The lack of a well-delineated hypothesis is not necessarily a barrier to acceptance of new directions in medical practice. The classic example is John Snow's demonstration that the 1854 cholera epidemic in London was attributable to contaminants in the water. When he removed the handle from the Broad Street pump, the number of cases in the area served by that pump promptly began to wane. Exactly what was in the water that caused the cholera would not be demonstrated for more than a quarter of a century. Still the results of Snow's intervention were so dramatic that no one questioned the cause-and-effect relationship even in the absence of an explicit hypothesis. However, when the causal linkage is less obvious, the absence of a plausible hypothesis can be a significant deterrent to action.

To return to the case at hand, it was difficult for several reasons for physicians to accept the idea that the concentration of blood cholesterol could be a major factor in determining the chances of myocardial infarction decades down the road. As discussed in Chapter 3, it was not appreciated that the average blood cholesterol level in the United States, the so-called normal level, was actually abnormal. It was accelerating atherogenesis and putting a large fraction of the so-called normal population at a high risk for coronary heart diseases. Also, very little was known about the structure and metabolism of these recently discovered and still mysterious cholesterol-protein complexes -- the serum lipoproteins -- and almost nothing was known about how they got into the vessel wall and contributed to the development of the lesions. A degree of skepticism was understandable.

--Daniel Steinberg, The Cholesterol Wars, 2007, Elsevier Press, p. 89