There’s a fascinating feature on the nocebo effect in this week’s New Scientist. Basically, nocebo is the opposite of placebo: it makes people unwell, or causes them pain, through the power of suggestion. The article tells the fascinating (and rather disturbing) tale of Sam Shoeman, who was diagnosed with end-stage liver cancer in the 1970s and given just months to live:

“Shoeman duly died in the allotted time frame - yet the autopsy revealed that his doctors had got it wrong. The tumour was tiny and had not spread.”

He died as a result of believing he was dying. How scary is that? Hypochondriacs, look away now.

Ben Goldacre has outdone himself – I’d be tempted to call this column his best to date.

It’s too easy to snipe at homeopaths or purveyors of crystal healing: science has its own issues, and really ought to put its own house in order over some things. Like someone once said, when there’s a plank in your eye, it’s hard to see other people’s faults clearly. Or something.

Anyway, Ben’s column is about an anomaly in science publishing, and one that urgently needs attention. He highlights the fact that research studies funded by the pharmaceutical industry are “massively more likely to get into the bigger, more respected journals.”

There is, Ben points out, no explanation for this other than pharmaceutical companies having undue influence over the most prestigious journals.

Journals are businesses, run by huge international corporations, and they rely on advertising revenue from industry, but also on the phenomenal profits generated by selling glossy “reprints” of studies, and nicely presented translations, which drug reps around the world can then use.

There is a possible solution:

In an ideal world, all drugs research would be commercially separate from from manufacturing and retail, and all journals would be open and free. But until then, since academics are obliged to declare all significant drug company funding on all academic articles, it might not be too much to ask that once a year, since their decisions are so hugely influential, all editors and publishers should post all their sources of income, and all the money related to the running of their journal. Because at the moment, the funny thing is, we just don’t know how they work.

It's a very good call. And if this leaves you thinking that Big Pharma are the root of all evil, please read this Guardian story about GlaxoSmithkline rewriting the Big Pharma Book of Evil. They are changing the way they work in order to provide medicines for the world’s poor, and are going to start sharing information that might help speed up drug development. Read it and weep. I have rarely had the cockles of my heart so warmed.
 

A little more homeopathic stuff. I blogged on the Guardian’s science pages about homeopathy and the NHS yesterday. Go and read it, but basically, I suggested that homeopathy is most probably a placebo, and one that is potentially useful to physicians looking for an easy placebo treatment – which is not the same as doing nothing.

The entry provoked a lot of thoughtful comments. Here’s a taster from one, written by Le Canard Noir:

Homeopathic retailers sell their customers sugar pills to protect themselves against malaria and Fellows of the Society of Homeopaths try to conduct AIDS trials in Africa using magic water….If placebos are ever ethically justified then deluded people are not the best set of people to be dishing them out.

I completely agree, but I’m not talking about the way I would set the system up. I’m talking about what we’ve got to work with now. To quote 13 Things:

According to the World Health Organisation, it now forms an integral part of the national health care systems of a huge swathe of countries including Germany, the United Kingdom, India, Pakistan, Sri Lanka, and Mexico. London’s Royal Homeopathic Hospital, part of the UK’s national health service, employs a staggering 6,000 staff. Forty per cent of French physicians use homeopathy, as do 40 per cent of Dutch, 37 per cent of British and 20 per cent of German physicians. In 1999 a survey revealed that 6 million Americans had used homeopathic treatments in the previous 12 months.

I think it would be wrong to impose a ban on something that so many people have faith in. That carries the risk of pushing people further away from sensible healthcare.

Of course there are dangers from the extremes, but I’m not talking about doctors referring HIV prevention, cancer treatment or malaria prophylaxis to homeopaths. That would be ridiculous. The people who already go straight to homeopaths for this kind of thing will continue to do so, no matter what the system does or doesn’t endorse. There’s nothing you can do about that, just as you can’t stop people believing in horoscopes, or the power of psychics. People make life-threatening decisions on the basis of these hokum ideas too. People are human. What are you going to do?

Since this is Darwin Year, and 13 Things… comes out in the UK this week, I had a thought about blogging Darwin’s experience with homeopathy. The big H, after all, is the one that most people (including me, and almost certainly Darwin) would like to see removed from the list.

As it turned out, Le Canard Noir has done a fantastic job of this already, and encountered the weirdness of debating the efficacy of homeopathy with homeopaths. You can never win, they can never convince you…it’s the very definition of the word impasse.

So why re-invent the wheel? My advice is, read to the end of the official entry, but don’t get drawn too far into the comments. You may never get out alive…

 
I’m back from New York now, and wondering where my jet lag ended and that oh so predictable British winter lethargy kicked in. I’m one of those people who functions better with a charge from a lightbox, and the time has most definitely come to be using it.

Seasonal Affective Disorder is all in the mind, of course, but that doesn’t mean it’s not real – it’s like placebo. I was interested when I visited a neuroscientist at University College London and saw that he has the same lightbox model as me. I asked him if he thought it was actually a placebo. “Who cares how it works?” he said, laughing. “It works - that's enough for me.”

Actually, there’s evidence to show it has a biochemical effect (as there is for placebo; when will we stop saying "just a placebo" as if it wasn't a powerful effect?). Last year, a paper in – wait for it – Neuropsychopharmacology showed that it’s to do with serotonin (the happy molecule) being removed from cells too efficiently. In those who suffer from winter depression, the serotonin transporter molecule is getting on for twice as active as it should be. The removal rate returns to normal levels in summer, but can be slowed down in winter by light therapy. There’s a New Scientist story about the study here.

I’ll get round to blogging about my experience of talking at the Hayden Planetarium very soon, but – well, you know: I’m seasonally affected, aren’t I? There’s something pleasingly poetic about a sluggishness that results from overactive serotonin transporter molecules. Those babies are really going for it. No wonder I’m so tired…
 

Dan Ariely of Duke University in North Carolina won an Ig Nobel prize last week for showing that expensive placebos work much better than cheap ones. People who believed that the pills they were given cost $2.50 each reported feeling less pain from a series of electric shocks than people who thought their pills had been discounted to 10 cents each.
 
The Ig Nobels are traditionally meant to celebrate humorous but essentially pointless science – other winners this year included researchers who had proved that Coca-Cola douches do not provide effective contraception and University of New Mexico psychologists who proved that lapdancers make more tips when in the most fertile periods of their menstrual cycle.
 
However, the placebo research is far from pointless. It illustrates a point that leading researchers are only just beginning to acknowledge, and could have implications for clinical practice, the regulation of complementary medicines and the way we conduct clinical trials of pharmaceuticals.
 
We have long known that belief and expectation play a powerful role in the biochemistry of the human body, but the placebo effect is a much more powerful and mysterious phenomenon than we have been led to believe.
 
As I outlined in 13 Things…placebo researchers have learned, for instance, that diazepam doesn't reduce anxiety in patients after an operation unless they know they are taking it (it's not yet clear if this is also true of diazepam's other effects). National Institutes of Health researchers have shown that cocaine abusers who know they are receiving the drug can get by on half the amount required by those given a covert dose. If you don't tell people that they are getting an injection of morphine, you have to inject at least 12 milligrams to get a painkilling effect, whereas if you tell them, far lower doses can make a difference. This has obvious implications for the way we run clinical trials.
 
It turns out that Ariely  (check out his web page here – it’s crazy and intelligent stuff) may not even have needed to deceive his subjects into thinking they were getting a medicine at all, whether cheap or costly. It is possible to bypass common sense with the placebo effect. When, as part of research for 13 Things… I asked researchers to elicit a placebo response in me, they had no trouble doing it. Even though I knew I was being tricked, the placebo conditioning procedure still allowed me – like Ariely’s subjects – to experience a series of electric shocks as nothing more than a light touch on the arm. (I blogged about this for New Scientist here.)
This is a potentially useful discovery, allowing doctors to bypass the ethical problems of deceiving patients. Researchers at the University of North Carolina have shown, for instance, that ADHD-affected children can manage on reduced stimulant medication – reducing side-effects – when given a placebo. The twist is, the children, the doctors and the parents all knew they were using something with no active ingredient, but it worked anyway. Such “open-label” use of placebos holds great potential for improving health care, the researchers say.
 
Ariely’s findings could help lay to rest one of the great arguments of modern science: whether homeopathic remedies and other complementary medicines have any medical benefit above placebo. Science has struggled with the question because there are indications in the literature that these interventions do have some effect beyond what the placebo effect can explain. But now that we are beginning to understand that placebo response depends on previously unexplored factors like perceived cost of the medicine (and homeopathic medicines are certainly not cheap), perhaps we can find a way out of this quagmire.
 
Add in the idea that some chemicals are only efficacious when in contact with the chemicals our bodies produce when we have our hopes raised, and we start to see that we have some seriously murky waters to explore before we can claim to understand how and why many medical interventions work – or don’t. The placebo effect is not at all as we have imagined. And it is certainly not that funny.