Deoxyribonucleic Acid (DNA), Ribonucleic Acid (RNA), Genes and Proteins

One of the most powerful pieces of evidence for evolution, I believe, is the universality of DNA. It is common to all forms of known life. Even viruses, which cellular biologists argue are non-living (incorrectly IMHO) are, at their most basic, either DNA or RNA and a protein wrapping.  All living things pass their information from one generation to the next coded in DNA. All living things. Not all living things except for the Asian Pygmy Elephant (which I have seen in the wild) and tarantulas (which I haven’t). ALL living things pass their genetic information to their children coded in DNA. Some, like bacteria, undergo binary fission, doubling their looped chromosome and dividing in two. They pass their DNA on in entirety and the daughter cells produced are clones, identical to the parent cell in every way. For other sexually reproducing organisms, it’s a case of pros and cons. Pros: your genetic information is passed on and you’re having sex. Cons: Only half of your information is passed on, there is no guarantee that this information will be expressed and you’re having sex. Sex is a pro and con? Just think of that male praying mantis, having its head eaten off in the act of passing on half its genetic information.  

So what is this DNA/RNA stuff? And how does it make me me, you you, us people and not a cactus? As you should have learned, DNA and RNA are polymers, the subunits are comprised of a sugar- this is the deoxyribose in DNA and ribose in RNA. DNA also has a phosphate attached to the sugar. So far these components are just structural. What makes these molecules so special are the nucleic acids attached to the sugars: guanine, cytosine, adenine and thymine. RNA uses uracil instead of thymine, chemically a closely related molecule. Thymine is formed by the methylation of uracil– ask your chemistry teacher. So you know that guanine and cytosine join via three hydrogen bonds, adenine and thymine (or uracil) via two hydrogren bonds. You also know that DNA is a double-stranded molecule that is often represented as a twisted ladder. The rungs of the ladder are the paired nucleic acids and the up–righty bits (what are the vertical parts of a ladder called?) are formed from the sugar phosphates.  It is then twisted to form the helix, making a complete rotation every ten or so base pairs. RNA is single stranded. What you might not yet know about RNA is this single-strandedness (just invented a word!) is vital in its role and function. As it is a single strand, and as it has nucleic acids that will readily bond with their complementary partner base, they can be folded on themselves and form a three-dimensional shape that, in a similar way to a protein, defines what and how it can then do. Just like proteins, shape is important. Ribosomes are comprised of r-RNA, ribosomal RNA. It is the shape of them that allows for amino acids to be arranged in the primary protein structure. t-RNA, or transfer RNA, facilitate amino acids moving from the cytoplasm to the ribosome and being placed in the correct position in the growing protein. Again, the shape of the molecule determines its role and function. 

Another difference between RNA and DNA is size. RNA are much shorter molecules than DNA which, depending on the text you read, could be between 1.6 – 2 metres in length. In the nucleus of every diploid cell in your body is nearly 2 metres of DNA. This makes packaging a bit of an issue. How small are cells? Really, really small. We measure them in microns. And this length of DNA is found in the nucleus of each and every one of these cells. So how does this length of DNA manage to fit in the nucleus? The first stage of this process is the twisting which I’ve already mentioned. This shortens the entire length. Next, the DNA is tightly wrapped around a protein called histone at intervals along its length, into units called nucleosomes , again shortening the molecule. Experiments have shown that these nucleosomes are on average 200 base pairs in length. This is the basic structure of chromatin and is how DNA is packaged within the nucleus unless it is going through mitotic or meiotic division. When new somatic or gametic cells are produced this chromatin is condensed into chromosomes.  The molecule is coiled to roughly look like a telephone cord (for those of you who can’t remember these speak to your history teacher) and coiled again. This supercoiling is done with the aid of further protein molecules and results in 23 pairs of short chromosomes forming in a human. Chromosomes, genes and the relationship between genotype and phenotype will be the subject of my next rave.

I want to step back from the structure and packaging of DNA at this stage and have a look at chromosomes and genes. DNA packaging is pretty straight forward and your teacher or textbook can paint a pretty good picture. Even Wikipedia doesn’t stuff this up too much. If you are struggling conceptually, have a look at this link. 

To talk about chromosomes and genes, first you must have a clear understanding of what DNA does. DNA codes for protein, or more simply, your DNA dictates what proteins are made in what quantities in what cells throughout your body. It tells your cells to make protein. That is all. Protein. Not carbohydrates or lipids. Proteins. And this is what is passed from your parents to you and from you to your children: a list of proteins to be made and a biological timeline for this production. You need to think of your DNA as a novel. It is a book all about you. And the language or code that this is written in is the nucleic acids. It is a four letter alphabet (well, five if you include uracil). Our alphabet uses twenty six letters, the language of DNA uses four. And the words these spell are only three letters long. The three letter DNA words are called codons and each of these biological words represents an amino acid. Like our language, the letters are arranged into words, but these words need to be in sentences to make sense. A DNA sentence is made of a string of codons and this sentence will say “Histone” or “Collagen”. The codons spell out the sentences that are the primary protein structure. We call these codon sentences genes.

A gene is a discrete section of DNA that provides the instructions to construct a protein. Of the 20,000 to 25,000 genes found in the human genome, an incredible percentage of this genetic information is shared with a vast number of animals. We share genes with other forms of life. Our closest genetic relative is the chimpanzee. Around 6 million years ago there were no humans or chimps but an ancestor that contributed genetic information to both lineages, and still today 98% of our genes are IDENTICAL to those of a chimp. But it is not just our close relatives, we share genes with organisms as morphological and phylogentically distant as earthworms. For example, humans have different versions of the gene to produce haemoglobin. These different versions are called alleles. We can have either A, B, or O haemoglobin. Chimpanzees also have the same ABO blood group system with the same genes. Now, if you have the haemoglobin genotype AA and a chimp has a haemoglobin genotype of AA you are more closely related to the chimp for that gene than you are with another human with a blood group of BO, for example. But only for that gene. And maybe for the gene for arse-scratching. 

While I was joking about the arse-scratching gene, let’s think about innate behaviour for a second. Innate, not learned behaviour. Your DNA instructs your body to make proteins. All other compounds and structures results from the interactions of these proteins. But what about innate behaviour? Things an organism does but is never taught. Sex for example. Or nest building in birds. Or walking for a new born foal. Birds do not pass a series of genetic instructions from one generation to the next on how to build a nest. Or instructions for the rifle bird of Papua New Guinea on how to perform an intricate mating dance. This knowledge is innate. They are born with it. And, to the best of our knowledge results from the interactions of different proteins found wit in the animal’s genome. This blows me away. Excuse me while I stop to ponder...

Now, not all DNA codes for proteins. The length of your DNA is much greater than the sum of the genes it contains. In fact only about 5% of your DNA codes for protein. To return to the analogy of our DNA being like a novel, there are spaces between the gene words and sentences. Within genes are areas of non-coding (not involved in protein synthesis) regions called introns. And between the genes are sections of non-coding DNA called Spacer DNA. This Spacer DNA was once commonly called Junk DNA because it was thought that this DNA was useless. It was named ‘junk’ in 1972 and for nearly 30 years was thought of as junk. However, this non-coding DNA maybe extremely important in the regulation of gene expression (when, where and for how long a gene is turned on) and may also be a significant player in diseases such as breast cancer, HIV, Crohn’s disease, Alzheimer’s, heart disease, ovarian and skin cancer. Our understanding of the relationship between coding and non-coding regions of DNA is at its infancy. 

All life shares the same code. This is powerful evidence for evolution from a common ancestor and allows us to transplant a human gene for insulin production and place it successfully into a bacterium alongside the bacteria’s genes. I will get to this later when I talk about genetic modification.

Unit 4 Intro

I hope you survived the exam.

Unit 4 is my favourite unit of work in the entire Victorian High School curriculum. This unit covers evolution, the evidence for this and the mechanisms by which this occurs. Once you have got a handle on this human evolution is covered.

You start examining DNA, which you were introduced to in Unit 3. The relationship between DNA, RNA and protein synthesis is studied in detail. Your knowledge of transcription and translation is extended and forms the basis of one of your SACs.  This then leads to where DNA is found, organised and packaged within a cell (chromosomes) and how discrete units of DNA that code for certain proteins, genes, are located on chromosomes. The concept of variation within a population is introduced whereby members of a population may have different versions of the same gene (alleles), which you are later shown to be at the very core of evolution. Mitosis and meiosis and the stages of these are also studied to establish a foundation from which Mendelian genetics and heredity are examined: Punnet Squares, monohybrid crosses, dihybrid crosses, the relationship between genotype and phenotype and patterns in the expression of traits through pedigrees are all studied. Somewhere in amongst this you will also cover the tools, techniques and ethics of genetic engineering.

Once this area of study is complete you leap into evolution. Evolution is made to sound complex but all evolution is is the change in allele frequency in a population over time. Evolution is placed in a historical context with an examination of the work of Lamarck and Darwin/Wallace. How evolution occurs is covered from random matings through to bottle-necks in a population and mutations. The evidence for evolution is also presented (as there are always people out there who place belief over fact and would prefer a flat world that is orbited by the Sun). This evidence is varied and irrefutable and forms the basis of all modern Biology and Medicine.

Finally, you will get an introduction to human evolution and look at the path we believe our ancestors took, by pure chance and with no implied direction, from ape-like ancestors to the magnificent example of modern human best encapsulated by looking in the mirror. I truly love evolution, the process and the implications, the subtle nuances... Please, if early posts in this blog bore you, come back and read my (factual but bias) rants on evolution later in the course. 

This blog is not a substitute for your teacher or your textbook. I won’t be covering the course in detail. I’ll be covering the material in generalities and talking about things that I find interesting.

Until then let me start with DNA, which I shall soon post. But I’ll give you  a little time to recover from the exam first!

Funny but wrong look at evolution 

What do I need to know for the exam?

A non-relevant crab. Nice photo though

Nothing. I'm not sitting the exam. You are. And what do you need to know? Well, everything. At this level, Biology involves a lot of memory work. The exam gets you to recall information and in a few cases apply this information.
A few hints:


Read the question.
I mean really read the question. What is it asking you? Sometimes there might be a slab of information and a nice little diagram of say, a cellular response to insulin. But the question may be something like "Define homeostasis". You're not required to talk about insulin, biochem pathways, signal transduction. Its asking for a definition.


Rule out answers.
Sometimes you might get a multiple choice question you don't know. Instead of not answering, rule out answers that are definitely incorrect. If you know that A and D are NOT the answer, but you are unsure about B and C, just by ruling out two of the answers you've increase the chance of getting that question right from a 1 in 4 chance to a 1 in 2.


Limit your answers:
You've studied hard and when you come to the short answer question you want to demonstrate this. Try and hold back a little. If the question is worth 1 mark, they are after a term or word or definition. If the question is worth 2 marks the question requires you to answer two things. Writing a mini essay may make you feel better but the examiner does not want to know everything you know about hormones for example, but may just need to know that steroid hormones are lipid-based and the receptors for these are within the target cell. Writing slabs of information runs the risk of contradicting yourself (no marks), writing something that is incorrect (no marks) or running out of time for a later question (no marks). Be clear and concise.


Practice:
Do previous exams. As many as you can. And complete them under exam conditions. Limit yourself to 1.5hrs. Then go back and read the examiners report/check your answers. Make a list of questions you got wrong. Know why you got these wrong. Is the list similar over several different exams? Are there areas you need to revise? Don't do prac exams while listening to music. It makes it harder to recall the information without the music. Also, I don't believe in study groups. I don't think they benefit everybody equally and tend to waste a huge amount of time but that is a personal view.


Seek help:
See your teacher, ask for their help. And when seeking help ask specific questions. Rather than "explain immunity to me", perhaps a better approach might be "I'm a little confused over the difference between humoral and cell mediated immunity". If help is offered, take it. If it isn't offered, ask. And a couple of days before your exam is too late. See your teacher. Email them. Pester your tutor / older sibling at university / cousin Jimmy who is smart.  Believe it or not, teachers love students who ask them questions or seek their help. It validates an otherwise meaningless existence. And for those of you who know me, email me anytime.


Don't study the night before:
If you don't know it by now, you are up the proverbial creek. You will get out of this exam a result proportional to the effort you have put in this year and over the last 13. Relax, watch TV, go out for dinner with a friend and get an early night. I suggest drinking several large mugs of chamomile tea before you go to bed. Might make you want to pee, but will help you sleep.


Believe in yourself:
You are awesome. Yep, you. Remember this always.


Good luck!

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Here is a practice exam. Here is another. Answers for the first and second. And a third with answers.

Here is a link to the VCE study guide. Look at the dot points on pages 21 -23. This is what you need to know. Make a list of dot points for each of the points in the study guide.

Here is something I found online. It's a 37 page Unit 3 summary

And here is a link to podcast for the entire Unit 3. Return to this link as they'll be posted over Unit 4 as well.

Allergies and Autoimmune disorders

Our immune system is incredible in its complexity and efficiency . However, occasionally, stuff goes wrong. Your body many initiate an immune response to an injury such as a sprain or over-respond to a foreign body, such as pollen and the hay fever that comes with it, or at the more severe end of the scale, fail to recognise self cells as self and begin to attack them, such as some forms of arthritis.

Autoimmune Disorders

It is not clear why the immune system initiates a response against its own tissues in the case of autoimmune disorders. In some cases foreign pathogens and antigens the body has been previously exposed to are similar in structure to some of our body’s own protein markers which can cause immune cells to ‘see’ these cells and tissues as foreign and commence an immune response by attacking them. Rheumatoid arthritis is an autoimmune disorder that primarily affects synovial joints such as the joints in your fingers and hand. Contracting rheumatic fever earlier in life may lead to the formation of antibodies that later mistakenly attack the connective tissue in your joints causing this type of arthritis. (Note: Not all arthritis is an autoimmune disease. If mentioning this in an exam you must say rheumatoid arthritis)

Autoimmune disorders may cause destruction of tissues, changes in organ function or abnormal organ growth. Examples of autoimmune disorders include Multiple Sclerosis (MS), Type 1 Diabetes and Celiac Disease.

This is not that detailed but the information you are required to retain and regurgitate come exam time is not in that much depth. If you don’t believe me, look at your textbook.

Allergies

Allergies are a term that covers the hypersensitivity response of the body. This is a response that is more severe or exaggerated than a response that is considered normal and differs from person to person. The reactions to an allergen is a response to immunological memory – your body remembers these antigens and renewed exposure triggers a fast and massive response. Come spring when the warm northerly winds bring high levels of pollen south to Melbourne, there is a dramatic increase in the cases of hay fever. It works like this: your body develops specific IgE on lymphocytes in response to first exposure to the pollen (or any other antigen). The next year when the winds blow the pollen south again the lymphocytes rapidly produce a large number of antibodies that are secreted and attach to mast cells. When the antibody-attached mast cells come in contact with the pollen the mast cells rupture releasing histamine, triggering an inflammatory response. Swelling of the tissues around the eyes, nose and throat, excessive mucus production, itchiness and all the other symptoms of hay fever. In an allergic or hypersensitive person this reaction is much more severe.

To counter these reactions we take antihistamines which reduce the impact of the inflammatory response and the symptoms of hay fever but blocking the body'd histamine receptors.

This animation shows histamine being released from a mast cell in response to pollen

This is a better animation in response to venom such as a bee sting

(I've just quickly rewritten this while supervising a test - original article was way too detailed. While this is short and brief, it is what you need to know. Hope it helps)


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And, on a completely different topic, here is a herd of 30 pygmy elephants and a group of 25 excited students. This trip to Malaysia left 6 months ago today...

Coordinating your defences

So you’re trekking through the rainforest in the Danum Valley trying to find the elusive orang utans and you slip twisting your ankle. As you fall you reach out and grab a vine which leaves you with several deep splinters from the thorns. Your friend, who has been feeling unwell ever since the flight to Malaysia, rushes over to help you up and in the process coughs in your face spreading the influenza virus that she has to you.

Your body is now dealing with three different injuries/diseases and I shall discuss the role of the specific and non-specific immune system as it fights to get you healthy again.

I’ll start with the injury to the ankle. Your ankle is injured and is not responding to a pathogen therefore all responses to this injury come from your non-specific defences. What you have done is stretch and stress the ligaments that connect the bones in your foot. In response to tissue damage and damage to blood vessels mast cells and platelets release histamine. The platelets work to repair any damaged blood vessels however the histamine has caused these vessels to dilate and become permeable. More blood is transported to the area and fluid moves into the interstitial fluid around the injury bringing many of the body’s white blood cells with it. These leukocytes run around looking for pathogens, often releasing more histamine as a result. At the same time the damaged capillaries are leaking blood into the interstitial fluid that will result in a bruise. The damage to the blood vessels causes a class of hormones, endothelins, to be released that act as vascular constrictors narrowing the damaged vessels to limit blood flow. These hormones work in antagonism to histamine, histamine causing the dilation in non-damaged vessels. The blood that has leaked into the interstitial fluid is gradually broken down by phagocytosis and this causes the changes in bruise colour over days.

So you are left with a sore, swollen, hot, bruised ankle as your body begins to repair the damaged tissues.

The splinters in your hand have allowed foreign particles to enter your body. Some of the splinters unfortunately had some dodgy bacteria on them. As the thorns pierced your skin they breach the skin barrier. In response, platelets begin the blood clotting around the site of the wound and release histamine. Mast cells, also present, release histamine and now the inflammatory response is triggered, the capillaries dilate, become permeable and neutrophils arrive on the scene. These neutrophils begin the phagocytosis and chemical attack of both the splinter (relatively unsuccessfully) and the bacterial pathogens that were also introduced to the wound. Responding a little slower than the neutrophils, macrophages arrive and continue the digestion of the bad guys while releasing cytokines that attract more leukocytes to the area of infection.

After destroying around 100 bacterium each the macrophages die and become the wonderful stuff we refer to as pus.  But before they die the macrophages have done something else. They have taken MHC markers from the surface of the pathogens and placed them on their own cell membrane. This allows T helper cells, that have now arrived on the scene, to recognise the antigen and kick start a clonal response and release of specific antibodies in B cells. It takes a bit of time but the specific and non-specific defences have defeated the nasty bacteria, however, the splinter, now surrounded by interstitial fluid and pus, is sore. The pressure of the fluid around it, combined with a little squeezing from you, force the splinter from the wound site. Platelets respond to repair the wound again and hopefully, no further pathogens got in this time. If they did, the process starts again.

Now you’re sitting on your veranda with a sore foot and hand but you are starting to get better, however, by now your body is responding to the flu virus you inhaled. When your friend coughed at you many of the virus particles landed on your skin and face. As they didn’t reach the host tissues they didn’t infect you. It was the particles you breathed in that have caused the problem. Influenza virus, or the flu as I’m going to call it from now on, infects the epithelial cells of the respiratory tract (the surface cells). The mucus lining of the respiratory tract provides some form of protection as a barrier both physical and chemical. And in this mucus will lurk IgA B cells, ready to respond to known pathogens. Unfortunately for us, the flu mutates rapidly and regularly changing its external surface markers so it is not immediately recognised by our lymphocytes and further, the flu virus diffuses rapidly through this mucus to the epithelial cells beneath. Once it has reached the target cells, the flu, an RNA virus, injects its genetic instruction into the cell. Here it is integrated into the cell’s genetic instructions, hijacking the cells organelles causing them to make many, many copies of this virus. Eventually the cell will lyse spreading the virus to neighbouring cells and, via coughing and sneezing, to people around us. In response to the invading virus, the cells produce interferon and cytokines. This works to interrupt viral replication, ‘warn’ neighbouring cells and attract NK cells to the area. I’ve explained the role of NK cells earlier but in a nutshell they use a one-two chemical combo to force the infected cells to undergo apoptosis. While you get a fever when battling the flu, this is not a non-specific response, rather, fever as well as muscle aches, tiredness and general feelings of crappiness result from the effects of interferon.

The infected cell also fights back by placing viral antigens on its surface. Cytotoxic T cells recognise these foreign non-self antigens on the surface of a self cell and respond by producing proteins that punch holes in the infected cells membrane. While this doesn’t necessarily kill the virus, it interrupts its life cycle preventing further spread. By now, your body has begun to defeat the flu and is rapidly producing antibodies and creating memory cells for future infections. Your antibody defences are relatively limited in response to a new virus, however, it is very effective in response to future infection by the same virus.

So, your ankle, hand and respiratory system have healed themselves. Your body has responded with generic and specific defences, some chemical, some cellular, and it has added these new pathogens to its biological database for quick and efficient response next time. After a couple of days in bed, feeling a fair bit better you limp to the restaurant to finally get something to eat and hear everybody else’s tales of jungle encounters . Unfortunately, the cook didn’t wash his hands properly and the bacteria Salmonella sp has now entered your system and is starting to multiply in your gut...

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Disclaimer: The Danum Valley is a magical place and your chances of getting sick there are probably significantly less than in Melbourne. I have never been to a place before that has filled me with such awe. Pygmy elephants, orang utans, hornbills, so many types of primate and reptile... And the food is amazing and the cooks DO wash their hands! If you ever get the chance, visit. But bring leech socks.

Immunoglobulins - Ig

Immunoglobulins are Y shaped glycoproteins that bond with antigens. We referred to these as antibodies in previous essays. The difference in terminology is this: immunogloblins that are on the surface of lymphocytes are called immunoglobulins, those that are secreted into the blood by plasma cells are called antibodies. It’s all about location. They are made of four polypeptide chains – two ‘heavy’ chains and two ‘light’ chains with a hinge in the neck region to allow easier coupling with antibodies. The binding sites on these molecules are at the tips of the Y arms. Have a look at this picture I pinched off the internet: 

There are five types of heavy chain peptides used to construct these molecules, resulting in five different classes of immunoglobulins or antibodies. We abbreviate immunoglobulin to Ig and the types of immunoglobulins are called IgA, IgD, IgE, IgG, and IgM. Due to their different structures they have different properties when it comes to battling antigens.

In alphabetical order the general roles of the different classes of immunoglobulins are:

• Ig A – these occur on surface tissues that are likely to be infected such as the lung and the gut lining. They are also found in tears and sweat. These work in conjunction with barriers to prevent infection.
• Ig D – Discovered in 1965 but what it does is still a mystery – potential PhD thesis for some budding young scientist?
• Ig E – These activate mast cells and get them to release histamine
• Ig G – These kick start macrophages and the complementary protein system into action. They primarily attack bacteria and viruses
• Ig M – These are the most numerous on the immunoglobulins and Ig M's are the first class of immunoglobulins to be produced during an antibody response. The role of these is very similar to that of Ig G and at this level, that’s all you need to know.

Here's a 3D model showing protein structure:

Remember: that these are broad classes of immunoglobulins and specific antibodies within these groups target specific, individual pathogens/antigens.

Lymphatic System

Blood circulates through the blood in a closed but leaky series of tubes. Leaving the heart these are the arteries which branch into smaller arterioles which again branch into tiny capillaries. The capillaries then come together to form larger tubes called venuoles and then finally return to the heart as veins. It is as capillaries that these vessels exchange gases, minerals, sugars and other substances with the interstitial fluid. Cells are bathed in this interstitial fluid and get the materials they require and release their wastes into this fluid via diffusion, osmosis and active transport. Cells and chemicals involved in the body’s immune response also reach the body's cells in a similar manner.

Also involved with our circulatory system is another system called the Lymphatic System. This system comprising Lymph Vessels and Lymph Nodes has three main roles, two of which I’ll discuss in some detail. One thing the lymphatic system does is aid in the absorption of lipids from the intestine. That’s all I’m saying about that role. The other two jobs the lymphatic system does is to clean ‘plasma’ and return it to the circulatory system via the vena cava near the heart, and, the most important for this topic, the lymphatic system helps fight infection. Lymph vessels are thin walled and located throughout the body. They carry a clear liquid called lymph which is comprised of water, ions, proteins, fats and leukocytes (white blood cells). Lymphatic circulation transports material from tissues towards the heart. Fluid is forced from capillaries due to pressure and accumulates in the interstitial tissue, which is then reabsorbed by the lymphatic capillaries. This is due to pressure in the interstitial fluid and the thin walled (highly permeable) nature of lymph vessels. This fluid contains cellular wastes as well as pathogens. At intervals along the lymph vessels are lymph nodes sometimes incorrectly referred to as glands. These nodes are small masses of lymph tissue, up to 25mm long. Lymph nodes house phagocytes and T and B lymphocytes and, as lymph travels through the nodes, phagocytes filter out foreign matter. T & B cells respond to foreign antigens and multiply rapidly initiating antibody mediated responses previously mentioned.

When fighting a pathogen, lymph nodes swell (particularly in the neck). We often refer to these as swollen glands. Remember that these are not glands, but lymphatic tissue. Tonsils are masses of lymph tissue and sometimes the pathogens they are fighting manage to infect the cells of lymph nodes themselves. This is what tonsillitis is.

There are other masses of lymph tissue in the body including the thymus and spleen. The thymus is the site of maturing T-lymphocytes and produces a hormone which stimulates T-cell synthesis and maturation. We discussed this briefly in the Specific Immunity essay. The spleen is the largest mass of lymph tissue in the body. It is an important reservoir of lymphocytes  and also regulates the removal of old red blood cells and platelets from circulation and their replacement with newly synthesised cells.

There is no pump to move the lymph through the lymph system. The circulatory system has the heart to pump blood around but movement of lymph through these vessels relies on muscle movement. The more active you are the more the faster the lymph moves through the vessels. Snakes inject their venom into the skin and muscles where it moves from the cells and tissues into the interstitial fluid, ending in the lymphatic vessels where it is transported. This is why if someone gets bitten by a snake you tightly bandage the limb and limit their movement. Unless you don’t like them.

Who says nothing exciting happens in South Australia?

For hundreds of millions of years life on Earth was prokaryotic. Bacteria thrived and was the only form of life. The environment was relatively stable. Until one day a 5 kilometre wide asteroid hit South Australia creating a crater 90km in diameter with an impact of an estimated 5,200,000 megatonnes of TNT. This asteroid, named the Acraman Asteroid, and the soil and dust ejected as a result had an extreme impact upon atmosphere and the biosphere, changing the global environmental status quo. This change has been argued recently to be the major selective pressure that triggered the Cambrian explosion and all ‘higher’ life – eukaryotes and ultimately us – to evolve.

So as I said in the title, who says nothing exciting happens in South Australia?

Article

And on a completely unrelated topic there was an awesome doco on last night on the Pygmy Elephants of Borneo.  It was filmed exactly where I saw a herd of 30 just on 6 months ago. What an amazing trip that was!

Specific Immunity

The non-specific immune responses of animals provide a versatile system of defence, able to respond to pathogens in many ways simultaneously. While the non-specific immune system responds to pathogens and allergens such as pollen, it does this by recognising them as not being part of the host and attacks them in several generic ways.

Once the barriers have fallen and the non-specific defences overcome, the third line of defence involves special white blood cells, called lymphocytes. The specific immune system recognises the individual pathogens and responds directly to them. It is able to not only tell that the pathogen is foreign, it is able to recognise the specific, individual pathogen. It does this through the surface markers and receptors on the invading cells. Further, it is able to remember these pathogens and respond quicker to future infections.

Lymphocytes, Antigens and Antibodies

The lymphocytes involved in the specific response are T cells and B cells, sometimes called T lymphocytes and B lymphocytes, and they have distinctly different roles in the immune response which will be the main focus of this essay. In very general terms these cells either produce antibodies which bind with antigens and inhibit their function or remember specific antigens and initiate a rapid response to any future invasion.

I’ve just used two terms, antigen and antibody, that I haven’t introduced yet. I’ll give a brief definition that I will expand on later. An antigen is a substance, usually a protein or glycoprotein, that when recognized as non-self by the immune system stimulates the production of an antibody that specifically reacts with it. An antibody is a specific protein produced by animals in response to antigens. Antibodies recognise and bind to the specific antigen that induced its production. Seem a circular definition? Think of it this way. Antigens are receptors on the pathogen that identify it. Antibodies block these receptors stopping it from infecting the host. These are shape specific and I will discuss in more detail in a second. First watch this.

Before I go any further I want to talk about the recognition of self and non-self. This is done via a series of proteins that protrude from the cells membranes and like any receptors shape is extremely important in how they function.  We call these Major Histocompatibility (MHC) markers, and these are like an individual’s unique barcode. They come in two varieties MHC Class 1 markers which are found on all cells within the human body except red blood cells, and MHC Class 2 markers which are found on T & B cells and some macrophages along with MHC Class 1 markers. We first came across MHC markers in my essay on pheromones. These are the things you ‘smell’ when assessing the reproductive value of a potential partner. You are attracted to someone who has MHC markers on their pheromones that are most different to your own. Back to immunity, B & T Cells ignore cells with the same MHC markers. It is when MHC markers of a foreign body are recognised that they react.

Antigens receptors on B & T cells that recognise non-self molecules/cells are called immunoglobulins. Immunoglobulins have a specific nature and recognise only one antigen. Like the lock and key of enzymes they are shape specific. During development in the bone marrow variations occur producing literally millions of B cells with different immunoglobulins on the surface. Some of these are genetically encoded, some of these as a result of previous exposure to a pathogen, some as a result of mutation.

Humoral Immunity - B Cells

Develop and mature in the bone marrow. Once mature they leave the marrow and migrate where they are found in the blood, tissue and lymph nodes (lymphatic system will be in one or two essays time). While there may be millions of different types of immunoglobulins on millions of different B cell, the numbers of these individuals are low. For example, there may be millions of B cell but only a handful with a particular receptor. When one of these comes in contact with a specific antigen a series of responses are triggered. The B cell under goes rapid clonal division, it makes many, many copies of itself. These then differentiate into plasma cells that have the role of producing and releasing antibodies into the body’s fluids.  The antibodies bind with the antigens on the pathogen preventing it from infecting the body further and making it easier for macrophages to come along and eat them. Some of the B cells become what is called B memory cells and hang around in the blood for years waiting for that pathogen to invade again. Initially, the B cell response to a pathogen is slow due to the fact that they have to undergo clonal division before they can be effective. The presence of B memory cells insures that future infections by this pathogen are responded to much faster.

A response that involves the production of antibodies is called a Humoral Response or Humoral Immunity.
B Lymphocyte rave

Cellular Immunity - T Cells and Phagocytes

While Humoral Immunity referred to an immune response involving antibodies and therefore B cell, Cellular Immunity is the term for a response that involves T cells and some phagocytes. Immature T cells leave the bone marrow and move to the thymus where they mature. T cells are the second type of cell involved in specific immunity. When discussing macrophages a blog or two ago I said that they had a role in the specific immune response. When they phagocytise a cell they take the MHC markers from that pathogen and stick them to their own cell wall alongside their MHC Class 1 markers. Like this. Specialised T cells, called T helper cells recognise these foreign class 2 markers on the phagocytes, this causes them to initiate a clonal response and production of antibodies in B cells, not the T cells. They help the B cells respond. In fact this type of B cell only responds to stimulation from a T cell. T Helper cells

Another important type of T cell are the Cytotoxic  T cells. Cells infected by a virus display the viral antigen on the surface of the membrane as well as its own MHC markers. The cytotoxic T cell recognises the infected cell by the presence of the foreign antigen and responds by producing proteins that cause holes in the membrane of the infected cell, destroying it.Cytotoxic T cells

Evolution and why we get the flu year after year

To a pathogen living in a Darwinian world, our immune system is a powerful selective pressure. Heritable variations and mutations that provide a pathogen an advantage lead to an evolutionary ‘arms race’ between it and the host. One strategy evolved by viruses, bacteria and protozoans to avoid the body’s defences involves constant change in the three-dimensional structure of these markers on their surface. Regular mutations in the antigen genes create different variant of the MHC markers allowing these pathogens to dodge our immune system – at least over the short term. Our body also produces millions of different variant immunoglobulins on the B cells and some of these can and do match up with the antigens eventually. The problem for us lies in how well these organisms evolve and change. The HIV virus is a master of this. I could spend an hour raving about this one virus. Instead, I’m going to end here after a brief recap.

Recap

• ·         Specific Immunity involves two main cell types T cells and B cells. Both of these are lymphocytes
• ·         B cells respond to antigens (receptors) on the pathogen by rapidly cloning themselves and producing antibodies
• ·         Antibodies bond with the antigens rendering them useless and encouraging phagocytes to come and eat them
• ·         Some B cells become memory cells so future invasions by the same pathogen are responded to quicker
• ·         T helper cells recognise foreign MHC marker on the body’s phagocytes after they ingest pathogens. They then kick start the B cells
• ·         Other T cells called Cytotoxic T cells recognise virus receptors on the surface of infected cells. This causes them to destroy these cells with a protein arsenal

UPDATE: Just noticed I didn't include many of the cells mentioned in non-specific immunity again here as I earlier promised. And I'm not going to. I'm tired and this is more than enough depth for Yr12

Natural Killer and Mast Cells

These are two cells that I should have mentioned in the last essay but I should also include in the next. Instead, I’ll write about them here and leave them in limbo between the two articles.

Natural Killer Cells

Natural Killer (NK) cells are involved in hunting down and killing the host’s own cells that are either infected by a virus or are cancerous. Like T-cells and B-cells which we shall discuss in specific immunity, NK cells are lymphocytes, and all three of these cells arise due to the differentiation on a cell called a lymphoblast. While many of the cues other cells previously discussed used to find pathogens are chemical, NK cells look at differences in the surface of host cells to determine which are infected or tumorous. A cell that is infected by a viral pathogen release stress molecules, called cytokines, and the NK cells will zero in on these via chemotaxis. Both cytokines and interferons trigger NK cells into activation. Tumour cells signal the NK cells in a different manner. The tumour cells produce less Class 1 MHC markers than regular cells (we’ll get to MHC when we look at Specific Immunity) and in response to these low levels of MHC markers the cell is attacked.

So how do NK cells destroy virally infected and tumorous cells, you ask? They do this chemically in a two-step process. NK cells are granular and contain several types of chemicals in these vesicles. When they come in close contact to one of these dodgy cells they first release perforin. This creates pores in the cell membrane by which the second chemical, protease, enters the cell. Protease is an enzyme that causes protein catabolism (breaks down proteins). We call these protease enzymes collectively granzymes. As opposed to most of the other cell death discussed in this blog so far they do not cause cell lysis. Lysis would spread the virus further. Instead they trigger apoptosis, cell death. The cell and all the virus particles within die.

Mast Cells

Mast cells are large cells found in connective tissue and are responsible for histamine release in response to injury and allergic reactions. They are similar to basophils in role and function. While basophils leave the bone marrow completely differentiated, mast cells leave the marrow and migrate to tissues where they mature. There are two types of mast cells, connective tissue mast cells and mucosal mast cells which I’ll discuss in specific immunity. In response to injury and chemical signals produced by and because of pathogens mast cells release chemicals, primarily histamine, which trigger the inflammatory response. Mast cells can take on the antibodies released by lymphocytes and place them on their membrane. Then when they come across an antigen act a little like a landmine.

Both mast and NK cells have roles in both specific and non-specific immunity.

White blood cells involved in non-specific immunity

This essay shall focus on the cellular components of the non-specific immune system as well as the role of some chemical responses such as histamine. Some of the cellular components of the non-specific system also have a role in the specific immune response and I will revisit them when we look at specific responses, antibodies etc.

Once I’ve completed Specific Immunity and the Lymphatic System, I’ll tie all this together using the example of a bacterial pathogen invading a cut. It will all make sense then.

In response to an emailed request, I’m going to end with a brief summary/recap similar to the one I did for non-specific immunity.

Cellular components

White blood cells are the cells involved in immune responses and are called leukocytes (leuko means white, cyto means ‘a hollow, receptacle or basket’ and refers to cells). There are many different types of leukocytes but, as general rule, all leukocytes are nucleated cells (have a nucleus, red blood cells don’t), originate in the bone marrow where they differentiate from stem cells, have a role in the body’s immune system and (this is pretty cool) are capable of independent movement. Yep, they creep around in a very similar manner to amoebas, through blood and tissue.

Some of these cells are termed phagocytes. Phage means ‘to eat or digest’, so a phagocyte is a cell that eats or digests stuff. This is a good little summary of how they work in general: phagocytes The two main phagocytic cells are neutrophils and macrophages, both of these I’ll get to later.

Leukocytes are broadly grouped into two main groups based on morphology. There are Granular Leukocytes, which have visible granules in their cytoplasm and a nucleus that is irregularly shaped, and Agranular Leukocytes, which as the name suggests, does not have granules in the cytoplasm. The agranular leukocytes also have a more typical round nucleus.

Granular Leukocytes

These are your ‘phils. Neutrophils, Eosinophils and Basophils. The ‘phils are named because the ‘like’ stuff; ie they are phillic for different things.

Neutrophils are the most numerous of the leukocytes comprising between 33 – 75% of all white blood cells in the blood depending on the species of mammal examined. Neutrophils are the first cells to respond to a pathogen, and after about 6 hours are gradually replaced by macrophages at the site of the infection until, after about 48 hours, they are completely replaced. The name neutrophil (neutro means neutral, phil means loving) comes from the fact that granules found within their cytoplasm are pH neutral. Neutrophils primarily hunt down invading bacteria and fungi and engulf these cells, attacking them with a diverse and powerful chemical arsenal contained within those granulated vesicles. The process they use to find these pathogens is called chemotaxis. Chemotaxis is the directed movement of a cell along a chemical concentration gradient. They sniff them out in a similar way that a male moth finds a female (read the Pheromones essay). They are primarily active in tissues, not the blood. Neutrophils grow from stem cells within the bone marrow and once mature do not differentiate again or divide. They have about a two week life span and most neutrophils don’t leave the bone marrow but are held back as an ‘in case of emergency’ supply. When they die within tissues at the end of their two week life span they release compounds that act as powerful fungicides.

Eosinophils

Eosin is a dye used to stain cells. Eosinophils respond well to this stain and are therefore named after their ‘love’ of this stain. Like all the cells discussed in this essay they differentiate from stem cells in the bone marrow then spend the rest of their ‘life’ in the blood or gut lining. Their primary role is to defend against parasitic organisms such as worms. These comprise about 1-3% of the body’s leukocytes. Again, it’s the chemicals contained within the granulated vesicles that are used to attack the parasites. When abnormal levels of eosinophils occur in the blood they can have an adverse effect on the body. Conditions such as asthma are triggered by eosinophils.

Basophils

Basophils are quite rare in the leukocyte population, comprising less than 1% of the total number. Basophils are transported by the circulatory system and are found in blood and tissue. They are poorly understood when compared to other leukocytes, however, we know they are responsible for the release of histamine and herapin, two chemicals I will get to later.

Agranular Leukocytes

There are two types of agranular leukocytes: monocytes and lymphocytes. Lymphocytes are primarily involved in the specific immune response so I will talk about them in the Specific Immunity essay. For the next little while, I’m going to rave about monocytes.

Monocytes aka Macrophages

Like the ‘phils monocytes originate in the bone marrow. They enter the blood stream and then migrate into different tissues where they differentiate into what we call macrophages. There are several different types of macrophages that do slightly different things, but primarily these are large phagocytes involved in the ingestion and destruction of pathogens. They are also involved in wound-cleaning (the attack of pathogens entering a wound), inflammation, have a regulatory role in insulin production. But for Yr12 and for non-specific immunity, you need to know that they are large phagocytes that are found in the blood and tissue.

As you can see, several of these cells have a role in both specific and non-specific immunity. Both specific and non-specific responses occur in reaction to a pathogen, usually simultaneously. I will revisit several of these leukocytes when discussing specific immune responses.

Non-cellular Components

Platelets

Platelets are cellular fragments that are found floating in the blood. They have two main roles: they aid in blood clotting at the site of a wound and they release histamine. When exposed to air at the site of a wound, platelets break apart releasing a series of chemicals. One of these helps form thread-like fibrin, which in turn forms a net-like mesh that inhibits blood flow. This hardens into a scab, preventing blood loss and creating a barrier.

Other chemicals released by the breakdown of platelets include histamine which I shall discuss now.

Histamine

Histamine is a protein based chemical that is involved in the inflammation response by causing vasodilation, increasing blood flow to the site of infection and causing the blood vessels to become permeable. This allows more leukocytes to reach the invading pathogens. Leukocytes are also attracted to the site because of the chemotaxic effect this chemical has. Histamine is released by many of the cells already mentioned and some you are yet to meet. Sometimes these cells attack things like pollen causing a massive release of histamine leading to hayfever. It is histamine that makes a mosquito bite red , swollen and itchy. We then take antihistamines. I’ll talk about this later.

Putting it all together

• ·         There are many types of leukocytes, some eat pathogens some, attack them with chemicals, some release chemicals such as histamine that increase blood flow and attract more leukocytes to the site of the infection.
• ·         Many leukocytes have a role in the non-specific and specific immune responses
• ·         There are chemical responses, such as histamine release, which also help fight infection but can itself become a problem

Hope this helps!

Non-specific Immunity

Over the past three blogs I’ve briefly spoken about the things that can make us sick and some of the issues arising from our treatment of these diseases. This essay is going to briefly look at the generic types of defences the human body has against invading pathogens. Next week I’ll start looking at specific defences and responses to pathogens. In vertebrates, non-specific immunity includes physical barriers, physiological mechanisms, chemical mechanisms, phagocytes and inflammation.

First line of defence

Barriers, physical and chemical

The first line of defence our body has against the hoard of invading pathogens is barriers. Our major barrier is the skin. The immediate layer of cells exposed to the external environment are dead. Pathogens need to get past these dead cells to the living cells beneath. This provides a physical obstruction and prevents pathogens entering our bodies. On the surface of our skin are many, many naturally occurring, beneficial bacteria. These also help by occupying all the available space on you skin’s surface so when a nasty little pathogenic microbe lands on our skin it is out-competed by the good guys. All available resources, including space, are taken. These natural non-pathogenic bacteria are also found in the gut and vagina as well as on the external surface. When a cut becomes infected, this is because there is a break in the skin barrier allowing a pathogen to enter. Our skin is generally acidic and has a coating of oils, lipids, that help create an environment unsuitable to many potential pathogens.

Other barriers include the mucus lining of your nose and throat, lungs and gut and this provide an obstacle to pathogens inhaled or ingested. Another powerful barrier is stomach acid, which destroys many pathogenic organisms you may have swallowed. Chemical barriers also exist. Your tears contain the enzyme lysozyme, which is also found in sweat and in many of your body’s tissues. This enzyme causes lysis in invading pathogens, destroying them.

Second Line of Defence

When we talk about second line of defence it is not a list of things that happen in a certain order. These usually happen at the same time and often one response makes another more effective.

Fever

Despite our best efforts, a pathogen manages to get past our barriers. There are then a series of non-specific responses our bodies go through to try and fight off disease. Fever is one of these. In response to the pathogen, macrophages – which we shall learn about in a while – release chemicals that cause the hypothalamus to reset the body’s thermostat to an elevated temperature. This aids recovery by killing some pathogens, facilitating the death of infected cells and increasing the activity of some lymphocytes and phagocytes – which we will also learn about in a bit. Fever can also be triggered by toxic by products of some bacteria such as pyrogens, however, the effects of elevated temperature on the bacteria is similar.

Protein based responses

Let’s say that the pathogen that invaded you was viral and has invaded your cells in the manner described in previous blogs. Another non-specific response your body undertakes is the release of antiviral proteins called Interferons. Interferons, as the name suggests interferes with stuff. In this case interferons interfere with virus replication and stimulate macrophages to come along and eat the infected cells. One other incredibly beneficial thing they do is they make non-infected cells more resistant to viral infection. Again, we’ll talk about this in a future blog.

I’m going to stick with proteins and talk about Complimentary Proteins. There are about twenty of these originally synthesised in your liver and are found floating around in your blood in an inert state. They become active when they come into direct contact with a pathogen. Another trigger for their activation is when antibodies and antigens combine (future blog). They defend us against pathogens in four main ways. They cause cell lysis in pathogens – our immune system really likes lysis as a response ; they can coat the pathogen which makes it easier for phagocytes to recognise and engulf them; they attract a type of cell called leukocytes to the area of infection to attack the pathogen; and, finally, they trigger the release of a chemical called histamine, which we will soon get to, and is involved in the inflammatory response. Complimentary Proteins are also involved in Specific Immunity and will be discussed later.

Cellular components: white blood cells and stuff

White blood cells, or phagocytic leucocytes, are a group of cells that engulf, ingest and destroy invading pathogens. They eat them!  Before we go any further, watch this: Phagocytosis

I’m going to talk about the cellular components of our non-specific immune response before returning to some more physiological and chemical responses.  I’ve mentioned phagocytes, macrophages and leukocytes so far. There are many more including: Lymphocytes, Basophils, Neutrophils,  Mast Cells & Natural Killer (NK) Cells. I’ll write a short essay about all these dudes plus a few more later. What you need to know now is that phagocytic cells originate in bone marrow and destroy pathogenic cells by eating them. I will expand on this in future essays. Pinky promise.

Inflammatory Response

Inflammation is when there is swelling and usually a localised temperature rise in an area of infection. The term for this is edema. This happens because enzymes and hormones such as serotonin are released as a response to a pathogen (I keep saying this but it will be in the next essay!). These compounds cause the arterioles to dilate and become ‘leaky’. There is increased blood flow to the site of infection transporting a greater number of defensive cells and compounds and as these arterioles become permeable (leaky), these cells and compounds move out of the blood and into the interstitial fluid to the site of infection where they attack the pathogen.

One of the compounds that cause the permeability and dilation of the blood vessels is histamine. We will look at where this comes from and exactly what it does in the next essay. (I’m building this next essay up. Hope it’s good!)
Inflammatory Response 

A quick recap

Our first line of defence is barriers, both physical and chemical. If these barriers are breached we have a second line of defence. This creates a hostile environment for the pathogen (fever) causes the release of chemicals that inhibit the pathogen’s functioning and cause phagocytic cells to eat them. The second line of defence also changes conditions within the body to increase blood flow to the site of infection, which in turn brings defensive cells and chemicals to the area.

The next blog will cover: the cells involved in our non-specific immunity including platelets and the role and production of histamine. I’ll put it all together and discuss our response to a pathogen infecting a small cut.

Until then, here is some Dave Graney for you

Vectors

A vector is something that transmits a pathogen but isn’t itself a pathogen. The classic example of a vector is the mosquito. Later we will look at vectors as things used to transmit genetic information from one organism to another in genetic engineering but when discussing disease a vector transmits a pathogen.

A mosquito itself is merely annoying. It buzzes in your ear just when you are on the point of sleep waking you and maybe, if you don’t notice, lands on you and draws some blood. Or rather, she does, leaving a small, itchy bump. It is the female mosquito that feeds on humans and other mammals as she needs the nutrients from blood to develop her eggs. Males and non-pregnant females are actually vegetarians! Generally, a mosquito is nothing other than irritating. Unless of course she happens to be a vector for a disease such as Malaria, or Ross River Fever, or Dengue Fever or Yellow Fever, or Japanese Encephalitis or... Mosquitoes are vectors for many, many diseases. Malaria is spread by the mosquito vector but is actually the protozoan, Plasmodium, that causes the disease. I’m not going to discuss the life cycle of plasmodium or what it does to the human body, this can be found in most textbooks. However, I will mention that according to WHO in 2008 there was almost a quarter of a billion (247 million) cases of malaria globally resulting in approximately a million deaths. Most of these deaths were in African children.

One of the most important ways to stop the spread of diseases such as malaria isn’t to target the plasmodium, instead it is to control the mosquito. Remove the vector and the disease’s spread is contained. This is the main focus of global anti-malarial programmes.

The mosquito is not the only vector though. There is a huge catalogue of animal vectors that include insect, mollusc and vertebrate. Bubonic plague is spread by fleas, bats are vectors for the Hendra virus, dogs, monkeys and other mammals can spread rabies but the example I would like to finish with is a case that occurred in Sydney last year (2010). I don’t know what the inspiration was, maybe alcohol, Jack Ass movies or a combination of both, but boys being boys one mate dared another to eat a slug. Unfortunately for the slug-eater, this slug was a vector of a rat lungworm, a nematode that causes a rare type of meningitis. It left him fighting for his life with doctors hoping his immune system would fight it off.
Malaria Life Cycle 1
Malaria Life Cycle 2 

We're in serious trouble

We’ve only been able to treat bacterial infections for the past 70 years or so. Other than our natural defences, which will be the subject of my next blog, we had no means to fight off these infections. None of our medicines were effective against bacteria. Then came the discovery and use of penicillin, first widely used by Allied troops during WW2. This discovery led to a class of drugs we refer to as antibiotics and these have revolutionised how we treat disease. Before this, what we see as minor, easily treated infections could often be fatal.

Penicillin and antibiotics were seen as a panacea. Until chinks began to appear in our medical armour. Let me start this with the story of syphilis. That is syphilis the sexually transmitted infection, not Sisyphus, the man from Greek mythology. Apart from sounding similar these two have a lot in common as we shall soon see. Bear with me. Soon after the use of penicillin to treat syphilis in hospitals, doctors noticed a strain of syphilis had emerged that was resistant to treatment by penicillin. The new uber-medicine was not as effective as thought. Now, not all bacteria were as susceptible as when treatment with penicillin was first used. Why? Bacteria reproduce rapidly via binary fission. One becomes two, then four, then eight. Like this. You get the picture. And due to binary fission they are all clones. Except for the occasional, rare, genetic mutant. As we will discover in Unit 4, which is just around the corner, often these mutations lead to death or suboptimal functioning but sometimes the mutation causes the organism to have an advantage. The competitive edge in the case of this bacterium was resistance to penicillin. When hit with a dose that killed all its non-mutant siblings, this bacterium survived. And reproduced passing that trait for resistance on to its daughter cells. And soon a strain had evolved that was resistant to treatment. But here comes the interesting part. While bacteria reproduce asexually, they also perform an incredible evolutionary act, they swap genes in an act called conjunction. Two bacterium can come together and exchange genetic information. It’s like a brunette going up to a red-head and taking a copy of the red-head’s gene for hair colour, while the donating a gene for lactose tolerance. The brunette now expresses the red-hair phenotype and the red head can now tolerate lactose. A resistant bacterium could, did and still does come in contact with non-resistant bacteria and swap genetic information, passing on this gene for resistance. New mutations can rapidly spread throughout populations. The drugs we use became less effective, so we would use a different antibiotic. Successfully at first, then, over time, less so. Hmmmm, a strain now resistant to two treatments. That’s OK, we have another drug...

Then humans come along and start over using and misusing antibiotics. Prescribing antibiotics for viral infections, using them at the wrong dosage level, or not for long enough. Placing antibiotics into the food we give farm animals. How many of you have started a course of antibiotics and not finished them? Every time you do this you are establishing the perfect evolutionary pressures for drug resistance to evolve. And it has. Rapidly. Each year nearly 500,000 cases of multi-drug resistant tuberculosis are diagnosed. Half a million cases that are resistant to all known treatments. 150,000 fatalities occur as a result. According to WHO extensively drug-resistant tuberculosis has been reported in 64 countries to date.
Many articles in the mainstream media refer to the 'superbug NDM-1'. A bacteria that is resistant to all of our medicines. This is pretty scary but it is also wrong. NDM-1 isn't a bacterium, it's a gene. And this gene is readily passed from one species of bacteria to another, through bacterial conjunction termed horizontal gene transfer (the passing of genetic information to an organism that is not a decendant). The media do have it right about one thing though. Bacteria that have the NDM-1 gene are resistant to all treatments we have available.

But it is not just bacteria. Plasmodium, the protozoan that causes malaria, is also developing resistance to many forms of treatment. Areas of Thailand, Burma, Laos and Cambodia now have malaria with resistance to some of the most effective treatments and preventatives. As do other regions in the world.

Anti-viral treatments for disease such as HIV/AIDS have been shown to be losing their efficacy as these viral strains evolve into new types as a direct response to the drug treatment. In a recent article I read, which I have attached, the idea of a world in the not-too-distant future where disease is resistant to our treatments is suggested by WHO. We will potentially be in a situation where ‘minor’ disease become fatal again. Scary shit.

I mentioned a Greek guy at the start with a name similar to a sexually transmitted disease, Sisyphus. Sisyphus was cursed to spend his life pushing a bolder up a hill and just when he would near the top the bolder would roll to the bottom and he would be back where he started. As we look at drug resistant syphilis taking us back to where we were 70 years ago I think syphilis and Sisyphus have more in common than similar sounding names.

http://www.abc.net.au/news/stories/2011/04/07/3185138.htm

UPDATE 15/5:
Todays's RadioTherapy program on 3RRR had an interesting discussion on NDM-1 and other bacterial infections. Listen to it here while studying