As soon as Pam knocked on the office door, Karl Meyers jumped up from his desk and greeted her with a hug. What a difference from two weeks ago. This was the old Karl and she felt warm and comforted in his embrace.
Without delay he said, “Let’s go see your cultures,” and led her across the hall to his new lab. It was a model of contemporary lab design, similar to Pam’s lab at the Langmere and very different from the old quarters in which she’d worked years ago. But she recognized most of the equipment from her postdoc days. A comfortable feeling of déjà vu.
They spent almost two hours together at the microscope, studying and photographing the cultures from his experiment. As he’d said, the results were unambiguous. Like Pam had first seen a year ago, one of the compounds completely blocked plaque formation and cell death. She’d finally been vindicated.
Pam followed Karl back to his office, simultaneously feeling exhilarated and exhausted. The ordeal will soon be over.
Karl closed his office door and settled into the old-fashioned swivel chair behind his desk. Pam sat across from him in one of the wooden side chairs. The sun from the window behind the desk was bright in her eyes, but Karl noticed and got up to close the shades.
Then Pam asked the question that had been on her mind since he’d phoned. “Now that your experiment shows there really is an active drug, what do you see as the next move?”
Karl sat back and stroked his beard, as Pam remembered him doing whenever he was thinking about something. “That’s the question isn’t it. These results will restore your reputation, probably put you back in line for that Nobel Prize everyone was talking about. But first, I think we should try to identify the compound and make some sense out of what’s happened.”
“I agree,” Pam said. “We need to figure out what this stuff actually is.”
“At this point, all we know is that it’s not the aneurinide the Langmere is sending out. We just saw them side by side in the same experiment. One works like you said, the other does nothing. So what would you say to my calling a colleague in the Chemistry Department? There must be some analysis they can do to confirm that the active compound is different from aneurinide. And maybe start to identify it.”
“Good idea,” Pam said. “I’m pretty sure there are sensitive analytical methods that should be able to do just that.”
Karl reached for the phone. “Let me see when my friend can get together with us.”
• • •
Ed Coleman knocked on Karl’s door less than an hour later. He was a heavyset man, Pam guessed fortyish, with long red hair pulled back in a ponytail.
“Thanks for coming over so quickly,” she said when Karl introduced her.
“No problem,” Coleman responded cheerfully. “This got me out of grading exams for my Organic Chem class. I’ve taught the class for ten years, and this year I tried some of the new active learning techniques that are supposed to get the students more involved. But they don’t seem to be doing any better on the exam than they always have. So much for the latest educational fad.”
“Hopefully we have something more stimulating for you than grading exams,” Karl said. “We have a sample of a compound that’s supposed to be a drug called aneurinide. But our sample has an interesting biological activity that other batches of aneurinide don’t show. So we’re wondering if the stuff we have may actually be a different compound. Is there any kind of analysis you could do that would tell us whether it’s really aneurinide or not?”
Pam watched Coleman’s face as Karl talked. He didn’t seem to have recognized either her name or that of the drug.
“So basically what you want is to see whether your mystery compound, let’s call it an unknown so this sounds like chemistry, is the same as another compound you call aneurinide,” Coleman said. “That should be pretty straightforward. I assume you have the structural formula for aneurinide?”
“Sure, we can pull it up on Karl’s computer,” Pam said.
“Don’t bother doing that now, you can just send it to me later,” Coleman said. “Even better, do you have a sample of aneurinide here? What I can do is to run mass spectrometry on your unknown. That’ll give us an exact molecular mass, and we can see whether it’s the same as the molecular mass of aneurinide. If you have some aneurinide, I can also run it in parallel and we can see if the spectra of fragments produced during the analysis are the same. Or if you don’t have any, we can do some computational analysis to see whether the spectrum of your unknown is consistent with the aneurinide structure.”
“I have plenty of aneurinide in the lab, just give me a minute,” Karl said.
He went out briefly and returned with the compound.
“Unfortunately, we don’t have much of the unknown, though.” Karl held up what was left in the tube Pam had given him. It contained only a small amount of liquid, about a tenth of a teaspoon. “This is it, in a one millimolar solution. Pam, do you have more?”
“I have a bit more at home, but not a lot. I gave you about half of what I have.” This was scary. The tiny amounts left in those tubes were her last link to reality.
“No problem,” Coleman said. “Mass spectrometry is super sensitive. I’ll need only a small fraction of what you have. A microliter or two will be plenty.”
Karl had brought a pipette and a clean test tube in from the lab when he’d gone for the aneurinide. Now he transferred a tiny amount of liquid from the sample Pam had sent him to the test tube and handed it to Coleman.
“Here you go,” he said. “How long will it take for you to get the results?”
“Not long at all,” Coleman said. “It’ll just depend on when an instrument is available. I’ll shoot you an email as soon as I have something.”
• • •
Karl greeted her with a grin when Pam knocked on his office door the next morning. “I just got a message from Ed Coleman.”
Pam felt the adrenaline start to surge. “Is he going to get the results today?”
“He already has. No surprise, the drug that works is not aneurinide. He’s free until ten and says he’d be happy to show us the data. Want to pay him a visit?”
The door to Coleman’s office was closed when they got there. Karl started to knock, but they heard voices inside and he held up his hand to indicate they should wait. A few minutes later, the door opened and two students, a man and a woman, came out and walked away rapidly with their heads down. Coleman followed them out, an angry look on his face.
“I can’t believe it,” he said. “I just got the grades posted last night and here they are already, fighting with me about their scores. I love it when they tell me how hard they worked so they deserve an A, even if they got the answers wrong!”
Karl laughed and shrugged his shoulders. “I guess you can’t blame them for trying.”
“I suppose,” Coleman said. “Anyway, come on in. There’s no question about your results. The molecular mass of the sample of aneurinide you gave me was 354, which exactly matches the structural formula. But the molecular mass of your unknown was 388, not even close. And the spectra are totally different as well.”
He showed them two tracings with several peaks in each. Even to Pam’s untrained eyes, they were unrelated.
“This is great,” Karl said. “It certainly explains why our unknown behaves differently from aneurinide, even though that’s what it’s supposed to be. You’ve solved a mystery for us.”
Coleman smiled. “Just an everyday miracle of modern chemistry. I’m happy to have been able to help.”
“But now we of course have another question,” Karl continued. “Can you figure out what our unknown actually is?”
“I thought you’d ask that. I already ran your unknown’s spectrum against the National Institute of Standards and Technology database. It contains mass spectra for over two hundred thousand compounds, but unfortunately none was a match.”
Pam felt a surge of disappointment, but Coleman continued. “Don’t worry, that’s not a big surprise. But it does mean we have to do more analysis to determine the structure. And we need more material for that. Can you figure out where this stuff came from? You must have some idea of possible sources.”
Pam looked at Karl as she answered. “I suppose it must have come from the Langmere chemical library. I don’t see how else it could have appeared in the lab.”
“What’s the Langmere library?” Coleman asked.
“That’s the Langmere Institute in Boston,” Pam explained. “They have a chemical library of about a hundred thousand compounds that’s available for investigators to screen, and that’s what we were doing when we came upon the stuff we gave Karl. But when we tried to get more, we somehow got aneurinide instead, so we don’t know what the active compound really is.”
“That doesn’t sound too hard,” Coleman said. “Why don’t you just search the chemical library database for compounds with a molecular mass of 388, the same as your active material. That should whittle it down to a few dozen possibilities. The library folk may very well have the mass spectra of their compounds, in which case you could identify it directly. If not, we could either run mass spectra of the candidates or you could test them in your biological experiments, whichever is easier. Either way, problem solved.”
“That sounds great,” Karl said. He turned to Pam. “I’ll be more than happy to test whatever candidates you come up with.”
The end was in sight. Although it might not be so easy to access the Langmere database.
“Thank you both, you’ve been great,” she said. “I’ll need to go back to Boston to do the database search. I’ll get back to you with a list of candidates soon.”
• • •
Pam grabbed a cab to the airport in time to catch an afternoon flight. She was about to text Jake the good news when she saw there was an email from her lawyer. She recoiled in shock when she read it.
Please call me as soon as possible. They’ve decided to file criminal charges.