What lies beneath

Deep-sea chimaera by NOAA, Ocean Explorer on Flickr

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How does a fish see where there’s no light? To find out, you have to join them in the gloomy nether reaches of the ocean. At a recent Packed Lunch, Professor Ron Douglas described his life as a visual science researcher, and Lydia Harriss was there to hear tales of the deep sea…

Out of the watery gloom, there comes a small, dark shape. It looks rather like a small fish. A tasty snack, perhaps? It’s definitely worth a closer look… Before you know it, something clamps on to you with sucker-like lips, digs in with razor sharp teeth, and twists to cut out a circular plug of flesh!

It sounds like the stuff of nightmares, but it’s not. It’s the cookie-cutter shark, and, as I discovered at a recent Wellcome Collection event, it’s real.

Speaking to Wellcome Trust’s Dr Daniel Glaser at a Packed Lunch session entitled ‘The Deep’, Professor Ron Douglas opened a window onto the secretive world of deep sea biology. He is Professor of Visual Science at City University and an expert on the visual systems of deep sea creatures.

The ‘deep sea’ describes the region from 200 metres below the surface down to the seabed, which can be 11 000 metres deep in some places. This means that his lab is the ocean and he does many of his experiments on board boats in warm and exotic locations. Costa Rica, Nicaragua, Samoa, New Zealand, Hawaii… his gleeful list of research destinations had me contemplating a dramatic change in career direction.

Although the locations sound idyllic, the research itself can be pretty tough. Catching the deep sea creatures that Professor Douglas studies is a “lucky dip” exercise. Despite dragging nets the size of a football goal behind the boat for up to ten hours at a time, a catch will often barely cover the bottom of a domestic-sized bucket.

As boats cost £25 000 per day to hire and run, scientists work as close to non-stop as they can manage, on trips that last for four to six weeks. In vision research, it’s important to minimise the amount of light that the animals come into contact with, so they usually fish at night and try to persuade the captain to switch off the deck-lights (captains are normally reluctant to oblige, as “people tend to fall off the back”). Weather conditions can also be very rough, so good sea legs are a must. And then there are the other scientists…

To spread the research costs, a single boat may carry 20 scientists from, say, 10 different labs. Living and working at such close quarters with collaborators, and perhaps potential rivals, is bound to be difficult at times. Although cruises are carefully planned to avoid having multiple scientists with the same research focus, there’s likely to be competition over who gets first dibs on what’s in the bucket.

This is where Professor Douglas has the advantage, as his experiments require the animals to be kept in the dark. Thus, the first port of call for the bucket and its contents is his dark room. “I get to see what’s there first, and then I hand the bucket out into the light and I say ‘no, there’s nothing of interest in there’”, he jokes. His particular expertise is finding out what colours animals can see, by extracting and analysing the chemicals found within their eyes.

There’s an intriguing and rather enchanting alternative to fishing for “a few mangled creatures in the bottom of a bucket” (Professor Douglas’ choice of words). Namely, going down to observe these animals in their natural environment.

The conversation between Professor Douglas and Dr Glaser carried us into a submersible and down through clear blue Caribbean water. The deeper we went, the darker and bluer it became, as though we were descending through a cathedral of blue light. This is because water more readily absorbs light of longer wavelengths, such as red and yellow, than light of shorter wavelengths, such as blue. The blue component of sunlight therefore penetrates further into the ocean than other colours of light and is the last to fade out.

By 700 metres, we were beyond the reach of sunlight, but it was not completely dark. Many of the creatures living in the deep sea make their own light through a chemical process called bioluminescence. This light is almost always blue, probably because it can travel further through water than light of longer wavelengths. The chemical reactions that produce it are similar to those found in fireflies or glow sticks (the sort that you activate by bending, which breaks an internal glass separator and allows different chemicals to mix and react).

Bioluminescence occurs in tiny pits known as ‘light organs’, which may be covered with filters that are used to expose or hide the light. Often located under an animal’s eyes or on their forehead, light organs can help to illuminate the way ahead. They are also distributed across the bodies of some fish, in characteristic patterns that may help the fish to identify each other.

In the case of the cookie-cutter shark, which can migrate between the surface and depths of as much as 3700 metres on a daily basis, light organs act as camouflage. They produce a glow that helps the cookie-cutter to blend in with sunlight from the surface, rather than appearing as an ominous silhouette likely to scare away its prey. Light organs are absent from a dark patch around the shark’s neck, which is shaped roughly like a small fish. It’s thought that this may lure the shark’s prey, who are themselves hunting for food. Many fish, whales and dolphins have been found with circular ‘crater wounds’ characteristic of cookie-cutter bites. Although these sharks have been known to attack humans, they are not usually considered a serious threat.

The majority of the deep sea creatures that we know about only see blue light, enabling them to detect most bioluminescence and any residual sunlight from the surface. Single-colour vision is also more sensitive than multicolour vision, which is a real advantage where light levels are so low.

In this mostly monochrome world, there is at least one animal exploiting the evolutionary niche of multicolour vision. Dragon fish, named for their monstrous teeth, are able to bioluminesce and see both red and blue light. A large light organ beneath their eyes produces red light, effectively giving these fish their own private wavelength. The potential advantages are huge. Imagine being able to flash your lights as a signal to potential mates without drawing unwelcome attention from your predators, or hunting with a bright searchlight that you can see but your prey cannot.

Unlike dragon fish, the humans investigating the deep sea are far less stealthy. Professor Douglas likens going into the deep sea with a submersible to going into the savannah with a Land Rover to see lions. At night. With the headlights on, the stereo blasting, and a blue flashing light on the roof. “All you really see are the deaf, the blind, the stupid and the old. In other words: the things that can’t get out the way.” Despite this, researchers reckon that roughly one in three dives find an entirely new animal that no one has ever seen before. “Deep sea biology is one of the few fields where you really can just be an explorer.”

At present, submersibles can go down as far as about 4000 metres. As we develop technology that will take us further into the depths of the ocean, allow us to stay down there for longer and enable us to switch off the metaphorical stereo, we are likely to discover more incredible creatures. Creatures that are already lurking out there in the deep, just waiting to be discovered…

Lydia Harriss is a graduate trainee at the Wellcome Trust.

Not to be sneezed at

Influenza virus by Sanofi Pasteur, on Flickr

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With the flu season upon us, at the first Packed Lunch talk of 2012 in Wellcome Collection, Professor Wendy Barclay – Chair of Influenza Virology at Imperial College – discussed her current research. Penny Bailey was there to hear about the race against a constantly changing virus.

We think of flu as a human disease, but its main hosts are birds (particularly wild waterfowl), with whom the virus enjoys a very successful relationship. It causes few symptoms in birds and passes easily from one host to the next, courtesy of the waterholes where large flocks of migratory birds gather to defecate and drink. Infected birds shed the virus in their gut into the water, which others then imbibe.

Occasionally the virus crosses to pigs and chickens on nearby farms. From pigs it can pass to humans – not through pork products, but through contact with the live animals. It can also pass directly from birds to humans, as the H5N1 virus did in Southeast Asia in 2007. This ability to move around in lots of different ways is crucial both to its ‘success’ and to the threat it poses to people.

Influenza’s new clothes

Like many viruses, the flu’s genetic material is made of RNA. RNA is much more mutable than the DNA in our human chromosomes, the extreme stability of which restricts our evolution to a leisurely pace over millennia. The flu virus, by contrast, swaps bits of RNA around to change its coat of surface proteins within months – that rapid evolution allowing it to elude the host’s immune system, and any new vaccines aimed against it.

The flu virus is too small to see without an electron microscope, but Wendy brought along a model – a sparkly, remarkably symmetrical ball with spikes sticking out of it – to demonstrate how it changes its protein coat. The spikes (or surface proteins, or ‘antigens’) are shaped like lollipops, each comprising a head on a stalk that sticks out of the body of the virus. Our immune systems detect these antigens and generate specific antibodies against them that target the virus for destruction.

The flu virus ‘wears’ two main types of spike or antigen, labelled ‘H’ and ‘N’. Each of these has a number of subtypes: there are 16 known ‘H’ antigens (H1 to H16) and nine ‘N’ antigens (N1 to N9). Combining the two gives the names of particular strains of the virus, such as H1N1 (the strain responsible for the 2009 swine flu and 1918 Spanish flu pandemics), H5N1 (the 2007 avian flu pandemic) and so on.

The numerous possible combinations of ‘H’ and ‘N’ – plus the fact that an antibody against any one subset of either won’t protect against another subset – pose a challenge for vaccine makers, who have to design a new vaccine each year to target the most prevalent strains circulating.

The dream is to develop a once-only, one-size-fits-all vaccine that will protect us from all possible strains of the virus. In a bid to realize it, researchers are attempting to design a vaccine that will target the stalks, rather than the heads, of the lollipop-shaped antigens because these are structurally similar across all different types of H and N antigens. At present our immune systems don’t readily make this type of antibody, so it’s a question of finding a way of persuading them to do so.

Until we can do that, our bodies will be constantly running to keep up with the flu virus’s rapidly changing genome and ‘coats’.

Altruism and silence

It’s not a battle to the death. In fact, Wendy points out that it’s in the interest of the virus not to kill its host. If it only makes 100 copies of itself, that’s still enough to pass on to a new host. A million copies would overwhelm our bodies and kill us (as probably happened in the 1918 flu pandemic), effectively making the virus ‘homeless’. The most successful viruses are ‘silent’ and cause few symptoms in the host, like those living in wild waterfowl or the numerous viruses all of us humans harbour but are unaware of because they don’t make us ill – the herpes virus, for example.

Our bodies compromise in turn. When we catch a flu virus, some of our cells die an ‘altruistic’ death, to protect the rest of the cells in our bodies by limiting the number of copies the virus can make of itself.

We also have to keep a balance between by releasing inflammatory chemicals (such as cytokines and chemokines), which push up our temperature and destroy the virus, and damaging our own tissues with those same chemicals: a ‘cytokine storm’ can be fatal. The jury is still out on whether we should take paracetamol to lower our temperature during flu or let it take its course.

The 2009/2010 H1N1 swine flu turned out to be far more harmless than we first feared, and most people infected didn’t even notice they had it – but it did kill some people. Wendy believes the different impact of the virus on different people may be due to subtle changes in our genomes that protect some of us from infection (like mice, nearly all of whom have a gene that prevents them getting flu).

Alternatively, some people who got off lightly may only have received by a low dose of the virus that their body could deal with efficiently, generating antibodies against it (the basis of vaccination). Or they may have better innate barriers to infection, such as mucus and cilia. They may even have been First Defense users. Apparently it does work – Wendy confessed to using it herself on occasion. It’s very acidic (and viruses are sensitive to low pH), so it kills them in our nose and throat when they first infects us. But, she warned, we would have to ‘sniff a lot’ for continuous protection.

Ferret flu

Since mice have a protective gene that rules them out as models for human flu, the ferret is the gold standard model for laboratory studies. Ferrets and humans have the same molecules on their respiratory tract that allow the virus to stick to and invade the cells there. And ‘ferret flu’ follows the same course as human flu: two to three days of fever, 12–24 hours after infection, followed by coughing and sneezing two or three days later (the virus denudes the protective layer of mucus and cilia in our respiratory tract).

Wendy used a ferret flu model during the 2009/2010 swine flu pandemic to try and answer a question numerous journalists were phoning her to ask: at what stage of the illness were people most infectious? And when could they return to work without risk of infecting their colleagues?

One ferret (the ‘patient’) received a dose of flu on a known day and then had two ferret ‘visitors’ – one on the first day before the infected ferret was symptomatic, and one on day five when fever had abated and the animal was coughing and sneezing. Unexpectedly, the first ‘visitor’ developed a worse case of flu, pointing to the unfortunate conclusion that we’re most infectious when we don’t even know we have the flu yet.

Genetically engineered flu

Wendy also gave her opinion on the controversial study published in November 2011 showing that five tweaks to H5N1 (that has killed 500 people) make it more contagious. She believes the scientists were trying to answer a very vital question – how likely is H5N1 to jump from birds to humans, or to another species? – by anticipating the mutations the virus would need to jump from birds to ferrets, then ferret to ferret.

We spend vast amounts of money globally stockpiling vaccines and drawing up plans to protect people from a possible H5N1 pandemic. But there are 16 (or more) types of bird flu virus – any one of which could mutate and jump species to humans. If the research showed that H5N1 would never pass to humans, we might want to change our priorities and look at other strains.

The researchers also used the genetically engineered virus to look at whether the drugs and vaccines we’ve developed against H5N1 actually work – something that hasn’t yet been tested on a real human virus.

Living on the edge

We talk about the behaviour of the flu virus, its ‘success’ and its ‘relationship’ with its host. Does this mean it is actually alive? Wendy’s take on that (still hotly debated) question is ‘almost’. The flu virus is, she believes, on the brink of life.

Finally, how worried should we really be about a possible global flu pandemic? That it will happen is a certainty, she says. There are so many viruses in the wild, in pigs and birds, more of which will definitely emerge and jump to humans, and overcrowded populations of people offer perfect conditions for a new strain to take off and spread rapidly. On a brighter note, however, not all strains will be deadly.

Penny Bailey is a writer at the Wellcome Trust.

All ears

BIO 120 Lab Inner Ear 001 by djneight, on Flickr

You’re listening to this Packed Lunch podcast, but how are the sound waves converted into what you hear? And how could understanding their amplification help those who can’t hear? UCL’s Ifat Yasin has been researching the inner ear, and Benjamin Thompson was there to hear what she said…

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The final Packed Lunch event of March saw Dr Ifat Yasin, Lecturer in Auditory Anatomy and Physiology at the UCL Ear Institute, come and discuss her research and the science behind hearing to a room full of interested guests.

A new addition trialled during the talk were two large speech-to-text screens allowing those with lower levels of hearing to follow all the details. Dr Yasin talked us through her work, and explained what can go wrong within the ear and how it can lead to hearing difficulties.

Yasin described the current focus of her work. Picture yourself sitting in a sound-proofed room, in front of a computer monitor showing two lit squares. With a set of headphones on you’d have to listen carefully and press a button when you think you hear a ‘peep’ sound between two ‘shhh’ sounds.

These experiments can be very long: an hour, ten hours, 60 hours. That’s a lot of listening time. Thankfully the volunteers get lots of breaks! Yasin explained that many of the volunteers find the downtime really relaxing. These volunteers have hearing levels within normal limits – important given the subtle differences in volume and duration between the ‘peeps’ and the ‘shhh’s. By manipulating these parameters, Yasin can map out how the ear amplifies sound.

The talk moved on to discuss how amplification occurs. This happens inside an organ found within the inner ear called the cochlea. This is a snail-shell-shaped structure filled with liquid. Sound waves picked up by the ear cause the liquid to move. In turn this causes a membrane within the cochlea to vibrate. Very fine ‘hair’ cells detect these vibrations and turn the movement energy into electrical energy, sent to the brain via nerves attached to the cochlea. These hair cells only look like microscopic hair, but it turns out they’re not made of the same stuff as those on the top of your head.

Dr Yasin is investigating how the cochlea is able to act as an amplifier. Cleverly, it can amplify quieter sounds more than mid-level sounds. It turns out that low-level sounds make the membrane within the cochlea vibrate more than mid-level sounds. The response to rising noise levels is known as ‘nonlinear’ and is important for normal ear functioning.

‘Auditory illusions’ were also discussed. These aren’t quite illusions in the sense of hearing things that aren’t there, but are very useful for us day-to-day. When we’re in a noisy environment it can be difficult to pick out individual sounds. Thankfully our brains help to collate sounds of a similar pitch or loudness – helping us pick out relevant sounds within noise. This is known as the ‘cocktail party effect’.

Dr Yasin’s current round of experiments will take another three years. She hopes by understanding how a healthy ear is able to amplify sounds, the tests (when drastically reduced in length) can be used to diagnose those with cochlear problems.

Benjamin Thompson is a writer at the Wellcome Trust.

Stars, Mars and the vomit comet

Greenwood Space Travel Supply Co. by WordRidden, on Flickr

Space travel might sound glamorous, but it’s not all playing golf on the moon. For a start, in zero gravity your bone and muscle start to rot. February’s Packed Lunch featured a scientist whose speciality is keeping spacemen healthy. Benjamin Thompson found out more…

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February’s Packed Lunch at Wellcome Collection concentrated on the subject of space and space travel – along with dinosaurs, one of the two things that got me hooked on science as a child. This month’s interviewee was Dr Kevin Fong, anaesthetist, Lecturer in Physiology and co-director of the Centre for Aviation Space and Extreme Environment (CASE) Medicine at UCL: you might have seen him on TV.

Fong discussed a variety of topics, including why being in space is bad for our health, whether astronauts really do have ‘The Right Stuff’ and why humanity needs to continue exploring the heavens.

The lunch began with Dr Fong describing an experiment he participated in at the Johnson Space Centre, Houston. It involved being strapped to a plank and spun at 45 rpm for an hour, watching a Harry Potter film. The point of this? To experience an artificial gravity. Being spun like this forces the blood to your feet, making you feel bent over for the time you’re spinning. The reason for Harry Potter? That was the only DVD available.

While this might seem a bit daft, it’s all preparatory work for sending people to Mars. It turns out that over long periods of time, weightlessness is very bad for our bodies. As humans we are entirely designed to live under the Earth’s gravitation pull of one g (what are the chances?), so as soon as we encounter zero gravity, Fong explained, we basically we begin to rot. This might sound extreme, but it makes sense. When weightless our skeleton and muscles no longer need to support our weight so they begin to degrade. Add to this an inability to sleep or eat healthily (no refrigerators in space) and the astronaut has a multitude of problems to deal with both in space and when re-acclimatising after returning home.

Health maintenance of astronauts is very important and this is the role of a space doctor, or flight surgeon. Space is not an easy place to practice medicine, with many of the procedures we take for granted on terra firma not working under zero g. There’s not much spare room in a rocket to take medical supplies with you on a mission, and everything has to be thoroughly tested in weightless conditions on Earth using the delightfully titled ‘vomit comet’, an aeroplane that through clever flying can provide short periods of zero g.

Thus far, doctors haven’t been specifically sent on space missions. Fong explained that given the relatively short distance between here and the International Space Station, if you are taken ill, you can be home in a few hours and cared for by the cream of the US Army Medical Services. Currently the biggest danger from spaceflight is the travelling. Either everyone returns safe, or no one does…

This will all change, though, if/when humans are sent to Mars. If you’re a year and a half away from home, becoming seriously ill is bad news. Fong explained that risk analysis from activities carried out in extreme environments, such as Antarctica, or in submarines, suggests that it is more likely than not that something will go wrong. This suggests it’s best to send a doctor on the mission. But what if the doctor gets sick? Do you send one or two? The debate is raging, and is likely to for a while.

Fong was asked if, in today’s testing economic climate, he thought that space exploration could still be justified. He wondered whether space travel be viewed in future times in the same way as we do the pyramids now, a one-off project achieved at massive cost, both human and economic? Or will commercial bodies step in, reducing the cost and boosting the speed of knowledge creation?

He explained that although expensive and dangerous, manned space travel can teach us things that robotic missions simply can’t. For example, we only know how old the rocky planets in the solar system are by studying and ageing moon rocks brought back from the Apollo missions and counting the numbers of craters seen on the other planets to extrapolate their ages. In total, all the robotic missions have brought back a sum total of 37 grams of rock, whilst manned missions have brought back around 500 kilos. If we truly want to look for evidence of life – extinct or otherwise – beyond our own planet, we’re going to have to send people.

Benjamin Thompson is a writer at the Wellcome Trust.

Lunch on drugs

Joint, by Marcos Fernandez, on Flickr

Packed Lunch returns soon with more tales of research from local scientists. To get you in the mood, we’re catching up with some of last year’s, via the Packed Lunch podcast. In December, Benjamin Thompson went along to hear from a scientist who comes round to your place when you’re getting high…

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This month’s Packed Lunch at the Wellcome Collection concentrated on the study of illegal drugs. The room was full to bursting, leaving many of the guests sitting on the floor. Whether they were there because the Collection’s excellent High Society exhibition had raised their intrigue in the illicit, or because they were active users of non-prescription medications, the talk raised a huge amount of questions and stimulated a high level of debate.

This month’s interviewee was Dr Celia Morgan, a research fellow in clinical psychopharmacology from UCL. Dr Morgan’s area of research focuses on both cannabis and ketamine.

With her recent cannabis studies, Morgan described an interesting approach to gathering data, very different to what I perceived most drug studies to be like. Rather than exclusively observing the effects of the narcotic in a lab based environment, she goes round to people’s houses to test them at home.

Volunteers are all students from UCL, who have been checked to ensure they have no family or personal history of psychosis, nor any serious head injuries in the past. Dr Morgan and colleagues visit the volunteers twice; on the first visit the team take a hair and urine sample, then ask the volunteer to skin up, get high, and undertake some cognitive tests. A sample of weed is also taken for analysis.

A week later the same volunteer is visited and the tests are repeated, except this time the subject is ‘straight’. Saliva samples are taken to ensure no drugs have been taken in the past few hours.

Why are the hair samples taken? It turns out that hair acts like the rings of a tree, keeping a record of all the drugs you’ve taken in the past. On average a person’s hair grows about 1 cm per month, so by taking a 3 cm length a record of all drugs ingested over the past 3 months is available. This can be more useful than asking the volunteers themselves to remember what they’ve taken, especially as the substances used can impair memory!

What about the weed samples? Why are they taken? Dr Morgan explained that these are tested to assess the levels of two active compounds: tetrahydrocannabinol, or THC, is the most well known and produces the ‘high’ associated with cannabis, but also assessed is the level of cannabidiol, or CBD, which appears to reduce anxiety at high doses and may act as an antipsychotic, counteracting the effects of THC.

Levels of CBD in cannabis are dropping, not due to consumer demand for more potent strains with higher levels of THC, but due to modern growing conditions – indoors, frequently under constant lighting in UK factories – which appear to be lowering the plants’ natural levels of CBD.

Too little CBD may lead to acute memory loss over time and an increase in levels of proneness to psychosis.

Dr Morgan’s other research is on ketamine, a substance developed as an anaesthetic in the 1960s. Ketamine is still used today, mainly due to its safety, as it doesn’t interfere with a patient’s breathing. However, the drug has several unpleasant/pleasant side effects, depending on how you look at it. Patients described vivid hallucinations after surgery, and because of this the drug became popular for recreational use.

Ketamine began being used in the UK during the rave scene in the 1990s, when it was frequently cut with ecstasy. At low doses the drug is a stimulant, whilst a mid-strength dose may cause the user to experience bodily distortions, with limbs feeling much longer or shorter than they really are. A high dose can result in the user becoming catatonic, known colloquially as a ‘k-hole’. There is no comedown associated with ketamine as there frequently is with other drugs.

So far this sounds interesting. Sadly, however, there are a number of dangerous downsides associated with the use of this drug. Ketamine is addictive, and Dr Morgan suggests that this may be due to its short action time. Heavy users may experience both mental and physical issues, including severe memory problems and the charmingly named ‘ketamine-associated ulcerative cystitis’. This irreversible condition is caused by the drug physically binding to the bladder, which can ultimately result in bladder removal.

Dr Morgan is interested in the drug as its use is becoming more popular in the UK, but little research has been undertaken on its mode of action and long term effects. She hopes the work on this drug, and that on cannabis, will help inform the public and hopefully drive future government drugs policy in an evidence based, rather than media frenzied, direction.

Benjamin Thompson is a writer at the Wellcome Trust.

Packed Lunch: Turning your brain off

When Simon had his brain switched off by SBishop, on Flickr

Packed Lunch returns soon with more tales of research from local scientists. To get you in the mood, we’re catching up with some of last year’s, via the Packed Lunch podcast. In November, Benjamin Thompson went along to hear about a scientist whose work involves using a giant magnet to stop you thinking…

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The theme of November’s first Packed Lunch at the Wellcome Collection was the neurological basis of language recognition. Dr Joe Devlin from the UCL Division of Psychology and Language Sciences came by to talk about a technique he uses to investigate the inner workings of the brain.

Joe’s research involves using strong magnetic fields to stimulate different areas of the brain known as Transcranial Magnetic Stimulation (TMS). The machine used to provide the magnetic field looked fairly innocuous, two doughnut shaped rings of wound copper covered with insulating tape. But as Joe described what it was capable of initially, it seemed rather terrifying…

In order to create the magnetic field a huge current needs to be passed through the coil. This current is lethal, so it is imperative that the insulating tape is checked frequently! The magnetic field that is created is as strong as those used in junkyards to pick up cars, but it only lasts a fraction of a second and extends for a few centimetres.

So what can this strong magnetic field achieve? By placing the TMS machine next to a volunteer’s head Joe is able to externally stimulate a very precise area of the brain. The magnetic pulse causes brain cells to fire, interrupting the task they would normally be doing and introducing ‘noise’ to that particular brain area. This noise only lasts for a fraction of a second before returning to normal, but this time period allows for some interesting experiments.

The experiment that Joe described showed how the understanding of spoken words and the ability to read are linked. The experiment involved playing a volunteer a list of words, some of which were real and some which were false, but sounded real. The volunteer had to press one button when they heard a real word and another when they heard a false word. This allowed Joe to measure how quickly and accurately the volunteer responded to the words.

Typically the volunteers were highly accurate and had a response time of around one second. This included half a second needed to hear the word and about half a second to respond to it. When subjected to TMS, the response time of the volunteer increased by about a third of a second, but only for certain words.

Amazingly, it was simple words with a regular spelling that the volunteers were slower to recognise during TMS. This seems totally counterintuitive so I asked Joe if he could explain it to me a bit more. He told me that adding brain noise using the TMS machine makes normally easy to understand words not so easy to understand.

He likened the recognition of a word to being on a hill. The word is found at the foot of the hill and you have to descend the slope in order to recognise it. With difficult words, that are spelt differently to how they sound, you’d begin at the top of the hill, with a long distance to travel, but with easy words you begin much lower down the hill so the time needed for recognition is much lower.

During TMS, you get pushed back up the hill when recognising simple words which results in the increase in time seen in the button pressing experiments.

It turns out that learning to read changes the way we recognise speech. We get better at recognising speech when the word and its spelling correspond closely. This increase in speed is not down to visualising the words, as using TMS to disrupt the visual recognition centres has no effect on the speed of word recognition, it’s all down to the way in which you hear the words themselves.

Joe’s talk really clicked with the audience, who raised many questions about a variety of topics, such as adult illiteracy, Alzheimer’s disease and synaesthesia – associating colours with sounds. People were also intrigued by the potential of using TMS for therapeutic purposes. The one question that everyone was thinking, but only one asked was  “Are you looking for volunteers?”

Benjamin Thompson is a writer at the Wellcome Trust.

Making your mind up

Decisions 2 by cuellar, on Flickr

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I stood in the lunch queue, a string of anxious people behind me, the server tapping impatiently on the counter with his spoon, clock ticking down, minutes to go before I had to be at Wellcome Collection for the latest Packed Lunch talk. Yet I still couldn’t decide… what did I want for lunch?

The irony was not lost on me. This Packed Lunch was on decision-making.

Would I have fared any better had the speaker, Peter Ayton of City University, been next to me in the queue? A Professor of Psychology, Ayton studies human judgement and decision-making, and he said one thing that might explain my lunchtime dilemma: our reaction to choice.

You’d think that the more options we have the better able we might be to pick the one most suited to us. But we humans need things simpler than that. Ayton described an experiment where shoppers in a department store were offered different samples of jam to try and buy.  When 24 jams were offered, many people tried them, yet few bought them. But when just 6 jams were on offer, many more people followed through and bought a jar. The theory goes that when you have more variables to contend with, it actually makes you less likely to make a decision.

And we’re worse when re-evaluating a decision we’ve already made. Ayton told us of the Sunk Cost Fallacy. According to this behaviour, we find it difficult to cease the pursuit of a goal even if a better option comes along later, because we’ve already invested so much in the current course of action.

And it seems to take hold relatively early in life. In an experiment, Ayton’s team of researchers asked children to imagine that they had to eat their least favourite breakfast cereal in order to save up tokens for a toy reward. They were then told that on the last day, a kind Uncle gifted them the money to buy the toy, so they wouldn’t have to eat that last box. Would they still eat it? Younger children of 4-5 years old wouldn’t eat the final packet of cereal. But older children would. It’s the Sunk Cost Fallacy at work.

The behaviour is, as Ayton discovered in 1998, remarkably similar to a theory zoologists refer to as the ‘Concorde fallacy’. Coined by Richard Dawkins, it refers to the British and French governments continued funding for the supersonic Concorde aircraft, even after they realised it would never be economically viable.

One of Ayton’s biggest achievements was uncovering this unlikely synergy between the two completely separate fields of psychology and zoology. And it’s been a fruitful discovery, as Ayton says, there is much we can learn about human behaviour from studying that of animals.  Animals, he says, are “exquisitely adapted to their environment” – they only take risks (e.g. going for a risky food source) when they absolutely have to. Animals don’t tend to commit the Sunk Cost Fallacy, but humans do, and that’s what’s interesting.

During the talk, Packed Lunch host Dan Glaser wondered if this deleterious effect was the result of our having evolved to be self conscious and socially aware. Is this the reason for our irrationality? Here, Ayton revealed that it wasn’t just humans that are irrational. Bees do it too. Studies have shown that when presented with different flowers to feed from, bees showed a distinct preference for flower A over flower B. and flower B over flower C. Yet they also chose flower C over flower A!

“Bees have been bees for longer than people have been people, so irrationality is something that has evolved in different species,” said Ayton.

The question on everybody’s lips was, as a Professor of human judgement, is Ayton any better at decision making himself?

Sadly, the answer is no.

“Many people get into this field because they recognise their flaws. But we’re no better at decision making than anyone else. When I think about a decision, I see not only the options but all the fallacies I might commit!”

Burning passions

Colour-enhanced scanning electron micrograph of a meshed skin graft over a burn. Wellcome Images.

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I have a guilty pleasure: British medical TV series. I love the melodrama of ‘Casualty’, and ‘Holby City’s’ intense-but-predictable storylines. So imagine my delight when Isabel Jones, consultant burns and plastic surgeon at Chelsea and Westminster Hospital, was announced as the next Packed Lunch interviewee. A chance to experience a real-life account of the drama of medicine, I hoped.

I wasn’t disappointed. Isabel arrived at the Wellcome Collection straight from an operation that had started at 8.30 in the morning. Her day had begun at half past midnight, when she received a call to say a young woman had been brought in to the hospital with severe burns to her chest – caused by a fire she had accidentally set in her house after a drunken night out.

There was a tingling sense of shock in the audience, yet Isabel spoke matter-of-fact. She explained that Chelsea and Westminster Burns Unit is a specialist referral centre for Greater London and the South-east, meaning anyone within the M25 with significant burns comes to them for treatment. Dealing with this kind of injury is a regular part of her job.

Any burn over 15 per cent of the body’s surface is life-threatening. Isabel’s patient had 25 per cent. When skin cells are damaged and die, the body’s barrier to the outside world is breached. Risk of infection increases, fluid is lost. The body undergoes a massive inflammatory response that can be fatal. The first 24 hours are crucial to the long-term outcome of the patient. At this stage, Isabel’s job is to remove the dead skin tissue causing this response. Previously, burns were left until a scar began to demarcate, nowadays, early excisions of burns is one of the most important modern progressions in the treatments of burns and is ‘critical for survival’.

Isabel prefers to plan a surgical procedure in advance, hence the midnight call. At 04.30 she went back to bed, waking again in time for the start of the procedure. She set the scene of the operation: three consultant surgeons, scrub nurses, intensivists. Sometimes, music is played in theatre. Not today though, as a lot of communication between the team is required during a procedure on a patient with injuries that could cause them to die.

Isabel is one of many in a team dedicated to the patients on the 20-bed burns unit. There are microbiologists, focused on the threat of infection; physiotherapists who get the patients back on their feet; psychotherapists to help them through the psychological consequences of their injuries. Isabel had spoken to the woman she was operating on this morning. She told us this woman knew her actions caused the injuries that will stay with her for the rest of her life. If she lives. When Isabel told us that the psychotherapists are available to staff too, you could see, and hear from her voice, that however much steely resolve and professional detachment she has, she is strongly affected when a patient she has cared for loses their battle for life.

When a critical patient comes in to the unit, the first priority is the quick and safe healing of their burn. Cosmetic outcome is kept in mind, but can be improved later with grafts and reconstruction. Another concern is the cause of the burn – why did this patient faint into the bonfire they built? Is this child’s scald the result of carelessness in the kitchen, or something more sinister? The burns unit works closely with social services. In the case of Isabel’s patient today, the large amount of alcohol she had drunk caused the careless lighting of a match and too slow a response to the resulting flames that burned her body.

It is likely that Isabel’s patient will need skin grafts to replace her damaged tissue. Grafts cannot come from another person, as this skin is antigenic: the body will recognize it as foreign and reject it. When performing a skin graft, Isabel will take a layer of skin from the thigh, buttock or scalp where there is minimal visibility of scarring. This is then carefully stitched onto the ‘wound bed’, using the wound as a template. A murmured laughter went through the audience when Isabel revealed her mother was a seamstress.

Artificial skins and skin substitutes are being developed, but the technology has not been perfected. The problem is creating something that is non-antigenic and can work universally for all skin types. Biotechnology is used, however, in the form of dermal replacements that enable a thinner graft to be used on the wound. This means less skin needs to be taken from the healthy site, and there is less scarring. I can only imagine the scars that Isabel’s patient will have when her trauma is over.

Reconstruction takes place long after a patient has received initial treatment. This is done to improve the cosmetic appearance of burns, and functionality. Sometimes contractures of the skin will form around joints, where the healed skin becomes very tight and restricts movement. Isabel will release these contractures, and perhaps move scar tissue around from one site to another, where there is more movement. The relationship between a patient and a surgeon can be lifelong.

At the end of the interview, Isabel was asked if she felt frustration about the cosmetic outcome of some burns. Her answer was yes, but the satisfaction of taking a seriously ill patient back to full health outweighs that. “The human level of positive feedback from patients is very rewarding,” she said. And as Isabel left the room, I could only hope that the young woman she was returning to operate on would live to thank her fantastic surgeon.

Louise Crane is a Project Officer at the Wellcome Trust.

Eating, walking, stretching and bubbles

A Packed Lunch event at Wellcome Collection

Can summer be over already? It’s sunny outside as this post is written, but autumn must surely be upon us soon, because we’ve just unveiled our new season of events. It’s quite a selection, ranging from London-wide health issues to microscopic bubbles, taking in skin both stretchy and perfect, packed lunches, delicious suppers and several intriguing strolls. Booking opens tomorrow at 14.00: our events fill up fast, so be ready to book online. And all (except the excellent value Supper Salons) are free.

Nursing and midwifery take over the entire building for an evening in Handle with Care, dedicated to the science and senses of caring professionals. Sick City? takes the form of a balloon debate: four experts each put their case for what they consider to be London’s public health priority. You the audience decide who wins, in a series of votes. And the Pars Foundation take an oblique look at our remarkably flexible skin in their Treats on Elasticity event (more on Pars and their stretchy work in a future blog post).

Lunchtimes will get interesting, as our Packed Lunch series of talks with local scientists returns. Taking her cue from our current exhibition, Isabel Jones kicks off by talking about her work repairing the skin’s delicate structure at the Chelsea and Westminster Hospital’s burns unit. UCL’s Nick Lane looks into how complex organisms evolved from simple bacteria (it’s all about the mitochondria), and Peter Ayton from City University explains how we make decisions in a bewildering and complex world. Then it’s back to UCL with Eleanor Stride, who works with microbubbles. It all sounds unmissable, but if you can’t get there in person, the ever-reliable Packed Lunch podcast will be there for you to catch up.

If dinner is more your thing, then Supper Salon will be right up your street. We skip straight to dessert with jelly-makers extraordinaire Bompas and Parr, whose gelatinous creations do so much more than wibble-wobble on your plate. But if you prefer giant crabs to jelly you’ll be in good company with our next guest, Robin Ince, a writer, comedian and collector of very bad literature including tales of the aforementioned crustaceans.

Having filled yourself up with food and ideas, some exercise might be in order, and what better way to take it than with our series of medical walking tours guiding you through the hidden corners and recondite histories of Bloomsbury. Explore the medical marketplace in ‘Conspicuous Consumption’, take a walk on the dark side with ‘Dead Famous’, recall the poverty in Bloomsbury’s history ‘In Sickness and in Health’, and get a taste of the scientific and occult in ‘Secret Bloomsbury’. Walks are led by Richard Barnett, author of Medical London, Strange Attractor‘s Mark Pilkington, and the Wellcome Library’s very own Ross MacFarlane. If you’re taking photographs on the walks (or if you take photographs of medical sites and  scenes anywhere in London), we’re always grateful if you add them to our Medical London Flickr pool, helping us build up a composite contemporary picture of London’s illness and cures.

And don’t forget our events looking at the Wellcome Library and its collections. Investigate the relationship between our heads and our hearts in Mind and Body: Heart and mind, and discover the multimillion-pound industry that feeds our Quest for Perfect Skin. Find out more about Henry Wellcome himself, and about William Morris’s collection of manuscripts in the Library. Focus on lurid tales of London life in Anatomies of London, and the 19th-century enthusiasm for ‘reading faces’ in London Faces. And then see Africa from another angle with a special tour for Black History Month.

Looks like a busy autumn for us. Hope to see you here soon.

Cold nights on Mars

Mars

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Cold War nuclear radiation testing and the inhospitable living conditions on Mars was the subject of this month’s Packed Lunch at Wellcome Collection. Dr Lewis Dartnell, an astrobiologist at the Centre for Planetary Sciences at UCL, was in to discuss his research into whether some forms of life might be able to survive on Mars.

From what we know of it, Mars isn’t the friendliest of places. It’s bitterly cold; the air temperature is rarely above freezing. And it’s very dry. Although we can see that the planet has polar ice caps, there’s no sign of any liquid water – which is essential for life – anywhere. It all seems to be either frozen or evaporating into the atmosphere.

To make matters worse, Mars has no magnetic shield, no ozone layer, and only a very thin atmosphere, so its surface is exposed to intense levels of radiation, including UV and ionising cosmic rays, which damage and destroy DNA.

As Dartnell explained, we’re protected from cosmic radiation by our planet’s “lovely deep atmosphere,” which absorbs high-energy particles in cosmic rays, and a magnetic shield, which deflects them. The high-energy radiation that reaches the surface of Mars would kill us.

But what about other forms of life, such as microbes? Might they be able to survive the harsh cold and fierce cosmic radiation on Mars?