544 THE LANCET
FILM REVIEW
Lorenzo’s Oil
Directed by George Miller. Starring Nick Nolte, Susan Sarandon.
Universal studios. USA. 1992. Certificate 12. 135 mins.
Lorenzo’s Oil is a film about a couple whose
extraordinarily intelligent and promising 6-year-old son
became progressively disabled by adrenoleukodystrophy
(ALD), an X-linked disorder that affects 1 in 20 000 males.
After their initial shock, disbelief, and despair, the parents
were determined to learn complex medical and biochemical
facts that enabled them to contribute substantially to the
understanding and possibly the therapy of this disease. The
movie is deeply touching and demonstrates the power of
total commitment and the refusal to give up hope. As a work
of fiction, Lorenzo’s Oil is an excellent film. However, as a
factual documentary it has three main flaws: it overstates the
success that can be achieved with the oil, it invents conflicts
between the parents and the medical establishment, and it
presents an inaccurate and malicious portrayal of a valued
parents’ organisation.
Lorenzo’s oil (a mixture of erucic acid and oleic acid)
returns the raised plasma concentrations of saturated
very-long-chain fatty acids, the principal biochemical
abnormality in ALD, to normal. The National Institutes of
Health and the Food and Drug Administration are funding
a five-year study of the clinical efficacy of the oil, which is
now in its third year and has involved 257 patients with
ALD. I direct this study, and since its existence is widely
known, I am dismayed that the film’s producers did not
acquaint themselves with the study’s findings. Our results,
and also those from Italy, indicate that the oil does not slow
the rapid progression of the childhood neurological form of
the illness. The motion picture attributes Lorenzo’s nine-
year survival after onset of symptoms to the oil, but 12
untreated boys who became ill at the same age have survived
to their late teens or early twenties. It is encouraging that
Lorenzo is reported to have acquired new skills
demonstrable through subtle testing procedures, but this
might be the result of his unique circumstances rather than
because of the oil itself.
Lorenzo’s oil at best provides very limited benefit for the
milder adult form of ALD. Our studies, which involve more
than 100 patients, suggest that functional impairment
continues to progress slowly. A crucial but still unresolved
question is whether the oil can prevent or postpone the onset
of neurological disability in boys who are neurologically
intact. We are following 61 such patients. 53 have remained
well, but the follow-up time is still short. 1 patient who was
started on the oil at 3 years of age developed the severe form
of the childhood illness at 5 years despite excellent control of
his plasma very-long-chain fatty acid concentration, and in 7
boys the lesions shown by brain magnetic resonance
imaging studies have increased in size. The oil is therefore
not an absolute preventive treatment. Longer follow-up is
required to determine whether it has a significant effect.
Moreover, 50% of untreated patients escape the childhood
form of the illness, so that half of the 61 patients would be
expected to remain well during the current follow-up period
even without therapy.
The film cites fundamental differences between the
priorities of the parents and of the medical establishment,
represented in this instance by Dr Nicolai (played by Peter
Ustinov who, except that he wears a bow tie, has copied my
appearance and speech with remarkable accuracy). The
movie shows that we had proposed that Lorenzo took part in
a controlled study of dietary very-long-chain fatty acid
restriction alone. That study, which had a sound rationale,
had been completed in 1982, two years before I met
Lorenzo. Hesitancy to use erucic acid in ALD patients was
based on the concern that the acid itself is of the
very-long-chain type and that ALD patients could not
metabolise it; the capacity of normal Eskimos to tolerate
erucic acid might not assure its safety. Once this concern was
relieved, approval by the institutional review board and the
Food and Drug Administration was obtained within 30
days. Because of the severity and relentless progression of
ALD, an open rather than a randomised study was
undertaken. All ALD patients who request to take part in
the study can receive Lorenzo’s oil, although in the USA the
cost of the oil presents a serious difficulty.
I find it hard to understand the reasons for the movie’s
inaccurate and mean-spirited representation of the parents’
organisation (the United Leukodystrophy Foundation).
The scene in which parents demand access to Lorenzo’s oil
over the objections of the organisation is not only
preposterous, it simply did not occur. The topics discussed
at the meetings are decided by the membership of the
parents’ organisation. For scientific issues, the organisation
obtains the opinion of a 13-member international scientific
advisory committee that represents many points of view.
Contrary to the film’s presentation, the organisation has had
an important role in making the oil available to patients. The
organisation has also supported research, including very
recent work that has led to the isolation of a putative gene.*
This work acknowledges the support of the United
Leukodystrophy Foundation.
The treatment of ALD is under intense investigation.
Bone marrow transplantation seems to be helpful under
carefully selected circumstances and may prove to be the
most effective approach. The impending isolation of the
ALD gene raises the long-term hope that gene therapy will
become possible. The rapid neurological progression
associated with ALD seems to be due to a cytokine-
mediated inflammatory response, and therapeutic trials to
counteract this are in progress. It is essential that the current
evaluations of the efficacy of Lorenzo’s oil be brought to
completion. At this time the jury is out.
Department of Neurogenetics,
Kennedy Krieger Institute,
707 North Broadway,
Baltimore, Maryland 21205, USA HUGO W. MOSER
*A mutation in a gene that codes for a peroxisomal transport protein has
recently been reported in 6 of 85 patients with ALD (see p 552).-ED. L.
 THE LANCET
BOOKSHELF
Oxford Textbook of Clinical Pharmacology and
Drug Therapy
Second Edition-D. G. Grahame-Smith, J. K. Aronson.
Oxford: Oxford University Press. 1992. Pp 756. 25. ISBN
0-192616757.
With the publication in the UK of new General Medical
Council guidelines on undergraduate medical education,
there will be considerable debate between curriculum
committees and heads of medical school academic
departments as to the definition of "core" versus "optional"
subjects. Clinical pharmacology and therapeutics occupies
an interesting position in this debate. There is, I hope, little
doubt that medical students will continue to need a firm
foundation of knowledge of both mechanisms of drug action
and of when and how drugs should be used in clinical care.
In addition, the economics of drug use remains an important
area of concern in professional circles and the public
domain.
Exactly how clinical pharmacology should best be taught
to medical students is less certain. In the past the teaching of
clinical pharmacology has been thought of by some
clinicians in the same terms as a basic science-a necessary if
somewhat boring evil and, in any case, students will learn
therapeutics on the job after they qualify. Fortunately, this
attitude is now far less prevalent. Yet it is still difficult to
encourage students to take a particular interest in clinical
pharmacology when they are struggling to understand the
complexities of physical examination and clinical medicine.
Even pathology seems more exciting when the student is
confronted with the choice between a post-mortem
demonstration and a lecture on the pharmacokinetics of
phenytoin. Presentation is all important and the way in
which clinical pharmacology is presented to the medical
undergraduate will determine how much time they will be
prepared to spend on the subject and how much of it will be
retained for future use. Textbooks play a vital part in this
strategy. Getting the balance right between
overburdensome factual information and the presentation of
the important basic principles is not easy. The Oxford
Textbook of Clinical Pharmacology, despite its unimaginative
title, goes a long way to achieving this difficult balancing act.
The text is divided into four sections. First, and probably
most important, are the basic principles of clinical
pharmacology, which can be simply divided into: what do
drugs do to the body and what does the body do to drugs?
This part is well written and the introduction of the student
to the notions of pharmaceutical, pharmacokinetic,
pharmacodynamic, and therapeutic processes is clearly and
concisely presented. However, I remain sceptical about the
need to include 40 mathematical formulae in the
pharmacokinetics section. We may be guilty of shooting
ourselves in the foot over this issue if the end result is that
medical students see pharmacokinetics as being of little
direct relevance to their needs. The main body of the text
deals with disease-oriented clinical pharmacology. This
multi-author section is again well written with clear
subheadings and several helpful figures and tables to distract
the student.
545
My only serious criticism of what is otherwise a valuable
textbook in this area is the inclusion of the section entitled
"Pharmacopoeia" of almost 200 pages (about one quarter of
the total text excluding the index). In this section the authors
list "... those drugs which are most commonly used in
clinical practice (a total of about 300 compounds)". The
definition of a commonly used drug is loose and includes
some that are rarely encountered by most clinicians and
others that are probably never now used by any. That aside,
I question the need for inclusion of material in this format
which adds to the bulk and cost of the book without an
equivalent increase in usefulness. Similar information is
available in standard formularies that are more regularly
updated and are free of charge.
The success of most textbooks rests with students and not
with their teachers. Students must feel that a particular text
satisfies their need, in terms of both content and readability.
In a competitive market, the Oxford textbook is well placed.
Department of Pharmacology and Therapeutics,
Leicester Royal Infirmary,
Leicester LE2 7 LX, UK D. B. BARNETT
Diet, Demography, and Diseases
Changing Perspectives in Anaemia. Edited by P. Stuart-
Macadam, S. Kent. Berlin: Aldine de Gruyter. 1992. Pp 296.
DM128. ISBN 3-110138344.
The first description of what was probably anaemia is
found on a papyrus dated 1500 BC. In England, known as
chlorosis until the nineteenth century, it was the "green
sickness" of Shakespeare’s heroines. Iron seems to have
entered therapeutic practice 350 years ago and today is freely
added to foodstuffs to combat iron deficiency anaemia. But
can one have too much of a good thing? The authors of this
polemic believe that the answer is yes.
They train their sights on a single target, striding
geographical space to examine peoples living in different
environmental conditions and on vastly different diets.
They pace evolutionary time, investigating porotic
hyperostotic lesions in neolithic hunter-gatherers and the ills
of our own sedentary, settled style of life, with its increased
incidence of disease. The viewpoints are many but,
irrespective of whether their data are palaeoanthropological
or collected by studying the Afro-Americans or Kung
populations of today, the authors conclude that the
hypoferric anaemia associated with settlement is more likely
to be due to increased pathogen load than to inadequate
dietary iron intake. Because, in the anaemia of chronic
infectious disease, witholding iron deprives pathogens of the
iron required to prosper, it is of paramount importance to
differentiate true iron-deficiency anaemia from that of
chronic disease by measuring serum ferritin concentrations
(which are normal or raised in chronic disease). The
administration of iron in such cases may serve only to thwart
the body’s natural defences.
Diet, Demography, and Disease is a notable attempt to
provide information through multidisciplinary networking.
The modern haematologist, though aware of the theories,
should find much of interest. Others, not least the family