What do we mean when saying that the etiology of a disease is known?  The  answer seems  obvious. The etiology of a strep-sore-throat  is  the  streptococcus. However, the microbe is only one cause of strep-sore-throat. There are other causes, like the patient's condition, or manifestations arising during an infection, like fever. Nevertheless, medicine regards the microbe as the sole cause of sore throat. What if the other causes are as significant as the bug?

Medicine lacks a procedure for systematically examining causes of a disease. Such a method already exists, and was proposed by Aristotle in his  "Physics, Book II, Part 3" .  In order understand the nature of a disease, we ought to employ four very different kinds of explanatory principle, and  these are the four causes:

1. Material cause  Available resources (Tolerance)
2. Formal cause:  Manifestation of a disease (Disease indicator)
3. Efficient cause: The agent  driving the disease.
4. Final cause: To make the disease most optimal.

When speaking of “Causes”, Aristotle meant causes of “motion” (movement) which has a wider meaning than “locomotion”. It seems more appropriate to replace “Cause” with “Change”. Disease progression is a change with four components.

Sore throat

1. Material cause: Biochemical, physical and psychological resources of the patient.
2. Formal cause: The set of symptoms and signs observed during disease evolution, e.g., inflammation, pain and fever.
3. Efficient cause:The process which drives the disease, e.g., infection by a microbe.
4. Final cause: To make the disease most optimal.

Each component contributes to the appearance of an evolving disease:

Material cause: An undernourished patient  responds differently to sore throat than a well nourished one.
Formal cause: These are processes mobilized by WOB to withstand the infection (driver). Inflammation curbs the microbe. Elevated temperature may activate processes to resist the bug, and impede with processes operating in the bug.
Efficient cause: Infection intensity.
Final cause: WOB applies means that are most effective and require the least resources. WOB optimizes the disease process.
Optimization depends on the other three causes. For instance, in a mild infection WOB will not raise temperature, and save resources necessary to raise it.

Cause in Physics

Medicine regards Efficient cause a "real" cause of a disease, or its etiology. The other three are regarded as factors operating during disease evolution. Causes are regarded as events which have to precede the disease which they cause. Given two events involved in a causal relationship, the occurrence of the first (the cause) is supposed to bring about or produce an occurrence of the other (the effect). This is how cause is defined in Physics. Only Efficient cause is considered.

Medicine inherited this causal relationship from Physics, and it is applied during diagnosis. Yet this practice is adequate only for a fraction of diseases, like infections or vitamin deficiencies. If the streptococcus had appeared after the sore throat started, it would not be regarded  as its cause. Since fever is triggered by the microbe, it is not regarded as cause. In most chronic diseases a temporal relationship between Efficient cause and effect is either blurred, or does not exist. For instance, the cause (etiology) of rheumatoid arthritis is unknown, and yet during its evolution all four causes shape the disease, and have to be considered.

Aristotle the biologist

Aristotle was a biologist interested in medicine. His books "On the Soul", should be regarded as treatises in biology and physiology. He  believed that Nature behaves like a living organism and can therefore be understood only by applying  the four explanatory causes. He erred since applying this method  to physical phenomena, like falling bodies:

1. Material cause: Weight - Heavier objects fall faster.
2. Formal cause: Surface/ Volume ratio. Paper falls down slower than a stone.
3. Efficient cause: How fast the falling body is pushed.
4. Final cause: The aim of the falling body is to unite with mother earth.

For centuries, philosophers (scientists) applied the four causes to explain phenomena in Nature, until Galileo demonstrated that one can ignore three of them and keep the Efficient cause. Which paved the way to Newtonian mechanics and the great achievements of the  exact sciences.

However this does not mean that the other three do not affect a falling body. In vacuum their effect vanishes, however, they ought to be considered when describing the behavior of falling bodies in water or honey. In other words, the laws of physics describe a model of a universe in which the three causes can be ignored.

Medicine lacks such a prerogative, and has to consider all four causes in describing the disease. Nevertheless it follows the advice by William of Occam who said that "it is vain to do with more what can be done with fewer", and ignores the three causes. However Nature does not shave with Occam's, razor. As disease evolves its four causes change and have to be adjusted frequently. The narrow (reduced) explanation of disease progression harms the patient and breeds iatrogenesis.

Additional reading: Physics as fable

Angina pectoris

1. Material cause: Biochemical, physical and psychological resources of the patient. (Tolerance)
2. Formal cause: Narrowing of coronary arteries due to the proliferation of smooth muscle cells in their walls.
3. Efficient cause: ?
4. Final cause: To slow down disease progression.

Medicine regards an increased cholesterol intake, and/or diminished cholesterol catabolism as Efficient cause of angina pectoris. It ought better be regarded as Material cause.

In order to make the disease most optimal (Final cause) WOB impedes the patient's activity by signaling pain whenever he starts walking. Anginal (precordial) pain results from the narrowing of the coronary vessels.  Since oxygen supply is limited the pain (caused by ischemia) prevents the patient from excessive exercise that might increase ischemia and damage his heart. On the other hand, anginal pain (or ischemia) triggers the formation of collateral vessels, increasing oxygen supply to the heart muscle.

From WOB perspective, the patient is advised to rest. Yet from the physician's perspective the patient ought to be encouraged to suffer some pain and so stimulate the formation of collateral vessels. The physician has to find a compromise between WOB demand for a complete rest, and the patient's life quality in the future. This implies also on the medication of vessel dilating drugs. Given too early, they hinder the formation of collaterals.  On the other hand, given too late, they endanger the heart. The final decision depends on the patient’s resources (Material Cause).

Diabetes mellitus, adult type (Without secondary complications).

1. Material cause: Biochemical, physical and psychological resources of the patient. (Tolerance).
2. Formal cause: Elevated blood sugar, overweight, insulin resistance polyuria.
3. Efficient cause: Increased sugar demand by the brain (Diabetes).
4. Final cause: To supply the brain needs with minimal resources.

Further reading: Diabetes mellitus

Cancer

1. Material cause: Biochemical, physical and psychological resources of the patient. weight loss,  cachexia (Tolerance).
2. Formal cause: Tumor, paraneoplasia
3. Efficient cause: metabolic deficiency.(v. Pernicious cachexia)
4. Final cause: To slow down disease progression.

Further reading: Cancer

References

1. Aristotle Physics
Translated by Hardie R P.  Gaye  R K
http://classics.mit.edu/Aristotle/physics.htm

2. Aristotle: On the Soul
Translated by J.A.Smith
http://classics.mit.edu/Aristotle/soul.html