“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.”
Kaye frowned in concentration.
“We calculate that a full-bore SHEVA infection could produce enough of the new prostaglandins to abort any fetus in a pregnant woman within a week.”
“As if that isn’t strange enough,” Bierce said, and pointed to series of glycoproteins, “the infected cells make these as byproducts. We haven’t analyzed them completely, but they look a lot like FSH and LH — follicle stimulating hormone and luteinizing hormone. And these peptides appear to be releasing hormones.”
“The old familiar masters of female destiny,” Kushner said. “Egg maturation and release.”
“Why?” Kaye asked. “If they’ve just caused an abortion . . . why force an ovulation?”
“We don’t know which activates first. It could be ovulation, then abortion,” Kushner said. “Remember, this is a liver cell. We haven’t even begun investigating infection in reproductive tissues.”
“It doesn’t make sense!”
“That’s the challenge,” Kushner said. “Whatever your little endogenous retrovirus is, it’s far from harmless — at least to us women. It looks like something designed to invade, take over, and screw us up royally.”
“Are you the only ones who’ve done this work?” Kaye asked.
“Probably,” Kushner said.
“We’re sending the results to NIH and the Genome Project today,” Bierce said.
“And giving you advance notice,” Kushner added, putting her hand on Kaye’s shoulder. “I don’t want you to get stepped on.”
Kaye frowned. “I don’t understand.”
“Don’t be naive, dear,” Kushner said, her eyes bright with concern. “What we’re looking at could be Biblical bad news. A virus that kills babies. Lots of babies. Someone might regard you as a messenger. And you know what they do to messengers who bring bad news.”
14
Atlanta
Dr. Michael Voight strode ahead of Dicken on long, spidery legs down the hallway to the residents’ lounge. “Funny you should ask,” Dr. Voight said. “We’re seeing lots of obstetrics anomalies. We’ve had staff discussions already. But not about Herod’s. We see all kinds of infections, flu, of course, but we still don’t have the test kits for SHEVA.” He half-twisted to ask, “Cup of coffee?”
Atlanta’s Olympic City Hospital was six years old, built at city and federal expense to take the pressure off other hospitals in the inner city. Private donors and a special set-aside from the Olympics had made it one of the best-equipped hospitals in the state, attracting some of the best and brightest young doctors, and a few disgruntled older ones, as well. The world of HMOs and managed care was taking a toll on skilled specialists, who had seen their incomes plummet in the past decade and their patient care practices controlled by accountants. Olympic City at least gave the specialists respect.
Voight steered Dicken into the lounge and drew a cup of coffee from a stainless-steel urn. Voight explained that interns and residents alike could use this room. “It’s usually empty this time of night. It’s prime time out there — time for life to lurch on and deliver its careless victims.”