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Lorenzo’s Oil

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.

Posted in: Neuroscience/Mental Health, Science and Medicine

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33 thoughts on “Lorenzo’s Oil

  1. Rob Cordes, DO says:

    It’s been years since I saw the movie but didn’t it portray Lorenzo improving on the oil and dramatic regression of his illness?

    1. goodnightirene says:

      No, it portrayed the oil as arresting the progression. The worst aspect, though, was the montage at the end that showed dozens of little boys supposedly and miraculously “cured” by use of the oil.

      I heard a similar report on the BBC the other night and was shocked at how far afield the film went as I had always figured that the substance of it was true. I also recall that the film left me thinking doctors were a bunch of cold, calculating snots who haughtily rebuffed caring parents–yikes!

  2. windriven says:

    “Such stories are like catnip to journalists and Hollywood; they cannot resist them, or resist shoehorning them into their preferred narratives. ”

    I think you’ve hit on the root problem here and its application isn’t limited to journalists and filmmakers. Reality, as Mark Crislip says, is a honey badger. Unfortunately, the vast majority of people would rather imagine reality to be Whinnie the Pooh. Scientists study honey badgers. Non-scientists weave narratives about Whinnie that are pleasant enough to mask their inaccuracy.

  3. Kathy says:

    Unfortunately film isn’t a suitable medium for conveying a complex real-life story. Even for a fictitious story, that has already been subjected to the various limitations of print, is difficult to “translate” adequately into film. I can remember my disappointment, seeing the film of “National Velvet”, one of my favourite books, which seemed to abandon everything that made the book good and Hollywoodify it into a sort of Supergirl cartoon strip. Even Velvet herself (Elizabeth Taylor) could never in a million years have pased herself off as a male jockey (essential to the story in the book) … she was completely the wrong shape.

  4. goodnightirene says:

    OMG, the article (BBC) that you link to is awful. It perpetuates the idea that Odone was a brave maverick parent who ultimately saved his son because he refused to accept the medical prognosis. Nowhere does it question or explain why Lorenzo lived longer, but rather leaves the impression that the docs were wrong and only the brave parents were responsible for Lorenzo’s increased survival time.

    Overall I think the BBC is a cut above most of US journalism, but they certainly have their failures as well–as I note from time to time. There have been a couple of very credulous altie podcasts in the last year that caused me drop them from my library.

  5. Ed Whitney says:

    Perhaps this is an illustration of a common situation: suurrogate outcomes do not always predict clinical outcomes. This is why the GRADE initiative for grading evidence for clinical guidelines will subtract one point for indirectness when an othwise well-designed study measures an outcome not directly related to the outcome that matters most to patients.

  6. Carl says:

    I guess I can’t complain. I used to pull that trick all the time when I was supposed to write a report about something. Just watch the movie, it’s way easier than reading a bunch of boring crap.

  7. Paul De Boer says:

    I was skeptical about the movie and did some basic research and came to the conclusion that the oil showed almost no success in any situation. I wrongly guessed that its continued use was likely pseudoscientific due to the fame and heart warming hollywood story.

    I was not aware of the preventative use of the oil. I’m glad to see that it likely has some significant effects and is not another snake oil.

    1. Ed Whitney says:

      It does not seem to me to be such a big discrediting factor that the oil has to be given early. After all, a low phenylalanine diet has to be started very early in the setting of PKU. For an inborn error of metabolism with severe neurological consequences, the intervention has to happen before the damage has occurred. No one thinks that a low phenylalanine diet is snake oil simply because no benefit occurs when you start it after the window of opportunity has closed.

  8. EDTA says:

    My first opinion was the same as Paul De Boer’s, but this seems very interesting – although the small number of patients in the linked study on preventive effects might urge caution about unknown adverse effects. Such a small number of patients is little in the face of ordinary toxicity studies, if I recall correctly.

    Still, I think this kind of study is what actually defines scientific medicine, and it would be fascinating to see more of this kind of content on SBM – as far as such is available. I occasionally get involved in discussions of “scientific medicine” (It’s called school medicine around here, which is probably more derogatory ..) versus this kind of grassroots efforts, and I hope that this counter-example to the common claim of dogmatism will be immensely helpful if presented carefully.

  9. Taurus says:

    “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 unbelievably ironic given the terrible professional and personal cost exacted by the (medical) scientific community at large against the (increasing) number of scientists who see senescence as a worthwhile target for plausible therapeutic intervention

    Considering the inextricable link between age-associated pathology and aging itself, it’s hard to understand the furor of those who control the purse strings of institutional investment as anything other than nihilistic and obstructionist.

    Future generations will have a grim appraisal of the priorities of scientists still entrenched in the 20th century’s Sisyphean disease-treatment paradigm.

    - Taurus Londono, student (Biochemistry & Molecular Biology)

    1. Young CC Prof says:

      Yes, it would be great to find a cure for old age. But do you have any plausible lines of inquiry? Why do you think they are plausible? Have you achieved any notable successes in animal models? Do you have specific biological targets for drugs or other interventions?

      When you can provide positive and helpful answers to all these questions, then you can call your critics obstructionist.

    2. WilliamLawrenceUtridge says:

      What you see as “nihilistic and obstructionist”, people who actually control the purse strings doubtless see it as the recognition that resources are limited. When you have ten, twenty times the number of research applications than you have money to fund (what was the NIH’s success rate for first-tier grants again? 7%? Or has it dropped), you have to decide who gets the money – and it’s usually the person with the best idea, track record and application. Within the overall grant funding budget, too many applications are chasing too little money. Outside of the budget, funding for scientific research is competing with a host of other priorities (defence, schools, medicade, medicare, infrastructure, and the list goes on), during the worst economic crisis seen in a generation or more. If you push more money towards senescence research, you’re taking money away from cancer, or vaccination, or some other, doubtless worthy topic.

      But I don’t really understand your comment – are you saying researchers who specialize in preventing senescence are persecuted for it? Or are you talking about anti-aging quackery which is justifiably ridiculed for pushing high-dose hormones, vitamin and nutritional supplements as magic potions that will supposedly stave off the effects of aging?

      1. Andrey Pavlov says:

        I actually met my co-author on this blog doing senescence research. He has done a lot more with it than I have and our old lab is still thriving. There are definitely interesting things to be learned and a lot of very interesting things learned (did you know, for example, that all animals tested stop aging including humans? We stop at around 95-105 years of age). Understanding the how and why of senescence is useful well beyond simply “fountain of youth” type dreams.

        But the real point is that there is no obstructionism – the field is young, the data preliminary, and funding is always hard. And yet, somehow, the director of the pharmaceutical sciences department at my undergrad alma mater and a number of other folks there get money to fund their senescence research. Just because we aren’t funding someone’s particular research or to the extent of their liking doesn’t equate to obstructionism. It’s a facet of limited resources, as you pointed out WLU.

    3. Marion says:

      Taurus:
      More hypocritical & baseless attacks on the scientific community.
      Do you vote Green Party?
      Do you support and vote for politicians who will take aggressive action (i.e. PUTTING PEOPLE IN PRISON OR EXECUTING THEM) against massive wealth inequalities, which have NOTHING whatsoever to do with actual differences in how hard people work?
      Put banksters and Wall Street traders and financial terrorists in prison or execute them for doing nothing of value to society, except push money around?
      That’s what traditional Marxists & Communists did, and that’s what the Chinese still do today (sometimes – though not nearly enough, unfortunately), rather than get diverted with this “cultural Marxism” garbage.

      I’ve taken & easily passed chemistry courses and lab courses. They are nothing in difficulty compared to higher abstract graduate level math courses. Graduate school in math was terrifying for me. But, like my undergraduate engineering courses, which changed the direction & course of my life for the better forever, math & math modeling did the most important thing:

      understand & compute the order of magnitude of things.

      Those without this training do not have the mental capacity to comprehend the consequences of actions or the magnitude of things.

      So, only after you do all those things I suggest
      e.g. push your figure in the voting booth once a year for someone OTHER than the 2 biggest political terrorist organizations (“parties”) in whatever country you’re in (invariably, ) it seems to always be 2 parties which get grossly more undeserved support than all other parties combined – whose only objective is to give even more money and more money to billionaires and banksters

      then you can complain about “the scientific community” having any negative effect on the availability of funds.

  10. windriven says:

    Curious. Everybody wants to get to heaven but nobody wants to die. ;-)

    So Taurus, you discover the Ponce de Leon pill and we all live forever. What then? One presumes that procreation will continue. People will continue to die off of course from accidents or ennui but the population will climb and stress on resources will escalate. War and pestilence seem likely side effects to the PdL pill. And to what end? Interminable lines at the 4 o’ clock buffet at the Golden Corral?

    We do lots of things that are technically feasible but ethically bankrupt. I, for one, vote to spend scarce medical research dollars on cures for diseases and conditions that truncate the lives of the young and the productive.

    1. mousethatroared says:

      Windriven “Curious. Everybody wants to get to heaven but nobody wants to die.”

      I suspect many people don’t want to live forever. They are just procrastinating.

      I wouldn’t mind having the same lifespan (whatever that will be) with less symptoms of aging though. All that joint, tendon and spinal spondylosis and disk aging – and the companion pain and radiculopathy – would be nice to avoid that.

  11. Thisguy says:

    Great article; I particularly like the point on how grassroots funding/movements could jump right over basic science in the rush to find a treatment or cure. I guess you can have treatment without basic science, but it’s very difficult to find a cure without doing the necessary basic research first.

    However, seems to me that too many basic scientists are focused on just conducting research, not translating their findings into treatments or cures. Proof now is the trend toward “translational medicine,” when it should have been that way all along.

    1. Young CC Prof says:

      Good point. Just this afternoon, I got a solicitation from a cancer research group, bragging about how they’d convinced researchers to abandon their silly cell-line and animal-model research at move to actual people. I was like, “WHAT? Sure, you can do epidemiological research most effectively on people, but how can you possibly develop new treatments?”

      That line was so bizarre I might reconsider my decision to participate in one of their studies.

    2. rork says:

      There’s been translational emphasis in public medical research funding since about 2001. Too much emphasis in my opinion. The argument sounds good: do stuff directly benefiting patients. But is there evidence about what tactics actually work best in the long-run? Since Tocqueville some have argued that the US public should fund allot of very basic research, stuff that the companies won’t do. Gotta keep the start of the pipeline filled to have good things fall out of the tail end of it. Perhaps slightly less translational emphasis from NCI since Varmus appeared, at least I was hoping for that.

    3. WilliamLawrenceUtridge says:

      I wouldn’t say they jumped over basic science. From my reading of Dr. Novella’s summary, they based the treatment on basic science (and understanding of how the VLCFA are processed by the disease’s victims) but the step they skipped was testing on animal models first. But perhaps we merely draw the line of where “basic” ends and “applied” begins :)

      That whole “now we’re doing translational medicine” line always bugged me. I think they’ve always been doing translational medicine; treatments that are tested and work are promulgated through the literature, CME credits, conferences and the like. In my mind, “translational medicine” is a way of repackaging grant funds (for the NIH) and an extra, unnecessary layer in the way researchers are doing what they would do anyways – publishing their findings in expert-specific venues. Want to fund translational medicine? Set aside a couple hundred million per year to fund Cochrane reviews and UpToDate updates. It seems like a whole lot of the “translational medicine” crap really comes down to press releases and fame-sucking.

      But perhaps I’m just crabby :( :( :(

  12. Scott Myers says:

    Hugo Moser was a great scientist and a great man. The way he was portrayed in the movie was dishonest, hurtful to him and sad to see.

    1. mousethatroared says:

      Here is a good article on Hugo Moser, the movie and his ALD research.

      http://www.washingtonpost.com/wp-dyn/content/article/2007/01/27/AR2007012701542_pf.html

  13. Flower says:

    If genetically elevated VLCFAs is the key problem in ALD, why hasn’t anyone tried (and trialled) the use of coconut oil with its high level of medium-chain triglycerides? It’s inexpensive and readily available and does not need to be preformulated.

  14. mousethatroared says:

    Never saw Lorenzo’s Oil although it was recommended to me. For some reason the medical miracle (often brave maverick) movies always have made me cringe and I avoid them. Don’t know why, it’s just a visceral reaction.

    Interesting reading about the science behind the story, though.

    1. Ed Whitney says:

      If you want to experience a visceral reaction to such a “maverick” movie, see “Patch Adams.” There is a scene where a bunch of doctors are on rounds and young Patch Adams is tagging along. The doctors all act as if the patient were some kind of specimen in a laboratory, when Adams asks, “What is his name?” The doctors all turn on Patch as if he had asked “Can I take him home with me?” I do not know what the hell kind of medical school Patch Adams went to, but anyone who did not greet a patient by name and address him with respect would be lucky to escape with a good dressing down at any school I know about.

      1. mousethatroared says:

        Ed W. I saw Patch Adams. Perhaps my viceral reaction is Post Traumatic Patch Adams Disorder.

        I think I good movie could be made on these topics, but it would take more of the approach of Crash, less, the predictable heroic maverick narrative.

      2. Wolpertinger says:

        I sometimes wonder why there are not more adaptions of existing Hollywood-ready Maverick stories like the discovery of insulin, something which only got an almost forgotten TV movie called “Glory Enough for All”.

        You even get a miracle cure in the end, only this time it actually works… although the fact that everybody involved would be a giant jerk throughout most of the movie might be a little off-putting for an audience expecting clear-cut hero figures.

  15. corky says:

    Can we please get the terminology correct? It is not “boys with the X-ALD gene”. The gene underlying the disorder is the ABCD1gene and it is boys who inherit a mutation in that gene who develop the disease. This makes it sound like they inherit a gene that other people do not have, rather than that it is the inheritance of an altered or non-functional gene that causes the problem.

  16. I disagree to an extent with the blogger’s comments that basic science is only altruistic and interested in progressing research in the hope of furthering treatment for a specific disease. Academic research is a mixed bag; there are such programs that are interested in speed and effective treatments, however, a very large cross-section of academic research is interested in building fiefdoms, and in garnering funding in pursuit of building ivory towers. The blogger identifies the danger in justifying “mythical” or unproven treatments, or medicines which can take the context of disease research for treatments off track. But I do not see in the commentary a similar critical glance being cast upon academia who seldom produce effective drugs, or contribute in large ways to the development of effective treatments. In the current system, that privilege (largely due to money) is reserved for industry, and only when specific treatments prove economically beneficial, or provide impact to disease beyond a shadow of a doubt (for smaller, orphan diseases). Academia is largely content to receive funding from industry (and donors) to perform R & D work that is (if interesting) gobbled up and put into the industry bucket to decide whether or not investment is prudent, and will result in the development of treatments. Like the financial markets, the pipelines are largely sewed up, controlled and moved forward at the discretion of industry. Smaller independently led efforts in drug development (both for profit and non-profit) have pushed industry in some disease indications to invest in their ideas, and force academia to be more collaborative. Unfortunately, those are largely exceptions to the framework, and have as much impact as Congress trying to hold financial institutions accountable.

    This paradigm will not fully change until funding changes, and drive academia to be more conscious and desirous of working faster, and to try and solve a problem, and until industry becomes more bold in its support of marginal disease indications that might not be as safe, or as profitable. This necessity and reality will not occur until someone of significant wealth finds one of their family members with a rare disease that they will be forced into investing in multiple ways to solve the problem. The path to solving any disease is an inverse relationship between time and money. More money, less time.

    1. Chris says:

      “But I do not see in the commentary a similar critical glance being cast upon academia who seldom produce effective drugs, or contribute in large ways to the development of effective treatments.”

      Then you have not read this blog enough. Here, you can start with this category:
      http://www.sciencebasedmedicine.org/category/pharmaceuticals/

      Oh, and you might want to read this book that was reviewed here:
      http://www.sciencebasedmedicine.org/lessons-from-the-history-of-insulin/

      Unless, of course, you don’t think insulin is an effective treatment.

  17. Christopher Stuart, DC says:

    I came to this site following a google scholar search on ALD and doing research on biochemical pathways/competitive inhibition. It made me think of the movie (“It’s the same bloody enzyme!!!” – Nick Nolte)

    It was an inspiring movie and I agree with the tenants of this blog post and I appreciate the author bringing forward the reality of Lorenzo’s Oil vs. the Hollywood portrayal as a cure. The last scene with the collage of patients on Lorenzo’s Oil as a prevention is very misleading, making me think it halted the disease in it’s tracks, but maybe forgivable because of the time of production, not knowing long term this therapy would not succeed. I haven’t made my mind up on that yet, if the writers and producers are intentionlly misleading an audience to get an Oscar.

    That being said, I think it’s oversimplistic to say the writers of the movie made the researchers out to be cold villains and the parents on a lone quest to thwart the villianous efforts of disinterested researchers. I don’t think it was an indictment on science-based medicine. I think the movie correctly illustrated the relationship between research, science-based medicine, patients, and ethics is complex. There was even a small commentary on how the mother wanted to tend to Lorenzo’s mind/spirit (holistic approach to palliative care – this was relatively new stuff in 1992, fairly standard and accepted now) as he deteriorated.

    I just don’t think any researcher or practitioner need to be defensive about their portrayal in this movie. This movie will continue to be tops because I think the writers/producers succeeded in bringing these issue to light for the lay public.

    I am only an amateur movie buff critic though :-) .

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