“It was the same story with a different emphasis. It was all about the path in your mind that not trusting makes. You know, it leaves a trail like the stones. She was telling me that my dad left a trail in my mind. Of course the moral had to be that it’s up to me to give the stones a new meaning. In the story the woman’s husband and the whole tribe gave the stones a new meaning. With the new trust came new feelings. It’s a versatile story.”
“Funny. I wrote this poem. It seems like she would have told me the meaning she told you. The part about reinterpreting something that happened in the past.
“Anyway did the story soften you up, Sam?”
“Give me a break. What man with any balls is going to be softened by a story?”
The phone rang. It was T.J.
“We got an e-mail. They’re ready to talk at Harvard.”
“Okay. We’ll come to the scrambler and place the call.”
Sam turned on the speakerphone and everyone but Sam, Anna, Grady, and T.J. cleared the office area that had been set up in the house’s spacious library.
“I think we have it licked,” Fielding began. “We elected George to explain it.”
“I don’t know how much you want me to try to cover on the phone.”
“The whole thing,” Anna said. “I want to know what’s wrong with Jason.”
“Well, as you know there were two codes just to get into the main files. Paul cracked the second, but then individual files were encrypted and we had to go back to Big Brain four times. Jason had hacked into various parts of the Grace computer and downloaded backup files from the lab in Kuching. We are the first to read them, and it took a whole team of us including some folks from the University of Washington and a private foundation lab. But we got their game or at least part of it. And it is fascinating.”
“How does it affect my brother?”
“Okay, maybe I should start with the rather glum conclusion and then explain it.”
“Yes.”
“They altered his DNA. The DNA of his neurons. His brain. It’s probably permanent unless the lab that did it has a fix. But there does seem to be a treatment and we know the active ingredient. It is a temporary antidote that will relieve the effects of the DNA alteration for about twenty-four hours. If he takes it every twenty-four hours, he may not feel the effects of what has been done to his brain.”
“So he’s paranoid because of this?”
“I’m afraid so.”
“This seems incredible.”
“Well, there is a lot to it. I can explain if you like. I will tell you that we can send you some hormone that will make him feel better.”
“Yes. Yes.”
“All right Where to start… let’s see… they needed to alter just certain of his brain cells. They started with neurons in the limbic system, the prefrontal cortex, and the amygdala. They alter them genetically. Once changed, they have radical effects on people’s state of mind. To change them genetically they alter the DNA. To do that they deliver new DNA that affects certain predetermined neuron cell types.”
Anna seemed to pale.
“Okay. We’re all ears,” Sam said.
“Okay, to begin with, if we’re trying to influence anxiety we go to the cells that influence that mental state. Anxiety is largely controlled by certain brain cells in the limbic system, amygdala, and prefrontal cortex.”
“Okay.”
“There are two kinds of cells there. Some enhance a response, such as anxiety, and others reduce it. Activator cells or inhibitor cells, we call them. Grace calls the inhibitor cells suppressor cells, so we’ll go with their lingo. If you increase the sensitivity of anxiety-suppressor cells, you will actually be suffering less anxiety, whereas the opposite is true if you increase the sensitivity of an activator cell. To increase sensitivity to a neuron they add what we call a receptor. It’s actually a molecule on the dendrite.”
Sam let George know that they’d become familiar with the workings of dendrites and synapses, courtesy of Dr. Yanavitch.
“If I understand this,” Sam said, “my next question is how they forced the DNA changes in Jason’s brain.”
“To deliver the DNA coding sequence they use a structure that is in some respects like a virus and it is called a vector. To make it they break apart a virus and strip away its protein coating. Then they insert two pieces of DNA. One causes the formation of the extra receptor molecule on the dendrites and that is called the coding sequence. The other is called the promoter strand and it identifies the cells that are to be changed by the coding sequence. It’s like the passkey to changing only the neurons that make a difference in the anxiety response.
“Specifically, Grace breaks down a monkey herpes virus. They splice in the coding DNA and the promoter DNA, reinstall a new protein coat around this new ring of DNA, and bam, they have a delivery vehicle that infects a foreign cell and installs new coding sequences. All body cells of different function are defined by the proteins that they make. What defines those special proteins that make a cell unique are the promoters that are active in the cell to produce their unique proteins. For cells that have specialized functions like a cell in the amygdala of your brain, involved in an anxiety response, there must be unique proteins produced by that cell and cells of the same function. Each cell type will have its own promoter.
“If the vector enters a neuron that doesn’t recognize the promoter, then there is no change in that cell. They introduce the vector (which for these purposes is like a virus that won’t replicate) and it invades all or most brain cells indiscriminately. The protein changes forced by the changed DNA will only apply to the desired cells of the brain. So if any given neuron happens to be a brain cell concerned with anxiety, the vector basically says, ‘Honey, I’m home,’ and the cell recognizes that voice.
“Now this is something of a simplification because Grace has identified over a dozen unique cell types involved in the anxiety response; therefore they used a dozen different forms of the vector, each with a different promoter but all having the same coding sequence. Remember that the coding sequence is just the formula for producing the extra receptors.”
Sam looked at Anna, who was nodding her head as if in shock.
“Here is how the research progressed. Grace started with rats and mice but moved to monkeys in their Kuching, Malaysia, lab. First thing they discovered was that it’s easier to take a calm monkey and make it permanently nervous than vice versa. So that is how they started. In effect, to learn about making nervous monkeys calm, they initially studied the reverse process. To make a monkey nervous all the time you put extra responders in those activator brain cells concerned with the fear response. You just turn up the sensitivity of the activator cells.”
“And this is what they did to Jason?”
“Well, we’re not there yet but this is the research track they were taking. They were making calm animals nervous as a prelude to curing anxiety disorders. Now remember that a vector is just DNA with a protein coat, and-”
“We understand,” Sam cut in. “What about the opposite process?”
“I was just getting to that. To make Jason calm they don’t touch the activator cells or turn down their sensitivity; they use a hormone to stimulate an inhibitor or as they call it a suppressor cell.”
“A hormone?”
“Yes, and get this, it turns out they use insect hormones, called juvenile hormones. They aren’t produced in mammals.”
Sam looked to Anna, shaking his head, wondering what was next.
“The activator cell receptors and the suppressor cell receptors are sensitive only to juvenile insect hormones. Each to a different hormone. They got part of the DNA sequences for the receptor molecules from insects and mass-produced the hormones in the lab.”
“This is sick,” Anna said.
“Yeah. So they can install receptors that make the calm person nervous by making activator cells more sensitive. To counteract the effect you introduce the hormone that sensitizes the suppressor cells to make the subject calm again. To make him very calm you just superboost the suppressor cells.”
“Or you could do the same thing in reverse,” Sam said.
