Genetic Modification of crops has always been a thorny issue. Shock headlines and contrived ‘public debates’ have left scientists and communicators alike quaking at the prospect of navigating the muddy waters, with an at best ill informed, and at worst downright hostile, public in tow. One could be forgiven for considering this a disaster for public dialogue with science. That is of course, if consensus and consumer acceptance are the aim…..

Going back to the root of the matter, the 2011 British Science Association’s Science Communication Conference planted the science firmly in context of its application and the policy making system. A panel, chaired by Fiona Fox from the Science Media Centre, and consisting of Jack Stilgoe from the Royal Society, Professor David Baulcombe from Cambridge University, and Andrew Wadge from the Food Standards Agency, debated with an audience of science communicators. They identified real issues, tangled and deeply buried, which extend to moral values and personal taste.

The moral imperative to feed the planet’s population sustainably is the key to a much needed policy discussion which considers all options and which recognises multiple views, messy and chaotic as this may be. This means that the challenge is to cultivate confidence in the scientific process and enable scientists to have a view on how their research is employed.

According to Jack Stilgoe, the GM crop debate has defined a shift in the science and society relationship. The majority of issues sprouted from the very first dialogue experiment in 1994, with understanding deepened by Social Science. As he noted, “GM is not one issue”.

Moving away from mainstream media presentation of polarised debate about isolated technologies, towards looking at issues in order to advise government on what to do next. He asked: “How did we get to a stage where nobody listened and the conversation broke down?”

He floated the need to debate new possibilities presented by science, upstream of regulation. “GM embodies the idea of seed as a product”. This poses a threat of disruption in developing countries where farmers save and regrow seed.

There is a tendency for scientists to retreat into the novelty trap, to determine need for revised labelling and regulation. But he asked “Do we have the right sort of system to govern these technologies if we buy the fact they are new?”

In these situations, regulation and academic independence become complex and highly politicised. When it comes to safety, there is concern over assessment systems and the degree people are put at risk. There are also issues of patenting and control over the markets and food chain by monopolistic companies, begging the question “Is government genuinely interested in opening up debate, or in ‘selling’ to an oppositional public?”

Feeding the Planet
Professor David Baulcombe discussed dealing with the challenge of providing global sustainable food in light of climate change, population growth, shortage of land and other resources. Biological Science offers two approaches: firstly, science-based enhanced crop management, and secondly, the genetic improvement of crops, which was his focus for this discussion. He noted that “Plants evolved to produce babies that survive harsh natural environments, not big fat juicy fruits… What we are trying to do is redirect the legacy of millions of years of evolution towards sustainable food production.”

Drought, heat, stress, and mineral uptake are complex traits governed by several genes. They are key challenges for sustainable intensification of food production to provide sufficient food for the planet. He explained that conventional breeding shuffles characteristics and introduces complexities, whereas with GM original characteristics can be retained while changing a few traits at once. Using closely related species for GM gives a similar end result to conventional breeding, noting that “Both GM and conventional breeding are long term solutions. They need to be assessed side by side in terms of risk.” GM can also be used for grand challenges like enhancing the efficiency of photosynthesis, remodelling crops to regenerate yearly, stabilise and fertilise soil, and turning different plant varieties into useful crops.

Crossed Wires
Andrew Wadge from the Food Standards Agency explained how the FSA had been established after a series of scares culminating in the BSE crisis. He went on to describe GM as part of a series of technological developments impacting on the food we eat, with the public asking questions like “is it safe for me and the environment?, What’s in it for me? Who benefits and what’s in it for them? Is it natural or human made?”

The debate gets skewed around whether GM is more harmful to health than its counterparts because it is based on scientific assessments which exclude moral and ethical considerations.However, our judgements as individuals are based on values, especially where we don’t necessarily understand the wealth of complex science. He suggested that “Our minds run through a process of weighing risks and benefits, balancing how to respond and deciding who to trust. “

Cracking Up

Jack Stilgoe explained that the Food Standards Agency was asked to deliver a further dialogue exercise in 2010 as a trusted agency. Their responsibility is regulatory with no mandate for agriculture, developing world markets or industrial policy in biotech.

A political timescale meant that the process was too rushed to frame a productive dialogue. The resignation of two steering group members and the pretence it was about science alone led to its abandonment.

Citing a lack of clarity from ministers and the coalition government wanting to save money, Andrew Wadge explained: “The public is interested in the issue as a whole but government departments are organised in silos with food standards separate from environment.” David Baulcombe added: that the “advantages of products like purple tomatoes and golden rice are difficult to prove. Scientists may not have made the case about the environmental benefits strongly enough.” While there is a moral imperative to feed the world sustainably, it is irresponsible to get angry, and likewise not address the issue and force a technology on a reluctant public. For fellow scientists he suggests it is important to recognise that they may not seem trustworthy if they present themselves merely as “a humble seeker of the truth” for society to make of as they will. He also felt that intellectual property is a significant issue. Scientists should take a view over the context where their science is deployed. “I want technology for my lab to support small business and diversity in agriculture with commitment to open source”.

Cracking on

On the way forward, Jack Stilgoe said: “There is a need to appreciate the political nature of the topic, and be honest about debating values not science.” He argued that a purely scientific debate presents the risk of a diversity of opinions being put into a monolithic view of science. “A huge amount of effort is needed upfront to design a representative conversation based on shared understanding”.

This will also require consideration of who to include. Stilgoe suggested that publically funded scientists have found themselves bound up in issues driven by large companies with which they have little in common. On the other hand an employee of Astra Zeneca indicated similar conflicts in the industrial scientific community. Andrew Wadge pointed out that Scientific Advisory Committee members don’t get paid yet have to publish all their interests: “Openness about conflicts is important but everyone needs to be there.”

The panel were agreed that despite frustrations, consultation is worth pursuing. David Baulcombe said:
“I know others with a different view have also been frustrated but I think the end result is move towards a better agriculture”.

Andrew Wadge cited need for framing the debate and instilling confidence in the scientific process where they may be different views. Jack Stilgoe suggested: “You can take general principles from topics like Nanotechnology, Synthetic Biology and Climate Change and apply them to develop principles for governing technology in uncertain and highly politicised environments.” He recommended training scientists to participate, removing barriers and supporting not forcing them to get involved. “Science speaking with many voices is a more productive conversation.”

How should we in determine what nature of genetic manipulations are acceptable interventions?

From my perspective the potential to mitigate the effects of climate change, reduce agricultural pollution and preserve biodiversity would be deciding factors. Interventions which tackle the social systems of distribution and consumption are not to be ignored.

As a supporter, through the Voice of Young Science network, of Sense About Science, I was fortunate enough to be invited to the charity’s 2011 annual lecture. Unusually for a ‘science’ event, this year’s lecture was given by a historian, Professor Richard Evans of the University of Cambridge.

But let me take a step back first and introduce Sense About Science itself and its aims. Sense About Science (SAS) is a small charity that equips people to make sense of science and evidence by promoting good science and evidence for the public. It does this by responding to misrepresentations, in the public domain, of science and scientific evidence on issues that affect society, from vaccine scares, through GM crops, all the way to nuclear power station explosions.

As for the lecture itself, Prof. Evans demonstrated rather well that even a historian can have something to teach to scientists. He chose to discuss 19th century epidemics of cholera, from Hamburg, Russia and Naples, in parallel with more recent public health crises such as the Haiti cholera epidemic and the BSE (mad cow disease) crisis of the 1980s and 1990s in order to pose questions about how the interaction between politicians, scientists, and the general public influences the acceptance of new scientific theories, as well as key decisions about public health.

When cholera first spread from Asia to Europe in the 1830s, ideas varied as to the mode of spread of the disease. It wasn’t until the 1860s that the germ theory of disease was postulated; up until then, the prevailing theory was that of spontaneous generation of disease and infection from inanimate matter. Yet, even after that, the germ theory was highly controversial and in late 19th century Hamburg, a group of “scientists” called the miasmatists, suggested that cholera is caused by local pockets of bad air (miasma) and, importantly, that it cannot be spread by person to person contact. In Hamburg, in 1892, an epidemic of cholera ensued that killed more than 8500 people. At the time, the germ theory was becoming accepted throughout Europe and some suggestions had been made that cholera is spread through contaminated water and that quarantine and strict hygiene are good countermeasures. Nevertheless, Hamburg was an independent self-governing city at the time and it didn’t suit the rich governing classes to impose quarantine conditions because it would reduce trade. As a result, they supported the mismatists and did nothing about the disease spreading through the poor area of the city, continuing to deny that there was a problem (panic would also have an ill effect on trade), and thus not enabling the prevention of a large number of deaths amongst the working classes.

On the other hand, government intervention can also have negative effects, as was demonstrated in a Russian cholera epidemic at a similar time. Here, the government heavy-handedly imposed quarantines, forbade the selling of food on the streets and heavily restricted people movement. Whilst a good idea in theory, it was the fact that the population was given no explanation for the draconian measures that were being imposed. This resulted in riots where the general population fought the restrictions, going as far as storming hospitals and releasing the ill. This was in stark contrast with the Naples cholera epidemic of 1910-1911, where government had learnt from a previous outbreak in the city where heavy-handed quarantining tactics had led to rioting. Now, instead of sending in police, they recruited enforcers (or, more accurately, coercers) from amongst the population they wanted to inform of the measures that had to be taken to prevent spread of the disease. They sent these coercers out to explain why it was important that ill people were quarantined, that dead bodies were buried away from the general population and that strict hygiene was essential. As a result of using education rather than force (as was the case in Russia in the 1890s), the government found that it was trusted much more by the general population, which helped reduce the spread of this new epidemic.

Prof. Evans argues that we may think that historical case studies are just that: history. However, he continued to argue that similar crises in the 20th and 21st centuries suggest that even though science is a lot more advanced these days, the general public still need to understand the science behind government decisions because otherwise the governments (and government scientific advisors) lose trust. This was exemplified in his talk with the Haiti cholera epidemic of 2010, following a devastating earthquake and hurricane that resulted in large numbers of people living in rather squalid conditions in refugee camps. Here, the controversy apparently arose because some of the public believed that the infection spread as a result of a sewage spill from a base used by the UN-peacekeeping force, resulting in protests and requests for the peacekeeping forces (seen by many as the enemy) to leave the country. When experts explained that the government’s priority wasn’t to identify the source of the outbreak but the need to control it, this presumably just stoked the anger of the Haitians who believed that they were being hoodwinked. Similarly, when the extent of the BSE crisis of the 1980s and 1990s in Britain became evident as more and more infected cattle were identified, early noises from the government went along the lines of “don’t worry, this cannot cause disease in humans”. The government was later accused of acting too slowly in informing the public about the possibility of contracting vCJD (variant Creutzfeld Jakob diseases, the human equivalent of BSE) as a result of eating infected beef. Indeed, the infamous picture of the former agriculture minister Gummer feeding his daughter a burger and declaring beef absolutely safe has become iconic of the misrepresentation of the issue. At the time, it was alluded that the government tried to protect the farming community by hiding the possible problem, which arguably led to wide mistrust in government and its scientific advisors that had later repercussions during the (now discredited) MMR vaccine scare.

Prof. Evans’s lecture led to much discussion about the use of scientific evidence in unfolding public health crises, when the need for decisive action coincides with unclear evidence. Can overreaction to an epidemic be riskier than the epidemic itself? The debate continues below Evans’ opinion piece in the Guardian, and you can contribute to it on http://www.guardian.co.uk/science/2011/may/09/epidemics-cholera-aids-trust-scientists?INTCMP=SRCH

You can listen to the lecture as a Guardian podcast, and the lecture transcript is now available on the Sense About Science website, so you can form your own opinion about the issues raised in the talk.

Key links:

Transcript of the lecture: http://www.senseaboutscience.org.uk/PDF/EPIDEMICS%20AND%20REFUSENIKS.pdf
Podcast of the lecture: http://www.guardian.co.uk/science/audio/2011/may/12/epidemics-sense-about-science-lecture-podcast
Sense about Science: http://www.senseaboutscience.org.uk/
Prof Richard Evans’ website: http://www.richardjevans.com/

I am an enzymologist, and so study the chemistry, function and mechanisms of enzymes. For many of you, the word enzyme will probably ring a bell and take you back to school biology and the lock and key theory of substrates ‘clicking’ into a matching enzyme active site. But what exactly is an enzyme?

Basically, enzymes are proteins. Proteins in turn are long chains of amino acid monomers. There are twenty naturally occurring amino acids, all with the same backbone structure but with chemically varied side-chains. Although there are some exceptions in the remnants of what is thought to have been a chemically simpler RNA-based world prior to the evolution of protein and DNA, proteins provide the ‘machinery’ of living cells, with their roles ranging from structural support to catalysis.

Enzymes are a sub-group of proteins which are biological catalysts that help specific biochemical reactions to proceed at a faster rate. Although many biochemical reactions do occur in the absence of enzymes under extreme conditions, they would only happen very slowly at physiological pH and temperature. The half-times of the uncatalysed reactions can be millions of years, so if Nature depended on reactions taking place without catalysis, life as we know it would simply not be possible.

My research is into the activity of an enzyme called flap endonuclease, which acts a bit like a pair of molecular scissors that cut a DNA strand at a structurally defined position. Whilst DNA breakages in general are likely to be a bad thing because they can lead to mutations, it is important to remember that controlled cleavage is absolutely essential for cells to be able to replicate and repair DNA, because both damaged sites and primers initiating DNA synthesis have to be removed. This is where our particular enzyme, flap endonuclease, comes in.

So how can we go about trying to work out the cutting mechanism? In the protein world, it is the amino acid side-chains that provide the functionality of the enzyme, sometimes supplemented by co-factors such as vitamins and minerals from our diet. Using the earlier machinery analogy, the amino acid side-chains and key chemical groups of the co-factors can be likened to levers and cogs. However, unlike real machinery, proteins are too small to see so we have to design indirect experiments to work out where the levers are and what they do.

One option is to determine their structure by the use of X-ray crystallography or NMR spectroscopy. Nevertheless, such structural studies only provide a static picture, like seeing the machine stopped and not knowing how the levers move. In addition, enzyme structures are often determined in the absence of reactants and products so do not tell us how these molecules fit in. This is where enzymologists have work to do, carrying out solution studies to further develop mechanistic knowledge about the activity of enzymes. Unlike many other proteins, with enzymes there is usually a way of measuring the appearance of a product or disappearance of a reactant, thus allowing us to measure the enzyme efficiency. Subtly changing the conditions of the reactions – which may be by mutation of one or more of the amino acids to change the shape of a particular ‘lever’, or by changing the pH of the reaction to alter the level of protonation and therefore the state in which the ‘levers’ are in – and then comparing the rates at which each reaction proceeds can tell us something about how an enzyme catalyses the reaction.

Finally, you may ask yourself why we should spend time investigating how enzymes work. A better understanding could potentially provide new leads for the pharmaceutical industry. Some enzymes can be malfunctioning or missing, or conversely over-produced, in diseased as compared to healthy cells. It could be possible to play molecular Lego and fill in the missing or broken bits using small drug molecules to restore or inhibit function, a process which clearly becomes much easier if we know how the enzyme works.

“Deforestation contributes about one fifth (20%) of global carbon dioxide emissions ….

We need to reduce deforestation, introduce new forests, manage them sustainably and adapt to meet the challenge of climate change which is now inevitable.” UK Forestry Commission

2011 has been declared the international year of the forest, placing recognition and responsibility on the boughs of the world’s forests, in terms of their potential to help secure the future of the planet. Forests provide habitats for an enormous variety of creatures, a source of sustainable energy and building materials. Most of all, they absorb carbon dioxide from the atmosphere, converting it into life giving oxygen during the day, the reason they are sometimes called ‘the world’s lungs’. While currently under the spotlight, their role in sustaining the planet stretches back thousands of years. Today, the woods can no longer be left to nature and must be nurtured by humans. There are international management standards to attain with the European Union leading the way.

Community care for trees has a long tradition across the world. As well as featuring in the Lion King, the Baobab tree has been worshiped for centuries across Africa, Sudan, indigenous Australia and the Caribbean. It forms a central pillar of communities. The whole tree is used for food and materials, including sap for medicinal purposes. In 2008 its fruit was approved for distribution in EU.

Trees are completely intertwined with my family history, originating from my Grandfathers walking stick factory, taking my parents across the sea to New Zealand on a boat. My first ladybird book told the story of the Oak, one of the few truly indigenous British trees, beautifully illustrating the balance of animals, birds and insects it sustained. Marvelling at David Attenborough gazing up into the Amazon canopy through the TV screen was a regular winter time activity.

As an adult, I camped at the foot of two ancient Oak Trees believed to be over one thousand years old. Their names Gog and Magog, feature in folklore and legends from many cultures, the Bible, and Qur’an. In London’s Guildhall, two carved wooden statues represent them as giants according to the ancient British version. The oaks bearing their names stand at the entrance to the mythical Isle of Avalon where they were worshipped by pagans. At sunrise one morning, I woke and saw a white rabbit scamper along the grassy precession towards them. The two were knotted together, gnarled and twisted one bald, its split branches stretching slowly toward the sky, the other, withered and sprouting sheltering beneath it. A few hours later I got a call on my mobile about my Granddad, Arthur…..

When I was at University trees became political. Swampy and the Newbury bypass protestors were notorious alternative media icons. Even the most conservative members of the British public were forced to admire their spirit, finding it hard to disagree that trees were nicer than roads, especially on their doorstep. Today, once again trees grace the headlines, only this time Swampy and co can stay at home and protest by internet if they choose. It is difficult to say how much internet outrage led the government to abandon its recent plan to sell off the national forests.

Buying a newspaper is a very effective way to stay informed politically and help preserve forests, flying in the face of the idea that saving paper equals saving trees. Of course everyone should use recycled paper, then all forests could stay exactly as they are. Not quite, recycling, needs energy to transport and pulp the paper, and chemicals to bleach and colour it. Paper on average can be recycled 6 to 7 times. As long as there is demand for forest products then land must be managed to produce trees, surely more environmentally friendly than PC manufacturing and disposal plants?

Trees are big business. They provide renewable, non toxic raw materials for building, packaging and publishing. Forests can generate and store real quantifiable energy. Unlike coal and oil, wood is a renewable fuel. Across Europe the area of land covered by forest is increasing. In the UK, forests cover 12% of the land area compared to 5% at the start of the twentieth century, which it should be remembered represents an all time low.

Perhaps best known in the form of graphite, forming the black shiny soft slidey lead in our wooden pencils, it is carbon that is key to the forests role in energy storage, production and climate regulation. When fuel burns and creatures breathe, carbon combines with oxygen to produce carbon dioxide (CO2). Too much of this in the atmosphere is the primary climate culprit.

During the daytime, trees and plants convert carbon dioxide into oxygen through photosynthesis. In the dark, the process is reversed. Carbon is stored in trunks, leaves and roots, returning to the soil through death and decay, for life to start again. Mature forests reach a steady state where carbon storage and production are balanced. Growing forests act as ‘sinks’, absorbing more than they produce. Alarms should ring when a forest is felled, destroying a store, allowing carbon to escape.

The critical factor is to manage the forests, selecting types of tree to plant and balancing the rate of cutting and replanting to sustain the level of tree growth. Clearing some trees is often good for modern forests, making room for others to spread out and a variety plant species to flourish.

Visible, in book and furniture shops world wide, the Forest Stewardship Council FSC, logo on timber products is more than an attractive design. It provides assurance that that the source of wood or paper is certified, having achieved management standards meeting vigorous legal and environmental criteria.

Only products from certified forests can carry this logo through supply chain to the consumer. It guarantees there must have been a permit to log the timber. Different countries are free to interpret the guidelines for themselves. Independent international auditors inspect the forests and issue certification where requirements are achieved. The UK (especially Wales), with Germany and Holland and a push from the NGOs have led the world in helping the EU position these standards at the forefront of the move to stop illegal logging.
If, importers and consumers insist on certification, demand for illegally logged timber can be reduced, completely removing the second largest incentive for clearing irreplaceable rainforests after agriculture. The international year of forestry encourages combination of forestry and agriculture, emphasising both preservation and reforestation, with the single goal of increasing forest cover.

While developing countries in the tropics don’t have the resources to manage and police forests there is little to stop illegal loggers. If compensation could be paid to for loss of illegal logging profits and sustainable agriculture prioritised, then deforestation could be rapidly reduced, as if by magic.

Far from the mythical Avalon, on a real island, also a favourite for Druids and Witches, it is hard to believe that an idyllic pine scented forest on the edge of a sandy beach, at one time provoked a hotbed of controversy. Newborough on Anglesey is one of the few places that native red squirrels have been successfully reintroduced and are capable of surviving the competitive greys. Corridors are being created to enable them to navigate around the island. However, this idyllic pine needle scented scene is artificial. The trees were planted by humans, the species are not indigenous and their positioning could damage the natural sandunes, contravening an EU directive on habitat preservation. While there was talk of replacing them with willow to preserve the dunes, plans were scrapped in favour of the squirrels following talks between Forestry Commission Wales branch, community groups and stake holders. They all worked together to agree a forest partnership action plan.

This scheme provides a snapshot of the complex global reality of moves to increase land mass covered by trees. This kind of dilemma is likely to become more frequent as the need to position trees to prevent floods, cool cities and offset choking carbon emission rises. Adaptable resilient varieties capable of fast growth, surviving adverse whether events and habiting environments they might not usually will be needed.
Clearly reducing emissions is the ideal solution for tackling climate change. Unfortunately it may well be too late to rely on alone. Compromises will have to be made, especially regarding mixing indigenous species and introducing new ones.

The priority is to act fast and bring CO2 and temperature levels, not trees, down. Internationally recognised standards can help forests be part of the solution not the cause.

“We need to act fast. Forests are disappearing at an alarming rate. International measures to STOP deforestation as part of international negotiations on climate change are needed. Timber certification is one way to STOP illegal logging”.
Roger Cooper, MBE Services to Forestry

More Information:
http://www.fsc.org/
www.forestry.gov.uk/publications

In so many newspaper articles about scientific and technological discoveries, you find the phrases “researchers showed”, “scientists suggest” and similar. Many lay readers will associate a scientist with a white coat and possibly a bearded old man, but is this really true? In my view, this image is really rather outdated and although I do wear a white coat when doing my lab work, I also do much other stuff in my daily life as a biochemist/protein scientist/enzymologist. Nevertheless, the fact remains that most members of the general public do not really know what a scientist does (even my parents, when asked to describe what I do, are often stumped to do this). So here’s my attempt at explaining what the daily life of a scientist might actually involve.

Unlike a growing number of researchers in the field of bioinformatics, where much work is done by analysis of the growing amount of data (from the humane genome project, from proteomics, metabolomics, microarrays and other fields that produce data in high-throughput fashion) with the help of powerful computers, I still do what is called ‘wet work’. This means I get to spend some time at the bench, mixing solutions and seeing what happens to them after you mix them. To put it very simply. As I am an enzymologists, I work with very tiny things, that you can’t even see under a microscope, so much of my lab work involves mixing colourless solutions with other colourless solutions (if I’m lucky, something that contains metal ions or fluorophores might be green, yellow or pink!) of microlitre quantities (a microlitre is a thousandth of a millilitre and you have about 500 millilitres of liquid in your pint glass) in small tubes of about 1.5 mL. Because I can’t see directly what is happening in my experiment, I have to have indirect ways of monitoring the readout of my experiment. In the past, this has involved looking at the changes in fluorescence (fluorescence happens when you shine a light onto your sample and it emits light of a different wavelength which you can measure, which requires the sample to contain a fluorophore) and more recently I have looked at the chopping up of DNA strands to give me a set of radioactive products which can be quantified because of the radioactivity readout.

On an average day, I will usually spend the morning and first part of the afternoon doing the experiments that were designed, more often than not, on a previous day so that I can get straight into it and get it done. Once finished, the experiments have to be analysed – in the past I have used a machine called a denaturing HPLC which did this for me. This was great, because you put your samples on, started the analysis programme and came back the next morning to get your results. But on the downside, it meant that all of us in the group were using the same instrument and time on it was pretty precious. These days, I analyse my experimental samples (which are effectively DNA fragments of different sizes) by running them on a gel, which separates them based on size (the shorter fragments run more quickly, because they don’t get stuck in the matrix that is the gel). And the gels can then be exposed by putting them in a light-tight cassette together with photographic film, which when developed, show you the location of the DNA fragments of different sizes.

And voila, here’s your result. Well, nearly, what comes next is the analysis phase and I generally spend some time in the afternoons analysing my data and working out what the images actually mean, which is as important, if not more so, as doing the experiments in the first place. So I get to work out what my data means and then promptly go on to design the next experiment based on it to ask the next question or repeat the observation I’ve just made so that I can be sure your result is not just a fluky one-off that happened because of one particular set of conditions and that cannot be actually repeated.

Which all sounds very simple and you might ask yourself whether all scientists have such an easy life. Well, it’s not quite all that we do. In theory, all the experiments work very well and you get a result from them that tells you something useful. In practice, not every experiment is conclusive, perhaps because there was something wrong with the buffer (the solution added to the experimental set-up to make the conditions as constant as possible), the enzyme you were adding has gone off or you forgot to add a component (it does happen even to the best of scientists!). Or the machine that you were going to use to analyse your data has been broken and you need to wait for it to be fixed. Or your reaction component has run out and the person who finished it didn’t order it at the time so you’re now waiting for a delivery. Or the fire alarm went as you were taking the critical time-points so you had to evacuate the building and start the experiment all over again. What I’m trying to say is that not every experiment is going to be usable so whilst it would be nice to think that everything you do will end up being part of that Nature paper, it is regrettably not so…

Which brings me to an important aspect of being a scientist, and that is the need to disseminate and publish your results. This is a key part of a scientist’s daily life, because, if the work is simply filed in your lab-book, there’s no point in doing it in the first place. You need to get others to hear about it so that they can repeat the work and build on it in their own research. Therefore being a scientist requires some time to be spent on reading other papers (for background and to work out how your work fits in with the work of others – but hopefully you’ve already spent some time reading the papers when you started the project!) and writing manuscripts to be sent to academic journals for peer review. Sometimes you are trying frantically to get things done in time for a deadline or because you know another group is working on the same problem and you do not want to be ‘scooped’, meaning that they publish their results first, leaving you to publish in a journal with a lower impact factor or, worse, not being able to publish at all because the work is no longer novel enough. Not only is the writing required but once the peer reviewers get back to you, more often than not they will have come up with some more experiments for you to do in order for them to find the paper acceptable. Often, this means you have a very short period to do the experiments which means you have to quickly reprioritise your time in the lab and try and deal with those things first, above everything else that you may have been working on. Of course, if you get senior enough/experienced enough in your field of expertise, you might yourself get asked to peer review papers, which is seen as part of a scientist’s responsibility to the community.

Whilst doing all the lab-work and data analysis, paper writing and dealing with referees comments, you will also have other responsibilities. Apart from perhaps being in charge of the upkeep of certain instruments (if you’re lucky to be in a large department, you may have a lab manager to do this), many departments run seminars where people regularly give talks about their ongoing work, and very often your turn ends up being at a time when you are most busy in the lab. (This is called Murphy’s Law, I think, but not scientifically proven). Other talks that you may be giving include sessions with your own lab/group, where the data is possibly taken apart more thoroughly, but which are often very useful because you get genuine feedback and are able to work out new avenues to explore in your research.

Openness and willingness to share data is a great thing in science and this is what leads to some useful discussions at conferences. Conferences have speaker sessions, where participants give talks about their data (or their group’s data, if it is the lab-head speaking), and poster sessions where individual researchers present their research in poster format, chatting informally to other conference participants who may be able to provide feedback. Conferences are great places to reinvigorate your interest in science in general and get excited about what goes on in other parts of the scientific world (when working in the lab, the daily grind can often be a bit repetitive and tedious, so it’s good to get out and talk to others and find that they’re all in the same boat). Of course they take a bit of preparation and in the run up to the conference you need to write an abstract to explain what you plan to present (often about 3 months before the actual conference so you need to be vague enough to fit in all the data that you may yet get in the next few weeks) and just before-hand you need to prepare your talk or poster (not forgetting that getting the University printers to print it the night before your 6am flight is just not an option!).

So I guess it is all very varied even if there is some sort of regularity to my average lab day. If I had any recommendations to budding scientists, I would say you should be prepared to change the plans and improvise if last minute requests come in for something urgent. But then most jobs are like that, right? I hope I’ve given you a bit more of an insight of what a lab-based scientist like me does. If you’re interested in the details, see below for a link to some information about the peer review process and, totally unrelated, a slightly tongue-in-cheek parody of Lady Gaga’s Bad Romance song describing the difficulties of being a PhD research student in biology.

Some useful links:
Something about the peer review process: http://www.senseaboutscience.org.uk/index.php/site/project/29/
A tongue in cheek parody of life in the lab (not everyone feels like this, I promise!): http://www.youtube.com/watch?v=Fl4L4M8m4d0

Inside our bodies, from the top of our heads to the tips of our toes, blood, carrying energy giving nutrients and oxygen flows around the body in time to the heart’s rhythmic two step. Sustaining our hearts desire is really an issue of life and death. The ultimate symbol of love, is the target of one of the biggest killers in the western world, Cardiovascular Disease. While new treatments give hope, it remains on the increase globally.

Philosopher Descartes described the body as a machine controlled by the spiritual soul acting on the material brain. If we take this view then the heart acts as a pump to circulate our blood. Heart attacks happen when the arteries leading out of it become blocked by fatty deposits, hardly the most romantic notion.

In Shakespeare’s poems the hearts status in our wellbeing is elevated far beyond the role of a simple pump;
“Mine heart doeth charge the watch, the morning rise
Doth cite each moving sense from idle rest,
Not daring trust the office of mine eyes.”

He describes it as governor of senses and emotions:
“ Love is dying, faith’s denying’
Heart’s denying, causer of this.
All my merry jigs are quite forgot”.

In science it is true that blood flow and emotions influence each other. Together with breathing, digestion, excretion and sexual arousal our heart is controlled by the opposing forces of the parasympathetic and sympathetic nervous systems, largely outside the detection of conscious awareness. The two need to work in harmony so that we don’t become sluggish or over-stimulated. Where the brain does get involve a tiny almond shaped structure called the amygdala is a prime centre for relaying emotional signals.

The heart is at the mercy of hormones, which rage at stimuli that provoke strong emotions like sexual desire and fear, leading it to pump faster and increasing oxygen supply to the brain. Scary stimuli increase epinephrine (adrenaline) producing the ‘fight or flight’ reaction where we may experience palpitations. Norepinephrine produces feeling of alertness, arousal and reward. Prolonged raised blood pressure is a major risk factor for attack.

Emotional reactions and responses to stress can be major indicators of who may be at risk of a heart attack. Newer research finds genetic risk links between heart disease and rheumatoid arthritis and it is possible that a third party such as response to stress or disposition is a culprit. A healthy diet and plenty of exercise are well known ways to control stress, prevent heart disease, boost wellbeing and altogether please our sweethearts.

If the worst does happen life saving interventions like transplants and bypasses are incredibly successful. The newest therapies make use of stem cells, traditionally an emotive issue. This time, an individual’s own bone marrow cells are encouraged to act like stem cells producing cells capable of repairing blood vessels and muscle. Such cells can be used to coat stents, tiny tubes inserted into blocked blood vessels in heart disease patients.

Medical science really can provide a ‘kiss of life’ and people live healthy happy lives for many years following a heart attack. Nevertheless, treatments can be expensive, time consuming, painful and risky. The age old cliché of ‘prevention is better than cure still rings true. As a romantic gesture, it could be wise to hold back on the champagne and chocolate.

On February the 14th we will be inclined to show our loved ones what they mean to us with tacky sentiments and novelty merchandise, but I’ve noticed we seem to be lacking something that most other corporate holidays cash in on – a mascot. Christmas has the reindeer and the robin, Easter has the bunny and the chick, and Valentine’s? Well yes it has the cupid, but flying chubby children just don’t say “I love you” the way a little fluffy creature from nature can. So here, I present to the corporate world the money makers – the top five creatures that will do anything for love.

The Bowerbird Bachelors

When I think of the term “bachelor pad” it conjures up images of unwashed undies, old beer cans, and questionable décor – but not if you were a Bowerbird. The Bowerbird gets its name from the males’ elaborate attempts at attracting a mate. They build structurally complicated and eccentric nests out of sticks and saplings – some even construct thatched roofs. Once their feat of engineering is complete, these multi-skilled birds decorate their “love nest” with the finest riches a lady Bowerbird could ask for. Precisely what the Bowerbird decorates his bower with differs between species and usually follows some sort of colour scheme. For example, the female Satin Bowerbird seems to go gaga for blue, and so the male busies himself for days hoarding any blue knick-knacks he can find. People have found shells, leaves, flowers, feathers, stones, and berries littering the nest sites, but Bowerbirds don’t discriminate against the man-made merchandise, they have also been found to collect discarded plastic items, coins, nails, rifle shells, and pieces of glass. The bird will spend days, arranging each piece just so. Ladies will visit many nest sites within her area and spend time carefully inspecting each of the efforts, sometimes returning to a prospective nest multiple times. Once confident she has identified the bower that satisfies her tastes, she will copulate and leave. Perhaps not the most romantic ending, but the male certainly deserves points for effort.

Scorpion Seduction

Dinner and dancing is a pretty standard date in the life of a female scorpion – the only thing is, the dance is actually a life-threatening battle between potential mating partners, and if it goes badly for the male, he could end up being served up as dinner. The ritual is usually held on a moonless night, in open expanses where males and females can be seen to judder and gyrate before contact. This process allows scorpions to recognise and assess each other’s compatibility through vibration and pheromone cues. After twenty minutes or so the male will approach the female, and grab her by the pincers. Holding her, face to face, they commence a sensual dance known as the “promenade à deux”, males have even been seen to “kiss” the female, nibbling her large pincer-like jaws. The real purpose of this, it is thought, is to inject a small amount of venom into her body, making her a more docile, and the encounter a little less risky for the male! During this elaborate dance, a space is cleared to enable him to safely deposit a package of sperm – known as a spermatophore. He then carefully directs her over the package, and when in position, she will take the deposit up into her reproductive tract. After fertilization the male doesn’t hang around for a cuddle, he must make a quick escape or run the risk of being eaten by the female – charming!

Snail Sex

You would think, perhaps, that snail sex would be a rather slow and sticky affair – and well, you’d be right – but couples pre-copulatory behaviour has shown snails to be very attentive and gentle lovers, spending between fifteen minutes and twelve hours “kissing” and “caressing” their partners before sex occurs. This rather graphic display of public affection does have a purpose; the male must locate the right location for which to fire his love dart – and that’s not just what the cool kids are calling it, it is in fact the scientific name for the male reproductive organ. Like cupid’s arrow, covered in mucus, the male lines himself up for the shot, and fires. The mucus causes the female’s reproductive tract to contract and greatly increases the amount of sperm she stores. It seems this process is not particularly enjoyable for the female, who suffers significant damage from the ordeal. Although, researchers have seen males with chronically poor aim fire a mis-shot through a female’s brain, and the females still live to tell the tale. Who knew snail sex was such a messy and hazardous business!

Squid Adoration: More hearts = More love

If, when it comes to love it’s not the size of the heart that matters but the number, the squid definitely wins hands down. Yes, oddly enough the squid has three hearts – two which take blood to and from each of the gills, and a larger one which pumps blood around the rest of the body. In terms of reproduction, there’s not a whole lot of romance and the job is undertaken fairly matter-of-factly, although, deep sea squid are known for their exceptionally long penises. When erect, the penis can grow as long as the head, mantle and tentacles combined. “So in the words of Lionel Richie, when it comes to hearts, ‘she’s once, twice, three times a lady’, and when it comes to penises, ‘he’s once, twice…’”.

Anglerfish: “’til death do we part”

And our final candidate is one of the few truly monogamous creatures in nature, the Anglerfish. Interestingly, when scientists first started collecting samples of this alien-like deep sea fish, they couldn’t understand why they were only able to find females. Then they began to notice and unusual trend, that most of the specimens had small “parasites” attached to them, which later they found out to be the males – “insert inappropriate joke here”.

These deep sea fish live a life down in the depths of the oceans, too deep for even light to reach – although I think if they could see what each other looked like the survival of their species might be under threat. In order to find and keep a mate under these conditions, you need to have a trick or two up your sleeve. From birth, the males have a highly developed sense of smell which allows them to detect the proximity of any nearby females by identifying the pheromones she releases into the water. When he finds a mate, he bites down into her skin and latches on. As he bites, he simultaneously releases an enzyme which digests the tissues of his mouth and her body, causing the remaining flesh to fuse together. The male then slowly becomes completely dependent on the female for survival, first losing his digestive tract, then his brain, heart, and eyes, until he is nothing more than a pair of gonads – “there are just so many jokes to be made here it almost seems too easy”. The male will then continue to periodically release sperm into the female, initiating egg release and fertilisation. The pair will remain together until the death of the female, which unavoidably, also results in the death of her partner.

So when it comes to presents this Valentine’s, try showing your partner you really care with a personalised gift inspired by nature. Perhaps deliver them a garden snail in a box with the message, “you’re love dart, went straight to my heart”, or a cuddly stuffed Anglerfish that when you squeeze its belly says “I’ll stick to you like a parasitic male Anglerfish”.
“Ah, doesn’t it just make you feel all warm and fuzzy inside?”

Sources
Wikipedia entries:
http://en.wikipedia.org/wiki/Bowerbird
http://en.wikipedia.org/wiki/Scorpion
http://en.wikipedia.org/wiki/Squid
http://en.wikipedia.org/wiki/Anglerfish
National Geographic:
http://animals.nationalgeographic.com/animals/fish/anglerfish.html
Lovebirds and Love Darts: The Wild World of Mating; Reported in National Geographic News, by Hillary Mayell, 13 February 2004

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It has recently been reported that one in six people in the UK today will live to see their 100th birthday. Interestingly, there was quite a loud outcry from the public who voiced their fears over reaching such a grand old age, but what do we really understand about ageing? In this article I will look at ageing from the genetic, cellular and multicellular level to find out what we know, what we don’t, and whether there’s anything we can do about it.

Growing old is one of life’s inevitabilities and we can see the symptoms of ageing all around us, in the colour of our hair, the texture of our skin, and the functionality of our mind… “What was I saying? Oh yes!” Despite its omnipresence, ageing remains one of science’s great mysteries – why do we age? Is our degenerative destiny mapped out from birth in our DNA? We all know ‘those’ stories of heavy smokers who lived to be a hundred and marathon runners who dropped dead at fifty. Or is it an effect of environment? A morbid summation of the general stresses and strains our body is exposed to during a lifetime which ultimately equals our expiration date. The truth is it is likely to be a combination of the two, but to what extent? And is the science out there which could let us stay forever young?

Geriatric Genes and Senior Cells

Evidence shows there is a heritable component of life span. “So, does this mean it’s all in our genes?” The short answer is, no. If it were “all in our genes” we would expect genetically identical individuals to die at approximately the same time. In humans, scientists have found identical twins to have very different life spans, and studies looking at large groups of animals with identical genetic backgrounds – such as honey bees – found huge variability in longevity. “So, does that mean there are no genes which determine ageing, and it’s all about lifestyle?” Well, again the answer is no. In recent years, many genes have been identified which contribute to an animal’s lifespan, however, further research found the actual contribution of these genes to the realised lifespan of the individual appeared to be very variable. Interestingly, the one result the scientists can agree on is the effect of food. Way back in 1934 Clive McCay and Mary Crowell from Cornell University found underfeeding (without malnutrition) increased a rodent’s lifespan by as much as 50%, and this result has been replicated many times since. However, more than 70 years later the “hows and whys” behind the mechanisms underlying this phenomena are still unknown – so don’t beat yourself up about that festive overindulgence.

“Ok, so the detail’s from the genetics seem to be a bit sketchy. But, what can we see in the ageing cell? How are the cells in someone who is old different from those in someone who is young?”

It was Peter Medwar who put forward the idea that overtime DNA would get worn out and damaged, a lot like the human body. He said that the probability of mutation accumulation (mistakes in the genetic code) increases over a longer period of time, and it is this deterioration of code that influences the ageing process. The genome – or the DNA that makes up your genes – is the recipe for all the proteins in your body. Proteins are like the cogs in a machine – they must be exactly the right shape and size to do their job. If they’re just a fraction off then the mechanism fails, and the machine starts to slow down as efficiency is reduced. There is evidence that such mistakes in protein production are involved in age-related degenerative diseases such as cataracts, Alzheimer’s disease and Parkinson’s disease.

“Ok, now we’re getting somewhere. But how does the body get rid of these old cells which are rusting up the cogs?” All cells come with a built in ticking time bomb in their DNA in a region called the telomere. The telomere gets shorter with every cell division, and when the code runs out, the cell has two options, either it will go into a suspended state called “senescence”, or it will initiate a “self-destruct mode” whereby intracellular proteins are released which destroys the cell. When this system breaks the cell becomes immortal, and will continue to replicate beyond its expiration date – this is how tumours arise. It is predicted that 85% of tumours are caused by a mutation in the telomere.

The Fountain of Eternal Youth

There is a multi-billion dollar cosmetic industry dedicated to anti-ageing products. Potions and lotions which promise your Grandmother the face of a teenager, and your mother a booty like Beyoncè. The unfortunate truth is, most are just re-packaged moisturisers – but science is making some major leaps forward in masking, and even reversing the effects of ageing.

A team of scientists from Harvard Medical School have managed to reverse the effects of ageing resulting in worn out old wrinkly rodents being rejuvenated into versions of their younger selves. They did this by breeding genetically engineered mice that were unable to produce the enzyme which caused the telomere to shorten during cell division – called telomerase. Mice without this enzyme aged prematurely, however, when the mice were given an injection to reactivate the telomerase enzyme, the signs of ageing were reversed. It is currently under further investigation as to whether this procedure actually increases longevity, but it might help improve the quality of life of individuals showing signs of age related degenerative diseases. This study is still in its early days and not yet safe for human testing, but it is certainly an important discovery into the secrets of the ageing body.

Who Wants to Live Forever?

There are some scientists that believe they will ‘cure’ ageing, allowing us to live… indefinitely. But, is that a good idea? For many, growing old gracefully isn’t an option– just take a look at the profits made by the anti-ageing cosmetic companies. It seems likely that within the next few decades the science behind ageing will take huge leaps forward, to places we find hard to contemplate. There will undoubtedly be companies looking to make some cash, and people willing to put some pretty toxic stuff into their bodies to cover the signs of ageing. I’m reminded of the dark comedy “Death Becomes Her” where two ladies who learn the secret of eternal youth end up, literally, in pieces. Research which carries with it such ethical responsibility is always tricky, but I do not believe in the stifling of knowledge due to fear of the unknown – just in its careful and responsible monitoring and application. However, it’s easy to get up on my high horse when I’m twenty five and the science isn’t there yet – but could I honestly say no? If fifty years from now someone offered me a magic potion which would literally take decades off, allow me to go running again, travel the world, see my great grand-children grow up, would I walk away? … Ask me in fifty years.

Sources
One in six people in the UK today will live to 100, study says; Reported in the Guardian by David Batty, 30 December 2010
Jaskelioff, M. et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469 (7328), 102.
Kirkwood, T. B. L. Understanding the Odd Science of Aging. Cell 120 (4), 437 (2005).
McCay, C. M. & Crowell, M. F. Prolonging the Life Span. The Scientific Monthly 39 (5), 405 (1934).
Harvard scientists reverse the ageing process in mice – now for humans; Reported in the Guardian by Ian Sample, 28 November 2010
Vijg, J. & Campisi, J. Puzzles, promises and a cure for ageing. Nature 454 (7208), 1065 (2008).

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Why human flu sufferers are far from alone. Tiny organisms, minor illness, massive influence.

In stuffy offices and classrooms dramatic stories and terrifying statistics spread like wildfire. From killer pandemics to man flu, viruses are hard to escape. In reality severity varies and human targets are not alone.

Angela McLean, professor of Mathematical Biology (University of Oxford), examines patterns underlying virus infection. As human flu suffers retreat, huddling cosy duvets and lemsip powder, it is easy to forget the world outside. Nevertheless, tiny viruses continue to have a massive effect in the animal and plant kingdoms. Dr Chris Gower (Oxford) and Dr Lawrence Kenyon (Head of Virology, AVRDC World Vegetable Centre) illustrate virus emergence in animal ecosystems and agriculture.

While scare stories abound, we are reminded that viruses are highly specific and leaps between species are unusual and limited in size. Understanding virus and earth systems interaction, and maintaining hygiene are perhaps the most effective defences. Just sometimes the best advice might really be to slow down, avoid crowded habitats, and stay home.

What?

To recap, a virus is an infectious agent, consisting of genetic material DNA, RNA wrapped up in a protein coat. One hundred times smaller than bacteria, barley visible through a light microscope, they come in many varieties and reproduce inside cells of other organisms. These tiny, relatively simple microorganisms are perhaps one of the most powerful forces on earth, present in all ecosystems, with the ability to devastate entire populations of almost all other forms of life, generating immensely complex questions for science.

How?

Professor McLean explains, viruses spread in cramped conditions where members of the same species are forced together in a small space. For animals this can happen when habitats are destroyed, even where only a few of the species survive as they crowd together in small remaining areas of habitat.

Virus pandemics emerge through a mixture of ecological and evolutionary processes. When one happens, like Swine Flu the viruses work on ‘power and competition’. From this, in June 2010 Prof McLean predicted the new H1N1 Swine Flu virus will become the regular strain, replacing the previous seasonal flu. It is entirely possibly, although as yet unconfirmed, that this is happening now, as the World Health Organisation (WHO) reports cases of Swine Flu virus alongside other strains. A case of ‘watch this space?’

“I am interested in how distribution of people such as movement from villages to towns affects how a virus spreads. The more a virus spreads the more it evolves.

In history when Europeans first went to the ‘New World’ devastating outbreaks of smallpox and measles occurred in people who had never encountered these diseases before.”
Professor Angela McLean

Prevention and Treatment

Luckily it is not all doom with preventative vaccines and anti viral medication available. Professor McLean takes a closer look.

“It is amazing how successful vaccinations for viruses have been. The same measles vaccine has been effective for over forty years and the virus has not been able to evolve resistance despite selection pressure put on it by humans. In contrast new flu vaccines are needed every year, reflecting the changing underlying biology of the microorganism, different every year whether you vaccinate or not.”

For viruses where no vaccine is yet available e.g HIV, anti viral drugs are the first line of attack. When using antiviral drugs it is important to use genetic screening in a laboratory to check for resistance and help doctors decide which to use.

“We use information encoded in the RNA extracted from a blood sample (genetic material) to make real treatment decisions in real clinics. The right combination of antiviral drugs will not cure HIV but it can nearly completely suppress the virus and stop it reproducing, so as long as the person is able to continue to take it they will remain well. Failing to screen and using treatments where a patient has natural resistance is harmful in that it delays effective treatment and resistance not previously there can develop, burning through patients options for treatment.”
Professor Angela McLean

Out in the Wild

Our four legged friends can also suffer and domestic animals such as dogs are major virus carriers. Surprisingly it is wild populations like Ethiopian wolves who are left vulnerable, Chris Gower from Oxford University talks about protecting them.

“Ethiopian wolves are smaller than the European wolves that they descended from when they migrated from Europe to Africa. They are a flagship for the Afro Alpine habitat, when they are there you know everything else is present in the habitat ecosystem, including rodents. This important region supplies water for Somali, Egypt and Sudan.” Chris Gower

These wolves are an endangered, not dangerous, with less than 500 remaining in the world. As people move into their habitat in the Ethiopian highlands with dogs and livestock the threat from the transfer of a rabies virus to such a small population is potentially devastating. Strategic vaccination creates barriers of immunised dogs to contain the outbreak. It would be quicker to inoculate the wolves directly, however the only available vaccine now uses Genetically Modified Organisms and is currently not allowed.

Feeding a Cold

What better way to beat the snuffles than vitamin C packed juicy tomatoes? Dr Lawrence Kenyon Head of Virology at the World Vegetable Centre (AVRDC) demonstrates that they too are not immune, often at the mercy of virus carrying insects.

Plant viruses are transferred from plant to plant either by insects such as whitefly or infected plants rubbing together through human and animal contact. Tomato leaf curl is an example of a major crop virus, the leaves of infected plants show symptoms first, curling up to a dry withered crunch before the entire plant dies.

“Plant viruses do have pandemics but it is not so dramatic as seen with swine flu because as a rule plants don’t get on aeroplanes, requiring insects for transmission.”
Dr Lawrence Kenyon

In Taiwan ‘power and competition’ is in action as indigenous tomato leaf curl virus is being replaced by the more aggressive Thailand leaf curl virus, affecting peppers as well as tomatoes.

Plants like cabbages can act as whitefly sources, encouraging virus spread. Measures to prevent this in crops include; careful choice of species planted together, regular clearing of dead and dying plants, and housing in net cages. Spraying can also be used with more or less toxic agents. Reflective distracts the insects’ visual systems stopping them from landing on surrounded crops, and artificial coatings can be used on fruits. Selective breeding and genetic interventions to produce disease resistance, provide an alternative where other methods are too expensive or impractical.

Commercially desirable characteristics such as sweet juicy fruits make plants more vulnerable to viruses. Insects find hairy plants less attractive to land on, increasing their resistance to infection. This principle explains why commercial thorn less roses can only be grown in glass houses.

Non native environments also increase vulnerability. Cassava or Manioc now a widely grown staple crop in Africa was introduced from South America over two hundred years ago. Cassava Mosaic virus is now a major agricultural problem in Africa.

“If you go back to the centre of origin of Cassava it is not found at all, or anything like it. Scientists think it must have come from the native African plants and found Cassava to be a better host.”
Dr Lawrence Kenyon

Making a Leap?

I asked the scientists just how big a leap can virus species make between hosts. They agree;
“Viruses can jump from dogs to wolves, pigs to people and some of the genes move between species. They get inside cells where they can grow so there needs to be enough similarity between the cell types. Every gardener knows humans don’t get sick from plant viruses, the cell receptors are too different. The biggest jump we have seen in nature is SARS, from birds to people. This is exceptional and still within vertebrates.”
Professor Angela McLean

“Plant viruses have evolved to affect plants, just a few will also affect the insect carrying vector. Animal cells produce antibodies to foreign material and a plant virus will be recognised as such so animals don’t get infected.”
Dr Lawrence Kenyon

Who’s Life is it Anyway?

Personally I consider finding acceptable mechanisms of virus prevention an example of a really difficult dilemma and wonder whether ‘natural’ gene pool conservation can be considered desirable and achievable in today’s fast moving society. I would also like to know whether human created computer viruses exhibit similar emergence patterns to human, animal and plant varieties. Certainly, migration and translation generate immensely complex evolutionary effects across the earth’s systems.

Imagine this situation: You are trying to interview someone who apparently has no recollection of a crime that they have committed. You have enough evidence to suggest that this person is ranked very high in the wanted list for this crime, but not enough to take to court, and you need some certain way of telling if it is a lie or the truth. You think about using a polygraph (the technical name for a lie detector machine) but you read somewhere that you can’t be sure that these are unreliable (61% accurate according to a survey of 421 Psychologists), and are easily tricked. Then you think about body language, and seeing if that would help with judging if the person is guilty, but you remember that it can be very easily controlled. You can’t think of anything else, so you continue with the interview, although a little exacerbated.

At certain times in the interview however, you seem to think that you may have noticed a slight twitch in the persons face, or some kind of fleeting expression, that was too quick for you to see what it was. The chances are, you may forget about this, or dismiss it as nervousness; however, in 1966 Haggard and Isaacs discovered that these fleeting expressions were ‘micro-expressions’ and were involuntary movements of facial or body muscles in response to thought processes by the brain, happening in around 1/15th to 1/25th of a second.

Firstly, let us examine why the old way of lie detection (a polygraph) isn’t as reliable as people thought. A polygraph is a machine that measures the blood pressure in the body, pulse, respiration and skin conductivity, which were all discovered to be symptoms of people telling a lie. However, these variables are far too susceptible from outside stimuli (if it is humid or dry, or if it is hot or cold, and if the air is thin or thick) and the power of the mind, which leads to its surprisingly low success rate.

Because of this unreliability, polygraphs shouldn’t be used as a way of prosecuting a criminal, only to give the detectives a slightly more than half chance of getting the right offender. This is why studying body language (more specifically micro-expressions) can be much more accurate, since they are governed by the subconscious. The problem arises when the psychologist giving the evidence in court is accused him or herself of lying by the prosecuted, since it depends on a psychologist’s judgment of the person, and it can be skewed towards either side of the case.

However, we shall delve into the legal implications of accusing someone on such evidence, and when it should or should not be used in conjunction with other techniques and hard evidence after looking at how someone is trained to recognize these micro-expressions. Anyone can learn the basics of micro-expressions, which is seeing them in the first place, but training someone to accurately discern what the expressions actually mean is another problem.

To combat this, a technique known as Micro-Expression Training Tool (or METT for short) was developed by a Professor Paul Ekman, which teaches the user to recognize these expressions in under an hour, and an METT advanced online tutorial, which when completed along with the final test will make you eligible for a certificate, provided that you have reached over 80% (over 95% and a certificate of expertise will be given).

There are ways however of training yourself without the cost of buying the METT. There are several websites which have a way of testing yourself on recognizing split second expressions, which are aimed not at getting you to see the micro-expressions, but to actually recognize which emotions are being expressed, usually some of the larger emotions, such as anger, happiness, disgust, surprise, contempt, etc. However, this way isn’t usually practical since in these tests, it is just two pictures, where one has a distinct version of the expression, and the other is normal, and it flicks once in about a millisecond; this is not ideal for accurate diagnosis of emotions in the subtleties of micro-expressions, but is an alternative to buying METT.

Further reading:
http://en.wikipedia.org/wiki/Microexpression
http://www.sciencedaily.com/releases/2006/05/060505161952.htm

I am not a geneticist or plant scientist, with no knowledge of Mandarin or Taiwanese, so a visit to the World Vegetable Centre (AVRDC) home for the World’s largest public vegetable gene bank, in Taiwan, tested my skills of interpretation and translation to the limit.

Working especially with farmer’s co-operatives across Asia, India and Africa, AVRDC supplies crop seeds, adapted to survive whatever misfortunes an increasingly fickle climate and trails of over breeding and overcrowding throw at them.

Headquarters for the World Vegetable Centre, an international Non Governmental Organisation is located in the region of the old Taiwan capital, Tainan County. The centre attracts scientists across the world, while retaining strong ties to the local community of Shan Hua, a town with a long established agricultural tradition.
Providing the roots for the Centre’s activities, Dr Andreus Ebert from Germany and Taiwanese Mr Whan share responsibility for curating Gene Bank’s the vast collection. I had the chance to glimpse inside the heart of this real life archive and out in the fields, speak to researchers using the records to conserve rare indigenous vegetables and create hardy new varieties of familiar favourites like tomatoes.

Approaching the bank my steps fall into the sifting rhythm, transmitted from a circle of people in conical straw hats, crouching among the trees, shifting and shaking pans of seeds. Like most things in Taiwan it was important to move beyond first impressions. I was soon to learn that this was more than a musical accompaniment, and in fact an ingrediant of the scientific process of sorting and selecting seeds for preservation in the gene bank vaults.

Changing into slippers so that I don’t carry spores, viruses or other plant pests in on my shoes, I accompany Dr Ebert on a guided tour of the bank.

1. Processing – Within the walls, genetic inheritance information from over 56,000 global varieties, collected over 30 years, is identified, coded and stored. Records in this unusual library are in the form of germplasm, the genetic information that allows plants to reproduce. While most is seeds, there is also an alium store for onions, shallots and garlic and tubors like potatoes as their structure and high moisture content needs different treatment.

   Shuffling into the first space, we see seeds being processed, extracted and cleaned, mostly by hand. Seeds are selected, bad seeds, very small seeds damaged seeds or those not confirming to the standards are removed. For long term preservation, temperature and humidity must come down. In this short term storage and processing area the temperature is cooled from the average 25-30 °C outside to 15°C.

2. Storage – The door of the cavernous chamber for medium term storage, clunked shut behind us. Here, temperature is reduced to 5°C like the inside of a domestic fridge, giant fans reducing the humidity to 45%. Different species require slightly different treatment to balance the temperature and humidity levels with the viability limits of the variety. Some seed surfaces will crack at lower temperatures, affecting their ability to grow outside. Coco seeds are not suitable for long term storage as they quickly loose viability, and coffee can only be stored for a few months.

   I was lucky enough to catch a rare glimpse inside the second chamber. The long term store can’t be opened very often as this will increase the already enormous amount of energy needed to regulate its environment. The humm of fans and giant fridges became a roar as the door sealed. Temperature is below 0 °C, with humidity of -10 to 18%. Under these conditions seeds are expected to last between 50 and 70 years.
   They must not however, be forgotten, samples are grown outside at regular intervals. I am told that farmers would soon complain if the proportion of viable seeds is low and they regularly fail to germinate. First seeds must be mobilised by imbibing to take up water. Plants can then be grown outside, and their seeds harvested to maintain the variety. Wherever possible, it is best to use the originals, as each time seeds are grown outside they start to adapt to the conditions in Taiwan, losing their native characteristics.

   Care is taken to preserve indigenous crops, defined as those that are not immediately of major commercial importance world wide, in line with national programmes across the World. Examples include, egg plants, okra, loofah and bitter gourds, rich in antioxidants under investigation for treating diabetes. Older varieties may be more hardy with better resistance to disease than cultivated hybrids with desirable commercial characteristics and a narrow genetic basis.

   Dr Ebert tells me, small farmers need to use a risk management strategy of growing mixed crops together so they are less vulnerable to specialist insect attack. Failure to do this was responsible for totally wiping out coffee in Shri Lnaka which had to be replaced by tea. It was necessary to return to the origin of the crop in Etheopia to find older varieties with natural genetic resistance. The gene bank exists to help manage such eventualities.

3. Conserving Indigenous Vegetables – Out in the sunshine, heavily pregnant Mandy Li-Ju Lin took me on a tour of the indigenous vegetable garden. Here, lesser known species with promising characteristics, either for commercial development or crossing with current popular varieties are grown. Tiny wild tomatoes gleam like holy berries, inedible for humans yet more hardy and resilient than their cultivated cousins. Creamy white African egg plant nestles among lush green and purple African cassava (sweet potato leaves) and, and I spot pink tarot popular in hotpots and markets across Taiwan. I am intrigued by the thorny coriander, popular in Thailand, exotic, pungent and aromatic for humans but far less attractive to insects than the commonly available round leafed type.

   Mandy told me many of these vegetables are considered to have strong unpleasant tastes and smells making them less popular candidates for commercial development. She reminded me they have uses beyond food like washing skin and clothes and water purification. As well as climate resilience plants can also be selected for nutritional properties such as high antioxidant or beta carotene content (vitamins). This is often indicated by deep colour, greens, purples and yellows, and can help human immunity. Plants shelter in net cages to protect them from virus carrying Taiwanese whitefly and avoid cross pollination, maintaining the purity of the lines.

   Transferring the information to records library helps prevent less immediately commercially attractive crops disappearing from existence, as farmers feel pressure to replace local varieties with high yield hybrids. Plants are measured, observed and photographed, recording days to flower and fruit, and fruit size and weight. I set out to discover how to identify which ones have the real X factor.

4. New Stress Resilient Varieties – In the greenhouse scientist Rachael Symonds (UK), described how she combines indigenous genes with commercial varieties to improve survival in extreme conditions.
   ‘I have been working at an international research centre with an international community for the global public good’
   “Why we are doing the research is to help plants survive under stress, for example tomatoes with thicker skin may be more resilient. This is vital now as the climate is changing and the world is getting drier and hotter. Plants, especially vegetables won’t be able to live where they do at the moment. We need to produce high value nutritious crops for areas most affected like Sub Saharan Africa.”

   She told me, commercial varieties can be crossed with wild types that you can’t eat to help their tolerance to stress. For example some types of inedible wild tomato growing naturally near the sea may be more resistant to drought and dehydration from salty soil by having a different type of cell membrane barrier structure. These can then be bred with some of the more commercial varieties to produce food crops better able to survive.

   “We’ve got a gene bank with thousands of varieties so we select types of interest, often going back to the wild type to cross them with cultivated varieties. Seeds that don’t get selected for one experiment are returned to the bank for use at another time and place.”

   Controlled experiments are used to test this out, comparing samples of tomatoes with known characteristics with the new varieties in controlled dry and wet conditions, artificially created in pots. Water and salt level are carefully measured and the resulting crop yields dried and weighed to establish whether or not there is a significant advantage, and if so its extent.

   “ I can take many types of measurements to describe the plants and their interaction with the environment. A breeding programme for a new variety can take three years to produce vegetables to eat.”

5. Packing and Labelling – Back inside the bank, Dr Ebert explained how packing and labelling is an essential step towards distribution of identified seeds. First, in the processing area, they are weighed and stored 20 – 30 in paper packages. A barcode system is used to identify the seeds and labels are placed on them by hand. Each time the packets are labelled there is a danger that two numbers could be exchanged and the barcode system is used to reduce errors.

   In the long term store, seeds are packed into vapour proof aluminium packets. Unlike the organic paper material this doesn’t have the same interaction with moisture in the environment. Before putting in these final bags seed samples are tested for moisture content, comparing it with the baseline. Given even the slightest hint of moisture seeds could germinate, rendering them useless for storage and future planting and breeding. The aluminium packets are kept in sealed drums for future.

6. Passport Data – ‘Integrated passport data’ for seed lines is represented on a freely accessible database. This information includes, a unique number to identify the lines, and like your own birthday, their date and place of collection. Nutritional information is also stored and used to inform the breeding process, together with research information from other parts of the Centre, to produce a well documented profile. The computerised records are freely available for anyone interested enough to browse them.
7. Safety Back Up – When disaster strikes such as the 2004 Boxing Day Tsunami in Shri Lanka is, this preserved collection enabled the farmers to go back to the seeds and start production again. Just like backing up your hard drive, a safety back up is made in a secure sister site in Korea. This is reassuring given that Taiwan is prone to earthquakes, and like anywhere is not without is vulnerabilities to climate catastrophe as demonstrated by the landslides shortly after my visit in 2009. Unlike a computer the genetic information is stored in the seeds themselves. Even in long term storage viability beyond fifty to seventy years is precarious, requiring a considerable energy.
8. Distribution – There is a small charge for distribution of seeds from the gene bank, staggered according to means, lower for national programmes and higher for seed companies. Co-ordinating distribution flow is tricky, as the Rio conference on Biodiversity in 1992 gave countries of origin ownership of seeds and plant materials. They can choose whether or not to make it available to the bank, grant or refuse permission for countries beyond their own borders to use them, placing restrictions on the bank. Dr Ebert suggests the current legislation is complex to implement because plant species don’t stick to international geographical and political boundary limits making it hard for any one country to prove which plants are native.

   “Co-operation and collaboration are needed to continue with the exchange to produce new varieties and feed a still growing world population with always less and less land which is more difficult with this legislation.”

   Balancing the need for movement with ecosystem preservation is a critical challenge. As sea levels rise in response to climate change, so does demand for heat, drought, flood and salt tolerance species, accelerating global redistribution of genes. At the same time, recognition of the importance of wild and domestic varieties is higher than ever, as farmers need to incorporate characteristics from wild types, more hardy to poor soil and extreme temperatures into the higher yielding varieties. Seeds are treated for pests before leaving the bank and quarantine encouraged in the receiving country.

9. Consumer Choice – World Wide, Who’s to say what happens to the gene lines on leaving the bank, as on reaching their destination seeds will enter agricultural production as the farmers see fit exposing them to cross breeding at the discretion of local humans, animals, birds and insect behaviour. Despite best efforts, it is not possible for the gene bank to certify that seeds are virus and pest free. Post entry quarantine and growing out isolated samples in the destination country is required to check for disease that might be present but not show up in Taiwan. Success now, is dependent on local knowledge and expertise, and outcomes cannot be completely controlled.

   The gene bank is vital in countering the threat of a narrowing gene base as farmers select for specific traits, leaving commercially valuable crops with large juicy fruit crops that are both attractive to insects and vulnerable to devastation by viruses. The coffee crisis in Shri Lanka, demonstrated this threat is real. Today, thanks to consumer’s preference for flavour, taste and colour, older stronger varieties are becoming more popular, despite having lower yields. This trend for quality has allowed niche markets for unusual varieties to develop, powerful encouragement for preserving the world’s diverse genetic heritage.

For more information visit:
http://www.avrdc.org/index.php?id=13

An audience braving the bitter cold were rewarded with a warm welcome at Science Oxford Live on the 25th November 2010 to explore the five senses of touch, taste, hearing, sight and smell, with neuroscientist Professor Charles Spence. They cringed at the world’s loudest crisp packet, now withdrawn from sale as found to be too irritating and lingered over chocolate and wine, while an explanation of innovative packaging for cleaning products set the mood for spring. Speaker Charles Spence took the time to satisfy their questioning in full, explaining how designers of all kinds delight in playing with the sensory experiences scientists seek to understand.

He illustrated how this is all in the spirit of science as combining different sensual elements can both entice and confuse our response. More red colour and things taste sweeter as we naturally think of ripe berries and listening to chicken noises can enhance the taste of egg. Our brains mix the cocktail of information from our senses to produce our overall experience. Could this be why as the saying goes, ‘food always tastes better outdoors?’ Familiarity can influence this super additive sensual effect, a drop of sugar on the tongue can increase ability to smell almond with salt having the same effect for a Japanese palate more used to this taste combination.

Celebrity chef Heston Blumenthal is capitalising on this phenomenon, pairing blood orange with orange beetroot for an unexpected colour and taste combination and using digitised sea sounds to accompany fish. This interesting innovation can be sampled in his restaurant the Fat Duck near Slough. The Science Oxford audience suggested that while the medium is novel the idea of using sounds, especially music to enhance the eating experience is age old. I will resist the temptation to quote Shakespeare for fear of sounding too cheesy.

The audience were very willing to test things out for themselves by sampling dark and milk chocolate squares. For me, it was absolutely certain even before catching a whiff, milk chocolate was clearly wobbly rounded shape buba with a medium deep not played on a woodwind. Dark high percentage coco could only be spiky tuki played on a violin. While this seemed to reflect the audience consensus, and previous studies, there was plenty of space for individuality. A musician pointed out that he is so in tune with sound elements that other sensual cues fade into the background.

The audience were intrigued about how sensory cues could be used to influence settings for social benefit, such as painting walls in prison a particular shade of pale pink, shown to be calming, and careful choice of colour and scent in hospitals to appropriately stimulate and relax. They warned that in some situations reactions could be mixed if people suspect artificial sense enhancement is at work. Charles Spence emphasised that he considers the underlying intent and execution of manipulation is the important issue. Personally, he appreciates sensual enhancement where it increases enjoyment of an experience. A starter for a sizzling debate?

‘Mind Change’

Baroness Susan Greenfield outlines the concept of ‘Mind Change’, which could be as significant as ‘Climate Change’ for the future of the human race, taking our brains to another dimension.

Mind Change describes the outcome of changes to the way our brains take in and process information becoming ‘hard wired’ as a result of prolific connection to digital technologies. This could have a profound effect on our thoughts, feelings, behaviour and relationships, ultimately affecting the cultural fabric of society.

Potential culprits are prolonged exposure to action packed sensory stimulation through computer games and bombardment with disjointed information from the internet, social networks and advertising. Neurological and psychological testing and informal reports indicate that on the one hand rapid decision making, co-ordination and performance on traditional IQ tests may improve. However, distracted attention resulting in shallow processing and reclusive individualistic behaviour with increased risk taking, could be a drawback.

Lady Greenfield acknowledges that effects visible in humans may be complex and subtle while technology develops so rapidly that scientific measures struggle to keep pace, creating uncertainty for legislators and policy makers. Nevertheless, she reasons we cannot afford to ignore the possibility that our thought patterns could change beyond recognition, with implications as serious as climate change in terms of human sustainability and longevity.

By telephone, Lady Greenfield discussed her ideas for a novel which have emerged during her lifetime researching neuroscience, pharmacology and the brain.

Describe your current interest?

One hundred years from now, we could be creating a society where cybernisation of the planet is the norm, especially as innovations like high definition TV become more and more vivid. This could have a profound effect on human consciousness, skills and relationships. While prolonged participation in activities such as computer games can improve skills like sensory motor co-ordination and response speed they may reduce concentration and empathy resulting in shallower information processing and dramatically different ‘mindsets’.

This might sound speculative because it is difficult to prove effects when you can’t control what people take in from screens day to day. Scientists can’t prove a negative and safely say it hasn’t had an effect. All they can do is look at trends. As brains attempt to keep up with proliferation of media in the environment we could be looking at an economy of attention.

How are our brains affected by information in the environment?

Minds are like a mobile phone network with cheaper calls for more frequently used numbers, numbers can become blocked or be forgotten if rarely used. This mechanism is called synaptic plasticity. This network is vulnerable to ‘lost and stolen’ processes, ‘hacking’ and ‘spam’.

How would you describe a ‘sensory’ and a ‘cognitive’ experience?

A sensory experience provides sights, sounds, smells, and movement, for example going to a disco or skiing. A cognitive experience involves reading a book, having a conversation, looking for meaning and narrative. People need a balance of both. Screen technology encourages a bias towards the sensory and can literally ‘blow your mind’.

Beyond receiving digital information from screens, what are the possible effects for developments such as Nanotechnology and Synthetic Biology?

Emerging technologies, such as body monitoring systems using nanotechnology challenge the notion of the body’s firewall with the outside world, eroding our sense of privacy which opens us up to third party intervention and scenarios such like ‘Brain Hacking’.

What would you say to those who might call you a scare monger?

This is only justified only if you know it is not a problem and it isn’t too complacent to suggest everything is just fine. I would prefer to be called a scare monger and be proved wrong than sleepwalk my way into a future where it is too late.

Mind change is a neutral term which doesn’t imply a good thing or a bad thing, it is simply a description of how we may evolve. In writing a novel I am aware it is a personal view, not a textbook, a little like ‘brave new world’. I allude to where the science is real and introduce people to democracy, concepts and possibilities, ideas and predictions that emanate from science and are interesting enough to read for pleasure.
“We need to think ahead, becoming the master not the servant of technology, defining what we want it to do, otherwise we are not serving the next generation well”.

How effective are current methods for studying brain activity?

Brain imaging acts like a ‘virtual photograph’. You can’t see the movement and the exposure is too slow. It is also invasive and expensive. Tests given to people in the imager are ‘blunt tools’ and there are many effects occurring in a person’s individual internal environment during the scanning process that are difficult to control and affect the result. It is still better than doing nothing. Studying mechanisms such as attention bias in addiction in a laboratory can inform brain scanning, indicating what to look for.

Scientists need to collaborate with web designers and educators to decide new things that could be done to develop software and focus the many possible tasks for studying cognition, attention, emotion and behaviour.

How are our brains affected by the way we interact with technology?

Our interaction with computers is an ongoing two sided dialogue. We design them to help us in learning e.g. developing cognitive processes such as driving. At the same time our brains adapt to this environment and our skill base changes becoming more machine like.

Simulations are very powerful e.g analysis of electrical signals in the brain which occur before a movement is initiated still happen in people who are paralysed. Tapping into this could further our intimate connection with technology for example, using it to control a robotic arm.

What do you think about techniques such as Neuro Linguistic Programming (NLP)?

Neural connectivity is the basis of how we come to see the world a different way, working with different problems. This can involve responses to words as well as actual things. Presentation can affect development of goods and services, influencing risk taking and leadership in the workforce.

How does ‘climate change relate to the concept of ‘mind change’?

Mind change and climate change are both critical scenarios concerning governments and negotiations between countries. There is sometimes an idea that science can save us through climate policy and eco products. An example of how quickly mind change can happen is the way that everyone now recognises the telephone. It may affect boys and girls differently according to the technologies they interact with and influence relations with developing countries. Time spent in virtual environments could lead to behaviour which is individualistic, reclusive, and child like with a high level of greed, impulsivity and disregard for consequences.

How can scientists and society at large tackle Mind Change?

Scientists need to anticipate and ‘see’ potential future impacts, considering economics and taking a multidisciplinary approach with dialogues transcending academic disciplines.
Regulation sometimes isn’t helpful and the processes happen too late. It can appear negative, stopping people from doing things. Instead it is better to be constructive, consulting people and giving them alternatives.

“We need to focus on, education, not regulation and work with the art of the possible. I would like to hear what parents and children think.”

We could devise a questionnaire to measure parents concerns and look for effects of age and gender, making observations and looking for consensus.

How would you define Progress?

“Enabling people to reach their full potential, which is now higher than ever before, using the best mixture of skills and talents.”

Having spoken to Baroness Greenfield the concept of ‘mind change’ is a great way to describe something that is already here, with individuals affected to a matter of degree. At a societal level there are already signs of a backlash from screen addiction. In the UK on trains and buses, casual observation suggests that books and newspapers are as popular as mobile phones and laptops. On the high street the stationary market appears to be booming while people are flocking to spas retreats, fleeing the countryside in droves at the weekend, weather permitting.

From my point of view, while the science remains uncertain, nourishing my brain is a top priority. This involves participating in activities, and discussion including both sensory and cognitive components. Making it acceptable to rely solely on technology for information could allow new embodied cultural divides to really set in. Given its elusive nature, here is a danger that the concept of Mind Change could disappear from our conscious awareness and fail to benefit from the attention it deserves, leaving us wide open to isolation and erosion of our autonomy and identity.

Continuing to allow machines to shape us could affect our ability to deeply engage with complex material and relate to others, essential attributes for collectively combating global climate change. Our minds are perhaps the most important tool we have in terms of conserving the planet, so it seems essential the two concepts are considered hand in hand.

More Information:
Baroness Greenfield: http://www.pharm.ox.ac.uk/research/greenfield

It’s Halloween: time to turn down the lights, and gather round for a horrific tale of what waits for you in the shadows… luring you into its lair… creatures capable of turning ordinary souls into monsters… and beasts that can control your mind to carry out their evil bidding. This is a true story of some unpleasant parasites that might just be coming, for you.

Parasites survive by exploiting their hosts. A parasitic way of life is arguably one of the most successful on the planet. For every organism, there are parasites which can infect it. There are even parasites of parasites, and like a Russian doll, these get smaller still, until you begin to consider genetic parasites, which are no more than rogue pieces of DNA, manipulating the host genome to do its dirty work. What’s more, parasites have evolved some very sneaky ways to manipulate, control and deceive their hosts to ensure their survival and transmission. Here are a few particularly gruesome examples of parasitic tricks of the trade.

MASTERS OF MIND CONTROL

“Brainwashing” hosts to increase transmission rates is a common ploy for parasites. One of the better understood mechanisms is that of the parasitic protozoa; Toxoplasma gondii. T. gondii has two life stages, a sexual stage which takes part inside the gut of a cat, and an asexual phase where the parasite forms cysts within the brain and muscles of an intermediate host which can be any small mammal or bird. The parasite relies on the intermediate host falling prey to a feline in order to complete its lifecycle, and it has evolved a rather ingenious way of ensuring its transmission. Ajai Vyas and his team from Stanford University found that rodents infected with T. gondii seemed to be attracted by the smell of cat urine, an aroma uninfected individuals would actively avoid. Vyas found parasitic cysts tended to concentrate in the amygdala in the rodent’s brain. This part of the brain is associated with fear and anxiety, and they believe the parasite is able to target specific neural pathways in order to manipulate normal behavior of cat aversion, and as such, significantly increase the chances of the rodent becoming feline food.

Mosquitoes are a human ectoparasite (a parasite which lives outside the host), but these are not the pests I want to talk about. At times they can be a nuisance, but they can also make a deadly delivery. Malaria is one of the most important causes of human mortality in the modern world. The mosquito acts as a vector for the protist, Plasmodium falciparum (the organism which causes malaria), which uses the mosquito as an intermediate host in order to reach its target – humans. Research by Lacroix and his team found the malaria parasite was able to manipulate the behaviour of the mosquito, to find humans infected with the transmissible stage of malaria to be more attractive than other potential hosts. Others studies also showed differences in biting behaviour, with a decreased biting frequency during early infection (thus increasing the chances of host survival until the protist has time to develop), and increased biting frequency once the protist was infective to humans (thus increasing transmission rate). The mechanisms which the protist uses to alter its host’s behaviours are not understood, but research such a Vyas’s team into Toxoplasma gives hope that one day we might understand such mechanisms which could help develop better prevention strategies and ultimately save lives.

INVASION OF THE BODY SNATCHERS

Some parasites are small and subtle, stealthily changing the characteristics of their host to increase transmission. Other parasites have more of a “bull in a china shop” approach with their host, as is the story of the hairworm and the grasshopper. Hairworms excrete a cocktail of chemicals into the grasshopper which mimic the natural neural signals, and so, highjack the grasshopper’s nervous system. This triggers suicidal “death leaps” into water, where the parasite needs to reach in order to complete its lifecycle. A grasshopper becomes infected after drinking larvae infested water. Once ingested, the worm will grow inside the grasshopper until it takes up almost its entire body cavity (only the legs and head will be unoccupied). At this point the grasshopper can been observed to take a suicidal spring into water, where (and here’s the gruesome bit) a worm, which is up to four times larger than the grasshopper, emerges from its rear end and swims off to find a mate. Hugh Loxdale, president of the London-based Royal Entomological Society, said “It’s one of the most horrific things I’ve ever seen… It makes the science fiction film Alien look pretty tame in comparison.”

Figure 1: The sequence of events as the hairworm emerges from its grasshopper host. The grasshopper irrationally jumps into the water (due to neural cues induced by the hairworm), and once in contact with the water, the worm emerges and swims away to find a mate. The grasshopper, inevitably, dies.
Credit: VB Films/CNRS Images Media

Figure 2: The tongue-eating louse eats and replaces its host’s tongue and feeds.
Credit: Dr. Nico Smit

Talking of Alien, does figure 2 remind you of anything? This terrifying invader is Cymothoa exigua, more commonly known as the tongue-eating louse. This little louse enters its host fish through the gills, and attaches itself to the base of the tongue. Frontal claws are used to drain blood from the tongue until it wastes away. The parasite then attaches itself to the muscles of the tongue’s stub, and replaces the organ. Gruesome as it seems, the parasite does not appear to cause any additional damage to its host, feeding only on small amounts of blood and mucus from the fish’s mouth, and the fish can use its new squatter almost as it would its old tongue. It is unknown how long this association can last, but neither the host nor the parasite benefit from the fish’s death, and so it seems, the partnership could potentially last a lifetime.

THE PARADOXICAL PARASITE

As a final note, I thought I’d end on a horrid high note. The concept of a harmonious hookworm might seem contradictory, but sometimes the dark forces can be used for good. The hookworm is very prevalent within the third world. Infection is usually caused by walking barefoot in soil contaminated with faecal matter. The worm will burrow into the foot and migrate through the vascular system to the lungs. From there they crawl up the trachea, and are swallowed in order to reach the digestive system. Their final resting place is in the intestine where they latch onto the intestine wall and feed off the host’s blood. In large numbers these critters can cause anaemia and protein deficiency, including emaciation, cardiac failure and abdominal distension. So why, you might ask, would people in the developed world be purposefully infecting themselves with such vile creatures?

Autoimmune diseases; such as Crohn’s disease, asthma, irritable bowel syndrome (IBD), multiple sclerosis, type I diabetes and allergies, are common in the developed world. In these diseases an over-reactive immune system begins to attack the body, which can result in some serious complications. The “hygiene hypothesis” proposes that the increased rate of autoimmune diseases has been caused by over-sterility of the environment during early childhood. Reducing exposure to infectious agents such as microorganisms and parasites (which in evolutionary terms our body is evolved to encounter) during the maturation of the immune responses might have negative effects. Under-stimulation of the immune system during early years can lead to an overactive long term response to foreign agents in the body; the result is an autoimmune disease.

This has led to the development of “helminthic therapy”, which is the use of parasitic helminths (worms) to “dampen down” the response of the immune system. It is not entirely clear how the immune responds to the worms, but patients suffering from autoimmune disorders have too many over-sensitive T-helper cells (which identify potentially dangerous agents and mark them for irradiation by the body’s “solider cells” such as macrophages and antibodies). T-cells are self-regulating, and so activation of certain types (in this case, by the presence of the worms) will result in the deactivation of others. Under these conditions a negative feedback is established, and eventually, a healthy balance can be established.

So would you be tempted to take a drink of probiotic parasitic worms to treat your hay fever, or IBD? There are now many subscribers to the new treatments, and so far the reports back are very positive. But more research is required to understand the specific relationship between the parasite and host, and how numbers and transmission rates are to be controlled.

And so, perhaps you were disgusted, intrigued, or even converted by my horrific tales of parasite behaviour. Writing this article, I for one was amazed at how parasites have evolved so many ways to manipulate and deceive their hosts, but I’m not sure I want one of my own yet!

SOURCES

• Parasite “Brainwashes” Rats Into Craving Cat Urine, Study Finds By Ben Harder for National Geographic News, 2007
• Vyas A, Kim SK, Giacomini N, Boothroyd JC, Sapolsky RM (2007). Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proceedings of the National Academy of Sciences of the United States of America 104: 6442-6447.
• Lacroix R, Mukabana WR, Gouagna LC, Koella JC (2005). Malaria Infection Increases Attractiveness of Humans to Mosquitoes. PLoS Biol 3: e298.
• Suicide Grasshoppers Brainwashed by Parasite Worms, By James Owen for National Geographoc News, 2005
• Biron DG, Marche L, Ponton F, Loxdale HD, Galeotti N, Renault L et al (2005). Behavioural manipulation in a grasshopper harbouring hairworm: a proteomics approach. Proceedings of the Royal Society B-Biological Sciences 272: 2117-2126.
• Brusca RC, Gilligan MR (1983). Tongue Replacement in a Marine Fish (Lutjanus guttatus) by a Parasitic Isopod (Crustacea: Isopoda). Copeia 1983: 813-816.
• Eat worms – feel better, Reported on BBC news, 2003
  Reddy A, Fried B (2009). An update on the use of helminths to treat Crohn’s and other autoimmunune diseases. Parasitology Research 104: 217-221.
• McKay DM (2006). The beneficial helminth parasite? Parasitology 132: 1-12.

Article by Tiffany Taylor

The reign of Big Brother may have come to an end, but relatively recent craze of reality TV shows have allowed us to become bystanders to the lives of strangers, and the increasing usage of surveillance technology means there are few places we are completely “off the radar”. But can the knowledge of being watched change our perception of decency? And perhaps, could it be used to create a more honest and generous society?

In the University of Newcastle an ethologist, Melissa Bateson, wanted to see whether she could manipulate her colleagues’ generosity through subtle visual cues. An honesty box had been in use for many years in the University staff room to cover the cost of tea and coffee. Above the honesty box at eye level an image was placed which alternated weekly between eyes and flowers (Figure 1). The results showed that just the photocopied image of a pair of eyes was enough to significantly increase the weekly contribution compared to an image of flowers. This suggested that people were more likely to contribute if they felt like their actions were being watched. The researchers believed this behaviour was driven by a desire to maintain a positive reputation within a social group.

This result is perhaps not surprising, but it conjured up a number of questions for me: why do we feel the need to maintain this reputation, is it through fear of punishment, or hope of reward? Can such behaviour be observed in other animals? And, can it be used to influence and manipulate social groups?

The Evolution of Being Nice

It’s not only humans that have this concern for social perception, Bshary and Gutter found the cleaner wrasse fish (which forms a mutualism with larger fish helping clear them of parasites) must be seen to be honest before it will be allowed a meal. Occasionally cleaner fish will “cheat” and take small nips out of a bigger fish’s flesh, however, if caught in the act by another potential customer they are less likely to get a feed and may also be subject to punishment by the violated client. As such, it’s been shown that the presence of bystanders will reduce the frequency of cheating behaviour. Punishment for bad behaviour is also used by meerkats. In this hierarchical society it is only the dominant female who is allowed to breed, as she requires the help of the whole group to maximise the survival of all her offspring. If however, a subordinate female is showing signs of pregnancy, the dominant female will harass the subordinate resulting in the abortion her foetus. These examples are based on punishment, but there are also social groups which reward “good” behaviour. The vampire bat requires a nightly blood meal in order to survive, but sometimes they inevitably come home after a night foraging with empty bellies. The bat will beg to a neighbour in the hope that they may take pity and share a small amount of their blood meal, the neighbour can either choose to regurgitate a small amount or keep his dinner to himself. However, those which are not charitable are more likely to be refused a meal in the future when it is their time of need. As such, it pays to be seen being sympathetic, as the donator knows they are likely to be returned the favour in the future. Explaining the maintenance of cooperation in a group has been a tricky biological problem, what is to stop free-loading and uneven contribution? But “enforced cooperation”, i.e. a mechanism which rewards those that cooperate and punishes those who exploit, could help explain how cooperative behaviour is maintained. In terms of human evolution it is thought this theory of reciprocity, that is be nice to those who have been nice to you in the past, has been an important mechanism in the evolution of our own cooperative behaviour, therefore it makes sense that being “seen to be kind” might be engrained in our psychology and provide a direct benefit in a highly social group, such as humans.

“Did you see that?”

Psychologists are well aware of people’s desire to appear to be contributing to society or “prosocial” behaviour to use the jargon. This made me contemplate ways that we could be influenced, and even manipulated, by clever use of an implied witness to our actions creating a sense of accountability. Two very interesting studies showed how people might be manipulated subconsciously to become more generous by invoking the thought of an invisible presence. The first study was by Azim Shariff and Ara Norenzayan who invited participants to play a game whereby they were given $10 each, and could choose whether to share any of it with an anonymous player. Before the game commenced, participants were asked to unscramble sentences which were designed to prime either the notion of a God, thoughts of a civic institution, or some other neutral prime. Results showed that participants who had been primed to invoke the image of a God or a non-religious altruistic community gave more than $4 on average (this was independent of whether the participant claimed to be religious or not), compared to $2.56 which was the average amount given away by those primed with neutral content.

In the second experiment, Kevin Haley and Daniel Fessel played an identical game to that described above, however this time the experimenters had one of two images displayed on a computer desktop when the participant entered the room. Half the participants saw a stylised depiction of the human eye, whereas the others saw a warehouse background (Figure 2). Here, the results show participants exposed to the eyes gave on average 55% more, compared to those which were not exposed ($3.79 compared with $2.45).

“With great power, comes great responsibility”

I find this potential for subtle manipulation a bit disconcerting and wondered what role it might play in policing and consumerism today. Here is an example of research which could theoretically be applied for “the greater good”. Using psychology to influence the perception of being watched giving accountability for our actions might, in fact, encourage cooperative and prosocial behaviour, but can we justify using manipulation and subconscious stimuli to control social groups based on this fact? Or am I being naive to think it isn’t already used as a tool in today’s society? In my opinion, it’s all seems a bit nineteen eighty-four to me.

SOURCES
Bateson M., Nettle D., and Roberts G. (2006). Cues of being watched enhance cooperation in a real-world setting. Biology Letters 2: 412-414.
Bshary R., and Grutter A.S. (2006). Image scoring and cooperation in a cleaner fish mutualism. Nature 441: 975-978.
West S.A., Griffin A.S., and Gardner A. (2007). Evolutionary Explanations for Cooperation. Current Biology 17: R661-R672.
Jaeggi A.V., Burkart J.M., and Van Schaik C.P. (2010) On the psychology of cooperation in humans and other primates: combining the natural history and experimental evidence of prosociality. Philosophical Transactions of the Royal Society B: Biological Sciences 365: 2723-2735.
Shariff A.F., Norenzayan A. (2007). God Is Watching You. Psychological Science 18: 803-809.
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Article image credit: Big Brother 2011: The eye has been revealed Photo: ©Channel 4

In Egypt there are stories of supernatural activities surrounding the tombs of ancient kings. It is said that the hieroglyphics etched into tomb walls frequently carry warnings of ‘Pharanoic hexes’ for those who may wish to steal from or disturb the resting king. So when a number of people present at the excavation of Tutankhamen’s tomb died under mysterious circumstances, was it down to black magic, bad luck or biological bugs?

On February 17th 1923, a crowd gathered in the ‘Valley of the Kings’ to witness Howard Carter’s team unseal the infamous Tutankhamen’s burial chamber. The excavation revealed treasures fit for a king, whose body still lay resting in his extravagant solid gold coffin.

However, this tale of discovery took a more gruesome turn when in April 1923 a number of those which were present at the excavation allegedly began dying under mysterious circumstances. First to meet his maker was the project’s chief financier, Lord Carnavon, though this was equated to a mosquito bite that he received while on expedition which later became infected. Still, rumours began to flourish and reports of a “mummy’s curse” hit the headlines.

Soon after, the media reported many other deaths which were claimed to be linked to the curse: Lord Carnavon’s brother; Howard Carter’s assistant; Lady Elizabeth Carnarvon; Carter’s partner; two Egyptian workmen; and the financier, George Jay Gould I.

HEX OR HOGWASH?

Along with these deaths followed a media runaway reporting curses and black magic. Such fantastical claims enraged the archaeological and scientific communities and researchers made every attempt disprove the sensationalist stories emerging from the press. Until eighty years later when an Australian scientist, Mark Nelson, published a study which showed the survival rates of forty-four Westerners connected with the excavation, twenty-five of which were present at the opening of the tomb, or examination of the mummy. He found no significant difference in the average age of death to those which had been exposed to the ‘mummy’s curse’ by physical contact with the tomb or mummy, and those which were unexposed. And so it seemed the deaths surrounding King Tut’s final farewell were a concoction of coincidence and media hype.

CASE CLOSED?

But like all good ghost stories, the tales continued to be told, and this has resulted in some interesting research which might reopen the case of ‘the mummy’s curse’.

Modern studies have shown pathogenic microbiological agents such as bacteria and fungal moulds are present in Egyptian tombs. Food was left for the deceased deity as part of the burial ritual and combined with rotting flesh this would encourage the growth of microbiological nasties. Theoretical work initiated by a French scientist, Sylvain Gandon, has hypothesised that the longer a pathogen is able to survive outside the host in a dormant state (such as a spore), the more harmful the infection is likely to be; and pathogens with such life-histories, like Anthrax, could have described Lord Carnavon’s demise. Since this paper was published in 1998, there have been a large number of theoretical and empirical studies to extend the hypothesis, but the jury is still out as to whether such competition between infective agents is common in nature – but there is certainly an argument for its existence in certain scenarios. Kenneth Feder (co-editor of the book Dangerous Places: Health, Safety, and Archaeology) agrees that there is “at least a possibility of being exposed to some nasty stuff”.

MORAL OF THE STORY

I believe the morals of this story are twofold. Firstly, it is an important science lesson not to immediately dismiss the improbable as impossible; by approaching such myths and magical tales with a logical and scientific head, what was once a bedtime story can become a route to discovery and innovation. For example, Darwin’s theory of natural selection, or Einstein’s general theory of relativity, could never have been developed had they just believed what they had been told. Secondly, this story highlights the dangers of sensationalised science. The media has a reputation for dramatising its articles in order to sell stories, and science has in no way been spared. Ignoring expert advice and favouring scaremongering has led to a drop in MMR vaccinations due to its unverified links with autism, and the media are now moving to attacking the cervical cancer vaccination with headlines like “Eight deaths linked to labour’s new sex jab for school girls” (source article). I don’t think calling it a “sex jab for schoolgirls” was really the message the scientists who developed this revolutionary drug were trying to send. That is not to say scientists are faultless in this relationship. Poor communication between public and academic factions means messages can get lost in translation, and it is often this misunderstanding which can lead to fear and suspicion of new scientific advancements in the public eye. Either way, mutual trust must be established between the media and scientific communities to ensure the public are aware of new research and discoveries being made today; otherwise science just becomes a ‘secret club’ and the consequence is surely a stifling of discovery.

And so, I will end with this thought: whether it was deadly spores, ghostly curses or natural causes which resulted in the deaths surrounding King Tut’s excavation, it has produced some interesting research; some lessons in exploration and science communication; and, a great bedtime story.

SOURCES
The Curse of the Pharaohs: Truth, Myth or Microbiology? By Tracy Morris for Firefox News, 2009

Kamo M, Boots M (2004). The curse of the pharaoh in space: free-living infectious stages and the evolution of virulence in spatially explicit populations. Journal of Theoretical Biology 231: 435-441.

Researchers at the J. Craig Venter Institute (JCVI) published results today describing the successful construction of the first self-replicating, synthetic bacterial cell. The team synthesised the 1.08 million base pair chromosome of a modified Mycoplasma mycoides genome. The synthetic cell is called Mycoplasma mycoides JCVI-syn1.0 and is the proof of principle that genomes can be designed in the computer, chemically made in the laboratory and transplanted into a recipient cell to produce a new self-replicating cell controlled only by the synthetic genome.

This research will be published by Daniel Gibson et al in the 20th May edition of Science Express and will appear in an upcoming print issue of Science.

‘For nearly 15 years Ham Smith, Clyde Hutchison and the rest of our team have been working toward this publication today – the successful completion of our work to construct a bacterial cell that is fully controlled by a synthetic genome,’ said J. Craig Venter, Ph.D., founder and president, JCVI and senior author on the paper. ‘We have been consumed by this research, but we have also been equally focused on addressing the societal implications of what we believe will be one of the most powerful technologies and industrial drivers for societal good. We look forward to continued review and dialogue about the important applications of this work to ensure that it is used for the benefit of all.’

According to Dr Smith, ‘With this first synthetic bacterial cell and the new tools and technologies we developed to successfully complete this project, we now have the means to dissect the genetic instruction set of a bacterial cell to see and understand how it really works.’

To complete this final stage in the nearly 15 year process to construct and boot up a synthetic cell, JCVI scientists began with the accurate, digitised genome of the bacterium, M. mycoides. The team designed 1,078 specific cassettes of DNA that were 1,080 base pairs long. These cassettes were designed so that the ends of each DNA cassette overlapped each of its neighbours by 80bp. The cassettes were made according to JCVI’s specifications by the DNA synthesis company, Blue Heron Biotechnology.

The JCVI team employed a three stage process using their previously described yeast assembly system to build the genome using the 1,078 cassettes. The first stage involved taking 10 cassettes of DNA at a time to build 110, 10,000 bp segments. In the second stage, these 10,000 bp segments are taken 10 at a time to produce eleven, 100,000 bp segments. In the final step, all 11, 100 kb segments were assembled into the complete synthetic genome in yeast cells and grown as a yeast artificial chromosome.

The complete synthetic M. mycoides genome was isolated from the yeast cell and transplanted into Mycoplasma capricolum recipient cells that have had the genes for its restriction enzyme removed. The synthetic genome DNA was transcribed into messenger RNA, which in turn was translated into new proteins. The M. capricolum genome was either destroyed by M. mycoides restriction enzymes or was lost during cell replication. After two days viable M. mycoides cells, which contained only synthetic DNA, were clearly visible on petri dishes containing bacterial growth medium.

The initial synthesis of the synthetic genome did not result in any viable cells so the JCVI team developed an error correction method to test that each cassette they constructed was biologically functional. They did this by using a combination of 100 kb natural and synthetic segments of DNA to produce semi-synthetic genomes. This approach allowed for the testing of each synthetic segment in combination with 10 natural segments for their capacity to be transplanted and form new cells. Ten out of 11 synthetic fragments resulted in viable cells; therefore the team narrowed the issue down to a single 100 kb cassette. DNA sequencing revealed that a single base pair deletion in an essential gene was responsible for the unsuccessful transplants. Once this one base pair error was corrected, the first viable synthetic cell was produced.

Dr Gibson stated, ‘To produce a synthetic cell, our group had to learn how to sequence, synthesise, and transplant genomes. Many hurdles had to be overcome, but we are now able to combine all of these steps to produce synthetic cells in the laboratory.’ He added, ‘We can now begin working on our ultimate objective of synthesising a minimal cell containing only the genes necessary to sustain life in its simplest form. This will help us better understand how cells work.’

This publication represents the construction of the largest synthetic molecule of a defined structure; the genome is almost double the size of the previous Mycoplasma genitalium synthesis. With this successful proof of principle, the group will now work on creating a minimal genome, which has been a goal since 1995. They will do this by whittling away at the synthetic genome and repeating transplantation experiments until no more genes can be disrupted and the genome is as small as possible. This minimal cell will be a platform for analysing the function of every essential gene in a cell.

According to Dr Hutchison, ‘To me the most remarkable thing about our synthetic cell is that its genome was designed in the computer and brought to life through chemical synthesis, without using any pieces of natural DNA. This involved developing many new and useful methods along the way. We have assembled an amazing group of scientists that have made this possible.’

As in the team’s 2008 publication in which they described the successful synthesis of the M. genitalium genome, they designed and inserted into the genome what they called watermarks. These are specifically designed segments of DNA that use the ‘alphabet’ of genes and proteins that enable the researcher to spell out words and phrases. The watermarks are an essential means to prove that the genome is synthetic and not native, and to identify the laboratory of origin. Encoded in the watermarks is a new DNA code for writing words, sentences and numbers. In addition to the new code there is a web address to send emails to if you can successfully decode the new code, the names of 46 authors and other key contributors and three quotations: ‘TO LIVE, TO ERR, TO FALL, TO TRIUMPH, TO RECREATE LIFE OUT OF LIFE.’ – JAMES JOYCE; ‘SEE THINGS NOT AS THEY ARE, BUT AS THEY MIGHT BE.’ – A quote from the book, ‘American Prometheus’; ‘WHAT I CANNOT BUILD, I CANNOT UNDERSTAND.’ – RICHARD FEYNMAN.

The JCVI scientists envision that the knowledge gained by constructing this first self-replicating synthetic cell, coupled with decreasing costs for DNA synthesis, will give rise to wider use of this powerful technology. This will undoubtedly lead to the development of many important applications and products including biofuels, vaccines, pharmaceuticals, clean water and food products. The group continues to drive and support ethical discussion and review to ensure a positive outcome for society.

Funding for this research came from Synthetic Genomics Inc., a company co-founded by Drs. Venter and Smith.

Bats’ remarkable ability to ‘see’ in the dark uses the echoes from their own calls to decipher the shape of their dark surroundings. This process, known as echolocation, allows bats to perceive their surroundings in great detail, detecting insect prey or identifying threatening predators, and is a skill that engineers are hoping to replicate.

A team of British researchers has worked with six adult Egyptian fruit bats from Tropical World in Leeds to record and recreate their calls. These calls are pairs of ‘clicks’ from the bats’ tongues that they use to fill their surroundings with acoustic energy; the echoes that return allow the bats to form an image of their environment.

New research published today, Tuesday 11 May, in IOP Publishing’s Bioinspiration & Biomimetics, describes how engineers and biologists from the Universities of Strathclyde and Leeds worked with the bats to record their double-click echolocation call, and its returning echoes, using a miniature wireless microphone sensor mounted on the bat whilst in flight.

During echolocation, some bats are known to use a natural acoustic gain control. This allows them to emit high-intensity calls without deafening themselves, and then to hear the weak echoes returning from surrounding objects. The researchers replicated this system in electronics to allow the sensor to record both the emitted and reflected echolocation signals, providing an insight into the full echolocation process.

The six bats performed up to sixteen flights each along a flight corridor. Each flight was short – lasting only about three seconds – but, with the bats’ clicks only lasting a quarter of a millisecond, a large number of calls were recorded for the scientists to analyse.

Once back into the laboratory, the researchers were able to accurately recreate the echolocation calls using a custom-built ultrasonic loudspeaker. This technique will allow the signals and processes bats use to be applied to human engineering systems such as sonar. Specifically, the researchers are looking to apply these techniques in the positioning of robotic vehicles, used in structural testing applications.

Lead author Simon Whiteley from the Centre for Ultrasonic Engineering at the University of Strathclyde, said, “We aim to understand the echolocation process that bats have evolved over millennia, and employ similar signals and techniques in engineering systems. We are currently looking to apply these methods to positioning of robotic vehicles, which are used for structural testing. This will provide enhanced information on the robots’ locations, and hence the location of any structural flaws they may detect.”

A team of scientists from Columbia University, Arizona State University, the University of Michigan, and the California Institute of Technology (Caltech) have programmed an autonomous molecular “robot” made out of DNA to start, move, turn, and stop while following a DNA track.

The development could ultimately lead to molecular systems that might one day be used for medical therapeutic devices and molecular-scale reconfigurable robots—robots made of many simple units that can reposition or even rebuild themselves to accomplish different tasks.

A paper describing the work appears in the current issue of the journal Nature.

The traditional view of a robot is that it is “a machine that senses its environment, makes a decision, and then does something—it acts,” says Erik Winfree, associate professor of computer science, computation and neural systems, and bioengineering at Caltech.

Milan N. Stojanovic, a faculty member in the Division of Experimental Therapeutics at Columbia University, led the project and teamed up with Winfree and Hao Yan, professor of chemistry and biochemistry at Arizona State University and an expert in DNA nanotechnology, and with Nils G. Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan in Ann Arbor, for what became a modern-day self-assembly of like-minded scientists with the complementary areas of expertise needed to tackle a tough problem.

Shrinking robots down to the molecular scale would provide, for molecular processes, the same kinds of benefits that classical robotics and automation provide at the macroscopic scale. Molecular robots, in theory, could be programmed to sense their environment (say, the presence of disease markers on a cell), make a decision (that the cell is cancerous and needs to be neutralized), and act on that decision (deliver a cargo of cancer-killing drugs).

Or, like the robots in a modern-day factory, they could be programmed to assemble complex molecular products. The power of robotics lies in the fact that once programmed, the robots can carry out their tasks autonomously, without further human intervention.

With that promise, however, comes a practical problem: how do you program a molecule to perform complex behaviors?

“In normal robotics, the robot itself contains the knowledge about the commands, but with individual molecules, you can’t store that amount of information, so the idea instead is to store information on the commands on the outside,” says Walter. And you do that, says Stojanovic, “by imbuing the molecule’s environment with informational cues.”

“We were able to create such a programmed or ‘prescribed’ environment using DNA origami,” explains Yan. DNA origami, an invention by Caltech Senior Research Associate Paul W. K. Rothemund, is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns (such as smiley faces or maps of the Western Hemisphere or even electrical diagrams). Exploiting the sequence-recognition properties of DNA base pairing, DNA origami are created from a long single strand of DNA and a mixture of different short synthetic DNA strands that bind to and “staple” the long DNA into the desired shape. The origami used in the Nature study was a rectangle that was 2 nanometers (nm) thick and roughly 100 nm on each side.

The researchers constructed a trail of molecular “bread crumbs” on the DNA origami track by stringing additional single-stranded DNA molecules, or oligonucleotides, off the ends of the staples. These represent the cues that tell the molecular robots what to do—start, walk, turn left, turn right, or stop, for example—akin to the commands given to traditional robots.

The molecular robot the researchers chose to use—dubbed a “spider”—was invented by Stojanovic several years ago, at which time it was shown to be capable of extended, but undirected, random walks on two-dimensional surfaces, eating through a field of bread crumbs.

To build the 4-nm-diameter molecular robot, the researchers started with a common protein called streptavidin, which has four symmetrically placed binding pockets for a chemical moiety called biotin. Each robot leg is a short biotin-labeled strand of DNA, “so this way we can bind up to four legs to the body of our robot,” Walter says. “It’s a four-legged spider,” quips Stojanovic. Three of the legs are made of enzymatic DNA, which is DNA that binds to and cuts a particular sequence of DNA. The spider also is outfitted with a “start strand”—the fourth leg—that tethers the spider to the start site (one particular oligonucleotide on the DNA origami track). “After the robot is released from its start site by a trigger strand, it follows the track by binding to and then cutting the DNA strands extending off of the staple strands on the molecular track,” Stojanovic explains.

“Once it cleaves,” adds Yan, “the product will dissociate, and the leg will start searching for the next substrate.” In this way, the spider is guided down the path laid out by the researchers. Finally, explains Yan, “the robot stops when it encounters a patch of DNA that it can bind to but that it cannot cut,” which acts as a sort of flypaper.

Although other DNA walkers have been developed before, they’ve never ventured farther than about three steps. “This one,” says Yan, “can walk up to about 100 nanometers. That’s roughly 50 steps.”

“This in itself wasn’t a surprise,” adds Winfree, “since Milan’s original work suggested that spiders can take hundreds if not thousands of processive steps. What’s exciting here is that not only can we directly confirm the spiders’ multistep movement, but we can direct the spiders to follow a specific path, and they do it all by themselves—autonomously.”

In fact, using atomic force microscopy and single-molecule fluorescence microscopy, the researchers were able to watch directly spiders crawling over the origami, showing that they were able to guide their molecular robots to follow four different paths.

“Monitoring this at a single molecule level is very challenging,” says Walter. “This is why we have an interdisciplinary, multi-institute operation. We have people constructing the spider, characterizing the basic spider. We have the capability to assemble the track, and analyze the system with single-molecule imaging. That’s the technical challenge.” The scientific challenges for the future, Yan says, “are how to make the spider walk faster and how to make it more programmable, so it can follow many commands on the track and make more decisions, implementing logical behavior.”

“In the current system,” says Stojanovic, “interactions are restricted to the walker and the environment. Our next step is to add a second walker, so the walkers can communicate with each other directly and via the environment. The spiders will work together to accomplish a goal.” Adds Winfree, “The key is how to learn to program higher-level behaviors through lower-level interactions.”

Such collaboration ultimately could be the basis for developing molecular-scale reconfigurable robots—complicated machines that are made of many simple units that can reorganize themselves into any shape—to accomplish different tasks, or fix themselves if they break. For example, it may be possible to use the robots for medical applications. “The idea is to have molecular robots build a structure or repair damaged tissues,” says Stojanovic.

“You could imagine the spider carrying a drug and bonding to a two-dimensional surface like a cell membrane, finding the receptors and, depending on the local environment,” adds Yan, “triggering the activation of this drug.”

Such applications, while intriguing, are decades or more away. “This may be 100 years in the future,” Stojanovic says. “We’re so far from that right now.”

“But,” Walter adds, “just as researchers self-assemble today to solve a tough problem, molecular nanorobots may do so in the future.”

The other coauthors on the paper, “Molecular robots guided by prescriptive landscapes,” are Kyle Lund and Jeanette Nangreave from Arizona State University; Anthony J. Manzo, Alexander Johnson-Buck, and Nicole Michelotti from the University of Michigan; Nadine Dabby from Caltech; and Steven Taylor and Renjun Pei from Columbia University. The work was supported by the National Science Foundation, the Army Research Office, the Office of Naval Research, the National Institutes of Health, the Department of Energy, the Searle Foundation, the Lymphoma and Leukemia Society, the Juvenile Diabetes Research Foundation, and a Sloan Research Fellowship.

Contact: Kathy Svitil ksvitil@caltech.edu

Image Credit: Courtesy of Paul Michelotti