The Homunculus Inside

Jan27

Paracelsus‘ homunculus, the result of complicated alchemic recipes, is an allegorical figure that fascinated the collective uncoscious for centuries. Its fortune soon surpassed the field of alchemy, and the homunculus was borrowed by literature (Goethe, to quote but one example), psychology (Jung wrote about it), cinema (take the wonderful, ironic Pretorius scene from The Bride of Frankenstein, 1935), and the world of illustration (I’m thinking in particular of Stefano Bessoni). Even today the homunculus hasn’t lost its appeal: the mysterious videos posted by a Russian youtuber, purportedly showing some strange creatures developed through unlikely procedures, scored tens of millions of views.

Yet I will not focus here on the classic, more or less metaphorical homunculus, but rather on the way the word is used in pathology.
Yes beacuse, unbeknownst to you, a rough human figure could be hiding inside your own body.
Welcome to a territory where the grotesque bursts into anatomy.

Let’s take a step back to how life starts.
In the beginning, the fertilized cell (zygote) is but one cell; it immediately starts dividing, generating new cells, which in turn proliferate, transform, migrate. After roughly two weeks, the different cellular populations organize into three main areas (germ layers), each one with its given purpose — every layer is in charge of the formation of a specific kind of structure. These three specialized layers gradually create the various anatomical shapes, building the skin, nerves, bones, organs, apparatuses, and so on. This metamorphosis, this progressive “surfacing” of order ends when the fetus is completely developed.

Sometimes it might happen that this very process, for some reason, gets activated again in adulthood.
It is as if some cells, falling for an unfathomable hallucination, believed they still are at an embryonic stage: therefore they begin weaving new structures, abnormal growths called teratomas, which closely resemble the outcome of the first germ differentiations.

These mad cells start producing hair, bones, teeth, nails, sometimes cerebral or tyroid matter, even whole eyes. Hystologically these tumors, benign in most cases, can appear solid, wrapped inside cystes, or both.

In very rare cases, a teratoma can be so highly differentiated as to take on an antropomorphic shape, albeit rudimentary. These are the so-called fetiform teratomas (homunculus).

Clinical reports of this anomaly really have an uncanny, David Cronenberg quality: one homunculus found in 2003 inside an ovarian teratoma in a 25-year-old virginal woman, showed the presence of brain, spinal chord, ears, teeth, tyroid gland, bone, intestines, trachea, phallic tissue and one eye in the middle of the forehead.
In 2005 another fetiform mass had hairs and arm buds, with fingers and nails. In 2006 a reported homunculus displayed one upper limb and two lower limbs complete with feet and toes. In 2010 another mass presented a foot with fused toes, hair, bones and marrow. In 2015 a 13-year-old patient was found to carry a fetiform teratoma exhibiting hair, vestigial limbs, a rudimentary digestive tube and a cranial formation containing meninxes and neural tissue.

What causes these cells to try and create a new, impossible life? And are we sure that the minuscule, incomplete fetus wasn’t really there from the beginning?
Among the many proposed hypothesis, in fact, there is also the idea that homunculi (difficult to study because of their scarcity in scientific literature) may not be actual tumors, but actually the remnants of a parasitic twin, incapsulated within his sibling’s body during the embryonic phase. If this was the case, they would not qualify as teratomas, falling into the fetus in fetu category.

But the two phenomenons are mainly regarded as separate.
To distinguish one from the other, pathologists rely on the existence of a spinal column (which is present in the fetus in fetu but not in teratomas), on their localization (teratomas are chiefly found near the reproductive area, the fetus in fetu within the retroperitoneal space) and on zygosity (teratomas are often differentiated from the surrounding tissues, as if they were “fraternal twins” in regard to their host, while the fetus in fetu is homozygote).

The study of these anomalous formations might provide valuable information for the understanding of human development and parthenogenesis (essential for the research on stem cells).
But the intriguing aspect is exactly their problematic nature. As I said, each time doctors encounter a homunculus, the issue is always how to categorize it: is it a teratoma or a parasitic twin? A structure that “emerged” later, or a shape which was there from the start?

It is interesting to note that this very uncertainty also has existed in regard to normal embryos for the over 23 centuries. The debate focused on a similar question: do fetuses arise from scratch, or are they preexistent?
This is the ancient dispute between the supporters of epigenesis and preformationism, between those who claimed that embryonic structures formed out of indistinct matter, and those who thought that they were already included in the egg.
Aristotle, while studying chicken embryos, had already speculated that the unborn child’s physical structures acquire solidity little by little, guided by the soul; in the XVIII Century this theory was disputed by preformationism. According to the enthusiasts of this hypothesis (endorsed by high-profile scholars such as Leibniz, Spallanzani and Diderot), the embryo was already perfectly formed inside the egg, ab ovo, only too small to be visible to the naked eye; during development, it would just have to grow in size, as a baby does after birth.
Where did this idea come from? An important part was surely played by a well-known etching by Nicolaas Hartsoeker, who was among the first scientists to observe seminal fluid under the microscope, as well as being a staunch supporter of the existence of minuscule, completely formed fetuses hiding inside the heads of sperm cells.
And Hartsoeker, in turn, had taken inspiration precisely from the famous alchemical depictions of the homunculus.

In a sense, the homunculus appearing in an ancient alchemist’s vial and the ones studied by pathologists nowadays are not that different. They can both be seen as symbols of the enigma of development, of the fundamental mystery surrounding birth and life. Miniature images of the ontological dilemma which has been forever puzzling humanity: do we appear from indistinct chaos, or did our heart and soul exist somewhere, somehow, before we were born?

Little addendum of anatomical pathology (and a bit of genetics)
by Claudia Manini, MD

Teratomas are germ cell tumors composed of an array of tissues derived from two or three embryonic layers (ectoderm, mesoderm, endoderm) in any combination.
The great majority of teratomas are benign cystic tumors mainly located in ovary, containing mature (adult-type) tissues; rarely they contains embryonal tissues (“immature teratomas”) and, if so, they have a higher malignant potential.
The origin of teratomas has been a matter of interest, speculation, and dispute for centuries because of their exotic composition.
The partenogenic theory, which suggests an origin from the primordial germ cell, is now the most widely accepted. The other two theories, one suggesting an origin from blastomeres segregated at an early stage of embryonic development and the second suggesting an origin from embryonal rests have few adherents currently. Support for the germ cell theory has come from anatomic distribution of the tumors, which occurs along the body midline of migration of the primordial germ cell, from the fact that the tumors occur most commonly during the reproductive age (epidemiologic-observational but also experimental data) and from cytogenetic analysis which has demonstrated genotypic differences between omozygous teratomatous tissue and heterozygous host tissue.
The primordial germ cells are the common origins of gametes (spermatozoa and oocyte, that are mature germ cells) which contain a single set of 23 chromosomas (haploid cells). During fertilization two gametes fuse together and originate a new cell which have a dyploid and heterozygous genetic pool (a double set of 23 chromosomas from two different organism).
On the other hand, the cells composing a teratoma show an identical genetic pool between the two sets of chromosomes.
Thus teratomas, even when they unexpectedly give rise to fetiform structures, are a different phenomenon from the fetus in fetu, and they fall within the scope of tumoral and not-malformative pathology.
All this does not lessen the impact of the observation, and a certain awe in considering the differentiation potential of one single germ cell.

References
Kurman JR et al., Blaustein’s pathology of the female genital tract, Springer 2011
Prat J., Pathology of the ovary, Saunders 2004

A precariously balanced wonder

Nov11

An interview with a pathologist

Some days ago I was contacted by a pathologist who recently discovered Bizzarro Bazar, and said she was particularly impressed by the website’s “lack of morbidity”. I could not help but seize the opportunity of chatting a bit about her wonderful profession: here is what she told me about the different aspects of this not so well-known job, which is all about studying deformity, dissimilarities and death to understand what keeps us alive.

What led you to become a pathologist?

When I was sixteen I decided I had to understand disease and death.
The pathologist’s work is very articulated and varied, and mostly executed on living persons… or at least on surgically removed parts of living persons; but undoubtedly one of the routine activities is the autoptical diagnosis, and this is exactly one of the reasons behind my choice, I won’t deny it. Becoming a pathologist was the best way to draw on my passion for anatomy, turning it into a profession, and what’s more I would also have the opportunity of exorcising my fear of death by getting accustomed to it… getting my hands dirty and looking at it up close. I wanted to understand and investigate how people die. Maybe part of it had to do with my visual inclination, and pathology is a morphologic discipline which requires sharp visual memory and attention to macro and microscopic details, to differences in shape, to nuances in color.

Is there some kind of common prejudice against your job? How did you explain your “vocation” to friends and relatives?

Actually the general public is not precisely aware of what the pathologist does, hence a certain morbid curiosity on the part of non-experts. Most of them think of Kay Scarpetta, from Cornwell’s novels, or CSI. When people asked me about my job, at the beginning of my career, I gave detailed explanations of all the non-macabre aspects of my work, namely the importance of an hystological diagnosis in oncology, in order to plan the correct treatment. I did this to avoid a certain kind of curiosity, but I was met with puzzled looks. To cut it short, I would then admit: “I also perform autopsies”, and eventually there was a spark of interest in their eyes. I never felt misjudged, but I sometimes noticed some sort of uneasiness. And maybe some slightly sexist prejudice (the unasked question being how can a normal girl be into this kind of things); those female sexy pathologists you find in novels and TV series were not fashionable yet, and at the postgraduate school I was the only woman. As for friends and relatives… well, my parents never got in the way with my choices… I believe they still haven’t exactly figured out exactly what I do, and if I try to tell them they ask me to spare them the details! As for my teenage kids, who are intrigued by my job, I try to draw their attention to the scientific aspects. In the medical environment there is still this idea of a pathologist being some kind of nerd genius, or a person who is totally hopeless in human interactions, and therefore seeks shelter in a specialization that is not directly centered on doctor-patient relationship. Which is not necessarily true anymore, by the way, as often pathologists perform biopsies, and therefore interact with the patient.

Are autopsies still important today?

Let’s clarify: in Italy, the anatomopatologo is not a forensic pathologist, but is closer to what would be known in America as a surgical pathologist. The autopsy the pathologist performs is on people who died in a hospital (and not on the deceased who fell from a height or committed suicide, for instance) to answer to a very specific clinical inquiry, while the legal autopsy is carried out by the legal MD on behalf of the DA’s office.
One would think that, with the development of imaging radiology tests, the autoptic exam would have by now become outdated. In some facilities they perform the so-called “virtual autopsy” through CAT scans. In reality, in those cases in which a diagnosis could not be determined during the deceased’s life, an autopsy is still the only exam capable of clarifying the final cause of death. Besides direct examination, it allows to take organ samples to be studied under the microscope with conventional coloring or to be submitted for more refined tests, such as molecular biology. In the forensic field, direct examination of the body allows us to gather information on the chronology, environment and modality of death, all details no other exam could provide.

There is of course a great difference (both on a methodological and emotional level) between macroscopic and microscopic post mortem analysis. In your experience, for scientific purposes, is one of the two phases more relevant than the other or are they both equally essential?

They are both essential, and tightly connected to each other: one cannot do without the other. The visual investigation guides the following optic microscopy exam, because the pathologist samples a specific area of tissue, and not another, to be submitted to the lab on the grounds of his visual perception of dissimilarity.

In my experience of autopsy rooms, albeit limited, I have noticed some defense strategies being used to cope with the most tragic aspects of medical investigation. On one hand a certain humor, though never disrespectful; and, on the other, little precautions aimed at preserving the dignity of the body (but which may also have the function of pushing away the idea that an autopsy is an act of violation). How did you get used to the roughest side of your job?

I witnessed my first autopsy during my first year in medical school, and I still remember every detail of it even today, 30 years later. I nearly fainted. However, once I got over the first impact, I learned to focus on single anatomical details, as if I were a surgeon in the operating room, proceeding with great caution, avoiding useless cuts, always keeping in mind that I’m not working on a corpse, but a person. With his own history, his loved ones, presumably with somebody outside that room who is now crying for the loss. One thing I always do, after the external exam and before I begin to cut, is cover up the face of the dead person. Perhaps with the illogical intent of preventing him to see what I’m about to do… and maybe to avoid the unpleasant feeling of being watched.

Are there subjects that are more difficult to work with, on the emotional level?

Children.

Are autopsies, as a general rule, open to a non-academic public in Italy? Would you recommend witnessing an autopsy?

No, all forensic autopsies are not accessible, for obvious reasons, since there is often a trial underway; neither are the diagnostic post mortem examinations in hospitals. I wouldn’t know whether to recommend seeing an autopsy to anyone. But I do believe every biology or medicine student should be allowed in.

One of the aspects that always fascinated me about pathological anatomy museums is the vitality of disease, the exuberant creativity with which forms can change: the pathological body is fluid, free, forgetful of those boundaries we think are fixed and insurmountable. You just need to glance at some bone tumors, which look like strange mineral sponges, to see the disease as a terrible blooming force.
Maybe this feeling of wonder before a Nature both so beautiful and deadly, was the one animating the first anatomists: a sort of secret respect for the disease they were fighting off, not much different from the hunter’s reverential fear as he studies his prey before the massacre. Have you ever experienced this sense of the sublime? Does the apparent paradox of the passionate anatomist (how can one be a disease enthusiast?) have something to do with this admiration?

To get passionate, in our case, means to feel inclined towards a certain field, a certain way of doing research, a certain method and approach which links a morphologic phenomenon to a functional phenomenon. We do not love disease, we love a discipline which teaches us to see (Domine, ut videam) in order to understand the disease. And, hopefully, cure it.
And yes, of course there is the everyday experience of the sublime, the aesthetic experience, the awe at shapes and colors, and the information they convey. If we know how to interpret it.

Speaking of the vitality of disease: today we recognize in some teratologic specimens a proof of the attempts through which evolution gropes around, one failed experiment after the other. How many of these maladies (literally, “being not apt”) are actually the exact opposite, an adaptation attempt? Is any example of mutation (which a different genetic drift might have elected to dominant phenotype) always pathological?
What I really mean to ask is, of course, another one of those questions that any pathological anatomy museum inevitably suggests: what are the actual boundaries of the Norm?

The norm is established on a statistical basis following a Gaussian distribution curve, but what falls beyond the 90th percentile (or before the 10th) is not forcibly unnatural, or unhealthy, or sick. It is just statistically less represented in the general population in respect to the phenotype we are examining. Whether a statistically infrequent character will be an advantage only time will tell.
The limits of the norm are therefore conventionally established on a mathematical basis. What is outside of the norm is just more uncommon. Biology undergoes constant transformation (on the account of new medicines or therapies, climatic and environmental change, great migrations…), and therefore we are always confronted with new specimens coming in. That is why our job is always evolving, too.

I didn’t expect such a technical answer… mine was really a “loaded” question. As you know, for years I have been working on the concepts of dissimilarity, exoticism and diversity, and I wanted to provoke you – to see whether from your standpoint a mutant body could also be considered as a somewhat revolutionary space, a disruptive element in a context demanding total compliance to the Norm.

Ask a loaded question… and you’ll get a convenient answer. You’re talking about a culture demanding compliance to a social norm, I replied in terms of the biology demanding compliance to a norm that is established by the scientific community on a frequency-based statistic calculation — which is therefore still conventional. In reality, deformity appears in unexpected ways, and should be more correctly described following a probabilistic logic, and not frequency. But I’m beginning to sound technical again.

I have seen respected professors lighten up like children before some pathological wet specimens. The feeling I had was that the medical gaze in some ways justified an interest for extreme visions, usually precluded to the general public. Is it an exclusively scientific interest? Is it possible to be passionate about this kind of work, without being somehow fascinated by the bizarre?

There could be a little self-satisfaction at times. But in general there is sincere passion and enthusiasm for the topic, and that surely cannot be faked. It is a job you can only do if you love it.
All our discipline is based on the differential diagnosis between “normal” and “pathological”. I could say that everything pathological is dysmorphic in respect to the norm, therefore it is bizarre, different. So yes, you have to feel a the fascination for the bizarre. And be very curious.

The passion for the macabre is a growing trend, especially among young people, and it is usually deemed negative or cheap, and strongly opposed by Italian academics. This does not happen in other realities (not just the US, but also the UK for instance) in which a common element of communication strategies for museums has become the ability of arousing curiosity in a vast public, sometimes playing on pop and dark aspects. Come for the macabre, stay for the science. If young people are drawn to the subject via the macabre imaginary, do you think in time this could lead to the education of new, trustworthy professionals?

Yes, it’s true, there is a growing interest, I’m thinking of some famous anatomical exhibitions which attracted so many visitors they had to postpone the closing date. There is also my kids’ favorite TV show about the most absurd ways to die. I believe that all this is really an incentive and should be used as a basis to arouse curiosity on the scientific aspects of these topics. I think that we can and must use this attraction for the macabre to bring people and particularly youngsters closer to science, even more so in these times of neoshamanic drifts and pseudo-scientific rants. Maybe it could also serve the purpose of admitting that death is part of our daily lives, and to find a way to relate to it. As opposed to the Anglo-Saxon countries, in Italy there still is a religious, cultural and legislative background that partially gets in the way (we have laws making it hard to dissect bodies for study, and I also think of the deeply-rooted idea that an autopsy is a violation/desecration of the corpse, up to those prejudices against science and knowledge leading to grotesque actions like the petition to close the Lombroso Museum).

Has your job changed your relationship with death and dying in any way?

I would say it actually changed my relationship with life and living. My worst fear is no longer a fear of dying. I mostly fear pain, and physical or mental decay, with all the limitations they entail. I hope for a very distant, quick and painless death.

With your twenty years experience in the field, can you think of some especially curious anecdotes or episodes you came across?

Many, but I don’t feel comfortable relating episodes that revolve around a person’s remains. But I can tell you that I often do not wonder how these people died, but rather how in the world they could be alive in the first place, given all the diseases I find! And, to me, life looks even more like a precariously balanced wonder.

I fratelli Collyer

Jul7

Langley Collyer

Figli di un ginecologo di prestigio e di una cantante d’opera, i fratelli Collyer, Homer e Langley, sono divenuti nel tempo figure iconiche di New York a causa della loro vita eccentrica e della loro tragica fine: purtroppo la sindrome a cui hanno involontariamente dato il nome non è affatto rara, e pare anzi sia in lenta ma costante crescita soprattutto nelle grandi città.

Nati alla fine dell’ ‘800, fin da ragazzi i due fratelli dimostrano spiccate doti che lasciano prospettare una vita di successo: dall’intelligenza acuta e vispa, si iscrivono entrambi alla Columbia University e guadagnano il diploma – Langley in ingegneria e Homer in diritto nautico. Homer è anche un eccellente pianista e si esibisce al Carnegie Hall, ma abbandona la carriera di musicista abbastanza presto, in seguito alle prime critiche negative. Langley sfrutta le sue conoscenze ingegneristiche per brevettare alcuni marchingegni che però non hanno successo.

Fin dal 1909 i Collyer vivono con i genitori ad Harlem: all’epoca si trattava di un quartiere “in“, a prevalenza bianca, in cui risiedevano molti professionisti altolocati e grossi nomi della finanza e dello spettacolo. Ma nel 1919 il padre Herman abbandona la famiglia e si trasferisce in un’altra casa: morirà quattro anni più tardi. La madre dei due fratelli muore invece nel 1929.

Harlem in quel periodo sta cambiando volto, da zona residenziale sta divenendo un quartiere decisamente malfamato. I fratelli Collyer, rimasti orfani, reagiscono a questo cambiamento facendosi sempre più reclusi, e più eccentrici. Cominciano a collezionare oggetti trovati in giro per le strade, e non gettano più l’immondizia. La loro casa al 2078 della Quinta Avenue si riempie a poco a poco degli utensili più disparati che i Collyer accatastano ovunque: giocattoli, carrozzine deformate, pezzi di violini, corde e cavi elettrici attorcigliati a pile di giornali vecchi di anni, cataste di scatoloni pieni di bicchieri rotti, cassepanche ricolme di lenzuola di ogni genere, fasci di decine di ombrelli, candelabri, pezzi di manichini, 14 pianoforti, un’intera automobile disassemblata e un’infinità di altre cianfrusaglie senza alcun valore.

Come il poeta greco dell’antichità di cui porta il nome, negli anni ’30 Homer diventa cieco. Langley, allora, decide di prendersi cura del fratello, e la vita dei due si fa ancora più misteriosa e appartata. I ragazzini tirano i sassi alle loro finestre, li chiamano “i fratelli fantasma”. Homer resta sempre sepolto in casa, all’interno della fitta rete di cunicoli praticati all’interno della spazzatura che ormai riempie la casa fino al soffitto; Langley esce di rado, per procurarsi le cento arance alla settimana che dà da mangiare al fratello nell’assurda convinzione che serviranno a ridargli la vista. Diviene sempre più ossessionato dall’idea che qualche intruso possa fare irruzione nel loro distorto, sovraffollato universo per distruggere l’intimità che si sono ritagliati: così, da buon ingegnere, costruisce tutta una serie di trappole, più o meno mortali, che dissemina e nasconde nella confusione di oggetti stipati in ogni stanza. Chiunque abbia l’ardire di entrare nel loro mondo la pagherà cara.

Eppure è proprio una di queste trappole, forse troppo bene mimetizzata, che condannerà i due fratelli Collyer. Nel Marzo del 1947, mentre sta portando la cena a Homer, strisciando attraverso un tunnel scavato nella parete di pacchi di giornale, Langley attiva per errore uno dei suoi micidiali trabocchetti: la parete di valigie e vecchie riviste gli crolla addosso, uccidendolo sul colpo. Qualche metro più in là sta seduto Homer, cieco e ormai paralizzato, impotente nell’aiutare il fratello. Morirà di fame e di arresto cardiaco qualche giorno più tardi.

La polizia, allertata da un vicino, fa irruzione nell’appartamento il 21 marzo, 10 ore dopo la morte di Homer. Ma il corpo di Langley, sepolto sotto uno strato di immondizia, non viene trovato subito e gli investigatori attribuiscono l’insopportabile odore all’immensa quantità di immondizia. Viene scatenata una caccia all’uomo nel tentativo di localizzare il fratello mancante, mentre le forze dell’ordine procedono, con estrema cautela per evitare le trappole, a svuotare a poco a poco l’appartamento.

Gli agenti, dopo quasi due settimane di ricerche fra le ben 180 tonnellate di rifiuti accumulati dai Collyer negli anni, trovano Langley l’8 aprile, mentre il cadavere è già preda dei topi.

I fratelli Collyer sono divenuti famosi perché incarnano una realtà tipicamente newyorkese: gli appartamenti sono spesso talmente piccoli, e la gente sedentaria, che il problema dei cosiddetti hoarders, cioè i collezionisti compulsivi di spazzatura, finisce spesso fuori controllo. Ma il fenomeno è tutt’altro che circoscritto alla sola Grande Mela.

Gli hoarders purtroppo esistono ovunque, anche in Italia, come vi racconterà qualsiasi vigile del fuoco. Normalmente si tratta di individui, con un’alta percentuale di anziani, costretti a una vita estremamente solitaria; la sindrome comincia con la difficoltà di liberarsi di ricordi e oggetti cari, ed è spesso acutizzata da timori di tipo finanziario. L’abitudine di “non buttar via nulla” diventa presto, per questi individui, una vera e propria fobia di essere separati dalle loro cose, anche le più inutili. Chi è affetto da questa mania spesso riempie le stanze fino ad impedire le normali funzioni per cui erano originariamente progettate: non si può più cucinare in cucina, dormire in camera da letto, e così via. L’accumulo incontrollato di cianfrusaglie rappresenta ovviamente un pericolo per sé e per gli altri, e rende difficoltose le operazioni di soccorso in caso di incendio o di altro infortunio.

La disposofobia è nota anche come sindrome di Collyer, in ricordo dei due eccentrici fratelli. Sempre in memoria di questa triste e strana storia, nel luogo dove sorgeva la loro casa c’è ora un minuscolo “pocket park”, chiamato Collyer Park.

Ecco la pagina di Wikipedia sulla disposofobia. E in questa pagina trovate una serie di fotografie di appartamenti di persone disposofobiche.