By Shankar Vedantam
Washington Post Staff Writer
Sunday, January 28, 2007
Most people in the world who knew anything of Hugo Moser knew him only as Professor Nikolais, the impersonal scientist largely impervious to the suffering of his patients in the hit 1992 movie "Lorenzo's Oil." Which is to say most people didn't know Moser at all.
One person who did know the Baltimore neurologist, who died eight days ago of pancreatic cancer, is Augusto Odone, father of the real-life Lorenzo. Though terribly disabled by the cruel genetic disease depicted in the movie, Lorenzo is still alive at age 28.
Odone, now 83 and living in Fairfax, was once Moser's critic, but he became one of the scientist's biggest fans. He knows that right up to the day Moser died at age 82, the scientist was passionate about fighting Lorenzo's disease, known as adrenoleukodystrophy or ALD.
Moser cared so much, in fact, that even as his strength slipped away after surgery for cancer and painful blood clots, and as doctors debated whether to amputate his legs, he and his lab team kept working on a long-sought screening test that could soon eliminate much of the suffering caused by ALD -- the suffering that Moser's character in the movie supposedly cared so little about.
In a final interview shortly before he died, Moser reflected wryly on the movie: "The good guys were given real names. The bad guys were given pseudonyms."
But Moser turned his hurt over his portrayal in the movie into a weapon against the rare disease, which mostly targets young boys and sends them spiraling into brain failure and death. If the movie could spur public interest and help find a cure, he was more than willing to accept the public distaste for his character in the movie.
"He was angry," his wife, Ann, said.
Moser gently contradicted her. "In the long run," he said, "I have been immensely helped by the movie."
Cable television still regularly runs "Lorenzo's Oil," which depicts how Odone discovered that patients with ALD could benefit from a derivative of olive oil and rapeseed oil. But it was Moser who took that inspiration and demonstrated the oil's uses -- and limitations -- by doing methodical science, the very science disdained in the movie as impersonal and cold.
As the years progressed, Moser and Odone came to an understanding very different from the one portrayed in "Lorenzo's Oil" -- each man realized that whatever he had achieved against ALD would have meant little without the other's contribution.
Moser showed that treatment with the oil was useful, but only if given before the afflicted boys began to show symptoms. Because most parents have no way of knowing that their sons have the disease until symptoms occur, treatment with Lorenzo's oil has turned out to have limited value.
His father's discovery came too late for Lorenzo. He has not spoken a word for 23 years as a consequence of ALD's pervasive -- and apparently irreversible -- neurological damage.
For the oil to be useful, all newborn babies would have to be tested for ALD using the nationwide screening program that detects many other genetic disorders. But no one had a test that worked.
Until now.Finding a Marker
Augusto Odone and his wife, Michaela, were referred to Moser shortly after Lorenzo was diagnosed; the neurologist at the Kennedy Krieger Institute in Baltimore was one of the few experts in the country interested in the rare disease.
The Odones already knew that there was no cure for the genetic disorder, which causes a buildup of substances known as very long chain fatty acids and strips nerve cells of their protective myelin sheaths. (Multiple sclerosis causes similar damage, but much more slowly and for different reasons.)
ALD causes a host of terrible problems, including deafness, seizures and difficulty with movement. Once symptoms appear, the Odones learned, the children die within a few years.
Refusing to accept this death sentence, the Odones began their own search for a treatment. Reading obscure scientific journals and drawing on a wide range of scientific experts, they discovered that a derivative of olive oil and rapeseed oil might counteract the buildup.
Scientists thought that the oil was dangerous, but as Lorenzo went downhill rapidly, the Odones took a chance on it. They found out that rapeseed oil was widely consumed in many parts of Asia and, after testing the oil derivative on a family member, they gave it to Lorenzo. Augusto Odone believes his son is still alive today because of the treatment.
The dramatic arc of the movie explored the tension between a parent's desire to do anything for a sick child and a scientist's impulse to gather data in a precise and methodical manner. The Odones were in a race against time to help their son; Moser was cautious about spreading false hope and wanted to collect evidence, not anecdotes.
Hollywood found the idea of intuitive leaps of faith more appealing -- and the movie strongly suggests that the only thing keeping brilliant cures from the public is the stubbornness of scientists who insist on their plodding ways. In the movie, the Odones accuse Moser's character of being more interested in scientific accolades than in helping their son. In one climactic scene, Lorenzo's mother, played by Susan Sarandon, accuses the neurologist Nikolais, played by Peter Ustinov, of being a callous coward.
"The life of one boy," Michaela Odone venomously tells Nikolais, "is not enough reward for you to risk the reputation of the institution and the esteem of your peers."
Parents and scientists do have conflicting motivations, but the movie's narrative failed to see two things. Moser's methodical steps masked a passion and determination that would far outlast those of families focused on a single patient. Hollywood also failed to see how the separate motivations of parents and scientists could work well together, and it was left to real life to provide that happier ending.
Moser said that even as the Odones were accusing him of going too slow, he was hearing from medical colleagues outraged that the oil treatment was being oversold; some families spent fortunes getting their hands on it only to find it didn't help. "There was a feeling it was snake oil and people were taking financial advantage of desperate patients," Moser said.
He decided to do what he always did -- look for evidence. He started recruiting children for a clinical trial.
Because ALD runs in families, Moser identified several dozen boys from families who had other children with the disorder. He conducted complicated tests to spot boys at risk for the disorder but not symptomatic. He gave them Lorenzo's oil and followed them for as long as 10 years, eventually showing that the treatment was useful, but only if started early enough.
It took more than a dozen years after the movie hit the screen to reach this sober finding.
But even that was not enough. Because the complex tests used in the study were impractical to use on a mass scale, Moser knew he needed a simple blood test that could be incorporated into the national newborn screening program, which uses splotches of blood collected from the heels of all newborn babies to test for other disorders.
Only late last year, Moser's team discovered a way to spot a telltale sign of ALD in the kind of blood samples collected by the national screening program. It looked as if they had found the marker they had long pursued.A Test That Would Work
Moser wanted to celebrate, but there were things left to do. The first was to prove that the test could detect ALD in actual samples from the newborn screening program.
Forty-eight squares of filter paper lie today in a Ziploc bag with a blue seal inside a refrigerator at the Kennedy Krieger Institute. Each square has a splotch of red that looks like a Rorschach test. With them is a letter dated Oct. 10, 2006, addressed to Hugo Moser. Inside the bag, the letter says, are eight samples of blood from newborns who later developed ALD, and 40 samples from newborns who turned out to be healthy.
The samples were sent to Moser by the state of California, which, through a combination of foresight and good luck, has preserved blood samples from millions of newborn babies, including several later found to suffer from ALD.
The pieces of filter paper look identical, but each has a unique code. Only the California officials know which ones belong to the ALD children. Federal officials watched closely as Moser prepared to apply his new diagnostic test. His task was to spot the eight positive samples and correctly identify the 40 negative samples.
Anticipating he had a winner on his hands, the neurologist applied for a patent on the test -- but only, he said, to keep the technique from being commercialized by others. If it worked, he wanted the discovery he had taken so many years to find to be free to the public.
In Fairfax, Augusto Odone was also keeping his fingers crossed. Moser's test could finally make Lorenzo's oil really useful.
The crucial experiment was about to get underway when Moser died. His wife, Ann, back in the lab last week only days after her husband's death, said the team was fine-tuning the test. The ALD samples obtained from California are so rare that the scientists want to make sure they do the test right the very first time. And it won't be enough just to prove the test works. Ann Moser and her colleagues need to make sure the technique they use is something that can be ramped up to a mass scale.
"He gave us all a mandate to continue with the work, particularly the newborn screening for ALD," Ann Moser said.
Results from the trial are expected in about six months, and the lab is confident. Federal officials are equally confident, which is why the Mayo Clinic in Rochester, Minn., is planning a trial with several thousand samples after the laboratory test is completed. Only when that study is done will the Moser team's inspiration have passed the rigorous tests of science, allowing officials to incorporate the test in the national screening program.
In the final days of his life, recognizing his time was running out, Moser seemed as frustrated with the slow pace of his own methodical science as the Odones once were with him. His life as a scientist had given him the long view on fighting a deadly disease; his own mortality had shown him what desperate parents of dying children feel.
"If I had a son with ALD and someone said, 'Put your boy in a controlled trial,' " Moser said, "I would say, 'Go to hell.' "