The human machine: obsolete components

The previous post in this series can be found here.

In my last post in this series I described some of the ways in which gene therapy is beginning to help in the treatment of genetic disorders. A caveat of this (which was discussed further in the comments section of that post) is that currently available gene therapies do not remove the genetic disorder from the germline cells (i.e. sperm or eggs) of the patient and so do not protect that person's children against inheriting the disease. This could be a problem in the long run as it may allow genetic disorders to become more common within the population. The reason for this is that natural selection would normally remove these faulty genes from the gene pool as their carriers would be less likely to survive and reproduce. If we remove this selection pressure by treating carriers so that they no longer die young, then the faulty gene can spread more widely through the population. If something then happened to disrupt the supply to gene therapeutics - conflict, disaster, etc. - then a larger number of people would be adversely affected and could even die.

Although this is a significant problem to be considered, it is one that is fairly simply avoidable by screening or treating the germline cells of people undergoing gene therapy in order to remove the faulty genes from the gene pool. This is currently beyond our resources on a large scale, but will almost certainly become standard practice in the future.

All of this got me thinking: are there any other genes that might be becoming more or less prevalent in the population as a result of medical science and/or civilisation in general? If so, can we prevent/encourage/direct this process and at what point do we draw the line between this and full-blown genetic engineering of human populations? This is the subject of this post, but before we get into this, I want to first give a little extra detail about how evolution works on a genetic scale.

Imperfect copies

Evolution by natural selection, as I'm sure you're aware, is simply the selection of traits within organisms based on the way in which those traits affect that organism's fitness. An organism with an advantageous trait is more likely to survive and reproduce and so that trait becomes more and more common within the population. Conversely, traits that disadvantage the organism are quickly lost through negative selection as the organism is less likely to reproduce. The strength  of selection in each case is linked to how strongly positive or negative that trait is - i.e. a mutation that reduces an animal's strength by 5% might be lost only slowly from a population, whereas one that reduces it by 90% will probably not make it past one generation. In turn, the strength of that trait is determined by the precise genetic change that has occurred to generate it.

The human machine: replacing damaged components

The previous post in this series can be found here.

The major theme of my 'human machine' series of posts has been that we are, as the name suggests, machines; explicable in basic mechanical terms. Sure, we are incredibly sophisticated biological machines, but machines nonetheless. So, like any machine, there is theoretically nothing stopping us from being able to play about with our fundamental components to suit our own ends. This is the oft feared spectre of 'genetic modification' that has been trotted out in countless works of science fiction, inexorably linked to concepts of eugenics and Frankenstein-style abominations. Clearly genetic modification of both humans and other organisms is closely tied to issues of ethics, and biosafety, and must obviously continue to be thoroughly debated and assessed at all stages, but in principle there is no mechanistic difference between human-driven genetic modification and the mutations that arise spontaneously in nature. The benefit of human-driven modification, however, is that it has foresight and purpose, unlike the randomness of nature. As long as that purpose is for a common good and is morally defensible, then in my eyes such intervention is a good thing.

One fairly obvious beneficial outcome of genetic modification is in the curing of various genetic disorders. Many human diseases are the result of defective genes that can manifest symptoms at varying times of life. Some genetic disorders are the result of mutations that cause a defect in a product protein, others are the complete loss of a gene, and some are caused by abnormal levels of gene activity - either too much or too little.  A potential means to cure such disorders is to correct the problematic gene within all of the affected tissue. The most efficient means to do that would be to correct it very early in development, since if you corrected it in the initial embryo then it would be retained in all of the cells that subsequently develop from that embryo. This is currently way beyond our technical limitations for several reasons. Firstly, we don't routinely screen embryos for genetic abnormalities and so don't know which ones might need treatment. Secondly, the margin for error in this kind of gene therapy is incredibly narrow as you have to ensure that every single cell that the person has for the rest of their life will not be adversely affected by what you do to the embryonic cells in this early stage - we're not there yet. Thirdly, our genetic technology is not yet sophisticated enough to allow us to remove a damaged gene and replace it with a healthy one in an already growing embryo - the best we can do it stick in the healthy gene alongside the defective one and hope it does the job. There is certainly no fundamental reason why our technology could not one day reach the stage where this kind of procedure is feasible, but we are a long way off yet.

So, for the time being what can we do? Well instead of treating the body at the embryonic stage, the next best approach is to treat specifically the affected cells later on in life.  This involves identifying the problematic gene and then using a delivery method to insert the correct gene into whatever tissues manifest the disease, preferably permanently. This is broadly known as gene therapy, and is one of the most promising current fields of 'personalised' medicine.  

The human machine: finely-tuned sensors

The previous post in this series can be found here.

All good machines need sensors, and we are no different. Everyone is familiar with the five classic senses of sight, smell, touch, taste, and hearing, but we often forget just how amazingly finely tuned these senses are, and many people have little appreciation of just how complex the biology behind each sense is. In this week's post, I hope to give you an understanding of how one of our senses, smell, functions and how, in light of recent evidence, is far more sensitive than we previously thought.

Microscopic sensors

The olfactory system is an extremely complex one, but it is built up from fairly simple base units. The sense of smell is of course located in the nose, but more specifically it is a patch of tissue approximately 3 square centimetres in size at the roof of the nasal cavity that is responsible for all of the olfactory ability in humans. This is known as the olfactory epithelium and contains a range of cell types, the most important of which is the olfactory receptor neuron. There are roughly 40 million of these cells packed into this tiny space and their job is to bind odorant molecules and trigger neuronal signals up to the brain to let it know which odorants they've detected. They achieve this using a subset of a huge family of receptors that I've written about before, the G protein-coupled receptors (GPCRs). These receptors are proteins that sit in the membranes of cells and recognise various ligands (i.e. molecules for which they have a specific affinity) and relay that information into the cell. There are over 800 GPCRs in the human genome and they participate in a broad range of processes, from neurotransmission to inflammation, but the king of the GPCRs has to be the olfactory family, which make up over 50% of all the GPCRs in our genome.

The human machine: picoscale engineering

The previous post in this series can be found here.

Over the course of my 'human machine' series of posts I've tried to convey the intricacy and beauty of our biological engineering, and demonstrate that we are incredibly well-engineered machines whose complexity and originality go all the way down to the atomic level. In this week's post, I will be exemplifying this with one of the best cases that I can think of; how we transport oxygen around our bodies. I feel that this is a great story to tell because it is one that most people might think that they know well, but that actually is far more complex and subtle than it may appear, and that demonstrates how our lives are highly dependent on perfectly evolved processes working on the subatomic scale.

"It will have blood, they say."

I'm sure that anyone reading this blog is fully aware that we need oxygen to survive (although if you want a more detail explanation of exactly why then I direct your attention to a previous post of mine available here), and anyone remembering their primary school biology will know that oxygen is transported around the body by the circulatory system, i.e. the blood. Most of the cells within your blood are the famous red blood cells (to distinguish them from the immune cells - the white blood cells), which are, unsurprisingly, responsible for blood's distinctive colour - earning them the respect of horror movie aficionados everywhere. You have roughly 20-30 trillion red blood cells in you as you read this, each of which is about 7 microns (i.e. 7 millionths of a metre) in diameter. They shoot around your body, taking roughly 20 seconds to make one circulation, and have just one job; take oxygen from the lungs (where there's lots of it) to the tissues (where there's not). So specific are they to this job that they don't even bother having a nucleus, thereby removing all possibility of them doing anything else. 

Human red blood cells - you make 2 million every second!

The human machine: non-standard components

The previous post in this series can be found here.

In a previous post I alluded to the origins of mitochondria, the tiny chemical power plants found within all our cells. These hard-working machines are responsible for aerobic respiration, which is the way in which the vast, vast majority of the energy you use is released from the chemical energy in the food you eat. The way in which they do this is very cool, involving currents of electrons and protons in a manner very similar to standard battery. If you're interested in this then I direct you to my earlier post on this topic here, but in this post I will be discussing a rather odd thing about mitochondria: they're not in fact human...

What do I mean by this? Well, obviously they are, kind of, human since they're inside all of us, they're born with us and die with us, they don't wander off on their own to live an independent life elsewhere. Nonetheless, mitochondria are different to the rest of the machinery in our cells - they have their own genomes, they regulate their own replication, they make proteins their own unique way - in fact they closely resemble lifeforms that we might consider to be evolutionary polar opposites of ourselves: bacteria. That sounds pretty odd, right, that there might be bacteria living inside our cells that somehow want to help us by churning out energy for us to use? Seems pretty implausible, but there is a mountain of evidence supporting it.

If it barks like a bacterium...

Firstly, mitochondria do, kind of, look like bacteria. They are about the right size to be bacteria (0.5-1 micron in length) and have internal structures similar to many bacteria. The main difference is that mitochondria possess two membranes and no cell wall, whereas most bacteria for one membrane and a robust cell wall. The inner membrane of mitochondria is also far more ruffled than most bacteria, creating a much larger surface area - this is highly important for reasons that I'll come to!

Spot the difference: mitochondria on top, bacteria on the bottom. 

The business of ignorance

Those of you who read this blog regularly may well be waiting on a post on the latest developments in stem cell therapy that I promised recently. I want to reassure you that this is coming, don't fret! However, a story has come to my attention of late that made me reconsider the topic of this post. The story has shocked, saddened, and angered me in equal measure and I felt that it needed sharing with you, dear reader, as it is a prime example of why the public engagement of science is a vitally important task. Given Shaun's heroic efforts last month to bring us the news from the latest  Cosmological Perturbations post-Planck conference, I thought it was fitting to exemplify just why this kind of science reporting is important.

I was first made aware of the story that shocked me so much by an excellent Panorama documentary that aired last month (UK readers can still watch the show online here). For those non-Brits amongst you, Panorama is a highly respected investigative documentary show produced by the BBC, not the kind of programme that bothers with unimportant issues. You can imagine, therefore, that my interest was piqued by the title "Cancer: hope for sale?". I had expected perhaps an exposé on some counterfeit medication ring, or maybe a look at a big pharmaceutical company pushing drugs through ahead of time in countries with lax regulation laws. I could not in my wildest dreams have imagined just how scandalous the actual story turned out to be, nor could I believe that this was the first I was hearing about it.

The main protagonist of this story is a Polish doctor called Stanislaw Burzynski - I had never heard of him before last week but he may be more familiar to those of you from the States. Dr Burzynski has been running a clinic out of Houston, Texas for over 30 years that offers treatment to cancer sufferers and has had thousands of patients through its doors. Burzynski's treatment is based on the notion that there exists a group of peptides (very short proteins) that exist within our bodies and have an immunoprotective effect against the development of cancer and other diseases, which he has given the reassuringly scientific-sounding name 'antineoplastons'. Cancer sufferers, it is claimed, can be treated by oral and intravenous administration of cocktails of various antineoplastons alongside a number of other components of the medication, such as steroids and anti-inflammatories. The antineoplastons used at the Burzynski clinic used to be purified from human urine but are now artificially synthesised from basic chemicals, and, it is claimed, are little short of a miracle weapon in the fight against cancer. The Burzynski clinic proudly asserts that not only do antineoplastons boost the immune response against cancer, but that the correct combination of antineoplastons can be used to generate therapies targeted against specific genes involved in different cancers and so allow for effective, personalised treatment.

This is close enough to real science to sound fairly convincing to the non-specialist. Some peptides are well known to have roles within the immune system (defensins, for example), and gene-targetted therapies represent a huge and promising area of oncology research. It all sounds pretty technical and reassuringly complex. That is enough for desperate individuals looking to cure themselves or loved ones when all else has failed; they're on the first plane to Texas.

Stem cells 2.0

It's been a divisive issue for as long as it's existed, but the topic of human embryonic cloning has been thrust back into the spotlight this week with the news that researchers in the US have successfully produced human embryonic stem cells (hESCs) from adult cells for the first time. This is big news because hESCs have the potential, in theory, to become any type of adult cell - opening the possibility for repairing damaged tissues in previously unthinkable ways. Neatly, this was exemplified this month by the revelation that a blind patient has had his sight restored so significantly using hESC therapy that he is now legally able to drive. Such therapy could also be used in therapies for paralysis, myocardial damage, diabetes, and many other disorders. 

This new method for generating hESCs relies on harvesting cells from an adult patient (typically from the skin) and then fusing them with oocyte (egg) cells that have been emptied of genetic material. This, in effect, generates a single-cell embryo with the genome of the original adult cell, which can then begin to develop into a multi-cellular body. The most recent work has identified the precise chemical signals that need to be applied to the cells, and at which stages, to generate hESCs. At present, it is illegal in most countries to allow such clones to develop beyond 14 days of age, yet it is still feasible that useful numbers of hESCs could be obtained from even such young embryos. 

This promising development hopefully represents the start of an increased investment in the field of therapeutic human embryonic cloning, but is also very likely to reignite the fierce debate over the ethical issues linked to the generation of human clones. Such debate led to severe restrictions in funding and autonomy in hESC research in the United States during the Bush regime, which was subsequently overturned by the Obama administration in 2009. It is my sincere hope that the typically alarmist ways that this kind of work is often portrayed in the mainstream media (such as those that accompanied the cloning of Dolly the sheep) do not hamper scientific policy or public acceptance of such potentially ground-breaking advances. 

This is, admittedly, a short post about something that you may already have read, but I am using this, dear reader, to whet your appetite for stem cells as I will be finding my way to writing a much more in depth and revealing post soon about what stem cells actually are and how the abstract 'treatments' that I mention above actually work. Watch this space for more soon.

The human machine: setting the dials

The previous post in this series can be found here.

It may seem sometimes that nature is a cruel mistress. We are all dealt our hand from the moment of  liaison between our lucky gold-medalist sperm and its egg companion. We are short or tall, broad or skinny, strong or weak because of the haphazard combination of genes that we wind up with, and that should be the end of the matter. Yet, as any seasoned card player will tell you, it is not the hand that matters, but how you play it! This, it turns out, also holds true when it comes to our genetic makeup - we can only play the cards we're dealt, but we don't have to play them all and can rely on some more heavily than others. In this post I'm going to discuss the ways in which DNA is organised and its activity regulated, and how this regulation is a dynamic, ever-changing process with cards moving in and out of play all the time. What's more, we'll explore the ways in which we can all consciously take control of our own DNA to help promote good health and long life!

Esoteric instructions laid bare

Most people are familiar with the concept of DNA - the instruction manual for every component that makes you you - but most are perhaps unaware of how DNA is actually organised within your cells. The importance of DNA has led to it achieving a somewhat mystical image in the public perception: a magical substance that sits inside you with omnipotent influence over every aspect of your construction. This perhaps might lead a layperson to think that we don't really understand how genes work, a perception that is encouraged by the abstract way in which the link between genetics and diseases is reported in the mainstream media. However, this impression is entirely false; we understand very well how genes work: DNA acts as a template for the generation of information-encoding molecules called RNA, which are in turn used as templates to make proteins, which then make everything else. This is called the 'central dogma' of molecular biology, which I'm not going to go into in detail now but have touched upon more thoroughly in a previous post: here.

The mystification of genetics in the mainstream perception can encourage people to forget that DNA is just a molecule, with as much physical presence and chemical potential as any other molecule in your body. As such, its supreme influence over you is dependent on pure chemistry and physics. The most obvious consequence of its being a physical entity is that it needs, in some way, to be arranged and organised. DNA exists within the nuclei of your cells, but it doesn't just float around randomly and aimlessly - its organisation is tightly regulated. First of all, DNA exists as a number of different strands, each its own molecule. These are chromosomes, humans have 46 in each cell nucleus, 23 of which you inherit from your mother, and 23 from your father. The classic image of a chromosome is the tightly packed 'X' shape like those in the image below, but actually this is a comparatively rare structure in the life of DNA as this only forms as the cell is dividing.

Chromosomes seen under an electron microscope. Image is from http://trynerdy.com/?p=145.

In non-dividing cells, DNA does not exist in the cosily familiar 'X' shapes, but instead spreads out to fill the whole nucleus. This is out of physical necessity - the DNA in compact chromosomes like those above is simply too tightly packed to do anything! Proteins and other molecules that need to interact with the DNA in order for its influence to be felt just can't get to it because there's no space. If the DNA spreads out to fill the nucleus, however, there's plenty of room for manoeuvre. Nonetheless, this organisation is not random and is still highly organised. DNA never exists on its own in a live cell - it is always bound to proteins called histones, which act as a scaffold around which DNA is able to wind, like a string around a ball. There is about 1.8m of DNA in each cell of your body, but once wound around histones it has a length of only around 0.09mm - a pretty significant space saving measure! Each little ball of DNA and histone is called a nucleosome; it is held together by attraction between the negatively charged backbone of the DNA and the positively charged side chains of the amino acids making up the histone proteins. 

DNA wrapped around histone proteins to form nucleosomes. Adapted from Muthurajan et al. (2004) EMBO J. 2004; 23(2):260-71

The human machine: probing the mechanics

The previous post in this series can be found here.

This week, inspired by Shaun's most recent post covering exciting new results in cosmology, I have decided to also take a quick look at one of the fascinating recent findings of molecular biology. I hope to give some insight into how this work is done, and why it is not only intellectually interesting, but also potentially practically useful. 

What do we know?

Those of you who have been following this series for a while might remember a post that I wrote last year (biological batteries and motors) where I discuss how energy is converted from myriad chemical forms in your food into the single energy currency of the cell, ATP. The system by which this is achieved is quite beautiful, chemical energy is converted into an electrical current within the mitochondria of your cells, which is in turn converted into a current of protons. This proton current drives a motor (ATP synthase) that churns out ATP, thereby converting it back into chemical energy. I'm not going to go into the whole process again here, but if you'd like a quick refresher then just hop back to my older post here, go on - you know you want to! I don't mind waiting.

So, a key player in this whole process is the so-called respiratory complex I (or NADH dehydrogenase), which is the first link in the chain that converts electrical current into proton current. Complex I takes electrons from a molecule known as NADH, which is produced from energy in your food by a range of complex metabolic chemical reactions. It moves the electrons that it takes from NADH and sticks them onto a molecule called ubiquinone, which then moves on to the next stage in the process: the perhaps confusingly named complex III.

The human machine: decommissioned components

The previous post in this series can be found here. 

Happy 2013 from all of us here in the Trenches! We successfully made it one more time around the sun, and if that's not a good excuse for a party I don't know what is! Sadly, however, not all of your cells have been having such a swimmingly good time since the calendar ticked over to January the first - in fact nearly one trillion of them have died in the past fortnight alone, at a rate of roughly 70 billion a day, or 800,000 per second. Don't be alarmed, however, as this has been going on for your whole life and is a vitally important part of being a multicellular organism such as yourself. A human without cell death would be like society without human death - overcrowded, unpleasant, and rife with infirmity. Your body needs a system by which damaged, old, or infected cells can be removed in a controlled manner; this process is known as apoptosis.

In this post I will be discussing what we know about how apoptosis works and how it is a key player in the development of cancer and the fighting of infectious disease. I'll also show how our understanding of how this process works has allowed us to devise targeted therapeutics against a number of debilitating conditions.

Cellular suicide - picking the moment

Your cells are team players - they're willing to do anything to serve you, including laying down their lives. Apoptosis depends on this loyalty because it is actually a form of suicide that your cells perform on themselves. Arguably the most important aspect of this is timing - if your cells are in the habit of committing suicide before it is necessary then you'll waste a lot of energy and resources building replacements that shouldn't be needed. On the other hand, if the cell leaves it too late to kill itself then it may find itself incapable of doing so.

So, how does a cell know when to die? Well the most obvious markers for cell death are simply the various forms of damage that can occur to the components of the cell itself. If a cell's membrane becomes damaged, for example, this can cause excess calcium to leak into the cell and so be sensed by a number of calcium-binding proteins, such as calpain, which in turn signal that apoptosis should begin. Similarly, damage to DNA is sensed by the complex machinery of the DNA repair pathway. For example, PARP is a protein that binds to single-strand breaks in DNA caused by DNA damaging agents such as radiation (think sunburn!) or chemical mutagens like free radicals. PARP and other DNA damage sensors relay their information to a number of signalling proteins, most importantly p53. If p53 is activated in response to DNA damage it signals to stop the usual processes of cell division and begin DNA repair, but if the damage is just too bad it makes the call to start apoptosis and destroy the cell.

Cinema verité - biology style

Animations of scientific principles are becoming more and more popular as a way of condensing complex data into an easily accessible format, particularly in the field of biology. Nonetheless, a recent article in Nature has raised a number of interesting points about how the visualisation of biological processes should not be taken lightly. Biology is unnervingly complex and there is still much that we don't understand - how are we to know how much of an animation is based on actual data and how much is just 'filling in the gaps'? This is not limited to the layperson - humans are very visual creatures and we are more easily swayed by pictures than words, experts are no exception. This is not new, journals have included idealised representations of biological processes for decades, but the advancement in computer animation has opened the door for more sophisticated animations that may imply a more thorough understanding where one does not exist. 

That said, I don't believe that researchers actively seek to mislead when presenting their findings in animated form, rather that they have to take the necessary steps to complete the movie - inherently requiring some artistic licence. And, for the most part, the bits being filled in are done so with reasonable scientific assumptions in mind and are not wild fantasy. The medium is an exciting one, and one that will hopefully play a significant role in not only disseminating scientific understanding, but also help to further research by highlighting gaps in our understanding. We must, however, always be vigilant when interpreting these animations as they are exactly that - animations - and not actual footage of molecular biology.

An excellent example of biological animation is the 'Inner Life of a Cell' video by a group in Harvard. I love this video, which depicts the events that occur upon the activation of T cell, and is pretty accurate in that almost everything show is backed up by real evidence. The 'motor protein' kinesin at 3:40 is particularly impressive because its mechanism of 'walking' along microtubules is backed up by extensive structural and biochemical studies, yet it just looks so much like a drunk guy who's been pulled over by the police and is trying to walk in a straight line! If you get the chance, I really recommend watching the video and reading the article mentioned above. Enjoy!

The human machine: circuits and wires

The previous post in this series can be found: here.

In the first post of this 'human machine' series, I explained how 'energy' (that abstract entity) is processed and used by our bodies in order to converted the chemical energy in our food into the work energy required to keep us ticking over nicely. I discussed in this how we are all actually powered by electrical circuits that buzz along in the internal membranes of our cell's power stations, the mitochondria. Better yet, not only are we powered by currents of electrons, familiar to us as standard electricity, but also by currents of protons, and so are actually working off energy being extracted from two forms of electrochemical potential. We're pretty sophisticated machines!

The work energy generated by these processes is used in myriad ways, but one very important one is the creation of another electrical current that is the foundation of everything you've ever done and every thought you've ever had: the neuronal action potential. This is the electrical signals that run along the neurons in your brain and body in general, constantly relaying information back and forth throughout the whole complex machine. Without it we would be like plants, with one part of our bodies completely unaware of what's happening to the rest of it, and animal life as it is familiar to us would be entirely impossible. Most people have, I expect, heard of the notion of electrical signals running throughout our bodies (it's why the machines built the Matrix, right?), but few will actually know what that means. In today's post I'm going to be talking about what neuronal signals actually are, and so explain why being hit by lightning is a bad thing but being defibrillated (like in ER) can be a good thing.

Shaken not stirred - how to extract your own DNA

Last week I eagerly sat down to watch the first episode of a new series: Dara O Briain's Science Club. For those of you from outside the British Isles, Dara O Briain is an Irish comedian who, in recent years, has become one of the most popular comedians and broadcasters in the UK. Not only is he a very funny guy, he's also got a pretty sharp mind inside his (frankly massive) shiny head: he studied mathematics and theoretical physics at University College Dublin and has managed to hang on to his love of science despite moving into the world of entertainment. He, along with other big names like Brian Cox and James May, has been instrumental in advancing British popular science broadcasting in the last decade and has presented a number of science programmes, such as School of Hard Sums and Stargazing Live, giving science that much-needed welcoming and friendly face. 

His new series is most definitely worth watching and I await the next episodes with bated breath. The first was on the subject of genetics and epigenetics and my curiosity was more about how these complex topics would be presented rather than actually learning something (I'm already fairly familiar with the fields)! I was delighted by the casual and approachable way in which it was structured, and how debates about scientific funding and application were mixed in with the hard facts. 

Possibly my favourite moment, however, was when we were shown how to perform a simple task that I am very used to doing in the lab, but in your own home: extracting DNA. Perhaps appropriately given the latest addition to the James Bond franchise, this entailed the use of cocktail-making equipment and the kind of very strong vodka needed to make that perfect Martini. Some might think of this as a big gimmicky and irrelevant, but I quite like the idea of making somewhat abstract scientific principles more tangible in the mind of the general public. Bringing such a standard research procedure into people's homes helps to demystify the scientific method and hopefully give people a greater sense of ownership over this work than they might otherwise have.

So, today's post is a shameless plug for Dara O Briain's Science Club with the aforementioned DNA recipe thrown in for those of you unfortunate enough not to be able to watch it online! Enjoy.



1. Collect some of your cheek cells by swishing some (around 100ml) salt water around your mouth for 30 seconds or so. The solution will be a bit cloudy afterwards.

2. Add a few drops of washing-up liquid (to dissolve the cells' membranes) and a shot of pineapple juice (the proteases in this will degrade the myriad proteins found in your cells). Pop it all into a cocktail shaker and give it your best shake!

3. Pour through a cocktail strainer to remove bubbles, ideally into a martini glass or something in which it's easy to layer different liquids.

4. Chill some very strong (>80% abv) vodka on ice and they carefully layer over the top of your mushed up cell solution. At such a high concentration of alcohol DNA comes out of solution and so precipitates at the boundary between the two solutions. This looks like a white cloud forming at the bottom of the vodka layer, which can be scooped out by wrapping it around a toothpick or something similar. Et voilà! It may not look like much, but you have successfully extracted the chemical instructions that make you you. Not bad for 5 minutes work.

The human machine: communication technologies

The previous post in this series can be found here.

Have you ever stopped to consider what makes you a single organism? It might sound strange, but it is a question dripping in biological significance. You may think of yourself as a neatly packaged single unit, yet you are probably also aware that this one unit is made up of tiny individual cells working together. But how do 75,000,000,000,000-odd cells cooperate with such precision? Why your cells work together is entirely separate question with answers to do with filling evolutionary niches and delegating functional roles; I'm talking about how they do it. That's the million dollar question! 

Well, to be precise, it's the $1.2 million (or 8 million Swedish Krona) question, as it was announced last week that this year's Nobel Prize in Chemistry (and the accompanying monetary reward) has been awarded to Robert Lefkowitz and Brian Kobilka for their outstanding work into the biology of G protein-coupled receptors (GPCRs). In this post I hope to give you an understanding of how GPCRs work, why they're important enough to deserve a Nobel Prize, and how they relate the question of how you stay as just one you.

GPCRs - the eyes and ears of the cell 

If you were a cell, how would you know what to do? When should you divide, where should you move, what should you make? You couldn't just do it randomly or to some pre-determined schedule because the human you're in is unpredictable and its cells must be flexible in their behaviour to match that. So, what you really need to make these decisions is information. This is exactly the same as how humans make decisions about our behaviour, we gather information about the surrounding environment through our senses and then act appropriately. A cell that receives no information from outside its own membrane is as impotent as a human with no sense of sight, smell, touch, taste or hearing. Ok, so they need information, how do they get it? As you've probably guessed given my snappy subtitle and general build-up, the answer is receptors!

The human machine: coding and decoding

The previous post in this series can be found here.

It's been an exciting week for molecular biologists, and should have been for everyone else too! This week, the Encyclopaedia of DNA Elements programme has revealed its first results about the role of the 99% of the human genome that has, until now, represented a fairly sizeable gap in our understanding of how DNA works. This has made big waves in biological circles and has to some extent penetrated the mainstream media, on the BBC for example, but I thought I'd herald this great work by giving you a brief explanation of what DNA is, how it works, and why so much of it was a bit of mystery until now.


From humble beginnings

DNA is unbelievably complex yet unbelievably simple at the same time. The principles upon which it is based are extremely simple: a string of code made up of four chemical units (called nucleotides: G, C, A and T) on two intertwined strands where units on opposite strands are paired either G:C or A:T. The complexity that arises from such a basic principle emerges much in the same way that vastly complicated computer programs can emerge from the binary 1 and 0 system of computer code; principally, that it is a code there to store information that, when read correctly, is vast. And when you have around 3 billion units of this code in every cell in your body, that vastness can quickly become unfathomable! 

Nonetheless, we've come a hell of a long way in the last 60 years. It was only in 1952 that the Hershey-Chase experiment conclusively demonstrated that DNA and not protein, as had also been suggested, was the information-carrier of the cell. Just a year later Watson, Crick, and Franklin discovered the now famous 'double-helix' structure of DNA, and the race was well and truly under way to decipher this mysterious molecule. 

Pushing back the boundaries

The Red Planet?

The adventure of NASA's Mars Curiosity Rover took an exciting step forward today as the pioneering little machine vaporised its first rock with its cheerfully named 'ChemCam' laser. The Curiosity mission has tapped into a huge vein of public enthusiasm for investigation and the exploration of the unknown, exemplified by the fact that over a thousand people gathered in New York's Times Square to watch the live landing. Space exploration has often occupied a romantic place in the heart of public opinion, in part because of the wonderful images that can be beamed back, which can offer a more personal connection to the work being done and give people a greater sense of ownership over scientific endeavour. The Curiosity mission is no exception - NASA is dutifully publishing the images being sent back from Mars to the delight of those of us on Earth.

The potential for images to capture the public imagination has not gone unnoticed by other branches of science. Last year I published a post about the Cell Picture Show, a project by the biology journal Cell to highlight the most striking images emerging from the ever expanding field of biological microscopy. In this post I wanted to highlight a recent edition to the project: the super-resolution gallery.

Super-resoltion is a fairly recent step forward in microscopy that allows biologists to observe life's molecular events on an unprecedentedly small scale using a range of cunning technical tricks. Researchers can now follow individual molecules as they move across the surface of a cell, or observe the machinery of processes like DNA replication in fine detail. Just like Curiosity, the missions of super-resolution are pushing back the frontiers of knowledge and exploring the unknown; not going further, but looking smaller. I would definitely recommend giving this new gallery a look: here.  

Image is property of Cell and National Institute of Health - microtubules imaged by conventional (right) and super-resolution (left) microscopy within a Drosophila cell.

The human machine: different models

The previous post in this series can be found here.

You may have noticed, but we're holding a little sporting shindig here in London over the next two weeks that's got everyone rather excited. I myself am going to be spending a lot of time shuttling back and forth between the Olympic park and my house in Oxford and most of the rest of the time glued to my laptop watching as many sports as is humanly possible! Thanks to this busy sporting schedule, this week's post will be somewhat shorter than some of my others in the past, but I hope you still find it interesting. You may think, dear reader, that I will be shirking my scientific duties by devoting myself so fully to the Olympic smorgasbord but my enthusiasm is born out of pure biochemical curiosity and the sporting element is, I can assure you, wholly secondary! 

How does biochemistry fit into the greatest show on Earth, you may ask? How does it not, I would respond! All of the athletes competing in this year's games have spend years training to improve their body's biochemical response to stress and physical exertion in order to fulfil the Olympic ideal of 'faster, higher, stronger'. In my last post of this series I described the molecular processes that allow muscle contraction and in the preceding post I talked about how energy is processed within your cells to produce the 'energy currency' of your post: ATP.  In this post I will bring these two topics together and discuss how energy is regulated in different muscle types and how the biochemical situation varies hugely between the 100m and the marathon.

The human machine: pistons and ratchets

The previous post in this series can be found here.

In my last post I talked about how we are all powered by tiny spinning motors that work tirelessly to convert the chemical energy of our food into electrical potential energy, and then back into chemical energy in the form of the cellular energy currency, ATP . This week, I thought it would be interesting to look at how that ATP gets used up in a process that will be very familiar to you but that you probably know little about: muscle contraction.

As I mentioned last time, ATP is used by just about every active process that takes place in your cells. Most of these processes siphon only tiny amounts of ATP from the ever-replenished pool that is available in your cells – as far as they’re concerned there is an infinite amount of ATP available because they could never use is all up on their own. For this reason, a lot of our cellular machinery is, frankly, wasteful. The mechanisms that regulate DNA repair, movement of organelles within cells, and many other processes consume ATP with gay abandon because their impact is so miniscule on the total energy consumed by your body as a whole. There has been no need to evolve more cost-efficient mechanisms, such as those employed by our single-celled relatives for whom every ATP counts!

For some components of the human machine, however, their impact on total ATP consumption is far from insignificant. One often overlooked example is neural transmission, which is why the brain consumes around 20% of your total calories on an average day, and why you may find yourself famished after a tough exam even though you’ve just been sat down for three hours! Nonetheless, the clear winner in the ATP-expenditure competition is muscle contraction. Your muscles are responsible for using nearly 60% of your total calories on an average day – potentially far more if you’re very active (or very muscular!). Motile animals have to consume far more energy to survive than non-motile animals or plants, and this is primarily down to their muscles. Fortunately, this is very much worth it because being able to move gives you far broader options in terms of finding food in the first place. Moreover, because of its huge significance in terms of total energy consumption, the molecular basis of muscle contraction has evolved to be a highly efficient affair. In fact, in terms of work achieved per ATP used, muscle contraction is one of the most efficient processes in your body – it’s simply the fact that it’s used on a huge scale that makes it such an ATP-hungry mechanism. 

The human machine: biological batteries and motors

So far in my series of posts, I’ve tried to give you an appreciation for how war is fought on a microscopic level, which is to say: how invading pathogens try to consume our body’s resources, and how our immune system fights back. In my last post, I also tried to convey some of the contemporary research that is expanding our understanding of this system. While this is (to me at least!) a fascinating topic, I am going to put it to one side for the time being. The reason for this is that there are just so many enthralling topics to talk about when it comes to molecular biology! So, I have decided to concentrate a new series of posts on various interesting snippets of biology and biochemistry that I hope you will find intriguing and allow you to understand your own body a little better. In doing this, I don’t want to lose sight of the purpose of this blog – i.e. to convey a sense of the ongoing work taking place – and so will try to include cutting-edge research into each post whenever possible.

Preamble over, let’s get started...

Looking deeper and deeper

‘How does my body actually work?’ It’s a question that’s likely occurred to most of us at some point in our lives. Most people know how our skeleton is arranged and how our muscles tug at various parts of it to allow movement; similarly we all know how our hearts pump blood around this vast system, and what our various internal organs do. But science is all about finding something out and then saying ‘sure...but how does that work’ and then taking it down to the next level. When physicists discovered protons and neutrons, they weren’t content to leave it there; they took it to the next level and found out what those are made of, and then what the things they’re made of are made of, and so on to the present day. The same is true for biology – sure your muscles contract, but what are they made of, how do they contract and where do they get the energy from? It is this last point that we will deal with today: where does our body get energy from?

The simple answer to the above question is just: food. We all know we need to eat to have energy; if you’re a bit of an athlete or diet-enthusiast then you might know about the different components of food (carbs, fats, protein etc.) and how they affect the body. But have you ever wondered how all those varieties of different foods end up powering your body at the molecular level?

Treason in the immune army - betrayed by your own

The previous post in this series can be found here.

So far in my series of posts, I’ve tried to give you an insight into how your immune system is organised into divisions with specific roles: B cells  produce antibodies against pathogens; killer T cells demolish infected cells; and helper T cells act as the battle strategists, determining the tactics that will be used to destroy the invaders. Alongside these high-ranking immune cells are innumerable other footsoldiers that take their orders from T cells and sometimes from the antibodies released by B cells: neutrophils, eosinophils, basophils etc.

In any army there is the odd defector, a rogue agent who changes sides or simply goes it alone, and your immune system is no different. The lowly footsoldiers mentioned above are not capable to acting without orders from higher up and so when a turncoat T or B cell starts to send out treacherous commands that you might be in trouble.  In this post, I’m going to explain the different forms of autoimmunity (when the immune system attacks the body) and allergy (when it attacks innocuous molecules). I will also explain how our understanding of the immune system is starting to allow us to treat these disorders and save or improve countless lives.

Autoimmunity and allergy – T and B cells gone bad

Autoimmune diseases affect roughly one in twenty people in the western world; allergies, far more. Their symptoms are hugely variable and range from mild rashes to fatal anaemia. All are caused by misdirection of the adaptive immune system and are driven by conspiratorial T or B cells. Luckily for you and me, immunologists have been working furiously for the last century or so to unravel the causes behind these disorders and are now starting to produce fairly effective and specific cures. As you might expect, the effect of an autoimmune response depends very heavily upon what is rebelling: antibodies fired out by a B cell, for example, will have a very different outcome to a psychotic killer T cell.