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Avogadro – DC's Improbable Science

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Avogadro

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gphc

The General Pharmaceutical Council (GPhC) has been the statutory body responsible for the regulation of pharmacy since 2010. It’s status is similar to that of the GMC and. heaven help us, the GCC. Before that the regulator was the same as the professional body, the Royal Pharmaceutical Society of Great Britain (RPS). The RPS proved to be as useless as most other regulators, as documented in detail in my 2008 post, At around the time it stopped being a regulator, the RPS started to condemn quackery more effectively, but by then it had lost the power to do much about it (I hope the latter wasn’t the cause of the former). The body that could do something, the GPhC has done essentially nothing. as described in this post.

I did a 2 year apprenticeship in Timothy White’s and Taylor’s Homeopathic (yes, really) Chemists in the 1950s.
My first degree was in pharmacy. I got my interest in pharmacology from reading Martindale’s Extra Pharmacopoeia in the shop. I soon decided that I didn’t really want to spend the rest of my life selling lipstick and Durex. The latter was quite a big seller because the Boots across the road didn’t sell contraceptives (they changed their minds in the 1960s).

In those days, we spent quite a lot of time making up (almost entirely ineffective) ‘tonics’ and ‘cough mixtures’. Now the job consists largely of counting pills. This has exacerbated the ‘chip on the shoulder’ attitude that was present even in the 1950s. For a long time now, pharmacists have wanted to become the a ‘third tier’ in the NHS, alongside GP practices and hospitals., after hospitals and doctors". . Here are a few comments on this proposition.

First let me say that I’ve met some very good and ethical pharmacists. I did a vacation job in a hospital pharmacy where the boss had an encyclopaedic knowledge of the effects and side effects of drugs, and of their dosage. His advice was often sought by doctors, and rightly so. He had no way of knowing at the time that his advice to replace barbiturates with thalidomide would lead to such a tragedy, because the evidence had been concealed by the manufacturer. Some of the problems alluded to here have already been highlighted by two excellent pharmacists, Anthony Cox and @SparkleWildfire, neither of whom work in pharmacists shops. They are absolutely spot on but they seem to be in a minority among pharmacists.

The problems seem to lie mostly in retail shops. Their shelves are laden with ineffective pills and potions. And the pharmacist has every incentive to sell them. His/her income depends on it directly if it’s a privately owned pharmacy. And his/her standing with head office depends on it in chain store pharmacies. This conflict of financial interest is the prime reason why pharmacists are not qualified to form a third tier of healthcare. The avoidance of conflicts of interest among doctors was one of the great accomplishments of the NHS. In the USA there are huge scandals when, as happens repeatedly, doctors order expensive and unnecessary treatments from which they profit. It’s no consolation that such problems are creeping back in the UK as a result of the government’s vigorous efforts to sell it off.

Here are few examples of things that have gone wrong, and who is to blame. Then I’ll consider what can be done.

Ineffective medicines

In any pharmacy you can see ineffective ‘tonics’ and ‘cough medicines’, unnecessary supplements with dishonest claims and even, heaven help us, the ultimate scam, homeopathic pills.

What’s worse, if you ask a pharmacist for advice, it’s quite likely that they’ll recommend you to buy them.

I was amazed to discover that a number of old-fashioned ‘tonics’ and ‘cough medicines’ still have full marketing authorisation. That’s the fault of the Medicines and Healthcare Regulatory Auhority (MHRA) who are supposed to assess efficacy and totally failed to do so, Read about that in “Some medicines that don’t work. Why doesn’t the MHRA tell us honestly?” . It’s hard to blame a pharmacist for the bad advice given by the MHRA, but a good one would tell patients to save their money.

benylin

Big corporate pharmacies

Companies like Boots seem to have no interest whatsoever in ethical behaviour. All that matters is sales. They provide “(mis)educational” materials that promote nonsense They advertise ridiculous made-up claims in the newspapers, which get shot down regularly by the Advertising Standards Authority, but by that time the promotion is over so they don’t give a damn. See for example, CoQ10 scam and the ASA verdict on it. And "Lactium: more rubbish from Boots the Chemists. And a more serious problem". And "The Vitamin B scam. Don’t trust Boots"

Recently the consumer magazine Which? checked 122 High Street pharmacies. They got unsatisfactory advice from 43% of them, a disastrously bad performance for people who want to be the third tier of healthcare.

Even that’s probably better than my own experience. Recently, when I asked a Sainsbury’s pharmacist about a herbal treatment for prostate problems, he pointed to the MHRA’s kite mark and said it must work because the MHRA approved it -he was quite unaware that you get the THR kite mark without having to present any evidence at all about efficacy.

mhra

Of course that is partly the fault of the MHRA for allowing misleading labels, but nevertheless, he should have known. See “Why does the MHRA refuse to label herbal products honestly? Kent Woods and Richard Woodfield tell me” for more on how the MHRA has betrayed its own standards.

When I’ve asked Boots’ pharmacists advice about persistent diarrhoea in an infant, saying I wanted a natural remedy, I’ve usually been guided to the homeopathic display. Only once was I told firmly that I should use rehydration not homeopathy (something every good parent knows) and when I asked that good pharmacist where she’d been educated, she said in Germany (mildly surprising given the amount of junk available in German pharmacies)

Regulators

Anthony Cox, a pharmacist who has been consistently on the side of right, says

"This is something that needs to be dealt with at a regulatory and professional body by the whole profession, and I am certain we have the majority of the UK pharmacy profession on side."

But the regulator has done nothing, and it isn’t even clear that there is a majority on his side.

At a 2009 meeting of Branch Representatives of the RPS a motion was proposed:

“…registration as a pharmacist and practice as a homeopath are not compatible, and that premises registered with the Society should not be used for the promotion of homeopathy”

Although that is obviously sensible to most people, the proposal was followed by a speaker from Leicester who thought it right to keep an open mind about Avogadro’s number and the motion was defeated. So much for the "scientists on the High Street" aspiration.

There have been two major scandals surrounding homeopathy recently. Both were revealed first by bloggers, and both came to wide notice through television programs. None were noticed by the regulators, and when they were brought to the attention of the regulator, nothing effective was done.

The malaria scandal

A lot has been wriitten about this here and on other blogs e.g. here and here. The idea that sugar pills can prevent or cure malaria is so mind-bogglingly dangerous that it was condemned by the Queen’s Homeopathic Physician, Peter Fisher. It was exposed on a BBC Newsnight programme in 2006. Watch the video.

The Gentle Art of Homeopathic Killing was an article that originally appeared on the excellent Quackometer blog produced by Andy Lewis. "The Society of Homeopaths were so outraged about one of their members flouting the code of ethics so blatantly that they took immediate action. That action was, as expected, not to do anything about the ethics breach but to threaten Andy and his hosting ISP with legal action for defamation. The article is reproduced here as a public service".

Some of the people involved in this bad advice were pharmacists, Very properly they were referred to the RPS in 2006 qnd 2009, the regulator at that time. They sat on the complaint so long that eventually the RPS was replaced by the GPhC as regulator. Nothing much has happened.

The GPhC did precisely nothing. Read their pathetic response.

Homeopathy for meningitis

An equally murderous fraud, "homeopathic vaccines" by Ainsworth’s has long been targeted by bloggers. In January 2013, Samantha Smith made an excellent BBC South West programme about it. Watch it and get angry.

Anthony Pinkus, pharmacist at Ainsworths, has been referred to the then regulator, the RPS, in 2006 and 2009. It’s said that he took "remedial action", though there is little obvious change judged by the video above. No doubt some of the most incriminating stuff has been removed from his web site to hide it from the ASA. It’s safer to mislead people by word of mouth. Since the last video more complaints have been made to the GPhC. So far, nothing but silence.

Why doesn’t the regulator regulate?

This pamphlet is reproduced from the July 2011 Quackometer post, “Ainsworths Pharmacy: Casual Disregard for the Law

ainsworth

It’s almost as though those royal warrants, enlarged on right, acted as a talisman that puts this dangerous company outside the grasp of regulators. I hope that the GPhC Council , and Duncan Rudkin (its chief executive and registrar), are not so worried about their knighthoods that they won’t risk upsetting the royal family, just to save patients from malaria and meningitis. Their CEO, Robert Nicholls is only a CBE so far.

warrants

Another reason for their inaction might be that the GPhC Council members, and Duncan Rudkin (its chief executive and registrar), lack critical faculties. Perhaps they have not been very well educated? Many of them aren’t even pharmacists, but that curious breed of professional administrators who inhabit the vast number of quangos, tick their boxes and do harm. Or perhaps they are just more interested in protecting the income of pharmacists than in protecting their customers?

Education

The solution to most problems is education. But there is no real knowledge of how many pharmacists in the UK are educated in the critical assessment of evidence. A recent paper from the USA did not give cause for optimism. It’s discussed by the excellent US pharmacist, Scott Gavura, at Science-based medicine. The results are truly horrifying.

“Few students disagreed with any CAM therapy. There was the greatest support for vitamins and minerals (94%, mean 4.29) which could include the science-based use these products. But there was strong support for demonstrably ineffective treatments like acupuncture, with 64% agreeing it was acceptable. Even homeopathy, which any pharmacy student with basic medicinal chemistry skills ought to know is absurd, was supported by over 40% of students.”

If the numbers are similar in the UK, the results of the Which? magazine survey are not so surprising. And if they are held by the GPhC Council. their inaction is to be expected. We just don’t know, and perhaps someone should find out.

I suspect that sympathy for quackery may sometimes creep in through that old-fashioned discipline known as pharmacognosy. It is about the botany of medicinal plants, and it’s still taught, despite the fact that very few drugs are now extracted from plants. At times, it gets dangerously close to herbalism. For example, at the School of Pharmacy (now part of UCL) a book is used Fundamentals of Pharmacognosy and Phytotherapy  by Michael Heinrich, Joanne Barnes, Simon Gibbons and Elizabeth M. Williamson, ot the Centre for Pharmacognosy and Phytotherapy at the School of Pharmacy. The introductory chapter says.

“TRADITIONAL CHINESE MEDICINE (TCM) The study of TCM is a mixture of myth and fact, stretching back well over 5000 years. At the time, none of the knowledge was written down, apart from primitive inscriptions of prayers for the sick on pieces of tortoise carapace and animal bones, so a mixture of superstition, symbolism and fact was passed down by word of mouth for centuries. TCM still contains very many remedies, which were selected by their symbolic significance rather than proven effects; however, this does not necessarily mean that they are all ‘quack’ remedies!”

Well, not necessarily. But as in most such books, there are good descriptions of the botany, more or less good accounts of the chemical constituents followed by uncritical lists of things that the herb might (or might not) do. The fact that even the US National Institutes of Health quackery branch, NCCAM, doesn’t claim that a single herbal treatment is useful tells you all you need to know.

Joanna Barnes is Associate Professor in Herbal Medicines, School of Pharmacy, University of Auckland, New Zealand. She has written a book, Herbal Medicines (“A useful book for learning holistic medicine”) that is desperately uncritical about the alleged theraputic effectiveness of plants. ("Simon Gibbons is on the editorial board of The Chinese Journal of Natural Medicine. Elizabeth Williamson is editor of the Journal of Phytotherapy Research, a journal that has a strong flavour of herbalism (take the infamous snoring remedy). These people aren’t quacks but they are dangerously tolerant of quacks.

The warning is in the title. "Phytotherapy" is the current euphemism for herbalism. It’s one of those red light words that tells you that what follows is unlikely to be critical. Exeter’s fantasy herbalist, Simon Mills, now describes himself as a phytotherapist. What more warning could you need?

Perhaps this explains why so many pharmacists are unworried by selling things that don’t work. Pharmacy education seems not to include much about the critical assessment of evidence. It should do.

Chemist and Druggist magazine certainly doesn’t help. It continually reinforces the idea that there is a debate about homepathy. There isn’t. And in one of its CPD modules Katherine Gascoigne says

"Homeopathic remedies are available, but are best prescribed by a homeopath"

Ms Gascoigne must be living on another planet.

Conclusions

The main conclusion from all of this is that the General Pharmaceutical Council is almost criminally negligent. It continues to allow pharmacists, Anthony Pinkus among them, to endanger lives. It fails to apply its own declared principles. The members of its Council, and Duncan Rudkin (its chief executive and registrar), are not doing their job.

Individual pharmacists vary a lot, from the superb to those who believe in quackery. Some, perhaps many, are embarrassed by the fact that their employer compels them to sell rubbish. It’s too much to expect that they’ll endanger their mortgage payments by speaking out about it, but the best ones will take you aside and explain that they can’t recommend it.

The GPhC itself is regulated by the Professional Standards Authority, the subject of my last post. We can’t expect anything sensible from them.

In the USA there is a shocking number of pharmacists who seem to believe in quackery. In the UK. nobody knows, though judging by their failure to vote against the daftest of all scams, homeopathy, there is no cause for complacency here.

It seems that there will have to be big improvements in pharmacy education before you can have much confidence in the quality of the advice that you get in a pharmacy.

Follow-up

Yesterday a talk was given at the School of Pharmacy, organised by the “The Centre for Homeopathic Education” (an oxymoron if there ever was one). The flyer had all the usual nonsense. Its mention of “Remedies & Tonics for Cancer Recovery” might well have breached the Cancer Act (1939). When I asked whether the amount received in room rental was sufficient to offest the damage to the reputation of the School of Pharmacy resulting from hosting a nutty (and possible illegal) event, I had the greatest difficulty in extracting any sort of response from the school’s director, Duncan Craig. I’m told that he considers “the policy on space rental to be a UCL management issue, rather than a matter of discussion on scientific ethics with a colleague”. Oh dear.

Samuel Hahnemann (1755 – 1843) was the originator of homeopathy. He was clearly a well-intentioned man.. There is good reason to believe that he thought dilution could not go on for ever, but he died 22 years before it became possible to calculate that his favourite 30C dilution already contained nothing at all.

The bible of homeopaths is Hahnemann’s Organon der rationellen Heilkunde, “Organon of the Medical Art”. His views on dosage, as expressed in the six editions of this book are almost as self-contradictory as the other bible. Hahnemann’s writing about ‘vital spirits’ sounds very silly now, but it is language that was quite common at the end of the 18th century, before much was known about medicine or physiology. But his interest in chemistry was entirely sensible.

Before 1800 Hahnemann started out with the very high doses that were conventional at the time. Unlike most of his contemporaries, he was smart enough to realise that giving 50 g of antimony was killing people so he kept reducing the dose until it was no longer toxic. Unfortunately he (like almost everyone else at the time) didn’t know about controls so he mistook lack of toxicity (because the dose was zero) for a beneficial effect. Nonetheless, for most of his life he did not advocate the extreme dilutions that many modern homeopaths use routinely.

In The Life and Letters of Dr Samuel Hahnemann by Thomas Lindsley Bradford, M.D.(or see Google books edition of the Organon), there is an interesting passage. According to the edition here pp. 237 – 238), this was a note attached to para. #283 in the first edition of the Organon.

” The doctrine of the divisibility of matter teaches us that we cannot make a part so small that it shall cease to be something, and that it shall not share all the properties of the whole.”

Here Hahnemann refers to the doctrine of divisibility, but appears to be saying that dilution can go on for ever. But he also says something that directly contradicts this view (Organon, Dudgeon’s translation see also here, page 239 ). The emphasis is mine.

“I must say that these procedures seem to show chiefly how high one can go with the potentized attenuation of medicines without their action on the human health becoming nil.

Although this claims that you can dilute a lot, it also admits that if the dilution goes too far the effect would eventually vanish, contrary to the usual homeopathic “principle” that it should keep getting stronger and stronger. and contrary to Hahnemann’s suggestions in other places that he thought matter was infinitely divisible.

This passage shows quite clearly that Hahnemann did not believe that his medicines would work if they were diluted so much that that there were no molecules left. That he believed this is confirmed by a letter that Hahnemann wrote in a letter to a Dr Schreter dated September 13th, 1829. This letter reprimanded Schreter for advocating extremely high dilutions.

there must be some limit to the thing. It cannot go on to infinity


The original German version was

“Es muss ein Ende geben, es kann nicht bis ins Unendliche weitergehen”

This confirms that Hahnemann was aware of, and accepted, that matter was not infinitely divisible and his medicines would not work if they contained nothing of the original material.

This attitude is actually not at all surprising, because Hahnemann was an educated man and he had a particular interest in chemistry. He cannot have failed to be aware of Dalton’s atomic theory, which was published between 1805 – 1810, while Hahnemann was writing the first edition of the Organon.

Peter Morrell, in Hahnemann and Homeopathy, says

“These were obviously developments that Hahnemann could not have failed to know about and indeed, was thoroughly excited about, It is clear from many of his asides that he regarded chemistry as the most important science.”

What is astonishing is that I can find no example of Hahnemann ever having mentioned Dalton or Avogadro. Perhaps he was a bit scared by the implications of their suggestions that molecules could not be divided without changing their nature.

The first edition of the Organon was published in 1810. but in the 5th edition appeared 1833, ten years before his death, These dates turn out to be important.

John Dalton (1776 – 1844) was able to estimate relative atomic masses of various molecules, the smallest unit that a chemical can exist in without losing irs identity. His values were soon improved by Amadeo
Avogadro
(1776 – 1856), in 1811. Avogadro made the very important proposal that the volume of a gas (strictly, of an ideal gas ) is proportional to the number of atoms or molecules that are present. More precisely, the relationship between the masses of the same volume of different gases (at the same temperature and pressure) corresponds to the relationship between their respective molecular weights. Hence, the relative molecular mass of a gas can be calculated from the mass of a sample of known volume.

BUT neither Avogadro nor Dalton knew how many molecules there were in a given mass of a substance

This is absolutely crucial because it means that, although Hahnemann realised that there was a limit to the dilutions that could be used, he had no way of knowing what that limit was,

The answer to that question was discovered only in 1865, 22 years after the death of Hahnemann.  It was discovered not by Avogadro, but by Johann Josef Loschmidt (1821 – 1895). It is Loschmidt, not Avogadro, who discovered the crucial numerical value of ‘Avogadro’s number‘, and in the German literature it is known, properly, as Loschmidt’sche Zahl.

This number is 6.022 x 1023 molecules per mole. One mole of a pure compound is its molecular mass in grams. The molecular mass of carbon (relative to hydrogen) is 12, so 12 grams of carbon contain 6.022 x 1023 carbon atoms. The molecular mass of of strychnine is 334.4 so 334.4 grams of strychnine contain 6.022 x 1023 strychnine molecules.

Armed with the numerical value of Avogadro’s number, it is easy to calculate that a 30 C homeopathic dilution contains nothing whatsoever. More precisely, it would contain, on average, a single molecule in spherical pill with a diameter equal to the distance from the earth to the sun.

But Hahnemann could not have known that. If had lived another 25 years he would almost certainly have renounced the idea of using 30 C dilutions.

He had a good excuse for getting it wrong. He was dead before the knowledge existed to do the calculation

But modern homeopaths have no excuse whatsoever for believing the impossible.

Hahnemann would have thought they were nuts, I suspect. He was too intelligent to believe that medicines that contain no medicine could be effective. In his words, “It cannot go on to infinity”.

Acknowledgement

I very grateful to ‘ Lindy’ for help in checking the references that are cited here, and for helpful discussions.