Thread: The most poisonous biological substances known, from plants and microbes.

When challenged recently about the most toxic substance known, I was informed it was ricin. Prior work told me this was not true. It isn't even the most toxic plant substance.

So many people think ricin is the most toxic substance known? It isn't even close. Ricin is poisonous all right, but there are several toxins well above its capacity.

From plants, the most toxic is abrin (1), a product found in the seeds of the jequirity bean (rosary pea) and is a relative of ricin. Its toxicity upon injection into mice is about 30x that of ricin (2). Both are proteins which inhibit ribosomal activity, so this disrupts translation and the production of proteins. A very nasty thing to do.

Abrin likely has a much higher affinity for the ribosome's target which it binds to, in order to disrupt translation, with a binding constant likely at the picomolar level. Its primary purpose is to protect the plant from herbivores.

The medium lethal dose of abrin is variable depending on the target species. For humans (injected IV), the estimated fatal dose is 0.1-1 microgram/kg.

But even abrin yields to botulism toxin, which is also a protein and requires injection for maximum toxicity. It is also believed to be the most poisonous substance known.

Remarkably, Clostridium botulinum, while it is "the source", the gene which codes for this protein is actually from a virus (phage) that infects the microbe. And we think the coronavirus is bad!

Botulinum toxin (3) has been estimated, by some sources, to be lethal when injected into humans at only 1 nanogram/kg. The mechanism behind this remarkable toxicity is proteolysis. The toxin is actually a zinc-dependent enzyme (4), and when it enters nerve cells, it begins to chew up internal membrane proteins, rendering the neurons inoperative. As an enzyme, it doesn't take many molecules in each nerve cell to do its job.

So the catalytic nature of enzymes provide the remarkable effectiveness seen with this toxin. Other toxins typically bind one-to-one with its target. Botulinum toxin can repeatedly destroy multiple targets as it eats its way around the inside of your nerve cells, catalytically "poisoning" those unfortunate enough to be exposed to it. This is one reason why it is so deadly even when eaten. Much of it would be degraded by gut proteases, but if one consumes enough, some will escape destruction (with a protective "coat"), enter the bloodstream, and wreck havoc. No other poison works like this toxin - catalytically destroying vital neurological activities.

Unlike abrin, which protects the plant, the evolution and appearance of Botulinum toxin is unknown, but some have worked on this aspect of such a remarkably effective toxin (5).


1. https://pubmed.ncbi.nlm.nih.gov/15181663/


2. https://en.wikipedia.org/wiki/Abrin


3. https://en.wikipedia.org/wiki/Botulinum_toxin


4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153231/


5. https://pubmed.ncbi.nlm.nih.gov/29684130/



Comparisons with other poisons would be appreciated, as would any data which adds or clarifies the above.

Originally Posted by Double Helix

When challenged recently about the most toxic substance known, I was informed it was ricin. Prior work told me this was not true. It isn't even the most toxic plant substance.

So many people think ricin is the most toxic substance known? It isn't even close. Ricin is poisonous all right, but there are several toxins well above its capacity.

From plants, the most toxic is abrin (1), a product found in the seeds of the jequirity bean (rosary pea) and is a relative of ricin. Its toxicity upon injection into mice is about 30x that of ricin (2). Both are proteins which inhibit ribosomal activity, so this disrupts translation and the production of proteins. A very nasty thing to do.

Abrin likely has a much higher affinity for the ribosome's target which it binds to, in order to disrupt translation, with a binding constant likely at the picomolar level. Its primary purpose is to protect the plant from herbivores.

The medium lethal dose of abrin is variable depending on the target species. For humans (injected IV), the estimated fatal dose is 0.1-1 microgram/kg.

But even abrin yields to botulism toxin, which is also a protein and requires injection for maximum toxicity. It is also believed to be the most poisonous substance known.

Remarkably, Clostridium botulinum, while it is "the source", the gene which codes for this protein is actually from a virus (phage) that infects the microbe. And we think the coronavirus is bad!

Botulinum toxin (3) has been estimated, by some sources, to be lethal when injected into humans at only 1 nanogram/kg. The mechanism behind this remarkable toxicity is proteolysis. The toxin is actually a zinc-dependent enzyme (4), and when it enters nerve cells, it begins to chew up internal membrane proteins, rendering the neurons inoperative. As an enzyme, it doesn't take many molecules in each nerve cell to do its job.

So the catalytic nature of enzymes provide the remarkable effectiveness seen with this toxin. Other toxins typically bind one-to-one with its target. Botulinum toxin can repeatedly destroy multiple targets as it eats its way around the inside of your nerve cells, catalytically "poisoning" those unfortunate enough to be exposed to it. This is one reason why it is so deadly even when eaten. Much of it would be degraded by gut proteases, but if one consumes enough, some will escape destruction (with a protective "coat"), enter the bloodstream, and wreck havoc. No other poison works like this toxin - catalytically destroying vital neurological activities.

Unlike abrin, which protects the plant, the evolution and appearance of Botulinum toxin is unknown, but some have worked on this aspect of such a remarkably effective toxin (5).


1. https://pubmed.ncbi.nlm.nih.gov/15181663/


2. https://en.wikipedia.org/wiki/Abrin


3. https://en.wikipedia.org/wiki/Botulinum_toxin


4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153231/


5. https://pubmed.ncbi.nlm.nih.gov/29684130/



Comparisons with other poisons would be appreciated, as would any data which adds or clarifies the above.

Not my scene.

Maitotoxin is the most toxic known non-protein toxin:

Fabulous space-filling illustration of maitotoxin. Amazingly complex structure. Quoting from (1):

"it is one of the largest and most complex non-protein, non-polysaccharide molecules produced by any organism."

Who can imagine such a thing appearing, and made up by complex enzymatic pathways evolving to produce just this compound? Certainly bizzare.

Maitotoxin appears to be just about as lethal as abrin if the dosing reported elsewhere is accurate (1), at least in mice. It is made by a dinoflagellate, many of which are known to produce nasty compounds. Maitotoxin's mode of action is to enhance the Ca++ channel activity, which causes many system to fail or malfunction, resulting in cell lysis. Very effective toxin.

Appreciate the addition. This substance is no joke, and it, or a related compound from dinoflagellates could be the cause of mass fish kills seen in various parts of the world due to plumes of these surface microbes which release such toxins.


1. https://en.wikipedia.org/wiki/Maitotoxin