Principle of Recursive Genome Function Supersedes Dogmas; By Andras Pellionisz, Online Ahead of Print; (Scientific Visionary Vindicated)

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A Eureka Moment concerning the fractal character of neurons led in turn to a novel picture of genomics where protein structures act back recursively upon their DNA code -- in outright contradiction to prevailing orthodoxy. A household name in neuroscience for his tensor network theory, Dr. András Pellionisz has recently had another far-reaching discovery borne out. This insight has now received striking confirmation in stunning results from the new field of epigenetics -- promising a whole raft of novel medical diagnoses and therapies.

into a solid scientific foundation of HoloGenomics.

A landmark article on "The Principle of Recursive Genome Function" (received December 7, accepted December 18, 2007) by András J. Pellionisz appears online in Springer's e-Journal Cerebellum.

The paper marks the first anniversary of an historic event--the release of pilot results for ENCODE, the Encyclopedia of DNA Elements project. Building on the results of the Human Genome Project, the ENCODE effort revealed a far more complex DNA coding sequence than was ever previously imagined. "There's a lot more going on than we thought," said Collins, who is director of the National Human Genome Research Institute (NHGRI). Dr. Collins issued a mandate a year ago "the scientific community will need to rethink some long-held views".

A happy few did not need to rethink either the "central dogma of molecular biology" (Crick, 1956) or the misnomer of "junk" DNA (Ohno 1972), since they never believed them in the first place. The dictum claiming that a flow of information from proteins back to DNA "never happens" or the idea that 98.7% of the human genome should be disregarded as junk was never very believable.

As a direct response to Dr. Collins' call, the principle of recursive genome function (PRGF) in one stroke sweeps away two dogmas which prevailed for over 50 years concerning the function of the double helix.

Recursive genome function is a process whereby proteins iteratively access information packets of DNA to build hierarchies of more complex protein structures. Such recursive development is illustrated in the fractal growth of cerebellar Purkinje neuron.

Starting from a primary information packet, a Y-shaped, fractal protein template is constructed by a "forward growth" process - in accord with the traditional picture - via transcription of DNA to RNA (where, in turn, RNA builds nucleic acids up into structural protein). In the course of constructing the Y-shaped template, the primary gene is turned on. Thus, the most primitive part of the process retains Watson's simplified scheme. The principle does not contradict the 'DNA makes RNA makes proteins' picture, but rather goes beyond it - dispensing with both the hitherto forbidden feedback mechanism as well as the entire notion of junk DNA.

On the contrary, the genetically crucial process known as methylation demonstrates just such a "backward" flow. In a stunning reversal of long-held views, it now appears that environmental influences can act directly on the genetic code. Moreover, methylation of DNA is not merely epigenetic, but HoloGenomic:

Dr. Alexandre Akoulitchev, Oxford University, UK (not involved in the study) says: "The PRGF of Pellionisz is helping not only his recursive algorithmic approach to the genome (FractoGene), but puts the various meanings of 'epigenetics' into the perspective of clearly defined novel axioms. The PostModern Age of Genomics (starting with his, synthesizes inconsistent interpretations and haphazard notions of "epigenetics" into a solid scientific foundation of HoloGenomics."

Leroy Hood (2003) and finally Richard Dawkins (2008) have suggested that genomics is now a branch of information science. With modern genomics becoming postmodern genome informatics, a natural question arises: What axioms will take the place of outmoded assumptions?

The traditional axioms could not put to a dignified rest because, as the wisdom has it, "data never kill theories, only better theory can kill less tenable theories."

The principle of recursive genome function addresses this fundamental, decisive role. The time has come to go public, after more than a decade of clandestine work - not even asking for support.

András Pellionisz is a biophysicist, formerly of New York University. Since heading up HelixoMetry in Silicon Valley, he has been busy assembling a portfolio in anticipation of the time when the imposing dogmas and their bulwarks would give way. A widely published author, Pellionisz remained largely silent for 15 years to spare him a collision with the powers that were.

His pioneering work in biological neural networks, aired in over a hundred publications, won him both NIH support and recognition by way of the Alexander von Humboldt Prize for Senior Distinguished American Scientists.

When Pellionisz also made a bold step and published his research on the fractal geometry of cellular development based on a recursive DNA paths (1989), his next NIH application was overlooked by his peers and the establishment maintained a double lock on genomics. Their ideology was: Don't look back on DNA, since recursion can "never happen" and even if you would, "there is only junk."

As a scientist with his first degree in engineering, he developed a neural net application for NASA, using the parallel computers of the time (so-called Transputers).

By 2005 fundamental problems with underlying axioms of genomics became too obvious. Meanwhile, millions, if not hundreds of millions were dying of junk DNA diseases while 98.7% of the human DNA was officially still considered untouchable.

Together with his fellow pioneers, Dr. Pellionisz launched the trial balloon of International PostGenetics Society. Indeed, almost a year ahead of disclosing the official conclusions of ENCODE that "junk" DNA is anything but, the IPGS became the first organization to officially abandon the misnomer at its European Inaugural in 2006. At that meeting, Pellionisz pioneered the approach of diagnosis (leading to therapy and eventual cure) of junk DNA diseases caused by fractal defects in genomic regulatory sequences.

In late 2006 a manuscript attempting to close the chapter on junk DNA was co-authored by 20 Founders of IPGS. Those suffering from "junk DNA diseases" probably wish that the manuscript was given the benefit of a peer-review.

Instead, the mounting pressure caused publication of ENCODE results 3 months earlier than planned. Thirty major papers shredded long-held views and printed staggering statements such as "the concept of genes is a myth." A deafening silence ensued.

Rather than heeding advice of Dr. Collins of "re-thinking long-held beliefs" research went "genome-wide" for more data, as next-generation sequencing made the entire genome of many species (including humans) available with rapidly melting price tag.

Application of brute force to turn out more data instead of revising axioms created its own problems, however. A dreaded DNA data deluge looms large. Without a combination of algorithmic reduction as well as building the proper computing architecture, the brute force approach of full genome sequencing and genome-wide analysis have already hit a compute- and data-wall.

The old bottleneck "get info" (sequencing to obtain data). The new bottleneck is "use info" (understanding what sequenced data mean). The promise inherent in the Principle is that an algorithmic reduction delivers us an understanding of physiological and therefore pathological genome function in a new light. This clears the road for rapid advancement beyond a long-overdue breakthrough. In HoloGenomics, all, including non-genic conditions can now be focused upon. This is the direct response to consumers, including those who are not even patients. For those impatient enough to prevent some undesirable conditions, the principle opens an opportunity.

Brian Flanagan
Phone: (+1) 319-338-6250


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