3D printing lab ware

I’ve been interesting in 3D printing and its application in the lab for a while now. I’ve argued elsewhere online about how I think that a 3D printer is a smart move for any lab or department, offering a handy way to easily produce a wide array of custom lab equipment. I’ve also posted on this blog in the past about my own use of 3D printing to make immune molecules and my first custom plasticware – an adapter to allow 50 ml conical use with a 15 ml tube rotater.

However I’m lucky enough to be in a lab with a PI who also sees the potential of 3D printers for a biology lab – so he bought one! This has given me more leeway to play around designing labware, as I can squeeze prints and measurements to refine models in between experiments.

I thought I’d start simply with the basics; tube racks. Or more specifically, tube holders which can be easily configured in different arrangements into racks (e.g. using something like Tinkercad, which I used to make the models). So far I’ve made holders for (micro-) centrifuge tubes of the three tube sizes most important to a wet lab biologist: 1.5 (2), 15, and 50 ml.

All of these STL models are freely available on my Thingiverse page, as are the few larger racks I’ve made and tested out, along with a few other bits and bobs. I encourage those of you out there with printers to try them out - please let me know if you do. 

More importantly, I’d invite everyone to think about what tasks in the lab could be made easier, quicker, or even possible, through the addition of pieces of plasticware that don’t currently exist. Think about them, then find someone with a printer and have a chat about making them real!

DNA in different cells, preventing autolysis and foetal cells in vaccine production

Continuing on the theme from my last post, here's a selection of my answers to recent questions that I saw on Reddit which I thought were interesting.

Is every cell [in our body] carrying the same DNA?

"The standard answer is usually yes, apart from...

• Mutations are the most obvious differences between cells, which usually comes up when this question gets asked. This happens in non- and pre-cancerous cells, but as genetic instability is a common property of cancer it tends to be much worse in cancer cells. It's also worth remembering that doesn't just mean the wrong base of DNA at a position, but can include insertions, deletions and duplications, not just of a base or two but potentially up to whole or huge chunks of chromosomes, even fusion between different chromosomes (which can make fusion proteins with novel functions). This is why you sometimes see aneuploidy (an atypical number of chromosomes) in some cancer cells.

• Gametes (i.e. sperm and egg cells, and their precursors). These germline cells aren't always grouped in when people ask this question, but they are definitely 'in our body' so I am! Not only are these cells haploid (only containing one copy of each chromosome) but during meiosis (the kind of cell division that produces them) the chromosomes undergo recombination, so the pairs of each chromosome will swap bits; this means that the gametes you produce won't have the same versions of the chromosomes that you inherited from your parents, but something in between. This helps keep our gene pool diversified.

• My particular favourite, as it's what I work on - adaptive immune cells. There are potentially infinite different kinds of viruses, bacteria and fungi etc which could infect us and do us harm, which we need to protect ourselves against. This is pretty hard to do with a finite, static genome, as the pathogens could quickly evolve around it. What we evolved is a branch of immunity - our adaptive immunity - which anticipates this huge diversity of infectious agents and responds in kind, by pre-emptively shuffling bits of DNA around to make millions of different receptors, to try to recognise as many different (non-self) things as possible. This happens in developing B-cells and T-cells, which is used to make B-cell receptors (which when released in a soluble form become antibodies) and T-cell receptors (BCRs and TCRs). This is acheived through a process called VDJ recombination, named after the segments of DNA which get recombined together to form a new gene. This provides the basis for how our immune systems learn - if you get infected with something that a particular TCR can bind say, that T-cell will divide and differentiate, which means that the next time you get infected with it those T-cells are already in place, waiting to go and fight it off.

• Microchimerism. In biology a chimera is an organism that contains cells from more than one zygote (fertilised egg). This happens in labs lot for various reasons (which is why you get mice like the one on the right, made up of cells from black-furred and white-furred mice zygotes), but it also happens naturally at some rate (with only a few cells making it microchimerism). The most common example we know of (at least for us placental mammals) is foetal chimerism, where cells from a developing foetus pass through the placenta and establish themselves - sometimes permanently - in the mother (which may help prevent her immune system rejecting the foetus). There are case reports where cells can go the other way (so say cells from the mother can be detected in the circulation of her child), although I think this mostly occurs when one or other seems to have some genetic condition. There also of course exist actual human chimeras - anyone who's ever had an organ or bone marrow transplant will have a large number of cells in which the DNA will be very different (although hopefully not at the MHC alleles, which mediate rejection), as it all came from the donor."

Why aren't cytoplasmic granules of natural killer cells degraded by the potent enzymes that they contain?

"There's a number of different mechanisms by which cytotoxicity is controlled. There's also some disagreement, and a lot we still don't know (which is always a good sign that someone's asking a good question!).

In terms of perforin specifically, there's two factors that come to mind that are probably the best answers to question. Note that they also all largely apply to cytotoxic T-cells as well as NK cells, as they use the same basic cytolytic machinery:

• Perforin requires calcium to form pores and insert to membranes, at concentrations that are typically only found outside (and not inside) cells. This means that the perforin should only work once its been secreted across an immune synapse.

• It also requires a pH above ~6, in order to adopt the correct conformation. Stored lytic granules are pretty acidic, which helps maintain the contents inactive (unless they are release and the acid is diluted out)

These points are covered pretty well in this detailed review, if you're interested. There are a number of other possibilities - like there may exist certain chaperones or regulatory proteins which help keep the perforin inactive, or that cleavable post-translational modifications may help keep in an inactive form. That latter one was quite notable, although it seems opinion has moved towards the glycosylation actually helping guide perforin along through the ER quickly during synthesis, to stop it lingering in calcium-rich/pH neutral compartments where it might do some damage."

[How is the HepA vaccine ethical when it uses MRC-5 cells?]
(NB: I think that this was probably just an anti-vaxxer account trying to colour people's views against vaccines given that it's the sole post from this user in a sub that gets high traffic from anti-vaccine proponents, but it is a valid question that a quick google doesn't produce many good answers for, so I thought it was worth addressing.)

"I'm presuming the ethical problem you're having is that some people have here is that the vaccine production involves MRC-5 cells, which are derived from an abortus foetus?

First off it's worth correcting one thing - the vaccine won't actually contain MRC-5 cells - it just uses the cells to grow the virus, which will then be inactivated to make the vaccine. Remember that viruses cannot grow on their own, they need to use cells to do so, so it's impossible to make an inactivated viral vaccine without cells. (It's also mostly impossible to make protein-subunit vaccines without cells, although you can use non-mammalian cells like bacteria or yeast in that case.)

However if your issue is with the fact that foetal cells were used at all, that's slightly trickier, and your interpretation of the facts may change depending on your viewpoint.

My view point is that early stage embryos are not sentient, and certainly not sapient, and aren't really 'people' as such (there's actually some great discussion on this in a thread that came up earlier in /r/biology today, which deals with this topic very well). MRC-5 cells came from a 14-week old foetus that was aborted for psychiatric reasons, well before the demonstrably concious stage of development.

Another way to look at it is like organ donation. If a baby died (for whatever reason), would you think it was unethical to transplant any organs from that child to others to save their lives? Despite a tragic thing happening, one, two, maybe even three other lives might have been saved or prolonged. If that's acceptable to you, consider that the foetus cells have basically been donated, more than forty years now, to an effort to protect millions of people from a horrible disease. Over 188 million doses of Hep A vaccines have been given; as just under 1% of infected people would be expected to die, a rough estimate would be that Hep A vaccination has probably saved at least 17 million lives (and prevented a great deal of non-fatal yet horrible disease).

(In fairness I'm not sure how many of those doses used MRC-5 derived vaccines, but then these cells are also used in the production of vaccines for other diseases too.)

From a different perspective, even if you don't accept the evidence that foetuses aren't sentient, even if you don't care and think that humanity begins at conception, even if you don't buy the organ/tissue donation analogy, there's a final pragmatic argument: we have the cells, and they work. If we want to stop people contracting, suffering or dying from preventable diseases, we need to use the tools that we have available. Hep A is a nasty disease, and we have a highly safe and effective vaccine - to my mind, advising people to not get the vaccine (in the absence of an equally good alternative) would be a much more unethical alternative."

The Inner Army Crept Up On Me

Tonight saw my maiden voyage into the world of giving public engagement talks about science. It came as a particular surprise because I thought I was just the delivery boy.

The event was The Inner Army, an hour of immunological discussion at the CheltenhamScience Festival, with Professors Susan Lea and Clare Bryant presenting.

I'd been approached by the British Society of Immunology (BSI) about perhaps 3D printing some immune molecules for the talk, after seeing some of my previous models. I'm a big public engagement proponent, and a big fan of the festival, having blogged about it for my university in the first year of my PhD, so I leapt at the chance to help out*. Plus it gave me a nice chance to show off the demonstrative use of my models (and help justify the time I've spent making them!).

Little did I know that on arrival the chair for the event, the illustrious Vivienne Parry (who was originally an immunologist herself) decided to get hold of an extra chair and mic and throw me up on stage as well!

It was – I think – a fun and informative event. However, I can take no credit for any of it (except for most of the models): I choked! Give me small numbers of people and I'll happily ramble on about adaptive immunity to the cows come home. Sit me down next to two prominent professors in front of ninety people and ask me to talk about structural innate immunity and it turns out I get a bit tongue-tied. Live and learn!

I was very happy to see how involved the audience seemed to be with the models (particularly the first row, which seemed to be largely composed of BSI and British Crystallographic Association (BCA) members), which was very gratifying. It was also lovely to see the general public engaging with immunology in person, which isn't something I get to see on a daily basis.

For the moment I'd be lying if I said I wasn't more comfortable on the other side of the spotlights blogging about the event (which I suppose is what I'm doing now). This isn't something that comes naturally to me, or (I suspect) a lot of science post-graduates; it just isn't a skill we get to practise much in our day-to-day workings.

However, engaging with the public remains an important task for scientists, both to justify the tax-payer money we spend and to share the love of uncovering the secrets of the universe with fellow curious minds, so I shall definitely try again. Next time though, I plan to stick to TCRs.

* NB I plan to share photos of the models I made for the speakers in a future post, but as the models dispersed to the relevant speakers after the talk I have to dig them

Max Perutz 2012 entry

Wow, I hadn't realised how long it's been since my last blog post - I blame the copious amount of food I ate over the holidays, and then the giant pile of work I've been doing since.

So, in order to keep the ball rolling, I thought I'd post a bit of science communication I wrote for my entry in last year's Max Perutz writing competition.

I was going to write an entry for the recent Euro-PMC competition, but I only got as far as deciding on the theme of the pun for my title (I was thinking something cheesy like 'Genius, or geneious?').

Anyway, here's the article as I wrote it last May (I didn't win).

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Unravelling the secrets of our immune system

Sometimes we only realise how important something is when it goes wrong. In the case of adaptive immunity, things going wrong can be fatal.

Adaptive immunity is one of the systems we have evolved to keep infectious germs at bay. It is our intelligent protection system, a biological firewall, where white blood cells patrol our bodies, keeping us safe from disease. Not only does it stop intruders in their tracks, it remembers the threats it's seen before, so it can defend against them faster the next time they attack.

There are two medical conditions in humans that reveal to us how important it is to have a working adaptive immune system. The first occurs when some children are born without working copies of genes that encode important immune molecules. This means they don't make some of the proteins that are required for adaptive immunity to develop.

Alternatively, people can lose their resistance to microbes later in life. This can happen when untreated HIV positive individuals develop AIDS, or in transplant patients who have taken suppressive drugs to prevent organ rejection.

People without a functioning adaptive immune system are compromised, exposed. They are at risk from any stray infection, vulnerable to all manner of viruses, bacteria and fungi. A simple bug that might not even give you a temperature could spell death to them.

This makes it important for us to know how adaptive immunity works. This is what I do in my research; I look at a particular aspect of this system, to try and understand what a healthy adaptive immune system 'looks' like, and how it goes wrong in disease.

In order to explain my work, you have to know a little bit about how our bodies generate this powerful immunity.

Cells don't have eyes or ears, so they have to use receptor molecules on their surface to detect what's going on around them in their environment. These receptors are proteins, the blueprints for which are encoded in the genes in our DNA.

This means white blood cells could have a receptor that recognises a certain bit of a bacteria say, or the fragment of the outside of a virus. If the receptor finds and binds its target, then that cell can tell that the body is infected with a particular parasite.

The problem lies in that there are far more bugs and germs out there that could potentially infect us then there are genes in our genome. How can we have evolved ways to detect and protect against such a barrage of disease with so few genes?

Maturing adaptive immune cells overcome our finite genomes by shuffling pieces of it around, making unique receptor genes out of genetic building blocks that all our cells contain. These cells, called T cells and B cells, physically loop the DNA over itself, and then cut out the chunks in between.

This means different sections can be moved next to each other, recombining to create new genes. Incidentally, this extraordinary feature makes them some of the only cells in the body that don't share the same genome as all the other cells.

Each developing cell shuffles their DNA around independently, stitching different gene segments together in order to produce its own distinctive receptor. As there are many segments to choose from, the number of different combinations is huge.

Moreover, the DNA sequence at the join sites can be randomly altered, meaning the eventual number of possible different receptor genes is truly phenomenal. The fact that we have millions of white blood cells inside us, each bearing one of the trillions of different potential receptors, has historically kept researchers from measuring this diversity.

My project is to use DNA sequencing technology – developed during the Human Genome Project – to read as many of these uniquely generated adaptive immune genes as we can. By doing this we can characterise a person's immune repertoire, seeing how prepared their body is to fight off infection, and perhaps even see what they’ve been infected by in the past. 

The hope is that we can use this technology to understand what it is that makes a healthy human immune system. Once we know this, we can compare this to the compromised or failing immune systems that we see in infection, cancer and autoimmunity, and maybe get an insight into how to treat or avoid these conditions.

Science has brought a lot of relief to those suffering from disease, and has prevented many more from joining them. However, the challenges faced in curing our ills can only be surmounted by learning as much as possible about the way that our bodies work, as well as the diseases that threaten us. Unravelling the secrets of our immune systems is another step towards that goal.

Vaccination is literally awesome

One short thought turns into epic ramble

 I am a scientist. Or rather, I am a PhD student in training to be a scientist[1]. Either way, I love science, and I love reading and talking about it, so I thought I’d try writing about it.

  Having recently two excellent book offerings from Paul Offit[2], an American paediatrician and Professor of Vaccinology, shortly followed by the recent publication of journalist Brian Deer’s damning three-part exposé into the Wakefield saga[3], I’ve been thinking about vaccination a fair bit lately, hence my choice to write a piece about them. However, unlike a great deal of the reporting of vaccines that we’ve been bombarded with over the last two decades, I shall be weighting my article based on the credible, reliable and repeatable evidence that we have available. As such, I shan’t be pandering to the false dichotomy of vaccines vs. autism (or any other number of perceived pathologies) set up by rogue scientists, questionable personal injury lawyers, irresponsible or impressionable reporters and celebrities (which unfortunately is often then absorbed by anxious and misled parents)[4]. Instead, I am going to try to illustrate why vaccines are one of the greatest forces for good that humanity possesses, and why it’s so important that people care about them.

  Hands up if you know anyone with smallpox. No? Anyone? Of course not. That’s because vaccines are literally awesome, and no-one has smallpox anymore[5].

  Vaccines work by making use of our immune systems; in particular, the branch of these systems that we call the adaptive immune system. Adaptive immunity has evolved as a way for large, complex organisms (like us) to resist the parasitic advances of smaller, pathogenic organisms of varying complexity (such as viruses, bacteria, fungi and eukaryotic parasites), by finding them within the body and dealing with them. The key thing about adaptive immunity is that after encountering a particular bug, it remembers how it dealt with it the first time, and can then do it much better and much faster if it ever runs in to the same bug again[6].

  Broadly speaking, it does this through the generation of a vast diversity of two kinds of cells. B-cells (produced in the bone marrow) produce antibodies, which are small proteins that bind to foreign molecules (such as are found on the outside of infectious agents) and either neutralises them, or flags them up as suspicious for the second type of cell, T-cells (which mature in the thymus). T-cells come in two flavours, which can either kill infected cells directly by squirting them with self-destruct proteins, or release chemicals to orchestrate further immune responses from other cells[7].

  The general concept behind vaccines is to present someone’s adaptive immune system with either a weakened or inactivated version of a pathogen, or even just whatever bit of the microbe that the immune system happens to ‘see’.  When we immunise someone they shouldn’t get sick with whatever they’re being immunised against (as it’s not a functioning, virulent agent used), but their adaptive immune system ‘remembers’ that pathogen or molecule. Then, if this person is unlucky enough to encounter this particular bug, their immune system recognises it from the immunisation, and makes the appropriate biological response, clearing the infection and keeping the vaccinee healthy.

The UK currently encourages vaccination of children, and provides free jabs for the following eleven diseases: diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B, pneumococcal bacteria, meningitis C, measles, mumps, rubella and human papilloma virus[8]. Thankfully, looking at the 2009 uptake of vaccinations versus the estimated herd immunity requirement (which is the threshold of the population that needs to be immune to protect those who lack immunity) it seems that the diseases for which there are data surpass the lower estimate, meaning that those diseases should not be able to take root here[9]. However, seeing as these diseases are all but eliminated in the here and now it is very easy for us to take our immunity for granted, and forget what horrible sickness these pathogens cause. So, to keep things fresh in your mind, I’ll just run down a few of the delightfully horrible symptoms, complications, and possible outcomes of these conditions.

  As with a great many infections, most of these diseases start off soft, with general, make-you-feel-rubbish symptoms, causing fatigue, malaise, nausea, coughs, sneezes, and fevers both high and low. They might hit different parts of the body, with running noses, sore throats, aching heads, chests, neck, ear infections, bull necks, genital warts, or locked-jaws, maybe turning you blue, red, or (gan)grene along the way. Then you reach the difficulties; difficulty breathing, swallowing, going to the toilet, not going to the toilet, or even remaining conscious. By now we're up to the big boys of complications. Meningitis. Bacteremia or septicaemia. Blindness and deafness. Partial or complete paralysis. Encephalitis. Sterility. Birth defects and spontaneous abortions.  Oh, and don't forget the death. Death from respiratory failure, death from pneumonia, death by suffocation, death from inflammation, death by cancer, death by chocolate and yet more death, death, death[10]. All this morbidity, all this mortality, all this human suffering, misery and pain, all prevented when enough of a population is vaccinated against the pathogens that cause them.

  Granted, a lot of these more severe complications may be rare events in infected individuals, but that is not to belittle them. If a virus or bacteria only kills 0.01% of the people it infects, it doesn’t sound like much, that’s only one in 10,000 people. The only problem is, there are a lot of people in the world. The UK has about 68 million people living in it; even if only half of them get infected with this imaginary bug, a fatality rate of 0.01% still kills 3,400 people. Before vaccination and treatment, some of these diseases used to cause hundreds of thousands of deaths annually, sometimes laying waste to huge swathes of the populace. We’re lucky to live in a time and a place where such horrific diseases can be and are prevented, but we cannot take this for granted. Even as late as 2002, the World Health Organisation (WHO) estimated that globally, there were as many as 2.5 million deaths worldwide from vaccine-preventable diseases, 1.4 million of which were in children beneath the age of five[11]. It seems to me that the death of a child is one of the worst tragedies imaginable, surpassed only by the fact that so often that life could have been saved by a simple, safe, reliable vaccination.

  Clearly, vaccines are of tremendous worth in preventing and controlling infectious diseases. However, in an exciting twist researchers are increasingly looking at using vaccines to solve conditions that you might not expect.

  Among more developed populations, where health care and preventative measures are likely to be relatively strong, cancer is probably among the most feared health conditions. Perhaps the most insidious of all diseases, cancer involves the very cells of a person’s body turning against them, throwing off the shackles that control cellular growth and turning renegade, dividing uncontrollably with no regards for the host from whence they came.

  Much cancer treatment involves using drugs that non-specifically target rapidly dividing cells (chemotherapy), which hits the cancer cells, but also hits any other cells in your body that happen to be dividing (such as the parent cells of the immune, gastrointestinal, reproductive systems). Cancer vaccination works by trying to co-opt your immune system to prevent cancer, or even treat it therapeutically.

  One way in which vaccination can prevent cancer is by vaccinating against pathogens that cause or contribute to cancer[12]. If the infection that causes the cancer can’t take root, then that cancer cannot grow either. When the cancer is not due to an infectious agent, then a more direct approach can be taken. Patients can be immunised with antigens[13] that the cancer cells express, but normal healthy cells don’t, in order to provoke an immune response specifically against the cancer, a strategy which makes use of the fact that cancer cells often aberrantly express proteins (or combinations of proteins) that a normal, healthy cell wouldn’t. Alternatively, scientists have taken a craftier tactic, where they inject people with a virus they’ve modified to exclusively attack tumour cells; when these cells lyse (or break apart) thanks to this oncolytic virus, their contents spill out into the tissues of the body, providing the immune system with buckets of cancerous proteins, effectively immunising against the cancer from within.

  All the vaccines I’ve mentioned so far involve stimulating or promoting immune response against a particular target. However, it is also possible to make a vaccine that dampens or suppresses an existing immune response, a technology which theoretically could be used to treat any number of autoimmune diseases[14]. This might be achieved by targeting the immune cells that are responsible for the disease directly, or by targeting regulatory cells whose job it is to make sure that other cells don’t cause autoimmunity. This avenue could offer treatments for a plethora of conditions, from diabetes to allergies, or from MS to Alzheimer’s.

  Perhaps most surprisingly, vaccines are even being considered to fight drug addiction. That’s right, you can vaccinate against drugs. Specifically, vaccines are in development to treat nicotine and cocaine addictions. Both strategies work in a similar manner; the drug (or a chemical analogue, or look-alike) is stuck to something that’s known to stimulate an immune response. This hodgepodge molecule can then be used to immunise an addict, who then will hopefully develop immunity against the nicotine or cocaine. When they next spark up (or otherwise imbibe) the theory goes that the immune response will kick in, the drugs will get coated in antibodies and then won’t be able to carry on chilling you out or getting you high, and the addict gets less (or no) bang for their buck, before deciding it’s a fool’s game and throwing away their junk[15]. Whether you agree or not that this is a good idea, it is a good demonstration of the power of vaccination, and a good illustration of what we might be capable of if only we have the imagination[16].

    It would be remiss of me to ignore the mistakes that the field of vaccinology has made. There have been vaccines that have been ineffective, or – more rarely – even harmful. However, these incidents are largely historical, and the few incidents there have been have been thoroughly investigated so that they do not happen again[17]. It is also worth noting that the most successful vaccination strategy ever was not without risks; the vaccinia virus vaccination that eradicated smallpox caused serious complications in a very small minority of people, even killing one in a million of those who received it. However, compared to fatality rates of 20 to 60% when infected with smallpox (or even greater than 80% in children), the risk from the vaccine was by far the wiser choice[18].

Of course, even if we could make vaccines for all communicable diseases, and we could get these vaccines distributed to all the corners of the world, it would not stop these diseases in their tracks, particularly in the developing world. Vaccines are a wonder, but – as with all aspects of applied biology – they are not perfect, and require functioning immune systems in order to provide immunity. In addition to vaccination there needs to be provision of general health care and infrastructure, clean water and adequate nutrition. Even in a well-fed well-cared for society, where everyone who can be is vaccinated, there is still a chance of infection, as vaccines (as with all treatments) are not 100% effective; there will always be individuals who either are unable to get the treatment (perhaps due to some underlying immunodeficiency) or who fail to generate an appropriate immunological response. This is why it’s important for everyone who can be vaccinated to get vaccinated; once a herd immunity threshold is met, then there isn’t enough tinder of susceptible individuals for the flame of infection to ignite and spread.

 Vaccines aren’t the answer to solving the burden of disease. They’re just a fantastically important part of it. We have made tremendous advances in our understanding of life, bounding along at an exponential rate for the last 500 years or so. However, infectious disease-immune system interactions have had a bit of a head start in their development, of about 3 billion years[19]. We’ve got a long way to go to fill in the gaps in our knowledge, or even to find out what shapes those gaps are, but thousands of researchers all around the world are working hard at it, and it’s humanity that benefits along the way.

 [1] Depending on the definition you use, I may already be. Wikipedia broadly defines a scientist as one who “[engages] in a systematic activity to acquire knowledge”, or one that uses the scientific method, of which I do both. Dictionaries however tend towards requiring some knowledge of expertise, in which case proper experts might say I’m not a scientist yet. Damn dictionaries. But hey, I’m trying.

[2] Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases, and Autism’s False Prophets.

[3] Published in the prestigious, high impact journal BMJ, the articles are freely available at http://www.bmj.com/content/342/bmj.c5258

[4] In fact, just by acknowledging the existence of the anti-vaccine movement has given them more credence then their ‘evidence’ deserves (the acknowledgement makes up about 5.5% of the word count of this article, which is far greater a weighting then their contribution is to good science). There is no need to “teach the controversy”, as scientifically speaking, there isn’t one. The data is out there, it’s just up to people to read it.

[5] I was pretty tempted to end the article here, having already summed up most of my argument. You might be sorry I didn’t.

[6] This is in contrast to the innate immune system, which protects us from pathogens non-specifically, and doesn’t keep records of what it’s already dealt with, hence immunity is provided by the adaptive system. However, they are both just two sides of the same coin, and there’s a lot of interplay between the two.

[7] These types relate to CD8+ cytotoxic killer T-cells, and CD4+ T-helper cells respectively. The latter cells (CD4+) are the cells that are depleted during HIV infection, which causes the immunosuppression that occurs in AIDS.

[8]  Further vaccinations are available for certain at risk groups, such as for tuberculosis, hepatitis B, or chickenpox. Full details of the recommended UK vaccination strategy can be found at http://www.nhs.uk/Planners/vaccinations/Pages/Vaccinationchecklist.aspx

[9] The World Health Organisation provides vaccination uptake estimations by country here: http://apps.who.int/immunization_monitoring/en/globalsummary/wucoveragecountrylist.cfm. Estimates of herd immunity levels can be found at http://www.bt.cdc.gov/agent/smallpox/training/overview/pdf/eradicationhistory.pdf.

[10] You can check these out for your self at http://www.medicinenet.com, but personally I recommend doing a google image search. Nothing drives a point home like pictures of a festering brain abscess. Also worth noting that I made up one of those causes of death, but I’ll let you figure out which. Here’s a mini-glossary for some of those symptoms: meningitis, an inflammation of the meninges, the membranes the surround the spinal chord and brain tissues; bacteremia or septicaemia, bacteria present in the blood; encephalitis, inflammation of the brain.

[11] See http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5518a4.htm and http://www.who.int/immunization_monitoring/diseases/en/ 

[12] Both viruses and bacteria are implicated in human cancer formation, such as Human Papilloma Virus, HPV, or Hepatitis B Virus which cause cervical and liver cancer respectively, and Heliobacter pylori, which causes stomach cancers.

[13] An antigen is the part of a molecule which is recognised or ‘seen’ by cells of the immune system.

 [14] An autoimmune disease or disorder is when an individual’s immune system mistakenly produces an immune response against other cells of that individual, meaning that a person’s own immune system will start attacking other cells in their body.

 [15] Or they just take more and bigger hits until they start to feel something, maybe. Who knows; it’s all still in development. But it’s still damned interesting.

 [16] Along with the time, money, resources and inclination. But the imagination is the important bit.

[17] The most notorious of these in recent memory are probable the Cutter Incident of 1955, where live polio virus contaminated stocks of polio vaccine (through industrial carelessness and poor monitoring standards), and the 1976 U.S. emergency swine flu vaccination program was associated with a slightly increased risk of developing the neuropathic Guillain-Barré syndrome.

[18] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/?tool=pmcentrez

[19] Or 3 thousand million years, depending on which definition of ‘billion’ you use.

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NB This was originally posted on my Newsgrape account. I think I originally started writing about something else, for a competition, but got completely sidetracked and wandered off with this.