Bio-Revolution to Emerge Amid Aging Society [Korean Male and Female Genome - Securing $ 52.9 Billion in Pharma]

Arirang News, South Korea
September 3, 2008

The human genome, where the entire hereditary information of an individual is encoded, is where our development and our aging, our similarities and our differences lie.

Since May, a medical department at Seoul National University has been mapping out the full DNA sequence of a Korean male and female. This is the first time this has happened in Korea and only the fifth such attempt in the world.

In the U.S., scientists have begun mapping the informational content of the human genome on 1,000 subjects to manage medical disorders and hopefully find a cure by discovering the differences by race and region. Korea has narrowed the scope to only Asia to conduct studies on 100 subjects.

Korea's first bio-medicine, developed last year, is an antibiotic that treats cardiovascular diseases by preventing blood clots. Sold at W370,000 or around US$325 a bottle, it has already secured a W60 billion (US$1=W1,134) export contract as more international pharmaceutical industries are turning toward a safer and more effective bio-medicine instead of chemical compounds.

Although Korea's world market share barely cracks 4 percent compared to the 13 percent annual growth chalked up by the world's bio-medicinal market, experts say they have a positive outlook for the bio-industry's future.

As the world's population continues to age and more emphasis is put on health matters, analysts say a new "bio revolution" is to be expected, just as the industrial revolution and the IT revolution once swept the globe.

Market Research Available on Principles of Eukaryotic Genome Control

Business

Research and Markets
Laura Wood
Senior Manager

Epigenetics: Principles of Eukaryotic Genome Control is an Indispensable Guide for Any Graduate Student in Genetics, Molecular Biology, and Biochemistry

Research and Markets has announced the addition of John Wiley and Sons Ltd's new report "Epigenetics: Principles of Eukaryotic Genome Control" to their offering ...[it]... provides an integration of classical and molecular genetic perspectives to highlight underlying principles of gene and genome control in eukaryotes, with an emphasis on relevance for human disease. Among epigenetic phenomena discussed in this thorough treatment are imprinting, X chromosome inactivation, and DNA methylation, with specific examples from model systems and clear explication of experimental methods.

Key features include:

- Provides a cutting edge review of the concepts, findings, and techniques in this exciting field
- Highlights relationship to development of cancer and other human diseases throughout
- Presents an extensive annotated bibliography
- Written at a technical level suitable for anyone with an introductory knowledge of genetics and biochemistry
- Integrates classical and molecular viewpoints
- Summarizes major methods of molecular genetic analysis

Epigenetics: Principles of Eukaryotic Genome Control is an indispensable addition to the bookshelf of any advanced undergraduate and graduate student in genetics, molecular biology, and biochemistry.

About Research and Markets:

"We are the leading source for international market research and market data. We hold ‘000’s of major research publications from most of the leading publishers, consultants and analysts. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends"

[Is there a Business Market to novel Scientific Principles? Well, we can consider some precedents. The Dogma of old Physics maintained that the atom was the smallest particle of elements that axiomatically could be splitting into smaller entities. As we know from modern physics, the Principle of Relativity and Principle of Uncertainty opened not only new chapters in science (quantum mechanics and nuclear physics) - but created quite a sizable market of obtaining unimaginable abundance of energy for peaceful and defense applications. Another example was the discovery of Principle of Antibiotics; Alexander Fleming opened an enormous new market of antibacterial drugs. Epigenomics (or Epigenetics) are only half of the story (at best) - since an interaction of the Gene/Genome with (proteins) of the environment is admitted - but the holistic scientific principle that their recursion is the key has not been deployed. Entire schools (e.g. Prof. Bakker at Yale) are researching new types of antibiotics that would kill bacteria by shutting down their genome regulation. Or, if regulation is not shut down - cancerous uncontrolled growth ensues. "John Wiley and Sons" and "Research and Markets" projection of the market opportunity that HoloGenomics is about to tap, once a holistic view of recursive regulation is understood to the degree that we can influence it, is not readily available. Probably wise not even to guess while we don't know. pellionisz_at_junkdna.com, Aug, 8, 2008]

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Resignation of Dr. Collins. The begining of a New Era

Francis Collins, in a video interview to Charlie Rose on July 29, 2008 said (at 7:40" of the clip):

"That's the "function" question. How would we figure that out? Ah - so much of the genome - after all only about 1.5% of it is coding for protein. The rest of it is probably involved in this regulatory stuff, and for a long time were were a bit dismissive about that 98.5% of it and said that a lot of it was kind of a junk. I don't think people are using the word "Junk" any more when they are talking about the genome, because the more we study, the more functions we find in that "filler" - which is not a "filler" at all."

deCODE and SGENE Consortium Discover Deletions in the Human Genome Linked to Risk of Schizophrenia

Findings may provide the foundation for a test to complement standard clinical diagnosis, potentially enabling earlier intervention and treatment

Last update: 1:25 p.m. EDT July 30, 2008

REYKJAVIK, Iceland, July 30, 2008 /PRNewswire-FirstCall via COMTEX/ -- In a major paper published today in the online edition of the journal Nature, scientists from deCODE genetics (DCGN:decode genetics inc com DCGN 1.55, +0.02, +1.3%) and the University of Iceland, along with academic colleagues from the deCODE-led European SGENE consortium, China and the United States, report the discovery of three rare deletions in the human genome that confer risk of schizophrenia. Such deletions are gaps in the normal sequence of the genome that can arise spontaneously during the recombination or reshuffling of the genome that takes place in the creation of sperm and eggs. The deletions reported in today's study are located on chromosomes 1q21, 15q11 and 15q13, and confer, respectively, 3, 15 and 12 times greater than average risk of schizophrenia. These are the first such deletions to be associated with risk of mental illness using large sample sizes and validated across many populations. The substantial increase in risk they confer make them a valuable basis upon which to develop molecular diagnostic tests to complement standard clinical diagnosis. The study, 'Large recurrent microdeletions associated with schizophrenia,' will appear online today at www.nature.com.

"Schizophrenia is a disorder affecting thoughts and emotions. It is therefore a quintessentially human disease, but one that is little understood biologically and which is difficult to diagnose. These findings are important because they shed light on its causes and provide a first component to a molecular test to aid in clinical diagnosis and intervention. These discoveries also demonstrate one way in which we can use SNP-chips to find rarer genetic factors conferring risk of disease. In many disease areas we have had great success of late in identifying what these chips are best suited to find: common variants conferring relatively modest increases in risk. But we know that individuals with certain mental disorders such as schizophrenia tend to have few children, and thus that we may have to identify a larger number of rare but high risk variants to understand the genetic contribution to susceptibility. It is encouraging that our efforts to use SNP chips to detect rarer variations such as spontaneous deletions and duplications is now bearing fruit," said Kari Stefansson, CEO of deCODE.

In the recent wave of discoveries of risk variants for common diseases, those associated with mental disorders such as schizophrenia, autism and others have been conspicuously absent. This phenomenon, and the fact that people with these disorders tend to have few children, suggest that rarer and perhaps spontaneously generated variants may account for a greater proportion of the disease burden in these conditions than in others. SNP-chips are not well suited to finding rare SNPs but can, with sufficiently large sample sizes, be used to identify deletions and duplications -- known as copy number variations, or CNVs -- which can also be carried by healthy individuals in one generation and contribute to risk of disease in the next.

In order to identify novel CNVs, deCODE first analyzed the genomes of a total of approximately 15,000 parents and offspring taking part in deCODE gene discovery programs and who had been genotyped with the more than 300,000 SNPs on the HumanHap300 chip. The deCODE team discovered 66 de novo CNVs, that is, CNVs present in the genomic DNA of the offspring but not in that of their parents. deCODE then tested these variants for association with schizophrenia in more than 1,400 schizophrenics and 33,000 control subjects. The deletions on chromosomes 1q21, 15q11 and 15q13 were suggestively associated with schizophrenia in this first phase, and then validated in 3,300 cases and 8,000 controls. The SGENE consortium is comprised of deCODE genetics, the National-University Hospital in Reykjavik, the University of Aberdeen, the Ravenscraig Hospital in Greenock, the Institute of Psychiatry at King's College London, the National Public Health Institute in Helsinki, the Ludwig Maximilians University and GlaxoSmithKline's Genetic Research Center in Munich. The SGENE affiliated groups taking part in the second phase of the project were the University of Copenhagen, the University of Oslo, the University of Heidelberg, the University of Bonn, the University Medical Center of Utrecht, Nijmegen Medical Center, the University of Verona, the Duke University Center for Population Genomics and Pharmacogenetics and the University of Sichuan, China.

deCODE and the SGENE consortium gratefully acknowledge the participation in this study of the thousands of patients, family members and control subjects from these eleven countries. This study was supported by the European Union through the SGENE consortium ( www.SGENE.eu), by grants LSHM-CT-2006-037761 and PIAP-GA-2008-218251.

About deCODE

deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of diagnostics and drugs for common diseases. deCODE is a global leader in gene discovery -- our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. Through its CLIA-registered laboratory, deCODE is offering a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2(TM) for type 2 diabetes; deCODE AF(TM) for atrial fibrillation and stroke; deCODE MI(TM) for heart attack; deCODE ProCa(TM) for prostate cancer; and deCODE Glaucoma(TM) for a major type of glaucoma. deCODE is delivering on the promise of the new genetics.(SM) Visit us on the web at www.decode.com; on our diagnostics website at www.decodediagnostics.com; and, for our pioneering personal genome analysis service, at www.decodeme.com.

Rewriting Darwin: The new non-genetic inheritance

New Scientist
Magazine issue 2664

09 July 2008
Emma Young

[When experimental evidence is show by New Scientist on YouTube, "Rewriting Darwin and Dawkins", it may be time for a holistic view of the Genome Informatics, together with the environment. Time for HoloGenomics - AJP]

HALF a century before Charles Darwin published On the Origin of Species, the French naturalist Jean-Baptiste Lamarck outlined his own theory of evolution. A cornerstone of this was the idea that characteristics acquired during an individual's lifetime can be passed on to their offspring. In its day, Lamarck's theory was generally ignored or lampooned. Then came Darwin, and Gregor Mendel's discovery of genetics. In recent years, ideas along the lines of Richard Dawkins's concept of the "selfish gene" have come to dominate discussions about heritability, and with the exception of a brief surge of interest in the late 19th and early 20th centuries, "Lamarckism" has long been consigned to the theory junkyard.

Now all that is changing. No one is arguing that Lamarck got everything right, but over the past decade it has become increasingly clear that environmental factors, such as diet or stress, can have biological consequences that are transmitted to offspring without a single change to gene sequences taking place.... fully accepting the idea, provocatively dubbed the "new Lamarckism", would mean a radical rewrite of modern evolutionary theory. ... "It means the demise of the selfish-gene theory", says Eva Jablonka at Tel Aviv University, Israel. "The whole discourse about heredity and evolution will change"...

That's not all. The implications for public health could also be immense. Some researchers are talking about a paradigm shift in understanding the causes of disease. For example, non-genetic inheritance might help explain the current obesity epidemic, or why there are family pattern for certain cancers and other disorders, but no discernible genetic cause. "It's a whole new way of looking at the inheritance and causes of various diseases, including schizophrenia, bipolar disorder and diabetes, as well as cancer", says Robyn Ward of the cancer research centre at the University of New South Wales in Sydney, Australia.

...recent research... has a firm basis in biological mechanisms - in so-called "epigenetic" change.

... Inside the nucleus, the DNA is packaged around bundles of proteins called histones, which have tails that stick out from the core. One factor that affects gene expression is the pattern of chemical modifications to these tails, such as the presence or absence of acetyl and methyl groups. Genes can also be silenced directly via enzymes that bind methyl gropus ont the DNA. The so-called RNA interference (RNAi) system can direct this activity, via small RNA strands. As well as controlling DNA methylation and modifying histones, these RNAi molecules target messenger RNA - much longer strands that act as intermediaries between DNA sequences and the proteins they code for. By breaking mRNA down into small segments, the RNAi molecules ensure that a cerain gene cannot be translated into its protein. In short, RNAi creates the epigenetic "marks" that control the activity of genes.

We know that genes - and possibly also non-coding DNA - control RNAi and so are involved in determining in individual's epigenetic settings. It is becoming increasingly apparent, though, that environmental factors can have a direct impact too, with potentially life-changing implications. The clearest example of this comes from honebees [here the article explains the discovery of the Australian team lead by Ryszard Maleszka, Science, DOI:10.1126/science.1153069, and describes the work of Randy Jirtle in 2000 at Duke University as a groundbreaking experiment on a strain of genetically identical mice, and a diet rich in methyl groups before conception and during pregnancy made them different - AJP]...

These and other animal studies strongly suggest that a pregnant woman's diet can affect her child's epigenetic marks. So perhaps it is not surprising that the effect of certain nutrients is being called into question. Folate, for example, is a potent methyl donor. It is routinely recommended during pregnancy and added to cereal products in certain countries, including the US, because it reduces the risk of spinal tube defects if eaten around the time of conception...

The legacy of stress

Diet is not the only environmental factor that can influence the epigenetic setting of some genes. Michael Meaney at McGill University in Montreal, Canada, and colleagues have found that newsborn mice neglected by their mothers are more fearful in adulthood and that these mice show much higher than normal levels of methylation of certain genes involved in the stress response...

There is recent evidence that abnormal epigenetic patterns play a role in mental health disorders. In March, Arturas Petronis at the Centre of Addiction and Mental Health in Toronto, Canada and colleagues reported the first epigenome-wide scan of post-mortem brain tissue from 35 people who had suffered from schizophrenia. They found a distinctive pigenetic pattern, controlling the expression of roughly 40 genes (The American Journal of Human Genetics, vol 82, p. 696). Several of the genes were related to neurotransmitters, to brain development and to other processes linked to schizophrenia. These findings lay the groundwork for a new way of understanding mental illness, says Petronis, as a disease with a significant epigenetic component..... Intriguingly, ...the abnormalities in DNA methylation in Petronis' subjects were not restricted tot heir frontal cortex: they were also present in their sperm". "[This] suggests that it is possible that inherited epigenetic abnormalities may be contributing to the familial nature of schizophrenia and bipolar disorder" says the team member Jonathan Mill at the Institute of Psychiatry at King's College London...

This work is only suggestive, but when it comes to cancer, the evidence is stronger. Some colorectal cancers are known to develop when a key DNA-repairgene called MHL1 becomes coated in methyl groups, preventing it from working. In 2007, Ward and her colleagues published a study of a woman with this type of cancer and her three children, but one son had a heavily methylated, silenced gene like his mother (The New England Journal of Medicine, vol 356, p. 697)....

Some epigenetic marks may also be inherited from fathers, however. In a now classic study published in 2005, Matthew Anway at the University of Idaho in Moscow and colleagues showed that male rats exposed to the common crop fungicide vinclozolin in the womb were less fertile and had a higher than normal risk of developing cancer and kidney defects. Not only were these effects transmitted to their offspring, they were passed from father to son through the three following generations as well (Science, vol. 308, p. 1466). The team found no DNA changes, only altered DNA methylation patterns in the sperm of these rats, suggesting that epigenetic factors were to blame. ...

Nutrition does seem to have some lasting effect, according to a study by Marcus Pembrey of the Institute of Child Health at University College London and his colleagues. They analysed records from the isolated community of Overkalix in northern Sweden and found that man whose paternal grandfathers had suffered a shortage of food between the ages of 9 and 12 lived longer than their peers (European Journal of Human Genetics, vol. 14, p. 159). ...

Also in 2006, Tony Hsiu-Hsi Chen at the National Taiwan University in Taipei and colleagues reported that the offspring of men who regularly chewed betel nuts had twice the normal risk of developing metabolic syndrome during childhood. Betel nuts are also associated with several symptoms of metabolic syndrome in chewers including increased heart rate, blood pressure, waist size and body weight. ...

[BOX]

Rewriting Darwin and Dawkins?

The realisation that individuals can acquire characteristics through interaction with their environment and then pass these on to their offspring may force us to rethink evolutionary theory... [This sounds very familiar to Francis Collins' statement upon the release of ENCODE results a year ago, concluding that "the concept of genes is a myth", that "the scientific community need to re-think long-held beliefs; see "The Principle of Recursive Genome Function" that opens up the recursive system to protein-to-DNA interaction, of course including not only proteins generated by the DNA, but also to proteins from the envirionment - most spectacularly with prions, bovine proteins causing "mad cow disease" in humans - AJP]...

"There was a trickle of findings of epigenetic inheritance in animals through the 20th century, and it is turning into a flood about now" says Russel Bonduriansky at the University of New South Wales in Sydney, Australia. ...

For Bonduriansky the accumulating evidence calls for a radical rethink of how evolution works. Jablonka, too, believes that "Lamarckian" mechanisms should now be integrated into evolutionary theory, which should focus on mechanisms, rather than units, of inheritance. "This would be very significant", she says. "It would reintroduce development, in a very direct and strong sense, into heredity and hence evolution. It would mean that pre-synthesis view of evolution, which was very diverse and very rich, can return, but with molecular mechanisms attached". ..

What does Dawkins himself think?

...He suggests, though, that the word "gene" should be replaced with "replicator". [Which is a profoundly holistic view, since "replication" is the propensity of the entire Genome - AJP]

[The heretofore restricted views, neither Darwinian evolution, nor modern Genetics permitting "feedback" (with the key of recursion from proteins to DNA), restricting our views only to 1.3% of the Genome (falsely labeling 98.7% as "Junk DNA"), and by adhering to the Central Dogma that information from proteins to DNA "never happens", thus e.g. external proteins were particularly excluded from interaction with growth and evolutionary processes, have to come together now into a new holistic approach by HoloGenomics, pellionisz_at_junkdna.com, July, 26, 2008]

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How the Personal Genome Project Could Unlock the Mysteries of Life

WIRED MAGAZINE: 16.08
By Thomas Goetz 07.21.08

George Church is dyslexic, narcoleptic, and a vegan. He is married with one daughter, weighs about 210 pounds, and has worn a pioneer-style bushy beard for decades. He has elevated levels of creatine kinase in his blood, the consequence of a heart attack. He enjoys waterskiing, photography, rock climbing, and singing in his church choir. His mother's maiden name is Strong. He was born on August 28, 1954.

If this all seems like too much information, well, blame Church himself. As the director of the Lipper Center for Computational Genetics at Harvard Medical School, he has a thing about openness, and this information (and plenty more, down to his signature) is posted online at arep.med.harvard.edu/gmc/pers.html. By putting it out there for everyone to see, Church isn't just baiting identity thieves. He's hoping to demonstrate that all this personal information - even though we consider it private and somehow sacred - is actually fairly meaningless, little more than trivia. "The average person shouldn't be interested in this stuff," he says. "It's a philosophical exercise in what identity is and why we should care about that."

As Church sees it, the only real utility to his personal information is as data that reflects his phenotype - his physical traits and characteristics. If your genome is the blueprint of your genetic potential written across 6 billion base pairs of DNA, your phenome is the resulting edifice, how you actually turn out after the environment has had its say, influencing which genes get expressed and which traits repressed. Imagine that we could collect complete sets of data - genotype and phenotype - for a whole population. You would very quickly begin to see meaningful and powerful correlations between particular genetic sequences and particular physical characteristics, from height and hair color to disease risk and personality.

Church has done more than imagine such an undertaking; he has launched it: The Personal Genome Project, an effort to make those correlations on an unprecedented scale, began last year with 10 volunteers and will soon expand to 100,000 participants. It will generate a massive database of genomes, phenomes, and even some omes in between. The first step is to sequence 1 percent of each volunteer's genome, focusing on the so-called exome - the protein-coding regions that, Church suspects, do 90 percent of the work in our DNA. It's a long way from sequencing all 6 billion nucleotides - the As, Ts, Gs, and Cs - of the human genome, but even so, cataloging 60 million bits multiplied by 100,000 individuals is an audacious goal.

The PGP stands as the tent pole of what Church calls his "year of convergence," the moment when his 30 years as a geneticist, a technologist, and a synthetic biologist all come together. The project is a proof of concept for the Polonator G.007, the genetic-sequencing instrument developed in Church's lab that hit the market this spring. And the PGP will also put Church's expertise in synthetic biology to use, reverse engineering volunteers' skin cells into stem cells that could help diagnose and treat disease. If the convergence comes off as planned, the PGP will bring personal genomics to fruition and our genomes will unfold before us like road maps: We will peruse our DNA like we plan a trip, scanning it for possible detours (a predisposition for disease) or historical markers (a compelling ancestry).

Bringing the genome into the light, Church says, is the great project of our day. "We need to inspire our current youth in a way that outer space exploration inspired us in 1960," he says. "We're seeing signs that knowing about our inner space is very compelling."

To Church, who built his first computer at age 9 and taught himself three programming languages by 15, all of this is unfolding according to the same laws of exponential progress that have propelled digital technologies, from computer memory to the Internet itself, over the past 40 years: Moore's law for circuits and Metcalfe's law for networks. These principles are now at play in genetics, he argues, particularly in DNA sequencing and DNA synthesis.

Exponentials don't just happen. In Church's work, they proceed from two axioms. The first is automation, the idea that by automating human tasks, letting a computer or a machine replicate a manual process, technology becomes faster, easier to use, and more popular. The second is openness, the notion that sharing technologies by distributing them as widely as possible with minimal restrictions on use encourages both the adoption and the impact of a technology.

Inside the Personal Genome Project

The project will turn information from 100,000 subjects into a huge database thath can reveal the connections between our genes and our physical selves. Here's how. - Thomas Goetz

1. Entrance Exam

Volunteers take a quiz to show genetic literacy. One question: How many chromosomes do unfertilized human egg cells contain? a) 11, b) 22, c) 23, d) 46, or e) 92? (Answer: c.) Only those with a perfect score proceed, but retests are allowed. 2. Data Collection

Volunteers sign an "open consent" form acknowledging that their information, though anonymized, will be accessible by others. They fill out their phenotype traits, listing everything from waist size to diet habits. Suitable respondents go on to the next step. 3. Sample Collection

Volunteers hit the medical center, where they are interviewed by an MD. Then a technician draws some blood, gathers a saliva sample, and takes a punch of skin. Don't worry: It hurts about as much as a bee sting.

4. Lab Work

The tissues are sent to a biobank, where DNA is extracted from the blood. One percent of it — the exome — is sequenced. Meanwhile, bacteria DNA is extracted from the saliva and sequenced to reveal the volunteer's microbiome. 5. Research

Now the fun part: Crunching the numbers. PGP scientists and other researchers start working with the data assembled from 100,000 individuals to investigate potential links between phenotypes and genotypes. The team will look for patterns and statistically significant anomalies. 6. Sharing

The volunteers get access to not only the raw data from their genome, but anything the research team gleans from their information. Insights - a newly discovered cancer risk, for example - are posted in a volunteer's file, which they'll be free to share with other PGP participants.

"I always tell people, your biggest problem in life is not going to be hiding your stuff so nobody steals it," Church says. "It's going to be getting anybody to ever use it. Start hiding it and that decreases the probability to almost zero."

For most of his career, Church has been known as a brilliant technologist, more behind-the-scenes tinkerer than scientific visionary. Though he was part of the group that kicked off the Human Genome Project, he's far less known than scientists like Francis Collins or J. Craig Venter, who took the stage at the end. His obscurity is due partly to his style. He talks about his accomplishments with a certain detachment that one might mistake for ambivalence. "He's not without ego; it's just a different sort of ego," says entrepreneur Esther Dyson, a friend and one of the first 10 PGP volunteers. "Everything is a subject of his intellectual curiosity, including himself."

His low profile may be the result of his tendency to get too far ahead of the curve, working a decade or two ahead of his field - so far that even the experts don't always get what he's talking about. "Lots of George's work is so advanced it's not ready to become standard," says Drew Endy, a professor of bioengineering at Stanford and cofounder with Church of Codon Devices, a synthetic-biology startup. "He's perfectly happy to spin out tons of ideas and see what might stick. It's high-throughput screening for technology and science. That's not the way most people work." [Unfortunately - AJP]

But thanks to the PGP, the Polonator, and the fact that the rest of the world is finally starting to understand what he's been talking about, Church's obscurity is coming to an end. He sits on the advisory board of more than 14 biotech companies, including personal genomics startup 23andMe and genetic testing pioneer DNA Direct. He has also cofounded four companies in the past four years: Codon Devices, Knome, LS9, and Joule Biosciences, which makes biofuels from engineered algae. Newsweek recently tagged him as one of the 10 Hottest Nerds ("whatever that means," Church laughs).

For someone who has spent his whole career ahead of his time, he is suddenly very much a man of the moment.

Most historians would cite Prague or Paris or Berkeley as the intellectual hub of the 1960s, but for people interested in computers, there was no place so significant as Hanover, New Hampshire. There, at Dartmouth College, an experiment in time-share computing was flourishing. Developed by professors John Kemeny and Thomas Kurtz, the Dartmouth Time-Sharing System let students remotely access the power of a mainframe computer to do calculations for mathematics or science assignments or to play a simulated game of college football. It ran on an easy-to-learn, intuitive program that Kemeny and Kurtz called Basic.

In 1967, the DTSS transitioned to a more-powerful GE-635 machine and offered remote terminals to 33 secondary schools and colleges, including Phillips Academy, a prep school in nearby Andover, Massachusetts. The terminal - not much more than a teletype machine, really - sat in the basement of the school's math building, forgotten until the next fall, when a young George Church showed up for his freshman year and began asking whether there was a computer on campus. Someone pointed Church to the basement. "There wasn't even a chair in the room. I had used a typewriter before, but never a teletype. And so I just started pressing keys," Church recalls. "Eventually I hit Return, and it came back with 'What?' And so I started typing in stuff like crazy and hitting Return. And it kept coming back with 'What?' At that point, I was pretty convinced it wasn't a human, but it was actually talking in words. So I just hadn't asked the right question or given the right answer."

Soon, Church found a book on Basic. "I was just sailing," he says. He spent endless hours in that basement - he eventually borrowed a chair - and taught himself the intricacies of coding, learning to program in Basic, Lisp, and Fortran. Indeed, thinking in code came so naturally to Church that he stopped going to his classes (a habit that would later get him kicked out of graduate school at Duke) and taught the computer linear algebra instead.

It turns out that learning how to write code - change it, hit Return, see what it will do - was ideal training for Church's eventual career in computational biology. "That's how we reverse engineer things like E. coli - you change something, and you see how it behaves," he says. "Little did I know that 30 years later, we would use almost exactly the same operations to optimize metabolic networks."

Church first hit on the power of computation to automate biology in the mid-'70s when he was in graduate school at Harvard. At the time, he was working on recombinant DNA, a then-new technique to splice a gene from one organism into another. Identifying a sequence of 80 or so base pairs of genetic code was a slow, tedious process. "You had to literally read off the bases and write them on a piece of paper, one by one," Church says. "So I wrote a sequence-reading program that would crunch it out. When the senior graduate student heard I had automated that, he said, 'What do you want to do that for? That's the only fun part.'"

By 1980, when Church's adviser, Wally Gilbert, won the Nobel Prize for DNA sequencing techniques, the process was still slow and expensive, executing one DNA strand at a time. So Church began working on one of his earlier targets for automation. His idea was to sequence several strands together by combining them into a single sample mixture. He called it multiplexing, drawing an analogy to signal multiplexing in electronics, in which more than one signal flows through a current at the same time. Church thought most of the work could even be integrated into one device rather than numerous machines.

It was a provocative idea, not just because he was substituting several human tasks for machine-driven ones, but also because he didn't make the usual false promise that technology would simplify the process. On the contrary, multiplexing would be complicated, Church maintained. But technology was up to the task.

Four years later, Church was invited to present his work on multiplexing at a small meeting in Alta, Utah. The Department of Energy had gathered about 20 scientists to mull over one question for five days: How might recent advances in genetics be used to measure an increase in genetic mutations arising from radiation exposure, as in Hiroshima? The group quickly reached the conclusion that technology circa 1984 couldn't answer that question. Meanwhile, they still had several more days in the mountains. "There were a bunch of us there who could talk about genomics as if it were an engineering exercise. And then we said, well, as a kind of booby prize, we could think of other things you could do," Church recalls, "like, say, sequencing the human genome."

Though Church was almost entirely unknown before the meeting, his presentation on multiplex sequencing methods stole the show. When he fell into a huge snow drift during a break one afternoon, one participant worried that the future of sequencing had disappeared with him.

That Alta brainstorm would become the Human Genome Project - the effort, adopted by the National Institutes of Health, to sequence one human genome for $3 billion within 15 years. However audacious the HGP seemed, Church was disappointed by it almost from the start. "We could have said our goal was to get everybody's genome for some affordable price," he says, "and one genome would be a milestone" on the way toward that goal.

The HGP also played it safe with its choice of technology. Despite the promise of Church's multiplexing system, the HGP instead used a more established instrument manufactured by Applied Biosystems, based on a technique developed by biochemist Frederick Sanger. As Church saw it, this meant that the project had failed to put its $3 billion toward improving the state of the art. Even worse, the HGP consumed so many of the resources available to the field of genetics that it effectively locked that state of the art into 1980s technology.

The result was nearly two decades of inertia. It wasn't until 2005, when the Human Genome Project was complete and new goals were put forth, that Church finally perfected the multiplexing approach he had presented 20 years earlier at Alta. In a paper published in Science, Church demonstrated a technique that could analyze millions of sequences in one run (Sanger's method could handle just 96 strands of DNA at a time). And Church's method not only accelerated the process, it made it far cheaper, too, elegantly demonstrating the power of automation to drive exponential advances and bring down costs. Church's approach, and a competing innovation developed by 454 Life Sciences that same year, inaugurated the second generation of sequencing, now in full swing.

In the past three years, more companies have joined the marketplace with their own instruments, all of them driving toward the same goal: speeding up the process of sequencing DNA and cutting the cost. Most of the second-generation machines are priced at around $500,000. This spring, Church's lab undercut them all with the Polonator G.007 - offered at the low, low price of $150,000. The instrument, designed and fine-tuned by Church and his team, is manufactured and sold by Danaher, an $11 billion scientific-equipment company. The Polonator is already sequencing DNA from the first 10 PGP volunteers. What's more, both the software and hardware in the Polonator are open source. In other words, any competitor is free to buy a Polonator for $150,000 and copy it. The result, Church hopes, will be akin to how IBM's open-architecture approach in the early '80s fueled the PC revolution.

In the sequencing game, though, the cost of the machine is only half the equation. The more telling expense is the operating cost, particularly the cost of sequencing entire human genomes. Executives at 454 estimate that their latest machine can pull off a whole genome sequence for $200,000. Applied Biosystems claims its instrument has completed a genome for just $60,000. Church maintains that, while the Polonator isn't up to whole-genome reads, it is clocking in at about one-third the cost of Applied Biosystems' estimate. A whole sequence from Knome, the retail genomics firm cofounded by Church, goes for $350,000. (It's worth noting that these figures are only roughly comparable, since each company uses slightly different quality measures and specifications.)

As these numbers continue to drop, the mythical $1,000 genome comes ever closer. Sequencing a human genome for $1,000 is the somewhat arbitrary benchmark for true personalized genomics - when the science could become a component of standard medical care. An important catalyst in achieving that point is the Archon X Prize for Genomics, which is offering $10 million to the team that can sequence 100 complete genomes in 10 days for less than $10,000 each. As of June, seven teams, including Church's lab, had entered the competition. Church, who served for a time on the advisory board of the contest, says that the prize will drive costs down further and help publicize the potential of personalized whole-genome sequencing.

That's important because Church hopes the Polonator and other next-generation instruments will inspire a new generation of smaller labs to begin work in personal genomics, as well as other genetic sciences. Already, the onslaught of technology has jump-started new projects, like sequencing part of the Neanderthal genome, examining extremophile microbes in old California iron mines, and studying the regenerative properties of the salamander. In medicine, cheaper sequencing has enabled research into drug-resistant tuberculosis; the genetics of breast, lung, and other cancers; and the DNA architecture of schizophrenics.

But if the Polonator is going to lead that charge, it has to work - and work on a massive scale. And that means passing a major test: successfully sequencing the 100,000 exomes in the PGP.

All of us know our height, weight, and eye color. Fewer of us know our arm span or resting blood pressure. But who among us knows the direction of our hair whorls or the Gell-Coombs type of our allergies? This is the level of detail that the PGP requires the 100,000 volunteers to reveal about themselves, a list staggering in its exhaustiveness. The PGP will tally head circumferences, injuries, chin clefts and cheek dimples, whether volunteers can roll their tongues or hyperflex their joints, whether they dislike hot climates or are hot tempered, if they've often been exposed to power lines or wood dust or diesel exhaust or textile fibers. The project questionnaire asks how many meals they eat a day and whether they prefer their food fried, broiled, or barbecued. It even demands to know how much television they watch. And, of course, PGP volunteers will hand over most aspects of their medical history, from vaccines to prescriptions.

This phenotype data will be integrated with a volunteer's genomic information, then combined with statistics from all the other subjects to create a potent database ripe for interrogation. In contrast to the heavy lifting that genetic research requires now - each study starts from scratch with a new hypothesis and a fresh crop of subjects, consent forms, and tissue samples - the PGP will automate the research process. Scientists will simply choose a category of phenotype and a possible genetic correlation, and statistically significant associations should flow out of the data like honey from a hive. A genetic predisposition for colon cancer, for instance, might be found to lead to disease only in connection with a diet high in barbecued foods, or a certain form of heart disease might be associated with a particular gene and exposure to a particular virus. Genomic discovery won't be a research problem anymore. It'll be a search function. (This helps explain why Google, among others, has donated to the project).

The process began last year, and each of the first 10 volunteers has a background in medicine or genetics. They include John Halamka, CIO of Harvard Medical School and a physician; Rosalynn Gill, chief science officer at Sciona (a personalized genetics nutrition company); and Steven Pinker, the noted psychologist and author. The other 99,990 participants won't be expected to be so elite, though they will have to pass a genetics-literacy quiz to demonstrate informed consent. The general selection process, which starts with registration at personalgenomes.org, is scheduled to begin later this year.

Besides offering up their genomes, subjects will have to part with some spit and a bit of skin. The saliva contains their microbiome - the trillions of microbes that exist, mostly symbiotically, on and in our bodies. If phenotype is a combination of genotype plus environment, the microbiome is the first wash of that environment over our bodies. By measuring some fraction of it, the PGP should offer a first look at how the genome-to-microbiome-to-phenome chain plays out.

The skin sample goes into storage, creating what would be one of the world's largest biobanks. Members of Church's lab have devised a way to automate turning the skin cells into stem cells, and they hope to publish the technique later this year. (Similar work has been done at the University of Wisconsin and Kyoto University.) By reprogramming the skin cells using synthetically engineered adenoviruses, Church's team can transform the skin cells into many sorts of tissue - lungs, liver, heart. These tissues could be used as a diagnostic baseline to detect predisposition for various diseases. What's more, the reprogrammed cells could be used to treat disease, replacing damaged or failing tissue. It's an intriguing hint of how Church's work with synthetic biology complements genomic sequencing.

If the PGP were simply an exercise in breaking down 100,000 individuals into data streams, it would be ambitious enough. But the project takes one further, truly radical step: In accordance with Church's principle of openness, all the material will be accessible to any researcher (or lurker) who wants to plunder thousands of details from people's lives. Even the tissue banks will be largely accessible. After Church's lab transforms the skin into stem cells, those new cell lines - which have been in notoriously short supply despite their scientific promise - will be open to outside researchers. This is a significant divergence from most biobanks, which typically guard their materials like holy relics and severely restrict access.

For the PGP volunteers, this means they will have to sign on to a principle Church calls open consent, which acknowledges that, even though subjects' names will be removed to make the data anonymous, there's no promise of absolute confidentiality. As Church sees it, any guarantee of privacy is false; there is no way to ensure that a bad actor won't tap into a system and, once there, manage to extract bits of personal information. After all, even de-identified data is subject to misuse: Latanya Sweeney, a computer scientist at Carnegie Mellon University, demonstrated the ease of "re-identification" by cross-referencing anonymized health-insurance records with voter registration rolls. (She found former Massachusetts governor William Weld's medical files by cross-referencing his birth date, zip code, and sex.)

To Church, open consent isn't just a philosophical consideration; it's also a practical one. If the PGP were locked down, it would be far less valuable as a data source for research - and the pace of research would accordingly be much slower. By making the information open and available, Church hopes to draw curious scientists to the data to pursue their own questions and reach their own insights. The potential fields of inquiry range from medicine to genealogy, forensics, and general biology.

And the openness doesn't serve just researchers alone. PGP members will be seen as not only subjects, but as participants. So, for instance, if a researcher uses a volunteer's information to establish a link between some genetic sequence and a risk of disease, the volunteer would have that information communicated to them.

This is precisely what makes the PGP controversial in genetics circles. Though Church talks about it as the logical successor to the Human Genome Project, other geneticists see it as a risky proposition, not for its privacy policy but for its presumption that the emerging science of genomics already has implications for individual cases. The National Human Genome Research Institute, for example, has cautioned that the burgeoning personal-genomics industry, which includes research-oriented projects like the PGP as well as straight-to-consumer companies like Navigenics and 23andMe and whole-genome-sequencing shops like Knome, puts the sales pitch ahead of the science. "A lot of people would like to rapidly capitalize on this science," says Gregory Feero, a senior adviser at the NHGRI. "But for an individual venturing into this now, it's a risk to start making any judgments or decisions based on current knowledge. At some point, we'll cross over into a time when that's more sensible."

Church cautions, however, that keeping clinicians and patients in the dark about specific genetic information - essentially pretending the data or the technology behind it don't exist - is a farce. Even worse, it violates the principle of openness that leads to the fastest progress. "The ground is changing right underneath them," he says of the medical establishment. "Right now, there's a wall between clinical research and clinical practice. The science isn't jumping over. The PGP is what clinical practice would be like if the research actually made it to the patient."

In the not-too-distant future, Church says, hospitals and clinics could be outfitted with a genome sequencer much the way they now have x-ray machines or microscopes. "In the old books," Church says, "almost every scientist was sitting there with a microscope on their table. Whether they're a physical scientist or a biological scientist, they've got that microscope there. And that inspires me."

Wired deputy editor Thomas Goetz (thomas@wired.com) wrote about personal genomics in issue 15.12.

What You Should Know Before You Spit Into That Test Tube

By Rick Weiss
Washington Post

Sunday, July 20, 2008; Page B01

Jeffrey Gulcher had no reason to think much about prostate cancer. He was just 48, and the disease typically strikes later in life. Even the most cautious medical groups agree that most men need not begin annual prostate screenings until age 50.

But Gulcher happens to be the chief scientific officer of deCODE Genetics -- one of several companies that, amid some controversy, have begun offering direct-to-consumer DNA tests that can help people predict which diseases they are likely to get. So in April, he spat into a test tube and, without giving the matter much thought, sent the sample in for analysis by his own company.

He was in for a shock. The test indicated that he carries a genetic variant that nearly doubles his lifetime risk of getting prostate cancer: While the average man has a 15 percent chance of being stricken, Gulcher had a 30 percent shot. That spurred his physician to order a standard blood test for prostate cancer. The result was toward the high end of the range considered normal, which, together with the DNA test, worried the doctor. He referred Gulcher to a urologist, who performed an exploratory biopsy -- and found that Gulcher's prostate gland was riddled with cancer, and a fairly aggressive version of it at that.

Gulcher is going in for surgery tomorrow, and not a moment too soon. Tests suggest that the disease has not yet spread to other parts of his body, a milestone that often portends death and that may well have been passed had he waited until he turned 50 to get a standard prostate-specific antigen (PSA) test.

Did genetic testing save Gulch er's life? I think it may have. His dramatic story seems to illustrate perfectly the claims, made by his company and others, that an open market of DNA tests is the 21st century's ticket to a healthier nation. But a closer look suggests that this fast-growing industry, with its snazzy Web-based come-ons, could benefit from some temperance and independent oversight.

The technology is undeniably impressive. For as little as $1,000, anybody who can drool into a mailing tube can now find out his or her genetic odds of getting any of 20 or more potentially debilitating diseases, including cancer, heart disease and diabetes. Most of these tests will not lead to a frank diagnosis, as happened with Gulcher. But discovering an inherited propensity toward a particular illness can motivate consumers -- or, as they used to be known, patients -- to get more frequent checkups, take preventive medicines or make lifestyle changes to try to ward off the specter of disease. At last, we seem to be on the cusp of the long-promised personalized-medicine revolution in which gene tests allow physicians to craft far more individualized and effective ways of keeping us well.

But tests that look into the fog of people's medical futures are freighted with tricky medical, economic and bioethical implications. For one thing, most genes are not determinative, so these tests can convey only odds, not destinies. Even with the doubled lifetime risk for cancer that's associated with Gulcher's prostate gene variant, two out of three men who receive a "positive" test for that gene will never get the disease. And many of those who do will get it so late in life and in such a benign form that no treatment would be justified. So that's at least two new members of the "worried well" who could be losing sleep and spending money on unnecessary follow-up tests for every person who would arguably be appropriately forewarned.

Moreover, the tests are still new and easily misinterpreted, even by professionals. Online results may be subject to security and privacy breaches. And some companies are using people's gene profiles to conduct independent research. That suggests to many ethicists and lawyers that these firms' paying clients ought to be informed that they are subjects in experiments, with full disclosure of potential risks and rights.

Most worrisome of all, at least a few companies seem to be peddling DNA-based versions of snake oil. Some firms claim to be able to identify inherited nutritional deficiencies that -- guess what? -- are treatable with pricey supplements that they just happen to sell. Some even promise to discern from your genes what kind of person you should marry to ensure a blissful sex life and healthier babies. Welcome to the Wild West of personalized genomics.

These problems are not insurmountable. But there is precious little oversight of this burgeoning new industry, in part because genetic analysis does not fit cleanly into any existing category of medical practice. And if the first wave of DNA-screening companies to hit the market gets its way, there won't be any more adult supervision in the foreseeable future. In a blatant effort to stave off regulation, top officials from all the major competing gene-test companies met early this month and quietly agreed to spend this summer hammering out a "best practices" document that they would promise to follow. This is a great idea, but it's not enough.

No state or federal agency can today assure consumers that the DNA tests they order will give accurate results -- or that the results, even if technically accurate, will have any practical value. The Food and Drug Administration says it has the authority to regulate all gene tests but has decided, at least for now, to ignore the vast majority of those developed so far. The Federal Trade Commission (FTC), which is supposed to protect consumers from fraudulent claims, has never taken an enforcement action against even the most transparently deceptive gene-test companies. And the Centers for Medicare and Medicaid Services, the division within the Department of Health and Human Services that oversees clinical laboratories, has so far opted to steer clear of the genetic-testing world, despite pleas from federal advisers to ensure a minimal standard of gene-test proficiency.

The companies say that what they do is different enough that they should not be shoehorned into the conventional medical-testing rules. "For the first year and a half of our existence, all we did was try to figure out how to fit into the regulatory environment," said Dietrich Stephan, co-founder of Navigenics, a leading California-based gene-test company, adding that the effort cost an estimated $10 million.

That's real money. Yet even with all that preparation, Navigenics and a dozen other testing companies recently received warnings from individual states accusing them of violating state rules for labs. Situations such as this cry out for the guiding hand of the federal government -- not necessarily through cumbersome regulations, which can be too rigid to keep up with quickly changing science, but through formal guidelines, at least, promulgated by HHS. These could set clear expectations about how accurate gene tests should be -- and what it means to be "accurate" in the brave new world of predictive health -- and what level of informed consent should be obtained from clients. The promulgation of such standards will take real effort from HHS Secretary Mike Leavitt, who has championed personalized medicine but who has thus far been largely AWOL on the gene-test issue and has little incentive to push hard in the final months of the Bush administration. The FTC also needs to show that it has teeth and can bite.

Genetic-testing companies need to ante up, too. The responsible ones could buy a lot of good will by offering the public easily accessible scientific details (online and elsewhere) about the specific genes or genetic markers they are testing for; citations for the published studies they use to justify their claims that those genes have real medical relevance; the privacy and security systems they have in place; and the protocols for any experiments that clients' specimens may be used in. The firms should also disclose any approvals they have sought, obtained or denied from independent scientific and ethical review boards.

I took heart that such a future is possible when, at an HHS meeting two weeks ago, I saw chiefs from the five major competing gene-test companies sitting next to one another, speaking cooperatively to federal advisers. If these executives move aggressively to do the right thing, and if federal officials help them with some smart but tough guidance, perhaps those corporate heads can avoid a future in which they are called upon to appear side by side again -- this time before Congress, looking more like those famously photographed tobacco CEOs, being asked tough questions about what exactly they have been selling, and at what cost to American health.

rweiss@americanprogress.org

Rick Weiss, a former science reporter for The Post, is a senior fellow at the Center for American Progress.

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

[The Principle of Recursion comprised in a single color Fig. (Not in the paper; see Supplementary Information)]

[Free Full Text of Journal Article, with clickable references, plus Supplementary Information is available]

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.

Sunnyvale, Calif. (PRWEB) July 16, 2008 -- 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 was 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:

[See all Figs. plus color versions here]

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 PostGenetics.org), 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 was "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.

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

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Intel, Others Back New DNA Sequencer

By BRIAN GORMLEY

July 14, 2008; Page B6

[Technology demo video: <$100 full sequence - AJP]

Investors are pumping $100 million into a start-up developing technology to propel DNA sequencing into mainstream medicine.

The infusion is expected to enable Pacific Biosciences of California Inc. to introduce in 2010 its high-speed system for reading the chemical "letters" of DNA. The technology is designed to expand the use of sequencing to develop treatments tailored to patients' genetic makeup.

In time, for example, pharmaceutical researchers may routinely use sequencing to identify people who respond well, or poorly, to a drug based on specific genetic markers.

The federally funded Human Genome Project, completed in 2003, took 13 years and cost $450 million. In five years, Pacific Biosciences will make it possible to sequence a genome in 15 minutes, Chief Executive Hugh Martin said. The initial product will facilitate genome sequencing in a matter of days, at an undisclosed cost, he said.

Corporate investors, asset managers and venture-capital firms are taking part in the latest funding round for Pacific Biosciences, of Menlo Park, Calif. They include Intel Capital, an arm of Intel Corp.; Deerfield Capital Management LLC; T. Rowe Price Group; Morgan Stanley; FMR LLC; Allian ce Bernstein Holding LP; Maverick Capital Ltd.; Redmile Group; Alloy Ventures; DAG Ventures; Teachers' Private Capital; Kleiner Perkins Caufield & Byers; and Mohr Davidow Ventures.

A key part of Pacific Biosciences' system is an enzyme called polymerase that human cells use to copy DNA. With the system, scientists break double-stranded DNA molecules into single strands and then fragment the strands. These fragments are fed into chambers on sequencing chips. Then, individual nucleotide letters, each linked to a fluorescent marker, are added.

Inside each chamber, the polymerase enzyme pairs these letters to their corresponding nucleotides on the DNA fragment. As letters bind, they emit flashes of light, enabling scientists to read the DNA fragment's sequence.

Other companies seeking to cut the time and cost of DNA sequencing include publicly traded Illumina Inc. and Helicos BioSciences Corp., and closely held Complete Genomics Inc.

Write to Brian Gormley at brian.gormley@dowjones.com