Now, it seemed, dozens of labs and research centers were eager to have her see the results of the work they had done to confirm her speculations. For the sake of her own peace of mind, she chose to accept invitations from those faculties, centers, and labs that had shown her some encouragement in the past few years — and in particular, the Carl Rose Center for Domain Research, based in Cambridge, Massachusetts.
The Rose Center stood on a hundred acres of pines planted in the 1950s, a thick forest surrounding a cubical lab building, the cube sitting not flat on the earth but elevated on one edge. Two floors of labs lay underground, directly beneath and to the east of the elevated cube. Funded in large part by an endowment from the enormously wealthy Van Buskirk family of Boston, the Rose Center had been doing molecular biology for thirty years.
Three scientists at Rose had been given grants by the Human Genome Project — the massive, heavily funded, multilateral effort to sequence and understand the sum total of human genetics — to analyze archaic gene fragments found in the so-called junk regions of human genes known as introns. The senior scientist managing this grant was Judith Kushner, who had been Kaye’s doctoral advisor at Stanford.
Judith Kushner stood just under five and a half feet high, with salted and twisted black hair, a round, wistful face that seemed always on the edge of a smile, and small, slightly protuberant black eyes. She was known internationally as a true wizard, someone who could design experiments and make any apparatus do what it was supposed to do — in other words, to fashion those repeatable experiments necessary to make science actually work.
That she spent most of her time nowadays filling out paperwork and guiding grad students and postdocs was simply the way of modern science.
Kushner’s assistant and secretary, a painfully thin young redhead named Fiona Bierce, led Kaye through the maze of labs and down a central elevator.
Kushner’s office lay on the zeroth floor, below ground level but above the basement: windowless, concrete walls painted a pleasant light beige. The walls were crammed with neatly arranged texts and bound journals. Four computers hummed faintly in one corner, including a Sim Engine supercomputer donated by Mind Design of Seattle.
“Kaye Lang, I am sopmud\” Kushner got out of her chair, beamed, and spread her arms to embrace Kaye as she entered. She gave a little squeal and waltzed her former student around the room, smiling in professorial joy. “So tell me — who have you heard from? Lynn? The old man himself?”
“Lynn called yesterday,” Kaye said, blushing.
Kushner clasped her hands together and shook them at the ceiling like a prizefighter celebrating victory. “Wonderful!”
“It’s really too much,” Kaye said, and at Kushner’s invitation, took a seat beside the Sim Engine’s broad flat display screen.
“Grab it! Enjoy it!” Kushner advised lustily. “You’ve earned it, dear. I saw you on television three times. Jackie Oniama on Triple C Network trying to talk science — wonderfully funny! Is she so much like a little doll in person?”
“They were all very friendly, really. But I’m exhausted from trying to explain things.”
“So much to explain. How’s Saul?” Kushner asked, doing well to hide some apprehension.
“He’s fine. We’re still trying to pin down whether we’ll be going into partnership with the Georgians.”
“If they don’t partner with you now, they have a long way to go before they can become capitalists,” Kushner said, and sat beside Kaye.
Fiona Bierce seemed happy just to listen. She grinned toothily.
“So…” Kushner said, staring at Kaye intently. “It’s been kind of a short road, hasn’t it?”
Kaye laughed. “I feel soyoungl”
“I am so envious. None of my crackpot theories have gotten nearly as much attention.”
“Just gobs of money,” Kaye said.
“Gobs and gobs. Need any?”
Kaye smiled. “Wouldn’t want to compromise our professional standing.”
“Ah, the big new world of cash biology, so important and secret and full of itself. Remember, my dear, women are supposed to do science differently. We listen and slog and listen and slog, just like poor Rosalind Franklin, not at all like brash little boys. And all for motives of the highest ethical purity. So — when are you and Saul going to go public? My son is trying to set up my retirement account.”
“Probably never,” Kaye said. “Saul would hate reporting to stockholders. Besides, we have to be successful first, make some money, and that’s a long way down the road.”
“Enough small talk,” Kushner said with finality. “I have something interesting to show you. Fiona, could you run our little simulation?”
Kaye moved her chair to one side. Bierce sat by the Sim Engine keyboard and cracked her knuckles like a pianist. “Judith has slaved on this for three months now,” she said. “She based much of it on your papers, and the rest of it on data from three different genome projects, and when the word came out, we were ready.”
“We went right to your markers and found the assembly routines,” Kushner said. “SHEVA’s envelope, and its little universal human delivery system. Here’s an infection simulation based on lab results from the fifth floor, John Dawson’s group. They infected hepatocytes in dense tissue culture. Here’s what came out.”
Kaye watched as Bierce played back the simulated assembly sequence. SHEVA particles entered the hepatocytes — liver cells in a lab culture dish — and shut down certain cellular functions, co-opted others, transcribed their RNA to DNA and integrated it into the cells’ DNA, then began to replicate. In brilliant simulated colors, new virus particles formed naked within the cytosol — the cell’s streaming internal fluid. The viruses migrated to the cell’s outer membrane and pushed through to the outside world, each particle neatly wrapped in a bit of the cell’s own skin.
“They deplete the membrane, but it’s all rather gentle and controlled. The viruses stress the cells, but they don’t kill them. And it looks like about one in twenty of the virus particles are viable — five times better than HIY”
The simulation suddenly zoomed in to molecules created along with the viruses, wrapped in cell transport packages called vesicles and pushed out with the new infectious particles. They were labeled in bright orange: PGA? and PGE?
“Hold it there, Fiona.” Kushner pointed and tapped her finger on the orange letters. “SHEVA doesn’t carry everything it needs to cause Herod’s flu. We kept finding a large clump of proteins in SHEVA-infected cells, not coded for in SHEVA, and like nothing I’ve seen. And then — the clump would break down, there would be all these smaller proteins that shouldn’t have been there.”
“We looked for proteins that were changing our cell cultures,” Bierce said. “Really doing a number on them. We puzzled over this for two weeks, and then we sent some infected cells over to a commercial tissue library for comparison. They separated out the new proteins, and they found—”
“This is my story, Fiona,” Kushner said, waggling her finger.
“Sorry,” Fiona said, smiling sheepishly. “It is just so cool we could do it this fast!”
“We finally decided that SHEVA turns on a gene in another chromosome. But how? We went looking … and found a SHEVA-activated gene on chromosome 21. It codes for our polyprotein, what we call the LPC, the large protein complex. A unique transcription factor specifically controls expression of this gene. We looked for the factor and found it in SHEVA’s genome. A locked treasure chest on chromosome 21, and the necessary keys in the virus. They’re partners.”
“Astonishing,” Kaye said.
Bierce ran the simulation through again, this time focusing on the action in chromosome 21 — the creation of the polyprotein.
“But Kaye — darling Kaye, that is far from the last of it. We have a mystery here. The SHEVA protease cleaves three novel cyclooxygenases and lipooxygenases from the LPC, which then synthesize three different and unique prosta-glandins. Two of them are new to us, really quite astonishing. All look very powerful.” Kushner used a pen to point out the prostaglandins being exported from a cell. “This could explain the talk about miscarriages.”