Choices For his birthday, Daddy gave him a time bomb. Britain's #1 killer can be hereditary. Help us fight it. --British Heart Foundation billboard For some couples the news is real, it's bad, and it won't be gone by morning. Consider now Jonathan and Kris Vander Plaat. They are here because they have faced a genetic verdict--a final, unequivocal verdict--and carried on, and because they are willing to share the experience. For one week in April 1993, while he drove back and forth every day between his home in Bergen County, New Jersey, and Columbia Presbyterian Medical Center in New York City to visit his baby, Jonathan Vander Plaat told himself there was still hope that it was all a terrible mistake. Everyone knows the feeling: I can cope with this. Yes, I can. Here is what comes now--one foot, and then the other. Because of the temporary commute and his own state of mind, Jonathan completely missed the sad news back home. A different set of parents were burying an eighteen-year-old son, who had died the day before he was due to give the valedictory speech at his high school graduation. The teenage boy died in the same hospital where Jonathan's infant daughter, Meghan, was now staying, of the same illness that kept her there: cystic fibrosis. Jonathan's own brothers were the undertakers who buried the young man that week. (The Vander Plaat family operates three funeral homes in Bergen County.) They certainly didn't involve Jonathan in that particular funeral. He learned about it only several weeks later. The owner of a luncheonette near the Vander Plaat funeral home asked Jonathan how he had ever handled burying that high school kid, knowing he had cystic fibrosis just like little Meghan. Afterward, Jonathan blew up at his father. "You had no right!" he said. "I'm going to have to deal with things like that!" Jonathan's daily labor involves embalming the dead and counseling their families. He knows well enough to keep an eye out for those families who seem to go on after a funeral as if nothing is wrong. He knows he has to try to find a way to help them get started on the hard work of grief. Secrecy and pretending are out of the question. Living in the dark is no strategy. In addition to their regular duties, the Vander Plaats inter, free of charge, miscarried fetuses--small bodies who are mourned for who they might have been rather than for who they are. Asked how his profession has affected his attitude toward his little girl's illness, Jonathan responds without a pause. "I guess I value each day more than I would if I were not a funeral director," he says, "and I value infants even more." That doesn't mean he will ever coddle Meghan. Quite the contrary: just a month after her illness was diagnosed, when Jonathan and his wife Kris were certain at last that their three-month-old daughter had cystic fibrosis, they took her on a camping trip. They did come home earlier than planned, because the baby coughed too much and no one was having fun. But what obviously matters to Jonathan Vander Plaat is that they went in the first place. "A lot of people are consumed with the disease," he says. "They don't let their child who has it have a life. There are those who build their life around the disease. We want to build the disease around our life." At two, Meghan Vander Plaat is enchanting and wispy-haired, quite a talker. Her father, a pragmatic man, makes the path that led up to the present sound almost easy. Not so Kris Vander Plaat, who sits beside him at the dining table and apologizes for feeling guilty about her daughter's condition. "I knew I couldn't help but feel guilty," she says. "I knew there was no way I could change it. I'm a carrier. I have no symptoms, but she's the one who's going to suffer." Except for her brief hospital stay in 1993, Meghan does not actually seem to have suffered much. She evidently enjoys the gentle pounding she gets, on her upper chest and back and underarms, several times daily, as well as her regular sessions breathing in from the nebulizer, all of it necessary to break up the mucus that builds in her lungs. As far as she knows, the enzymes she must take to help her faulty digestion are just pretty sprinkles on her yogurt. If anything, other children might have reason to envy Meghan all that loving attention. Meghan does not live inside a glass ball--far from it. She goes into the nursery at church. She has regular contact with other children. Her mother has long since put away the bib that reads "Look but don't touch." Meghan has been so robust that Kris once actually contemplated asking the doctors whether she could have outgrown cystic fibrosis. But at heart, she knew better. It's in the genes. What It Means to Be A Carrier, Part II Carrier status is invisible, but it's hardly insignificant. To many carriers of the cystic fibrosis (CF) gene, Iike Kris Vander Plaat, the ambiguities are painful. Studies of CF testing programs show that when people are found to be carriers, they have an immediate depression and may have anxiety for long periods afterward. Carrier status implies possessing a flaw and the ability to pass it on, without oneself suffering the consequences of the flaw. Thus carriers may, like Kris, experience survivor syndrome--guilt for having gone untouched by something that has harmed or even killed a loved one. Carrier status can easily affect relationships--especially future relationships, if the carrier is not currently involved. Outside Dor Yeshorim, the world leaves carriers with the full burden of deciding whether, when, and how to raise the issue. Carrier status may also threaten someone's insurance coverage. Studies by psychologist Joanna Fanos show that even people who are tested and shown not to be carriers can experience survivor guilt and may even wish they were carriers after all. "I felt like, God, why do I get off scot-free?" said one subject who had a sibling with cystic fibrosis. "Give me some burden to carry. I still feel bad about it." Judging from the recent past, Meghan's prospects look quite rosy. In the less than two decades that separate her from the young man who died before he could graduate from high school, improved medical care has transformed the prognosis for children born with cystic fibrosis. "My view and that of most CF specialists is extremely different than even ten years ago," says Meghan's doctor at Columbia-Presbyterian, Lynne Quittell. "Now it's not necessary to have to present parents with a death sentence for their children, the way it was ten years ago." As she speaks, Dr. Quittell is in charge of the care of a sixty-year-old man with cystic fibrosis--an exception, someone at the far edge of the statistical curve, but also a testament to the variability of the disease. She says that one of the leading research scientists in the field, a man old enough to have earned a Ph.D., himself has cystic fibrosis. A 1995 survey showed that one in three young adults with cystic fibrosis worked full time and 90 percent finished high school. Ten years ago, the average life expectancy for cystic fibrosis was about seventeen. Today Meghan can expect to live beyond thirty. "That may sound like a horrible number to you," says Dr. Quittell, who herself passed that birthday the previous year. "To me it's amazing." Because a field once so desperate is now so full of hope, she adds, "it's a fair statement that most cystic fibrosis caretakers find a death now much more frustrating than it ever was. We're always on the cusp of being able to save them. It's harder to accept the natural history of the disease." Medication for cystic fibrosis was improving dramatically even before the gene responsible for the condition was discovered in 1989. Isolation of the gene led directly to the root problem: a molecular defect in a channel that carries salts across cell membranes. It may be that the change in salt concentration inactivates a natural antibiotic that protects body fluids. That knowledge should lead to even better medicines in the near term. Then there's always the possibility, somewhere just over the horizon, that a child like Meghan can benefit from gene therapy--if researchers can find a way to deliver to her cells a functional gene for this channel. In the same month that Meghan entered Columbia-Presbyterian, Dr. Ronald Crystal began testing gene therapy on a few children with cystic fibrosis, down and across town at the New York Hospital Cornell Medical Center. Earlier, he had tried out his strategy on rats, and found that the gene transfer worked safely. After gaining approval from the hospital ethics board, he proceeded to try the transfer strategy on humans. He infected nine children with a cousin of the cold virus, which he had engineered so that it became a sort of drug delivery system: genetically altered so that it could not cause disease but was able to infect a cell with the gene that creates a normal salt channel across membranes. "Have we cured the disease? Absolutely not," Dr. Crystal says. "It will take years to prove it." That will require trials in hundreds of patients. "Don't take this as anything but anecdotes," he goes on. There are still many technical problems to resolve and questions to answer. Gene therapy to date has not improved salt transport, and of course the immune system responds to the virus that carries the beneficial gene. What exists now, he adds, is the potential. "In the same way we knew in the 1980s that finding the gene was going to be a reality, only we didn't know when," says Dr. Quittell, "one day, we're going to wake up and find that gene therapy is a reality." Awaiting that day, she keeps after her families to be faithful in doing the therapy that exists for them today, to use antibiotics and pummel the child's back to help keep the lungs clear. "They have to be well!" Dr. Quittell's brightness and optimism helped the Vander Plaats begin to regain the equilibrium they had lost on the evening of income tax day, when two-month-old Meghan suddenly stopped coughing. It was cold and snowy. Jonathan was standing at the living room door, ready to go out to play tennis. Meghan was in her grandfather's arms. "Already at two months," Jonathan says, "she was very verbal. I mean she babbled all the time. Suddenly, everything just stopped. You could say she was just--stuck.... She was coughing and coughing." All of a sudden she stopped. Jonathan flipped Meghan over and pounded her back. He was afraid she had stopped breathing. She gasped and seemed to gulp for air. They bundled her against the snow and drove straight to the pediatrician, who examined her and told the couple to take her home. Everything appeared to be fine, he said. Jonathan was not reassured. "Can you guarantee us she will live through the night?" he asked the doctor. He would not say. Rather than returning home, they drove to the local hospital. The doctor who examined Meghan there ran down a list of possible explanations for her breathing problem. The last item on the list was cystic fibrosis. He passed over it quickly. "Don't even think it could be CF," he said. "It's a horrible, horrible, horrible disease." Kris remembers clearly: he repeated "horrible" three times. Three nights later Meghan was still in the hospital, and all the other possibilities had been ruled out. No alternative remained except the time-honored diagnostic for cystic fibrosis: the sweat test, a check for excess salt in the perspiration on the surface of her skin. Kris and Jonathan were in the waiting room when the phone call came from the doctor in charge of her case. Cystic Fibrosis It was the kiss of death: if kissing a child on the forehead left a salty taste, said an ancient European proverb, the child was bewitched and would soon die. The modern version of that test for cystic fibrosis is the sweat test, which measures the amount of chloride (a component of salt) in the perspiration. CF is a defect in the transport of chloride into and out of cells. It disrupts the secretion of digestive enzymes, endangering the pancreas and liver; of mucus in the lungs, making breathing labored and encouraging infections and of fluid in the reproductive tract, rendering many CF patients infertile. CF chiIdren no longer die early, and the course of the disease is highly variable. Many now survive well into their twenties or longer, because they can take antibiotics for infections and digestive enzymes in pill form. They also need to have their chests pounded on a regular basis, to loosen mucus in the lungs About 30,000 Americans live with cystic fibrosis. Another 5 percent of the population are carriers of a cystic fibrosis mutation--capable of conceiving a child who will have cystic fibrosis, if the other parent is also a carrier with the same mutation. Some 650 different mutations have now been identified that can cause CF, but geneticists know the list is not yet complete. Therefore testing will not leave someone in the clear about carrier status unless doctors know the precise mutation passed down in his own family. Looking back now, Kris can remember noticing the classic symptoms of CF from the first few weeks of her baby's life: the salt taste on her lips when she kissed Meghan's forehead, and her distended abdomen. But until that moment, she says now, she had been certain the problem would be "something they could cure." Jonathan came back to the waiting room after taking the doctor's call. "I knew the result by his face," says Kris. "He was glassy-eyed." In that instant she sketched out for herself a bleak image of the future. Her first child would die by the age of three or four. There would be no tearful first day at kindergarten. I'm never going to be able to handle this, she thought. The next morning the Vander Plaats grimly checked Meghan out of the local hospital and drove her a half hour into Manhattan, to the specialty clinic at Columbia-Presbyterian Medical Center. There they met Dr. Quittell, who had to start them all over and guide them, step by step, to a new understanding of their situation. She gave them brochures about the disease, and a coloring book that would explain it to Meghan's cousins. She told them what could be done. "Suddenly everything was so much more relaxed," recalls Kris. "She talked to us about patients she has that are over forty years old. She told us that some patients do really well. She kept repeating over and over the fact that Meghan was only two months old, that we could take control and slow the progression of the lung damage." To the Vander Plaats, Dr. Quittell talked about the nature of the disease. To herself, she muses about the nature of the Vander Plaats. What determined Meghan's general good health in her early years? Perhaps something about her genes. Perhaps the large extended family that enveloped her, the hopeful resolve with which her parents managed the extra chores involved in caring for a child with cystic fibrosis. Lucky child. Wonderful family. Variable condition. Responses to the situation are also variable. Although the rest of the Vander Plaat family is dealing admirably with the reality of Meghan's illness, one member of the extended family cannot bear even to see a photograph of Meghan. For some reason that puzzles Kris and Jonathan, he can't handle the thought of it. Genetic risks "tend to make ourselves 'the enemy,' end we are not conditioned to enjoy that message," observes one visionary geneticist, Charles Scriver. "We have been taught to wage war upon disease; and why not? Past crusades and campaigns against scourges have been very successful.... We use the language of World War I to describe our victorious attack on disease." But now, he went on, "how do we understand the enemy when it is partly ourselves? Our cherished medical paradigms fail us when we try to understand." How can one vanquish a genetic disease without somehow threatening the one who bears it in the process? Who is the enemy, the disease or the diseased? Once when Meghan was still in the hospital, Kris Vander Plaat asked Dr. Quittell about their risk of bearing another child with the same disease. "Don't worry about that yet," she replied. "Let's get through this, and then we'll go through the options." They were ready to think seriously about it when Meghan was two. The fact of her illness dramatically altered the elements of the reproductive question for them. The fuzzy hypotheticals that haunt ordinary expectant couples now coalesced into some firm realities. She and Jonathan had only a few possible rolls of the genetic dice: a healthy child (three chances in four, either a carrier or a totally unaffected child) or another child with CF (one chance in four). When they returned to Dr. Quittell to talk about it, she presented them with four options. They could conceive the usual way, have prenatal testing, and if they chose, terminate the pregnancy if the fetus was affected with CF. They could play it completely safe and adopt their second child. Or Kris could be artificially inseminated with sperm from a man who was not a carrier of the cystic fibrosis gene. Finally, the truly high-tech alternative was: preimplantation diagnosis. They could opt for in vitro fertilization, supplemented by a DNA test on the fertilized eggs in that laboratory dish. Based on the results of the test, they could choose which embryos to reimplant. Kris and Jonathan took note of their options and went home to think. Adoption was out of the question. The reasons had nothing whatever to do with a preference for their own genes. Rather, Kris's sister and her husband were trying to adopt. What if the Vander Plaats somehow managed to adopt a second child before the sister received her first? "Maybe it was a naive train of thought," says Jonathan, "but we knew that wasn't the way to go." The artificial insemination option was an equally delicate issue for them. "Neither of us were really comfortable about that," Kris admits. As to the possibility of terminating an affected fetus, this was another non-option, because of their religious faith. "We would go to a long length [to avoid aborting a fetus]," says Jonathan. "Let's talk about quality of life. I think the quality of life of my daughter is just fantastic." What if Meghan had been sicker? What if, like other children they know, she was in and out of the hospital every few weeks? What if the option that faced them was a child who would live for a few years and then, for certain, die? "That is one of those [questions that] I don't know if I can answer," says Kris. "It would have been a lot harder." "If my child had been very, very ill," Jonathan says, "that doesn't mean the second child would be that ill. I could still probably have played it out." The way Kris sees it, once sperm and egg have joined, they form a human life. At least it has that potential, Jonathan says. Jonathan talked about the matter of abortion with several ministers, who told him that nothing in the New Testament forbids it. Still, it was not an alternative he and Kris could choose. In vitro fertilization was "a real big moral issue," Jonathan says. "What do you do with the ones that come out positive [for CF]? . . . Who are we to say, 'Sorry, you're not what we wanted'?" "Then we look at Meghan," Kris breaks in. "She's such a joy. That would be like saying her life wasn't worth it." At some stage they asked Dr. Quittell if in vitro testing could assure, with hundred-percent odds, that their fetus would be normal. Not a hundred percent, she replied. "That's when we stopped troubling about it," Jonathan says. They don't even mention whether they ever discussed with Dr. Quittell a different option entirely, the one they finally chose. As Kris puts it, they looked to their faith. They decided just to go for it, to put the matter in God's hands. They would conceive a child, and they would bear it. Come what may, they would bear it. "Human nature tells us we want to have a healthy child," Jonathan says. "By the same token, who are we to decide?" "God knows what we can handle," Kris adds quietly. "And He won't give us what we can't handle." What God gave them, almost as soon as they had resolved the matter in their own minds, was a pregnancy. God did not give them peace of mind, however. It was, in Jonathan's words, a rough decision. They knew they could deal with whatever happened, but they were desperate to know what they would be dealing with. As soon as possible after Kris conceived, they traveled to Philadelphia for CVS, chorionic villus sampling. This is a test similar to amniocentesis, but it can be done earlier. A couple can get results within eight weeks of conception. It poses some additional risk to the fetus, but Jonathan and Kris were told that the center where they would have the CVS test had one of the best records for not harming a pregnancy. Knowing the outcome would be important even for the fetus itself, because in the delivery of a child with cystic fibrosis, special matters need to be attended to. The Vander Plaats placed the matter in God's hands, and as they see it, God spared them the same challenge again. Their genes recombined such that their second child is not affected with cystic fibrosis. Ryan Kristopher was born in May 1994, as healthy as predicted, but also (as predicted) a carrier, inheriting Jonathan's gene for CF. As carefully and seriously as anyone on earth could have done, one couple from New Jersey faced up to their options. And now Jonathan Vander Plaat is exercising another option. "I'm done having kids," he says bluntly. "That's it." Excerpted from Unnatural Selection: The Promise and the Power of Human Gene Research by Lois Wingerson All rights reserved by the original copyright owners. Excerpts are provided for display purposes only and may not be reproduced, reprinted or distributed without the written permission of the publisher.
