The Central Dogma of Molecular Biology

“One never hears of a martyr in history whose notions are seriously disputed today. The forgotten ideas are those of the men who put them forward soberly and quietly, hoping fatuously that they would conquer by the force of their truth; these are the ideas that we now struggle to rediscover.” —H.L. Mencken 

  

Selye hypothesized that the extracellular stress mechanism works closely with eukaryotic DNA to convert genetic information into multicellular structures (embryological development), whereupon the nuclear DNA resumes quiescence, while the stress mechanism remains active for the duration of life to maintain and repair multicellular tissues and regulate hemodynamic physiology to maintain the "internal milieu" that sustains cell survival and function in complex multicellular plants and animals, which are composed exclusively of eukaryotic cells. This was the simplest explanation, and therefore the most promising, but Selye's ideas were abandoned after an intense international search failed to find his putative stress mechanism. However, Selye's hypothesis was never disproved. 

The “central dogma of molecular biology” (aka "genomics") became the prevailing paradigm of medical research by default after the demise of stress theory. Few pause to consider that this paradigm is founded on a flawed premise. Almost all DNA knowledge is founded on prokaryote (bacterial) research. Prokaryotic cells are profoundly different from eukaryotic cells. In prokaryotic cells, DNA floats free in the cytoplasm in the form of simple strands and circles. Its genetic information is converted into enzymes and proteins via a simple “transcription/translation” mechanism. RNA "transcribes" (copies) genetic information from DNA and “translates” the information into enzymes and proteins that govern intracellular bacterial biology, but prokaryotes are incapable of multicellular existence. 

The DNA that determines embryological development in plants and animals is confined within a thick nuclear membrane in the form of chromatin (which forms into chromosomes during cell reproduction). The means by which this chromosomal DNA communicates outside the nucleus, let alone outside the cell, remains unknown.There is no evidence that chromatin utilizes the transcription/translation mechanism found in prokaryotic cells. Researchers suspect that chromatin governs embryological development via an undiscovered mechanism.(1) 

The shortcomings of DNA dogma became acute after the Genome Project cost billions and successfully identified the human genetic code, but failed to produce promised treatments and theoretical advance.(2) Medical research has consequently entered a period of crisis, wherein the prevailing paradigm is exhausted, and theoretical advance has stagnated. A new paradigm is needed to reinvigorate research and restore progress.(3)

1. J. S. Mattick, The hidden genetic program of complex organisms. Sci Am 291, 60-67 (2004)

2. J. Pontin, in Technology Review, J. Pontin, Ed. (MIT, MIT, 2010), vol. 114, chap. 8, pp. 1.

3. T. S. Kuhn, I. Hacking, The structure of scientific revolutions.  (The University of Chicago Press, Chicago ; London, ed. Fourth edition., 2012), pp. xlvi, 217 p.