BlueSci Issue 39 - Easter 2017

Easter 2017 Issue 39 www.bluesci.co.uk

Cambridge University science magazine

FOCUS

How do we communicate the urgency of climate change?

Interview Special . Reaching Mars . Fad Diets Lord Martin Rees . Sketchcrawl

Easter 2017 Issue 39

Contents

Cambridge University science magazine 3 4 5

On The Cover News Reviews: Bluesci Recommends

Interviews 6

8

Speak More Act More

Shakes and the City

Seรกn Thรณr Herron talks to Dr Emily So about urban earthquakes and disaster preparedness

Food for Thought

Dr Giles Yeo explains to Zi Ran Shen why experts have to work even harder when it comes to diets 10

Where Art Meets Science

12

Understanding the Irrational

Elsa Loissel meets sketch artists drawing scientists at work in laboratories around Cambridge

Laura Nunez-Mulder and Professor Paul Fletcher discuss the future of psychiatry 14

Planting Ideas

Caitlin Walker and Ramya Gurunathan talk to Professor Beverly Glover about iridescence and the Botanic Gardens 16

Words of Wisdom

Lord Martin Rees shares his insight on the future of humanity from his experiences of astronomy, politics, and academia 18

FOCUS

Standing on the Gene

Jiali Gao and Salvador Buse talk to Professor Wolf Reik about why his work in epigenetic intervention might be the future of medicine

BlueSci was established in 2004 to provide a student forum for science communication. As the longest running science magazine in Cambridge, BlueSci publishes the best science writing from across the University each term. We combine high quality writing with stunning images to provide fascinating yet accessible science to everyone. But BlueSci does not stop there. At www.bluesci.co.uk, we have extra articles, regular news stories, podcasts and science films to inform and entertain between print issues. Produced entirely by members of the University, the diversity of expertise and talent combine to produce a unique science experience.

20 Paul Cohen and Kelsey Reichenbach ask experts how they can convince people to keep caring about climate change

Irregulars What if We Touched Mars?

24

Patrick Lundgren finds that space exploration is more than a technological challenge

The Drug that Brought the Dress Back Atreyi Chakrabarty profiles the life-changing career of Professor Dame Frances Ashcroft

26 28

The Inexpert Ape

28

Laura van Holstein explores whether expertise and evolution are compatible

30

CamBRAIN: A Psychedelic Conversation

30

Antonina Khouli and Bart Nieuwenhuis review a panel discussion on a controversial area, and we present CamBRAIN NeuroArt winner David Jane

Weird and Wonderful

32

Headless chickens, an unboiled egg, and orange skin

President: Alexander Bates....................................................................... president@bluesci.co.uk Managing Editors: Amelia J. Thompson/Elsa Loissel.................managing-editor@bluesci.co.uk Secretary: Mrittunjoy Majumdar ..............................................................enquiries@bluesci.co.uk Treasurer: Shan Chong.........................................................................membership@bluesci.co.uk Art Editor: Oran Maguire .......................................................................arts-editor@bluesci.co.uk Radio: Rebecca Richmond-Smith....................................................................radio@bluesci.co.uk FIlm Editor: Sarah Madden..................................................................................film@bluesci.co.uk News Editor: Stephanie Norwood................................................................. news@bluesci.co.uk Web Editor: Letitia Birnoschi..............................................................web-editor@bluesci.co.uk Webmaster: Adina Wineman.................................................................webmaster@bluesci.co.uk Biosciences Editor: Atreyi Chakrabaty..................................biosciences-editor@bluesci.co.uk Biomedical Sciences Editor: Jenni Westoby............................biomedical-editor@bluesci.co.uk Physical Sciences Editor: Seรกn Thรณr Herron.................................physics-editor@bluesci.co.uk Technology Editor: Hannah Thorne........................................technology-editor@bluesci.co.uk

Contents

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Issue 39: Easter 2017 Issue Editor: Martha Dillon Managing Editors: Elsa Loissel, Amelia J. Thompson Second Editors: Jamie Armitage, Alex Bates, Alexander Harris, Seán Thór Herron, Antonina Khouli, Eleanor Leydon, Harry F. Lloyd, Elsa Loissel, Bart Nieuwenhuis, Sufia Rahman, Jordan Ramsey, Rebecca Richmond-Smith, Amelia J. Thompson, Hannah Thorne, Kyle Turakhia, Jenny Westoby Copy Editor: Janina Ander Art Editor: Oran Maguire News Editor: Stephanie Norwood News Team: Matthew Harris, Anjali Shah, Bryony Yates Reviews: Alex Bates, Nelli Morgulchik Writers: Salvador Buse, Atreyi Chakrabarty, Jiali Gao, Ramya Gurunathan, Seán Thór Herron, Laura van Holstein, Antonina Khouli, Elsa Loissel, Patrick Lundgren, Gabija Maršalkaite, Deyan Mihaylov, Laura Munez-Wilder, Bart Nieuwenhuis, Stephanie Norwood, Zi Ran Shen, Caitlin Walker Focus Team: Carys Boughton, Paul Cohen, Kelsey Reichenbach Weird and Wonderful: Rachel Crosby, Bart Nieuwenhuis, Joy Thompson Production Team: Alex Bates, Martha Dillon, Elsa Loissel, Oran Maguire, Amelia J. Thompson Advertiser: Julie Skeet Illustrators: Carys Boughton, Sophie Buck, Nina Capes, Martha Dillon, Alex Hahn, Olivia Healy, Laura van Holstein, Oran Maguire, Susannah McLaren, Thierry Porter Cover Image: Martha Dillon, Oran Maguire ISSN 1748-6920

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (unless marked by a ©, in which case the copyright remains with the original rights holder). To view a copy of this license, visit http://creativecommons. org/licenses/by-nc-nd/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA.

2

Editorial

Bluesci Believes in Experts

On the Cover

“When I say peer, you say review! Peer! Review! Peer! Review!” chanted members of the 500 Women Scientists movement at the Women’s March on Washington in January. That a movement dedicated to female representation in science has to campaign for the field as a whole is hard to comprehend. That scientists have been tweeting grant proposals in #ALLCAPS to highlight the difficulty of finding funding is funny and thought-provoking, but fundamentally it is pretty gloomy that substantially more people will read (and probably forget) PARASITES ARE EVIL. WE CAN KILL THEM WITH LITTLE TINY MAGNETS (HONEST). SEND CASH $$$ (@ helenpprice) than Dr Price’s actual research on Leishmania major and Trypanosoma brucei.

It was no overstatement when Scientific American announced that the ‘War on Science’ had shifted into a higher gear: the list of recent events where political administrations and public opinions have been at odds with expert consensus is long and well discussed. No matter how many articles decry the phrase ‘alternative facts’ (a GoogleNews search for the term returns over 3 million headlines), politicians continue to exploit the fact that their words will not be analysed in any forum more serious than opinion pages. The requirement for science to constantly self-criticise and re-examine makes it less exciting reading than many news headlines, but all the more vital.

We have a duty in this war, Scientific American writes, to “get political” and “be forceful”, so in this ‘interview’ edition of Bluesci we want to champion the experts involved in the work that goes on here at the University of Cambridge. The issue focusses on conversations with scientists from such diverse fields as epigenetics and seismic architecture to understand some of the fascinating questions being asked in today’s research, and discuss how they may impact real lives.

Professor Lord Martin Rees gives his insight into our futures from a life spanning science and politics, Dr Giles Yeo notes that the diet industry has for some time been plagued by ‘fake news’, and Professor Beverly Glover describes how the Botanic Gardens have managed to engage young people. In our focus article we go on to ask leading scientists and specialists about the tools they have developed to engage people with arguably the most pressing but among the most strongly contested issues facing humanity. We also look into communication and scientific development more generally, examining the limitations of space travel, an area of science that has very successfully inspired the public, and presenting ‘Sketchcrawl’, an initiave where artists depict scientists at work, and engage in conversation about their fields.

In a very small way, Bluesci wants to show that we have resolutely not had enough of experts.

The cover, by Martha Dillon and Oran Maguire, captures this issue’s response to a quote from a Scientific American blog post by Jonathan Foley and Christine Arena (February 27, 2017).

It has been almost a year since Michael Gove claimed that “Britain has had enough of experts.” Even if this were generously interpreted as a repudiation of “expert opinion,” of the sort which has far too often been misinterpreted as fact to shut down political and economic debate, such rhetoric risks poisoning a host of urgent discussions where science and politics intersect. It risks cheapening hard-won knowledge, and casts false aspersions on the people who have worked hard to gain and share it. A society that turns its back on scientific expertise is one which has lost faith in its ability to improve. No doubt it is a dark time then. However, the twilight backdrop is not necessarily dusk, as this could as readily be the dawn of a period in which experts themselves appreciate the need to reach out directly and effectively to the public, and become better communicators of the opportunities and threats the world poses today. We should know ‘experts’ as otherwise ordinary people who channeled their energies into disentangling some part of the big, complicated problems: ones which bear on people’s safety, wellbeing and livelihood than the fortunes of political parties. It is only right that all our contributors should appear together as Martha Dillon’s sketches, injecting the scene with the brightness and clarity that experts bring to problems. Because Bluesci believes in experts.

Martha Dillon Issue 39 Editor

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Oran Maguire, Art Editor

News U.S. ARMY MATERIEL

as a 2d of carbon atoms, graphene is a strong, light,

Check out www.bluesci.co.uk, our Facebook page or @BlueSci on Twitter for regular science news

flexible material. As a consequence it has proposed uses in everything from clothes to electronics. Now Di Bernardo and colleagues at the University of Cambridge have shown that graphene also possesses superconductive properties. It has been a topic of debate for the last two decades whether graphene has this capability without aid from other materials, which would dilute the benefits of graphene’s physical properties. The paper published in Nature Communications couples graphene to a surface of the superconducting material praseodymium cerium copper oxide (PCCO) to switch on its superconducting ability.

Using spectroscopic methods the scientists showed that graphene has its own superconductivity by observing a new type of superconductivity that has been hotly speculated about: p-wave superconductivity. As PCCO does not have this property, the researchers concluded that it must be due to graphene’s intrinsic superconductivity. The potential for traditional superconductors to have low electrical resistances and generate strong magnetic fields has wide applications, from levitating trains to generating magnetic fields for MRI scanners and particle accelerators. It is currently being tested whether superconductors can transmit power commercially; 150,000 residents of Copenhagen receive power via superconductors. The authors of this study conjecture that this newly discovered characteristic of graphene could be used in quantum computing to further reduce the size of components and increase computing power, but given graphene’s other physical properties, who is to say its uses would be limited to this. mh

NOAA PHOTO LIBRARY

The Man Who Mistook His Wife for a Hat and Other Clinical Tales - Oliver Sacks

A Potential New Treatment for Parkinson’s Disease? the steroid squalamine has previously been tested

as a treatment for a range of diseases, including cancer and visual impairment. Now a team of scientists, led by the Centre for Misfolding Diseases at The University of Cambridge, have shown that it could be a potential treatment for Parkinson’s Disease. Squalamine was first discovered in dogfish sharks in 1993, but is now made synthetically. In this study the researchers found that squalamine blocks one of the initial steps in Parkinson’s Disease - the aggregation of alpha-synuclein, a protein found primarily in the brain. In Parkinson’s disease, alpha-synuclein clumps together to form toxic aggregates in the brain. Treatment with squalamine decreased the aggregation of alpha-synuclein and was also able to reduce the toxicity of the aggregates. The scientists tested squalamine in both human cells and in worms, a wellestablished model of Parkinson’s Disease. Worms with too much alpha-synuclein become paralysed, but feeding these worms with squalamine led to them regaining some of their motility. Given that the main symptom of Parkinson’s Disease is problems with movement, this was an encouraging result. Professor Dobson, an author of the study said: “it is possible that a drug treating at least some of the symptoms of Parkinson’s Disease could be developed from squalamine.” While this is a very early finding, the aggregation of alpha-synuclein is common to other diseases, including certain types of dementia. The study could therefore lead to advances in the treatment of a number of other diseases. as

MICROBE WORLD

Superconducting Abilities Unlocked

Bluesci Recommends:

Touchstone, 1998

The Physics of Star Trek - Lawrence Krauss

Basic Books, 2007

UNCLIMATECHANGE

4

News

change. One vaccine was general, whilst the other focused on the source of the specific climate misinformation used in the study (the Oregon Petition) – among other things it drew attention to the many fraudulent signatories, including Charles Darwin and members of the Spice Girls!

Both vaccines successfully counteracted some of the effects of the false information, with the specific vaccine being twice as effective as the general. In the current climate of fake news, in which the internet provides a breeding ground for virulent myths and a means for their rapid transmission, psychological vaccination could offer a solution. However, it is not solely a force for good. Similar techniques have been used in the past by tobacco and fossil fuel companies for the exact opposite reason: to foster doubt in scientific consensus. This makes psychological vaccination a weapon which could be potentially be wielded by both sides. by

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Have you ever wondered whether warp speed, time travel, teleportation, inertial dampers quite mundane in the universe of Star Trek, could be in our future? Lawrence Krauss, who is a distinguished popular physics author and a long-time fan of Star Trek, pins some answers on these questions with an enthralling discussion of whether any of these concepts and inventions are or may be possible with our present-day understanding of physics. It and its sequel, Beyond Star Trek, is worth a read for anyone who is into ‘the science of science fiction’, even if you are the serious type. Indeed, what is science fiction today may become the science fact of tomorrow. Nm

Eureka: An Infographic Guide to Science - Tom Cabot

Harper Collins, 2016

Tom Cabot aims to make science more accessible through the use of visuals, which demonstrate the fundamentals of sciences from the Big Bang to Artificial Intelligence. The book invites the readers on a narrative-less journey, from the creation of the universe through the emergence of life and up to the today’s hot topics in the modern exploration of medicine and computer technology. It will not replace a textbook or a regular popular science book, to each their own, but it works well to introduce scientific concepts across a breadth of subject areas with information-rich infographics. Inspirational and visually outstanding, it gives more reasons to be amazed at the beauty and complexity of the world. Nm

Citizen Scientist: Searching for Heroes and Hope in an Age of Extinction - Mary Hannibal

‘Psychological Vaccine’ Offers Hope for Combatting Fake News Epidemic inaccurate information can behave very much like a virus: transmitted from one mind to another, and socially infectious. Protection from biological viruses is provided by vaccines, where exposure to an inactive form of the virus pre-emptively protects against later infections.

Now researchers in the UK and USA have taken similar approach to preventing the spread of misinformation.

The study investigated how people respond to facts and misinformation about the scientific consensus on climate change. When participants were shown only a fact, their estimates of the levels of scientific consensus increased, whereas their estimates decreased when they were shown only misinformation. When participants were treated with both consecutively (the fact first) the effects cancelled eachother out – there was no significant change in opinion.

“Psychological inoculations” were trialled in some groups.

Extra data was included, warning of the use of misleading tactics to undermine public understanding of climate

The books of the late, world-renowned neurologist Oliver Sacks are, in the words of the New York Times, the works of a ‘philosopher-poet’. In his most popular book, he takes us on a journey through a series of fascinating and little-known neurological case studies in an intense mix of medicine, empathy, humour and beating human lives: a man who cannot recognise objects and faces including his own wife’s, autistic twins with ‘documentary’ memories, a young man with Tourette’s syndrome and a remarkable ability for music, brain tumour symptoms mistaken for enlightenment, his examples lay bare the many ways by which our brains construct our perception of the world. Nm

Workman Publishing, 2016

With improved technology, data analysis in science has become a piece of cake but data collection is a challenge in many disciplines because a team of no more than a dozen researchers struggle to gather information. Here citizen scientists come to save the day. Mary Ellen Hannibal dedicates her book to science enthusiasts, who do not confine themselves to popular science books and news articles but participate in science research and contribute to driving progress forward. Translating the loss of her father into motivation for fighting for species conservation, she produces a literary spectacle, weaving research and memoirs into an exploration of citizen science. Nm

The Secret Lives of Flies - Erica McAlister

Natural History Museum, 2017

Erica McAlister, Curator of Diptera at the Natural History Museum, and occasional contributor to BBC comedy shows, has condensed her sense of humour and rabid love of flies into one slim book. From flies with sperm longer than they are, to near headless bat flies that look arachnid, to flies that mimic bees and Beyonce, to minuscule flies that live inside the heads of ants, to flies crucial to cocoa plant pollination, to flies with rotating genitalia, to flies used by forensic scientists to crack cases, Erica shines a light on an insect order that evolution has thrown into all sorts of fantastical directions. If you find the existence of vaults under the Natural History museum that are chock-a-block with millions of insect specimens enthralling, this book will get you. asb

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“A must for anyone who wants to glimpse how it feels to live with a neurologically different perception of the world” Antonina Khouli, Writer

“This book blew my mind off the planet and into the stars to join the USS Enterprise” - Seán Thór Herron, Physical Sciences Editor

“A great way to promote true understanding in science by appealing to the visual learner” - Jordan Ramsey, Collaborations Officer

“A warm-hearted and inspirational reminder that anyone can make the world a better place” - Nelli Morgulchik, Writer

“It’s a geekily specific revel in the littleknown, the underappreciated and the unexplored.” - Alex Bates, President

Recommendations

5

Shakes and the City

MD

Seán Thór Herron talks to Dr Emily So about preparing for earthquakes in urban areas

“Like other public health campaigns in the past where diseases have been eradicated, earthquake protection needs to be seen as a public health issue”

6

Shakes and the City

at a quarter to three on Friday, 11th March 2011, as the citizens of the Honshu island of Japan were looking forward to the weekend, tectonic stresses caused a massive slip on the ocean floor off the East coast. The sea floor jerked as much as ten metres upward and fifty metres horizontally. The rupture length totalled 500 kilometres, the width 200 kilometres. If harnessed, the seismic energy from this earthquake could have powered a city the size of Los Angeles for a year. The Tōhoku earthquake measured a magnitude 9.1: it shifted the Earth’s axis twenty centimetres, changing the length of a day by a measurable 1.8 microseconds. 25,000 people died (mostly because of the resulting tsunami), a tragic death toll, but one that only accounted for 0.4% of the population affected by the disaster.

In striking contrast, the 2005 Kashmir earthquake measured a magnitude of 7.6, which is 200 times less powerful than the Tōhoku earthquake and yet killed around 90,000 people. In fact, death rates in earthquakes within continental interiors, which are generally around a hundred to a thousand times less powerful, often exceed 5%, and can be as high as 30%.

Geography and geology conspire so that many of the high-risk areas, where earthquakes are unpredictable and poorly understood, fall in developing nations.

“Population growth and rapidly increasing levels of urbanisation in many earthquake-prone regions of the world are contributing to accelerating levels of risk for billions of people,” writes Dr. Alex Copley, a lecturer in the Department of Earth Sciences in the University of Cambridge, and a fellow of Robinson College. It is not obvious how to provide the modern engineering solutions and political rethinking required to prevent damage and death. How can we prepare societies for these unpredictable earthquakes now and ensure better planning in the future?

Assuming the Japanese do not somehow have a natural resilience to earthquakes, there must be a reason why cities located far from subduction zones (like those on the East coast of Japan, which produce the largest and most frequent earthquakes on the planet) experience a much greater impact.

Why were cities in Kashmir less prepared than in Tōhoku?

The Japanese have spent a lot of time learning how to anticipate earthquakes, and so have Californians. These communities sit near boundaries between the tectonic plates comprising the Earth’s crust and upper mantle, where a great deal of tectonic activity is observed and expected. The same is not true if you live in the middle of a plate, or far from obvious zones of tectonic activity.

Intraplate earthquakes are far less frequent and much more difficult to predict. The bending of rock that occurs before an earthquake can take place over timescales as long as tens of thousands of years – longer than human civilisation has existed. Since we have never seen them slip, the location of many intraplate fault lines’ is hidden to us. Researchers continue to search for the causes of these earthquakes, and especially try to find out how often they recur. This requires dense arrays of expensive seismometers that are difficult to put in place in some of the less developed regions of the world, the very same regions often at the highest risk of intraplate earthquakes.

Finding fault lines is not the only problem, however. In the Middle East and surrounding areas with arid climates, you will often find cities built on recently discovered fault lines. This is not mere coincidence. The vertical slip on these faults actually raises the water table nearer to the surface, which attracts unwitting settlers. Since many of these regions have no history of earthquakes, today’s inhabitants often build their houses out of stone and concrete, which are cheaper and more abundant.

This is an unfortunate recipe for tectonic disaster. When an earthquake does hit, these brittle houses collapse easily, virtually turning to rubble on shaking. Collapsing buildings kill people, more than anything else in an earthquake.

The issue is also political. Nicholas Ambraseys and Roger Bilham, from Imperial College London and the University of Colorado respectively, calculated that 83% of all deaths from building collapse during earthquakes over the past 30 years occurred in countries that are anomalously corrupt. Such countries see funds provided to prepare for future seismic events siphoned off towards ‘more pressing’ projects, such as those important for reelection. Corruption, quite literally, kills.

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A region’s vulnerability to earthquakes has little to do with the frequency of earthquakes occurring there. For areas where earthquakes do occur, but are rare and unpredictable, the problems are manifold. Even if the active faults are found, providing funding and expertise for preparation is problematic because of corruption and how difficult it is to predict the recurrence of these quakes. Convincing politicians and citizens that it is worth investing in preventative measures over other issues such as healthcare or housing therefore becomes a complicated task. To top it all off, existing housing in developing regions is often exactly the opposite of what an earthquakeresistant design would prescribe.

Dr. Emily So, Senior University Lecturer in the Department of Architecture, Fellow of Magdalene College, advises on how cities – particularly those less financially able to provide for themselves – can prepare for earthquakes. “Awareness is key,” says Dr. So, who also leads the Cambridge University Centre for Risk in the Built Environment. “Like other public health campaigns in the past where diseases have been eradicated, earthquake protection needs to be seen as a public health issue.” Dr. So suggests that a staggered approach to earthquake proofing is a method of saving lives while keeping costs down.

“Earthquake proofing and building codes have different design levels. Nuclear power plants for example, are designed to withstand very large events with no damage as the consequences do not bear thinking about. “On the other hand,” continues Dr. So, “life safety may be the level at which residential housing in developing countries could be designed to.” Houses can be built so that while they feel the effects of an earthquake and become damaged, they will not fall apart, collapse and kill people. Such houses could need repairs or partial reconstruction after a large earthquake. However, it would still be cheaper than clearing the foundations of houses not built in this way and rebuilding them from the bottom up.

How can the suggestions of researchers like Dr. So be implemented? Both in Cambridge and beyond scientists and engineers are involved in various steps of reducing the risk, and ultimately the death tolls, of these disasters. Geologists play a vital role in identifying faults that are likely to rupture in the future, not by turning their heads to the ground but to the skies instead. Satellite data is incredibly valuable in tracking the slow bending of the rocks surrounding fault zones. Due to the motion along a fault, the satellite will detect the ground as being farther away, or closer, than it was on previous passes.

Tell-tale signs of past events may also be preserved in the landscape, for example, earthquake-induced landslides.

While this does not allow geologists to definitively predict an event will occur, they are able to suggest likely locations and magnitudes of future earthquakes. This can be used to create the political pressure necessary to take action, such as enforcing regulation on construction, and raising public awareness. In this way, the knowledge that underpins successful earthquake resilience in communities in Japan, California and Chile can be extended to other areas.

Finally, housing must also be improved. The cities of the future may in fact be moving away from modern construction techniques, says Dr. So. “[Collapsed buildings are] one of the main “killers” in earthquakes.

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NINA CAPES @ninacapesart

In recent years, we have seen more and more shoddy ‘modern’ buildings, built without correct code enforcement, collapsing. Communities in the developing world want to use modern engineered materials, but without the engineering input, these become dead weight and dangerous. We must find new ways of making traditional, vernacular [designed based on local need] forms of construction into attractive alternatives.”

Hopefully, through the cooperation of researchers and engineers across many disciplines, we can understand more about the mechanism of these devastating earthquakes, raise awareness, and begin to resolve the international discrepancy in earthquake preparedness. Strong political action, as well as good engineering and careful planning will be required to ensure cities across the world improve their structures and infrastructures for a disaster-proof future.

Seán Thór Herron is an undergraduate in Natural Sciences at Magdalene College

Shakes and the City

7

Zi Ran Shen talks fad diets and pseudoscience with Cambridge’s Dr Giles Yeo

MD

the post-truth era has taken over — beliefs are emphasised while cold hard facts are ignored.

From Kellyanne Conway’s insistence that falsehoods were “alternative facts”, to Nigel Farage’s flipflopping on the promised £350m for the NHS, nothing seems to be untouched by the post-truth haze. But perhaps all this is not so very new. We have seen questionable ‘facts’ before, ofen with a hefty sprinkling of pseudoscience on top. The shining spearhead of pseudoscience is perhaps the fad diets industry, which claims to serve up a trim waistline on a silver platter. Unfortunately, the holy grail of weight loss with minimal effort is just that, an age-old myth. The renowned Cambridge scientist, Dr Giles Yeo, recently appeared in an episode of the BBC’s Horizon entitled “Clean Eating — The Dirty Truth”. In the program, he tore down some of the fad diets plaguing the nutrition industry. BlueSci asked for his thoughts on the post-truth era of diets and how we can control what we put into our mouths.

Dr. Yeo believes that people’s attraction to pseudoscience over ‘experts’ is two-fold. “[First], science, in trying to determine if something works or not, takes a long time. [However], people are impatient, particularly in situations where they need

BALLOOKEY KLUGEYPOP

Dr Yeo’s research looks at how the brain controls body weight

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Food for Thought

a quick answer. The second thing is that scientists always argue with each other [and we] always change our minds. We’re paid to argue with each other as scientists, and we change our minds [when] data emerges to prove or modify our previous hypothesis.

It’s [then] our duty to change our minds.” The trouble with fad diets, he says, is that they instead “mine something out of a kernel of truth and then run with it. Because they provide a clean, crisp, and pretty answer, people prefer to listen to them.

Ultimately - because losing weight and controlling your diet is inherently difficult - [it] is therefore particularly amenable to easy answers. Our biology makes it difficult to lose weight, because we’ve always evolved through a time where there’s been too little food, only now there is too much food. Therefore, any time [our] body starts losing weight, [our] brains are programmed to prevent it. On top of that, there is also a variation in terms of how hard [our] brains fight [weight loss].”

Dr Yeo’s research is focused on the genetic causes of obesity, but he believes that the environment we find ourselves in also plays a large role. “The problem is, obesity and diet-related illness […] is a product of the changing environment. The variation in why some people get fatter than others, that’s genetic, but the drive of the increase in body weight is the environment. The big problem is, if we don’t change the environment, we’re not going to fix the problem. Now there are going to be, to differing levels, pharmaceutical, surgical, and other interventions, [but] are we really expecting to give all the people suffering from overnutrition drugs to cure their disease? I just don’t think so. That’s the pessimistic view; I am an optimistic person at heart.”

When speaking of environment, Dr. Yeo defines it “in its broadest context, not only in terms of physical activity or our food environment. Even if you look at socio-economic class, that influences the type of foods you may get. It is going to Easter 2017

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going to have more of it. Supermarkets are another trick. Most people tend to go around the ends [of the aisles] quickly and slow down as they get to the middle of the aisle. So the stuff on the edges of the aisles are all on sale to make you stop, and the stuff in the middle of the aisles at eye level are never on sale. That tends to be where the most expensive stuff sits. Imagine if only broccoli was put [in the middle of the aisles]. [One] can shift people [into] buying things one way versus the other.”

Dr Yeo says the information that he has gathered over the years has yet to be concisely put together into a book. “There are books out there which sell specific diets, but is there a book out there which actually brings together all the information? I don’t think it exists.” In terms of educating the public, he believes that “education in the most [basic] sense is not going to help because people already know what they need to do to lose weight. We need to show people how to eat less, rather than tell them to eat less, but it’s going to take time, and we’re going to argue with each other, [meanwhile] people are going to turn to fad diets. Pessimistic hat on again.”

“There are books out there which sell specific diets, but is there a book out there which actually brings together all the information? I don’t think it exists”

Zi Ran Shen is a Biochemistry PhD student at Wolfson College

ORAN MAGUIRE

Food for Thought

be difficult to change the environment— and more crucially, the solution is going to be different for different people. That is the problem [with] a lot of dietary advice [where] it tends to be ‘one size fits all’. The general physics of it [is the same of everyone] — if you eat less and move more, you’ll lose weight; however, the way you achieve that is layered and mired in complexity. Some people are more psychologically responsive to [focusing] on [a] diet two days a week, the rest of the five days [eating] what [they] want. Some people would prefer to lower [their] carbs and increase the numbers of proteins, but do it every single day.

[Some] people respond to stress by eating, and some people respond to stress by stopping eating — it’s bimodal. We know the phenotypes, and [there is] a genetic basis for it. We need to be able to understand how each of us is going to respond to these environmental changes. Then, by some evidence-based method, put together some kind of [weight loss] strategy.”

Dr Yeo also gives his opinion on the food industry: “[There are] a lot of people who blame the big companies — McDonalds, Nestlé, Unilever — but they’re not out to make us fat, they’re there to make money, and we have to interact with them. If we don’t interact with the people who make our food, how are we going to solve the problem? I think, in my perhaps naïve ‘Shangri-La’ view of things, the companies might realise that if they give us healthy food we’ll stay alive longer [to] spend more money with that company. At the end of the day, the most effective way to change the environment is if the market forces make them change.”

Though he is optimistic that market forces can cause a shift in the larger food environment, the realities of the current environment still look grim. Dr Yeo clarifies the idea of food addiction and outlines some of the ways the environment manipulates the psyche to encourage consumerism.

“Food addiction does not exist chemically.

[However], there are situations in which specific behaviours hijack some of the addictive pathways.

[You can eat] for reasons which have very little to do with hunger, and that’s what I call the “oooh” factor, which are hedonic pathways that makes you [eat] more. I think you can get addicted to the actual eating behaviour. Nonetheless, food companies are trying to hijack those addictive pathways, those hedonic pathways, to make us buy more [with] for example something called the incidental virtuous food. Cereal, for example, always has strawberries on the [box]. The strawberries act as an incidental virtuous food, so [consumers think] this is healthy cereal, it’s got strawberries in it, so therefore I’m

Food for Thought

9 9

Where Ar t Meets Science Colourful felt tip pens amongst pipettes; sketchbooks next to lab manuals; quiet silhouettes in jeans and tee shirts mingling with busy figures in white coats.These are the unusual sights caught at over twenty University of Cambridge laboratories for the past two years. An ongoing collaboration between Pint of Science and Cambridge Urban Sketchers, the Creative Reactions Sketchcrawl gives the opportunity for sketch artists to shadow a scientist for a day, immersing themselves in the world of a laboratory while capturing on paper researchers’ daily work.

SSUSANNAH MACLAREN

On drawing the scientists pipetting: “You can tell the scientists here have been doing this for several years. I like to see how people, when they do the same thing over and over, their hands become experts in doing the movements.

I’m drawn to the memory of the hands.”

Artist Sophie Atkins at the Gurdon Institute

Left to Right,Top to Bottom: Artist Rikki Morgan-Tamosunas drawing PhD student A. J.Thompson, - Department of PDN, 2017 Sketch by Allison Henderson - Department of Oncology, 2016 Yasmin Gyford’s artwork “Departrment of Engineering Sketch“- Department of Engineering, 2016 Reporting and Photographs by Elsa Loissel

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Where Art Meets Science

Pint of Science Creative Reactions will be holding a ScienceArt exhibition at St Paul’s Church, CB2 1JP, on the 18th and 19th of May 2017 Easter 2017

“For me it’s important to show we are not sitting in ivory towers, hiding somewhere. Finding a way of showing the beauty of spending money on science is what I enjoy.When my parents were visiting last year, I tried to explain to them what I was doing in the lab. The drawing the artist created hopefully gives me a simpler way of understanding what things they see first - and that I should probably tell them about - even if they are not the most interesting to me.”

Scientist Jens Abraham at the Battcock Centre for Experimental Astrophysics

Left to Right,Top to Bottom: Sketch by Andrea Malaskova - Department of Computational Biology , 2017 Rikki Morgan-Tamosunas - Department of PDN, 2017 Sketch by Karoline Leopold - MRC, 2016 Sketch by Lele Saa - Department of Biochemistry, 2017 Artwork by Janet Hathiramani - Department of Earth Science, 2016

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Where Art Meets Science

11

Understanding the Irrational

OLIVIA HEALY @OLIVIAMHEALY

psychiatry is changing . Historically, the field has been dynamic, undergoing transformation as institutions and asylums have come in and out of fashion. Over the last century, the Diagnostic and Statistical Manual of Mental Disorders (DSM), a handbook of checklists by which psychiatrists can make diagnoses, has been overhauled time and time again. The DSM is a controversial manual.

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Understanding the Irrational

MD

Laura Nunez-Mulder discusses psychiatry’s future with Professor Paul Fletcher

Many disorders overlap, and the requirements for diagnosis can seem arbitrary, reflecting how little is known about the causes of mental illness. But behind the diagnostic tools, researchers are changing the way they approach the difficulties of understanding the mind.

Neurology, psychology and psychiatry are no longer distinct and independent fields. Collaborations with geneticists and immunologists are increasingly common.

Professor Paul Fletcher has seen first-hand the changing attitudes in the field. He initially trained to be a medical doctor, specialising in psychiatry. “When I was a junior doctor, there was not much cooperation, not much common ground between psychiatry and neurology – not even psychiatry and psychology. But the development of neural imaging has led to psychiatrists and neurologists being in the same room and looking at the same problem. There is more recognition that both have something to say about the mindbrain interface.”

Fletcher is himself a prime example of interdepartmental cooperation. His original research interest was psychosis – how the perceptions and beliefs of his patients changed to produce delusions and hallucinations. “Being a clinician was unsatisfying. Of course, it felt rewarding, but none of us knew what the heck we were talking about.”

Frustrated with the knowledge gap between diagnoses and the underlying causes of symptoms, Fletcher followed his curiosity down the rabbit hole of cognitive neuroscience, even administering the class B drug ketamine to volunteers to model the distortions of reality often experienced in schizophrenia. Since 2008, Fletcher Easter 2017

has held the position of Bernard-Wolfe Professor of Health Neuroscience at Cambridge. Alongside his ongoing research into the mechanisms of psychosis, Fletcher is now exploring how humans make choices about food, with implications for understanding obesity and binge-eating.

Hearing voices and filling a trolley at the supermarket – what links these seemingly disparate experiences? “Being interested in psychiatry, in what it is to be irrational, psychotic, led me to normative research on human learning, judgement and decisionmaking, and got me interested in rewards processing, predictive coding, those sorts of ideas, applied to psychosis,” says Fletcher.

“The same sorts of mechanisms underlie food choices – we often make irrational decisions, and do things that are not good for our health, but why is that? Rewards processing and motivation are a way of understanding food behaviours, why people are engaged by external stimuli to then engage in certain behaviours.”

A tool that Professor Fletcher and his colleagues use to guide them in both areas of research is a ‘predictive coding model’ of the brain. The model is one of several ways of explaining how the brain makes sense of the perplexing array of incoming sensory information - non-stop light waves, sound waves, temperatures, vibrations and so on. Some information is filtered out if it meets our expectations based on previous experiences. Signals that do not fit the prediction can receive attention. In psychosis, a slight shift in the predictive coding may lead to unimportant stimuli seeming highly significant, which may explain why some people become convinced that the newsreaders on TV are speaking directly to them, or that their internal thoughts are being projected out loud. In health neuroscience, the predictions that influence future choices are updated every time you enjoy a meal and feel full, modifying your expectations about the food you choose. “What does it mean to feel full? It isn’t a full stomach. It’s a change in sensory input, associated with not being able to eat anymore.” So Fletcher and his colleagues investigate, amongst other things, how predictions based on prior experiences can modulate that sensory input of fullness.

The research done under the Bernard-Wolfe Health and Neuroscience fund may be led by a psychiatrist, but it requires a diverse team. Fletcher works alongside neurologists and endocrinologists, and is painfully aware of how narrow his early training was. During a medical degree, students spend several weeks on a placement of their own organising, doing something related to medicine almost anywhere. Fletcher spent his elective on a psychiatry placement. “In retrospect, it was far too early. People should look around medicine as much as possible. I was encouraged to pin my colours to a particular mast, but I think it would have been good to do something in surgery.” Surgery seems a Easter 2017

ORAN MAGUIRE

surprising digression for a psychiatrist, but Fletcher thinks a broad knowledge is important. “It is known that physical health can lead to mental problems. It would be good to know more about the body.”

To bridge the gap in understanding between tiny neurochemical changes and actual human behaviour, it is important to recognise that the mind is not separate from the body, or even from the brain. Experts in brain structure and activity, hormones, or genes are pitching in to contribute their knowledge to the study of the mind. Recently, an invitation to psychiatry research has been extended to immunologists, who study how the body responds to infection.

Inflammatory responses have been implicated in the onset of depression, a mental disorder that affects one in five people in the UK. This is no trivial insight.

If the symptoms of depression are attributed to inflammation of the brain, then future antidepressant medicines could become far more effective by targeting inflammatory molecules. The growth of ‘immunopsychiatry’ excites Fletcher. “I fantasise that there will be opportunities for junior doctors to study two fields as one.”

Professor Fletcher hopes that the different science departments will be able to bridge the gap in knowledge together. “Has my work changed clinical practice? That’s an unequivocal no. The gap is huge.”

But is it possible? Fletcher thinks so. “Ultimately, I have to say yes. But I have a slight fear that, just because we’re heading in the right direction, it doesn’t mean that we’ll get there. I may want to reach the moon, and if I climb a tree, I can get a little closer, but it doesn’t mean that I’ll reach it that way.” Psychiatry will never reach the moon in isolation. As Fletcher says, the gap is huge, and it will take an interdisciplinary approach to make it any smaller.

Laura Nunez-Mulder is a 3rd year Medical Student at Emmanuel College, reading NST Part II Psychology

Understanding the Irrational

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ORAN MAGUIRE

Planting Ideas MD

Ramya Gurunathan and Caitlin Walker talk to Professor Beverly Glover about communication, collaboration, and botanical research

ORAN MAGUIRE

“ IT ’ S IMPORTANT FOR SCIENTISTS to be able to communicate about their research, we all know that, but sometimes it’s hard to know quite how to,” explains Beverly Glover, Professor of Plant Systematics and Evolution at Cambridge.

Glover is not only Director of the Botanical Garden but also the leader of an active research group and an award winning author, so communication in science has been central to her career.

Alongside its perfection of a flower-filled stroll, the Garden boasts over 8,000 species and has a wider role in research and education. It is this union of an idyllic setting with the scientific research taking place that creates such an ability to aid communication between academics and members of the public. From “cradle to grave”, says Glover, the aim is to engage all ages. Catering for this vast diversity of visitors involves a lot of thinking and “making sure you pitch the right message to that audience”. This ranges from trails for toddlers, to the ‘Science on Sundays’ series that covers the latest research presented by experts. As Glover realises, people may think they are “coming for the coffee and the sunshine”, but learn something about the University’s research as a result.

Glover also talks of the “Cambridge phenomenon,” arguing that the close-knit nature of the community adds to the Garden’s popularity and boosts interest in the scientific goings-on. The attendance of 12,500 patrons over two nights when the Garden’s Titan Arum flowered illustrates this shared excitement about plants. The tight community and opportunity to collaborate is also responsible for keeping Professor Glover in Cambridge throughout her research career.

It is not only engaging with the public that the Garden team takes pride in. The facilitation of

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Planting Ideas

“research in chemistry, zoology, archaeology and architecture across the university” also adds to the collaborations which are promoted through use of this resource.

Glover’s own research has been heavily reliant on the collaboration of distinct disciplines, including work with “physicists, chemists, mathematicians and behavioural scientists”. The prospect of language barriers and confusion in this type of work may be enough to nauseate many scientists, but “always fun” and “energising” are Glover’s typically enthusiastic opinions of such collaborations: “You can take a strongly interdisciplinary approach to give you an integrated overview of a problem… I guess that approach is one of the things I am proudest of.”

With an initial ambition to study Marine Biology, Professor Glover’s academic journey has been full of surprises. Realising “how much fun plants were” was a lucky outcome of the obligatory breadth of her undergraduate course at St Andrews University. Following this passion, she has taken further inspiration from the Gardens themselves. For example, after spotting a Hibiscus trionum growing in the Garden one day, she realised “that’s funny, I don’t know how you make that funny-coloured texture on that surface.” This unusual epiphany sparked her interest in plant nanostructure, forming the basis of an inspirational research programme.

Have you ever thought of flower petals as the roadside billboards of the natural world?

They encourage the travelling pollinator to stop and stay for a while, making sure to carry some pollen with them on the way out. This suggests that a plant’s ability to propagate is very much dependent on the quality of their petals’ “display technology.” Glover is interested in that very idea, and studies how flower petals

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manipulate light and colour to provide a signal to pollinators.

The light display produced by the flowers studied in Professor Glover’s group are unique in that they use surface structures rather than chemical pigments to produce colour.

According to Professor Glover, “most of the colours you see in plants are produced in the same way as the colours in the clothes we are wearing. So it’s a chemical pigment that absorbs light of some wavelengths and we see the colours that are left behind.” However, in the flowers her group studies, the colours are produced by structures on the surface of the petal which have dimensions measured in nanometres (one billionth of a metre).

This infinitesimal length scale is similar to the wavelength of light, so organizing these structures in an ordered way causes it to interact with light in such way that some colours, and not others, will reflect off the surface in different directions. This kind of structure is called a diffraction grating. It is the same type of feature that produces different rainbow-like effects on CDs depending on how the disk is tilted. As with a CD, the observed colour of the petal will change as the angle of view changes, an optical effect known as iridescence.

The motivation for the project actually came about through a stroll in the Cambridge Botanical Garden. One of Professor Glover’s students picked a hibiscus flower one day and was surprised to see a rainbow-like colour effect like the kind you see in an oil slick or the surface of a soap bubble. Intrigued by what was causing this effect, they studied the petal under an electron microscope and noticed nanometre-scaled ridges producing the diffraction grating on the surface.

The Glover group was also interested in whether the petal’s iridescence influenced the behaviour of pollinators approaching the flower. They found that bees locate iridescent flowers more rapidly than non-iridescent flowers. Since the colour of the flower changes as the bee hovers around it, the bee receives an increased signal to the receptors in its eye.

When asked about future directions of this project, Professor Glover answers: “What I really want to know is how you build

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it—how a living tissue builds a nanostructure so regular that it interferes with light in a predictable way.” Glover’s group is creating their own line of hibiscus plants using genetic modification techniques to study how these petal nanostructures begin to form.

According to her, although iridescence in flowers is a rather uncommon trait, plants which have this trait have very distinct evolutionary histories. This suggests that the trait evolved separately multiple times. Since the nanostructures of various iridescent plants appear very different when studied under a microscope, the Glover group is interested in determining whether or not they have also formed using different mechanisms.

The Cambridge University Botanical Garden is more than just a beautiful place to spend an afternoon. It is also an important research tool for numerous Cambridge scientists from a wide range of disciplines.

Professor Glover’s own research is a prime example of how the garden even inspires curiosity about new research topics, like a flower petal’s captivating light show.

ORAN MAGUIRE

Nanotextures that create colours are found outside of the realm of plants.

The intricate patterns and dazzling colours present in butterflies also arise from the nanostructures created by the microscopic scales on their wings

Ramya Gurunathan is a MPhil student in Scientific Computing at Churchill College Caitlin Walker is a 1st year studying Biological Natural Sciences at Fitzwilliam College

Planting Ideas

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Lord Martin Rees is a former Master of Trinity College and an accomplished cosmologist and astrophysicist. He has been Astronomer Royal since 1995, and was President of the Royal Society between 2005 and 2010 Cambridge is a good place to convene experts who can try to decide which threats can be dismissed as science fiction and which are worth thinking about. There is not very much study of these

possibly devastating, albeit unlikely, events, especially those that are becoming more likely with technological advances. We are familiar with cyber-attacks but we also have to worry about pandemics - both natural and artificiallyinduced ones - and think how to minimise their impact. I think all these extreme risks, which are unlikely but would have colossal consequences, are understudied.

Panic and rumour can spread via social media literally at the speed of light. This rapid spreading means that

it’s very hard to implement an optimum response if one has not foreseen such an event beforehand and taken precautions. It also means that serious catastrophes are more likely to cascade globally. In the past, there have been catastrophes which have affected certain societies - even causing their collapse - but they have not been global, whereas now it would be unlikely that a really severe setback could occur in one particular country without it cascading to the rest of the world.

It’s most unlikely anything could happen that would wipe out all humanity. I think what is frighteningly

possible, however, is a real setback to civilization and to the way society is now organised. We’re very vulnerable because we have high expectations. To give you one example of this: a severe pandemic would of

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Lord Martin Rees on the Future and Catastrophe

course produce a large number of casualties.

Even if the fraction who were infected was only one in 1000, that could already cause social unrest because it would overwhelm the capacity of hospitals and people would then clamour for access to treatment they felt entitled to. Does the fact that most people have mobile phones make things better, or even worse? It allows people to be warned of risks, and given advice.

But it also allows panic and false news to spread. So we don’t know the net effect of the interconnectedness of everyone today.

In the future, we will develop the capacity to augment human beings through genetic and cyborg techniques. If you ask what my scenario

would be for these developments, I’d conjecture that they’ll be spearheaded away from the Earth.

A century from now, there will be a few bold pioneers living away from the Earth, maybe on Mars. They will of course be living in an environment to which they are badly adapted, so they would have a massive incentive to modify themselves or their progeny by genetic techniques or cyborg techniques to adapt to that environment. So I think if there is going to be evolution to a posthuman stage, it will happen away from the Earth where there is no regulator that can reach them and they have strong incentives to adapt. That’s my scenario. And of course it has huge implications on the even longer term. Evolution up ‘till now has happened on a rather slow time scale of Darwinian selection, where it has taken maybe a million years for species to evolve significantly. Now these changes will happen on a technological timescale - maybe just one or two generations.

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I think being an astronomer gives me a greater awareness of the long-term future. Most of us are

familiar with the vast timescale of biological evolution that led to humanity’s emergence.

All educated people realise that we are the outcome of 4 billion years of evolutionary history. But many people tend to think that we are the culmination of it all. Astronomers can’t really believe that – indeed, they would guess that we may be barely at the half-way stage - because we’re aware that the future of our Sun and our Solar System, and certainly the Universe, is probably far longer than the past. This perhaps offers an extra motive for ensuring that there’s no catastrophic setback that would foreclose the future, which otherwise could extend not just for centuries, but for billions of years.

NASA, HUBBLE

Lord Martin Rees: the Future and Catastrophe

So this posthuman evolution is going to happen far faster than any evolution that has happened until now. And we have no idea what is going to evolve, whether it will be mainly genetic modification, or cyborgs, or whether we will even be downloading our brain to machines. This is where we have to hand over to science fiction writers!

I think it is important for students to be activists. One hopes they’re more

rational than most citizens. And because they’re young they’re likely to be alive at the end of the century, and so care about the longer term.

That’s important because what’s worrying is that the focus of politicians is on the local, the parochial, and the short-term. They care about what happens here, and they care what happens before the next election. Politicians will, however, be more likely to engage with an issue if it features in their inbox, or gets regular highprofile coverage in the press. It’s therefore very important for us in academia to discuss these issues, make sure they are widely understood, and thereby help to raise them high on the agenda.

Especially things like energy and climate, which are very long-term.

This is the first century when one species, ours, can determine the future of the planet. The main dangers come not from nature but from us. Through our everheavier collective footprint on the Earth, we can produce catastrophes in a way that earlier

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generations could not. And small groups or even individuals, empowered by new technology, could have global impact – for good or ill. I think there will be a rising tension between privacy, security and freedom. So the stakes are higher, the responsibilities are greater, and there is ever more need for a global perspective. I think it’s sad that so few young people want to embark on a political career. That is understandable because such careers are now less attractive, and more pressured, than they were, but we do need to ensure that enough really capable people have the dedication to go into straight politics. But even if one is not a politician, one can affect public opinion, through the media, through pressure groups, through blogging, through movements like Effective Altruism, all of which involve students. I think it is very encouraging that such movements are gaining traction with the student body, not just in this university, but in all the major universities around the world. So that’s a hopeful sign for the future.

Lord Rees spoke to Deyan Mihaylov, a 2nd year PhD student in Theoretical Astrophysics and Gabija Maršalkaite, a Part III student of Earth Sciences

Lord Martin Rees on the Future and Catastrophe

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Standing on the Gene

SUSANNAH MCLAREN @imsusiem

MD

Salvador Buse and Jiali Gao discuss the emerging field of epigenetic modification, and ask Professor Wolf Reik where it might take us

IN THE NEWS, IN CONVERSATION, in the cafe - you have probably heard of epigenetics. But what exactly is it?

Epigenetics literally means ‘on top of genetics’. Whereas genetics is the study of genes, which are stretches of DNA containing the information needed to make proteins, epigenetics is the study of how the cell uses those genes to make proteins.

Consider a cell in your brain and one in your liver.

Each of these cells is genetically identical, and yet they are extraordinarily different in appearance. How can this be?

The answer is that the cells are epigenetically different. To understand this, it is first essential to clarify the central dogma in molecular biology. Your genome consists of about three billion base pairs of DNA, containing about 25,000 genes. To make a protein from a gene, enzymes bind to the gene and

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Standing on the Gene

‘transcribe’ it into an intermediate called mRNA. A second set of enzymes then ‘translate’ the mRNA into protein.

Some of the proteins encoded by those 25,000 genes, such as ones involved in cellular respiration, are essential to life, and must be continuously produced in every cell. However, most proteins are not expressed in all cells. As cells in an embryo become specialised to form tissues such as brain or liver, they permanently alter their patterns of gene activity, and so produce different proteins, to take on the characteristics of brain or liver cells. Epigenetics manifests these great changes in gene activity by altering the accessibility of genes to the enzymes involved in transcription.

Research suggests that epigenetics can confer some cellular ‘memory’ of past stress, and that changes in the epigenome may even be transmitted between generations, though this is still controversial. The go-to example for epigenetics researchers is the Dutch Hunger-Winter of 1944-1945. This was a deadly famine in the Netherlands lasting three months, precipitated by a German blockade, and worsened by an unusually harsh winter. It was a tragedy, but presented researchers with a unique ‘natural experiment’. It was found that babies born to Dutch women who had good access to food during the initial six months of pregnancy, but starved for the last three months, were underweight, whereas mothers starved during the first three months but well fed during the final six gave birth to babies of healthy weight. This is logical, considering that most foetal growth occurs during the final months of pregnancy. More surprising was data showing that the babies born underweight had, on average, a substantially lower incidence of obesity than the general population for the remainder of their lives, whereas those malnourished early in gestation, but born at a healthy weight, had a higher incidence of obesity. These same effects were even observed to occur in the subsequent generation, decades after the original famine.

Epigenetics can explain this environmentally induced, but heritable, difference between the weights of these two

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groups.It has been shown that those individuals starved early in gestation had comparatively reduced methylation of the gene encoding an insulin-like growth factor (IGF2), and so higher levels of the protein. This protein is a hormone that promotes glucose metabolism in a similar way to insulin. In short, these individuals have developed a ‘thrifty’ metabolism.

To find out about current epigenetics research, we spoke with Professor Wolf Reik, associate director of one of the largest institutes of epigenetic research in Europe, the Babraham Institute. One of the most exciting recent developments in epigenetics, actively researched in Professor Reik’s lab, is technology for editing the epigenome. This makes use of the revolutionary CRISPR-Cas9, originally a remarkably precise technique for cutting DNA, modified to alter epigenetic marks. Though still is in its infancy, CRISPR-Cas9 and the modulation of the epigenome have the potential to be used in the treatment of a vast range of diseases, including cancer. Cancer is caused by aberrant activity of the genes controlling cell division, in some cases arising from epigenetic mutations. Changing the epigenetic marks on these regulatory genes could therefore be a target of novel cancer therapies. Promisingly, epigenetic silencing of the gene SOX2 in human breast cancer cells grafted into living mice (a good model for breast cancer) caused inhibition of tumour growth for more than one hundred days. Nevertheless, success in mice is a far stretch from success in patients, Professor Reik also cautions that most cancers involve so many genetic and epigenetic changes that it would be difficult to halt a tumour’s progress by epigenetically modifying a single gene, except in the very early stages.

Nonetheless, epigenome editing has generated much excitement in the scientific community.

What will it be used for? Professor Reik does not know: the possibilities are simply too numerous. Already, scientists are attempting to use the technique to learn more about how exactly epigenetic marks regulate the activity of different genes. With this understanding would come the ability to turn genes on and off at will. With that power, could we wipe the epigenome clean to generate stem cells?

Could we program stem cells to develop into nerve cells for the paralysed, or pancreatic cells for the diabetic, or retinal cells for the blind?

If we could understand how the epigenome changes with age, could we even reverse ageing?

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SUSANNAH MCLAREN @imsusiem

Doubtless, these prospects are all a long way off, and a lot of basic science is needed before we consider them too seriously.

Some question the ethics of editing the epigenome in this way. Is it not just as contentious as genome editing, associated with designer babies (or worse)? Professor Reik’s view is nuanced, but overall, he believes that epigenome editing ‘is not playing God’.

Reik argues that epigenetic changes are not permanent – with exceptions (such as IGF2), they are generally thought to last only for one generation, before the slate is wiped when sperm and egg cells are generated. Epigenetic changes are therefore more similar to conventional medicines in that they affect only the individual consenting to the treatment.

We are not altering the hereditary code which ‘makes us human’. However, we are potentially changing that individual’s life for the better.

Could this be the middle ground we have all been waiting for?

Accessibility of DNA determines what genes are active in body tissues. In muscle (pictured), genes encoding the musclespecific proteins actin and myosin are in ‘open’ configuration via the addition of acetyl groups (-Ac) to the DNA packing proteins.

In contrast, the skinspecific gene melanin is ‘switched off’ because the methyl groups (-Me) attached to the DNA render it inaccessible

Jiali Gao is a 3rd year student studying Medicine at Selwyn College Salvador Buse is a 1st student studying Natural Sciences at Trinity College

Standing on the Gene

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FOCUS

CARYS BOUGHTON @CARYSBOUGHTON

Speak More Act More With ongoing political and public apathy surrounding sustainability and development, Paul Cohen and Kelsey Reichenbach ask the experts Professor Simon Schaffer, Professor Eric Wolff, Dr Hugh Hunt, Anthony Haynes and Ian Ellison how we can better communicate the urgency of Climate Change 16

Focus

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in the famous words of George Bernard Shaw, “the single biggest problem in communication is the illusion that it has taken place.” Scientists and engineers spend between 20% and 40% of their time writing; from grant proposals to fund their research, to scientific papers carefully crafted to meet the rigorous standards of academic journals. In this world of academic dialogue, these peer-reviewed papers are overwhelmingly the dominant currency. Communication with the world outside of academia, however, is a matter that can be easily overlooked.

For climate scientists, the ability to connect with this outside world is becoming more and more vital. The consensus gap between scientists and the public is still widening, and recent political developments suggest that this uphill struggle is getting steeper. From the burying of the Department of Energy and Climate Change in the UK, to the G20 countries continuing to shell out $444 billion a year in support for the production of fossil fuels, climate change is intentionally being shifted out of the public focus.

Nevertheless, the evidence supporting anthropogenic climate change is there, and has been for quite some time.

How can scientists make sure their message is being heard in the face of such political undermining of their work? To find out, we spoke to an array of experts around Cambridge at the intersections of climate science, education, and communication. From their insight into historical, political, academic and corporate approaches to communication, we hope to understand the most effective tools available to scientists and engineers to better engage people with this formidable and complex issue.

Our starting point was to investigate the current state of affairs, in particular the recent emergence of the concept of a ‘post-truth’ society. Writing in the Guardian in July 2016, Katherine Viner describes the situation. “When a fact begins to resemble whatever you feel is true, it becomes very difficult for anyone to tell the difference between facts that are true and ‘facts’ that are not”, she says. With the huge amount of information available on the Internet and social media, separating well-researched, credible facts from opinions becomes exceedingly difficult. Case in point, while the opening quote to this article is widely attributed to George Bernard Shaw, its first recorded usage was not until 1950 - the year that Shaw died - by journalist William Whyte in Fortune Magazine. On the stages of television and Twitter, politicians’ opinions on climate change are pitted against scientific findings on an equal footing, regardless of the credibility and validity of the supporting evidence. Often, it can be the best soundbite that wins out, rather than the most accurate fact. This could be due in part to the rhetoric that has grown up around the idea of expertise that ‘the public’ is tired of ‘experts’, and conversely that the ‘the public’ has become too stupid to understand said ‘experts.’

There were some nuanced opinions from those we interviewed over whether we are actually living in a post-truth society. The assessments ranged from simple media-hype over healthy and expected scepticism towards experts, to sections

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Get out of of the public who do not like their suggested solutions and fossil fuels consequently argue against the science. Regardless, it is certain that we have too much to lose in the face of climate Zero Carbon Society is a destabilisation for experts to view the public as hopelessly student group unteachable. The notion of a ‘post-truth’ society, where urging the hyperbole is used in place of fact, cannot be used as an excuse to give up communicating; it does, however, suggest University to move that something needs to change in the way the facts are endowment presented in the public sphere. investments Professor Simon Schaffer, a historian who focuses on out of the fossil sciences in the 17th-19th centuries, reassures us that this fuel industry. tension between ‘the public’ and scientists is not new.

Find them on What has changed is the meaning of the term ‘expert’ as Facebook it is commonly used today. In the word’s earliest usage, “expert” was a verb, and ‘becoming expert’ in something was linked to direct experience. The scientists of the early modern era understood that people find it less easy to accept what they have not directly experienced. They therefore attempted to engage both their patrons and the public with flamboyant displays of their experiments. They would attempt to explain a range of phenomena, sometimes using the responses of untrained people to help demonstrate the objectivity of their claims. From Otto von Guericke’s impressive demonstrations of the remarkable powers of the air and the vacuum, to Christiaan Huygens’ ingenious proofs of his new model of Saturn’s ring, this notion of showing the story behind a fact or phenomenon is a communication tool with a very long history.

Professor Schaffer argues that climate change is not unique in its complexity, but that unlike many other scientific demonstrations, a shared understanding of climate change could and should provide the ability to alter impending reality, not merely describe it. Schaffer suggests expanding our democratic representation to encompass not only human and industry constituents, but also environmental features.

To better represent all the interests involved in decision making, he urged scientists to not view politics as dirty or polluting of their work: “Once you identify the political as the pollution, you’ve basically left the game.” Instead, they need to see politics as the natural progression in actively Get educated representing their work in the public sphere. He warns that The Royal it will not be a magic bullet, but will be a key approach to Society building bridges between the lab and other institutions. “The climate most political thing you can do,” he says, “is to just tell people what’s going on”. Politics is how agreement is produced within change evidence a group of heterogeneous perspectives. The end goal of a and causes political deliberation is for a group to hold a common truth booklet lists or shared understanding. For non-scientists to hold the same frequently understanding of truth as lab-based researchers, this bridge of asked active representation of one’s work in spheres outside of the questions laboratory is crucial. with simple Representing one’s work in a public setting is not without answers, and its pitfalls, however. Professor Eric Wolff has been studying a few key ancient climate through ice cores for over 30 years, but the statistics relevance of his research to the climate change issue has thrust him and his research into the limelight. He talks about the Focus

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FOCUS

learn how to talk about it

Pint of Science brings the best academic scientists in the UK and globally to local pubs so that they can explain their latest research to the public.

Next event is on the 15th of May

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need to be aware of and transparent about the limits of what you represent: “I feel responsible for explaining what the problem is, but I think we can only go so far”. Clearly signposting the firewall between scientific facts and personal opinions about potential solutions is just good housekeeping, to ensure that any objections to opinions do not also end up becoming a rejection of the science.

For climate scientists like Wolff, the key avenue for disseminating research to the public - at least formally - is through the Intergovernmental Panel on Climate Change (IPCC). The most recent report from the IPCC tries to reflect the high level of consensus by being direct in its conclusion that “human influence on the climate system is clear, and recent anthropogenic emissions of greenhouse gases are the highest in history.” One way it tries to reach the widest audience possible is by presenting the information at various levels of summary. As Wolff says, “If you want to know about what the latest IPCC report said, there’s the 1000 page, the 20 page, the 2 page version, or I could tell you it in one sentence: ‘Yep, we still believe it’s happening’.”

Unfortunately, while the IPCC reports may be effective in reaching policy makers, it is not a document that often finds itself in the hands of the general public. As a researcher, one of the most important things for Wolff is convincing the public of the validity and relevance of his work, and he has noticed that graphs and statistics are not the most useful tool at his disposal: “From my own experience, when we show people an ice core, let them touch it, and tell them it backs up the results we just told them, they are much more convinced”. Allowing people to come closer to the experience behind the scientific findings, to see what scientists work with every day, seems to be as much a part of ‘telling the story’ today as it was in the 17th century.

While Wolff focuses on helping make science tangible to communicate facts, Dr Hugh Hunt is more concerned with how visualisations can help people better understand their personal, every-day contribution to climate change.

Personal CO2 emissions are directly linked to how people live their lives, but a change of lifestyle can be a difficult pill to swallow. “Do I really want to know that I have to stop flying, I have to stop heating my home, have to stop driving the car?” says Hunt, “Do we really want to hear this?”

Dr Hunt teaches Mechanics to undergraduate engineers here in Cambridge, participates in outreach events around the country and has created a number of popular science and history documentaries. As a big proponent of live demonstrations, he thinks that people need a way of seeing how their lifestyle contributes to the problem in order for them to accept responsibility for it: “Quantifying your personal impact is the beginning of a discussion.”

But how do you quantify climate change? Average surface temperature rises, increasing atmospheric CO2, acidifying oceans - these are all vitally important consequences, but talking about a 0.85°C rise in global average surface temperature since 1880 does not mean much to a lot of people. Hunt thinks that making people aware of their own carbon emissions is one way to engage with them: “Your yearly total kitchen refuse weighs around 250 kg. Your

annual carbon footprint is 20,000 kg. The problem we’re having to deal with in climate change is 100 times bigger than the closest waste issue we have.” This approach can be applied to all aspects of life. Consider air travel, for example.

For each hour airborne I generate 100 kg of CO2. A 20 hour flight from London to Sydney? “I would have 2500 kg of CO2 to dispose of when I got there – that’s 125 suitcases.”

Converting one’s impact into units that people can relate to, visualise, and compare is essential.

Hunt wants to see these sorts of visualisations become commonplace, with airlines displaying them in-flight, petrol stations clocking carbon next to the price, even getting Cambridge colleges using it as a basis for awarding travel grants. However, until that starts happening, it is down to the individual to be aware of their impact, which relies on them being able and willing to sit down and do the calculations.

paramount in maintaining the type of common truth noted

by Schaffer. Haynes mentions public scepticism about “socalled experts – people who are not as expert as is claimed and who over-reach themselves.” He explains that “it can be difficult to distinguish genuine experts from pseudo-experts, but generally the former are more likely to speak in plain language and provide concrete examples.”

Haynes advises his clients and mentees to put together a “communication portfolio” to escape the stagnant standard of exclusively focusing on peer-reviewed journals. By learning how to exploit other media of communication effectively, such as presenting, blogging, demonstrating, even tweeting, Haynes encourages an unabridged shift of focus towards the listener or reader. He asserts that what an expert knows needs to become a shared understanding between them and their audience. Creating that shared understanding can be approached in two ways, which

CARYS BOUGHTON @CARYSBOUGHTON

Being confident of the empirical basis to your opinion should not turn the conversation into a monologue, however.

Anthony Haynes, founding director of communication consultancy Frontinus, says that from working with a wide range of disciplines and levels of expertise, he believes that people who welcome questions and are willing to address the fundamentals behind their work are typically the true experts. Those with confidence in their subject shine when discussing their ideas in the face of healthy scepticism from their audience. The willingness to explain complicated work in plain language, while not over-simplifying the phenomena, is not only a challenging skill to master, but Easter 2017

Haynes calls ‘knowledge transfer’ or its converse ‘knowledge exchange.’ He criticises knowledge transfer as rigid, ‘unidirectional flow’ of understanding that presumes one’s inability to learn from their audience.

He describes the knowledge exchange approach as more ‘agile’, self-reflective and creates the possibility for greater contextualisation of one’s work. But again, this change in mindset requires some form of humility and an internalised acceptance of the value in alternative perspectives. Can one practice effective communication without understanding the point of reference of their audience and seeing it as valuable and legitimate?

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Ian Ellison, a senior engineer working in Sustainability in Product Development in the automobile industry, agrees with the idea of communication flow. Echoing similar sentiments to Haynes’, he urges us not to meet in the middle when attempting to communicate one’s findings, but to ‘meet at the other end’. Ellison warns that the logic-laden language of scientists, while “precise and conservative” in its estimates, can seem “dispassionate and lacking conviction”.

He explains that for those not particularly inspired by tables of numbers or graphs, “an emotive response presented with absolute conviction can feel more reassuring than a technical one presented devoid of emotion.” This presents a dangerous situation for climate scientists, one where the ‘alternative facts’ can take precedence over scientific ones if their delivery is better tuned to the audience. To stand a chance in this environment, scientists need to be able to speak the language of the debate.

According to Ellison, they need to “learn the worldview of others and be prepared to use it to fully engage and persuade.”

Ellison recognises that becoming an effective engineer was more than physics and maths. “To make a real difference”, he recalls, he needed to “learn to argue and to communicate [and] practice empathy at every available opportunity.”

Technology does not succeed in a vacuum. Mitigating the effects of climate change will require a huge effort to encourage changes to our lifestyles and business operations, based on scientific findings and socially-just technologies.

As scientists, we need to recognise and accept the political role we play in representing the work done throughout our academic institutions. Conversations with a wide range of audiences need to be initiated, using a much broader variety of communication techniques than those prevalent in the academic science community today. Where are we supposed to learn these skills if we do not use them in our day to day life? “Your career will not give you very much free time” says Schaffer. He elaborates that “involving oneself in and committing oneself to that movement between the laboratory and other institutions” needs to be seen as essential rather than optional and extra-curricular.

Pragmatically, as Wolff says, “there is a no-cost argument to it.” He says that learning how to tailor your approach to different audiences, empathising with them, and embracing the art of telling the story are skills that can be used every time you write a grant proposal.

Opportunities to practice this communication need to be sought beyond the confines of academia, from local events to global institutions. A number of routes to getting involved are shown in the sidebar. If we are unhappy with the state of affairs in this so called ‘post-truth’ society, or the lack of political support for our research, then we as scientists have an important part to play in ensuring that scientific truths play a larger role in climate politics in the near future.

Get out there

Cambridge Hands-on Science (CHaOS) is a student society that gets school kids excited about science by doing handson events and demonstrations

do the leGwork Cambridge University Environmental Consulting Society is a student society, where students gather energy and water usage for their colleges, and identify where the college can improve.

Find them on Facebook

Paul Cohen is a 4th year Engineer at Emmanuel College Kelsey Reichenbach is an MPhil student in Engineering for Sustainable Development at Newnham College Focus

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THIERRY PORTER @THIERRYPORTER

Patrick Lundgren reflects on the scientific and moral implications of humanity’s dream of space exploration coming true

Humans have always been captivated by the beautiful bright speckles of light scattered across the night sky and the prospect of exploring these unknown worlds beyond ours.

Therefore, it is not surprising that the sciences pertaining to outer space (astronomy and its derivatives astrophysics, astrochemistry, astrogeology, and astrobiology) have successfully appealed to a wide audience. This is likely to become even further intensified given the recent surge of interest in the exploration of Mars.

To date, samples from Mars have never returned to Earth and no human has ever touched the surface of the Red Planet.

But this is likely to change soon. NASA’s Mars 2020 Rover aims to collect samples of soil and rock and cache them on Mars’s surface, to be returned to Earth by a future mission.

Additionally, according to the Journey to Mars report, NASA 24

What if We Touched Mars?

aims to send humans to Mars in the 2030s.

While pondering the most significant steps in the evolution of life, Elon Musk said that “there was the advent of single-celled life, the differentiation to plants and animals, there was life going from oceans to land, there was mammals, consciousness. And I would argue, also on that scale should fit life becoming multiplanetary.”

Indeed, making humans an interplanetary species would allow us to avoid a potential mass-extinction event localised to one planet, and could also help us understand more about our solar system and universe.

However, there are many questions we need to answer before we become interplanetary and set up a Mars colony. First, what will the colonists do on Mars? What will the economy look like? It is clear that the first colonists will rely heavily on resources from Earth to sustain themselves, and the possibility of ever creating a self-reliant settlement in such an inhospitable world is itself debatable. Surface temperatures can range from -17°C to -143°C, and the thin atmosphere means radiation poses a real problem. Second, how should we choose the first settlers? Whose laws will they follow?

Who will own Mars? Article II of the UN Outer Space Treaty prohibits countries from claiming territories in outer space including the Moon and other celestial bodies. But this may exclude private individuals and companies. Therefore, one view is that we should, similar to the first settlers of the New World, simply let the first Martian settlers start their own civilisation anew. Let them write their own Martian Constitution.

This creates its own set of problems. It is highly unlikely that single private individuals or companies would be able to fund a Martian colony. Price estimates for a human Mars mission have ranged from $6bn for Mars One’s one-way trip, to Musk’s $10bn (for rocketry alone), to $100bn according to a 2014 review by an expert NASA panel. The $100bn is probably the best estimate. Such a price tag will mean that national governments would have to become involved and national interests would inevitably come into play.

The first people to touch Martian soil will go down in history, but it is important that we first think through whether we even want to ‘touch Mars’. In fact, a community of scientists has formed the International Committee Against Mars Sample Return, and even Nobel laureate Carl Woese argued that “when the entire biosphere hangs in the balance, it is adventuristic to the extreme to bring Martian life here. Sure, there is a chance it would do no harm; but that is not the point. Unless you can rule out the chance that it might do harm, you should not embark on such a course.” He refers to the issue of back Easter 2017

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contamination, meaning that a sample return could bring back a Martian life form or pathogen that we have not been naturally selected to have resistance against. This is why the Apollo 11 astronauts were quarantined for three weeks after they returned from the Moon.

But what about the reverse process, or forward contamination? This not only has similar implications with Earth life killing potential Martian life, but also creates the need to distinguish between the two. NASA has a number of dedicated people working in the Office of Planetary Protection to reduce the possibility of such forward and back contamination by employing both microbial reduction and microbial monitoring methods.

Mars clearly does not contain any macroscopic life; however, we still cannot rule out the existence of microbial life. Indeed, in 1996 the Antarctic Search for Meteorites (ANSMET) project famously found the Martian meteorite ALH84001, and received a lot of attention when David McKay suggested he had evidence of microscopic fossils based on scanning electron microscopy (SEM) of parts of the meteorite.

President Bill Clinton even said in a speech: “Today, rock 84001 speaks to us across all those billions of years and millions of miles, it speaks to the possibility of life. If this discovery is confirmed it will surely be one of the most stunning insights into our universe that science has ever uncovered.” However, it was later shown that similar morphological signatures could be recreated without biological inputs. It would also be reckless to suggest that morphology alone is a sufficient tool to detect primitive life.

But an important question remains: how can we prove that any life we find on Mars is not simply terrestrial life we have brought with us? Despite our hard work in planetary protection, this must be considered. One way would be to show that they have separate origins of life – perhaps by looking at their chemical composition, heritable material, genetic code, or stereochemistry (e.g. L– vs D–amino acids). However, a paper published by Cleland and Copley in 2006 argues that we may not even able to recognise microbial life from an alternative origin currently present on Earth – so-called ‘shadow microbes’ – so why would we be able to do so on Mars? An easier situation would perhaps be if the ‘Panspermia Hypothesis’ holds true. It posits that life can be distributed throughout the universe by meteoroids, asteroids, comets, and planetoids. In this case, Martian and Earth life would share the same origin, and we could simply perform genomic comparisons to see how the different selective pressures exerted by the different changing environments, separated by vast amounts of time, have resulted in diverged genomes.

Either way, if Martian microbial life exists, an important question we need to ask ourselves is how we should act towards ‘them’. This touches on what we consider to be our purpose in this universe. One view would be that we have no ethical obligation towards Martian microbes at all and are free to terraform Mars however we deem desirable; alternatively, on the other side of the spectrum, we have no right to set foot on Mars (or any other celestial body) and alter it at all. But what

High resolution microscope images of meteorite surfaces have shown features associated with carbonates. These have been used as part of research into primitive life detection

StereochemiStry involves the study of stereoisomers, which are isomeric molecules that differ in their three-dimensional arrangements of atoms in space. L– and D–amino acids represent a certain type of stereoisomerism, known as optical isomerism. This means they are non-superimposable mirror images of each other, also known as enantiomers. With a few exceptions, terrestrial life is known to only use L-amino acids probably due to an initial modest imbalance in the abundance of amino acid enantiomers when life originated, leading to a self-reinforcing evolutionary process to select one over the other. It has been shown that D-amino acids can form functional proteins so the decision between D and L.

if we do find life on Mars, a curious vestige from an era when Mars was better suited for harboring life? Should we then change Mars to help these organisms flourish?

At the moment, these questions may seem rather futuristic, but with NASA forecast to send the first humans to Mars in the 2030s and with samples likely to return even earlier, these are questions we need to contend with now. Ultimately, the universe would not care if human civilisation was destroyed tomorrow. The laws of physics would not change; everything would be the same. The universe would continue expanding, galaxies would continue moving beyond the observable universe, and distant planetary worlds would continue orbiting their stars. But whatever our purpose, sustaining and conserving Life could be up to us, and to do this effectively space exploration must be interdisciplinary.

The most significant missions will draw on expertise from and collaborations with people from backgrounds in engineering, science, philosophy, law, and politics. What good does life do the universe? Perhaps none. But we might be its only chance of finding out.

Patrick Lundgren is a 3rd year student in Natural Sciences at Robinson College

What if We Touched Mars?

25

MARTHA DILLON

Following Professor France Ashcroft’s 2015 damehood, Atreyi Chakrabarty examines how the work of one woman transformed both treatment and understanding of a debilitating childhood disease.

NEONATAL DIABETES is a myth. At least that was what Frances Ashcroft was told in 1997 on her quest to find newborns with the condition.

Yet her persistence and determination to find the cause and cure of this unique condition was unfailing. Not only did she discover the disease, she also pioneered a better treatment that would prove invaluable to patients. One young girl burst into tears telling Ashcroft, “I can wear a dress again!” because she no longer needed to wear a belt for her insulin pump, avoiding the dreaded daily insulin injection. Not only had Ashcroft replaced needles with an oral drug, she had allowed these children, and their parents, to lead a more normal life.

It was previously thought that there were only two types of diabetes: a type of diabetes caused by several genetic factors, and a type of diabetes caused by environmental factors, such as diet. This assumption led to the misdiagnosis of newborns who suffered from a third type of diabetes caused by a mutation in a single gene. This was often accompanied by delayed development and neurological disorders. If Ashcroft had not dug deeper, the simple treatment for these conditions may have remained buried.

4.5 million people in the UK currently suffer from diabetes. Diabetes occurs when there is insufficient insulin to maintain blood glucose levels, which can lead to numerous health problems. Insulin, discovered in 1922, is the hormone released by the pancreas following a meal, which keeps blood glucose levels stable.

There are two common types of diabetes called

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The Drug that Brought the Dress Back

Type 1 and Type 2 diabetes. In Type 1 diabetes the immune system attacks and destroys the beta cells of the pancreas, which are responsible for the production of insulin. In Type 2 diabetes, the pancreas fails to produce enough insulin or the body becomes insensitive to it.

After completing her degree in Natural Sciences and her PhD at Cambridge, Ashcroft joined the University of Oxford as a research fellow in 1984. She wanted to use this position to research something of medical relevance, unlike her previous work on the muscles of stick insects. She decided to explore why increased blood glucose levels cause the pancreas to release insulin. In her initial experiments on rats, she found that glucose closes a pore in the surface of specialised cells in the pancreas. This pore, called a potassium channel, normally allows potassium ions to flow out of the cell, closing when insulin is released.

In 1985, Ashcroft discovered the role of the pore. Glucose is taken up by the cell and used to produce a molecule called ATP. ATP binds to the potassium channel. This leads to some electrical activity in the beta cells and insulin release.

A drug called Sulphonylureas is able to induce low glucose levels, a state known as hypoglycaemia. It was discovered after World War 2 in 1942 and used widely thereafter to treat Type 2 diabetes by increasing a cell’s sensitivity to insulin. Ashcroft made the link between the similar role of ATP and Sulphonylureas on insulin release. In 1986, she tested it on individual potassium channels found in the insulin releasing cells. The drug was shown to bind to

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the potassium channel and cause it to close, triggering the release of available insulin from cells in the pancreas.

Ashcroft’s research also pointed towards the existence of a third type of diabetes: a type caused by a mutation in a single gene. Discovering the importance of potassium channels in insulin release, she believed that a certain type of diabetes was likely to be caused by a genetic mutation to the potassium channel. Yet to search for mutations, she first had to determine the protein structure of the potassium channel and find the DNA sequence which coded for it. It took her almost 10 years of arduous gene cloning to pinpoint the functionality of the channel protein.

By 1995, she had revealed the structure of what turned out to be a very complicated channel and by 1997, the function of each of its components were determined. By this time, Ashcroft knew the DNA sequence and could finally start screening patients for mutations.

Ashcroft was convinced that a single gene mutation of the potassium channel must be present in newborns who had diabetes. These patients were diagnosed as diabetic at the unusually young age of around 6 months, which was never the case for the traditional Type 1 or Type 2 diabetes. It was wrongly assumed that, because no insulin was found being secreted, this was a rare form of Type 1 diabetes. Thus, the young patients were given insulin injections from birth: an intensely unpleasant experience for both them and their parents.

On the quest to find a mutation in human patients, Ashcroft collaborated with Professor Andrew Hattersley. In 2004, his lab tested and screened the blood from diabetic newborns and sure enough found just the mutation Ashcroft was looking for. About 50% of newborns with symptoms of diabetes had a mutation to the potassium channel protein, proving that the existence of neonatal diabetes is caused by a single genetic mutation. The mutation causes the channel to be insensitive to ATP and remain closed, preventing the release of insulin from otherwise functioning cells in the pancreas. This was a big eureka moment because there was already a well researched and readily available drug, Sulphonylureas, for related conditions.

Neonatal diabetes is often accompanied by several neurological disorders, since the mutated potassium channels are present throughout the nervous system. Many children have impaired language development or motor coordination as a result. Sulphonylureas also successfully treats these conditions. The earlier the treatment

is started, the more effective it is in treating neurological symptoms, allowing children to walk and talk at a normal age.

After successful clinical trials in 2006, 90% of patients with neonatal diabetes have been transferred from insulin injections to the oral tablets of Sulphonylureas. The patients’ blood glucose levels were more stable with the tablets than they ever had been with insulin injections.

The drug had a huge impact on the daily lives of many young children. They were no longer bound by strict dietary requirements or a rigid regime of insulin shots, all they needed was the tablets.

After this twenty-year odyssey, Frances Ashcroft’s endeavour to treat neonatal diabetes more effectively is still going strong. Questions remain for scientists to address: why do younger patients transfer more easily and successfully, and why does the required drug dose decrease with time? While neonatal diabetes is a rare condition, with only one in every 200,000 babies being diagnosed, it is debilitating for its sufferers. The treatment is an example of highly personalised medicine. The efforts of Ashcroft and other scientists have helped improve the quality of life of many children for years to come. Her ground-breaking, life-changing work has earned her the title of Dame Professor Frances Ashcroft, and she remains a true inspiration for a new generation of scientists.

Atreyi Chakrabarty is a 2nd year student of Clare College studying Natural Sciences

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LAURA VAN HOLSTEIN

Laura van Holstein explains why none of us is a specialist, and why this makes us so successful

we belong to a remarkably successful species. By comparison, our closest living relatives, chimpanzees and bonobos, never experienced a population boom or geographical sprawl on the scale of Homo sapiens.

The key to our curious reproductive overdrive and environmental infidelity is our place at the bottom of the Scala Naturae, if it were ordered by degree of ecological specialisation. In other words, we have become evolutionarily successful because we are nature’s greatest anti-experts.

Biologists generally recognise a spectrum of ecological strategies. These range from specialists, who are experts at extracting energy within a particular niche (like koalas), to generalists, whose extractive repertoire is much more varied (like raccoons). Both

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strategies make sense: specialists fulfil a specific niche and exploit resources within it more efficiently, but are very vulnerable to extinction when environments change or become fragmented. Generalists face more competition since they are not the only ones exploiting a given resource, but they are flexible and can adapt more easily to changes in resource distribution.

If a generalist strategy is favoured by selection, different roads might lead to Rome. An omnivorous diet, like that of chimpanzees, might suffice. Or a species might develop physical adaptations to survive in wide-ranging environments, as tardigrades can – these tiny invertebrates survive in hot springs, under ice, and even in outer space. However, those roads to generalism are purely physiological. Humans are Easter 2017

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The Inexpert Ape

ecologically extraordinary because we took the road less travelled: a largely non-physiological one. In fact, our generalism is based on extreme behavioural flexibility, stored and transmitted in human culture.

Humans learnt to exploit resources in new environments more quickly than other animals by consciously tailoring their hunting or gathering strategies to their surroundings. Even within niches, we constantly adapted to changing conditions.

Dr. Alex Wilshaw, from Cambridge’s Leverhulme Centre for Human Evolutionary Studies, is studying diversity in an unprecedentedly large collection of bone harpoons made by early modern humans in on the shores of Lake Turkana. He believes some differences in harpoon size and shape are attributable to specialised hunting of fish species, some of which reached up to two metres in length. The diversity of the collection, he says, likely reflects intentional flexibility within hunting kits.

But early human pioneers could also invade foreign environments on far shorter timescales than other animals, because unlike them, we did not have to spend many generations genetically adapting to stressful habitats. As an example of this, it is generally accepted that we colonised Europe only after we had mastered fire and had begun actively hunting.

Cambridge’s Dr. Jay Stock has argued that it was our species’ phenotypic plasticity (environmentallyinduced changes in phenotype, including behaviour) that allowed African apes to survive extreme cold without committing to a specialist cold-adapted physiology. Our behavioural flexibility buffered our genome from selective pressures also faced by other animals, which solved the problem genetically.

Eurasian woolly mammoths and African elephants, species adapted to extreme cold and arid heat, respectively, arose from a common ancestor following population migrations. Humans, on the other hand, did not undergo such genetic changes as we spread across the globe. In fact, we have remained remarkably genetically unified. Chimpanzees and gorillas are genetically more diverse than humans, for example, even though we occupy a far greater variety of environments than they do. The same goes for species less related to us, like gray wolves.

Our generalism is responsible for some of our most unusual features. Our ability to support multiple dependent offspring simultaneously is at the root of our explosive population dynamics. We do not have to wait for children to mature before having more, like other great apes do. Our inter-birth interval is therefore extremely short, meaning that the number of babies a woman can have in her lifetime exceeds that of other apes, even though pregnancies are of similar lengths and infants depend on adults for similarly long amounts of time. Generalism is the culprit: behavioural flexibility required cooperation

within human groups, and this cooperation extended to alloparenting - childcare by non-parents. Mothers could entrust some energetically costly childcare to other members of the group, leaving her free to have more children.

We are, as a species, also exceptionally big-headed.

Flexible culture relies on us processing information about the environment and being conscious of ourselves in this environment, necessitating an exceptionally large brain. In fact, we are the most encephalised creature in nature. In other words, our brains are, relative to our body size, the largest in the animal kingdom.

Our evolutionary success has been attributed to many factors - intelligence, culture, and high fertility, and so on - but these are consequences of a behaviour-based generalist ecological strategy.

Generalism is not unique in the animal kingdom, but ours is a generalism on steroids. It buffers our genome from selection and has resulted in Homo sapiens successfully exploiting an exceptionally wide range of environments. You might say we have become experts at not being experts.

Diversity in bone harpoon size and shape can be linked to differences in fish size

Laura van Holstein studied Biological Anthropology and is a PhD candidate in Evolutionary Anthropology

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A Psychedelic Conversation: Tackling the Taboo

SOPHIE BUCK

Antonina Kouli and Bart Nieuwenhuis report on the CamBRAIN panel discussion of psychedelic drugs’ medical potential

as strange as it sounds today, psychedelic drugs like LSD and psilocybin (magic mushrooms’ active ingredient) showed great clinical promise in the early 1960s. Several early scientific papers suggested that psychedelics could be used to treat psychiatric disorders and even for pain relief. However, the simultaneous rise in psychedelic use by the public at that time and the so-called youth counterculture led to their prohibition in many countries, including the UK. After that, research into psychoactive compounds took a dramatic dip – until now.

To discuss how the tide is now turning in this controversial research area, Cambridge’s neuroscience society, CamBRAIN, organised a panel discussion last term. The discussion was chaired

by Professor Ed Bullmore, Head of the Cambridge University Psychiatry department. Paul Fletcher, Professor of Neuroscience at Cambridge, shared his expertise on ketamine’s use as a model to explore psychosis. Leor Roseman contributed his experience as a neuroscience PhD student in the Beckley-Imperial Research Programme, studying the neural correlations of the LSD experience.

Also present was Amanda Feilding, founder and director of the Beckley Foundation, a leading charitable trust based in London that promotes and funds psychedelic research. Amanda is at the forefront of drug policy reform, aimed at encouraging research into the spiritual and medical use of psychoactive compounds.

Studying the effects of psychedelic drugs helps scientist understand psychiatric disorders. Fletcher is interested in psychosis, an abnormal condition that causes hallucinations, among other symptoms. “The [hallucinogenic] drug ketamine can be used to study psychosis”, said Fletcher. Amusingly, Fletcher’s ketamine study captured the Daily Mail’s attention in an article entitled “Cambridge students paid £250 to take horse tranquilliser drug ketamine for schizophrenia research”. Fletcher clarified for the panel that ketamine is a suitable research model: participants take it in safe doses and in constrained and controllable experimental settings.

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Importantly, psychosis – often defined as a ‘separation from reality’ – is a symptom of schizophrenia. Psychedelic drugs like ketamine can answer questions that other research tools cannot address.

For example, animal models are not suitable, since examining their emotional and perceptual experiences is problematic. Using ketamine, Fletcher and his team can answer questions like, “What are the mechanisms by which the psychotic symptoms emerge? Why do people have different psychotic experiences? What interventions can weaken the effects of ketamine?”

Psychedelics are also being revitalised as treatments for psychiatric illnesses. Roseman discussed his recent work, which uses fMRI to determine if psilocybin-assisted therapy can alleviate major depression. One experiment involved giving patients with treatmentresistant depression psilocybin, followed by brain imaging and clinical assessments. “We saw a marked improvement in depressive symptoms compared to the pre-treatment baseline, which was sustained [for at least 3 months],” Roseman explained. This longterm effect, achieved by just two increasing doses separated by one week, is remarkable, considering that most anti-depressants need to be taken continuously.

So what distinguishes psilocybin therapy from conventional antidepressants like selective serotonin reuptake inhibitors (SSRIs)?

“SSRIs lead to a reduction in the activity of the amygdala [a brain area associated with fear and emotional learning], thereby suppressing feelings of negativity. In contrast, psilocybin led to increased amygdala activation in the depressed subjects. We think that through the psychedelics, the participants were able to confront and deal with their emotions, rather than avoiding them”, Roseman said. He hopes that larger-scale trials will follow these small, promising studies.

The CamBRAIN panel has highlighted that psychedelic drugs can be useful models for research and may even help treat psychiatric disorders. Thus, Amanda Feilding and other experts in the field advocate making psychedelic drugs legal for research purposes. Nonetheless, psychedelic drugs can have harmful physical and psychological effects, even when used with medical assistance. The pros and cons of legalising psychedelic drugs for research will therefore need to be carefully considered, while keeping an open mind.

Bluesci Presents CamBRAIN NeuroArt Competition Winner: David Jane

Above & below: David Jane, Self Portrait

after loss of memory and speech due to encephalitis, Jane turned to the scans of his brain for inspiration and to explore how the incident could be understood. These works are created from paintings made by combining pigment with wax. Jane photographs the works and digitally manipulates and layers the image until it becomes a new image. He says:

“We can meld science and art together… and we’ll do that not to obscure what’s going on, or prettify it, but to make it clear. I want to open the doors of understanding into the scientific interpretation and artistic vision of brain scan images, so that people can see them as things of beauty as well as knowledge.”

Bart Nieuwenhuis and Antonina Kouli are PhD students in Clinical Neurosciences Easter 2017

Easter 2017

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Weird and Wonderful

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A selection of the wackiest research in the world of science Like a Headless Chicken ever been accused of running around like a headless

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chicken? Between 1945 and 1947, Colorado farmer Lloyd Olsen owned the original headless chicken, known as ‘Miracle Mike’. On 10th September 1945, the bird was supposed to be Lloyd’s supper, but survived decapitation by axe. Despite being headless, Mike lived for another year and a half, earning up to $50,000 a month appearing in sideshows and magazines. He could walk and gurgle, and was fed water and grain via his oesophagus. After Mike died, the corpse was sent for analyses to unravel how it survived. It appeared that the axe missed the brain stem and the two jugular veins, found on either side of the neck. The brain stem, located in the lower part of the brain and connected to the spinal cord, controls essential functions like breathing, heart rate, and reaction to basic stimuli. The jugular veins collect deoxygenated blood from the brain, head, and neck and it was a clot in these that saved Mike from bleeding to death after decapitation. The jugulars ensured a blood supply to the brain stem, allowing key bodily functions of the chicken to continue, even without higher brain centres. So, next time someone makes the analogy, think of Mike, and be glad you’ve at least got your head on straight. bn

Un-boiling an Ig protein chemists chemists around the world would have cracked up at the announcement of the 2015 IgNobel for Chemistry. Tom Yuan and colleagues were awarded the much-coveted prize for discovering new methods to re-fold misshapen proteins…or, putting it another way, to ‘un-boil an egg’. Proteins need to be folded within the cell to produce the distinct 3-D structures essential to their function, much like origami on a cellular scale. If folding goes wrong, however, the proteins end up non-functional or harmful. This also happens during the industrial production of therapeutics like insulin or antibodies, where separating out misfolded protein and re-folding it in the correct conformation is time-consuming and expensive. Yuan

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and colleagues’ refolding method, which requires spinning the offending protein in a small tube, could therefore be big business for the biotech industry. But what about the egg connection? To test their protocol, the researchers used a protein called hen egg lysozyme, found in egg white. They first destroyed the protein’s structure by boiling some eggs, purified the misshapen protein, spun it, and presto! it regained its normal function after ‘un-boiling’. Such hard-boiled science truly makes food for thought. ajt

in 1999, Sunny Delight, the artificial citrus drink,

was struck by rumours of a 4-year-old whose skin had turned orange after downing 1.5 litres of the drink a day. Surprisingly, this story wasn’t just playground myth but actually had an explanation in the form of a skin discolouration known as carotenosis. This is an entirely reversible condition cause by the overconsumption of carotenoids, a pigment found in carrots, oranges and many other fruits and vegetables. Sunny Delight in fact only had very low levels of citrus juice (just 2% in the US, and 5% in the UK) and high levels of betacarotene were added to return an orange colour. The little girl probably consumed no more than 2-3mg of beta-carotene a day, not very different from the average adult consumption. However, for a small child with fair skin this consistent dose was enough to build up a significant level of orange pigmentation. Carotenosis also commonly occurs in young children with a high consumption of carotenoid-rich foods, and, although benign in this case, yellowing of the skin can also be a sign of jaundice and organ failure, causing many parents to panic. If you’re a sweet potato fanatic, watch out for that orange tinge; your friends might accuse you of whipping out the fake tan! rc

ALEX HAHN

Easter 2017

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