Make no mistake about it, we’re in the midst of a socio-scientific revolution that aims to reclassify the once-feared parasitic tapeworm into a mere mutualistic symbiont. Anyone doubting this need look no further than the recent hype surrounding efforts to get FDA approval to use these helminths as treatments, much as live maggots or leeches can be medicinally prescribed today. For migraines, the recommended dose is just a trifling 30 worms per month, while for more serious bowel issues, up to 2,500 may be par for the course.
But there are persistent warnings that tapeworms are not creatures anyone should be messing around with. The latest report, a study just posted in the New England Journal of Medicine, pertains to a subspecies that infects over 75 million worldwide — Hymenolpis Nana. The authors reveal that in a patient whose immune system has been severely compromised (in this case by a lengthy bout with AIDS), tapeworms can transmogrify into a bona fide cancer.
To be clear, many parasites have previously been shown to cause host tissues to transform into cancer. For example, eating raw freshwater fish can sometimes transfer a species of tapeworm known as O. viverrini, which can then colonize the human bile duct and gall bladder. Chronic infection over the course of years can lead to liver cancer or cholangiocarcinoma. Some of the exuberant tapeworm love that we hope to caution against can be traced to the unexpected finding that this same species secretes a useful growth factor that boosts blood vessel development. Most dramatically, this effect can greatly speed the healing of chronic wounds.
In contrast to a standard host tumor made out of host cells, what we have here in this latest saga is that the cells of the tapeworm itself are transforming into a cancer. The authors were tipped off to this seemingly outrageous possibility by the fact that the cells in the patient’s apparent ‘lung cancer’ were much too small to be typical human cells. They then proved the tapeworm origins of the tumor cells by sequencing select indicator genes whose base pair and amino acid sequence both remain fairly stable over time.
How did the tapeworm actually become cancerous?
That’s still a bit of a mystery. However, we can suggest one theory based on a few observations the authors made about the tapeworm mitochondria. In particular, they unexpectedly found that a mitochondrial protein of the tapeworm cells in the patient’s lung tumor harbored certain peculiar mutations. Of note, there were three insertions of extra nucleotide basis in a highly conserved domain of the gene that codes for a critical component of the mitochondrial respiratory chain. This component is known as CO1, for cytochrome oxidase 1, which is the workhorse subunit of the final enzyme complex in mitochondrial electron transport.
Although most of the original proto-mitochondrial genes expressed in any higher organism are gradually transferred over to the nucleus for long term storage, all card-carrying mitochondria maintain control over a small handful of pet proteins and RNAs. There are at least three good reasons why this is so: 1) Mitochondria can quickly respond to local changes in energy demand by upregulating the key players; 2) The few retained proteins are just about as hydrophobic and as membrane-loving as a protein can get, and therefore transferring them to the nucleus would likely make it extremely hard to eventually re-target the product back to the mitochondria where it is utilized; and 3) The secondary assembly of mitochondrial RNAs into ribosomes is tightly linked to their expression, and critically depends on their close sequential reading.
We shouldn’t underestimate the power of these recent postulates to explain the ever-vexing questions not just of how, but why an endosymbiont is retained by the host cell, and ultimately worked into an efficient protein-generating organelle. While this tapeworm mitochondrial mutation business may sound fairly complex, one way to boil it all down is to say that at some point in the life history of the tumor-founding tapeworm, the respiratory functioning of at least one its mitochondrial lineages was compromised. Ultimately, these three deleterious mutational events may have caused the cells to go rogue.
The latest cancer research suggests that what often causes tumor cells that are otherwise proliferating locally, to then become invasive, is actually the functional recovery of the previously ailing mitochindria. In some more typically human lung cancers, this kind of mitochondrial rescue has been shown to be mediated by donation and/or recombination of mitochondria from neighboring human cells.
The further possibility that there are similar cross-species mitochondrial games going on between the human and worm cells is something that would need to be tested. However, one way the mitochondria could readily be introduced to each other in this fashion would be through cell fusion. Fusion is known to occasionally occur when different kinds of cells are induced to take up shack together in the same body. Typically this is seen in transplants, pregnancy, or certain stem cell studies. The idea that human and worm cells may have been temporarily fused is not only still on the table, but it could potentially explain some of the strange transformations that have just been seen.
As we indicated in the beginning, to go so far as to say that helminths are good for you, as many now do, may be premature. For example, worm justice warriors frequently point to studies showing that helminths in pregnant rats protect their newborns from brain inflammation, or reduce the severity of various immune conditions. However, when you look closer at many of these studies, the results are far from convincing. Typically, the alleged benefit is only found in these kinds of ‘softer’, highly-derived maladies, and typically only across a some kind of generational gap.
Lamenting the perceived loss of our own microbial diversity, often under the general rubric of what has been alarmingly called ‘biome depletion’, is perhaps also of questionable value. ‘Rebooting’ your gut microbriome by transplanting various potent concoctions may be fashionable, but probably not as beneficial as the gut mavens might imagine. If tapeworms still sound appetizing to you, we want to refer you to a few recent stories about what can happen when they get into your brain.
One particularly ghoulish headliner appeared yesterday about a guy in Napa valley who showed up in the ER with a massive headache. Reportedly, after realizing that tapeworms were blocking the proper drainage of his CSF (brain fluid), the attendings told him he had just 30 minutes to live. Fortunately, they were able to drill a hole above his eye and pluck the still wiggling monsters out of his brain.
Even more astounding, we might recall the story of the Chinese man from Britain who gave us an incredible sequence of MRI images. They revealed a particularly motile tapeworm giving itself a self-guided tour of his cerebrum. As the worm traversed some of the more hallowed parts of the man’s inner sactum, its tail tickled different neurons into action, treating him to all manner of hallucinatory smells and inexplicable sensations. While thrills like that may be worth the risk to some, for many the potential rewards of tapeworm co-habitation will never exceed its pitfalls.