On the other hand, if Laura Manuelidis is correct and spongiform encephalopathies are the results of viruses, it would be wise to remember one of their key characteristics: Viruses mutate.
Back in Chelsea, Manuelidis and I were seated in the back of a 9th Avenue bar. As she explained why viruses and not prions were the real culprits in the transmissible spongiform encephalopathy story, we sipped a pair of melon-based something-or-others. In retrospect, given the fact that my understanding of biochemistry was already more than a bit wobbly, a weak drink was probably a good thing.
“What do you make of the fact that researchers in the 1960s never saw an immune response during their experiments with kuru extracts?”
“There is an immune response,” she replied. “They just didn’t see it because it was transient or diminished. Like with HIV, there are many mechanisms that can make something not apparent as an immune response.”
Manuelidis explained that with diseases like kuru, CJD, and BSE, “what we found is that there are innate immune responses, very early in the disease.”
I shifted easily into Insistent Mode. “All right, but why couldn’t prions be the TSE pathogens?”
“Because that stuff [anything composed of protein] gets digested in the gastrointestinal tract, while viruses can go through gastric and intestinal juices unscathed. Viruses are built to be protected from the body’s defense mechanisms—and proteins are not.”
“But what about the reports, by Prusiner and others, indicating that prions couldn’t be destroyed by digestive enzymes like proteases?”
Manuelidis shook her head. She was wearing a look that suggested the question was one she’d heard plenty of times before. “Bill, everyone knows that PrP [prion protein] is relatively resistant to limited exposure to PK [a protein-dissolving enzyme found in our digestive tracts], but it breaks down if given a longer time to digest. In fact, it disappears.”
I was reminded of earlier studies in which lab chimps did not become infected with kuru after being fed infected material through a gastric tube. “So you’re saying that these seemingly immortal proteins can be broken down by our own digestive juices?”
“They’re not immortal,” Manuelidis replied. “And yes, all detectable forms of PrP are digested in the gastrointestinal tract, yet the invasive infectious particle [that causes TSEs like kuru] is not destroyed.”
“The same way that many viruses aren’t destroyed in our GI tract?”
“Right.”
If this was in fact true, then how were the prions, which researchers like Prusiner claimed to be the cause of kuru, getting past a gastrointestinal tract that had evolved to digest dietary proteins? At the very least, if prions did exist, then their spread through the Fore via cannibalism no longer made sense—since their digestive tracts would have broken down the proteins during the normal process of digestion. But if the infective agent causing kuru had been a virus, then transmission through the practice of ritual cannibalism made even more sense, since viruses weren’t broken down by our digestive systems.
Although the majority of the scientific community had clearly accepted prions as the pathogens behind a range of neurological diseases, there are still some strong voices besides Manuelidis’s opposing this view. In a new afterword of his 1998 book, Deadly Feasts, Richard Rhodes admitted to being intrigued by the very real possibility that Dr. Manuelidis could be right.
“I raise the virus issue,” he wrote, “partly because I now believe I gave it less than a fair hearing in the body of this book and partly because the arguments I’ve heard in its favor since I wrote, especially from Laura Manuelidis, seem to me compelling.”
Clearly there remains much for science to explore regarding transmissible spongiform encephalopathies. One can only hope that the funding agencies that poured tens of millions of dollars into prion-related research will not see this story as a fait accompli or that researchers who challenge the very existence of self-replicating, infectious proteins won’t have their voices silenced by skittish granting agencies or peer reviewers, perhaps too set in the conviction that prions are the cause of transmissible spongiform encephalopathies from kuru to mad cow disease and beyond.
* * *
52 According to Noel Gill, lead investigator of the “Appendix” study, further research is now underway to determine whether prion proteins also occurred in samples from the 1970s and earlier—before the appearance of BSE in the UK. Such a finding could reduce the significance of the 2013 study, since it would suggest that prion proteins in a population do not necessarily translate to a major outbreak of spongiform encephalopathy.
Epilogue: One Step Beyond
Hunger hath no conscience.