TCS Daily

Missing Links

By Derek Lowe - January 21, 2003 12:00 AM

Looking for controversy? Then come on down and join the thimerosal debate. It has everything needed to keep going for years: a terrible medical condition with a mysterious origin, shady politics, and plenty of lawyers.

Thimerosal is a preservative that (until recently) was added to many standard childhood vaccines. It's an old compound, first used in the 1930s, and it stayed in use because it was an effective broad-spectrum antibacterial and antifungal. It's so effective because it's an organomercury compound, and that's where things start to get troublesome. Mercury derivatives have a well-deserved reputation for toxicity, especially to the central nervous system. But thimerosal has a sulfur-mercury bond, which generally tames its reactivity, and it was given in such small amounts that no one had ever noted any problems with it other than occasional allergic reactions.

But then two trends of the last few years intersected: a rising suspicion of vaccines among parts of the public, and a rising number of autism diagnoses. That latter statistic may or may not indicate a rise in autism itself; the debate is far from settled. Some children only begin to show signs of the condition after their first year or two, which is the same period while they're being vaccinated. This led to suspicions that one might be causing the other.

An attempt was made to link autism to the MMR vaccine (measles, mumps, and rubella) - at the time, the hypothesis was that the vaccine caused some sort of gastrointestinal effect. There may be an intestinal syndrome associated with some autistic patients, but it's not clear what its features are, how prevalent it is, or whether it's a cause of autism or an effect of it. But on closer study, MMR vaccination didn't seem to cause this sort of intestinal trouble, and no one could find a statistical link between vaccination and the development of autism.

The idea kept going, though, and suspicion next turned to the thimerosal additive. Perhaps the growing number of childhood vaccinations had led to an overload of thimerosal, producing autism in some susceptible children. The vast majority of children go through the vaccination process with no problems. But there's probably a genetic component to autism, and perhaps this was where it showed up.

A recommendation was made to eliminate thimerosal from vaccines on general principles: other preservatives could probably be used, and eliminating an organomercury compound seemed like a prudent precaution. But this move fueled suspicion in some advocates (if the compound wasn't harmful, why get rid of it?). The government-sponsored Institute of Medicine studied the issue and stated that there was no evidence that thimerosal was causing neurological problems, but that there wasn't enough evidence to completely rule it out, either.

Since then, there's still no epidemiological study that supports a thimerosal-autism link. The latest data on mercury levels in vaccinated children show that the compound seems to be cleared from the body a lot faster than anyone had supposed. This would seem to make the thimerosal-buildup idea less likely, but advocates of a thimerosal connection say that this work ignored the early period after a vaccination, when levels would be the highest.

As a medicinal chemist, I think that response confuses two issues (total exposure versus peak exposure,) but it's true that the two could still be connected, if there's some effect that only shows up at the peak concentration. Peak mercury levels are the object of the next study from the same research group, which should help answer the question. The gradual removal of thimerosal from vaccines has also provided a chance to test the autism link. If there is a connection, we should see a decrease in autism over the next two or three years. I think that that's unlikely, both because I doubt the thimerosal theory, and because the general increase in autism diagnosis is probably not slowing down.

So, we could be heading toward some sort of conclusion, as the data make competing hypotheses more or less likely. But there are some factors that might keep this going for a long time. First, of course, are the parents of autistic children, who are understandably highly motivated to find any potential cause of the disease. They're being sought out by plenty of highly motivated trial lawyers. Any Internet search for terms like "thimerosal" or "autism" brings a flood of offers of legal help. Many of these act as if a thimerosal link to autism was beyond any doubt - autism isn't something that happened to a child, it's something that was done to a child. The only questions left are who to sue first and how much they're going to have to pay. It's a depressing spectacle.

What hasn't helped is a rider to the recent Homeland Security bill. It had a more or less pasted-in provision to move thimerosal lawsuits into the Vaccine Injury Compensation Program, which limits liability. There's a case for doing this, a good one if you believe (as I do) that thimerosal is probably not causing any injuries at all. But this was exactly the wrong way to do it: it's not like there wasn't plenty of shark attractant in the water before. The "where'd-that-come-from" nature of the rider only made it look like there was something to hide.

To his credit, Senate Majority Leader Bill Frist has said that he's going to have this language removed from the bill, and brought up later on a separate vote. That's the hard way (but the right way) to do it. As long as parents of autistic children suspect that their tragedy might be the result of wrongdoing, they'll never stop asking questions. Who could blame them? And as long as the trial lawyers see a case for going after a deep-pocketed industry, they're never going to stop, either. Fighting this issue out in the open is the only way it's ever going to go away.

Derek Lowe is a medicinal chemist with 12 years of experience at major pharmaceutical companies. He conducted PhD and postdoctoral work on natural products synthesis and free radical chemistry. Lowe has worked on drug discovery projects targeted against schizophrenia, Alzheimer's disease, diabetes, osteoporosis and other diseases. He edits the Lagniappe website.

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