Animal Toxins: Snakes

Today, in a special issue of this blog, I'm going to be looking at animal poisons (toxins), specifically snakes. Despite their reputation there are only about 300 poisonous species of snakes, which is about 10% of all known species of snakes. Nevertheless, snakes do possess some of the most deadly toxins, especially cobras, vipers and sea snakes. While snake toxins are not nearly as dangerous or fast acting as some of the toxins found in plants and fungi (think ricin in castor beans, or death cap mushrooms), they can be far more deadly for two main reasons:

   1. While plants and fungi only contain a single type of toxin, snakes often utilise a mixture, making it much more difficult to treat.

   

   2. While plant or mushroom poisons have to be ingested, snake toxins are forcibly injected into your system. 

The likelihood of you dying from a snake bite is pretty much proportional to how good your country's infrastructure is. For example in North America only about 5 people per year die of snake bites, however about in India and Pakistan there are about 50,000 to 70,000 deaths per year due to snake bites.  We can tell that this is not just due to a differing number of poisonous snakes as Australia, the country with the greatest concentration of poisonous snakes has one of the lowest snake death rates.

So why is there such a discrepancy in the snake bite mortality rates. Well as with all medicine speed of response is absolutely essential, and a good infrastructure improves this. Snake bites also require adept medical professionals to treat, as I have mentioned they contain many different types of venom. North American rattlesnakes, for example, utilise at least nineteen different types of toxin. In many cases these toxins can work in a sort of perverse harmony, increasing each others' damage and rapidity of action. 

Toxins have two main ways of killing:

   1. Neurotoxins: As you may have guessed neurotoxins act on the neurons. Neurotoxins are chemical agents that affect the transmission of chemical signals between neurons. Neurotoxins affect this process in a number of different ways. They may block receptors, stopping the flow of transmission, or damaging microtubules or vesicles which carry the chemical messages. This can lead to death by asphyxiation, as chemical communication in the lungs and diaphragm is restricted, obstructing ability to breathe. 

   2.De-clotters: Ok, that 's a made-up word, but I couldn't find the technical term for this. Basically the toxin stops your blood clotting, giving you a sort of impermanent haemophilia, meaning you could actually bleed to death through the bite. The toxin may do this by inhibiting the action of coagulases. These are enzymes that convert fibrinogen into fibrin, which forms the thread of the clots. If these enzymes do not function, the blood will not clot. 

So how do we stop this? Antivenoms are the answer. Antivenoms are actually types of 'two-layer' vaccines. First the animal from which the venom comes has to be milked for its venom. The venom is then diluted to non-lethal levels and injected into an animal (a rabbit for example). The rabbit produces an immune response to the venom. These antibodies are then collected and injected into the person, defending them against the venom. 

The availability of antivenoms and the speed with which they can be received are the main factors affecting how safe you are, although not being around particularly poisonous snake infested areas cant hurt. 

Until next time people!

Gas Chromatography: Method and Applications

I've covered thin-layer chromatography previously in this blog, however chromatography is a big field, and the precision to which it can analyse samples is increasing rapidly, not to mention how widespread the apparatus required to carry it out is becoming. As such I would say it merits a lot of attention as a field of study.

Unlike in thin-layer chromatography, the mobile phase is an inert gas (for example helium), or an unreactive gas (for example nitrogen). The stationary phase is a liquid coating the walls of the column. The stationary phase is chosen to be as close to the polarity of the solute as possible.

The gas chromatograph uses a column (flow through narrow tube). The different constituent chemicals from the analyte are carried up the column by the mobile phase at different rates. The rate is dependant on the chemical and physical properties of the chemicals with the stationary phase. This causes each constituent to exit the column at a different time.

You may be wondering why such complex, and often expensive techniques need to be employed, well fear not I hear your worries and I'm going to illustrate the value of gas chromatography, thin-layer chromatography and mass spectrometry with a couple of case studies.

1. FBI's analysis of EDTA in blood at O.J. Simpson trial:
    Agent Martz and the FBI forensics team used a combination of the aforementioned techniques to detect the presence (or in this case absence) of EDTA in a blood sample from socks and a watch. EDTA is a preservative for blood. If found in high levels it would indicate that the blood samples had been tampered with. The high level of precision, and ability to remove background peaks, of the mass spectrometer meant that this case was where it really established its role as a reliable form of evidence.

2. Analysis of Fire Debris for ignitable liquids:
    In January 2002 there is a fire. One person dies in the fire, and the police decide to bring in a forensics team to investigate. The result is a piece of vital evidence, showing the fire could not have been an accident. The forensics team, using Gas-Liquid Chromatography and Mass Spectrometry find gasoline present on weathered debris. The presence of ignitable liquids (where there should be none) is fairly damning.

Anyway thank you for reading, until next time people.

Dose-Response Relationships

 I'm back, and this time we're going to be learning about the wonderful world of dose-reponse. In the words of John Timbrell: "There are no safe drugs, only safe ways of using them". In a high enough quantity any drug can be dangerous. But how do we assess what this threshold?

One problem is what the real dose is. Different chemicals are absorbed in different ways with different efficiencies, for example cyanide really has to be absorbed through the mouth to be dangerous, however thallium can be potent even when only applied to the skin. It is not only the method of absorption that affects the 'real dose', but also may be metabolised or excreted more or less rapidly.

however well the chemical is absorbed, metabolised or excreted, the higher the external dose, the higher the internal dose. Eventually the internal dose will reach a high enough level that the body's detoxification and excretion processes can not keep up and are overwhelmed, resulting in toxic levels of a chemical. It is particularly important to be familiar with the dangerous dose, as low doses may cause internal damage which is not detectable until it has progressed to the point where it compromises a bodily function.

According to the Paracelsus Principle, as the dose level rises the body cells will show an increasing level of dysfunction and damage up to a maximal effect (function completely inhibited).

As an example consider a drug that lowers blood pressure. The higher the dose of the drug the larger the decrease in blood pressure, up to a fatal decrease. This can be plotted as a sigmoid curve graph.

Another way in which dose-response relationships are represented is if the effect can be measured in a sort of binary way, either present or absent. The number of people displaying the measured effect at each dose is used to plot the graph.This relationship can represent both negative and beneficial effects.

So why does the larger the dose mean the greater the effect? Well for almost every effect in the human body caused by chemical, interaction with some kind of molecule is necessary, for example the receptor on an enzyme. In order for an effect to occur enough of the receptors must be occupied. The higher the concentration of drug, the more receptors are filled by the drug (this is especially important in competitive inhibitors, where they have to have a high concentration of drug in relation to whatever it is competing with). The threshold is where not enough of the receptors are occupied to have an effect. Ultimately this is what you have to think about when assessing the danger of a chemical. Ultimately the lower a dose required to cause the greater an effect the more potent the drug. 

Thanks for reading, over and out!

Ethyline Glycol (A.K.A. Antifreeze)

Antifreeze is a sweeting, but deadly lethal substance. Once used (illegally) for increasing the sweetness of Australian wines. It is technically an alcohol, but while it initially mimics the effects of a glass or two of wine, it quickly turns to something much more serious.

Name: Ethyline Glycol

Formula: C2H6O2

Effect on Victim: Ethylene glycol becomes poisonous when in the body as it is metabolised into several different chemicals. This is caused by the same enzyme that metabolises the alcohol in common alcoholic drinks. The main product is oxalic acid which is poisonous. Also found in rhubarb leaves, oxalic acid causes the pH in the blood to drop (meaning the blood becomes more acidic), inhibiting normal metabolic processes. As if this wasn't bad enough the oxalic acid can also crystallise on the brain and kidneys, resulting in damage. On top of all this oxalic acid reduces calcium, removing it from the body. This produces effects similar to that of tetanus, causing muscles to contract uncontrollably.

Lethal Dose: Has a comparatively high lethal dose compared to other substances we've looked at. of about 100 ml

Diagnosis: Ethylene glycol is a poor choice for a poison as it is relatively easy to spot and takes a comparatively long time to kill. Ideally an analysis of the concentrations of oxalic acid in the blood by gas chromatography would diagnose antifreeze poisoning, however the equipment to perform this is expensive and rare. A much simpler but less accurate diagnosis is analysis of urine, as this will reveal oxalate crystals when ethyl glycol is at deadly levels. Another common test is to take advantage of the fact that fluorescein is often added to antifreeze to help detect radiator leaks. A Wood's Lamp will reveal fluorescence in the patients mouth.

That's it for this rather un-subtle poison. Hopefully now you can see why it's coloured brighter than a poisonous insect. Unfortunately the bright colours and sweet taste mean children are particularly at risk of drinking it. Anyway thanks for reading, see you soon!