6.

"How are you feeling?" Yoshizumi said to Mariko and flashed a smile.

Five days had pa.s.sed since the operation, and everything was going smoothly. Two days ago they had removed the upper drainage tube from her kidney and today the urinary catheter. The bladder tube was still in place, but would be removed tomorrow.

Barely glancing at Yoshizumi's face, Mariko looked away.

Didn't think so... Trying not to betray his disappointment, Yoshizumi said, "It seems your fever's gone down, and so has your CRP value. Don't you feel better? You're still slightly anemic, so let's adjust your transfusion level."

He then explained the test results in a way Mariko would understand. If she knew about her condition fully, he thought, she would have a much more positive att.i.tude towards the treatment this time around. She should also be relieved to learn that there were no symptoms of organ rejection or serious infections.

The real transplation treatment didn't begin until after the operation. In the case of kidney transplants, the surgery itself was relatively simple, something any trained surgeon could perform. The problem was what happened afterwards.

A transplanted organ was a foreign body and inevitably elicited resistance from the recipient's immune system. It was to minimize this that HLA compatibility checks were made. Yet, immuno-suppressants were always necessary, and the dual use of prednine, an adrenal steroid, and azathioprine used to be common. The success rate for transplants shot up, however, with the development of more effective suppressants like cyclosporin and FK506. Because these drugs are renotoxic, today they are used only in conjunction with other drugs. Based on clinical data, Yoshizumi's group favored a three-drug combo consisting of a minimum of cyclosporin, some adrenal steroid, and mizoribrine, an antibiotic. Since this wasn't Mariko's first transplant, she'd been prescribed a relatively small volume. Suppressing the immune system helped the new kidney survive but made the patient vulnerable to infections, a potentially lethal outcome given the lowered barriers. This was the crux of a transplant procedure, which was often compared to tightrope walking. The patient had to be kept under close watch for signs of organ rejection on the one hand and infections on the other. Yoshizumi was painfully aware that transplants were the work not of the surgeon alone but of the nurses, clinical technicians, and pharmacists who had to stay in close touch during the post-op period.

Mariko was still turned away. Yoshizumi cast a backwards glance at her father, but he, too, looked away.

Yoshizumi sighed in his heart.

Mariko was clearly not in the mood for small talk. She had been acting this way with her father and the nurses as well. It seemed she wanted to forget, even deny, that the transplant had ever occurred.

In the eyes of a young patient, parents and doctors were dignified, powerful figures and therefore understandably intimidating. Yoshizumi remembered having similar instances with other transplant patients under his care. However, in Mariko's case, he suspected there were other issues. He had no idea why she was so adamantly opposed to the transplant, even after the fact.

Maybe I failed the last time because 1 couldn't figure out why. At a loss, Yoshizumi shook his head to dispel his self-doubt.

"You should be able to stand up and move around a bit the day after tomorrow. You'll get to eat some real food then, too," he said and patted Mariko on the head. The nurse at his side smiled rea.s.suringly. But Mariko still made no effort to look in their direction. As if to shut out the existence of Yoshizumi's hand, her head lolled lifelessly under his touch.

Yoshizumi removed his hand.

It was quite a different story after her first operation, when Mariko looked gratefully at Yoshizumi with tears in her eyes and thanked him countless times. He had smiled in return and patted her head as he'd done now.

Until her first transplant, Mariko underwent dialysis for about one year. After that, her father offered his own kidney, to which Yoshizumi gratefully obliged.

When Mariko first appeared before them, the cherry blossoms were in full bloom. They all watched from the waiting room window as petals fell plaintively in the courtyard. Mariko was charmed by the pink scenery fluttering outside, as if seeing it for the first time.

She had just started sixth grade. She wore a white top with a green skirt and sported a bobbed hair style. Her large, round eyes were wide with joy. She listened closely to what Yoshizumi had to say and even laughed at his jokes. Her cheeks were still slightly swollen, making her all the more charming. She had hardly grown at all in the preceding two years.

Even in cla.s.s, she was usually moved up to the front during gym or morning a.s.sembly, a fact that made her feel a little uncomfortable.

There were a number of orientation sessions with patients before the actual transplant took place. They were informed in detail about the types of treatments they could receive, the pros and cons of each, the truths of the operation itself, and how they were to carry on with their fives after recovery. Their goal was to alleviate any misconceptions or anxieties born of ignorance. Nurses also carried out a similar duty, but in Mariko's case Yoshizumi had taken it upon himself to provide any and all explanations.

Mariko listened to his words enthusiastically, but was devastated to learn that she had to continue taking immuno-suppressants even after the operation. Nevertheless, she accepted it soon enough.

"So how long do I have to take them?" implored the young Mariko, staring at Yoshizumi intently.

"For as long as you live," he answered, not taking his eyes away from hers.

"Always...until I die?"

"Yes, but I know you can do it."

Mariko covered her eyes and was silent for a long while. She seemed to be thinking seriously about what this meant. She then looked up, her lips tightly sealed, and nodded firmly.

She progressed well for a number of days following the operation. She was beside herself with joy and spoke to everyone smiling, exhibiting a happiness and talkative disposition typical of successful patients. This was usually a result of being released from dialysis and was in proportion to how much the patient had hated it. Still, Yoshizumi didn't feel bad seeing her so happy. The dialysis experience must have been hard on her, and she genuinely seemed to appreciate having a new kidney. She seemed simply moved that she was urinating again, and when he visited her a week after the operation, she cried out and buried her face in his white coat with tears of grat.i.tude, he patting her head.

Even after Mariko left the hospital, Yoshizumi met with her several times for checkups. Her face had rounded a bit, a side effect from the steroids he prescribed, but she was as darling as ever. She was delighted to be eating the same school lunch as everybody else, freed from her strict diet. She repeated over and over how good her meals tasted, how happy she was that she'd had a transplant.

"Doctor, I'm all healed now, I'm not sick anymore, right?" Mariko interrupted their conversation one day, smiling broadly, peering into his eyes.

For a moment Yoshizumi was silent, not taking her meaning.

"You can live normally now like everybody, so in that sense you're cured. But with transplants, you can't let down your guard. You're still taking the immunosuppressants, right?

You absolutely mustn't forget to take them. Without them, even a successfully transplanted kidney will stop working. You must promise me that you'll always take your medicines. Can you promise me?"

"...yes," she nodded.

Yes. She'd nodded. She did nod...

And yet she would return to the operating room only four months later.

"We haven't discovered any pathogens yet," said Yoshizumi as he walked Anzai out of Mariko's room now. He invited Anzai into his office to tell him about her post-op condition.

Yoshizumi offered him a seat.

"Our nurses have been taking samples of Mariko's fluids and sending them for a.n.a.lysis.

We haven't found anything, so I wouldn't worry."

Anzai looked relieved and wiped the sweat from his brow.

"But as long as we're here, there's an issue I feel I must address..." he said gravely.

"Just why is Mariko acting that way?"

Anzai looked downward.

"Mr. Anzai?" he asked again.

"I...don't know," he responded. Yoshizumi's silence urged him to continue. "Ever since the first transplant failed, I haven't been able to tell a single thing she's thinking. She's kept her emotions hidden from me all this time. I'm beginning to wonder if this is all my fault..."

"Did Mariko not want this transplant?"

That's not the case!" Anzai looked up to say, but his voice was shaking.

Yoshizumi tried to wear a warm smile. "Please tell me the truth, Mr. Anzai. I realize a parent such as yourself has only his child's best interests in mind and naturally wanted this operation... But Mariko didn't, did she?"

"No," Anzai confessed, his head drooping. "I don't know what to say, after all you've done for her. It was the same when the coordinator called. Mariko kept it from me at first. I was surprised to learn we'd been contacted about a transplant. And when I returned the call to give the go ahead, Mariko was so furious that she was spasming... She was abnormal."

"Abnormal...?"

"She yelled, 'I'm not a monster'..."

Yoshizumi didn't know what to make of this and changed the subject. "She's been having constant nightmares since the operation. Any idea?"

"None." Anzai shook his head in despair.

"I think she's afraid of something. She might have developed a bad image of transplants. So she didn't want one and is having nightmares now. She wasn't this way the first time. It's as though it's not being operated on that she hates, but transplants and transplant doctors like me. Any idea why she feels this way?"

"I'm sorry, but I really have no clue." Anzai could only hang his head in shame. He seemed to be pleading for an answer himself.

Yoshizumi felt much sympathy for the man. He said gently, "I've been informed that the other recipient's been diagnosed with accelerating rejection."

"Accelerating?"

"It can occur anytime from twenty-four hours to a week after the operation when the recipient turns out to have had an antibody against the donor's antigen. He's being treated as we speak."

Anzai was speechless.

"Thankfully, Mariko's condition is stable. But I can't predict how it will turn out in the long run. I will, of course, do anything in my power. If she has no will to get better, though, we could lose her to an infection. We have to get her to open up to us."

"...how wonderful that would be..."Anzai a.s.sented feebly.

7.

Toshiaki sat before a co-focal laser scanning microscope and entered his calibrations with an external computer mouse. After staining the Eve 1 cultivation with Lodamine 123 stain, he placed its flask onto the platform inside the machine.

Toshiaki had cloned Eve in the past few days. The batch that displayed the strongest propagative abilities he named "Eve 1allowing it to multiply for experimental use. The laser microscope had just been installed in the joint lab on the second floor this past spring. It was an ACAS ULTIMA, the newest model. A rather large piece of equipment, it took up the s.p.a.ce of an entire business desk. An inverted microscope was fitted on the left side while the right was furnished with a command monitor that displayed all the data. Behind it was the laser tube. The central computer itself was located underneath the desk.

Toshiaki examined Eve l's mitochondrial structure. The Lodamine 123 stain caused the mitochondria to glow with a distinct fluorescence that made them more visible. The laser activated a fluorescent agent that emitted photons of certain wavelengths. These pa.s.sed through an optic cleansing filter and clearly outlined the shape of each mitochondrion. The most remarkable feature of the ACAS ULTIMA was that any part of a cell could be isolated.

Cells themselves had a thickness and weight to them and one could not completely lay out their structural details using standard microscopic technology. Gathering information through the latter therefore had its limitations. But with this machine, one could cut many tens of layers from top to bottom of any cell and view images of individual sections on the monitor.

After this, the image data were rendered into a three-dimensional model of the cell. This device exhibited unsurpa.s.sed accuracy in the research of nerve cells and others requiring 3-D constructive a.n.a.lysis.

Toshiaki clicked to start the program. Mitochondria appeared in succession as slender green shapes, scattered here and there against the black background of the screen.

When he was finished looking over the data, he entered a series of commands into the computer and a 3-D blot graph appeared. At that moment, Toshiaki simply couldn't contain the sudden exhalation that left his lungs. These mitochondria were unlike any he had ever seen before. They were expansive and fused together in a vast, advanced network, as if energy superhighways had been built between them.

He felt a thrill of hope throbbing in his heart. He selected other cells inside the flask and performed similar scans to identical results. A radical change had occurred in Eve 1's mitochondria.

Toshiaki printed out his findings and shut down the machine, then returned to his lab on the fifth floor to check how many stained Eve 1 cells were left by using the flow cytometer, a device which measured the intensity of fluorescence in cellular material through a process known as a histogram.

He collected cells from the flask and placed them into a centrifuge. After purifying them with a buffer, Toshiaki took the cells and returned to the joint lab once again. He turned on the flow cytometer. A moment later, the previous images reappeared on the monitor. He put in a new set of parameters.

Toshiaki hooked up a nozzle from under the machine to the tube. The cells were then sucked into the cytometer and sent to a laser apparatus. Because the collection tube was so thin, cells pa.s.sed through it in a linear fashion and were hit by a laser one at a time to detect their fluorescing properties, the levels of which were dependent on the amount of agent used.

This machine differed from the microscope in that it calculated the degree of stain in each cell individually, plotting their distinctive features on a graph.

Toshiaki set the tube in place and clicked on the word "GO" above the image. At once, countless dots appeared on the monitor, each denoting a single cell. Toshiaki focused on the histogram to the right as its line graph moved in short spurts.

"My G.o.d..."

The intensity was off the charts. Beyond comprehension. The mitochondria in each cell of Eve 1 were indeed increasing and their forms undergoing dramatic changes. The mechanisms which normally governed them were causing anomalies via excessive mitochondrial production. Toshiaki knew of no research having ever reported anything remotely like this. "Astounding" was the only word he could think of to describe it. That the cells had acquired some strange propagative capability suggested a sudden change in gene-linking proteins. There was a high possibility that this was influenced by the mitochondria within the cells themselves.

Toshiaki was shaking with excitement. Something new and unknown had awakened in Kiyomi.

He printed out these results immediately and ran back to his lab, where Asakura was performing a DNA extraction.

"Asakura, come here for a moment."

Toshiaki grabbed her and rushed her to the Cultivation Room. He showed her the Eve 1 flasks in the incubator. She eyed them with suspicion.

"Can you extract the mRNA from these cells for me?"Toshiaki placed a flask under the microscope and urged her to look. "I want to determine the induction of beta oxidation enzymes in a Northern blot."

"...these cells, what are they?" Asakura asked as she took her eyes from the lenses, clearly shaken from what she saw. Toshiaki lied, explaining he had received them as a laboratory sample from another university. Asakura's face did not indicate acceptance, but she pried no further into the matter, choosing instead to nod her head in resignation.

That evening, Toshiaki dreamt about something other than Kiyomi for the first time in a long while. He was back to grade school days, sitting on his bedroom floor in knee-highs and a T-shirt, working on a toy model. An electric fan blew cool air onto Toshiaki's back at regular intervals. Wind chimes echoed faintly outside and sweat dotted his forehead from the hot summer day.

Unlike his peers, Toshiaki preferred to stay at home all day reading books and sharpening his engineering skills. He enjoyed educational magazines, had a particular fascination for dinosaurs, loved zoos and museums.

The end of summer vacation was already approaching. His father had taken him to a science museum earlier that day, where Toshiaki spotted an unusual plastic model on display at the gift shop. A group of life science researchers had created a robot which mimicked the movements of a crab, manipulated freely by remote control. A plastic model version was soon merchandised, eventually finding its way to the display window which graced Toshiaki's curious eyes. Seeing how much his son was drawn to it, Toshiaki's father bought it for him and he began putting it together the moment he was home.

The model had very few parts, so a.s.sembly was effortless. When he switched on the remote, its joints began moving and large claws swayed back and forth, feeling their way around. To his young eyes, the crab appeared to be truly yearning for the ocean. With quiet awe, he pressed another b.u.t.ton on the remote. The legs moved in alternating motions, propelling the crab sideways just like its natural counterparts. More than ecstatic, he made his new creation walk all around the house.

Toshiaki was startled when he realized that the crab's movements were being driven by uncomplicated mechanical parts. A single small motor gave it life. He wondered if all creatures were so simple, but knew this was impossible. He remembered raising tadpoles some years before, when he watched with great antic.i.p.ation as they sprouted hind and front legs from nowhere then lost their tails. Robotics would never be able to replicate such mystery.

A revolving lantern turned slowly in the corner of his room. He had made it during his free time last summer with veneer and cellophane from the stationery store. At night, Toshiaki took it out onto the verandah. He lit a candle inside and the paper propeller on top turned slowly, making the cellophane cylinder spin. It changed to purple in the darkness, then to red and green, quietly turning around and around...

Before long his dream flashed to middle school, then to high school, when Toshiaki learned that all living organisms were governed by their DNA. He was impressed by the perfection of this system. Why did existence have the ability to design such a beautiful code?

And how could such a simple structure account for the endless diversity of life forms?

Again, the dream switched scenes. Toshiaki was now in his lab, but it was very outdated, not even the most basic equipment to be found.

A conversation from his senior year at college followed: "I think you should concentrate on studying mitochondria," said Professor Ishihara to a still young Toshiaki overflowing with vitality. The professor had just been appointed to the School of Pharmaceutical Sciences the year before and was searching for a new research topic. "These days, there are few researchers, if any, who are really thinking about extranuclear genetics. Sooner or later, n.o.body will be able to talk about the essence of human life without some understanding of it. We tend to forget there is also a society among cells on par with the center we consider so superior. If any one part of that microcosm becomes dysfunctional, the whole thing's a goner. I believe it's our duty to look at the whole picture.

What do you think, Nagashima? Would you be willing to give it a shot? I'd like you to come up with some ideas."