“It’s definitely not stopping,” Melanie said. “As I’ve mentioned, two of the patients scheduled for this afternoon have some of the same initial symptoms as the first dozen, a mix of muscle spasms, memory loss, gait problems, and personality changes, and boththese new patients are particularly young. One is still in his twenties, the other in her thirties. I won’t be at all surprised if later on today we have two more significantly younger cases to add to our series.”
“All the more reason we have to come up with a diagnosis,” Jack said. “People in their twenties don’t develop Alzheimer’s.”
“That’s not true,” Laurie interjected. “I remember reading that a nineteen-year-old boy in China was diagnosed with Alzheimer’s a year or two ago.”
“You are joking,” Jack said, staring at Laurie.
“I’m not,” Laurie said.
“Well, if it’s true, it’s certainly an outlier,” Jack said. “Besides, according to NMS Labs, we’re not dealing here with Alzheimer’s, so it doesn’t matter. But we are dealing with a neurodegenerative disease. That’s perfectly clear considering the symptoms the patients are experiencing and especially with our having just had an opportunity to look at Stanley Kramer’s brain. And what we could see grossly, which I admit was on the subtle side, will undoubtedly be more pronounced when we get to look at the histology.”
“So, what’s the point you are trying to make?” Bob asked, staring at Jack, as were Laurie and Melanie.
“My point is that we have to go back to basics if we are going to have any luck solving this current outbreak of dementia and give up trying to put a convenient, familiar name, like Alzheimer’s or mad cow disease, on it. My sixth sense is telling me it’s neither, considering its unusually rapid course.”
“What do you mean ‘go back to basics’?” Laurie questioned.
Just as Jack opened his mouth to explain, the waitress appeared, and she was defying gravity. Somehow she was carrying four hamburgers, two large French fries, and a generous container of Heinzketchup. Wasting no time and needing little help, she was able to distribute the hamburgers and set the ketchup and French fries onto the table. After asking if there was anything else anyone wanted at the moment and getting noes for an answer, she took her leave.
“I’ll let us all enjoy our burgers,” Jack said before taking his first welcome bite and enjoying it thoroughly. Just a few minutes later, after inhaling his hamburger, he pushed his empty plate away and leaned forward, forearms on the table so he didn’t have to speak so loudly in the noisy environment. “While you eat, I’ll carry on where I left off. I’m sure all of you are aware that it is generally believed that all neurodegenerative diseases, including those that are being seen here in Essex Falls, are caused by a rather peculiar protein culprit, called a prion.”
Jack purposely paused and stared at each of his lunch companions in turn. Everyone kept chewing, staring back at him, hoping one of the others would say something. He knew that no one felt all that comfortable talking about prions, even himself for that matter. Although the name had been devised a bit more than forty years previously by taking the first two letters of the wordproteinand combining them with the last four letters of the wordinfection,he knew it was still a controversial or even contentious subject, since its basic tenet—of an inanimate protein being infectious—was so revolutionary. Prior to the advent of the concept of prions, it was an accepted tenet of biology that for something to be infectious it had to involve genetic material either in the form of DNA or RNA and reside in a virus, a bacterium, or a fungus.
“I’ve heard the term but I couldn’t tell you much about it,” Melanie admitted when Jack looked at her directly. “So, you think they are causing this outbreak we are seeing here in Essex Falls?”
“The current theory is that all neurodegenerative diseases are caused by infectious prions,” Jack said.
“All I know about prions is that they are proteins mostly associated with the brain with an unknown function,” Bob said. “The problem with them is that they can go haywire and start interrupting brain function, which happens in Alzheimer’s disease. They cause extensive nerve cell death and ultimately death of the individual.”
“They are definitely proteins,” Laurie added. “Infectious proteins, which means that somehow they have the ability to cause their normal, noninfectious brethren to become infectious and form fibrils inside neurons and plaques outside, and it happens in an exponential fashion.”
“All true,” Jack said. “Unfortunately, I’m afraid we are a case of the blind leading the blind. My sense is that none of us know much about prions, which is obviously an enormous handicap if we are trying to understand, diagnose, and hopefully stop an outbreak of what must be a prion disease. Let’s think about what we do know. Laurie, you are first up. Tell us more about how prions work their black magic.”
“I wish our neuropathologist, Christine, was here,” Laurie said. “She could fill us in a lot better than I.”
“True, but she’s not here,” Jack said. “Maybe we can get her to come for a night or two, or in a worst-case scenario, we can organize a Zoom. In the meantime, let’s pool what we do know. You said that prions are infectious proteins. Tell the group what you mean.”
“All protein molecules are long chains of specific amino acids held together by peptide bonds,” Laurie began, mimicking Jack by leaning forward to be better heard. “Because each protein is an invariable sequence of amino acids, each molecule ends up having avery specific physical shape, which is vitally important as it is a protein’s three-dimensional shape that determines its function, like acting as a catalyst for a vital chemical reaction. Normal prions are unique proteins that are necessary for the function of the neurons in our brains but which can be coaxed to assume a nonfunctioning shape even though this nonfunctioning shape is the exact same molecule in terms of its amino acid structure. This aberrant shaped prion has the ability, when it comes in contact with the normal prion, to cause the normal prion to change its shape. This newly reshaped form can go on to alter another normal prion creating a chain reaction, or it can combine with other misshapen molecules to form fibrils and amyloid plaques. Currently the thought is that these fibrils and plaques ultimately interrupt brain function and kill the neuron.”
“Well said,” Jack complimented and even clapped quietly. “These bad protein prions, once they get on the scene, cause the normal, good prions to change to a dysfunctional state, which eventually kills the neuron, causing a progressive neurogenerative disease. So, let’s review. We’re dealing here with an unknown neurodegenerative disease caused by a particular infectious prion. Okay, now let’s talk about transmission. Bob and Melanie, this is your area of expertise being out there in the clinical trenches, so to speak. What can you tell us? Have you any thoughts, knowing the patients and their families as well as you do?”
Bob and Melanie exchanged a quick, mildly nervous glance after which Melanie responded, “I’m not sure exactly what you mean by ‘transmission’.”
“Simply, how do we think these people have gotten this disease,” Jack explained. “We have to figure that out if we are going to have any chance of stopping this outbreak, if it is an outbreak. For themoment we are going to consider it an outbreak. My understanding is that all twelve cases and potentially the two more you will be seeing today have all occurred in the last month or so and they all live here, in Essex Falls.”
“Yes, that’s correct,” Melanie said. “Obviously we’ve had our share of Alzheimer’s patients over the years, but seeing this many with such similar, rapidly developing symptoms is definitely new for us, especially with three progressing to death within weeks.”
“It’s shocking, the more I think about it,” Bob added.
“I guess the idea of how they’ve gotten this disease hadn’t occurred to me,” Melanie said, “but I suppose it should have. What I’m remembering from courses I’ve taken over the years is that the three main methods of getting a disease are ‘acquired,’ ‘familial,’ and ‘sporadic.’ We can immediately eliminate the ‘sporadic’ because that requires a very specific random mutation and the chances of that happening suddenly in this many people is almost zero. We can also eliminate familial because only two of the twelve patients are related in any way and that’s by marriage, not by genetics. So, we are left with it being acquired.”
“My thoughts exactly,” Jack said. “Mad cow disease was acquired by eating cows infected with a specific infectious prion. Could something like that be involved here in Essex Falls? These patients of yours had to have gotten their infectious prions from someplace.”
“I can’t imagine,” Bob said. “You’re talking about someone having an infected herd of cattle.”
“Something like that,” Jack said. “But I don’t think it has to be necessarily beef. Maybe it could be pork or even chicken. My guess is that all live animals, particularly mammals, have prions. We’ll have to ask Christine if it’s possible for other species’ prions to beinfectious for us humans. They must be, or at least some, because those were definitely cow prions that killed all those people in England during the mad cow outbreak.”
“I suppose Melanie and I can start asking those infected families about their eating habits,” Bob said. “We can find out if they share any unique similarities.”
