Graham Lappin

Christmas Pudding and the Atom

Screenshot 2022-12-16 at 10.37.14 What we now call Christmas Pudding is not what it used to be. In medieval times, they knew it as Christmas pottage, made from hulled wheat boiled in milk along with spices and sugar. It evolved into a more recognisable pudding in Victorian times when it was commonly called figgy or plumb pudding. Amongst the fans of Victorian plumb pudding, as we will see in a moment, was the British Physicist, Joseph John Thomson (1856-1940).

It was in the latter stages of Victoria’s reign, in 1897, when Thomson discovered the electron. Until that time, many believed atoms were just tiny solid objects, but Thompson’s discovery showed atoms were constructed from electrically charged particles. Since atoms have no overall charge, and electrons are negatively charged, clearly there had to be an equal number of positive charges so they cancelled each other out. At the start of the 20th century, how these charges might be arranged within the atom was the subject of much scientific debate.

Perhaps because of his love of all things Christmas, Thomson came up with what he called the “plumb pudding model of the atom”. He surmised electrons were like negatively charged plumbs, all held together in an atomic matrix analogous to a positively charged pudding. Thomson’s plumb pudding was the accepted atomic model for several years, until Hans Geiger (1882-1945) of Geiger counter fame, and Ernest Marsden (1889-1970) tried to measure the size of Thomson’s plumb pudding. Geiger and Marsden worked for Ernest Rutherford (1871-1937), First Baron Rutherford of Nelson at Manchester University in the UK. Together, they fired positively charged atomic particles (known as alpha particles) into gold foil and measured the angle of deflection as they passed through. The angle, they postulated, should be proportional to the size of the pudding component of the atom.

There has been much speculation as to why Rutherford came up with the idea, but he asked Geiger and Marsden to check if any alpha particles were bouncing off the gold foil, rather than passing through it. There was nothing in the plumb pudding model to suggest this was even possible, but when Geiger and Marsden conducted the experiment, to their astonishment, they found about one in eight thousand bounced back the way they came. Rutherford said of the discovery, “it was as if you fired a 15-inch shell at a sheet of tissue paper and it came back to hit you.”

It was clear the alpha particles bounced off some concentrated spot of positive charge inside the atom in a metaphorical game of atomic tennis. Rutherford called this concentrated spot of positive charge the nucleus and postulated it contained positively charged particles called protons. And so the plumb pudding atomic model died and the solar system model was born; the positive nucleus was analogous to the sun and negative electrons were like planets in orbit around it. This has since been modified with quantum models, but we still use the solar system model today as a simplified description of the inner workings of the atom.

So as you enjoy your festive dinner this year, give a thought to Joseph John Thomson and how his thoughts of Christmas pudding led to modern atomic theory.

Merry Christmas everyone.

Shortage of antibiotics

The news media is full of reports of shortages of common antibiotics. Focus has been on penicillin-based antibiotics like amoxicillin, but the shortages have extended to other classes, including macrolides, such as erythromycin. The stories, at least in the United Kingdom, circle around the death of 16 children (total at the time of writing) from scarlet fever, a disease caused by invasive group A streptococcal infection (commonly known as strep A). There are obvious reasons for concern with children, but we should not forget the numbers are still tiny in respect to the population at large. For the most part, strep A manifests as a sore throat or relatively mild skin infection. In rare cases, the bacteria can get into the bloodstream, resulting in sepsis, a life-treating condition. On a personal level, the accompanying Ear infection photograph is of my own ear with a streptococcal infection. It occurred when I was travelling around the United States and so I left it untreated – until I ended up in hospital on an antibiotic drip.

So what has led to the current shortage of antibiotics? The British government seem to deny there is a shortage, with the Prime Minister, Rishi Sunak, stating in Parliament, “there are no current shortages of drugs available to treat this [strep A] and there are well established procedures to ensure this remains the case”. This comes as a surprise to many pharmacists who are having significant problems getting antibiotics and moreover, the problem is world wide. In the United States, for example, the FDA announced there was “currently a shortage of antibiotic amoxicillin due to higher-than-usual demand to treat secondary infections caused by RSV, Covid-19, and the common cold which have surged this fall.”

The occurrence of strep A infection commonly rises during winter, but there appears to be an unusual increase in the number of strep A infections in the northern hemisphere this year. There is a widely circulating claim that lockdowns imposed because of Covid have weakened people’s immunity to bacterial infections, but the evidence for this is far from compelling. There is a possibility that reduced exposure has resulted in a lower immune response, but there are many other possible causes – the truth is we just do not know at present.

The increase in demand, plus what has been loosely termed, “supply chain issues” has resulted in the antibiotic shortage. These supply chain issues appear to revolve around covid restrictions in China, where many of the ingredients for antibiotic medicines originate, exacerbated by an explosion in the main Chinese production facility. The British Medical Journal* lists a number of factors besides those in China that have compounded to cause the current shortages. These include suspension of manufacture during the covid pandemic, increase in demand because drug use has been extended to other conditions and problems complying to Good Manufacturing Practices.

Reading the general press, you might believe the supply chain problems have just occurred and therefore caught us by surprise. But here’s the rub. The above mentioned British Medical Journal’s article was published in November last year and so governments and authorities were pre-warned. I have blogged previously on how warnings of a viral pandemic were ignored and how the conventional commercial model of antibiotic discovery has failed. It appears that once again lessons of the past go unheeded. I’ll end this blog post with the words of Friedrich Hegel that echo to us from almost two hundred years ago, “We learn from history that we do not learn from history”.

* Shafiq, N. Et al (2021) Shortage of essential antimicrobials: a major challenge to global health security. BMJ Global Health 2021;6:e006961. doi:10.1136/ bmjgh-2021-006961

Personal take on the Theranos Fraud

Screenshot 2022-11-19 at 11.12.16
The headline this morning: “Theranos founder Elizabeth Holmes sentenced to more than 11 years for defrauding investors”.

The case centred around her false claims that her technology could detect hundreds of diseases from a single drop of blood. The BBC reported, “Silicon Valley is a place where fortunes can be made and squandered. It’s not unusual for investors to lose big sums of money. It’s also not unusual for founders to make grandiose claims about their tech. What is different about Holmes’ case, though, is that Theranos’ unwinding, actually led to fraud charges that stuck”.

I have a slightly different, and perhaps, more personal take on all this.

I was once the Research Director, later to become the Chief Scientific Officer, for a company offering high-tech solutions in drug development. Unlike Theranos, the technology did work, although the BBC’s observation that, “it’s also not unusual for founders to make grandiose claims about their tech…” does ring some bells. As the company became established so it searched for venture capital. I sat through many meetings with potential investors and they all had one thing in common. The Venture Capitalist brought along business managers, accountants and lawyers, but not one brought along a technical expert. They focused their investment decisions on business plans, projected sales, market share and profits, but to my knowledge, not one assessed the technology itself. The company eventually attained investors, which meant they asked me to attend the occasional board meeting to provide scientific updates. It didn’t take long before I realised the investors had little comprehension of the technology, and at times had some rather skewed views on its capabilities. After one board meeting. I asked whether they had ever considered including a technical expert in their decision-making team. I thought it an obvious question, but they didn’t seem to get it; they saw no need for a boffin, (and I quote).

In my general dealings with the healthcare industry, I came across another company that had acquired Venture Capital. It was, however, an alternative medicine-type company, selling cures with no convincing evidence any of it worked; although they were very careful in their claims, so as not to overstep legal lines. Given the size of the alternative medicine market, estimated to be $100 billion worldwide, perhaps the Venture Capitalists made a financially wise investment, but this doesn’t alter the fact, they had little idea they were putting their money into a baseless technology.

Theranos reminds me of the case of the fake bomb detector scam, which resulted in the businessman, James McCormick, being jailed for 10 years in 2013. The detectors could apparently detect explosives, money and drugs from a distance using nothing more than a plastic box fitted with an aerial. They sold the detectors to governments all over the world, including the United Nations. If anyone had taken the trouble to look inside the box, instead of finding space-age electronics, all they would have seen is empty space.

Technical scrutiny for investments in technical companies seems a complete no-brainer to me. To be honest, I have been asked to conduct technical scrutiny on behalf of investors a couple of times but this does not seem to be the norm. Walgreens Pharmacy, for example, did a deal with Theranos without conducting a full independent validation of the technology. Instead they believed Theranos’ claim that several pharmaceutical companies had conducted the validations previously.

I admit it’s easy to judge with 20:20 hindsight but given the “it’s too good to be true” claims of both the fake bomb detector and Theranos, it seems a safe bet that robust technical scrutiny, at least in these cases, might have saved a lot of money and heartache. Certainly caveat emptor (let the buyer beware) seems to be good advice. But that’s just the option of a boffin.

Atomic Time Machine

Screenshot 2022-07-27 at 15.27.29 This day, 6th August, marks the anniversary when in 1945, the first, and to date only, nuclear weapons were used in war. A uranium bomb nicknamed Little Boy, exploded over the Japanese city of Hiroshima and three days later a plutonium bomb nicknamed Fat Man detonated close to Nagasaki. By the end of that year the death tolls from the detonation and subsequent injuries were between 90,000 to 120,000 in Hiroshima (population 330,000) and 60,000 to 80,000 in Nagasaki (population 280,000). In amongst horrendous death and suffering, in the aftermath of the Japanese surrender on 2nd September 1945, medical researchers gathered data on the biological effects of radiation, especially from Hiroshima and the surrounding area. Known as the Life Span Study run by the Radiation Effects Research Foundation, scientists looked at the long-term effects of radiation and incidences of cancer in exposed and unexposed individuals.

Results from this study are used as part of modern risk assessments in setting limits for radioactive exposure in medicine and the nuclear industry. These data are only useful however, when correlated to radioactive exposure from the atomic explosions. Those measurements were impossible at the time of the detonation and so radiation exposure had to be based on theoretical estimations. That was until the 1980s, when science ever ingenious, found a way of effectively going back in time to measure the radioactive density which hit those Japanese cities in the last days of World War II.

In the city of Hiroshima, there’s a memorial called the atomic bomb dome. It’s what Screenshot 2022-07-27 at 15.30.42 survives from the Prefectural Industrial Promotion Hall and its oval dome of copper. The bomb vaporised most of the copper but some fragments survived. Copper has two principal isotopes, 63Cu and 65Cu. Isotopes are elements that have different numbers of neutrons in their atomic nucleus and consequentially, neutron bombardment can transform one isotope into another. In the case of 63Cu, neutron bombardment switches it to an isotope of nickel – 63Ni. This isotope is extremely rare in nature and so any 63Ni found in the remains of the copper dome had to result from neutrons released during the atomic explosion. By measuring the amount of 63Ni versus 63Cu in the surviving dome fragments, scientists could calculate the neutron density of the bomb. The original theoretical calculations didn’t exactly agree with measured values, but were nevertheless close enough to allow a recalibration of the risk assessments.* Isotopes, in this case, got us as close to a time machine as we’ll probably ever get.

* – W.C. Roesch (Ed.), US-Japan joint reassessment of atomic bomb radiationdosimetry in Hiroshima and Nagasaki, vols. 1 and 2, Radiation Effects Research Effects Foundation, Hiroshima, Japan, 1987.

An historical scandal

This blog post is a little different to my pharmacological posts, because instead I want to recount a little history of science. It’s a story of tragedy, scandal, blackmail and a delicious happy ending.

Screenshot 2022-07-26 at 16.14.57 Yesterday, 26th July, marked the anniversary when, in 1895, Marie Sklodowska married Pierre Curie (their wedding photograph is shown on the left). Marie Curie, of course, became one of the most famous names in science. She was the first women to win a Nobel prize and the first person to receive two Nobel prizes, one in physics and one in chemistry.

Born Maria Salomea Skłodowska in Warsaw in 1867, her family called her by her nickname, Manya. Warsaw was part of the Kingdom of Poland in the Russian Empire, and Czar Alexander II was not too keen on educating the masses. Manya became a member of a group known as the Floating University, where gatherings took place in secret, because discovery would have meant imprisonment. In 1891, with the financial help of her sister, Bronisława, Manya moved to Paris to become a student at the Sorbonne, one of the few institutions to admit women. In Paris, she adopted the more French name of Marie. Before she embarked on her famous work on radioactivity, Marie researched the magnetic properties of steel and it was during this research she met Pierre Curie, who later became her husband.

Marie and Pierre were happily married for eleven years and had two daughters, Irène and Ève^* (more on Irène shortly). Then, on April 19, 1906, Pierre was run over by a horse-drawn carriage and killed instantly. Pierre’s death devastated Marie, but as time heals, in around 1910, she fell in love with a physicist and former student, Paul Langevin. The problem was Langevin was a married man. They kept the affair secret for a year, but his estranged wife, Jeanne, hired a private detective to steal love letters from the couple, which she then made public.

Today, perhaps, adultery is almost a qualification for high office, but in the early 1900s, Marie Curie and Paul Langevin’s affair was pure scandal. This went as far that when Marie was awarded her second Nobel prize in 1911, there were moves to keep her out of the ceremony. The King of Sweden, Gustav V, intervened and insisted she should attend. At the banquet that followed the ceremony, Gustav sat with Marie, and they seemed to get on well. In the years that followed, Gustav was also plunged into scandal over an alleged homosexual affair with a married man, Kurt Haijby. It didn’t end well for Haijby because he was jailed in 1952 for attempting to blackmail the King.

To round this story off, we end up with Marie Curie’s granddaughter, Helene Joliot. She was the daughter of Irène Curie, who had become Irène Joliot-Curie, when she married the chemical engineer Frédéric Joliot. Like her mother, Irène Joliot-Curie also won a Nobel prize for her work on radioactivity. Helene Joliot, in her turn, married, but by one of those great coincidences of history, to Michel Langevin, the grandson of Paul Langevin, with whom Marie had had the affair years before. Marie Curie and Paul Langevin never ended up together, but at least their grandchildren did.

(*- Ève Curie wrote “Madame Curie – A biography” The book is available in English, translated by Vincent Sheean).

Hangover cure – I’m sceptical

If, like me, you’re a fan of P. G. Wodehouse, then you might know the short story, “Jeeves Takes Charge”. Bertie Wooster has had one-over-the-eight the night before and is complaining of a hangover. Jeeves presents him with “a little preparation of my own invention” and upon drinking it down, Bertie is instantly revived. Hangover cures like this are the stuff of legend, but in reality, anyone trying them might well have doubts about their effectiveness. There is however, a new pill on the market called Myrkl, hailed to be a “game changer”.

To be more accurate, Myrkl isn’t really a hangover cure rather than a proposed way of reducing the amount of alcohol that gets absorbed into the bloodstream. The pill contains two species of bacteria: Bacillus subtilis and Bacillus coagulans, along with the amino acid L-Cysteine and Vitamin B12. I’m not entirely sure what the L-Cysteine and Vitamin B12 does because there’s no evidence they have any effect on hangovers. Regulatory authorities do not classify Myrkl as a drug, rather than as a supplement, or more precisely, a probiotic, which means it can be sold over the counter or on-line, which to my sceptical mind also looks like “a little preparation of my own invention.”

Myrkl is taken about an hour before consuming alcohol in order to load the gastrointestinal tract with alcohol-metabolising bacteria. The pill is coated to protect it from stomach acid, so the bacteria are released in the duodenum, where most alcohol absorption takes place. The claim is that the bacteria breaks down 70% of the alcohol over the next hour, thus reducing the alcohol-blood concentration, and hence easing any hangover the next morning. It all sounds feasible, but the evidence is largely anecdotal and I can’t see it’s supported with much science.

There’s a lot of hype around Myrkl with some journalists testing it on themselves and many testimonials; none of which are good science. There is a peer reviewed study, which seems reasonably well designed, being randomised, placebo-controlled and double-blinded, but it was conducted in only 24 subjects (13 male and 11 female) and so is somewhat at odds with the hype, in my opinion. There’s also a claim that Myrkl is “vegan, all natural and boosts immunity and natural energy levels” (this claim is linked to B12 apparently). The “boosts immunity and natural energy levels” is a big red flag to me, as these are common claims made by supplements everywhere, but are scientifically meaningless. To my eye, the claims have echos of my spoof “Metalo-Lappin-Detox” blog post.

There are also societal questions surrounding Myrkl, such as will it encourage binge drinking and will people be more likely to drink and drive? The CEO of Myrkl, Håkan Magnusson, has said, “this is no way designed as an excuse to drink beyond NHS guidelines” and there is a drink responsibly page on the website. I’m not sure however, such proclamations will hold in the real world. I remember once being in a meeting where the caterers only provided decaf coffee in error. We didn’t know until the end of the meeting and then realised everyone had drunk several times their normal amount in anticipation of the caffeine-hit that never occurred. I wonder if the same might be true with Myrkl and alcohol consumption.

Compared to the amount of data and years of research that is necessary to launch a new drug, there’s very little barrier to marketing supplements. This market is, I’m afraid, buyer beware.

Weight loss drugs of a new class

I once attended a pharmacology conference at McCormick Place in Chicago. It’s a huge conference centre and navigating its many halls is daunting for someone like me who has no sense of direction. Ambling towards the lecture theatre I wandered through the exhibition hall festooned with donut stands, pretzel stalls, breakfast burritos, waffles and pancakes. If my breakfast then left me thirsty, I could wash it all down with a morning caramel macchiato from the ubiquitous Starbucks booth. The irony on this day was the morning lecture was on the development of anti-obesity drugs.

Around 9% of the world’s population is undernourished (660 million people) while about twice that number are classified as obese. In the United States, 42% of the adult population is classified as obese, with around 28% in the UK. But before I get too holier-than-thou, there’s evidence to suggest humans are evolutionarily hard wired to overeat when there’s an abundance of food and so perhaps obesity is an inevitable consequence of a developed economy? Obesity leads to other conditions such as cancer, diabetes and heart disease, putting pressure on already stretched clinical services, and therefore represents a genuine medical need.

Anti-obesity drugs have a rocky history. Drugs such as fenfluramine, phentermine and lorcaserin have all been withdrawn, at least in some countries, because of serious side effects. But there may, just possibly, be two new drugs that offer some hope. They started out as treatments for type-2 diabetes – and are still prescribed as such, but a serendipitous observation in the clinical trials led to a redirection towards appetite suppression.

The two drugs are semaglutide and tirzepatide. They are both small proteins (more accurately termed polypeptides) with lipid molecules attached to facilitate their crossing of biological membranes. Semaglutide and tirzepatide are made from 31 and 39 amino acids respectively and are classified as recombinant DNA produced polypeptides, meaning they are manufactured through genetically engineered bacteria. These drugs are therefore a long way from traditional chemical synthesis and exemplify how modern biochemical technology has impacted on healthcare. (Incidentally, insulin is manufactured through genetically engineered organisms, a technology first identified in 1978, and so the process has a reasonable track record).

How do semaglutide and tirzepatide work? The story starts, perhaps unsurprisingly since we’re talking about weight gain, with eating. As food passes from the oesophagus into the gastrointestinal tract, the duodenum releases two hormones. One is called gastric inhibitory polypeptide (GIP) and the other is called glucagon‐like peptide‐1 (GLP‐1). Although each of the two hormones has their own receptors, they nevertheless have similar actions. Combined, they signal the pancreas to release insulin and suppress the production of the glucagon, two hormones involved in regulating blood sugar (for a more detailed account of the pharmacology of GIP and GLP-1 see here).

Semaglutide mimics the action of GLP-1 and tirzepatide mimics both GLP-1 and GIP, explaining why they were originally developed to treat type-2 diabetes. But the release of GIP and GIP-1 has effects other than on glucose metabolism. They slow gastric emptying and signal the brain’s hypothalamus to suppress the feeling of hunger. (The rare genetic disorder Prader-Willi Syndrome, where patients overeat because they constantly feel hungry, may be caused by a dysfunctioning hypothalamus). Semaglutide and tirzepatide therefore, in effect, highjack the body’s hormonal signalling system, resulting in apatite suppression. Clinical trials of the two drugs have achieved weight loss of between 15 and 22%, which is pretty impressive.

These drugs do not however, offer the “eat anything you like without consequences” panacea that some may seek but are reserved for those patients with obesity at the more severe end of the spectrum. They might for example, offer an alternative to bariatric surgeries. The drugs, being peptides can’t survive the digestive processes of the gastrointestinal tract and so have to be administered by weekly injection; as far as we know currently, this would be for a lifetime. Moreover, side effects vary from patient to patient but include vomiting, nausea, diarrhoea and constipation (the effects can be eased to some extent by increasing the dose over time). So at least for now, weight management for the majority of us remains very much in the balance between calorific intake and expenditure.

Osteoarthritis

an image of the author’s ankle taken by gamma-scintigraphy. The darker areas show regions of osteoarthritis. Arthritis is a term used to describe several inflammatory conditions affecting joints. As is so often the case with medical history, the name was derived from observed symptoms but subsequently it was found these were the result of a plethora of different causes. Today, “arthritis” covers around 100 different conditions associated with joint disease. Rheumatoid arthritis, for example, is an autoimmune condition, where the patient’s immune system attacks the tissues of joints. Osteoarthritis, on the other hand, is caused by physical damage to joints, particularly protective cartilage. Osteoarthritis has particular interest for me as I am a sufferer. It started with a motorcycle accident when I was in my early 20s and over the years damage to cartilage in my ankles has worsened to the point it can now be difficult to walk for more than a few meters. The condition leads to chronic pain, sometimes severe enough to be debilitating. There are few drugs available to manage osteoarthritis. Sometimes anti-inflammatories have benefit and opioid-type drugs are used to ameliorate pain. Opioids over the long term however, become less effective and have problems of their own.

The reason osteoarthritis is painful might seem obvious. Bones of the joins rubbing on each other, leading to inflammation and sometimes bleeding within the joint. The complexity of biochemistry however, is not something which should be taken for granted. Recent research suggests an unexpected pathway triggers osteoarthritic pain.

Artemin is a protein released from vascular smooth muscle, which then binds onto another protein called GFRα3. One artesian protein binds centrally to two GFRα3 proteins, which triggers nerves acting as relay stations between neurones (known as preganglionic neurons) near to the inflamed joint. This mechanism is already known as a response to heat and cold. If you want to trigger artemin-GFRα3 simply place your hand in a bowl of ice cold water. What’s new is the association of artemin and GFRα3 with arthritic pain.

Opioid-type drugs bind to receptors in the spinal cord or brain (the three main receptors being known as mu, delta and kappa) and have a generic effect on the sensation of pain. These drugs also cause sedation and euphoria, patients can become dependent and they can have adverse effects on the gastrointestinal tract. If the artemin-GFRα3 pathway effect is confirmed, then this may offer a new more specific target for pharmacologic intervention of osteoarthritic pain, something likely to be welcomed by the 8.5 million suffers in the UK, including me.

Being realistic however, and knowing how long new medications take from concept to market, then I doubt I will see this potential new class of drugs in my lifetime. But all new treatments start somewhere and so perhaps in the next 20-years, we might see some long awaited advances. Non-arthritic fingers crossed.

Homeopathy Awareness Week

It’s world homeopathy awareness week and so I thought I would oblige and make people aware of one of the most prevalent and pernicious forms of alternative medicine in existence. There are many who steadfastly believe in homeopathy even though the foundations not only have no basis in reality, they are really quite bizarre.

Preparation of a homeopathic remedy involves taking a substance which causes similar symptoms to some disease or ailment, followed by an enormous dilution of the substance to the point where not a single molecule remains. The resulting “therapy” (which is now just water) is then claimed to have therapeutic benefit while being devoid of side-effects.

To give an example, a dripping nose and running eyes are symptomatic of the common cold. According to the homeopathic ethos, onions offer treatment because they cause similar symptoms. The homoepath dilutes an extract of onion to make, for example, a 30C preparation. The 30C notation shows that the extract undergoes a one in a hundred dilution, thirty times over. To put this level of dilution into context, it is equivalent to ten billion times more dilute than a single atom contained within the planet Earth.

So what’s the harm if some gullible people want to spend their money on rather expensive water? If homeopathy only applied to treating running noses, then perhaps that’s not so bad. The trouble is however, some homeopaths claim to treat serious conditions such as haemophilia, AIDS, a replacement for vaccination, diabetes and infectious disease including Covid-19. Some homeopathic organisations are careful about what they recommend and may even say 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 also claim 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 trying to sound scientific. Perhaps at the more bizarre end of homeopathy sit remedies such as Murus Berlinensis – a scientific sounding name for an ultra dilution of pieces of the old Berlin wall – yes the Berlin wall, the one that was demolished in 1989.

The counter argument for homeopathy has focused on the huge dilution factors. Skeptics point out that the idea that ultra-dilution increases potency contradicts the laws of physics, chemistry, biology and just about any other legitimate science. Homeopaths respond by saying that water has a memory of the starting material, although there is no evidence for such an effect. Homeopaths also claim preparation of the dilutions are special through striking the vial in a process they call “succussion”. The physics behind succussion remains unclear.

There are many 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. Of course, bad science can provide evidence for whatever you choose.

For my part, I don’t find the clinical studies that helpful as the fundamental premise of homeopathy is so implausible. And for my money, although the theory of increased dilution leading to increased potency is absurd, this does not deliver the homeopathic coupe de grass. There is another aspect of homeopathy that is often overlooked, the one that claims a substance that causes similar symptoms to some ailment will also 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 had a ‘memory’. Homeopathy proven, right? Well no, because it still doesn’t explain how (to use the above example) onion is an effective treatment for the common cold. Back before it was known germs caused disease, back when leeches were state-of-the-art medicine, back when people died of what we might consider minor ailments today, a teleological philosophy prevailed. Plants effective against heart disease, for example, had heart-shaped leaves. Walnuts were good for the brain because they looked like little brains. If you are not familiar with the mushroom Phallus impudicus, then Google an image and take a guess 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. That the shape of a plant directs a physician towards its therapeutic use is not part of modern science. Those who 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 a synergistic double whammy.

Homeopaths often provide lists of credentials (sometimes rather dubious) and lists of celebrities and other famous people, including the British Royal Family, who believe in homeopathy. Some 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 to win the argument. Not all homeopaths do this and some may genuinely believe in what they do, but none of these things makes it real, none of these things makes it science.

Is Chocolate Toxic?

It’s rare that governments of the world act in unison and so today goes down in regulatory history as the day the US FDA, the European EMA, the UK MHRA and the Australian TGA have simultaneously issued restrictions on the use of theobromine.

I suspect most people are not aware of theobromine or this new legislation and so a little background. Theobromine is an alkaloid stimulant and a vasodilator (meaning it causes an increase in blood flow). It has been on the list of prohibitive substances for race horses since the 1970s and its adverse effects in dogs are also well established. It is only now, however, that authorities have extended restrictions to humans. Why has it taken so long? Part of the problem is that theobromine is present in chocolate – the world’s favourite confectionary. Regulatory agencies therefore agreed an outright ban of chocolate was impracticable but have instead issued regulations limiting its sale. Different countries are taking different approaches, but here in the UK, from the end of this month, chocolate will only be available through a doctor’s prescription. A government spokesperson said that, “we have delayed bringing in this legislation because we do not want to spoil Easter – it’s what the people would have wanted.”

Pharmacologists have pointed out that humans metabolise caffeine to theobromine and other alkaloids and so they are concerned restrictions on chocolate may be extended to tea and coffee. But there’s no sign of this yet – we will have to wait and see.