Box Jellyfish Venom Under The Microscope
Good news all round. Scientists are getting closer to discovering an antidote to toxic box jellyfish venom and their hungry laboratory mice were given carte blanche to "chow" down "ad libitum".
According to a 2019 study published in nature.com (Nature Communications), these very well-fed mice feasted then made the ultimate sacrifice in the name of a "molecular dissection of a jellyfish venom-induced cell death pathway by screening for host components required for venom exposure-induced cell death using genome-scale lenti-CRISPR mutagenesis".
Yes. This was a serious scientific study at a microscopic molecular level that makes for challenging reading if you prefer BuzzFeed to Biochemistry.
Put simply, science is exploring the make-up of box jellyfish venom so it can isolate and manipulate its deadly components.
The study, published as "Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote", was undertaken in Australia on Chironex fleckeri species and is the first of its kind to identify "the genomic characterisation of the venom death pathway" so as to develop new theories that "directly target pain and local tissue necrosis".
Cytotoxicity with box jellyfish refers to the cell-killing ability of the venom that can lead rapidly to excruciating pain and death. However, death by box jellyfish is not explored here as the scientists focused on what is considered the more common outcome of a sting - intense pain and the annihilation of cells.
The CRISPR (bacterial clustered regularly interspaced short palindromic repeats) system is an approach used to identify genes in cancer research and in this case it provided "molecular insights ... that identified a new box jellyfish venom antidote that can suppress tissue destruction and attenuate the excruciating pain associated with envenoming".
How they went about "identifying hundreds of host candidate genes and pathways critical for venom action" makes for fascinating, if not heavy reading.
The upshot is that cholesterol and sphingomyelin (major components of the blood plasma membrane structure) have been identified as prime targets of box jellyfish venom and that reducing these ultimately blocks cytotoxicity. The pharmacological approach to depleting cholesterol and sphingomyelin is by using methyl-β-cyclodextrin (MβCD) or 2-hydroxypropyl-β-cyclodextrins (HPβCD) compounds as a treatment.
Voila!
But wait, there's more. It was also found that the venom forces its way into living cells leading to lysosomal cell death, or the destruction of vital organelles within a cell. The drug Chloroquine often associated with malaria treatment blocks lysosomal functionality and effectively protects the cells.
As the study points out, "C. fleckeri venom-induced cell death occurs through multiple mechanisms" and that "essential genes and cellular pathways involved in the jellyfish venom mechanisms of triggering cell death" have been identified. The result is the discovery of "venom antidotes capable of suppressing pain and tissue destruction".
The venom that acts with lightening-fast speed to kill a human is also likely according to this study to lead to new medicines. The fight against our biggest killers and chronic pain needs all the help it can get and an unlikely ally is the box jellyfish. It is expected that DNA identification of certain other venom components will in time make a significant contribution towards developing cancer, heart disease and pain relief drugs.
The search continues for an antidote to the mysterious cardiac arrest capabilities of the venom that puts the heart in an irreversible paralysed state of contraction rapidly resulting in a box jellyfish induced death.
However, hopefully soon, somewhere along the line, the ground-breaking work of these scientists (and the heroics of these martyred mice!) translates and transforms into practical, easily-obtainable, affordable solutions to preventing pain and suffering from a box jellyfish sting.
In the meantime, make a mouse happy and wear a full-length stinger suit when in seas known to be home to box jellyfish and you're guaranteed not to need an antidote.
Read the Nature Communications citation:
Further Reading:
diagrams from "Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote" publication in Nature Research.
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