Posts Tagged ‘Eric Lander’

Reporter: Aviva Lev-Ari, PhD, RN


Harvey Prize Awarded to MIT and UC Berkeley Professors

Tuesday, May 14, 2013
By: Jennifer Frey

To watch Prof. Lander’s talk on “Secrets of The Human Genome/Biology,” click here.

To watch Prof. Lander’s talk on “Secrets of the Human Genome/Medicine,” click here.

To watch Prof. Yablonovitch’s talk, entitled “Photonic Crystals in Science, Engineering and the World of Nature, click here.

Biology Professor Eric S. Lander of the Eli and Edythe Broad Institute of the Massachusetts Institute of Technology and Harvard University, and Eli Yablonovitch, Professor of Electrical Engineering and Computer Science at the University of California, Berkeley, were awarded the 2012 Harvey Prize in a ceremony April 30 at the Technion-Israel Institute of Technology in Haifa, Israel.

The awarding of the Harvey Prize is watched closely worldwide, as it is often regarded as a strong predictor of future Nobel Prize laureates. The international prize is awarded annually by the Technion in a variety of disciplines within the categories of Science and Technology and Human Health. It has also been awarded for contributions to Peace in the Middle East.

Prof. Lander, the founding director of the Broad Institute and one of the principal leaders of the Human Genome Project, received the award in the area of Human Health for his contributions to the field of genomics. Calling Prof. Lander a “driving force behind most of the major advances in this field,” the citation for the prize read: “He has made important contributions by both developing methods to exploit the power of genetic information and leading large endeavors to identify and annotate entire genomes. Most notably, he consolidated the efforts of the Human Genome Project and first authored the resulting historic manuscript. Prof. Lander also pioneered the analysis of the genetic components underlying complex diseases, including cancer.”

Prof. Eric Lander
Prof. Eric Lander speaks during the Harvey Prize Ceremony.
Also pictured is Technion Prof. Eliezer Shalev

In accepting his award, Prof. Lander credited his success to a series of “lucky accidents,” including a chance meeting with Princeton University Professor David Botstein, who invited Prof. Lander to work with him on mapping diseases. “I had no inkling of what was yet to come. But the idea of the Human Genome Project was in the air.” He recounted an unlikely career, in which he studied mathematics and taught business before discovering the sense of “shared purpose” in working collaboratively on a larger project.

Prof. Lander, who is the Professor of Biology at MIT and Professor of Systems Biology at Harvard Medical School, has received numerous awards including the MacArthur Foundation Fellowship, the Gairdner Foundation International Award, the Max Delbruck Medal, the American Association for the Advancement of Science’s Award for Public Understanding of Science and Technology, among others, and eight honorary doctorates. In 2009, President Obama appointed him to co-chair the President’s Council of Advisors on Science and Technology.

Prof. Yablonovitch, the Director of the National Science Foundation Center for Energy Efficient Electronics Science at UC Berkeley, received the award in the area of Science and Technology in recognition of “his pioneering discoveries in the fields of photonics, optoelectronics and semiconductors.” In his photovoltaic research, Prof. Yablonovitch introduced the 4n2 light-trapping factor that is in worldwide use for almost all commercial solar panels. This factor, sometimes called the “Yablonovitch Limit” increased the theoretical limits and practical efficiency of solar cells. Prof. Yablonovitch is also regarded as the Father of the Photonic BandGap concept, and as having coined the term “Photonic Crystal.”

Prof. Eli Yablonovitch
Prof. Eli Yablonovitch

In accepting his award Prof. Yablonovitch, who holds the James & Katherine Lau Chair in Engineering, credited Israel for its success in educating young scientists. But he noted that Israel should provide job opportunities for “graduates to further develop their scientific potential” post-graduate school, as he was able to do at Bell Laboratories.

Prof. Yablonovitch has received numerous awards including the Institute of Electrical and Electronics Engineers’ (IEEE) Photonics Award, The Institution of Engineering and Technology’s Mountbatten Medal, the Julius Springer Prize, the R.W. Wood Prize, the W. Streifer Scientific Achievement Award, and the Adolf Lomb Medal. He holds two honorary doctorates, is a Fellow of the IEEE, and a member of both the National Academy of Sciences and the American Academy of Arts & Sciences.

The Harvey Prize was first awarded in 1972 from a fund established by the late Leo M. Harvey, and maintained by his son, Technion Guardian Homer Harvey and the Harvey Family of Los Angeles. Some 13 Harvey Prize recipients have also been awarded the Nobel Prize including former Soviet Union leader Mikhail Gorbachev, and Israelis Robert Aumann and Ada Yonath.

Below please find links to films from the event, including the musical performances from the ceremony, acceptance speeches and academic lectures.

To watch the ceremony speech given by Prof. Lander, click here.

To watch the ceremony speech given by Prof. Yablonovitch, click here.

To watch Prof. Lander’s talk on “Secrets of The Human Genome/Biology,” clickhere.  To see his talk on “Secrets of the Human Genome/Medicine,” click here.

To watch Prof. Yablonovitch’s talk, entitled “Photonic Crystals in Science, Engineering and the World of Nature, click here.

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Innovation Institute is a vital component of Cornell NYC Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.

American Technion Society (ATS) donors provide critical support for the Technion—more than $1.9 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.



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The Binding of Oligonucleotides in DNA and 3-D Lattice Structures

Curator: Larry H Bernstein, MD, FCAP


This article is a renewal of a previous discussion on the role of genomics in discovery of therapeutic targets which focused on:

  •  key drivers of cellular proliferation,
  •  stepwise mutational changes coinciding with cancer progression, and
  •  potential therapeutic targets for reversal of the process.

“The Birth of BioInformatics & Computational Genomics” lays the manifold multivariate systems analytical tools that has moved the science forward to a ground that ensures clinical application. Their is a web-like connectivity between inter-connected scientific discoveries, as significant findings have led to novel hypotheses and has driven our understanding of biological and medical processes at an exponential pace owing to insights into the chemical structure of DNA,

  • the basic building blocks of DNA  and proteins,
  • of nucleotide and protein-protein interactions,
  • protein folding, allostericity, genomic structure,
  • DNA replication,
  • nuclear polyribosome interaction, and
  • metabolic control.

In addition, the emergence of methods for

  • copying,
  • removal and insertion, and
  • improvements in structural analysis as well as
  • developments in applied mathematics have transformed the research framework.

Three-Dimensional Folding and Functional Organization Principles of The Drosophila Genome Sexton T, Yaffe E, Kenigeberg E, Bantignies F,…Cavalli G. Institute de Genetique Humaine, Montpelliere GenomiX, and Weissman Institute, France and Israel. Cell 2012; 148(3): 458-472. Chromosomes are the physical realization of genetic information and thus form the basis for its

  •   readout and propagation.

Here we present a high-resolution chromosomal contact map derived from a modified genome-wide chromosome conformation capture approach applied to Drosophila embryonic nuclei. The entire genome is linearly partitioned into well-demarcated physical domains that overlap extensively with

  •   active and repressive epigenetic marks.

Chromosomal contacts are hierarchically organized between domains. Global modeling of contact density and clustering of domains show that

  •   inactive domains are condensed and confined to their chromosomal territories, whereas
  •  active domains reach out of the territory to form remote intra- and interchromosomal contacts.
  •  we systematically identify specific long-range intrachromosomal contacts between Polycomb-repressed domains

Together, these observations allow for quantitative prediction of the Drosophila chromosomal contact map, laying the foundation for detailed studies of

  • chromosome structure and function in a genetically tractable system.

“Mr. President; The Genome is Fractal !” Eric Lander (Science Adviser to the President and Director of Broad Institute) et al. delivered the message on Science Magazine cover (Oct. 9, 2009) and generated interest in this by the International HoloGenomics Society at a Sept meeting. First, it may seem to be trivial to rectify the statement in “About cover” of Science Magazine by AAAS. The statement

  • “the Hilbert curve is a one-dimensional fractal trajectory” needs mathematical clarification.

While the paper itself does not make this statement, the new Editorship of the AAAS Magazine might be even more advanced if the previous Editorship did not reject (without review)

  • a Manuscript by 20+ Founders of (formerly) International PostGenetics Society in December, 2006.

Second, it may not be sufficiently clear for the reader that the reasonable requirement for the

  • DNA polymerase to crawl along a “knot-free” (or “low knot”) structure does not need fractals.

A “knot-free” structure could be spooled by an ordinary “knitting globule” (such that the DNA polymerase does not bump into a “knot” when duplicating the strand; just like someone knitting can go through the entire thread without encountering an annoying knot):

  • Just to be “knot-free” you don’t need fractals.

Note, however, that the “strand” can be accessed only at its beginning – it is impossible to e.g.

  • to pluck a segment from deep inside the “globulus”.

This is where certain fractals provide a major advantage – that could be the “Eureka” moment. For instance, the mentioned Hilbert-curve is not only “knot free” – but provides an easy access to

  • “linearly remote” segments of the strand.

If the Hilbert curve starts from the lower right corner and ends at the lower left corner, for instance

  • the path shows the very easy access of what would be the mid-point if the Hilbert-curve
  • is measured by the Euclidean distance along the zig-zagged path.

Likewise, even the path from the beginning of the Hilbert-curve is about equally easy to access – easier than to reach from the origin a point that is about 2/3 down the path. The Hilbert-curve provides an easy access between two points within the “spooled thread”; from a point that is about 1/5 of the overall length to about 3/5 is also in a “close neighborhood”. This marvellous fractal structure is illustrated by the 3D rendering of the Hilbert-curve. Once you observe such fractal structure,

  • you’ll never again think of a chromosome as a “brillo mess”, would you?

It will dawn on you that the genome is orders of magnitudes more finessed than we ever thought so. Those embarking at a somewhat complex review of some historical aspects of the power of fractals may wish to consult the ouvre of Mandelbrot (also, to celebrate his 85th birthday). For the more sophisticated readers, even the fairly simple Hilbert-curve (a representative of the Peano-class) becomes even more stunningly brilliant than just some “see through density”. Those who are familiar with the classic “Traveling Salesman Problem” know that “the shortest path along which every given n locations can be visited once, and only once” requires fairly sophisticated algorithms (and tremendous amount of computation if n>10 (or much more). Some readers will be amazed, therefore, that for n=9 the underlying Hilbert-curve helps to provide an empirical solution. refer to Briefly, the significance of the above realization, that the (recursive) Fractal Hilbert Curve is intimately connected to the (recursive) solution of TravelingSalesman Problem, a core-concept of Artificial Neural Networks can be summarized as below. Accomplished physicist John Hopfield (already a member of the National Academy of Science) aroused great excitement in 1982 with his (recursive) design of artificial neural networks and learning algorithms which were able to find solutions to combinatorial problems such as the Traveling SalesmanProblem. (Book review Clark Jeffries, 1991; see  J Anderson, Rosenfeld, and A Pellionisz (eds.), Neurocomputing 2: Directions for research, MIT Press, Cambridge, MA, 1990): “Perceptions were modeled chiefly with neural connections in a “forward” direction: A -> B -* C — D. The analysis of networks with strong backward coupling proved intractable. All our interesting results arise as consequences of the strong back-coupling” (Hopfield, 1982). The Principle of Recursive Genome Function surpassed obsolete axioms that blocked, for half a Century, entry of recursive algorithms to interpretation of the structure-and function of (Holo)Genome.  This breakthrough,

  • by uniting the two largely separate fields of Neural Networks and Genome Informatics,

is particularly important for those who focused on Biological (actually occurring) Neural Networks (rather than  abstract algorithms that may not, or because of their core-axioms, simply could not represent neural networks under the governance of DNA information). If biophysicist Andras Pellionisz is correct, genetic science may be on the verge of yielding its third — and by far biggest — surprise. With a 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. 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 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 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 for example, many researchers

  • now refer to with a far less derogatory term: introns.

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. His patent application covers all attempts to

  • count,
  • measure and
  • compare

the fractal properties of introns for diagnostic and therapeutic purposes.

The FractoGene Decade from Inception in 2002 Proofs of Concept and Impending Clinical Applications by 2012Junk DNA Revisited (SF Gate, 2002)The Future of Life, 50th Anniversary of DNA (Monterey, 2003)Mandelbrot and Pellionisz (Stanford, 2004)Morphogenesis, Physiology and Biophysics (Simons, Pellionisz 2005)PostGenetics; Genetics beyond Genes (Budapest, 2006)ENCODE-conclusion (Collins, 2007)The Principle of Recursive Genome Function (paper, YouTube, 2008)You Tube Cold Spring Harbor presentation of FractoGene (Cold Spring Harbor, 2009)Mr. President, the Genome is Fractal! (2009)HolGenTech, Inc. Founded (2010)Pellionisz on the Board of Advisers in the USA and India (2011)ENCODE – final admission (2012) Recursive Genome Function is Clogged by Fractal Defects in Hilbert-Curve (2012) Geometric Unification of Neuroscience and Genomics (2012) US Patent Office issues FractoGene 8,280,641 to Pellionisz (2012)

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 nonsmooth 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. 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. In a move sure to alienate some scientists, Pellionisz chose 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. Pellionisz’ idea is that a fractal set of building instructions in the DNA plays a role in organizing life itself. Decode the language, and in theory it could be reverse engineered. Just as knowing the radius of a circle lets one create that circle. The fractal-based formula

  • would allow us to understand how a heart or disease-fighting antibodies is created.

The idea is  encourage new collaborations across the boundaries that separate the intertwined

  • disciplines of biology, mathematics and computer sciences.

Hal Plotkin, Special to SF Gate. Thursday, November 21, 2002.

Human Genome is Multifractal

The human genome: a multifractal analysis. Moreno PA, Vélez PE, Martínez E, et al.    BMC Genomics 2011, 12:506. Several studies have shown that genomes can be studied via a multifractal formalism. These researchers used a multifractal approach to study the genetic information content of the Caenorhabditis elegans genome. They investigated the possibility that the human genome shows a similar behavior to that observed in the nematode. They report

  • multifractality in the human genome sequence.

This behavior correlates strongly on the presence of Alu elements and to a lesser extent on CpG islands and (G+C) content.

  1. Gene function,
  2. cluster of orthologous genes,
  3. metabolic pathways, and
  4. exons
  • tended to increase their frequencies with ranges of multifractality and
  • large gene families were located in genomic regions with varied multifractality.
  • a multifractal map and classification for human chromosomes are proposed.

They propose a descriptive non-linear model for the structure of the human genome. This model reveals a multifractal regionalization where many regions coexist that are

  • far from equilibrium and this non-linear organization has significant
  • molecular and medical genetic implications for understanding the role of Alu elements in genome stability and structure of the human genome.

Given the role of Alu sequences in

  • gene regulation
  • genetic diseases
  • human genetic diversity
  • adaptation and phylogenetic analyses

these quantifications are especially useful.

MiIP: The Monomer Identification and Isolation Program

Bun C, Ziccardi W, Doering J and Putonti C. Evolutionary Bioinformatics 2012:8 293-300. Repetitive elements within genomic DNA are both functionally and evolution-wise informative. Discovering these sequences ab initio is computationally challenging, compounded by the fact that sequence identity between repetitive elements can vary significantly. These investigators present a new application, the Monomer Identification and Isolation Program (MiIP),

  • which provides functionality to both search for a particular repeat as well as
  • discover repetitive elements within a larger genomic sequence.

To compare MiIP’s performance with other repeat detection tools, analysis was conducted for synthetic sequences as well as several a21-II clones and HC21 BAC sequences. The main benefit of MiIP is

  • it is a single tool capable of searching for both known monomeric sequences
  • discovering the occurrence of repeats ab initio

Triplex DNA: A third strand for DNA

The DNA double helix can under certain conditions accommodate

  • a third strand in its major groove.

Researchers in the UK  presented a complete set of four variant nucleotides that makes it

  • possible to use this phenomenon in gene regulation and mutagenesis.

Natural DNA only forms a triplex if the targeted strand is rich in purines – guanine (G) and adenine (A) – which in addition to the bonds of the Watson-Crick base pairing

  • can form two further hydrogen bonds,
  •  the ‘third strand’ oligonucleotide has the matching sequence of pyrimidines – cytosine (C) and thymine (T).

Any Cs or Ts in the target strand of the duplex will only bind very weakly, as

  • they contribute just one hydrogen bond.

Moreover, the recognition of G requires the C in the probe strand to be protonated,

  • triplex formation will only work at low pH.

To overcome all these problems, the groups of Tom Brown and Keith Fox at the University of Southampton have developed modified building blocks, and have now completed

  • a set of four new nucleotides, each of which will bind to one DNA nucleotide from the major groove of the double helix.

They tested the binding of a 19-mer of these designer nucleotides to a double helix target sequence in comparison with the corresponding triplex-forming oligonucleotide made from natural DNA bases. Using fluorescence-monitored thermal melting and DNase I footprinting, the researchers showed that

  • their construct forms stable triplex even at neutral pH. 

Tests with mutated versions of the target sequence showed that

  • three of the novel nucleotides are highly selective for their target base pair,
  • while the ‘S’ nucleotide, designed to bind to T, also tolerates C.


DA Rusling et al, Nucleic Acids Res. 2005, 33, 3025 KM Vasquez et al, Science 2000, 290, 530 Frank-Kamenetskii MD, Mirkin SM. Annual Rev Biochem 1995; 64:69-95. Since the pioneering work of Felsenfeld, Davies, & Rich, double-stranded polynucleotides containing purines in one strand and pydmidines in the other strand [such as poly(A)/poly(U), poly(dA)/poly(dT), or poly(dAG)/ poly(dCT)] have been known to be able to undergo a stoichiometric transition forming a triple-stranded structure containing one polypurine and two poly-pyrimidine strands. Early on, it was assumed that the third strand was located in the major groove and associated with the duplex via non-Watson-Crick interactions now

  • known as Hoogsteen pairing.

Triple helices consisting of one pyrimidine and two purine strands were also proposed. However, notwithstanding the fact that single-base triads in tRNA structures were well- documented, triple-helical DNA escaped wide attention before the mid-1980s. The interest in DNA triplexes arose due to two partially independent developments.

  1.  homopurine-homopyrimidine stretches in super-coiled plasmids were found to adopt an unusual DNA structure, called H-DNA which includes a triplex.
  2. several groups demonstrated that homopyrimidine and some purine-rich oligonucleotides
  • can form stable and sequence-specific complexes with
  • corresponding homopurine-homopyrimidine sites on duplex DNA.

These complexes were shown to be triplex structures rather than D-loops, where

  • the oligonucleotide invades the double helix and displaces one strand.

A characteristic feature of all these triplexes is that the two

  • chemically homologous strands (both pyrimidine or both purine) are antiparallel.

These findings led explosive growth in triplex studies. One can easily imagine numerous “geometrical” ways to form a triplex, and those that have been studied experimentally. The canonical intermolecular triplex consists of either

  • three independent
  • oligonucleotide chains or of a
  • long DNA duplex carrying homopurine-homopyrimidine insert
    • and the corresponding oligonucleotide.

Triplex formation strongly depends on the oligonucleotide(s) concentration. A single DNA

  • chain may also fold into a triplex connected by two loops.

To comply with the sequence and polarity requirements for triplex formation, such a DNA strand must have a peculiar sequence: It contains a mirror repeat

  1. (homopyrimidine for YR*Y triplexes and homopurine for YR*R triplexes)
  2. flanked by a sequence complementary to one half of this repeat.

Such DNA sequences fold into triplex configuration much more readily than do the corresponding intermolecular triplexes, because all triplex forming segments are brought together within the same molecule. It has become clear that both

  • sequence requirements and chain polarity rules for triplex formation

can be met by DNA target sequences built of clusters of purines and pyrimidines. The third strand consists of adjacent homopurine and homopyrimidine blocks forming Hoogsteen hydrogen bonds with purines on alternate strands of the target duplex, and

  • this strand switch preserves the proper chain polarity.

These structures, called alternate-strand triplexes, have been experimentally observed as both intra- and inter-molecular triplexes. These results increase the number of potential targets for triplex formation in natural DNAs somewhat by adding sequences composed of purine and pyrimidine clusters, although arbitrary sequences are still not targetable because

  • strand switching is energetically unfavorable.

References: Lyamichev VI, Mirkin SM, Frank-Kamenetskii MD. J. Biomol. Stract. Dyn. 1986; 3:667-69. Filippov SA, Frank-Kamenetskii MD. Nature 1987; 330:495-97. Demidov V, Frank-Kamenetskii MD, Egholm M, Buchardt O, Nielsen PE. Nucleic Acids Res. 1993; 21:2103-7. Mirkin SM, Frank-Kamenetskii MD. Anna. Rev. Biophys. Biomol. Struct. 1994; 23:541-76. Hoogsteen K. Acta Crystallogr. 1963; 16:907-16 Malkov VA, Voloshin ON, Veselkov AG, Rostapshov VM, Jansen I, et al. Nucleic Acids Res. 1993; 21:105-11. Malkov VA, Voloshin ON, Soyfer VN, Frank-Kamenetskii MD. Nucleic Acids Res. 1993; 21:585-91 Chemy DY, Belotserkovskii BP, Frank-Kamenetskii MD, Egholm M, Buchardt O, et al. Proc. Natl. Acad. Sci. USA 1993; 90:1667-70 Triplex forming oligonucleotides Triplex forming oligonucleotides: sequence-specific tools for genetic targeting. Knauert MP, Glazer PM. Human Molec Genetics 2001; 10(20):2243-2251. MP/10.2243/ Triplex forming oligonucleotides (TFOs) bind in the major groove of duplex DNA with a

  • high specificity and affinity.

Because of these characteristics, TFOs have been proposed as

  • homing devices for genetic manipulation in vivo.

These investigators review work demonstrating the ability of TFOs and related molecules

  • to alter gene expression and mediate gene modification in mammalian cells.

TFOs can mediate targeted gene knock out in mice, providing a foundation for potential

  • application of these molecules in human gene therapy.

The Triplex Genetic Code

Novagon DNA John Allen Berger, founder of Novagon DNA and The Triplex Genetic Code Over the past 12+ years, Novagon DNA has amassed a vast array of empirical findings which

  • challenge the “validity” of the “central dogma theory”, especially the current five nucleotide
  • Watson-Crick DNA and RNA genetic codes. DNA = A1T1G1C1, RNA =A2U1G2C2.

We propose that our new Novagon DNA 6 nucleotide Triplex Genetic Code has more validity than

  • the existing 5 nucleotide (A1T1U1G1C1) Watson-Crick genetic codes.

Our goal is to conduct a “world class” validation study to replicate and extend our findings.

Methods for Examining Genomic and Proteomic Interactions.

An Integrated Statistical Approach to Compare Transcriptomics Data Across Experiments: A Case Study on the Identification of Candidate Target Genes of the Transcription Factor PPARα Ullah MO, Müller M and Hooiveld GJEJ. Bioinformatics and Biology Insights 2012;6: 145–154. Corresponding author email: An effective strategy to elucidate the signal transduction cascades activated by a transcription factor

  • is to compare the transcriptional profiles of wild type and transcription factor knockout models.

Many statistical tests have been proposed for analyzing gene expression data, but

  • most tests are based on pair-wise comparisons.

Since the analysis of microarrays involves the testing of multiple hypotheses within one study,

  • it is generally accepted to control for false positives by the false discovery rate (FDR).

However, this may be an inappropriate metric for

    • comparing data across different experiments.

Here we propose  the simultaneous testing and integration of

  • the three hypotheses (contrasts) using the cell means ANOVA model.

These three contrasts test for the effect of a treatment in

  1. wild type,
  2. gene knockout, and
  3. globally over all experimental groups

We compare differential expression of genes across experiments while

  • controlling for multiple hypothesis testing,
  • managing biological complexity across orthologs
  • with a visual knowledgebase of documented biomolecular interactions.

Vincent Van Buren & Hailin Chen. Scientific Reports 2012; 2, Article number: 1011 The complexity of biomolecular interactions and influences is a major obstacle

  • to their comprehension and elucidation.

Visualizing knowledge of biomolecular interactions increases

  • comprehension and facilitates the development of new hypotheses.

The rapidly changing landscape of high-content experimental results also presents a challenge

  • for the maintenance of comprehensive knowledgebases.

Distributing the responsibility for maintenance of a knowledgebase to a community of

  • experts is an effective strategy for large, complex and rapidly changing knowledgebases.

Cognoscente serves these needs

  • by building visualizations for queries of biomolecular interactions on demand,
  • by managing the complexity of those visualizations, and
  • by crowdsourcing to promote the incorporation of current knowledge from the literature.

Imputing functional associations

  • between biomolecules and imputing directionality of regulation
  • for those predictions each require a corpus of existing knowledge as a framework.

Comprehension of the complexity of this corpus of knowledge will be facilitated by effective

  • visualizations of the corresponding biomolecular interaction networks.

Cognoscente ( was designed and implemented to serve these roles as a knowledgebase and as

  • an effective visualization tool for systems biology research and education.

Cognoscente currently contains over 413,000 documented interactions, with coverage across multiple species. Perl, HTML, GraphViz1, and a MySQL database were used in the development of Cognoscente. Cognoscente was motivated by the need to update the knowledgebase of

  • biomolecular interactions at the user level, and
  • flexibly visualize multi-molecule query results for
    • heterogeneous interaction types across different orthologs.

Satisfying these needs provides a strong foundation for developing new hypotheses about

  • regulatory and metabolic pathway topologies.

Several existing tools provide functions that are similar to Cognoscente.

Hilbert 3D curve, iteration 3

Hilbert 3D curve, iteration 3 (Photo credit: Wikipedia)

3-dimensionnal Hilbert cube.

3-dimensionnal Hilbert cube. (Photo credit: Wikipedia)

0tj, 1st and 2nd iteration of Hilbert curve in...

0tj, 1st and 2nd iteration of Hilbert curve in 3D. If you’re looking for the source file, contact me. (Photo credit: Wikipedia)

8 first steps of the building of the Hilbert c...

8 first steps of the building of the Hilbert curve in animated gif (Photo credit: Wikipedia)

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Reporter: Aviva Lev-Ari, PhD, RN

At $3 Million, New Award Gives Medical Researchers a Dose of Celebrity

By  in the New York Times
Published: February 20, 2013

Eleven scientists, most of them American, were scheduled to be named on Wednesday as the first winners of the world’s richest academic prize for medicine and biology — $3 million each, more than twice the amount of the Nobel Prize.

Gonzalo Fuentes/Reuters

Yuri Milner, an entrepreneur.

Science Twitter Logo.


Justin Sullivan/Getty Images

Sergey Brin of Google.

Fred Prouser/Reuters

Anne Wojcicki of 23andMe, a genetics company.

Stephen Lam/Getty Images

Mark Zuckerberg of Facebook.

The award, the Breakthrough Prize in Life Sciences, was established by four Internet titans led by Yuri Milner, a Russian entrepreneur and philanthropist who caused a stir last summer when he began giving physicists $3 million awards.

The others, whom Mr. Milner described as old friends, are Sergey Brin, a co-founder of Google; Anne Wojcicki, the founder of the genetics company 23andMe and Mr. Brin’s wife; and Mark Zuckerberg, the founder of Facebook. They plan to give five awards annually.

Ms. Wojcicki said the prize was meant to reward scientists “who think big, take risks and have made a significant impact on our lives.”

“These scientists should be household names and heroes in society,” she said.

Many of the first winners have done work on the intricate genetics of cell growth and how it can go wrong to produce cancer. The new prize was scheduled to be announced at a news conference in San Francisco, along with the following recipients:

Cornelia I. Bargmann, who investigates the nervous system and behavior at Rockefeller University.

David Botstein of Princeton University, who maps disease markers in the human genome.

Lewis C. Cantley of Weill Cornell Medical College, who discovered a family of enzymes related to cell growth and cancer.

Dr. Hans Clevers of the Hubrecht Institute in the Netherlands, who has studied how processes in adult stem cells can go wrong and cause cancer.

Dr. Napoleone Ferrara of the University of California, San Diego, whose work on tumor growth has led to therapies for some kinds of cancer and eye disease.

Titia de Lange, who works on telomeres, the protective tips on the ends of chromosomes, at Rockefeller University.

Eric S. Lander of the Broad Institute of Harvard and the Massachusetts Institute of Technology, a leader of theHuman Genome Project.

Dr. Charles L. Sawyers of Memorial Sloan-Kettering Cancer Center, who has investigated the signaling pathways that drive a cell to cancer.

Dr. Bert Vogelstein of Johns Hopkins University, who discovered a protein that suppresses the growth of tumors and devised a model for the progression of colon cancer that is widely used in colonoscopy.

Robert A. Weinberg of M.I.T., who discovered the first human oncogene, a gene that when mutated causes cancer.

Dr. Shinya Yamanaka of Kyoto University and the Gladstone Institutes in San Francisco, who has done groundbreaking work in developing stem cells.

In an interview, Dr. Lander said he was shocked to win the award, calling it “a staggering sum for an individual prize.”

“Their idea seems to be to grab society’s attention, to send a message that science is exciting, important, cool, our future,” he said. “It’s a very important message here in the U.S.” Dr. Lander said he would use the prize money to help pay for new approaches to teaching biology online.

The new awards are in some ways an outgrowth of Mr. Milner’s Fundamental Physics Prizes. In July, he gave $3 million each to nine theoretical physicists, and the next round is scheduled to be awarded on March 20 in Geneva.

But even as Mr. Milner was starting the physics prize, he was thinking of extending the concept to the life sciences. He reached out to Arthur D. Levinson, the chairman of Apple and a former chief executive of Genentech, the biotech company, and Dr. Levinson, in consultation with his colleagues, helped Mr. Milner select the first Breakthrough winners. These winners will form a committee that will select future winners, Mr. Milner said.

The founders said their goal was to “move the needle” of public awareness of scientists who have spent their lives advancing human knowledge.

With so much focus on sports and movie celebrities, Dr. Levinson said, the prizewinners “can share the stage with the people who on some deeper level have made important contributions.”

The founders said they hoped to attract more sponsors and increase the number of annual winners. Anyone can send a nomination to the foundation’s new Web site.

There are no age or other limits on who can win. Any number of people can share an award. And in particular, Mr. Milner said, there are no limits on how many times one individual can win. “If you’re Einstein,” he said, “you will be getting three.”

This article has been revised to reflect the following correction:

Correction: February 23, 2013

An article on Wednesday about the Breakthrough Prize in Life Sciences quoted incorrectly from comments by Eric S. Lander, one of the recipients. He called the award “a staggering sum for an individual prize,” not “a staggering amount of money for a scientist.” An accompanying picture caption repeated the erroneous phrase “a staggering amount.”


Scientists Receive a New Physics Prize


Published: July 31, 2012

Physicists are rarely wealthy or famous, but a new prize rewarding research at the field’s cutting edges has made nine of them instant multimillionaires.

Yuri Milner
Simon Dawson/Bloomberg News

Yuri Milner

Science Twitter Logo.

The nine are recipients of the Fundamental Physics Prize, established by Yuri Milner, a Russian physics student who dropped out of graduate school in 1989 and later earned billions investing in Internet companies like Facebook and Groupon.

“It knocked me off my feet,” said Alan H. Guth, a professor of physics at the Massachusetts Institute of Technology who was among the winners. He came up with the idea of cosmic inflation, that there was a period of extremely rapid expansion in the first instant of the universe.

When he was told of the $3 million prize, he assumed that the money would be shared among the winners. Not so: Instead, each of this year’s nine recipients will receive $3 million, the most lucrative academic prize in the world. TheNobel Prize currently comes with an award of $1.2 million, usually split by two or three people. The Templeton Prize, which honors contributions to understanding spiritual dimensions of life, has been the largest monetary award given to an individual, $1.7 million this year.

The $3 million has already appeared in Dr. Guth’s bank account, one that had had a balance of $200. “Suddenly, it said, $3,000,200,” he said. “The bank charged a $12 wire transfer fee, but that was easily affordable.”

Mr. Milner said that he wanted to recognize advances in delving into the deepest mysteries of physics and the universe. “This intellectual quest to understand the universe really defines us as human beings,” he said.

Four of the physicists work at the Institute for Advanced Study in Princeton, N.J.: Nima Arkani-HamedJuan MaldacenaNathan Seiberg and Edward Witten. They work on theories trying to tie together the basic particles and forces of the universe, particularly with a mathematical machinery known as string theory.

The other winners are Andrei Linde, a physicist at Stanford who also worked on cosmic inflation; Alexei Kitaev, a professor of physics at the California Institute of Technology who works on quantum computers; Maxim Kontsevich, a mathematician at the Institute of Advanced Scientific Studies outside Paris whose abstract mathematical findings proved useful to physicists unraveling string theory; and Ashoke Sen, a string theorist at Harish-Chandra Research Institute in India.

Mr. Milner personally selected the inaugural group, but future recipients of the Fundamental Physics Prize, to be awarded annually, will be decided by previous winners.

He declined to explain in detail how he selected which accomplishments to honor or why all of the winners are men. “I truly see this as a start,” Mr. Milner said. “Going forward, it’s going to be up to the committee to make those considerations.”

According to the rules, the prize in future years may be split among multiple winners, and a researcher will be able to win more than once. Mr. Milner also announced that there would be a $100,000 prize to honor promising young researchers.

Unlike the Nobel in physics, the Fundamental Physics Prize can be awarded to scientists whose ideas have not yet been verified by experiments, which often occurs decades later. Sometimes a radical new idea “really deserves recognition right away because it expands our understanding of at least what is possible,” Mr. Milner said.

Dr. Arkani-Hamed, for example, has worked on theories about the origin of the Higgs boson, the particle thought to have been discovered recently at the Large Hadron Colliderin Switzerland, and about how that collider could discover new dimensions. None of his theories have been proved yet. He said several were “under strain” because of the new data.

Several of the winners said they hoped that the new prize, with its large cash award, would help raise recognition of physics and draw more students into the field. “It’ll be great to have this sort of showcase for what’s going on in the subject every year,” Dr. Arkani-Hamed said.

The winners said they had not yet decided what to do with their windfall.

“There are some rather mundane things, like paying out the mortgage,” said Mr. Kitaev, who added that he was thinking about putting some of the money into education efforts.

“My success is in large part due to good education, my teachers and the atmosphere of excitement in science when I grew up,” he said. “I might try to help restore this atmosphere as much as I can.”

Dr. Guth agreed. “I do think prizes like this help put across to the public that fundamental physics is important, and it’s not just heavyweight boxing that’s worthy of prizes,” he said.

But he was going to warn his students not to get the wrong idea. “Certainly, it’s still not a great idea to go into physics for the money,” he said.

This article has been revised to reflect the following correction:

Correction: August 1, 2012

An article on Tuesday about the new Fundamental Physics Prize misattributed a quotation by a winner about how he would spend the $3 million in prize money. It was Alexei Kitaev, a professor of physics at the California Institute of Technology — not Maxim Kontsevich, a mathematician at the Institute of Advanced Scientific Studies outside Paris who is among the eight other prizewinners — who said, in part, “There are some rather mundane things, like paying out the mortgage.” The article also gave an outdated amount for the monetary award to winners of the Nobel Prize. The prize was reduced this year to about $1.2 million, from about $1.5 million.


Read Full Post »

Genomics and Ethics: DNA Fragments are Products of Nature or Patentable Genes?

Curator: Aviva Lev-Ari, PhD, RN


Experts say court’s decision on human gene patents is a win-win

Jun 16, 2013

Jun 16, 2013 (St. Louis Post-Dispatch – McClatchy-Tribune Information Services via COMTEX News Network) — The Supreme Court ruling Thursday that naturally occurring human genes cannot be patented effectively ended the monopoly that Utah-based Myriad Genetics had on breast and ovarian cancer tests.

The news was hailed as a victory by health advocates and medical researchers, who can now not only access the genes at issue — the BRCA1 and BRCA2 — but all other patented human genes without infringement. In the wake of the decision, several other testing companies, including Quest Diagnostics, announced it would perform the tests — and at far cheaper prices than Myriad’s.

The court’s unanimous ruling, however, was mixed. It said that naturally occurring DNA could not be patented, but synthetic DNA can still be, giving patent protection advocates and Myriad a victory, too. The decision also means that methods of isolating genes still qualify for patent protection.

The Post-Dispatch interviewed experts from a broad range of fields, from medicine to law, about the court’s ruling.

Here’s what they had to say about what was at stake and what the decision could mean.

Christopher Mason

Professor of physiology, biophysics and computational biomedicine, and author of a study showing that 41 percent of the human genome is covered by patents, Cornell University

I’d say this represents a great win for genetic liberty, both for patients and for doctors. The American Medical Association said it was a big win for patients, and I couldn’t agree more — especially for breast and ovarian cancer, but for all types of cancer. This is an important cancer gene and now it’s open for study to everyone.

(Myriad) didn’t just own a test or a method, they owned anyone’s DNA as soon as it was isolated. They didn’t say we patented a series of letters, they said we patent anything that remotely looks like that, which the court correctly said is not patentable.

It would have been great to have both the patents (on natural and synthetic DNA), but of the two this is the most restrictive one — 99.9 percent of testing is done on DNA not cDNA.

Plenty of companies aren’t scared anymore. This is going to open the floodgates on new research and ideas.

Dr. Julie Margenthaler

Associate professor of surgery and breast cancer specialist, Siteman Cancer Center

This ruling has important implications for physician scientists actively engaged in genetic research. We are on the brink of significant strides in our understanding of the genetic links to many diseases.

For those of us who care for cancer patients, personalized cancer care hinges on the ability to genetically examine the pathways that result in a normal cell becoming a malignant cell. Because some companies held patents to pieces of the genome involved when whole genome sequencing is performed, there was at least some concern over patent infringement. With this ruling, we can continue to move our research forward and benefit the lives of our current and future patients.

Michael Watson

Executive director, American College of Medical Genetics and Genomics (plaintiffs in the case), and former professor of pediatrics at Washington University

It has enormous implications for labs and the public, certainly for breast cancer and for many other cancers. Since the case was settled (Thursday), at least four labs have put the test online. Prices are about half of Myriad’s — $3,500 down to $2,000 overnight.

It’s a win-win for everybody. It used to be when you had the tests done by Myriad, you couldn’t get that test confirmed by anyone else. Now the public can confirm the test and get second opinions, and that has a lot of value for patients. And I think it’ll open up the research.

There are two aspects of this that still remain open. Because 4,000 to 5,000 genes have patents on them, many people signed licensing agreements to use the gene. One of the questions is about the contract they signed. They will probably be able to challenge their contract now.

Nathan Lakey President and CEO, Orion Genomics

I think the ruling is positive because it removes a cloud of uncertainty as to where the Supreme Court stood on patents relating to gene sequences. I appreciate the thoughtfulness that went into the ruling. Justice Thomas adds a section that talks about what the ruling did not address that’s interesting. He emphasizes that method patents, or patents covering gene sequences that apply knowledge of those sequences, are patentable. I think this is what the justices sought to do, to not limit science and to not limit innovation and improvements in patient care. I think they do a markedly good job laying out the framework by which the business of science needs to consider the issue going forward as we all seek to lower the cost of care and improve outcomes.

We’re thrilled because our patents have been crafted primarily as method patents that involve naturally occurring gene sequences, and at the same time we add on to that a novel method that was not known and is quite valuable. We have biomarkers that we believe will be able to predict the risk of an individual getting colon cancer in the future, not unlike the Myriad test, but this is for colon cancer. We feel that our path forward is actually more clear and more positive given the clear line that the Supreme Court drew around what is and what isn’t patentable.

Janet S. Hendrickson

Patent attorney, specializing in chemical, pharmaceutical and food science companies, Senniger Powers law firm

They split it down the middle, and it seems to be, when looking at the commentary, that most people agree with that. They didn’t preclude the patenting of everything related to DNA, just natural DNA.

There are so many considerations and it’s hard to know what ramifications there are going to be, and what might be the best policy. It does mean that for companies that have these claims on natural DNA in their portfolio, they need to make sure they have the other range of claims for the cDNA (synthetic DNA). For companies that have past patents, it’s going to figure into those claims for those natural DNA products.

So it’s hard to tell whether it has broader implications for other things, that when you take them out of their natural milieu we thought were patentable.

Kevin Emerson Collins Professor, Washington University School of Law and patent law expert

This is going to mean one thing for patent lawyers and another thing for biotech companies. For patent lawyers, we now have a new source of business. The court hasn’t given us precise guidelines that say exactly when in other situations do we pass from something being a product of nature to a patentable invention. That’s a new frontier that patent lawyers are going to have to advise companies on.

For biotech companies it’s going to mean they pay patent lawyers a little more. Although the Myriad Genetics ruling deals with DNA, it would seem from the language of the opinion that the ruling should also apply to nongenetic, naturally occurring materials, but exactly how is yet to be determined.

A historical example that predates the Myriad controversy is the debate over the patentability of insulin in the early 20th century. A very famous lower court opinion held that isolated and purified human insulin was patentable so long as it became isolated insulin with impurities removed and took on new commercial value. I bet that case might well come out differently under the Myriad Genetics ruling. The insulin question is moot; that patent has expired. Similarly there a number of other therapeutics which are components that nature already makes that are isolated in a way they can be used in medicine but not in their natural state. Those are the kinds of things we’re going to have to grapple with.

Josh Newby-Harpole Founder, Theresa Harpole Foundation for Metastatic Breast Cancer in Alton

We have a foundation we started this year in honor of my mom. She was diagnosed over seven years ago with stage zero breast cancer. They did genetic testing and found out she had the BRCA gene. In 2010 she got diagnosed with metastatic breast cancer after she had a lump in her neck and it had spread to her bones. I needed to get tested at that point. I had testing done in Chicago and found out that I had the BRCA gene. As a male I’m lucky she had a son and not a daughter. My mom has been on different courses of treatment, and I monitor my health as well as I can, because I have a higher risk for certain kinds of cancer such as prostate and skin cancer and a higher than 3 percent chance of breast cancer.

The cost was probably over $2,000 to have the test done, and I paid close to $1,000 for it. We’re very excited about the Supreme Court ruling. I think a lot of people are hesitant to get the test done because of the cost. It’s exciting because it means possibilities. More people are going to be motivated to do research in labs to try to find a cure. Maybe they can come up with better treatment options for women because some of them will find out they have the gene and they don’t have evidence of disease. It’s something that is really getting a lot of attention right now, and the population is maybe not as aware about things like BRCA and metastatic breast cancer.

Yvette Liebesman Assistant professor of law, St. Louis University

It’s very good for research and in fact it’s very good for health care in the sense that already today a competitor for Myriad said they would run the same test for thousands less. Already we’re seeing a good thing happening that more women are going to be able to be tested for this gene. Now we’re talking about more women being aware of their health risks. Now a company that wants to develop a drug isn’t going to have to go through Myriad to isolate this gene in order to test drugs for breast cancer.

If Myriad won this case it would be like saying while a tree is made by nature, if I find a way to pick the leaves off it, the leaf is my patented product. Myriad did win in one sense, that there is a form of DNA not found in nature that is patentable. This is very logical. I think that like with most things, the people who are doomsayers will say it’s not going to have as great of an impact. The idea that now this opens up the ability to develop treatments is going to be huge.

___ (c)2013 the St. Louis Post-Dispatch Visit the St. Louis Post-Dispatch at Distributed by MCT Information Services

Georgina Gustin and Blythe Bernhard

Copyright (C) 2013, St. Louis Post-Dispatch

SOURCE: Comtex

UPDATED 6/13/2013, following the new Supreme Court Decision on 6/13/2013 to include it, below.

The Supreme Court ruled unanimously Thursday that human genes cannot be patented, a decision that could shape the future of medical and genetic research and have profound effects on pharmaceuticals and agriculture.The ruling was a split decision for Myriad Genetics Inc., which holds patents on genes that have been linked to breast and ovarian cancer.

Justice Clarence Thomas, writing for the court, said that merely isolating those specific genes — called BRCA1 and BRCA2 — was not worthy of a patent.

“Myriad found the location of the BRCA1 and BRCA2 genes, but that discovery, by itself, does not render the BRCA genes . . . patent eligible,” Thomas wrote.On the other hand, Thomas wrote, Myriad’s creation of a synthetic form of DNA — called cDNA — based on its discovery does deserve patent protection.“The lab technician creates something new when cDNA is made,” Thomas wrote.Responding to the decision, Myriad focused on the favorable cDNA ruling. “We believe the court appropriately upheld our claims on cDNA, and underscored the patent eligibility of our method claims, ensuring strong intellectual property protection for our BRACAnalysis test moving forward,” said Peter D. Meldrum, company president and chief executive. “More than 250,000 patients rely upon our BRACAnalysis test annually, and we remain focused on saving and improving peoples’ lives and lowering overall health-care costs.”DNA research is a vital component of personalized medicine. The challenge to Myriad’s patents came from scientists and doctors who said that allowing patents on genes inflated the cost of testing and hindered research.

The American Civil Liberties Union praised the high court’s ruling as a victory. “Today, the court struck down a major barrier to patient care and medical innovation,” said Sandra Park of the ACLU, which represented the groups that brought the challenge. “Because of this ruling, patients will have greater access to genetic testing, and scientists can engage in research on these genes without fear of being sued.”

The test that Myriad offers for determining whether a woman contains the genetic mutation that heightens her chance of cancer has received much attention lately after actress Angelina Jolie wrote about it in a letter to the editor to the New York Times. In the letter, Jolie revealed that she had a double mastectomy because the test showed she carried the defective gene.

[bold and green added by the Curator]


1 (Slip Opinion) OCTOBER TERM, 2012


NOTE: Where it is feasible, a syllabus (headnote) will be released, as is being done in connection with this case, at the time the opinion is issued.The syllabus constitutes no part of the opinion of the Court but has been prepared by the Reporter of Decisions for the convenience of the reader. See United States v. Detroit Timber & Lumber Co., 200 U. S. 321, 337.






No. 12–398. Argued April 15, 2013—Decided June 13, 2013

Each human gene is encoded as deoxyribonucleic acid (DNA), which takes the shape of a “double helix.” Each “cross-bar” in that helix consists of two chemically joined nucleotides. Sequences of DNA nucleotides contain the information necessary to create strings of amino acids used to build proteins in the body. The nucleotides that code for amino acids are “exons,” and those that do not are “introns.” Scientists can extract DNA from cells to isolate specific segments for study. They can also synthetically create exons-only strands of nucleotides known as composite DNA (cDNA). cDNA contains only the exons that occur in DNA, omitting the intervening introns. Respondent Myriad Genetics, Inc. (Myriad), obtained several patents after discovering the precise location and sequence of the BRCA1 and BRCA2 genes, mutations of which can dramatically increase the risk of breast and ovarian cancer. This knowledge allowed Myriad to determine the genes’ typical nucleotide sequence, which, in turn, enabled it to develop medical tests useful for detecting mutations in these genes in a particular patient to assess the patient’s cancer risk. If valid, Myriad’s patents would give it the exclusiveright to isolate an individual’s BRCA1 and BRCA2 genes, and would give Myriad the exclusive right to synthetically create BRCA cDNA. Petitioners filed suit, seeking a declaration that Myriad’s patents areinvalid under 35 U. S. C. §101. As relevant here, the District Court granted summary judgment to petitioners, concluding that Myriad’s claims were invalid because they covered products of nature. The Federal Circuit initially reversed, but on remand in light of Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U. S. ___, the Circuit found both isolated DNA and cDNA patent eligible. 2 ASSOCIATION FOR MOLECULAR PATHOLOGY v. MYRIAD GENETICS, INC. Syllabus

Held: A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but cDNA is patent eligible because it is not naturally occurring. Pp. 10–18. 

(a) The Patent Act permits patents to be issued to “[w]hoever invents or discovers any new and useful . . . composition of matter,” §101, but “laws of nature, natural phenomena, and abstract ideas”“ ‘are basic tools of scientific and technological work’ ” that lie beyond the domain of patent protection, Mayo, supra, at ___. The rule against patents on naturally occurring things has limits, however. Patent protection strikes a delicate balance between creating “incentives that lead to creation, invention, and discovery” and “imped[ing] the flow of information that might permit, indeed spur, invention.” Id., at ___. This standard is used to determine whether Myriad’s patents claim a “new and useful . . . composition of matter,” §101, or claim naturally occurring phenomena. Pp. 10–11. 

(b) Myriad’s DNA claim falls within the law of nature exception.Myriad’s principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes. Diamond v. Chakrabarty, 447 U. S. 303, is central to the patent-eligibility inquiry whether such action was new “with markedly different characteristics from any found in nature,” id., at 310. Myriad did not create or alter either the genetic information encoded in the BCRA1 and BCRA2 genes or the genetic structure of the DNA. It found an important and useful gene, but ground breaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry. See Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U. S. 127. Finding the location of the BRCA1 and BRCA2 genes does not render the genes patent eligible “new . . . composition[s] of matter,” §101. Myriad’s patent descriptions highlight the problem with its claims: They detail the extensive process of discovery, but extensive effort alone isinsufficient to satisfy §101’s demands. Myriad’s claims are not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together. The claims are not expressed in terms of chemical composition, nor do they rely on the chemical changes resulting from the isolation of a particular DNA section. Instead, they focus on the genetic information encoded in the BRCA1 and BRCA2 genes. Finally, Myriad argues that the Patent and Trademark Office’s past practice of awarding gene patents is entitled to deference, citing J. E. M. Ag Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U. S. 124, a case where Congress had endorsed a PTO practice in subsequent legislation. There has been no such endorsement here, and the United States argued in the Federal Circuit and in this Court that isolated DNA was not patent eligible under §101. Pp. 12–16. 

3 Cite as: 569 U. S. ____ (2013)


(c) cDNA is not a “product of nature,” so it is patent eligible under§101. cDNA does not present the same obstacles to patentability as naturally occurring, isolated DNA segments. Its creation results in an exons-only molecule, which is not naturally occurring. Its order of the exons may be dictated by nature, but the lab technician unquestionably creates something new when introns are removed from a DNA sequence to make cDNA. Pp. 16–17.

(d) This case, it is important to note, does not involve method claims, patents on new applications of knowledge about the BRCA1 and BRCA2 genes, or the patentability of DNA in which the order of the naturally occurring nucleotides has been altered. Pp. 17–18. 

689 F. 3d 1303, affirmed in part and reversed in part. 

THOMAS, J., delivered the opinion of the Court, in which ROBERTS,  C. J., and KENNEDY, GINSBURG, BREYER, ALITO, SOTOMAYOR, and KAGAN, JJ., joined, and in which SCALIA, J., joined in part. SCALIA, J., filed an opinion concurring in part and concurring in the judgment.

1 Cite as: 569 U. S. ____ (2013) Opinion of SCALIA, J.


No. 12–398



[June 13, 2013]

JUSTICE SCALIA, concurring in part and concurring in the judgment. 

I join the judgment of the Court, and all of its opinion except Part I–A and some portions of the rest of the opinion going into fine details of molecular biology. I am un-able to affirm those details on my own knowledge or even my own belief. It suffices for me to affirm, having studied the opinions below and the expert briefs presented here, that the portion of DNA isolated from its natural state sought to be patented is identical to that portion of the DNA in its natural state; and that complementary DNA (cDNA) is a synthetic creation not normally present in nature.



Evolution of the case ASSOCIATION FOR MOLECULAR PATHOLOGY ET AL. v. MYRIAD GENETICS, INC., ET AL. priot to 6/13/2013 Supreme Court decision

Curator: Aviva Lev-Ari, PhD, RN

In an amicus brief, the Broad Institute‘s Eric Lander shares his personal view of the ongoing gene patenting case between Myriad Genetics and the American Civil Liberties Union, saying that isolated DNA fragments are products of Nature.

The central issue of the case revolves around Myriad’s patents on the BRCA1 and BRCA2 genes. In a mixed ruling, the federal appeals court found that while some of the company’s methods patents may not be patentable, its BRCA1 and BRCA2 gene patents, as they concern isolated DNA fragments, are patentable items as human intervention is needed to isolate DNA.

Lander argues that that is not true, though, as the Boston Globe points out, his brief was not filed in support of either side. Isolated DNA, he says, happens all the time in nature. “It is well-accepted in the scientific community that

(a) chromosomes are constantly being broken into DNA fragments by natural biological processes that break the covalent bonds within DNA chains;

(b) these DNA fragments can be routinely found in the human body … and

(c) these fragments cover the entire human genome and, in particular, include many of the DNA fragments claimed by Myriad’s patents,” the brief says.

The US Supreme Court announced in December that it will re-hear the Myriad gene patenting case.


Eric Lander weighs in on gene patenting case

By Carolyn Y. Johnson


FEBRUARY 26, 2013

Late last year, the nation’s highest court said it would consider a legal challenge to patents that biotechnology company Myriad Genetics holds on breast cancer genes. Now, Eric Lander, head of the Broad Institute in Cambridge, has filed an amicus brief that he says reflects his personal opinion. Utah-based Myriad, Lander argues, has patented products of nature, and its patents are an “insurmountable barrier” to studying DNA, with serious repercussions for medical progress.
In the Supreme Court of the United States – On Writ of Certiorari to the United States Court of Appeals for the Federal Circuit
The Association for Molecular Pathology, et al., v. Mariad Genetics, Inc, et al.,
Brief for Amicus Curiae Eric S. Lander in support of neither party
Eric S. Lander et al., Initial Sequencing and Analysis of the Human Genome, 409 Nature 860 (2001)
Eric S. Lander, Initial Impact of the Sequencing of the Human Genome, 470 Nature 187 (2011)
It is well-accepted in the scientific community that isolated DNA fragments of the human genome – including isolated DNA fragments of the BRCA1 and BRCA2 genes – are found routinely in th human body and are thus patent-ineligible products of Nature. The biotechnology industry would not be substantially affected by a narrowly crafted decision here holding that
1) fragments of human genome DNA are patent-ineligible where the claimed molecules themselves are routinely found in Nature and where the process for purification or synthesis of such molecules iS routine and
(2) cDNAs are patent-eligible.

Susan McBee and Bryan Jones Guest

Posted Thu, February 7th, 2013 10:16 am

The Supreme Court should be mindful of naturally derived products other than nucleic acids when deciding Myriad

The following contribution to our gene patenting symposium come from Susan McBee and Bryan Jones. Ms. McBee is the Chair of the Life Sciences Intellectual Property Team for Baker, Donelson, Bearman, Caldwell, and Berkowitz, P.C. Bryan Jones is a registered patent attorney in the Washington D.C. office of Baker, Donelson, Bearman, Caldwell, and Berkowitz, P.C.  

In April, the Supreme Court will hear oral argument in Association for Molecular Pathology v. Myriad, ostensibly on the question whether so-called “gene patents” satisfy 35 U.S.C. § 101.  However, Myriad is about more than whether “genes” can be patented.  It is about what types of activities justify patent protection.  Does one need to create something that is unlike anything else that has ever existed in order to justify a patent?  Or is it enough to discover something that was previously unknown, remove it from its natural environment, and show that it has a practical application?

This is a critical question to the biotechnology industry, because many biotechnological products are not novel chemical structures, but naturally occurring products.  Between 1981 and 2006, approximately forty percent of all pharmaceuticals approved for use by the FDA were a biologic, natural product, or derived from a natural product.  Moreover, for start-up biotechnology companies, patents covering such products are incredibly important, “as they are often the most crucial asset they own in a sector that is extremely research-intensive and with low imitation costs.” Strong and enforceable patents to these core products therefore are vitally important to the healthy development of the biotechnology industry.

Before the Myriad case, the Court has not had an opportunity to consider the patentability of such products.  Therefore, this case has the potential to have an enormous impact on the viability of the business model in this industry.

In Myriad, Judge Lourie and Judge Moore both found “isolated” nucleic acids to be patentable, but for different reasons.  Judge Lourie was convinced that isolated nucleic acids are patentable because isolation “breaks covalent bonds” relative to the longer native nucleic acid, thereby resulting in a new chemical entity.  Judge Moore reasoned that, if analyzed on a blank slate, she would require the product to have a “substantial new utility” relative to its natural function in order to satisfy 35 U.S.C. § 101.  While we agree that the generation of a novel chemical entity or demonstration of a new utility would be sufficient to satisfy 35 U.S.C. § 101, we do not believe these to be necessary requirements.

Consider, for example, Taq polymerase.  The inclusion of Taq into a process called polymerase chain reaction (PCR) has often been credited as being the single most important technological advance to the modern biotechnology industry.  PCR uses repeated cycles of increasing and decreasing temperatures in the presence of a polymerase to amplify a target nucleic acid.  In the original iteration of PCR, new polymerase enzyme had to be added to the reaction mixture after each heat cycle, because the high temperature permanently deactivated the enzyme.  Taq, however, is heat stable and thus does not lose activity when subjected to high temperatures.  Because of this stability, Taq only needs to be added to a PCR reaction mixture once, thus greatly reducing the costs and the time of performing the process, and permitting easy automation.  Clearly, then, the identification and characterization of this enzyme is a significant technological advance, from which the public obtains a significant benefit.  Yet the properties of Taq that make it so attractive for PCR are a consequence of its structure and function in the natural world.  Taq is naturally produced by Thermus aquaticus, a bacterium that is naturally found in hot springs.  Therefore, in nature, just like in PCR, Taq functions as a thermostable enzyme that catalyzes the amplification of a nucleic acid.  Why should this render Taq unpatentable?

The Constitution does not require a claimed compound to have a formally “new” chemical structure or new function to justify a patent.  Article I, section 8 of the Constitution authorizes patents “[t]o promote the Progress of Science and useful Arts . . . .”  As explained by the Court:

Congress may not authorize the issuance of patents whose effects are to remove existent knowledge from the public domain, or to restrict free access to materials already available.  Innovation, advancement, and things which add to the sum of useful knowledge are inherent requisites in a patent system which by constitutional command must ‘promote the Progress of useful Arts.’  This is the standard expressed in the Constitution and it may not be ignored.

Thus, the Constitution only limits patents that “remove existent knowledge from the public domain” or “restrict free access to materials already available.”  Assuming that Taq was not previously known, a claim to it in isolated form simply cannot “remove existent knowledge from the public domain.”  Because Taq naturally exists only in the context of a living organism, claiming it in “isolated” form cannot “restrict free access to” its source.  Thus, constitutional limits cannot justify a prohibition on patents covering isolated naturally occurring products.

Nor does 35 U.S.C. § 101 clearly prohibit such patents.  The statute specifically encompasses “discoveries,” so long as those discoveries relate to processes, compositions of matter, or articles of manufacture that are “new” and “useful.”  In most cases, naturally occurring products are found in very minute quantities in complex association with other molecules inside living organisms.  The act of isolating the natural product removes them from this context, thereby inevitably resulting in a composition that is materially different than anything that exists in nature.  An “isolated” natural product therefore is “new” compared to the same product in its natural state.  Its discovery thus could justify a claim under 35 U.S.C. § 101.

Finally, Supreme Court precedent does not clearly prohibit patenting of such claims.  Under the closest Supreme Court precedent, a patent that is limited to a “non-naturally occurring article of manufacture or composition of matter” satisfies 35 U.S.C. § 101.  Although it is often convenient to describe naturally occurring compounds in terms of chemical structure or nucleotide or amino acid sequence, they rarely if ever exist in nature as isolated compositions.  Rather, they are found in complex associations with other compositions, usually within living organisms.  The removal of these products from their natural context sometimes results in distinct chemical entities, such as the isolated nucleic acids in Myriad.  Other times, the result is a highly purified form of the compound, such as isolated adrenaline or purified vitamin B12.  In each case, however, the intervention of man is required to produce the “isolated” composition.  Claims directed to “isolated” natural compounds thus are limited to purely artificial, non-naturally occurring compositions of matter.  This should make them patentable, irrespective of whether they have a novel chemical structure or new utility in isolated form.

It is our sincere hope that the Court will not only find isolated nucleic acids to be patentable, but that it will do so under a rationale which allows for other naturally derived products to similarly be patentable.  In as much as a possible test can be garnered, our recommendation is to find that a naturally derived product satisfies 35 U.S.C. § 101 as long as it is claimed in a purely man-made form (and thus is “new”), and the form in which it is claimed has a practical utility disclosed in the Specification (and thus is “useful”).  This test closely aligns with the plain language of 35 U.S.C. § 101.  Challenges to the eligibility of such claims could then focus on two clear issues: (1) whether the claim encompasses the product in its natural state; and (2) whether the claim is reasonably commensurate in scope with the disclosed utility (i.e., is the claim narrowly tailored to products that possess the disclosed utility?).  This allows overly broad claims to be invalidated without resorting to a categorical ban on a broad class of subject matter.  Moreover, it would not require courts to answer the philosophical question of whether something has enough of a structural or functional change to justify a patent.

Posted in Association for Molecular Pathology v. Myriad GeneticsFeaturedGene Patenting Symposium

Recommended Citation: Susan McBee and Bryan Jones, The Supreme Court should be mindful of naturally derived products other than nucleic acids when deciding Myriad, SCOTUSblog (Feb. 7, 2013, 10:16 AM),

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Appeals Court Affirms Isolated DNA Patents in Myriad Case

August 16, 2012

NEW YORK (GenomeWeb News) – A federal appeals court today has for a second time reversed a lower district court’s decision that isolated genes are not patentable, but it also partly affirmed the District Court’s decision that certain methods patents “comparing” or “analyzing” gene sequences may not be patentable.

The Supreme Court recently asked the US Court of Appeals for the Federal Circuit to reconsider its earlier decision in the case, The Association for Molecular Pathology v. the US Patent and Trademark Office and Myriad Genetics, in light of its ruling in another lawsuit, called Mayo Collaborative Services v. Prometheus Laboratories.

AMP v USPTO focuses on the patentability of Myriad Genetics’ claims on isolated gene sequences and diagnostic methods related to its BRACAnalysis test. In Mayo v Prometheus, the Supreme Court recently invalidated patents held by diagnostics firm Prometheus because they merely described laws of nature, and did not apply those laws of nature in a markedly different manner as to warrant a patent.

Despite the Supreme Court’s ruling in Mayo, the CAFC in a 2-1 decision maintained that although isolated gene sequences may be derived from naturally occurring substances, their isolation requires human intervention in order to make them useful in medical care and so are deserving of patent protection.

“We are very pleased with the favorable decision the Court rendered today which again confirmed that isolated DNA is patentable,” Myriad Genetics President and CEO Peter Meldrum said in a statement. “Importantly, the court agreed with Myriad that isolated DNA is a new chemical matter with important utilities which can only exist as the product of human ingenuity.”

The decision was met with disappointment by those opposing gene patenting.

“It is extremely disappointing that despite the Supreme Court’s ruling, the appeals court has failed to fully re-consider the facts of this case,” Chris Hansen, a staff attorney with the ACLU Speech, Privacy and Technology Project, said in a statement.

The case against Myriad was filed in 2009 by the Public Patent Foundation, American Civil Liberties Union, AMP, and others who claim that patents cannot cover natural phenomena and that Myriad’s patents, and others like them, will hinder genetics research and keep some people from accessing tests and second opinions.

“This ruling prevents doctors and scientists from exchanging their ideas and research freely,” Hansen added the ACLU statement today. “Human DNA is a natural entity like air or water. It does not belong to any one company.”

Myriad said again today what it has argued all along, that gene patents have not thwarted research, that the cost of its BRACAnalysis test is not prohibitive and is covered through most insurance for “appropriate” patients, and that second opinion testing is available in many US labs.

“Certainly, you could hear a collective sigh of relief from the biotech industry, as of this decision,” Jennifer Camacho, an attorney and shareholder with law firm Greenberg Traurig, told GenomeWeb Daily News today.

“Isolated DNA patents remain intact. We still have patent eligibility for isolated DNA,” Camacho said, explaining that the court’s decision to uphold the patentability of isolated DNA may be seen by the biotech industry as more important than its reading of the reach of the Prometheus decision.

“They did actually take [the Prometheus decision] into consideration,” Camacho said, adding that it did not change the judges’ analysis.

“This puts a narrow interpretation of Prometheus in the books, as being limited to the ‘laws of nature’ exclusion, she added.

Camacho told GWDN that she was struck by how similar today’s CAFC ruling was to the original. She pointed out that part of one judge’s opinion, which argued that whether some patents should or should not be awarded are policy questions that are best left to Congress, was the same language as in the first opinion.

For Myriad, the ruling provided mixed results, Goldman Sachs Investment Research analyst Isaac Ro said in a note today.

On the positive side for Myriad, the patent eligibility of its BRCA1 and BRCA2-based tests was upheld again based on its isolated DNA claims and screening method claims. But a potential negative is that the CAFC also upheld the District Court’s opinion that Myriad’s method claims for comparing DNA sequences are not eligible.

“The outcome is modestly disappointing,” Ro stated, adding that the critical question now is whether or not the Supreme Court will agree to hear the case next year.

US Supreme Court Agrees to Hear Myriad Patent Case Again

NEW YORK (GenomeWeb News) – The US Supreme Court decided on Friday to once again hear the American Civil Liberty Union’s case against Myriad Genetics challenging the firm’s patent rights related to BRCA1 and BRCA2 genes.

The decision by the court to hear the case — originally filed by ACLU, the Public Patent Foundation, the Association for Molecular Pathology and others in 2009 — comes a little more than three months after a federal appeals courtissued a mixed ruling in which it found that isolated genes are patentable, but that certain methods patents that compare or analyze gene sequences may not be.

The US Court of Appeals for the Federal Circuit issued its decision in August after the Supreme Court asked it in March to reconsider a decision rendered by the appeals court in 2011 in light of the Supreme Court’s decision in another case, Mayo Collaborative Services v. Prometheus Laboratories. In that case, the Supreme Courtinvalidated patents held by Prometheus, saying the patents merely described laws of nature but did not apply those laws of nature in a markedly different manner as to warrant a patent.

The appeals court originally ruled in July 2011 that Myriad’s patents covering isolated DNA are patentable under Section 101 of the US Patent Act, reversing a decision by the Federal District Court for the Southern District of New York that isolated DNA is not much different from gene sequences found in nature and therefore is not patentable.

This past September, ACLU and the Public Patent Foundation asked the Supreme Court to once again take up the issue of whether Myriad’s claims on genes that predict the risk of ovarian and breast cancer can be patented. ACLU and the foundation contend that Myriad’s BRCA1 and BRCA2 gene patents should be invalidated because the genes are products of nature and allowing Myriad patent protection stifles scientific research and patient access to medical care.

“Myriad did not invent human genes, and has no right to claim ownership of them just because they removed them from the body,” Daniel Ravicher, executive director of PUBPAT, said in a statement on Friday. “The government does not have the right to give a corporation the exclusive power to control what we know about our own genetic makeup.”

Myriad President and CEO Peter Meldrum said in a statement, however, that patent protection is necessary to drive technological innovation.

“Two previous decisions by the Federal Circuit Court of Appeals confirmed the patentability of our groundbreaking diagnostic test that has helped close to 1 million people learn about their hereditary cancer risk,” he said. “Myriad devoted more than 17 years and $500 million to develop its BRACAnalysis test. The discovery and development of pioneering diagnostics and therapeutics require a huge investment and our US patent system is the engine that drives this innovation.

“This case has great importance for the hundreds of millions of patients whose lives are saved and enhanced by the life science industry’s products,” he said.

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