While I'm on the subject, I'll mention some details that will be familiar to my fellow medicinal chemists. The body has a lot of mechanisms to deal with foreign substances. We assume that all our drugs are going to be handled by them, one way or another, and we just try to keep the stuff around long enough to work. (And that's usually the case - once in a while you'll come across a compound that binds to some protein so tightly that it doesn't disappear until that population of protein molecules is metabolically recycled, and that's bad news. Altering a protein that permanently can cause more effects than you're looking for, the worst of which is setting off an immune response.)

The two sorts of systems that clear out unrecognized molecules are divided into Phase I and Phase II enzymes. The Phase I crowd rips into anything that fits into their active sites, which are biased toward greasy structures, and tears the molecules up in ways to make them more water-soluble. The so-called P450 enzymes in the liver are the big players here, and they can oxidize just about anything that comes their way. If the newly torn-up substance is sufficiently water-soluble, out it goes into the urine next time it hits the kidneys.

If it isn't, it hangs around long enough for a Phase II enzyme to get ahold of it. These attach what are basically disposal tags to molecules, groups that are made to be pulled out of the blood and into the urine. A sugar called glucuronic acid is a common tag, and another molecule called glutathione does a lot of this, too. Sometimes Phase II pathways are the main way a drug is eliminated - depends on its structure. One way or another, the body finds a way to get rid of things.

And if it doesn't, that can mean trouble. If the body's exposed multiple times to something that isn't cleared well, the stuff can accumulate in one tissue or another. And while that's not always harmful, there's no way it can help, either. This is the problem with heavy metals like lead or mercury. They're not the sort of thing that can fit well into the P450 enzymes, and they're generally already oxidized as far up as they can be, anyway. Compared to drugs, they're handled poorly. Metals are often excreted bound to sulfur-containing proteins, or as the salt with cysteine itself (the amino acid unit that contains the reactive SH group.) There's a lot of oxidation-reduction chemistry involved - a dose of a metal salt may end up being excreted as the reduced element itself.

That takes us back to tonight's thimerosal theme. The recent Lancet study found that most of the mercury was eliminated through the GI tract, mostly as inorganic (elemental) mercury. The faster it gets converted to that, the better, I'd say, because doses of mercury metal itself are virtually harmless. It's just too insoluble to get into trouble. They also found much quicker excretion than they expected, which was good news, too (as I mentioned on December 4, below.) The follow-up study is going to look at the early pharmacokinetics of thimerosal, to see if there's some sort of maximum-concentration spike that's being missed.

As has been pointed out, if thimerosal is a cause of autism (I'll reiterate that I doubt it,) then it only happens in a few children. So the criticism can always be made that a small study would likely miss testing the sort of child that might be affected. This is true, but if the levels are low, with little variation in the individuals studied, then you have to assume that there's a subpopulation that is quite different. If you have to string together enough assumptions, then you start to rule out the hypothesis - that's as close to proving a negative as you can get in science. We'll see what the numbers have to say.