"C'est moi, le chef! Suivez-moi!" ("I'm the boss! Follow me!") Those were among Lorenzo's first words in French, and a phalanx of local kids fell in behind him as he trooped across the front lawn of his parents' place in Itsandra, Comoro. His mother was chagrined and amazed. "God help us, I dove behind the papaya tree, thinking, 'Lorenzo, couldn't you say, "Shall I be the leader this time, and you be the leader next time?" ' " Michaela recalls. "But Lorenzo is very comfortable with his own sense of being a leader." It was an idyllic life for a child—in the evenings, boating with his father among the dolphins in the lagoon by their house, traveling to see the wild monkeys in the mountains of neighboring islands. "He was an exceptional boy," Augusto remembers.
Now Lorenzo is 13 and still remarkable. He loves opera and Dickens and Kipling and still understands three languages. But he has not spoken in six years. He has a handful of attendants and nurses for round-the-clock care. His friend Oumouri Hassane, now 26, came from the Comoros in 1985 to help. They watch him constantly, careful to notice when he wiggles his fingers or blinks or moves his head. These are the ways in which he communicates.
Had events taken their normal course, Lorenzo would have died in 1986 or 1987—two years after he was stricken with a rare genetic disease called ALD (adrenoleukodystrophy), which strikes young boys and slowly paralyzes, Then kills them. He is alive today because his mother and father, with virtually no scientific training, threw themselves into medical literature in a desperate effort to find a cure for his disease. They didn't find one, but against all probability, they did find a way to halt the progress of ALD and prevent susceptible children from developing the symptoms.
In their search, the Odones faced condescension, disbelief, even outright hostility from some in the medical community. They ignored the advice of doctors ranging from hospital residents to world-renowned experts. Theirs is a stunning achievement in research, a remarkable act of faith and an amazing medical detective story. "Mind you," says Augusto, "I wouldn't like it that people think all of our efforts were out of intellectual curiosity. This is a love story."
AT FIRST, THE CHANGE in Lorenzo was so gradual that only his parents could detect it. In 1984, a year after they returned to the U.S. from Africa, their perfect child suddenly became difficult. "He began having temper tantrums every afternoon," Michaela remembers. "They were very self-contained. They would go away, and he would be quite wiped out by them." Psychologists told the Odones that Lorenzo was just having trouble adjusting to a new life—a plausible explanation, until more symptoms appeared.
"Next, I thought he was occasionally slurring his words," Michaela says. "Everyone really laughed at that. They said, 'Leave the kid alone. He's becoming Americanized.' " As Michaela sits on the terrace behind her home, her voice drops almost to inaudibility as she remembers the beginning of the nightmare. "In kindergarten he was having a great deal of trouble finding the bathroom. A lot of people said. 'That's what kids do.' "
But after Lorenzo twice fell backward in their home, the Odones consulted a pediatric neurologist. "He said the CAT scan was fine and Lorenzo was probably hyperactive," Michaela recalls. Months later, the Odones learned that a radiologist had noticed irregularities on the scan and alerted the neurologist, who ignored his colleague's concern. Even now, seven years later, that memory rankles. "The neurologist was not only arrogant," Michaela says. "He was dead wrong."
Four months went by, and Lorenzo's hearing deteriorated badly during a bout with the flu. Seeking a second neurological opinion, the Odones consulted Dr. Donald Fishman. Like most specialists in his field, Fishman had never seen a case of ALD. "My guess would be that 50 percent of neurologists would not know even the name of the disease," Augusto says. In fact, ALD has been identified in no more than 1,000 American families. But Fishman, after examining Lorenzo and consulting medical texts, admitted the child to Children's Hospital in Washington, D.C., for tests. His hopefully worded instructions to the hospital staff: "Rule out ALD." They could not.
Augusto Odone is a large man, with a great mass of curly graying hair and a manner that can be close to overwhelming. But he chain-smokes and talks softly in his Italian-accented English when he recalls the day the diagnosis was made. "Dr. Fishman sat us in a room without windows," Odone recalls. "He is a very intense type of person, usually dressed in black. He said, very matter-of-factly, 'It's ALD. It's neurologically progressive, and children survive on an average only two or three years after diagnosis.' "
Augusto asked, "Are there any exceptions?" The answer was no.
"We were really, completely destroyed," says Odone. "He said that Lorenzo would lose his gait, his speech, his sight. Dr. Fishman didn't use the word, but he was telling us Lorenzo would be a vegetable. And then he'd die. Even before we left the hospital, my wife went to a phone. She called all the priests she knew and asked them to start praying. Then she called the Comoros and asked our friends there, who were Moslems, to go to the mosques and pray."
As the Odones learned, the characteristic trait of an ALD victim is the excessive buildup of certain substances, in this case, very long chain saturated fatty acids (VLCFAs), known as C24:0 and C26:0. With nowhere to go, these fats accumulate in the cells of the body. By some mechanism that doctors don't yet understand, VLCFAs are presumed to destroy myelin, the material that coats and insulates the body's nerve fibers, making if increasingly difficult for ALD victims to move, eat and, ultimately, to breathe. ALD is a genetic disease, linked to the X chromosome; only sons contract the severe form.
HERE THE ODONES' STORY diverges from that of all the other ALD parents who have heard their children receive a sentence of death. "According to the psychologists, you're supposed to go through denial, then all these other stages, then acceptance," says Augusto. "I thought that was all baloney." As Michaela recalls, "Our immediate reaction was, 'This may be what happens to everybody else, but not to our kid.' "
Even before the ALD diagnosis was confirmed in April 1984, the Odones had decided to learn about the disease. "We asked a resident, who was otherwise a nice guy, to recommend some reference material," Augusto remembers. "He said, 'Don't bother. There isn't very much written on the subject, and that little you can't understand.' "
Augusto Odone is accustomed to being taken seriously; when he wants something, his resolve is granitic. Michaela is equally strong-willed. Predictably, the young doctor's curt dismissal was all it took to send both parents racing off to the library of the National Institutes of Health, beginning the odyssey that would save their son's life. "People always ask us win we did it. Michael a says. looking mystified. "I tell them they wouldn't ask if they knew Lorenzo."
Augusto and Michaela soon learned that no effective therapy existed for ALD. Dr. Hugo Moser, then president of the Kennedy Institute for Handicapped Children in Baltimore, is the acknowledged expert in the disease; his laboratory confirmed Lorenzo's illness. Dr. Moser had created a low-fat diet devoid of VLCFAs in an attempt to reduce their levels in the body, but results were mixed, at best.
The Odones and Dr. Moser began a curious relationship that persists to this day, tinged with mutual respect and mistrust. They have worked together, yet at times have argued publicly. "I think if I lived in the same town with this man and knew him under other circumstances, we would become good friends," Augusto says.
But that was not to be. " 'I come from a family where we never accept the conventional wisdom," Augusto says. For her part, Michaela came to Lorenzo's crisis a few years after her father had suffered a life-threatening bleeding ulcer that was exacerbated by inadequate treatment. Neither she nor her husband was willing to defer to experts on the question of their child's life. "It wasn't that we wanted to show the doctors anything," Augusto says. "We thought, 'We love this kid, and we don't want to lose him. What is the enemy in this business? The bad fatty acids. Let's find a way to kill them.' "
THE INTENSITY THE ODONES bring to whatever they do probably saved their son's life. But it did not always endear them to doctors. By his own account, Augusto has been relentlessly on the phone to researchers, prodding, suggesting, questioning in a way in which scientists are unaccustomed to being treated by lay people. Yet though their relations are strained today, Dr. Moser and the Odones worked closely together after Lorenzo's ALD was diagnosed, and the Odones made a remarkable proposal to the doctor: They would organize—and somehow pay for—the first world-wide conference on ALD if the Kennedy Institute would sponsor it. Dr. Moser agreed, and the Odones raised $36,000 for the two-day seminar, attended by 38 experts from Japan, Europe and North America. (They persuaded two airlines to provide free flights for the attendees, used neighborhood volunteers to feed and transport the visitors, and later spent $6,000 of their own money for research equipment.)
Even before the conference began, the Odones went to work, poring over medical journals. The breakthrough came after one of Michaela's visits to the NIH library. "People with scientific training cringe when they hear what I did," she laughs. "After taking the orderly approach and not finding anything, I went zigzagging through the index, speed-reading anything related to storage diseases." In a medical journal from Poland, she found the English-language abstract of an article about rats with a genetic defect. A researcher had discovered how to lower their level of certain fatty acids by feeding them other fatty acids of a different molecular composition. If this technique had worked in rats, Michaela reasoned, perhaps a similar therapy might work in humans.
At the conference, Dr. William Rizzo of the Medical College of Virginia announced he had demonstrated that oleic acid—a major component of olive oil—can lower levels of VLCFAs. But Rizzo had done his work in the test tube. "The doctors told us, "We know that oleic acid works in vitro, but it won't work in living beings,' " Augusto recalls.
IN FACT, DIETARY TREATMENTS for ALD had been largely ineffective. "All these guys were working on how to repair the gene," Augusto Odone says. "That is the elegant solution; the gene is where the screwup is, and you repair the screwup." But gene therapies were a decade or more from completion. Lorenzo probably had at most two years to live—and four months had been lost already to misdiagnosis. By the end of the conference, Lorenzo had stopped walking. His speech was gone. Now he was having trouble swallowing and had to be fed through a tube. "Dr. Fishman said it might be a matter of weeks before he died," Augusto recalls. "We decided to look at the other side and try to shut down the sources of the disease." Michaela went to work finding an edible form of oleic acid.
It took more than 40 phone calls to chemical companies around the country, and many of the firms she contacted gave her short shrift. "They would ask, 'Are you a doctor?' and when I said no, that was the end of it," she says. But one firm in Columbus, Ohio—then a subsidiary of Stokely-Van Camp—told her it manufactured an edible form of the oil and agreed to send her a liter.
Before the Odones administered it to Lorenzo, they needed to test its efficacy. Michaela's sister, Deirdre Murphy, offered to be the human guinea pig. Since she carried the defective gene (after Lorenzo's illness was diagnosed, all family members were tested), Deirdre had a high level of VLCFA in her system, although she did not suffer from the symptoms of ALD. Augusto, an excellent cook, blended the oil into a variety of dishes; within two weeks, Deirdre's VLCFA level dropped by half. Without hesitation, the Odones started Lorenzo on the oil.
Oleic acid worked, but only partly. Although Lorenzo's VLCFA levels dropped significantly, they were still double what they should have been. Dr. Moser, who had been skeptical, was impressed enough to recommend oleic acid to other patients.
While they did their research, the Odones also had to care for Lorenzo—and Augusto had to hold down his job. So Michaela looked after her son during the day, and Augusto took the night watch. They saw each other only briefly each day. "We were ships passing in the night," Michaela says.
STILL LORENZO'S PARENTS kept at it, reading, thinking, reading, thinking. "I thought that if we could figure out why oleic acid works, we could improve the treatment," Augusto says. Then he had a brainstorm: If he could find another monounsaturated edible fat, he might lower VLCFAs even further. If he could fill the body's machine with more of the "good" monounsaturated fats, he thought, he could keep it from making the "bad" fatty acids, C24 and C26.
In a few weeks Augusto hit upon erucic acid, which is found in rapeseed oil—a compound similar to mustard oil. But most medical literature said erucic acid was toxic in rats and mice. Only one group, in Canada, had continued research into erucic-acid tolerance in humans, and it found that toxic problems had not surfaced. The Canadians pointed out that rapeseed oil was a dietary staple in India and Eastern Europe. The Odones decided to take the chance.
No company in the U.S. made an edible form of erucic acid, but the Odones finally found one that would—Croda International, in England. One of Croda's senior biochemists, Don Suddaby, himself wheelchair-bound by a genetic disorder, agreed to take on the job. In December 1986, Croda shipped its first batch of erucic acid to the Odones.
Once again, Deirdre was the guinea pig. In 11 days, her VLCFA reached normal levels for the first time in her life. The Odones had found a way to "kill the C26"—the first time in medical history that had been done. Quickly Augusto began administering a mixture of erucic and oleic acids to Lorenzo. Within two weeks, the boy's VLCFA levels dropped to normal. The progress of his ALD had been stopped.
WHEN REPORTS OF the Odones' discovery were published in Italy, their telephone started ringing constantly with calls from anxious parents in Europe. But the medical establishment reacted more cautiously. Augusto thinks that some scientists resent the notion that two lay people could solve a problem that had baffled professionals. Today, although Dr. Moser is overseeing tests of the oil, he refuses to endorse it fully, arguing that it must be subjected to the same rigorous testing as any other scientific discovery. "I would call what [the Odones] have done a moderately significant achievement," Moser says. "You must remember that it built on the work of medical researchers, especially Dr. Rizzo's work on oleic acid."
Croda has begun manufacturing the oil and supplying it to ALD patients; it has also filed a patent application for the combination of erucic and oleic acids that recognizes Augusto Odone as the inventor. At the Odones' request, the product is known as Lorenzo's Oil; according to Augusto, at least 30 boys who were presymptomatic carriers of the ALD gene have remained free of symptoms while taking it. But the oil came late in the day for its namesake. Lorenzo was immobile, speechless and hearing impaired by the time Augusto first administered the oil to him. He is still bedridden or confined to a special wheelchair, but his parents believe his condition is slightly improved. Michaela spends hours with her son, reading to him, working to keep his motor skills and intellect alive. On a recent test of his comprehension of Kipling's Captains Courageous, she says, Lorenzo answered 28 out of 30 questions correctly.
The collaboration of mother and son will produce a children's book about Lorenzo's adventures in the Comoros; he would signal when he wanted an episode included or deleted, and would even indicate words he preferred. "Lorenzo's going to be a published author at 13," his mother says proudly. A feature film about the family will be made this fall, with Susan Sarandon and Nick Nolte playing Michaela and Augusto.
Having performed one miracle, Lorenzo's parents are now determined to perform another. Since his destroyed myelin will not regenerate itself, they have decided to find a way to bring it back. They have founded the Myelin Project, a foundation to promote research on repairing damaged myelin. "This is our version of the Manhattan Project or Project Apollo," Augusto says. "The idea is to bring together the work of labs in different countries and encourage them. By coordinating them, perhaps what could take 10 years to accomplish might be done in two weeks."
Myelin defects play a part in a number of diseases, including ALD, Guillain-Barré syndrome and multiple sclerosis. Some of the work the project is supporting has already shown promising results—particularly in Dr. Ian Dancan's laboratory at the University of Wisconsin. A veterinarian, Duncan is looking for a cure for inherited myelin defects in animals—and he has found that transplanting myelin into the brains of rats can cause some spontaneous regrowth of the material. "We should know within two years or so whether this approach has promise for humans," he says.
The Odones are realistic-about the future. "We don't know how many of Lorenzo's nerve cells have been destroyed," Augusto says. "And if remyelination works, we don't know how long it might take. It could take 10 or 15 years to restore the myelin that has broken down over all those years. But if we can develop some kind of remedy, that would be fantastic."
"YOU NEEDN'T WORRY," Michaela tells Lorenzo when she wants to keep his spirits up. "You're a leader. Probably, through some terrible twist of destiny, you were intended to lead all the other children in the world out of this situation to Actory." Dr. Duncan would agree. "The Myelin Project has given us more than money," he says. "It has given us inspiration. It added a focus to our work and provided us with a human context. Our people are working harder; we see the urgency. The project has provided us with a goal."
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