In most scientific disciplines, medicine included, hypotheses start with observations. When John Snow became curious about a London cholera outbreak, he looked for patterns and found that many cases centered around a local well. While he didn’t have a clear idea what caused cholera, he suspected the water as a source, and tested his hypothesis by having the pump handle removed, which appeared to help stem the epidemic. Eventually it was discovered that that a bacterium was the cause of cholera and that is was transmitted in drinking water contaminated by feces.
More modest hypotheses are the grist of the science mill. Researchers may observe a new trait in a fruit fly and hypothesize that it is due to a novel genetic change. They then do the hard work of looking for correlations and associations, and the bench work involved in pursuing an answer. In medicine, testing a hypothesis at the bench is followed by testing on real people, a significant scientific and ethical shift.
There are a myriad ways that medical science can go awry, and as in much of human thinking the root of many of these mistakes is our own fallible brains. We see patterns, and when we see patters, we often assume that post hoc, ergo propter hoc, that is, if one event precedes another, it is the cause. When you take the tinder of this human tendency, and ignite it with human emotion, we can end up consumed by medical catastrophes.
Fellow Scientopia blogger Female Computer Scientist tipped me off to a piece in The Scientist, one that demonstrates how a father’s desperation and a doctor’s desire to please led to a terrible medical decision. The article tells the story of the Johnson’s, whose autistic son developed intractable behavior problems. The family pursued all of the usual conventional medical approaches, purposely avoiding much of the autism quackery that so many others fall prey to. As their son worsened, Mr. Johnson started doing his own research—and stumbled onto something interesting:
He discovered the work of a trio of physician/researchers at the University of Iowa who had successfully treated patients with Crohn’s disease and ulcerative colitis using a nematode parasite found in the intestines of pigs—Trichuris suis, the pig whipworm. Both are autoimmune disorders in which the immune system essentially attacks the intestinal walls. Stewart also found data that pointed to a link between some autism symptoms and inflated levels of proinflammatory cytokines, an apparent result of the immune system attacking glial cells in patients’ brains.1 Putting these bits of information together, Stewart wrote a short review paper and presented it to Hollander. His central hypothesis was that parasitic worm infection would modulate Lawrence’s immune system and calm inflammation that was causing his disruptive behaviors.
This hypothesis—that autistic behaviors can be modulated by parasitic infection—is not as insane as it sounds. Rabies increases aggressive behavior in animals, causing them to bite and spread the virus. The parasite Toxoplasma has been hypothesized to change human behavior. But in the Johnsons’ case, an unbroken chain of faulty assumptions led them to try something foolish.
The basic syllogism is this:
- Inflammatory diseases can be treated by a parasite.
- Autism is an inflammatory disease.
- Autism can be treated by a parasite.
First, can “inflammatory diseases” really be treated with pork whipworms? The studies are unimpressive. The few studies done found some minor statistically significant improvement when whipworm infestation was tested against placebo. The inflammatory response generated by parasitic infection is a bit of a blunderbuss. Compare it to something like infliximab, a monoclonal antibody very successfully used in Crohn’s disease that targets a specific immune molecule and doesn’t involve ingesting worm larvae.
Many diseases fall under the category of “inflammatory”, and inflammation is a complicated process, one that can’t be nailed down as something to be turned “on” or “off”. This makes analogies between one inflammatory disease and another problematic.
Is autism an “inflammatory disease”? One study cited in The Scientist looked at a very small sample of autistic people, without a control group, and found evidence of inflammation in their neural tissue. There is no clinical evidence that autism has an “inflammatory” cause that can be affected by immunomodulation with, say, corticosteroids which are a non-specific immunologic treatment effective in many inflammatory diseases.
Given that statements one and two are false, number three is ridiculous. But the Johnsons were understandably desperate and tried worm therapy. At low levels of infestation, they saw little improvement, but at high infestation levels, there was a change:
The Johnson family anxiously awaited the effects of the full dose of TSO on Lawrence’s violent behavior. Within 10 weeks of the higher-dose treatment, the autistic boy stopped smashing his head against walls. He stopped gouging at his eyes. The paralysis and frustration that held him and his family prisoners in their own home lifted. The freak outs ceased. “It wasn’t gradations,” remembers Stewart, who had always kept meticulous notes on Lawrence’s disorder and the interventions they had attempted. “It just went away. All these behaviors just disappeared.” Elated, Stewart called Lawrence’s doctor, Eric Hollander. “He was stunned, because all of that behavior set was gone,” Stewart says. “He was speechless, as I was.”
As Lawrence’s previous behaviors demonstrated, there was a certain unpredictability to his disease. He sometimes worsened, sometimes improved, and in cases like this, we are even more easily fooled by our post hoc ergo propter hoc thinking. There is no way of knowing, in this single case, whether or not worm infestation had a clinical effect on autism.
I suspect this story is going to continue on two separate paths. Quacks are going to take it and run, marketing expensive whipworm therapy to desperate parents. Real scientists and clinicians are going to take a step back, and examine the possible role of inflammation in autism on the one had, the the possible role of parasites in various inflammatory diseases on the other. The work will be hard, slow, and lead to many dead ends, but eventually we will learn important scientific facts.
The slow pace of science can be torture for those who are suffering, but turning individuals into uncontrolled experiments helps neither the patient nor science as a whole. We treat lab rats better than that.
SUMMERS, R., ELLIOTT, D., URBANJR, J., THOMPSON, R., & WEINSTOCK, J. (2005). therapy for active ulcerative colitis: A randomized controlled trial Gastroenterology, 128 (4), 825-832 DOI: 10.1053/j.gastro.2005.01.005
MAYER, L. (2005). A novel approach to the treatment of ulcerative colitis: Is it kosher? Gastroenterology, 128 (4), 1117-1119 DOI: 10.1053/j.gastro.2005.02.038
Vargas, D., Nascimbene, C., Krishnan, C., Zimmerman, A., & Pardo, C. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism Annals of Neurology, 57 (1), 67-81 DOI: 10.1002/ana.20315