How Doctors Think (16 page)

"The HIV tests came back negative," Rachel told me. Shira definitely did not have AIDS. While Shira's T-cell count was somewhat low, Rachel continued, the major problem was that they weren't working. Her T cells couldn't muster the slightest response when challenged by microbes in the test tube. This paralysis of her immune system made her susceptible to a multiplicity of devastating infections.

In addition to the Pneumocystis, the cultures from Shira had shown cytomegalovirus, or CMV. This highly destructive virus not only can infest the liver, lung, and bone marrow, causing hepatitis, pneumonia, and a reduction in blood counts, but also can grow in the retina, risking blindness. Next was Klebsiella. This bacterium causes widespread inflammation in the lungs. The sputum it generates is called "currant jelly," because it is so viscous and bloody. Then there was Candida albicans, the fungus seen in Shira's mouth in the ER. Now it was growing in other orifices.

I counted in my mind four deadly microbes: Pneumocystis, CMV, Klebsiella, and Candida. Then Rachel told me of a fifth: parainfluenzae. The doctors informed her there was little they could do—no specific therapy existed against this virus. "The working hypothesis is that Shira has an unusual, atypical form of SCID," Rachel said. SCID is an acronym for severe combined immunodeficiency disorder. It is a rare inherited disease caused by the absence of a key part of the machinery of the T cells. This results in low numbers of T cells, and even those remaining do not work effectively. The gene for the disorder is carried on the X chromosome. Because males have one X chromosome, inherited from their mother, the disease is mostly seen in boys. Girls, who are XX, with one X chromosome donated from each parent, would have to inherit two defective genes. In Shira's case, it would require that both her father and her birth mother carry the trait. The doctors said it was rare for a girl to have SCID. The fact that Shira's T-cell count was only somewhat low made her an "atypical" case.

"You haven't seen Shira yet," Rachel said. "Come, you'll meet her. She's a beautiful baby." At the entrance to the room, we put on sterile gowns, gloves, and masks to limit the transfer of microbes from our hands, clothes, and mouths to the defenseless infant. The bed was surrounded by machines and equipment—the Hi-Fi respirator, cardiac monitor, oximeter, intravenous pumps. On a small table was a pile of books. During the rare quiet times of the day, Rachel read to Shira.

I gazed down at the infant. She was turned on her side to accommodate the stiff tube in her mouth, which was attached to a large corrugated hose that led to the Hi-Fi respirator. The settings showed that the machine was delivering the maximum concentration of oxygen under the highest possible pressure. I looked at the red numbers on the oximeter and saw that this was barely enough to sustain her blood oxygen. "She's a beautiful child," I said. And she was. Looking beyond the tubes and catheters that entangled her, she had fine sculpted features, unblemished skin, and delicate limbs.

Rachel nodded. "Shira is going to live," she said. "I can feel it inside of me."

Glancing again at the numbers on the oxygen monitor, I said nothing.

Every morning and every evening, Rachel told me she stood next to Shira's bed and prayed. She read from a pocket-sized prayer book, well worn from daily use. Years ago, she had inserted a prayer of her own. It spoke to what she personally sought from God:

Dear Lord,
Having been created in Your image
I am full of unrealized potential
The realization of which
Depends upon my acknowledgment of the potential,
My recognition of all the gifts from You with which I am endowed,
And my exploitation of the opportunities that lie open before me.
Please Lord, help me rise to meet the challenge.
Let me use those gifts for the benefit of all people.
Dear Lord,
For all that I am
And all that I can be
I thank You.

Never before did Rachel pray with such fervor for help to "rise to meet the challenge."

"What could cause a baby to have so many infections other than AIDS or SCID?" Rachel asked.

"I'm not sure. I'm not an expert in this area."

Rachel trained her amber eyes on mine. "I know you're not. Neither am I." But she explained she had been looking on the Web, and after learning about SCID and talking with affected families online, she was growing convinced that Shira had something else. "I think it's a nutritional problem causing her immune system to not function."

When Rachel had raised this idea, one of the residents mentioned reports of malnourished infants whose immune systems collapsed and who developed Pneumocystis. Several cases occurred in Tehran in the early 1960s, and in Vietnam between 1974 and 1976, when the country was in the final throes of war and food was scarce. But, the resident emphasized, while Shira was a slim baby, she did not fit the picture of severe malnutrition—essentially skin and bones—described in those reports. He dismissed the possibility.

I reiterated that I really didn't know enough to offer opinions about children. My understanding was that in adults, the immune system collapsed only in cases of extreme starvation.

"Since the consensus is atypical SCID," Rachel said, "there's talk of doing a bone marrow transplant."

Bone marrow transplantation is the most extreme measure in medicine to cure a disease. In essence, a person is given lethal doses of radiation and chemotherapy, doses that destroy the blood and immune system. Into this void, stem cells from the bone marrow of a compatible donor are seeded. These marrow stem cells have extraordinary biological potential. They grow and mature into all of the elements that have been destroyed: red blood cells, neutrophils, monocytes, platelets, T cells, and B cells. As the donor stem cells grow and mature, they begin to perform the chores that immune cells are programmed to do. Primary among these is to recognize foreign invaders, like microbes, and to purge them. That was precisely what Shira needed at this point: cells that could recognize, confront, and destroy Pneumocystis and Klebsiella and CMV and Candida and parainfluenzae.

Yet within this promise of biological resurrection was also the potential for biological rebellion. Immune cells are also programmed to recognize foreign tissues as well. The patient's new immune system can perceive the surrounding body as foreign. The transplanted T cells then go on the attack against vital organs like liver and skin and bowel. This is so-called graft-versus-host disease, because the grafted donor cells are pitted against the recipient host tissue. If the donor and patient are genetically closely matched, like siblings, graft-versus-host disease is mild. If they are genetically disparate, however, it can be severe. In that case, after a successful transplant, just when life seems to be restored, the very procedure that renewed life spirals into debility and death.

After I left, Rachel decided to proceed on parallel tracks. She would continue to pointedly question the diagnosis of SCID while helping prepare for its treatment. She e-mailed the agency in Vietnam and informed them of Shira's need for a donor. The next day, the officials replied that the birth mother had readily agreed to be genetically typed. Blood would be drawn to see how closely her cells matched Shira's. The doctors were pleased, but Rachel found little comfort in this reply.

Shira struggled to live. There were hours when she seemed to improve, her oxygen level rising. Then, for no apparent reason, she would deteriorate, the neon numbers on the oximeter plummeting. At each downward turn, Rachel felt trembling in her bones and the pace of her breathing quicken. She closed her eyes and prayed intensely, and the feelings gradually subsided.

Then, slowly over the course of the next week, Shira's oxygen level began to rise consistently. A chest x-ray showed that the ground glass was receding; a black penumbra surrounded the heart like the night sky around a pulsating star. "It looks like we can try to wean her," the resident said cautiously.

Rachel could not believe her ears. Weaning here did not refer to the breast, of course, but to the life support of the respirator. Every few hours, the ICU team dialed down the pressure and the level of oxygen. Then they waited, observed Shira, rechecked her blood oxygen. All the while, Rachel sang. She sang show tunes, Cole Porter, children's songs—playful, lilting, carefree melodies. And when Shira struggled, her chest heaving, her arms tensing, Rachel sang more forcefully.

After thirty-three days in the ICU, Shira was breathing room air through the respirator, without added pressure or added oxy gen. The doctor extracted the tube from the baby's throat and the machine was shut off. The loud
woosh
of the respirator that had filled every moment of the day and night suddenly was gone. Rachel savored the silence. Her tears slowly collected as Shira comfortably inhaled and exhaled. Rachel had not broken. If a transplant was necessary, she would endure that harrowing treatment as well.

Shira was transferred to a regular hospital ward to await the bone marrow transplant. Rachel felt as if she had stepped through a looking glass into a different world. On the ward, she and Shira were largely left alone through the day. Nurses came on every shift to check vital signs. The dietician helped with liquid feedings, since Shira still was not able to feed by herself; the formula was passed via a tube that went down the esophagus and into the baby's stomach.

With quiet and time to think, Rachel investigated the manifold aspects of SCID, its genetics, diagnosis, and treatment outcomes. And as her knowledge grew, her sense solidified that her child did not have it. She clung to the idea that Shira had a nutritional deficiency, but was at a loss to say what nutrient might be missing. The right choice, Rachel realized, would be known only in retrospect.

Shira gained weight from the tube feedings. Her arms and legs filled out. Over the course of a week, her low-grade fevers abated, and some of the antibiotics were stopped. Rachel observed Shira's every move. There was an alertness to her eyes and, Rachel sensed, a deep hunger to encounter the world. So, to satisfy this imagined need, Rachel sang and talked to Shira about the wonders of God's creation, the sun and moon and stars, the earth with its forests and seas.

Not long after Labor Day, the bone marrow transplant team convened to discuss Shira's case. Three donors were found in the National Marrow Donor Program Registry, and each was willing to give marrow stem cells for Shira's transplant. The blood of Shira's birth mother in Vietnam, when tested, proved less compatible than that of the unrelated registry donors. Graft-versus-host disease would likely occur even when using the registry donors, the doctors said.

When the resident from the transplant team came on his morning rounds, Rachel decided she had to meet her doubts head-on. "I want Shira's immune testing to be repeated."

The resident looked at her uncertainly. The medical team had come to appreciate the intelligence of Rachel's questions and the efforts she made to research topics. But what more could be learned from repeating the tests?

"Her T-cell numbers have increased," Rachel continued, struggling to maintain a calm, even voice.

"That happens sometimes with SCID, particularly after recovering from a major infection," the resident replied. "It's just expected fluctuation."

"But I don't think she has SCID," Rachel said, her voice rising. "I think ... I think she has some nutritional deficiency."

The resident looked tiredly at Rachel. He had heard her idea countless times before. Rachel felt her pulse quicken.

"We know you think that, and of course we respect a parent's feelings. But Shira has a variant form of SCID. It's not a typical picture, as you know, but we've discussed it on rounds many times, with all the senior attendings."

Rachel paused and exhaled slowly. "I want ... her blood ... retested." She hammered each phrase as if it were a stubborn nail.

Pediatricians are acutely aware of the anguish that mothers and fathers experience when their children are gravely ill. The doctors are trained to respond compassionately even to what they view as misconceived demands born of desperation. In this instance, the resident took pains to explain to Rachel that Shira had already been tested and that retesting would require a laboratory researcher to needlessly put aside other work.

"If Shira is an atypical case," Rachel said, her tone softening, "then an ambitious scientist might be able to publish a paper on her. He could look more closely at her cells, get more data on why they don't function."

The resident considered this, and agreed that an immunologist he was friendly with would be sufficiently intrigued by Shira's case to study her cells. Yes, two sets of data would strengthen a manuscript submitted for publication in a prestigious journal. Rachel stopped her hands from trembling as she watched the resident draw the blood.

Shortly after dawn on the morning of September 11, 2001, the doctor from the transplant team knocked loudly on the door to Shira's room. Rachel quickly fixed her hair and tied the belt on her robe.

"I can't believe it!" the resident exclaimed. "I just can't believe it."

He handed Rachel a printout of the second set of blood tests done on Shira's immune system. One by one he went down the column with her:

Total T cells: normal
Helper T cells: normal
Suppressor T cells: normal
B cells: normal

"Not only are there normal numbers of all her cells," he continued, "but they're all working perfectly."

When Shira's T cells were exposed to microbes in a test tube, they immediately recognized them and went through the elegant choreography of their biological responses, coordinating scores of enzymes and releasing a repertoire of proteins that, in the body, amounts to a solid wall of immune defense.

"Shira doesn't have anything like SCID," the young doctor said, his face brightening. "She's normal, healthy, fine. I think she should be able to go home by the end of the week."

Rachel closed her eyes. Her heart beat with such force that she felt it would burst through her chest.