Lessons from Lorenzo
New Scientist vol 173 issue 2327 - 26 January 2002, page 44

Seventeen years ago, Augusto Odone's six-year-old son, Lorenzo, started bumping into furniture and losing his hearing. Doctors diagnosed a rare degenerative condition called ALD and gave him two years to live. But Odone had other ideas. Racing against the clock, he and his wife pestered scientists, devoured neurology textbooks and learned the language of biochemistry. The result was a controversial do-it-yourself treatment known as Lorenzo's oil-and a heart-rending Hollywood movie of the same name. Today, Lorenzo is alive but unable to move and being cared for at the family home. This isn't good enough for Odone, who has set up a pioneering funding organisation to continue the fight. As he tells David Concar, medical research is still too slow and bureaucratic-or mired in competition
Do you see yourself as a scientist? After all, you made an important contribution ...
No, I am a father. My drive comes not from a love of science but from the love I have for Lorenzo and the desire to help him.
What has happened to Lorenzo in the nine years since the film appeared?
Lorenzo should have died 12 years ago. Now he's 23. He has some good days, some bad days. He is bedridden, he cannot eat except through a tube, but his mind is there. He enjoys being read to, we play music to him, he knows who is around. This summer we put him in the swimming pool many times. He seemed to enjoy it.
Your wife played a huge role in looking after Lorenzo but she died last year. How has that affected him?
Michaela would sometimes spend up to 16 hours at a time at his bedside. I think that put a strain on her immune system and contributed to her lung cancer. After Michaela died, Lorenzo often tried to vocalise certain sounds. I believe that what he wanted to say was, where is Mummy? Then I told him. Michaela left him some tapes in which she narrates stories dear to Lorenzo when he was growing up, so we play him those.
How much is known about Lorenzo's disease now?
We know that the devastating symptoms are caused by the progressive loss of myelin. This is the fatty sheath that surrounds nerve fibres, enabling them to conduct impulses properly. Also, we know that the underlying cause is genetic, and that boys who have the defect have very high levels of very long chain saturated fatty acids in their blood. But then as now, everything else is hypothetical. At the time of the film, a lot of scientists believed the fatty acids caused the inflammation and destruction of the myelin sheath. But they didn't know for sure and they still don't. It's complicated because more than one gene seems to be involved and the progress of the disease varies. Some victims, like Lorenzo, get the childhood form, which usually kills within just two years. Others get the adult form of the disease, which strikes people in their late twenties and acts more slowly.
Your instinct was to find something that would get rid of the very long chain fatty acids in Lorenzo. How did the scientists respond?
Lorenzo was diagnosed in April of 1984 and he was deteriorating fast. In October, we organised an international symposium. One of the doctors said that giving patients oleic acid might reduce levels of the very long chain fatty acids. The reasoning, though I didn't know it at the time, was that such a substance might block the enzymes that synthesise very long chain fatty acids in the body. My wife tracked down a supply of pure oleic oil, and sure enough Lorenzo's very long chain fatty acids did go down. However, it was still too high. So I looked at animal experiments done over the past 50 years with different oils and decided to add a second ingredient called erucic acid. That is where the dispute started. The dogma was that erucic acid was dangerous in people.
But they were wrong?
Yes. If you give Lorenzo's oil to rats or mice their hearts clog up with erucic acid and they die. But this doesn't happen in people. I found this out by tracking down the few scientists who'd actually studied its effects. We found a retired English chemist capable of synthesising erucic acid and after six months, he had produced a kilo. After two weeks on the mixture, Lorenzo's very long chain fatty acid levels were normal. I started to write reports like crazy and send them to doctors. I wanted to tell everyone.
How did they react?
As soon as other parents heard about the oil, of course they demanded that their doctors prescribe it for their kids, including those who had yet to develop any symptoms. And Hugo Moser, the world authority on ALD, was one of the first to oblige. But the other doctors weren't happy about it. As far as I was concerned, the oil had arrested Lorenzo's decline. But the doctors thought it could have been the quality of the nursing care he was getting. Their most optimistic view was that Lorenzo's oil might help to prevent the disease provided it was given to children two or three years before any symptoms appeared. But they weren't even sure of that. And all I knew for certain was that the oil normalised the very long chain fatty acids.
The movie triggered protests from scientists who claimed it was anti-science and misleading. How do you feel about that now?
There were violent articles in Nature, Science and The New York Times suggesting that Lorenzo's oil was good for nothing. Some of the critics had themselves tried like hell to normalise the long chain fatty acids and probably could not stomach the idea that a layperson had done it. Others thought in good faith that the film might have raised false hopes. But I still think the movie was good. Moser came out of it looking bad, and that was a bit unfair. He is a very compassionate man. He wrote me a letter when my wife died saying, now Augusto, we must work together. I was very moved.
At the end of the movie the oil is shown being given to boys at risk of developing disease. What became of them?
None that I know of has gone on to develop symptoms. They are at university age now. Some doctors, such as Moser, believe this still doesn't prove Lorenzo's oil has preventive action. They might have escaped childhood ALD, but because it is genetic, who is to say they will not get the adult form? If those children all escape the adult form, then it's because of Lorenzo's oil, no question about it. If they get to 30 without developing the disease, it will be conclusive.
When you thought that Lorenzo was going to live, what did you want to do next?
Restore his myelin sheath. It was a long shot, but worth a try. So I shifted gear and instead of thinking about fatty acids I studied the central nervous system. And in doing so I saw a little bit of light at the end of the tunnel, because I discovered that in certain strains of mice scientists could grow myelin back. The problem was that the scientists were not talking much to each other, or even worse, they were competing. And so the idea of setting up the Myelin Project came to me.
What's different about what you do?
First, the scientists don't get a blank cheque -they have to send me a report every two or three months. Second, while I always consult scientists for technical advice, I call the shots and decide which projects get funded. And I only fund proposals likely to produce practical benefits in the near future. Scientists are very nice people who work very hard. But their main goal is to put their name on a paper reviewed by their peers and publish it in a major journal. I am not interested in funding science for the love of science.
You say you refuse to accept the idea that science cannot be hurried. Why?
The National Multiple Sclerosis Society in the US is led by scientists. When I was starting the Myelin Project I had a discussion with one of their top executives and he said, Augusto, you cannot hurry the pace of science, it has its own time. I told him to his face, that's baloney. If a scientist applies for money to the National Institutes of Health or a big medical research institution, it can take up to two years. If the Myelin Project says yes, they get the money a few weeks later. If scientists ask a big institution for money to carry out more experiments on mice, rats, cats, dogs and monkeys, it will often say, that's fine. We say, no, you have done enough animal experiments, move on to people.
Are you on a mission?
No. I can't afford to care about the whole of humanity. But if people want to copy me, that's fantastic. And some are. At least 15 other organisations have adopted the formula of the Myelin Project. Before, small funding charities saw the doctors and scientists as "up there". Now we talk to them on the same level. But the big old institutions and medical charities don't change. They have their own ingrained culture. Their science has to be exact, slow and often very basic.
The most exciting research you've funded involves transplanting new cells into the brain
The trial involves taking Schwann cells from a patient's leg, drilling a hole in the head and putting the cells inside. It has been shown that the cells can produce new myelin in monkeys, but nobody knows whether this will happen in the human brain.
What's the news so far?
So far, all we know is the operation is safe. The patient has not experienced adverse side-effects. Next month the team will check to see if the cells survive. What's frustrating is it could have been carried out two years ago. It took us four years to convince other doctors and ethicists it was safe enough to carry out.
Why?
The Institutional Review Board. Who belongs to it? Doctors. And the first thing they will say is, why should they be the first to do that? I want to do it myself sometime. One doctor wrote to the IRB saying the trial was dangerous and too risky. In fact, the risk is minimal. When the idea of the transplant first came up, I asked several neurosurgeons what the risk of drilling a hole in the head and transplanting Schwann cells might be, and they said there was perhaps a 2 per cent chance that something could go wrong.
But what about the benefits?
The lady in the trial is unlikely to have any benefits because too few cells have been transplanted, but it's a start. Let's say the cells survive and myelin is produced and nerve axons can be re-myelinated. At some point a patient involved in this research might get up from his wheelchair. Can you imagine what the impact would be? So is it worth doing this trial? Yes.
Would you have moral qualms about using embryonic stem cells?
I would hesitate to sacrifice an embryo that is going to develop into a baby. But if the embryo is destined for destruction anyway, what's the problem?
Would you clone an embryo from one of Lorenzo's cells to make transplant tissue?
I've never thought about it. It's a provocative question. Right now I'm not going to answer.
Is biomedical science promising far more than it can deliver?
Who the hell can know? Let's not kid ourselves that just because we study something in cells or in animals we can predict what is going to happen in patients. The human body is too complex. But you never know until you try. That's my motto for the Myelin Project.

David Concar

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