Science behind Spiciness

Whether for pain or pleasure, at some point in your life you will probably have eaten a hot chilli. Having lost a bet at lunch, It makes a great forefit for any competition between school friends.

While my mouth was on fire after eating a "birds eye" chilli I wondered exactly what it is about chillis which causes such a reaction, so I decided to do some research on it.

The tongue has a multitude of different receptors for different flavours and sensations, including one called "TRP-VR1" (Vanilloid Receptor 1) which detects  actual heat- if you were to eat something which has a high temperature these receptors are activated, letting a flood of ions through a protein channel, travelling through the nervous system and reaching the brain, which interprets the signal as "ouch", and so pain is felt.

Capsaicin

The active ingredient in any chilli is a molecule called capsaicin- C₁₈H₂₇NO₃. This molecule binds to the receptor, forming a waxy layer over it and signals it to open the protein channels making your brain feel heat pain on your tongue or wherever the capsaicin contacted. (The eyes, inside of the nose and other mucous membranes also contain these receptors, which is why getting any in your eyes or up your nose hurts all the same) the waxy nature of capsaicin from its hydrocarbon tail means it is non soluble in water, explaining why water does nothing to help wash away or cool down the mouth.

Bird's eye chilli

There is a scale to measure the "heat" of a chilli called the Scoville scale, devised by an American pharmacist, Wilbur Scoville in 1912 (whose birthday happens to be toady). In the test to determine how hot a chilli is, a panel of at 5 "expert taste testers" eat an exact weight of dried chilli dissolved in alcohol to extract the capsaicin and then are given a sugar water drink until at least 3 of the 5 agree there is no heat left. Of course the test is no perfect and often has varying ranges for the same chilli due to the human perception of when there is any heat left. The scale graduates in 100s of Scoville heat units (SHU). At the lowest end is a bell pepper, at 0 SHU and paprika at 100 SHU. Nice heat you might find in a mild tesco curry would be around 500 to 1000 SHU. Above 20,000 SHU is usually not considered to be a nice heat on its own, like Tabasco sauce. Hot supermarket curries may have 100,000 SHU. The birds eye chillis we buy and use in school are about 200,000 to 300,000 SHU. When I eat them my eyes and nose stream and I can't feel my mouth for a good 15 minutes, past this point there is only discomfort. My uncle
used to keep some naga chillis which are 750,000 SHU, and I have seen videos of people who do the most ridiculous chilli challenges online  using the famed "ghost pepper" which comes in at 1,000,000 SHU. The hottest pepper officially ever grown was the Carolina reaper, achieving a painful 2,200,000 SHU- about 10 times as hot as the ones I have had. 

The Carolina Reaper

But all of these chillis have extra flesh and other chemicals in them which hold off the heat of pure capsaicin. The chemical is used in higher concentrations in pepper spray, which comes in at 5,000,000 SHU. Pure crystal capsaicin  is pretty awful stuff, peaking at between 15,000,000 to 16,000,000 SHU. This kind of heat can just blow your head off-and has been made illegal in the United Kingdom as of 2013. 

Chillis make these chemicals as a defence mechanism, as most animals are affected by it, and wouldn't ever dare eat it again after the painful ordeal. Farmers who try to breed the hottest chillis tend to make harsh environments, apparently sometimes even cutting off branches of the plant in an effort to make them "feel as if they are being eaten, so they make their chillis hotter" I have heard stories about some chilli farmers verbally abusing their plants in an effort to make them hotter, although I don't really see the science behind it. 

Birds are one of the few animals which are not affected by hot peppers because they don't possess any TRPVR1 receptors. 

In nature there are compounds made by specific plants which actually do a better job than capsaicin can do on your receptors. 

Euphorbia poissonii, a highly toxic plant grown in Nigeria contains a chemical called Tinyatoxin, which clocks in at 5,300,000,000 SHU- over 300 times hotter than pure capsaicin, and 1000 times hotter than law enforcement grade pepper spray. Nigerian farmers reportedly use the plant's fluids as a pesticide.

Euphorbia Poisonii

Above: Tinyatoxin-(5,300,000,000 SHU)

Below: Resiniferatoxin-(16,000,000,000 SHU)





Even Tinyatoxin's heat pales in comparison to the King of chemical heat: Resiniferatoxin. Although the only difference between it and Tinyatoxin is the ether group on the carbon ring on the right side of the diagram this chemical is the ultra active analog of capsaicin, making the police's pepper spray seem harmless. It weighs in at 16,000,000,000 SHU of course this and Tinyatoxin's Scoville heat ratings have been estimated based on chemical analysis, because as little as 10 grams of it is a fatal dose, overloading the nerves which signal pain, and giving respiratory failure. Very very small mixtures of these chemical, although it seems illogical, have been used as effective pain medication due to numbing effects and are even being used in treatment of Peripheral neuropathy, to help nerve pathways refire.

 Left: Euphorbia Resinifara

Resiniferatoxin is found in Euphorbia Resinifera- a type of little cactus in north Morocco. As if spikes weren't enough to keep animals away from a cactus! I think I'll stick to the bird's eye chillis...

Pharmacogenomics & Stem Cell Banking- Dr. Nick Hole

I attended this lecture by Dr. Nick Hole on the 16th of November

 Above: Undifferentiated stem cells as seen under a microscope

This lecture's title interested me, as I have been told that the future's medical procedures may rely on genetics and stem cells and it is a much talked about subject and increasingly interesting. Dr Hole organised everyone who attended the lecture into 4 groups to understand how the ethics and business sides of stem cell banking may work in the future. The basic idea we were given was that all stem cell banking would be made legal by the government, and that each group must give their opinions on how the process should proceed. The groups were acting as the NHS, the private stem cell bank, a group of parents who wish to use the service and a pro-life group.

 Being in the private stem cell bank, our team's job was to be able to offer a different service to the NHS. We agreed would be targeted towards parents who may wish stem cells to be taken from bone marrow and embryonic stem cells at an annual cost until used with a few specific guarantees in place: that we would keep the stem cells safe and available at any time, that the stem cells are only available to the particular family who donated them, they will not be shared to anyone else. This was almost the opposite to the NHS who agreed that they would offer this service of donation to everyone, there would be total anonymity when donating (like a blood bank) and that the stem cells could not be kept under the specific conditions to keep them fresh so must be renewed every few months due to the cost of deep freezing for extended periods of time. The family group agreed that they would pay around £100 annually per person for a proportion of healthy stem cells to be frozen in the event that they or their future child may have a need for them, the pro life group were of course debating on the use of the our company's embryonic stem cells, believing all human life is sacred, and banking the stem cells lacked humanity and killed people, however our group countered that the government had passed law that allowed embryonic stem cell banking and it was an entirely optional process which a family could take part in which may save a future child or family member- (of course the pro-life group was comprised entirely of 6th form scientists who were more likely to view stem cell banking as a good idea)

The next topic that was brought up by Dr. Hole was the use of genes and the future of medicine in recombinant DNA technology, coding and altering genomes to find new drugs, which may be biologically synthesised. Cyclin genes control most of the growth and division, and are conserved throughout evolution. By synthetically regulating where genes are expressed we can regulate almost anything about any eukaryotic cells- around 210 types with 25,000 genes between them. This prompted Dr. Hole's question: can redevelop bespoke drugs by coding one's genome which are specific to that individual? In a way this process has already begun on a simple level, with synthetic biologists engineering microbes to produce useful molecules and biofuels. there is no large input of energy to synthesise these compounds, they are generally far greener and less industrial methods of producing desired compounds also. 

Diagram of the Telomeres

Genes govern everything about our body. Telomeres are repeat sequences of chromosomes which accumulate mutations. These telomeres naturally shorten with age and as you get older this is one reason why cancer becomes more likely, the cancer cells don't 'commit suicide' because of telomerase, an enzyme which actually repairs the cancer cells and allows them to continue dividing rapidly and dangerously  when repairs to the telomere begin to fail. Genetic alterations could vastly change the way these parts of our genes function, and anti cancerous telomerase drugs are being produced. Dr. Hole predicted that over 4000 genetic diseases could be cured with new drug sequences- the very day I was in this talk, I had an allergy test, where small pins coated with with allergens were pricked onto my skin to see which of them produced antihistamine reaction and left a bump on my skin, in the future the nurse would have my Genome coded and find the relevant gene which caused the antihistamine reaction to be released to the grass pollens which I am allergic to!

    Artemisinin

Craig Venter coded an entire genome of 'Mycoplasma Mycoses' - a 1.08 million long sequence and inserted this genome into an empty cell... which began to divide and grow, proving specific genetic cloning may be possible, and along with it complex alterations, known as designer organisms. for example, a malarial combatting drug called artemisinin may be coded for in terms of genes, and then these gens inserted into bacterial cells which produce the drug and has a much higher yield than obtaining it from plant which requires separation from other unwanted compounds. The only downsides to these genetic 'cures' is that the long term effects are not known.

The future of medicine will most likely incorporate stem cells and genetics, and it is an interesting take to view genetics as we currently view drugs.

Formation of an embryo- Dr Ian Keenan

I attended this lecture on the 24th September from Dr Ian Keenan from Newcastle university. 

The pre-birth section of human life is something which is mostly glossed over in the GCSE and most of the A level courses, even though it is a very important and interesting time in life. At GCSE the entire process was called "fertilisation period" and at A level the most detail we go into is just that the embryo grows from a ball of cells into a foetus and then a neonate. Dr Keenan's talk explained some of the processes behind making you from two haploid cells.

Gastrulation is the period of fertilisation following the blastula where the entire embryo is a "hollow cup" shaped structure with three layers of cells; the outer layer (ectoderm) will later be formed into the central nervous system, the middle layer (endoderm) will mainly consist of muscle tissue and the inner layer will form vital organs. 

This is also the time that the embryo forms it's body axes (cranial, dorsal, ventral, proximal, distal etc) with a particular family of genes controlling the process.

The embryo then plays a molecular "pass the parcel" as Dr Keenan put it, using an analogy of retailers and large companies distributing goods to model the way genes are first expressed to signal growth and begin to form a foetus: the customer orders online from a large company like Amazon, requesting a package. Amazon is an online retailer which models the signalling proteins BMP Shh FGF and Wnt, in organisers in the cell. 

left: FGF protein, used in embryonic formation and also used to heal wounds, because both processes need to form new cells.

To get to the customer, the package must travel on roads which are signalling pathways in the embryo. The package itself is a phosphate group (PO₄) transported by a kinase- an enzyme which catalyses the transfer of this phosphate group like a courier. To enter the correct part of the body the courier must press the "doorbell" which is a transcription factor in the targeted cell, delivering it to the customer, a gene. 

The talk by Dr Keenan made me realise how important this stage of life really is, that without it we would still be just a ball of cells in complete disorder, and that this tells our body where to grow muscle, bone, skin and organs. I found it very interesting to learn more than the A level course offers, and in particular this links to the chapters we have completed on protein synthesis so far, how complex and specific they are to perform these certain functions.