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:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2629177&dopt=Abstract&itool=iconabstr
And here is a list of additional related articles, the abstracts of
which you may read by clicking on the title:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=6523515
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
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T8D-475BBSK-T&_user=10&_coverDate=07%2F31%2F1982&_rdoc=1&_fmt=summary&_orig=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=411a04f4e72ffe943291c8b1a7cdc30a
=============================================================
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
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:
://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:
://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:
http://216.239.39.104/search?q=cache:L_9p5kQHyuYJ:www.uphs.upenn.edu/bugdrug/antibiotic_manual/whoct.pdf+%22what+is+a+toxin%22&hl=en&ie=UTF-8
or in PDF format if you prefer, here:
http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/whoct.pdf
But from all the definitions, ?toxin? at its most basic, simply means
a poison. Here are links to some additional definitions:
://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
Additional search strategy:
I began by reading through the text of the one study I was able to
access in its entirely (noted above), and through the abstracts of
those for which abstracts were available. From information gleaned, I
was then able to make use of several search terms leading to a fuller
understanding of the results, which I then reread in that light.
Additional terms used included:
[?what is a protein?]
[?what are amino acids?] and [?what is an amino acid?]
[?what is a toxin?]
[?what are peptides?]
I searched on these terms both generally, and using the site:.edu and
site:.gov qualifiers to limit the results to educational or
governmental reports, which ultimately were the most useful for this
purpose.
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