Monday 28 March 2011

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.