Children of The Night

Chapter Seventeen

The summer of 1991 was as wet and rainy as anyone in Boulder could remember, but still, by late August, the foothills below CDC were brown, the meadow beyond Kate's. house was dustdry and browning, and lawns in town needed daily watering. Just as the local children were heading back to school on the week before Labor Daya schedule which Kate, born and raised in Massachusetts, found appallingly prematurethe stormy weather disappeared and the forecast changed to a regular schedule of hot, dry, summerlike days.

Kate hardly noticed. The world outside her office and the CDC labs seemed more and more unreal. Rising before sunrise, at work by seven A.M., rarely home before ten or eleven at night, it might as well have been midwinter for all the sunlight and fine weather she had appreciated.

She remembered a few nonresearch events of the month. Tom had lost his temper when she had shown him Lucian's letter, wondering just what that “ghoulish son of a bitch” was trying to do, scare her to death?

Tom had gone on his Canyonlands trek in August, but had called her whenever he could. After returning he spent a few days at the house but then moved his stuff to an apartment in Boulder, no more than ten minutes away. He still stopped by most eveningsat first to talk to Kate, and then, as her hours in the lab grew longer and longer, to check on Julie and Joshua before he drove home.

There had been a few calls and visits from Lieutenant Peterson or the older sergeant, each time to report no progress. After a while she instructed her secretary not to interrupt her when the police called unless there were something new to report. There never was.

Kate did remember the phone call she received at home near the end of the summer.

“Neuman? Is that you?”

It was almost midnight, she had just come indog tired but buzzing with excitement as usualhad checked on Josh, poured herself some iced tea, and was nuking a microwave dinner. The ring of the phone had startled her. The voice on the other end seemed vaguely familiar to her tired mind, but she could not quite place it.

“Neuman? I'm sorry to bother you this late, but your babysitter said that you wouldn't be home until after eleven. “

“O'Rourke!” she said, suddenly identifying the soft Midwestern accent. “How are you? Are you calling from Bucharest?”

“No, from that other drab secondworld city . . . Chicago. I've rotated back to the World for a while.”

“Wonderful.” Kate sat on a kitchen stool and set her iced tea on the counter. She was surprised at how happy she was to hear the priest's voice. “When did you get back from Romania?”

“Last week. I've been doing my dog and pony show at parishes around the country, trying to raise money for the ongoing relief program. It's not so easy now that Romania has been out of the news for so long. It's been a busy summer . . . newswise. “

Kate realized how insane the entire year had been in terms of news. First the Gulf War and the national jubilation at its quick resolutionmuch of which she had missed during her Romanian stintand now the upheaval in the Soviet Union. Two weeks earlier, the morning paper had heralded Gorbachev's removal from office because of illness. That night, when she had switched CNN on for the eleven-thirty headline news, word was that Gorbie was a prisoner and that the coup might be in trouble. The next time she took a break from lab work to check the newsWednesday the nineteenth of AugustGorbachev was back in power, sort of, and the old U.S.S.R. was breaking up forever.

Kate now realized that she had never taken time to wonder how all of this distraction and disruption might be affecting the orphanage situation in Romania. “Yes,” she said at last, “it has been busy, hasn't it?”

“How about you?” asked O'Rourke. “Have you been busy?”

Kate smiled at this. She had almost grown used .to the eighteenhour days. It reminded her of her residency, although her body had been much younger and more resilient in those days. “I've kept myself out of trouble,” she said, wondering at why she used that phrase even as she heard herself say it.

“Good. And how is Joshua?”

Kate could hear the anxiety in the priest's voice and realized that it took some courage for him to ask. When she had left the country she had promised to write and keep him informed about the child's welfare, but except for one note in early June, she had not taken time to do so. She remembered how sick Josh had been when they had left the country and realized that the priest must halfexpect to hear of the baby's death.

“Joshua's good,” she said. “Almost all of the symptoms have been stabilized, although he still requires a transfusion about every three weeks.” She paused. “We're doing some experiments on the cause of his problem. “

“Good,” O'Rourke said at last. It was obvious that he had hoped to hear more. “Well, there is a reason for this latenight call.”

Kate glanced at the kitchen clock and realized that it must be almost one A.M. in Chicago.

“I'll be bringing my plea for funds to the Denver Council of Churches next monthon September twenty-sixth, to be preciseand I wondered if you'd like to get together for coffee or something. I'll be in Denver all weekend.”

Kate felt her heart accelerate and frowned at the response. “Sure,” she said. “I mean, I'm awfully busy right now and my guess is that I will be in September, too, but if you'd like to come out to Boulder some evening when you're here, maybe that Friday the twenty-seventh, perhaps you could come up to the house and see Josh.”

“That would be great.”

They talked schedules and directions for a moment. O'Rourke would have the use of a car, so there was no problem with his driving from Denver to Boulder. When that was finished, there was a pause for a second.

“Well,” said the priest, “I'll let you get some rest.”

“You too,” said Kate. She could hear the fatigue in his voice. There was an awkward moment when neither took the opportunity to end the conversation.

“Neuman,” he said at last, “you were lucky to get the baby out when you did. You're aware that the government shut off new adoptions only a week or so after you left. “

“Yes. “

“Well . . . we were lucky.”

Kate tried to put a lightness in her tone. “I didn't think that priests believed in luck, O'Rourke. Don't you believe that everything is . . . pardon the expression . . . ordained?”

She heard a sigh. “Sometimes,” he said, his voice very weary, “I think that the only thing one can believe in and pray for is luck.” She heard him shake the exhaustion out of his voice. “Anyway, I look forward to seeing you and Joshua next month. I'll call when I get into Denver and doublecheck our plans.”

They had said goodbye with as much energy as they could muster. Then Kate had sat in the dark house and listened to the midnight silence.

The RSProject continued on several fronts and each area of investigation thrilled and terrified Kate.

While she was in charge of the overall project, Chandra was the actual boss of the retrovirus search, Bob Underhill and Alan Stevens had taken over the analysis of Joshua's bloodabsorbing “shadow organ,” and Kate herself was trying to unlock the mechanism by which Josh's body liberated the donor RNA from blood and transcribed it to proviral DNA, ready to be distributed to cell nuclei throughout his body. Her second and more immediate goal was to devise a way for this same immunerepair mechanism to work without a massive transfusion of whole blood every three weeks.

Working with Chandra in the ClassVI lab was an education. The HIV specialist had taken less than forty-eight hours to get her “virus factory” up and running at RMR CDC. Kate had given her another three days of uninterrupted work before showing up for a briefing.

“You see,” Chandra had said while showing Kate around the innermost biolab, the two of them in pressurized anticontamination suits and trailing oxygenhose umbilici, “ten years ago we would have had to start from scratch in an attempt to isolate the Jvirus.”

“Jvirus?” Kate had said through her intercom radio.

“Joshua virus,” said Chandra. “Anyway, even five years ago we would have had to cover a lot of ground before we could find a starting place. But with the HIV research of the last few years, we can take some shortcuts.”

Slightly distracted by the hiss of oxygen in the suit and the sight of technicians working with gloves and remote handlers through the clear plastic window behind them, Kate had concentrated on listening.

“You know that retroviruses are just RNA viruses that express their gene products after their RNA is transcribed to DNA by the reverse transcriptase enzyme, which has DNA polymerase and ribonuclease activities,” said Chandra.

Kate did not mind being lectured on the obvious, because she knew it was just the way that Chandra framed her explanations to everyone. She nodded through the clumsy headpiece.

“So,” continued Chandra, “the polymerase makes a singlestranded DNA copy of the viral RNA and then a second DNA copy using the first template. Ribonuclease eliminates the original viral RNA. Then this new invader DNA migrates to the cell nucleus and gets integrated into the host's genome under the influence of the viral integrase enzyme and stays there as a provirus. “

Kate waited.

“Well, we assume that the Jvirus behaves just like any other retrovirus,” said Chandra, lifting a culture dish and setting it closer to a technician's gloved hand. “Only we're guessing that it models itself after the HIV life cycle . . . or perhaps HIV mutated from the Jvirus, we just don't know. At any rate, we're working on the assumption that Jvirus follows the path of least resistance and binds gp120 glycoprotein to CD4 receptors in Thelper lymphocytes, mononuclear phagocytes, and Langerhans cells. Now my research has shown that our old friend HIV never infects cells without CD4, but we don't know that about J. But CD4 is still the obvious place to start. “

Kate had understood immediately. The HIV provirus had infected cells and obstructed the immune response; the Jvirus, according to Chandra's reasoning, broke down RNA the same way, transcribed it to DNA the same way, and invaded cell nuclei the same way, but enhanced rather than inhibited the cell's immune system. “You're assuming the same vector for proviral integration,” said Kate, “but trying to find its footprints after transcription.”

“Of course,” said Chandra. “We can compare the cells after reverse transcriptase to the control cultures and find out just how the little fucker operates.” She glanced at Kate. “The Jvirus, I mean.”

Kate ran her gloved hand over the counter and stopped it next to a cultured specimen of Joshua's blood. There were thirty-four similar cultures on this counter alone. Farther down the line were row upon row of HIV and SCIDcultured specimens sent from CDC Atlanta. “Where do these come in?” asked Kate, gesturing toward the infected cultures.

“Assuming that the Jvirus doesn't differentiate between your son's SCIDinfected cells and other SLID specimens and there's no reason it should, retroviruses don't discriminatethen, theoretically, we can observe the action during the binding to CD4 cells in the precultured SCID templates. “

Kate looked at the other woman through their double layers of plastic. The experiments had been proceeding only a few days at this point, but she needed answers for her own work. “And have you witnessed what you expected to?” she asked, being careful to keep her voice steady.

“Shit,” said Chandra. She. had started to rub her nose before remembering that she was in a pressure suit. She wiggled to scratch the tip of her nose against her gloved hand through the suit's plastic window. “Sorry. Oh . . . yes, we've documented the Jbinding to both the patient's SLID cells and the precultured specimens. It's close to the HIV model.” Chandra was one of those researchers who almost seemed to lose interest in the previous step of a project once that step was accomplished. But Kate had deliberately allowed the woman several days of work without the interruption of briefings or memoranda; now she needed answers.

“When HIV binds to CD4,” said Kate, looking at her adopted son's culture as if she might see some activity there, “the infection of Tlymphocytes creates some cytopathic effects and obvious . . . footprints, I think you called them . . . such as formation of multinucleated synctia as the gp120 on the surface of infected cells fuse with the CD4 of other CD4 bearing cells. That's at least part of the reason we see such a dramatic loss of helper T cells despite the fact that the HIV retrovirus is infecting just . . . oh, I in 105 CD4 cells in the blood.”

Chandra looked at her as if she had forgotten that Kate was a research hematologist. “Yes?”

Kate kept sharpness out of her voice. “So do you see the same synctia formation?”

Chandra shook her head. “I helped pioneer the treatment of injecting HIVpositive victims with recombinant soluble CD4 protein to slow the infection at that point by inhibiting synctium formation. But it wouldn't work in the case of the Jvirus. “

Kate's heart sank. “Why not?”

“The Jviral integrase enzyme doesn't transfer the invading transcribed DNA on the I in 104 or 1 in 105 of the blood cells that we're used to here, Kate.” Chandra's eyes through the reflective plastic looked very intelligent and very bright.

“What is the ratio?” asked Kate. If it were too small, the chances of cloning an artificial Jvirus would go down markedly.

“From the first few hundred samples checked,” said Chandra, her voice constrained, “we estimate 98.9 percent infection. “

Kate felt as if someone had hit her in the stomach. She checked to make sure that the counter behind her was empty and sat on it. “Ninetyeight point nine?”

“That is conservative.”

Kate shook her head. AIDS killed its host by infecting one out of every thousand or ten thousand white blood cells. The Jvirus was so efficient that almost all of the cells in the host's body were reprogrammed within hours of infection.

“Cytotoxicity?” said Kate. Such a rapid and universal infection of cell nuclei must have terrible side effects.

Chandra shrugged. “Microbiologically . . . zip. Transfer and the transfection process require mucho energy, of course . . . but you've documented that with the baby's temperature rise during the process. The child is a chemical and genetic crucible after this blood absorption and reconstruction. But the deed is essentially done after a few hours, although our preliminary research suggests that it would take a week or so for complete genetic assimilation.”

Kate gestured with a gloved hand toward the other cultures. “And the HIV specimens?”

Chandra blinked. “Because we're so familiar with HIV diagnosis through viral detection, I'm using that as a second control. We take the patient's bloodsorry, Joshua'sand coculture it with the template SCID's and HIV, using a CD4 cell line or normal CD4 lymphocytes stimulated with phytohemagglutinin and IL2. With the HIV virus we do an assay for reverse transcriptase on some of the cultures, the presence of p24 antigen on others. Then we crosscheck that. with the SCID and Joshua cultures that were done at the same time. “

“And the result?”

“Reverse transcriptase is quite visible in the Jvirus cultures, although, as I said, without the cytotoxicity. The p24 antigen analysis doesn't work with the Jvirus, which is a shame because with HIV patients the antigen can sometimes be detected directly in a blood sample via an enzymelinked immunosorbent assay.”

Kate nodded. She had also hoped that this relatively simple avenue of diagnosis would be available for them.

As if to reassure Kate, Chandra hurried on. “We're still assuming that the Jvirus creates a Jantibody, even though the results of the infection are immunoreconstructive rather than immunosuppressant. We should have that antibody for you today or tomorrow.”

Kate looked out at the dozen or so technicians working in the outer lab. Even though it was a shirtsleeve environment compared to the ClassVI inner lab,, the technicians wore coats, surgical masks, cotton booties, and rubber gloves. Kate knew that the entire lab was pressurized, with the internal pressure lower than ambient pressure in the rest of the building. If the biolab leaked, it would leak inward. Even the apparently nontoxic Jvirus was considered guilty until proven innocent.

“What techniques are you using to isolate the antibody?” asked Kate.

“The usualenzyme immunoassay, Western blot, immunofluorescence, radioimmunoprecipitation assay.” Chandra's voice revealed her eagerness to get back to work.

“Fine,” Kate said crisply. “From now on I'd like daily reports sent upyou can have Calvin follow you around and type them up if you want,” she added quickly to head off any protests. “But Bob's blood absorption work and my hemoglobin studies will be piggybacking on your breakthroughs, so we need daily updates. And I'd like half an hour of personal briefing every Monday and Saturday.”

Kate saw Chandra's eyes flare with angernot at the thought of giving up her weekends, Kate was sure, since she worked weekends anyway, but at the idea of wasting time explaining her work. But the professional side conquered the researcher's momentary pique and she merely nodded. Kate was, after all, in a position to take away all of Chandra's toys and games if she wished.

By Friday, September 5, the Jvirus antibody was isolated and tagged. By Wednesday the 1lth, the Jretrovirus itself had been identified. Two days later Chandra began her attempts to clone the retrovirus. The same day, she revealed her hidden agenda for coculturing the HIV specimens: Chandra was wasting no time in experimenting with the Jvirus as a possible AIDS cure. Kate was not surprised; indeed, she would have been amazed if the dedicated HIV researcher had planned anything else. As long as it did not slow down the RSProject, Kate had no objections.

Alan and Bob Underhill had completed a hypothetical schematic of the absorption organ by Thursday, September 19, and a fullteam seminar was scheduled for Wednesday the 25th so that everyone could listen and comment. By this point, getting the entire team together was only slightly more difficult than assembling a dozen of the world's political leaders, given everyone's imperative to avoid interruptions.

Kate's work on both the DNA transfer mechanism and the bloodsubstitute problem was also going well. Almost too well, she thought. Not only did she see a way effectively to cure Joshua of the SCID aspect of his disease, but she was confident that her work would help Chandra in the HIV breakthrough.

Things were going too well. Not in any way superstitious, Kate still had twinges of anxiety that the balance of pain in the universe would reassert itself soon.

And then, late on Sunday the 22nd of September just another workday as far as she was concernedthe calendar in her Wizard electronic organizer told her that the next day was the autumnal equinox, that Tuesday was Joshua's birthday, or at least the day they had chosen to celebrate his birthdayand that Father Michael O'Rourke would be visiting before the end of the week.

Kate knew thateven without compromising the details of the projectshe would have wonderful things to tell him. What she did not know was that within the week her life would be changed forever.