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Augusto Odone is an Italian economist best known for his son, Lorenzo, after which Odone named the oil that he helped develop to treat his son’s neurological disease. Lorenzo’s oil was the subject of a 1992 movie starring Nick Nolte and Susan Sarandon, and of course what most people think they know about the story they learned from the Hollywood version.

This past week Augusto Odone died at the age of 80, prompting another round of media reporting about Lorenzo’s oil.

Probably because of the Hollywood movie, this story more than any other is an iconic example of the disconnect between the simple narratives the media love to tell (and we love to tell ourselves) and the more complex reality.

The basic facts of the story are not in dispute. Lorenzo Odone, son of Augusto and his wife, had a neurological disease known as X-linked adrenoleukodystrophy (X-ALD). This is a devastating genetic disease in males, with two basic forms. Childhood onset tends to progress rapidly and typically death occurs by age 10, although lifespan can be increased if an early bone marrow transplant is given. In adult onset, symptoms may not appear until adulthood, and then tends to progress more slowly, over decades. Some boys with the X-ALD gene do not develop clinical findings. Women are carriers, with partial protection from their second X chromosome. About half of female carriers become symptomatic, with the slower adult form of the disease.

The disease is a metabolic disorder that results in the buildup of very-long-chain fatty acids (VLCFA) in nervous tissue and the adrenal glands. This leads to disruption of the myelin, the insulation around nerve cells that helps them conduct signals efficiently. Buildup of VLCFA in the adrenal glands causes adrenal dysfunction, which needs to be treated with hormone replacement.

Lorenzo Odone started to develop neurological symptoms at the age of 5. He was diagnosed with X-ALD, and given a prognosis of surviving for a few years. His parents, however, were not content to accept this prognosis and began their attempt to find a cure, or at least a treatment. Augusto, who apparently had significant financial resources, organized an international meeting of X-ALD specialists to discuss possible strategies. The idea for Lorenzo’s oil was inspired by insights that came out of this conference.

The oil itself is a 4:1 mixture of oleic and erucic acids – found in common cooking oils. Consuming the oil reduces the serum level of VLCFAs. When the oil was first given to Lorenzo, his VLCFA levels reduced rapidly from very high to normal. Lorenzo survived until age 30, far longer than his original prognosis. The oil did not seem to reverse any of his neurological deficits, but did seem to slow progression.

The Hollywood version of this story annoyed and dismayed scientists and families with X-ALD for various reasons. By the time the movie came out many children with X-ALD were taking Lorenzo’s oil, as it was rapidly adopted by the medical community and routinely prescribed. Most of these children, however, did not seem to benefit from the oil and were progressing despite treatment. Many doctors, in fact, had stopped prescribing the oil. The movie, therefore, seemed to promote false hope in a miracle cure that did not work for most children.

The Hollywood narrative also followed the fairly standard plotline of plucky parents who would not give up on their child and had to struggle against an uncaring medical system. However, the facts don’t seem to support that narrative. I’m sure the Odones encountered some resistance or doubt along the way, but the facts support a narrative in which the medical community was largely cooperative with the Odones’ quest.

In fact, the real story of Lorenzo’s oil represents a fruitful collaboration of a disease advocate and the professional community. Augusto Odone started the process by convening the world experts on the disease, and then listening to them. He collaborated with scientists to develop and purify the oil, and of course the oil was prescribed by physicians, and ultimately scientifically studied by physicians and scientists.

This is an excellent model identifying a disease, getting or providing funding, and then using those resources to do science targeted at understanding and curing the disease. Hollywood, however, decided to portray this relationship as antagonistic in order to play up the Odones as maverick crusaders succeeding despite (rather than with) the medical community.

The story of Lorenzo’s oil also carries another lesson – science and medicine often turn out to be more complex than it may seem at first. It is likely that there was cautious skepticism regarding Lorenzo’s oil when first proposed. Initial cautious skepticism is appropriate. It is unfair and misleading, for those new ideas that turn out to be true, to look back at previous skepticism as nihilistic or obstructionist. This is the scientific version of Monday morning quarterbacking.

It also turns out that the caution of scientists was vindicated in part, as was the hope of the parents. The longest study we have of Lorenzo’s oil found that it was of no benefit at all to people with symptomatic X-ALD.

However the same study, and others, show that if Lorenzo’s oil is given to asymptomatic boys with the X-ALD gene then their chance of going on to become symptomatic is significantly reduced, by about half. Lorenzo’s oil is therefore currently recommended for preventive therapy in asymptomatic boys with X-ALD.

Why the oil works for prevention but not treatment is unclear. It is interesting that even though the oil reduces VLCFA in symptomatic people with X-ALD, that does not affect the disease itself. There therefore must be more going on than just increased VLCFA. Perhaps VLCFA are just a marker for some other metabolic process that is truly pathological, or it’s a trigger, but once that process has started (and sufferers are symptomatic) it is no longer dependent on VLCFA levels.

It is exactly these kinds of complexities, frequently encountered in science and medicine, that result in cautious skepticism when new treatments and ideas are proposed. This is also why, no matter how good the story sounds, we still have to do the detailed science, ask all the hard questions, and show that a new treatment actually works.

Contrast this to the way CAM operates – which would have adopted the oil as a miracle cure and not questioned it further, or continued to use and promote the oil after it was shown not to work for symptomatic individuals.

Conclusion

The story of Lorenzo’s oil is a fascinating but complex one. It does show how collaboration between families and disease advocates on one side, and scientists and physicians on the other, can be fruitful in advancing our medical knowledge toward a goal of treatment.

There are important caveats, of course. Such stories are like catnip to journalists and Hollywood; they cannot resist them, or resist shoehorning them into their preferred narratives. This has the tendency to promote false hope or premature hope, and can reduce confidence in the medical community even while they are working to advance medical knowledge.

Second, as I have pointed out before, and was also pointed out in this Lancet commentary regarding Lorenzo’s oil itself, grassroots effort to fund medical research sometimes has the unintended effect of directing research in a counterproductive way. In short – there needs to be a proper balance between basic research to understand mechanisms of disease, and clinical research to develop treatments. Grassroots funding tends to favor clinical research. People want a cure. But this can shift the balance prematurely from basic to clinical research and actually slow scientific progress and even delay an ultimate cure.

There is also one enduring mystery in this story. We now know from extensive research that Lorenzo’s oil does not seem to work in symptomatic individuals. Why, then, did Lorenzo himself survive to age 30? Every account of his case I can find credits the oil, but this is likely not the situation. His neurological condition continued to progress despite use of the oil.

This, of course, is the problem with anecdotal evidence. There are too many unknowns. He may have simply had an unusual case. It is also likely that he received excellent supportive care (given his family’s resources and the special attention his case drew), and this supportive care may have resulted in his long survival despite the illness.

Lorenzo’s oil continues to be a focus of scientific research. Clearly, there is something here of benefit. Perhaps tweaking the formula will provide symptomatic benefit, or perhaps it is just part of the puzzle, with the other pieces remaining to be discovered.

The real story of Lorenzo’s oil is inspiring and hopeful, but complicated by scientific reality, and containing many lessons and nuances. If only Hollywood could see the power in such real stories, rather than their simplistic fairy tales.