So much of what passes as "Alternative Medicine" is mere fuzzy thinking, based on anecdote and hope. But it sells — it offers a quick fix, one that doesn't require hard work and years of study to understand.

But in real medicine, as in all fields of knowledge, a deep understanding of fundamental processes is the first step toward doing something useful. Case in point: a couple of paragraphs from an article on the history behind Viagra (in Modern Drug Discovery, Nov/Dec 1998, by Jim Kling — see http://pubs.acs.org/hotartcl/mdd/98/novdec/viagra.html ). Jump straight into the deep end of the swimming pool and skim the following:

Rather than trying to administer ANP or an ANP mimetic, Campbell and Roberts proposed augmenting ANP activity with a drug that would manipulate the secondary intracellular signals that occur when ANP binds its receptor. ANP receptor binding activates guanylate cyclase, allowing it to convert guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). The general cellular response to a buildup of cGMP levels is to reduce the amount of free intracellular calcium, either by flushing it from the cell or sequestering it within. The physiological consequence of decreased calcium depends on the location and function of the cell. In platelets, which cause blood clots, the result is platelet deactivation. In the kidney, the result is smooth muscle cell relaxation and release of sodium. Elsewhere, vascular muscles relax and allow blood vessels to fill with more blood, lowering overall blood pressure.

Levels of cGMP are held in balance by enzymes known as phosphodiesterases (PDEs), which convert cGMP into GMP by breaking the cGMP's cyclic phosphate ring. GMP is subsequently converted to GTP by another enzyme, completing a cycle: from GTP to cGMP, then GMP, and finally back to GTP. It was the PDEs that Terrett and his team decided to target for drug develpment, reasoning that a PDE inhibitor could prevent the breakdown of cGMP created in response to ANP. cGMP concentations would then increase, thanks to PDE inhibition, and if in response smooth muscle cells in the kidney and blood vessels did their part and relaxed, blood pressure would drop. And Pfizer might have a winner in the hypertension market.

Whew! Are your eyes glazed over yet? (Biochemists in the audience are excused.) I don't follow the acronym-jargon either — but the guts of what the above excerpt describes is much more general, and important. It's a beautiful, intricate clockwork mechanism with springs and balance-wheels and gears and regulators ... or in the steam-engine metaphor world, a contraption with valves and flywheels and governors and pressure gauges and reservoirs.

This is a system, in other words, with positive and negative feedback loops. It maps into a mathematical set of coupled differential equations. And that means that the situation can be understood, predicted, and controlled. We've got ~400 years of experience with this kind of thing. It's comfortable, like a familiar path through the forest or a well-worn pair of shoes. (for earlier comments on "systems thinking" see TransientBehavior, 11 May 1999, and FifthDisciplinarians, 10 Sep 2000)

The cGMP –> GMP –> CTP –> GTP cycle is one piece of a gigantic multidimensional jigsaw puzzle. It fits, almost perfectly, with thousands of other quantitative chunks of knowledge. Together these puzzle pieces form an amazingly resilient network, a coherent theory. The data — accumulated by hosts of careful researchers, critiqued by their expert colleagues, and published in selective journals — hang together. (see WebsOfEvidence, 15 Feb 2000)

Contrast this, to be blunt, with the quality of evidence for most "Alternative Medicine" hypotheses. (I won't name names here, to protect the not-so-innocent and to avoid hurting too many feelings among True Believers.) It's the difference between a child's sand castle and a gothic fortress, between a lightning bug and a lightning bolt.

Sure, most real-world day-to-day physicians — overworked, overspecialized, overwhelmed — don't have a vision of anything like the matrix of biochemistry and clinical medical knowledge. Most patients don't have a single well-defined problem; they display a thicket of conflicting symptoms. And then Money pushes it way into the halls of Science, in the persona of bottom-line-driven pharmaceutical companies, for-profit health care providers, and hungry professors who bend their principles to get grants.

It's not perfect; nothing human is. But it's a lot better than the Alternative....

(See also KnowHowAndFearNot, 19 Nov 1999, or ScienceAndPseudoscience, 6 Oct 2001)

TopicScience - 2002-01-24

(correlates: InFoamation, TemporalUtilitarianism, SomebodyElse, ...)