These tapeworms spontaneously transformed into a cancer inside their victim
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By John Hewitt
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.
E1KHFK Artwork of an intestinal tapeworm.
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.
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