DEBATE ON PLAGUE TIME


The heated and sometimes nasty debates over infectious causation of multiple sclerosis took an interesting turn after Plague Time was published. After reporting an association between C. pneumoniae and multiple sclerosis, researchers at Vanderbilt University received a great deal of criticism from other researchers whose experiments did not confirm the association. The Vanderbilt group explained the discrepancy by pointing to several features of their own protocol that they had introduced to make it much more sensitive than previous protocols. The other labs, however, did not replicate exactly the Vanderbilt protocol. Instead, as is often the case in modern medical research, each lab used its own particular variations. Such quasi-replication has been good enough to generate agreement on infectious causation for many diseases during the first century of experimental validation of the germ theory, but that success has now left the health sciences with diseases for which quasi-replication may be insufficient.
To resolve the issue the Multiple Sclerosis Center of the Carolinas Medical Center recently set up an experiment. Each of the labs received twenty-two samples of spinal fluid from multiple sclerosis patients and twenty-two control samples from people who did not have multiple sclerosis. The specimens were coded so that the researchers running the tests had no knowledge about the identity of each sample. Only the Vanderbilt group detected the C. pneumoniae at a significantly higher rate than in the samples that actually had been laced with C. pneumoniae. As they had claimed, their protocol was more sensitive.
While this work was going on, another research group found that people with the epsilon 4 allele were also more vulnerable to multiple sclerosis. Still, another group found that smokers were more vulnerable to multiple sclerosis. As with atherosclerosis, the evidence now warrants a shift in the debate, to consider whether C. pneumoniae is causing multiple sclerosis or just an innocent bystander.
The evidence for an association between C. pneumoniae and Alzheimer's has taken a similar turn. As Plague Time was going to press there had been the initial confirmation of the association and then three failures to confirm. As with the multiple sclerosis research, none of the three failures repeated the protocol exactly, leaving a great amount of room for ambiguity of interpretation. A fourth attempt by James Mahoney's lab at McMaster University also failed to confirm the results, at which point Mahoney called Alan Hudson, who was one of the senior authors of the original study to check the protocol. Hudson told Mahoney that the chance of detecting the organism on one test is so small that each brain sample needs to be tested many times. Each brain then needs to be assigned as positive or negative for C. pneumoniae depending on whether at least one of the tests for the sample was positive. When Mahoney's lab ran multiple tests on each sample, they, like Hudson's lab, found that the Alzheimer's brains came up positive for C. pneumoniae significantly more frequently than the control brains. Once again, the controversy is shifting from the presence to the role of C. pneumoniae: cause or bystander?
These studies all pertain to the portion of the new germ theory that emphasizes the broadening recognition of infectious causation of chronic diseases. But the part of the theory that emphasizes evolutionary solutions to acute infectious diseases also has been reinforced during the year since Plague Time was initially published. The need for an evolutionary strategy for vaccination was underscored during the summer of 2001 by a report of evolutionary change in the bacterium that causes whooping cough. The report found that the causal organism has evolved to evade control by the whooping cough vaccine. Now would be a better time than later for vaccine developers to generate a whooping cough vaccine that would guide such evolutionary changes toward benignity by selectively knocking out the harmful variants.
Most of these developments went largely unnoticed by a popular media preoccupied with mad cow disease and foot-and-mouth disease. These stories are disturbing and worthy of attention, but I think not as important globally as some of the stories that have been smoldering largely below the lens of the media. The greatest uncertainty with regard to mad cow disease is whether the latency between infection and the human version of the disease, new variant Creutzfeldt-Jakob Disease (nvCJD), is less than about fifteen years or substantially greater. If the latency is about fifteen years, then the United Kingdom is already about halfway through its epidemic with a current total of about one hundred cases of nvCJD. If the latency is twenty to thirty years then the U.K. may have witnessed just the beginning of a regional disaster that could result in many thousands of painful deaths. The answer will be known in a few years as the timers tick away in an unknown number of future victims. But even at its worst the global threat to human health from mad cow disease will be nothing like the disastrous effects of diseases such as AIDS, or even influenza. There are too many controls that are now in place or can quickly be enacted to control nvCJD. Just as importantly, the prions that cause nvCJD do not have the evolutionary flexibility that would transform them into new agents of global disaster. They are simply a normal protein that has folded in a damaging abnormal conformation. They don't have the virtually limitless scope for change and adaptation that allows our more familiar DNA-or RNA-based pathogens to persist and sometimes thrive in the midst of our collective efforts to destroy them.
Except for the pain and suffering of the unlucky cows attacked by foot-and-mouth disease, its threat is mainly economic. Cows may need to be destroyed to keep the disease from becoming established in the few places in the world where it is not already established. Where these efforts fail, cows will need to be vaccinated and the economic prices of vaccination paid.
The examples mentioned above are just a few of the discoveries relevant to the new germ theory that have occurred during the first year since the hardback edition of Plague Time went to press. The long list includes many more: an association between number of lifetime sexual partners and prostate cancer, providing further evidence that prostate cancer is caused by a sexually transmitted pathogen; the discovery of a virus associated with low sperm counts m men; evidence that head and neck cancers are caused by papilloma-viruses, which apparently infect the head and neck region through oral sex; historical evidence from the islands north of Scotland indicating that some childhood leukemia is caused by infection; immunological and virological evidence implicating infectious causation of type 2 diabetes; an association between adenovirus and obesity; positive effects of antibiotics on irritable bowel syndrome, implicating infectious causation; and evidence showing that stomach cancers are caused by the peptic ulcer bacterium, H. pylori, and can be cured with antibiotic treatment. Stay tuned.
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