I have yet to hear one argument against the ALS icebucket challenge that isn’t either fundamentally flawed, or simply petty when put next to the giant sum of money that has been raised to help sufferers of one of the most brutal and relentless diseases that can befall a human being.

This post, however, is not about the absurdity (or hypocrisy) of criticising the challenge on the basis of clean water shortage in the third world, or the fact that the uncomfortable symptoms of “FB peer-pressure” tend to dissipate naturally over a short period of time, whereas ALS causes an inexorable disabling of all the body’s faculties until the sufferer can no longer breathe on their own, and results in death, always. No, this is about medical pseudoscience at its very, very worst. And I’ve seen it shared by some pretty sensible people, which has been disturbing. To those people:

Please be aware that most articles posted on social media that talk about health, disease or science, are BULLSHIT. A good rule of thumb is to type the author’s name into Google followed by the word ‘skeptic’. Then do the same with the word ‘rational’, ‘quack’ (or ‘quackery’), ‘debunked’ and ‘pseudoscience’. Repeat this process for the name of the website, and key words from in the article.

I was ‘inspired’ to write on the subject of ALS charlatanism by this profoundly misleading article, authored by conspiracy-mongering pseudowhistleblower and all-round crank Anthony Gucciardi. The article is first and foremost a libellous denigration of the ALSA. He couples this with a few references to some cherry-picked studies he either hasn’t read or doesn’t understand, which he uses for the purposes of implying, strongly, that ALS is a disease which can be easily prevented or reversed through diet. Hint: it isn’t. The most flabbergasting aspect of Gucciardi’s article is how outrageously, wantonly, and shamelessly lazy (or calculatedly deceitful?) a mere couple of clicks around the ALSA’s website reveals him to have been.

I’ll be focusing mostly on what Gucciardi has actually written, though I will broaden the discussion at times. I would also point out that numerous members of the ‘alternative’ crowd, such as Joseph Mercola, have posted articles or videos encouraging members of the public not to donate to the ALSA – the whole incestuous ‘alterweb’ is buzzing with them. Take your pick – they are mostly variations on one quack theme: don’t give money to ALS charities; buy our supplements instead.

Disclaimer

What follows is a long article, and no doubt there will be sections that for some readers will represent a case of tl;dr. That’s fine. I just wanted to be as thorough as possible, because that’s what I think this topic deserves. So I’ve said everything I think needed to be said. I could have summed the whole thing up like this: “Gucciardi and his cronies are spreading misinformation about the charity they are publicly slamming, and if you want to verify that for yourself, all you need to do is to do is visit the ALS Association’s website. None of the studies he cites say what he thinks they say and, in any case, knowing a few risk factors for a complex disease doesn’t mean the disease is preventable or reversible. Furthermore, what is he doing citing scientific studies when they come from institutions that are just as (inevitably) tied up with the pharmaceutical industry as the ALS Association is? His article and the principles upon which it is based are a mess of double standards and illogic. He’s out of his depth and I think he knows it. Next!” But if I did that, I’d only end up having to write a patchwork version of my essay in the comments thread anyway. Instead, I will now be able to refer commenters to relevant sections, if they respond in disagreement, having not read them.

Who is Anthony Gucciardi?

To give you a better idea of the kind of person we’re talking about here — and I highly recommend following some of these links if you are new to medical pseudoscience — Gucciardi is a frequent guest on Infowars (a show hosted by Alex Jones, who is quite possibly the most deluded person in the world), a writer for Natural News (known to be the Internet’s #1 anti-science website), and a specialist in grossly misrepresenting scientific studies, often with the aid of outright lies. Here is a crystal-clear demonstration of him wilfully and grossly misrepresenting a fluoride study; here is a discussion about him and Mike Adams proudly exhibiting their failure to grasp basic scientific concepts (while ‘critiquing’ a scientific paper); here is documentation of him spreading falsehoods about vaccines; and here is a report of lies he’s told about five further topics. He is the founder of naturalsociety.com and storyleak.com, where he publishes re-cycled myths and long-debunked conspiracy theories dressed up as STUNNING NEW INFO.

Who is Sayer Ji?

In his article, Gucciardi references this almost identical blog post on the ALS icebucket challenge, by Sayer Ji, founder of GreenMedInfo, another hive of quackery. Just like Natural News, GMI deals in regurgitated anti-vaccine myths, dangerous misinformation about chronic diseases like diabetes, and all things anti-science and anti-medicine. In order to legitimise his career in cherry-picking, Sayer Ji labels objections to this abuse of the scientific literature as ‘scientism’. He buys into just about every conspiracy theory on the market, compiling and proudly presenting them as “conspiracy factualities.” He denounces evidence-based medicine, calling it nothing more than a “coin’s flip of certainty”, something for which he was rightly ridiculed by science blogger and surgical oncologist David Gorski.

Though it includes much more extensive (professional-standard!) cherry-picking, Sayer Ji’s article doesn’t add anything qualitative to Gucciardi’s, so my focus will remain mostly on that. However, this is arbitrary, resulting from the fact that I discovered Gucciardi’s first. I will comment on Sayer Ji’s misinformation campaign at the end, because I think it will be doing more damage than Gucciardi’s, and is arguably a couple of orders of magnitude more disgraceful.

To any scientifically-literate person, especially anybody with an understanding of complex disease (on which more later), it is plain as day that Gucciardi’s and Ji’s take on ALS stems from ignorance and delusion. But I dread to think how many well-meaning people without the necessary background knowledge to see this will have been roped in by their sleazy impersonations of people who know what the hell they’re talking about.

Rebutting attacks against the ALS Association

The opening section of Gucciardi’s article revolves around a pie chart published by the ALSA on their website, displaying the various ways in which their finances were allocated, and in what proportions, over the financial year ending January 2014.

Gucciardi introduces his pseudo-exposé with the heading:

“$95 Million Later: Only 27% Of Donations Actually Help ‘Research The Cure’”

But of course the pie chart tells us nothing about how the ice bucket donations will be used. It tells us how the ALSA apportioned their funds last year, when they had about $25 million to work with. There is no reason to expect the slices of this pie to increase proportionately with respect to one another in the wake of a sudden influx of over $100 million. And besides, there is a button you can press when you make your donation, if you want 100% of it to go to research. The unctuous preface for the paragraph headed by this baseless claim reads, “But don’t just take my word for it”. Well, thanks, Anthony, we won’t.

Readers should be aware that the ALSA made a correction to this pie chart. The one shown here is correct.

Since ALS is currently incurable (and care for a patient can cost upwards of $200K per year), one of the single most important resources for patients and their families is access to support, which the ALSA calls patient and community services. In his piece, Gucciardi mentions twice that even more important than supporting local communities “the spread of information.” What, you mean, like, public and professional education, Anthony? You know, that thing represented by the largest slice of the pie you just shat all over?

Just so we’re really clear on this, there absolutely is no grand secret being revealed here. If he had bothered to look, Gucciardi would have seen that the official remit of the ALSA’s charitable work is three-pronged, entailing research, patient services, and education.

So, this leaves only two slices that don’t represent one of the ALS Association’s core activities, as declared in their manifesto. These core activities, incredibly, cost money. (I know, right?) There’s a name for the systematic gathering of money. It’s called fundraising. The more you publicise your cause, the more funds you’re likely to raise. Being a businessman, Anthony, presumably you are aware of the costs associated with publicity. One slice left.

Where Gucciardi really goes to town is with administration costs, particularly via his having copied and pasted the salary figures for the ALS Association’s executives, including — gasp! — the CEO’s salary of $339,475. He has this to say on the matter:

“And let’s be clear: I am a huge proponent of prosperity and business expansion. When it comes to private business and commerce, it benefits us all to see growing numbers among a company and its members. This, however, is not the case for a ‘non-profit’ organization that is based around the concept of ‘searching for the cure’ and ‘funding research’ as its primary goal. Especially when this organization is being funded with close to 100 million dollars through a viral social media campaign in which it appears no one truly took the time to investigate the very company they are shoveling their assets into.” [Emphasis his]

Congratulations, Anthony, on finding such a convenient way to cover your back: It’s perfectly virtuous to want to earn a large salary, but if you accept one and play an instrumental role in the running of an organisation that works directly to improve the lives of other people, then you become immoral. Duh!

Good logic right there.

I fail to see how it could be the case that “when it comes to private business and commerce, it benefits us all to see growing numbers among a company and its members“, but when it comes to the non-profit sector, it doesn’t. I’d say that the downstream effects of charity CEOs having substantial financial incentives are probably much more beneficial “to us all” than are the consequences of private business CEOs having them. Gucciardi seems to be expressing a feeling, apparently shared by many, that someone who heads a charitable organisation ought to have no desire to earn a good living – that there is something hypocritical about accepting a good wage if you’re receiving that wage from the non-profit sector. Personally, I’d say that someone who earns a six-figure salary heading a furniture (or supplement) company deserves fewer ethical brownie-points than someone earning the same amount of money via activities that directly help people with a crippling disease. As devil’s advocate, I’d turn the tables and say of those working in the profit sector that not only are they not working to improve the lives of others, but they’re also accepting a large wage! Shocking!

If you object to large salaries per se, given how many people in the world live in poverty, then I’d suggest that your campaigning efforts would be better directed towards people who have hundreds of billions of dollars squirreled away in vaults, doing nothing; you know, that 1% of people who control half of the world’s ‘wealth’, in the form of little bits of paper. If you’re coming at this from a Marxist perspective (which Gucciardi clearly isn’t, since he expressly doesn’t object to “growing numbers” in the profit sector) then forgive me but you seem to be forsaking one of your own core principles: what $300K a year can buy you under our current system is within what the world could theoretically provide for every person living in it. If you’re attacking this individual CEO, you’re doing it because the opportunity to do so has been served up for you on a plate; not because you’re an activist. Every minute you spend attacking this person is a minute you could have spent campaigning against real corporate juggernauts. It’s a simple case of lazy scapegoating.

Besides, the moral status of this one person is not the relevant issue. We have to think of this from the perspective of the ALSA, which has an official moral duty to perform as well as it can. To make a large-scale charity as innovative and successful as possible, you need a leader with maximum experience, business know-how, connections, and an intimate knowledge of the sector’s infrastructure and dynamics, working full-time. In other words, you need a CEO who can command a high salary. One could just as well argue that it would be immoral for the ALSA to scrimp on such an integral component of their organisation. The ALSA do not set salary standards – it’s not their fault that high-level CEOs are in a high wage-bracket.

In a document addressing the various accusations levied against them by misguided characters from the ‘alternative’ crowd, the ALS Association writes:

The salaries of our executive staff are in line with the job markets where they are located—and in line with those of other national charities. Salary review is part of the accreditation process for the watch dogs mentioned above and is a requirement of the National Health Council (NHC), of which we are a member. In fact, The ALS Association is the only ALS charity that has qualified for membership. Read what this journalist has to say about The ALS Association’s executive salaries: “they are all well within the range of nonprofit salaries; the compensation for ALSA’s CEO compares favorably with that of his peers, including some who run low-performing nonprofits.” [Emphasis my own.]

As his final word on the way in which the ALS Association spends its funds, Gucciardi references Sayer Ji, who he says

“points out in his breakdown of the ice bucket phenomenon [that] even the smaller portions spent on ‘research’ for ALS are actually going towards pharmaceutical interventions and the pharmaceutical industry at large.” [Emphasis my own]

So, after all that fuss about not enough money going towards research, Gucciardi reveals that he doesn’t support research anyway. Sigh.

In any case, this statement is absolute bullshit. There is no evidence that the ALSA give money to “the pharmaceutical industry at large”, much less that the money they spend goes there rather than on research.

The ALSA’s research and its links to ‘big pharma’

One of the things the ALSA do is award grants to independent scientists who can demonstrate strong scientific merit and present promising research proposals, through their Investigator-Initiated Research Grant Program. I had a look through the grants that the ALSA have awarded to past and ongoing studies as part of this initiative. Gucciardi either didn’t bother, or is simply a liar – evidenced by the fact that:

Nearly all of them have been awarded to researchers looking at care protocol and equipment. Things like how to measure respiratory impairment and assist ventilation in the best way, how best to support patients nutritionally, keep their muscles moving, support their families, and generally maximise their quality of life. In other words, NOT pharmacological interventions. Of the eighteen grants awarded over the last several years, as far as I could tell, only two have been for pharmacological studies. One of these looked at whether the substance used in botox treatments could help prevent patients drooling, and the other (prepare yourself for some truly savage irony) was on…

*drumroll*

THC.

Amazing, isn’t it? The alternative crowd devote all that time to criticising “the medical industry” for not funding research on cannabinoids, because “pharma companies aren’t interested in something they can’t profit from it”. And then they’re so blinkered in their approach, so damned lazy, and so lacking in even the measliest morsel of integrity that they end up actively dissuading people from supporting one of the very few institutions that actually happens to have done so. One of Gucciardi’s other ‘articles’ is entitled Cannabis Treatment Threatens Deadly Painkiller Industry. The THC study that the ALSA funded through their grant scheme was on whether it could reduce painful cramps in ALS sufferers. This calls for a *facepalm*. Ouch, that one’s going to bruise.

The ALSA are also currently recruiting for a clinical trial they’ve funded to ascertain whether THC helps with spasticity. I found it using this search tool (via the ALSA’s website), which can pull up a list of all the clinical trials they’ve ever funded. Again, only a small fraction of these studies are on pharmacological interventions, because, unfortunately, our understanding of ALS is still not good enough for there to be lots of potential drugs discovered and ready to test. Part of the reason for this is that ALS is a rare disease, so it’s not an attractive research area for pharmaceutical companies. Which is precisely why charities like the ALSA end up contributing towards the cost of clinical trials on the very few drugs that are worth investigating.

It is true that if a new drug were shown to be effective in treating ALS, pharmaceutical companies would manufacture it, and benefit (though on a relatively small scale). It is also true that pharmaceutical companies certainly deserve the (intelligent) criticism they have received (though things really are improving). However, all too often, a vague, hand-waving mention of “big pharma” is used as an opportunity and justification to dismiss medicine all together, which is a terrible mistake.

The two main prongs of argument against pharmaceutical companies surround 1) transparency and 2) profiteering. Regarding transparency, pharma studies that have been part-funded by an independent organisation like ALSA should garner less, not more, suspicion than those which are purely industry-funded. And with respect to profiteering, if you don’t like the fact that medicine is tied up with this, then you need to be campaigning against our political system in the large – against the privatisation of medicine, and against capitalism, at least in its current form. Campaigning against pharmaceuticals per se, like the alt-med crowd do, is bad reasoning at best, and outright hypocrisy at worst, namely when it concludes — as it usually does — with “so, buy our health products instead!”

Drug discovery requires large numbers of scientists, doing difficult science, working full-time jobs. Pharma companies do have enormous incomes, but they also have enormous expenses. Getting a drug approved costs about a billion dollars. (Even if every penny of the icebucket challenge’s $100 million were handed over to big pharma, it would represent but a teeny drop in this ocean.)

Many of the arguments used by pro-alt-med bloggers and commenters break down when you consider countries that offer universal healthcare. But wherever you’re from, and whatever you feel about the privatisation of medicine, or capitalism in general, pharmaceutical companies are currently the only organisations that are able to properly test and manufacture drugs, and drugs are what ALS sufferers desperately need because unfortunately…

ALS Cannot be Cured ‘Naturally’

We should start this section with a brief consideration of complex diseases, which can be contrasted with ‘simple’ Mendelian disorders with clear inheritance patterns like Huntington’s disease, that result from a single mutation with powerful a effect whereby if you have the gene, you will get the disease.

Heart disease is an archetypal example of a complex disease. It is weakly associated with heaps of common genes, as well as various environmental risk factors that seem, statistically-speaking, to slightly increase a person’s risk of becoming a sufferer. Like other complex diseases (such as arthritis, most cancers, and ALS), it doesn’t usually have clear, straight-forward inheritance patterns, though it does often run in families.

However, as with cancer, where some rare genes confer a greatly increased — or even 100% — risk of developing disease, there are some rare genes which are very strongly associated with ALS and, like all genes, they are heritable. Inherited forms of ALS are called ‘familial ALS’, and account for about 10% of all ALS cases. Roughly half of these cases can be explained by around 17 known genes. (Some are discussed by the ALSA on their website, and a comprehensive database of all genes which have been found to be linked to ALS can be found here.)

To give an example, depending on which population you look at, between 20% and 40% of familial ALS cases are caused by inherited mutations (in this case, repetitions) of a gene called C9ORF72. (An inherited mutation is often just called ‘a gene’, which can be confusing.) This gene was discovered recently through studies conducted by two different research groups, independently of each other. Both were funded by the ALS Association.

Importantly, however, as this twin study, and this (free) paper on ALS as a genetic disease point out, the distinction between spontaneous and familial ALS is largely artificial. This starts to make sense if you think of ALS-causing genes as sitting on a continuum of effect-size, or ‘penetrance‘. At one end are genes with complete penetrance, which are certain to manifest in ALS, like the C9ORF72 repeat expansion discussed above. As you move along the spectrum, certainty becomes likeliness, which gradually peters out, with associations becoming ever weaker. (Also, de novo mutations — occurring spontaneously during the very early stages of development, rather than being inherited from a parent — can produce the same effects as inherited ones.)

The evidence we have points towards a ‘liability threshold’ model of ALS, under which disease manifests only once a critical tipping point has been reached. Everyone is born with a pre-determined genetic liability and, over time, this liability can be modulated by the environment. The fewer environmental risk factors you are exposed to, the less likely you are to reach the tipping point, provided your initial genetic liability, or ‘genetic load’ isn’t so high in the first place as to completely flood the effects of environmental influences.

There is an enormous variety of ways in which one might reach the threshold. The ‘easiest’ way is to carry a gene from right at the top end of the effect-size spectrum. But you could also do it by carrying lots of genes from somewhere in the second quartile of the continuum, and then exposing yourself to some environmental risk factors. Or you could do it by carrying a very, very large number of genes right from the low end of the spectrum.

And here’s the thing. It is much, much, much easier to identify genes that greatly increase disease liability, compared to genes that only increase it a little bit. These big bruisers ‘stand out’ when you compare large enough samples of cases (ALS patients) with samples of controls (people without the disease). But the potentially huge number of mutations that ever-so-slightly increase ALS risk sink into the background and are virtually impossible to distinguish from random ‘noise’, since they are each found almost just as often in healthy controls as they are in ALS cases – it is their collective presence in a person’s genome that causes disease. However, these low-penetrance genes are just as heritable as genes with high or complete penetrance.

Genetic material is shuffled and split in half during reproduction. In the case of one, fully penetrant gene that is sufficient to cause ALS without the ‘help’ of others, or of environmental factors, since a sperm or egg either ends up with this gene or not, the resulting person is either destined to develop the disease, or not, manifesting in a classic Mendelian inheritance pattern (autosomal dominant, for C9ORF72 mutations). When we’re talking about a large number of low-penetrance genes, however, a sperm or egg could, by chance, end up with anything from 0% to 100% of those genes (50% on average). This can explain the fact that we often see striking familial clustering of ALS cases, despite the fact that none of the 17 big genetic players are contained within their DNA – something that is enhanced by the fact that people from the same families tend to have more shared environmental influences than two people picked at random.

You could also inherit ‘sporadic’ ALS in the absence of any family history, if the combination of genes you inherit from your parents happens to place you at or beyond that threshold, even though neither of them were particularly close to it themselves.

To make things even more unpredictable and hard to shed light on, genes modulate other genes. And they often act differently depending on which other genes they end up with. Different versions of the same gene can also interact differently with the same environment and, conversely, a single gene variant can act differently in different environments. It is feasible that the same environmental factor could increase or decrease your risk of ALS, depending on what your genome looked like.

All this ferocious complexity is part of the reason why studies looking at environmental risk factors for ALS have been inconsistent in their results, with some finding associations, and others failing to reproduce these. It is also immensely difficult to tease out causation in a world teeming with correlation, or to eliminate the numerous forms of bias which can so easily creep into observational studies (as opposed to randomised, controlled trials). Finally, publication bias skews the picture too. Some associations that have been flagged up will turn out to be spurious; others will turn out to be explained by other, unseen variables. Others won’t be found, even though they really do exist. Please keep this in mind as you read the rest of this article.

Gucciardi’s cherry-picking trip

Starts with:

“Numerous studies available through the United States National Library of Medicine have demonstrated the natural preventative effects of key substances…

Vitamin E: Shown by research to exhibit a whopping 50-60% decreased risk of developing ALS when taken alongside powerful polyunsaturated fatty acids.”

The vitamin E research Gucciardi is referring to was headed by Jan H. Veldink, who is based at the University Medical Centre, Utrecht. The UMCU is one of the partners of Euro-MOTOR: European multidisciplinary ALS network identification to cure motor neurone degeneration. Also based there are Bryan J. Traynor, who headed the ALSA-funded Netherlands study that identified the role of C9ORF72 in familial ALS, and Leonard H. van den Berg, who was awarded a $25,000 research grant by the ALSA. After telling people to shun the ALSA because of its connections to the pharmaceutical industry, Gucciardi shows that he is nonetheless happy to cite studies that are connected to the ALSA (and, of course, to the pharmaceutical industry too, in similar ways to the ALSA), so long as he reckons they can slot nicely into his ideology.

Irrespective of the quality of the vitamin E/ALS research he cites, a reduced risk does not equate to a preventative, and in any case applies at a population level, though as we’ve seen, some individuals are born with a 100% risk of developing ALS, regardless of environment. What about them? Don’t they deserve access to the drugs that might be discovered through pharmacological research?

Critically evaluating individual studies was not what I set out to do here. I mentioned earlier that there are various inherent weaknesses of observational studies, and I would have left it at that, but since this study is being flaunted so widely (it features on GreenMedInfo too, and therefore on scores of other popular alternative/conspiracy websites), I couldn’t help but feel that a brief critique was warranted.

Not that the authors claim it is, but we should be clear that this study is not a randomised trial. The researchers didn’t give one group of people vitamin E and polyunsaturates and one group a placebo and then wait to see whether either group had higher rates of ALS. They sent questionnaires to patients in clinics, both ALS and healthy, asking them to “recall their dietary habits during the period 1 year before the onset of muscle weakness or bulbar signs”. Then, amongst 15 micronutrients, they looked for associations with ALS. The authors apparently did not apply a correction for multiple comparisons, which is a serious oversight, and it makes the study seem like something of a fishing expedition, since the more things you compare, the more likely you are to get a ‘significant’ result, just by chance. This is called a ‘false discovery’. One would expect the false discovery rate (FDR) to be pretty high with this many comparisons.