Mood Is Chemistry. No Really, It Is.

What goes on in the brains of people who are depressed? For a lot of us, the answer is remarkably straightforward - they don't have enough serotonin, innit? The belief that serotonin is somehow the brain's "happy chemical" is almost folk wisdom nowadays - I just searched for serotonin on the Guardian website and clicked on the top article, this gem which describes serotonin as "the feelgood hormone".

Now, some more informed people don't like this pop psychopharmacology. The esteemed Dr. Ben Goldacre, for example, wrote that

That’s the serotonin hypothesis. It was always shaky, and the evidence now is hugely contradictory. I’m not giving that lecture here, but as a brief illustration, there is a drug called tianeptine – a selective serotonin reuptake enhancer, not an inhibitor – and yet research shows this drug is a pretty effective treatment for depression too.

Meanwhile in popular culture the depression/serotonin theory is proven and absolute, because it was never about research, or theory, it was about marketing, and journalists who pride themselves on never pushing pills or the hegemony will still blindly push the model until the cows come home....

The serotonin hypothesis will always be a winner in popular culture, even when it has flailed in academia, because it speaks to us of a simple, abrogating explanation, and plays into our notions of a crudely dualistic world where there can only be weak people, or uncontrollable, external, molecular pressures.

It's an excellent article and you should read the whole thing. Goldacre is far from alone in his skepticism towards to the serotonin hypothesis. Indeed in certain circles, the idea that the serotonin hypothesis is basically just drug company propaganda is almost folk wisdom nowadays (stop me if you've heard this one before).

Now, I'm not going to defend the idea that all depression is caused by "low serotonin".That's almost certainly wrong, and the very best you can say about it is that there's no strong evidence for it. In fact, it's not even clear, from a neurobiological perspective, what "low serotonin" means - low in which parts of the brain? Are we talking about low firing rates of serotonin neurons, or low amounts of serotonin released each time they fire, or low levels of serotonin just hanging around the synapses all the time? (And the next time someone tries to sell you a supplement or a herb or other short-cut to higher serotonin levels, just remember that there is such a thing as too much happy hormone.)

But - it's possible to be too skeptical. Serotonin does, unquestionably, play an important role in mood. Rumors of the death of the serotonin hypothesis have been greatly exaggerated. Ironically, the best evidence for the mood-relevance of serotonin doesn't come from antidepressants. Most common antidepressants, e.g. the famous Prozac, are said to work by "boosting serotonin levels", but actually it's far from clear that they do. Although these drugs inhibit the transporter protein which gets rid of serotonin after it's been released, which should in theory increase serotonin levels, in fact the picture is more complex, because serotonin inhibits the firing of the very cells that release it. Ironically, Prozac might even decrease serotonin levels in the places where they matter, at least in the short term. (For pharmacology geeks, see here).

The best evidence that mood is chemical, and that serotonin is one of the chemicals involved, comes from a foul-tasting, frothy, nausea-inducing milkshake known as the acute tryptophan depletion (ATD) mixture. The ATD mixture contains 100g of amino acids, which are what the body uses to synthesize proteins. You put the amino acids (white powders) into 200 ml of water. Some of them dissolve, some don't, so it's pretty lumpy. When (if) you manage to drink it all, interesting things happen. The influx of extra amino acids stimulates protein synthesis in your body. Some of the amino acids also get transported into the brain via certain proteins.

The key ingredient of the ATD mixture is the absence of tryptophan. Tryptophan is an amino acid, and like all amino acids it's used to make proteins, but it's also necessary for the production of serotonin in the brain. When you drink the ATD mixture - containing no tryptophan, remember - all of the tryptophan already in your blood gets used up in the burst of protein synthesis. Any that survives can't get transported into the brain, because other amino acids are already using the transporter proteins. The result is that tryptophan levels in the blood, and the brain, drop dramatically over the course of several hours.

ATD has been used in research for over a decade. The ATD procedure is unpleasant - volunteers have to consume the drink, which is truly horrible, on an empty stomach, and then not eat anything for the next 7 hours. Sometimes people vomit while trying to drink the stuff, or shortly afterwards, or two hours later. It's not much fun. But ATD has proven, to my mind, beyond any doubt, that the link between serotonin and mood is more than just a myth. The reason is that if you give ATD to people who have previously suffered clinical depression, a large proportion of them become depressed again, just for a few hours. This has been replicated several times. The effects can be dramatic (although not always, and sometimes there is no discernible effect) -

A feature of particular interest was that the participants who had full relapses of symptoms described a reappearance of some of the depressive thoughts they had experienced when previously depressed. One of these participants whose previous episodes of clinical depression were associated with the loss of important friendships had, while depressed, been preoccupied with fears that she would never be able to sustain a relationship. She had not had such fears since then. She had been fully recovered and had not taken any medication for over a year. About 2 h after drinking the tryptophan-free mixture she experienced a sudden onset of sadness, despair, and uncontrollable crying. She feared that a current important relationship would end. She recognised that she was depressed but still considered that her fears were appropriate. The evening of the test day she started to feel better and the next day was fully recovered. She said that her fears about her current relationship had been unfounded and she now saw them as unrealistic.
From Smith, Cowen & Fairburn Lancet (1997)

Good skeptics will immediately notice that everything I've just described could be a reverse placebo effect - people are warned to expect to get depressed, and then they have to drink a god-awful mixture that makes them feel sick, so it's no surprise they feel down. This is a real concern, so for comparison there is a placebo drink - exactly the same, but with plenty of tryptophan - and everything is done double blind. The placebo drink does not produce the same effects (although occasionally there are placebo responses - sometimes very striking ones.)

So does this mean that low serotonin = depression after all? No, for the very simple reason that if you do the exact same experiments on people who have never suffered from depression, they feel fine and dandy (well, except that they feel sick.) A few people say they feel a bit down, but the reactions are nowhere near as strong as those seen in many people with a history of clinical depression. Yet the biochemical effect - reduced brain tryptophan and hence (presumably) reduced serotonin synthesis, is the same.

If we knew what made some people vulnerable to the effects of tryptophan depletion, we would be a long way towards understanding depression. We still don't. But it's something to do with serotonin. In some people, in some circumstances, serotonin is the only thing between happiness and despair. No, really.

Nuts about Chocolates

Ishiya is the most prominent chocolate factory in Hokkaido. Its flagship product is the Shiroi Koibito which is a thin slice of white chocolate sandwiched between two thin butter cookies. Shiroi Koibito literally means the white lover and it is a signature souvenir for tourists to bring back from Hokkaido.

The chocolate factory now houses a theme park using the same name as its signature product, the Shiroi Koibito Park. Being the most prominent chocolate maker in Hokkaido, it just doesn't stop at only one flagship product. There are many more types of mouth-watering chocolates.

I am now craving for some fine chocolates myself!

fMRI Reveals True Nature of Hatred

Given that I've taken to calling myself Neuroskeptic, I feel it's time to take a skeptical line on some neuroscience. Fortunately, an ideal example has just popped up. The paper, ominously titled "Neural Correlates Of Hate", was published in the open-access journal PLoS One. It's been picked up by the major science news sites and various newspapers, with headlines generally some variation of

Brain's 'hate circuit' identified

Those of us who keep up with the news won't be surprised. It seems like every week, reports come in that scientists have discovered the brain circuit for something.

By and large, these reports are nonsense. I will now explain why, and then tell you my theory of why everyone is so fascinated by neuroscience (and especially neuroimaging), before finishing by explaining why people aren't actually interested in neuroscience at all. Nice twist, eh? First, I'd like to make it clear that I'm not out to criticize the paper itself or the authors, Dr. Zeki and Dr. Romaya. No doubt the methodology of the experiment could be critiqued, but this is true of all such research, and I think the data from this study are valuable and interesting - to a specialist. What concerns me is the way in which this study and others like it are reported, and indeed the fact that they are repored as news at all.

So what did the authors do? They posted some adverts and recruited seventeen healthy volunteers. They showed them photos, which the volunteers had previously sent them. Some of the photos were of someone who the volunteer really hated - generally either ex-lovers or work rivals, predictably enough. Others were of people that the volunteer knew, but had "neutral feelings" towards. This was an fMRI study, so the whole process took place inside an MRI scanner configured to measure changes in blood oxygenation levels across the brain (which is considered a proxy for metabolic activity, itself a proxy for neural firing.) They then calculated which areas of the brain showed greater oxygenation changes when people were looking at their own personal hate figures than at the other faces. They found several areas in which the difference was statistically significant, which is what the yellow areas on this picture represent:

(Taken from Zeki & Romaya PLoS One 2008, without explicit permission)

This is all very well and good. Some people take a skeptical line on the whole business of fMRI, and they would probably consider these blobs-on-the-brain to be pretty much meaningless. I'm not one of them - I think these data tell us something about the human brain, although only in the context of other research, and only when the limitations of fMRI are borne in mind. (I hope to expand on my views of fMRI soon.) This is one piece of a big puzzle.

But one thing is clear, the brain's "hate circuit" is nowhere to be found in this study. This phrasing doesn't appear in the paper: it seems to have originated in the university press release (as this kind of stuff generally does.) What this data shows is that certain parts of the brain become more active when people are looking at pictures of people that they hate, and presumably therefore experiencing the emotion of hatred. These areas are not only activated by hatred; the putamen, for example, is known to be involved in the control of all movements. Every area which lit up in this study has lit up in a hundred other experiments which have nothing to do with hate. It's not as if scientists have just found a new bit of the brain tucked away somewhere, which turns out to be the root cause of all human evil. (Which is a pity, because that would look great on a grant application.)

Now, given that, I really can't see why anyone but a professional neuroscientist would want to know which parts of the brain activate when you look at pictures of a hated rival, not least because most laymen wouldn't know their putamen from their parietal lobe. (That's like saying "arse from their elbow," for non-neuroscience geeks.) And there's no reason they should. Neuroanatomy is very difficult, as any undergraduate neuroscientist knows. The brain is just an organ. It has various parts. Some people, like me, spend our lives trying to figure out how it all works, and we would say that it's very interesting. Of course, we would say that, because the brain pays our bills. To anyone else, it's just a grey lump.

Except, of course, that it's not. People are fascinated by the brain. We can't get enough cognitive neuroscience and fMRI images. They're a staple of the newspaper science pages. Does this mean people are interested in neuroscience? No. People don't understand neuroscience, because it's bloody hard. What interests people is not specific findings about the brain but the fact that science is "discovering things" about the brain and by implication, human life. At the back of all of our minds is the exciting feeling that whenever scientists find "the circuit" associated with some emotion or some behavior, an important truth about human nature has been revealed. (Neuroscientists get this feeling too, but we know it's more complicated than that. Some of us anyway.)

Sometimes this feeling surfaces and is expressed in words. Terence Kealey is a biochemist and head of the UK's only private University, The University of Buckingham. He's known for his libertarian politics. About a year ago he penned a profoundly revealing article for the Times. I would encourage you to read it, but you might need a dangerously large spoon of salt. Essentially, Kealey reads an fMRI study in which social science students were able to donate money to charity, and thinks it proves that

...people like being taxed for charity, but they like giving money to good causes even more... [which] challenges so many political assumptions. First, it disproves the Left’s belief that only the state will succour the poor: actually, philanthropy is hardwired into our brains and, in the absence of state aid, private giving is biologically determined...

Nothing in this paragraph is implied by the brain images which Kealey is talking about. Not a word. It's really quite impressively divorced from reality. In particular, there is absolutely no good reason to think that because a certain part of the brain is activated when we do something, that thing is "hardwired" or "biologically determined". This is because the brain is the organ of learning, and if we learn to do something, some part of the brain will be involved in that learning. Neuroimaging has very little to do with the nature / nurture debate. But my goal is here is not to bash Terence Kealey. Well to be honest it is a bit, but the main point is that the mistake that Kealey makes - seeing fMRI as a way of investigating the roots of human behavior - is very common.

The idea of a "hate circuit" is beguiling, I think, because it seems to show that hatred is a deep-seated human emotion with a biological basis. Personally, I think that's probably true. But I don't think that because of brain scans. I think that because I read the news and I read history. People across the world have been hating other people, in depressingly stereotypical ways, for as long as we can determine. That's human nature, but brain scans don't tell us anything about that. They tell us about the brain, which is a grey lump. Some of us have a professional interest in grey lumps, but everyone else would learn much more about hatred by going to see some Shakespeare or reading a history of the Balkans or something.

To sum up, neuroimaging and neuroscience in general are fascinating in their own right, but highly technical. As such there's no good reason why lay people should be any more interested in them than they are in chemistry. Given that they are in fact very interested, logically there must be bad reasons for this, such as the mistaken belief that brain scans can tell us about human behaviour, human nature, or everyday life. They don't and they probably can't. Vulgarized neuroscience now takes the place that Freudianism did 30 years ago, in that it offers simplistic, mechanistic explanations for complex behaviours, whose only claim to credibility is that they are "scientific". This kind of thing does real neuroscience, including fMRI, no favours.

Wordless Wednesday – Punk Fashion @ Takeshita Dori

Location: Takeshita Dori, Harajuku, Tokyo, Japan
Date taken: August 10^th, 2008
Camera equipment: Nikon D300 + Micro-Nikkor 105mm f/2.8D

Cheer Up, Citizens

Does anyone else find this here video (via BBC) very odd? It's what can only be described as a government propaganda clip, but rather than trying to persuade or inform it's basically telling you to cheer up. Or as they put it "Increase your wellbeing today!" - they must have a jargon quota to meet. Maybe this is what happens when media-obsessed politicians listen to people to Lord Layard who say that they should be trying to make the population happier?

Also - a lot of psychologists and philosophers would say that everything we do is motivated by the desire to increase our own well-being, which would make the advice a bit redundent. Is this video proof that this theory of human nature is wrong? I wonder what Jeremy Bentham would say.

Galileo Strikes Again!

Link: I write further on this topic in a subsequent post.

Some interesting comments over at Respectful Insolence got me thinking about the "Galileo Gambit". This is when people with unpopular ideas compare themselves to Galileo with the implication that, like him, they're being persecuted for their unorthodox views but that they will eventually be proved right. Everyone wants to be the underdog, and the Gambit has become such a cliché that several writers are famous for denouncing it. Michael Shermer gave us the snappy aphorism -

Heresy does not equal correctness.

While Carl Sagan went for the comedy angle -

The fact that some geniuses were laughed at does not imply that all who are laughed at are geniuses. They laughed at Columbus, they laughed at Fulton, they laughed at the Wright brothers. But they also laughed at Bozo the Clown.

And so on. In fact, pointing out that not everyone with weird ideas is Galileo, seems to be almost as popular as claiming to be his spiritual heir. Hmm.

Some people don't like this, such as this HIV/AIDS denier who takes issue with those who accuse others of using the Gambit. He's right (about this, not about AIDS) - Shermer and Sagan are attacking straw men, if you take their words literally, because no-one ever claims that just because their ideas are unorthodox, this makes them right. People generally invoke Galileo either as a rhetorical device - to give themselves a cool sense of rebelliousness - or as a defence against the "Argument from Consensus", which says that we should believe something just because most scientists do.

I'm now going to argue that if most scientists believe something you probably should believe it, just because scientists say so. I'm aware that this is an unorthodox view (oh, the irony.) After all, the motto of the Royal Society is Nullius in Verba - "Take nobody's word for it". The oldest scientific society in the world doesn't want you to take their word for anything! I think they're wrong, but the idea that we should "think for ourselves" is fundamental to the way that we in the West argue and think. Once, "heretic" was a serious accusation, now, "not a heretic" is almost as bad. If there's one thing everyone agrees on, it's that everyone should be an indepedent thinker.

But if you take this even vaguely literally, it's obviously bollocks. You take someone's word for it whenever you read a newspaper. Scientists do so whenever they read a journal article - they trust that the results presented weren't made up. "Heretical" science is no exception - if you believe that the MMR vaccine causes autism, it's because you take Dr. Andrew Wakefield's word for it that he did some experiments and got certain results. This is fairly trivial, and you might object that even if we decide to trust the published evidence, we should still insist on evaluating it and interpreting it for ourselves. The idea that anyone can look at the evidence and reach their own conclusion seems only fair and democratic. Just because, say, almost all climate scientists think that the evidence implicates human activities in global warming, this doesn't make it so!

Yet again, it's balls. Unless you are a professional climate scientist (or whatever), or an amateur with an unhealthy amount of spare time, the chances are that you just don't know enough to come to an informed conclusion. Galileo could prove his points by getting people to look down a telescope, but modern science has grown so large and complex that you now need to read and digest dozens of papers to even understand most controversies. Even with life-or-death stuff like the question of whether antidepressants cause suicides, I'd bet that there are only a few dozen people in the world who know all of the relevant evidence. (I say this as someone who knows people whom you would expect to know it, and they don't.)

Ultimately, most of us just can't have an informed opinion about complex issues like evolution, climate change, vaccine safety, or the roots of the economic crisis. Life's too short, and 21st century knowledge is just too much for our brains to handle. It's easy to pick up a few statistics and a couple of stock phrases and think you're informed, but the chances are, you're unskilled and unaware of it. The most rational thing to do, therefore, would be to be agnostic about such matters. This is hard though, so as a second best, we should accept the experts' consensus. Academics are generally pretty intelligent, and if thousands of intelligent people freely discuss something and reach a certain conclusion, that in itself is evidence (although not proof) that what they conclude is true.

So: In theory, we should take no-one's word for it. Ideally, we should gather all the evidence about everything ourselves, and then draw our own conclusions. No-one would deny that this is the ideal, but equally, no-one can deny that this is not actually going to happen. Unless you're an expert on a topic, you have to take someone's word for it if you want to know anything about it. You are taking people's words for it right now. You might as well take the word of the majority of experts.

[BPSDB]

Desserts Made in Heaven

When I was in Sapporo, I visited the most prominent Ishiya Chocolate Factory expecting to see only chocolates. I was very surprised to see the display of desserts even finer than the ones I saw in Tokyo!

Are you craving for dessert already? ;)

New Age Experiment Goes Wrong, Hundreds Dead

What with all the fuss over the Large Hadron Collider being about to suck us all into a black hole or blow up the world or something, it's easy to forget that it's not just cutting-edge, incredibly cool physics research that can be dangerous. Even seemingly benign New Age woo can go awry and end up killing hundreds - at least judging by the results of the fascinatingly flaky Peace Intention Experiment, an update of the famous Transcendental Mediation crime reduction studies.

The Peace Intention Experiment, or as I call it the PIE (in the sky?), is the latest project from Lynn McTaggart, New Age author and alternative health guru. McTaggart's previous research has investigated whether human intention can make plants grow better and whether it can "change the structure of water". This time around, she set her sights higher - the goal was nothing less than saving lives by stopping violent conflict. But the method was very similar to that used previously: McTaggart invited her fans to think really hard about something for ten minutes or so, all at the same time (coordinated via the internet). McTaggart claims that her previous studies have already proved that the collective mind of thousands of internet users can influence events thousands of miles away, sometimes even backwards in time. Then again, it's not hard to get positive results if you perform enough statistical tests.

Anyway, this might sound harmless, but the preliminary results of the PIE have just been released and they make disturbing reading. The PIE was intended to reduce violence, but tragically, it made matters much worse. I mean obviously it did bugger all in reality, but if you go along with McTaggart's usual reasoning processes and persistently confuse correlation with causation, you'd have to conclude that it had killed hundreds. Except that Lynn McTaggart doesn't think that - we'll see why later.

Here's what happened: For ten minutes each day for eight days, 11,468 intentioneers looked at pictures of Sri Lankan people while intending - hard - that peace should come to war-torn Wanni, Sri Lanka. Specifically they intended thus -

My intention is for peace and cooperation to be restored in the Wanni region of Sri Lanka and for all war-related deaths and violence to be reduced by at least 10 per cent

It's a modest ambition - if I thought that I had the power to magically alter reality, I'd probably wish for deaths in Sri Lanka to be reduced by more than 10%. But I'm not an expert in these things. Anyway, since you've probably never heard of it, Wanni is a town in Sri Lanka which has suffered badly in the ongoing civil war between government forces and the Tamil Tiger rebels. Why Wanni, you ask? Well, McTaggart tells us that one of her main reasons for choosing it over, say, Baghdad, was that

In order to get robust experimental results, I was interested in choosing an area that the West was NOT focused on. Many areas of violence around the world are already the subject of prayer groups and intention; if we were to focus on one of them, it would be more difficult to demonstrate scientifically that the Peace Intention Experiment had a significant effect in lowering violence.

This shows some basic knowledge of the problem of confounding factors in intervention studies. Interestingly, she also seems to believe that only Western people have the power to change the world through their intentions. I bet that there are a lot of people in Sri Lanka who very much wish that their country would stop being a war zone, and they probably pray for peace - and indeed their lives - quite a lot. If I lived there I certainly would, and I'm an atheist. However, Lynn doesn't think that this is a problem. Clearly non-white people don't have the Power of Intention.

Anyway, that was the plan. What happened? Well, according to the statistician involved, before the experiment started, people were getting killed in Wanni at an average rate of 102 per week. So there was plenty of room for improvement. However, sadly, during the 8 days of the experiment, 461 people died! That's an extra 45 deaths each day. Pretty impressive - if you were trying to remotely kill civilians with some kind of psychic super-weapon. Fortunately, McTaggart et. al. have an explanation for this unexpected result:

there was a last surge of attacks by the Sri Lankan government, who wanted to quash the Tamil Tiger rebels once and for all.

So that explains the extra deaths - government forces launched a surge of attacks. People tend to die in attacks. Whether the government's decision to launch these attacks was caused by the Peace Intention Experiment is not clear, but if the human mind can magically make a plant grow to twice its normal size, surely it could make a Sri Lankan general decide to attack a town. But there's more:

In the 24 days following the experiment, violence levels immediately plunged down and stayed low ever since. The weekly average death rate in the Wanni region dropped by 49 per cent!

Interestingly enough, the Eastern part of Sri Lanka, experienced the same evolution. The death rate heightened during the experiment period, and then fell by 68.4 per cent.

Of course it's hardly surprising that deaths fell in the period following a major offensive - maybe the government was in control of the area, or maybe everyone had run away. Still, maybe McTaggart could claim credit even so - human intention works in mysterious ways after all. The death rate did fall by 49%, meaning 50 fewer deaths per week, so 171 lives were saved over the course of the 24 days after the end of the experiment. PIE worked! Unless you consider the extra 360 dead during the 8 days that the PIE was actually in progress, meaning that on balance 189 extra Sri Lankans died. Oops!

The sensible thing to do at this point would be to declare the experiment a failure and blame it on, oh I don't know, the sheep/goats effect or something. But McTaggart seems instead to be claiming that the experiment was a success, on account of the reduced violence which followed the initial terrible explosion of violence. This is known as "cherry picking". She is not perturbed by the fact that the Eastern Sri Lanka region which was not targeted by the PIE experienced an even greater reduction in violence over the same period. To me this suggests that, if anything, PIE increased violence, but McTaggart believes that it shows that PIE is so powerful that it affects whole countries even if it's only aimed at one region, like a nuclear bomb of peace. This is known as "coming up with a story to explain the data".

Naturally, McTaggart wants you to give her money to keep doing this kind of thing. After all, the PIE was only a pilot study.

So Lynn McTaggart continues to wage, and win, her ongoing battle against those who would parody her, by doing it better than they ever could. (For previous episodes see Hawk/Handsaw). But this sorry spectacle is more than just a source of cheap laughs for bored bloggers. Honestly, it is. It's actually a fascinating case study in the psychology and sociology of science. McTaggart's efforts to extract a positive result are far from unique - they are only marginally more strenuous than those of some respectable researchers.

PIE shows that if you look hard enough you can literally find any conclusion in any data set. All it takes is enough post hoc statistics and a willingness to overlook those parts of the data which don't turn out the way you'd want. The problem is that in academic science, and especially in neuroscience and psychology, there is a strong pressure to do just that. If you report that gene X is not associated with disease Y, or that brain region A does bugger all when people are thinking about B, you're going to have a harder job getting it published than if you "find something". Perhaps even more importantly, scientists can be surprisingly attached to their pet genes / brain regions / treatments and really, genuinely want to find something interesting about them. Luckily, with enough clever mathematics and creative writing up, it's possible to find something almost anywhere (details in a future post.) There's a little Lynn McTaggart inside all of us.

Is this a problem for science? Hell, yes. Can we do anything about it? Sure. I'll elaborate in a future post, but basically we need to introduce pre-registration of studies - like the current systems for the Registration of Randomized Controlled Trials, but covering pre-clinical research as well. Why hasn't this happened? Because no-one's got around to it - we're all too busy dredging our data for positive results and publishing them. Hmpf.

[BPSDB]

Twenty Five Years of Friendship

I met up with my friends whom I know for twenty five years the other day and I took this opportunity to photograph them. There is this wonderful feelings that they never grow old since the day I met them.

They still can be as naughty as the time when we were in the classroom together.

When Ah Beth asked me: "How do I look in the photo?" It took me only a second to answer: "A caring mother!"

I knew from her facial expression that she was not pleased by my answer, but that was my thought after seeing her through my lens.

Well, at least she is a caring mother to a lovely daughter!

Sarah is a self-acclaimed babe, but I always like to tease her that she is an old babe! But honestly, she is as beautiful as twenty five years ago.

She even wanted a car babe shot, so I did this for her.

It was not an easy task finding the good angles as she was very demanding, wanting me to make her look at least ten years younger!

I told her jokingly that I need to do very heavy post processing work for that, but I didn't.

When I put Ah Beth and Sarah together, they became such natural posers.

Susan on the other hand was a bit timid, so I only took one shot of her.

All three of them were the Charlie's Angels in our class twenty five years ago. I wonder whether Charlie is going to recruit them back or not.

After twenty five years, I can still talk to them like when we were in the classroom together. I think it is going to be the same for another round or two of twenty five years. I really treasure their friendship.

Wordless Wednesday – Street People @ Takeshita Dori

Location: Takeshita Dori, Harajuku, Tokyo, Japan
Date taken: August 10^th, 2008
Camera equipment: Nikon D300 + Micro-Nikkor 105mm f/2.8D