Why the movie ‘Don Jon’ has nothing to do with porn (also, spoiler alert)…

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(… and why the image above is VERY much porn)

There are only a few things he cares about: his body, his car, his place, his church, his bros, his girls and his porn. This guy is the definition of a narcissist. He’s in his mid-20’s, still goes out to clubs, has a job as a bar-tender, no permanent relationship. He clearly doesn’t care about anyone. But, at the same time he sells the “cool bachelor” image very well. Of course, who doesn’t want to be like him: fit, popular, lots of girls. Except of course he admits that he likes porn more than sex. Porn lets his imagination do whatever it wants, real girls don’t – that’s the definition of narcissism.

But this movie isn’t about Don Jon because he admits that he has a problem. He says it, right at the beginning of the movie. Yes he has an addiction. But he realizes it. He asks for weekly forgiveness for it. What you thought adding church and porn in the same movie was a coincidence?

This movie is not about porn at all. It is about everyone else in the movie. It’s about narcissism and addiction.

Notice how the father is oblivious to the world while watching TV. Notice how the mother is insistent on Jon getting a girl and having kids. Notice how Barbara is looking for a “perfect man”.

This movie is not at all about porn. The porn is just a distracter so that the movie can sell you a whole other kind of “porn”.

It’s a movie about narcissists for narcissists because some will criticize how shallow the characters were, how shallow the plot was, how repetitive it all was. But that’s the whole point. The characters are shallow because they don’t care about anything or anyone.

Notice how the father couldn’t care about what happens to his son. There wasn’t a single time when he asks him how his job is, how his night-school course is. He just lives in his own fantasy of TV-sports [addiction]. He snaps out of it to comment on the hot girlfriend but only so that he can comment on how Don Jon “scored” on this one and how his wife used to look exactly like that.

The mother is pretty much the same way. She is focused on Don Jon having kids, so that she can have grandkids. She is focused on the image of looking like a grandmother and therefore needing HIM to produce grandchildren to support this image [addiction]. She also never cares about how his life goes. She is so focused on her fantasy that she can’t even notice how his father is macking on the hot girlfriend. She can’t even snap out of it when he finally tells them that he broke up with Barbara.

The girlfriend, Barbara, is so clearly a narcissist that I don’t think I need to explain it. Her fantasy is finding that perfect man who will live up to her every dream [addiction]. This is exactly why she will never find one. But the point is exactly NOT to find one. A narcissist can never find what she wants because she is incapable of loving any one thing. The point is to live in a fantasy – that is the addition.

There are some interesting characters placed in the movie, specifically – the sister and Don Jon’s friend. They’re not real characters. They’re just there to demonstrate a point.

The sister initially comes across as a typical, always-on-the-Smartphone [addiction], narcissistic teenager. But she drops one line in the whole movie and that line is just to make it painfully obvious, for those that still haven’t figured it out – THIS MOVIE IS NOT ABOUT PORN.

Don Jon’s friend exists just to make a contrast to a non-narcissistic character. Think about it, he is the only one that makes an effort to come and find out how Don Jon is doing. He supports him and convinces him to go back to school. He’s probably the ONLY non-narcissistic character in this whole movie. But wait, he might not be a narcissist, but your fantasy certainly is. Because your fantasy needs this (otherwise) barely involved stranger to randomly come and save Don Jon. Save him from the narcissistic injury – of course the girlfriend was a bitch for dumping him!

But what about Esther (Julianne Moore)? She’s not narcissistic at all. Hold on, she’s not even a character!

But what about her back-story? Well, for one, she’s obviously the therapist. For a random lady taking a night-class with her back-story she is surprisingly insightful. She is also stubbornly interested in solving Don Jon’s addiction to porn, pretty much the moment she catches him watching it in class. Oh yeah, she also smokes pot [addiction].

Finally there’s another addiction hidden in the plot – the idea that some life changing event is all that’s needed to make your life better. Call this the “American Dream” if you want or believing that you have a special place in the universe. All of this feeds into the plot. The church places people and Christians in a special place in the universe. The movie places the viewer in a special place. Specifically, the viewer is placed in the seat of the priest to judge Don Jon. You’re almost forced to guess how many Hail Mary’s Don Jon will have to say to atone for his “sins”.

The movie makes a special contrast between porn love and non-porn love. It builds the characters especially grey and shallow, so that you cannot sympathize with any of them. None of them have anything special to offer. But this is perfect for a narcissistic audience because then you don’t need to make a decision on who is a protagonist or antagonist – every opinion is valid, right? But surprisingly, the movie still pulls off a fairy-tale happy ending. There you go; you’ve been sold another “porn” piece.

You’ve been again sold a fantasy that any problem can be solved over-night with some magical, wise, intervention. That some external, all-knowing, insightful, source can be the solution to your problems. All you need to do is find the love of your life and your porn-addiction will go away right? All you need is a wise, usually silent little sister, who can drop the right line at the right time and solve your family problems, right? THAT is the real porn that is sold to you at the end of the movie. All the stuff at the beginning – just plot building.

Since it’s not obvious how any of this has to do with science, let me tell you why it does. This last part, the part the movie REALLY sells to the viewers is exactly why all the “integrative medicine” is proliferating. People are addicted to many things in many forms. If you think that when you use a homeopathic product you are any better than Don Jon, think again. With the advent of Dr. Google and patient-centered care, healthcare stopped feeding into people’s narcissistic addiction to magical solutions that require no effort on their part. Unfortunately “integrative medicine” is still selling this addiction. That is exactly what this movie is trying to tell you – wake up, you’re being sold an addiction. You will buy it, even if they tell you right on the label – “this is not real”.

Society – 0, Joseph Gordon-Levitt - 1

Google “breasts” to find good science

Why can't I find that prolactin pathway in Google Images?

Why can’t I find that prolactin pathway?

Recently I was reflecting on the utility of fighting un-scientific and often outright quack medicine. ScienceBaseMedicine does a great job of explaining why all the un-scientific and unproven treatments out there don’t work. But sometimes it feels like an analogy of telling kids not to smoke or do drugs. The ones already convinced won’t do it, the ones that already do it will find reasons not to listen. The real concern is the naive audience. This third group of kids were blissfully ignorant of all the addicting stuff out there, and with some luck, they might have remained so. Yes, I hear you, there’s hardly a kid out there who is truly ignorant of cigarettes, marijuana and other drugs. But there’s a large group that simply don’t care enough to do it. In high-school senior year (grade 12) about 13% of students smoke, about 25% smoke marijuana. [Disclaimer: maybe a higher percentage try smoking/drugs throughout high-school and there is certainly under-reporting happening, but on the same note, the two groups are not mutually exclusive either].

So, say I’m Jenny McCarthy and I think vaccines are the spawn of devil. I go on air and just shout down any reason and rationality, drag my autistic child into it, make the bleeding hearts sympathize with me.

What happens then? Something like ScienceBasedMedicine can come along and try to prove that I’m wrong. Every doctor and scientist in the world can cite data and provide evidence but the Joe Smith in the crowd will just look at them blankly and say “but her child is autistic”. Done. Argument over. You lost.

Not only that, but increasing publications online bring up more keyword searches on things like homeopathy, touch therapy, energy therapy and what-have-you. In other words – any publicity is good publicity. Google doesn’t generate search results based on good vs. bad evidence. Google generates searches based on key words. (Yup, I just did it too).

So when you type “touch therapy” into Google, you get nice relaxing pictures. Most of the websites that come up promote it. And even skepdic.com [the skeptic dictionary] says “Therapeutic touch (TT) is a type of energy medicine whereby the therapist moves his or her hands over the patient’s “energy field,” allegedly directing the flow of chi or prana so the patient can heal.” These are the first thing that people see in the definition. What, you thought that you put “allegedly” in there and now people will become skeptical? What if you already believe in energy fields? Then you just copy and paste the first line of the definition from skepdic.com and there you have it, skepdic.com just effectively defined (and thus supported) touch therapy.

“But, that’s not all that skepdic.com says!”

Nope, but who cares? Scientists and doctors fighting the anti-vaccine movement also say a lot of stuff. But people only hear “autism” like it’s some kind of satanic possession to be exorcised. Bring in the exorcist [ahem, I mean, Jenny McCarthy]!

When you type in “breasts” into Google images you don’t expect to see anatomic diagrams and endocrine glands do you? Remove the filters and try it. You know what, don’t remove the filter. You still get porn. Don’t argue with me about the definition of porn – if the image isn’t there for surgeons and physicians, it’s porn.

So get this, your kid goes to school and he gets told that smoking is bad because it’ll cause cancer, so maybe your kid is smart and won’t smoke. He gets told that drugs are bad, but not very specifically, so very few kids will do crack cocaine but (and thus the above statistics) but more will smoke pot than cigarettes.

Now, go visit their science class. What’s the last time the biology or chemistry teacher made a link between medicine (applied science) and basic chemistry? So now you expect this kid to graduate and make the link himself?

“My kid is smart, he got 90% in Chemistry“. You’re missing the point. He didn’t get 90% in Applied Pharmacology did he? It’ll be another 12 years until he can get a PhD in that. But before he does, Google will make the link for him. And Google doesn’t even have a filter for “bad science”.

Now, obviously we can never get rid of all the crazies. There may still be people out there that believe that the Earth is flat, but just because they do, doesn’t mean we’re duty bound to give their voice value and send expeditions to look for the edges of the world. So if we don’t do that, why do we keep on commissioning publicly funded trials and laboratories to test completely unscientific practices in health care?

The point that I’m trying to make is that, while writing about how un-scientific medicine is wrong is important, it is also important to expand our scope to teach people, and especially children about science. And for god’s sakes, please make the links for them. Don’t leave Google to teach the rest of the chemistry lesson to your child.

P.S. I’m hoping that Google will associate “satanic”, “possessed” and “Jenny McCarthy” and the Catholic Church will exorcise her.

Bad science, bad reporting and will somebody think of the children!

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We all know that smoking is bad, and marijuana smoking is bad, and alcohol is bad. And obviously obesity is bad and having a sedentary life style is bad. And eating your fruits and veggies is good. And we’re mulling the same, non-actionable information over and over. In the Globe and Mail and on CTV and on the Canadian Healthcare Network and of course the Huffington Post.

“It shows that over the four years of high school, the number of smokers went up 170 per cent, binge drinking jumped 167 per cent and marijuana use rose by 124 per cent.” … Also, they got taller [shocker]!

Is this research really adding anything to what we already know?

Here’s the ACTUAL graph from the article (something the Globe and Mail won’t show you):

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1. The study does not and cannot show that the number of anything went up, or down or make any claims about the rate of change of anything. It’s a cross-sectional study for god’s sake! This graph only shows what the difference is between the different grades. It’s entirely possible that we’re doing a good job and those Grade 9 kids won’t smoke any more than they already do.

In order for them to show that the numbers “went up” they should have done a cohort study, where they followed Grade 9 students throughout highschool and found that more smoked by the end. But they didn’t do that.

2. What’s up with the relative percent reporting?

What they should have done is say 5 out of 100 Grade 9 students smoke, in comparison to 13 of 100 in Grade 12 [1]. Same goes for all the other “relative increases”.

Now, I want 0% of people to smoke obviously, because it’s bad for you. Causes respiratory diseases, cancers and all kinds of other nasty things (like impotence in males). But the question is, are we doing a good job of decreasing the number of smokers?

The Health Canada Youth Smoking Survey (incidentally done between the same years 2010-2011 as the study in question) reports 10% of Grade 10-12 students smoked (similar to this study, nothing new there) [2]. Here’s the caveat, the same survey showed that 13% of Grade 10-12 students smoked between 2008-2009 [2].

If we reported these numbers in the same “relative” percentages we could say that between ’08-09 and ’10-11 there was a 23% decrease in smokers among high school students!

So while, it’s not perfect, but we’re improving pretty quickly. In fact, if we maintain this “23%” reduction every 3 years or so, in a decade we’ll have almost no smokers.

“But Pharmer, you can’t extrapolate numbers like that!”… why not? They do it in national publications!

3. Other things are more worrisome.

Absolute numbers are VERY important here. 13/100 – 5/100 = 8/100 extra smokers in Grade 12 vs. Grade 9 [1]. BUT marijuana, while having a lower relative percent difference (123% vs. 170%) actually looks something like this in absolute terms: 26/100 – 12/100 = 14/100 [1]. Although according to Health Canada, this was a decrease from 2008-09 as well [2].

So they make tobacco look like a big problem, but we’re doing pretty good at reducing that. Why such a absolute jump for marijuana? Are students switching from tobacco to marijuana? Are we sending conflicting public health messages? How do students perceive the risks of smoking, alcohol and drugs? Can a well designed argument flip students to the dark side? [3]

4. Alcohol use.

Same thing as with smoking. Relatively speaking the percentages went up but according to Health Canada, that’s actually a decrease compared to how many were binge drinking in 2008-09 (it actually went down from 33% on average to 39% on average) [2].

Also, “binge drinking” is defined as “5 or more drinks on a single occasions in the past 5 months” [1,2]. While this is fine as an operational definition for public health (and these kids shouldn’t be drinking anything anyway, because they are under the legal age), 5 drinks is hardly “binge drinking” in terms of the real world. It’s certainly “social” drinking but few people will be trashed after 5 drinks. It’s also bizarre to me that 2 drinks/day is OK according to Health Canada, but 5 drinks on one occasion every 5 months, and you’re a binge drinker?

5. I’m not against getting students to stop smoking/drinking/using drugs. I’m against bad science and bad reporting. Both this study and Health Canada reported similar statistics and these come from the same place – the School for Public Health at the University of Waterloo, so why are they painting a different picture? Is the message “we’re doing good, but we need to continue improving”? That’s fine, but why not conduct a well designed cohort study and actually track how many students will take up smoking/binge drinking/what-have-you?

How about adjusting for bias? The Health Canada website reports extremely overlapping ranges between the different grade levels [4].

6. It’s all political

Healthcare budgets are getting thin and everyone wants a piece of the pie. Obviously it’s more dramatic to report on increasing numbers than on the successes. The way forward should never be based on misrepresenting reality, after all such data manipulation gets pharmaceuticals withdrawn from the market (case-in-point Vioxx).

Just because getting students to quit smoking is a noble goal, doesn’t mean that white lies are OK. Stop publishing incomplete and poorly interpreted data in popular news outlets!

References

1. ALeatherdale ST, Rynard V. cross-sectional examination of modifiable risk factors for chronic disease among a nationally representative sample of youth: are Canadian students graduating high school with a failing grade for health? BMC Public Health. 2013 Jun 11;13(1):569. [Epub ahead of print]. http://www.biomedcentral.com/1471-2458/13/569/abstract

2. http://www.hc-sc.gc.ca/hc-ps/tobac-tabac/research-recherche/stat/_survey-sondage_2010-2011/result-eng.php

3. Anna V. Song, PhD, Holly E. R. Morrell, PhD, Jodi L. Cornell, MSW, MA, Malena E. Ramos, EdM, Michael Biehl, MA, Rhonda Y. Kropp, MPH, and Bonnie L. Halpern-Felsher, PhD. Perceptions of Smoking-Related Risks and Benefits as Predictors of Adolescent Smoking Initiation Am J Public Health. 2009 March; 99(3): 487–492. doi: 10.2105/AJPH.2008.137679 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661432/?report=classic

4. http://www.hc-sc.gc.ca/hc-ps/tobac-tabac/research-recherche/stat/_survey-sondage_2010-2011/table-eng.php#t1

Science Based-Evidence Ship (Replacing the EBM Pyramid)

It is enough to do a quick Google Images search for the words “evidence based medicine” and you get a whole bunch of pyramids (aside from other irrelevant stuff).

Of course, when looking at a pyramid you can get a sense that you can look at only the top 2 layers and disregard the rest. In fact, sometimes, you can even get a sense that you could simply discard the rest. Conceptually this makes sense when you look at something like a pyramid. Although the top layers build on the bottom layers, the layers appear largely independent.

In fact, the relationship is very bizarre. For example, if you place a meta-analysis at the top of a pyramid you can understand that you couldn’t have a meta-analysis without some clinical trials, such as randomized controlled trials (RCT). But a good meta analysis will usually critically appraise the studies included and strive to include only high quality RCTs. You can certainly include case-control and other cohort studies in a meta-analysis, but this mixing of studies would usually weaken it. It is also obvious that we cannot skip from basic science to a meta-analysis (because there would be no patient data to combine) [1].

Aside from this connection of clinical trials to a meta-analysis, it is quite unclear how other types of evidence in the EBM hierarchy of evidence are linked to each other. Is a case-control conducted to look for side effects of a drug linked to an RCT of the drug’s efficacy in any way? How does animal research fit in? How does basic, fundamental science, link to the top of the pyramid? Can we simply skip the “rungs” in the pyramid and hop directly from basic science to an RCT? And while the definition of EBM calls for the use of clinical experience and patient values, it is quite unclear how these interplay [2].

When you look at things like homeopathy it becomes clear, that they simply skip the basic science and jump straight into clinical trials. Sometimes they make a crude attempt at basic science but that is flawed and rarely makes the leap to construct higher levels of evidence [3,4].

There have also been proposals to utilized lower levels of evidence on the pyramid when higher levels are absent. This makes sense, but only for those treatments that have a solid scientific base. But what if there is no scientific base, what can we move down to? Once one can assure a solid scientific base, one can move on and think on a higher level of clinical trials and meta-analyses. This does not work for treatments that lack any background evidence and do not stand on a good base.

There are also proponents of the approach “if it’s stupid and it works, it’s not stupid”. In other words, if we took a homeopathic treatment and ran it through a whole bunch of clinical trials and got good results, we could then accept it as valid. Never mind the fact that we haven’t the slightest clue about how it works. The end justifies the means? I think not. The scary thing is that it’s already happening – we are chasing our own shadow. Every time the results are no better than placebo and yet every time we see a new shadow we chase it again, expecting different results.

“Insanity: doing the same thing over and over and expecting different results” [5]

Looking back at things like mathematics and physics where you are always urged to “show your solution” it becomes clear that simply guessing the answer is not a good approach. It’s not a good approach because you don’t really understand what has been done and quite possibly could not repeat the process. Since EBM stands firmly on frequentist statistics (hence the meta-analysis being the king of the pyramid) it implies that we need to be able to replicate every step in the process of evidence building. Not just repeat the experiment, but repeat every step. A treatment that was pulled out of the ether however can only be expected to work on one premise – blind luck. We could not hope to improve it or refine it. Imagine if the Wright brothers, instead of building an airplane, found an already built model. They could have then flown it and shown that it flies, but since they didn’t build it, they would have had no idea how it works. Without this knowledge of inner workings we’d still be toying around with flimsy cardboard planes.

This is where the pure EBM-ists rush in and criticize that seemingly “scientific” theories have failed in practice. They are of course right in pointing out that certain theories haven’t panned out in practice. Unfortunately they are victims to the “science god complex”. They assume that if things are based on basic science, then they must be 100% true. Perhaps there’s some misconception and disillusionment in science. Perhaps an expectation that science must always produce amazing positive results.

Unfortunately, by driving this divide between science and clinical testing, EBM opens up to pseudoscience. Both EBM and pseudoscience can say “since basic science has been shown to be false before, we should not rely on it”. But without basic science, clinical research would have nothing to direct, it would be based on blind prodding and poking with occasional success in RCTs (if you’re blindly stumbling around, blind luck can occasionally still give good results).

I would like to propose a different conceptual structure for viewing evidence in health care. This structure would have to include a base without which the entire structure collapses. The base would include all the basic science, animal research and essentially any research required to validate the reality of a drug. On top of this base we can build the levels of evidence proposed by EBM in essentially the same way as they are in the pyramid. The point is that without the base, the entire structure collapses.

Here is what I would like to propose:

SBM Structure

(Click to enlarge)

Unlike the EBM pyramid this structure makes basic and clinical sciences connected but interdependent.

1) The ship: it is the foundation consisting of physics, chemistry, biology, physiology, biochemistry, animal research, etc. Without basic science everything else drowns.

2) The sails: these are clinical sciences (roughly in the same order as the EBM pyramid puts them). Without clinical studies and clinical practice basic science on its own is immobile. It stagnates, generating knowledge without ever applying it. Without clinical science, basic science cannot be moved and directed.

Expert opinion and clinician experience can also direct science, but since they only make up part of the directing force, they would be insufficient on their own. I also placed retrospective/case-control studies on the same level as RCTs because they often study fundamentally different things. For example, RCTs are suitable for efficacy studies and can never be employed for safety studies.

This then is the interdependency of basic science and clinical science. It is not that either one is subservient to the other. Notice also the “good quality” prefix assigned to all the clinical studies. That is because “low quality” clinical studies can be rejected based on the internal validity flaws. Low quality studies do not contribute anything. They are like ripped sails, the only thing that can be concluded from them is that they should be replaced (i.e. conducted with a higher quality).

References

1. CEBM. March 2009. Levels of Evidence. http://www.cebm.net/?O=1025

2. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. BMJ. 1996 Jan 13;312(7023):71-2.

3. http://sciencepharmer.wordpress.com/2013/06/06/homeopathy-or-how-to-misapply-evidence-based-medicine-part-2/

4. http://sciencepharmer.wordpress.com/2013/06/03/homeopathy-or-how-to-misapply-evidence-based-medicine-part-1/

5. http://en.wikiquote.org/wiki/Albert_Einstein

Evidence Based Medicine and Prior Plausibility

unicorn dust

Want to “Randomize, Double-Blind, Control” this?

 

In my last post I mentioned that prior plausibility is important. I’d like to touch here on what prior plausibility means.

If basic science (the principles of which are based on physics and chemistry phenomena and have been proven beyond reasonable doubt) states that the likelihood of something being true is close to zero, it does not matter what clinical studies can show [1]. In fact, if further clinical studies show a non-null outcome of a treatment which contradicts basics laws of physics and chemistry, we must suspect something unwholesome happening. Furthermore, conducting clinical trials or meta-analyses may be a waste of (already) thin healthcare resources, or be downright dangerous [1].

This may be counter-intuitive for those who have been heavily indoctrinated by evidence based medicine (EBM). It’s counter-intuitive because EBM states that you may make conclusions based on the outcomes of one publication (be it a randomized controlled trial or a meta-analysis). While EBM principles allow you to judge about the internal validity of one study (how well was the study designed), they say precious little about how you can incorporate the results and conclusions of a study into practice (which is what we care about at the end of the day).

By relegating all evidence except clinical trials, RCTs and meta-analyses so low on the ladder that one may simply altogether ignore it evidence based medicine opens itself to exploitation by those looking for pseudo-scientific ways to promote their products/work.

Now, I am not arguing that EBM in itself is flawed. It is not. But it can only be applied in its pure form to those studies which have irrefutable underlying scientific evidence.

As biased as pharmaceutical companies are made out to be, their products are largely based on a solid base of scientific work. Usually a drug is tested in-vitro. The drug is then tested in animals. Only after these two steps which eliminate a good 95% or more of drug candidates does a drug molecule make it to human trials [2]. These human trials (usually phase II or phase III) are the ones being assessed by evidence based medicine methods.

The reason why EBM has to be applied at the large human trial stage is because it serves as a form of check and balance. Sometimes despite all the rigorous science behind drugs, clinicians and researchers still don’t know what happens in the human body. So having invested upwards to $1 billion dollars into a drug, the bias formed is immense (not because the companies are evil, that’s just human nature) [2]. This is certainly not an excuse but that’s why we have EBM methods to assess validity of trials based on good fundamental science.

Now, you might say, why conduct all the basic research if these drugs might still fail at treating diseases in humans?

That’s because the alternative is that we synthesize millions of chemicals/molecules and blindly give them to clinical trial participants. Without knowing prior pharmacology, how they may affect a living organism, what their degradation products are, what the predicted mechanism or action might be and how it may translate into side effects and much more.

So, if we didn’t do any studies before hand and just gave random molecules to people, would that be ethical? In fact, how could we recruit clinical trial participants and have them signed informed consent forms if we have nothing to inform them of? Would you sign up for a study which said “This consent form is to waive any legal responsibility that absolutely anything can happen to you, from mild diarrhea to death AND we don’t have a single intelligent way of even remotely informing you of what the likelihoods of these might be”. Of course you wouldn’t.

So, in a nutshell, this is prior probability (or plausability). Given all we know about a treatment AND judging from the results of THIS particular clinical trial, what can we conclude?

EBM which currently does not take prior plausibility into account say “Given THIS clinical trial, what can we conclude?” Well, I’m not sure what we can conclude. The only thing we can reliably assess is how well THIS particular study (internal validity) was conducted. But conclusions, these we cannot possibly begin to form without assessing prior knowledge about the subject matter.

It is conceivable to design a rigorous clinical study on the effects of unicorn dust on preventing heart disease and possibly even show some margin of clinical benefit. But would you in your right mind believe it?

So why then believe all the other nonsense, albeit much better disguised, as valid? What is the sense of assessing how technically sound a study was conducted if its underlying premise was flawed?

The same applies to EBM. Why spend a tremendous amount of time (and in a busy clinical practice, 1 hour of time IS a tremendous amount of time) analysing the internal validity of a study when regardless of what you conclude will be inapplicable?

References

1.  Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ. 2003 Dec 20;327(7429):1459-61. [LINK]

2. SISCRP. 2013. Clinical Trials Facts & Figures. http://www.ciscrp.org/professional/facts_pat.html

Homeopathy or how to misapply evidence based medicine – Part 2

Homeopathic remedies don’t follow conventional chemistry, it seems they prefer cosmic proportions [1]. What about what happens in-vitro? Apparently some places use homeopathic preparations to treat cancer, so they decided to test what homeopathic remedies can do in-vitro to the cancer cells [2]. 

1. Can HPLC detect homeopathy? 

They ran the solvent on HPLC and got only 1 peak, they then tested if “shaking” the solvent would change the chromatogram. It didn’t. Shaking chemicals doesn’t change their HPLC profile, unless you call it “succuction” instead of “shaking”, so that might have some magical powers. But the really neat part comes next:

“All four remedies had very similar HPLC chromatograms to each other, with only trace amounts of limited number of peaks. They were not significantly distinct from the solvent and they lacked the distinct peak seen in the solvent.”

So… they weren’t different, but they they weren’t the same as the solvent? What did these “trace amounts…peaks” look like? What do the authors conclude to be “not significantly different”?

HPLC doesn’t work by some magical means. It uses distinct wavelengths of light and detects how the sample molecules absorb this light [3]. If the chances of any molecules of a homeopathic remedy being in the sample are infinitesimally small, then what is the HPLC detecting [1]? Perhaps there are impurities in the sample? Did the samples get contaminated?

If we believe homeopathic theory that water has “memory” then HPLC shouldn’t be detecting anything in the homeopathic samples. It shouldn’t be detecting anything, because there shouldn’t be any compounds to absorb any wavelengths of light apart from what the alcohol/water in the mixture could absorb.

But even more suspicious is the fact that the authors don’t demonstrate the HPLC spectra to certify that indeed there were no differences. Showing these spectra is not difficult, the HPLC produces graphs that are easily visually compared [4].

2. Contaminants, I mean homeopathy, in a sample can affect cancer cells?

Since they felt that HPLC analysis was necessary but failed to show the data, I feel no further discussion is really necessary. For the sake of the argument however let’s look at some other aspects of the study.

The first question of course is – where was their positive control? We have many substances known to be cytotoxic, why didn’t they have this control? Would the extent of cyctotoxicity be much greater with established cytotoxic agents? For example, why not use a chemotherapy agent like doxorubicin or cyclophosphamide?

Finally, it doesn’t matter what you add to the cells in-vitro, some cytotoxicity will be evident. This is evident from the fact that any cell line has optimal growth conditions. Once the optimal growth conditions are altered, the cells begin to die. In this study they used 87% alcohol and added up to 10 microliters/ml of cell culture [2]. Just to give you a proportion that’s approximately 1% alcohol by volume! Say you weigh 70kg and you drank 700 mL of 87% alcohol (that’s like drinking two 26′ers of vodka), do you think that would induce some cell death?

Capture

Notice how in both cases adding more alcohol to the cells kills more cells consistently. Notice also that the differences between each concentration between the two graphs are very very small, but since HPLC probably showed some contamination, adding high concentrations of contaminated alcohol will kill slightly more cells. No surprises there.

Finally, cytotoxicity in non-cancerous cells indicates that something other than homeopathy was used because the claim of homeopathy is that it has no side-effects compared to conventional medicines. If whatever they used in this study could harm non-cancerous cells means that it will have unfavorable side effects.

3. Prior plausibility is important

The point I’m trying to make is that if the chances of something working are impossibly small and then it all of a sudden works, it’s suspicious. But attention grabbing graphs in papers are much easier to get distracted by than to simply analyse the underlying principles. I would not question the cytotoxicity of chemotherapy agents in-vitro because the likelihood that they kill cells is very high. I question homeopathic remedies killing cells because it makes me think that some contaminant made its way into the cultures in the process of dilution. This contaminant could have altered the optimal growth conditions beyond what the solvent could have done by itself.

References

1. http://sciencepharmer.wordpress.com/2013/06/03/homeopathy-or-how-to-misapply-evidence-based-medicine-part-1/

2. Frenkel M, Mishra BM, Sen S, Yang P, Pawlus A, Vence L, Leblanc A, Cohen L, Banerji P, Banerji P. Cytotoxic effects of ultra-diluted remedies on breast cancer cells. Int J Oncol. 2010 Feb;36(2):395-403.

3. How does high performance liquid chromatography work? http://www.waters.com/waters/en_GB/How-Does-High-Performance-Liquid-Chromatography-Work%3F/nav.htm?cid=10049055&locale=en_GB

4. Simirgiotis MJ, Schmeda-Hirschmann G, Bórquez J, Kennelly EJ. The Passiflora tripartita (Banana Passion) fruit: a source of bioactive flavonoid C-glycosides isolated by HSCCC and characterized by HPLC–DAD–ESI/MS/MS. Molecules. 2013 Jan 28;18(2):1672-92. doi: 10.3390/molecules18021672.

Homeopathy or how to misapply evidence based medicine – Part 1

Solar system final

Somewhere out there (not to scale)

In the late 18th century Samuel Hahnemann (a German physician) proposed that “like cures like” [1]. He proposed that if a substance causes disease in a healthy person then a very small amount of the same substance can help a sick person [1].

“Hmm, hold on”, you might say “isn’t this sort of what we do with vaccines?”

Well, let’s look at some chemistry (if you don’t want to see all the math, skip to the conclusion below):

1. How much vaccine is there in each “shot”? 

A conjugated polysaccharide vaccine can have a molecular weight anywhere between 10,000 g/mol – 100,000 g/mol [2, 3].

There are 25 micrograms of each polysaccharide isolate in Pneumovax 23 [4]. That’s 23 x 25 = 575 micrograms (or 0.000575 g).

Let’s take 100,000 g/mol as the weight of the polysaccharide (that’s fairly consistent with weight required to make a polymer).

0.000575 g / 100,000 g/mol = 5.75 x 10^-9 mol

How many molecules of vaccine are there in each vaccine “shot”? Avogadro’s number is 6.0221413 x 10^23/mol, so…

(5.75 x 10^-9 mol)(6.0221413 x 10^23/mol) = ~3.5 x 10^15 (that’s 3,500 TRILLION molecules).

So, perhaps “like” can “cure like”, but you still need some molecules to be present. Ok, you need 3,500 TRILLION molecules.

2. Can homeopathic remedies match this chemistry? 

Let’s look at a preparation called “China 30″ because this product will make another appearance in a later post.

China stands for Cinchona officinalis which is a medicinal plant [5].

The “30″ means it has a “potency” of 30C. A potency of 1c is when you take 1 part of something and dissolve it in 100 parts diluent (making a 1:100 dilution). So you repeat this process 30 times. The result is a dilution of 10^-60. Not sure what the Cinchona officinalis preparation itself entails, but I’m going presume there’s some quinine in it. Also not sure how much of the original substance is used, but to be very generous, let’s say they use 1 kg (1000 g) and then dissolve that (which I doubt, but I’m feeling generous today). Quinine HCl salt has a solubility of about 1g/ml in warm water and alcohol [7].

So, quinine’s MW is 396.91 g/mol (quinine hydrochloride [7]). Take 1 kg and you have 2.5 moles of quinine.

2.5 moles would contain (2.5 x Avogadro’s number) 1.5 x 10^24 molecules.

But we had a dilution of 10^-60, so we have to multiply:

1.5 x 10^24 molecules x 10^-60 = 1.5 x 10^-36 molecules/liter. But, there’s no such thing as a 10^-36 of a molecule. Molecules either are or aren’t. So how many liters of this “30C” preparation would you have to drink to get just 1 molecule of quinine? Well…

1 liters / 1.5 x 10^-36 molecules/liter = 6.7 x 10^35 liters.

That seems like a large volume, but how large? Well, there are about 1.4 x 10^21 liters of water on Earth (that’s ALL the water on Earth; oceans, lakes, underground, everything!) [8].

So to get just ONE molecule of quinine from a “30C” preparation of China 30, you would need to drink all the water on Earth 482 TRILLION times. That’s still very hard to imagine.

Ok, the volume of the solar system filling all the space from the Sun to Mercury would be 8.2 x 10^35 liters (I got this by calculating the volume of a sphere with a radius of the distance from the Sun to Mercury, which Google and Wikipedia tell me is 58 million kilometers) [9]. So with a “30C” dilution you would need to drink as much of that preparation as would fill all the space from the Sun to Mercury!

3. What can we conclude about the basic chemistry of homeopathic preparations?

“Like” can “cure like” but you still need some real drug in the preparation. One shot of a Pneumovax 23 vaccine contains TRILLIONS of molecules of the drug and saves countless lives. On the other hand to get ONE molecule of drug from China 30 into your body, you would need to drink so much of it that it would fill all the space between the Sun and Mercury! I guess if you want quinine from China 30, you better get drinkin’!

P.S. If you’re wondering what this has to do with evidence based medicine (EBM), I promise you, I’m getting there.

References:
1. Briggs J.P., Straus S.E. (2012). Chapter e2. Complementary, Alternative, and Integrative Medicine. In A.S. Fauci, D.L. Kasper, J.L. Jameson, D.L. Longo, S.L. Hauser (Eds),Harrison’s Principles of Internal Medicine, 18e.

2. Mallick J. (2009). Extraction and purification of capsular polysaccharide from streptococcus pneumoniae and Escherichia coli for conjugate vaccines preparation – Thesis Paper. [Link to PDF]

3. Ellis RW and Brodeur BR (Eds). (2003). New Bacterial Vaccines (Medical Intelligence Unit). Springer. [Google book link]

4. Lexi-Comp Online (TM). Hudson, Ohio: Lexi-Comp, Inc.; June 02, 2013.

5. Rajan A, Bagai U. SEM studies on blood cells of Plasmodium berghei infected Balb/c mice treated with artesunate and homeopathic medicine China. J Parasit Dis. 2011 Oct;35(2):134-9. Epub 2011 Aug 10. [PubMed Link]

6. Morgan J. Homeopathic Pharmacy. [Link to PDF]

7. The Merck Index. 14th edition.

8. USGC. How much water is there on Earth? http://ga.water.usgs.gov/edu/earthhowmuch.html

9. Have to admit, I just Googled this one.

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