A 2003 paper in the International Journal of Toxicology suggests the answer is yes. A Baton Rouge doctor named Amy Holmes, who herself had an autistic child, wondered if mercury was involved. She tested the hair of a series of autistic children from her practice and found, to her surprise, that they had less mercury in their hair than other children. Then she and two other scientists did a well-controlled comparison of normal and autistic children that confirmed her original observation. These are the data in the 2003 paper. Here is its abstract:

Reported rates of autism have increased sharply in the United States and the United Kingdom. One possible factor underlying these increases is increased exposure to mercury through thimerosal-containing vaccines, but vaccine exposures need to be evaluated in the context of cumulative exposures during gestation and early infancy. Differential rates of postnatal mercury elimination may explain why similar gestational and infant exposures produce variable neurological effects. First baby haircut samples were obtained from 94 children diagnosed with autism using Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria and 45 age- and gender-matched controls. Information on diet, dental amalgam fillings, vaccine history, Rho D immunoglobulin administration, and autism symptom severity was collected through a maternal survey questionnaire and clinical observation. Hair mercury levels in the autistic group were 0.47 ppm versus 3.63 ppm in controls, a significant difference. The mothers in the autistic group had significantly higher levels of mercury exposure through Rho D immunoglobulin injections and amalgam fillings than control mothers. Within the autistic group, hair mercury levels varied significantly across mildly, moderately, and severely autistic children, with mean group levels of 0.79, 0.46, and 0.21 ppm, respectively. Hair mercury levels among controls were significantly correlated with the number of the mothers’ amalgam fillings and their fish consumption as well as exposure to mercury through childhood vaccines, correlations that were absent in the autistic group. Hair excretion patterns among autistic infants were significantly reduced relative to control. These data cast doubt on the efficacy of traditional hair analysis as a measure of total mercury exposure in a subset of the population. In light of the biological plausibility of mercury’s role in neurodevelopmental disorders, the present study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism.

The abstract omits the most important piece of information: There was little or no overlap between the hair mercury of the control and autistic groups. (It is hard to tell exactly, the data are badly plotted.) Given the size of the two groups, this is highly persuasive. The abstract also omits the basic conclusion: In autistic children, a mechanism that gets rid of mercury is broken. As a result, they get poisoned by levels of environmental mercury that would otherwise be safe.

Holmes started treating autistic children by (a) giving them a compound that tends to bind to mercury and form a compound that is excreted and (b) reducing their mercury exposure. The results of this treatment have been very impressive. As children get older, it becomes less effective. Here are details:

We currently have over 500 autistic patients under treatment with DMSA ranging in age from 1 to 24 years old. In general, we do not expect to see any behavioral, language, or social improvements until at least some of the CNS mercury has been removed. As of 1/15/01, we had 85 patients who had finished DMSA alone and had completed at least 4 months of DMSA + lipoic acid. The results of treatment in these patients are presented below:

n = 85 Improvement (%)
Age Number Marked Moderate Slight None
1-5 40 35 39 15 11
6-12 25 4 28 52 16
13-17 16 0 6 68 26
18+ 4 0 0 25 75

Once lipoic acid is added, we usually track mercury excretion via tests of fecal mercury. We have noticed a large dependence of excretion on age of patient with the younger patients excreting much more mercury than the older patients. We think this difference in rapidity of excretion may explain the differences in response between the various age groups.

We have 6 patients, all 1 to 2 years of age who are finished with treatment by measurements of urinary and fecal mercury excretion. These 6 patients are “normal” by parent reports and repeat psychological testing. We have no children over the age of 2 who are finished with treatment. The rapidity of excretion seems to decrease markedly with each additional year of age. There are several children, mostly in the younger age groups, who have made remarkable progress to the point of being able to be mainstreamed in school, but who are still have some “oddities” of behavior — none of these children have completed treatment yet.

Unfortunately I cannot find later results. An undated announcement says “due to health reasons, Dr. Amy Holmes is no longer able to continue in her practice.” Miscellaneous comments by Holmes. SafeMinds, a Cambridge, MA nonprofit devoted to this issue.

Addendum. A new TV series (Eli Stone, rated B+ by Entertainment Weekly) will consider this issue. According to the NY Times TV reporter, “Reams of scientific studies by the leading American health authorities have failed to establish a causal link between the [mercury-containing] preservative and autism.”

Andrew Clavell writes a blog called Financial Crookery. A recent post about bonuses included this:

Due to the apparent ease of this management game [“managing upward” = convincing your superiors you are doing a good job without actually doing so] compared to the grisly business of finding actual customers and making them want to do profitable business with you, it is no wonder foot soldiers vie to join management ranks.

What is the scientific equivalent, I wonder?

I recently blogged about a surprising association between ALS and loss of a child: Losing a child reduces your chance of getting ALS. I wrote to the lead author of the study, Dr. Fang Fang, to ask how this study come to be. Here is his reply:

Severe emotional stress, as in the case of loss of a child, has previously been associated with health consequences such as psychiatric hospitalizations, cardiovascular morbidity, etc. Our initial hypothesis was that severe emotional stress might also contribute to the development of ALS. We thus used the unique settings in Sweden including the population based registration of in-patient hospitalizations and familial link registration to explore the relationship between loss of a child and the risk of developing ALS. It was surprising for us to see an inverse association between loss of a child and the risk of ALS. After a series of careful checks on data quality, we came to believe this association was not due to systemic errors.

In other words, they did the study because they expected the opposite result.

INTERVIEWER My book came out of an accidental observation, which is that I lost weight when I drank sugar soft drinks. Lost weight, not gained weight. That happened in Paris, and I came back to Berkeley, and I found out it was the sugar. In other words, if I drink unflavored sugar water, I lost weight. Not so obvious, right? But Israel Ramirez, who I mentioned a few minutes ago — his experiments with rats are what led me to this discovery. Because I don’t think most people would have thought it was possible to lose weight by drinking Coke, or whatever. But it has to be unflavored. Anyway, the effect never wore off. I drank sugar water for three years, and my weight went down and stayed down. There was no sign that it was ever going to wear off. So this seems to me to be a big problem with your theory, which is that I drank something which obviously raised my insulin level, sugar water. I didn’t measure it. I lost weight and not only did I lose weight, but I kept the weight off, and I lost it without being hungry; I was less hungry than usual. I mean, you’re right, you know, set points, settling points, who cares. . .

TAUBES It’s important to think of it as a settling point. Because it’s important to have this concept of dynamic equilibrium. As long as you’re thinking about what’s happening in the brain, which is what set point implies. My question is, what did the sugar water do to your fat tissue? It should have caused you to accumulate fat, or at least hold on to the fat you had, according to what I know of the underlying regulation of fat tissue. The question is, why did it do what it did?

INTERVIEWER I was less surprised than you are, or than most people are, let’s put it that way, because I was led to this observation by a theory. I had a theory which pre-dated all of this. I was kind of surprised my theory was so helpful, because it hadn’t been that helpful before. But, lo and behold, it really turned out to be helpful and it led me to other ways to keep my weight off, and I’m still way down from where I was.

TAUBES What I ask when I talk with these people. What I say is: Look at the regulation of fat tissue. The question is, how can you lose weight, or gain it — how can you gain weight without either increasing insulin secretion, or increasing the relative insulin sensitivity of the fat tissue to the muscle tissue. Basically, the way we work, at least if you believe the biology that I describe, is that as we secrete insulin in response to the carbohydrates we consume and the insulin works, among other things, to facilitate the movement of glucose into the cells of your muscles and other lean tissues. But blood sugar is kind of toxic, so your muscle tissue doesn’t want the insulin pushing all this blood sugar in, and it becomes insulin resistant. Your fat tissue now remains insulin-sensitive, because your body doesn’t like to waste fuel. So if you eat a high-carb diet, your lean tissue takes up some of the glucose for fuel, and the rest gets dumped in your fat tissue, and your fat tissue remains insulin-sensitive for a long time — far longer. Because once your fat tissue becomes insulin resistant, then you just become diabetic; you have no place to put the glucose. You just pee it out. That’s the last resort, because your body doesn’t want to waste fuel.

The thing that Rosalyn Yalow and Solomon Berson reported forty years ago is that organs respond differently to high levels of insulin, and they get insulin resistant at different periods. One of the things I put into a paragraph in the book is that I can imagine a scenario where fat tissue becomes insulin resistant prior to muscle tissue, and the result would be anorexia or bulimia. The person would eat a meal and would have no place to store the calories temporarily. So they would either lose their appetite and not be interested in eating at all (anorexia), or they might just throw it up afterwards. Because they have no place to temporarily store the calories that aren’t being used immediately. Bulimia would be another option. A third option would just be to get on an exercise bicycle and ride for three hours and burn the calories off — be Lance Armstrong, in effect. So what I’m trying to figure out is what did the sugar water do, unflavored? And it’s interesting — the idea that it’s unflavored might disconnect some of the sort of Pavlovian responses that you’ve developed.

INTERVIEWER Yeah, I think that’s what was key. The reason I lost my appetite in Paris was that I was drinking unfamiliar sugar water. I think this is the reason that so many diets work in the beginning: because people eat unfamiliar food. Once the food becomes familiar, the diets don’t work so well.

TAUBES This is the problem with anecdotal evidence. The idea that oil could suppress your appetite I could understand, because, as I said in my lecture, you need alpha glycerol phosphate to fix fatty acids as triglycerides. You get the alpha glycerol phosphate from eating carbohydrates, so if you only ate oil it would be shipped off to the fat tissue as triglycerides, then broken down by lipoprotein lipase into fatty acids, but those fatty acids couldn’t be stored in the fat. So it would raise the fatty acid level in your blood, and your body would switch over to burning fatty acids, and this would effectively suppress hunger. That makes sense. But I can’t see why unflavored sugar water would be any different than say, Coca Cola itself, which is just flavored sugar water, for all intents and purposes.

INTERVIEWER Well, when I talked about it in the beginning, I was using fructose.

TAUBES Well, pure fructose, I can also understand. Friedman and Ramirez did an experiment showing that fructose suppresses hunger apparently because it is metabolized in the liver and they believe that the liver monitors fuel status in the body…

INTERVIEWER This is very interesting: someone who is not dedicated to my being wrong.

TAUBES I’m open-minded.

INTERVIEWER Your book proved that.

TAUBES The experiments that Freedman and I think Ramirez did to demonstrate that the liver must sense hunger, must sense fuel availability, is they did intravenous infusions of fructose, Fructose is metabolized only in the liver. It’s not metabolized in the brain. So they infused fructose into the blood stream of rats and it suppressed eating behavior. That’s one of many experiments they did that suggested that somehow what we sense as hunger is being communicated by the liver. It’s always made sense to me. So if you only use fructose, and you don’t get an insulin response to fructose, it would make sense that it suppresses hunger. In my book, I discuss the hypothesis that whatever prompts an insulin response is what causes us to get hungry. So, the fructose, I can understand. Actually, if you’re now eating real sucrose, that’s where it gets complicated, because with sucrose, you’re going to get an insulin response. Unless the fructose component outweighs the glucose, but then, what is it about the absence of taste? Why would Coke make you fat, and sugar water not?

INTERVIEWER Well, first it was it was that flavorless fructose worked. Then it was flavorless sucrose worked. Then it was flavorless oils work. Then it was flavorless any food worked, in particular flavorless protein.

TAUBES When you talk about flavorless protein, what do you mean? The oils, I understand; the fructose fits with everything I know. The sucrose starts getting tricky. What do you mean by flavorless protein? Give me an example.

INTERVIEWER Oh, for example, eating chicken holding your nose clipped. It’s flavorless in the sense that you don’t smell it.

TAUBES That’s interesting. Remember I told you that Jaques Le Magnen started his career studying olfaction (because he was blind). He was curious why the smell of a particular food can go from being very pleasurable when you’re hungry to being nauseating when you’re full. The example I used in the book was the smell of a cinnamon bun cooking. You can imagine that being unbelievably enticing when you’re hungry, and then nauseating if you’ve already eaten three cinnamon buns. Le Magnen moved from that to asking similar questions about the taste of a food, which he thought was determined by our level of hunger. It’s conceivable that if you don’t taste a food it somehow works to suppress hunger, but I have no idea why.

Interview directory.

This is one of the most unusual research findings I have ever encountered. From the American Journal of Epidemiology:

Between 1987 and 2005, the authors conducted a case-control study nested within the entire Swedish population to investigate whether loss of a child due to death is associated with the risk of amyotrophic lateral sclerosis (ALS). The study comprised 2,694 incident ALS cases and five controls per case individually matched by year of birth, gender, and parity. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by using conditional logistic regression models. Compared with that for parents who never lost a child, the overall odds ratio of ALS for bereaved parents was 0.7 (95% confidence interval (CI): 0.6, 0.8) and decreased to 0.4 (95% CI: 0.2, 0.8) 11–15 years after the loss. The risk reduction was also modified by parental age at the time of loss, with the lowest odds ratio of 0.4 (95% CI: 0.2, 0.9) for parents older than age 75 years. Loss of a child due to malignancy appeared to confer a lower risk of ALS (odds ratio = 0.5, 95% CI: 0.3, 0.8) than loss due to other causes. These data indicate that the risk of developing ALS decreases following the severe stress of parental bereavement. Further studies are needed to explore potential underlying mechanisms.

I would love to learn how the authors decided to look into this. There are a variety of “stress is good for you” results (e.g., low calorie intake increases rat longevity) but this is the most puzzling.

I attended the Electronic Freedom Foundation’s 17th birthday party.

It was a highly frustrating party because (a) there were many fascinating guests and (b) the music was so loud it was hard to talk to them. Every conversation was at least a little difficult. Still, I learned a few interesting things:

1. Around 5 p.m. that day, as a BART train pulled into the 16th Street stop, the driver announced, “16th Street, EFF.”

2. Every EFF employee was required to wear a name tag that said “Hello, my name is” along with their name. Underneath the name box it said “Don’t ask me about XXX” where XXX was about 30 or 40 possibilities, including “drugs”, “P2P”, and “Open Government”. This was so amusing it would have been nice if the room had been a little bit brighter so I could have read more of them. The “Open Government” one was worn by a woman named Marcia, who was responsible for the FOIA request that caused Attorney General Alberto Gonzales to resign. “The straw that broke the camel’s back,” said Marcia. In a little speech by one of EFF’s leaders, this was mentioned as one of the year’s two biggest accomplishments. The other was the success so far of their lawsuit against AT&T for allowing the government to tap everyone’s phone without a warrant.

3. Marcia was impressed that I knew Aaron Swartz. She didn’t know him personally but she admired the breadth of his activities. “Like what?” I asked. “The 12-part novel he’s writing,” she said. This was a surprising answer. “You read his blog?” I asked. “No, I just heard about it,” she said.

4. Graffitti Research Lab exists.

5. I met a guy named Jason who had recently graduated from the University of Rochester and is now working at a small (12-person) start-up in San Francisco. He had wandered over to the EFF party from another get-together. We talked about working conditions. Most people don’t like their jobs, I said. That was a strange concept to him, he said, since he had enjoyed the two jobs he had. “It’s a job, you’re not supposed to like it, my friends tell me,” he said.

6. When I was a grad student, I studied how rats measure time on the order of minutes and seconds. (They have a clock that resembles a stopwatch, I found.) Surely humans have a similar clock, but why? One use of such a clock, I realized, is to measure how long it’s been since the last good conversation. When that time gets large enough, you leave the party.

Addendum. Me comparing chocolates: Photo 1. Photo 2. Photo gallery.

Part 1
Part 2
Part 3
Part 4
Part 5