Synapse Science Magazine #9

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SYNAPSE THE SCIENCE MAGAZINE WRITTEN BY STUDENTS FOR STUDENTS

ISSUE 9 - December 2014

Poison was the Cure Realism in Mass Effect The Ebola Virus

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EDITORIAL

The Team Rosie Hayward Editor in Chief

Thien Ho

Vice President

Amy Newman

Secretary & Senior Editor

Louisa Cockbill

Treasurer & Senior Editor

Nick Henden

Head Graphic Designer

Jake Ayres

Graphic Designer

Melissa Levy

Welcome to

SYNA PSE Science Magazine

Welcome to the 2014/15 academic year and also to the ninth issue of Synapse Science Magazine, the University of Bristol’s Science Magazine. In this issue we explore a range of scientific ideas, from abstract concepts such as a holographic universe to current affairs like the Ebola virus.

Synapse is written for students, by students, and there are many ways to get involved for members old or new. If you are interested in writing, editing, photography, graphic design or even becoming a topical science radio show host, join Synapse on the UBU website, or email us at

E: synapsebristol@gmail.com

Managing Editor Managing Editor

Mutanu Malinda

Media Co-Director

Tom Stubbs

Media Co-Director

Daisy Dunne Senior Editor

Felicity Russell Senior Editor

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Editors

Toby Benham

Rosie Hayward Sarah Boyle Lauren Atherton Dom Wooding Jordan Davis Melissa Levy Amy Newman Louisa Cockbill Andy Jones Daisy Dunne Jessica Towne Rachel Greenwood Ines Wood

CONTENTS

Hypatia of Alexandria:

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The First Female Mathematician

Mobile Genetic Elements:

5

An Introduction

The Ebola Virus:

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Everything You Should Know

Spinal muscular atrophy: The first neurodegenerative disease to be cured?

The Monstrous Truth of Moby Dick Poison Was The Cure: The medical applications of lethal snake venom

Scientific realism in BioWare’s Mass Effect The Future of Medicine All Hail the Shale: Is fracking the long term energy solution the UK requires?

Black Holes & Revelations: Is the Universe actually a hologram?

The Eyes Have It: The Origin of Sight

What The Eph!?

Review: @Bristol After Hours

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synapsebristol.blogspot.co.uk | 3

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Hypatia of Alexandria

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ypatia is said to be the first female mathematician in history that we possess detailed knowledge about. As the head of the Platonist school at Alexandria, she taught Pagans, Christians and people who had journeyed there from other parts of the world the wisdom of Plato and Aristotle. She was born in A.D. 370 and died in A.D. 415.

Hypatia’s written works have not survived to this century. Most of her works share credit, many with her father; a common arrangement for female mathematicians in Antiquity. She is said to have contributed to science as one of the inventors of the hydrometer, and is credited as the first.

A hydrometer is a tool used in physics to determine the specific gravity of liquids; this is to say the ratio of the density of the liquid to the density of water. Her other contributions to maths and science include a commentary on Arithmetica

by Diophantus, and editing her father’s commentary on Euclid’s Elements. She is described by Socrates Scholasticus as a woman who: “made such attainments in literature and science, as to far surpass all the philosophers of her own time.”

However, her love of mathematics was often questioned, as was her decision not to marry. Clifford Pickover describes her as physically attractive and fiercely celibate; it was said she would respond to

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interrogation by claiming she was ‘wedded to the truth’. Hypatia was murdered as a result of a political and consequently religious feud between Orestes, the governor of Alexandria, who is said to have often sought her counsel, and Cyril, the city’s Bishop. She is said to have died at the hands of a mob after rumour spread that she was the reason the leaders were unwilling to reconcile.

One thousand, five hundred and ninety nine years later, Maryam Mirzakhani is the first woman, and also the first Iranian, to win the Fields Medal. It has been proposed that Hypatia’s murder marked the end of Classical Antiquity, and the downfall of Alexandrian intellectual life.

Perhaps this is not true; there are claims that Hellenistic philosophy continued after Hypatia’s time. Nevertheless, Hypatia’s life marked the start of something very important for women, and in fact all people. The recognition of her work led to the start of people being recognised for their achievements, regardless of their gender, or their willingness to conform to society’s norms. I believe she is a scientist worth remembering.

Rosie Hayward

O

ur general perception of DNA is that of a relatively static, stable, and simple entity.

However, a concept that we don’t classically associate with DNA is mobility. This mobility is inherently present within all our DNA, coming in the form of specific sequences called mobile genetic elements (MGEs), of which there are different types. Some MGEs are confined to moving DNA between particular regions, which is known as conservative site specific recombination. Other elements are capable of autonomously removing themselves and subsequently reinserting themselves in a different, seemingly random location. These types of MGE are called transposons.

While there are many different types of transposon, each with its own unique mechanism of action, the general premise of these mechanisms remains the same. All MGEs are reliant on a family of enzymes called recombinases.

Recombinases all recognise specific sequences which are found at either end of MGEs. In conservative site specific recombination, these sequences are cleaved and then recombined with identical sequences found elsewhere in the genome. In transposition the cleaved transposon can be recombined with any sequence of random host DNA. Chunks of DNA being randomly inserted into our genome can potentially have a disastrous effect. For example, disrupting the coding region of a gene, or inserting into a regulatory region, subsequently changes the expression of that gene. This is most noticeable in plants, where it led to the discovery of transposons through their disruption of gene expression in maize. Equally, and more probably, the transposon could insert into a non-coding, non-regulatory region, and therefore have no

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Mobile Genetic Elements

An introduction to

noticeable effect on the cell. Considering the risk that is associated with these elements, an important question to consider is: why do they exist?

MGEs would not be such a prominent part of our genome if genetic rearrangement did not serve an evolutionary purpose. The introduction of mutations caused by the movement of transposons creates genetic variation within populations, which in turn facilitates evolution.

Another important role of genetic rearrangements is in the production of an extensive range of antibody specificities from a limited number of genes. This occurs via a conservative site specific recombination process called V(D)J recombination. Without this functionality we would lose the ability to mount specific antibody responses to pathogens. Furthermore, many bacterial transposons carry genes that confer resistance to certain antibiotics, such as the Tn10 transposon, and therefore their presence confers a large selective advantage.

The concept of mobile genetic elements is somewhat foreign to us, yet is happening ubiquitously amongst almost all walks of life, and has been for billions of years. Ironically, what we consider to be the hallmark of our genome (coding DNA), makes up less than 2% of the human genome, whilst MGEs make up over 50%. Our understanding of MGEs is increasing rapidly, yet there is still much that remains to be elucidated. Considering that not too long ago the 98% of our genome that does not encode genes was coined “junk DNA�, the progress that has been made since is astounding, and the future of this area looks promising.

Deniz Kent synapsebristol.blogspot.co.uk | 5

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The Ebola Virus S

ince March 2014, countries in West Africa have been on high alert due to an Ebola virus outbreak. As of October 2014, over 4400 people have died and about 5000 cases have been confirmed, with Liberia and Sierra Leone being the most affected according to the WHO report. Living in Europe, we rarely hear of such threatening diseases and in most cases only when they become a danger to us. The media often refers to the disease as the most feared virus known to science, but what exactly is Ebola? How does it work and how dangerous is it?

The first cases of the Ebola virus disease, also known as Ebola haemorrhagic fever, were detected in Sudan and the Democratic Republic of Congo, near the river Ebola from which the virus takes its name. It is part of the Filoviridae viral family which includes two other members; Marburg virus and Cueva virus. The Ebola virus comprises 5 different species which are mainly found in Africa but one species has also been found in the Philippines and China. This species can infect humans however it does not cause disease.

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Jontana Allkja

Ebola spreads to humans through direct contact with body fluids, organs or the excrements of infected animals. In Africa, the main hosts are fruit bats; especially the genus Hypsignathus monstrosus. However, chimpanzees, gorillas, monkeys, antelopes and porcupines are also affected. Once a person is infected, he/she can spread the disease through direct contact with broken skin, mucous, organs or bodily fluids, like semen, and indirect contact by contaminating the environment with such fluids. One of the main challenges when trying to contain the disease is the traditional practice of West African burial ceremonies, as the deceased are handled in such a way that propagates infection.

Ebola virus disease has a mortality rate of 50-90% and there is no known cure or vaccine. It is characterised by a sudden rise in fever, intense weakness, muscle pain, vomiting and diarrhoea. Usually, these are followed by more serious symptoms such as the impairment of liver and kidney function or extensive internal and external haemorrhaging.

Unfortunately, most of the symptoms shown are similar to other diseases

commonly seen in Africa thus making its diagnosis, as well as its containment, very difficult. The best way to diagnose Ebola is through various laboratory analyses of a patient’s blood, or other fluids, under maximum biological containment conditions.

Preventive measures are taken by the World Health Organisation in order to avoid outbreak and potential spread in various countries. These include the education of the community on the various ways they can get infected, how to tell when someone is infected and what to do when this happens. However, the WHO has had difficulties lowering the number of healthcare workers infected whilst examining patients in Ebola-prone regions. Cultural practices and traditional beliefs in the areas affected contribute in spreading the disease further. However, there have been many reports of attacks towards healthcare workers who were trying to change these traditions.

The WHO is also trying to prevent animal-human transfer by informing communities on how to handle and cook animals as to not get infected from eating raw meat. The health experts sent to the West African countries have been

instructed to quarantine anyone that shows signs of the disease until the cases have been confirmed and more clinics are being built to accommodate the large number of patients. Furthermore, Sierra Leone and Liberia have already closed their borders in order to prevent further spread to neighbouring countries.

Ebola is still far away from the UK and thus not an immediate danger to us. However, the historical spread of Malaria away from the Equator should serve as a reminder how quickly disease can migrate across the globe. It is also worth keeping in mind that cases of Ebola have been reported in the US due to people returning from West Africa.

Researchers at the University of Oxford have now entered phase I clinical trials for a potential vaccine and similar trials are being conducted in the US as well.

Hopefully the vaccines will prove effective in stopping this epidemic and preventing future ones.

synapsebristol.blogspot.co.uk | 7

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Could Spinal Muscular Atrophy Be The First Neurodegenerative Disease To Be Cured?

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pinal muscular atrophy (SMA) is a hereditary neuromuscular disease.

Despite being relatively unheard of, SMA affects approximately one in 6000 births and the most severe sufferers are unlikely to see their second birthday. This makes it the leading genetic cause of infant mortality.

This has resulted in huge interest from the pharmaceutical industry, which begs the question: could SMA be the first neurological disease to be successfully treated?

How Does It Manifest?

SMA is characterised by the inability of the central nervous system to communicate with the muscles, due to dysfunction of the motor neurones. This causes muscles to disintegrate, causing a range of symptoms affecting movement, the respiratory system and swallowing.

There are four types of SMA, of decreasing severity. Type 1 is the most common, bringing with it a limitation of life expectancy and minimal quality of life.

The cause of death of infant sufferers is often respiratory infection, due to the difficulty breathing and coughing. It may also be malnutrition, as swallowing difficulties make feeding problematic.

Less severe forms are diagnosed in childhood, and result in muscle degeneration, scoliosis and other developmental deformities. These may not be fatal, and sufferers of milder forms can lead almost normal lives.

There are currently no treatments available for the disease, so it is made tolerable for suffers by palliative care.

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How Is It Caused?

SMA is a genetic disease, predominantly caused by a loss of function mutation in the SMN1 (Survival of Motor Neurone) gene on chromosome 5. In healthy individuals, SMN1 encodes a protein, SMN, with an important role in the development of axons in neuronal cells.

Elsewhere on the same chromosome, there is a gene called SMN2. This is almost identical to SMN1, but unlike SMN1, expression of this gene results in very little functional SMN protein. This is due to exon 7 of the unprocessed mRNA being removed during the splicing process, resulting in a truncated protein, which the cell speedily destroys. The presence of this poorly functioning duplicate gene is not well understood, but it is thought that SMN2’s purpose may be to attempt to compensate for the loss of SMN caused by mutation of SMN1. SMA sufferers will, therefore, produce a very small basal level of SMN protein due to the expression of SMN2, but not sufficient for axon development. This leads to the neurological symptoms of the disease.

What Research Is Taking Place?

SMA is an exciting area of research, with multiple pharmaceutical companies racing to get ahead in the fight for an effective compound. Various approaches are being considered as potential drug targets. The splicing problems of SMN2

can be corrected, so that the SMN supply can be produced from this gene. Pfizer is attempting to do just that.

The molecule that Pfizer are pursuing is an inhibitor of an enzyme involved in the removal of the methyl guanine cap from the mRNA produced from SMN2. It is orally administered, and can cross the blood-brain-barrier, to enter the neurones.

The molecule is based on quinazoline, and is currently in phase 1b human clinical trials.

Avexis (an American Biotechnology company) are doing phase 1 clinical trials on a gene therapy treatment called chariSMA. This aims to correct the dysfunctional SMN1 gene by providing a dominant functional gene, to be expressed into SMN protein. On 24th June this year, this therapy was given to a patient for the first time. It consisted of an intravenous injection of the gene, along with a specific receptor to allow passage of the gene into the neurones of the central nervous system. This is essential for the treatment of any disease concerning the nervous system.

To conclude, spinal muscular atrophy is a devastating genetic disease of the motor neurones, causing high infant mortality and poor quality of life for long-term sufferers. Given the extensive research that’s taking place, it’s likely that a cure will be readily available within a decade. This will be a triumph for the company whose drug makes it to the market first, revealing the best approach for treatment of the disease.

Lindsey Millward synapsebristol.blogspot.co.uk | 9

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The Monstrous Truth of Moby Dick

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hales are the largest animals that have ever lived. As such, it is of little surprise they are often treated with reverence and fear. Nowhere is this more obvious than in Herman Melville’s Moby Dick, an epic narration of a fictional battle with a great white sperm whale capable of destroying entire ships.

However, the events of the novel may not be entirely fictional. On November 20th 1820, during the height of the whaling industry, a 20 metre bull sperm whale rammed a whaling ship twice, buckling the hull and forcing the crew to abandon ship. Trapped on lifeboats the crew eventually resorted to cannibalism to stay alive. This macabre tale barely scratches the surface of what geological time can show us of the sperm whale family.

The Modern Sperm Whale The modern sperm whale is the largest predator on the planet, with bulls measuring 20 metres and weighing 57 tonnes. They dive to depths of up to 3 km to feed on cephalopods such as colossal squid. Many whales bear scars inflicted by the hooks and suckers of these animals.

The sperm whale’s name comes from the spermaceti, an organ in the whale’s head

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which gives its distinctive bulbous shape.

The spermaceti was orginally thought to contain the whale’s semen, but is now known to contain fats and waxes and thought to be important in changing the whale’s buoyancy, allowing it to dive to great depths.

Sperm whales are very social animals.

They have the largest brain in the animal kingdom; up to 5 times heavier than a human’s. Female sperm whales form groups of between 6 to 20 and spend up to a quarter of their day socialising.

They emit high pitched clicks and rub against each other. This normally takes place in the afternoon; a sort of sperm whale afternoon tea. Males tend to live solitary lives, although occasionally form bachelor groups which demonstrate some cooperative behaviour, such as beaching themselves. Mature bulls have no natural enemies besides man and are believed to be too large to be at risk from orcas, a serious threat to female sperm whales.

Livyatan melvillei Livyatan melvillei (named after Herman Melville) was an ancient species of sperm whale that pervaded the Miocene seas 12-13 million years ago alongside such

13.5 - 17.5 m

Livyatan

monstrous predators as Carcharodon megalodon, the giant shark and largest predator Earth has ever seen. Whilst modern sperm whales have lost the teeth in their upper jaw and those in the lower jaw serve little to no use when capturing prey, Livyatan had teeth over 36 cm long and instead of eating squid‌ ate whales.

Whilst slightly smaller than the modern sperm whale at 13.5-17.5 metres, Livyatan cut a much more imposing figure, hunting giant baleen whales as well as dolphins, porpoise, sharks, fish and sea birds.

We can conclude Livyatan probably fed on baleen whales for several reasons: 1. Skull morphology/dentition: Livyatan had a 3m wide skull and the largest tetrapod bite ever found. Such enormous teeth indicate its prey was very large.

2. Size: Based on comparisons with the modern sperm whale, its closest relative, Livyatan was likely to weigh between 15 to 40 tonnes and require a great deal of food to survive.

3. Baleen whale diversity: Livyatan and megalodon existed at the same time; when baleen whales were beginning to reach reasonable levels of diversity. The presence of two apex predators shows a rich ecosystem must have existed.

4. Fossil evidence: Livyatan remains have been found amongst those of sharks, seals, whales, sea birds, turtles and sharks suggesting many of these featured in Livyatan’s prey base.

Although modern toothed whales such as killer whales hunt in large social groups there is so far no evidence that Livyatan performed similar behaviours. Modern sperm whales tend to show limited cooperative hunting behaviour. It seems reasonable to conclude that Livyatan was also a solitary hunter, although it could well have had advanced social behaviour.

The big question is what would happen if a megalodon and Livyatan bumped into each other in primordial seas? Both behemoths had a profound impact on the ocean ecology but which would come out on top?

Megalodon could reach up to 20 metres or more in length. Livyatan’s bony skeleton would make it slightly more robust but less flexible. However, it seems unlikely, with their torturous dentition, that a slight difference in robustness or flexibility could win the day.

Our lack of information about the behaviour or confrontations of such large animals leaves us unable to declare a winner. However, it is clear that this confrontation probably did occur and was likely to have been the most ferocious battle in all natural history.

Robert Cooper

20 m

Megalodon

synapsebristol.blogspot.co.uk | 11

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Poison was the cure The medical applications of lethal snake venom

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enom is one of the most remarkable evolutionary innovations that has ever been.

From the ravaging bite of the king cobra, which packs enough neurotoxins to kill a fully grown elephant within three hours, to the lacerating anticoagulant laden maw of the Komodo dragon, which subjects its prey to a latent death from bleeding out; venom has allowed the minute to pose a significant threat to the greatest of behemoths.

The most sophisticated kind of venom evolved from the very proteins and molecules that allow the brain and blood of vertebrates to function. This deadly cocktail of proteins goes some way to explaining why venom can be so precisely lethal and simultaneously why the reverse engineering process of anti-venom can effectively limit the effects of even the most potent of envenomations. Owing to the fact that it has taken millions of years for venom to evolve to its modern complexity; it is perhaps no surprise that many of the active ingredients can be isolated and utilised in many medical contexts such as:

[1]

Treating Strokes

From biochemically analysing the venom of the Malayan pit viper, scientists were able to uncover a surprising protein called Ancrod that can help dissipate blood clots if administered 6 hours after the strokes initial symptoms. Unfortunately many people fail to recognise the symptoms of a stroke in time for these drugs to be applicable although it is entirely possible that future research into proteins like Ancrod could unlock vital treatments for those suffering from strokes and other conditions relating to blood clotting and high blood pressure.

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Reducing Blood Pressure

Whilst stroke treatment is still largely in the research phase, the Ancrod protein is currently being confidently utilised in Europe as a treatment for high blood pressure in addition to a similar protein extracted from the venom of the Brazilian pit viper. Ironically, the medicinal benefits were first remarked upon when banana plantation workers were discovered to have collapsed after being bitten, due to a sudden drop in blood pressure. Drugs produced using similar synthetic proteins (ACE inhibitors) help prevent heart and kidney disease in middle aged to elderly adults around the UK.

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Combatting Cancer

Cancerous cells are generally only dangerous when they can spread around the body via the blood stream and access the necessary nutrients for further division. Incredibly, a protein from the venom of the south copperhead snake which prevents platelets sticking together and thus reduces the risk of blood clotting has been used as a means of preventing cancerous cells attaching to other cells within blood vessels; drastically reducing the ability of cancerous cells to travel around the human body.

By experimenting on mice with implanted breast cancer genes, scientists found that the protein from the venom of the South Copperhead snake prevented the spread of cancerous cells to the lungs of the mice by a staggering 90%.

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Mental Illness

Mamba snakes, such as the infamous Dendroaspis polyepis, commonly known as the black mamba, have a remarkably fast acting neurotoxic venom that causes severe paralysis and can kill a human in less than 20 minutes. Ironically, even fatality causing venom can be medically utilised by humans. When researching brain receptors involved in diseases such as Parkinson’s and Huntingdon’s disease, it has proved difficult to locate molecules that can accurately bind to receptors associated with one disease; without imparting any possibly dangerous side effects. However, the mamba’s venom accurately and rapidly targets only specific receptors associated with discrete mental conditions. In the future this could lead to the development of many specific drugs that help to alleviate the suffering of those with mental disorders.

Whilst the focus on this article has been the venom of snakes, it is worthwhile to note that the venom of many other fantastically deadly creatures has and is being used to help research cures and treatments for many significant ailments. For example, the venom of the beaded lizard of Mexico and its component protein exedin-3 is being used to combat many diseases including Alzheimer’s, diabetes and even HIV. In light of this should we perhaps extend slightly more courtesy to our far removed serpentine cousins of the reptile world? For if anything, venom is a reminder that all life is linked together. The lethal cocktail of proteins can be taken apart and remade to the benefit of many human lives despite the fact that the venom evolved for no such purpose. The utility of these proteins in the bodies of so many different animals ought to remind us just how closely connected we all are and should inspire both a healthy respect and a rational fear of these macabre masters of biochemical warfare.

Robert Cooper synapsebristol.blogspot.co.uk | 13

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Scientific Realism In BioWare’s Mass Effect Series

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cience fiction, unsurprisingly, tends to feature fictional science. From Jules Verne’s imaginings of space travel to the lightsabers and Force of the Star Wars universe, imagined technologies and phenomena are a staple of the genre. The Mass Effect series of video games shows a particular creativity and attention to detail in its use of science, whether real or invented, and it makes good use of both to make its fictional world more believable and rewarding to explore.

The franchise is itself named after a fictional scientific phenomenon: the ‘mass effect’, by which the mass of matter can be increased or decreased using dark energy, by passing electric currents through a substance called ‘Element Zero’. This concept is the root of most of the Mass Effect universe’s technologies, and while it is not itself particularly plausible, the way it is built on and exploited to make otherwise impossible technologies is more believable than might be expected.

The ‘mass effect’ is given many applications in weaponry, transport, manufacturing and more, but its most

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important use is for FTL (faster-thanlight) travel. The in­game ‘Codex’ describes this as being made possible by reducing the mass of a spacefaring vessel to the point where velocities greater than the speed of light are possible and time dilation is negligible. According to relativity as we currently understand it, this is not possible – even massless particles cannot travel faster than lightspeed ­– but it is necessary from a story perspective, as without some way of bypassing the universal speed limit, travelling the vast interstellar distances would take far too much time. Also, although the writers’ explanation of FTL travel doesn’t ‘work’, it does at least make mention of important related concepts such as space­time curvature and time dilation, rather than simply hand­waving or ignoring them entirely.

Such scientific terminology (particularly from the field of physics) crops up everywhere in the games, from the placement of space stations at Lagrange points, to heavy weapons that generate Bose­Einstein condensates. At one point, the player can even overhear a military

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drill sergeant lecturing his ensigns on Newtonian mechanics.

With the numerous alien species encountered in the games, chemical and biological matters are also considered.

One frequently­mentioned example of this is amino­acid chirality. Chirality is a property of certain molecules, mostly organic ones, where the molecule can take one of two forms (enantiomers) which are ‘mirror images’ of one another. In some situations, the molecules behave identically, but in others they do not. Life on Earth uses almost exclusively the ‘left­

From Lagrange Points To Bose Einstein Condensates... ...Such Scientific Terminology Crops Up Everywhere handed’ or levo versions of amino acids.

It is possible that the amino acids of life developing on other planets might have the reverse chirality, and Mass Effect uses this concept: two of its alien species have dextro­amino acids, and it is described as being unsafe for them to eat levo­based species’ food, and vice versa.

The games do a good job of reflecting the statistics of astronomy, particularly in the portrayal of exoplanets. It is rare to come across a garden world (a planet possessing the attributes needed to support life), and

even rarer to find one with a size, climate and atmosphere resembling Earth’s. Most visitable planets are barren or hostile.

From the biological side of things, every species has clear evolutionary adaptations to its home planet’s environment.

Unfortunately, there are also times when the games just get it plain wrong.

In the second game of the trilogy, the main character uses a device called a ‘Quantum Entanglement Communicator’ to converse with his mysterious benefactor. This supposedly uses a pair of quantumly entangled particles to transmit data instantly (and without any risk of interception) between users.

While quantum entanglement does have considerably useful applications in cryptography, the method described would simply destroy the entanglement, rendering the communicator useless.

It’s not too hard to suspend disbelief in these cases, though. When Mass Effect doesn’t follow real physics, it is normally for good reason: ultimately, the story must take precedence, and things like FTL travel and instant communications serve to advance the plot. Mass Effect executes succeeds in embellishing so many aspects of its story and world with convincing science. This makes its world feel immersive and genuine in a way that is not easily matched.

Gabriel Penn synapsebristol.blogspot.co.uk | 15

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THE FUTURE OF

THREE BIG IDEAS ABOUT STEM CELLS AND HOW THEY ARE CHANGING THE WAY WE TREAT DISEASE

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n spite of a sustained and unjustified political siege, the field of regenerative medicine is currently enjoying a much deserved renaissance. In our lifetimes, it is now plausible to consider that future generations may one day think of diseases like diabetes or Alzheimer’s as ours does about whooping cough or polio. And it’s all thanks to a revolutionary new approach to treating disease: to rebuild or regenerate our bodies using the building blocks that made us in the first place – stem cells.

STEM CELLS WILL ONE DAY BE USED TO REGENERATE WHOLE LIMBS, ORGANS, AND EVEN HUMAN BODIES

The number of organs grown in vivo and ex vivo has grown exponentially over the past decade, with complex structures

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MEDICINE

including hearts and kidneys having been regenerated by scientists. A mouse heart, for example, was stripped of all cardiac muscle cells so only cartilage remained.

After reconstituting the remaining bioscaffold with embryonic stem cells, scientists were astounded to observe that not only did the stem cells regenerate the heart tissue, the resulting structure started to beat. Similar experiments on ischaemic livers produced equally impressive results. Reconstitution of the decellularised bioscaffold with nonparenchymal cells and adult liver cells produced a functioning liver that was metabolically active when transplanted back into murine test subjects. The results have huge ramifications in our approach to treating degenerative diseases. It shows that we now have a real chance of developing therapies for serious illnesses such as myocardial infarction, cirrhosis of the liver and even congenital blindness.

Those born without sight can now benefit from treatments pioneered in Germany which involves injecting autologous adult stem cells into the macular area of the eye. Though the treatment is yet to cure absolute blindness, it can provide patients with a perception of light and dark and has also been shown to significantly slow the progression of macular degeneration.

STEM CELL RESEARCH IS HELPING US TO DEVELOP TREATMENTS FOR CANCER

STEM CELL RESEARCH IS MAKING VAST IMPROVEMENTS TO OUR DRUG DEVELOPMENT PROCESS

Our understanding of cancer is constantly evolving, with prevailing opinions now suggesting we should think about cancer as a disease of stem cells. Correlations exist, for example, between the incidence of bone fractures and bone tumours, indicating that problems occurring during the bodies’ normal repair process can contribute to the excessive proliferation that ultimately leads to cancer. Stem cells in an affected area repopulate the damaged tissue in a self-renewing manner; a loss of control of this process results in dysregulated tissue homeostasis.

Additionally, cancer stem cells are thought to drive metastasis: the process of cancerous cells travelling to distant sites in the body. Such cells have now been identified in both haematological and solid tumours, suggesting that their selfrenewing and pluripotent properties are crucial to the development of malignant cancer. Research into these cells is therefore providing novel insights into the causes and progression of cancer.

Understanding how the loss of tissue homeostasis occurs, and how the unique properties of stem cells drive metastasis is enabling researchers to develop novel therapies for cancer, especially those that target late stage cancers, where current treatments are particularly lacking.

When a system has a 99% failure rate, and a single drug takes an average of 13yrs and $4bn to develop, the need for change becomes all too clear. Current efficacy and safety tests rely on animal models, usually rodents, to ascertain the effects of the drug on living tissue. All too often however, later trials show that the desired effect is not mimicked in humans, and the trials are abandoned. In short, these models are not an accurate reflection of how the human body works. But stem cells are.

Scientists are now working to develop up to 25,000 stem cell lines to investigate how drugs affect real human tissues. Each cell line represents an individual; the array represents a sizable human population, enabling researchers to essentially execute large-scale clinical trials, quickly, efficiently, and most importantly, in the laboratory. Pioneered by the New York Stem Cell Foundation, the team hopes to one day produce cell lines that are personalised to an individual, so that the exact side effects, appropriate dosage and efficacy can be determined before the patient starts a course of drugs. Don’t expect this new approach to be without its critics, however. Stubborn and entrenched ideas about rodent testing are likely to persist, as is all too often the case in science when radical paradigms challenge rooted dogma.

Michael Whitehead synapsebristol.blogspot.co.uk | 17

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All Hail the Shale Does fracking offer the long term energy solution the UK requires?

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racking offers the UK a new method in which to achieve energy security.

Or at least that is the message sent by George Osborne in his latest budget which featured a heavy 50% tax break for the process. Fracking (or hydraulic fracturing) involves the liberation of natural gas (namely methane) from natural underground, porous shale rock formations. After the creation of a borehole, horizontal drilling combined with the injection of a cocktail of water, sand and chemicals shatters the rock and initiates the release of gas. Some hope that the UK can jump on the bandwagon started by the US where fracking has been very successful and has had a wider positive effect on the economy . The problem is that the successes on the other side of the Atlantic will be very hard to replicate in Europe.

USA vs Europe Shale gas extraction led to price drops of natural gas in the US, but this drop was mainly due to the sudden surplus available which was difficult to export.

This same price drop isn’t expected to happen in the UK and George Osborne has confirmed that. In the US it was easy

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for fracking to be put into action due to a well-established onshore drilling industry. This infrastructure doesn’t exist in Europe. European countries also tend to have higher population densities than the US which means there is more local resistance to drilling due to closer proximity to housing. In the US, drilling can take place in more rural areas and there is often greater incentive for local landowners because the mineral rights on personal property are owned by the individual rather than the state.

is thought to ”bethere only 9 billion m of 3

recoverable gas in the UK... only enough to meet UK demands for 10 years!

”

The resistance to fracking has included campaigners and outspoken anguish from members of organisations such as ‘Friends of the Earth’. Safety concerns have been raised by several US studies which found that faulty well-casings could allow methane to seep into groundwater.

FRACKING In addition, some people are concerned that the injected chemicals themselves may contaminate the groundwater. An additional threat is posed in the form of earthquakes caused by the shattering of rock formations while drilling. In fact, two earthquakes were caused by fracking in Lancashire in 2011, although these were both lower on the Richter scale than the vibrations caused by a passing HGV. Overall, the Royal Society has suggested fracking poses no greater threat than any other industry with the appropriate regulation.

Future prospects

will be back to square one. Furthermore, optimistic forecasts predict that shale gas could meet no more than 10% of total European gas demand by 2030.

While shale gas may provide some shortterm respite, it’s certainly not going to provide for the country in the same way that has been seen in the US. The media tends to focus on the safety issues associated with fracking and perhaps are missing the important question that needs addressing; that of its long term prospects.

Toby Benham

The US has been estimated to have between 10-45 trillion m3 of recoverable gas, enough to provide gas security for 100 years. However there is thought to be only 9 billion m3 of recoverable gas in the UK (over 1000 times less), only enough to meet UK demands for 10 years!

While this may provide the UK with some energy independence, it can hardly be thought of as energy security. After all, once this fossil fuel is exhausted it

synapsebristol.blogspot.co.uk | 19

ARTICLE

Black Holes & Revelations: Is the Universe actually a

hologram?

T

here have been many theories attempting to ascertain the true nature of the universe, and to nonphysicists the daunting mathematics and abstract concepts can be very difficult to comprehend. If you thought the idea of a universe endlessly exploding and collapsing in on itself like some cosmic grenade stuck in Doc Brown’s flux capacitor was hard to grasp then wait till you hear this: the “volume” of the universe may actually be an illusion, with everything in existence encoded as information on a 2-dimensional boundary. This is a relatively controversial idea in physics as it is very difficult to explain experimentally; even theoretically.

It was inspired by the immensely puzzling work on black hole thermodynamics.

Other aspects of black holes were found to be explainable using a “holographic” approach implementing string theory. One such feature is the Black Hole Information Paradox. Stephen Hawking didn’t think that black holes could radiate anything; they only sucked stuff in that was never seen again, but he proved himself wrong with the discovery of Hawking Radiation.

This in turn implied that black holes do have entropy and to maintain a balance of finite entropy and temperature they would have to both absorb and emit particles.

Objects in the universe have something called entropy, a degree of “randomness”.

It was hypothesised that black holes had no entropy, but the physicist Jacob Bekenstein highlighted that this would violate the second law of thermodynamics because if a hot gas enters a black hole its randomness is lost. This would not make sense unless black holes themselves have entropy, and lots of it, therefore making them the most “random” objects (relative to their volume) in the universe.

The problem was that particles emitted from black holes are not the same as those absorbed. If a photon of light falls into a black hole, another photon is emitted that is “thermally mixed”; it represents a mixture of possible states displaying a change in its information which violates certain aspects of quantum mechanics.

If left unexplained then all of quantum physics would need an overhaul.

20 | SYNAPSE

...a universe in ”which volume is in fact an illusion ”

Gerard t’ Hooft attempted to solve this paradox by investigating just how this change in state occurred. He reasoned that

the gravitational field of infalling particles caused the event horizon of a black hole to deform. The precise deformation pattern that occurred was directly related to the infalling particle’s properties of mass and location, rather like the particle having a “shadow”. This caused an interaction with outgoing particles which, through Hawking Radiation, produced a different outgoing particle than would be produced by an undeformed event horizon.

Leonard Susskind elaborated on this idea by applying similar ideas found in string theory, eventually allowing the Black Hole Information Paradox to be solved under certain assumptions. The oscillations seen on the event horizon surface of a black hole effectively describe the matter falling into and coming out of it, and these oscillations are described as being like a hologram. After the description of black holes using holographic ideas from string theory, the step was made attempting to apply this idea to ordinary matter.

Entropy can be equated to information (information about the whereabouts of particles and sub-particles) because thermodynamic entropy as described

by Ludwig Boltzmann in the 19th Century has the same type of formula as information content as described

by Claude E Shannon in the late 20th Century. Bekenstein’s Holographic Principle states that the physical universe is just information. Energy and matter are simply minor products of this information. Since entropy increases with energy, which in a given region of space is finite, then eventually if you subdivide particles enough times you will reach a fundamental particle that cannot be subdivided further. This fundamental particle represents one “bit” of information.

If entropy is proportional not to volume but area, does that mean that there’s technically no such thing as volume? The holographic principle predicts almost exactly that. The mass that makes up your body, your house, the Earth and everything else has entropy, and hence information, that is proportional to its surface area. What follows is a universe in which volume is in fact an illusion, where all of the information is projected onto an external boundary as a hologram.

What we see could just be a manifestation of information encoded on a twodimensional surface!

But before you start telling everyone that we live in some Matrix-like illusion it is worth noting that this principle is not well-supported. So far experiments into background noise in gravity waves (a predicted source of evidence of holography) have yielded unconvincing results. In addition to this, classical solutions to Einstein’s equations contradict the existence of holography which could throw the entire concept into jeopardy. Nevertheless, Bekenstein and others continue to investigate the notion of a holographic universe.

James Ormiston synapsebristol.blogspot.co.uk | 21

ARTICLE

The Eyes Have It: The Origin of Sight

S

ight is considered by many people to be their most treasured sense, an understandable attachment given the enormous evolutionary advantage that having eyes provides. You can only smell something if it produces a smell, hear something if it makes noise and touch something only when in direct contact with it. Sight is something many other organisms are unable to escape from, or at least this would have been the case when eyes first evolved. Some have suggested that the evolution of eyes could have driven the “Cambrian Explosion” which produced most of the world’s modern animal groups.

But when and how did this evolutionary leap occur?

The earliest known preserved visual systems are found in trilobites; an extinct group of arthropods which can be likened to a cross between horseshoe crabs and underwater woodlice. This group emerged around 520 million years ago and flourished for around 270 million years before going extinct. During this time they became highly diverse and the types of eyes they possessed varied hugely depending on their lifestyle. Most had compound eyes similar to those in modern insects. Some lived in mud and were blind, whilst others swam freely and had huge eyes wrapped around their whole head.

Other evidence of sight manifests itself less directly in the adaptations of prey to avoid being eaten by predators that could see them. Such evidence is found in the 515 million year old Canadian Burgess Shale, arguably the most famous

22 | SYNAPSE

example of Cambrian faunal preservation.

Wiwaxia, a potential mollusc, has been found fossilised with a diffraction grating like structure running along its spines.

Diffraction gratings serve to reflect certain colours when exposed to sunlight, producing a specific lustre depending on the wavelengths it reflects. This indicates that Wiwaxia could have been using colour to emphasise its spines and ward off predators, a useless adaptation unless such predators could see it.

It follows that whenever eyesight first developed, the entire ecosystem had to adapt to either be seen or not be seen.

Some prey needed to not only develop armour, chemical defence and so on but would also need to display such defences.

At the same time predators needed to improve their eyesight to find prey that hid and discern between prey that could and could not be eaten; an evolutionary arms race of sorts. It has been estimated that to evolve a simple light sensitive patch into a complex camera-like eye could take only around 370,000 years, meaning that since eyes first appeared in the fossil record they could have evolved around 1,500 times over! So why hasn’t everything evolved to possess a complex eye structure since then? The answer is simple: most organisms don’t need it. A worm can’t make use of complex eyes because its nervous system isn’t advanced enough to process the optical signals. If it did, it would need so many other adaptations to its nervous system and musculature that it might as well become a fish!

James Ormiston

E

phs are receptors on the outer rim of cells, like the lock in the front door of a house which only recognises the correct key. In the case of the Eph receptors, they recognise the correct ephrin key expressed on the outer rim of a neighbouring cell.

Ephs are what is known as promiscuous receptors, which means that a number of ephrin keys will fit into the Eph ‘lock’.

There are many types of Ephs and ephrins, the response of the cell after the key has fitted into the lock depending on the specific key and lock combination.

Broadly, the A category of Ephs recognise the A ephrins, and the B category of Ephs recognise the B ephrins. When EphAs from one cell recognise an ephrin A from another cell they sense they are getting in the way and are repelled from one another. However, in the case of the B type Eph-ephrin interaction the opposite effect occurs; the EphB cell recognises the ephrin B on the other cell and takes it as a sign to get friendly and so shimmies on closer to its neighbour.

Ephs are important for function in many tissues of the body. For instance, during development of the foetal brain, cells move to different areas to establish sections important for particular functions. In this example Ephs act as a guidance system for the cells, with the repelling A type ephrins lining the path edge to keep cells from meandering and a gradient of B type ephrins beckoning the cells onwards into position.

ARTICLE

What the Eph?!

Ephs and ephrins activate a stream of knock-on events which can alter cell behaviour such as growth, cellular death etc. As the Eph system sits in a position to control various cellular behaviours it often means that the Eph-ephrin status is manipulated in cancer for the cancer cell’s survival.

Research from the Nobes lab, here at the University of Bristol, investigates the Eph role in prostate cancer. EphA2 along with EphB3 and 4 are found to be expressed at higher levels in prostate cancer than compared to benign tumours. This combination of highly expressing Ephs is thought to enable cancer cells to be both repelled away from other tumour cells via EphA2 interactions and to move towards and past healthy neighbouring cells through attractive EphB3 and 4 interactions. These Eph interactions in prostate cancer are linked to migratory behaviour of cells which is prevented when the Eph interactions are blocked.

The Eph interactions’ involvement in cancer cell movement raises the possibility that Ephs contribute to cancer cell migration away from the original tumour to form metastatic tumours in other organs of the body.

If you want to know more about Ephs and ephrins and their role in the movement of prostate cancer cells, check out the Nobes lab in Bristol’s School of Biochemistry at: www.bris.ac.uk/biochemistry/people/ catherine-d-nobes

Louisa Cockbill synapsebristol.blogspot.co.uk | 23

REVIEW

Synapse reviews:

After Hours: Brains O

n the 23rd of October, At-Bristol Science Centre was overrun with more brains than people to house them. This wasn’t a mad scientist’s lab, but rather part of their series of popular ‘After Hours’ events, open to adults only.

At-Bristol runs four After Hours events each year. The theme of this one was ‘Brains’, so, as a psychology student and aspiring neuroscientist, I was particularly looking forward to this event. I had attended last year’s After Hours event on Space and had a lot of fun – this year did not disappoint, either. “It was nice to be able to see this amazing organ that we’ve been learning about literally ‘in the flesh’”, said Joe Daly, a psychology finalist at the University of Bristol.

The brainy activities on offer included a ‘Brain Game’ room, sheep’s brain dissection, cockroach leg stimulation, and brain food. The ‘Brain Game’ room consisted of a darkened room dotted with experts to demonstrate various psychology experiments and activities.

These hands-on events included a suit dotted with glow-in-the-dark patches on major joints to illustrate visitors’ perceptions of biological motion. As well, there was a desk showing the rubber hand illusion which involved an experimenter stroking a rubber hand that was positioned to look like your real

24 | SYNAPSE

hand. After a minute, you start to get the illusion that the experimenter is stroking your hand. The well-known study popped up in my lectures, so it was fun to see it in action at the event. “I’m currently reading a book about phantom limbs so for me it was particularly illuminating to have first-hand experience of the rubber hand illusion”, echoed Arif, one of the visitors and a psychology graduate.

...sheep’s brain dissection, “cockroach leg stimulation and brain food. “ In particular, I was intrigued by the offer of ‘brain food’, cooked by Bordeaux Quay chef Kelly Seeley. At first, I thought they were simply shaping food to look like brains. However, as I watched the demonstration, I saw they were cooking real pig’s brain. I tried a dish called ‘devilled brain’, which consisted of a pig’s brain sautéed with sauce and put on toast.

While this might sound a bit disgusting,

The science centre was packed to the brim with all sorts of visitors, including plenty of psychology and neuroscience students. The event consisted of a reasonably priced bar, a selection of snacks and lively music. Most importantly, the hundreds of science exhibits were available to visitors without the commotion of children running about.

it actually wasn’t bad! It definitely beats the recent trend of eating fried insects.

brain sauteéd “...pig’s with sauce and put on toast. “

Of course, as mentioned, there were the usual fun science exhibits to play around with. Highlights for me included an exhibit where you stood in front of a screen that mirrored your movements – as a skeleton. In addition, I enjoyed the psychology-relevant visual illusions mounted on the walls. The University of Bristol has a history of strong vision psychology research, so it was great to see a nod to that in the science centre.

After Hours is a great idea and ideal format for letting adults unleash their inner kids. In particular, the Brains event was successful as it tapped into a subject that fascinates us all: the brain. AtBristol is a leading science centre in the UK with over 250,000 visitors each year and over four million since its opening in June 2000. This fact isn’t surprising – it really has fun for the whole family. Plus, unique events such as After Hours: Brains really encourages you to go more than once. I look forward to other After Hours events and would definitely encourage anyone who has never had the chance to visit At-Bristol to go to the next one.

Julie Lee

synapsebristol.blogspot.co.uk | 25

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