Maybe every five or 10 years I run into a medical article that is stunning. Steve Blair's paper on the relation of fitness to all cause mortality in 1989 in JAMA (1) and Mike McGinness's paper on the actual causes of death also in JAMA 1993 (2) are two of my most treasured resources.
Now a third. Just last week a new brilliant statement emerged, "Preventing Alzheimer's Disease by Means of Natural Selection." The authors are Lloyd Demetrius and Jane Driver, both of Harvard. It is published in the Journal of the Royal Society Interface (3). It had earlier been excerpted by the Harvard Gazette It could not have more substantive impact. The authors brilliantly display why the dominant current genocentric view of the cause of Alzheimer's is wrong. We have spent decades of intellectual effort and many billions of dollars looking in the wrong place. We have developed NO, NO effective therapy as the result of our missed focus. Current insight is inconsistent on many regards. I have long been disenchanted with this emphasis, but until now we've had only a skimpy alternative paradigm. The Harvard authors alternatively propose the etiology of Alzheimer's Disease is what they call "the entropic selection theory." Their idea proposes that A.D. results when the basic determinants of the brain cells' mitochondria are disrupted by a number of harmful assaults. Their formulation reconciles all of the earlier inconsistencies that are inherent in the discredited amyloid cascade proposition. The new statement is internally consistent and practically of immense value.
Demetrius and Driver base their proposition on the Second Law of Thermodynamics that holds that any open system will inevitably go to greater disorder, entropy. Such directionality derives from basic cosmic principles which are often said to be "the arrow of time."
Twenty years ago I posited that aging itself was a direct result of the second law, aging as entropy (4) but I lacked a rigorous mechanistic argument. D and D base their Alzheimer's disease projection on specific biologic formulae arguing that the bombardment of the little brain mitochondria by varying insults leads to their damage; such chaotic turbulence leads eventually to the clinical picture of Alzheimer's disease. Their arguments are sound and display a grasp of the fundamental conditions which have eluded our understanding until now.
Several months ago I devoted this blog to a comment made by British historian and author CP Snow who said that a person who is unfamiliar with the Second Law of Thermodynamics is equivalent to a person who has not read Shakespeare. My blog was entitled, "Medicine Has Not Read Shakespeare," reflecting my insistence that my major domain of medicine remains ignorant of the critical fundamental biologic energy flows that lie at the heart of the Second Law.
Thank you therefore Demetrius and Driver for your understanding. I'm sure that you have read Shakespeare too.
References:
1) Blair, S. et al Physical Fitness and All Cause Mortality 1989, JAMA 262;2395-3401.
2) McGinnis, MD and Foege R. Actual Causes of Death 1993, JAMA 270:2207-2212.
3) Demetrius L and Driver J Preventing Alzheimer's Disease by means of Natural Selection J. R. Soc. Interface 2015, 12:20140919.
4) Bortz, W. Aging as Entropy J Exper Geront. 1986, 21: 321-328.