2 Pichler wrote that the surgeon, Dr. Marcus Hajek, "performed an excision at the right anterior palate arch because of a proliferative papillary leukoplakia [papillären wucherunden Leukoplakie]" (from the note of September 16, 1923).  Please note that Irma's white patch was also on the right.

Elsewhere in Irma's mouth, Freud saw "extensive whitish grey scabs upon some remarkable curly structures which were evidently modelled on the turbinal bones of the nose." This can be correlated with the "proliferative papillary leukoplakia" described by Pichler in the above note (papilla: "a small nipplelike projection or elevation" [Churchill]).

It is as if Pichler's description of what Hajek saw when he looked into Freud's mouth in 1923 is a technical rephrasing of Freud's description of what he saw when he looked into Irma's mouth in 1895.3 Further, from 1926 through 1939, Freud suffered over thirty treatments (excisions, electrocoagulations, or both) for "an endless cycle of leukoplakia, proliferation, precancerous lesions" (Schur, 1972, p. 364).

Knowing Freud's later medical history, even the following scene from the Irma dream sounds familiar: "I took her [Irma] to the window and looked down her throat, and she showed signs of recalcitrance, like women with artificial dentures." Following Pichler's radical cancer surgeries of October and November of 1923, Freud, like Irma, had to wear a prosthesis (which was a denture by Churchill's definition of denture — "a removable prosthesis replacing natural teeth and associated tissues"). Because of the trismus (lockjaw) that accompanied Freud's operations it was often difficult for Pichler to insert the prosthesis (for example, "It was not possible to insert the inferior plate because of the lockjaw" — note from September 30, 1923).  As an example from another source, Max Schur, Freud's internist from 1928 to 1939, wrote that, at the beginning of 1938, Freud suffered severe pain and "could not open his mouth" (1972, p. 492). We may picture these doctors struggling to open Freud's mouth in a manner analogous to how Freud struggled to open Irma's mouth (in his dream) many years before.

It is time for an aside. After completing the above, I came across a book on Freud's cancer by an eminent Argentinean cancer surgeon, now psychoanalyst, named José Schavelzon (1983). Dr. Schavelzon has gone to the extraordinary trouble of finding the histological preparations of Freud's oral lesions from the period 1927-1939, twenty-six of which are reproduced in his book. His goal was to understand the causes of Freud's death.

Chapter 4 of Schavelzon's remarkable book (a book that should be published in English) is devoted to the Irma dream. There he presented (in 1983, ten years before me) almost the exact observations I have presented above. In addition, he suggested that the surgeries in Freud's mouth had left the nasal cavity visible from the oral cavity — hence the "structures ... modelled on the turbinal bones of the nose" seen by Freud in Irma's mouth. He also took the "whitish grey scabs" as referring to the results of the numerous operations and electrocoagulations. In Irma's infections he saw the infections Freud suffered over the years from the surgeries and x-ray treatments for his tumors. Finally, he referred Irma's "pale and puffy" appearance to Freud's appearance in 1939 when he lost his beard and became pallid (Schavelzon, 1983, pp. 77-78).

That a cancer specialist in Argentina in 1983 made essentially the same observations as a psychologist in Los Angeles in 1992, does not prove, but does attest to the reliability of  observations correlating images from the Irma dream and Freud's cancers.

We must now face the difficult and important question of how a dream of 1895 could have prefigured a disease process first noticed in 1923.

Perhaps the Parallels are Coincidental

PERHAPS THE PARALLELS ARE COINCIDENTAL

Someone might argue that, when Freud wrote, "on the right I found a big white patch," he meant his own right, not Irma's, (although "right" is certainly closer than "left"). Or, it might be argued that "proliferative papillary" is not congruent with "curly structures," since papillae are not necessarily curly. Arguments such as these could be made to prove that there are no substantial parallels between Freud's dream and the later physical reality.  Alternatively, someone might accept that the parallels are substantive but attribute them to chance.

Doubts such as these in my own mind led me to examine all the dreams in The Interpretation of Dreams. By my criteria (which I cannot present in this paper), at least twenty percent of the dreams in the book (including those of Freud and of others), describe some discomfort or disfigurement of the head.

One dramatic example is a dream of a woman patient who "had been obliged to undergo an operation on her jaw which had taken an unfavourable course." In the dream she heard an acquaintance of hers "complaining bitterly of pains in his jaw" (Freud, 1900, p. 125). This dream may be correlated with the operations Freud himself suffered on his upper and lower jaws in 1923.

Still, it is possible to challenge the criteria I used to select the dreams and/or the significance of twenty percent.  It might be argued, with some justification, that "significance is in the eyes of the beholder." In what follows I accept that Freud's dream mirrored a future reality. The problem becomes not if there is a connection but, given that there is, how to explain it. I will now discuss four possible explanations.

1. Was the Irma Dream Precognitive?

1. Was the Irma Dream Precognitive?

We cannot reject this view out of hand. It is possible that the Irma dream was a paranormal precognition showing Freud his mouth as it would appear in the future. However, usually precognition is reserved for a mental image that corresponds to a future, unrelated event in the external world. If both events occur in the same person (as in the case we are discussing), there does not seem to be a need to raise the question of precognition.

In this section I also include the possibility that the parallel between the 1895 dream and the 1923 reality is an acausal, meaningful coincidence (an example of what Jung and Pauli called synchronicity) as well as the possibility that there was a psycho-physical parallelism between the dream and reality of a type we can not yet, and possibly never will be able to understand.

2. Did the Dream Contain a "Blueprint" or a Wish for Cancer?

2 Did the Dream Contain a "Blueprint" or a Wish for Cancer?

Sometimes a person's obsessive fears come true, and it may seem as if the person unconsciously manufactured the feared event. For example, to an outside observer, a jealous husband may seem to engineer the very infidelity he consciously dreads. A similar mechanism might explain the Irma dream, a compulsion to cancer that produced both the dream and its translation into reality.4

Pattern

Another version of this view is that there is some sort of pattern that molds a person's life both mentally and physically. It might account for what dreams a person has as well as what illnesses a person develops, to pick two examples. This pattern or blueprint may be thought of as archetypal or genetic or both. Or it may be conceived metaphysically as a form that stamps its images on substances, or, again, as a fractal whose degree of irregularity is identical at all scales of a human life (mind taken as one dimension, body as another).

Applying this to Freud, we might try to intuit a life pattern. Even in childhood, his physical problems focused in the head. Between the ages of two and three he fell from a stool, and its corner struck him behind his lower jaw (Freud, 1900, p. 560). In his teens he suffered terrible toothaches (Freud, 1990, pp. 1, 18), and in 1880 he wrote that "two of the best teeth in my mouth have just broken, which will cost me a lot of money to repair" (p. 179). In The Interpretation of Dreams, Freud presented many dreams of teeth being knocked out, and the Irma dream was not the only one to contain dentures. And, of course, later in life he lost many teeth in Pichler's surgeries and had to wear a prosthesis.

In 1873 Freud wrote his friend Silberstein that "my natural good looks had been robbed of their symmetry by the rebellious encroachments of a bedbug" (1900, p. 40). In 1933 he wrote Lampl-de Groot complaining about his "immortal catarrh" (Freud, 1992, p. 168). He suffered from headaches off and on throughout his adult life. He applied cocaine to the inside of his nose during the 1890's and smoked from the age of twenty-one on. He had close associations with the German nose and throat doctor, Wilhelm Fliess, a man who thought that the nose was the center of all problems, and Freud allowed him to operate twice on his nose. He had oral cancers and precancerous lesions along with many oral surgeries from the year 1923 on. At the very end, cancer reached the orbit of his right eye, making Freud, like so many of the figures in The Interpretation of Dreams, a one-eyed man.

I find the idea of an unconscious blueprint quite attractive and would adopt it except that I think the Irma dream itself points in another direction.

3. Did Freud's Smoking Provoke the Irma Dream?

3. DID FREUD’S SMOKING PROVOKE THE IRMA DREAM?

It is possible that Freud had been smoking the night preceding the Irma dream, the evening of July 23, 1895. It is also possible that abrasions on the oral mucosa from this smoking stimulated the Irma dream and explain many of its images.5 The dream would have been neither pre-monition nor pre-cognition but a present visual representation of a bodily state mixed with knowledge of the effects of smoking.

Was Freud smoking on the evening of July 23, 1895?

I have not found any substantial evidence to prove that Freud smoked on the evening of July 23, 1895, but it is not unreasonable to assume that he did. It is well-known that under the influence of Fliess, an adamant non-smoker, Freud made repeated attempts to stop smoking from 1893 to the early 1900's. These attempts are documented in his letters to Fliess (Freud, 1985). Following a period of abstention of almost twelve months (Freud wrote fourteen months but see Schur [1972, p. 6]), Freud began smoking again on June 12, 1895. On June 17, he apparently gave it up again. Then, on June 22, about one month before the Irma dream, he wavered, and his words may possibly be construed as an admission of some smoking: "So I shall come [to Berlin] early in September. How I shall manage to do without you afterward, I do not know. I am having enough troubles with smoking." The next mention of smoking is in the letter of October 16, in which Freud renounced smoking again and implied that he had been smoking heavily: "I completely gave up smoking again ... to be rid of the miserable struggle against the craving for the fourth and fifth [cigar]; I prefer struggling right away against the first one."

We also know that Freud smoked under pressure ("smoking ... has served me for exactly fifty years as sword and buckler in the battle of life" [from a letter to Lou Andreas-Salomé, May 8, 1930, quoted in E. Freud {1976, p. 252}]) and that he was under pressure the night of July 23 when he was writing "late into the night" (Freud, 1900, p. 113) "to justify" himself (p. 108). Later in life Freud would write long hours into the morning "wreathed in tobacco smoke" (Engleman, 1976, p. 64).

So, though there is no direct evidence that he smoked on the night of July 23, 1895, I think it is a reasonable assumption.

Irma's complaints

In light of this assumption, we may examine Irma's complaints: "If you only knew what pains I've got now in my throat and stomach and abdomen — it's choking me." These complaints might well have been Freud's own if he had been smoking the night before the dream.

Regarding the choking, it may be relevant to quote Martin Freud who wrote about having once entered his father's waiting-room of the Bergasse flat after a meeting of the Vienna Psychoanalytic Society.

The room was still thick with smoke and it seemed to me a wonder that human beings had been able to live in it for hours, let alone to speak in it without choking. I could never understand how father could endure it, let alone enjoy it: which he did. (my emphasis, Martin Freud, 1957, p. 110)

Regarding stomach and abdominal problems, Max Schur wrote that during the years he cared for him, Freud's "`irritable,' spastic colon attacks ... were prevalently precipitated by excessive smoking" (1972, p. 58). In a letter to Max Eitingon dated May 1, 1930, Freud admitted the connection.

Cardiac and intestinal symptoms have forced me to go to a sanatorium ... Here I have made a quick and satisfactory recovery ... by an act of painful autonomy. For 6 days now I have not smoked a single cigar, and it cannot be denied that I owe my well-being to this renunciation.

(quoted in Schur, 1972, pp. 410-11)

And, finally, regarding the mouth and throat pains I quote from a lab report by the pathologist Jakob Erdheim who did the reports on many of Freud's lesions: "Specially noticeable this time is the widespread inflammation which covers the whole of the mucous membrane and is the consequence of excessive smoking" (quoted in Schur, 1972, p. 411).

To repeat, all of Irma's complaints are complaints Freud could easily have had if he had been smoking the night of July 23, 1895.

Freud saw concern about his health as one of the major themes of the Irma dream (1900, p. 120). Concerns about his health also filled his letters to Fliess in the period before the Irma dream. Blum (1981, p. 543), as far as I can tell, was the first to suggest that the Irma dream reflected a concern about his smoking: "The suggestive physical examination of Irma ... may also be an allusion to ... Freud's own cardiac and oral-respiratory (smoking) concerns."

However, if Freud was concerned about the effect of smoking on the tissues of his mouth, I can find no mention of it. He wrote of his concern over his cocaine use, his migraines, his catarrh, and his rheumatism. And, though very worried about the effect of smoking on his heart, apparently he was not worried about the effect on his mouth. He would certainly have been conscious of any unpleasant sensations in his mouth caused by smoking, but maybe not of their significance and ultimate importance. It is just such a gap of consciousness that produces dreams. Achilles had his heel, Freud his mouth.

Given Freud's alienation from the medical community of Vienna and his struggle to define his theory and find his unique place in society and history (themes that can be followed in the Fliess letters), it would have been natural for him to force his attention away from "minor" irritations in his mouth and view them the way he viewed Irma's problems — as hysterical symptoms, psychological and imaginary. Still, troubling sensations may have escaped suppression and found their way into his dreams, not labelled as his own, but as Irma's.

Unconsciousness of the "messages" from ones own body is characteristic of ambitious, inspired people who push on and on in high gear. A misunderstood Irma lives in many of us. The following note from Freud to his fiance on February 2, 1886 can be taken as expressing the sentiment of many Jewish men throughout history, even in this day: "I have often felt as though I had inherited all the defiance and all the passions with which our ancestors defended their Temple and could gladly sacrifice my life for one great moment in history" (Freud, 1960, pp. 202-3). The fact that this note was written under cocaine adds to the impression of a man who pushed himself without "listening to" his body (to Irma). (Here cocaine is the intellectual's version of the steroids taken by athletes.)

I will review what irritating sensations would have meant to Freud if he had attended to them: He would have had to admit that cigar smoking did not agree with him. And he would have had to face the prospect of giving up smoking, not because of Fliess' complaints, but because of the "complaints" of his own body. But this would have interfered with his work. In the letter of June 12, 1895 from which I have already quoted, Freud explained that he had returned to smoking after his long abstention because "I constantly missed it ... and because I must treat this psychic fellow [psychischen Kerl] well or he won't work for me. I demand a great deal of him. The torment, most of the time, is superhuman."

In short, if Freud had become fully conscious that Irma's complaints were his own, he would have had to consciously weigh the relative value of health and work, and he might not have been able to push himself as hard. To Fliess he wrote, "Psychology is really a cross to bear. Bowling or hunting for mushrooms is ... a much healthier pastime" (August 16, 1895). If he had gone for health — if he had allowed his psychischen Irma to guide him instead of his psychischen Kerl —, there might have been no psychoanalysis, perhaps not even a need for psychoanalysis.

The Irma dream may have fascinated Freud so much, because he may have sensed that it contained a "picture" of how he would die. This would explain the almost infinite importance he attached to this dream (and to dreams in general). Since he never did understand the dream from this point of view, his fascination with dreams persisted. If he had understood the physical meaning of the dream, he might have lost interest in dreams, and hence in psychoanalysis. [This line of thought becomes muddied if we accept the bold conclusion of Schavelzon [1983] that the cancer of 1923 was a slow-growing verrucous carcinoma and that the squamous cell carcinoma that developed later was caused, not by his smoking, but by the trauma to the oral tissue from all the unnecessary excisions, electrocoagulations, and x-ray treatments performed by his doctors. — Dr. Schavelzon was kind enough to send me copies of the histological preparations. I showed these to members of the Department of Pathology at UCLA Medical Center, and they agreed with him that Freud's tumor was a veruccous carcinoma!]

The doctors in the Irma dream

Let us continue to assume that some of Freud's physical problems were embodied in, and voiced by, the dream figure of Irma. Let us go on to assume that the doctors who examined Irma in the dream expressed medical views within Freud himself as he introspectively examined his own physical symptoms.

In real life, Dr. M. was Dr. Joseph Breuer, Freud's mentor and benefactor. In the Spring of 1894, Freud had consulted Breuer for a second opinion regarding his heart condition. Fliess had been insisting that it came from the toxic effects of nicotine. Breuer vacillated between this diagnosis and Freud's diagnosis of chronic myocarditis saying that "it might be the one thing or the other" (emphasis in text, letter to Fliess of April 19, 1894). A few days later, Freud wrote that Breuer had "quietly accepted the possibility of a nontoxic heart condition" (April 25). By June 22 Freud was smoking again, supporting his decision with an argument he badgered Breuer into accepting. The argument was that two of Freud's women patients had the same heart problem he had, and one had never smoked and the other had given up smoking. Therefore, he concluded, smoking was not causing his heart problem and abstinence would do no good. He wrote Fliess: "Breuer, to whom I repeatedly said that I did not consider the affliction to be nicotine poisoning, finally agreed and also pointed to the women."

I conclude that Freud saw Breuer as a man he could manipulate into giving medical judgments allowing him to smoke. The Breuer of the dream, who pronounced a cheerful prognosis for Irma, would have been the part of Freud who let his need to smoke nudge his medical thoughts away from nicotine poisoning. (In real-life the two men focused on Freud's two women patients; in the dream they focused on Irma.)

Leopold represents a stricter medical view point.  Freud described the real Leopold as a "slow but sure" doctor (1900, p. 112). In the dream, it was Leopold who percussed Irma saying, "`She has a dull area low down on the left'" and who indicated "`that a portion of the skin on the left shoulder was infiltrated [infected].'" In other words, a "slow but sure" part of Freud was wondering if the problem in Irma's shoulder (that is, in his shoulder) was tuberculosis.

In those days it was known that tubercular patients should not smoke. On January 18, 1884, Freud wrote to his future wife, Minna Bernays, regarding a box of cigars she had sent him: "Schönberg [a tubercular friend of Freud], much as I like him, won't get one [of the cigars], my reason being that he shouldn't smoke. But the truth is: I give nothing away that comes from you" (Freud, 1960, p. 91). This letter shows Freud would never have allowed a tubercular patient to smoke. If the Leopold line of thought in him, the "slow and steady" approach to the problem, prevailed, the patient (that is, he, himself) could not smoke.

The waking Freud, however, did not take Leopold's diagnosis seriously but recognized in the infiltrated shoulder the rheumatism in his own shoulder "which I invariably notice if I sit up late into the night" (1900, p. 113) as, presumably, he had been doing the night of the Irma dream. I would argue that even this rheumatism might have been aggravated by smoking. Films and photos of Freud, albeit from a later period, indicate that he held his cigars primarily in his left hand, usually between the second and third fingers.6 It is all but obvious that when he wrote and smoked he held his pen in his right hand and his cigar in his left.7 My guess is that, on the night of July 23, 1895, Freud was up late writing and smoking. He smoked with his left hand, perhaps one or two, maybe even three cigars. It may seem far-fetched to someone who has never smoked, but I think holding cigars up to the mouth throughout an evening could have aggravated (and even caused) a shoulder pain.

The dirty syringe

We must now examine the conclusion of the dream in which all the doctors — Dr. M., Otto, Leopold, and Freud himself — suddenly dropped their previous theories and became "directly aware ... of the origin of the infection." They saw that the cause was an injection from a dirty syringe given to Irma by Otto.  The needle contained "a preparation of propyl, propyls...propionic acid ...trimethylamin," and Freud saw the formula for trimethylamine (English spelling) "printed in heavy type."

We must take this very seriously, because it represents, not abstract theory, but a direct medical intuition on the part of Freud, the collaboration of all the views in him--psychological and medical — representing his deepest and perhaps most correct understanding of the cause of dream Irma's problems.

Freud gave his associations to the "preparation of propyl...propyls...propionic acid" (1900, pp. 115-16):  The evening before, his wife had opened a bottle of liqueur given to them by Otto, a friend described as having "a habit of making presents on every possible occasion." Freud added that he hoped that Otto "would some day ... find a wife to cure him of the habit." He went on to say that the liqueur gave off such a strong smell of fusel oil that he refused to touch it, and he identified this smell with that of amyl-alcohol, the fifth in the homologous series of aliphatic alcohols beginning with methyl-, ethyl-, propyl-, butyl-, and amyl-alcohol. Hence the propyl of the dream (with propyl replacing amyl — the kind of substitution common in dreams) (p. 116). Historically, propyl alcohol (propanol, n-propyl alcohol) was discovered in crude fusel oil by Chancel in 1853, three years before Freud was born, and it is possible that Freud was confusing amyl with propyl in his memory.

Turning to trimethylamine, in the dream the formula had been printed in heavy type "as though there had been a desire to lay emphasis on some part of the context as being of quite special importance" (p. 116). To trimethylamine Freud associated Fliess's view that it was a product of sexual metabolism. This fit the dream, since Freud thought the cure for Irma's problem was sexual intercourse (Irma was a widow). Trimethylamine also led to thoughts of his friendship with Fliess who had physical problems of his own (pp. 116-17).

However, there is another possible interpretation of the dirty syringe. It is difficult to think of a better metaphor for a cigar than a dirty syringe that can inject strong smelling chemicals capable of causing pains, stomach problems, and white patches in the mouth. This reading suggests the possibility that Otto, who gave presents "on every possible occasion," had given Freud a gift of cigars, and, that on the night of the Irma dream, Freud had been smoking these cigars. In dream language: Otto had injected Irma (Freud) with a strong smelling preparation. On this reading, the dream's conclusions could hardly be more appropriate: "Injections of that sort ought not to be made so thoughtlessly...probably the syringe had not been clean."

Otto — Dr. Oskar Rie

In real life Otto was Oskar Rie, a younger colleague of Freud who became a close personal friend and remained so until Rie's death in September, 1931. In the late 1890's, Rie was the Freud family pediatrician. For years, Rie, Freud, and two other friends played a card game called taroc every Saturday night.

As one might expect, I have not been able to establish whether or not Dr. Rie gave Freud a present of cigars sometime before the Irma dream. For example, I can find nothing in Freud's letters about such a matter. But it can be established that Rie smoked at the Saturday night card games. His grandson, Henry Rie recalls that

my father had a cigar cutter (a device for cutting a small hole in the closed end of a cigar) which had belonged to our grandfather. I remember hearing that Oskar Rie smoked cigars at the weekly card games at Freud's ... I [do not] know whether he smoked cigars on any other occasions. (a response to an inquiry by me to his cousin, Dr. Anton Kris, conveyed to me by Dr. Kris)

Therefore, Rie probably would not have been an adamant anti-smoker.

Coming at the gift issue from another angle, on May 10, 1923, two and a half weeks following his first cancer surgery, Freud wrote a letter to Lou Andreas-Salomé describing his recuperation: "I can again speak, chew and work, indeed even smoking is permitted — to a certain moderate ... degree. The family doctor himself supplied the cigar holder for my birthday" (Freud, 1960, p. 343).

Who was this family doctor who supplied the cigar holder? Romm (1983, p. xii) says Felix Deutsch to whom Freud showed this first tumor, but Schur, who was very close to Freud from 1928 on, contradicts this. Concerning the time period of the first operation, Schur wrote, "At that time [just before Freud showed the tumor to Felix Deutsch] ... Freud had no physician whom he consulted regularly. His friend Otto [sic] Rie, his family pediatrician, was his trusted advisor" (Schur, 1972, p. 348).

We know that Rie was the children's doctor in the late 1890's, and Schur tells us here that Rie remained Freud's "trusted advisor" even in 1923. Therefore, it would have been natural for Freud to have slipped into referring to Rie as his "family physician" in his 1923 letter to Lou Andreas-Salomé. The idea that Rie was the family doctor who gave Freud the cigar holder in 1923 following surgery for oral cancer is consistent with the image of the doctor who injected Irma with a dirty syringe and who may have given Freud a box of cigars somewhere before July 23, 1895, in spite of Freud's attempts to abstain.

However, the idea that Rie gave Freud cigars in 1895 is contradicted by a letter Rie wrote Fliess on June 12 of that year reporting that Freud was smoking again (Schur, 1972, p. 86).  It will be remembered that Freud also wrote Fliess on this date admitting he was smoking again. If Rie was assisting Fliess to keep Freud from smoking, then it could have been Freud's irritation at Rie (as described in the preamble to the Irma dream [1900, p. 106]) that converted Rie into the negligent figure appearing in the dream.

"Propyl, Propyls...Propionic Acid...Trimethylamin"

If the dirty syringe was a cigar, how do propyls, propionic acid, and trimethylamine fit in? In fact, all of these are chemicals found in tobacco smoke. Propionic acid is a rancid smelling oil that was identified in cigar smoke in 1871 (Johnstone; Plimmer, 1959) and has also been isolated in tobacco leaf (Stedman, 1968).

Tobacco contains many agents with the propyl moiety as well (the dream speaks of propyls). Propyl alcohol, which was found in fusel oil in 1853, was identified in cigar smoke in 1961 (Berry, 1961). 1-Methyl-4-isopropyl-1-cyclohexene; 6,8-Dihydroxy-11-isopropyl-4,8-dimethyl-14-oxo-4,9-pentadecadienoic acid; 5-keto-2-isopropylhexanoic acids; Dipropyl phthalate; Isopropyl formate, and 2-methyl-5-isopropylacetophenone are some of the components with the propyl rest in tobacco leaf and/or smoke (my italics, Stedman, 1968).

As for trimethylamine, in Freud's day it was known to be in tobacco smoke and was incorrectly thought, along with other volatile amines, to cause the aroma of the smoke. The volatile trimethylamine has a pungent, fishy odor and contributes to the "off flavor" of cigar smoke (Schmeltz; Hoffmann, 1977).

In the late 1800's very few compounds had been isolated from tobacco.  By 1959, with the growing interest in tobacco carcinogenesis, four hundred had been found in the leaf and in the smoke.  By 1968, over twelve hundred chemicals had been identified (Stedman, 1968), and, by 1988, over three thousand had been reported to be present in tobacco and about four thousand in tobacco smoke (Roberts, 1988).

Whether or not it is a coincidence that propyls, propionic acid, and trimethylamine all occur in tobacco, I leave open.

Trimethylamine

In 1873, Albert Cottard published a book called De la Valeur de Triméthylamine dans le Traitement du Rhumatisme Articulaire in which he gave case studies to prove that trimethylamine was a cure for rheumatism of the joints.

Cottard mentioned various fishes, including herring and sturgeon, in which trimethylamine had been found.8 He wrote that Russian doctors were prescribing the eating of herring milt or whole herrings soaked in milk or caviar or the like for chronic catarrh and for the beginning of tuberculization of the lungs, among other things (p. 17). He wrote that it was the trimethylamine in cod-liver oil that led, Kaleniczenko, to report "l'action bienfaisante" of that oil (p. 18).

It is possible that Freud, who lived in France in the mid-1880's, knew of this cure and even entertained the idea of using some form of trimethylamine for his catarrh and for the pains in his left shoulder that he diagnosed as rheumatism (it could not have been pure trimethylamine, since trimethylamine is a gas at room temperature).

Cottard's book points to the high reputation enjoyed by trimethylamine at the end of the nineteenth century and makes its dream portrait as a poison stand out even more clearly. In fact, the emphatic nature of the dream makes it almost necessary for us to inquire further into the possible toxicity of the preparation. If the white patch and curly structures in Irma's mouth point to Freud's future cancer, then the dream is stating that the cancer came from a preparation of propyls, propionic acid, and trimethylamine (presumably from a cigar). Generalizing, and putting it into contemporary terms, Freud's dream theorizes that the preparation of propyls, propionic acid, and trimethylamine in cigar smoke is carcinogenic.

Though there is no way, in practice, for us to find out what caused Freud's tumor, we are entitled to ask if it could possibly have been the trimethylamine from one of his cigars. Though trimethylamine is not considered to be a carcinogen, when mixed with nitrites in an acidic environment, it can be nitrosated into a very powerful procarcinogen, dimethylnitrosamine (DMNA) (N-nitrosdimethylamine).

This suggests two questions. First, could cigar trimethylamine nitrosate in the mouth of a cigar smoker? And, second, if so, could the resulting dimethylnitrosamine cause oral cancer? Based on the latest research, the answer would seem to be "Yes" to both questions, though these specific hypotheses have not been tested.9

In Appendix 2, I explore, in more detail, a possible pathway from cigar trimethylamine to Freud's cancer as "proposed" by the Irma dream. Appendix 2, combined with Appendix 3, constitutes speculation on the type of biochemical pathways that might have led from smoking a cigar to the Irma dream.

How could Freud's dream have implicated trimethylamine?

It is likely that Freud knew of the theory that smoking caused oral cancer. In 1761, the London physician, Dr. John Hill, had connected the use of snuff with oral cancer (Redmond, 1970), and, in a book published in Frankfurt/Main, Germany, in 1795, Sömmering had proposed that pipe smoking could cause carcinomas of the lip (Wynder & Hoffmann, 1964). Though the view was not as widely accepted in medical circles as it is now, it had its advocates.  Further, in his own medical training, Freud must have seen cigar smokers with leukoplakia and oral cancers.

It would also have been natural for him to have identified trimethylamine with cigar tobacco, given that, as we said, in his day, it was correlated with the aroma of cigars. In his dream, Freud could have connected unpleasant oral sensations with cigar smoke trimethylamine and concluded, in images, that leukoplakia might follow. Not only did the Irma dream contain a picture of Freud's future cancer, but it also contained a reasonable theory of its etiology.

4. Did Freud's Cancer Provoke his Irma Dream?

4. Did Freud's Cancer Provoke his Irma Dream?

Hypothesis

Hypothesis

Before returning to Freud's case, I will state the general theory to be discussed in this section. The hypothesis is that disease states produce aberrant chemicals that can provoke dreams. To use cancer as our example, the hypothesis is that some tumors produce chemicals that can provoke dreams. If true, these dreams can be thought of as "psychological" tumor markers and might conceivably be used in diagnosing diseases (also see Smith, 1990). (A tumor marker is a chemical associated with a developing tumor. Many researchers have been trying to identify tumor markers to aid in early diagnosis.)

Most cancer researchers today think that carcinogenesis is a multi-stage process.  The view is that tumor development can be divided into at least three stages. Initiation consists of a single, datable, and irreversible event apparently consisting of a mutation in one key gene in one single cell (Solt, 1980). This initiated cell may sit dormant for years, or even decades, until a promoter stimulates it to divide repeatedly. The result is a visible growth of millions of cells each bearing a copy of the original mutated gene. Progression occurs when one of these cells acquires a second growth-promoting mutation that allows for uncontrolled growth into a carcinoma (Varmus & Weinberg, 1993).

At some point in the development of a tumor, often only surprisingly late, a person becomes conscious of discomfort. It may be that before this there is a dream recognition of a problem. Future research can tell if such dream recognition occurs, and, if so, at which stage of tumor development. For the sake of argument and for the sake of simplicity, let us assume that an initiated cell can provoke a dream and try to imagine how. The reader will please remember that this discussion is hypothetical and theoretical.

It seems to me that, if a tumor cell can provoke a dream, either it would be through a paracrine action (on neighboring cells) or an endocrine action (on far away sites) or through a combination of both. In the first case, via a paracrine effect, there might be a secretion or excretion or shedding of a cellular product capable of stimulating a neighboring nerve ending which would then relay information into the brain. In the second case, via an endocrine effect, one or more products of the cell (or metabolites of these products) would travel in the blood, through the blood-brain barrier, and directly stimulate a brain neuron. In the third case, there might be both paracrine and endocrine effects bringing a large assortment of information into the brain such as exactly where the cellular events were occurring, just what substances were being produced, how much was being produced, and for how long. All this information would merge with information from short-term memory (day residues), long-term memory (including repressed material), and archetypal-genetic memory (helping to determine which images would be used), as well as with phosphenes and other data to form dream experiences such as: Woman, Right Upper Mouth, White Patch, Growth, Choking.

At some stage in the development of a tumor — possibly just after initiation, definitely during progression, and, obviously, at least somewhere in between — the immune system will respond to the substances produced by the cells. Cells of the immune system that arrive on the scene will secrete modulating substances that may effect the brain. (Study of the effects of these substances on the brain is just beginning, more focus up until now having been placed on the effect of the brain on the immune system.10) If the immune system contributes to the formation of some "cancer dreams," then these dreams must be considered part of the body's immune response to a cancer and not just epiphenomenal by-products of the cancer.

In Appendix 3, I list substances produced by oral cancers (and the immune response to them) and try to imagine how they might, in accordance with the hypothesis of this section, lead to dreams.

How might this hypothesis apply to Freud's case. The idea would be that a tumor or premalignant lesion (presumably caused by chemicals in cigar smoke) was in Freud's mouth in July, 1895 and provoked the Irma dream.

In 1895, Freud might have had a premalignant leukoplakia in his mouth that he felt with his tongue and that led to the Irma dream (a possibility expressed by Dr. George Bernard of the UCLA School of Dentistry, personal communication). It is even possible that Freud's oral cancer was initiated by cigar smoke some time before the Irma dream and that the substances produced by the initiated cell caused the dream. Promotion and progression would have occurred some years later, with the tumor becoming palpable and visible only in 1923. (Presumably, initiation represents an earlier stage of tumor development than leukoplakia).

And it is even conceivable that initiation occurred on the night of July 23 or the morning of July 24, perhaps moments before the Irma dream. In this case the dream would have contained Freud's vague perception of the beginning of his cancer, his subjective awareness of its initiation. This would certainly explain why the dream exercised such a fascination on him and why he felt a compulsion to analyze just this dream. Of course there is no way to prove or disprove this thesis.

A biological function of dreams in fighting diseases?

A biological function of dreams in fighting diseases?

To help conceptualize the theorized place of dreams in the flow of experience, I will divide the flow into an afferent and an efferent arm. Using Freud's dream as an example, we might arbitrarily say that the afferent arm began with the manufacturing of trimethylamine in a tobacco plant in Cuba. It continued with the leaves being picked and processed, rolled and packaged, and then shipped to Vienna. When Freud smoked one of the cigars, trimethylamine (or more likely the tobacco alkaloids) entered his mouth and was nitrosated to DMNA (or to carcinogenic, tobacco-specific N-nitrosamines [TSNA]) whose metabolites penetrated the tissue in the oral mucosa, entered a nucleus of a cell, and alkylated DNA (see Appendix 2). This cell then began to produce abnormal products or normal products in abnormal amounts. Some of these products (or products of the immune cells that "noticed" them) stimulated peripheral and central neurons (see Appendix 3). So much for the afferent arm. Next came the dream. And then, following the dream, the efferent arm began, which consisted of outgoing responses on many levels: Molecular, electrical, behavioral, and the like.

Let us call the afferent arm A, the efferent arm B, and the brain state associated with the dream, DB. The temporal sequence is A-DB-B. And let us call the phenomenological experience of the dream, DE. Even if DE is only an epiphenomenon of DB, it is still a psychological tumor marker, since it is an indirect product of the tumor. The question arises, is there any biological function of DE? DB is a biological state that leads to a whole series of biological states in the efferent arm of the process. DE, however, is an experience that would seem to be outside the biological sequence A-DB-B. For example, it is not an antigen to which an antibody might respond. It might seem, therefore, that DE could not have a biological function.

However, if we keep focused on a strictly phenomenological-behavioral level and do not slip into the biological point of view, it is quite clear that DE, the dream experience, can have just as much a subjective push to action as pain or fear. The Irma dream, for example, at the very least, stimulated Freud to self-analysis. Shortly after the dream, Freud began work on The Interpretation of Dreams which he described as "a portion of my own self-analysis" (1900, p. xxvi). The intense struggle to understand his own dreams may even have prolonged his life. Perhaps he smoked just a few less cigars or puffed just a little less on those he smoked or aimed the smoke into his mouth in a slightly less noxious direction. Even if he did not consciously understand the Irma dream as a biological response, it may have functioned like a "No Smoking" sign placed into the dream by an oral mucosa demanding more temperate and careful smoking. (Cf., the sign in one of Freud's dreams that reminded him of notices "forbidding one to smoke in railway waiting-rooms" [1900, p. 317]. Jung actually gave up smoking because of a dream [in March, 1953, Jung, 1975]. For traumatic dreams as warnings see Smith [1990]).

It is possible that, in a thousand years, Freud may be remembered, not for any specific aspect of his psychoanalytical theory, but as the first ambitious European intellectual to take his dreams seriously.

Discussion

DISCUSSION: POSSIBLE RESEARCH STUDIES

Historical anecdotes

I would like to propose that an all-out, scientific investigation be launched into the relation between dreams and disease states (assuming, of course, that pilot studies prove the subject fruitful). The promise is a cost-free, non-invasive form of diagnosis (with brain as diagnostic "machine"). The justification are anecdotal reports from antiquity to modern times (e.g., the two cases where Jung diagnosed illnesses from dreams of patients referred to him for that purpose by their physicians, [Davie, 1935; Jung, 1954]).

We are designing an exploratory study to see if there might be a possibility.

A definitive research project in this area would take people who feel healthy and who test healthy in their medical checkups and see if their dreams predict what illnesses they will develop. Studies of this type would require large numbers of subjects and would have to be longitudinal. They would be extremely expensive.

An intermediate stage of research would be to work with people who know they are sick but where the diagnosis is still unruse. We are proposing a study in which dreams will be collected from people entering head and neck clinics with suspicious, but still undiagnosed, lesions. It will be seen if the dreams can be used to differentially diagnose malignant from benign tumors.11 Other such studies might easily be imagined (e.g., one in which the dreams of people exposed to a particular virus are examined).

If simple studies like these, with their obvious conceptual and methodological complexities, produce results, long-term studies on larger populations might be attempted.

Some complexities of such research

Not all dreams predict illnesses, and probably not all illnesses produce dreams. The situation is quite complex. A dream registering a minuscule event inside the body would be like the human eye picking up a supernova in the vast regions of space: Everything would have to happen just right — the event would have to be large enough and emit enough perceptible data, at just the right time and in just the right direction. For a body event "B" to register in a dream, not only would it have to emit (or stimulate the emission of) one or more psychoactive substances, but these substances (or their effects) would have to arrive in the brain at just the right moment. Unless the brain could store them in memory, they would have to arrive just before, or during, a dream (during REM sleep). If they missed this opening, they would go unrecognized. On the other hand, if they came too often, adaptation might occur with neurons ceasing to respond. Here, though there might be a few relevant dreams, if the dreamer was unable to recall them, the opportunity for diagnosis would be lost.

It also might be that some parts of the body are more able to produce dream markers than others. Areas like the mouth (where there is rich sensory innervation and a copious blood supply) may be the areas best able to translate their problems into dreams (for example, the Irma dream).

But even if a body event registered itself in a dream, for a dream analyst to recognize the connection would be extremely difficult. It would be similar to the problem of recognizing the connection between movies and historical events. No doubt, WWII stimulated films that contained images of the war. But when did films begin to "pick up" the pre-war situation, and when could someone have figured out from a movie that there was going to be a war? Looking back at 1930's films, we might agree on some as definite pre-war films. But who, at that time, could have known and by what criteria? And how can we know what today's films tell of our future even though there probably are connections that future generations will see clearly when they look back?

We are in a similar position with dreams. It is easy to hold Freud's dreams and his later illnesses in front of us and compare them and find similarities. It is an immensely more difficult job to look at present dreams of apparently healthy people and say what developing illnesses they may be recording. Therefore, it has been easier for researchers studying connections between dreams and illnesses to select people with given illnesses (like asthma) and then study their dreams — a review of many such studies can be found in Warnes & Finkelstein (1971). As far as I know, there are no studies going the other direction, that is, starting with dreams and trying to diagnose illnesses. So far, this direction has only produced anecdotes.

The main difficulty in studying dreams as perceptions of objective events is the great variation in how a physical event can appear for different dreamers and for the same dreamer at different times. Sleep lab experiments, designed to reveal effects of external stimuli on dreams, show that stimuli often appear symbolically and in a manner dependent on the background and symbolic style of the dreamer — for a review of the literature see Arkin & Antrobus (1991).

To give an example available to everyone, just before waking from sleep because of a full bladder, it is common to dream, but it seems impossible to predict what the dream will be. Rarely will the person think of having to urinate. The dream will be of running down a hill next to a stream or of a man drinking a cup of skim milk with ice cubes in it or of a sea battle or of a car leaking gasoline or of a stranger urinating or of wearing a tight belt causing pressure in the lower abdomen or there may be no dream at all. (For psychoanalytic interpretations of such dreams, see Freud, 1900, pp. 402ff.)

Not only can the same stimulus apparently produce different images, but the same image can represent different stimuli, even in the same dream.  If the dirty syringe stood for a cigar, it also reminded Freud of needles he used to give injections, and who knows what other layers of more symbolic meaning it may have had?

To hint at the subtleties and complexities of the problem, we might imagine a large toy store just before Christmas in which some of the toys have been sold.  At opening hour, hundreds of children come in. Among them are those who bought the toys and are coming to pick them up. Though we know that some incoming children have bought toys, how can this help us with specifics? If we pick a toy and wonder which, if any, of the hundreds of children have come to pick it up, how can we answer? Equally, if we pick a child walking into the store, how can we know which toy, if any, he or she is coming to pick up?

Similarly with dreams and illnesses: Even assuming we know that some images are connected to some illnesses, how can this help us in specific cases? If a person wakes with a dream image, how can he or she know what, if any, physical state led to it? Or, if we think of a particular illness, how can we predict what dream images, if any, it might provoke?

Moving on in spite of the complexities

In spite of these immense difficulties, I will present five generalizations from my own clinical experiences with dreams. I present them to open the discussion and stimulate debate, and not to add to the list of dream books dating back to antiquity:

1) Discomfort in a dream is identical with discomfort the dreamer will experience when he or she awakens. (Not all waking discomfort, though, appears in dreams.)

2) It does not matter who in the dream feels the discomfort (the dreamer or another dream figure — animal or human): It is always the dreamer's discomfort.

3) Wherever in the body the discomfort is experienced by the dream figure, that is where the discomfort will be felt by the dreamer when he or she awakens.

4) The discomfort in a dream tends to be more severe than the discomfort the dreamer experiences when he or she awakens. (This is Aristotle's idea.)

5) Which subjective feeling of severity — dream or waking — more accurately reflects the objective, physical danger to the dreamer, varies from dream to dream: Sometimes the dream exaggerates the problem, but sometimes waking consciousness underestimates it.

Here are four examples where these rules apply: A man dreams of being shot in the stomach by the Mafia and wakes with indigestion; a man dreams of a lion biting a bull on the back of the neck until it is dead and wakes with a headache at the base of his skull; a woman dreams of an airplane crash where some passengers are decapitated and awakens with a head cold. And the Irma dream seems to fit the rules.

Concluding thoughts

I conclude by repeating that I think dreams may have many meanings, and so I do not think that the Irma dream was only a representation of a physical state nor do I think that dream analysts ought focus only on physical states underlying dreams. I do feel though that, given our present state of limited knowledge, it is always appropriate to scan dreams for possible underlying physical states. And I will add on behalf of my interpretation, that if it had been accepted by Freud (alongside his own), it could possibly have headed off much suffering for him and those who loved him.

Appendix 1

APPENDIX 1

Dream of July 23-24, 1895

A large hall — numerous guests, whom we were receiving.— Among them was Irma. I at once took her on one side, as though to answer her letter and to reproach her for not having accepted my `solution' yet. I said to her: `If you still get pains, it's really only your fault.' She replied: `If you only knew what pains I've got now in my throat and stomach and abdomen — it's choking me' — I was alarmed and looked at her. She looked pale and puffy. I thought to myself that after all I must be missing some organic trouble. I took her to the window and looked down her throat, and she showed signs of recalcitrance, like women with artificial dentures. I thought to myself that there was really no need for her to do that. — She then opened her mouth properly and on the right I found a big white patch; at another place I saw extensive whitish grey scabs upon some remarkable curly structures which were evidently modelled on the turbinal bones of the nose. — I at once called in Dr. M., and he repeated the examination and confirmed it....Dr. M. looked quite different from usual; he was very pale, he walked with a limp and his chin was clean-shaven....My friend Otto was now standing beside her as well, and my friend Leopold was percussing her through her bodice and saying: `She has a dull area low down on the left.' He also indicated that a portion of the skin on the left shoulder was infiltrated. (I noticed this, just as he did, in spite of her dress.)...M. said: `There's no doubt it's an infection, but no matter; dysentery will supervene and the toxin will be eliminated.'...We were directly aware, too, of the origin of the infection. Not long before, when she was feeling unwell, my friend Otto had given her an injection of a preparation of propyl, propyls...propionic acid...trimethylamin (and I saw before me the formula for this printed in heavy type)....Injections of that sort ought not to be made so thoughtlessly....And probably the syringe had not been clean. (ellipsis points in text, Freud, 1900, p. 107)

Appendix 2

APPENDIX 2

Could DMNA, applied to the oral mucosa, cause tumors?

Since its discovery as an hepatocarcinogen in 1956, dimethylnitrosamine (DMNA) has been associated primarily with liver tumors.  Researchers, trying to understand its metabolic pathways, have generally administered it to animals orally or by injection. It is not surprising, therefore that, when Pool-Zobel et al. (1992) administered DMNA in vapor form, via inhalation, and found that nasal tumors developed, they described these results as "exceptional."

Dimethylnitrosamine is a member of the class of chemicals called N-nitrosamines. N-nitrosamines that exist only in tobacco and tobacco smoke are called tobacco-specific N-nitrosamines (TSNA). Hecht et al. (1986) were able to induce tumors of the oral cavity in eight of thirty rats by swabbing the mouth with two TSNA. Studies such as these have convinced researchers that TSNA can cause oral cancers in users of some smokeless tobaccos (e.g., Hoffmann et al., 1991).

DMNA also exists in tobacco smoke (as does a propyl rest, N-Nitrosodi-n-propylamine, Hoffmann & Wynder, 1986), and it seems reasonable to propose that it too might induce oral tumors, though this has never been studied.

Will trimethylamine nitrosate turn to DMNA in the mouth of a cigar smoker?

Since we are constructing a possible pathway (I emphasize possible) to Freud's cancer based on his Irma dream, the other relevant hypothesis is that trimethylamine will nitrosate to DMNA in the mouth of a cigar smoker as do the tobacco alkaloids.

Lijinsky et al. (1972) found that trimethylamine converts at an optimum range of pH 3-6 but will proceed even at pH 6.4.  This fits the pH of saliva, which, according to Rao (1978), varies between 4.5 and 7, depending on many factors in the mouth.

According to Dietrich Hoffmann, an expert in the field of tobacco carcinogenesis (personal communication), trimethylamine is water soluble and hence soluble in saliva; cigar smoke is particularly rich in the nitrous oxides, more so than cigarette smoke, and so the cigar smoker would have plenty of nitrous oxide for nitrosation; cigar smokers tend to have thiocyanate in their saliva, a chemical that is known to catalyze the nitrosation process; and, finally, saliva is acid enough to allow the reaction to take place.

I must add that another expert, John Wishnok of M.I.T. (personal communication), thought that the reaction would not proceed rapidly enough to take place in the mouth, and that DMNA would not produce oral tumors. However, it has been shown that the TSNA can be formed in the oral cavity by nitrosation of the alkaloids (Tsuda, 1991).

I have no intention of trying to design a study that would answer these questions definitively. If someone ever did, however, I would be curious to see if the adding of propionic acid and a component with a propyl rest (as "suggested" in the Irma dream) would have an effect.

Possible mechanisms for tumor carcinogenesis from DMNA

It seems that DMNA and TSNA do not produce tumors directly but break down into intermediate products that cause the tumors. Bartsch & Montesano (1984) have described studies showing that DMNA is metabolized into such products in the buccal mucosa (as has also been shown for TSNA [Murphy et al., 1990]). The exact mechanism by which intermediate products cause cancer remains unknown, though many accept that it is often via alkylation of cellular DNA (e.g., Elespuru et al., 1993). An alternative mutation site is cellular RNA which may have a greater propensity for alkylation by DMNA than DNA (discussed by Hradec, 1989).

A possible pathway to Freud's tumor, based on the Irma dream, might run as follows: Trimethylamine from a cigar was nitrosated in his mouth to DMNA which was then metabolized into intermediate products that, in turn, alkylated DNA or RNA in one or more epithelial cells in the right, upper oral mucosa of Freud's mouth.

Appendix 3

APPENDIX 3

The goal of this section is to show, hypothetically, how an illness might provoke a dream. To narrow the discussion I focus on cancers, in particular, on oral cancers and precancers. Ideally I would like to focus on Freud's case where, apparently, there was a verrucous carcinoma that originated on the right glossopalatine arch (Schavelzon, 1983; Romm, 1983). Unfortunately, there is little research on verrucous carcinomas and not that much is known about the biochemistry of oral cancers in general, especially at their very early stages.  Therefore, I am forced to include studies on all types and stages of head and neck lesions.

The normal oral mucosa

The following is a simplified version of the histology of the normal oral mucosa of the soft palate (taken from Ten Cate, 1989, Chapter 18). (The soft palate and glossoplatine arch are histologically similar).

Looking at soft palate tissue from the top, down we have: First, the submucosa containing blood vessels and nerves; second, the lamina propria consisting of a supportive matrix made of collagen and other substances such as laminin; third, a basement membrane separating the submucosa and the lamina propria from the oral epithelium; and fourth, the stratified squamous epithelium arranged into a layer of well-ordered squamous epithelial cells called the basal layer on which are layers of cells, the outermost ones of which get sloughed off. New cells continually form from the basal cells and migrate out (down). Basal cells themselves are apparently produced by stem cells in the basal layer.

The lamina propria contains cells of the immune system such as macrophages and mast cells (capable of secreting histamine, leukotrienes, serotonin, etc.) and other inflammatory cells which tend to arrive on the spot when needed.

Capillary networks of the oral mucosa reach to just before the basal epithelial cells coming down from larger vessels in the submucosa above and are much more profuse than in the skin. There are no blood vessels in the epithelium itself.

There is dense sensory innervation of the oral mucosa from the lesser palatine branch of the maxillary branch of the trigeminal nerve, the tonsillar branch of the glossopharyngeal nerve, and the nerve of the pterygoid canal. This area is one of the most sensitive in the body, ranking a little below the fingertips.

There are free nerve endings in the lamina propria and in the epithelium. There are also many specialized nerve endings in the lamina propria including Meissner's corpuscles, Ruffini's corpuscles, bulbs of Krause, and mucocutaneous end organs. And there are some taste buds in the epithelium of the soft palate. Warmth, cold, touch, pain, and taste are the primary sensations experienced in the mouth. Touch receptors in the area are involved with the swallowing, gagging, and retching reflexes.

Oral carcinomas

Precancerous and cancerous lesions are distinguished microscopically by abnormal divisions, variations in cell and nuclear sizes and shapes, disturbed polarity of basal cells, loss or reduction of cellular cohesion, and cell crowding, among other things (Kramer, 1980).

Presumably, one day researchers will be able to account for these abnormalities by pointing to changes in cellular molecules, changes that begin at the stage of initiation. We might imagine a stem cell on the basal membrane of the oral mucosa with a gene that has just been mutated by a carcinogen. This gene would soon encode an abnormal protein or its normal protein in an abnormal amount. Depending on which gene was mutated, the cell's structure might begin to break down, and its attachments to other cells and to the basal membrane might become disrupted in various ways. This cell may begin to wobble and to travel and to lose orientation with respect to its neighbors, and it may begin to secrete or shed products that will be received by other cells and that will affect them in various ways. Some of the products may diffuse through the basal membrane and into the lamina propria and even into the capillaries. Some that are moved to the membrane surface or placed in the extracellular environment may encounter cells of the immune system surveillance "team" which, in turn, will mobilize an immune response.

This is not science fiction. Just such cellular products have been found in oral cancer cells, though it is not yet possible to determine which products are produced at which stages. Unfortunately for the sake of diagnosis, none of these substances has been found to be specific for head and neck tumors, and no one substance occurs in all head and neck tumors. Substances produced by oral lesions

I group these substances into eight overlapping classes. Most of them have been found to be overexpressed in head and neck malignant and/or premalignant lesions. I do not include all substances found, and, in some cases, there are conflicting studies. Since we are engaged in an exercise in imagination, there is no need for completeness.

1) Factors contributing to cell structure and cell attachment: The intermediate cytoplasmic filaments keratin and vimentin (de Araujo et al., 1993); filaggrin (Scully & Burkhardt, 1993); the integrin α6β4 (Van Waes & Carey, 1992); sialic acid (Xing et al. 1991); gangliosides (Ruoslahti, 1991); carcinoembryonic antigen (CEA) (a glycoprotein) (Kurokawa et al., 1993); urokinase-type plasminogen activator (Clayman et al., 1993); and, since the tumor suppressor gene, p53, has been found to be mutated in oral cancers (references in Scully, 1992), and since this gene seems to effect expression of the DCC gene, we may guess that, in some tumors, there is an abnormal expression of the DCC protein, a NCAM-like adhesion molecule (Varmus & Weinberg, 1993).

2) Factors that may, in different ways, lead to increased cell division: Products of the mutated p53 gene; products of the mutated Ha-ras, Ki-ras, N-ras genes (references in Scully, 1992); products of the mutated c-erbB-1 gene (Maran et al., 1993) and c-erbB-2 (neu) gene (Hou et al., 1992) both via production of faulty receptor proteins; proliferating cell nuclear antigen (PCNA) that is necessary for replication of nuclear DNA (Coltrera et al., 1992).

3) Secreted growth factors:  Proteins of the fibroblast growth factor family that are encoded by the mutated gene, int-2, (references in Scully, 1992); transforming growth

factor-β (TGF-β) (Maran et al., 1993).

4) Membrane carbohydrates detectable by antibodies from the immune system: Aberrant histo-blood group antigens including incomplete antigens of the ABO, Lewis, TTn, and P blood group systems (under- or overexpression, Bryne et al., 1991); antigen H, a precursor of A and B (under- or overexpression, Bryne et al., 1991); (most cells in verrucous carcinomas express antigens in a way similar to cells in normal adjacent mucosa [Bryne et al., 1991]).

5) Factors shed by tumor cells that modulate the immune response: Gangliosides (Chu & Sharom, 1993); TGF-β (as a cytokine); leukotriene B4 (el-Hakim et al., 1990).

6) The immune system's direct responses to the tumor: Serum IgA; higher levels of CD4 ("helper") cells (Maran et al., 1993); HLA class I and II antigens (in verrucous carcinomas, Mattijssen et al., 1991); beta 2-microglobulin (Manzar et al., 1992)

7) Products of immune cells that modulate the immune response: Interleukin-2 (secreted by Th cells) that promotes gamma-interferon production; prostaglandins (Maran et al., 1993).

8) Products whose functions are unclear or difficult to place in one of the above categories: Products of the mutated c-myc and N-myc genes (references in Scully, 1992); products of the mutated bcl-1 gene (Scully, 1992); gamma-glutamyl transpeptidase (Schwint et al., 1992); glutathione-S-transferase-pi (Hirata et al., 1992); the transferrin receptor (Tanaka et al., 1991).

Possible pathways from initiated cells to dreams using the Irma dream as our example

With the above list in hand, it is time to speculate on possible connections between cancer cells and dreams.  I continue to use Freud's case for this exercise in imagination.

1)  It is theoretically possible that an initiated cell could have shed a chemical that could have stimulated a neighboring nerve ending (say a twig from the lesser palatine nerve). The signal would then have been transmitted, through the foramen rotundum, to the pontine trigeminal nucleus where the primary neuron would have synapsed with secondary neurons. Axons of these secondary sensory neurons would have relayed impulses to the sensory cortex (that is, to the postcentral gyrus of the parietal cortex) and deposited them there in their proper somatotrophic position in relation to other sensory input. In some cases, the firing of one neuron in the mouth can be consciously experienced, and this may have been the case with Freud. The sensation would then have been mixed with other data and a dream would have occurred. On the other hand, the firing might have been below the normal threshold but somehow capable of being experienced in a dream. (I have not been able to locate any theory attempting to explain pathways for subliminal perception. This subject is very complex conceptually).

TGF-β and the product of the int-2 gene are both known to stimulate neural growth. One may wonder if they will be shown to create action potentials as well. It is also possible that other chemicals (such as G-proteins or Substance P), that are already known to create action potentials, will one day be shown to be produced in abnormal amounts by cancer cells and excreted into their environment. These are all testable hypotheses.

 2) Smoke (its heat or its chemicals) or tumor chemicals could have stimulated touch, temperature, pain, and olfactory receptors and/or taste buds in Freud's mouth and might have led to the symptoms of choking and pain appearing in the Irma dream. Leukotrienes and prostaglandins are found in some oral tumors and are known to sensitize nociceptors. Possibly one or both of these chemicals contributed to the dream.

3) At a stage in tumor development when cell proliferation had already begun, increased pressure from crowded cells could have activated sensory mechanoreceptors that led to bodily sensations that, in turn, became included in the dream. This might have occurred before Freud ever focused on these bodily sensations in waking consciousness.

4) Prostaglandins and interleukin-2 are both known to effect the brain and can induce somnolence. It has also been theorized that systemic cytokines, like interleukin-2, can reach the central nervous system where the blood-brain barrier is absent and possibly where it is made more permeable by a pathological condition (references in Nisticò & De Sarro, 1991). It would be interesting to study the effects of these substances on dreaming.

We might guess that oral tumors produce other substances that can be active in, and transportable to, the central nervous system (perhaps chemicals not quite as virulent as the anti-Purkinje cell antibodies produced by tumors from other parts of the body). It is even possible that some tumor substances can induce REM sleep (the sleep in which most dreams seem to occur) as well as determine the content of dreams.

5) Once one starts thinking about how dreams might come from physical states, there is no end to the number of ideas that arise. Those sketched out in this section are only a few that come to mind. They happen to be testable, but others may not be. For example, what if the dream state is a rudimentary stage in the development of consciousness? One may wonder if evolution is not moving towards making creatures that are more and more conscious, not only of the external world, but also of inner events. The initiation of a tumor is a small event from one angle, but a very important event from the point of view of the individual (and, perhaps, the species). Perhaps, in a million years, people will know immediately and directly that a tumor has been initiated, as clearly as we now know when we stub a toe. Perhaps receptors and ligands are evolving at this very moment towards this end. And, perhaps, a million years after that, it will be only necessary to think certain thoughts and the initiated cell will dissolve. Perhaps events on this continuum happen even now, occasionally and in certain people. Perhaps Freud was one such person.

References

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End Notes

End Notes

1.The identity of the real "Irma" has been debated and discussed in many articles since Schur (1966) first suggested that she was a patient of Freud named Emma Ecstein.

2.For a history of Freud's illnesses and treatments see Schur (1972), Romm (1983), or Schavelzon (1983).

3.Pictures of the turbinate bones of the nose (the nasal conchas) can be found in any standard anatomy text. An artist's rendition of what Freud's initial cancer may have looked like can be found in Romm (1983, p.19, Fig.7).

4.This seems to be at least part of the view expressed by Schavelzon (1983, p.79).

No creo que el inconsciente "sepa" de una enfermedad 24 años antes de que se manifieste, aunque sí que a menudo guía nuestros actos de un modo que puede dar pie a esa suposición. Cabe agregar que para el inconsciente no existe el factor tiempo, de modo que "24 años antes" no es un dato invalidante. [I do not think that the unconscious knows about a sickness 24 years before it is manifested. Even so it does often guide our actions in a way that may encourage that supposition. It can be added that, for the unconscious, the time factor does not exist. So, "24 years before" is not an invalid datum.]

(I thank Errick Clarke and Alicia Amador for this translation; similar views are expressed by Resnik, 1987, p.188)

5.This explanation was suggested to me by my wife who was concerned with my own cigar and pipe smoking at the time.  My struggle with cigar smoking helps explain my fascination with the Irma dream.

6.Photos in which Freud held a cigar in his left hand can be found in E. Freud et al. (1976, pp.179 [c.1906], 201 [c.1912], 212 [1917], 223 [1920], 200 [1922], 236 [1925], 250 [1929]) and Freud (1992, pp.120 [1909], 118 [c.1932]; 141 [probably from the 1930's], 160 [probably from the 1930's], 164 [probably from 1933]). Photos in which he held a cigar in his right hand can be found in E. Freud (1976, pp.222 [c.1921], 296 [probably 1938]). Film taken in 1928 by the analyst Phillip R. Lehrman show Freud holding his cigar sometimes in one hand and sometimes in the other.

7.Freud wrote a letter from the house of his Hungarian host and hostess, Anton and Rozsi von Freund, describing how he arranged his desk for writing.

"I have simplified the writing table considerably. The picture of our hostess and little girl remains standing in the middle, on the right a bowl of fountain pens, on the left another filled with cigars." (dated August 9, 1918, Freud, 1960, p.322)

8.In humans, trimethylamine is formed, in part, from the breaking down (metabolizing) of dietary choline (which comes from lecithin, a major component of animal fat) by bacteria in the intestine, and it is excreted in the urine. Trimethylaminuria, a fish-odor syndrome, occurs in humans when trimethylamine is not broken down properly.

9.Today it is believed that it is primarily the nitrosamines from nicotine and nornicotine that are associated with the increased risk of smokers developing oral cancer, especially if they also drink alcohol (U.S. Department of Health and Human Services, 1989; Hoffmann et al., 1991).

10.In the 1950's and early 1960's, the Soviet Academy of Sciences directed medical researchers from Korea to East Germany to prove that the nervous system,(especially the cerebral cortex as the "highest" human organ), must direct the process of carcinogenesis. There are hundreds of articles on this research in "Eastern Bloc."

11.Assuming that one pathway between diseases and dreams begins in the peripheral nervous system, it is useful to begin with lesions of the mouth because of the high innervation of the oral cavity.