IN-DEPTH

 

Question


Posted: 21 Jan 2004 10:10 PST 
Expires: 20 Feb 2004 10:10 PST 
Question ID: 298778 

What is the active ingredient in the arrow poison which the African Bushman                                      make from the grubs of the diamphidia beetle, and what symptoms would it                                       cause in a human? 

Answer

Subject: Re: Chemistry of the San Arrow poison
Answered By: byrd-ga  

http://answers.google.com/answers/ratings?user=71578948671974115                                              on 22 Jan 2004 09:31 PST 
Rated: 

Hello fredht, 

What an interesting question! You’ll be glad to know there are a 
number of studies on the main active ingredient and mechanism of 
action of the arrow poison used by the San people (Bushmen) of 
Southern Africa. As you know, the substance they use is taken from 
the larvae of the diamphidia beetle, and this substance appears to be 
a unique one. I’ll address the two parts of your question separately. 

=======================
ACTIVE INGREDIENT 
=======================

The earliest complete published study on the San arrow poison I was 
able to locate was published in 1983 in “The Journal of Biological 
Chemistry” by Jon de la Harpe, E. Reich, Karl A. Reich, and Eugene B. 
Dowdle. These scientists claim to have isolated the principal toxin, 
a protein, and named it “Diamphotoxin.” 

Furthermore, their paper states their findings that the mechanism of 
action of this toxin is “cardiotoxic and hemolytic” and “blocks 
neuromuscular function.” However, they also clearly say that is 
hypothesis only, and do allow room for further analysis and study.                                                     You may find the full text of their report, here: 
“Diamphotoxin: The arrow poison of the !Kung Bushmen” 
http://www.jbc.org/cgi/reprint/258/19/11924.pdf  Note that this file 
(and some others following) requires Adobe Acrobat Reader in order to 
read. If you don’t have that, you can download a free copy here: 
http://www.adobe.com/products/acrobat/readstep2.html  

So it is no surprise in reading in a later study, “Diamphidia toxin, 
the bushmen's arrow poison: possible mechanism of prey-killing”, by 
Kao CY, Salwen MJ, Hu SL, Pitter HM, Woollard JM, which says they find 
no support for the hypothesis of Diamphotoxin as a neurotoxin, but 
rather postulate that death is caused by “the extensive hemolysis, 
reduced oxygen-carrying capacity, and generalized tissue hypoxia.                                                   ” You can read the abstract of that study, here

And here is a list of additional related articles, the abstracts of 
which you may read by clicking on the title: here

The full text of these articles is available if you’d like to read 
them. However, you will need to register and pay a fee to gain 
access. 

Here’s one direct link to the applicable journal for purchasing one of 
the listed articles: 
“Preliminary studies on the chemical properties of the toxic principle 
from Diamphidia nigroornata larvae, a source of Bushman arrow poison” 
--D. Mebs, F. Brüning and N. Pfaff H. D. Neuwinger - here

====== SYMPTOMS ======

Although the main active ingredient in the San arrow poison has been 
identified and its effects described, I was unable to locate any 
published reports of the effects of this particular toxin on humans 
specifically. However, from reading the abstracts of the later 
studies, most seem to agree that severe and extensive hemolysis is the 
main action of the principle active ingredient, diamphotoxin. And 
death by hemolysis can be caused by other agents, so it is possible to 
infer from those other descriptions what might happen if a human being 
were to be poisoned with diamphotoxin by some means. 

This page from Namibia confirms that this is the action of the toxin, 
as it describes how they use, "the poison from the diamphidia beetle 
which has a haemtoxic venom, slowly attacking the animals blood 
corpuscles." 
http://www.namibweb.com/people.html (Scroll down the page) 

So first of all, it is important to understand what hemolysis is.                                                           “Hemo” (alternate spelling: Haemo) of course refers to the blood.                                                       “Lysis” means (in biochemical terms), “the dissolution or destruction 
of cells, such as blood cells or bacteria, as by the action of a 
specific lysin that disrupts the cell membrane.” “Hemolysis” means 
destruction of the red blood cells with a subsequent release of 
hemoglobin, or the protein in the blood that carries oxygen from the 
lungs to the rest of the body. 

See these links for definitions (be sure to scroll all the way down the pages):

Hemo: http://dictionary.reference.com/search?q=hemo 

Lysis: http://dictionary.reference.com/search?q=lysis 

Hemolysis: http://dictionary.reference.com/search?q=hemolysis 

Hemoglobin: http://dictionary.reference.com/search?q=hemoglobin 

Globin: http://dictionary.reference.com/search?q=globin  

So again, by searching for the mechanism of death by massive 
hemolysis, we might infer the symptoms of diamphotoxin toxicity. Here 
is a page on possible use of the gas, arsine, in chemical warfare. Inhaled                                           arsine also causes death by hemolysis, though the article 
states, “The mechanisms of hemolysis are not elucidated fully.” However,                                          it does say that hemolysis “can lead to global cellular 
hypoxia,” or cell death from lack of oxygen. It then goes on to list 
a number of symptoms by the system of the body affected: 

General - Fever, chills, shivering, thirst, malaise 
Neurologic - Headache, confusion, dizziness, paresthesias (which is a 
skin sensation of tingling, burning, itching, etc.) 
Pulmonary – Dyspnea (or difficulty breathing, often called “air hunger”) 
Gastrointestinal - Nausea, vomiting, abdominal pain, anorexia, jaundice 
Genitourinary - Red or dark-colored urine, flank pain, decreased urine output 
Muscle - Weakness, cramping 

Ultimately death occurs as the various organs shut down from lack of 
oxygen. You can read more specifics, here: 
http://www.biochemhazard.com/arsine.htm 

Here is another, even more graphic description of the sudden onset of 
acute hemolysis (also due to arsine poisoning), which begins with “abdominal                                    paint bloody urine, and jaundice (yellow discoloration of 
the skin). Initial symptoms of arsine poisoning are headache, malaise, 
weakness, dizziness difficult breathing, abdominal pain, nausea, and 
vomiting, which are usually first noticed 2 to 24 hours after 
exposure. Bloody urine, light to dark red, is frequently noticed 4-6 
hours after exposure to arsine and is often followed by jaundice 12-48 
hours later. An unusual bronze discoloration of the skin can often be 
observed accompanying the jaundice. If the arsine exposure is severe, 
the products resulting from the breakdown of red blood cells and 
hemoglobin will clog the kidneys, causing a reduction in the amount of 
urine formed, sometimes to the point of complete blockage of urine 
formation. Other toxic effects ... include damage to the liver and 
heart ....” 
http://www.cdc.gov/niosh/79142_32.html  

Underscoring the relevance of the above (that is, using the symptoms 
of hemolysis cause by arsine toxicity in the absence of any specific 
description of the effects of Bushmen arrow poison in humans) is this 
related report on the possible use of various substances as chemical 
warfare agents. Along with Arsine, Diamphotoxin is also included in 
the list: 
http://www.bradford.ac.uk/acad/sbtwc/2ndsesswp/doc19.pdf  

=======================================

I hope this information is what you were looking for. If anything 
isn’t clear, please use the “Request Clarification” feature before 
rating and closing the question so I might have the opportunity to be 
sure you’re satisfied with the information provided! 

Best wishes, 
Byrd 

Search terms used: 
[bushmen "arrow poison" action OR "active ingredient" OR symptoms OR 
cause OR chemistry] 
--The above term resulted in a number of relevant sites, which I then 
followed and read in order to arrive at the following additional 
terms: 
[diamphidia toxin] 
[diamphotoxin] 
[mechanism diamphotoxin] 
[symptoms toxic hemolysis –anemia] 
[mechanism toxic hemolysis –anemia] 

------------------------------------------------------------------------


Clarification of Answer by byrd-ga

http://answers.google.com/answers/ratings?user=71578948671974115                                              on 24 Jan 2004 16:33 PST 

Hello Fredht, 

Thank you so much for your kind words and the five-star rating! They 
are greatly appreciated, and I'm very glad you were pleased. I'm also 
happy to try to provide you with the clarification you've asked for. 

Of course you’re entirely correct in observing that saying 
diamphotoxin is the poison derived from the diamphidia larvae is a 
semantic distinction merely, without value as a comparison against 
other toxins. However, there are a couple of things to keep in mind 
here. 

One is that the studies cited in the first part of the original answer 
do show that diamphotoxin IS in fact chemically unique, bearing little 
to no resemblance to substances previously discovered, hence its being 
uniquely named for its source rather than identified as some already 
existing toxin. 

Secondly, its chemical properties have indeed been studied and noted, 
but in the available abstracts, the specific information is a little 
sketchy. I would expect that the full text of these studies might 
have the more specific information you’re looking for, but as I’m sure 
you can appreciate, their price precludes me from being able to access 
them in connection with this answer. And of course, some do not even 
have abstracts available, but one would need to purchase the full text 
in order to read even a summary of conclusions. 

However, I did go back and reread the applicable abstracts, as well as 
the one complete text I had, and was able to glean some detail as to 
the specific chemical composition of this toxin. In particular, I 
learned the following facts that hopefully will be of some use to you: 

First, in order to understand the significance of some of the facts 
and results noted, it would be a good idea to understand the 
definitions of several terms, especially protein, amino acid, and 
toxin. 

======================
PROTEIN 
======================

A protein may be defined as “large organic molecules, which are made 
of the elements carbon, hydrogen, oxygen and nitrogen .... Proteins 
are actually composed of lots of smaller sub-units called amino acids, 
which are joined together into chains of different lengths.” See this 
link: 

http://www.cherrybyte.org/Articles/bugbytes/proteins/Protein.htm  

as well as these additional ones for more information about proteins: 

http://www.google.com/search?q=define:Protein  

http://www.paulingexhibit.org/exhibit/protein.html  

http://www.concord.org/~barbara/xhoms/protein1.html 

======================
AMINO ACID 
======================

And then it becomes necessary to know that “Amino acids all have the 
same basic structure. They have an amino group (NH2)on one end, a 
carboxyl group (COOH) on the other end and a side group called the R 
group. It is the R group which differs considerably in the different 
amino acids. For example in the simplest amino acid glycine, the R 
group is a hydrogen atom but in tyrosine the R group contains an 
aromatic carbon ring.” (also from the cherrybyte.org site listed 
above). Here are a few more sites that talk about amino acids: 

http://www.google.com/search?q=define:Amino+Acids  

http://www.yourgenome.org/primer/proteins/aminoacids.html  

http://www.bgsu.edu/departments/chem/midden/chem308/slides/Pro1BW.pdf  

======================
TOXIN 
======================

Finally, it’s important to understand the definition of toxin. In 
this excerpt from “Annex 2: Toxins” of the “University of Pennsylvania 
Medical Center Guidelines for Antimicrobial Therapy” we read first 
that “Toxin’ has no commonly accepted meaning within the scientific 
literature.” But the report then goes on to provide a broad 
definition nonetheless, taken from the 1993 Chemical Weapons 
Convention, which defines a toxin as “any chemical which through its 
chemical action on life processes can cause death, temporary 
incapacitation or permanent harm to humans or animals.” See the 
complete document for a very interesting discussion. You can get it 
in html here or in PDF format if you prefer, here .
But from all the definitions, “toxin” at its most basic, simply means 
a poison. Here are links to some additional definitions: 

http://www.google.com/search?q=define:Toxin  

http://www.adelaidecc.com.au/pdf/upload_msr/issue-4-november-2003.pdf  

======================
DIAMPHOTOXIN 
======================

All right then, despite the conclusions of one group of scientists 
(specifically the paper immediately preceding the first study cited in 
this answer, i.e. “Preliminary studies on the chemical properties of 
the toxic principle from Diamphidia nigroornata larvae, a source of 
Bushman arrow poison.” Mebs D, Bruning F, Pfaff N, Neuwinger HD. 
Journal of Ethnopharmacology 1982 Jul; 6(1): 1-11), it seems to be 
fairly well agreed that diamphotoxin acts as, indeed IS a protein.                                                       And there IS a little specific information about it, particularly in 
the first study I cited in the beginning of this answer, i.e. 
“Diamphotoxin: The arrow poison of the !Kung Bushmen,” which is the 
only study that I was able to read in its entirety. 

In the summarizing its results, the authors of this study state that 
“isoelectric focussing of the purified molecule yielded a sharp peak 
of activity at a pH of 9.5, in accord with the observation that the 
toxin behaved as a basic protein. The results of amino acid analysis 
are shown in Table II. Only one NH2 terminal amino acid (glutamine or 
glutamic acid) was detected ... The isolated protein was identified as 
the toxic factor .... Hemolytic activity was clearly associated with 
the single band of highly purified protein .... there appears to be 
little doubt that the molecule we have isolated is responsible for the 
activity of the Bushman arrow poison.” 

So the specific identity of diamphotoxin is that 1) it is a protein; 
2) its specific identity is that it contains only one amino acid, i.e. 
glutamine (or glutamic acid); 3) the specific arrangement of the amino 
acid chains is unique to this protein, that make of it a toxin that 
has hemolytic action when injected into a biological specimen, and 
that is absorbed or “used up” in the process. 
What I could not ascertain without recourse to the full text of the 
other studies cited was the exact arrangement, the “R” side of the 
amino acid chain in this protein, nor whether or not it might somehow 
be synthesized. 
I hope this additional information will prove useful to you. Please 
let me know if there is any additional clarification I can provide. 

==============================================

I am also, of course, very interested in your offer, and would love to 
do more research on this topic or a related one. However, Researchers 
are not permitted to have contact with customers outside the service, 
so I’m very sorry I will not be able to undertake an arrangement such 
as you suggest. Still, if you should find it possible in future to 
access this service more easily than you’ve been able to so far, you 
might consider posting another question(s), directed to me if you 
choose. You can do that by putting something like “For Byrd-ga only” 
in the subject line, and my colleagues will respect that and not 
answer. 

Again, thank you very much! I do look forward hopefully to being able 
to work with you again. Best of luck to you and your wife on your 
project! I must confess to a pang of envy on hearing of what sounds 
to be not only a fascinating project, but an immensely interesting 
lifestyle as well. Much success to you both! 

Warmest regards, 
Byrd