The Boy in the Moon: A Father's Search for His Disabled Son

by Ian Brown

  I thanked Kate Rauen shortly after that, left her office, crossed the street outside her building, and sat down on a bench to think about what she had said. The scientific definition of evolutionary success, of a successful random mutation, is one that allows the organism to survive and reproduce. Nature alone would not have allowed my son to survive.

  By the judgment of a geneticist, Walker was a deleterious effect of nature.

  But he wasn’t a product of nature alone. He had survived, and his survival was also a product of medical technology and human concern—the result of a G-tube and drugs and the steady attention of teams of people who believed their interaction with him was worth his and their while, even if the results were hard to measure. Walker wasn’t much to brag about, intellectually or physically. But like many other CFC children, he had changed lives, mine as much as anyone’s—deepened and broadened me, made me more tolerant and durable, more ethically dependable. He had given me a longer view. That felt like some form of evolution too, a positive ethical evolution, albeit not the kind modern genomic science tends to measure.

  I looked up then, and discovered I was sitting in front of a street sculpture, “Regardless of History,” created by an Englishman named Bill Woodrow. It was seven feet high, and bronze—a thin tree, blighted and leafless, stunted and growing out of a rock. But growing.

  I flew back to Toronto. The summer became the fall. Our search for some insight into Walker’s condition resumed.

  On a Wednesday morning in October, I met Tyna Kasapakis, the manager of Walker’s other home, at the genetics clinic of the Hospital for Sick Children. Walker was there too. The genetics clinic occupied a corner of the fifth floor of a downtown Toronto office building. From the front, the building looked like a giant tube of lipstick. It had once housed the corporate headquarters of a Swiss bank. The security guard behind the desk in the lobby nodded good morning to me. He had to have seen some sights. I took the elevator up and got off at the fifth floor and walked down the hall to the genetics clinic and sat in the same spotless waiting room in which I had cooled my heels nearly twelve years earlier, when Walker was diagnosed with CFC. I’d arrived early, before Tyna and Walker, and had to wait, as I had back then, for someone to arrive at the front desk. I didn’t mind. I loved the optimistic calm of the office before 9 a.m. I sighed and breathed in, once more, the odourless still air of the empty hallways, under the usual fleeting illusion that we were the only people who ever came here, a rare breed that had strayed into a pristine, otherwise mutant-free world. (Appointments in the genetics clinic were spaced out, to guarantee a minimum of interaction between the aberrations.)

  After living for eleven years with a clinical diagnosis of CFC, Walker was now to be tested genetically. Under the Canadian system of publicly funded medicine, a genetic test for CFC entailed a six-month wait: three months for the provincial health-care bureaucracy to approve the cost of the test, and another three months to organize a sample of Walker’s DNA, fill in the paperwork, send the sample to the testing lab, have it tested and get the results back.

  The usual routine ensued. While Walker threw toys around the playroom and moved onto and off my lap, a genetic counsellor (and sometimes two) ran through the standard disclaimers. There was no guarantee they would find an aberration in his genes, but that didn’t mean he didn’t have CFC. If these tests of three genes returned negative, we would look further afield, at rarer (and more expensively tested-for) genes. Even so, a diagnosis wasn’t a cure. The state of genetic research was proceeding rapidly, but the technology was more advanced than any scientific understanding of what the technology revealed. A genetic diagnosis might or might not confirm that Walker was CFC, but even if it didn’t he was still Walker, the same boy. Did we have any questions …? I was close to being able to recite this entire spiel from memory, like a soliloquy out of Shakespeare. To test, or not to test: that is the question. Whether ‘tis calmer in the mind to ignore the touts and dreams of genetic research, or to scan each cracked gene known to man, and by testing think we have an answer. To test and test and test some more, and by this test pretend it ends the heartache and the thousand natural shocks his small flesh is heir to. ’Tis a consummation devoutly to be wished!

  Then the hard part: collecting the genetic material. Walker’s DNA had been taken and sorted for a chromosome test when he was an infant (unbelievably, it showed no aberrations), and was still on file. But this morning the clinicians would take a new sample, just in case. I knew my part. Even doctors were afraid of how Walker might react; they couldn’t tell the difference between what hurt him and what merely upset him because it wasn’t part of his usual routine. I held him tight in my arms, my left hand across his chest to control his head, to keep it pointed in the same direction and keep his mouth open while the doctor stood back like the great white safari hunter, waiting to take a shot. I knew to hold him firmly, that control was the answer, but my thorough grip startled most doctors we saw, as much as they appreciated it. It made me feel useful, and it made me feel closer to my boy; his trusted handler, a strong man who still would never hurt him. And then the opening—now!—and the doctor swabbed the inside of his mouth with what looked like an extra-long Q-Tip. The Q-Tip went into a plastic tube. Done. Winter came. It was a cold one, with lots of snow. Walker developed the habit of crooning along with me as we drove back and forth to the group home to Ray Charles singing “What Kind of Man Are You?” and “I Had a Dream.” Sometimes the moist air in the car condensed on the inside of the windows; I could hear Walker’s fingers squeaking on the glass as he rubbed the fog away, as we drove north and east, singing the blues, Olga laughing with Walker in the back seat. Some days, to give Olga a break, I took him back by myself, but it was tricky: he relished the chance to sit in the front seat, liked to lower the windows in order to throw my maps out into the rushing highway air. Now, that was a metaphor. He was a ball of writhing glee in the front seat, but he loved to chat—or to have me chat at him—as we sped up the fine wide highway. Christ it makes me ache to think of how much I adored him on those funny rides. Dad and boy, driving—how much more obvious does it get? But they were lonely rides, too, because I was often faintly, subliminally panicked when Johanna wasn’t with us. But of course we were efficient: she and I took turns driving him because there was no point in two people spending two hours in the car, not with everything else there was to do.

  Spring arrived. The trilliums I planted came up in the front garden. Then a young genetic counsellor named Jessica Hartley telephoned with some unusual news. None of the genes commonly associated with CFC—BRAF, MEK1 and MEK2—were mutated in Walker’s DNA.

  I made another appointment, and Walker and Tyna and I headed back to the building shaped like a lipstick. The genetic testing was my idea, hence my duty, not Johanna’s.

  Hartley seemed impossibly young to be so knowledgeable. She had black hair and a mild Goth style. She was joined at our appointment by one of her superiors, a slim, middle-aged scientist named David Chitayat, a senior genetic scientist at the Hospital for Sick Children. The fact that Walker had shown no mutations in three genes commonly associated with CFC, the counsellors were keen to assure us, didn’t mean much. “If we don’t find something, that doesn’t necessarily mean he doesn’t have CFC,” Hartley said in an apologetic tone. “If everything comes back negative, we can revisit the test. CFC is definitely the most likely possibility.” She suggested retesting, this time looking for other mutations too, notably Noonan and Costello syndromes.

  As their understanding of CFC and its sister syndromes evolved, more and more researchers were once again thinking of CFC, Noonan and Costello as related syndromes—“RAS pathway disorders” or “Noonan spectrum disorders.”

  The genome was slowly yielding its arcane secrets, and scientists were beginning to attribute a wider and wider array of mental retardations—particularly if accompanied by facial disfiguration and heart conditions—to disruptions in intracellular signalling pathways. The
bodies of these children couldn’t seem to figure out when to build cells, and when to stop.

  Chitayat was a widely respected geneticist with a long history in the field. The mutation would have occurred, he said, in the first two weeks of Walker’s life in his mother’s womb. Each of the different genes associated with CFC was supposed to perform its on/off signalling job at a different stage in the “cascade” of communication that occurred within a cell: the mutated BRAF gene came into play (or “phosphorylated”) earlier, and therefore corrupted the cell’s message at a more fundamental level than the MEK genes did. But the pathways fed back into themselves as well, with the (possible) effect that MEK-mutated CFC kids seemed to have frailer physical selves but milder cognitive problems. That was one theory, in any event—and it was all theoretical. Geneticists had uncovered a vast realm of human physiology, but it often seemed that the more they uncovered, the less they understood about the ways the details fit together.

  Jessica Hartley and David Chitayat and Kate Rauen worked on the genuine frontiers of science, and based their hypotheses on known and testable biochemical interactions, but there were days when their speculations didn’t seem to me much different from the medical purification rituals of seventeenth-and eighteenth-century France, when coffee and chimney soot were confidently prescribed for madness, and melancholia was considered curable by drawing ten ounces of a man’s blood and replacing it with the blood of a calf. In any event, Chitayat added, “The important thing for us to find is a diagnosis for what he has. But jumping to the cause of what he has is not so easy.”

  After an hour of talking, the next steps became clear. We would retest for CFC, to make sure we hadn’t been dealt a false result. We would test for Noonan and Costello mutations, as well as for several other RAS-pathway cousins. If those tests also came back negative, we’d step back, and run a microarray of Walker’s chromosomal DNA. Microarray scanning of chromosomes was infinitely more sensitive than the chromosome screen that had been conducted when Walker was a baby. “The microarray is looking for missing or extra bits in the chromosomes,” Dr. Chitayat explained—missing words in the genetic sentence of his life—“whereas the gene testing is looking for spelling mistakes as well.” If Walker had a mutation in an as yet undiscovered gene that led to a chromosomal disorder, the microarray might reveal where in the genome his abnormality was. We knew I had parked the car in Ontario, I just didn’t remember what city—that was the gist of it.

  Some of the new tests (the microarray, for one) could be conducted in Canada, but others were possible only at certain approved labs in the United States. If Walker turned out to be positive for CFC, and his DNA was to be available for scientific studies, the result had to come from an approved lab. The tests cost $1,500 to $2,000 each; all required provincial approval if they were to be covered by the provincial health plan; the U.S. tests cost more, and required even more rigorous review and approval if my provincial health plan was to pay for them. The doctors submitted formal reasons for the tests, which were based on the need to find a genetic diagnosis for what Walker had—a reasonable enough request, given that a proper diagnosis might lead to a more complete understanding of his needs, and better treatments. This time around we could expect results in seven to nine months.

  In the meantime all we could do was wait. It was as if a small part of Walker’s body had been mailed out into the world, and was trying to mail itself back again. Not that anyone felt any need to rush. Whatever the diagnosis, it wouldn’t change Walker.

  The results finally arrived in the fall of 2008. I headed back to the lipstick clinic. Jessica was there again, and this time so was Dr. Grace Yoon, a Toronto neurogeneticist whose work on the neurological effects of CFC had led to an association with Kate Rauen’s research team. She was a beautiful woman in her thirties, recently married, with a precise and careful way of speaking.

  The latest round of genetic tests, alas, had only deepened Walker’s mystery. He was still negative for BRAF, MEK1 and MEK2, the standard CFC genes. Nor did he test positive for KRAS, the gene for Costello syndrome, or for Noonan syndrome. His PTPN11 gene, associated with neurofibromatosis, showed no mutation, and neither did SOS1 and BRAF1, two newly unearthed genes thought to have a connection to CFC.

  “It does not mean that he doesn’t have CFC. There are always genes that we don’t know of yet,” Dr. Yoon explained in one of the tiny consulting rooms at the clinic. “There’s no question in my mind that he has something genetic. But at the moment I don’t know what it is. CFC is the diagnosis made by earlier doctors, and I think that’s still the best guess.” Only 65 percent of people thought to have Noonan syndrome, for instance, display the “correct” gene.

  Yoon added that researchers in the United States and Japan had more recently linked the SPRED1 gene to neurofibromatosis. “But to be honest the patients who have that kind of genetic disorder are much milder,” Yoon admitted. CFC, she repeated, “is the perfectly reasonable conclusion.” Walker might have a more severe manifestation, and thus a rare mutational version, of CFC. But she wanted to consult her colleagues. She took some photographs of his face and feet and hands, conducted a physical exam, measured the space between his eyes (they are wider apart than those of most CFC kids), noted his coarser features as well as his more familiar epicanthal folds and the thickened skin over his ears. The familiar chant of symptoms. She would e-mail the photographs and the data to her international team, to canvas their opinion.

  In the meantime we would wait some more. I felt the same way I did when I woke from a dream that at first I didn’t remember having: something had happened, but all I could recall was a mild, faintly disturbing residue.

  “Our knowledge is way behind the genetic-testing technology’s capabilities,” Yoon said, sensing my bewilderment. Her area of expertise was the effects of genetic mutation on cognition—an explorer at the far edge of not one but two frontiers of medical research, the barely known genes and the still unknown brain. Out where she worked, researchers didn’t so much make discoveries as discover how much they didn’t understand. “There are only three things in medicine that have made any real difference to the quality of human life,” Yoon said, as our meeting ended. “Clean water, vaccinations and antibiotics.” Genes don’t yet make the list.

  Memories of my many meetings in the well-swept clinic lingered like a mild virus. I didn’t resent the geneticists: they were the first to admit how little they knew, and at the same time they were obviously the promise of the future. Kate Rauen’s isolation of the main mutating CFC genes has already contributed significantly to the welfare of the syndrome’s children by making the condition easier to diagnose. Early diagnosis in turn permitted early enrolment in a raft of therapies to diminish the syndrome’s effects. The identification of the RAS pathway as a prominent culprit responsible for a wide array of developmental delays, to say nothing of an entire family of mental retardations, is an enormous finding.

  There was lots of promising research that buoyed my spirits—at least until the research amounted to nothing, and my spirits sank again. Two years after Rauen published her findings, for instance, researchers based in Rotterdam discovered that simvastatin—a common cholesterol-lowering drug—can reverse the cognitive deficits caused by neurofibromatosis in rats, especially spatial learning deficits and attention disorders. (I learned about the study when I was contacted out of the blue by Dr. Paul Wang, the developmental pediatrician who had assessed Walker at the age of two in Philadelphia—the doctor who told me that, as far as knowing how to be in the world, Walker was miles ahead of the rest of us.) Unfortunately, the astonishing results demonstrated in rats weren’t replicated in humans. The halting progress of genetic research was a given, and hardly cause for discouragement. What was discouraging was that to a laboratory geneticist who studied CFC as a genetic disorder, the syndrome was always only that: a disorder, an unfixable spelling mistake in the grammar of humanness. I understood that stance, and also hated it. Seeing Walker onl
y as a genetic disorder was a guaranteed way for me to remember that there is such a thing as genetic order; that for each Walker, there are millions of genetically complete children. In a genetics lab, Walker would always be a deleterious effect of nature and evolution, and little more.

  As Walker’s test results wandered back to the lab in the fall of 2008, the genetic testing industry was gearing up for a major burst of hyperbole. In December, Sequenom, Inc., a biotechnology firm in San Diego, announced a new non-invasive prenatal genetic test, to be sold online starting in June 2009. The test licensed procedures developed at Oxford and Stanford universities.

  Until Sequenom came along, there was one medical option available to a pregnant woman who had reason to be worried she might give birth to a child with a defect or syndrome: she could submit to a standard blood serum screening test. The blood test was (and is) famously unreliable, and given to false positives: in one study, 136 out of 199 women tested positive for Down syndrome, but only six had a Down baby. Roughly 2 percent of women who test positive at that stage abort the fetus; the rest move on to amniocentesis, a much more accurate but invasive procedure that draws fluid from the amniotic sac, with occasional complications.