Science, Sobriety and Snake Oil: The Electrifying Story of the Overbeck Rejuvenator by James Ormiston

Here’s a challenge for you: name an inventor of an electrical device from before the Second World War.  Who springs to mind? Thomas Edison? Graham Bell? Maybe William Sturgeon, Samuel Morse or Alessandro Volta? If you’ve been caught up in the recent surge of near-mythological interest in Nikola Tesla maybe you think of him? Well here’s one person on the list who you’ve probably never heard of: Otto Christoph Joseph Gerhardt Ludwig Overbeck. Overbeck was a man of many interests, and during his life he was a chemist, inventor, curio-collector, writer, artist and, most notably, a self-proclaimed discoverer of the key to youth and vitality. The device with which he believed he had unlocked the secret of a long and healthy life was the Overbeck Rejuvenator, and armed with a qualified fascination in science and a canny business mind he marketed one of the most commercially successful electrotherapy devices ever made.

Born in 1860, the son of a Vatican priest, Overbeck began his career as a chemist, studying the subject at University College London until 1881. After becoming a Fellow of the Chemical Society in 1888 he went on to work at a brewery in Grimsby as scientific director. Here he was responsible for a few interesting developments, including an early attempt at making alcohol-free beer and a food extract product called Carnos which was in fact a forerunner to Marmite.  Even at this stage he had begun a rigorous habit of patenting everything he thought would become a successful invention, Carnos being his first, which would become a staple of his approach for years to come. His broad interest in science was evident in his personal library, which included books not only on chemistry but biology and geology among numerous other subjects. Such was his enthusiasm that he claimed at one point to have discovered an element new to science.

 Self-portrait (1902)

In the following years leading up to the development of his most famous invention, the Rejuvenator, Overbeck became increasingly interested in the prospect of restoring youth, seeking a sort of “elixir” with which he could help people live longer with better health. His artistic side demonstrated this in a poem written in 1889 called “The Alchemist”…

“Yet one more drop, & now! What do I see!

The forms of early youth! Forgotten dreams to me;

Rise with the misty clouds from age’s wintry rime;

and boyhood’s joy & health & summer clime

With scent of roses fills the air!

Old age be-gone!

For eternal youth prepare!”

He was a strong believer in the idea that electricity was the unifying key to not only life but the entire universe, and whilst electrotherapy was not a new idea at the time Overbeck was very keen to demonstrate its benefits to human health.  In 1924 he took out a patent for an “Electric Multiple Body Comb for Use All Over the Body”, the first patent relating to the invention of the Overbeck Rejuvenator. The Rejuvenator consisted of insulated metal combs which, when connected to a battery, applied a weak electrical current to the area of the body the combs were in brought into contact with. The patent made no reference to rejuvenating properties, but nevertheless the product was intensely marketed as a medical miracle. Overbeck frequently backed up his advertising with testimonials from satisfied customers, with such whimsical quotes as:

“…elderly members of an east coast golf club have practised with the rejuvenator, and their handicap has been halved, and they can play three rounds as against two formerly.”

“I have been using your Rejuvenator for about five months…and have found it of great benefit. I was suffering from Neuritis, but [am] pleased to say I have scarcely felt any pain this winter. I have worn spectacles for 25 years, and now my eyes are wonderfully improved…my hair, which was white, is being replaced with new dark hair. I think your Rejuvenator is a wonderful invention.”

In 1925 he published a book on the subject, “A New Electronic Theory of Life”, in which he presented the importance of electricity in conventional medicine. He cited numerous eminent scientists of the time to back up his ideas, but he also frequently referred to the Rejuvenator itself throughout as a cunning marketing strategy. This was a rolling theme in the promotion of his device: using his position as a scientist as a role of authority through which he could persuade people to buy the Rejuvenator. Overbeck claimed it could treat all kinds of ailments from asthma to psoriasis, and the BMA (British Medical Association) was becoming increasingly concerned that the layman would start to ignore conventional medicine in favour of this “easy fix” which had so far not shown much, if any, quantifiable medical success. A model of the device was acquired for testing, and they found that whilst the device was not necessarily dangerous there was potential for its misuse to cause ulcers in the mouth. More worryingly, there was good reason to believe that people using this form of alternative treatment to treat chronic conditions like diabetes would put off seeking established medical advice until it was too late.

The Overbeck Rejuvenator was sold across the British Empire and had a number of variants at prices starting at around 6 guineas. Overbeck even adjusted his advertising campaigns depending on where it was being sold in order to further publicise it, encouraging users in the Colonies to write back to him about their experiences. One of the key parts of the Rejuvenator’s marketing was a focus on its ability to treat certain conditions that people felt embarrassed to talk about, such as hair loss. So successful was the device that he was able to buy a house in Salcombe, Devon (now a National Trust site dedicated to his work and collections), where he was able to engage in his other passions of curio-collecting, art, music, natural history and all other manners of hobbies and interests. But soon the Rejuvenator would begin to lose traction as Overbeck’s advertising strategies came under fire from the scientific community…

Demonstration of the Rejuvenator as a treatment for hair loss. 

Investigations were mounted by the BMA in the early 1930s to contact members who had been apparently quoted in the Rejuvenator’s advertising campaigns in Australia and elsewhere. Intriguingly many of the responses said that whilst they had bought the devices, they had not given permission for their opinions (genuine or not) to be published. Some outright denied any involvement with the company and demanded an official explanation. A number of attempts were made to ban the Rejuvenator on both medical and legal grounds, but none seemed to be successful (probably in part due to the ruthless patenting and numerous user testimonies which protected the device). Otto Overbeck died in 1937, but the device remained on the market up until the Second World War, when resources needed to build it became too difficult to acquire. Amazingly however, over 30 years after he filed the original patent for the product, in 1955 an order for a new battery to power an Overbeck Rejuvenator was received by one of his associates.

Whilst the Overbeck Rejuvenator was not proven to be of any real benefit to health (despite its inventor’s insistence), it was one of a number of early electrical devices to appear in British homes and elsewhere which aided the mainstream acceptance of a relatively new and revolutionary power source. It also provided a valuable lesson of the power of advertising, especially when coupled with the authority of science to persuade the public to buy a product. This is a theme that continues to this day, see how many toothpaste adverts feature an interview with dentists! Overbeck may have been mistaken in his faith of medicinal electricity, he may have even known it was of little use and was simply a very good seller of his contraption, but one thing remains certain: his multi-disciplinary life story is one of both eccentricity and intrigue.  

Synapse Science Magazine Issue 9

An interview with Professor Bruce Hood, School of Experimental Psychology, 11/11/2014 - by Melissa Levy

Professor Bruce Hood is a Professor of Developmental Psychology in Society. He is specifically interested in cognitive development from a neuroscience perspective, but also works on face and gaze processing, inhibitory control of thoughts and actions, spatial representation and action, naïve theories and the origin of adult magical reasoning from children’s natural intuitions. If you want any more information about what he and his group then follow this link: http://www.bristol.ac.uk/expsych/people/bruce-m-hood/

Where did you go to university and what did you study?

“My first university was the University of Dundee in Scotland where I did an arts degree. In Scotland you can do a four year degree and take lots of different topics, I didn’t know anything about psychology and I was doing things like economics, accountancy and finance but I had to take another subject and so I took psychology and fell in love with it! This made me decide that I wanted to be a psychologist! So I went to Cambridge and did my PHD there, so I’ve been in Scotland and Cambridge.”

How did you get from there to where you are now in Bristol?

“How long have you got?!

After Cambridge I had a position at UCL and then I got a MRC (medical research council) travelling fellowship which enabled me to go anywhere in the world and I went to MIT. So I did my post-doctorate at MIT and then I applied for a position at Harvard and I was an associate professor there for five years. Then I came to Bristol.”

How would you describe your area of research to someone who’s not in the field?

“Well I have very diverse interests but I suppose they all deal with aspects of development of mind - in the childhood origins of how we think as adults. I’m interested in children not because they’re kids but because I think they give a great insight into the complexity of adult behaviour and the human mind and also some indication as to how we’ve evolved complexity.”

How would you describe your typical day and your typical research? It’s obviously different to that of a chemist let’s say…

“Well unfortunately I don’t have the luxury of doing the research myself directly, although occasionally I will help out. I really love conducting research and collecting data but because I’ve got so many projects running simultaneously I can’t actually collect data myself. So usually it’s working with my post-docs and my grad-students to devise and design experiments, piloting them here in the centre and then very often taking them out into the community.

We do research at the @Bristol Science Museum, but we also collect data in the schools, so it’s a lot of what you would regard as field work. But if we were using a technology which doesn’t transport like eye-movement recordings or ERP (Event Related Potentials –brain signals) then we would do that in the lab.”

If you could go back to conducting the field work yourself would you do that or are you happy with where you are now?

“Yeah I am happy where I am now, but I’ve not lost touch with the sheer joy of data collecting. For me, experimentation is just wondrous and the fact that I can be paid for something that I enjoy so thoroughly is fantastic and I love to share that! I mean there are so many questions that I’d like to answer and I couldn’t answer them myself so I need to have people doing it for me and that’s why we have research students doing that all. I mean I would be delighted if I was just doing research.”

What advice would you give to someone looking for a career in science?

“Passion! That’s what gets you out of bed in the morning!

You have to have a sense of wonder and joy and curiosity, and if this is what you want then this should be enough to drive you forward, and if you have the confidence to do so then you should be fine.”

What has been your proudest achievement to date?

“Well I suppose it has to be giving the royal institute Christmas lectures on the BBC. I’m very passionate about what I do and I really want to take science out into the community and that is the pinnacle of public engagements so that gave me, for a very short time, a platform and a spotlight, which was really quite exceptional. I got to meet so many amazing people, I got to inspire people and I’ve had email correspondence from parents of young children – they still contact me three years later keeping me up to date with their achievements in science and I find that extraordinarily valuable to realise that what you do actually changes people’s lives and makes a difference.

 I’ve always felt that we (psychologists) have a bit of an identity problem that people don’t see us as a real science and that really annoys me. So that’s my other agenda, to make sure people understand how complex the mind can be and that it’s not common sense at all. There are some extraordinary things that we are yet to discover. So yeah I’m passionate about science communication.”

If you could do science with anyone, dead or alive, who would it be?

“Gosh, so many to choose from!

One of my greatest mentors was Richard Gregory. You may not know, but Richard Gregory was and still is a great influence on many of us. Richard effectively started the first science museum, the Exploratorium here in Bristol, and he was a great and passionate science communicator. He did some really brilliant work on vision and perception, has illusions named after him – everyone who works in my field of perception will know of Richard Gregory. He was of a genre with a connection to the past, he knew Wittgenstein, he was taught by some of the great names, so he made this connection for me with the past. But he was just so enthusiastic and so passionate – it was infectious, he was like a little child at times when he was talking about things! And really that’s what’s so important to me about science.

People think that science is dull and boring and of course it isn’t! You and I know that it’s actually very fulfilling, and  communicating that passion in a way which is sensible to the general public is what my agenda is.”

Jaws: the impact of media on shark declines by Rachel Baxter

One of Hollywood’s favourite villains, sharks have always been dubbed as horrifying man-eaters. However, this is more fictional creation than fact, and as shark populations rapidly decline, are creations like ‘Jaws’ partly to blame?  

In 1975 when ‘Jaws’ hit our screens, sharks swam into the spotlight as malevolent killers lurking in the deep. Following the film’s release, shark fishing increased rapidly, especially in the USA, as many wanted to emulate the heroic protagonists, whilst others wanted to cull sharks to make the seas safer. This reduced shark populations and 40 years later they are still deteriorating, due to overfishing for sport and meat, particularly for use in shark fin soup, a traditional Asian delicacy.

Scientists estimate that shark finning kills up to 100 million sharks a year. Finning involves catching any shark, regardless of species or size, and removing its fin and discarding the body back into the water. This is often carried out whilst the shark is still alive and subsequently leaves the animal to die a slow and painful death. The heightened demand for shark fins is due to increasing prosperity in Asian countries such as China. This has resulted in a higher demand for expensive delicacies like shark fin soup, which costs up to $100 a bowl. Consequently, the value of shark fins has soared, meaning that thousands of sharks are killed for their fins daily. As a result, many shark species such as tiger sharks and hammerheads have experienced population decreases of over 90% in recent years.

Sharks are an apex predator throughout the world’s oceans. This means that they are at the top of the food chain and significant decline in their numbers has the potential to impact nearly every organism living in our seas. One issue is that in the absence of shark predation prey species populations will proliferate, thus decimating populations of their own prey. An example of this is already occurring in the eastern Pacific Ocean, spanning from California to Tierra del Fuego, at the southern tip of South America. The decline of sharks here has led to a huge increase in Humboldt squid, a predatory species of squid whose populations were historically controlled by sharks. However, due to the reduction in their natural predators, their populations have expanded rapidly and this is having an impact on fish stocks, as the squid will consume nearly any fish that they come across. The true impact of shark declines is still unknown but it is likely to change population numbers of a vast variety of different species and seriously upset the balance of marine ecosystems, all over the world.

Therefore, the conservation of sharks is key. Current conservation efforts include discouragement of shark consumption, especially in shark fin soup through methods such as petitions. Also, more and more sharks are becoming protected. In 1991 South Africa became the first country to protect great white sharks. Furthermore, many countries, including the UK, have now implemented restrictions on shark fishing and finning. Therefore there is hope for sharks, but attitudes need to be changed in order to increase support of conservation efforts.

To change attitudes, it is essential that people understand that sharks pose very little danger to humans; in fact we pose much more danger to them. Whilst an average of 4.2 humans may be killed by sharks each year, humans kill an estimated 100 million sharks annually. There are over 400 species of shark, whilst only 4 of these species have ever been involved in attacks on humans (great white, tiger, bull and oceanic whitetip), yet almost all shark species are affected by fishing. In fact, the chance of a shark attack is minute. Millions of people swim in the sea every year whilst only about 4 fatalities occur annually. In contrast, every year 150 people die due to falling coconuts, 10,000 die by lightning strike, and 24 are killed by flying champagne corks!

What’s more, many shark attacks on humans are thought to be accidental. Shark attacks often occur on surfers. This is because from below, a surfboard with four legs resembles the shape of a seal. In fact, sharks are never out to get humans, as we are not their natural prey. Humans are much larger and bonier than prey organisms such as fish and seals, and wetsuits are not part of a shark’s ideal diet! Also, the vast majority of shark attacks on humans involve only one bite. This is interesting as hunting sharks use an initial bite to weaken their prey, and then use further bites to kill. This indicates that most sharks that attack humans immediately realise that they have made an error, and consequently back away. So, is the revengeful, human-hunting shark from ‘Jaws’ simply an entertaining invention?

It is true that ‘Jaws’ is based on real events; the Jersey Shore attacks of 1916. These attacks involved four fatalities and one injury during the summer of 1916 off the Jersey Coast in North America. However, scientists concur that these attacks were a freak incident, and the same scenario has never been repeated. Ironically, Peter Benchley, the author of ‘Jaws’, became a keen shark conservationist, regretting his portrayal of sharks as monsters as it had such a significant impact on the world’s perception of them.

Perhaps, one day, films will undo what they have done and depict sharks in a new light. Swimmers will no longer be haunted by ‘ba-dum ba-dum’ and more people will be concerned by shark declines. This could reduce shark fishing and improve attitudes towards conservation, so that shark populations are saved before it is too late and the balance of our oceans changes forever.

The IgNobel awards

The ‘stinker’. Official mascot of the IgNobel awards

“For work that first makes people laugh and then think”

by Felix Kennedy

September 18th saw the 24th annual IgNobel awards ceremony take place. Now, almost as famous as the Nobel Prize awards they aim to mimic, prizes are given for research that ‘first makes you laugh, and then makes you think’. The prizes are intended to celebrate the unusual, honour the imaginative and spur people's interest in science, medicine, and technology.

Past notable winners have included University of Bristol professor, Sir Michael Berry, who won the prize along with Sir Andre Geim, for floating a frog in a strong magnetic field. This is possible as almost all material displays a very weak type of magnetism called diamagnetism. Even material that would never usually be regarded as magnetic, such as water, contains electrons. Under a strong enough magnetic influence, the electrons within a material align and develop a magnetic field of their own that opposes the magnetic field they are in. This causes the material to be repelled from the magnet and if the repulsion is strong enough, the material will simply float, in this case the frog. Although the feeling of weightlessness was probably rather disconcerting to the frog, I would like to point out that no animals were hurt in the undertaking of this experiment-the frog was completely fine afterwards!

A weightless frog, floating in a magnetic field

Historically, IgNobel prizes have been awarded for rather obscure work, but real world applications have been found for discoveries that may seem merely interesting at first glance. A good example is a study that won the IgNobel prize in Biology showing that malaria mosquitoes (Anophelese gambiae) are equally attracted by the smell of Limburger cheese and human feet. Since then traps have been baited with Limburger cheese across Africa to help combat the epidemic of malaria. Another such example was in the field of Chemistry when the 2011 Chemistry IgNobel prize went to researchers who determined the ideal density of airborne wasabi to wake people up. The research has now been incorporated into some alarm systems to help wake deaf people in the case of an emergency.

On the other hand, some winners have produced work where it hard to find an application in the real world. This rather extensive list includes the 2008 IgNobel prize in Biology that was award to researches for discovering that fleas on dogs jump higher than fleas on cats. In another case a prize was awarded researchers from Scotland’s Rural College for their work on bovine behaviour. They found that cows that have been lying down longer are more likely to stand up soon, however once a cow has stood up it is much harder to predict when it will lie down again. Other cow related IgNobel prizes include one given to Newcastle University researchers who found that cows with names produced more milk than those without names, and one given to researchers who developed a method to extract vanilla flavour from cow dung. In this instance vanillin was extracted in a more cost efficient method than taking it from vanilla pods. This means if you want cheaper vanilla extract for your cakes, then look no further a field of cows!

With other winning pieces, if you really try, you might just be able to find some useful information. For example, unless you have rather stubborn sheep and are looking for the easiest floor to pull them across, I can’t see why a paper written by Australian scientists entitled "An analysis of the forces required to drag sheep over various surfaces” would be of any interest to you. Despite this, the paper still won the IgNobel prize in Physics in 2003.

Some prizes are award in jest to people you may not think deserve recognition for their work. One that falls into this category is the 2005 IgNobel award for literature, given to the ‘internet entrepreneurs of Nigeria’. You may know these people as the ‘lost relative’ scam artists, where an email will pop into your inbox from some distance relative explaining that they are in line to inherit a large sum of money. The catch is they need a small amount of cash to pay some legal fees and, if you are able to pay the fees, then you would be rewarded handsomely once they receive their money. Unfortunately the story is a fable, but the less savvy amongst us have sent money abroad in a hope of receiving part of the fortune anyway. The organisers of the IgNobel awards found that this fraud showed ingenuity and imagination, awarding the prize for literature to these con artists. Another controversial winner was the president of Belarus, Alexander Lukashenko, who won the IgNobel peace prize rather ironically, in 2013. He received the Ig Nobel award for decreeing that it would now be illegal to applaud in a public area and he shared the award with the Belarus state police department for arresting a one armed man for clapping in public.

Sheep pulling over the preferred surface

The breadth of work that the prizes cover and the weirdness of some of the academic work complied here, I believe, is outstanding. I think it is also interesting how the IgNobel awards are also used to highlight questionable work, such as the distant relative scam and the odd laws that have been introduced in Belarus. If you have enjoyed this article I suggest you have a look at the rather extensive IgNobel award Wikipedia page. There are many more interesting winners that I have not been able to list here and I am certain many will ‘First making you laugh and then making you think’

All that is left to say is that I hope you are looking forward to the 2015 IgNobel prizes as eagerly as I am!

Meet the cells that keep neurons running

by Jonathan Smith

When watching a Formula 1 race, it’s easy to forget that the racing drivers, skilled as they are, don’t work alone. When the car pulls into a pit stop, however, you see a bustling team of mechanics and other experts eagerly rush out to keep the car and driver in top condition. Meanwhile, security staff stand by, blocking public access and keeping a watchful eye on any danger that may present itself. Similarly too, the F1 drivers of the nervous system, neurons, get a lot of attention due to their unique information-processing properties. However, there’s a diverse team of specialised cells that beaver away in the background of the nervous system, carrying out essential tasks analogous to the F1 driver’s pit stop team. Without these plucky little cells, neurons wouldn’t propagate information properly and the nervous system would cease to function. With that in mind then, let’s give some of the most important overlooked cells the limelight for a change, starting with the ‘security guards’ of the mammalian nervous system.

Endothelial cells form the Great Wall of the Brain
As we eat, sleep and move about, our blood ion and sugar levels are constantly in fluctuation. For our neurons that require tightly controlled conditions, exposure to this would be highly detrimental. Thankfully, we can look to endothelial cells, which line the interface between brain tissue and the bloodstream, forming a shield against peripheral influence known as the Blood-Brain Barrier (BBB). By surrounding blood vessels and plugging gaps in the line with protein complexes called Tight Junctions, these endothelial cells and their buddies the pericytes not only cushion brain tissue from fluctuating ion and glucose concentrations but also block passage to many complex molecules, including foreign pathogens.

Figure 1: The endothelial Blood-Brain Barrier around a capillary (red chamber) combines with glial cells such as microglia and astrocytes to form a safe nutrient delivery system to neurons. Pericytes and tight junctions help the endothelial cells to seal the boundary and astrocytes use an end foot process to suck up the nutrients passed along by the barrier. Microglia wait on the side, checking for hazards. Source: SR Yusof and NJ Abbott, from Abbot, 2013, doi: 10.1007/s10545-013-9608-0

Not content to simply act as a wall, these cells also tirelessly shuttle essential ions, sugars and other chemicals into the brain and remove toxins through their own cytoplasm, ensuring that neurons are both protected from the outside world and aptly supplied with the nutrients they require. Furthermore, white blood cells of the immune system - the body’s police force - regularly squeeze through the barrier in order to check for danger. However, this also works against the brain in conditions such as strokes in which the BBB becomes leaky and can’t limit the passage of white blood cells, thus increasing inflammation and exacerbating the problem.

You won’t like microglia when they’re angry
Inside the BBB we encounter the glial cell population. Glial cells - named after the Greek word for ‘glue’ - share many characteristics with neurons but lack the unique structures and functions that specialise neurons for information transmission. Instead, glial cells play a diverse set of roles maintaining the nervous system. Numbering at around 15% of all glial cells, security guard microglia are the subject of intense research because of their incredible versatility. These cells spend the majority of their time simply sitting in the brain tissue, waving their dainty branch-like processes around in a constant search for signs of danger. When they pick up a scent of damage or invasion, however, microglia turn ugly. These sentinels kick off tissue inflammation and undergo an Incredible Hulk-esque transformation into a blob that engulfs and digests the offending party before innocently reverting back to its original state. 

Figure 2: Microglia (green) detects a tissue injury and springs to action. Its extended processes detect signs of damage and trigger the cell’s transformation into a big blob that engulfs the debris. Source: adapted from Nayak et al, 2014, doi: 10.1146/annurev-immunol-032713-120240

With this astounding response to hazards, microglia make impressive enforcers. However, mountains of research have revealed that they can do much more than this. They communicate with cells of the immune system that pop in every so often. In addition, microglia have been found to nurture the growth of neurons in embryonic development and help to prune unwanted cells from the nervous system in developing juveniles. They could even play an important role in synaptic function, making them crucial for normal information processing. However, these eager cells may also work against us in neurodegenerative diseases such as Alzheimer’s Disease and Parkinson’s Disease, believed to involve high inflammation that proves to be neurotoxic in the long run. By better understanding the role these cells play in the pathology, we might able to devise new strategies for treating these conditions.

Insulating the wiring with oligodendrocytes
Mammal neurons are small, thin cells compared to some of the whoppers found in invertebrate animals such as the giant squid. Most neurons output their information through a long process called an axon and, due to electrical resistance inside the cell, neurons with thinner axons propagate information more slowly than those with thicker axons. How then could a nervous system operate with such small neurons? The answer is myelination. This is the process by which specialised glial cells called oligodendrocytes and their peripheral cousins Schwann cells tightly wrap their own fatty membrane - the myelin sheath - around the axons, leaving little gaps of axonal membrane that allow electrical potentials to ‘jump’ significant distances along the axon. This increases possible propagation speeds up to 100 metres per second in humans - perfect for neuronal communication.

Figure 3: Oligodendrocytes (blue) ensheathe many axons (brown) in myelin to facilitate electrical transmission. Source: Wikipedia

Insulation might not be the only function for these ‘mechanics’ of the nervous system. Recent research indicates that oligodendrocytes can not only insulate axons, but may also directly support the axon’s energy requirements by supplying substrate molecules used in metabolic reactions such as lactate. Further studies indicate that oligodendrocytes promote neuronal survival and axonal growth. The importance of these cells and Schwann cells is further underscored by the fact that the disorder Multiple Sclerosis (MS) arises from demyelination of axons throughout the nervous system. For a multitude of reasons, the immune system attacks myelin and thus deprives neurons of essential support, causing neurodegeneration and, as a consequence of this, ultimately life-threatening paralysis in MS patients. However, strategies are now being trialled that may be able to divert or retrain the immune system and prevent the progression of MS.

Astrocytes - star players in the nervous system
Astrocytes are star-shaped glial cells thanks to their many fine processes, hence the name. Acclaimed as the most abundant type of cell in the human brain, these cells have the chief responsibility of transporting nutrients from blood vessels to nearby neurons by means of a long ‘foot’ process. Astrocytes also oversee chemical synapses - vital junctions at which neurons communicate using neurotransmitters - and each astrocyte can monitor up to a whopping 140,000 synapses! Taking roles analogous to trainers, medics and mechanics in the F1 team, astrocytes are absolutely essential for the survival of the nervous system and by extension, the entire organism.

As can be expected, lots of research gets devoted to unraveling the precise roles that astrocytes play in the nervous system. It’s now clear that these ubiquitous cells encourage the formation and pruning of synapses in the developing brain. In addition, they fine-tune synaptic activity by supplying necessary energy substrates, hoovering up and recycling excess neurotransmitters, prevent seizures by clearing away potassium ions and physically ensheath the synaptic space, reducing spillover of neurotransmitters to nearby cells. Unfortunately, astrocytomas are among the most common cancers in the nervous system and have a relatively high mortality rate. They damage the brain tissue by increasing pressure inside the skull, compete for nutrients and releasing toxic chemicals into the brain, resulting in varied symptoms including headaches, seizures and occasionally personality changes. Though the classic cancer treatments are available such as surgical removal, it’s hard to cut away all of the high-grade tumours due to their rapid infiltration into the brain.

Collective thinking
Aside from the heroes discussed in this piece, there are also tons more subsets of cells that deserve honourable mentions, including parenchymal cells that circulate cerebrospinal fluid around the brain and the somewhat enigmatic NG2 glia, whose precise function still eludes us. While staying mostly in the background, these other cells all have vital functions that serve to ensure that our neurons keep running smoothly. 

Neurons tend to be the main focus of neuroscientific studies. This attention is well deserved considering that they are the substrates of our very thoughts. However, after examining some non-neuronal cells, it’s clear that neurons wouldn’t last a minute without the help of their expert team on hand. By exerting modulatory influence on neuronal development and synaptic activity, it could be argued that the support cells similarly affect our thinking and learning processes, an argument particularly evidenced by complex neurodegenerative diseases involving lots of cell pathologies. With this in mind then, let’s all watch some F1 and spare a thought about the collaborative efforts involved in securing first place!

Transcranial Direct Current Stimulation: Remoulding the Brain by Duncan Ware

A transient tingling sensation on my scalp, accompanied by an equally fleeting phosphene across my visual field, alerts me to the fact that 2 milliamps of direct current are now passing through my brain, the dorsolateral prefrontal cortex (DLPFC) to be specific. No, I haven’t been denied extradition from a pro-electric chair state, I willingly made myself a component in the circuitry of a technology known as transcranial direct current stimulation (tDCS).

It is widely accepted that everything we do has an effect on the ‘wiring’ of our brains, a fact proposed most succinctly by neuropsychologist Donald Hebb, whose words are forever paraphrased as “neurons that fire together, wire together”. Hebb’s law is now known to rely on long-term potentiation (LTP) and long-term depression (LTD), the enhancement and reduction of synaptic efficacy, respectively. These mechanisms of synaptic plasticity are thought to be the fundamental processes which underlie learning and memory, and perhaps even mood disorders and addiction. It is therefore of little surprise that tDCS, a technology capable of modulating synaptic plasticity, has become subject to a great deal of research in recent years.

TDCS involves the application of electrodes to the scalp above particular regions of the brain, as determined by the Brodmann area map used for electroencephalography (EEG); the regions stimulated dictate the effects of the session. The anode exerts a depolarising influence on the neuronal somata (neuronal cell bodies) of the cortex and hyperpolarises the apical dendrites, whereas the cathode induces hyperpolarisation of the somata and depolarisation of the apical dendrites. Relating this back to synaptic plasticity, the areas affected by the anode become more likely to ‘fire’, meaning their synapses are more prone to LTP, and, conversely, regions of the brain affected by the cathode become less active and are more likely to undergo LTD. This is more or less the extent to our understanding of the mechanism by which the effects of tDCS are manifested.

The clinical applications of an electrical current applied to the scalp have been known for years. As far back as 43 AD, in fact, Roman emperor Claudius’ physician used the shocks of electric eels to abate the pain of headaches! Today it is known that tDCS is capable of ameliorating a multitude of pathological afflictions, from stroke damage to schizophrenia, but also that you and I, as presumably healthy individuals, might derive benefit from the occasional zap.

Attending to the former claim of therapeutic potential in the ill, the montage (electrode placement) with which I am, to use the term most loosely, experimenting today has been found to remediate depression. Some studies have found that just 20 minutes of 2 mA anodal stimulation over the DLPFC to reduce self-reported depression by as much as 10% for every week of daily use. Unfortunately, many of the studies I have come across regarding tDCS are ‘open-label’, science jargon denoting clinical trials in which both the researchers and participants know which subjects are receiving which treatments (in this case, the real treatment or a ‘sham’ control). Unlike its ‘double-blind’ antithesis, open-label studies are plagued by the expectancy effects of both the researcher’s overt enthusiasm, or lack thereof, for the treatment and the subject’s expectations of its outcome. Consequently, one might denounce the aforementioned results to be a direct outcome of the placebo effect. This criticism has been largely dismissed by more recent double-blind trials and studies investigating the relative efficacy of tDCS and established pharmacological therapies such as sertraline (an SSRI antidepressant). Such studies have found tDCS and SSRIs to be of equal efficacy, though a combination of the two was found to be of superior efficacy to either alone, a synergistic pairing I hope will soon be exploited in clinical practice.

For those who refrain from the use of recreational drugs due to their deleterious effects or illegality, perhaps you might consider potentiating your own endogenous substances for a similar effect? I recently came across a most intriguing montage which achieves just that. With the anode attached to the C3 Brodmann area, corresponding to the region of the scalp which lies above the primary motor cortex of the left hemisphere, and the cathode pressed against my upper right arm, effects reminiscent of those one might experience following consumption of a weak opiate such as codeine were elicited almost immediately. As someone who has done much experimenting, in the euphemistic sense, this was a most welcome experience I quickly sought to investigate. A google or two later and I found a publication released last year detailing the analgesic potential of tDCS, an effect they put down to the µ-opioid system. Opioid receptors are those which transduce the effects of opiates and opioids (substances of similar pharmacological profiles to opiates), like morphine and methadone respectively. But the body possesses its own painkillers, including enkephalins, endorphins and dynorphins to name but a few, and it is these substances whose production is upregulated upon stimulation of the motor cortex. What the paper failed to mention, however, was the euphoric sensations evoked by this montage. Feeling like a character from Huxley’s Brave New World, I amused myself with the idea of becoming a junky without ever having pierced a vein or ‘chased the dragon’.

Another, more frequently studied, area of tDCS research focuses on the technology’s potential as a cognitive enhancer. The phrase is employed with ever increasing frequency as we strive to match our efficiency with the demands of modern life, or perhaps to simply mimic Bradley Cooper’s character in the film ‘Limitless’! Whilst I shan’t delve too deeply into the ethical storm which stalks this phrase, I feel that the practice must be discussed. The majority of research in this area pertains to the augmentation of working memory, the ability to hold information in one’s mind to permit its manipulation and analysis. Such research supports the idea that anodal stimulation of the left prefrontal cortex, a brain region implicated in a variety of executive functions, results in a significant improvement in the working memory of healthy participants. However, some experts admonish users of the trade-off between anodal excitation and cathodal inhibition that is so integral to the device’s mechanism of action. By this, they refer to the fact that whilst you might enhance the activity of one area, with the anode, you will also suppress activity in the area beneath the cathode. Minimising the impact of this trade-off is undoubtedly a task we must prioritise in brain stimulation research, especially given the diffuse nature of tDCS’ influence on the brain, which it seems may extend to subcortical structures.

And so, whilst I must urge you to take caution, should you proceed to plug yourself into the mains (figuratively, a 9 volt battery is sufficient) tDCS is a wonderful medical development which, along with its successors: transcranial magnetic stimulation (TMS) and high-resolution tDCS, I predict we will be seeing much more of in the coming years. 

Synapse Review: Sir David Attenborough opens the Life Sciences Building by Daisy Dunne

On my first visit to Bristol’s Biological Sciences School back in 2011, I was marched across campus to stare at a giant empty crater on the corner of Tyndall Avenue, which I was assured would soon become the most impressive building the university has ever attempted to construct. Now, some three years later, the end result of the £54 million project is staggering – and who better to welcome in the new build than Biology’s biggest living legend, Sir David Attenborough.

At just gone 11am on Monday, I waited excitedly with an assortment of 200 distinguished guests, including senior lecturers and the city’s Mayor, for the esteemed naturalist and wildlife broadcaster to arrive and officially open Bristol’s new world-class Life Sciences Building. The university’s Vice-chancellor Professor Sir Eric Thomas welcomed us all before the now retired Vice-chancellor Professor David Clarke, who oversaw the building’s construction, regaled us with stories of some of the project’s difficulties – including the discovery of ancient gun powder under the old physics workroom that occupied the site.

Soon after, Sir David took to the microphone to deliver a compelling and personal speech, centralised around the importance of understanding the Natural Sciences to tackle the world’s most pressing problems. He stressed:

“The only way we will deal with the problems on this planet of ours that we have created is to understand what goes on… nothing, nothing could be more important in the area of scholarship than this.”

“Unless we understand the very systems on which we live, the food we eat, the air we breathe, unless we understand how our world affects us, we’ll be in real trouble.”

What’s more, he highlighted the importance of bridging the gap between science and the wider community, to make them realise “how important it is for us to do something”.

In addition to this passionate message, he also spoke of “the joy, resonance and delight” that can be conjured from the natural world, adding “understanding the natural sciences will give you joy for the rest of your lives, it brought great joy to me.”   

To finish, he professed: “I’m proud to be a freeman of this great city and also to hold an honorary degree from this very, very distinguished university”, before unveiling the building’s new plaque and declaring the building officially open.

After Sir David’s awe-inspiring speech, guests were given tours around the building to see some of the breath-taking features – including a 20 metre living wall, which houses 11 different species of plant as well as roosting spots for birds and bats. Also, guests visited the GroDome, a state-of-the-art tropical greenhouse that resides on top of the 13,500 square metre building.

For me, the most impressive aspect of the building is the five-storey glass laboratory wing, which supports ground breaking research from a multitude of different disciplines – from bat bioacoustics studies to virtual-led palaeontology. 

The new Genomics Facility is set to transform the university’s world class study into understanding the evolution and mapping of entire genomes. Professor Keith Edwards, a cereal genomics expert from the School of Biological Sciences, says:

"From the outset the new building was designed to have a state of the art genomics facility; including two next generation sequencers and a range of genotyping and robotic platforms. The new laboratories have been designed to minimise sample to sample contamination via the use of controlled air flow between rooms operating at different pressures.”

Image Credit: Nick Smith | University of Bristol

Tortoises master the tablet

by Daisy Dunne

A team of tortoises from the University of Lincoln have successfully learnt to use touchscreen technology to win treats from scientists, who hope to learn more about the reptile's unique method of processing spatial navigation. Whilst mammals use the hippocampus for matters of geography, reptiles are thought to use a similar enigmatic structure known as the reptilian medial cortex.

"Tortoises are perfect to study as they are considered largely unchanged from when they roamed the world millions of years ago,” says Anna Wilkinson, who trained the tortoises using strawberry rewards, “this research is important so we can better understand the evolution of the brain and the evolution of cognition."

Impressively, two of the tortoises even went on to use the information they had learnt in a real life scenario. After learning to peck blue circles on one side of a screen in exchange for a reward, the reptiles chose to approach the same side of an experimental chamber when presented with two empty blue bowls similar to the virtual circles.

This outcome suggests that like the majority of animals, reptiles rely on 'landmarks', and not just simple motor processing, to orientate in their environment. Wilkinson hopes this study will open the door for a wider adoption of touchscreens in animal behavioural studies.

“The touchscreen is a brilliant solution as all animals can interact with it, whether it is with a paw, nose or beak. This allows us to compare the different cognitive capabilities", she says.

Inside story: Professor Andrew Orr-Ewing - School of Chemistry

Interview by Melissa Levy

Q. Where did you go to university and what did you study?
I went to university in Oxford where I studied both an undergraduate degree in chemistry and also for my PhD in chemistry, so I was there a total of 7 years.

Q. How did you get from there to where you are now in Bristol?
When I finished in Oxford I went to work for two years at Stanford University in California which was a great experience as I worked with a very eminent professor there. Then I started thinking about my future and so I applied for something called a Royal Society University Research Fellowship which is a way in which you can move back to an academic position in the UK while having a lot of freedom as to where you go. It also gives you a chance to focus on your research. I was very fortunate in securing one of those which I chose to hold at Bristol. I didn't really know Bristol at the time, but I knew of some very good people here who I wanted to work alongside and so I selected Bristol as the best place to come to. I’ve never regretted that decision, it has turned out very well for me!

Q. How would you describe your research to someone who’s never studied chemistry?
There is quite a lot of different activity in my group but the connecting theme is that we use lasers to study interesting chemical processes, and those vary!
One of the things we do is look at gases in the earth’s atmosphere; either detect them at very low concentration with sophisticated laser spectroscopy methods or we study how these molecules react in the presence of sunlight. So we look at the photochemistry that is driven by sunlight and we quantify that in terms of rate constants and things like that. That’s one aspect of the work that we do!

The other work is much more fundamental. What we try to understand is how chemical reactions happen, and in the past four or five years we’ve started to ask how that happens in liquids which is a really complicated question because the molecules in liquids are colliding over very short time scales.  We use very fancy laser equipment which generates pulses of about 10-14 seconds in duration to follow chemistry as it’s happening in liquids. So what we do is really just infrared spectroscopy but on ridiculously short time scales and that allows us to follow chemical reactions in real time.

Q. How would you describe your typical day in the lab/at university in general?
Unfortunately I don’t spend very much time in the lab these days, just the nature of the job really – as you get older you tend to spend less time in the lab and more time in your office, so my research group do most of the activity in the lab these days.

But days are really varied, I do lots of different things so I don’t generally have a rigid plan. I come in and there’s always a pile of things that need doing; that might be writing papers, or it might be working on a PhD thesis draft that a student has sent me, or it might be refereeing a paper or a grant application, or it might be preparing for some teaching that I have to do that day. That’s one of the really nice things about the job – it’s very varied and it’s always intellectually challenging, so I’m happy to come in in the mornings. I do like to start quite early, it’s peaceful then and I can concentrate before all the interruptions start! The downside of it is what comes in on the email that you’re not expecting because that can disrupt any plans that you might have for the day.

But really it’s the variety that keeps most of us interested!

Q. If you had the choice to just do research instead of all of the other things you do as well, what would you choose?
I think that the teaching is a very important part of the job and it’s a part that I enjoy greatly. It’s very satisfying to be able to communicate things that excite you to other people and I wouldn't want to do a job that just involves pure research. The bit of the job that most of us don’t like is the more administrative side, it’s the more tedious aspect but it’s very necessary. But in general, the teaching is great fun and the research is great fun and for that reason I wouldn't want to be a pure researcher. Interacting with keen young students is one of the more rewarding aspects of the job.

Q. What advice would you give someone looking for a career in science?
Academic careers can be a challenging path, because there are a limited number of job opportunities in universities to hold teaching and research positions. As a result, you have to know that you really want to go down that path and be prepared to be patient for a good position to open up. But studying for a science degree and doing research for a PhD creates lots of other opportunities too, in industry or many other areas where you can apply your scientific knowledge. Increasingly these days in things like environmental consultancy. I’d never discourage someone from studying science! I think it opens your eyes to a lot of important questions in the world around us and allows you to understand really significant issues, such as climate change. 

Q. If you could do research with anyone, dead or alive, who would it be?
That’s a tricky one! I’ve been very fortunate to work with some really talented scientists and that is extremely stimulating, you learn something from everyone you engage with. When you’re an active researcher you go to conferences and you mix with lots of scientists and learn something from all of these people. Often you’re in awe of how clever they are and how much they know that you don’t think you understand, which is a great motivation to keep educating yourself.
But I’m not really interested in celebrity science, so I don’t see that I would want to work with one of the greats of the past. I’m more interested with working with people who are enthusiastic and motivated and share my passion for particular areas of science.

So I’m going to dodge the question a bit and say that I’m really happy with the people that I work with here, both in my research group and my colleagues, who keep me interested in the work that we’re doing all the time – in terms of enjoying research, that’s definitely the way to do it.

Transition in Pharma

What needs to be prescribed to an industry in distress?

by Toby Benham

Recent large scale closures of R&D sites in the UK from pharma giants Pfizer, Merck, GSK and now Novartis has led to the nationwide desolation of the pharmaceutical industry. With cuts extending around the world, and several big challenges ahead, it appears the industry is heading into a time of transition. To emerge through this transition stronger it is important for pharmaceutical companies to collaborate, working together for the collective good of the field.

Difficult times

The dominant business model adopted in recent times by pharmaceutical companies involved investing heavily into promising drug candidates, attempting to create the next big blockbuster. For associated with these iconic blockbusters are fame and fortune. Drugs such as Lipitor and Plavix have allowed their respective companies to thrive previously. However, the industry has been looming over the edge of the “patent cliff” (when many current blockbuster patents expire) for several years and now companies are lining up for the plunge. It means that these drugs can be manufactured and sold by any generics company at the detriment of the inventor company’s profits. This strategy relies on new blockbusters to come through the system but current pipelines appear relatively fruitless. 

Developing new drugs is an expensive business. Forbes estimates that it now costs approximately $5 billion per new drug created; this is not a sustainable figure. Costs spiral during the 15 years that contribute to getting a drug to market. The drug discovery, optimisation, clinical trials, patent protection and marketing involved are all long expensive processes. However, the main reason that the figure is so high is due to the unseen added cost of research into unsuccessful drug projects. Thus, there could not be a worse time for worldwide scandals to be breaking out in the news, smearing the image of pharma. Just last year, both GSK and Novartis were alleged to have bribed doctors and healthcare officials in China. There are also questions over the safety of some drugs already on the market.  GSK’s “Avandia” for diabetes treatment has been under intense scrutiny for several years now with restrictions in the US only lifted recently. With so many hurdles in the development process - ranging from toxicity to manufacturing - high risk, high reward projects may now be considered just that bit too risky. 

The future

Most importantly, big pharma need to ditch their profit alone method and support one another for their collective benefit. In 2013, data analytics company SAS announced the creation of a globally accessible but private bank of data for pharmaceutical companies to pool clinical trial data. GSK have been the first to share. Perry Nisen, the GSK senior vice president for science and innovation, announced that, “in sharing our data with researchers across the world, we hope to further scientific research and increase understanding about our medicines.”  This exemplary collaborative model will allow companies to improve efficiency and enhance the decision making progress which is so crucial in pushing forward drug candidates. Working on projects across companies should also be encouraged with the chance to explore new opportunities, widen portfolios and spread risk. GSK and Novartis recently announced an asset swapping deal, but this could go even further.

In addition, the big pharmaceutical companies can collaborate with the smaller businesses to flourish from symbiotic relationships. Companies such as Aurigene offer cost effective outsourcing of R&D in their respective areas of expertise, creating what Aurigene describe as a “win-win partnership” that accelerates discovery. The opportunities are not limited to industry with many experts in academia to link up with. Sanofi-Aventis and Pfizer have already created strong partnerships for drug development with Harvard University and UCFS respectively. Back in the UK, Astra Zeneca is building a new headquarters located in Cambridge with the intent to partner with Cambridge University and local hospitals.  By sharing scientific talent and resources, the drug development process gains extra quality and creativity from fresh perspectives. Diversity and partnerships lead to innovation which is essential to feeding hungry company pipelines. A wider communication with regulators would also be invaluable. Hopefully this could put an end to public scandals and improve the clinical trial process. 

Change is required to replace the current unsustainable business model in the pharmaceutical industry. With the right partnerships, a new streamlined, cost effective and innovative R&D system is possible. This will reduce the price of creating a drug by increasing productivity whilst simultaneously cutting expenditures. Through sharing scientific talent, resources and knowledge it is possible for the industry to return from the drop of the patent cliff to emerge stronger by optimising the potential of collaboration. Pharmaceutical companies should consider working in unison for the common goal and share the rewards. This is important not just for the companies concerned but for the patients that benefit as a result.