Complicated lessons: Lorenzo Odone and medical miracles.

888 www.thelancet.com Vol 373 March 14, 2009 There is no question that Lorenzo Odone lived until the age of 30 years because his parents, Augusto and Michaela Odone, defi ed doctors and developed a mixture of two cooking oils as a possible treatment for their son’s devastating disease. The 1992 fi lm Lorenzo’s Oil, which commemorated this heroic eff ort, became an inspirational saga for other patients and families dealing with incurable conditions. Yet Lorenzo’s story tells us as much about the limitations of medical research as it does about its triumphs. By this time, the story of Lorenzo, who died on May 31, 2008, is well known. He was an unusually precocious 5-year-old when he began acting oddly in 1983. Doctors eventually diagnosed him with adrenoleucodystrophy (ALD), a devastating genetic neurological disease of young boys that causes confusion, agitation, and eventually unresponsiveness and death within a few years. Doctors told his parents that no treatments existed and that Lorenzo was doomed. Unwilling to believe this, the Odones, neither of whom had medical training, became fi xtures at the nearby library of the National Institutes of Health. Within months, they had convened the fi rst international conference of scientists working on ALD. Using insights from this meeting and subsequent research, the Odones, in 1986, developed what became known as Lorenzo’s Oil, which successfully lowered their son’s concentrations of very long chain fatty acids, presumed to be the cause of neurotoxicity in ALD. As of 1992, when the fi lm Lorenzo’s Oil was released, it was not known whether lowering concentrations of very long chain fatty acids had actually helped Lorenzo and his fellow victims. This fact did not bother the director George Miller, whose fi lm unabashedly celebrated the Odones’ accomplishment and depicted ALD specialists as more interested in science than the welfare of their patients. At the end of the fi lm, dozens of boys are shown running and playing sports. They sequentially announce their names and state for how long they have been taking Lorenzo’s Oil. The implication was that the oil had either cured them or prevented them from getting ALD. Not surprisingly, the movie outraged scientists and families aff ected by ALD, both of whom believed the fi lm played with people’s hopes. But the Odones had the last laugh. When the late Hugo Moser, the world’s expert on ALD and one of Lorenzo’s physicians, fi nally published data in 2005, it became clear that although the oil did little for already sick boys, it prevented the onset of ALD in twothirds of susceptible boys who otherwise would surely have died from the disease. It was a breathtaking scientifi c achievement spearheaded by two laypeople. History can illuminate Lorenzo’s story. The fi rst voluntary health association in the USA was the National Association for the Study and Prevention of Tuberculosis (now the American Lung Association), founded in 1904. But it was the National Foundation for Infantile Paralysis, also known as the March of Dimes, that cemented the idea that funding for research initiatives could directly lead to medical breakthroughs. In this case, money raised not only supported the research of Jonas Salk and Albert Sabin but also the trials that showed the effi cacy of the polio vaccine. Nevertheless, the public remained suspicious of much experimental research which, as a result, was often done on prisoners, orphans, the mentally challenged, and other captive populations without informed consent. But with the emergence of AIDS in the early 1980s, everything changed. Highly organised groups of gay men, confronted with a mysterious life-threatening disease, aggressively advocated for greater research funding and for early inclusion in experimental trials. Their arguments were persuasive enough for the US Food and Drug Administration to revise its protocols, expediting the drug approval process. Once again, the connection between advocacy, funding, and hope for severely ill patients had been made. “People used to say it doesn’t help to throw money at things”, Hugo Moser refl ected late in his career. “But it does.” This history provides a backdrop for evaluating the Odones’ eff orts. At fi rst glance, Lorenzo’s story seems to be an uncomplicated triumph of devoted parents fi ghting the medical establishment. Yet although the Odones’ accomplishments were remarkable, the actual lessons of Lorenzo’s life are much more ambiguous. For one thing, the concerns of the Odones’ critics are of utmost importance. Desperate patients with fatal diseases may join risky research protocols believing that the intervention is likely to help their case; in reality, the sickest patients may be the least likely to benefi t. In other instances, such studies merely seek to accumulate scientifi c knowledge to benefi t future patients. Although groups such as Abigail’s Alliance have urged US courts to fi nd a constitutional right for terminally ill patients to get access to unapproved experimental therapies, recent rulings have gone in the other direction. Some of the judges’ scepticism in these cases stems from the fact that highly touted treatments that initially seem promising on the basis of anecdotal information often prove no more eff ective than standard regimens. For example, the enthusiasm of patients and oncologists for stem-cell transplantation of advanced breast cancer actually led insurance companies to pay for a highly expensive and risky experimental therapy. “I don’t feel that I have the right not to off er a transplant to a woman who wants one”, one oncologist stated. Ultimately, however, randomised trials showed the procedure to be of limited clinical value. The The art of medicine Complicated lessons: Lorenzo Odone and medical miracles