From: Michael M. Butler (mmb@spies.com)
Date: Thu Nov 21 2002 - 16:46:28 MST
------- Start of forwarded message -------
From: Dan Lynch <dan@sp3d.com>
To: Daniel Lynch <dan@sp3d.com>
Subject: Fwd: Junk DNA not so Junky
Date: 2002-11-21 10:52:44
JUNK DNA REVISITED
Silicon Valley startup claims
to have unlocked a key to its
hidden language
Hal Plotkin, Special to SF Gate
Thursday, November 21, 2002
http://www.sfgate.com/cgi-bin/article.cgi?file=/gate/archive/2002/11/21/jnkd
na.DTL
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 nucleotides (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.
What's Next
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."
________________________________________
Daniel J. Lynch
Sp3d, Inc.
http://www.sp3d.com
415-864-3302
888-9-CARROT
-------- End of forwarded message --------
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