Been there done that…or have I? Understanding the phenomenon of Déjà vu

dejavu1Have you ever experienced that overwhelming sense of familiarity with a place or situation, when it shouldn’t be familiar at all? For example, have you visited a restaurant in a city that you’ve never been to before and had this strange sense that you’ve been there even though you know for sure you haven’t?

This sensation is known as déjà vu which, when translated literally from French, means ‘already seen’.  It is also surprisingly common – around 70% of the population report these feelings, with most reports coming from those aged 15-25.

Déjà vu occurs randomly and with no prior warning of its onset.  Because of this unpredictability déjà vu is hard to study and, therefore, poorly understood – unfortunately scientists in white coats holding clip boards aren’t usually waiting around to attach electrodes to you when you experience this.

The earliest reports of this phenomenon came from as far back as 1876, when Emilie Bairac coined the term déjà vu. Psychics were quick to latch on to the phenomenon as evidence that we had all lived past lives; explaining that these strange feelings of familiarity, in unfamiliar situations, came from things we had encountered in our previous lives. However, soon more scientific reasoning began to gain credibility.

dejavu2Whilst déjà vu is reported in healthy individuals, there also appears to be a strong connection with epileptic patients. In fact, many of the earliest reports of déjà vu came from patients with epilepsy. These unusual experiences were thought to be linked to seizure activity in the medial temporal lobe – part of the brain involved in sensory perception, speech and memory association. During seizures, it was found that these neurons were ‘mis-firing’ and sending confusing messages to the brain and body.

We now know that a subset of epileptic patients regularly have bouts of déjà vu before a seizure. These seizures are evoked by changes in the brain’s electrical activity, which cause over-excitation to spread across multiple regions – much like a tidal wave rippling across the brain from the epicentre of a tsunami.  It is these electrical disturbances which create the feeling of déjà vu. Therefore, epileptic patients may hold the key to uncovering the origins of déjà vu – although the precise mechanisms likely differ to those in healthy individuals.

However, the precise mechanisms responsible for déjà vu in healthy patients are still highly elusive.

One theory is that the phenomenon has links to regions of the brain involved in recognising familiar objects and recalling memories. During an episode of déjà vu it is thought that these parts of the brain ‘mis-fire’ and produce the feeling of things being familiar when they actually aren’t.

Another theory is related to errors in memory processing. Usually when a memory is processed the new experience is first transfered to our short term memory and then, at a later stage, separately consolidated into long term memory. During episodes of déjà vu it is thought that a novel situation by-passes the part of the brain that processes short-term memory and instead is committed directly to our long term memory. A novel experience may then feel familiar when in fact it is not and the ‘memory’ you think you are recalling is in fact the present scene.

Despite being difficult to reproduce, scientists at Colarado State University think they may have replicated an experience similar to déjà vu in the lab. The study, headed by cognitive psychologist Anne Cleary, intended to identify whether déjà vu could be induced in participants exploring a virtual world. Subjects were given a head-mounted video screen to wear, which displayed 128 pictures of different villages that were split into pairs. Unbeknownst to the subjects, objects were positioned in the same place across the pairs to create a similar layout but with minor differences. Findings of the study suggested that déjà vu occurred most often when the layout of the new scenes were very similar to a previous scene, but not so similar that the subjects were able to recognise the new scene as being similar to the old one. In simple terms, déjà vu can occur when there are subconscious similarities between an old event and a new one, but the contrast between them is enough that you don’t recognise them as being similar.

Memories are stored in a region of the brain known as the hippocampus, these memory traces are held within groups of cells that have strong links with one another. Similar memories, such as sitting in a bar drinking a pint of lemonade and sitting in a bar drinking a glass of water a week later, are often stored across overlapping groups of cells. The brain needs a way to differentiate between these similar events and uses a process known as pattern separation.

dejavu3Scientists studying pattern separation manipulated a gene in mice, which they believed to be linked to this process. These mice were then left in a box and given a small foot-shock which made them freeze. The mice were then guided into another box but, this time, didn’t receive a shock. Mice that had an intact pattern separation gene froze in the ‘safe’ box and took a while to figure out they would not receive another. However, mice without the gene figured this out more quickly. Some scientists think that it is this circuit that can be used to explain déjà vu; this pattern separation circuit misfires so that the ability to separate new experiences from similar past experiences is lost, giving the feeling of déjà vu.

Déjà vu has also been linked to levels of the neurotransmitter dopamine, although research into this is sparse. This link was suggested after a healthy, middle aged doctor was prescribed drugs that are known to increase the activity of dopamine in the brain. After beginning his course of treatment, the doctor had recurrent episodes of déjà vu that subsequently disappeared after he stopped taking them. Despite this apparently obvious link little more is known about the role of dopamine during bouts of déjà vu.

Although early reports of déjà vu date as far back as the late 1800’s, we still know relatively little about exactly how and why it happens. There are many theories around that range from far-fetched ideas based on psychic and spiritual origins, to ideas that explain déjà vu as errors in the memory-making pathway. However, to elucidate the exact mechanisms, much more research is still needed.

Post by: Sam Lawrence

The decline of the antibiotic – taking medicine back to the dark ages?

Anti-bioticAfter being struck down with a particularly nasty chest infection, I initially put off going to see the doctor and instead opted for lots of rest, fluids and self-medication. After suffering at home for a few weeks with no alleviation of my symptoms, I eventually decided enough was enough and went to see the doctor. I was subsequently diagnosed with pneumonia and prescribed antibiotics to treat the infection, after which my  symptoms finally began to ease.

My reluctance to seek medical intervention was due in part to two reasons;

  • My general dislike for going to the doctors
  • Concern over recent news articles discussing the demise of the antibiotic due to over- prescribing.

It is the second of these reasons which seems to be a particular cause for concern.

The evolution of disease-causing bacteria, leading to antibiotic resistance, is a concern which has been high on the scientific agenda for decades. However, the media are only just starting to catch on to the stark reality that faces us. David Cameron has recently taken notice of this impeding issue, referring to the problem as ‘taking us back to the dark ages’. Cameron has called for a review into microbial resistance and has called for drug companies to invest in finding the next generation of antibiotics. But is this too little too late?

If our bodies become infected with foreign bacteria our internal immune system (white blood cells) act swiftly and efficiently to stop the spread of infection – usually before it has the chance cause noticeable symptoms. More often than not, our bodies are able to cope with such an attack without intervention. However, sometimes our bodies become overwhelmed and are unable to cope on their own – this is when we need to seek help from antibiotics.

Antibiotics have been relied on for the last 70 years and are vital in the treatment of bacterial infections (they are useless in the fight against viruses). These drugs work in one of two ways:

  • By interfering with the bacterial cell wall or the contents within – a process which destroys the bacteria (bactericidal).
  • By slowing down the growth of bacteria that can cause illness or disease (bacteriostatic). Thereby, ensuring that the bacteria is no longer able to multiply and infect us.
MRSA superbug showing resistance to antibiotics as the bacteria (yellow) overwhelm the white blood cells (red).

The development of antibiotics peaked in the 1950’s, after which there was a sharp decline in their development – no new classes of antibiotics have been developed since the ‘80’s! This is perhaps because there is not much money to be made from discovering new forms of antibiotics, so the pharmaceutical industry tend to focus on other, more lucrative, areas of research.

But how exactly does resistance to these drugs occur? When our bodies become infected with bacteria, there is a small chance that some of the bacterial cells show a natural resistance to antibiotics and therefore remain unaffected by the drug. This resistance could be due to a mutation that occurred by chance, or could be as a result of evolution – effectively the bacteria out-smarts the drug. These few remaining resistant bacteria survive, and rapidly reproduce so that the body becomes overwhelmed by this resistant strain. Drug resistance can then be transferred between bacteria through reproduction, physical connections between different cells and also through viruses called bacteriophages.

The mechanism of antibiotic resistance

Antibiotic resistance is accelerated by over-use in the health-care and farming industries. Which is a growing concern, as many patients fight with doctors to be prescribed antibiotics for all minor ailments without considering the consequences of using them unnecessarily.

Resistance 2
Bacteria presented with 4 different types of antibiotic. In three cases the bacteria is resistant to the antibiotic and in one case only the drug is sufficient to treat the bacteria.

Antibiotics are also heavily used for intensive farming. With such a demand on farmers to produce lots of cheap meat, animals are housed in cramped conditions where infections are easily spread. Of course to prevent this spread, copious amounts of antibiotics are often used. This overuse facilitates resistance. Resistant bacteria are then able to spread from farm animals to people via our water supplies, which can then spread further from person to person by physical contact, coughing and sneezing.

Now that we know the extent of the issue of antibiotic resistance, what can be done to tackle the problem both in the short and long term? Currently, drug-resistant superbugs such as MRSA and C.difficile cause 5,000 deaths a year in Britain. This has been controlled to some extent by implementing more stringent hygiene procedures in hospitals such as frequent hand washing and anti-bacterial hand scrubs. However, the occurrence of other resistant bacterial strains are on the rise; E.Coli cases have risen by two-thirds over the last few years.

In the short-term, a 5 year Anti-microbial Resistance Strategy has been put in place by the Department of Health which outlines a number of different points that are effective in the fight against antibiotic resistance;

Aim #1 To understand antibiotic resistance: to collect as much information as possible about the mechanisms that bacteria use to become resistant and to understand how the resistance spreads.

Aim #2 To conserve our current antibiotics: by improving hygiene in hospitals and by educating doctors and nurses about the issue of resistance, and encouraging them to only prescribe antibiotics when absolutely necessary.

Aim #3 To encourage the development of new antibiotics: by providing more incentives for pharmaceutical companies to invest in antibiotic development.

In terms of addressing antibiotic resistance in the long-term, several approaches can be taken. Firstly, we need to tackle the issue of over-prescribing. Currently, there are no diagnostic tests that allow doctors to determine whether infections are caused by bacteria or virus. So, developing a test that could determine the basis of aninfection would help doctors give the correct prescription. Secondly, drug companies need to create new classes of drugs to tackle bacterial infections. Thirdly, we can try to reduce the use of antibiotics in farming. Lastly more research needs to be conducted into a new innovative approach to tackling infections which uses viruses to treat bacterial infections.

A combination of over-prescribing and the lack of development of new antibiotics means that these drugs are rapidly becoming less effective in their fight against infections. There is the fear that, in the very near future, these drugs will cease working completely and simple things to treat such as cuts and flu will be likely to make us very ill and even cause deaths.  With no suitable alternatives to antibiotics we could be looking at a very bleak future for medicine.  With all of this in mind it is clear to see that the pharmaceutical and medical industry needs to make huge investments into developing new classes of antibiotics to fight these super-resistant bacteria. Alongside this, doctors need to be sure to prescribe these precious drugs sparingly and patients need to be careful not to rely on them so much for minor ailments.

Post by: Sam Lawrence

The elephant: the largest living land animal

Elephas_maximus_(Bandipur)From the killer whale whose heart is large enough to fit a small car inside, to the crocodile whose lungs are able to move around within its body cavity to alter its centre of gravity: the animal kingdom contains some of the most fascinating and unusual organisms that live on the Earth. It’s the fascinating adaptations found throughout the animal world that fuels our interests in these animals.

For years the extraordinary elephant has roamed south-eastern Asia and Africa.  Weighing up to six tonnes and reaching up to four metres in height, the elephant is an extremely impressive animal; in fact the largest of all land animals. Despite their vegetarian diet, getting into a fight with an animal of this size should be avoided at all costs!

The big question is how have their systems adapted to meet the needs of this monstrous body?

We know the elephant has in excess of 200 bones that make up its skeleton- hardly surprising given that it needs to support its sheer size. In keeping with its frame, the elephant also has a huge skull, but what is perhaps surprising is its relatively small mouth.  Due to the nature of the tough vegetation that elephants eat, they have evolved to have 8 teeth the size of bricks.  The surface of the teeth are covered in tough enamel ridges that grind vegetation into a pulp as the jaw moves back and forwards.  As old teeth become excessively worn, new teeth are produced at the back of the mouth. The new tooth gradually moves forward, pushing the worn one towards the front of the jaw.  It is this conveyor belt action that allows elephants to eat throughout their entire lifetime.

Another fascinating, and obvious, feature of the elephant is their tusks. They are basically huge incisor teeth, used primarily as a defence mechanism (who wouldn’t be scared of two huge sword-like projections?) as well as for foraging food.  Male elephants also use their tusks to dominate other males, and to help find themselves a mate. The pair of huge tusks is an obvious show of natural selection; in this case, the bigger the tusks the better. The largest known tusk was a whopping 3.5 metres in length.

However, in recent years we have seen a dramatic reversal in the tusk stakes. Due to pressures from hunters and poachers, having large tusks makes these elephants a prime target. It is for this very reason that we are now seeing a very obvious reduction in the size of elephant tusks.

Elephant_snorkelingYet another amazing adaptation we see in elephants originates from within their lungs. Unlike most other mammals, elephants’ lungs lack a pleural space separating their lungs from the ribs.  Instead, connective tissue connects the lungs to their ribcage and diaphragm. But what advantage might this have? Scientists believe that this incredible anomaly may have arisen to aid elephants in ‘snorkelling’; elephants are the only land mammal that are able to entirely submerge themselves in water whilst taking in air from above the surface. Without the lung-rib connective tissue, blood vessels in the lungs would most likely not survive the huge changes in pressure exerted on them whilst snorkelling. By covering these vessels in a much tougher membrane, they are protected from damage from changes in pressure. The downside to this tough casing is that the blood vessels aren’t able to produce a lubricating fluid necessary to ensure that the lungs and rib cage slide over one another during respiration. Without the fluid, the tough connective tissue only allows a small degree of movement. Despite perhaps negatively impacting upon respiration, the benefits that this connective tissue confers to the elephant far outweigh the negatives.

Angry_elephant_earsPerhaps even more fascinating is how an animal of this size, living in extremely hot regions of the world, manages to prevent overheating. They haven’t exactly been blessed with the ideal body shape to stay cool. To address this mystery, scientists used heat-mapping techniques to measure the external temperature of an elephant throughout the day, while also measuring the temperature from within the elephant.  Results found that whilst the surface of the elephant can reach up to 55 degrees Celsius, internal temperatures are kept far lower at around 35 degrees. So what exactly is allowing the elephant to remain cool?  We know that the answer lies with their ears. As with their skull, elephants have the largest ears in the animal kingdom. But these ears serve a very important purpose; they act as a massive fan working to cool down the elephant. By effectively ‘flapping’ the ears back and forth, air is forced back over the body. Big arteries from the body carry blood close to the ears surface via a series of smaller vessels. The ears are well equipped to deal with this, as they are extremely thin. It is this flapping motion of the ears that allow much of the heat from the body to be carried away, and hence prevents overheating.

Elephant_trunk_(1)And finally, I couldn’t talk about the mighty elephant without mentioning its most recognisable piece of anatomy. The trunk. This ingenious piece of machinery is involved in many things that elephants do; feeding and drinking, snorkelling, washing, playing, communicating, feeling, and manipulating amongst many others. This original piece of anatomy seemed to have evolved long ago through natural selection. The sheer size of an elephant’s body and head made bending down to pickup food an onerous task. This difficulty caused the trunk to evolve. Over many years it is thought that these animals slowly evolved to have a shorter jaw, but with a longer top lip.  As they became taller and taller, the upper lip gradually elongated until it resembled a trunk that was able to feed without having to bend down.

You might think of these animals as large, bulky and clumsy, but this is in fact far from the truth. They are amazing feats of engineering. We know that elephants are actually very elegantly made and adapted to suit their body’s needs from their trunk, their cooling system and to their lungs. Today elephants are the only animals of such size, so it is obvious that their size doesn’t hamper them; their body is doing something right.

Post by Samantha Lawrence

A smoking revolution – What’s in a cigarette?

CigaretteTravel back in time to the forties and fifties. Smoking was seen by some as a fashion statement. This was before we were clued-up on the abundant chemicals and the massive impact it could have on our health.  As research into cigarettes snow-balled, smoking became less fashionable. Even so, there are still many people around the world who smoke.

This week has seen a drastic change in UK laws regarding smoking.

The UK Government has decided to ban smoking in cars when children are passengers. This change has come after shed-loads of research over the last couple of decades has highlighted health risks associated with smoking that far outweigh the benefits.

But is smoking really as harmful as the Government drums into us on a daily basis?

The statistics seem to speak for themselves; almost 80,000 deaths occurred in the UK in 2011 as a direct result of smoking. What’s more, around 11,000 people die from passive smoking each year (according to Cancer Research UK), and around 9,500 children are admitted to hospital with smoking-related problems from passive inhalation.

So what exactly is in cigarettes that make them so addictive and what produces these toxic effects?

Nicotine–  a plant-derived chemical in cigarettes that is responsible for the addictive nature of smoking. The chemical enters the blood stream by inhalation and absorption through the air sacs in the lungs. It is then carried by the blood into our brains, where it binds to cholinergic receptors.  Usual functioning of these receptors helps to maintain some of our normal bodily processes, but  when nicotine is inhaled  it changes the number of these receptors and also alters their sensitivity to nicotine.  This is the mechanism responsible for smoking addiction- nicotine needs to be used regularly to keep the brain ticking over.

Tar– the gunky stuff in cigarettes that is deposited mainly in the gas exchange region of the lung, and carries all the nasty chemicals that are toxic to our bodies. Apparently there are almost 4,000 of these chemicals in each cigarette smoked, many of which can cause cancer.  Not surprisingly, tar can affect the proper functioning of the lungs. It also ‘clogs’ the cilia that trap bacteria and dirt, so that dangerous substances can enter our lungs.

Carbon monoxide– the chemical in cigarettes that significantly reduces the oxygen-carrying ability of our red blood cells, as it is 200 times more attractive to our blood than oxygen. As the lungs are no longer able to supply our bodies with enough oxygen, we start to have issues with our breathing as we try to take in more oxygen, and also put our heart under immense strain as it tries to supply us our organs and muscles with enough oxygen (amongst many other things!).

Cigarette 2

Arsenic– a carcinogen that affects how the body repairs DNA.

Benzene– a solvent and carcinogen used in petrol

Formaldehyde– a chemical and carcinogen most commonly used to preserve dead bodies.

Polonium – a radioactive substance

Hydrogen cyanide– poisonous gas that damages the heart and blood vessels

Yet despite these major health risks, large numbers of us are still regularly lighting up.

In 2012 approximately 20% of the UK population smoked cigarettes on a regular basis. Astonishing statistics also showed that 10% of school pupils aged 15 were regular smokers. Not only this, but the average number of cigarettes smoked per day was 12.  Despite these figures, many smokers say that they wanted to give up smoking.

Based on all the frankly quite frightening research that hasn’t been brought to our attention, reducing smoking and passive inhalation is something that the Government is beginning to take seriously. Some of the changes that have already been introduced are;

  • Government bans smoking in public buildings and enclosed places in 2007. Having just been old enough to go to clubs and pubs before the smoking ban came into place, I really reaped the benefits when smoking was banned in public places. I was able to enjoy a night out with my friends, without coming home smelling of an ash tray. I wouldn’t have minded so much if I actually smoked myself!
  • Stopping promotion of tobacco productsAdvertising of cigarettes is banned (2003), and supermarkets are permitted to hide tobacco displays (2012).
  • Tobacco taxTax rates on cigarettes are high, apparently with the aim to put people off smoking, and nothing to do with the revenue it makes them!
  • Anti-smoking campaigns– These campaigns aim to get people to quit smoking by making them aware of the health risks, dissuading young people from taking up smoking and trying to educate people on the risks of passive smoking.
  • E-cigarettes– These electronic imitation of cigarettes are currently a massive craze in the UK. In theory these are a great alternate to smoking; they retain all the ‘good parts’ of smoking, without all the added health risks. As these are relatively new they are not well regulated, so more research is needed to evaluate their health impact.

We know for certain that smoking is damaging to the body and has serious health implications. I have provided a (somewhat biased) summary of the health-related impact that smoking can have, from a non-smokers perspective. Another thing is also clear; the Government are taking smoking seriously. They are tackling this issue in a number of vital ways from trying to stop the ‘glamorisation’ of smoking by banning advertisements, reducing the impact on non-smokers, research and regulation into ‘better’ alternatives and in my opinion the best way possible; educating the public on the harmful effects of smoking. Next time you reach for a cigarette just cast a thought to some of the chemicals and toxins that you are putting into your body, and be aware of how this may be affecting yours, or someone else’s health.


Gambler’s mind: The thrill of almost winning

Taken from Sescousse et al 2013
Taken from Sescousse et al 2013

Almost three quarters of the British population participate in gambling of some form, despite the fact that we know the odds are so heavily stacked against us.  So why do we gamble despite the massive risk?

The answer to this question lies in the biology of our brains; exactly how does the brain change during addiction? Circuits known as the ‘reward system’ connect to regions of the brain involved in memory, pleasure and motivation. When we enjoy something these neurons release dopamine, a chemical neurotransmitter that makes us feel happy, a feel-good chemical that makes us satisfied and encourages us to continue our habits. This is similar to what happens in the brains of drug addicts.

A collaboration between Drs Luke Clark from the University of Cambridge and Henrietta Bowden-Jones from the only NHS clinic for gambling addicts is trying to address what makes some of us so hooked on gambling and what happens in our brains. We know that there are both external and internal factors that influence our gambling habits such as our personality type, neurobiological and neurochemical make-up, as well as the different features of the games themselves.

Using a number of control and ‘gambler’ subjects, behavioural tests looked at impulsivity, compulsivity and dopamine levels. As suspected, gamblers were more impulsive than controls; something which is mirrored in drug addicts and alcoholics. Brain imaging studies have shown that near-misses recruit areas of the brain that are associated with winning. The ‘near-miss’ phenomenon is the theory that losing a game acts as an aversive stimulus- it actually puts us off gambling. But, coming close to winning acts to fuel our desire to gamble. The fact that the same areas are activated when we almost win, and when we actually do win may encourage us to gamble – and this is something that can be exploited by game manufacturers.

Is the degree of brain activation during winning related to gambling severity? Subjects were asked to play on a slot machine whilst an fMRI machine measured brain activity in response to the game (functional magnetic resonance imaging- looking at the level of blood flow to areas of the brain in response to stimuli). Results found that those subjects with severe gambling addictions had the greatest activity in their midbrain in response to near-misses, but the activity to a real-win did not differ with gambling severity.  This brain region is of interest because dopamine is produced here, and is implicated in other addictive behaviours such as alcoholism.

This leads us to ask if there is a chemical basis to gambling addiction.  Well, scientists know that there are a decreased number of dopamine receptors in the brains of drug addicts, but is this mirrored in the brains of gambling addicts? Surprisingly, although there were no differences overall in the amount of dopamine receptors in gamblers compared to controls, gamblers that were more impulsive did have a lower number of dopamine receptors. Strikingly, when they studied the gambling behaviour of patients who had suffered a brain injury, the ‘near-miss’ response observed in gambling addicts was not seen in patients that had damage to their insula. The insula may be central to the distorted thinking patterns seen in gamblers.

Compulsive gamblers are not necessarily greedier than the rest of us, but their brains may be wired differently. Gamblers are more likely to prioritise money over other basic needs such as food and social interactions. Perhaps there are changes in a gamblers brain that render them hyper-sensitive to the ‘rush’ of winning. On the flip-side, it is possible that pathological gamblers are less sensitive to the things that the rest of us would find rewarding, such as alcohol or sex.

Brain 2
Taken from Ted Murphy

Healthy controls and pathological gamblers were put into an fMRI scanner to record brain activity during a task where they had to press a button in response to money-based or sexual images. The faster the button was pressed, the more motivated the subject was to get the reward.  Despite stating that they found both money and sex equally rewarding, results found that gamblers pressed the button 4% faster when viewing money-related images than sexual images. Indicating that gamblers attributed a higher value to money than sex. The gambling cohort had increased blood flow to the ventral striatum (part of the brain involved in reward processing) in response to monetary images, more than to sex. In contrast, no difference was found in the controls. Interestingly, they found altered activity in the orbito-frontal cortex of gamblers, which is also involved in reward processing. Past studies have shown that different parts of the orbito-frontal cortex are activated in healthy individuals in response to money and erotic images- which is thought to reflect the dissociation between rewards that are vital to survival such as food and sex, and secondary rewards such as money and power. In gambling addicts, the same region of the orbito-frontal cortex was activated in response to sex and money, suggesting that they have an altered perception of money as a more primal reward.

A large proportion of future work will focus on uncovering the precise role of the insula in addiction by observing how its activity changes whilst gambling. Another area of interest is looking at relatives of gambling addicts, and trying to identify if differences exist in both their brain activity and also in their behaviours when gambling. This may be of huge importance as therapies and treatments may be able to focus on targeting affected areas of gamblers’ brains.

For more information:

Clark L, Lawrence AJ, Astley-Jones F, Gray N. Gambling near-misses enhance motivation to gamble and recruit win-related brain circuitry. Neuron. 2009; 61(3):481-90.

Sescousse G, Barbalat G, Domenech P, Dreher JC. Imbalance in the sensitivity to different types of rewards in pathological gambling. Brain. 2013

Image taken from Ted Murphy, Flikr

Post by Samantha Lawrence




Printing human organs – is this the answer to solving the transplant shortage?

There are approximately 10,000 people on the UK transplant list waiting to receive an organ. Statistics show that, due to a shortage in organs available for transplant, every day 3 of these people will die before receiving their transplant. Unfortunately, we have not yet found a way to address this shortage. However, with this in mind, money is being poured into investigating new technologies aimed at tackling this problem.

But how? Well, the answer may have been under our noses all along. Using a popular everyday technology, we may be able to use printing with a modern twist to generate these desperately needed organs. Imagine being able to print out a new liver, or a lung, or in fact whatever organ you needed.

Kidney 1In 2011 Dr. Anthony Atala, director at the Wake Forest Institute for Regenerative Medicine, received a standing ovation when, on stage during a presentation, he printed out a prototype kidney made from living cells. Although far from perfect, the kidney was able to break down toxins and produce a waste-like product, just like the genuine thing. Despite their diminutive size, these ‘miracle organs’ have the potential to revolutionise medicine as we know it.

And these aren’t the only organs to have been produced using 3D printing. Scientists at Organovo, a bioprinting specialist, have now created miniature livers. These tiny livers are just 4mm wide and ½ mm in depth, but are still able to produce the proteins essential for carrying hormones and drugs. Importantly, the livers produce cytochrome p450, which is vital for breaking down drugs in the body. What’s more, cells from blood vessels can be incorporated into the livers to supply them with oxygen and other nutrients.

printer 13D printers work by printing out layer upon layer of ink (or any other substance) until a 3D object is achieved.   All we have to do is tell the printer what to print with a computer aided design program, hit the print button and let the magic commence. Hey presto- there you have a real-life 3D object.

When printing organs, layers of living cells are laid out in sheets upon each other and a scaffolding material called hydrogel is spread between the layers providing nutrition to the cells and helping them fuse together. The cells are able to survive for as long as four months in these conditions. Images of the patient’s original organs are generated using a CT scan which forms a template that instructs the printer on how to to produce a life-like replica of the organ.

Although 3D printing may seem ultramodern, it has actually been used in the medical field some time to produce things such as hearing aids and braces.  This technology has astonishingly also been used to create an entire lower jaw for an elderly women who was deemed too fragile to undergo reconstructive surgery. The jaw was designed to be realistic, with cavities and grooves in the mould to allow for the re-attachment of jaw muscles and nerves.

We are now at a stage where we are able to print sheets of living cells, but only on a small scale. Researchers have surmounted a massive hill, and have finally found a way to pass human embryonic stem cells through a 3D printer without sustaining any significant damage to the cells.

Researchers are hopeful that over the next few years we will be able to use these tissue strips to test the toxicity of new drugs before exposing living patients to these potentially dangerous substances, saving not only time and money but also reducing risks to patients. Using the so-called mini organs, researchers will be able to watch the progression of diseases in life-like organs outside of the body.

Over the course of the next 10 years we will most likely see 3D printing being used to assist in regeneration such as bone and skin grafts, patches for heart conditions, regeneration of sections of blood vessels and replacement cartilage for joints.

As for producing entire organs, there is still a long way left to go. The problem lies with being able to produce a fully functioning organ on a full-size scale with the ability to maintain its own oxygen supply via a vascular system, and to remove its own waste.           The hope is that researchers will be able to devise a way that will allow a printer to produce a full scale organ without any damage to the cells, and that is sufficiently supplied with oxygen and nutrients. If we manage to achieve this, then using ‘printed’ organs may cease to be something of a dream and become a reality. Over the next 10 or 20 years, the thousands of people likely to need a transplant could be lucky enough to receive an organ almost immediately instead of waiting months or even years as is the case now.

Post by: Sam Lawrence

For more information on organ donation or to join the organ donor register visit:

Body disorders that you never knew existed- Part 1

Welcome to the world of the weird and wonderful. You will be taken on a run down through five of the most unusual, rare, fascinating and possibly unthinkable disorders that we know exist.

1.  Hypertrichosis- ‘Werewolf syndrome’

HypertrichosisImagine having a body covered in so much hair that people mistake you for a werewolf. This is something that sufferers of hypertrichosis have to deal with on a daily basis. Hair growth isn’t restricted to the areas of the body that we consider ‘normal’, instead spreading to areas over their body and face in men, women and children alike. The disorder is extremely rare with fewer than 100 known cases worldwide. But how does this unusual condition come about? Scientists think that there are two causes; one of a genetic nature, and the other developing due to certain external factors. Researchers in China tested the DNA of two unrelated patients with the condition and found that there were extra genes present in the same region of the X chromosome. This extra DNA sits near to a gene involved in hair growth (SOX3) and is thought to switch on this gene, stimulating mass hair production. Next time you have a moan about having to shave or wax to get rid of your unwanted hair, spare a thought for hypertrichosis sufferers.

2. Foreign Accent Syndrome

Speech_2Whilst this sounds like something from a very strange medical drama, foreign accent syndrome really does exist. Usually occurring as a result of severe brain injury such as stroke or trauma, the patient ends up speaking with an accent distinct from the one they had before. One of the most recent cases occurred after a women suffered from a severe migraine. She woke up in hospital to find that she was speaking with a Chinese accent despite never having visited China. What is to blame for this sudden change in dialect? Scientists have found that damage to the parts of the brain required for speech and movement of muscles during speaking affects how we pronounce words. This changes the timing and rhythm of our speaking. As our tongue forms words in a different way, it sounds as if we are speaking with an accent.

3. Congenital pain insensitivity

SplinterA condition where you are unable to feel any pain sounds like an absolute blessing. No headaches, no pain when you’ve broken a bone, or when you whack your knee on the side of a table. But now think about it seriously, imagine not being able to tell if you’ve pushed your body too far exercising or cut your finger whilst chopping up a carrot. Pain is one of our body’s most protective mechanisms, alerting us that something is wrong and needs our attention. Without this basic mechanism we would have no way of knowing when something has gone wrong.  Individuals born with this condition have what we call a loss of sensory perception: they are unable to feel pain but can feel pressure and touch. A mutation affecting how the nerve cells form during development is thought to cause the improper functioning of these nerves in response to pain. Sadly, this is likely to occur with other deficits such as mental retardation and in some cases the ability to regulate body temperature. Not being able to feel pain would be extremely advantageous-…if you are a superhero that is. For us mere mortals, not so helpful.

4) Fibrodysplasia Ossificans Progressiva- ‘Stone man syndrome’

FOPStone man syndrome does what it says on the tin. Cue an image of The Thing from the Fantastic Four- a body essentially made of rock. Slowly over time, sufferers of this excruciatingly painful disorder start turning to bone. Due to a malfunction of the bodies repair mechanism, the gene that is responsible for ossification (bone growing) during development remains active. This gene is usually switched off after the development of bones in the fetus. In time, muscles, tendons and ligaments slowly begin to harden and turn to bone. As the degree of ossification worsens, everyday tasks such as tying your shoelaces or walking to the shop become an impossible task. Would surgery provide suitable relief? In short, no. Surgery is not considered an option as this type of trauma causes the body to attempt to repair the damaged area – creating more bone and more damage than before. Although there are around 700 confirmed cases of FOP worldwide, there is very little known about how to treat it. Remember next time your body feels stiff and uncomfortable that what you are experiencing couldn’t even scratch the surface of what these people of made of stone are subjected to.

5) Trimethylaminuria- ‘Fish odour syndrome’

FishTrimethylaminuria is a rare metabolic condition that can be embarrassing for individuals suffering from it. An enzyme (FM03) that is needed to breakdown trimethylamine (TMO) into a substance called trimethylamineoxide is absent from the body. TMO gradually builds up without the enzyme to break it down, and so has to be removed from the body through other outlets such as the skin, urine and breath.  Whilst sweating out toxins isn’t unusual, it is the strong fish-like odour that comes partnered with it that is considered abhorrent. The condition is more common in women, possibly irritated by female hormones. Despite the putrid odour, there are no other symptoms associated with it.

The mystery of the appendix

The appendix gets a lot of bad press. We often think of it as one of the most pointless parts of our body that lacks any real purpose or function. But this may actually be far from the truth, with eye-opening research pointing towards an important role for this organ.

The appendix is a small, worm-shaped structure Appendix 1
located on the lower right side of the abdomen, connected to the cecum. Many of us are naïve about what it does, and often the only time that we hear about the appendix is when it becomes infected. When infection occurs we remove it without much second thought. Unlike the majority of organs in the body, little is known or understood about this mysterious organ.

Often we think of the appendix as simply an evolutionary remnant from times gone by, much like the coccyx found in humans (what remains from ancient tails or vestigial hind limbs in snakes, a reminder of past legs). Scientists as early as Darwin have theorised about its purpose, and come to the conclusion that it is an archaic organ, which became useless millions of years ago. This theory proposes that long ago the appendix was important for digesting very tough food such as leaves and tree-bark, but as human diets began to transform, so did the appendix. As humans began to eat more fruit and less vegetation that was hard to digest, the appendix began to shrink into what we recognise today. Some have even gone so far as to say that in the future the appendix will disappear entirely as it becomes redundant.

Although this explanation seems plausible, it seems naïve of us to assume that the appendix has no purpose. Why would an organ that supposedly has been redundant for so long remain in our bodies? Bill Parker from the medical centre in Durham, North Carolina has suggested a rather radical U-turn for the role of the appendix.

Appendix 2Parker suggested that the appendix could be useful to the ‘good’ bacteria in our gut, ensuring the smooth running of our digestive system. We know that our bodies are made up of trillions of cells, but actually houses around 10 times that number of micro-organisms, most of which are found in our guts. We have a symbiotic relationship with these organisms; they use our energy by digesting our food, and in return these ‘good’ bacteria help to prevent the spread of harmful bacteria and this is vital to the health of our gut.

According to Parker, the appendix may be vital in protecting our intestines ‘good’ bacteria from the ‘bad’ bacteria that try to invade our gut. Essentially, you could think of the appendix as a sanctuary or a weekend spa retreat for our vital microbes. These tiny bacteria can use the appendix as an area of respite from the strain of the harsh environment in the gut. When the stores of bacteria in the gut become depleted, bacteria can be released from the appendix to fill their place.

Although this theory is interesting, there has been little in the way of supporting evidence. One study led by James Grendall at the Winthrop University Hospital in America agrees with Parker’s theory. This study involved 254 patients each of whom had a history of gut infections caused by Clostridium difficile, and had been on antibiotics as a result. Patients that remain on antibiotics for a prolonged period of time can suffer from depletion in the ‘good’ bacteria in their gut, making it harder to fight off the bad guys.

Based on Parker’s theory, those individuals with an appendix should have a better chance at fighting off the infection by producing and sending more of the ‘good’ bacteria into the gut. However, those who have had their appendix removed may be unable to release these protective bacteria to replenish the stock in the gut, and therefore the ‘bad’ bacteria can take over.

What they found was striking. Out of the 254 patients, those without an appendix and consequently the bacteria housed there, were twice as likely to have a recurrence of the infection. Recurrence was likely to occur in 45% of cases when there was no appendix, compared to 18% recurrence in individuals who did have one.

We also know that the lining of the appendix is rich in infection-fighting lymphoid cells that accumulate shortly after birth, peaking in our 20’s and 30’s but rapidly decreasing as we age. This lymphatic tissue encourages the growth of beneficial gut bacteria.

Although it is tempting to believe that our appendix is a redundant vestigial organ, there is the possibility that it plays a role in protecting the ‘good’ bacteria in our gut. There is however little in the way of research to confirm its role one way or another. I think for now the exact role of the appendix will remain a mystery, at least until more research is carried out.

Post by: Sam Lawrence

Fighting jet lag – a simple case of wearing more layers?

Pioneering research has found that one of the best ways to beat jet lag may be by wearing more layers, sitting by a fire and having plenty of cups of tea. Scientists have found that our biological clocks are driven not only by light, but also by our body heat.

fireImagine you’ve been on a relaxing holiday. You’ve done nothing more than catch some sun, top up your tan, and sip cocktails on the beach. Why, despite the relaxing nature of your holiday do you return feeling more tired and fatigued than when you went? It is all to do with jet lag.

After a long-haul flight that crosses over many time zones, you can feel excessively tired and nauseous, with poor concentration and memory. Usually the more time zones you cross, the more severe these symptoms.  It also takes longer to recover, the longer the flight.

So why do we get jet lag?

We suffer from jet lag because of disruptions to our internal body clock which regulates things called circadian rhythms. These rhythms control many of our bodily functions and behaviours such as body temperature, appetite, hormone release and sleep patterns. They are controlled by a part of the brain called the SCN – the suprachiasmatic nucleus, located just above the roof of our mouths.

Circadian_rhythm_labeledOur body clock is synchronised to our environment using light signals, which signal to our brain what time of day it is.  During long haul travel, the cells in the brain’s ‘body clock’ become confused by the change in the light and act out of sync with each other. This is the point where we experience symptoms associated with jet lag.

Scientists have known about jet lag for a long time, but we know little about how to treat it successfully.  If you look on the internet you can find numerous sites giving tips on how to beat jet lag- or at least improve the symptoms. From my own experience, every time I’ve travelled to America and tried some of these, they have rarely touched the surface.

If you want to avoid jet lag the advice is to establish a new routine so that you eat and sleep according to the time zone you’re in, avoid napping during the day, and making sure you get as much natural light as possible. Research has shown that experiencing light during the evening causes a delay in our body clock meaning our bodies rhythms move later in the day. If we are exposed to light during the early morning, our clock becomes advanced and our rhythms start earlier in the day.

This stuff is all pretty old news. The link between the circadian clock and temperature is, on the other hand, altogether remarkable.  Scientists have found lots of evidence that point towards our biological clocks being driven by our body heat. Fruit flies exposed to drastic changes in temperatures exhibited changes to their body clock. They found that cells in the back of the brain called ‘dorsal clock cells’ were important in synchronising the body clock at warmer temperatures. Cells at the front of the brain -‘ventral clock cells’, synchronised the clock at cooler temperatures.

These findings may be key in helping us defeat jet lag by easing our body clock back into its status quo. It may be as simple as piling on layers of chunky jumpers, scarves and hats if you come from somewhere blisteringly hot, to be plunged into a cold climate. Vice versa, stripping down to as little clothing as possible may help battle jet lag if returning from somewhere cold. It’s all about easing our bodies back into its normal routine; not plunging straight into the deep end.

Post by: Samantha Lawrence

Body donation: ‘life’after death

Mortui Prosumus Vitae

Even in death do we serve life’

After one of my many trips past our University’s dissecting room, I couldn’t help but think of all the bodies which lay inside; waiting to meet their fate at the hands of our medical students. This got me wondering – how did those individuals go about donating their bodies and what will they be used for?

The donation of a body, or pa786px-Mortui_prosumus_vitae_-_Bremgartenfriedhofrts of a body to science is a concept that many are familiar with, but in fact it is often poorly understood. Indeed, the topic is not often spoken about which, when you think about it, makes sense since those who donate their bodies are not around afterwards to talk about the experience.

However, after trawling the internet for information I came across a fair amount, including several websites detailing the various levels of body donation. It’s interesting to note that, along with whole body donation, there are many ways to contribute to science without offering your entire body both in life and after death:

At the lowest end of the scale, individuals can volunteer for scientific experiments, most commonly performing psychological tests or receiving brain scans. Following these procedures the body is (generally!) returned intact.

At the next level you can volunteer for a more invasive and intensive experiment such as trials for drug treatments, with a significant risk to the individual.

The third level, partial temporary donation, involves donation of a physical aspect of your body that is not permanently missed, such as blood.

The penultimate level involves permanent donation of a part of your physical body, most commonly organs. This type of donation usually occurs post-humously when an organ may be donated to another individual in a transplant procedure, or used for medical research.

Finally, the ultimate scientific contribution, complete body donation.

The_Anatomy_LessonHowever, this was not always the case. Indeed, although the bodies used by our current medical students were generously donated with prior consent, at the beginning of the 19th century, bodies used for teaching were usually those of criminals put to death for their crimes. As the study of surgery and anatomy began to explode, alongside a dramatic decrease in the number of executions, there developed a huge demand for bodies that exceeded supply. At this time in Edinburgh, demand was exploited by the infamous William Burke and Hare who were known to have killed more than 20 people before selling the bodies to anatomists. The success of this lucrative ‘business’ was short-lived when their plan was exposed, leading to creation and introduction of the original 1832 Anatomy Act.

At least in the UK, body donation is a tightly regulated process with many strict legal requirements. Regulation is necessary in order to secure a body for donation, since human tissues can be hazardous and may pose a risk to those who come into contact with it. The Human Tissue Authority (HTA) are the regulatory body in charge of controlling the use of organs and body materials. The Human Tissue Act (2004) requires that a written and witnessed consent to anatomical dissection is given prior to death and a copy left in your will. Donations needs to be in a relatively ‘normal and healthy’ state and individuals must not have died from any communicable disease but from natural causes. Bodies are usually required to be whole with no amputations or transplants given during life.

After donation, the body is embalmed in formaldehyde in order to stop the decomposition process and preserve the tissue. They are also pumped with phenol to prevent the growth of mould. The body is then transferred to a fridge for 3 months to allow the formalin to work (changing proteins in the body and halting degradation).

Donated tissue can be used for several purposes including: teaching, furthering research into human health and anatomical examination or educational displays (such as in museums). Therefore, the donation of tissue is vitally important to society.

The Royal College of Surgeons predicts that there will soon be a shortage of body donations which could threaten teaching and medical research. In 2008 there were approximately 45,000 trainee doctors and surgeons, but only 600 bodies were donated to medical schools for teaching. A number that the RCS predict will continue to fall as fewer people are made aware of this vital practice. The College predicts that the UK medical schools will need around 1,000 bodies each year to maintain sufficient teaching levels, but predict a 30% shortage in 2012.

800px-Body_Worlds_Exhibit_San_Diego_2009I was first made aware of body donation after visiting the Body Worlds exhibition in Manchester several years ago. I found myself faced with an intriguing collection of various human and animal forms partially dissected to expose their internal anatomy. The bodies were posed into various forms and positions, with the purpose of educating the lay person about the human body. Some displays also highlighted how disease affects the body, leading to better health awareness. The exhibition exploits a process known as plastination, invented in 1977 by German anatomist Gunther Von Hagen. Bodies are preserved by replacement of bodily fluids with a polymer to preserve tissues and cause rigidity. This also allows the body to be displayed in a desired position. This may be viewed as an extreme way of raising awareness, and it is one that has created its fair share of controversy. It cannot be denied that body donation is an important process, one which certainly requires greater public attention.

As a lasting thought:

By donating your body, you will be doing everything possible as a layman to improve doctors’ level of training. You will be passing the medical care given to you, which started with the treatment your mother received before you were born, on to future generations.’ GUNTHER VON HAGEN.

Post by: Sam Lawrence