BioEd Online

Day 5: Are you on drugs?

Does cannabis really relieve pain? Or ease muscle stiffness? Or just plain make you feel good? Studies have been bandied about, with various results. But researchers here today revealed a rather amusing reason why some of these trials can't really be trusted.

The rigours of scientific practice demand that half of a trial's volunteers be given a dummy drug without being told, while the other half un-knowingly get the real thing. As long as no-one knows if they have the real drug or not, researchers can weed out the real effects of the medicine from the 'placebo' effects that make people feel better simply because they're being given a dose of care and attention.

This strategy usually works well. But not if people figure out what group they're in.

Consultant neurologist John Zajicek found out he had just such a problem when he gave cannabis extracts to multiple sclerosis sufferers in Plymouth, UK, in a study published in the Lancet last year (see Cannabis study shows small MS benefit). Cannabis study shows small MS benefit. He quizzed the participants at the end of the trials to see whether they had sussed him out, and many of them had. Placebo patients were split 50-50 in their opinion of whether they had taken the real drug or not, showing that they were still in the dark. But a significant two-thirds of experimental subjects guessed that they'd been on dope.

This probably skewed the results, Zajicek told us today. But how did they figure it out? It's not as if doctors were walking around handing cigarettes to patients and saying "here, have a toke on that". The dope was nicely packed up in pills, just like the placebo.

The answer, in the end, isn't so mysterious. The patients in the study apparently reported feeling stoned.

The problem with all this, says Zajicek, is it's hard to separate the real effects of the drug from all the expectations surrounding them. Many multiple sclerosis sufferers are keen on cannabis, both for its pain-relief effects and the general feeling of well-being it induces. But for scientists trying to 'prove' these effects, such a reputation merely makes it more difficult to separate hype from reality.

Zajicek today revealed that after the end of the trial, he gave patients the option of continuing with the drug for a year in the hope of obtaining some more data - even if it is a bit biased.

His results continue to suggest that cannabis does in fact alleviate spasticity, or muscle stiffness, as well as the more distressing persistent pain associated with the disease. Though he points out that further, more rigorous studies into the effect are needed. So it seems that the drug really does represent a source of hope, as patient groups have vociferously maintained. But the hype makes proving it all the more difficult.

Day 5: Your grandmother was right

We're constantly told that we are what we eat. If that's the case, I would suggest that anyone who says they fully understand nutritional science needs a plate of humble pie. Who can honestly claim they can puzzle their way through the Atkins diet, the caveman diet, the 'no-diet' diet, journeying via the South Beach and Long Island diets, and come out with a unifying theory of what people should eat?

'Nutrigenomics' claims to transcend all this. By looking at the genes that run your individual metabolism, researchers hope that people can be issued with bespoke recommendations for what they should feed themselves. Over the next 20 years, personalized nutrition will become very big, according to Sian Astley of the European Nutrigenomics Organisation.

At risk of heart disease? We'll spot it for you - that's the mantra of the nutrigenomicist. Prone to osteoporosis? Modify your diet and minimize the risks. According to Astley, it's all about prevention.

But doesn't all this sound a bit obvious? We already know that fat-saturated foods place people at risk of heart disease, and that calcium strengthens bones. The back-to-basics, balanced-diet brigade have been saying this for ages. What new advice can genetics actually give us?

Not much, it seems. "Your grandmother was right," Astley says - a balanced diet is best. But she adds that some people follow all the rules and still have health problems. It seems a good bet that genetics will be able to answer the age-old conundrum of why some people still get fat even when they spend their time watching with jealous longing as their stick-thin friends wolf down pies.

Shining a light on a problem is one thing, but is there anything practical that nutrigenomics can do to make a difference? Perhaps, said Keith Grimaldi, who has developed a commercial gene test that gives customers tailor-made dietary advice based on submitted DNA samples.

He gives the example of homocysteine: an amino acid that, if not broken down and kept at low levels in the blood, is linked to heart disease. Grimaldi suggests that people who have defects in this pathway could help this process along by making sure they eat lots of folic acid. He suggests that by making sure everyone gets the folic acid they need we could reduce heart attacks in Britain by 20%, and strokes by 15%.

Such health-detective work would be potentially very valuable in the long term. So would people be treated with folic acid supplements on the basis of DNA evidence? Well, perhaps, said Grimaldi... or they could just eat plenty of wholegrains, spinach and liver, which sounds a bit like 'granny knows best' all over again.

Grimaldi also admitted that 80% of the recommendations made in a personalized dietary report would be standard advice given to everyone anyway - only 20% would be based on what's actually in the person's genes. Nothing would be banned (unless you're allergic), people who need extra vitamins like folic acid would simply be steered gently in the right direction. Oh, and everyone should eat less saturated fat, Grimaldi added. Which made me glad I left the black pudding on my plate at breakfast this morning.

Day 4: Coming soon to a planet near you...

Space missions are plain sailing once you get away from all that pesky gravity. The first and last few kilometres - those are the bits mission managers worry about. This nugget of wisdom was proved right once again yesterday when NASA's Genesis mission ended in disaster (see Genesis mission crashes). After two-and-a-half years painstakingly harvesting a miniscule crop of particles from the Sun, a high-speed nosedive into a dusty desert is not the ideal way to round things off.

A portion of the sample was earmarked for a British lab, as the Open University's Ian Franchi told the festival yesterday, declaring 8 September "a fantastic day for planetary science" - before he knew about the crash, that is. They do say that pride comes before a fall - an almighty one in this case.

It's the second high-profile disappointment for British space scientists, and for the Open University in particular. The scars are still fresh from Colin Pillinger's ill-fated Beagle 2 Mars mission last Christmas - another probe that tussled with gravity and lost. The frustration was palpable today, with Franchi and Pillinger offering up "heartfelt commiserations" to their colleagues at NASA, and lamenting "everything we've worked for over the past ten years".

But they also spoke of resilience and resolve, and promised that the Brit pack of planetary scientists would be back to fight another day. There followed a presentation by several other researchers either currently running missions or bringing one to a planet near you soon. The presentation had been planned for weeks, but yesterday's crash lent it a feel of being a something of a PR drive for space science.

That's not to say that these missions aren't doing some impressive things. Indeed, the Cassini mission to Saturn has found a new ring to add to the planet's jewellery box. There's a new moon too, or at least there will be as long as it's still there the next time we check (see Cassini special).

Meanwhile, Cassini is preparing to send its companion, the Huygens probe, on its way to investigate the moon Titan. The two will part company on 25 December - the anniversary of Beagle 2's splashdown.

Before then, in October, the Swift satellite will blast off from Florida (where its launch date has been put back by the recent hurricane devastation). The craft gets its name from the fact that, once deployed in space, it will have enough agility to whirl around to watch brief gamma-ray bursts - huge blasts of radiation that radiate as much energy in ten seconds as an average star produces in its lifetime.

We've got a lot to look forward to, then. But Mars won't give up its crown of 'most exciting place in the Solar System' without a fight. Mars Express, the European craft that delivered Beagle 2, has spotted signs of methane on the red planet. As Andrew Coates of the Mullard Space Science Laboratory told us, there are only two possible sources: volcanoes or microbes. And methane doesn't last very long in the atmosphere before it degrades, so any volcanoes would need to be active today.

If it turns out that there's no current volcanic activity, Coates said, then planetary scientists could conceivably have found life on Mars. And if they really are looking for good PR, it doesn't come much better than that.

Day 3: Sit still and listen

At a big conference like this it's all too easy to flit from event to event without really engaging with anything for more than a few moments. So would a discussion of attention deficit hyperactivity disorder (ADHD), which renders sufferers unable to sit through a five-minute cartoon, hold our attention? Actually, yes, because it was fascinating, and by far the day's biggest talking-point.

ADHD is thought of as a kids' disease, unsurprisingly given that it is characterized by overwhelming impulsivity and an inability to stay still. It's also a controversial topic - some 6% of children in the United States are prescribed 'calming' drugs such as Ritalin, a figure that horrifies those who favour behavioural therapy over mind-altering chemicals.

But many peoples' ideas about ADHD are wide of the mark, according to Eric Taylor of the Institute of Psychiatry, who gave a stimulating and animated (some might say slightly manic) talk. "We've all got a bit of it," he claimed. The problem is the 5% of children and 1% of adults for whom hyperactivity becomes an affliction.

The problem's even worse in places like China, Taylor continued, where people struggle to get on in life if they didn't sit still and get good grades in school. But here in Britain, it seems we can still carve out a niche even if we didn't pay attention. What kind of career could someone with ADHD pursue, then? "Anything fast-paced with deadlines," Taylor replied, to guffaws from the assembled press pack. Stock-market trader and stand-up comedian are apparently good choices too.

Taylor attacked the fears over prescribing Ritalin to British children, saying that 1% of kids need the drug, whereas currently only 0.3% get it. He likens the pattern to the scares over other juvenile medicines such as the MMR vaccine. He concedes, however, that US doctors may be too free with their prescription books.

Taylor knows what he's talking about, too. As a practising psychiatrist, he has prescribed Ritalin and even taken it himself (just so that he knew what he was dishing out, mind). The verdict: "It just made me want to sit down and read a lot."

Taylor says that without treatment, hyperactive teenagers are at risk of developing a suite of other mental problems as they realize that their 'class clown' antics have made it difficult for them to fit in properly with their peers. Potential problems include personality disorder, manic depression and violent behaviour.

So ADHD is a genuine public-health problem, then, rather than an excuse for being a reckless tearaway. But what causes it? David Daley of the University of Wales, Bangor, attempted to explain and unwittingly triggered yet more controversy.

There's no argument that the disease has an underlying genetic cause. Regions of the brain associated with self-restraint are demonstrably underdeveloped in those with ADHD. But Daley, who has surveyed the relationships between hyperactive kids and their sometimes hyperactive parents, told us that its bad parenting that brings out the bad behaviour.

Do we blame the parents, then? No, it's a genetic disease, he said. But it doesn't manifest itself unless the parents fail to provide sympathy, fun and stimulation. So does that mean it's not down to bad parenting, or it is? Nobody could seem to agree.

So despite the brain imaging, the genetic analyses, the drug trials and the behavioural studies, ADHD is still causing controversy. Sorry not to provide any firm bottom line on this one. But hey, at least you sat still long enough to read this.

Day 2: Mind boggling

Funny things, brains. A lot of scientists spend a lot of time studying them in a lot of different ways, without ever really figuring them out. There's a definite irony in the fact that not even the world's finest brains can understand their own inner workings, but I guess that's what happens when you try to fathom a machine with 100 billion working parts (or about that many).

The brain - and our general bafflement at its secret machinations - was today's recurring theme. What, for example, are memories made of? Medical Research Council chief Colin Blakemore attempted to enlighten us by telling us about 'adaptive plasticity', a process in which the brain responds to the outside world by forming a million new connections between nerve cells every second. Opening with the rather spooky "I am altering all of your minds", just by giving his speech, Blakemore described how these connections are marshalled to form memories.

So if someone invented a really good brain imaging gizmo, could scientists in the future look at the nerve connections in my head and say "Aha! There's that day he was in Exeter learning about brains!" Well no, Blakemore admitted, we've no idea how the connections represent pictures of the real world; we just know they involve a shed-load of computing power.

Things are no clearer if we try to side-step all the details of what's going on in the brain and simply try to work out the basic motivations people have for their behaviour. Exeter University's Carole Burgoyne has been probing the minds of newlyweds - and their bank accounts - to see if she can work out what they're thinking.

Burgoyne interviewed 42 couples (separately, since you ask) to find out about their various motivations for tying the knot. Rather depressingly, 59% said it was "the right thing to do", 44% talked of "a logical progression", and only 36% saw fit to mention that they thought their spouse was "the right person". Half of the couples maintained separate bank accounts, leading Burgoyne to suggest that they view marriage as an island of stability in the shifting social landscape, but aren't ready for full commitment just yet. But Burgoyne also found that couples were happy to share a bank account when considering getting a mortgage, which hardly sounds like a fear of commitment. So, in the end, who really knows what these people were thinking? Maybe they don't even know themselves...

Working out what happens when the brain goes wrong is equally tricky. We sometimes can't even agree on how to define or describe the various ways that a wonky brain can manifest itself. Exeter sociologist Cath Quinn proposed that we bring back a term from the nineteenth-century, then used to describe women who encountered any kind of mental difficulties around the time of pregnancy - from mild baby blues to full-on psychosis. In those days, such women were admitted to mental asylums with 'puerperal insanity'. Quinn suggests that the term be resurrected (as the slightly more sensitive 'puerperal mental disorders') to give women patients a sense of solidarity.

The one time we do seem to have some luck tracking down what's happening in the brain - or fixing it - is in the case of some emotional disorders, many of which arise directly from large-scale damage to nerve cells. Exeter neurological psychologist Huw Williams described one man who had Capgras syndrome, a rare disease that leaves patients devoid of emotion and therefore apt to assume that their close family have been replaced by imposters because they don't elicit any strong feeling. Williams's team paged the man every day to remind him to update his diary recording any and every twinge of emotion, however faint. When standing next to a stranger at a train station who happened to be wearing the same perfume as one of his former sweethearts, for example, the man experienced a fleeting feeling. Eventually, he learned to recognise such fleeting moments as real emotions, and overcame the problem.

This kind of brain science works because the path of cause and effect is often traceable. In other cases we can work out how the chemistry that bubbles away in our brains causes various effects. Although we don't fully understand mental problems such as depression, we've a fair idea of how they work on a biochemical level. But as today showed, as you try to work out more than that, you can easily find yourself lost in the corridors of the mind.

Day 1: Cutting edges and glass cliffs.

The British Association for the Advancement of Science (BA) quotes its brief as "connecting science with people". And so it was as the BA Festival began in earnest this morning, bringing a diverse line-up of scientists in touch with a pack of expectant journalists

But, being a festival designed primarily to raise the public profile of science, most of the studies being presented here today aren't exactly on the cutting edge of research. Quite a lot of the work on display has been around for years; while other theories are unlikely to be troubling the editors of science and technology journals any time soon.

The opening talk, while fascinating, managed to hit both of these extremes at once. Stuart Black of the University of Dundee mused on the use of radioactive isotopes in forensic science. The technology he describes has long been used by police specialists put a date on a victim's body, and in a couple of high-profile cases it has even pinned down the likely country in which an unknown victim was born and raised. One day, Black suggests, a study of the isotopes of hydrogen and oxygen from a crime scene might even pinpoint exactly where the murderer lives - unless he has been drinking Evian. Maybe. If we can get the money and the time to map every water source everywhere. So maybe that's "one day a very long time from now... if ever".

Next, a world away from the gory reality of forensics, we gained a taste of the rarefied world of top-end mathematics. This is, surprisingly, a high-stakes arena: the Clay Institute in the United States has offered a million dollars to anyone who can solve any of the seven most taxing unsolved posers around. Sadly for the assembled hacks, the mathematician and television presenter Simon Singh put paid to our dreams of achieving an easy life of luxury when he demonstrated the difficulty of such problems. Most of them require a hard slog of guessing-and-testing work, rather than a single elegant equation. Even working out the two two-digit numbers that multiply together to make, say, 323 is tricky enough (answer below). The Clay Prize puzzles would take infinitely longer to solve. Maybe literally.

Elsewhere there was alarming news for followers of public-health issues. The charity Cancer Research UK revealed that a quarter of drug trials go unreported, and called on pharmaceutical companies to make amends. Meanwhile, Faisal Khan, also at Dundee, highlighted his 2003 study showing that even normal young teenagers can show early signs of serious heart disease, in the form of damage to capillaries and other tiny blood vessels¹.

Such weighty issues are not the norm at the festival, however. By far the day's biggest talking-point was a piece of research presented by Exeter University's own Alex Haslam. A social psychologist, he has coined the term 'glass cliff' (a counterpart to the famous 'glass ceiling' allegedly encountered by career women) to describe the appointment of women to jobs that might seem glamorous but are in fact undesirable.

Haslam studied companies on the stock-market, and found that those whose share price had fallen were more likely to subsequently appoint a woman to the board. This suggests, he claims, that the old boys' clubs that run such institutions are unlikely to stick one of their (male) mates into a tough spot, preferring to give high-flying female candidates the daunting job and the precarious prospects. Others might suggest that women are simply better in a crisis, whereas still others (such as one person here who called it 'psychobabble') dismiss the entire trend, if it is a trend, out of hand. Haslam's message is: stick it out sisters, and don't stand for cleaning up anyone else's stock-market mess.

Haslam's methods are rigorous (his study is in press in the British Journal of Management), but it's hard to resist the feeling that this is just the kind of can't-really-prove-anything-by-it study that often grabs the press headlines. Interesting stuff, with a catchy catch-phrase? You bet. But maybe not all that much more.

Answer to puzzle: 17 and 19