New migraine drug hails the future of therapeutic development

If you follow the science sections of the general media, you may have seen reports of a new migraine drug called Erenumab. The drug is not yet on the market but shows promise having just come through the final phases of clinical testing.

Erenumab, made by Novartis, is one of several similar drugs being developed for migraine, including Eptinezumab (Alder Biopharmaceuticals), Fremanezumab (Teva) and Galcanezumab (Eli Lilly). All good news for migraine suffers but these drugs are also examples of modern drug development and that’s the story I want to tell here.

As a general concept, drugs are designed to correct, or adjust, some biochemical or physiological malfunction within the body. This requires the drug to interact with a biochemical process, either activating it, or blocking its action. Making therapeutics which interact with specific biochemical targets – or in the jargon of pharmacology, to develop drugs with high specificity, has been a major goal of pharmaceutical science for several decades. One of the founders of chemotherapy and winner of the 1908 Nobel Prize for Physiology, Paul Ehrlich coined the phase “magic bullet” to describe the concept of specificity. Achieving high specificity has been more challenging than Ehrlich expected however, as in reality rather than a sniper’s bullet, a shotgun blast would be a better metaphor for many drugs. And like a shotgun blast, non-specific drugs hit many unintended targets leading to unwanted side effects.

Traditional treatments for migraine have utilised drugs developed for other indications. Lisinopril, for example, can be prescribed as an anti-migraine drug, although its primary use is to treat high blood pressure. Drugs used for other indications such as depression and epilepsy are also sometimes used as migraine treatments, in effect exploiting their non-specificity for alternative uses. This new range of migraine drugs is different however, in that they were developed to block a specific target; that target being a peptide called calcitonin gene-related peptide, or CGRP for short.

Produced within nerve cells (neurones) it comprises 37 amino acids and comes in two forms known as alpha and beta. As an aside, capsaicin in chilli (the subject of another blog post ) mediates the release of CGRP which is one reason for its association with pain. Neuronal production of CGRP has also been correlated to the onset of migraine and therefore moderation CGRP was identified as a suitable drug target.

But how is a drug developed to block CGRP alone, and not other related peptides? To answer this, we turn to the immune system and the way it fights infection. If you want an example of biochemical and physiological complexity, then look no further than the immune system. Since I have to avoid the tomes of textbook explanations, I’ll over-simplify enormously and just explain that in response to infection the immune system produces proteins called antibodies. The three-dimensional shape of antibodies specifically recognises other proteins on the surface of infecting organisms, where they lock-on acting like flags to white blood cells which then attack and destroy the invaders.

Evolution has honed antibodies to be extremely specific as it’s important they attack invading organisms and nothing else, such as your own body tissues. Drug developers have exploited this high specificity so that instead of locking onto infective organisms, the antibodies bind to, and block, specific biochemical targets. You might say they are the laser guided equivalent to Ehrlich’s magic bullet. The antibodies are biologically engineered in sterile cell cultures with each cell being an exact copy, or clone, of each other. This gives them their name of monoclonal antibodies – or mABs for short. You may have noticed that the names of all the new migraine drugs above end in mab – indicating their origin.

Especially designed to block CGRP with great specificity, the new mAB drugs are the pinnacle of therapeutic pharmacology. Before we get too smug however, remember that the interactions within the human body are extremely complex and it’s impossible to predict all the implications of therapeutic intervention. Little is known of how CGRP is regulated for example, and so there’s always the possibility that some unforeseen side effect lurks in the fog of complexity. Moreover mAB-type drugs have to be injected as they are not absorbed if taken orally. Development of orally-administered mABs is something drug developers are now attempting but there’s still a long way to go. The job of pharmaceutical development is not over quite yet.

Now is not the time to be complacent about plastic pollution

Some of us are old enough to remember when a polyester suit was fashionable. Although still used in clothing today, polyester has diminished in appeal since the 1970s. There is however, plenty of polyester still around but in a different guise as PET or polyethylene terephthalate which is the major constituent of plastic drinks bottles.

Patented in the 1940s as a thermoplastic polymer, PET provided a cheap and readily available packaging material. That economic dream however has now turned into an environmental nightmare as a mountain of discarded plastic has built up across land and sea.

The news media over the past few days have hailed the accidental discovery of a mutant enzyme that breaks down PET as the solution to the plastic pollution problem. As a biochemist I thought the general news media was somewhat short on detail and so I thought I’d take a closer look.

PET comprises repeating units of a chemical called terephthalate and ethylene glycol joined together with oxygen-containing links called esters. Esters and related chemical bonds are common in nature and are generally vulnerable to enzymes collectively called hydrolases, which include esterases, lipases, and cutinases. They all add water across chemical bonds resulting in cleavage of the individual molecules. Blood, for example, is rich in esterases that break down a variety of chemicals, including neurotransmitters such as acetyl choline. The nerve agents recently featured in the news, work by stopping esterase from breaking down acetyl choline thus interfering with normal nerve function.

The trouble with PET however, is that because of its molecular structure the bonds are not accessible to hydrolases although the exact molecular process of enzymic PET hydrolysis is not clearly understood. This doesn’t mean PET is immune from biodegradation, it just means it happens very slowly. All enzymes are what are known as catalysts, in that they don’t react directly rather than just speed up existing chemical reactions. The discovery of the mutant enzyme in the news is just such a catalyst that speeds up the rate of hydrolysis of PET. The effect is highly significant, speeding up the natural process from hundreds of years to just days.

This new mutant enzyme is called PET hydrolase (or PETase for short) and was found in a species of bacteria called Ideonella sakaiensis that lives in the plastic mountains of Japan. This bacteria can live off plastic, breaking it down and using it as a carbon source in much the same way we utilise sugar.

It is however, not the first biological weapon against plastic to be discovered. Last year there were reports that wax moth larvae could break down PET although the effect was likely to be due to bacteria living in the worm’s gut.

The big question is, will these discoveries solve the problem of plastic pollution? The answer is probably, but there is always a lag of many years from the basic science until development of effective technologies. In the meantime, now is not the time to be complacent and reducing plastic consumption remains an important endeavour.

Hot stuff

A 34-year-old man has ended up in hospital after eating a Carolina Reaper chilli.

I have some sympathy because during my first post-doc, I was working in a laboratory at the University of Glasgow where a researcher was extracting capsaicin and some related compounds from chilli peppers. Capsaicin is the chemical that gives chilli its hot flavour and it’s pretty powerful stuff which is why it’s used in pepper spray. This particular researcher made the mistake of dropping a vial of capsaicin, which broke on the floor and spread into the laboratory. We had to evacuate in a manner resembling a teargas attack.

Capsaicin is not just the macho ingredient of curry, it is also used medically. Dermal patches containing capsaicin are used to treat neuropathic pain. It is also used under more dubious credentials such as oral tablets to treat osteoarthritis, and some even claim it cures cancer. Neither, in my view has any validity.

Brain cells and the atomic bomb

Reports appeared in the press recently proclaiming that humans produce new brain cells throughout their lives (for example, The Guardian ). This account appears to contradict previous reports such as

in The Conversation and in Discover Magazine

Don’t we all wish these scientists could make up their mind (pun intended)?

The most recent accounts that the brain generates new cells throughout life did not surprise me as it’s something that has been known for some time. The surprise was that the newspapers thought this was some new breakthrough. I had the enormous privilege of sitting on the Scientific Advisory Board of the Karolinska Institute’s Human Regenerative Map Project where this very subject was studied several years ago. Before I say anything about the results, let me explain the background to the experiments because that, at least for me, is the really interesting part.

The atomic bomb tests of the 1960s released radioisotopes into the atmosphere. One was a radioactive isotope of carbon called carbon-14. The amounts released were surprisingly high as the atmospheric concentrations almost doubled from the pre-1950s levels. (The absolute amounts are still tiny – in the parts per trillion and so there’s no need for alarm). Over time carbon-14 sequestrated into the oceans and following the 1963 treaty to limit testing, the levels fell again. The Figure shows a plot of atmospheric carbon-14 versus year which has become known as the bomb pulse (units of percent modern carbon represent atmospheric carbon-14 concentrations).

During the time of the bomb pulse everyone on Earth accumulated a little extra carbon-14. Let’s take some hypothetical person born in 1963 at the peak of the bomb pulse, we’ll call her Alice. When she was born, the cells of Alice’s body contained peak levels of carbon-14. As time went by and Alice grew up, some cells in her body died away to be replaced with new ones. The new cells, being formed at a later time along the bomb pulse had lower levels of carbon-14. Other cells in her body lasted much longer. In fact some cells in her body may never have been replaced, so they held onto the 1963 levels of carbon-14 to the day she died. This means that the levels of carbon-14 in the cells are proportional to the rate at which particular cells types are replaced by the body over time (known as the turnover rate). If Alice died in 2012 and some given cell type in her body had levels of carbon-14 equal to that of 1963, then the conclusion would be that these cells were the same as those she was born with, at least for the 49 years of her life. If another cell type dated to 2012, then these cells were recent and so were being replaced rapidly within her body.

As part of the human regenerative map project, samples of tissue were taken from consenting Swedish individuals after they died. The dates of birth and death had been recorded and so all that was necessary was to measure the carbon-14 in the tissue and the cellular turnover rates could be calculated. Of course it wasn’t really that simple because cells contain a plethora of substances all of which might be replaced within the body at different rates. To get specific results, it was necessary to measure carbon-14 in the cell’s DNA, which is technically very challenging. An extremely sensitive instrument called an accelerator mass spectrometer (AMS) was used to do this and a picture of an AMS control console decorates the home page of this blog.

Incredibly therefore, the death and destruction following development of the atom bomb has now been put to a much more beneficial use towards understanding the human body.

Before I leave this post, I should mention what the carbon-14 data told us. To do so, I need to give a little technical background. The hippocampus is the region of the brain involved in consolidating information from short-term to long-term memory. Within the hippocampus sits the dentate gyrus which is believed to be involved in new episodic memory and problems in this area are stereotypical of the older generation. The functioning nerve cells of the hippocampus, and the brain generally, are called neurons but unlike the majority of other cells in the body neurons cannot divide. This is itself evidence that brain cells are never replaced but as ever, let’s not make superficial conclusions and look a little deeper and consider where neurons come from.

Track them back and they originate from neural stem cells which then differentiate into a sort of primitive nerve cell called a neuroblast. Neuroblasts are then committed to divide and differentiate into neurons. Neurons themselves cannot divide and so when they die they are gone forever but is it possible for new neurons to be formed from the differentiation of neuroblasts? This has been a point of debate for many years bearing in mind there is a large number of neuroblasts in the dentate gyrus of infants that rapidly decreases and are virtually absent in the adult. This somewhat circumstantial evidence pointed towards minimal neurone regeneration at least in this area of the brain and so the old adage may well be correct.

What was actually found through measurement of carbon-14 from the bomb pulse, was that around a third of the cells of the hippocampus are subject to exchange, which is approximately 1.75% per day. This is good news for those of us who have more years behind us than to come, in that there was little decline in this regeneration with age.

There is however another side to this story. Within the forebrain of vertebrates sits the olfactory bulb. As its name implies, the function of the olfactory bulb relates to smell. The olfactory bulb in rodents changes markedly after giving birth as a result of the generation of new neurons. The same is observed in adult monkeys and is believed to be related to olfactory signals from the new born. The same is not true in humans however, and the neurons of the olfactory bulb date pretty much to the day you were born. Don’t ask me why, I don’t know. Perhaps humans have evolved other ways of recognising our young than smell and so it is no longer necessary but this is of course, pure speculation.

So the answer to the question, do humans produce new brain cells throughout their lives? It depends on which part of the brain you’re talking about. Now isn’t that a surprise.

Rerunning the great science experiment

A lawyer friend of mine once asked me what science is, and what separates it from any other intellectual discipline? The question followed a philosophical discussion where I claimed my friend, as a lawyer, had a tendency to decide upon his desired outcome and then search for the evidence to support it. Science, I explained, did things the other way round and based its outcomes upon a consilience of evidence. I had to think for some time about what differentiates science from other subjects, after all, it’s not the only evidenced-based subject. History, for example, relies on documentation and archeology. I came up with the following answer in the form of a thought experiment.

Imagine that it was possible to control-alt-delete and start human existence from scratch. In this new world our cultures would be different, our religions, our legal, economic and political systems all have a virtually infinite number of alternative options to choose from. Historical events would be different, we may or may not have fought wars and if we did, then they would be about different grievances than those in our own history.

At some point in the new history, great minds appeared and the scientific method would be developed. As science progresses so it uncovered the mechanics of nature, not necessarily in the same order as we did, but its discoveries would nevertheless be the same. Newton’s laws of gravity might have an alternative name, Slartibartfast’s laws perhaps, but those laws would be no different to the ones we know. The laws of chemistry would be identical and DNA would have the same molecular structure that rigidly obeys those laws.

The discovery of evolution of species by natural selection would emerge, perhaps bypassing Lamarckism, perhaps not. For science is not about making the laws of nature, science is a way of discovering them. The scientific method removes human subjectiveness and points us towards reality as best as anything we have found so far. Of all subjects science is unique in this respect. It discovers what is, irrespective of what we humans believe.

Surely we would, my lawyer friend argued, require a social and political system which allowed scientific enquiry to flourish? Without the freedom to challenge assumptions, and authority, or without the liberty to ask questions, science would remain a stifled backwater. On that, my lawyer friend and I can agree but that’s a whole new thought experiment.

Subjective experience is not evidence

We all have our own idiosyncrasies and habits which we learn mostly from personal experience. Formulating a useful mental model of the world is what’s kept our species alive over evolutionary time. If eating a particular plant made you ill, then you knew to avoid it in the future. The problem with this is that our personal experience is very susceptible to error. I strongly dislike cider and even the smell turns me away. The reason is that when I was about sixteen I got very, very drunk on scrumpy and the aftermath is not something I want to remember. I hate cider to this day but there are many who love the stuff and it does them no harm (within limits).

The personal experience effect, otherwise known as subjectivism, works in both a negative and positive sense. Getting fed up with the symptoms of a cold you take a heavy dose of vitamin-C and within a couple of days everything is back to normal. The chances are that things would have got back on track without the vitamin-C as colds only last for a finite time anyway. Now however, you’ve associated vitamin-C with curing the common cold and nothing will change your mind.

I suffer from osteoarthritis and I’ve heard no end of accounts of treatments from rhubarb leaves to fish oil. There are those who swear by these treatments but then another problem arises. Some claim fruit juice eases the symptoms of osteoarthritis and others claim the acids in fruit juice exacerbate the symptoms. Both sides firmly defend their conflicting positions while there is actually no evidence for either claim.

I have encountered some who take their own subjectivity to extreme lengths. I came across someone who claimed all modern medicine was a conspiracy by big Pharma and governments to poison a gullible populace for profit. This sounds delusional, but it turned out he had seen his Grandfather die after suffering from cancer and the effects of chemotherapy. His very strong emotional experience had a profound effect and no amount of reason or fact would ever have the same impact.

There are those who offer their well-meaning subjective advice to others and there are those who tell their own anecdotes of how vitamin-C cured their cold. I might disagree and challenge their views but it’s a human trait and so I’m careful not to make the arguments too personal. Then there are the quacks that offer wonder cures for serious disease to those willing to pay them enough money to reveal the secrets “that medicine doesn’t want you to know.” These are the charlatans, the shameless exploiters and they should be treated the same as any other con-merchant. Those are the ones that need the blunt end of verbal wrath but just remember there are also victims of the charlatans where we should be more empathetic.

World Immunisation Week

The World Health Organisation has declared this week (24-30 April) World Immunisation Week.

Development of vaccines has been one of the most signifiant medical advances in history and has led to the virtual eradication of many of the world’s most deadly and contagious diseases. Smallpox is now gone from the world and polio that used to infect over a third of million people per year in the 1980s has now been reduced by 99% worldwide thanks to introducing the first effective vaccine for this disease in 1955.

Despite overwhelming documented evidence of the success of immunisation, there is an anti-vaccination movement that has done innumerable harm by spreading irrational untruths that vaccines are ineffective and harmful. The consequences have been in the news over the past year or so, reporting the return of diseases such as mumps and measles. Parents have become confused and conflicted about vaccination since ever since the now discredited Andrew Wakefield’s claimed association between autism and he MMR vaccine. He was disclosed as a fraud but there are still those that hang on to his bogus claims.

The vast majority of medical doctors and scientists recognise the contribution vaccines have made to our health. The anti-vaccination brigade on the other hand is largely made from those with no credentials, or any particular knowledge of science. Their influence is surprising because, to me, it’s like trusting your car to someone who believes it’s powered by a hamster in a wheel instead of a qualified mechanic.

Such anti-vaccination campaigns are reprehensible but at the same time, perhaps, vaccines have become a victim of their own success. In the developed and western world, diseases such as polio, rubella, chicken pox and mumps are largely confined to history. Without direct experience of the ravages of these diseases, then a healthy population starts to forget what it was once like. In the words of Joni Mitchell’s Big Yellow Taxi – “don’t it always seem to go, that you don’t know what you’ve got, ‘till it’s gone.”

People who get sick will seek medical help but vaccines are prophylactic, they prevent the disease from occurring in the first place and so it’s easy for a population to lose its collective memory of what it was once like. All they see are the publicised false risks of vaccines and not the hugely greater risks of the diseases themselves. I am of an age to remember friends wearing leg irons because of polio – something now thankfully in the past.

Who will buy my supplement?

If I were unscrupulous and cared more about money than my reputation then I recon I could do well in the world of dietary supplements. Allow me to sell you my wonder supplement Metalo-Lappin-Detox.


The industrial age has seen an unprecedented increase in heavy metal pollution that can lead to mental and physical deterioration and accelerated ageing. The human body tries to protect itself from this onslaught through a protein called metallothionein-2A that detoxifies heavy metals such as cadmium. Metallothionein-2A is made from amino acids and its most abundant and important amino acid is cysteine. Innumerable scientific studies have shown how cysteine is incorporated into proteins and how its nucleophilic properties are essential to detoxification.

You can now enjoy the health benefits of cysteine through Metalo-Lappin-Detox, a unique combination of amino acids all contained within a fast release capsule especially formulated by the renown toxicologist, Dr Graham Lappin. The unique mixture is fortified with cysteine and its precursor, sulphur, critical to metallothionein-2A activity.

Dr Graham Lappin, is an expert in the metabolism of toxins. He has over 30 years experience and has held 3 professorships, including those from the Medical University of Vienna and Duke Medical School in the United States, the home of Nobel Laurette Robert J. Lefkowitz.

Metalodetox is only available from Dr Lappin’s website and is priced so you can afford it. Take just one 250 mg capsule per day and a week’s supply is just £10. What price would you place on your health?


The above description is a lot more accurate than many detox claims but is still bogus. And yet, everything it says is true (although “renown” toxicologist might be pushing it a bit). Heavy metal pollution has increased with industrialisation and is associated with mental and physical deterioration. Many heavy metals when ingested lead to oxygen radicals which are associated with ageing. The body has evolved systems to neutralise heavy metals, because life has been exposed to them (in varying concentrations) since it climbed out of the primordial ooze. Metallothionein-2A is one of the key proteins that protects the human body from heavy metals such as cadmium. Metallothionein-2A is made of amino acids and sulphur-containing cysteine is one of the most abundant. The links to the scientific literature are genuine and the studies are valid. My list of my credentials is also accurate.

All of these individual facts are verifiable via Google and all seem feasible. It is however a classic example of pseudoscientific exploitation. The trick is the way the individual claims are joined together – or more accurately the way they are not.

The biggest gap – the breadth of the grand canyon – is simply the notion that taking a cysteine supplement will somehow increase the ability of metallothionein-2A to do its job. Metalo-Lappin-Detox also contains sulphur which is present in cycteine but is not incorporated into protein in its elemental form. Furthermore, the body makes its own cysteine and we do not require a dietary source of this amino acid. A healthy person makes more than enough cysteine for incorporation into all of the proteins. A supplement of 250 mg per day will make no difference whatsoever to the body’s ability to cope with heavy metals.

Reference to the scientific literature is particularly convincing. The first study quoted, entitled “Role of metallothionein and cysteine-rich intestinal protein in the regulation of zinc absorption by diabetic rats” sounds right on the money. The paper has nothing to do with the claims of Metalo-Lappin-Detox but most of the public could not assess this – which is exactly what the sales pitch is relying on. In fact the claims for Metalo-Lappin-Detox are full of science-sounding terms such as “nucleophilic”, which again if Googled would appear to be used correctly.

The ploy of listing credentials is almost universal in pseudoscience, so much so it’s a trade-mark. At least in my case I hold a genuine PhD and not bought off the internet from the Hogwarts University of Technology. Robert J. Lefkowitz is indeed a Nobel Laurette at Duke University and I held a adjunct professorship there. I have however, never met him nor had any involvement in his groundbreaking work. If the reader makes any assumptions then that’s up to them.

The pricing seems reasonable until I tell you this is three times the price for analytically-pure laboratory grade cysteine. A fast release capsule is in fact, a capsule, just like the ones used for paracetamol (acetaminophen in the USA) you can buy cheaply over the counter.

Finally, I would keep a close eye out for any celebrities purchasing Metalo-Lappin-Detox and then make sure I add this to the website. I’d even give a year’s supply for a celebrity endorsement.

Many detox and other “natural” remedy claims are nowhere near as “scientific” as the one above. Many include explanations about energy flow or they invoke quantum effects. It’s all too easy to make this stuff up and it’s all big business.

Now anyone know of a good website where I can buy my yacht?

CAM preys on the vulnerable – and I should know

Those who know me, readers of this blog, or followers on Twitter know I am not a fan of so called complementary and alternative medicine (CAM). When asked why I care about CAM and why I spend my time attacking it in the way I do, it’s because of my own vulnerability.

I should start by saying I really don’t care if those with more money than sense indulge themselves in much of the nonsense of the naturopathic world. It’s impossible to remove every possible scam from people’s lives, be it the latest craze in shampoo, some new detox diet, sports enhancement bracelets, or even some of the legal but dubious financial offers. There is a slippery slope however, and there comes a point where certain practitioners of CAM offer cures for serious diseases. Not only do they do this, but they evoke the name of science to give it a patina of credibility. For the untrained, much of this woo is easily mistaken for the real thing.

I have a personal interest in all this because I suffer from a chronic incurable disease. I have osteoarthritis accompanied with general muscular-skeletal damage caused by a motorcycle accident many years ago. Chronic pain that oscillates from mild on some days to excruciating on other days is symptomatic of the condition. It’s very hard for those who don’t suffer from chronic pain to understand the effects, which are not just physical but also psychological. There are days where the despair becomes almost overwhelming and the frustration comes close to self-loathing triggered by the limitations the condition puts on me. I have friends (two in particular) who also suffer from chronic pain but for different reasons to my own. They understand what it’s like through personal experience, and that’s not something I am not going to wish on anyone, not even the worst CAM scam artist.

I say this not because I want sympathy – I cope reasonably well most of the time (with the support of my wonderful wife). I have described my condition because I’m trying to give a flavour of the desperation anyone in my situation might have for a cure. I would love to simply press a button and it all goes away. And with this desperation comes vulnerability; at times I feel like a wounded gazelle with the CAM lions circling.

Herbalists, acupuncturists and homeopaths have all offered cures. How easy it would be to give my money to these people in the hopeless desire to press that button. Some of the CAM practitioners may do it in good faith, others will be downright scammers with sociopathic tendencies. Deluded or fraudster however, the outcome is the same. A mountain of solid scientific enquiry has shown the vast majority of CAMs are not fit for purpose. Given the huge complexity of physiology and biochemistry of the human body, this is not surprising and over-simplistic solutions and pseudosceince have nothing to offer.

There have been innumerable cases when the CAM practitioner encouraged their client to stop their real medication so they could sell them more of their woo, and then the situation becomes downright dangerous.

And so, if my ranting can help prevent just one person from being taken in by pseudoscientific nonsense, then it will all be worth it. And so that’s why I do it, that’s why I will carry on doing it.

Everyday use of the Scientific Method

About a year ago I had an experience of how the scientific method could apply to a simple domestic situation. I thought I would share it as there are parallels between science and pseudoscience in this story of everyday folk.

I rented a house in Lincoln (UK) whilst I was an academic at the University’s School of Pharmacy. An electric immersion heater supplied hot water and that tank was kept full via a standard ball-cock valve on the cold water supply. All was not well with the hot water supply however, because there was a constant trickle of cold water into the tank irrespective of hot-water usage.

Curiosity

A lot of scientific discovery starts with pure curiosity, the “that’s interesting, I wonder what that is?” type question. A good example of this was when Richard Jorgensen became curious about patches of colour on petunia petals. His investigations led to the discovery of a whole new branch of genetics and won him the Nobel Prize in 2006.

Hypothesis

Although I was not about to win a Nobel Prize, the constant trickle of water was nevertheless intriguing. I therefore formed a hypothesis that there was a leak somewhere in a hot water pipe. I traced all the pipework to see if I could find a telltale pool of water. There was none and hence no evidence for a leak.

Perhaps I was misinterpreting things and the constant trickle of water into the tank was normal. But the investigation at that point was superficial and so I investigated further. I found the main valve feeding the tank’s cold water supply and turned it off overnight. The next morning the tank was empty, so where had the water gone? I found the valve for the tank’s hot water outflow which I turned off and the constant trickle of inflowing cold water stopped. With both the cold water feed valve and hot water outflow valve off, the tank remained full. Clearly that constant trickle of water was not normal.

With no visible signs of a water leak, the tank was still emptying in a matter of hours. Perhaps the water was leaking somewhere I couldn’t see? I knew one hot water pipe went under the floor to feed the kitchen tap. It was a concrete floor and so I couldn’t get to the pipe to observe if there was a leak or not.

Make predictions from the hypothesis and test them

Scientists figure things out all the time without making direct observations. Instead they look at the consequences that a particular hypothesis might have and then work out what’s happening from there. In my case, there were no valves to isolate the under-floor pipes and so I had to get a little more inventive. The underfloor pipe branched off from the main pipe at a T-junction. One end of the T went to the kitchen tap (under the floor) the other went into the bathroom. So I came up with an idea that involved the flow of heat, rather than water.

The house had copper pipes which are good conductors of heat. By opening or closing the kitchen and bathroom taps, I followed the flow of water simply by feeling the heat running along the pipes. In technical terms, the heat was a surrogate for the water flow. With the bathroom and kitchen taps off there should be no flow of hot water and therefore all pipes should remain cold. Over time however, the pipe that went under the floor became warm, while other pipes remained cold. The conclusion was that there was a flow of hot water (detected from the heat of the pipe) under the floor, even when there should be none. The most likely explanation therefore, was that the pipe was leaking somewhere along its length under the floor.

Hypothesis becomes a theory

On the weight of evidence, there was a leak in the hot water pipe under the concrete kitchen floor. The evidence was consistent with the known laws of physics – for example, water flows downwards under gravity, copper conducts heat etc. In science, a theory has to be consistent with what is already known. For example, if some theory of biology breaks a law of physics, then the biological-theory cannot be right. Science is joined up in that way, each part has to fit with all the other parts. Pseudoscience on the other hand has no problem believing all the textbooks can be re-written just to accommodate their particular ideas. Getting back to my leaking pipe, it was time to call the landlord and get a plumber.

I explained my diagnosis to the plumber but he did not like the outcome. I could tell that the thought of having to uproot the floor did not appeal to him. He therefore said he would replace the ball-cock valve, which he claimed must be leaking, causing a constant trickle of water.

Counter hypothesis

I explained to the plumber how changing the ball-cock valve was not consistent with the evidence. How, for example, did the hot water tank empty when the ball-cock valve was isolated by turning off the main cold water tap? But he didn’t want to hear it. He told me he’d been a plumber for 20 years and so he knew what he was doing. An appeal to authority however, was not consistence with the actual evidence. The problem was that he didn’t want to accept where the evidence was leading simply because of the personal consequences to himself. Science frequently encounters such self-motivated objections. The economic consequences of reducing carbon dioxide emissions, for example, are so profound that the theory of climate change must be wrong!

Getting back to the reluctant plumber, after a little discussion, I got him thinking and he said he would check something out.

Independent testing of the theory

He went outside the house and dug down by the wall next to the kitchen. It didn’t take long before he hit mud. What he was hoping for was dry soil which would be counter-evidence for a water leak. In fact, dry soil under these circumstances would not have been particularly diagnostic one way or the other because the leaking water could have been flowing in any direction under the house. In science, some evidence is robust and other evidence is more circumstantial. It’s a common fallacy to confuse the two as being equal. The wet ground in this case, was supporting evidence for the leak-theory but the plumber then rationalised the mud by saying it had been a wet year and it could just be ground water.

Unsinkable rubber duck!

This is a term used by rational thinkers when someone finds a way round every item of evidence presented to them to support their own preconceived position. Young earth creationists who believe the earth is less than 10,000 years old are masters of the unsinkable rubber duck. Point out that light from distant stars has taken many millions of years to reach the earth, then they will claim the speed of light has not always been what it is today. Likewise, no matter what the outcome from the plumber’s test-dig by the kitchen wall, it would reinforce his own viewpoint or at least not change it. But I had to be careful because although the mud seemed to support my leak theory, the possibility that is was a coincidental ground water could not be ruled out as there could have been multiple reasons for this observation. Scientifically, I could have added a tracer dye to the hot water to see if it ended up in the mud. Even for me however, this seemed a little over-the-top and so instead, I suggested that he dig another test hole around the other side of the house to see if that was wet due to the water table. He thought about it but declined. To him, unwillingness to further test his theory seemed to reinforce his own position.

Confirmation of the theory. In science my water leak would have been tested in a multitude of ways. Someone may have come up with some new ingenious methods and others would have confirmed or failed to reproduce my data. Then those tests repeated and so on, with the results either reinforcing the theory, leading to modifications of the theory or even to discard it and start again. Pseudoscientists on the other hand are content to accept the first whiff of flimsy evidence that might vaguely support their point of view and ignore far more robust evidence against them. The case of my hot water was a little more domestic and anyway, showering at work was getting tedious.

So what happened? The plumber and I did not pass on particularly good terms. I got on well with the landlord and so he let me find another plumber for a second opinion. The second plumber wasn’t that bothered about my method of diagnosis as he saw a simple solution. He simply put in a new pipe above floor level, bypassing the one with the leak. He took about an hour and afterwards the problem was solved. The constant trickle of water to the tank stopped.

In science, this would have opened other questions such as, exactly where was the leak and what was the cause? Even without knowing this level of detail however, the theory of an underfloor leak in a hot water pipe still stood firm. In contrast, pseudoscience often presents any gap in knowledge as evidence that the whole theory is wrong. You don’t know exactly where the pipe was leaking, therefore that was not the cause. You can’t observe every intermediate species between Hypohippus and the modern horse, so evolutionary biology must be wrong. Or the gap is filled with any old nonsense; aliens living under my house were stealing the water – that type of thing. Well, you can’t disprove it, can you?

And just a final note. My persistence with the first plumber was not about being right, it was about the evidence. All too often there are those who evoke the name of science to prove themselves right at any cost. Science is the exact opposite of this. Regarding the first plumber, if he could find better evidence to support a different theory then I would have been very pleased to change my point of view. Even if an alien had suddenly appeared out of the test-hole!