NOTICE: Posting schedule is irregular. I hope to get back to a regular schedule as the day-job allows.

Wednesday, July 22, 2015

...In which I "Hulk-out" on a conspiracy theory... [Full link to blog for email clients.]

I *really* try not to get drawn into discussions like this... as the man said, you wouldn't like me when I'm angry...

However, a friend posted this: 

[Image by the Skeptical Meme Society, shared by Dr. Mehmet Oz on Facebook.]

...and immediately ended up with people saying that there *were* conspiracies, and all it took was a few people at the top of the company, or a few peer reviewers, or sprinkling around some of the billions in profits...

So, I got a bit heated.  Here is my response:

First, most pharma companies have minimal laboratory facilities for advanced drug testing. If it takes animal research these days, it's largely done via Material Transfer Agreement and a Research Services contract to a university lab. In the long run, it is cheaper to contract out the work on a fee-for-service basis than to invest in the infrastructure and personnel to maintain all of the possible labs that are needed in the course of testing.

So there's no secret underground lair in the heart of an extinct volcano where the demon Big Pharma threatens investigative journalists with the piranha tank in order to keep the deep dark secret cures away from the public! To believe otherwise is really a condemnation of one's own rationale thought processes and education.

Those same universities have a research publication policy - if you've ever heard of "publish or perish" it applies to the research contracts, too. No university would agree to contract terms that prevent a scientist from publishing *any* results they obtain - it doesn't matter if they are positive or negative. I was once in a contract negotiation where the funding company wanted a 36-month embargo on publication to protect their process trade secrets - the university would not agree to the terms, and we did not get the contract. You see, agreement to the terms would have jeopardized the tax-exempt/non-profit status of the university.

So, no, there's no big conspiracy to keep cures away from the public. ...And no, it's not possible for only the people at the top to know about a cure and keep that secret - frankly, the people at the very top don't know that much - they are upper level managers. The scientists that do all of the development work are in middle management, with lab techs under them (who know of the results) and bosses above them (who also know the results).

As for Big Pharma profits - someone in the facebook thread read a profit-loss statement and commented on billions in profits - they do not go into some huge Scrooge McDuck giant vault where the CEO can sleep on a bed of gold coins at night! Profits go back into the company - they pay dividends to shareholders, they pay bonuses - yes, to the CEO - but also to most everyone who works for the company.

For John Ringo's The Last Centurion, I gave him a number (in 2007) of $2,000,000,000 to bring a new drug to market. Today, that's more like $10,000,000,000 (that's ten *billion* dollars, just for one new drug). That money has to come from someone-somewhere. It doesn't come from the president's magic pocket where he keeps "his" money to pay for all of those special programs like the so-called "Obama phones" (actually, he keeps those in his *other* pocket). No, that money comes from the sales of other products by the company - and that means the prior profits. Those profits are what exists after taxes, and thus reported on annual financial reports. Capital investment in the company is *also* post-taxes, so you have to really dig down to find out how that profit is distributed and re-invested in the next stage of the company.

Oh, and by the way, the shareholders are not money-grubbing elites eating up all the wealth stolen off the backs of the laborers - A company has a stock issue when they want to do something that requires investment - build a new lab, hire more people, try a new market - and they don't have the cash *now* to do it. So, they sell stock to people who *do* have the cash *now*. That way they raise way more cash than they could get with a bank loan. Later, once the investment pays off, they pay out to the investors - with interest, because that's what you do when people loan you money. However, in the public sector - when someone loans you money, they need some form of collateral to hold until the loan is paid off. In the case of stock, that is a small ownership share in the company. Stockholders are not merely investors, they are *owners* (and in many cases, they are also employees) and so they *do* deserve a cut of the profits (and frankly, it's a pretty small cut per stock).

What's also not obvious in the profit-and-loss statements is the cost of doing business in the global community - see, governments like to minimize prescription costs when *they* are paying - foreign aid, nationalized medicine, Congressional perks - any time a lower-than-cost price is negotiated. When a drug is new, the cost is high to recoup that $10 billion investment. Once patents expire and the drug goes generic, or *competitive drugs are released, all chance of recouping costs are over - so it makes sense to recoup those costs early. But international agreements often limit drug costs - plus Pharma companies are often "encouraged" (or blackmailed) into provide free or steeply discounted drugs for humanitarian reasons. China, frankly, steals the formula and copies it - and they aren't the only ones. Even our dear friends north of the border (i.e. the government of C-eh?-N-eh?-D-eh?) are on record as having told several U.S. pharmaceutical companies that they *would* provide drugs at the price the Canadian governemnt demanded - or else they government would allow Canadian generics manufacturers to violate the International Patent and produce cheap (in more ways than one) drugs.

So yeah, drug companies make profits, and still Americans pay higher prices for drugs than Canada, Mexico, China, Japan - but that's largely because our legal system limits the extent to which the government and healthcare can criminally extort those same companies.

Regarding those "magic" cures out there - I fight this all the time with medical marijuana claims. Let me state right out, that there are many positive medicinal benefits that the Medical Field can develop using components derived from Cannabis sativa. Smoking pot is of limited use - and really only medicinally sound in cases where the euphoria induced by smoking pot is one of the desired effects - for all other uses, synthetics and extracts are much more scientifically and medicinally sound - mainly because of control of dosing and route of administration. Ingestion is a *lousy* route of administration - and burning, baking and boiling alters the chemical compounds.

Hemp Oil is NOT a cure-all - half of the things it is claimed to do (the half that actually refers to scientific publications) is a result of using pure extracts or synthetics! - not street pot! I once had someone cite several papers at me concerning medical marijuana effects on cancer cells - one of those reported on the cancer that took my Father-in-Law's life - at a time when I was actively researching cannabinoid effects on brain cells. I pointed out that in each publication, the cannabinoid used was a *synthetic* - not occurring in nature, and considerably altered from the 63 different cannabinoid compounds found in marijuana smoke. Hemp Oil, Charlotte's Web*, and "pick-your-favorite-bud-at-the-medical-pot-shoppe" are the modern day equivalent of snake oil - yes, some people will see positive effects, but in the end, it's due to many more factors than just the medMJ.

Another such example is the recent craze for claiming medical marijuana treats (or cures) autism.  I was recently asked about the actual published research on the topic.  A Google search shows hundreds of search results on marijuana and autism, with sources such as "Natural News" touting the beneficial effects - but they are *all* anecdotal, and not based on scientific research.  It turns out that in 2013, there was an article in the scientific journal Neuron (volume 78, Issue 8, pages 498-509) that showed that one of the autism-related mutations (Fragile-X) caused a change in brain cell-to-brain cell signalling that involved the brain's normal neurotransmitter that acts at the same location as marijuana (known as the endocannabinoid 1, or CB1 receptor). These receiving sites for signals can operate in two modes - always on, or in pulses. It turns out that the autism-related condition does not have an always-on mode, only the pulse mode. The assumption from this study is that it is not the receptor that is faulty, but the cells producing the endogenous marijuana-like chemical normally present in brain. Thus, people surmise that replacing this chemical with medical marijuana would restore normal function. The truth is very likely that no, it won't, but that doesn't stop "Natural News" and other sources as claiming that Big Pharma is withholding evidence that marijuana cures autism. The authors never said this - and in fact, the endogenous cannabinoid signalling and receptors in the brain are tied into almost every brain function - such that if it really were the "root cause" of autism, or the cure, then the autistic brain wouldn't function at all (and we know that is not the case, it just functions differently).

Another article from 2013 in the Journal of Autism and Developmental Disorders (Vol. 43, Issue 11, pages 2686-2695) found that there is an excess of a different type of endogenous cannabinoid receptor in the blood of autistic patients. This "CB2" receptor occurs in high quantities than it normally does. In many cases, this pattern called "receptor upregulation" means that the receptors are being under-stimulated (hence too little of the triggering endogenous marijuana-like chemicals).

Again, this was latched onto by medMJ proponents as something that could be "treated" with medMJ. Two problems with that - (A) CB2 doesn't really react to THC - the main active ingredient in marijuana, and (B) CB2 and the cells in which the receptor is present are involved in immunity, not brain function.   

There is a tendency for the medMJ crowd - or frankly any group touting the latest miracle cure - to shout back at scientists urging restraint that "just because it isn't scientifically proven doesn't mean its not true." 

Well, it's not scientifically proven, there's no support for their claims, and in fact, it's probably *not* true.  As I wrote last year ( and what is difficult in science is proving something to be *true* - proving it to be false is actually quite easy - and many such claims are proven to be false.  In the case of many "quack" cures, there's even a fair amount of evidence that they could be harmful.

Frankly, people need to learn to read scientific papers - it's not hard to learn how to do, but it would require people to *work*, to *think* and to *read* more than 140 characters on their phone screen!

[*Charlotte's Web is a strain bred for high levels of cannabidiol, to enable use as a treatment for juvenile epilepsy and other disorders sensitive to CBD. It is a step in the right direction - selecting for the desired chemicals. However, *any* tetrahydrocannabinol content in the compounds shown to be *effective* against epilepsy negates the beneficial effect. Thus Epidiolex - the drug developed by medicinal cannabinoid research - is a pure extract, which known, controlled dosing and preparation. Charlotte's Web does NOT meet this standard. Epidiolex is in an oil-based spray absorbed through the mucus membranes in the mouth; however, it is *not* burned, smoked, baked, boiled, or digested. Any and all of those alter the drug - leading to much less certainty in effects!]

See, I *told* you that you wouldn't like me when I was angry!


  1. Great post! :) I do have two-ish questions for you, though, if you don't mind.

    1) I've never understood why phrama-companies don't just go public with the governmental threats/shakedowns and flat-out tell people "do you want to know why we're charging you $PriceYouThinkIsTooMuch for medication? Here's why! Convince your governments to respect our patents and everyone in the developed world pay a slightly higher price and we can charge less here."

    2) (This one is going to reveal my ignorance of biochemistry so please be gentle): Why are certain animals used in testing? I've never understood why researchers use rats. I could see using other primates (we have a lot more in common with them, don't we) but not rodents. Also, is our understanding of biochemical processes so primitive (meaning "still in its early stages" not "bad") that we can't run more accurate computer modules and skip some of the more costly early-round tests entirely?


    -- G.K.

    1. Thanks for the praise - in response to your questions - I suspect that since corporate execs are human - they resist making *everything* public on the general principle that *someone* will find *something* to protest. Thus, the reason could be politics, it could be the general "us against them" feeling that many in science have against the media, or it could simply be that they don't *have* to."

      #2 is in some ways harder to explain, but the plain truth is that model of biochemical and physiological processes just aren't that good. There is a strong nonlinear component to any biological process - meaning that subtle variations of outcome are dependent on very fine detail of starting conditions. On one project in which I work, there is a nonlinear model which requires over 1 million coefficients (i.e. variables) - just to track 32 inputs and 32 output signals. To model just 30 seconds worth of data requires a 1024-node computer cluster approximately 18 hours.

      ...and getting *more* accuracy makes the math even harder, with more coefficients and finer detail. When it comes to drug interactions, it is not enough to model just the drug-receptor interaction at the brain cell, but also drug/fat, drug/protein, drug/glucose interactions, and to model blood delivery. effects on blood cells, nerve cells, fat cells, immune cells, support cells, muscle cells, etc. Even with incredible advances in computing, the models just keep getting more complicated as we discover new features that *must* be included in the models.

  2. Excellent post. The same conspiracy exists around the auto industry (which we're told has been buying and suppressing 100 mile/gallon cars for decades).

    Even when there's a real conspiracy or cartel it isn't so clear cut. A recent article in IEEE Spectrum magazine (search "The Great Lightbulb Consipiracy", it says no links in comments) talks about a cartel in the 1920s to 1930s consisting of companies manufacturing light bulbs. The claim in the article is that the cartel artificially reduced the expected life of incandescent bulbs to 1000 hours to increase sales and profits (planned obsolescence). However, the article never asks why in the 80 years after the cartel disbanded the expected life of incandescent bulbs remained at 1000 hours.

    So is a 1000 hour incandescent light bulb a result of planned obsolescence or is it a good tradeoff between bulb cost, power per unit of light, and the hassle of replacing a bulb?

    1. Yes, it is easy to claim conspiracy... because doing the homework is too darned hard. More often that not, it seems that "conspiracy" was really just a matter of the best compromise - given facts that are not obvious to (or neglected by) those who would cry conspiracy.

  3. People love conspiracies. They make great boogie-men in the popular imagination, some faceless group of people doing shady things. To make matters worse, they occasionally exist (Iran-Contra, for example).

    However, I suspect that 99.9 percent of those high level conspiracies come to light in excruciating detail because while people may love money and/or power, many love attention more. The idea of book deals, TV interviews, movies about your life, all after you have leaked that Big Pharma has a cure for cancer but is sitting on it because it's more profitable to treat the disease...with documentation.

    Honestly, it's one of the most reassuring things I've discovered about humanity. :)

    On an unrelated note, can you recommend someplace to learn how to read and understand scientific papers? It may not be hard, but if you're not careful, you can buy into papers that offer up faulty research (see recent revelations about a study that said chocolate could help you lose weight).

    1. Biases are everywhere, but I would start with Nature, Science and New Scientist as examples of two scientific journals, and one science-news journal that use layman's language for complex scientific terms. They are a good starting point for learning the terms and structure of a scientific paper.

      In Science and Nature, particularly look at the Methods sections (they are often online, and not in the print journal itself. Go to Entrez Pub-Med - the National Library of Medicine's search tool - also PubMed Health. They provide specific links to the relevant science behind a finding (for medicine/life sciences).

      Then, ask a scientist to help explain what you've read.

  4. Thanks for putting this far better than I could.

  5. It is not "difficult" to prove anything via the scientific model - it is impossible.

    The method is designed to avoid error, not to divine truth. Hence falsifiability, and not provability.

    Provability is an interesting aspect of mathematical problems, and not strictly part of the scientific method (acknowledging it may come in to play in those statistical exercises such as you outlined in your recent articles on why the science is never settled. How can anything be proven but not settled? We might have a high confidence level due to repeated experimentation & observation, but then, so did Newton. So did Ptolemy.)


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