Wednesday, May 20, 2009

The Paradox Paradox

By denying scientific principles, one may maintain any paradox.
Galileo Galilei

Paradox: [Latin paradoxum, from Greek paradoxon from neuter sing. of paradoxos, conflicting with expectation, para-, beyond; see para–1, + doxa, opinion (from dokein, to think; see dek-).]

  1. A seemingly contradictory statement that may nonetheless be true: the paradox that standing is more tiring than walking.
  2. One exhibiting inexplicable or contradictory aspects: “The silence of midnight, to speak truly, though apparently a paradox, rung in my ears” (Mary Shelley)
  3. An assertion that is essentially self-contradictory, though based on a valid deduction from acceptable premises.
  4. A statement contrary to received opinion.
This morning I ran across an article discussing the "paradox" that obesity seems to play a protective role in heart disease. We seem to be presented with a flood of paradoxes relating to health and nutrition - and indeed said paradoxes present equal confusion to (too) many scientists. Let's talk a bit about what a paradox really is, and then I'll show why the Galileo quote was right on the money. To say it another way, any scientist who cries "paradox" is being fundamentally unscientific. You'd never get them to admit it (because they probably don't believe it), but their use of paradox is in the sense of the 4th definition above, rather than indicating a true logical paradox. And we all know how well science and opinion mix.

Most paradoxes are only superficially paradoxical, and can be resolved on deeper inspection. Real paradoxes are rare. Consider this example from the Wikipedia entry on "paradox":

... consider a situation in which a father and his son are driving down the road. The car collides with a tree and the father is killed. The boy is rushed to the nearest hospital where he is prepared for emergency surgery. On entering the surgery suite, the surgeon says, "I can't operate on this boy. He's my son."
Sounds paradoxical, right? But the issue is simply a bad assumption: since most surgeons are men, one erroneously extrapolates that ALL surgeons are men. Obviously the surgeon must be the boy's mother. This is a common source of claimed paradoxes in science: extrapolating something that is believed at some level (e.g. obesity causes heart disease) to a statement of absolute truth.

Let's consider mathematics, starting with simple Boolean logic. The point of logic is to reason deductively about the truth of a statement, given the truth of other statements. A paradox would imply you could get different answers depending on how you worked through the problem, i.e. two different sets of steps valid within the rules of logic would give different answers. If such paradoxes did exist, they clearly render logic useless, since you could never consistently prove something true. The dictionary definition of "paradox" admits a subtly different situation, which is a statement like "I am a liar". The rules of logic can neither prove nor disprove this statement. But this more an artifact of language and technical aspects of formal mathematical systems as opposed to the sort of "scientific paradox" claimed by the authors of the heart disease/obesity paper.

Generalizing the case of logic to all math leads to the same conclusion. A mathematical system which admits true paradoxes is pointless. A true paradox would indicate inconsistency in the rules and assumptions used to build the system. Problems labeled "paradoxical" in math are really counter-intuitive, like the Banach-Tarski Paradox, where one can prove that there is a way of dividing up a 3-dimensional ball, moving the pieces around without stretching them, and reassembling to get two balls of the same size as the original. Sounds pretty paradoxical, right? But it's really just counter-intuitive: the size of the set of points in the one ball (called the cardinality) is actually the same as the size of the set of points in the two balls. The size of a set is different than it's measure (which in this case would be the volume). The result that we can double the volume of a set of points without changing the cardinality of that set violates our intuition, but is consistent within the mathematical definitions of measure and cardinality (this is roughly equivalent to realizing that that size of the set of even integers is the same as the size of the set of all integers: they're both infinite).

Can we ever have a true scientific paradox? Mathematical truth is purely conceptual, and can thus be "absolute". We define the axioms and rules and mentally manipulate these to prove or disprove other statements. Science is messier. Nothing is absolute in science, because all scientific theories must be supported by observational evidence from the real world. Our observations are limited by various practical considerations. Our data is never 100% accurate, we can never be sure we've observed all of the relevant variables, etc. So our belief in a scientific hypothesis is always conditioned on the evidence which itself is subject to limitations of our ability to observe and collect information. Scientific belief thus exists in a continuum between absolute truth and falsehood, and is always conditioned on the available evidence. As new evidence is obtained, we update our beliefs accordingly toward greater or less truth as indicated by the new evidence.

So you can never have a scientific paradox. Scientific honesty demands that observation of evidence contradicting a hypothesis causes you to lower your belief in that hypothesis. A paradox requires two statements which can be shown to be contradictory yet simultaneous true. But neither evidence nor hypotheses carry absolute truth, and our beliefs in either are always conditioned on the other. The scientifically relevant method evaluates belief of hypotheses conditioned on evidence.

Science as most often practiced, using frequentist statistics, evaluates belief in data assuming the truth of a hypothesis, so it's no wonder scientists spend so much time confused about "paradoxes". Take a hypothesis and data that appears to contradict that hypothesis. Then try to test the hypothesis quantifying your belief in the data presuming truth of that hypothesis. When the number comes back low, you basically have two choices: come up with a reason why the data is "wrong" (e.g. a mistake in experimental design, broken instrument, drunken graduate student), or realize that your hypothesis (again, whose truth was assumed as part of the analysis) is possibly not true. If you believe your data AND are 100% convinced of the hypothesis (which begs the question of why you did the experiment in the first place), you'll think you've got a paradox. The only real paradox is that people get paid to make this fundamental error in inference - over and over and over . . .

Our friends who observed the apparently paradoxical protective effect of obesity in heart disease patients have fallen into this trap. The right thing to do upon observing this effect is to update belief in the hypothesis that obesity causes heart disease. The new evidence lowers our belief in that hypothesis, and simultaneously signals that we should evaluate competing hypotheses in the light of all of the available evidence. Indeed, if one were to do a proper analysis of the evidence, it would be clear that no more supports the hypothesis that obesity causes heart disease any more than it does the hypothesis that heart disease causes obesity. Not all heart disease patients are obese, and not all obese people suffer from heart disease. Further, there's no strong metabolic evidence indicating the arrow of causality.

The smart thing to do in such situations is to start looking at hypotheses where a third culprit is the underlying cause of the observed associated effects. So what might cause both obesity and heart disease, or in some people one but not the other?

A growing body of evidence links poor blood sugar control to heart attack risk (see this recent study, for instance). The body maintains blood glucose in a narrow range, because both too little or too much are dangerous. Too little and the brain starves. Too much and you overwhelm the systems which repair the damage caused by sugar, in particular that to the arterial lining. You cannot excrete excess blood glucose like you can excess water or salt (at least not without severely damaging the kidneys). So your options are to either store it, or turn it into something else. The muscles and liver have a limited capacity for storage of glucose. Once they're full, the liver, as directed by insulin, will turn the rest into fat, and your fat tissue, again as directed by insulin, will store that fat.

At least that's how it's supposed to work. Insulin is a hormone, and hormones activate genes to manufacture proteins. The response to a hormonal stimulus is thus partially determined by genetics. Your genes will determine, for instance, the relative expression of lipoprotein lipase and hormone sensitive lipase in response to insulin levels. This in turn governs the ability to take fat from the blood and store it, or release that fat from fat cells to be used as energy. Similarly one guesses that insulin sensitivity of muscle and liver tissue has some genetic basis, and these may further be altered by disease, nutrition, etc. (overconsuption of either alcohol or fructose will make the liver insulin resistant, thus impeding its ability to store glucose, transform it to fat, or scale back manufacture of glucose from protein).

In the framework of this hypothesis, a person with greater propensity towards fat storage has a potential advantage when it comes to heart disease, as it provides another "sink" for excess blood glucose. A perpetually skinny person may be at a disadvantage. If your fat cells don't respond to insulin signals, then the fat has nowhere to go and stacks up in your blood as "triglycerides". If your liver and/or muscle don't properly respond to insulin, glucose begins to build up in the blood. Neither situation is likely good for the development of heart disease, and in reality both seem to occur simultaneously for susceptible individuals.

The news blurb doesn't state whether blood glucose or triglycerides tested, and the publisher of Journal of the American College of Cardiology doesn't provide free access to the publication. Perhaps a reader with access can post a comment as to whether blood glucose was tested and the results. Regardless, it is the unwillingness or inability of the authors to consider alternative hypotheses which leads them to cry "Paradox!" in such a public manner. Such individuals are clearly mired in irrational dogma and/or trying to drum up extra funding. From a broader view, any hypothesis (like diet-heart) which embraces paradoxes (like the "French paradox") are probably junk science. Treat them accordingly lest you extinguish your own spark of reason.

Sunday, May 3, 2009

Pearls Before H1N1

The swine flu is making me sick. I don't have the virus (at least no symptoms), but the whole panic over it annoys me on multiple fronts. Take this recent AP story as an example. 241 cases? Is this really worth worrying about? I find the following quote particularly telling:

Even if the swine virus doesn't prove as potent as authorities first feared, Besser said that doesn't mean the U.S. and World Health Organization overreacted in racing to prevent a pandemic, or worldwide spread, of a virus never before seen.

With a new infectious disease, "you basically get one shot, you get one chance to try to reduce the impact," Besser said. "You take a very aggressive approach and as you learn more information you can tailor your response."

It was just over a week ago that authorities learned the new flu CDC had detected in a few people in California and Texas was causing a large outbreak and deaths in Mexico, triggering global alarm.

"We didn't know what its lethality was going to be. We had to move. Once you get behind flu, you can't catch up," Homeland Security Secretary Janet Napolitano said.

Maybe an informed reader can help me out here. Is there any reason to believe that the "very aggressive approach" makes any difference at all? Do all of these countermeasures have any effect? I get the feeling there's a whole bunch of "virus nerds" at the CDC just waiting for the opportunity to do something, which more than anything is to feed public hysteria and justify their existence. Maybe I'm being overly pessimistic, but the track record of government science types is pretty abysmal. I do think that they think they're being helpful, but I really have a difficult time shaking the feeling that anything public health authorities do to try and stop a virus (which has evolved over billions of years to be very efficient at spreading infection) is roughly equivalent to piling up cheesecloth to protect yourself from a tsunami.

Western culture seems to be developing increasingly extreme paranoia about all things health related. And of course, this is fueled by the media and other groups (like the CDC) who stand to benefit from spreading fear. Too many people spend too much time worrying about "silent killers": cancer, heart disease, viral diseases, you name it. Correspondingly, there exists as MASSIVE "industry" concerned with disseminating information and treatment. Just look at the amount of money spent helping us with that most deadly of conditions, "high cholesterol". Can you watch TV anymore without seeing at least one advertisment for statins (geez, there's one on now - GO TIVO) or a wonder food (like Ch**rios for crying out loud) that is going to save you from the "silent killer". Ch**rios and statins: the delicious and healthy way to start the day.

Fear is a complicated emotion, and that complication no doubt stems from the underlying complicated nature of trying to survive. I believe the major psychological source of fear is uncertainty, i.e. "was that sound Grog relieving himself due to over-consumption of cachonga root, or a bear coming to eat me?". I suspect the physiological source of fear is hormones, namely the stress hormones. Certainly stress brings about an increase in irrational fear (is there such a thing as rational fear?), and certain drugs can activate those same pathways and create tremendous fear. Our society seems now more than ever in the grip of fear inducers. Though science and technology have advanced human knowledge, the fact is that most of that knowledge is held by precious few. "Back in the day", when we all lived in the forest, you needed lots of knowledge to survive. The "unknown" was largely those aspects of Nature humans could not control, like the weather, hungry bears, and infection. Now we trust that to the "experts", tacitly ceding them control over our lives. And other aspects of lifestyle probably contribute to stress. Crappy nutrition certainly increases stress hormones, as does chronic illness. The diabetes "epidemic" is a pretty good sign that a major portion of the population is suffering from chronic illness due to poor nutrition (and a pronounced lack of sunshine).

The combination is a real mess: a sick and fear-filled population driving a culture of experts to save them from their own ignorance. And of course the experts turn out to have little relevant expertise. Their major source of validation comes from the feedback that we give them. How many people do you know whose doctor fills them full of pills to no effect? The patient experiences little actual improvement in health, yet they keep going back for more. What if people started thinking for themselves and kicked their doctor to the curb in favor of self-informed care? I suspect a swift kick in the pocketbook would change MDs' opinion of statins in a big hurry. Similarly, let's have some fun and watch the shakeout if (as I think is highly probable) swine flu turns out to be a dud. Congress and the media will praise the CDC for quick and decisive action, and they'll wind up with a nice budget increase, which is all the validation they need. I suspect we won't see any sort of critical introspection as to whether or not all of this flopping about and general panic has a measurable benefit on public health. Nobody gets budget increases for that.

In a really nice post on critical thinking, Dr. Mike Eades appropriated one of thousands of fabulous lines from George Carlin (who I personally think was probably smarter than everyone at the CDC - combined). I shall re-appropriate it here:

Think of how stupid the average person is, and then realize that half of them are stupider than that.
I spent about 10 years "in" science, 3 to get my M.S. and Ph.D. another 7 as a post-doc and researcher. I had the chance to interact with many scientists, mostly from physics, but also from other fields, and if there's one thing I can tell you with great certainty it is that the distribution of intelligence amongst scientists pretty much mirrors that of the population at large. By "intelligence", I mean the ability to rationally weight complex evidence as it relates to different hypotheses. My point here is not to say that scientists are dumb (though as we learned from Carlin, half of them are dumb, by definition), but that you likely have the same reasoning capability as the average scientist. In fact, you're probably a little better than the average scientist. Scientists favor complex solutions, precisely because they are hard to understand. This validates their own self-perception of being smarter than the average bear. As a scientist I've had more than one scientific discussion end with "That's too simple to be right." Not, mind you, "that idea contradicts this piece of evidence". It's just too simple for their taste. So I dressed up the same simple idea with complex-appearing math and verbiage, leading to acceptance.

The swine flu situation presents us with the opportunity to watch this in action. I was just watching a clip from a news conference, where some "expert" was simultaneously back-pedaling on the severity of the present threat, while drumming up some more fear about the future. The thrust of it was that the Spanish Flu "took a summer break", and then re-awoke to slaughter millions. So keep on wiping down those door handles and pouring in the taxpayer dollars for stockpiling flu vaccines and anti-virals. Yet our expert likely missed on the glaringly obvious simple hypothesis: people almost never get flu in the summer, an effect seen in both hemispheres. That applied also to the highly deadly Spanish Flu, which apparently spent the summer at the beach before coming back to clobber Western civilization. Or maybe something about the summer that made people more immune to a pre-existing infection. Gee, I wonder what that could be?

(For those in the cheap seats, it's Vitamin D3.)

Can I say with certainty that Vitamin D3 is the answer to the swine flu? No. But the CDC nerds also have no reason to say that it isn't, other than it's a) too simple, and b) puts a fair dent in their raison d'etre. Even WebMD, normally a bastion of medical orthodoxy, is at least considering the possibility. I presume flu cases are being tested for H1N1 antibodies. I wonder if anybody is bothering to test for Vitamin D3 while they're at it?

Nah, too simple. Ramp up that expensive anti-viral production. Far more tasteful.


I'm following the leads of Dr. Eades and Jimmy Moore on to Twitter. It's hard to find time to blog with my new job, and I wind up with stacks of links I want to talk about. Twitter seems like a good solution to at least push information I find interesting (and perhaps more often, incredibly dumb).