Why Plants Make Caffeine

It's Monday again, and somehow I have managed to convince myself over the weekend that waking at 11 is justice, and the natural human way. But here it is, Monday 10:30 am, and I've been up for 5 hours already....

I think it's time for a coffee break.

I rush around, juggling my workload until I can finally manage to fit in 15 minutes for a quick mug-full of that sacred, sacred Joe. But if I were a plant like Cocoa, Kola, Guarana, or Coffee, I wouldn't have had to make the time - I would already have the caffeine built in. Do these plants realize just how lucky they are? That is, of course, assuming that plants use their caffeine to get a buzz on.

In truth, scientists have only begun to guess why some plants produce caffeine. Caffeine is classified as a secondary compound which means it is not essential for the plant's survival. In fact there are many species of caffeinated plants with decaffeinated relatives (poor things), but, as a non-essential component, it can be harder to pinpoint exactly what the caffeine is doing there.

Chemically, caffeine is a methylxanthine. Many methylxanthines are used as pesticides both by humans and plants. It's possible, though not confirmed, that caffeine is used to poison herbivores and plant pests to discourage them from attacking that plant type again; that is, if they survive after metabolising the caffeine. But because caffeine is toxic to plant cells it's stored in specialised cell compartments called vacuoles which are rather like a medicine chest and keep the caffeine safely locked away from the rest of the cell contents until it's needed. Unfortunately this means that the plant doesn't get to enjoy the buzz from its own caffeine (assuming plants can experience a 'buzz'), but that's a necessary trade-off of having a toxic substance lying around.

So it seems that caffeinated plants are lucky to have this compound as part of their natural defences, but it doesn't deter all attackers. For instance, caffeine doesn't poison humans in the doses that we typically ingest (even a Monday morning dose), but it does cause addiction. It works by stopping the enzyme phosphodiesterase from breaking down a signalling substance called cyclic AMP (cAMP for short) and its close relatives. One of the actions of the stress hormone adrenaline is to increase the levels of cAMP in cells, so by preventing cells from breaking down cAMP, caffeine potentiates the action of adrenaline, and gives us a buzz. In even higher doses, and with prolonged use, it can trigger anxiety, muscle tremors, palpitations and fast heart rates, and profound withdrawal effects including headaches, inability to think clearly, and bad moods whenever you mistakenly switch to decaff !

Caffeine-containing plants may be safe from certain insects, vertebrates, bacteria and fungi, but they are preyed on by humans who love the rush it gives them. Not so lucky then, I guess? But there is a hypothesis that plants synthesise psychoactive compounds to target and manipulate humans in particular. In other words, if humans desire the plants, then they will cultivate them. The plants may get processed and eaten up by humans, but because they have been better cared for, they will be able to produce more offspring first. If this hypothesis is true, I think caffeine-producing plants should win whatever the highest international award is for human psychology.

Dalya Rosner

How does DNA Fingerprinting Work?

People everywhere expected the new millennium to bring surprises. But the particular shock and horror that rippled through the international viticulture community in 2000 was most unexpected. It had been found that sixteen of the most highly prized varieties of wine-making grapes were the product of mating between the classic Pinot and the classically undervalued Gouais grape.

This blew the proverbial cork off the industry because the Gouais was considered such an inferior specimen that there were even attempts to ban its cultivation in France during the Middle Ages. This proves that humble origins can still produce superior quality. More practically, though, knowledge of their heritage allows improved breeding of highly desirable subspecies of grape. And viticulturists everywhere had DNA fingerprinting technology to thank.

DNA fingerprinting is a term that has been bandied about in the popular media for about fifteen years, largely due to its power to condemn and save, but what does it involve? In short, it is a technique for determining the likelihood that genetic material came from a particular individual or group. 99% of human DNA is identical between individuals, but the 1% that differs enables scientists to distinguish identity. In the case of the grapes, scientists compared the similarities between different species and were able to piece together parent subspecies that could have contributed to the present prize-winning varieties.

The DNA alphabet is made up of four building blocks – A, C, T and G, called base pairs, which are linked together in long chains to spell out the genetic words, or genes, which tell our cells what to do. The order in which these 4 DNA letters are used determines the meaning (function) of the words, or genes, that they spell.

But not all of our DNA contains useful information; in fact a large amount is said to be “non-coding” or “junk” DNA which is not translated into useful proteins. Changes often crop up within these regions of junk DNA because they make no contribution to the health or survival of the organism. But compare the situation if a change occurs within an essential gene, preventing it from working properly; the organism will be strongly disadvantaged and probably not survive, effectively removing that altered gene from the population.

Left - DNA fingerprints from 6 different people, 1 in each lane (column). DNA can be cut into shorter pieces by enzymes called "restriction endonucleases". The pieces of DNA can then be separated according to their size on a gel. Each piece of DNA forms a band (the white lines on the gel). The smallest pieces travel the furthest and are therefore clostest to the bottom of the gel. The larger pieces travel shorter distances and are closer to the top.

For this reason, random variations crop up in the non-coding (junk) DNA sequences as often as once in every 200 DNA letters. DNA fingerprinting takes advantage of these changes and creates a visible pattern of the differences to assess similarity.

Stretches of DNA can be separated from each other by cutting them up at these points of differences or by amplifying the highly variable pieces. ‘Bands’ of DNA are generated; the number of bands and their sizes give a unique profile of the DNA from whence it derived. The more genetic similarity between a person – or grape – the more similar the banding patterns will be, and the higher the probability that they are identical.

In the non-coding regions of the genome, sequences of DNA are frequently repeated giving rise to so-called VNTRs - variable number tandem repeats. The number of repeats varies between different people and can be used to produce their genetic fingerprint. In the simple example shown above, person A has only 4 repeats whilst person B has 7. When their DNA is cut with the restriction enzyme Eco RI, which cuts the DNA at either end of the repeated sequence (in this example), the DNA fragment produced by B is nearly twice as big as the piece from A, as shown when the DNA is run on a gel (right). The lane marked M contains marker pieces of DNA that help us to determine the sizes. If lots of pieces of DNA are analysed in this way, a 'fingerprint' comprising DNA fragments of different sizes, unique to every individual, emerges.

But why bother? After all, I know where my wine comes from – Tesco's, right? Well, there are many relevant applications of DNA fingerprinting technology in the modern world, and these fall into three main categories: To find out where we came from, discover what we are doing at the present, and to predict where we are going.

In terms of where we came from, DNA fingerprinting is commonly used to probe our heredity. Since people inherit the arrangement of their base pairs from their parents, comparing the banding patterns of a child and the alleged parent generates a probability of relatedness; if the two patterns are similar enough (taking into account that only half the DNA is inherited from each parent), then they are probably family. However, DNA fingerprinting cannot discriminate between identical twins since their banding patterns are the same. In paternity suits involving identical twins - and yes, there have been such cases - if neither brother has an alibi to prove that he could not have impregnated the mother, the courts have been known to force them to split child care costs. Thankfully there are other, less “Jerry Springer-esque”, applications that teach us about our origins. When used alongside more traditional sociological methodologies, DNA fingerprinting can be used to analyse patterns of migration and claims of ethnicity.

DNA Fingerprinting can also tell us about present-day situations. Perhaps best known is the use of DNA fingerprinting in forensic medicine. DNA samples gathered at a crime scene can be compared with the DNA of a suspect to show whether or not he or she was present. Databases of DNA fingerprints are only available from known offenders, so it isn't yet possible to fingerprint the DNA from a crime scene and then pull out names of probable matches from the general public. But, in the future, this may happen if DNA fingerprints replace more traditional and forgeable forms of identification. In a real case, trading standards agents found that 25% of caviar is bulked up with roe from different categories, the high class equivalent of cheating the consumer by not filling the metaphorical pint glass all the way up to the top. DNA fingerprinting confirmed that the ‘suspect’ (inferior) caviar was present at the crime scene.

In the example shown on the left, DNA collected at the scene of a crime is compared with DNA samples collected from 4 possible suspects. The DNA has been cut up into smaller pieces which are separated on a gel. The fragments from suspect 3 match those left at the scene of the crime, betraying the gulty party.

Finally, genetic fingerprinting can help us to predict our future health. DNA fingerprinting is often used to track down the genetic basis of inherited diseases. If a particular pattern turns up time and time again in different patients, scientists can narrow down which gene(s), or at least which stretch(es) of DNA, might be involved. Since knowing the genes involved in disease susceptibility gives clues about the underlying physiology of the disorder, genetic fingerprinting aids in developing therapies. Pre-natally, it can also be used to screen parents and foetuses for the presence of inherited abnormalities, such as Huntington’s disease or muscular dystrophy, so appropriate advice can be given and precautions taken as needed.

Dalya Rosner

Big Fish, Little Sea

Alongside their neighbours on coral reefs, few fish come close. They can even outsize turtles and sharks. With sad-looking lips and inquisitive eyes their faces are decorated with intricate blue-green scribbles resembling New Zealand Maori war paint, hence their other name is Maori wrasse. Napoleon wrasses are found on reefs across the Indian and Pacific Oceans and for my PhD I study them both on a pristine, remote atoll in the South China Sea and around the coral fringed coast of the northern Borneo.

Sadly it is becoming increasingly rare to catch a glimpse of the majestic Napoleon wrasse in the wild. You are more likely to see them swimming around tanks in expensive seafood restaurants in Hong Kong or Singapore. Since the 1970's it has become a prestigious delicacy to dine on large, colourful coral reef fish that are killed moments before cooking. The Napoleon wrasse is an especially favoured status symbol. A plate of their rubbery lips sells for 250 US dollars and a magnificent 40 kilogram specimen can cost as much as 10,000 US dollars.

Despite the high value of these fish, and the growing demand, very little is known about Napoleon wrasses, their biology, how they are exploited, and how remaining populations might be protected from extinction. But what is clear is that this big fish is in big trouble.

Various features of the Napoleon wrasse biology make them especially vulnerable to overexploitation. Like many other large animals they grow slowly and take years to reach maturity, which means populations take a long time to recover from even low levels of hunting.

Their mating system also predisposes Napoleon wrasses to being heavily fished. During each new moon they congregate to mate at specific locations on the reef. Like lions in the African savannah, each group of Napoleon wrasses has a dominant male who does most of the mating. He stakes out his territory, fiercely chases off intruding males and mates with the dozens of females that arrive. The timing of these spawning aggregations is highly predictable. In the population I study the females begin to arrive at 12.30pm, and everything is over by 3pm. The problem is that if fishermen learn the precise timing and location of these aggregations, then they too can lie in wait and catch many more fish than they would at other times by painstakingly hunting for these otherwise solitary fish.

The live reef fish market demands two distinct sizes of fish, both smaller "plate sized" individuals enough for a single diner, as well as outsized adults that will impress guests at a banquet. Either way this spells bad news for the wild populations of Napoleon wrasses. The smaller fish are juveniles, taken from the wild before they have had a chance to reproduce. As for the large fish, these are all males and their removal potentially leads to a serious female bias. This is because Napoleon wrasses start off life as females and undergo a sex change when they grow to a large enough size, but this takes time.

It seems that Napoleon wrasses just aren't cut out for high levels of exploitation and my data are backing this up. I have collected thousands of records of Napoleon wrasse sales from fisheries in northern Borneo going back for nearly ten years. Graphs show that the number and size of Napoleon wrasses caught by each fisherman has taken an unmistakeable and disheartening nosedive over the years. This suggests that there are few Napoleon wrasses left and fishermen are struggling to find them.

The sales records also show another very worrying trend. As the Napoleon wrasse become a rarity their status and exclusivity escalate so that diners are prepared to pay even more inflated prices. As prices are driven higher, so is the incentive for fishermen to catch the last remaining fish.

What can be done to help? As with most fisheries, there is no easy answer. Just like the blue fin tuna or North Sea cod, there is too much demand for too few fish. If the trade were to be banned, fishermen would lose their jobs, but when the fish have gone there will be no trade and no jobs.

There is however a glimmer of hope for the Napoleon wrasse. Not all countries that could trade in live Napoleon wrasses actually do so. The trade is banned in the Seychelles and the Maldives and licences are strictly regulated in Fiji. These and other countries are beginning to realise that by leaving Napoleon wrasses on the reefs they can gain from scuba diving dollars.

The question is who is prepared to pay most in the long run, diners or divers?

Helen Scales

Transposons: Spam from the Dark Ages

Pretty much everyone who has ever had an e-mail address will have come across "spam", that trickle (or flood) of unsolicited junk e-mail offering to sell you anything from viagra to a share in a dead dictator's fortune. Most of us just delete them with a touch of irritation at their clogging up of our mailboxes, and promptly get on with whatever we were doing.

But looking inside ourselves, we discover that this phenomenon pre-dates the internet, and even cave drawings and flint axes. Each cell in our bodies contains thousands of copies of "biological junk mail", except this kind is made of DNA instead of words and data packets. Indeed, while only 2% of our genome directly codes for the proteins that make up our bodies, over 40% of the remaining 'non-coding' DNA is filled with spam! What are these biological "junk mails"?

They are called transposable elements, or transposons, and are ubiquitous throughout life. They were first discovered by Barbara McClintock in 1944 when, noticing some unusual and changing colour patterns in the kernels of some maize she was studying, she hypothesised the existence of mobile genetic elements to explain the phenomenon (see figure 2, below). With the explosion of molecular biology, much more is now known about these jumping pieces of DNA.

There are two broad classes of transposable elements. DNA-based transposons, which are responsible for the colour changes in maize, move around the genome in a "cut-and-paste" fashion, literally cutting themselves out of their original location and inserting somewhere else. RNA transposons, or retrotransposons as they are also known, work differently. They are thought to originate from viruses that have inserted (integrated) themselves into the genome of a cell they have infected, where they lie dormant and are passively copied along with the host cell's DNA every time the cell divides. Over time, these "sleeping" viruses can mutate, just like any other part of the host's genome, and these mutations can lead to them losing their ability form new virus particles and infect new cells. However, they often retain, at least for a while, the ability to copy themselves, and these copies can, in turn, be inserted somewhere else in the host genome. So while DNA transposons "jump", retrotransposons "copy" themselves to new locations. This is illustrated in figure 3, below.

Figure 2 : Colour variations in maize caused by DNA transposons. A normal gene (Bz) gives maize kernels a dark colour (left), whereas a mutant version (bz) confers an orange colour (middle). If the gene is disrupted by a transposon (bz-m) this also results in an orange colour, but in some of the cells in the kernel the transposon has jumped back out of the gene, restoring its function, producing dark spots where this has happened (right).

So what is the point of all these jumping bits of DNA? Can we simply ignore them as a biological oddity, or is it important to understand them? Well, just like the spam we receive by e-mail or post, most of them sit harmlessly in a corner of our genome, but some copy themselves and jump to new locations in our DNA where they affect adjacent genes. In their new location they can disrupt a gene completely, or subtly change the way it exerts its effects in the cell. This can have both positive and negative consequences.

Transposons have undoubtedly been a source of genetic diversity throughout evolutionary time, providing raw material on which natural selection can work. For example, every one of our genes is under the control of another stretch of DNA sequence called a promoter which influences when the gene is turned on and off, and what at level it is expressed. Parts of transposons are known to behave like promoter sequencess and when they jump next to a gene these extra promoter segments can change the way the gene is regulated. If this change happens to be beneficial, it will be selected for in evolution. Indeed this seems to have happened frequently, and it is estimated that 25% of human promoters contain sequences originally from transposons.

In rare cases, single transposons may have had a profound effect on human evolution. The most common transposon in humans is called Alu. Alu elements are DNA transposons found only in primates and seem to have been most active between 30 and 50 million years ago. Researchers have noticed that Alu contains sequence which looks very similar to other parts of the human genome that are regulated by hormone-binding proteins. These are proteins which allow hormones to interface with our DNA, regulating whole sets of genes at once. If Alu's also have this property, then they may have caused widespread changes in the way genes respond to hormones when they jumped near active genes.

Our immune system may also owe a lot to the action of a particular transposon. Our ability to make antibodies to any microbe that infects us relies on a particular set of genes in the B cells of our immune system that can be shuffled around in near-limitless combinations. This means that with a relatively small set of "base" genes, our B cells can produce antibodies on demand against whatever infection we might be facing, without needing one gene for every possible antibody. However, this requires proteins that can "cut-and-paste" DNA to create these new combinations. We've seen this phrase before already … this is how DNA transposons move around! Scientists have found that the proteins that make our antibody-shuffling system possible, called RAG proteins, entered the genome of our ancestors on a DNA transposon around 450 million years ago. This allowed the jawed vertebrates to adapt their immune responses to each case of disease, a major improvement on the more limited innate immune systems present before.

Figure 3: DNA and RNA transposons move around the genome. DNA transposons cut themselves out from their original location, and insert themselves somewhere else in the genome. RNA transposons make a copy of themselves that inserts into a new location, leaving the original transposon intact.

Negative consequences of a transposon jumping into a gene are more likely though. Transposon insertion into a gene can scramble the coding sequence, producing a defective or truncated gene product with little or no function. It can also be detrimental in other ways. Even if it doesn't insert into the coding part of the gene, it can still cause problems, such as altering its regulation in dangerous ways by disrupting the promoter sequence.

Figure 4: Xenotransplantation - pigs are a potential source of organs. But when scientists transplanted pig organs into mice, they found that a porcine (pig) endogenous retrovirus, which had been dormant in the pig genome, reactivated and infected the mice.

With more and more genomes being sequenced, transposons can help reconstruct the tree of life. By looking at the pattern of transposons present in different organisms, and how they have mutated over time, inter-relationships between species can be inferred. For example, three ancient retroviral insertions are present in exactly the same places in the genomes of deer, giraffes, hippos and whales. This is just one piece of evidence linking whales to their land-dwelling ancestors.

Transposable elements can also be both a blessing and a curse when it comes to manipulating technology for our own benefit. On the plus side, they are seen as one of a number of possible vectors, or delivery systems, for use in gene therapy. If an efficient way could be developed to smuggle engineered transposons into live human cells in the body, they could be used to deliver healthy copies of a gene that is defective in a patient suffering from a genetic illness.

One area where they can present an obstacle is xenotransplantation, the use of animal organs for human transplants. Pigs in particular are seen as a promising source of donor organs. However, when scientists transplanted pig organs into mice, they found that a pig endogenous retrovirus, or PERV, which had been "sleeping" in its host, became active and infected the mice (it had not yet entirely lost its ability to jump to new cells). Though the mice didn't seem to suffer any symptoms, it would be considered too risky to try on humans without a better understanding of the consequences.

So it seems that transposons have gone hand in hand with life ever since there has been DNA to hitchhike on, and there is certainly no delete button for this particular brand of spam. For better or worse, it's here to stay. Now if we could just do something about all these junk mails...

Jamil Bacha

What is the purpose of sexual reproduction ?

SEX: A short word. Often used. Often used to sell products in fact. Yet it is one of our base instincts, one of our prime motivations in life. I can't remember how many times I chose a seat on the train because a good-looking girl sat nearby, or bought a magazine because of the attractive woman on the cover. So why do we find the opposite sex so attractive?

I mean, the act of sex itself is a pretty bizarre thing to do, all that jigging around and what about the mess? I mean we all look pretty hilarious whilst we do it (and the only reason they don't look daft in films is because they are not really doing it). If we didn't enjoy it so much would we really bother?

Would you go through all that if it weren't for the orgasm at the end? After all, there is a lot more to it than just the act of sex itself. There is the whole elaborate (and expensive) courtship display beforehand: the "asking her out", the "first date", a bit of food, a bit of wine, one thing leads to another... (Not on the first date, of course). Then there's the "I'd like to do this again sometime" and the 'should I call today, or wait a few days? I don't want to seem too keen'. Countered by "I'm washing my hair tonight". And so back to square one, until you get past the 'hair wash barrier'. Now you're in with a chance!

So basically we are all driven with a deep desire to mate and we will go through just about anything to achieve it (girls, the best time to ask a guy for that expensive treat is just beforehand). I remember all the embarrassing episodes that happened when I was a teenager. Many left me scarred for life, but none stopped my adolescent craving to 'go all the way'.

Propagation of Species.
So a lot of questions, Adel, but what point are you trying to make? Well, I'm trying to make the point that sex is meant to be all about propagation of species or more specifically, it is all about propagation of our genetic material. But is the theory that we are simply vessels for the propagation of genetic material a little simplistic? As I alluded to above, there is a lot more to finding a mate than simply sex. If passing on genetic material is what it is all about why don't we just clone ourselves? No mess, no fuss, just pure transmission of your own genetic material! Many primitive animals do it every day. Some do it several times a day!

Which begs the question is there an advantage to sex? The whole point of sex is to mix the genes in the gene pool allowing the transmission of 50% your own and 50% your partner's genes to your young. The point of mixing the genes is to allow for variation in the gene pool. As genes are mixed new combinations arise some are useful to the survival of a species, others are detrimental. Those that carry detrimental genes are disadvantaged at mating and are thus less likely to pass on those detrimental genes. In contrast, those that possess genes, which confer an advantage, are more likely to survive predators and beat their competitors in the race to find a mate, and their genes are more likely to be passed on. This is the basis of Darwin's theory of evolution and the mechanism by which it happens is termed Natural Selection.

Monogamy versus Polygamy
So if the whole point of sex is to mix up the gene pool why not have multiple partners rather than a monogamous relationship? Why are humans (generally) monogamous, are we the only creatures to spend the majority of our lives with one partner? Is that what puts us apart from other animals? Not so. Take love birds for example, they remain in lifelong monogamous pairs, but they seem the exception rather than the rule. In contrast, many animals belong to the 'sowing wild oats' school of thought, for example, the male chimpanzee often invites females to mate by typically spreading his legs to reveal a bright red, erect penis that stands out against the black scrotum. Not recommended behaviour down the pub on a Friday. Similarly, some human males are of the 'kebab theory of women': a great idea after ten pints down the pub, but you wouldn't want to wake up next to one every day. More seriously, creatures such as fish and especially sea urchins release their eggs and sperm into the sea and hope that some of each meet up and fertilise. Not strictly polygamy, granted. But if humans mated with numerous partners their genes would be spread further and as such, is monogamy not a disadvantage? The answer here may be quality not quantity. Monogamy in humans may have evolved because we need to nurse our young for many years before they become independent. A stable family life is important in order to make our offspring high achievers and thus attractive to other high achievers. In other words, by improving the quality of young we increase the chances of propagating our own genes successfully.

What's Love got to do with it?
OK. I've established we need sex and that for humans monogamy is preferred. So where does love fit into all this? Pah! I hear you say. "Love? That's not very scientific, is it? This essay is about the science behind sex, not the spiritual and mysterious nature of love.

"Aha!" I reply. But has love evolved to maintain monogamy? Those possessed by love will do many (often strange) things and unless you experience it yourself, one cannot explain how it can be an incredibly strong motivator. Arguably stronger than lust, and that's saying something! Many people have married 'the One', citing that they just knew it in their heart 'that was it'. Love is strong enough to keep couples together through thick and thin. 'All you need is love'. I wonder if there is some physiological basis to love? Perhaps it could be a balance of hormones that subtly affect our mental perceptions of our chosen partner versus other acquaintances. A little like the release of endorphins during pleasurable activity. But I suspect it is a higher cerebral function modified by social conditioning and cultural values. I'm no neuroscientist so I won't explore avenues I know little about.

What I want to argue is that the whole point of falling in love is a complex form of mate selection. A bit like the female peacock (peahen) that picks the peacock with the biggest and best-kept tail. As I hinted at before, it is women that are the choosy ones; the men are less so (driven by a deep desire to distribute their genes far and wide). So men need to attract women, and women need to choose a good husband and father. It is not something taken lightly and so love has evolved as a mechanism to secure a good mate and keep them together, at least until the kids have flown the nest.

The Evolutionary Arms Race
But why should we evolve? What's the point? Is there some spiritual force behind it all pushing species to evolve to perfection? Possibly, but it is not for the scientific method to explain matters in that way, that is for the philosophers to argue. One interesting theory raised in the book 'The Red Queen' is that sex has evolved as a protection against parasites. Daft, eh? Well, no. Let's break it down a little. Sex evolved to allow genetic variation. Genetic variation allows evolution to select the most hardy. Why do we need to be the most hardy. The answer is to beat infections, especially 'genetic infections': the viruses. A virus is a small collection of genes that hijacks cells to take over their machinery to reproduce. Cells evolved mechanisms to keep viruses out, the viruses struck back by evolving ways around these defences. Cells retaliate by creating new and better defences. So the arms race continues. Such models have been run through computers comparing sexual versus asexual species and how they cope with a parasite invader. In all cases, asexual populations were wiped out within a few generations whilst sexual populations survived.

Of course there are other theories, such as sex was useful millions of years ago to ensure survival and was something we've been stuck with since, a sort of evolutionary left over. But the parasite theory is one that has a very convincing basis.

Outstanding questions to think about...
Why do we only have two sexes? Why not three or more?
Why is our sex ratio 1:1?
Why are we not hermaphrodites (both male and female at the same time)?

Adel Fattah

What is Living in my Mouth?

The last time you opened wide, did you ever imagine that you were opening the door to what is essentially home to thousands of bacteria? Living inside your very own mouth! Yes, hundreds of varieties of critters, eating for free every time you visit your favourite restaurant. The ultimate uninvited dinner guest.

Many of these bacteria are fairly benign and exist in your mouth without doing any harm at all, but there are some that have the capacity to do some impressive damage.

In the interest of keeping your attention, I'll dedicate another chat to my favourite villains and their superpowers.

One particular kind of bacteria that is both common and relatively abundant among oral flora is the mutans streptococcus group. These common bacteria are particularly good at existing in the oral environment. When you eat carbohydrates, so do they, which is significant because these carbohydrates are metabolized into acid. This acid can lead to cavities in unsuspecting teeth. This acid works to demineralize teeth, stripping the outer enamel layer of it's strengthening minerals. This usually happens slowly over time as the demineralization front moves deeper into the tooth, through the outer layer of enamel, then even faster through the porous dentine* layer to the core or "pulp" of the tooth where nerves and blood vessels reside. Bacteria can then move through the extent of the carious lesion and may result in a necrotic pulp. Hello root canal!
(* - Think of dentine as a layer made of drinking straws in parallel embedded in plaster.)

So, the formula for cavities can be thought of as: acid-producing bugs + carbohydrates + teeth. But that's not the whole picture. There are many factors that determine an individual's susceptibility to cavities, or in dental-speak, "caries". They include the relative amounts of acid-producing, (acidogenic) bacteria**, how often carbohydrates are consumed, and the rate of salivary flow, to name just a few.
(** - Such as the Streptococcus mutans group of bacteria.)

Some individuals have the good fortune of having relatively low numbers of pathogenic bacteria, whereas others have gobs of them. This means their mouths are charged and ready to produce lots of acid when given the right fuel (carbohydrates). One interesting study examined a population in Africa that, based on their high mutans strep counts, would have been considered a high-risk group for caries. However, the incidence of caries in this population was disproportionately low because of their diet, which was free of simple carbohydrates.

But jumping on the Atkins bandwagon is not necessarily the answer! If carbohydrates are consumed, say, three times a day with each meal, then there are really only three major "acid-attacks" to worry about. However, sipping tea with sugar throughout the day and then sucking on a few sugary after-dinner mints means a multiplicity of fuel blasts for the acid-producing bacteria! Here, frequency becomes an appreciable problem if you have the right type and amount of bacteria in your mouth.

This frequency problem is often the culprit when a patient with low salivary flow rate presents with a mouthful of cavities. "Xerostomia", or "dry-mouth", can be a side-effect of prescription drugs, smoking, radiation, chemotherapy or result from some diseases. These individuals have less saliva sloshing around to rinse the surfaces in their mouth and wash the acidogenic bacteria and their carb-fuel away. The bacteria can stick around longer, colonize and expand their communities into an acidogenic machine!

To temper their xerostomia, patients may try drinking juices or sodas frequently throughout the day or sucking on candies or mints. Unfortunately, sugar is virtually ubiquitous and many patients end up exacerbating, rather than diminishing, their high caries-risk. Drinking sugar-free liquids frequently, enjoying candy and food with sugar-substitutes, and using a saliva-substitute (a gel-like slop or mouthrinse that can be applied to the inside of the mouth and lasts for hours) may be a better solution.

So wait a minute… who invited these bacteria anyway?

Figure 2: Next time you kiss someone, remember this image, which is an electron microscope close-up of the chains of bacteria (cocci) that live on your teeth.

A newborn's mouth is initially sterile, but can become home to new flora as they pass through the birth canal (I'm not going to pretend I'm not grossed-out by this), get kissed by bacteria-laden relatives, and put their fingers, toes, objects galore, into their mouths (see references 1,2,3 below). One study examining the pattern of infectivity of common acidogenic bacteria from mother to child found that there may even be a "window of infectivity". The bacteria studied colonized the child's mouth at a median age of 26 months (reference 4, below).

Oral bacteria differ among sites in the mouth, even among sites on the same tooth, and the flora shifts as the infant begins to sprout teeth at around 6 months. There is a change in structural environment as hard tissues are exposed (tooth enamel) and bacteria that welcome the change can expand and proliferate in this new environment. Other bacteria that enjoyed the gummy environment may decrease in number and the population balance shifts.

How do these bacteria stick around with spit sloshing around and a big muscular tongue?

The resident microbes don't work alone. Together they form a biofilm, aka plaque, which begins with the interplay of electric charges. Certain bacteria can "stick" to oral structures through electrical interaction. Once their anchorage is established, they can bind to other bacteria floating around in the mouth through interesting appendages similar to the tentacles of an octopus. As this web of interacting bacteria builds, it's capacity to hold more bacteria increases and the plaque thickens as more microbes are added. Disrupting this biofilm with food, saliva, a toothbrush and floss is critical in dismantling the microbial community's ability to proliferate and harm teeth and gums. Floss becomes especially important since some sites are more protected than others from mechanical removal, such as between the teeth and along the gumline.

These bacteria are not your friends! They eat your French rolls without your permission! I suggest you blow them away with a nice toothbrush and floss.

Christa Favot

Herpes Simplex Viruses: Cold Sores and Genital Herpes

Most people have heard of Shakespeare's 'Romeo and Juliet', and the majority know that it is a tragedy based on a love story, but you could probably be forgiven for missing the subtle reference it contains to one of mankind's most common infections:

O'er ladies ' lips, who straight on kisses dream,
Which oft the angry Mab with blisters plagues,
Because their breaths with sweetmeats tainted are:
Act 1. Scene IV

The blisters that Shakespeare refers to are in fact cold sores produced by the herpes simplex virus (HSV) which comes in 2 types, HSV-1 and HSV-2. Type 1 herpes is carried by over 80% of the population; it's the culprit responsible for causing recurrent cold sores, and most people pick it up in the first few years of life, usually in the form of a loving kiss from a parent or sibling. HSV-2, on the other hand, affects between 5 and 10% of the population (including many individuals who are also infected with HSV-1), and is more often associated with genital herpes, although either virus can cause a similar disease at both anatomical sites.

Part of the reason that herpes infections are so common, and so easy to transmit, is that up to 30% of people previously infected with HSV go on to periodically shed the virus in their saliva or genital secretions (depending upon the site of infection) without suffering any symptoms. These individuals are known as 'asymptomatic shedders' and can transmit the infection to other susceptible individuals but without showing any obvious signs of the disease themselves.

Shedding, and recurrent lesions, occur because once a person is infected with herpes they carry the virus for life. This is because HSV has evolved a clever strategy, called latency, that enables it to escape from the immune system by hiding inside nerve cells. Then, in about 15% of people carrying it, the virus periodically reawakens producing recurrent, painful, infectious sores on the affected part of the body.

The herpes virus itself (left) consists of a tiny particle one five-thousandth of a millimetre across. It's so small that 100 million of them could fit on a pinhead. Each particle consists of a core, containing the viral DNA, wrapped in a protein-studded coat known as the envelope. These proteins are the viral equivalent of velcro and help HSV to lock on to, and invade, its target cells. Viruses are the ultimate parasite and comprise little more than infectious packets of genes. To reproduce they hijack healthy cells and turn them into viral production lines that churn out millions of new viral particles, which is how the infection spreads.

WHAT HAPPENS WHEN YOU ARE FIRST INFECTED WITH HSV ?
The first time someone encounters HSV, known as primary infection, they don't develop a classic cold sore like lesion, which is why many people often don't realise that they have been infected. Instead, most cases of primary herpes affecting the face present with a nasty sore throat, a sore mouth (which can occasionally ulcerate), swollen neck glands, and a temperature. Similarly, primary infection in the genital region usually produces a painful, red, ulcerating crop of lesions that can spread over a wide area and may involve the perineum and anus. Genital infection can also be associated with temporary numbness in the affected area, swollen glands in the groin, difficulty passing urine, and a temperature. Occasionally, primary infections such as these can also trigger viral meningitis.

WHY HSV INFECTION LASTS A LIFETIME
As HSV spreads through infected tissues it also penetrates nerve fibres which inadvertently provide the virus with the neurological equivalent of a getaway car. Indeed, as the immune system moves in to control the infection, the virus conceals itself within nerve cells and slips away from the scene by hitching a ride on a special transport system that nerves use to move materials from one end to the other.

In this way the virus is carried to the nerve 'cell body' in a swelling called a ganglion located close to the spinal cord. In the case of infection on the mouth or face this ganglion is known as the trigeminal ganglion, and in the case of genital herpes the 'sacral' ganglia are involved. When it reaches the cell body, the viral DNA is added alongside the nerve cell's own DNA in the nucleus. It remains there, hidden within the nerve cell and in an inactive state, for the lifetime of the infected individual. The purpose of this process is to provide a reservoir of virus within the body which can periodically be 'reactivated' to spread the infection to other susceptible individuals.

SO WHAT CAUSES YOU TO DEVELOP A COLDSORE ?
A number of things can trigger the virus to reactivate including being stressed or run down, menstruation, drugs that suppress the immune system, and skin damage including burns caused by the sun, heat, or chemicals.

In some way these 'stimuli' reawaken the virus and it begins to make new particles from the recipe stored in the viral DNA hidden in the nerve cell. These newly-assembled viral particles are then shipped back down the nerve fibre to the region of the skin that it supplies - for instance around the lips. The virus 'buds off' from the nerve ending and infects the surrounding epithelial (skin) cells, producing a painful cluster of pale blisters which are crammed with herpes simplex virus and highly infectious.

When this process first begins to happen, and before the blisters appear, most people notice a mild tingling sensation on the patch of skin supplied by the affected nerve cell. Soon after they form the blisters break open, releasing their infectious cargo, leaving a red raw patch - the cold sore - which measures about half a centimetre across and takes about 7 to 10 days to heal up.

How often the virus reactivates varies from one person to the next but, as a general rule, recurrences tend to occur most often during the year following infection, and then they tail off.

Significantly, cold sores and genital lesions remain infectious until they have crusted over, so contact should be avoided during this time because the virus can be transmitted to other parts of the body, and to other people, especially between the mouth and the genitals. Cold sores and genital lesions also create a breach in the skin's natural defences, producing portals of entry for other infections, like HIV, so extra care should be taken to minimise the risk of any exposure.

Between 5-20% of the population of western countries are affected by genital herpes, and the prevalence is increasing, making this one of the commonest sexually transmitted infections. Traditionally, most genital infections were caused by HSV-2, but more recently there has been a large increase in the number of cases caused by HSV-1, mainly due to changing sexual practices, and particularly oral sex.

COMPLICATIONS OF HERPES INFECTION
Apart from cold sores and genital disease, herpes simplex viruses can also cause more serious infections, although fortunately these are relatively rare.

The most important are HSV meningitis (a form of aseptic meningitis), HSV encephalitis (HSV infection of the brain), neonatal herpes (HSV infection in the newborn acquired from the mother around the time of birth), corneal ulceration, scarring, and visual impairment following eye infection, and more severe generalised infections amongst those with weakened immunity. Such patients include people with HIV, and those on immunosuppressive drugs (for instance transplant patients), who tend to suffer worse recurrent disease, and are also more likely to develop drug-resistant forms of the virus.

DIAGNOSIS
Herpes affecting the face (orolabial herpes) is usually diagnosed clinically - that is, the diagnosis is made solely on the basis of the symptoms. But in the case of suspected genital herpes, HSV affecting the eyes, or more severe skin outbreaks, it can be useful to confirm the diagnosis by means of a variety of laboratory tests which are outlined below.

Traditionally, herpes infection is confirmed by taking a swab from an active lesion, growing the virus in the laboratory, and then using colour-coded antibodies to pinpoint whether HSV-1 or HSV-2 is the culprit. This method can be useful in confirming the presence of asymptomatic shedding of the virus.

Another way, which is faster but yields less information, is to use an electron microscope to look for viral particles in fluid collected from the blisters.

More recently, however, many laboratories have moved to using a highly accurate DNA test which can rapidly pick up the presence of the virus in a sample, and at the same time tell whether it is HSV-1 or HSV-2. This approach is particularly useful in the diagnosis of viral meningitis, or encephalitis, caused by herpes infection. In these instances a sample of cerebrospinal fluid (CSF), the watery substance that bathes the brain and spinal cord, is collected by lumbar puncture, and analysed.

Doctors also sometimes take a blood sample, particularly in people with a history of possible herpes infection but no active lesions, in order to look for herpes antibodies. The benefit of this kind of blood test is limited, but it can sometimes be used to confirm whether a patient has been infected with herpes previously, and which type of virus they are carrying.

MANAGEMENT
Herpes causes a lifelong infection and there are currently no treatments capable of removing the viral DNA from the nerve cells that carry it. This means that treatment focuses on reducing the intensity of a primary infection, and the frequency and severity of subsequent viral reactivations.

COLD SORES
Prevention :
If you are prone to cold sores try to avoid the things that trigger recurrences - - When skiing or sunbathing use high-factor sun creams to avoid sunburn.

• Try to avoid becoming run down.
• Eat a healthy diet including plenty of fresh fruit and vegetables.

Treatment :
Uncomplicated orofacial herpes (cold cores) responds well to topical aciclovir cream (Zovirax), which is available over the counter. It is extremely safe (including during pregnancy) and can reduce the duration and severity of a recurrence. It should be applied as soon as the tell-tale symptoms heralding a cold sore appear. Warning signs usually include localised pain, or a tingling sensation on the lip. But remember, cold sores remain infectious until they have crusted over.

GENITAL HERPES
Genital infection with HSV also places partners and babies at risk, meaning that appropriate counselling, contact tracing, and exclusion of other co-existent infections play an important part in the management of this condition. For this reason, patients with genital herpes should be referred to a genitourinary (GU) medicine clinic for appropriate investigation and follow up. With any sexually transmitted disease it is always important to exclude the presence of other infections which may have been picked up at the same time as HSV, especially chlamydia which is very common, highly infectious, often symptom-free, and (left untreated) can lead to infertility.

Prevention :

• Always use barrier methods of contraception (e.g. a condom).
• If you have a partner with known genital herpes, try to avoid intercourse whenever they experience a recurrence.
• Avoid oral sex when you, or your partner, have a cold sore - the virus is readily transmitted from the mouth to the genital area, and vice versa.
• Like cold sores, genital lesions remain infectious until they have crusted over.

Treatment :
Initial (primary) infection with genital herpes can be extremely painful and very distressing, but prompt presentation to a doctor can help through the administration of antiviral drugs, and pain relief.

General measures to reduce discomfort :

• Bathing with saline - soaking the affected area in salt water can reduce pain.
• Analgesia - simple painkillers such as paracetamol provide effective relief.
• Topical anaesthetics - these can be very effective but should be used carefully owing to the risk of potential sensitisation to the agent.

ANTIVIRAL DRUGS
The drugs aciclovir, valaciclovir and famciclovir have all been shown to be effective at reducing the severity and duration of infection and, in general, they are more effective the earlier they are started. Ideally they should be introduced within 5 days of the start of the episode and continued for at least 5 days, or while new lesions are forming, whichever is the longer. On the grounds of cost, oral aciclovir is usually the drug of choice.

These antiviral drugs work by blocking the ability of the virus to copy its DNA, preventing it from growing. The agents themselves are active only in virally-infected cells, so healthy cells are not affected.

The drug molecules resemble one of the building blocks used to make new DNA but, critically, they lack a certain chemical group which is required for a DNA chain to continue growing. So when the virus inserts one of these drug molecules into its DNA, the DNA chain is prematurely terminated, stopping the virus from growing.

In general, oral agents are extremely well tolerated, have few side effects, and are more effective than topical agents. Trials have also shown that combining oral and topical medications is no better than oral medication alone.

IMMUNOCOMPROMISED PATIENTS
Patients with HIV, or other immune-disabling conditions such as organ-transplant recipients, are at increased risk of developing severe (and sometimes life-threatening) infections. They should receive prompt antiviral therapy which should be continued until fresh lesions have stopped appearing, and the existing lesions have crusted over. Lesions which are not responsive to therapy might be due to drug-resistant forms of herpes. Under these circumstances it may be necessary to switch to another class of antiviral drugs, and to collect samples of the virus for drug susceptibility testing.

RECURRENT GENITAL HERPES
Most HSV recurrences occur in the year following infection, and then the frequency of reactivation tends to tail off. But for some patients recurrences remain a problem and they may require regular use of antiviral agents.

For patients with infrequent herpes reactivations the condition can be controlled effectively by using oral antiviral medications, chiefly aciclovir, whenever they experience a recurrence. When used in this way, known as episodic therapy, antivirals have been shown to reduce the duration of symptoms by 1-2 days, and the clinical severity of the outbreak.

But patients with more frequent recurrences (6 or more per year) often benefit instead from 'suppressive therapy', which means taking antiviral medications every day to prevent the virus from producing clinical symptoms. In other words, whenever it tries to reactivate, the virus is immediately switched off by the antiviral agent. Again, aciclovir, valaciclovir, and famciclovir have all been shown to be effective at preventing recurrences, but this course of action must be balanced against the inconvenience and costs of taking regular medication. Again, on cost-grounds, aciclovir is usually the agent on choice.

Most doctors advise stopping suppressive therapy after a year in order to re-assess the activity of the disease, and to reduce the risk of developing viral resistance to the antiviral drugs. Because the clinical course of the condition varies between patients, treatment is tailored to the requirements of the individual, and based upon the severity and frequency of their symptoms.

GENITAL HERPES IN PREGNANCY
Genital herpes can be dangerous for the newborn, but the risks can be minimised by careful medical management. All women who develop new genital herpes during pregnancy should be referred to the genitourinary medicine clinic in order to exclude the possibility of other infections, and for advice on treatment. Aciclovir has been used extensively during pregnancy, it is well tolerated, and in over 20 years of use there have never been any reports of foetal toxicity or birth defects. It is not contraindicated in cases of primary genital herpes occurring during pregnancy.

All women with first-episode genital herpes lesions at the time of delivery are advised to deliver by caesarian section because the risk of transmitting the infection to the newborn under these circumstances is 40%. But caesarian is not recommended for women who contract HSV during the first or second trimesters, or for women with a past history of genital herpes but without any signs of recurrence, because the local infection will have cleared by the time of delivery, and protective antibodies will have been produced against the virus. These antibodies will be passed to the developing baby before it is born, greatly reducing the risk of transmission. The baby should, however, be monitored closely when it is first born for any signs that it may have picked up the infection, in which case treatment with intravenous aciclovir should be started immediately.

EYE INFECTIONS
Herpes infection involving the eye usually presents as single, sore, red eye which is extremely sensitive to the light. Often the virus attacks the cornea producing a dendritic ulcer which doctors can see by adding some coloured drops and examining the eye with a slit lamp. If these ulcers are allowed to recur (like the ocular equivalent of recurrent cold sores) they can lead to corneal scarring, opacity, and blindness. They should be treated aggressively with pain relief and aciclovir (or a topical equivalent), which can also be used to prevent recurrent lesions.

MENINGITIS AND ENCEPHALITIS
HSV can occasionally trigger aseptic (viral) meningitis. Patients usually complain of a severe headache, neck stiffness, nausea, fever, and a dislike of bright lights. Unlike meningitis caused by a bacterial infection there is usually no skin rash. Anyone with these symptoms should see a doctor urgently. Cases of HSV meningitis usually resolve rapidly with intravenous aciclovir therapy, and without long term consequences.

A very rare manifestation of HSV is encephalitis in which the brain tissue itself becomes infected by the virus. There are very few warning signs, but patients with encephalitis tend to become confused and drowsy. Without prompt treatment with intravenous antivirals (usually aciclovir) the condition is often fatal, and even when treated rapidly often causes long term neurological problems including memory loss and epilepsy.

ON THE HORIZON
Scientists are currently trying to identify the chemical signals responsible for providing the wake up call which causes the latent (inactive) viral DNA to reactivate and produce recurrent disease. Pinpointing these cellular messengers, or the means that the virus uses to detect them, would provide scientists and drug manufacturers with new targets to aim at in their search for novel antiviral agents capable of preventing reactivation, shedding and transmission of herpes infections.

But with no solution presently on the horizon, we will just have to cross our fingers, and possibly our legs, and hope that the answer is not too far away.

Chris Smith

Bio-plastics: Turning Wheat And Potatoes into Plastics

In the past, fields of wheat and rows of potatoes were seldom destined for anything more than a rumbling tummy. But bio-products have come a long way since people first branched out into weaving hemp into clothes and pulping papyrus into scrolls. Today the line between Mother Nature and man made has never been more blurred. Animals are re-engineered into living drug factories, crops fuel our cars and now plants are increasingly being repackaged as the epitome of the synthetic world – plastic. Wheat, maize, vegetable oils, sugar beet and even the trusty spud are finding new life as water bottles, car fuel lines and laptops.

Wheat, maize, vegetable oils, sugar beet and even the trusty spud are finding new life as water bottles, car fuel lines and laptops.

Bio-plastics harness the natural structures found in crops or trees, such as slightly modified forms of the chains of sugars in starch or cellulose, that share the ability to be easily reshaped that has made conventional oil based plastics so useful. Bio-materials scientists are also constantly tweaking these natural structures to try and better replicate the durability and flexibility of conventional plastics.
Global business is now turning to bio-plastics for an increasing number of applications, as consumers and governments demand cleaner alternatives to petroleum based technologies and their reckless production of the greenhouse gas CO2.

Worldwide players, such as DuPont and Toyota Motor Corp, are making vast investments in new technologies and processing plants with the hope of cornering a multi-billion pound industry.

The "BC" at Bangor University in North Wales has 18-years experience of working with large companies and Non-Governmental Organisations (NGOs) to find sustainable and viable bio-based alternatives to man-made materials.

BC director Paul Fowler points out that “practically anything that you can find as polyethene you can find as a bio-plastic. You are talking about a whole range of everyday products - cups, combs and wrappers, everything you can think of is out there. There are inroads being made all the time - on the one hand there is research into trying to get biological alternatives to replicate the properties of conventional plastics and on the other hand people are looking at the natural properties of these plants and trying to find an application for them. Most of the manufacture is happening in the US and continental Europe. The UK is a producer of wheat starch and biotimber but the only major bioplastic producer is Innovia Films in Cumbria, which produces cellulose films.”

Innovia Films has an annual turnover of £400m, employing 1,200 people worldwide and producing more than 120,000 tonnes of film – used in packaging to protect food. Japan is also forging ahead, from the leading role in bioplastic production played by Toyota to its recent passing of a triumvirate of laws pushing forward environmental initiatives.
In South Korea too there is a rapid drive to replace conventional plastic packaging with polylactic acid bio-plastics.

Fowler says bio-plastics also offer an opportunity to get a double return for the energy used in their manufacture – first as a useful item and secondly as a fuel source. “My view is that we should burn them at the end of their life to recover energy, which could be then used to produce new materials,” he said. “In the first instance you have a valuable resource can use, be it as packaging or a shopping bag, and then you are also getting some energy back at the end of it. The biggest advantage of such bio-materials is the reduction of CO2 emissions in their production over petrochemical-based plastics.”

He also suggests that burning bio-plastics would also avoid the problems caused by them breaking down and producing methane, which is 25-times more potent as a greenhouse gas than CO2.

The BC is currently looking at developing naturally-derived alternatives to phthalates, which are plasticisers added to PVCs to make them more flexible in products such as electrical cable flex. It follows concerns that phthalates are metabolised in the body into substances that can mimic the body's own hormones, including those concerned with fertility. The centre is also developing bio-resins, natural alternatives to synthetic resins such as phenol and formaldehyde.

What types of bioplastic are there?
The common types of bio-plastics are based on cellulose, starch, polylactic acid (PLA), poly-3-hydroxybutyrate (PHB), and polyamide 11 (PA11). Cellulose-based plastics are usually produced from wood pulp and used to make film-based products such as wrappers and to seal in freshness in ready-made meals.

Thermoplastic starch is the most important and widely used bioplastic, accounting for about 50pc of the bio-plastics market. Pure starch’s ability to absorb humidity has led to it being widely used for the production of drug capsules in the pharmaceutical sector. Plasticisers, such as sorbitol and glycerine are added to make it more flexible and produce a range of different characteristics. It is commmonly derived from crops such as potatoes or maize.

FOMA(TM) N701iECO phone made of PLA bioplastics reinforced with kenaf fibres developed by NEC, UNITIKA and NTTDoCoMo © Paul Fowler

PLA is a transparent plastic whose characteristics resemble common petrochemical-based plastics such as polyethylene and polpropylene. It can be processed on equipment that already exists for the production of conventional plastics. PLA is produced from the fermentation of starch from crops, most commonly corn starch or sugarcane in the US, into lactic acid that is then polymerised. Its blends are used in a wide range of applications including computer and mobile phone casings, foil, biodegradable medical implants, moulds, tins, cups, bottles and other packaging.

PHB is very similar to poylpropylene, which is used in a wide variety of fields including packaging, ropes, bank notes and car parts. It is a transparent film, which is also biodegradable. Interest in PHB is currently very high with companies worldwide aiming to expand their current production capacity. There are estimates that this could lead to a price reduction below five euros per kilogram but this would still be four times the market price of polyethylene in February 2007. The South American sugar industry has commited to producing PHB on an industrial scale.

PA 11 is derived from vegetable oil and is known under the tradename Rislan. It is prized for its thermal reistance that makes it valued for use in car fuel lines, pneumatic air brake tubing, electrical anti-termite cable sheathing and oil and gas flexible pipes and control fluid umbilicals. These are often reinforced with fibres from the kenaf plant, a member of the hibiscus family traditionally used to make paper, to increase heat resistance and durability.

At the cutting edge of bioplastic technology lie polyhydroxyalkanoate (PHA) materials. These are derived from the conversion of natural sugars and oils using microbes. They can be processed into a number of materials including moulded goods, fibre and film and are biodegradable and have even been used as water resistant coatings.

What are the benefits of bio-plastics?

- Reduced CO2 emissions.
One metric ton of bio-plastics generates between 0.8 and 3.2 fewer metric tons of carbon dioxide than one metric ton of petroleum-based plastics. Electronic giant Sony uses PLA in several of its smaller components, including one of its new walkmans, but in future hopes to use PLA-based polymers to reduce its carbon dioxide emissions by 20pc and non-renewable resource input by 55pc compared to oil-based ABS.

- Rising oil prices
Despite currently costing more to produce than conventional plastics bio-plastics are becoming more viable with increasing and instability in oil prices, which are in turn triggering spikes in conventional plastic costs, illustrated in a sharp upturn two years ago. Dwindling oil supplies means that man will eventually be forced to turn to a sustainable basis for plastics.

- Waste
Bio-plastics reduce the amount of toxic run-off generated by the oil-based alternatives but also are more commonly biodegradable. The US’s second largest biopolymer producer Metabolix, of Cambridge, Massachusetts, claims that its plastics are biodegradable in composting bins, wetlands and the oceans. On the flip side not all bio-plastics are biodegradable and there are a growing number of conventional plastics that can naturally break down. The downside of their biodegradability is the methane that can be released as the bio-plastics decompose is a powerful greenhouse gas.

- Benefit to rural economy
Prices of crops, such as maize, have risen sharply in the wake of global interest in the production of biofuels and bio-plastics, as countries across the world look for alternatives to oil to safeguard the environment and provide energy security.

- Enhanced properties
In some fields engineered bio-plastics are now beating oil-based alternatives at their own game. Multinational materials giant Arkema has produced a form of Rislan PA11 that is being used in Europe and Brazil in fuel lines to carry biofuels as it is better able to withstand the corrosive effects of biofuels than oil-based alternatives such as polyamide 12. Rislan is widely used in oilfield applications as well as automotive brake lines. Elsewhere innovations in PA11 production are helping increase car passenger safety and reduce the risk of accidents by inhibiting spark ignition in the fuel lines. US car giant General Motors has replaced its non-conductive fuel-pump modules for new North American car models as it felt it was the best material for the job. In the US chemical multinational DuPont says it has developed a bioplastic derived from corn sugar that has superior stiffness and strength to its naturally based competitors. Global electronics corporation NEC has produced a kenaf-reinforced laptop casing, made of 90pc PLA, which helps reduce overheating by conducting heat better than stainless steel coupled with high temperature resistance and increased strength.

Who are the flagwavers?
Bio-plastics are not being produced by a group of hippies brewing up in their garage. Some of the world’s largest companies including multi-billion dollar chemicals company DuPont, car manufacturer Toyota, UK-based Innovia, US food processing behemoth Cargill and electronics giants NEC and Fujitsu are pouring money into driving the technology and production forward.

NEC and its partners Unitika and NTT DoCoMo produce mobile phone and laptop casings based on plant-derived bio-plastics, mostly PLA. NEC plans to expand its green credentials by substituting more than 10pc of the oil-based plastics in its electronic products with bio-plastics by 2010.

Toyota Motor Corp uses mainly PLA bio-plastics, derived from sweet potatoes corn and sugar beet, reinforced with kenaf to produce components for its cars such as the Prius and Lexus. It hopes to grow its bio-plastics division into a four billion yen business by 2020 and capture two thirds of the global market for petroleum free plastics.

Fujitsu introduced its FMV BIBLO notebook PC series two years ago, which it has manufactured using a material called Ecodear, a combination of 50 pc PLA and an oil-based plastic. Fujitsu is now developing a castor oil derived PA 11 plastic with Arkema, which is more flexible and will help expand its use of bio-plastics in notebook computers. The material can withstand repeated bending thanks to scientists weakening the interaction of the chain molecule in PA 11 and relaxing the stereoregularity of their organisation. The improved durability means its prototypes of PC cover components consist of 60-80 percent of the new bioplastic, an unprecedented achievement to date. Fujitsu is also using high density fillers to increase strength and extend its use into notebook covers and other applications requiring high impact resistance. The new material is expected to cut carbon dioxide emissions by 42pc compared to oil-based nylon 6/6.

DuPont in particular is continuing to expand the market for bio-plastics and plans to continue to offer hybrid bio/conventional plastic materials until the market matures, which could eventually cost less than the oil-based alternatives. DuPont has teamed up with sugar giant Tate & Lyle to build the world’s largest aerobic fermentation plant in Loudon in Tennessee in the US for the production of bio-PDO, with a capacity of 45,000 metric tonnes a year.

The largest commercial producer of bioplastic in the US is NatureWorks, owned by Cargill. The company’s plant in Blair, Nebraska uses corn sugar to produce PLA plastics packaging material and its own Ingeo-brand fibres.

What lies ahead?
With US President George Bush’s recent pledge to produce 35 billion gallons of renewable and alternative fuel by 2017 - driving the price of maize up 60pc in the past two months - the farmer’s field is fast turning into a high tech bio-battleground.

Mr. Fowler warns that the still fledgling industry will have to fight for space and commercial viability as millions of hectares are given over to corn, rapeseed and sugarbeet for bio-fuel production. "There is a real tension between the use of agriculture for fodd versus plastics and other non-food uses and this whole move to produce new fuels," he said. Whereas only two years ago plant materials were at the cheap end of the market and bio-products such as straw had little value, now it is really much more costly. There would have to be a step change in the extent of the production to match oil-based plastics. The amount of bioplastics produced worldwide is less than 200,000 tonnes a year; contrast that with the more than 30 million tonnes of oil-based plastics. You can see we have a long way to go before they replace conventional plastics".

Nick Heath

Biomimetics: Borrowing from Biology

The idea of looking to nature for inspiration is a notion perhaps most notably associated with the arts, particularly painting and poetry. But Mother Nature isn't a muse exclusive to the artist; she can also inspire scientists, engineers and industrialists.

Nor is the concept of borrowing from biology new to us. More than 3000 years ago the Chinese craved a synthetic silk, and more recently the Wright brothers based the designs for their planes on birds' wings. George Mestral grasped the concept for his invention, Velcro, from the burrs that stuck to his dog’s coat, and the unique, super-efficient cooling system of the Eastgate Centre in Harare, Zimbabwe, is modelled on the system of ducts and passages used by termites to maintain a constant temperature in their mounds. It's on these foundations that the field of biomimetics has been built, and over the last 15 years it's gained momentum rapidly.

Also known as biomimicry and bionics, biomimetics can be defined as "the abstraction of good design from nature" and came about when engineers and medical researchers realised that many of the answers they sought were already available in nature. For example, why spend many years and colossal amounts of money trying to design a new building material from scratch when the chances are there is something in nature that can already do most of what you want? Better still it's likely to have been refined to near perfection during millions of years of evolution.

So, with a little ingenuity and some modifications, a once challenging problem can be elegantly resolved. Exploiting nature and avoiding the pitfalls that have already been ironed out by evolution is precisely what Thomas Speck of The University of Freiberg did when designing the "Technical Plant Stem", a novel material combining features from the stems of the giant reed (Arundo donax) and Dutch rush (Equisetum hyemale).

Inspired by the observation of these plants standing tall, swaying in the wind and yet never appearing to break, this new material combines both stiffness and elasticity with a resistance to breakage and has the potential to be used in the fabrication of a wide range of applications from building materials to snowboards.

This relatively new scientific field of Biomimetics is especially interesting as it brings together researchers from all disciplines to generate solutions to a vast array of problems and appears to be limited only by the imaginations of those involved.

Geckos, glue and sticky tape
Geckos are amazing creatures with the ability to walk up the smoothest of surfaces and even on ceilings, but quite how these lizards achieve their adhesive properties eluded scientists for a long time. One suggestion was that, just like cartoon villains with suction cups strapped to their hands and feet, the geckos used suction to adhere to walls. This was ruled out when these sticky little creatures were still able to cling on tightly in a vacuum. Instead, since even the smoothest of surfaces have microscopic undulations, it was suggested that the geckos used friction to climbs walls, but this couldn’t explain why they are able to walk on ceilings. Another hypothesis was that, like the cockroach, they exuded a glue-like substance from their feet, but this was not possible as their feet are dry and free from the glands required to excrete such a substance.

The answer to this conundrum came about in 2000, when Professor Full and colleagues at UC Berkley looked more closely at the toes of the Tokay Gecko (Gecko gecko). They discovered that each of the gecko’s toes were covered in thousands of tiny "nano-hairs", called setae, each less than one tenth the thickness of a human hair. At the end of each seta were hundreds to thousands of minute mushroom shaped structures called spatulae. The gecko’s super adhesive abilities are achieved because these minuscule structures allow the geckos feet to get so close to the surface, such as a wall, that the molecules of the spatulae and the surface are able to interact electrically. This generates tiny forces, known as van der Waals attractions, that lock the two surfaces together. Although individually they are extremely weak, with billions of molecules interacting with each other the combined force is more than ample for the Gecko to stick to pretty much any surface. If your own hand had the same sticking power, it would be able to hold about 40kg.

Once the mystery of the sticky footed gecko had been solved, the applications of this knowledge to technology were rapidly realised. Within three years a group of scientists from the University of Manchester, lead by Professor Geim, had produced a sticky tape that consisted of microscopic hairs of polyimide which mimicked a gecko’s toes. This sticky tape was believed to be as effective as the real thing, and the researchers were not short of offers from Spiderman wannabes who volunteered to be hung from the lab window by the tape. Unfortunately, the would-be spidys' dreams were never realised, mainly because of the lengthy and expensive process used to produce the tape.

	100g. This toy has been attached to several surfaces before this photo was taken." style="border: medium none ; padding: 0px; width: 202px; height: 356px;" title="Spiderman toy hanging from a glass plate, attached using the tape with a contact area of approximately 0.5cm2 with a carry load of >100g. This toy has been attached to several surfaces before this photo was taken © Andre Geim, University of Manchester">
Figure 1a: Scanning electron microscope image of a 1cm2 section of the Gecko-sticky tape.	Figure 1b: Spiderman toy hanging from a glass plate, attached using the tape with a contact area of approximately 0.5cm2.	Figure 1c: Bunching of the hairs is a problem that reduces the adhesive properties of the tape.

In 2006 BAE systems announced that they were able to generate a gecko-like adhesive using a modified version of photo-lithography, the method used to make silicon chips, that was economically viable and easy to scale-up. This super-adhesive was made using polyamide, like nylon, and like the design from Manchester consisted of mushroom shaped structures. While not as sticky as the gecko’s feet, it could quite comfortably stick an elephant to the ceiling, should you have any call to do so! However, unlike conventional adhesives, the gecko-inspired substance can be reused, easily peeling from the surface to which it was stuck, meaning that a Spiderman suit is now a possibility and no doubt likely to appear on a great number of childrens' (and adults') wish lists. The other advantage is that it doesn’t leave any sticky residues behind, so no more patches of blue fluff where something was once stuck. But there are still advances to be made, and the scientists involved hope to make this adhesive even stickier, so for now we’ll just have to wait and stick to using ladders for our window cleaning chores.

Leaves, Loos and the Lotus Effect
Despite preferring to grow in muddy rivers and lakes, the leaves of the Lotus plant (Nelumbo nucifera) remain clean and free of contaminants, even after emerging from the murky waters. This self-cleaning ability is believed to be why this plant is regarded as a symbol of purity in many Asian religions and has been the inspiration for many biomimetic inventions.

Instinctively you might think that smoother surfaces would be the cleanest, as grooves and ridges would only serve to trap dirt. However, on closer inspection two German scientists, Professors Barthlott and Neinhuis, revealed that the shiny detritus-free surface of the lotus leaf is anything but smooth. Scanning electron microscope images revealed that the leaves were very rough and covered in micro-lumps and bumps of protruding epidermal (outermost) cells, which were in turn covered in wax crystals around one nanometre (1 millionth of a millimetre) in diameter. The wax crystals are hydrophobic (water hating) and so they repel water droplets and help prevent wetting of the leaf surface. The combination of these micro- and nano-scale features greatly reduces the contact area between the surface and water molecules, which is the key to the cleaning process and explains how even a light rain shower is enough to wash the leaves clean.

Figure 2: The Lotus Effect. Water forms droplets on the tips of the epidermal protrusions and collects pollutants, dirt and small insects as it rolls off the leaf.

Instead of sitting flat along the surface of the leaf, the water only makes contact with the leaf at the top of the lumps (figure 2), which forces it into spherical droplets. Then, even with the slightest of angles, instead of sliding down the leaf surface the bead of water starts to roll and tumbles off the leaf picking up dirt particles and small insects as it goes. This process, called the Lotus Effect, is so efficient that even honey and water-based glues will roll straight off the leaves, leaving no trace behind.

So-well has evolution refined this system that even hydrophobic dirt particles, which would ordinarily repel water, are trapped by the rolling water droplet and washed away. This is because the particles on the leaves only make contact at the tip of the wax crystals and so do not adhere very well. This means that the energy required by the water to pick them up is much less than the energy required to stick them to the leaf and so they are washed off.

But this effective method of self-cleansing is not restricted to this sacred plant. It also operates naturally in cabbages, reeds and the wings of butterflies and dragonflies, and it has now been exploited by industry to produce several technologies including a water repellent spray developed by BASF. This agent uses nanoparticles and water resistant polymers such as polypropylene, polyethylene and wax that self assemble into tiny structures which can mimic the Lotus Effect. This spray can be effectively applied to a wide range of surfaces from masonry to textiles and leather. Other products in the same vein include Lotusan, a house paint that combines this effect with other characteristics of water-repellent paints, and a more water-efficient urinal that cleans itself using only a fraction of the water required by a regular facility.

I can't imagine many people wouldn’t be attracted by such technology: houses and windows that would clean themselves with every rain shower, shoes that no longer need polishing, clothes that shun dirt. And the technology can have a positive environmental impact too, dramatically reducing the water required to flush a toilet for example.

Blood clots, arteries and self-healing space craft
Nevertheless, inspirational as nature may be, not all biomimetic innovations are direct copies of their natural world counterparts. Instead, sometimes the concept provides the clue to a more advanced technological solution. Take the blood clotting system for example. When you cut yourself, it is not long before your blood clots to prevent further bleeding and a scab appears. Hidden and protected by the scab your body repairs the damage below and after a short period it is as good as new.

Figure 3a: Micro glass tubes used to contain the resin and setting agent.

So can a similar method be adopted to repair wounds in the skin of a spacecraft? Well yes and no. On the one hand a self-healing system would spare astronauts from having to attempt risky repairs in space, but a repair that worked on the relatively slow time-scale used by the body's clotting system would be of little practical benefit, so it would need to be speeded up.

With this in mind Drs Bond and Trask of Bristol University set about developing a composite material for use in space craft construction that would heal itself in the event of damage. Just as blood passes through tissues in tiny capillaries, the Bristol team have incorporated glass tubes (figure 3a), each only sixty microns (60 thousandths of a millimetre) in diameter, throughout the material (figure 3b). The tubes contain either a resin, or a chemical setting agent which triggers the resin to polymerise and set hard.

This arrangement means that if the material is stressed or cracked, the tubes will rupture, allowing the two "clotting" components to escape and mix. The resulting hard plug will block the breach and restore strength and integrity to the material. Indeed, by including a fluorescent dye to the tubes, it's possible to see the new hardened resin being deposited wherever the material was damaged (figure 3c).

Figure 3b: The glass tubes were set in the composite material in layers.

Although the inclusion of the glass "blood vessels" reduced the strength of the material by 16% and the healed section was only 87% as strong as the original, this piece of research demonstrates that the concept of self-healing materials is feasible and now research is on-going to produce stronger "healants". Also, unlike the mammalian vascular system where blood circulates and is topped up in the event of loss, the present system works only once. So the team are now looking at ways to allow circulation and re-filling of the vessels. And just as our own circulatory system plays a key role in transport and temperature regulation in the body, it may be that the vessels of the space craft could be used to serve similar purposes too, helping to keep down weight and save space.

Another feature of the mammalian response to wounding that would be useful in the vasculature of a space craft is bruising, which can indicate damage below the surface. Often fractures occur inside a composite material leaving no external sign of damage. But if a give-away "bruise" could be generated at the same time as the healant is deposited, it could be used to identify problem areas more speedily.

Figure 3b: Repairs are localised to the areas of damage as observed using a flourescent dye.

The idea of a self-healing spacecraft complete with vascular system may seem a little strange and even more advanced than many sci-fi movies, but with the speed at which these developments are being made it may not be too long before it becomes a reality.

The tip of the iceberg...
Sometimes inspiration can be gleaned from the strangest of places, such as worms inspiring the development of robots that could be used to carry cameras into your intestines, traffic systems modelled on the behaviour of ants, and the skunk cabbage that is revealing secrets of how to keep warm during the winter.

Perhaps the most quirky phenomenon that sparked some research was the observation of bullet-proof pheasants. Occasionally, a pheasant can be hit with shot from a shotgun and yet escape unscathed, possibly due to its feathers absorbing the shot’s energy. This sparked an interest in understanding the properties of the feather protein keratin and its potential use in high-velocity impact protection, such as bullet-proof vests.

Other bio-inspired inventions include the sharkskin swimsuit, worn by 28 of the 33 gold medal winners at the swimming events in the 2000 Sydney Olympics. The swimsuit was designed to channel water over the body in the same way that a shark's skin does, reducing drag. Researchers have also been looking at the humble pine cone for other clothing ideas such as anti-sweat ventilation flaps that open and close in response to moisture when things get a bit sweaty. Penguins are also helping to keep polar explorers warm thanks to synthetic insulators based on their feathers; the breakthrough here is that, unlike down, they don't lose their insulating capacity when they become wet.

Where the next invention or moment of inspiration will come from, is virtually impossible to predict, but nature appears to have an inexhaustible supply of answers. All we need is a little ingenuity an open mind.

Becky Poole