“That’s not true. Everything we’ve done, we would do again, regardless of whether you knew Vyrogen had commandeered your research or not. We needed proof. And now, I need you to help us understand the connection. To what end does Vyrogen intend to use your research? Why do they need it? It’s your turn to do the heavy lifting, AJ. So stop whining, and do what we hired you to do.”
The prideful, defiant side of him wanted to challenge her, but the scientist in him knew she was right. More importantly, she was in charge. The conversation was over.
Having witnessed the entire drama, Kalen swept in with perfect timing.
“Hey guys, you should come take a look at this,” he said. “You won’t believe what VanCleave found.”
VanCleave cleared his throat. “Do you remember the data anomaly that Veronika briefed us on when we first arrived in Prague?”
“Yes, the spike in homeless deaths and the coroner’s reporting of toxic shock as the cause of death,” Albane replied.
“I think I’ve figured out why. Chiarek Norse was a participating hospital in the free vaccination program this winter in Prague. That’s how they found their test and control groups of human subjects,” said VanCleave.
“Let me guess, they used homeless people to form the test group,” AJ said, aghast.
“Twenty-five homeless persons were involuntarily enrolled in a project code-named the Calypso Directive and received treatments which ultimately culminated in twenty-one of their deaths,” said VanCleave.
“Wait a minute, isn’t that unorthodox for a drug company?” Kalen interrupted.
“Unorthodox, unethical, unfathomable… not to mention entirely illegal,” said AJ.
“Why would they do something like that?” Kalen pressed.
“Expediency. Greed. Complete madness, who knows,” AJ sighed.
“Not true. You do know why,” Albane said.
“I do?”
“We all do. Project BioShield. Vyrogen needs to show BARDA proof of concept before the money dries up. They’re under pressure, racing against the clock, and so they’re rushing.”
“During her briefing in Boston, Meredith implied that her wonder drug was in the final stages of testing,” said Kalen.
“The evidence we’ve uncovered contradicts that,” VanCleave said.
AJ nodded. “I agree. Vyrogen is still early in the development phase. The data I looked at indicates at least four different AAV DNA prime-boosted vaccine formulations were evaluated over the past three months.”
“Say again, in English this time,” Kalen said.
AJ sat down and faced the group. “Is anybody interested in a five-minute Immunology 101 course?”
The group nodded.
“Like an army, the human immune system also uses scouts to identify and tag foreign invaders that enter the body. These scouts are called lymphocytes. The invading pathogens have proteins, called antigens, on their surface that the scouts use to identify the pathogen as self or not-self. When a lymphocyte finds a pathogen, it tries to connect to the invader’s antigens. If it recognizes the antigen, in other words if the immune system has a memory of the pathogen, then it activates other lymphocytes to rapidly produce millions of antibodies specific to that particular invader. The antibodies spread throughout the body, latching onto the antigens of the invading pathogens. Sometimes, by binding to the pathogen, the antibodies are able to neutralize it. In other cases, the antibodies simply mark pathogens for destruction by macrophages.
“But, if the immune system has no memory of a pathogen, the body doesn’t know which antibodies to produce. In these cases, the immune response takes longer. The scouts take the antigen back to the lymph nodes, aka central command, and recruit lymphocytes to manufacture antibodies that will work against the new threat. Once the antibodies are released, the rest of the immune system is alerted, and the macrophages and lymphocytes go to battle. The problem is that while the central command is gearing up for its retaliation, the invader is multiplying unfettered.”
“That’s the reason for vaccines,” Kalen said, “to give a small dose of the bad stuff so the body can fight back if it ever sees the germ again.”
“You get an A+,” AJ said.
“But that’s not what Vyrogen is after, is it?” Albane said.
“No. They’re investigating an entirely new path in medicine. They are trying to use gene therapy to prime or program a subject’s immune system to respond quickly to an infection, even in cases when the subject has no ‘memory’ of the invading pathogen.”
“How can they accomplish that with gene therapy?” Kalen asked.
“By copying my dissertation,” AJ said, laughing at the irony. “At BU, I was investigating the possibility of using gene therapy to program existing lymphocytes to recognize antigens they had never seen before and produce antibodies they had never produced before; thus, conferring immunity to the subject even after first contact with a new pathogen. I used a specific type of virus called an Adeno-associated vector virus, or AAV, to insert DNA into existing Memory B cells in mice. The new DNA contained instructions for making antigen-specific receptors and antibodies that the Memory B cells of the mice were not previously programmed to make. Then we injected the mice with a target pathogen to see if they would mount a robust immune response. To everyone’s utter disbelief, including mine, it worked.”
“Why is the gene therapy approach any different or better than using a vaccine?” VanCleave pressed.
“Aaahh. The billion dollar question. There are three main problems with vaccines. First, many vaccines require dosing regimens of multiple shots, spread out over many months, with periodic boosters to confer immunity. Vaccines must be administered prior to infection to be effective. Once a person is sick, administering a vaccine is like handing a bulletproof vest to someone who has already been shot. Second, vaccines are not without side effects. In addition to introducing DNA from the target pathogen, vaccines also contain toxic adjuvants and unintentional viral or bacterial DNA that can cause systematic and lasting side effects in patients. Third and finally, many pathogens exist — Lyme disease, Ebola, HIV/AIDS, to name a few — that we don’t have vaccines for.”
“Immune boosting through gene therapy appears to confer immunity much faster than vaccines do. Recent research on prime boosting for anthrax shows that subjects could have full immunity in as little as three weeks, as compared to eighteen months when relying on the existing anthrax vaccine. Even more exciting than that is the idea of using gene therapy as a therapeutic for patients that are already infected. In my experiment, I was able to elicit full-scale antibody production against a new pathogen in infected mice within seventy-two hours of treatment. Ideally, we’d like that surge to occur within half the time—”
“This is all fascinating, but what does gene therapy have to do with Foster? And more importantly, why the hell is Vyrogen decoding his genome?” Kalen asked.
AJ nodded. “Kalen is right, it doesn’t make sense. Back in Boston, Meredith Morley told us that Foster was infected with a mutated strain of H1N1, but I can’t see how sequencing Foster’s genome relates to that. As we collect more pieces of this puzzle, the less Foster seems like a mole and the more he looks like a test subject.”
“How can we confirm that?” Kalen asked.
“Maybe it’s time to ask him,” Albane said, with a straight face.
Kalen laughed. “I think you’re forgetting something, my dear. We still don’t know where Foster is.”
Albane smiled. “VanCleave, will you please show the others the probability matrix you’ve been working on?”
VanCleave grabbed his tablet computer. “Using the data the Coordinators compiled investigating Foster’s background, I built a probability matrix to analyze his social network. I wanted to identify and rank the people he is most likely to contact for help. The top ranked prospect is this woman, Julie Ponte,” he said, turning the screen so the others could see her picture. “Ponte is thirty-two, unmarried. Graduated from Tulane University, Foster’s alma mater, one year after he did. According to her work visa, she lives in Vienna and is employed by an Austrian contract research company called Wein BioScience which, I might add, was purchased eighteen months ago by Vyrogen Pharmaceuticals.”