Sunday, 19 October 2014

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 ยต-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. 

Tuesday, 7 October 2014

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

Sunday, 10 August 2014

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.

Saturday, 21 June 2014

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.

Saturday, 10 May 2014

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.

Wednesday, 30 April 2014

Inside story: Professor Andrew Halestrap - School of Biochemistry

Interview by Melissa Levy

Andrew Halestrap is a professor in the school of Biochemistry as well as as the head of his own research group who are interested in both the role of mitochondria in cell death and monocarboxylate (lactate) transporters. If you want more information about the work which he and his group do then click here.

Where did you go to university and what did you study?
“I was at Cambridge, where I studied Natural Sciences specialising in Biochemistry and then I came here to do my PhD. That was a long time ago and I stayed here ever since! I started my PhD working with Dick Denton (Professor Richard Denton), working on the regulation of fat metabolism in the epididymal fat pad. And then I branched out… I stayed in Bristol, got a fellowship and then a lectureship and I stayed here ever since. I’m very unusual [in that] l I stayed here ever since my PhD.”

If you had to describe the research you are doing to someone who doesn't understand the concepts, how would you describe it?
“Well I’ve got two areas of research that I’m doing at the moment. The bigger area of research is how you protect the heart from damage after a heart attack or during heart surgery. So during a heart attack when you have a coronary thrombosis (the coronary artery is clotted with thrombus) the blood supply stops and then the downstream area is gradually getting damaged because it’s got no oxygen. What they do when they bring you in to hospital is to clear the blockage (we call that reperfusion) and unfortunately the reperfusion, which you’ve got to do to restore the heart function…causes more damage. [It works by doing] something to the mitochondria, it turns them into reverse so instead of providing the energy to drive the cell they actually start breaking down ATP and destroying the cell.  This gives you a damaged area called the infarct, which is just dead necrotic tissue. We are understanding the molecular mechanism and developing treatments to prevent that from happening which will prevent the heart from this damage. And it’s relevant in surgery because when you have cardiac surgery you also have to stop the heart which means stopping the supply of blood, and if the surgery is long then you can get this same reperfusion damage. So we’re also working for cardiac surgeons and applying some of the stuff we do in the lab, understanding the mechanism and how we can prevent it, in the clinical field.  There are clinical trials going on with some of this stuff which is quite exciting! The first clinical trial was successful so we’ll keep our fingers crossed.  And then the other area is in lactic acid production in our cells, which is why I sometimes rabbit on about lactic acid (!!). The process whereby lactic acid gets in and out of cells is a process we discovered many years ago working on the molecular mechanism, and the particular interest at the moment is understanding the structure of the transportes so that we can design better inhibitors that could block the process in tumour cells. If you block lactic acid efflux from tumour cells you can actually kill them!”

How would you describe your typical day?
“A lot of my time is spent writing reviews on grant applications and reviewing papers because I act as an editor and referee of papers. A lot of time is spent writing papers, reading papers, talking with my research group; I don’t get to the bench much now. So I talk with my people regularly about what they’re doing and we think about the next set of experiments. Then sometimes of course (like today) I have a fair bit of teaching and marking to do, some days they’ll be very little teaching. And then there’s administrative jobs, various university committees and things that take up [time]”

What’s your favourite part of your job?
“Oh, well either doing bench research which is really fun but I rarely do it, or just thinking through data and deciding what experiments to do next; it can be very exciting but also very frustrating.”

Do you have any advice for someone who’s looking towards a career in science? 
“The first advice is that if you really want to be active in hands on research you’ll have to do a PhD, and you’ll probably end up doing some post-doctoral work as well. If you’re really good, and that’s only a very few now, you may then get a permanent research position as an academic or in a research institute. Other people will probably realise that they’re not quite good enough to get to the top of the pile so they can go off into maybe an industrial position acting as science officer. Realistically far more people will want to do research than will be able to… So some are going to end up, either after the PhD or the postdoc, going into other science related things. It could be teaching, it could be scientific journalism it could be a rep for a biotech company. There are many levels where you could use your science. And other people change completely and become a managing director and go and do an MBA - It’s very varied!”

What is the most memorable moment of your career so far?
“Ooooooh most memorable? Well I’ve had several that’s the problem! I had a eureka moment; I was literally in the bath and I was trying to work out a way of measuring how much this mitochondrial pore was opening in a heart. I was sitting in the bath and I had an idea, it was just a eureka moment and it worked and it’s one of my most cited papers. That was a good one! But there have been plenty of others.”

If you could do research with anyone in the world, dead or alive, who would it be?
“I was asked this by someone else in a different context and I found it very difficult to choose one person because, when you get to my age, you’ve worked with a lot of good people. I don’t know really… I think the scientist I admire most is probably Fred Sanger (who’s now dead). He took up a challenge that people thought was ridiculous - to sequence proteins - and he succeeded and then rather than capitalising on that he thought ‘well I’ll go off and sequence nucleic acids’. And he went and did that and got a second Nobel prize. He’s [also] a very humble guy, and when he was 65 and he decided it was time to retire he just left science and worked in his allotment. I think that’s a very special person.”

Saturday, 5 April 2014

It’s Worse in the Water

by Rob Cooper

The vast majority of the surface of planet earth is covered by water and considering this it should be no surprise that whilst terrestrial (living on land) creatures can get rather frighteningly large, the denizens of the depths are always one step ahead. In this article I’ll examine ten of the most fearsome, peculiar and benign ocean creatures with the hope of showing just how fantastic the diversity of ocean live has been over time.

1. Dunkleosteus
Back in the Devonian a peculiar group called the Placoderms developed to truly monstrous sizes. Characterised by their armoured bodies and bony plates instead of the teeth the Placoderms reached their most terrifying in the killer whale sized Dunkleosteus. Strangely for such a large predator the 8 metre long Dunkleosteus could suck prey towards its mouth by rapidly opening its jaws (in less than 1/15th of a second). Unhealed bite marks on the head guard of younger Dunkleosteus also lend evidence to a theory of cannibalism.

2. Helicoprion
If you thought Dunkleosteus had strange teeth you may be surprised to learn far stranger tooth morphologies existed in the prehistoric seas. Helicoprion is a fantastic example of this having a ‘toot whorl’ that looked remarkably like a circular saw inspiring many strange artists’ impressions of the creature. The function of the peculiar teeth has yet to be determined but it is thought that the successive rings of teeth are analogous to growth rings in trees and that teeth successively pushed up to replace those that were lost, similar to how its modern day relatives sharks replace their teeth today.

3. Megamouth Shark
To continue from shark like animals to true sharks we next encounter a very rare modern shark colloquially known as the ‘Megamouth shark’. Since its discovery in 1976 only 55 specimens of this elusive shark have been seen or caught. Like its larger relatives, the basking and whale sharks, the Megamouth has an enormous mouth full of very small teeth that are ideal for sieving plankton from the ocean. As it follows the movement of plankton down to over 200 metres in depth it has small photophores (light emitting organs) to attract plankton and small fish to its 1.3 metre wide mouth.

4. Megalodon
It would be an insult not to mention the mightiest of all ocean predators in this article and Megalodon certainly fits that title handsomely. Well respected as the largest and most powerful predator in the history of all life (with one competitor) megalodon is now estimated at lengths of at least 14-18 metres and up to 20 metres and weights of slightly over 100 tonnes. Megalodon has the largest jaws ever discovered in the animal kingdom large enough for a full grown man to walk through without bending down and an estimated bite force of over 180,000 Newtons. This, along with other palaeontological evidence, suggests that Megalodon preyed on large whales until its extinction 1.5 million years ago.

5. Livyatan 'the great whale'
But what animal was big and ferocious enough to rival Megalodon? Strangely enough the answer comes from a contemporary of Megalodon’s the titanic Livyatan. Livyatan was a raptorial sperm whale which lived between 12-13 million years ago in the Eocene period. Akin to megalodon Livyatan remains have been found alongside those of baleen whales, sharks, dolphins, porpoises and many other sea creatures supporting the hypothesis of Livyatan being an apex predator alongside Megalodon. Unlike modern sperm whales Livyatan had the largest teeth of any animal yet discovered (bar the tusks of elephants and walrus) at up to 36cm in length. Livyatan was thought to ambush prey swimming at the surface from beneath much like the modern great white shark.

6. Leedsichthys 'monster fish'
From two rather fear inducing giants to a rather more benevolent one. Meet Leedsichthys, the largest bony fish to have ever lived. Leedsichthys ranged from around 10 to nearly 15 metres in length so probably rivaled the modern whale shark in size although a heavier bone skeleton likely made Leedsichthys considerably heavier. A strange tendency in large oceanic animals is that of eating remarkably small prey and Leedsichthys was no different and likely fed on plankton either by pumping water through its huge mouth or actively swimming to filter small organisms from the water around it.

7. Giant Manta Ray
Benevolent giants still exist today in the form of the majestic manta ray. Gliding through the waters like marine birds these gentle giants can have a wingspan of up to seven metres and weigh over a tonne. Manta’s are also filter feeders and typically herd their tiny prey into tight balls and swim through at speed with their large rectangular mouths open. On occasion Manta’s have been observed somersaulting through particularly tight balls of prey presumably to catch more prey.

8. Predator X
Leaping back 155 years to the late Jurassic period we come to a group of marine reptiles called the Pliosaurs. Pliosaurs were characterised by short necks and immensely powerful large jaws, the largest specimens having estimated bite forces comparably or far greater than Tyrannosaurus rex. Predator X was one of the largest of all Pliosaurs reaching between 12-15 metres long and possibly weighing up to 45 tonnes. Strangely, compared to modern day marine species, Pliosaurs used their four flippers for locomotion and had no tail fins to speak of; two of these fins would be used for normal locomotion whilst the other two would be used to create a burst of speed when ambushing prey.

9. Plesiosuchus
Crocodiles are often said to be living fossils and quite rightly so for modern crocodilians have hardly changed at all for hundreds of millions of years. However back in the Jurassic period, something very strange happened in crocodilian evolution… They began to adapt fully to living in the sea. At around 6.8 metres in length Plesiosuchus was one of the largest marine crocodiles and like its kin had shed the heavy, restricting armour of its forebears in favour of a streamlined body. The skull of Plesiosuchus shows many similarities to modern killer whales implying it regularly predated on large marine reptiles of the time.

10. Shastasaurus 'ocean giant'
On the topic of marine reptiles, it would be immensely uncharitable of me to finish this article without mentioning the largest marine reptile yet discovered. Shastasaurus was a primitive ichthyosaur, a group of marine reptiles that in their later stages would bear many similarities to dolphins yet the primitive forms were quite unique. The prey base and feeding method of Shastasaurus remains a mystery as it seems to have had no teeth and the suggestion that it fed on soft bodied molluscs is generally not supported by ichthyosaur skull morphology, what this strange animal was specialised for we may never know but that hardly makes it a less thrilling creature to imagine.

The oceans simultaneously offer some of the most fearsome and most benevolent creatures that planet earth has ever harboured. From gentle filter feeding giants to titanic ambush predators lurking beyond the reach of light the oceans are a place where life has fully explored the limits of size. No dinosaur has even come close to the largest baleen whales of today and whilst we may be thankful that many of their huge predators such have Megalodon have finally passed on; we do ourselves a great service by remembering just how rich the oceans are and how important they are as an ecosystem to us and other terrestrial species.

Monday, 24 March 2014

Inside story: Dr Craig Butts - School of Chemistry

Interview by Melissa Levy

Dr Craig Butts is a reader for the school of Chemistry as well as a researcher in the area of structural and mechanistic chemistry, with special emphasis on Nuclear Magnetic Resonance. If you want any more information about what he and his group do then follow this link.

Q. Where did you go to university and what did you study?
“So I studied science at the University of Canterbury in New Zealand, I did a BSC honours in science and then majored in chemistry.”

Q. How did you get all the way from there in New Zealand to here at Bristol?
“I went into science in university basically because I had fun doing it at school! But up until I was about 16 I wanted to be an accountant (this was in the 1980’s and I wanted to be a yuppie (!)) [But] I suddenly realised that accountancy wasn't something I enjoyed a great deal and in fact I much preferred blowing things up in class. And so I went into science at university and…the bit that I really enjoyed was doing the research project in my final year, which made me want to carry on in academic research or in research at least. Particularly due to the encouragement of my supervisor who, about 6 weeks into my project basically just walked up and said “you obviously enjoy this, you’re good at it…do you want a PhD?”. The deal was if I got a first class honours then I could have a PhD place and so I then carried on to do my PhD with my project supervisor working on photochemical reaction mechanisms trying to work out how these photochemical reactions proceeded. In particular we were interested in nitration reactions using a compound that was only really studied in the 1950s as a rocket fuel adaptive by the Russians, tetranitromethane – it was hideous stuff… and we knew that it did this photochemical reaction but we wanted to know HOW it worked and why it worked, and the only evidence that there was in the literature we were pretty sure was wrong!  Near the end of my PhD realised that I hadn’t quite worked out what I wanted to do afterwards! In New Zealand there are not a lot of opportunities around for PhD trained chemists – which was a bit of an oversight on my part - but it never bothered me until that stage! 

So the first email I ever sent outside of the chemistry department in Canterbury was to Professor Rodger Alder here at Bristol and I basically said ‘What’s the deal? Are there any jobs over there? Can I get one?’ and he wrote back and said ‘yeah I’ve got some funding for a post-doctoral research post for 3 years’ and so I applied for that and got it…. I submitted the final draft of my PhD thesis on the morning and on the afternoon I got on a plane to Britain and started my postdoc!”

Q. How did you find his email address or him at all?
“How did I find his email address? I have no idea!! At that stage the web was really early on… I guess there must have been a Bristol website that I would have looked at but I knew to contact HIM because my PhD supervisor had sent students over to him in the past. Once I got over here my plan was always: come over to Britain for 3 years, get this postdoctoral experience which you had to have in order to go and become an academic there… and I never got around to leaving!  I was [now] 23 and I’d never had a job interview, so I applied for a temporary job at the university of Exeter as a lecturer thinking I’d never get it because I’m only 23 and I’ve no experience but I should at least have this practice! And blow me down if they didn’t offer me, not the job that was advertised… they actually gave the job to someone who was already at Exeter and I got his job. So yeah I got lucky basically! [When] I had just submitted the job application I went to the out to celebrate because I was just starting to think that I might actually stay in Britain. I went out to the pub on a Friday night and I started asking everyone in the pub (boys girls whatever) if they had a passport and if they would therefore marry me! And one of the people who walked into the pub subsequently married me! About 5 years later I mean she didn't agree to go out with me for another year! [So] I met my wife and got married and had kids and never quite got around to leaving. Simple as that! 

And then 2005 they closed the chemistry department at Exeter and at that stage I was contacted by my soon-to-be boss here and they said that they had a job here managing the NMR facility, so I took that. It wasn't actually an academic post and so I spent a couple of years getting back into an academic post here at the university and I've been going here ever since.”

Q. If you had to describe the research you do to someone who isn't an expert in chemistry how would you describe it?
“So what we do is primarily to work out the structure of chemicals and we use NMR spectroscopy to do this. NMR spectroscopy is basically the same thing as you do in MRI in hospitals, instead of doing it on a whole person we do it on a very small sample and we look at it on a molecule by molecule basis. My particular research interests are working out ways to better determine those structures and work out what shape they are and what size they are and how they are moving in solution and things like that.”

Q. And how would you describe your typical day?
“Ahh my days are very very varied!  So I split my time into three parts. One is running the NMR laboratory; so I manage the NMR laboratory and I have to, along with the technical staff, look after something like £3 million worth of NMR instruments (soon to be 4 million) and so I spend about a third of my day working with PhD students and post doc researchers who are using those instruments and have run into challenges and problems that they can’t solve without a bit of help, and trying to work out ways to get new instruments which have better or more capabilities. I spend about a third of my time doing research with my own group; so every morning 9 o’clock one of my group come in for their weekly meeting and we talk about how their research is going and what that’s doing. Then about a third of my time or so is spent doing all of the other things that come with academia so primarily teaching, both undergraduate where I teach to the chemistry students but also postgrad teaching which is aimed particularly at NMR spec and the more advanced applications of that to the huge variety of projects that we have in the university.  And then there’s the boring admin bits that we have to do as part of the job.”

Q. Do you have a favourite part of your job? If you had the choice would you chose JUST lecturing or JUST research?
“No… I’d chose to do all of them! To me research is a jigsaw puzzle, you’ve got a problem to solve and you have to know all the different ways of solving it.. Then you start with the corners you build up the edges and then you stick everything into the middle. That’s fascinating to me I mean I get to do that for a living – that’s great fun.  But it’s hard work, there are bits of it which are mind numbing and monotonous and so teaching is a completely different break from that. You get to stand up and get excited about what you do in front of a bunch of people, trying to get them to understand what you do and and why you do it and how you do it, hopefully to the point that at the end of that they know better than you do…I wouldn’t want to do one thing or the other really, if I did either full time I’d die! The paperwork [though] I could avoid quite merrily! “

Q. What do you do when you’re not at university? 
*laughing* “So there are three things I do when I’m not at university. First and foremost I’ve got three kids who are an absolute joy and I spend most of my time... well I’d like to say playing with them and teaching them and all the other things that parents are supposed to do but I think running around after them better describes it. Second thing, I’m a sports fanatic [and] I follow pretty much anything that involve a ball or a bat, so obviously football and rugby and cricket, and then when my wife can’t hear me on a Sunday night I’m often listening to American baseball and bizarre things like that. And the third thing I do is, sad to admit, research.... My research is a hobby for me, pretty much every day in some way fashion or form if I’m not on holiday I’ll be logging in to some of our spectrometers or checking what’s happening or I spend a lot of time talking to people in the states about different NMR techniques and tricks and tips that we can use. I’ve always looked at my job at being my hobby and so I have to come into the office to do my hobby sometimes and other times I get to do it from home.”

Q.What advice would you give to someone looking towards a career in science? Would you recommend academia?
“Absolutely! You have to have the right mind-set; you have to be the kind of person who likes puzzles and problems and likes long term challenges and targets. Academia is about saying ‘we’ve got this big long term goal, let’s start now to solve all the problems and the challenges on the way’ and that’s quite a hard thing to keep focused on over long periods of time. I've worked on projects that have taken over a decade to come to fruition, when they do come to fruition it’s a fantastic thing. I had a look at jobs in industry when I was younger and I just couldn’t do it! I couldn’t do that short term project focus that dominates in industry and commerce. [Academia] is hard work, particularly early on in academic careers, there are a lot of targets you have to achieve very quickly and at a very high level, and that’s very hard to do when you’re just starting out but it’s thoroughly enjoyable. I never ever (I keep telling people this it’s very sad) don’t want to come to work. I never sit here and think ‘oh it’s only 2 o’clock I’ve got another 3 hours before I get to go home’, never happens… I get ‘Oh it’s 4 o’clock I guess I have to leave!’ Not because I don’t want to leave *laughing* but because I have so many things to do and so many things I want to do.”

Q. If you could do science/research with anyone (dead or alive) who would it be?
“I want to do science with people who love science, who get as much enjoyment out of it as I do. To be honest I’m not interested in doing science with Einstein or Marie Curie (well particularly not Marie Curie…) or anything like that, I want to work with lots of people on lots of things and that’s one of the reasons I enjoy my job. I get to do chemistry with 250 side-kicks... Well I guess they’re not my side-kicks …. So I’m going to avoid the question and say that I want to keep on working with the people I’m working with, I mean I get to choose in my job who I work with what I work on when I work on it and to me is all part of the joy of it!”

Thursday, 20 March 2014

Life Without a Backbone

by Rob Cooper

It is a strange turn of phrase common today that having no backbone implies weakness and lack of stoicism. Whilst many of our most impressive contemporary animal species do have well developed backbones there are many critically important animals that lack such a feature. In this article I will attempt to illustrate and expose the diversity and nature of several extinct and extant species lacking said backbone and try to show why they should certainly glean more attention than they have until now.

1. The Colossal Squid 
A wonderfully accurately named animal, the colossal squid is the largest known invertebrate that has ever lived stretching to 14 meters and weighing up to half a tonne. Like all squid the colossal squid is equipped with arms and tentacles covered in suckers, but in contrast to the slightly smaller giant squid, this giant also has sharp hooks for catching large fish and bioluminescent squid species up to 1km below the waves. Once they are fully grown they are only predated regularly by sleeper sharks and sperm whales and still manage to give both predators nasty wounds with their hooks and suckers.

2. The Japanese Spider Crab
The largest member of the arthropod phylum (which includes: insects, arachnids and crustaceans) the Japanese spider crab can have a leg span of up to 3.8 metres and despite it’s rather fearsome appearance it is reported to have a rather gentle disposition. The crab acts as an omnivorous scavenger on the sea floor and like many crustaceans has very small planktonic larvae with transparent bodies and no arms or legs that floats in the water column.

3. The Japanese hornet
Sticking with the Japanese theme we move to a rather less benevolent creature; the Japanese hornet. The sting of the hornet reportedly induces the feeling of your flesh melting and releases a pheromone cocktail that attracts all the hornets in the local area. This pheromone is also used by hornets hunting bees. European bees, which have no defence against the hornets, are often slaughtered by the hive. Japanese bees however have learned to surround the hornet with their bodies and essentially cook the animal with their body heat. 

4. The bullet Ant
If the Japanese hornet wasn’t quite enough to freak you out I invite you to check out the infamous bullet ant. Why is it called the bullet ant? Well the sting of the bullet ant is, according to the schmitd sting pain index, the most painful of all stings and feels akin to being shot. Or if you prefer a slightly more vivid description… The sting is described as ‘waves of burning, throbbing, all-consuming pain that continues unabated for up to 24 hours’. This potent sting is thought to have evolved as a defence against predators that unearth the ant.

5. Anomalocaris
Delving back over 500 million years into the deep past a rather remarkable arthropod called Anomalocaris or ‘abnormal shrimp’ led the way in the evolution of large multicellular predators that would change the evolution of all future life. Anomalocaris was a truly gigantic animal in its time reaching two metres in length and probably preying on soft bodied organisms. The eyes of Anomalocaris like other ancient and modern arthropods were compound eyes and consisted of 16,000 lenses which represents some of the earliest evolved complex eyes able to tell friend from foe and discern environmental factors, which is clearly an incredibly important evolutionary step.

6. Arthropleura
The past often presents us with monolithic, giant versions of creatures we know today. Such is the case with Arthropleura, an ancient relative of millipedes and centipedes that stretched up to 2.6 metres in length and lived in the carboniferous period over 300 million years ago. The carboniferous period was characterised by huge amounts of vegetation and photosynthesis leading to a very high partial pressure of oxygen allowing arthropods such as Arthropleura to grow so large and is also responsible for many of earths current coal deposits hence the nomenclature of the period.

7. The Crown of Thorns 
Skipping forwards 300 million years in time, large invertebrates are still vitally important ecological factors. There is no better example than the mesmerizing crown of thorns star fish, so named for the hundreds of poisonous spines that covers its aboral (opposite to the oral, mouth containing, surface) surface. The crown of thorns feeds on coral polyps and can cause great damage to reefs if they gather en masse. However ecology is rarely so black and white. The crown of thorns provides a vital role in maintaining reef biodiversity by feeding on rapidly growing corals allowing slower growing corals to grow out and allow variance in reef composition. 

8. The Horse Conch
Fearsome snail is a term rarely used. However it is a term that perfectly describes the horse conch. A huge sea snail that lives of the coast of Florida in shallow waters up to 6 metres deep, the horse conch has made a name for itself by feeding on all manner of marine gastropods and arthropods. The horse conch has even been observed cannibalising younger members of the same species. The bright orange flesh of the animal is very striking and is perhaps a reminder of the incredibly diverse forms that even seemingly mundane animals such as snail have and do take.

9. Jaekelopterus
Sea scorpions such as Jaekelopterus were formidable ocean going predators from 460 to 248 million years ago. Jaekelopterus was discovered from a single 46cm long claw by Simon Braddy and Markus Poschmann of Bristol University in 2007. The full animal is estimated at 2.5 metres in length. Whilst not true scorpions, the sea scorpions were some of the largest arthropods that have ever existed and had the common feature of two large claws presumably used to catch prey such as trilobites that shared their primordial seas.

10. The Hagfish

The hagfish is a living fossil; that is a species that has existed relatively unchanged for a very long time period. The hagfish represents a period in evolutionary history just after the vertebrate skull had evolved but before the backbone had become prominent. The hagfish has a cartilaginous skeleton meaning it can literally tie itself in knots, and indeed does in order to provide enough force to tear chucks of flesh of whale carcasses that sink to the deep sea where it lives. The hagfish can produce huge amounts of slime on contact which increases in volume when exposed to water. This slime could be argued to be the most successful predatory fish repellent ever evolved as it clogs the gills of attacking fish preventing them from ‘breathing’. This is evidenced in how almost all known predators of hagfish are birds or mammals.

I hope I’ve demonstrated here that while many of vertebrates we see around us are certainly fascinating and incredibly important, aesthetically, ecologically and commercially, the invertebrates and strange missing links like the hagfish are not only crucially important to the working of our natural world but just as intriguing, beautiful and in some cases even terrifying, despite their disadvantage in size and complexity.