Standing on the Shoulders of Giants

“If I have seen further it is by standing on the shoulders of giants.” (Sir Isaac Newton, 1676)

Occasionally, when I am on in-patient rounds with residents and students, I ask them a few questions involving well known individuals who have played important roles in recent medical history, for example, “Who was Sir William Osler, and why is he relevant to what we are doing today?”

Very rarely do any of today’s trainees know the answer to this question which gives me an opportunity to both teach them a bit about Sir William and his contributions, as well as to suggest that they read one of the many short histories of medicine that are readily available through the internet or at our local medical school bookstore.1

Recently, I found myself on the other side of this question-and-answer when an internist from California sent me a link to a seminal paper on atherosclerosis published in The American Journal of Medicine more than 60 years ago.2 I tried diligently to remember if I had read this article as a medical student, and in the end I had to admit that I had no recollection of it. Later that day, I found some time to read this article in its entirety and discovered to my surprise how much was already known about the atherosclerotic process 63 years ago. For example, these authors commented extensively on the earliest stages of atherogenesis involving fatty streaks which eventually developed into atherosclerotic plaques. They also described plaque rupture with discharge of atherosclerotic material into the lumen of the artery with resultant thrombus formation: “Extension of necrosis [from large central collections of lipid material] toward the intimal surface ends with disruption of the lining membrane. In this event much of the gummous content of the atheroma may be discharged into the blood stream and the ragged defect becomes covered by thrombus material.”2 Other interesting facets of the atherosclerotic process are discussed including plaque erosion with ensuing thrombosis, development of fibrosis in lipid laden plaques, great variation in the presence and size of atherosclerotic lesions among individuals including the elderly, and the concept that hypercholesterolemia, hypertension, and diabetes predisposed individuals to accelerated atherosclerosis.

I was indeed surprised to see these concepts identified in 1951 since I believed—mistakenly, as it turned out—that much of this information was of more recent origin. Even more surprising was the statement: “…minute vascular channels [within the walls of the artery] may rupture and cause a hemorrhage into an atheroma with the formation of a hematoma and consequent distortion of the plaque. This may cause occlusion of the artery itself.”2 Again, I was astonished to find that this information greatly predated current similar thinking concerning the evolution of the atherosclerotic process and its relationship to arterial occlusion.

Finally, the concept of vascular injury involving inflammation in the arterial intima and wall was discussed extensively by Duff and McMillan. In this regard, these authors referred to seminal work on atherosclerosis done in the latter years of the19th century by Rudolf Virchow and Carl von Rokitansky.2 Both of these pioneering pathologists recognized that the atherosclerotic process involved inflammation.2, 3 However, Rokitansky felt that the inflammatory changes that he found in atherosclerotic plaques were secondary to the atherosclerotic process while Virchow alleged that inflammation was a primary process in atherogenesis.2, 3 Subsequent investigation has demonstrated that Virchow was correct.

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–Joseph S. Alpert, MD (Editor-in-Chief, The American Journal of Medicine)

This article originally appeared in the May 2014 issue of The American Journal of Medicine.