In a Nov. 17 article on Lorenzo Odone and the disease known as adrenoleukodystrophy (ALD) that afflicts him, the Myelin Project was misidentified. The story should also have made clear that the foundation raised more than $800,000 in the fiscal year ending in September 2001. (Published 11/19/02)
He is bearded now, and handsome, as anyone might have expected from seeing photographs of him as a boy.
Awakening from a deep sleep, he blinks his large brown eyes, and a vague look of alarm seems to flit across his face. He blinks again, languidly, as if brushing away remnants of a dream.
But the ruddy-faced young man, cocooned in blankets on a brisk autumn day, has been unable to escape his solitary dreamworld since a rare genetic disease began attacking nerve cells in his brain some 20 years ago. The disease -- adrenoleukodystrophy, or ALD -- has left him unable to see, speak or move.
That Lorenzo Odone is alive at all has made him famous, thanks to a seemingly miraculous potion that bears his name. His parents, Augusto and Michaela Odone -- he a former World Bank economist and she a linguist -- plunged into the unfamiliar world of biochemistry to discover "Lorenzo's oil," a controversial treatment made of rarefied oils normally used in the kitchen. The discovery has been celebrated in a Hollywood movie -- and ridiculed by some scientists. But now Augusto Odone is proclaiming vindication. Odone, 69, caring for his son in Northern Virginia since his wife's death of lung cancer two years ago, has been tirelessly touting a new study that he says proves Lorenzo's oil is an effective treatment.
The 10-year international trial, led by researchers at a Johns Hopkins University affiliate, focused on 105 boys under the age of 6 who carried the ALD gene but had not shown symptoms of the disease. All of the children -- 69 boys in the United States and 36 in Europe -- were started on Lorenzo's oil. Using magnetic resonance imaging and other diagnostic tools, researchers then followed the group from 1989 to 1999 to evaluate whether the disease produced neurological damage. The results suggest that boys who begin taking Lorenzo's oil early, take it religiously and follow a restricted diet are more than 73 percent more likely to remain healthy than those who are less strict.
The study, which has generated intense media coverage in the United States and abroad since its release in late September, has lifted Odone's hopes not only for finding a cure for ALD, but also perhaps for reversing the course of his son's disease. From Lorenzo's bedside and a nearby office in Fairfax County, Odone has launched an international media blitz to silence the skeptics. He has written told-you-so letters to scientists and reporters who had dismissed Lorenzo's oil as quackery.
"Now they don't say that anymore, because there is scientific evidence," Odone said. "It is, in fact, a fantastic thing."
But among professionals in the small field of ALD research, the latest study has failed to quell doubts about Lorenzo's oil -- and in some cases redoubled skepticism. The New England Journal of Medicine rejected the study for peer-reviewed publication, and critics point out that its design, duration and lack of a control group render any conclusions unreliable.
"It might be that Lorenzo's oil, for reasons we do not understand, has a slight effect. But in any case, the data do not demonstrate that Lorenzo's oil has a major effect," said Patrick Aubourg, Europe's leading ALD researcher. "I consider that its conclusions go far beyond the data themselves."
Along with pointing up the difficulty medicine has in deciding whether to endorse hopeful but still unproven treatments for catastrophic disease, the latest chapter in the story of Lorenzo's oil also highlights a parent's passionate dedication to alleviating his child's suffering -- or, at the very least, making sure that his child's suffering is not in vain.
Dismissing criticism of the study as "baloney," Odone shrugs off the medical journal's rejection and continues the battle against disbelievers.
"Why? Because I want children to live! I don't give a damn about publication after publication," he said. "I want the whole world to know that Lorenzo's oil might prevent -- may prevent -- the onset of this terrible disease!"
A Tiny Problem A single enzyme tied to a single gene on a defective X chromosome wiped away the life Augusto Odone had imagined for himself.
It nearly killed his son. It strained his marriage. It reshaped his religious beliefs. It kept him from returning to his beloved Italy. And it launched a 20-year crusade to find a cure for the rare disease that crippled his son with terrible swiftness.
The experience, even the suffering, has deepened his faith in God. But it shook it first.
"The first reaction was, 'Why of all people was it me?' " he said. "But then the second question was, 'Perhaps God sent him to me because we could do something.' "
Sitting at a table in his home near Fairfax City, Odone points to an early school photo of Lorenzino, as he sometimes calls his son. Nearby is a poster for the 1992 movie "Lorenzo's Oil" with Susan Sarandon and Nick Nolte that proclaims, "Some People Make Their Own Miracles."
The portrait shows a towheaded 5-year-old in bright red overalls, his face lit by a puckish smile. The framed picture, one of the last taken before the onset of the disease, has become a record of what was snuffed out.
At the age of 4, Lorenzino was able to speak English, Italian and a little French and, while listening to opera, gently chide his father for being unable to discern the difference between Luciano Pavarotti and Placido Domingo.
But soon after returning from a World Bank posting in the Comoro Islands in 1983, the family noticed changes in their delightfully precocious son: slurred speech, a loss of balance. He threw fits in school. Then his hearing began to go -- a frightening development discovered one day when his mother was reading to him.
"He said, 'Mommy, can't you talk louder? I can't hear you,' " Odone recalled.
Deadly Chemistry As they made the rounds of doctors, his parents feared he might have contracted an exotic disease in the Comoros. Eventually, doctors told them that Lorenzo had ALD, a rare, inherited disease marked by the accumulation of very long chain saturated fatty acids in the body.
These fatty acid molecules, based on strings of carbon more than 22 atoms long, are normally broken down in the process of metabolism. But those with ALD, because of an impaired gene, lack the necessary enzyme for the process.
In its most virulent form, the buildup of the very long chain fatty acids is thought to trigger an attack on myelin, the protective sheath that covers nerve fibers, in the brain and the adrenal complex. Known as demyelination, this process, like stripping insulation from electrical wires, disrupts the ability of the nerves to communicate with each other. The result is severe neurological damage and, eventually, breakdown of bodily function.
Though the symptoms and progress of the disease can vary greatly, when it strikes children, usually around age 7, its development is rapid and horrifying. In just two years, a child's first, often subtle symptoms -- trouble with schoolwork, behavioral problems or impaired eyesight -- can progress to a comalike state or death. Adrenomyeloneuropathy (AMN), a milder form of the disease, strikes later, between ages 20 and 30.
Because the disease is caused by a gene on the X chromosome, and women have two X's, they are far less likely to develop symptoms. But they can pass the defect to their sons, who have one X and one Y chromosome and more often suffer the disease's effects. About one in 20,000 people worldwide suffers from ALD. The only generally accepted treatment, bone marrow transplant, carries a high risk of death and is effective only when used early in the progress of the disease. Researchers also are exploring the prospects of treatment with gene therapy and cell cloning therapy.
Although some recent research suggests that the accumulation of fatty acids may be a marker of the demyelinating disease, and not its direct cause, scientists have theorized that controlling the level of very long chain fatty acids might halt ALD's progress.
That was the launching point for the Odones. Augusto and Michaela had no medical background. Their grounding in Latin and Greek, however, helped them pierce the dense language of science.
Eventually, their research led them to believe that a single enzyme was responsible for converting shorter-chain fatty acids into two kinds of very long chain fatty acids, one of which is dangerous and one of which is not. They hit on a brilliant idea: Perhaps, by introducing a certain type of fatty acid into the diet, they could trick the body into creating the benign form of very long chain fatty acids.
So they gave Lorenzo doses of oleic acid -- a substance found in olive oil. This cut the level of harmful very long chain fatty acids, but not enough. The Odones added erucic acid, which is found in rapeseed, and the fatty acid levels became normal.
Faith and Hope Odone still kicks himself that their discovery came too late to slow the disease's ravages in his son.
"It was fast. Very fast. Lightning fast," Odone said.
A machine, puttering intermittently beside his son's bed, clears away his son's saliva.
"But I don't want to record all those things, because they make me sad," Odone said. "Okay?"
These days, Odone looks after his son with the help of nurses and Oumouri Hassane, 36, who befriended the family years ago in the Comoros. They monitor Lorenzo's vital signs, take blood samples and supervise his four daily feedings. Each meal -- a soupy mix of meat and vegetables, sauteed in Lorenzo's oil -- is pumped through a nasogastric tube. Lorenzo, who weighs 105 pounds, consumes about 10ml of oil per meal.
The oil, manufactured by Gaithersburg-based SHS North America, costs about $73 for a 720ml bottle, or enough to last about two weeks. Odone owns the patent.
Though organized religion leaves him cold, Odone's quest to understand the workings of a living cell confirmed his belief that a superior intelligence created the universe.
That faith, in science and miracles, has convinced him that his son may step from his bed someday if the body can be coaxed into rebuilding myelin. The Myelin Foundation, a nonprofit group begun by him and his wife, has raised more than $800,000 to underwrite such research. And even if all is for naught, he believes it is enough that his son survived. Who is to say, he asks, what the quality of life is?
"He shows pleasure," Odone said. "For example, when I caress his face, when I talk to him in an affectionate way, he vocalizes," Odone said, imitating a sound that resembles an urgent hum of pleasure.
Before the disease, Odone imagined that he would retire from the World Bank and return to Italy. There is a house in the Piedmont that he bought, thinking of old friends and the tomatoes that grow in its rich soil.
"Instead, I'm stuck in Fairfax, talking to squirrels," Odone said, sitting in his Dunn Loring office. He gestures beyond the picture window where the animals come to feed. "Really -- you think that's a joke? Some of my best companions are squirrels."
There is no irony when he describes his marriage to Michaela Murphy Odone, a native of Yonkers, N.Y., as "the love story of the century."
But that, too, suffered. Michaela devoted her time almost exclusively to her son's care, while Augusto worked at the World Bank and both hunted for a cure.
"At the end, we had short fuses. But, really, we loved each other very much," he said.
Odone believes that the new study, as well as his 24-year-old son's survival, offers proof of the treatment's efficacy, and he cites other families that claim success.
"Trying Lorenzo's oil seemed like a no-brainer to me," said Patti Chapman, whose 23-year-old son, Michael Benton, has been taking Lorenzo's oil for about 15 years, since doctors discovered that he had the defective gene. He shows no symptoms of the disease.
"I feel pretty strongly this was a real proactive thing to do for Michael. In my heart, I feel it's what got him to this point," she said.
Chapman still remembers panicking when she learned what the disease could do. In the 1950s, one of her younger brothers died at age 4 of what was then believed to be a brain tumor but was later thought to be ALD. Another brother died a year ago of the adult form of the disease. He had been taking Lorenzo's oil.
Knowing that studies have cast doubt on whether the oil can penetrate brain tissue, she wonders whether the treatment will really protect her son.
He wonders, too.
"I'd have to agree with some of the people who say they're still not sure," Benton said.
Doubts on the Research No one disputes that Lorenzo's oil lowers the level of fatty acids. Even critics suggest that at-risk ALD children should take Lorenzo's oil as long as the treatment could still prove effective.
But Aubourg, a French researcher at the French Institute of Health and Medical Research in Paris who was the first to identify and clone the ALD gene, said at best the new study suggests that Lorenzo's oil might slow the brutal progress of the disease in some patients. But no one knows for sure whether the boys who have escaped ALD's debilitating symptoms did so because of Lorenzo's oil or a quirk of their own biology, he said. Further study is necessary to determine whether they will show symptoms of milder forms as they grow older.
William B. Rizzo, who as a doctor at the Medical College of Virginia was among the first to embrace Lorenzo's oil as a possible therapy, said the time has come to consider studies with placebos and control groups, as is done with any other uncertain remedy.
"I don't know that we should be making recommendations on therapy based on unpublishable studies," said Rizzo, who now teaches at the University of Nebraska Medical Center.
But Donald Hunneman, a researcher at the University of Gottingen who took part in the study, said he had been more pessimistic about the oil before he saw the results.
"It's proven that it does have an effect. The patients who keep their fatty acids below a certain level survive statistically better than those who don't," Hunneman said. "It doesn't work all the time. People do, nevertheless, get sick, even if you treat with the oil."
Even the study's lead researcher, Hugo W. Moser, director of the Neurogenetics Research Center at the Kennedy Krieger Institute in Baltimore, acknowledges its shortcomings.
But Moser, the preeminent U.S. authority on ALD, said he saw enough that was hopeful in the results that he felt an ethical obligation to publicize the findings.
"I find myself in a dilemma. Here I have data, flawed as they are, suggesting that this stuff, this medication, may be of help," Moser said. "On the flip side, there is nothing else."
Odone's face shows that he has heard all the skepticism before as the light pouring through the windows of his house plays up his monumental features: high cheekbones, deeply sunken cheeks, a large, almost Clintonesque nose and hair that is silvery and thick for a man nearing 70.
Years of smoking have imparted a mild grumble to his rich, Italian-accented voice and left him gobbling nicotine pills. His tone conveys casual surety whether discussing chains of carbon atoms or the merits of espresso.
Beneath the courtly bearing and Old World hospitality, however, is a relentlessly purposeful man. He does not suffer fools, and a certain sharpness emerges the moment the word "theory" is mentioned in regard to Lorenzo's oil.
"Don't call it a theory anymore, because it's been proven!" he says. "I don't want to sound angry, but it's 10 years I've been fighting this."