When they first encounter our collection, I think a lot of visitors wonder, at least transiently, about who these people were. I guess this reaction is most likely when looking at the bits we associate strongly with the self, like a heart or an intact brain, and less likely when viewing, say, a pancreas or gall bladder.
For the sake of confidentiality, our specimens are anonymised and any obvious identifiers are removed from their history. Still, a few personal details may slip into the records, giving just a hint about the life and more often the death, of the person in the bottle. This is what a UCT fine arts student, Juliet Forsyth, was looking for when she compiled “Exposing individuality”.
“I went searching for shreds of humanity that were captured amongst the clinical data which I then linked to the specific specimen kept at the Centre.”
Such detail turned out to be incredibly scarce, and a hunt through the records of approximately 3500 catalogued and uncatalogued specimens in the general pathology section turned up only 10 that Juliet felt were informative. “I attached (the) sentences which hint at the personality or life of the individual to the organ that remains, so that their life may be remembered when looking at these very detached objects.”
She transposed the text onto the specimen bottles, and one comes across these particular bottles unexpectedly among all the others. Some examples are shown in the slides below:
Another artist working in the genre of “art meets science”, Karen Ingram, has had a similar instinct with regards to the Hunterian museum. Hunter seems to have documented quite a bit about his patients, and since they died over 200 years ago, the need for confidentiality has arguably lapsed.
Ingram’s short film “narrative remains” translates the records into imagined commentary from the patients themselves, so reviving what is known of their histories.
I’d never heard of a hibernoma until I came across this specimen in our collection. The distinct dark tan nodule at top is a phaeochromocytoma, but the flabby grey lobulated mass that makes up the bulk of the specimen is a hibernoma.
And yes, hibernoma derives from hibernation.
A hibernoma is a benign tumour composed of the same heat-generating fat or brown adipose tissue (BAT) found abundantly in hibernating mammals. Since we are mammals, it’s not too surprising that humans have (BAT). It’s well known that BAT is important in newborns (who are very susceptible to cold), but at one time it was thought that BAT disappeared by adulthood. But brown fat depots in adults can be visualised on positron emission tomography (PET) scans in the same areas as it occurs in neonates, and especially if the person was in a chilly environment when the scan was done!
Hibernation is a state of inactivity and metabolic depression in endotherms. Hibernation (n.)1660s, from Latin hibernationem “the action of passing the winter”. [Image credit: Alex Martin]Sites of brown adipose tissue in adult humans, as revealed by PET scanning. [Image credit: Professor Jan Nedergaard, The Wenner-Gren Institute,The Arrhenius Labs, Stockholm University]Brown vs. White, and Brite:
BAT appears brown due to the iron content of its many mitochondria. At a microscopic level brown fat differs from white fat in appearance, and unlike white fat has a rich vascular and nerve supply. Brown and white fat have a different histogenesis or cellular origin (see the origins of BAT). The latest finding is that adults have classical or constitutive BAT as well as an inducible “brite” (brown in white) form of BAT interspersed in ordinary white fat.
Microscopy of a hibernoma showing the multivacuolated brown fat cells. The name “hibernoma” was coined by Louis Gery of the Institute of Anatomy at Strasbourg in 1914. [Image credit: Nephron]Phaeochromocytomas and hibernomas are both fairly rare, and their co-occurrence in a significant number of cases is not co-incidence. Phaeochromocytomas are tumours of adrenal gland neuroendocrine cells, usually producing high levels of nor-adrenaline, and nor-adrenaline stimulates thermogenesis. It seems probable that extreme and chronic thermogenic stimulus from a phaeochromocytoma leads to BAT cellular proliferation, giving rise to a hibernoma, often adjacent to the phaeo. In support of this theory is the confirmation that the BAT in hibernomas is metabolically active.
This is all very interesting, but currently the real excitement is around BAT being potentially manipulable for the control of diabetes, obesity and the metabolic syndrome. Weight loss is a prominent symptom in patients with phaeochromocytoma, and the stimulation of BAT may account for a good deal of it. BAT consumes more glucose than any other tissue and even small amounts substantially raise the metabolic rate. BAT can be switched off by a beta-adrenergic blocker (the sort commonly used to lower blood pressure).
I’ve studiously avoided the biochemistry of thermogenesis in BAT, which underlies this whole discussion, but it hinges on the unique uncoupling protein 1 (UCP1), also known as thermogenin, which operates in BAT mitochondria to divert the production of cellular energy (ATP) into the release of heat. Being able to switch on BAT is an enticing idea, and activating UCP1 is probably the key to such a designer drug.
References / readings
Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2007; 293(2):E444-52
Osborne AB, Johnson MH. Hibernoma, a special fatty tumor; report of a case. Am J Pathol 1949; 25(3):467-79
Nedergaard J, Cannon B. The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab 2010; 11(4):268-72
Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. Int J Obes 1986; 10(3):219-27.
English JT, Patel SK, Flanagan MJ. Association of pheochromocytomas with brown fat tumors. Radiology 1973; 107:2 279-281.
Vijgen GH, Bouvy ND, Smidt M et al. Hibernoma with metabolic impact? BMJ Case Reports 2012 Aug 21.
For our opening post I’ve homed in on some specimens that are interesting because of their place in medical history, specifically the history of xenotransplantation.
After his exceedingly well known first human heart transplant in 1967, Dr Chris Barnard continued experimenting. The rationale for the “piggy-back heart transplant” or heterotopic cardiac transplant is clear from this excerpt:
“In 1973, Barnard performed a heart transplant and the donor heart failed to function satisfactorily, so the patient died in the operating theatre. When Barnard came out to break the sad news, he was asked why he could not put the old heart back, as at least it had kept the patient alive. This struck Barnard as a distinct possibility. If the patient’s own heart had been left in place, and the transplant was inserted as an auxiliary pump, failure of the donor heart may not have caused the patient’s demise. Furthermore, during severe rejection episodes, which were common in those early days and a major cause of the poor results at the time, the native (i.e. patient’s own) heart might be able to maintain the circulation while rejection was reversed by increased therapy.”1
One thing led to another:
“On two occasions in 1977, when a patient’s left ventricle failed acutely after routine open-heart surgery and when no human donor organ was available, Barnard transplanted an animal heart heterotopically. On the first occasion, a baboon heart was transplanted, but this failed to support the circulation sufficiently, the patient dying some six hours after transplantation. In the second patient, a chimpanzee heart successfully maintained life until irreversible rejection occurred four days later, the recipient’s native heart having failed to recover during this period. Further attempts at xenotransplantation were abandoned and even now, more than 30 years later, xenotransplantation remains an elusive holy grail despite decades of research.”1
These are those two ragged-looking but seminal xenotransplants, preserved in the UCT pathology teaching collection:
Barnard’s own report of these two cases makes fascinating reading2.
In a similar vein, and from a similar time, this liver specimen dated 1968 is from a patient who suffered severe (sub)acute liver failure and went into coma. The catalogue description reads: “The liver is seen to be markedly reduced in size (885g), with the bulk of the surviving regenerated liver present as a large mass in the right lobe with occasional smaller nodules present elsewhere; the left lobe is shrunken, and slightly congested.”
But what is notable about this case is that a baboon liver perfusion had been performed, though unfortunately without response. The objective would have been to try to tide the patient over the acute liver failure, giving their own liver a chance to regenerate enough to resume functioning – analogous to the use of transient renal dialysis in acute kidney failure.
Between 1964 and 1970, one hundred and thirteen patients who had received extracorporeal liver perfusion or ECLP were reported (this case not among them). By 2000 the number reported was 270. Pig livers were most often used, but on review, baboon or human livers gave better long term survival (≈40% vs. ≈20%). But during this period the overall survival of acute liver failure patients receiving ECLP was no better than that of patients receiving conventional intensive care (≈25% for both)3. Today, artificial and bioartificial liver support can be part of the intensive care for acute liver failure, often as a bridge to liver transplantation, the optimal treatment. ELCP using whole human livers (not suitable for transplant) or transgenic pig livers is still an option for temporary liver support in this context, despite the technical challenges and concerns about the risk of transmission of infectious agents4.
The availability of non-human primates for medical research is now far more limited than it was in the second half of the 20th century from when these cases date, but aside from non-human primates, other animals appear to remain “fair game” in the modern field of xenotransplantation.
![Sites of brown adipose tissue in adult humans, as revealed by PET scanning. [Image credit: Professor Jan Nedergaard, The Wenner-Gren Institute,The Arrhenius Labs, Stockholm University]](http://digipathblog.files.wordpress.com/2013/06/brown-fat-distribution-nedergaard-e1370609910305.jpg)
