Theor. Biol. 67: 625-635, 1977;
in Advances 1(3): 53-59, 1984.
Theory of Diagnosis for Orthomolecular Medicine
Evolution of Disease (continued)
Consider the following scenario, in which disease X is
disease Y by defgh, and disease Z by dhjkm.
A patient possesses in-
anomalies dfm, and is seemingly healthy. After a period of
diet, anomaly e develops. The patient now has a sufficiently
to experience vague constitutional symptoms such as fatigue and
He consults his physician, who is uneasily aware that most
complaints do not resemble the textbook syndromes that he has
in the teaching hospital. The physician does not perform a battery
tests, as the health insurance will not pay for them; the physician
has not been properly trained to interpret the set defm. The physician
make a provisional diagnosis of Y-or-Z, for he knows
that both diseases
often associated in their early stages with vague constitutional symptoms.
clarify the diagnosis he tests for dgm. Finding dm, he
assumes Z and
excludes Y, which has actually evolved most closely toward a
stage. He prescribes a drug that has the unfortunate side-
of activating c. Additional symptoms arise, of an ambiguous nature;
patient is now chronically ill and the prolonged derangement in body
finally causes compensatory mechanism a to fail. The distraught
then consults a university medical school professor, who perceives
the symptoms that the differential diagnosis lies between X
for abcdefgh, and finding acdef, the professor
concludes that X is
correct diagnosis, Y is unlikely, and Z is erroneous.
This ritual, repeated
in medical centers throughout the world, serves to affirm the natural
of a universe in which professors of medicine possess more erudition
their brethren in private practice. In fact Y (in a
preclinical stage) has
neglected, and Z (in a potential stage) ignored altogether.
If by chance
test for m should be performed, the professor may publish a
the unusual occurrence of m in a case of X.
The point of the preceding scenario is that diseases progress through
stages, that several evolving diseases are likely to be present
that differential diagnosis is therefore a pointless exercise,
that insufficient data lead to inadequate conclusions.
It is presently exceptional for disease to be recognized in its preclinical
and indeed no unifying scheme exists for classifying preclinical
A suitable scheme might be classification according to subsystem
adrenal, hepatic, etc.) and process (e.g. insufficiency,
hyperfunction, congestion). Thus a hierarchy is established in
constitutional abnormalities combine with acquired anomalies to
derangements of subsystems; interactions among abnormally
subsystems result in clinically-apparent diseases. For example, a
with elevated excretion of metanephrines and pregnandiol, with low
and cortisol, may be said to have adrenal imbalance. Later,
subsequent exhaustion of the adrenal glands leads to widespread
disturbances, he can be diagnosed as having Addison's disease.
clinically-apparent disease diabetes mellitus may be preceded by dys-
states of the pancreas, adrenals, pituitary, thyroid and peripheral
as discussed by Loeb (1955) or by Medalie, Papier, Goldbourt
Herman (1975). The latter authors used a multivariate analytical tech-
to demonstrate that serum uric acid and cholesterol, among other
are major factors in the development of diabetes.
practice, a patient will usually be found to have several preclinical
at the same time. Examples of preclinical diseases with their com-
anomalies are presented in Table 1. Such sets of anomalies would
encountered fairly frequently were it not for inadequate laboratory
that test for only a few disease elements among the many
a set, an approach that is insufficiently multivariate. Unfortunately,
selected elements are most often those that differentiate the hospitalized
from the outpatients.
1. Diagnostic profile of a 40-year-old male physician
complained of chronic fatigue
Low beta globulin
Malabsorption dysnutrition syndrome
Deficient serum magnesium
High metanephrine excretion
High catecholamine excretion
High pregnandiol excretion
High lactic dehydrogenase (isoenzyme iii)
Abnormal glucose tolerance
categorical headings are followed by a list of the component anomalies.
final two diagnoses are isolated anomalies that do not yet form part
of a larger set. The data were obtained by standard biochemical and
cellular analyses of body fluids.
a discussion of orthomolecular therapy (Pauling, 1974) is
the scope of this paper, it is appropriate to mention that many of
biochemical anomalies within a disease set are in theory reversible by
methods. Preclinical disease ought to be more easily reversible
clinically-apparent disease, because preclinical-disease sets are smaller
clinical-disease sets. For example, examination of an infant's urine
reveal the diathesis phenylketonuria. Once recognized, the potential
can be treated by orthomolecular methods, thereby preventing the
disease phenylpyruvic oligophrenia, of which phenyl-
is a subset. As an additional example, I have observed a
woman who was treated for multiple clinical and preclinical
including chronic hepatic dysfunction. The latter condition was
by high serum copper, high cholesterol esters, high isocitric de-
low cholinesterase and low thermostable alkaline phosphatase
The patient responded to orthomolecular therapy with a reversion
normal of the anomalous esterified cholesterol, isocitric dehydrogenase
cholinesterase. Presumably, if this patient were subsequently to be
with a hepatotoxin, the now-latent anomalies would appear more
than would unrelated anomalies.
The art of clinical diagnosis conventionally rests on the assumption that
symptoms and anomalous laboratory findings follow from specific
each of which in turn follows from unique causes. By contrast, the
presented here holds that multiple non-specific causes give rise first
biochemical aberrations, which then result in symptoms and signs, from
a perceived disease state follows. The present theory thus constitutes
inversion of the usual conceptual hierarchy.
The present model is more deterministic than the conventional one, in
a more central role is assigned to genetic influences. The model predicts
unique sets of stable biochemical anomalies will be observable in each
regardless of his stage of development. It predicts further that
elements of such sets will become observable as components of the
that an individual will develop with the passage of time. Additionally,
model requires that disease states as conventionally defined be describable
polythetic classes of biochemical anomalies.
If the predictions of the theory are valid, the science of clinical diagnosis
become a process of multifactorial biochemical analysis, followed by
of biochemical anomalies (with probability weightings) to various
categories. By this means it will be possible to identify evolving
in early (preclinical) stages of development, or even as mere
predispositions. The diagnostic process would appear
lend itself well to electronic data-processing techniques (cf.
Pomeroy et al.,
In the final analysis, most diseases are traceable to molecular causes,
inborn or acquired during life. Present-day clinical-laboratory
is sufficiently advanced to detect the proximate effects of many
defects, and in some cases the defects themselves. Thus the
of disease along the lines elaborated above is presently feasible.
time, refinements in laboratory technology will permit
identification of a
broad range of molecular defects to make possible a true
classification of disease.
The theoretical analysis implies that laboratory tests should
to make a diagnosis before a patient becomes ill, not afterward. The
application of specific therapy can then prevent more serious disease.
biochemical defects can in principle be corrected with orthomolecular
and a small number of defects should be more easily correctible
a larger number. At present it is indifference, not technological im-
that offers the major obstacle to earlier disease detection and to
am profoundly grateful to the late Joseph D. Walters, M.D., for many dis-
concerning the diagnostic interpretation of his clinical data. These pages
descriptions of clinical cases observed by Dr. Walters and myself. I also
the helpful comments of Dr. Bernard Strehler and Dr. Leon Pomeroy
earlier versions of this manuscript. I thank Damon Medical
California, for donating the tests on which Table 1 is based.
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