Antibiotic from breastmilk - really?

The Newspaper headlines read:

-  New Drug to wipe out superbugs - antibiotic ‘bullet’ created from breast milk (The Times)
-  Breast milk could wipe out hospital superbugs and even incurable diseases (Express)
-  Breast milk protein could be used in fight against antibiotic resistance (Guardian)
-  Breast milk protein could destroy antibiotic resistant superbugs (Independent) 
- Drug resistant bugs destroyed by new antibiotic from breast milk discovered by British scientists (Mail)

The stories themselves contained very little information on what this new antibiotic was. The original story seems to have come from an interview with the Times but all the newspaper reports were remarkably similar containing all the same quotes and statistics. In fact they were all so similar that if I had seen these in student essays I would have very good grounds for a case of plagiarism.

The gist of the story seems to be that a breast-milk protein called lactoferrin was found to “kill bacteria and viruses on contact.” Most reports said that it was developed jointly between the National Physical Laboratory and University College London and some said it had been reported in Chemical Science (from the Royal Society of Chemistry).

The report on the Express website included a video clip of Dr Freya Harrison, of the “School of Life Science” who appeared to be proclaiming her surprise about how powerful the medication was. When I checked however, Dr Harrison had nothing to do with the so called breast milk antibiotic. She is in fact a respected academic at the Univeristy of Nottingham’s Ancient Biotics Project. The clip was about the antimicrobial properties of some ancient remedy, undefined in the video, and completely unrelated to the story, other than the word antibiotic was mentioned.

The story had certainly done the rounds as I also found it on websites such as The Economic Times Pharmaceuticals section, where incidentally they had a link to the Royal Society instead of the Royal Society of Chemistry.

Since the antimicrobial action of lactoferrin has been known for a long time, I wondered why this was considered a breakthrough and so I dug a little deeper.

The original paper that caused all this excitement was indeed published in Chemical Science (well done to the newspapers that got that right) and can be found here. It was a little tricky to track down from the information given in the press, as any search using “breast milk” came up blank (or to websites that I’m not going to mention!!!). The paper is very technical and I am pretty sure journalists without a great deal of specialisation would not be able to interpret it. I am a pharmacologist and I admit I had to spend some time on the various technical terms before I could grasp the meaning. This is, of course, absolutely normal with a scientific publication as it’s meant for the science community not the lay public. 

The antimicrobial is in fact a very innovative piece of protein engineering exploiting a naturally occurring protein called lactoferrin. Although, as I said above, lactoferrin is indeed found in breast milk, it is also found in saliva but I guess a headline proclaiming a new wonder drug has come from spit doesn’t have the same appeal to the media. Essentially the science behind this has nothing to do with breast milk at all other than the protein can be found there. I wonder, when penicillin was first discovered, if the headline was “mouldy bread cures pneumonia?” 

Lactoferrin was engineered so that it formed a self assembling virus-like structure they called plastic peptide capsules. The researchers chose lactoferrin because it does have antimicrobial properties in that it binds to the surface of bacteria and it is non-haemolytic (does not burst red blood cells). Once bound, it punches a hole into the bacterial cell wall. This in itself will effectively kill the bacteria but the virus-like structure could also be used to deliver an siRNA payload. siRNA (Small Interfering RNA) is a nucleic acid that interferes with the expression of certain genes. It was a serendipitous discovered by Richard Jorgensen when he was investigating stippling on the petals of petunias. Jorgensen won the Nobel Prize in 2006. The intrinsic therapeutic properties of siRNA are well recognised but the nature of these molecules makes them very difficult to deliver to their biological target. This new structurally engineered protein may be one approach for siRNA delivery but the researchers were careful to point out that this was a conceptual design.

The real story was therefore far more interesting and exciting than the newspapers actually reported. This is real cutting edge science where molecules are constructed for specific functions. Like virtually all of science, it wasn’t a breakthrough rather than a step in the painstaking process of research.  But there was not a whisper of this in any of the media reports I could find. It was, I guess, just easier for the journalist to take the original story,  jiggle a few words around and go to press without worrying if it was accurate or not.

Does it matter that the press didn’t report what was a highly technical piece of science properly? Well, yes, it is very important.  Surveys over many years have shown that the public’s main source of information on science comes from the general media (eg Ipos MORI Survey, commissioned by the Government Department of Business, Innovation and Skills in 2014). If the press cannot be bothered to do their job properly then how can the public’s understanding of science be anything than corrupted - the old adage garbage in, garbage out. The press seem able - some of the time anyway - to unpick the complexities of economics but science so often seems beyond them. What's more I don’t think it will change anytime soon, which is both worrying and sad.

Bial clinical disaster - a cautious tale

The news that a clinical trial being conducted in France has gone horribly wrong hit the headlines earlier this week.

Currently very little is known about the circumstances which is probably not surprising at this stage. Piecing together various sources, it seems that the drug is called BIA 10-2474 being developed for central nervous system indications such as chronic pain by the Portuguese pharmaceutical company Bial. I have searched for published data on this drug but failed to find anything, which is a little unusual as there’s normally something in the literature by the time of the clinical trials. It’s possible I have missed something but all I could find was the chemical structure and the drug’s target which are given in a US patent application .

BIA 10-2474 is an inhibitor of an enzyme called fatty acid amide hydrolyse (FAAH) which degrades endocannabinoid neurotransmitters. Overall the range of FAAH targets are well established and considered safe (I understand BIA 10-2474 targets FAAH2).  The clinical trial was a Phase-I study, where the drug was given to healthy human volunteers for the first time. It seems that the drug was given as single doses to the volunteers without any issues but problems started to appear when administered as repeat doses.  The media have also reported that the drug was previously tested on animals (which it would have to be under global regulations) but some reports say it was tested in the chimpanzee. 

There are some aspects of the reports so far that look decidedly odd to me. Such a significant switch in toxicity from single doses to repeat doses is extremely unusual and the use of the chimpanzee in toxicology safety testing is very surprising.  Such studies are virtually unheard of these days with the National Institute of Health in the US retiring such studies last year.  It is possible the chimpanzee studies were performed some time ago and it is known that the rodent is not a good model for the FAAH target, but even so this is still very rare.

In the vacuum of information, speculation has started to expand but I think we all have to be cautious, particularly since much of the information we do have comes from the general press, which has a notoriously bad track record when it comes to reporting technical detail. In the early reports the drug was described as cannabis related, presumably because a journalist saw the term “endocannabinoid neurotransmitters” then made an assumption.  Likewise, I wonder if the toxicology species was a monkey (perhaps cynomolgus) which then got translated to chimpanzee - but I could be wrong so this is purely my own speculation.

The incident with BIA 10-2474 has been likened to the previous clinical trial disaster in 2006 with TeGenero’s TGN1412 (TeGenero is now out of business). The two drugs however are very different, with TGN1412 being antibody-based and the resulting toxicity arising from a cytokine storm on the first administration.  BIA 10-2474 is a small molecule drug (molecule weight 327) and apparently only became problematic on repeat dosing. What the two drugs may have in common however, was highlighted in the findings of the TGN1412 enquiry in that animal studies do not always predict adverse effects in humans when the receptor is human specific. There is a smidgeon of this with BIA 10-2474 as the FAAH target is certainly not present in all animal species (and may explain the use of the chimpanzee if reports on the use of this species were accurate). 

There is an argument that the TGN1412 disaster could have been avoided if certain previous studies had been published thus providing a red flag prior to human administration (highlighted in Bad Pharma by Ben Goldacre, pages 8-10). Certainly the industry overall is still plagued with secrecy and remains reluctant to put data into the public domain. There is an ongoing campaign led by Ben Goldacre to make the Pharmaceutical industry publish all human data (http://www.alltrials.net) with some companies, such as GSK signing up but the majority still pushing back. It is my view that the regulators should make publication a requirement. Then there would be a level playing field which would remove many of the commercially-based arguments against publishing and the regulators would also be achieving their principal goal of strengthening public safety. Frankly in my opinion, keeping science secret that has such a profound impact on public health is nothing short of criminal. On this basis therefore, it is a little alarming that I can’t find any previously published data on BIA 10-2474.

Having noted the point about transparency in drug testing, we still have to be cautious in the specific case of BIA 10-2474 as we know nothing about the root cause of the disaster. It may, for example, have been a pharmacy dispensing error leading to overdose of the volunteers. (I stress this is pure speculation and there is currently no evidence for this that I am aware of). If it does turn out to be something of this type, then the cause of the BIA 10-2474 disaster would be unrelated to the cause of the one with TGN1412 or the lack of previously published information. We should all keep our powder dry at the moment, I think, on using BIA 10-2474 to promote any specific perceived preventative actions.

In the meantime all we can do is wait for the investigation to report their findings.  I hope the regulatory agencies do not surround themselves in a wall of secrecy and release information as they proceed rather than in a report that might take months or even years to publish. And as we wait, be just a little cautious of what you hear in the general press as it's not always as reliable as we might all want it to be.

Home again, for the scientific method

I have blogged about how the scientific method can be applied to everyday events before but here’s another example and one with echoes of how Nobel Prizes are won.

The scientific method starts with an observation followed by the formulation of a hypothesis to test that observation. This is the standard wisdom anyway, but it missis out a key ingredient and that’s curiosity. Sometimes it’s the most banal everyday observations that trigger an inner curiosity that leads to great discoveries.

Before I get too carried away, let me start with an everyday story, but one that nevertheless illustrates how the scientific method can be used, almost subconsciously, in everyday life.

One morning I sat in front of the TV eating my cornflakes when I noticed a little pool of water on the TV-stand. My first instinct was to look up at the ceiling to see if there was a leak but that was sound and dry. Odd, I thought I wonder where the water’s coming from? 

Rejecting the thought of a poltergeist, I struggled to form a plausible hypothesis. The TV-stand was too far away from the window for it to be condensation and there were no pipes anywhere nearby that might have sprung a leak. I wondered if it was indeed water, or perhaps something else? I tasted it. Thankfully it was just plain old water (perhaps I hadn’t thought that one through).

In an effort to solve the mystery, one night before bed I strategically placed strips of tissue paper along the TV-stand . The theory was that wet tissue would help me trace the direction of water egress. In the morning all the tissue was dry. I nevertheless left the tissue in place just in case the water came back.  It did, around lunchtime. One piece of tissue was soaked with water. That slice of tissue was right in the middle of the TV-stand with all the surrounding pieces of tissue completely dry. I lifted the TV to find water dripping out of one small spot at the base. I’m no expert on electronics but I was pretty sure water dripping out of an otherwise dry TV was not normal.  For a brief second I revisited the poltergeist theory.

I extended the tissue paper experiment over the next few days, trying to find the source of water.  For example, I taped some tissue to the coaxial cable of the TV areal to see if condensation was trickling along it.  But it was always the same result, one spot at the bottom of the TV was occasionally dripping water but all the surrounding pieces of tissue were completely dry. It was then I noticed a correlation. The water only appeared when it was raining, or very soon after. Here was a new question - how did rainwater get from outside of the house to one small spot on the TV-stand without touching anything in between? I resisted the urge to call David Blane and instead, extended my experiments.

When scientists are faced with similar problems, they try to isolate the various components and investigate them separately to see if any one of them might be the cause. I therefore moved the TV into another room and pulled the TV-stand out into the middle of the floor.  I then put the strategically located strips of tissue paper in place and waited for the rain to come (that never takes long in this part of the world). Next day, TV - dry. TV-stand - dry. Wondering how I was going to find David Blane’s telephone number I started to reassemble the TV when I made another observation. There was a small patch of water on the floor right next to the end of the TV areal coaxial cable.  The tissue I had taped to the cable was dry however, so wherever the water was coming from, it wasn’t running along the outside of the cable.

I examined the cable more closely and water was seeping out of the end where it was connected to the coaxial plug that went into the socket at the back of the TV.  In a sudden flash of realisation, I understood.  The cable runs from the aerial on the roof, down the side of the house, through a drilled hole in a window frame and finally into the back of the TV. Along the way rain was getting inside the coaxial cable which was acting like a tube, channeling the water to the back of the TV.  Obviously I needed to get the coaxial cable replaced but at least the mystery of the water pool was solved and without having to call David Blane or hold an exorcism.

The story does not quite end there. The window, through which the aerial cable passes, has an inner shelf holding some flower vases, and the occasional lost teacup. The coaxial cable sits tightly into a corner between the window shelf and the wall, cosmetically hidden away. Some time ago I’d noticed that when it rained a little pool of water formed in the corner of the window shelf next to where the coaxial cable came through the window. The cable was well-sealed into the frame and wasn’t leaking and so I assumed it was due to condensation.  But now I was wondering.

A little while ago the room had been redecorated and the cable re-sealed into the frame and painted. In fact the sealant had been run over the cable in the corner between the window shelf and the wall to help it blend in. I wondered if it was possible that prior to the room being redecorated, whether a crack in the cable had been leaking water onto the window shelf.  It explained the small pool of water that appeared on the shelf, always in one place. Once the cable, and presumably the crack, had been sealed, then the water had nowhere to go other than along the coaxial cable and into the back of the TV.

I therefore took the smallest drill I had and put a tiny hole into the coaxial cable where it ran over the window shelf.  It’s raining today and there’s a small puddle of water on the window shelf and the TV is dry.

So coming back to where I started, sometimes it’s the most banal observations that fire the curiosity. In my case, if I had been more curious about the initial pool of water on the window shelf and not just dismissed it as condensation, I might have saved myself a lot of time and effort.  It reminds me of one of my favourite science stories. A plant biologist called Richard Jorgensen wondered what caused the stripes on the petals of petunias. To many this seemed a daft question but Jorgensen didn’t just dismiss it, like I did the water on the window shelf.  His curiosity was further inspired when he found he couldn’t produce a petunia with just a pure purple colour.  He went on to investigate what was going on and discovered an entirely new molecular genetic mechanism called RNA interference, which is now being investigated as a way of treating certain diseases. Jorgensen won the Nobel Prize in 2006.  http://oxbridgebiotech.com/review/the-nobel-for-rnai-from-petunias-to-potential-cure

Of all human qualities, curiosity has to be the king.

Homeopathy - have we missed a trick?

Although I have written on the subject of homeopathy before, just when you think it’s safe to go back in the water (pun intended) it goes and rears it’s head again.  It has come back in the news this time, probably for the right reasons in that it could be blacklisted by the NHS.

On the today program on BBC Radio-4 this morning there was an interview between Simon Singh, the science writer and Dr Peter Fisher, Clinical Director at the Royal London Hospital for Integrated Medicine. The interview revolved around the evidence for homeopathy, with Simon Singh saying that there was none and Simon Fisher saying that there was.

As a scientist I agree with Simon Singh, of course, that homeopathy has no efficacious properties at all because it’s just water. The general public however are likely to be confused, and no wonder because how do they know who’s word to take?

The debate on homeopathy in my view, is not about the evidence but the science, because the two things are not necessarily the same thing. Steve Novella has said this many times, and he suggests we should not use the term “evidenced based medicine” but “science based medicine”.  This is not a contradiction nor just playing with semantics. It’s possible to find evidence for all sorts of nonsense but evidence is only part of the scientific method. To be considered scientific then a claim has to be consistent with the laws of Nature as we know them and that’s where homeopathy falls apart.

On the Today program this morning homeopathy was described as being very dilute solutions. This is an understatement in the extreme, as a typical homeopathic dilution of 30C is like diluting a single atom with all the atoms that exist in the solar system. But this is not, in my view its biggest weakness. It's not only about how huge the dilutions are, but what is being diluted.

Homeopathy is based on the “law of similars” (although it is not a law). If you have a cold, then one of the symptoms is a runny nose.  What else causes a runny nose - onions.  So take a piece of onion, place it in water and dilute it out of existence. The very concept of the law of similars has no scientific basis whatsoever.

Still don’t believe me, then take a look at some of the things homeopaths dilute:

How about some bits of the Berlin Wall

or my personal favourite, the light from venus

Now if this is not totally unscientific woo then I don’t know what is.  I don't think there would be many that would advocate these on the NHS.

I suspect that some homeopaths would dismiss the “extreme edges” of their profession, but I would ask why? If the law of similars applies to onion then why not pieces of the Berlin Wall?  Put like this and I think you might have a very different response from the general public and a lot of their confusion would morph into laughter.  And we all know, laughter is the best medicine.

What's the difference between a football manager and the Minister for Science?

Those who know me are well aware that I have no interest in football.  It’s not that I have any great aversion to the game, it’s just a personal thing.  I just don’t find it entertaining and, to be completely honest, I don’t see the point. My personal feelings aside however, there is one aspect of football where I think the government could learn a thing or two. It would be unthinkable to appoint a football manager without some experience of the game. Manchester City and United, Leicester City, Arsenal and West Ham, the top premier clubs, are all managed by ex-players.

Then how is it appropriate that the UK’s Minister of State for Universities and Science has no experience or education in science?  Jo Johnson (bother of Boris Jonson, London’s Mayor) was educated at Eton and studied modern history at Oxford with a background in banking and journalism. How you may ask, does this qualify him to be in charge of Science, Technology, Engineering and Mathematics (STEM) in the UK?  But there’s nothing unusual in this.  The previous Minister, Greg Clark was an economist and the one before that, David Willetts studied politics and economics.

Perhaps the difference is that although there are a plethora of ex-football players aspiring to be managers, there are only 26 out of the 650 MPs across all parties that have science degrees (that’s just 4%).

This is particularly disturbing to a scientists at a time when STEM is a relatively easy target for the government’s intended across-the-board 40% funding cuts.  The old adage that governments are obsessed with the cost of everything but know the value of nothing comes to mind as STEM is incredible value for money. The Large Hadron Collider, for example cost every UK citizen just £1.65 each in 2015

I wonder if an arts educated Minister of State for Universities and Science can really appreciate the technological, economic and societal benefits that such fundamental research can bring?

The profits of publishing

Scientific publishing is big business. More than half of scientific papers are published by just 5-publishing houses:  Reed-Elsevier, Springer, Wiley-Blackwell, Taylor & Francis and Sage. And they make big money, turning in profits of a $billion or more is not unusual.

There’s nothing wrong with business making a profit.  I have a one-person business that turns in a profit, although not quite on the scale of publishing houses. But there’s a difference.  If I use the expertise of others, then I am willing to pay for their time, it’s all part of doing business. Scientific journals however, rely heavily on the good will of scientists as editors and peer reviewers.  Without this highly qualified voluntary army of people, the scientific publishing industry just could not survive - or at least make the profits that it does. Publishing is the life blood of science in that we all need our research published and we all need access to the published research of others. The first part of that equation is covered by the aforementioned voluntary scientific army but the second part is where profiteering gets very much out of control. 

A scientist publishing a paper has to sign over the copyright to the publisher who then puts the research behind closely guarded paywalls. And these are expensive paywalls at that.  As an example, I recently purchased a paper from Wiley.  It was just one page published in 1983 and it cost a staggering $45.60 (£29.63). Just to reiterate - a 32-year old single page for $45.60 (£29.63). On that basis Harry Potter and the Sorcerer's Stone would cost around £7,000 and at least that would only be 14-year’s old!

There is a growing trend towards open access journals where the papers are free to access but there is a charge - often of a thousand pounds or more, for its publication. The bigger organisations and well funded academics might be able to afford this but the rest are compelled to publish behind the paywalls and add to the profits of the publishing houses.

The scientific publishing business model can be summed up as one that exploits unpaid workers and then charges exorbitant prices for the product.  This may have been an acceptable business plan in the days before William Wilberforce but today it just gives capitalism a bad name.  Recently scientists have been forced towards online piracy, which although illegal, who can really blame them?

I have no problem with the publishing houses making a profit but the current business model is almost psychopathically one sided. The profits need to be commensurate with the reliance on a voluntary workforce and papers need to be taken down from the paywalls - say after 10 years. It’s simple business ethics, although I think any publishing house reading this might have to reach for the dictionary and look up the word ethics.

In the meantime, I will continue writing papers and peer reviewing on a voluntary basis because that’s what scientists do. I do it to assist the progress of science and my fellow scientists, even though I know I am being exploited.

Elemental Beings (the mythical story of how radioactivity was discovered)

Residing in the deepest part of the Cosmos were some Supreme Beings. One of these beings was bored and so decided to take up a hobby.

    “I will become a collector,” said the Supreme Being. “I will collect everything that goes to make up the Universe. All the fundamental units that combine to construct every substance in existence. I will call these fundamental units –elements. Such a vast and impressive collection will take aeons to put together.”

    And so it started sifting through all the matter in the Universe and a short time later, it looked down upon its collection.

    “Just ninety two elements! That’s all,” exclaimed the Supreme Being. “Ninety two!”

    But it was inescapable; all the matter in the Universe was made from just ninety two elements. So the Supreme Being decided to take a closer look.  The first element in the collection was hydrogen.  The Supreme Being looked deep into the atom of hydrogen and saw at the centre a positively charged proton and circling around it, a negatively charged electron.  Oddly, when he looked at how fast the electron was going, he couldn’t see where it was located and when he stared hard enough to see where the electron was, he couldn’t see how fast it was travelling.

It shook the confusion out its Supreme mind and decided to take a look at the nucleus of the second element in the collection – helium.  There were two protons in this nucleus and circling around it were two electrons.  Then it examined the third element, lithium, and lo, there were 3 protons and 3 electrons.

    “Mmmm,” thought the Supreme Being. “Perhaps there’s a pattern emerging here.” 

    It then looked at the 92nd element in the collection – uranium - and unsurprisingly, there were ninety two protons and ninety two electrons.  Now completely bored with the stuff of the Universe, the Supreme Being gave away the collection to a friend and decided to go travelling through a black hole (which took considerably longer than collecting all the elements in the Universe).

    One day the new owner of the collection of elements was peering into a hydrogen atom and saw something a little strange. Its friend had said that the hydrogen atom was made of one positively charged proton and one negatively charged electron. But there in the nucleus of one of the hydrogen atoms there was something new; something without a charge, a neutron.  The Supreme Being at once realised that within any one element there were different varieties, depending upon the number of protons and neutrons in the nucleus. So the Supreme Being sifted through all the hydrogen atoms and divided them into three piles.  The first pile had one proton, the next pile had one proton and one neutron and the third pile had one proton and two neutrons.   Clearly, the nuclei of all hydrogen atoms contained one proton but there were three varieties, depending upon the number of neutrons in the nucleus. Those with one proton and no neutrons were by far the biggest pile and so the Supreme Being declared these were hydrogen atoms.  Those with one proton and one neutron it named deuterium and those with one proton and two neutrons it named tritium. Rather than call them varieties, the Supreme Being decided to call them isotopes. 

No sooner had the Supreme Being discovered isotopes, when a postcard arrived from his friend travelling through a black hole. It seemed as though time was standing still for his friend because the postcard was very long indeed. At last however, it was read and our Supreme Being returned to its collection.

    “Thief,” came a cry, which was odd because Supreme Beings are perfect and there were no thieves at that time.  “My tritium atoms have been stolen.” 

    Other Supreme Beings gathered around to see what the fuss was about. 

    “Look,” said one of the bystanders, “is that not them there,” mystically pointing.  

    “No,” said the owner of the collection of elements, “those are not tritium atoms, those are helium…”

    The Supreme Being suddenly realisedthat the tritium atoms had not been stolen, they had changed into helium-3 (two protons and one neutron).  With eternity available, the Supreme Being sat and observed its collection of tritium atoms.  Now and again, one of the neutrons flickered and vanished and in its place one proton, one electron and one anti-neutrino came into being. The tritium isotope that once had one proton and two neutrons, now had two protons and one neutron – it had become helium. As helium formed, an electron and an anti-neutrino sped out of the atom and vanished into the vacuum of space.  The electron collided with an interstellar cloud and ionised some of the gas.  The anti-neutrino arrogantly ignored everything around it and passed through clouds and planets alike as if they didn’t exist.

    “Well,” thought the Supreme Being. “If anti-neutrinos are so ignorant then I will ignore them and focus my interest on the electrons.” (Thus proving that even Supreme Beings can make mistakes as anti-neutrinos, and indeed neutrinos, are very interesting to those who study them).

    The Supreme Being then declared that the electrons speeding out of the tritium atom would henceforth be known as β-radiation – radioactivity had been discovered.

    An advantage of being a Supreme Being is that time means nothing.  Be it small amounts of time, a mere flicker of a fly’s wing, or immensely long periods of time where Universes wax and wane.  And so our Supreme Being was able to look through its collection and realised that all of the atoms consisted of isotopes; and the radioisotopes were changing into other isotopes, some in an instant and some over aeons.  A mystical, magical dance, the stuff of the Universe intertwining, changing, reacting, swirling, never ending!  The Supreme Being could see little minute specks of matter flash out of existence only to become energy that radiated away from the disintegrating atom. The Supreme Being looked down on its collection and said, “wow”!

    Uranium turned into thorium, then protactinium through radium and polonium and ending up as lead. From uranium to thorium the journey was long and slow and from polonium to lead it was but a blink of the Supreme Being’s eye (if it had eyes). 

    “How,” thought the Supreme Being, “can I distinguish between those isotopes that vanish quickly and those that seem to hang around for ever?”

    “There are one million atoms in my tritium collection,” it thought. Then it started a cosmic stopwatch and waited until half of those tritium atoms had transmuted into helium; the stopwatch read 12.35 years. The Supreme Being kept looking at the pile of 500,000 tritium atoms that remained and when these had become half that number (250,000) another 12.35 years had passed.

    “This,” thought the Supreme Being, “gives me a measure of the rate of atomic decay. Every 12.35 years my pile of tritium atoms reduces by half.  Therefore, I will call 12.35 years the half-life of tritium.”

    (The Supreme Being then worked out all the mathematical equations for exponential atomic decay but it is not in the nature of mythical stories to convey such convincing detail and so we will move swiftly on).

    The Supreme being then decided to catalogue all the isotopes in its collection.  It counted 246 isotopes that were stable and the rest were radioactive. Of the radioisotopes, many had half-lives so short that it was difficult to measure them (even Supreme Beings have some limitations).  A total of 289 isotopes had half-lives of between one day and 10,000 years and 84 had half-lives greater than 10,000 years. Tellurium-128 had a half-life of 2,200,000,000,000,000,000,000,000 years. In fact this was so long that several Universes were formed and ended before The Supreme Being could figure out a value for the half-life of tellurium-128.

      Just then however, the Supreme Being’s friend came back from its holiday inside a black hole. Seeing that its collection had turned from a boring pile of atoms into a psychedelic, intertwining, choreography of interchanging isotopes, the returning Supreme Being immediately demanded that its collection be returned.  The current owner of the isotope collection thought this a little unjust and refused. A little after this, the Supreme Beings invented war and the Universe was never the same again.  The study of the atom and radioactivity was therefore left to the inhabitants of a little blue-green planet called Earth. Ironically, the inhabitants of Earth often fought wars over which Supreme Being one side or another thought the most supreme– but that is a different story.

The everyday scientific method

I have never been entirely convinced that humans are an innately rational species.  We are all too easily fooled by the world around us.  For the best part of human history it was obvious that the sun went round the earth and those early pioneers of a heliocentric solar system certainly paid a high price for saying otherwise.  It takes some considerable effort to question the things around us and at times it takes considerable resilience to continue to question in the face of those that are just utterly certain. About a year ago I had an experience of how the scientific method could be applied to a simple domestic situation. I thought I would share it as there are parallels between science and pseudoscience in this everyday story.

I rented a house in Lincoln (UK) whilst I was an academic at the University’s School of Pharmacy.  Water in the house was heated through an electric immersion tank that was fitted with a standard ballcock valve, which opened to replenish the tank as the hot water was used-up. I noticed however, that there seemed to be a constant trickle of cold water into the tank irrespective of hot-water usage.

A lot of scientific discovery starts with pure curiosity, the “that’s interesting, I wonder what that is?” type question. A perfect example of this was when a molecular geneticist named Richard Jorgensen became curious about stippling on petunia petals. It was at first just a curiosity but his investigations led to the discovery of a whole new branch of genetics and won him the Nobel Prize in 2006.

I wasn’t going to win any prizes for it, but the constant trickle of water was something that needed to be investigated. At the offset it was just a superficial observation and in science these things can just vanish upon more robust inspection.  For example, the trickle of water may have only occurred under particular circumstances when I was coincidently in the house. One of the chracteristics of pseudoscience is to take the first superficial item of evidence that supports some preconceived idea and then never let go of it as proof of the position. The scientific approach on the other hand is to form a hypothesis and then test it. Richard Feynman used to say that first came a guess - if you have time then this video of Feynman is really worth watching.

So my hypothesis (guess) was that there was a leak somewhere along a hot water pipe and as the water slowly drained away, the ballcock value allowed a steady trickle of cold water to flow. I was fully aware however, that I could be wrong and so I needed to gather some data. 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. 

At first attempt my hypothesis seemed to be wrong and the constant trickle of water into the tank might have been quite normal.  The investigation so far was only cursory however, and so I decided further study was required. I therefore found the main valve feeding the tank’s cold water supply and turned it off for a day. The next morning the tank was completely empty; so where had the water gone?  I found the valve for the tank’s hot water outflow which Iturned 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.

Based upon my updated experimental evidence I needed to refine my hypothesis.  Although there were no visible signs of a water leak, the tank was still emptying in a matter of hours. The water had to be going somewhere but so far I could find no sign of it. Perhaps the water was leaking out somewhere I couldn’t see? I knew that 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. 

Scientists figure things out all the time without necessarily making direct observation. Electrons, for example, have never been observed but the resulting actions of their flow is what we call electricity. When we switch the light on we know there's a flow of electrons along the wire because of the glowing lightbulb. In my case, I couldn't see the pipe under the floor and so in order to investigate a possible leak, 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 pipes were made of copper which is a good conductor of heat. By opening or closing the kitchen and bathroom taps, I could follow the flow of the water simply by feeling the heat running along the pipes. In technical terms, the heat was a surrogate for the water flow.  With all the taps off there should be no flow of hot water but when I did the experiments I found that the pipe that went under the floor remained warm.  The pipe on the bathroom side of the T-junction remained cold. The conclusion was that there was a flow of hot water (detected from the heat of the pipe) going 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. To be fair if I was going to be really scientific about it I would have measured the temperature of the pipe in various locations and then plotted out the heat-flow data. The ability to measure some effect is a cornerstone of the scientific method. I am a nerd, I admit, but it would have taken things to new nerdy heights in this case if I had got out a thermometer and notebook. I admit therefore, I left that particular experiment out. 

On the weight of evidence, my hypothesis could now be promoted to a theory that there was a leak in the hot water pipe under the concrete kitchen floor.  The theory was consistent with the known laws of physics - for example, water flows downwards under gravity, copper conducts heat etc. In science, any theory has to be consistent with what is already known.  If some theory in biology has some aspect that breaks a law of physics, then the biological-theory is likely to be wrong. If my theory had demanded that water flowed upwards, for example, then my theory would obviously be wrong.  A hallmark of a pseudoscientist is when they demand that the whole textbook of scientific understanding has to be re-written to support their own ideas, typically based upon the most flimsy of evidence. In my own case however,  it was time to call the landlord and get a plumber.

I explained all the evidence of 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 that he would replace the ballcock valve, which he said must be leaking (hence the constant trickle of water). 

I explained to the plumber that the ballcock valve could not be the problem because turning off the hot-water outflow stopped the constant trickle of inflowing cold water. When the tank was full, the ballcock valve did its job perfectly well. The plumber however, really didn't want to hear it and discarded this evidence from his diagnosis. He told me that 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 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.

He went outside the house and dug down by a 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 more 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 presence of the mud by saying that it had been a wet year and it could just be ground water.

"An unsinkable rubber duck" is a term used by rational thinkers when someone finds a way round every item of evidence presented to them in order to support their own preconceived position. Young earth creationists who believe the universe 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 and they will claim that the speed of light has changed over time. Likewise, no matter what the outcome from the plumber’s test-dig by the kitchen wall, it was either going to reinforce his own viewpoint or at least not change it. The muddy ground by the outside wall was far from conclusive but put this together with everything else and the convergence of evidence all pointed one way.

I had to be careful however, because although the presence of the mud seemed to support my leak theory, the possibility that is was coincidental ground water could not be ruled out. 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. In science it is only when a theory stands up to attempts to disprove it, that it really becomes robust. Pseudoscientists rarely understand this. Instead of trying to disprove their beliefs, they do what this plumber did and simply select those items of evidence that support their view. There is then a reluctance to do further testing using any method that might illicit any doubt.

From the plumber’s perspective I was probably appearing to be a very difficult customer.  I stayed polite the whole time and even made light of some it, just to keep things convivial. The plumber however, was getting more and more irate. I was just following the evidence, albeit that it was with somewhat unpleasant consequences. Irateness and sometimes downright offensiveness is another hallmark of the pseudoscientist. Just question a homeopath on the validity that greater dilution leads to greater therapeutic potency and then wait for the torrent of abuse. 

Scientifically, my water-leak theory would have been tested by others. Someone may have come up with some new ingenious method and others would have confirmed or failed to reproduce my own data. Nothing would be taken for granted until tested and retested. Then those tests would be challenged and retested 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 in accepting the first whiff of flimsy evidence that might vaguely support their point of view and ignore far more robust evidence that is against them. The case of my hot water was a little more domestic and anyway, I was getting tired of having to shower at work. 

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 had a very different attitude. His curiosity was refreshing and he took great interest in the way I had diagnosed the problem.  He challenged my assumptions on several occasions, which led to some interesting discussions. Once he agreed that there was very likely a leak under the floor, he came up with a straightforward solution and simply put in a new pipe above floor level, bypassing the one with the leak. It took him about an hour and afterwards the problem was solved. The constant trickle of water to the tank stopped. Over a cup of tea to celebrate a job well done, the plumber looked down at the pipes, thought for a moment and said, "lucky there weren't two leaks in different places, because that would have really messed up your experiments".  This possibility had not occurred to me and of course he was right, two separate leaks could have made the results of my experiments very confusing. A scientific theory has to be repeated by others who may look at things a very different way. Our understanding is built piece my piece progressively until a coherent picture emerges. Of course, in science this whole affair 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 had been confirmed. This illustrates another trait of pseudoscience - any gap in knowledge of an opposing theory is evidence that the whole theory is wrong. "You can't show me every intermediate animal from a dinosaur to a bird, therefore the theory of evolution is wrong," for example.  The gaps can also sometimes be filled with any old nonsense, such as aliens that lived under my house were stealing the water - that type of thing.  Well, you can’t disprove it, can you? And it fits the evidence that you have. 

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 that evoke the name of science to try and prove themselves right at any cost. Science is the exact opposite of this.  For my own part in the situation with the first plumber, if he could find better evidence to support a different theory then I would have been very pleased to change my view. Even to the point if an alien had suddenly appeared out of the test-hole!

Why are there still monkeys?

This is not something I would normally blog about as it’s outside my bailiwick but it’s a question that I’ve been asked so many times recently, I thought I would provide a response. The question is, “if we evolved from monkeys, why are there still monkeys?”

The question comes from a Biblical perspective and so I will say up front that I do not intend to get into issues of religious faith here. My intension is to merely give an answer to the question on the basis of evolutionary theory. I’m honestly not trying to provide “atheist propaganda” I am merely attempting to clarify what the theory of evolution actually says and then you can make up your own mind from there.

The short answer is that we didn’t evolve from monkeys but I’ll expand on my answer by taking the analogy of linguistic evolution. (Not my original idea and so I’m not taking credit for it). Remember this is an analogy and so it’s not meant to be taken to extreme lengths. It’s merely being used as a method of explanation.

Just over 2,000 years ago the official language of the Roman Empire was Latin. Whether they spoke Latin in the same way scholars of Latin might speak it today is open to question. No one alive today was around during the time of ancient Rome, they didn’t have any sound-recording in those days and so no one has actually heard the way it was spoken. There is evidence that this language was spoken in ancient Rome because we have examples of their writing.  But writing does not tell us about pronunciation, which would have undoubtedly been influenced by other languages of the time, such as ancient Greek.

As with any language, changes occurred over time. The ancient Romans did not travel to the same extent as we do today and so pockets of local dialect arose. No doubt, colloquial terminology and slang words developed and so the language slowly changed over time. From one generation to the next, the differences would not be as great so they could not understand each other, but these small step-wise changes accumulated over time. Over many years, Latin started to diverge and today we see two main derivative languages, Spanish and Italian.  The two languages share many common words but generally it’s not possible for a Spanish speaker to hold an intelligible conversation with an Italian speaker. And yet both Italian and Spanish evolved from a common language - Latin.

Like Spanish and Italian, humans and the apes of today share a common ancestor. The human ancestor lived sometime in the Miocene period but is now long extinct. Humans, other species of apes and monkeys share common genes, in the same way Spanish and Italian share common words. The science of genetics and DNA analysis in particular allows us to track back that speciation over geologic time. The theory of evolution does not say that a gorilla in the zoo will give birth to a human, or indeed a cat will give birth to a dog. It does not predict that there should be intermediate forms between cats and dogs in the fossil record. That would be like asking for a hybrid Spanish-Italian language called Spanian.  If an explorer came across a lost tribe speaking Spanian, then this would seriously question the theory that they were both derived from Latin. Likewise an intermediate cat-dog fossil (or a crocoduck) would be a big problem for the theory of evolution.

Those small changes in language from one generation to the next would be like what creationists call microevolution. The Spanish spoken in Spain today for example, is somewhat different to that spoken in South America. The two languages are similar enough so speakers can understand each other but there are a number of examples where the languages have diverged enough so misunderstandings can arise. The same situation is likely to have arisen with Latin and over many generations, microevolution became macroevolution and so Spanish and Italian became their own separate languages. At no point did a Latin speaker suddenly give birth to a Spanish or Italian speaker. The languages evolved by small almost imperceptible steps over many generations. If you accept microevolution but not macroevolution then you have to ask yourself, what mechanism is stopping those small changes accumulating over time in respect to the evolution of language or species. 

Whilst language evolved over a few thousand years the evolution of species takes many millions. The average human lifetime is just 0.007% of a million years and so it’s not possible to observe the evolution of one species to another. But, as I said, it’s also not possible to observe the evolution of one language to the next and no one has actually heard the Latin of ancient Rome.

Of course many creationists believe the Universe was created less than 10,000 years ago. I am not going to comment on this as, I have said, my intention here is just to clarify what the theory of evolution says. It is certainly the case that many millions of years are required for evolution to produce the vast number of species seen on Earth today. The age of the Universe, as is the origins of life itself, is another topic.

Whilst on the analogy of language, the other assertion that often comes up is that there are no intermediate fossil forms between one species and another.  There are actually many. Just a quick Google search came up with the University of California, Berkley and the Smithsonian but there seems to be an expectation that transitional forms between every generation must be produced as proof of biological evolution. This would be like trying to produce recordings of every generation from Latin to Italian in order to accept Italian was derived from its Latin ancestor.  By not having this, would you deny Italian came from Latin?

I hope this explains why there are still apes and monkeys around today and why no one would expect a change in species over one generation.  I understand that a fundamentalist Biblical perspective might lead to a rejection of the theory of evolution but if it’s going to be challenged then at least the basic constructs should be understood first.  Now I have explained the principle, the answer to the question, “why are there still monkeys” is “because the presence of humans and monkeys together today is entirely consistent with the theory of evolution”.

Who will buy my wonder supplement?

If I were unscrupulous and cared more about money than my reputation then I reckon I could do well in the world of dietary supplements. Allow me to try and sell you my wonder supplement and see if I can convince you.

Metalo-Lappin-Detox: A breakthrough in health and anti-aging

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

Thanks to the unique formula of Metalo-Lappin-Detox you can now benefit from the health benefits of 100% natural cysteine, specially formulated within a fast release capsule developed by the renown toxicologist, Dr Graham Lappin. Boost your metabolism with a daily dose of cysteine, critical in the functioning of metallothionein-2A.

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.

Metalo-Lappin-Detox 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 only £9.99. What price would you place on your health?

The above description is actually a lot more accurate than many detox claims but nevertheless is still totally bogus. And yet, everything it says is true (although “renown” toxicologist might be pushing it a bit, I admit).  Heavy metal pollution has increased with industrialisation and does cause mental and physical deterioration.  Many heavy metals when ingested lead to the formation of oxygen radicals which are associated with ageing. The body has evolved systems to neutralise heavy metals, simply 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 indeed made of amino acids and cysteine is key to its effective function. The links to the scientific literature are genuine and the studies are valid. My list of my credentials is also accurate. 

If you Googled any of these individual facts then they could be verified and it would all seem perfectly 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.  There are huge gaps between the claimsthat are left to the reader to join together.

The biggest gap - the breadth of the grand canyon - is simply the notion that taking a cysteine supplement will somehow increase the ability ofmetallothionein-2A to do its job.  The body in fact makes its own cysteine in the absence of any from the diet. A normally healthy person makes more than enough cysteine for incorporation into all of the necessary proteins. A supplement of 250 mg per day will make no difference whatsoever to the body’s ability to cope with heavy metals.  Of course the claims in my advertisement above, very carefully steered around these inconvenient facts.

Reference to the scientific literature is particularly convincing.  The first study quoted is entitled “Role of metallothionein and cysteine-rich intestinal protein in the regulation of zinc absorption by diabetic rats” which sounds right on the money.  The paper has nothing to do with the claims of Metalo-Lappin-Detox but the majority of the public would not be able to assess this, one way or the other. 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 personal credentials is almost universal in pseudoscience, so much so that it’s virtually a trade-mark. At least in my case I do hold a genuine PhD and not bought off the internet from the University of Outer Northern Galapagos.  Robert J. Lefkowitz is indeed a Nobel Laurette at Duke University and I did hold an Adjunct Professorship there for two years.  I have however, never met Robert J. Lefkowitz nor had any involvement in his groundbreaking work. If he heard my name, he'd more likely ask, "who's he?" If the reader makes any assumptions because of the association of names, 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 purchase in the local chemist.

Finally, I would keep a careful 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, after all it wouldn't cost me that much.

Of course many detox and other “natural” remedy claims are nowhere near as scientific my Metalo-Lappin-Detox.  Many include explanations about energy flow or increasingly they invoke some quantum effect. It’s all too easy to make this stuff up and it’s all big business.

Pesky skeptics might start writing blogs or sending Tweets critical of Metalo-Lappin-Detox and asking for something they call "evidence".  The best form of defence in this case is attack, and I'd say things like "you are embarrassing yourself with your lack of scientific understanding".  Another great tactic is to say that the big pharmaceutical companies are conspiring to stop the sale of Metalo-Lappin-Detox to protect their profits.   Which is perhaps a little hypocritical of me as I'm not exactly giving it away for free.  In fact, anyone know of a good website where I can buy my yacht?

Medical science versus pseudoscience

I first became aware of pseudoscientific nonsense when I was a chemistry student back in the 1970s.  I particularly remember many of my fellow students buying little plastic pyramids in the belief it gave them more ‘energy’ or made them smarter - particularly around exam time. A good friend of mine was an acupuncturist and was prone to pointing out meridians on the diagrams in my anatomy textbooks, almost as if the authors had forgotten to include them.  I admit I was tempted by some of this but I never really bought into any of it. Perhaps my memory of events has edited itself since that time but I recall that when I challenged the dubious beliefs of some of those around me, I was answered with “science doesn’t know everything” and “there’s more to the world than science you know.” There seemed to be a dividing line between the natural and the supernatural and you either believed in the latter or you didn’t.

Nowadays I find things rather different. Many pseudosciences are trying to hijack real science and I don’t just mean those shampoo advertisements that plagiarise technical-sounding language. Some pseudoscientists are actually proclaiming themselves as the true scientists whilst portraying those who disagree with them as blinkered and ignorant. In many ways my early experiences when science was just dismissed as ‘not knowing everything’ was a more honest approach compared to the current trend that attempts to turn truth on its head.

There are creation scientists, for example, who try to prove the Earth is only 6,000 years old because of their particular interpretation of the Bible.  They believe in the literal truth of Noah’s flood and even have something they call ‘flood geology’.  This type of religiosity is in principle no different, in my view, to many of the medicine based pseudosciences. And of all the medicine based pseudosciences homeopathy above all has made a supreme effort to claim the scientific ground for itself. To illustrate my point, there is a website that promotes homeopathy called, ironically, Science-based medicine that says it "wants to differentiate good medicine from bad medicine, promote good medicine and watch for pseudo-medicine". The contradiction is breathtaking as there’s not only no evidence for the efficacy of homeopathy, its very premise is inconsistent with just about every known law of science.  Another website uses the term ‘homeopathic microdoses’ which is personally a little gruelling as I have conducted a great deal of research into microdosing which has nothing whatsoever to do with homeopathy. Like creationism, if the evidence doesn’t support the homeopathy fantasy, then the inconvenient science just has to be reinvented.  It’s easy to dismiss this as the work of cranks but homeopathy is perniciously dangerous as it’s been promoted to treat very serious conditions such as cancer, diabetes and infectious disease such as scarlet fever. People have died because they turned to homeopathy rather than effective medicine. 

Science has given us much in the modern world, including real effective medicines and vaccines and perhaps it’s this success that the pseudoscientists wish to latch onto. The problem is however, that the very way much of the gibberish is sold in the false name of science exposes its own perversion; for saying something is scientific is not synonymous with saying it is correct.  Science is not so much about facts but about a method of getting to the facts. It starts with a hypothesis (or just a guess as Richard Feynman used to say). The hypothesis is then tested to destruction with the very intent of proving it wrong. Only if it stands up to this deep scrutiny does it become promoted to a theory, but even then it is open to modification and disproof.  Science is the toughest of masters.  It is indifferent to egos or careers and can shoot down someone’s pet theory without a second glance (I have personal experience and so I know). Those that just want to evoke the name of science in an effort to support their own point of view find this very hard to grasp. And then criticism of their fantasy often triggers personal derision in response. 

The majority of pseudoscientists have had no scientific training. They are like someone proclaiming themselves a world-class concert pianist without ever having had a piano lesson. They get onto the stage and then just bang away at the keys. They might attain a following of those who enjoy such avant-garde music but then they claim that their rendition of Mozart's piano sonata is far superior to that played by professional pianists who have spent years perfecting their art. This does not mean that science is the exclusive property of scientists - far from it. It just means that if you don’t understand something, you can’t just make something up to fill the gap.

Our understanding of nature is evolving and changing all the time and it’s pretty likely that the physics of20 years time will be saying different things to what it does today.  The discovery of dark matter and dark energy, for example, are likely to lead to a rewriting of the standard model of physics. The rigour and robustness of this science however, versus that of homeopathy research (if that’s not an oxymoron) are light years apart.  For homeopathy to be proven correct, it would be like suddenly discovering the sun does orbit a 6,000 year old Earth after all. Not absolutely impossible but the evidence to prove it would have to be extraordinary.  In the meantime there will be those that will blur the edge between science and pseudoscience to sow the seeds of confusion. I find this worrying, not because I feel that science itself is threatened in any way but because healthcare should not be based on buyer-beware.

 

 

Drug driving laws and codeine

New regulations come into force in England and Wales today regarding driving under the influence of drugs.  These changes to the law came about because of campaigns following a number of tragic deaths caused by drivers under the influence. Enforcement of the regulations is made possible by the approval of a roadside test that can detect traces of drug in saliva. The test is based on the binding of the drug to a highly specific protein called an antibody, that then causes a colour change. (The device works in a similar way to a pregnancy test kit which detects diagnostic hormones in urine). A positive road-side drug’s test is only preliminary and a further blood test is necessary for confirmation in order to prosecute.

Most would argue that prosecution for driving under the influence of illicit drugs is a step forward for road safety.  But in addition to illicit drugs, the new regulations cover certain prescription medicines and here I have a few concerns. The situation with illicit drugs is straightforward in that they are illegal for drivers or anyone else. The situation with drink-driving is a little different because alcohol is not illegal in the UK but a responsible driver nevertheless has the choice not to drink before getting into the car. Prescription drugs are a bit of a grey area however, because they can potentially impair driving ability but they are a necessary medication for the driver.

I’ll take one drug from the list of those now being regulated in respect to driving: morphine (for chronic pain). Morphine can certainly cause drowsiness and the small-print in the information leaflet advises the patient not drive if they feel impaired. More patients might be taking morphine than they realise however, because the presence of morphine in the bloodstream results from taking another medication, codeine.  Many patients, when asked if they have taken morphine might truthfully reply that they have not, but nevertheless test positive because they have been prescribed codeine. I have a prescription for codeine to treat osteoarthritic chronic pain and I can state categorically, that I have had no warnings or information on this whatsoever.

Sufferers of chronic pain who take morphine (in the form of codeine) build up a resistance to its effects. A standard prescription dose of codeine is around 30-60 mg for chronic pain. Someone taking this medication on a regular basis would get pain relief without feeling any major adverse effects. If someone who was not on regular codeine took this dose then it would likely send them into a tail-spin. The maximum blood concentration of morphine after taking 30 mg codeine is typically around 200 ug per litre (a ug = a millionth of a gram), whereas the legal limit is now set at just 80 ug per L.  Over-the-counter codeine comes in typically 3-4 mg tablets and two of those will typically result in blood maximum concentration of around 40 ug/L, which although lower than the limit is starting to approach it. Codeine is also present in some cough medication. Moreover, someone not taking codeine regularly will certainly feel the effects of a 40 ug per L blood concentration and in some cases may not be fit to drive. It is therefore hard to legislate the genuine effects on driving prescription codeine might have, based purely on a blood concentration.

There is another side to this same coin, in that someone who is on a prescription for codeine could avoid prosecution based on a medical defence. In theory if they give a positive road-side test for morphine and they can provide evidence to the officer that they are on prescription medication, then no action should follow. In practice this is going to depend on what they have been stopped for and the judgement of the police officer. A car is a ton and a half of weaponry in the wrong hands, and we should all take the privilege of driving responsibly.  On the other hand, care has to be taken not to criminalise responsible drivers because they have to take prescription medication - as I say, this is a bit of a grey area.

I will end on what might be an urban myth, but then again might not. Poppy seeds contain opiates and substances such as morphine can be detected in the bloodstream after consumption. Could a driver be prosecuted therefore, for eating a bagel dusted in poppy seeds?  Studies have been conducted over a number of years and the answer is - probably not, but it couldn’t be ruled out. Poppy seeds contain quite high concentrations of opiates, in some cases up to 200 mg/kg (a mg is a thousandth of a gram). Eating a single bagel even liberally dusted with high opiate-containing poppy seeds is unlikely to result in blood morphine concentrations exceeding 80 ug/mL. One test in Germany resulting in blood opiate concentrations reaching 10 ug per L and so it’s not impossible that a poppy seed or bagel addict might fall foul of the law but it’s pretty unlikely and I would not advise trying it out as a legal defence.

The other side of Cannabis

Cannabis was in the news again recently with reports that prolonged and frequent use of a form of cannabis called skunk leads to a 5-fold increased risk of psychosis. Like no other illicit narcotic, cannabis has evoked more debate about its use with some proclaiming its dangers and others lamenting its therapeutic powers. The pharmacology of cannabis has become entangled in its politics which has unfortunately tarnished all sides of the argument.

Cannabis could be classified as a herb with particularly potent pharmacologic effects. Like all herbs (and herbal medicines) the product is a heterogeneous mix of chemicals that alters depending upon the plant variety and growing conditions. Skunk is at one end of the spectrum containing high quantities of tetrahydrocannabinol (THC) the main psychoactive component as well as a range of chemicals called terpenoids, that give cannabis its pungent aroma. At the other end of the (illegal cannabis) scale is hash, which contains lower amounts of THC but higher levels of another component called cannabidiol (CBD) which does not appear to be psychoactive and may act as an inhibitor of THC. This is not to say that hash is a safe drug, as CBD still has complex and only partly understood pharmacological effects. In fact this month the University Hospital Düsseldorf in Germany identified a number of deaths that were likely to be cannabis related (although others disagree - the arguments continue).

It may be surprising to some but there is yet another variety of cannabis that is low in THC and high in CBD that is sold legally - in some states in the USA anyway. The variety is called Charlotte’s Web, named after a 6-year old girl called Charlotte Figi who suffers from Dravet syndrome (a form of severe epilepsy). Her seizures have been controlled by the use of this particular variety of cannabis and CBD has now been developed into a pharmaceutical drug by GW Pharmaceuticals. The same company is developing cannabis-related drugs for multiple sclerosis and there is evidence to suggest CBD may have utility in cancer therapy.

Of course, the development of successful drugs from plants is nothing new; digoxin for the treatment of angina is probably the most commonly quoted. Development of legitimate pharmaceuticals from cannabis is marred on both sides however, as research is limited by inhibitory legalities on the one hand and on the other, there are those that will just believe in its magical properties irrespective of the evidence. Good scientific enquiry into cannabis related pharmaceuticals is clearly warranted and then let the science decide which side is right.

Can five Nobel Laureates be wrong?

If you were told of a health supplement that had the backing of five Nobel Prize winners, over a dozen leading research scientists and a plethora of industrial scientists, then you are more than likely to take it seriously. Most members of the general public may not need to look any further with such a recommendation and would probably take it on face value. Science however, doesn’t work like that.  The motto of the Royal Society is Nullius in verba - meaning take nobody’s word for it. Science does not follow the word of anyone, no matter how eminent, instead it follows the evidence.

There is indeed a company that markets a health supplement that has the backing of five Nobel Laureates, over a dozen leading research scientists and a plethora of industrial scientists.  It’s called Elysium Health and the product it sells is called BASIS, made of two ingredients, nicotinamide riboside and a polyphenol called pterostilbene. Nicotinamide riboside is a precursor of vitamin B3 (otherwise known as niacin) and is found in yeast extract. Pterostilbene is found in a number of plants but most notably in blueberries. Both of these substances are classified as supplements (for example, vitamins are supplements) and not drugs. The media are calling BASIS an anti-ageing supplement but it doesn’t seem Elysium are marketing on this basis. In fact I’m finding it hard to pin down exactly what the claims are as it seems to be something to do with ‘metabolic health’ but I don’t know what this means. Some reports state that riboside and pterostilbene have been validated in numerous laboratories to improve metabolic health but the Elysium website is a little more cautious in its claims. Few of the reports that I have seen take the trouble to make any informed critical analysis - skepticism in the media unfortunately is rather rare.  

There have been some laboratory studies in respect to the ingredients of BASIS and anti-ageing properties but the evidence in relation to the claims, I feel, is just a little thin. As an example, it has been shown that restricting calorific intake to mice increases longevity. There is evidence to show that the mechanism is via proteins called sirtuins, that require a co-factor called NAD+ in order to function. Nicotinamide riboside in BASIS is a precursor of NAD+. The trouble is however, that there are so many dots to join between taking a daily capsule containing nicotinamide riboside and anti-ageing effects that this is far from robust scientific proof of efficacy.  There is a paper reporting that nicotinamide riboside shows efficacy in a mouse model for Cockayne Syndrome (and ageing disease) but again, it’s quite a leap to then believe that a daily capsule of nicotinamide roboside will inhibit ageing in people. 

There was a review written in 2013 that lists many in vitro and animal studies on the anti-oxidant properties of pterostilbene (McCormack & McFadden (2013) Oxidative Medicine and Cellular Longevity) but I found it rather unconvincing. Scientific reviews should critically examine the evidence, balancing all sides of an argument, which this pretty much failed to do.  In addition, the evidence presented was very much based upon preliminary laboratory studies and as anyone who have been involved in drug development knows there are lightyears between that and showing clinical efficacy. The biochemical and physiological complexity of the body is more than likely going to thwart attempts at predicting the therapeutic outcome in humans from basic laboratory experiments. Moreover, arguments for the health benefits of pterostilbene are mostly based upon their anti-oxidant properties and the evidence for the efficacy of anti-oxidant supplements in general is controversial to put it mildly.

There have been reports that Elysium plan to collect data from their customers to demonstrate the health benefits but this is entirely the wrong way round. If true, then such uncontrolled anecdotal claims are utterly worthless and are not far from the type of “evidence” quoted by homeopaths. Of all the reports I’ve seen, I hope this one is wrong if Nobel Laureates are involved.

Nobel Laureates are certainly capable of weighing the evidence and it’s hard to say exactly by how much they have really bought into this. The general public however, will not have the same skills as Nobel laureates in weighing the evidence and this is the problem I have with such eminent scientists endorsing such products. I am therefore, surprised and saddened that Nobel Laureates, the pinnacle of scientific achievement, are lending their name to this. Instead they should asking: “what exactly does metabolic health mean”? “Is there a plausible mechanism”?  “Where are the clinical trials”? Because BASIS is being marketed as a supplement, rather than a drug, the regulation is very light-touch and so there’s no regulatory requirement to produce such answers.

Now don’t get me wrong, I am not saying BASIS doesn’t work.  What I am saying is that I can’t see any convincing evidence to demonstrate that it does. Given my age, I really hope that it does, but in the words of Louis Pasteur, “the greatest derangement of the mind is to believe in something because one wishes it to be so”. If convincing evidence came along then as a scientist, I would follow that evidence. All I am saying to Elysium is prove your critics wrong with reliable robust evidence and then market your product, not the other way round.  Otherwise, please give me my Nobel Prize now and I’ll produce the evidence to back up my theory a little later.

Science at the BAFTAs

So the 2015 BAFTAs were held last night. Amongst the glam and glitter and comments on who’s dress was the tightest fit, this year’s ceremony was a little unusual in that there were two films based on the lives of scientists. My congratulations to Eddie Redmayne who scooped the award for best actor for his portrayal of Stephen Hawking in the Theory of Everything. My commiserations to Benedict Cumberbatch because the Alan Turin biopic, The Imitation Game didn’t get anything (oh well, that's show biz). Viewing figures topped 7.3 million and although this is the lowest number for four years, it’s still a lot of people. The Oscars are a few weeks away and viewing figures for this event are predicted to be 40 million or more.  Glitz, glamour and celebrities, obviously attracts a lot of attention. 

It’s a personal opinion I admit, but I just don’t see the point of awards for well-paid actors who make a living pretending to be people they are not. It just seems odd to me that Stephen Hawking was at the ceremony last night, but it’s the actor that get’s the award.

If there’s going to be a celebration of this type, then I’d prefer it to go like this.

Commentator: “And the winner in the physics category is …..,. (the camera pans across the tense faces of the nominees)….. Shuji Nakamura, for his groundbreaking work on blue light emitting diodes.” (Applause and whistles of congratulations from the audience)

Shuji Nakamura: “Wow, a Nobel Prize” (laughter from the audience). “Thank you so much (choking back the emotion) this is the best night of my life…”. (He holds the gold medal aloft to rapturous applause). “Figuring out the role of electron re-combination through electron holes in electroluminescence was challenging, but we managed to do it. I accept this award on behalf of the whole team at the University of California.”

The next day the press has the Nobel celebrations on page one with headlines that say “Blue Diode Gets the Prize”, “Nakamura’s Prize for Having the Blues” and “What was the Most Revealing Dress of the Nobels”.

I can dream but I suspect this will be no time soon.

Dippy dinosaur

Things are buzzing in the sedate and cerebral corridors of London’s Natural History Museum. It’s the hottest debate since 2008, when the statue of Darwin was moved from its hiding place in the ground floor café to its current premier position half way up the main staircase. The stone eyes of Darwin have stared onto the iconic diplodocus skeleton in the museum’s Great Hall for just 6-years and now it’s all about to change again.

Did Sir Michael Dixon, the director of the museum, anticipate the backlash I wonder, when he announced that the great diplodocus, affectionately known as “Dippy” was going to be replaced with a skeleton of a blue whale?  Whether he anticipated it or not, the internet has been sparking with indignation. Some, it seems just do not like things to change; which in some ways is ironic as science is all about change. Our knowledge and understanding never stays still and what we know about diplodocus is no exception.

As a teenager, more years ago that I am going to admit, my cousin and I frequently visited the Natural History Museum. In those days however, our arrival was greeted by a display of life-sized elephants because Dippy wasn’t moved to the Great Hall until 1979. To be more precise, it was, and always has been a copy of the original skeleton which was discovered in Wyoming in 1898.  One of ten copies, it was donated to the museum and first displayed in May 1905. Since then has been in several locations, including the basement for safety during World War II.

In my childhood days, diplodocus was know as a brontosaurus and it was thought to live half submerged in water in order to support is 20 ton bodyweight. In fact the original display of the diplodocus in the museum’s Great Hall showed its tail laid flat along the floor, as it dragged behind the huge beast wading through the late Jurassic swamps 150 million years ago. It was even suggested that its nostrils were carefully placed high up on its head so it could hide underwater away from predators. 

Knowledge however moves on. Further skeletal finds, the ability for computer modelling and animation, a better understanding of skeletal strength and physiology, and our view of the giant sauropod evolved. We now know that it avoided swampy regions and its tail was likely used as a whip, a weapon to ward off its enemies. A more ferocious animal than one that cowered beneath the water, for sure. The museum updated the display in 1993 by lifting the tail into a more representative whip-like pose.  There was a scene in an episode of the TV programme “Parrot” (which is set in the period after Word War I) where the great detective walks past Dippy, shown in the Great Hall with its raised tail.  Parrot, so obsessed with tiny detail missed the fact that in the time he might have walked the hall, Dippy wasn’t there, let alone slashing its tail at its imaginary enemies. I don’t recall any great outcry about this at the time.

And so the museum wants to evolve. The skeleton of the Blue Whale that will replace Dippy was acquired in 1891 and it’s the genuine thing, not a copy. It represents a species going towards extinction and so is considered more relevant to the modern world.  The Great Hall itself is going to be renamed the Hintze Hall to recognise a £5m donation from the businessman Sir Michael Hintze. Even though I remember the Museum before Dippy was in the Great Hall (Hintze Hall) I’m not one of those protesting. The world evolves and things, including dinosaurs go extinct. 

 

What’s the link between South Georgia Island and the drug, warfarin?

If you were a Norwegian brown rat, then the island of South Georgia is probably a place you might want to avoid right now.  

South Georgiasits in the sub-Antarctic Atlantic Ocean about 2 thousand kilometres East of the southern tip of South America. It might appear a little bleak to us but it is a haven for wildlife. The Island has several webcams where you can see the terrain for yourself from the comfort of your own home.

One species of wildlife that is not welcome on the Island however, is the Norwegian brown rat. It is an invading species with no natural predators, lots to eat and it’s running amok.  Attempts are about to be made to cull the rat population by dropping nearly 100 tons of rat poison on the Island. As you might imagine there is some debate as to whether this approach is warranted or not, but I am not an ecologist, nor an environmental politician and so I’m staying clear of that argument. Instead, I want to take a look at rat poison, how it works and how it came about. A subject not so boring as you might think.

Under pressure rats will eat just about anything that’s available, which is one reason they are such asuccessful species. Of course, eating anything means that they often dine on the unfamiliar and so there are risks that the chosen meal of the day may well be toxic. Rats have a trick up their metaphorical sleeves however, in that they will just nibble at a food source initially and then only return to eat more if they don’t suffer ill effects. A successful rat poison has to take this behaviour into account.  It has to be slow acting to lure the rat back to the bait and it has to be as specific to rats as possible and not other species. Poisons such as arsenic were used to kill rats in Victorian times, but arsenic hardly fulfils either criteria of having a delayed action or having any specificity to rats.  

The first poison that made any attempt at making the grade was discovered, not because of dead rats but dead cattle. Farms in Alberta and Wisconsin in the United States of the 1920s suffered from a mystery illness where cattle died from internal haemorrhaging. The cause was eventually traced to cattle that ate mouldy silage made from sweet clover. The silage contained a naturally occurring chemical called coumarin that prevented blood from clotting.  Coumarin was in effect the chemical equivalent of the genetic disease haemophilia (a famous haemophiliac was Queen Victoria’s son, Leopold).

The problem with the cattle was solved by removing sweet clover silage but researchers at the University of Wisconsin realised that a coumarin-based anticoagulant would make a good rat poison (known in the trade as a rodenticide).  Dr Carl Link at the Wisconsin Alumni Research Foundation (WARF) chemically modified coumarin to make the first bespoke rodenticide, that was named after the research laboratory where it was synthesised: Warfarin.

Rats taking small amounts of bait laced with warfarin felt no immediate ill effects and so happily went back for more. (In the language of rodenticides, the rats did not become bait-shy). A fatal rodent mistake as the returning rat then received a higher dose and like the cattle before it, died of internal haemorrhaging.  By the 1950s the mechanism of how warfarin acted as an anticoagulant was understood.  Blood clotting relies on a biochemical cascade that involves vitamin-K. The vitamin is a substrate for an enzyme called vitamin-K epoxide reductase, which is a vital step in the clotting process. Warfarin inhibits this enzyme, essentially throwing a chemical spanner into the works. The discovery had a very important consequence as it led to the use of vitamin-K as an effective antidote to warfarin poisoning, if it occurred in people. 

By 1948 warfarin had been developed as a “blood thinning” drug, for use in patients were there was a risk from blood clots, such is deep vein thrombosis and pulmonary embolism.  One of the more famous patients treated with warfarin was President Dwight Eisenhower following a heart attack in 1955. Warfarin remains a somewhat tricky drug to administer as the dose has to be tightly controlled. Other anticoagulant drugs have therefore been developed such asapixaban, dabigatran and rivaroxaban but warfarin is still widely prescribed.

Warfarin is not being used as a rodenticide in South Georgia but another coumarin based rodenticide called Brodifacoum which is more potent that warfarin and somewhat more specific.  The biggest concern surrounding the use of rodenticides is the effects on other species.  Rats are particularly susceptible to Brodifacoum but other species, including birds are also affected. Effective use of rat poisons is partly down to the choice of bait, where the rat prefers the bait to other food sources but it is less appetising to other susceptible species. There are also concerns if scavengers eat rat carcasses containing high levels of rodenticide. It seems that “collateral casualties” (to use a military euphemism) are inevitable but it’s a matter of risk assessment at the end of the day, and the Norwegian brown rat is very likely to do far more damage to the ecosystem than Brodifacoum. I’ll leave that argument there.

Caffeine addicts

Most of us are drug addicts.  This might seem like hyperbole but if you enjoy caffeine on a daily basis, then you are very likely addicted to it.  If you don’t believe me then try a little self experimentation and stop taking caffeine and see how you feel. I tried it and the symptoms were relatively mild but nevertheless classic of withdrawal; headache, insomnia, irritability and a craving for some coffee.  Okay, caffeine is not addictive like cocaine or heroine, but nevertheless it is a stimulant of the central nervous system.  If you want to give up caffeine then you will find it much easier to withdraw slowly by reducing your intake day by day until you are caffeine-free. For most of us however, caffeine doesn’t do much harm in the amounts of everyday use. A cup of tea, on average, contains around 10 thousandths of a gram (10 milligram, abbreviated to mg) of caffeine.  If the 10 mg of caffeine were isolated from a cup of tea, then it would look like ten grains of table salt, in both amount and colour.  A double shot of espresso might contain approximately 150 mg and even the decaf equivalent contains around 10 mg.  The term ‘decaf’ is a little misleading in this respect perhaps. A Starbuck’s Grande coffee is reported to have around 300 mg of caffeine and if you are not used to that amount, it is likely to give you quite a buzz. Comparing weight on weight, black tea contains more caffeine than coffee but because of the amounts used in the brew, a cup of tea has less caffeine than coffee.

Chocolate also contains caffeine but the amounts are quite small with a whole 100 g bar of dark chocolate containing around 50 mg (milk chocolate is about half this amount).  You would have to eat over half a kilogram of milk chocolate to get the same amount of caffeine as a double espresso and this is not accounting for throwing up after eating so much chocolate in one go.  

Although the amount of caffeine in chocolate is low, it does contain another stimulant of the central nervous system closely related to caffeine called theobromine. (Theobromine by the way, has nothing to do with bromine or bromide, it just got this name because of its colour).  When you ingest caffeine, some of it gets metabolised in the body to form theobromine although I could not find any evidence that the metabolism works the other way round. Theobromine is pharmacologically active and is a banned drug for race horses, although horses are more susceptible to effects than people.  Grooms have to take care not to give chocolate treats to horses or they could fail a drug’s test.

Like anything, too much caffeine can be toxic and indeed it has caused a few deaths but mostly under unusual circumstances.   As a relatively recent example, in 2013 John Jackson of the West Midlands in the UK tragically died after overdosing on Hero Instant Energy Mints. Each mint contained 82 mg of caffeine and John Jackson could have consumed as many as 300 over 24 hours. Although tragic for John Jackson and his family, consuming this number of mints can’t really be seen as an everyday occurrence. Nevertheless, it is a cautionary tale as although we are aware that tea and coffee contain caffeine it may not be so obvious in the case of mints bought in the local sweetshop (the packaging did contain warnings). Another example product that contains caffeine where it may not be entirely obvious, is the majority of carbonated canned drinks. A can of typical cola for example, contains around 40 mg. 

It’s a little tricky to estimate because values vary but the average person in good health would require around 8 g of caffeine to stand a good chance of dying from a caffeine overdose. This is the equivalent of 200 cans of cola which sounds a lot but in 2010 a 30-year old New Zealander, Natasha Harris, died of a heart attack which was attributed to drinking between eight to ten litres of coca-cola per day.  The consumption of coca-cola would have been equivalent to just over a gram of caffeine per day. This level of consumption is classified as addiction - it even has a specific name of caffeinism. The volume of carbonated fluid would also be pretty unhealthy and so even in these amounts caffeine was probably not entirely to blame. 

The moral of all this is that everyday items of diet can contain pharmacologically active substances which taken in the appropriate amounts will do no harm. Anything taken in excess however can be harmful and so just watch the consumption and you should be fine.  With all this writing, I’m now off to have a cup of tea.

Homeopathy - whatever it is, it's not science

I have written on the subject of homeopathy a number of times before and it’s elicited some pretty ferocious responses. Not to be deterred, I thought no science blog could be complete without some comment on what is, in my opinion potentially one of the most perniciously dangerous piece of pseudoscience out there.

Very briefly, homeopathy is a form of alternative medicine that takes a substance which causes similar symptoms to some disease or ailment, then hugely dilutes that substance in the belief that it will then act as a therapy. To give an example, the common cold causes a dripping nose and running eyes. Onions also cause similar symptoms. Therefore the common cold can be treated by taking an extract of onion and diluting it typically by a factor of 10 followed by 60 zeros (ie one part onion to 1060 parts water). This dilution in the language of homeopathy is called 30C, because it is diluted a hundred-fold, thirty times. Of course at such a huge dilution there’s not a single molecule of anything from the onion left, which means that the homeopathic remedy is actually just water. To illustrate how dilute this is, the Earth contains an estimated 1050 atoms and so a 30C dilution would statistically be about ten billion times more dilute than one atom in the entire planet.

So what’s the harm if some gullible people want to spend their money on rather expensive water?  If homeopathy was confined to treating running noses, then perhaps that’s not so bad.  The trouble is however, that homeopathy has been advocated for much more serious conditions such as haemophilia, Aids, a replacement for vaccination and recently in the treatment of ebola. There are homeopathic organisations that are careful in what they recommend and some even say that homeopathy should not replace regular medication. I’ll give credit for an attempt at ethical behaviour, but not all homeopaths are so moral. Many homeopaths are also claiming that homeopathy is good science, and by inference all the genuine medical researchers in the world are bad scientists. Believe me homeopathy is not science by any definition of the word but this does not stop the proponents of homeopathy from attempting to sound scientific.

The counter argument for homeopathy has focused on the huge dilution factors. Skeptics point out that the idea that something can become pharmacologically more potent the more it is diluted contradicts the laws of physics, chemistry, biology and just about any other legitimate science. Homeopaths respond by quoting a theory that water has a memory of the starting material, although this has never been convincingly demonstrated. Homeopaths point out that it’s not just dilution that’s carried out but there’s a particular way the dilution-vial has to be struck in a process they call “succussion”. The physics behind succussion remains unclear.

There are numerous clinical studies that have looked at homeopathy.  The homeopaths will select those that claim to show efficacy, science will look at all the data and conclude there is no effect. For my part, I don’t find the clinical studies that helpful as the very premise of homeopathy is so utterly scientifically implausible in the first place. And for my money, although the theory of increased dilution leading to increased potency is absurd, this does not actually deliver the homeopathic coupe de grass. There is another aspect of homeopathy that is strangely often overlooked and that is the idea that a substance that causes similar symptoms to some ailment is going to be an effective cure. This is what’s known in homeopathic circles as the law of similars.

Let’s imagine that a scientist with the combined mental acuity of Newton, Einstein and Feynman won the Nobel Prize by showing that water did indeed have a ‘memory’. Homeopathy proven, right? Well no, because it still doesn’t explain how (to use the above example) onion was selected as a remedy for the common cold based upon the fact that both are symptomatic of a runny nose. Back before it was known that germs caused disease, back when leeches were state of the art medicine, back when people died of what we might consider minor ailments today, there was a belief that there were ‘signposts’ placed in nature to guide the physician towards the right cure. Plants with heart-shaped leaves, for example, could be used to cure cardiovascular disease. If you are not familiar with the mushroom Phallus impudicus then Google an image and take a guess as to what medical condition it might be used for. These were the origins of the law of similars based upon medieval superstitions. Samuel Hahnemann continued with those traditions and applied the law of similars when he invented homeopathy in 1796.  The idea that the shape of a plant directs a physician towards its therapeutic use is not part of modern science in any respect. Neither is the idea that because some substance in high concentration causes symptoms similar to those of a particular disease, then it can be diluted out of existence to cure that disease. It is no different to preparing a potion of mandrake and eye of newt whilst saying the magic words “expecto patronum",  in a Harry Potter fantasy.  Those that argue against homeopathy seem to focus on the ridiculousness of the dilution but not so much on the ridiculousness of the law of similars. I am not sure why because either one of these hypotheses invalidates homeopathy as a science but the two together are synergistic. 

Some homeopaths will provide lists of credentials (sometimes rather dubious) and lists of celebrities and other famous people who believe in homeopathy.  Some will pepper their narratives with the language of science. Some become indignant and fire off salvos of ad hominems at their critics. Some even just make stuff up in order to try and win the argument. Not all homeopaths do this and many may genuinely believe in what they do, but none of these things makes it real, none of these things makes it science.

First the ecstasy and then comes the agony

There have been several reports in the media recently of deaths resulting from what has been described as a “bad batch” of ecstasy. As a pharmacologist several alarm bells rang when I read these reports and so I looked into it a little deeper.

The general premise is that a rouge batch ecstasy tablets containing a toxic contaminant called PMMA have found their way onto the elicit drug’s market. The recent deaths are being attributed to the presence of PMMA but little is being reported on the intrinsic dangers of ecstasy itself. 

The chemical name of ecstasy is N-methyl-3,4-methyl enedioxy-amphetamine (otherwise known as MDMA).  The chemical name of the PMMA contaminant is para-methoxy-N-methylamphetamine, which has arisen, it is claimed, as a by-product of poor chemical synthesis.  The news story is reminiscent of the TV series, Breaking Bad and paints an image of a semi-competent Jesse Pinkman type character cooking up a batch of MDMA that would drive Walter White into a fit of rage because the temperature of the vat was half a degree out. (For the record, crystal meth of Breaking Bad fame and MDMA are chemically quite different). 

Personally, I am rather skeptical that the presence of PMMA is a result of incompetent synthesis. It seems more likely that it originates from one of the starting materials in MDMA’s manufacture.  In other words, it’s there from the start and once in the mix, it’s rather hard to remove unless the MDMA is manufactured in a modern, well equipped laboratory.  Perhaps this particular “cook” is not such an inept chemist after all, but whoever is sourcing the chemicals for the synthesis might consider a better quality control policy.

The other myth that has appeared in a few places, or at least is implied, is that ecstasy itself is a safe drug and it’s only the presence of the PMMA that is leading to the deaths.  Whereas the source of the PMMA is a matter of academic speculation the story that ecstasy in its pure form is safe is really quite perniciously dangerous.

MDMA started off as its close relative MDA, in the 1950s as a cough suppressant and it was once tried out as a weight loss drug. Development of MDMA for these uses soon stopped however, because of the inherent risks involved. MDMA and its derivatives work by increasing the release of several monoamine neurotransmitters including serotonin, noradrenaline and dopamine in the brain.  The increase in neurotransmitters leads to the well known effects of MDMA notably, increased wakefulness, a sense of energy, sexual arousal, and postponement of fatigue and sleepiness. The trouble is that tinkering with one area of highly complex brain chemistry inevitably results in ripple effects elsewhere.  In the case of MDMA, it messes up the brain’s temperature control mechanisms and can lead to a syndrome called hyperpyrexia, which essentially means the body temperature increases uncontrollably.

The dangers of hyperpyrexia is the reason why consumers of MDMA are advised to keep hydrated.  Such simple advice has some merit but unfortunatelysince the feedback mechanisms of the brain are messed up it’s not uncommon to over-compensate and drink too much.  Drinking too much water in a short period of time dilutes the body’s electrolytes and that in itself can be fatal.

The dangers don’t stop there, far from it, because consumers of MDMA are also playing a game of genetic Russian roulette. MDMA is removed from the body mainly by an enzyme with the snappy name of CYP 2D6.  The CYP denotes that it’s a member of the cytochrome P450 enzyme family, by far the most important mechanism the body has for removing toxins. About 7% of the caucasian population however, are genetically deficient in CYP 2D6.  These people find it hard to remove MDMA from the body and so they overdose much more readily than others that might have taken the same dose. CYP 2D6 is so notorious for causing these types of problems that pharmaceutical development conducts specific tests to see if this enzyme is involved in the removal of any particular drug.  If it is, then there’s a chance that the drug will never be allowed to go onto the market.

And finally back to PMMA, the presence of which just redoubles the risks.  PMMA has similar effects to MDMA but is sower acting and more toxic. If the ecstasy tablet contains a significant proportion of PMMA (and some have been found to contain 25%) then the onset of the ‘high’ is delayed.  This might then lead to redosing and overdose.

So if anyone says their particular brand of ‘high grade’ ecstasy is safe, check their qualifications to see if they have any idea what they are talking about. MDMA is a dangerous drug and made all the more so by the inclusion of PMMA. You have been given the science and so now there’s no excuse.