[...The late] Dr. Susumu Ohno, writing in the Brookhaven Symposium on Biology in 1972 in the article "So Much ‘Junk DNA' in our Genome" is credited with originating the term. As anyone can read below, he tried to (mistakenly) construct a scientific argument that the human genome can not sustain more than a very limited number of "genes" and argued for "the importance of doing nothing" for the rest. Though his misnomer was doubted from the outset (see the first question after his presentation calling his arguments "suspect"), the misnomer lived for a generation, in spite of ample evidence that it was false. The reason is, that "facts don't kill theories, only theories that exceed obsolete dogma can kill old theories. "The Principle of Recursive Genome Function", heretofore the only concise interpretation how directly amino-acid-coding regions (formerly called "genes") work together with intronic and intergenic sequences, carrying much auxiliary information that is perused in fractal recursive iteration, only appeared in 2008. There may be other mathematical algorithmic theories for genome function explaining why and how "Junk DNA" is anything but "Junk" - this author will be pleased to list them - Pellionisz_at_JunkDNA.com
Hal Plotkin, Special to SF Gate (San Francisco Chronicle) Thursday, November 21, 2002
When the human genome was first sequenced in June 2000, there were two pretty big surprises. The first was that humans have only about 30,000-40,000 identifiable genes, not the 100,000 or more many researchers were expecting. The lower -- and more humbling -- number means humans have just one-third more genes than a common species of worm.
The second stunner was how much human genetic material -- more than 90 percent -- is made up of what scientists were calling "junk DNA." The term was coined to describe similar but not completely identical repetitive sequences of amino acids (the same substances that make genes), which appeared to have no function or purpose. The main theory at the time was that these apparently non-working sections of DNA were just evolutionary leftovers, much like our earlobes.
But if biophysicist Andras Pellionisz is correct, genetic science may be on the verge of yielding its third -- and by far biggest -- surprise.
In addition to possessing an honorary doctorate in physics, Pellionisz is the holder of Ph.D.'s in computer sciences and experimental biology from the prestigious Budapest Technical University and the Hungarian National Academy of Sciences respectively -- institutions that together have produced nearly a dozen Nobel Prize winners over the years.
In a provisional patent application filed July 31, Pellionisz claims to have unlocked a key to the hidden role junk DNA plays in growth -- and in life itself.
Rather than being useless evolutionary debris, he says, the mysteriously repetitive but not identical strands of genetic material are in reality building instructions organized in a special type of pattern known as a fractal. It's this pattern of fractal instructions, he says, that tells genes what they must do in order to form living tissue, everything from the wings of a fly to the entire body of a full-grown human.
Another way to describe the idea: The genes we know about today, Pellionisz says, can be thought of as something similar to machines that make bricks (proteins, in the case of genes), with certain junk-DNA sections providing a blueprint for the different ways those proteins are assembled.
The notion that at least certain parts of junk DNA might have a purpose appears to be picking up steam. Many scientists, for example, now refer to those areas with a far less derogatory term: introns.
Other investigators are also looking into introns from a variety of perspectives. A group at UC Berkeley, for example, recently won $14 million from the National Institutes of Health to study the role introns might play in cardiovascular disease. Other researchers have begun looking at similar questions, with most focusing on intron strands located near genes whose functions are better understood. Scientists at UCLA, for example, recently made a promising association between what appears to be an intron abnormality and spinocerebellar ataxia, which is similar to Huntington's disease.
What makes Pellionisz' approach different is his suggestion that fractals will be found to play a critical role not only in these conditions but also in tens of thousands of others that have not been studied yet. His patent application covers all attempts to count, measure and compare the fractal properties of introns for diagnostic and therapeutic purposes.
"It's certainly possible that such a patent could be granted," says C. Anthony Hunt, Ph.D., a holder of nine patents who heads the Hunt Lab in the Department of Biopharmaceutical Sciences and Pharmocogenomics at the University of California at San Francisco.
To win a patent, Hunt notes, all an inventor must do is describe or teach some new skill that is not obvious.
"And this would certainly qualify as non-obvious," he says. "If it works, [fractal intron analysis] could become a very important tool."
Hunt adds that most biologists simply don't know enough about fractals or the advanced math behind them to understand how they might apply to the field of genetic medicine.
"We need someone to tap us on the shoulder and explain it to us," he says. "But if it clicks as a tool, we would be more than happy to use it."
"Overall, we know very little about what is referred to as 'junk DNA,'" he adds. "But every year that goes by, there are more insights into the possible role they might play."
Staking His Claim
Pellionisz hopes his patent application will help him launch his company and make him one of the field's key players. The provisional application lets him put the words "patent pending" on any related creations for one year, after which he must file a complete application. Like other inventors, he's also free during that time to disclose his concept through other means, such as in professional journals or at scientific gatherings.
In a move sure to alienate some scientists, Pellionisz has chosen the unorthodox route of making his initial disclosures online on his own Web site. He picked that strategy, he says, because it is the fastest way he can document his claims and find scientific collaborators and investors. Most mainstream scientists usually blanch at such approaches, preferring more traditionally credible methods, such as publishing articles in peer-reviewed journals. Scientists who don't follow that tradition are usually treated with suspicion.
But Pellionisz' credentials and prior accomplishments make him much harder to dismiss than the average cyberspace sci-fi wacko.
A biophysicist by training, the 59-year-old is a former research associate professor of physiology and biophysics at New York University, author of numerous papers in respected scientific journals and textbooks, a past winner of the prestigious Humboldt Prize for scientific research, a former consultant to NASA and holder of a patent on the world's first artificial cerebellum (a part of the brain), a technology that has already been integrated into research on advanced avionics systems. Because of his background, the Hungarian-born brain researcher might also become one of the first people to successfully launch a new company by using the Internet to gather momentum for a novel scientific idea.
The Hidden Fractal Language of Intron DNA
To fully understand Pellionisz' idea, one must first know what a fractal is.
Fractals are a way that nature organizes matter. Fractal patterns can be found in anything that has a non-smooth surface (unlike a billiard ball), such as coastal seashores, the branches of a tree or the contours of a neuron (a nerve cell in the brain). Some, but not all, fractals are self-similar and stop repeating their patterns at some stage; the branches of a tree, for example, can get only so small.
Because they are geometric, meaning they have a shape, fractals can be described in mathematical terms. It's similar to the way a circle can be described by using a number to represent its radius (the distance from its center to its outer edge). When that number is known, it's possible to draw the circle it represents without ever having seen it before.
Although the math is much more complicated, the same is true of fractals. If one has the formula for a given fractal, it's possible to use that formula to construct, or reconstruct, an image of whatever structure it represents, no matter how complicated.
Basically, Pellionisz' idea is that a fractal set of building instructions in the DNA plays a similar role in organizing life itself. Decode the way that language works, he says, and in theory it could be reverse engineered. Just as knowing the radius of a circle lets one create that circle, understanding the more complicated fractal-based formula that nature uses to turn inanimate matter into a heart might -- in theory, at least -- help us learn how to grow a living heart, or simpler structures, such as disease-fighting antibodies. At a minimum, we'd get a far better understanding of how nature gets that job done.
The complicated quality of the idea is helping encourage new collaborations across the boundaries that sometimes separate the increasingly intertwined disciplines of biology, mathematics and computer sciences.
Thinking about whether junk DNA has a purpose "is a rather obvious question for scientists to ask," says UC Berkeley mathematics Professor Jenny Harrison, a world-renowned expert on fractals.
When Harrison examined the strings of amino acids involved, the idea that had also dawned on the mathematically inclined Pellionisz, in addition to several other theorists, immediately jumped out at her: If junk DNA really is junk, some of it is certainly organized in a pretty peculiar pattern, one that looks amazingly like a fractal.
"This is a fractal form of nature that must stop at some stage," Harrison says simply, adding that the fractal pattern looks exactly like others that appear in nature. She's been batting the topic around with Pellionisz recently, and is continuing to think about it.
"I'm not sure he has the right answer," she says, "but he is asking a very important question."
Pellionisz has been working on understanding the possible linkages between math and physiology since his earliest days as a college student in Hungary, when he first decided to devote his life to understanding how the brain works. It's that pursuit that has helped lead him to his latest ideas, he says.
"When you consider how the brain tells the fingers to pick up a pencil -- all the many different muscles involved, the senses, vision, touch, the distances involved, and how it is all managed by the brain -- you quickly realize there has to be some form of math involved to coordinate everything," he explains. "I always knew from my earliest days that it had to be math, and I knew it wasn't calculus, because of the distances involved [e.g. from the brain to the tip of the finger]. So it had to be a form of geometry, but it had to be a very special kind of geometry."
Pellionisz has dubbed his new company Helixometry Inc. The name ("helix" refers to the unique spiral folded-over shape of the DNA molecule) alludes to what he says is the fractal math at work inside DNA.
His theory is highly speculative. But there is at least one other important piece of anecdotal evidence that he might be on the right track: As organisms become more complex, they seem to have more intron DNA.
"It's not a perfect correlation," says UCSF's C. Anthony Hunt, "but it is a trend. It's as if the more advanced organisms had made a larger number of steps to get to where they are now."
In other words, although people are made up of the same basic stuff as other organisms, the instructions for making a person should in theory be more complex, which could account for the large amount of intron DNA found in humans.
While they remain generally cautious, a number of top biomedical researchers and other scientists say Pellionisz might be onto something really big.
Experts generally agree that a breakthrough in figuring out the role junk DNA plays, if any, would represent a spectacular advance in our understanding about how DNA in general turns inanimate matter into living organisms. If that happens, humanity would take a giant leap toward gaining control of the machinery of life itself, which would open up a wild new frontier in medicine and science that could lead to everything from growing new organs designed for specific patients to preventing and curing any health- or age-related problems that have a genetic origin or component.
Pellionisz says his main goal is to set the stage for the next and even more promising generation of research into genetics. Given the fact that he may be the first person to assert a patent on intron fractal counting and analysis, it's also conceivable that Pellionisz could wind up with related commercial rights worth billions of dollars. If he's wrong, of course, any patent he might receive will be worthless. And even if he's right, he could have to contend with other inventors who may also have recently filed similar patent claims that, like his, have not yet been fully disclosed.
Meanwhile, Pellionisz has several additional patent applications in the works that he says will build on and further protect his original claims. At the same time, he's also looking for the investments he says he needs to move forward more quickly, including completing his formal patent application by the deadline, as well as ramping up his company's first commercial applications, which other researchers would use.
Wary of all the startup horror stories Pellionisz has heard, he's hoping to avoid working with a traditional venture-capital company. Instead, he says he's looking for a single "angel" investor, ideally someone knowledgeable and connected in the biosciences and database worlds who can help him develop his patent portfolio and formulate a business plan that links his efforts with those of some larger organization in a related field. Pellionisz even has a short list of names of specific people who he thinks would be ideal partners at this stage. He is, he says, more interested in building a successful company than in selling the idea for a quick buck. Given the stakes, additional competitors seem certain to join the fray.
It could be years, even decades, before the dust settles and Pellionisz learns whether his patent application has any real merit, as well as whether someone else beat him to the punch with an earlier enforceable patent claim.
"All I know is that I'm in a race," Pellionisz said last week. "And the clock is already ticking."
[SF Gate featured the above on their website in late November, 2002 - comment by Andras Pellionisz]
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FractoGene Patent on Mathematical Language of Genetic Code
Sunnyvale, CA, September 3, 2002
HelixoMetry, inc. announces that its FractoGene USPTO patent (pending) on the mathematical language of genetic code is available for exclusive or non-exclusive licensing.
Dr. Andras Pellionisz, Founder and CEO, is USPTO customer 32892, Associate Member of the National Association of Patent Practitioners, NAPP. He electronically submitted patent application called FractoGene and received hard copy confirmation.
When the human genome was mapped out little over a year ago, up to 97% of the DNA was found to contain, instead of genes, so-called non-coding sequences, termed in acute embarrassment "junk genes" says Andras Pellionisz, inventor of FractoGene. "One person's junk is an other person's treasure", he continues. Now he is proud to have incorporated his HelixoMetry Company, and to have submitted a Provisional patent application to protect FractoGene, his invention for the mathematical language of highly repetitious genetic code.
Dr. Andras J. Pellionisz, a former University Professor of New York University, 1976-1990 and Senior Research Fellow of the National Academy of the USA to NASA, 1990-1993, later senior Executive of Silicon Valley Internet Companies (of Ernst & Young, inc.). Subsequently, he was Chief Intelligence Officer and Chief Software Architect of Fabrik, inc, Verge, inc, Xmarksthespot, inc, and Mindmaker, inc. Dr. Pellionisz incorporated HelixoMetry in early 2002 in Sunnyvale. He is an internationally renowned inventor-scientist who pioneered pattern recognition neural network technology. His first patent was obtained in 1984, and in 1990 he received the Alexander von Humboldt Prize for Senior Distinguished American Scientist from Germany for his pioneering in neural networks...
Pending Patent of FractoGene is a utility to count the extremely repetitive number of base-pair sequences in the genetic code, based on the axiom that - contrary to current belief held by many - these supranumerary genes are not "junk" but constitute fractal sets. In turn, body organs and organelles (brain cell arborizations, coronaries, lungs, bowels) that are known to be most suitably modeled by fractal mathematics, develop in self-similar "generations", where the basic template determined by the undifferented genetic information encapsulated in the "stem cell" , and physiological and pathological differentiation governed by regular- or erroneous number of base-pair repetitions.
FractoGene Patent will be used to protect the intellectual property...
Information regarding the use of fractal mathematical language of genetic code is available in the websites http://www.fractogene.com.
Accomplishments of the inventor of FractoGene are shown in http://www.usa-siliconvalley.com
[The FractoGene approach was conceived on the 17th of February, 2002; one year and one day after the revelation that the already patented 140,000 human genes - were a myth. A. Pellionisz, an Information Technologist, never accepted either the notion (see below) that the paltry 30,000 genes [by 2006, only 19,000] contained enough information to determine a human, or that the paucity of the number of genes were compensated by "nurture". Most importantly, both from an Information Science viewpoint the "Junk DNA" notion of 98.7% of (human) DNA were rejected by AJP, and based on Evolution it was unthinkable that Nature carried in the most compact information depository (DNA) 98.7% "junk". The original FractoGene concept went beyond the state of art drawing practical utilizations of the causal relationship of DNA as fractal sets and the organismal fractality determined by them. From this core, the Intellectual Property of FractoGene Patent Group developed by 2006 - comment by Andras Pellionisz]
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The news that shocked the world: We have only about twice as many genes as your average fruit fly.
Nature vs Nurture Revisited
by Kevin Davies
The most shocking surprise that emerged from the full sequence of the human genome earlier this year [16 February, 2001] is that we are the proud owners of a paltry 30,000 genes -- barely twice the number of a fruit fly.
After a decade of hype surrounding the Human Genome Project, punctuated at regular intervals by gaudy headlines proclaiming the discovery of genes for killer diseases and complex traits, this unexpected result led some journalists to a stunning conclusion. The seesaw struggle between our genes -- nature -- and the environment -- nurture -- had swung sharply in favor of nurture. "We simply do not have enough genes for this idea of biological determinism to be right," asserted Craig Venter, president of Celera Genomics, one of the two teams that cracked the human genome last February.
Indeed, Venter has wasted little time in playing down the importance of the genes he has catalogued. He cites the example of colon cancer, which is often associated with a defective "colon cancer" gene. Even though some patients carry this mutated gene in every cell, the cancer only occurs in the colon because it is triggered by toxins secreted by bacteria in the gut. Cancer, argues Venter, is an environmental disease. Strong support for this viewpoint appeared last year in the New England Journal of Medicine. Researchers in Scandinavia studying 45,000 pairs of twins concluded that cancer is largely caused by environmental rather than inherited factors, a surprising conclusion after a decade of headlines touting the discovery of the "breast cancer gene," the "colon cancer gene," and many more.
But can the role of heredity really be dismissed so easily? In fact, the meager tally of human genes is not the affront to our species' self-esteem as it first appears. More genes will undoubtedly come to light over the next year or two as researchers stitch together the final pieces of the human genome. [In fact, the exact opposite happened. The original 30,000 genes melted to about 19,000 by 2006 - comment by A. Pellionisz]. More importantly, human genes give rise to many related proteins, each potentially capable of performing a different function in our bodies. A conservative estimate is that 30,000 human genes produce ten times as many proteins in the human body, and figuring out what these proteins do will be a challenge for a century or more. "This is just halftime for genetics," says Eric Lander, a leading member of the public genome project, alluding to decades of work ahead to unravel the function of all the proteins in the body... [Eric Lander was half right about halftime. Bateson originated the word "Genetics" in 1905. From 2001-2003 we lived in a "twilight zone" (between the revelation of human whole genome in 2001 to the 50th Anniversary of the discovery of Double Helix, in 2003). By 2005, "Genetics" became a 100-year old and demonstrably overly focused discipline - and PostGenetics was born. What a Century of PostGenetics will bring about, is entirely impossible even to envision. Only one axiom seems certainly clear. The question is not "all the proteins in the body" - but a re-conceptualization how *any* protein-structure is shaped, by the whole genome. By 2005, FractoGene's first ("Fugu") Prediction on recursive hierarchies became experimentally supported and was published in a peer-reviewed science journal - comment by Andras Pellionisz, 2006]
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