“Tangled Threads”

Mrs. K’s four students stand shivering as they follow their instructor and a Pierpont representative across the street from the white facade of the hotel to the grey and glass mountain of the pharmaceuticals plant. Despite the icy blasts that continue whipping through the narrow gap between the two buildings, their guide continues his speech.

“None of the facilities over here are actually over five years old,” he says. “Western development was impossible in Malkinagrad before the Soviet Union collapsed, and it took a decade after that for biotech industry to decide it was even a good idea to set up shop here.”

“So why did Pierpont move here?” asks Angelica.

“Well,” says the representative, “besides the declining property values – which makes a place like this a lot cheaper to build than it would be in, say, the US – we have an unprecedented chance to make a difference here. Any antibiotics we develop can go directly towards alleviating TB in the gulags, and a whole population in desperate need of the medical resources a firm like ours can provide.”

Waiting for the wind to pick up enough to obscure his comment, Lang leans over to the other students, whispering: “I bet they don’t mind the lack of FDA regulation either. I wonder what actually goes on in this place.” Fallon shudders (and not merely from the cold).

If Mrs. K is similarly skeptical about the charitable activities of their sponsor, she keeps them to herself. Instead, she examines the immense building before them, whose hundreds of windows must equate to an enormous heating bill in this weather.

“We heard about a bird flu outbreak last night,” she says, “has it been resolved?”

“Oh, that.” The representative pauses. “I think that the government had all the birds destroyed. We haven’t heard of any cases of human infection yet, but, then again, we have extremely strict quarantines. There’s not much that gets in or out of here without us knowing, microbial or otherwise. Which reminds me, you’ll have to leave most of your things in the waiting area when we get inside – can’t risk contamination.”

Up ahead, they can see the yawning profile of the park garage underneath the building along with the slender ramp leading up to the main entrance. Somewhere below, the sound of several engines reverberates loudly enough to be heard about the wind. The icy gusts pick up again, howling down the street as the group walks more quickly towards the door of the Pierpont facility.

***

After a lengthy check-in process, the group stands in the gigantic lobby of the Pierpont building, lit far overhead by a series of oblong fluorescent bulbs. Curiously, the music is the same as the hotel across the street. On the far side, near a bank of long windows, is a line of palm trees. Leaving the company representative and their teacher behind, the four students wander over to this odd garden. Fallon removes his baseball cap to examine the bark up close before noting the waxy texture of the leaf – it’s fake, though convincing from a distance.

“Class,” calls Mrs. K, her voice echoing against the ceiling, “don’t wander off. They have a tour planned for us.” Shuffling back towards the center of the lobby, the students approach just in time to hear the representative begin.

“This entire chamber is climate-controlled,” he starts. “There’s a set of enormous heaters on the roof that circulate air through the building – you can probably take your coats off, in fact.”

“And yet, they have fake plants,” mutters Maxine.

“Yeah . . . and for all the money they’re supposedly spending on health care, the surrounding area is a dump compared to this place,” adds Lang, making sure to stay out of earshot of their tour guide, who continues rambling about the facility.”

“If you follow me this way, we’ll proceed to the mezzanine, where most of the low-biohazard laboratories are located. The elevator here is actually powered by the same engines as a Boeing 747 – it can get to the top of the building in 20 seconds.”

“I wonder if it will take off,” snickers Angelica – unfortunately, Mrs. K hears and gives her a disapproving glare. The elevator door closes on the group, and, with a jolt, begins its climb.”

***

The group walks through seemingly endless halls of sterile laboratories, studying topics they’ve never heard, and which their guide makes little effort to explain. None of the technicians seem to notice them, adding to the mechanical – and unnerving – atmosphere of the facility.

“The labs in this corridor are all devoted to Marfan’s Syndrome . . .” the representative continues. Though Mrs. K continues to nod politely, her students can tell that she, too, is becoming bored – it’s the same expression she wears when one of their presentations in class runs too long. Finally, though they recognize a phrase in the representative’s speech.

“This over here is our prion laboratory . . .”

“Wait! Did you see prions?” asks Maxine, blushing a bit when she realizes how loud her exclamation was.

“Yes . . . you know something about prions?” asks their guide, seemingly amazed that any high school student knows anything about the research here.

“We studied Mad Cow disease and all the human ones in class,” she replies, rattling off a list of illnesses. “Kuru, Creutzfeld-Jakob . . .”

“It’s Yakob,” corrects Lang. “Like Yusef.”

“Thanks,” says Maxine, shooting him an irritated glare before turning back to the attendant. “What exactly are you working on?”

“A lot of things,” he says. “Actually, this is one of Pierpont’s big areas of research right now. On one hand, we’re simply interested in determining what makes a disease-causing prion different from the kind that is normally in a cell. More generally though, we want to know how information might be transmitted through proteins, just like it is through DNA.” He pauses for a moment, then adds, “If you’re looking for something to study, I guarantee you there’ll be a Nobel Prize for the lucky person who discovers protein-based inheritance.”

“Can we see inside?” asks Angelica.

The attendant looks at his watch. “I suppose . . . we have about an hour before I have to get back to work. Let me see . . . we can’t really go in the tissue prep room – as your probably know, it’s really hard to inactivate prions, so there are all sorts of safety precautions. But here, we can duck in and look at the modeling facility for a second.”

He leads them into a room very different from most of the laboratories they’ve passed. On the far wall is a small bench with the standard collection of bottles and tubes, but most of the room is taken up by computers.

“What is all this stuff?” asks Fallon, looking at one of the screens where what appears to be a piece of colored string periodically twists into odd shapes before unfolding again into a straight line.

“Well, as it so happens, a lot of the work we do here is theoretical,” says their guide. “That loop there is a rather simple representation of a prion protein – the program you’re watching is trying to predict what it will look like folded.

“Folded? You mean the three-dimensional structure that a protein possesses?” asks Maxine. On the screen, the thread unrolls again and repeats the folding process, undergoing a slightly different pattern of creases to reach the final product.

“Yeah….hard to believe such a small thing – such a small difference – can cause such horrible diseases,” says Angelica.

“Indeed,” agrees the representative. “But that’s what we have to figure out. How does a slight misfolding in a protein cause a brain to self-destruct? And how do we cure it?”

Questions:
1. What are prions? Why are they different than any other pathogen described in this course?
2. There is actually new evidence that chaperone proteins might be involved with prion transmission2. Find out why.
3. How might you suggest treating prion disease? What about halting its transmission?