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J. Craig Venter Institute Awarded $43 Million, Five Year Contract to Continue to Develop and Provide Sequencing, Genotyping, and Bioinformatics Expertise and Services in Infectious Diseases
ROCKVILLE, MD—The J. Craig Venter Institute (JCVI) announced that they have been awarded a $43 million, five year contract from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, as part of their Genomic Sequencing Centers for Infectious Diseases (GSCID). Led by co-principal investigators, William Nierman, Ph.D., and Robert Strausberg, Ph.D., the contract will enable JCVI to continue to expand its decades-long expertise in infectious diseases and human genomics by providing important genomic services to the broader scientific community.
“The current worldwide outbreak of H1N1 flu, and the increasing prevalence of new and emerging infectious diseases makes our work more necessary than ever,” said J. Craig Venter, Ph.D., founder and president, JCVI. “Since our first sequencing of the Haemophilus influenzae genome in 1995, to our most recent work in sequencing the isolates from the 2009 H1N1 flu outbreak, JCVI is committed to being a major source for leading edge genomic data and tools to further scientific understanding of the microbial world and how it affects humans.”
Over the course of the five year contract JCVI will work collaboratively with NIAID to provide genomics resources that are responsive to the needs of the global infectious disease community. To do this, JCVI investigators with scientific and technical expertise in infectious diseases, human genomics, DNA sequencing, genotyping, and bioinformatics, will continue to generate comprehensive genomic data sets that will enable pathogen countermeasures such as vaccines, therapeutics, diagnostics, and surveillance methods.
Since 2003, JCVI (and through legacy organization, TIGR) has been providing these important services as a contractor under what was previously referred to as the NIAID Microbial Genome Centers program. During that contract period JCVI sequenced and analyzed 185 eukaryotic and prokaryotic genomes, and more than 3000 viral genomes.JCVI’s participation in the NIH Human Microbiome program was also initiated under this contract program.
The recent work conducted at JCVI and led by David Spiro, Ph.D. in sequencing and analyzing the H1N1 (swine origin) influenza isolates, is supported by NIAID as part of the GSCID contract. Dr. Spiro and the team at JCVI continue to work closely with NIAID, NationalCenter for Biotechnology Information (NCBI), and the global scientific community to monitor and better understand the evolution of the current virus with the goal of anticipating and developing new and better therapeutics, diagnostics and vaccines to this constantly mutating viral threat.
About the J. Craig Venter Institute
The JCVI is a not-for-profit research institute in Rockville, MD and San Diego, CA dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c) (3) organization. For additional information, please visit http://www.JCVI.org.
Complete Genomes of All Known Human Rhinoviruses Are
Published
First comprehensive sequencing and analysis of strains
responsible for common cold and other respiratory illnesses, give clues to
evolution and diversity of the virus
ROCKVILLE, MD—A team of researchers from the J. Craig Venter Institute (JCVI); the
University of Maryland School of Medicine and the University
of Wisconsin, Madison; announced today they have sequenced
and analyzed the genomes of all known human rhinoviruses (HRVs). David Spiro,
Ph.D., JCVI, Steve Liggett, M.D., the University of Maryland School of
Medicine, and Ann Palmenberg, Ph.D., University
of Wisconsin, Madison led the team whose work was published
in Science Express, the online edition of the journal Science.
Rhinoviruses, part of the Picornaviridae family, are
immediately familiar as the cause of the common cold, but they are also
responsible for acute lower respiratory symptoms,and are a major cause of emergency room visits
for patients suffering from asthma and chronic obstructive pulmonary disease
(COPD). The direct and indirect cost of treating these illnesses is billions of
dollars yearly, thus finding new ways to treat and perhaps prevent these
illnesses could substantially cut health care costs.
Rhinoviruses are traditionally divided into two groups,
HRV-A and HRV-B, consisting of 99 viral serotypes.The extraordinary genetic diversity of
circulating rhinovirus serotypes has prevented the production of a universal
vaccine for the common cold.A recently
discovered third group of rhinoviruses, HRV-C, has swept the globe causing
severe lower respiratory symptoms in patients.
To better understand the biology, diversity and evolution of
human rhinoviruses, the researchers in this study sequenced and analyzed the
genomes of all known HRV-A and B reference strains, as well as 10 new field
isolates.The whole genome sequencing
and bioinformatic analyses on the rhinovirus evolution were conducted at JCVI.
By constructing a rigorous phylogeny of all complete HRV
genomes, the team gained new insight into rhinovirus evolution.They clearly showed that HRV-A and HRV-C
evolved from a common ancestor and that HRV-B is “sister” group to the other
two species. Interestingly, the team also uncovered within the HRV-A strain
what they believe could be a separate, distinct fourth HRV subgroup.
The authors demonstrated in this study that recombination,
the exchange of genetic information by breaking and rejoining nucleic acid
sequences, is a common evolutionary mechanism in rhinoviruses.Co-infection with multiple viruses in
individual patients can lead to the generation of novel rhinovirus
serotypes.The authors also saw a high rate
of diversity among field samples of the same HRV serotypes in the same geographic
area over a short time period, suggesting that rhinoviruses may escape
antiviral drugs through rapid mutation.
The researchers also found several areas of interest in the
HRV genomes which could help to better understand the infection mechanism. Specifically,
nearly all the HRVs displayed a hypervariable region in the 5’UTR. In the
poliovirus a similar region is found which determines the virulence of that
virus, suggesting that this genomic region could determine the pathogenicity of
individual HRV strains.
According to Dr. Spiro this study provides the scientific
community with an extremely valuable resource for studying viral
evolution.He added, “It is a very
exciting time in viral genomics.Next
generation sequencing technology will allow researchers to study as never
before the evolution of viral populations worldwide.The completion of the HRV reference data set
will open the door to mass comparative studies of rhinovirus evolution and
global migration patterns.”
Further full genome analysis with potentially thousands of
additional field strains should enable even better understanding of these
viruses leading to improved antivirals and vaccines.
This work was funded by a grant from the National Institutes
of Health and with internal funds from the University
of Maryland, School of Medicine.
About the J. Craig Venter Institute
The JCVI is a not-for-profit research institute in
Rockville, MD and La Jolla, CA dedicated to the advancement of the science of
genomics; the understanding of its implications for society; and communication
of those results to the scientific community, the public, and policymakers.
Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400
scientists and staff with expertise in human and evolutionary biology,
genetics, bioinformatics/informatics, information technology, high-throughput
DNA sequencing, genomic and environmental policy research, and public education
in science and science policy. The legacy organizations of the JCVI are: The
Institute for Genomic Research (TIGR), The Center for the Advancement of
Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the
Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The
JCVI is a 501 (c) (3) organization. For additional information, please visit
http://www.JCVI.org.
Research Teams at J. Craig Venter Institute and Ludwig Institute for Cancer Research Uncover New Chromosomal Alterations in Cancer Using Transcriptome Sequencing Approach
ROCKVILLE, MD and NEW YORK, NY—January 27, 2009— Researchers
from the J. Craig Venter Institute (JCVI) and the Ludwig Institute for Cancer
Research (LICR) have uncovered new genomic alterations that lead to gene
fusions in a breast cancer cell line by using 454 Life Sciences sequencing
technology. The work, led by Qi Zhao of JCVI and Otavia L. Caballero, of LICR,
is being published the week of January 26 in the early online edition of the
Journal of the Proceedings of the National Academy of Sciences (PNAS).
Previous studies have shown that gene fusions are key gene
alteration events in the development and progression of many kinds of cancers.
The discovery of the best known gene fusion, BCR-ABL, led to the development of
Gleevec® for the treatment of chronic myelogenous leukemia and other cancers.
In this proof of concept study the researchers focused on
the transcriptome, a subset of genes in the genome that code for proteins. It
has long been known that cancers arise from various types of genomic changes in
certain cells. Continued advances and cost efficiencies of next generation DNA
sequencing technologies are enabling this more precise and detailed examination
of changes in the human genome that could be directly involved in cancer.
The JCVI/LICR researchers began with a well-characterized
breast cancer cell line, HCC1954 and performed high-throughput transcriptome
sequencing. Previous studies on this cell line have uncovered certain types of
genetic mutations and chromosomal abnormalities associated with breast cancer.
By conducting the in-depth transcript sequencing in this study and comparing
these data to the previous studies a clearer picture is emerging of all the
expressed genes some of which present in altered forms in the cancer cell line.
The team began by generating more than half a million 454
reads of cDNA sequences. After extensive data mining, the team uncovered 496
sequences that indicate chromosomal translocations. Of these 496, the team
characterized 208 as inter-chromosomal abnormalities and 210 were
intra-chromosomal abnormalities. From here the team performed more detailed
validation experiments with a control cell line (HCC1954 BL).
Through further analysis the team confirmed six
inter-chromosomal changes and one intra-chromosomal change that have the
potential to affect the protein producing ability of at least nine genes. The
researchers also discovered that chromosome 8 in the cancer cell line seemed to
be very involved in some of the genomic rearrangements. This data confirms
earlier studies showing that genomic instability in this area is implicated in
breast and prostate cancers.
Most genes involved in the discovered chromosomal
rearrangement events in this study have been implicated in cancers, such as the
MRE11A protein that is associated with mutations in many types of tumors
including in breast cancer. The team also identified the SAMD12 gene as being
involved in both inter- and intra-chromosomal rearrangements. While not
previously thought to play a role in the development of cancer, this study
showed that this gene might be implicated in cancer.
The team concluded that transcriptome sequencing with next
generation sequencing technologies such as the 454 Life Sciences platform is
very adept at finding genomic rearrangements and mutations associated with
cancers. With deeper sequencing coverage this approach could be a powerful and
efficient way to discover all events associated with expressed genes including
gene fusions, somatic mutations and alternative trans-splicing that lead to the
development of cancer.
Robert Strausberg, Ph.D., Deputy Director of the JCVI and
leader of the Human Genomic Medicine team noted, “This approach reveals
alterations in the cancer genome within the active genes of cancer cells.
Through the comparison with related normal cells we can glean those that are
specific to cancer cells, thereby revealing their unique biology, as well as
suggesting new approaches to detection, diagnosis and treatment of cancers.”
According to Andrew Simpson, Ph.D., Scientific Director of
the LICR, “These studies are an important component of the Hilton-Ludwig Cancer
Metastasis Initiative, focused on preventing and treating cancer metastasis.
This program brings together interdisciplinary teams of expert scientists,
working together to improve the lives of cancer patients. The current study
represents one aspect of our teams’ creative approach in revealing previously
unknown features of cancer that together will provide a platform for cancer
prevention and intervention.”
About the J. Craig Venter Institute
The JCVI is a not-for-profit research institute in
Rockville, MD and La Jolla, CA dedicated to the advancement of the science of
genomics; the understanding of its implications for society; and communication
of those results to the scientific community, the public, and policymakers.
Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400
scientists and staff with expertise in human and evolutionary biology,
genetics, bioinformatics/informatics, information technology, high-throughput
DNA sequencing, genomic and environmental policy research, and public education
in science and science policy. The legacy organizations of the JCVI are: The
Institute for Genomic Research (TIGR), The Center for the Advancement of
Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the
Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The
JCVI is a 501 (c) (3) organization. For additional information, please visit
http://www.JCVI.org.
About Ludwig Institute for Cancer Research
The Ludwig Institute for Cancer Research (LICR) is the
largest international academic institute dedicated to understanding and
controlling cancer. With nine Branches in seven countries, and numerous
Affiliates and ClinicalTrialCenters
in many others, the scientific network that is LICR quite literally covers the
globe. The uniqueness of LICR lies not only in its size and scale, but also in
its philosophy and ability to drive its results from the laboratory into the
clinic. LICR has developed an impressive portfolio of reagents, knowledge,
expertise, and intellectual property, and has also assembled the personnel,
facilities, and practices necessary to patent, clinically evaluate, license,
and thus translate, the most promising aspects of its own laboratory research
into cancer therapies.
New Initiative to Study Societal Issues Associated with Synthetic Biology -- A Rapidly Developing Field where Novel Organisms are Constructed from The Building Blocks of DNA
NEW YORK, Dec. 18--
The Alfred P. Sloan Foundation announces a new initiative to study societal
issues associated with synthetic biology-- a rapidly developing scientific
field where researchers are constructing novel organisms from the building
blocks of DNA. This new effort brings together leading scientists, ethicists
and public policy specialists to explore the field's potential benefits and
risks, as well as ethical questions and regulatory issues. The new initiative
launches with three grants totaling more than $1.6 million to The Hastings
Center, the J. Craig Venter Institute, and the WoodrowWilsonInternationalCenter
for Scholars.
"The Foundation has a long and rich tradition of
funding scientific research," said Dr. Paul Joskow, President Alfred P.
Sloan Foundation. "With synthetic biology, scientists have gone from
reading to writing the genetic code; it's imperative that we take a carefully
reasoned and systematic approach to understanding the full spectrum of ethical
and policy issues that may arise as research and applications in this field
develop."
At the HastingsCenter
(http://www.thehastingscenter.org/), Foundation funding will allow for in-depth
investigation into ethical issues that may arise in connection with
developments in synthetic biology. The project aims to make serious
contributions to scholarly literature, produce a base for further scholarship,
and inform public policymaking.
Alfred P. Sloan Foundation funding will allow the J. Craig
Venter Institute (http://www.jcvi.org/) to examine potential societal concerns
associated with developments in synthetic genomics. The project will both
inform the scientific community about these issues while also educating the
policy and journalistic communities about the science. As a result, scientists,
journalists and policymakers will be able to engage in informed discussions.
A grant to the WoodrowWilsonInternationalCenter for Scholars
(http://www.wilsoncenter.org/) will analyze evolving public perceptions of
potential societal risks that may arise related to research in and applications
of synthetic biology, clarify whether our existing regulatory systems can
address relevant risks that may be associated with the science, and inform and
educate policymakers.
"This program builds on the Foundation's biosecurity
work and will establish a community of scientists, ethicists and policy
specialists who can work synergistically on these issues," said Paula
Olsiewski, Program Director, Alfred P. Sloan Foundation. "Ethical and
policy discussions must be informed by the realities of the science and
similarly the science must take into consideration societal concerns so that
synthetic biology can be applied both inventively and wisely."
About the Alfred P. Sloan Foundation
The Alfred P. Sloan Foundation, established in 1934, makes
grants to support original research and broad-based education related to
science, technology, and economic performance; and to improve the quality of
American life. The Foundation believes that a carefully reasoned and systematic
understanding of the forces of nature and society, when applied inventively and
wisely, can lead to a better world for all. Please visit the Foundation's Web
site at www.sloan.org.
SOURCE Alfred P. Sloan Foundation
Discovery of Common Versions of Two Single-letter Variations in the Human Genome (SNPs) that Confer Risk of Basal Cell Carcinoma (BCC)-Most Common Form of Skin Cancer
Latest discoveries add to understanding of individual risk of basal cell carcinoma, and are integrated into the deCODEme™ personal genome analysis scan
Scientists at deCODE genetics report the discovery of common versions of two single-letter variations in the human genome (SNPs) that confer risk of basal cell carcinoma (BCC), the most common cancer among people of European ancestry. Unlike the four sets of SNPs previously found by deCODE to confer risk of BCC and cutaneous melanoma, those reported today are not linked to fair pigmentation traits that also make certain people prone to freckling and sunburn. These SNPs, both located on chromosome 1, may therefore provide new insight into an underlying biological mechanism causing BCC, independent of the impact of exposure to ultraviolet (UV) radiation in sunlight. Approximately 2% of people of European descent carry two copies of the risk versions of both SNPs, and are at a 170% greater risk of BCC than those who do not carry the risk variants. The paper, entitled ‘Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigrmentation traits,’ appears today in the online edition of Nature Genetics at www.nature.com/ng.
“With this discovery we continue to build our portfolio of novel risk factors for common skin cancers, diseases that cause significant morbidity and that are on the rise in the industrialized world. Once again we have used our capabilities in human genetics to gain a new understanding of the root causes of a major disease, that appear to act independently of known environmental risk factors. These two SNPs can also be used to enable individuals to better understand their own susceptibility to BCC and thus to take measures to lower their environmental and overall risk, and we are pleased to have added them already to our deCODEme™ service,” said Kari Stefansson, CEO of deCODE and senior author of the study.
The SNPs were discovered through the analysis of more than 300,000 SNPs across the genomes of more than 900 Icelanders with BCC and more than 33,000 control subjects. The SNPs most strongly correlated with BCC were then validated through the analysis of additional Icelandic and Eastern European cohorts of approximately 4,000 cases and controls.The deCODE team then analyzed data from more than 42,000 individuals from Iceland, Sweden and Spain to demonstrate that these novel variants conferring risk of BCC do not correlate with either fair pigmentation or with risk of cutaneous melanoma. The SNPs reported today thus appear to confer risk independently of that of variants in or near the MC1R, ASIP, TYR and TYRP1 genes that deCODE has reported in earlier studies.
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™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProCa™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer™ for the common forms of breast cancer. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com; on our diagnostics site at www.decodediagnostics.com; for our pioneering personal genome analysis service, integrating the genetic variants included in these tests and those linked to another twenty common diseases, at www.decodeme.com; and on our blog at www.decodeyou.com .
deCODE and Radboud University Discover Common Variants in the Human Genome Conferring Risk of Bladder Cancer
--Detection may be used to complement and target screening for the disease; variants will be integrated into the deCODEme™ personal genome scan--
Reykjavik, ICELAND – Scientists at deCODE genetics and colleagues at Radboud University Medical Center in the Netherlands today report the discovery of two common single-letter variants in the human genome (SNPs) that confer increased risk of urinary bladder cancer. Approximately 20% of people of European descent carry two copies of the first variant, a version of a SNP on chromosome 8q24, putting them at a 50% higher risk of developing bladder cancer than those without the variant. Individuals who carry two copies of a common version of another SNP on chromosome 3 were found to be at a 40% higher risk of the disease than non-carriers. These are the best-replicated genetic variants ever linked to bladder cancer risk, and the study analysed genotypic data from more than 40,000 patients and controls from Iceland, the Netherlands and eight other European countries. The paper, entitled ‘Sequence variant on 8q24 confers susceptibility to urinary bladder cancer,’ will appear today in the online edition of Nature Genetics at www.nature.com/ng .
“In all cancers, the ability to identify individuals at high risk, screening them intensively and intervening early, is the key to improving prevention and outcomes. We expect that the detection of these and other risk variants will soon be employed to complement the assessment of standard risk factors for bladder cancer. As with all of our discovery work, we seek to publish our findings and establish a solid intellectual property position in order to bring these swiftly into the healthcare arena, and have already folded these variants into our deCODEme™ personal genome analysis service. At the same time, we are working to identify the common thread of variants we and others have discovered on chromosome 8q24 that confer risk of several forms of cancer, including prostate, breast, colorectal and now bladder. If a common molecular mechanism exists, it could provide an important insight into oncogenesis more broadly,” said Kari Stefansson, CEO of deCODE.
For a more detailed discussion of today's findings you can watch a video discussion between Dr. Stefansson and Dr. Simon Stacey on our blog, at www.decodeyou.com.
Urinary bladder cancer is the sixth most common type of cancer in the United States.It is estimated that 68,810 individuals will be diagnosed with bladder cancer in the United States during 2008 and that 14,100 people will die of the disease. Bladder cancer has been linked to exposure to various types of toxic substances such as cigarette smoke and industrial chemicals. Although it has been known for some time that genetic factors also play a significant role, identifying validated genetic risk variants had been problematic. Incidence of bladder cancer varies considerably between ethnicities, and as the risk factors reported here were discovered by analysing DNA from groups of European descent, it is our hope that the publication of these findings will contribute to the swift analysis of the impact of these variants in cohorts of other continental ancestries.
The authors wish to thank the thousands of patients and control subjects who participated in this study, and acknowledge the assistance of national cancer registries that worked to identify potential participants. Data and sample collection in Iceland and the Netherlands was funded in part by European commission grants LSHC-CT-2005-018827 and LSHM-CT-2004-005166.
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™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProCa™ for prostate cancer; and deCODE Glaucoma™ 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 site at www.decodediagnostics.com; for our pioneering personal genome analysis service, at www.decodeme.com; and on our blog at www.decodeyou.com.
Source: deCODE Press Release
New Analytical Tool to Discover Rare Genetic Risk Factors for Common Diseases
--A cost-effective method to enable deCODE to extend its leadership in gene discovery to the next challenge in developing market-leading DNA-based diagnostics—
A VIDEO discussion of the findings by deCODE’s CEO Kari Stefansson, lead statistician Augustine Kong, and Chief of Communication Edward Farmer at http://www.decodevideo.com/video/kong080818.html
August 17, 2008 – deCODE has developed a novel analytical method to increase several-fold the amount of information scientists can derive from the use of SNP-chips to discover novel variations in the human genome conferring risk of common diseases. The method has immediate practical utility for continuing to provide market-leading content for deCODE’s growing portfolio of DNA-based diagnostic tests and personal genotyping products.
In a paper published today in the online edition of Nature Genetics, deCODE describes a method for tracing how large haplotypes – unbroken segments of particular chromosomes – are inherited by individuals through their maternal or paternal lingeages. The ability to track haplotypes back through large family trees – called long-range phasing – resolves a longstanding challenge in genetic analysis. However the method can also be used to leverage the company’s existing genotypic and genealogical data in the search for rarer variants linked to risk of common diseases. Over the past eighteen months, deCODE has employed its population-based resources in human genetics to discover common variations in the human genome conferring risks of a broad and growing range of common diseases. The company’s success in gene discovery to date is underpinned by its ability to conduct genome-wide studies leveraging tens of thousands of participants in its gene discovery programs. The genomes of some 40,000 Icelandic participants have been analyzed with gene chips measuring more than 300,000 single-base variations in the genome (SNPs), common markers that are useful for discovering common variations in the genome linked to risk of disease. Moreover, all of these individuals are linked together in deCODE’s genealogical database covering the entire Icelandic population.
Employing this new method, deCODE can genotype with higher density SNP-chips or even sequence small regions of the genome in a small subset of these 40,000 individuals, and then use the genealogies to understand how many of the entire group carry rarer SNPs that lie within a given haplotype. This will enable large-scale, statistically powerful discovery efforts without having to re-genotype the entire cohort. As sequencing technologies and the highest density chips are currently too expensive to apply to large numbers of cases and controls, this may enable deCODE to time- and cost-effectively take the lead in the search for rarer variants that do not appear on lower-density SNP-chips. These variants may confer relatively high risk of disease in a small proportion of the population, and thereby provide important additional content for deCODE’s pioneering diagnostic and personal genotyping product portfolio.
You can see a video discussion of the findings by deCODE’s CEO Kari Stefansson, lead statistician Augustine Kong, and Chief of Communication Edward Farmer, on deCODE’s blog, www.decodeyou.com. The paper, ‘Detection of sharing by descent, long-range phasing and haplotype imputation,’ is published today on www.nature.com/ng, and will appear in an upcoming print edition of the journal.
Source: deCode Press Release
Archon X PRIZE of $10 Million for Human Genome Sequencing - Revolution through Competition
The Archon X PRIZE for Genomics of $10 million will be awarded to a privately funded organization that develops technology to sequence 100 complete Human Sequences in 10 days. Archon X prize challenges scientists and engineers to create better, cheaper and faster ways to sequence genomes. The knowledge gained by compiling and comparing a library of human genomes will create a new era of preventive and personalized medicine — and transform medical care from reactive to proactive.
Multi-institutional Team Led by Massachusetts General Hospital (MGH) Investigators has Developed a Powerful New Tool for Genomic Research and Medicine
--“Open source” strategy should be valuable tool for genomic research, gene therapy--
July 24, 2008– A multi-institutional team led by Massachusetts General Hospital (MGH) investigators has developed a powerful new tool for genomic research and medicine – a robust method for generating synthetic enzymes that can target particular DNA sequences for inactivation or repair. In the July 25 issue of Molecular Cell, the researchers describe an efficient, publicly available method to engineer customized zinc-finger nucleases (ZFNs), which can be used to induce specific genomic modifications in many types of cells.
“Recent work has shown that ZFNs can alter genes with high efficiency in cells from plants or model organisms like fruitflies, roundworms and zebrafish, and in human cells,” says J. Keith Joung, MD, PhD, of the MGH Molecular Pathology Unit, the paper’s senior author.“However, a significant bottleneck has been the lack of access to an effective method for generating the customized DNA-binding domains needed to guide ZFNs to their target sites.Our method will enable academic researchers to rapidly create high quality ZFNs for genes of interest and will stimulate use of this technology in biological research and potentially gene therapy.”
Zinc-finger peptides, which bind to DNA, occur naturally in many important proteins that regulate or otherwise interact with DNA.Zinc-finger nucleases are constructed from synthetic “designer” zinc-finger domains targeted to a specific genetic sequence and another protein segment that breaks both DNA strands within the binding site.Currently available methods for generating ZFNs are either inefficient or involve constructing and analyzing huge libraries of zinc-finger peptides, a task that exceeds the capabilities of all but a handful of laboratories in the world.
First author Morgan L. Maeder of the Joung lab led an effort by researchers from six institutions that demonstrated how this new method (termed OPEN for Oligomerized Pool ENgineering) can rapidly generate ZFNs that induce alterations at sites in three biologically important human genes and a plant gene.ZFNs made by the new OPEN method – which utilizes a new archive of reagents that will be made publicly available by the Zinc Finger Consortium – were so efficient that they could modify as many as four copies of a gene in human cells and two copies in plant cells.
“Our study provides the first evidence that ZFNs can make specific changes in plant genes with high efficiency and opens a new avenue for plant genetic modification,” says Daniel Voytas, PhD, of the University of Minnesota, whose lab conducted the plant cell experiments.Recently relocated from IowaStateUniversity, Voytas and his team are interested in modifying plant genes for crop improvement.
"With the development of OPEN, many more academic labs will be able to construct, test and use ZFNs in their biological research projects,” adds Joung.“OPEN should also stimulate additional research into the potential application of ZFNs for gene therapy of single-gene disorders, such as sickle cell anemia and cystic fibrosis.” Joung’s lab has already begun to explore ways to further simplify the OPEN method so that it can be performed more quickly and for a larger number of gene targets at once.He is an assistant Professor of Pathology at HarvardMedicalSchool and director of the Molecular Pathology Unit at MGH.
The Joung and Voytas teams worked jointly with labs from ChariteMedicalSchool in Berlin, the University of Iowa, Iowa State University, and the University of Texas Southwestern Medical Center to develop and validate this new technology.The participating teams are members of the Zinc Finger Consortium, an international group of investigators committed to the development of engineered zinc-finger nuclease technology.
The study was supported by organizations including the National Institutes of Health, the National Science Foundation, the Cystic Fibrosis Foundation, the European Commission’s 6th Framework Programme, and the Roy Carver Charitable Trust.
Massachusetts GeneralHospital, established in 1811, is the original and largest teaching hospital of HarvardMedicalSchool. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
The University of Minnesota’s AcademicHealthCenter is home to six health professional schools and colleges as well as several health-related centers and institutes. Founded in 1851, the University of Minnesota is one of the oldest and largest land grant institutions in the country. The AcademicHealthCenter prepares the new health professionals who improve the health of communities, discover and deliver new treatments and cures, and strengthen the health economy.
Carnegie Mellon Scientists Unveil New Tool To Understand Evolution of Multi-Domain Genes
--Results Herald New Way To Understand, Exploit Key Proteins in Cancer--
PITTSBURGH—Carnegie Mellon scientists have discovered critical flaws in the standard method used to analyze gene evolution. Standard methods fail when applied to genes that encode multi-domain proteins, an important class of proteins crucial to human health. Computational biologist Dannie Durand and colleagues have for the first time tackled the dilemma of how to study the ancestry of multi-domain genes.
Correctly identifying gene ancestry is a linchpin of computational genomics. Genes passed down from a common ancestor tend to perform similar functions in the cell. Scientists exploit this similarity to perform tasks such as predicting gene function, mapping human chromosomal regions to corresponding regions in model organisms, and reconstructing the regulatory circuitry that turns genes on and off.
Although computational biologists have developed methods to identify genes that share a common ancestor, current methods often lead to spurious conclusions when applied genes encode multi-domain proteins. Domains are sequence fragments that encode the basic building blocks of protein structure. Evolution makes new genes by mixing and matching domains in novel combinations, much like a child who builds a house, a car and a helicopter from the same LEGO kit by combining LEGO blocks in different ways. This process, called domain shuffling, creates complex proteins that perform specific, critical tasks such as cell communication and binding to other cells. When one of these proteins fails, cancer is often the result. Domain shuffling allows rapid evolution of new proteins, but it also makes it close to impossible for scientists to determine their ancestry.
In a paper published online in Public Library of Science Computational Biology today (May 16), Durand's team presents a novel method to determine whether a pair of similar genes evolved from a common ancestor, or whether they just look similar because the same domain was inserted into both genes. Their method, called "Neighborhood Correlation," is the first to tackle this problem.
"We needed a completely new approach to determine which multi-domain proteins share a common ancestor, and we are the first group to propose such a method," Durand said. "Ours is the first approach to define and analyze common ancestry in a traditional vertical way, even when domain shuffling occurs."
Neighborhood Correlation exploits the structure of a statistically weighted sequence similarity network to differentiate multi-domain genes with shared ancestries from multi-domain genes that result from domain shuffling. Gene duplication creates a specific signature in the network, while domain insertion creates a different characteristic signature. Neighborhood Correlation captures these signatures, giving pairs that arose through duplication, and hence share common ancestry, a higher score than genes that share an inserted domain, but not a common ancestor.
The Carnegie Mellon scientists tested Neighborhood Correlation against 20 protein families - including Kinases, the largest multi-domain family found in humans - whose ancestral relationships are well established through lab-based research. The tool worked remarkably well in verifying the ancestral patterns of multi-domain gene evolution for these families, much better than the tools we use today, Durand said.
Today's computational tools use sequence similarity, assuming that genes with similar sequences indicate common ancestry. Those methods also use the length of the similar region to rule out similarity that arose due to inserted domains. They reason that the longer the sequence shared by two multi-domain genes, the more likely that those two genes share a common ancestor.
But Durand's tests showed that this assumption often does not hold. Her team found disturbing results when they compared sequence similarity to their Neighborhood Correlation method in evaluating the 20 gene families with established histories. The sequence similarity method actually yielded false ancestral associations and missed true ancestral relationships.
Neighborhood Correlation is successful because it takes both gene duplication and domain insertion into account. "Not only do we show that Neighborhood Correlation works empirically, we also provide a sound evolutionary argument as to why it should work," Durand observed. "Our results show that the organization of sequence similarity network contains evidence of ancient evolutionary processes. This has exciting implications for future studies. We hope that comparing the sequence similarity networks of different species will reveal how evolutionary processes differ in plants, animals and fungi," Durand said. "Multicellularity evolved independently in each of those groups. To go from a single cell to many cells acting together, each time nature had to solve the same problems of cellular communication and control. But are the solutions the same in each lineage? How those problems were solved is a fascinating question."
Although designed for multi-domain families, Durand notes that Neighborhood Correlation also accurately predicts ancestry in single domain sequences. The researchers hope that scientists will begin to apply the analysis to genomic studies to better understand the role multi-domain proteins play in important evolutionary events, such as the emergence of multicellular animals and the vertebrate immune system.
Other study authors include Carnegie Mellon's Nan Song, Jacob Joseph and George Davis. Team members are affiliated with the Ray and StephanieLaneCenter for Computational Biology, the Department of Biological Sciences and the School of Computer Science. The study was funded by the National Science Foundation, the National Institutes of Health, and the David and Lucille Packard Foundation.
MCS maintains innovative research and educational programs in biological sciences, chemistry, physics, mathematics, and several interdisciplinary areas. For more information about Durand's research, visit http://www.cmu.edu/bio/contacts/faculty/durand.shtml.
deCODE Genetics and Merck Scientists Publish Major Mechanism Through which Genetic Factors Contribute to Obesity and Other Common Diseases
--Gene expression analysis of adipose tissue from some 1700 Icelandic participants in obesity research cohorts—
Reykjavik, ICELAND, March 16, 2008 – In a paper published online in the journal Nature, a team of deCODE scientists detail a major mechanism through which genetic factors contribute to major public health problems. In its work on the inherited components of dozens of common diseases, deCODE has discovered gene variants that significantly affect individual susceptibility or protection against disease. In the common forms of these conditions – such as obesity, type 2 diabetes and cardiovascular diseases – deCODE has previously shown that genetic variants confer increased or decreased risk by upregulating or downregulating the activity of major biological pathways. As a result, these variants place individuals on a spectrum of risk, with most of the population clustered at roughly average risk and a smaller number of people at either significantly higher or lower risk.
In the Nature paper, the deCODE team and collaborators from Merck demonstrate one of the principal ways in which the activity of biological pathways is functionally perturbed in a quintessentially complex condition: obesity. Through analysis ofadipose tissue from some 1700 Icelandic participants in obesity research cohorts, the deCODE team showed in data derived from primary human tissue that variations in gene expression – in the up-regulation or downregulation of how genes are translated into proteins – have a major impact on several parameters of clinical obesity. The deCODE team then used its unique resources for genome-wide linkage and association analysis to demonstrate that variability in gene expression, like overall risk for disease, has a significant inherited component that can be linked to specific versions of genetic markers. The paper, “Genetics of gene expression and its effect on disease,” is published on Nature’s website, www.nature.com, and will appear in a subsequent print edition of the journal.
“One of the observations we have made in our work on the isolation of disease genes is that the genetic risk of common diseases is often conferred by variations in the sequence of the genome that affect expression of genes. Hence, one of the ways to approach the study of common diseases is through the analysis of gene expression. This paper provides a substantial contribution towards the understanding of gene expression in man and one example of how it can be used to expand our knowledge of one disease, namely obesity,” said Kari Stefansson, CEO of deCODE.
About deCODE
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of drugs and diagnostics 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. deCODE is also leveraging its expertise in human genetics and integrated drug discovery and development capabilities to offer innovative products and services in personal genome analysis, DNA-based diagnostics, bioinformatics, genotyping, structural biology, drug discovery and clinical development. deCODE is delivering on the promise of the new genetics. 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.
Source: deCODE Press Release
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deCode Genetics Launches A DNA-Based Test Named deCODE PrCa™,For Assessing Risk Of Prostate Cancer
-New risk variants will also be folded into deCODEme™- -Another Step Towards Personalized Medicine-
Reykjavik, ICELAND- deCODE genetics announced the launch of deCODE PrCa™, a reference laboratory test for common, single-letter variations in the human genome (SNPs) that the company has associated with increased risk of prostate cancer. deCODE believes the test will be useful for better predicting risk of prostate cancer, helping to optimize both screening and treatment. deCODE PrCa™ detects a total of six previously discovered SNPs that have been confirmed in many populations, as well as two SNPs on chromosomes X and 2 that are reported by deCODE scientists in a paper published today in the online edition of Nature Genetics. Although most of the variants individually confer moderate risk, they are common and some are linked to more than less aggressive disease. Consequently, a substantial proportion of men have many risk variants that together confer clinically significant risk. Because of these variants, 10% of men are at twice the risk and 1% of men are at three times the risk of the disease in the general population.
"Through deCODE PrCa™, we are bringing together in one tool all of the major genetic risk factors for prostate cancer that we have discovered over the past eighteen months. We believe that this is a test with significant clinical utility for improving and personalizing the screening and treatment of one of the most common cancers. At the same time, we will integrate today’s discovery into the prostate cancer module in our personal genome analysis service deCODEme™, enabling our subscribers to stay abreast of how the latest discoveries in human genetics may relate to their genome,” said Kari Stefansson, CEO of deCODE.
Today's discovery is a result of the genome-wide analysis of over 300,000 SNPs in 23,000 Icelanders in deCODE’s prostate cancer studies, a finding subsequently replicated in a total of over 15,500 individuals from seven different cohorts from Europe and the United States. One of the SNPs is located on the X chromosome and the other SNP is located on chromosome 2p15 and is associated with a more aggressive form of prostate cancer. The paper, ‘Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer,’ can be found at www.nature.com/ng . deCODE PrCa™ is the latest in a series of reference laboratory DNA-based tests for assessing risk of and improving prevention and treatment for common diseases.
deCODE gratefully acknowledges the participation of the Icelandic patients and control subjects in its prostate cancer programs, as well as the patients and researchers from 15 academic medical centers in Europe and the United States who took part in the replication of the discovery published today.
How to order deCODE PrCa™
deCODE PrCa™ is performed in deCODE’s Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, and must be authorized by a qualified physician. If you are an individual who would like more information on deCODE PrCa™ to discuss with your doctor, or a physician interested in learning more about deCODE PrCa™ for your patients, please visit us at www.decodediagnostics.com .
About deCODE
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of drugs and diagnostics 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-certified laboratory, deCODE is offering a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; and deCODE PrCa™ for prostate cancer. 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.
Source: decode Genetics Press Release
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ROCKVILLE, MD—January 24, 2008—A team of 17 researchers at the J. Craig Venter Institute (JCVI) has created the largest man-made DNA structure by synthesizing and assembling the 582,970 base pair genome of a bacterium, Mycoplasma genitalium JCVI-1.0. This work, published online in the journal Science by Dan Gibson, Ph.D., et al, is the second of three key steps toward the team’s goal of creating a fully synthetic organism. In the next step, which is ongoing at the JCVI, the team will attempt to create a living bacterial cell based entirely on the synthetically made genome.
The team achieved this technical feat by chemically making DNA fragments in the lab and developing new methods for the assembly and reproduction of the DNA segments. After several years of work perfecting chemical assembly, the team found they could use homologous recombination (a process that cells use to repair damage to their chromosomes) in the yeast Saccharomyces cerevisiae to rapidly build the entire bacterial chromosome from large subassemblies.
“This extraordinary accomplishment is a technological marvel that was only made possible because of the unique and accomplished JCVI team,” said J. Craig Venter, Ph.D., President and Founder of JCVI. “Ham Smith, Clyde Hutchison, Dan Gibson, Gwyn Benders, and the others on this team dedicated the last several years to designing and perfecting new methods and techniques that we believe will become widely used to advance the field of synthetic genomics.”
The building blocks of DNA—adenine (A), guanine (G), cytosine (C) and thymine (T) are not easy chemicals to artificially synthesize into chromosomes. As the strands of DNA get longer they get increasingly brittle, making them more difficult to work with. Prior to today’s publication the largest synthesized DNA contained only 32,000 base pairs. Thus, building a synthetic version of the genome of the bacteria M. genitalium genome that has more than 580,000 base pairs presented a formidable challenge. However, the JCVI team has expertise in many technical areas and a keen biological understanding of several species of mycoplasmas.
“When we started this work several years ago, we knew it was going to be difficult because we were treading into unknown territory,” said Hamilton Smith, M.D., senior author on the publication. “Through dedicated teamwork we have shown that building large genomes is now feasible and scalable so that important applications such as biofuels can be developed.”
Methods for Creating the Synthetic M. genitalium
The process to synthesize and assemble the synthetic version of the M. genitalium chromosome began first by resequencing the native M. genitalium genome to ensure that the team was starting with an error free sequence. After obtaining this correct version of the native genome, the team specially designed fragments of chemically synthesized DNA to build 101 “cassettes” of 5,000 to 7,000 base pairs of genetic code. As a measure to differentiate the synthetic genome versus the native genome, the team created “watermarks” in the synthetic genome. These are short inserted or substituted sequences that encode information not typically found in nature. Other changes the team made to the synthetic genome included disrupting a gene to block infectivity. To obtain the cassettes the JCVI team worked primarily with the DNA synthesis company Blue Heron Technology, as well as DNA 2.0 and GENEART.
From here, the team devised a five stage assembly process where the cassettes were joined together in subassemblies to make larger and larger pieces that would eventually be combined to build the whole synthetic M. genitalium genome. In the first step, sets of four cassettes were joined to create 25 subassemblies, each about 24,000 base pairs (24kb). These 24kb fragments were cloned into the bacterium Escherichia coli to produce sufficient DNA for the next steps, and for DNA sequence validation.
The next step involved combining three 24kb fragments together to create 8 assembled blocks, each about 72,000 base pairs. These 1/8th fragments of the whole genome were again cloned into E. coli for DNA production and DNA sequencing. Step three involved combining two 1/8th fragments together to produce large fragments approximately 144,000 base pairs or 1/4th of the whole genome.
At this stage the team could not obtain half genome clones in E. coli, so the team experimented with yeast and found that it tolerated the large foreign DNA molecules well, and that they were able to assemble the fragments together by homologous recombination. This process was used to assemble the last cassettes, from 1/4 genome fragments to the final genome of more than 580,000 base pairs. The final chromosome was again sequenced in order to validate the complete accurate chemical structure.
The synthetic M. genitalium has a molecular weight of 360,110 kilodaltons (kDa). Printed in 10 point font, the letters of the M. genitalium JCVI-1.0 genome span 147 pages.
“This is an exciting advance for our team and the field. However, we continue to work toward the ultimate goal of inserting the synthetic chromosome into a cell and booting it up to create the first synthetic organism,” said Dan Gibson, lead author.
The research to create the synthetic M. genitalium JCVI-1.0 was funded by Synthetic Genomics, Inc.
Background/Key Milestones in JCVI’s Synthetic Genomics Research
The work described by Gibson et al. has its genesis in research by Dr. Venter and colleagues in the mid-1990s after sequencing M. genitalium and beginning work on the minimal genome project. This area of research, trying to understand the minimal genetic components necessary to sustain life, began with M. genitalium because it is a bacterium with the smallest genome that we know of that can be grown in pure culture. That work was published in the journal Science in 1995.
In 2003 Drs. Venter, Smith and Hutchison (along with JCVI's Cynthia Andrews-Pfannkoch) made the first significant strides in the development of a synthetic genome by their work in assembling the 5,386 base pair bacteriophage ΦX174 (phi X). They did so using short, single strands of synthetically produced, commercially available DNA (known as oligonucleotides) and using an adaptation of polymerase chain reaction (PCR), known as polymerase cycle assembly (PCA), to build the phi X genome. The team produced the synthetic phi X in just 14 days.
In June 2007 another major advance was achieved when JCVI researchers led by Carole Lartigue, Ph.D., announced the results of work on genome transplantation methods allowing them to transform one type of bacteria into another type dictated by the transplanted chromosome. The work was published in the journal Science, and outlined the methods and techniques used to change one bacterial species, Mycoplasma capricolum, into another, Mycoplasma mycoides Large Colony (LC), by replacing one organism’s genome with the other one’s genome.
Genome transplantation was the first essential enabling step in the field of synthetic genomics as it is a key mechanism by which chemically synthesized chromosomes can be activated into viable living cells. Today’s announcement of the successful synthesis of the M. genitalium genome is the second step leading to the next experiments to transplant a fully synthetic bacterial chromosome into a living organism and “boot up” the cell.
Ethical Considerations
Since the beginning of the quest to understand and build a synthetic genome, Dr. Venter and his team have been concerned with the societal issues surrounding the work. In 1995 while the team was doing the research on the minimal genome, the work underwent significant ethical review by a panel of experts at the University of Pennsylvania (Cho et al, Science December 1999:Vol. 286. no. 5447, pp. 2087 – 2090). The bioethical group's independent deliberations, published at the same time as the scientific minimal genome research, resulted in a unanimous decision that there were no strong ethical reasons why the work should not continue as long as the scientists involved continued to engage public discussion.
Dr. Venter and the team at JCVI continue to work with bioethicists, outside policy groups, legislative members and staff, and the public to encourage discussion and understanding about the societal implications of their work and the field of synthetic genomics generally. As such, the JCVI’s policy team, along with the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT), were funded by a grant from the Alfred P. Sloan Foundation for a 20-month study that explored the risks and benefits of this emerging technology, as well as possible safeguards to prevent abuse, including bioterrorism. After several workshops and public sessions the group published a report in October 2007 outlining options for the field and its researchers.
About the J. Craig Venter Institute
The JCVI is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org.
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Dr.J Craig Venter’s Lecture on BBC One -Presented as the Annual Richard Dimbleby Lecture On Dec 4th, 2007
The text of the lecture follows:
Thank you for the kind introduction. It is a great honor to be presenting the 2007 Dimbleby Lecture as only the third American, and one of just a handful of scientists out of the 32 Dimbleby Lectures.
I have called this lecture A DNA-Driven World, because I believe that the future of our society relies at least in part on our understanding of biology and the molecules of life - DNA. Every era is defined by its technologies. The last century could be termed the nuclear age, and I propose that the century ahead will be fundamentally shaped by advances in biology and my field of genomics, which is the study of the complete genetic make-up of a species.
Our planet is facing almost insurmountable problems, problems that governments on their own clearly can't fix. In order to survive, we need a scientifically literate society willing and able to embrace change - because our ability to provide life's essentials of food, water, shelter and energy for an expanding human population will require major advances in science and technology.
In this lecture I will argue that the future of life depends not only in our ability to understand and use DNA, but also, perhaps in creating new synthetic life forms, that is, life which is forged not by Darwinian evolution but created by human intelligence.
To some this may be troubling, but part of the problem we face with scientific advancement, is the fear of the unknown - fear that often leads to rejection.Science is a topic which can cause people to turn off their brains. I contend that science has failed to excite more people for at least two reasons: it is frequently taught poorly, often as rote memorization of complex facts and data, and it is antithetical to our visceral-driven way we live and interact with our world.
As a young student I was very turned off by the forced memorization of seemingly trivial facts which were, I felt, at the expense of true understanding. Instead I was much more interested in discovering and living in my world - I caught frogs and snakes, built boats and explored my surroundings.
In the past, science and the world used to seem easier to understand when discovery was based directly on our human senses. For example, when Darwin visited the Galapagos on his epic voyage he was able to see with his own eyes the flightless cormorants, the giant tortoises and the swimming and diving iguanas. From this sensory experience, he was able then to relate what he saw in the Galapagos to his other observations and develop a new context for understanding life by proposing the theory of evolution.
When Galileo developed the telescope, the wonders of the skies were truly illuminated for humans by expanding the capabilities of our visual system. Scientists have continued to extend our vision to glimpse distance galaxies that are not even faint stars in the sky to our naked eyes. Microscopes have helped us see further into the inner world of biology, first to cells then to molecules, all advances taking us well beyond our own physiological capabilities.
Our ability to see, hear, smell, taste, and feel the world around us are wonderful evolutionary developments upon which we base our daily lives. We can recognize and respond to the minor facial differences in how the 6.5 billion of us on Earth appear, but also to minute changes in facial expression indicating astonishment, pleasure, fear, love, and hate. We devote a substantial amount of modern human existence and our economy, appealing to our love of visual and audio stimulation.
In addition to our obvious senses, we have other remarkable capabilities that most of us are not aware of, but affect our lives from minute to minute. For example, while we cannot see, taste or feel carbon dioxide, we are extraordinarily sensitive to minute changes of CO2 concentrations in our bodies. It is carbon dioxide not oxygen that controls our breathing.
But as science has advanced, it has gone far beyond the immediately sensed world. It is now a world filled with dark matter in space, x-rays, gamma-rays, ultra violet light, DNA, genes, chromosomes, and bacteria that live in and around us in staggering numbers. We can't detect these directly, yet we feel the consequences of all of them. We are also now bombarded by information on wars, acts of terror, climate change and global warming, devastating storms, fuel shortages, emerging infections, flu pandemics, HIV, stem cells, animal cloning, genetically modified plants, and now the possibility of synthetic life forms, all while trying to cope with complexities of our daily lives. It is no great surprise then that there is a global resurgence of fundamentalism, a desire to get back to what appeared to be a simpler time, and a time when our primary senses and simple rules appeared to determine our life outcomes.
But I believe such a view is both simplistic and dangerous because it avoids the issues we need to face.Our planet is in crisis, and we need to mobilise all of our intellectual forces to save it. One solution could lie in building a scientifically literate society in order to survive.
While we share most of our senses with the rest of the animal world, we have a most unique and exciting evolutionary development - our brain. It provides us the ability to think, to reason, to predict and ponder the future. It enables us to ask questions and gives us the extraordinary capability to take over our own evolution by building complex tools that extend human capabilities millions of times further than would happen even with another billion years of evolution.
To begin the process of change we need to start with our children by teaching them in place of memorization, to explore, challenge, and problem solve in an attempt to understand the world around them, and most especially the world they cannot "see" or feel directly. Perhaps, we can also start by changing the way we teach science in our schools.
Many studies continue to relay sobering facts about the state of our science and math education in both the United States and the United Kingdom. A recent study compared math and science scores of 12 to 13-year-olds from each US state to their counterparts in both the developed and developing world. While it conveyed some good information, namely that the US and UK are doing better than in previous years, it still showed that compared to countries such as Singapore, Taiwan, Japan and China even the best US states and England still lag behind. The good news for England however, is that you've outperformed the US in science scores. This might be due in part to the fact that half of all US citizens believe that humans coexisted with dinosaurs, or the 25% who don't know the Earth revolves around the sun, and the 58% who cannot calculate a 10% tip on a restaurant bill. With this poor state of basic knowledge, how can we hope to survive the ever growing complexities of modern life?
This lack of knowledge is only part of the issue. In the US only 16% of all post-secondary education degrees are in math, science, or engineering, compared to 52% for China. And unfortunately those numbers are not all that different in the UK. If science and engineering are not national and global priorities how can we expect to cope with the complexities ahead and/or compete with nations that do value science?
So what can we do to change this situation? One solution could be new teaching methods aimed at exciting students about discovery.
I did not get excited about science until after I was drafted into the military during the Vietnam War and ended up in the medical corps. It was only there in the chaos of war that I learned firsthand that knowledge had real life and death consequences. While I went on to pursue a career in science after serving in Vietnam, I wish that my interest in science had been stimulated much sooner. We now know that to motivate students, particularly girls, for careers in science we need to capture their attention early.
At the Venter Institute we have developed a mobile genomics laboratory to bring the science of genomics to 12 and 13-year-olds to expose these students to scientific problem solving and the excitement of science. We started out with the simple idea of outfitting a large bus as a research laboratory, and then, working with schools, we developed learning modules taught by very enthusiastic and hands-on teachers. The results have been overwhelming. While many were at first skeptical of the program, because it was new and different from the standard lesson plans, we now have a waiting list for participants and we have constant calls and emails from parents and teachers who want the bus to come to their schools.
I think this program succeeds, because in each lesson plan we convey the wonderment of discovery and problem solving. For example, one lesson involves solving a crime scene investigation using DNA analysis much like is done in a popular TV program CSI. Had I been exposed to science in this real world manner I might have had a much better educational experience and at an earlier stage forged a stronger interest in science.
There are also science intensive schools that are trying alternative teaching methods. One such school in Virginia is teaching students to be more like scientists - to use inquiry-based learning and encouraging them to do experiments they designed themselves rather than age-old text book experiments and lessons heavy on memorization. These students are learning what I learned on my own while doing research as an advanced university student: that there is no greater intellectual joy than asking seemingly simple questions about life, then designing an experiment to find answers and uncovering a never before known discovery. We need generations of children who are grounded in reality and who learn evidenced-based decision making as a life-long philosophy. Teaching science as evidence-based decision making could have a profound impact on the pace of future discoveries and inventions. Simply asking what is the evidence behind any claim is a marked contrast to approaching life only upon a faith-based system.
Fostering such scientific literacy is crucial, because we and our planet are facing problems that, I believe, can only be solved by scientific advancement.There are those who like to believe that the future of life on Earth will continue as it has in the past, but unfortunately for humanity, the natural world around us does not care what we believe. But believing that we can do something to change our situation using our knowledge can very much affect the environment in which we live.
Perhaps an even greater problem than scientific literacy, is that almost every aspect of our modern society is geared toward only dealing with problems after they have occurred, rather than focusing on prevention. We have a visceral response to tragedies, to wars, floods, disease, and famine because we can see the problem and see the need to correct it. A much more difficult approach for societies is to use our intellectual capacity to understand the possibility of preventing wars by not invading countries but using diplomacy, or repairing infrastructure before bridges and dams fail, or preventing diseases by changing our diet.
Medicine and health care are areas that desperately need to move toward a preventive philosophy. We need to understand that it is far more cost effective, with better life outcomes to prevent diseases rather than treat them after they occur.
The cost of health care is one of the fastest growing expenses. In 2005 total US health expenditures rose 6.9% - twice the rate of inflation. Total spending was a staggering $2trillion. US health care spending is expected to increase at similar levels for the next decade reaching $4trillion in 2015. That's 20% of GDP. But all this money does not seem to guarantee the highest quality health care. The World Health Organization in 2000 ranked the US health care system as 1st by expenditure but only 72nd on health. In contrast the UK was 26th by total expenditures and 24th on health.
If we take a look at the cost burden of just one disease, diabetes, the figures are astounding. Diabetes is a disease that when poorly managed leads to serious complications such as heart disease, stroke, blindness, kidney failure, and nerve disease.
According to the US Centers for Disease Control, the total cost of diabetes to US society is $132billion each year. The average annual health care costs for a person with diabetes, is over five times that of someone without the disease. In the UK it is estimated that 9% of the annual NHS budget or over £5.2billion goes to diabetes care. Many studies have shown that simple preventive measures such as a healthier diet and moderate exercise such as walking can lead to dramatic reductions in the rate of disease onset and can eliminate or greatly reduce the incidence of complications.
Preventative medicine is the only way forward that I see for lowering the cost of health care other than the unacceptable approach of denying access. One of the keys to preventative medicine will be an understanding of our genetic risk for future diseases along with a greater understanding of the corresponding environmental influences of disease.
Just three months ago in September, we published the first complete human genome sequence and now it is available to all on the internet. The human genome comprises all the genetic information that we inherit from both of our parents in the form of 46 chromosomes, 23 from each parent. Chromosomes are in turn long stretches of DNA which is composed of four different chemical letters known simply as A, T, C and G. Our genome has six billion of these genetic letters. The genome we published contained both sets of chromosomes from each of my parents. I say my parents because it was my own genome that was sequenced and published.
I chose to decode my DNA because in the complex debate concerning deterministic views of genetic outcomes and the fears that many have voiced about revealing all their genetic secrets. I as a leader in this field, wanted to show that we don't have to fear our genetic information. Our genetic code is not deterministic and will provide us very few yes-no answers. It will, however, provide probabilities concerning outcomes that we will eventually be able to influence. It seemed far better to me to use my own genome, rather than trying to convince anyone else that it was ok for them.
One of the more exciting findings from our study is that any two humans differ from each other by about 1-2%, not the 0.1% that we thought was the case when we sequenced the first draft of the human genome earlier in the decade. This data is much more comforting as it is clear to me that we are all much more individualistic than previously thought. One of the key questions that I frequently get asked is what have I learned from my genome and is there information that I can do something about?
Let me give you a few examples to illustrate some of what I have found. For example, like many people, I reach for my inhaler in smoggy conditions. Genetics contributes to this susceptibility and researchers have focused on a certain family of enzymes that help detoxify everything from carcinogens to pharmaceuticals. There is a gene that is associated with the ability to degrade environmental toxins, however nearly half of the Caucasian population lacks that gene. In my own genome I found only one copy that I received from one parent and none from the other, so perhaps that is why I am more susceptible to environmental toxins.
As a depressing bonus, given its detoxifying role, this genetic deficiency may make me more susceptible to particular chemical carcinogens, and there is an association with lung and colorectal cancers.
From my genome I also became aware of genes that confirmed my increased risk for heart disease. The most common cause of heart disease is atherosclerosis, in which calcium, along with fats and cholesterol, collects in the blood vessels to form plaques, which can trigger a heart attack or stroke. One gene called APO E is responsible for regulating levels of certain fats in the bloodstream. Variants here have been linked with heart disease and also to Alzheimer's disease. Both of these could be in the cards for me. Fortunately, by reading my own genome, I have a chance to overcome my genetics by making changes in my diet and exercise. I am also taking a statin, a fat-lowering drug, as part of my preventative medicine paradigm. Statins also shows some hints of prevention of Alzheimer's disease.
Hundreds more genes are linked with coronary disease, from heart attacks to high blood pressure and narrowing of blood vessels. My genome carries lower risk versions of some genes and higher risks versions of others, but it will take time for us to understand the complicated way they interact with each other and how to predict a true risk profile.
However, one genetic change that probably lowers my risk for a heart attack is associated with my body's ability to rapidly metabolize caffeine. I drink many cups of coffee per day but fortunately, I carry the rapid metabolizing version of the gene. Some genes only become harmful in combination with a certain lifestyle - drinking coffee, tea or other drinks with caffeine. Some individuals carry a mutation that slows down caffeine metabolism and, as a result, increases an individuals' risk of having a heart attack on drinking tea or coffee. A study of around 4,000 people showed that the risk of heart attack increased 64% with four or more cups of coffee per day, compared with patients who drank less than one cup per day. However, the corresponding risk was less than 1% for individuals, who like me, had two copies of a rapid metabolizing version of the gene. These genetic differences may explain why many studies looking at the association between caffeine consumption and heart attack risk have been inconclusive, because we are not genetically identical and do not all respond in the same way.
These are just a handful of illustrations that hint at the type of information that will be possible for all of us in the near future.At my institute we are now scaling up to sequence the genomes from 10,000 people. This will provide a massive and powerful database, particularly when linked with clinical records and life outcomes. At that stage, we will have a much clearer view of the genetic basis of humanity.
I feel that new laws are needed to prevent an individual's genetic code from being used as a basis of discrimination in education, employment or access to health care. The genetic code will give us probabilities about disease risk and the ability to understand environmental factors linked to genetics. Will governments, businesses and insurance companies pay the smaller amount in advance to prevent disease? Or will we be locked into the current system of treating only what we can see?
Being an optimist I believe that we can ultimately solve the health care issue. But the fundamental problem facing our planet - that of climate change - is one that is far more grave. In fact, unless we tackle this head on, health care could be the least of our worries.
There has been much debate about climate change perhaps because we cannot see carbon dioxide when we exhale, or when we burn oil and coal to heat our homes, or use petrol to power our cars or fly planes. We do, however, have scientific instruments that can accurately measure what we humans produce and the increasing amount of carbon that we are adding to our environment.
The data is irrefutable - carbon dioxide concentrations have been steadily increasing in our atmosphere as a result of human activity since the earliest measurements began. We know that on the order of 4.1 billion tons of carbon are being added to and staying in our atmosphere each year. We know that burning fossil fuels and deforestation are the principal contributors to the increasing carbon dioxide concentrations in our atmosphere. We know that increasing CO2 concentrations has the same effect as the glass walls and roof of a greenhouse. It lets the energy from the sun easily penetrate but limits its escape, hence the term greenhouse gas.
Observational and modeling studies have confirmed the association of increasing CO2 concentrations with the change in average global temperatures over the last 120 years. Between 1906 and 2005 the average global temperature has increased 0.74 degrees C. This may not seem like very much, but it can have profound effects on the strength of storms and the survival of species including coral reefs.
Eleven of the last 12 years rank among the warmest years since 1850. While no one knows for certain the consequences of this continuing unchecked warming, some have argued it could result in catastrophic changes, such as the disruption of the Gulf Steam which keeps the UK out of the ice age or even the possibility of the Greenland ice sheet sliding into the Atlantic Ocean. Whether or not these devastating changes occur, we are conducting a dangerous experiment with our planet. One we need to stop.
The developed world including the United States, England and Europe contribute disproportionately to the environmental carbon, but the developing world is rapidly catching up. As the world population increases from 6.5 billion people to 9 billion over the next 45 years and countries like India and China continue to industrialise, some estimates indicate that we will be adding over 20 billion tons of carbon a year to the atmosphere. Continued greenhouse gas emissions at or above current rates would cause further warming and induce many changes to the global climate that could be more extreme than those observed to date. This means we can expect more climate change, more ice cap melts, rising sea levels, warmer oceans and therefore greater storms, as well as more droughts and floods, all which compromise food and fresh water production.
The increase in population coupled with climate change will tax every aspect of our lives. In a world already struggling to keep up with demand, will we be able to provide the basics of food, clean water, shelter and fuel to these new citizens of Earth? And will governments be able to cope with new emerging infections, storms, wildfires, and global conflicts?
So is there any way of avoiding these apocalyptic visions of the future coming true? Many have argued that we simply need to conserve, to alter and regress our standard of living and block the industrialization of developing countries. In my view this is extremely naive thinking. Furthermore, even the most optimistic models on climate change show a dramatically altered planet Earth going forward even if we embrace all alternative options such as wind and solar energy, and electric cars. Our entire world economy and the ability of modern society to provide life's basics, depend on the very industrialization that contributes to our possible demise.
Yet, sadly, very little thinking, planning or projections about how to cope with the carbon problem and climate change have taken into account the capabilities of modern science to produce what we have long needed to help solve these global threats.
It is clear to me that we need more approaches and creative solutions. We need new disruptive ideas and technologies to solve these critical global issues. This is where, I believe, biology and genomics, come in.
Wikipedia defines a disruptive technology or disruptive innovation as "a technological innovation, product, or service that eventually overturns the existing dominant technology or status quo product in the market." Well known examples of disruptive innovations include: telephones replacing telegraphs, cell phones replacing land lines, automobiles replacing horses and carriages and digital photography over film. We are clearly in need of a multitude of disruptive inventions to change our approach to energy and the challenges ahead of us.
Creating new technology is something my team and I have some familiarity with. When we joined the race to sequence the human genome in 1998 we did so with a completely new and relatively untried technique. I was called many things - audacious, arrogant, rebellious, and maverick - but the most flattering would have been disruptive. Few people thought our method would work but we proved them wrong. And within two years the first draft of the human genome was laid out for all to see.
Since then the field has advanced beyond all expectation. Utilising biology we have the ability to address every area of our lives - from medical treatment, to renewable sources of fuels. Plastics, carpets, clothing, medicines, and motor oil - all of these things can be created by biological organisms, and in an environmentally sustainable manner.
The pedantic argument concerning future inventions is how can we count on new technologies that don't yet exist? Some can look at the past and see no change for the future, while others will extrapolate forward in a liner manner. However, there are some fields where predicting and counting on exponential change has become reasonable and reliable. For example, Gordon Moore, a founder of the computer chip giant Intel, predicted that the density of transistors on integrated circuits would double every 2 years, a prediction that became referred to as Moore's Law. This rough rule of exponential change has now been applied to the electronics industry as a whole and specifically to computer memory and digital cameras. There is another version, called Butter's Law of Photonics. This law predicts that data transmission over optical fibers will double every nine months, and as a result, the cost of transmitting data decreases by half every nine months. We see the results of these predictions in ever faster, smaller and cheaper computers and faster data transmission which is probably a good thing as digital cameras with small memory cards exceed the capacity of computers on the market just barely a decade ago.
This kind of exponential growth is what has happened with our human population. It required close to 100,000 years for the human population to reach 1 billion people on Earth in 1804. In 1960 the world population passed 3 billion and now we are likely to go from 6.5 billion to 9 billion over the next 45 years. I was born in 1946 when there were only about 2.4 billion of us on the planet, today there are almost three people for each one of us in 1946 and there will soon be four.
If such predictions of exponential change have come true for the electronics industry, and the population, then isn't it possible the same could hold true for changing education, medicine, replacing the petrochemical industry, and saving the environment?
Similar exponential growth is seen in genomics - a term that did not even exist prior to the Eighties. While the initial discoveries came slowly, they were followed by an ever increasing pace of change. For example, in 1955 Fred Sanger at Cambridge determined the sequence of the protein insulin. It was the first protein to be sequenced in history. Twenty-one years later in 1976 and 1977 the first two viral genomes were decoded. However, it would be 18 more years in 1995 when my team used disruptive techniques to decode the first genome of a living organism, Haemophilus influenzae, a bacterium that causes ear infections and meningitis in children. This genome has 1.8 million letters of genetic code making it 300 times the size of the first viral genomes.
Armed with this new method only 5 years later, we increased the scale of what we did by 100 times by determining the first insect genome, the fruit fly, which had 180 million letters of genetic code. We followed this one year later with the 3 billion base pair haploid human genome which was equivalent to over 600,000 viral genomes and over 1,600 bacterial genomes.
So over a short period of time genome projects, which 10 years ago required several years to complete, now take only days. Within 5 years it will be common place to have your own genome sequenced. Something that just a decade ago required billions of pounds and was considered a monumental achievement. Our ability to read the genetic code is changing even faster than changes predicted by Moore's Law.
Using genomics has also rapidly accelerated the discovery of new species. Earlier this year from my institute's Sorcerer II Expedition, which included a sailing circumnavigation on my 95 foot yacht, Sorcerer II, we applied the tools we developed for decoding the human genome and used them to decode the DNA of the world's oceans. We published a single scientific paper describing over 6 million new genes. This one study more than doubled the number of genes known to the scientific community and the number is likely to double again in the next year.
We are now using similar approaches to identify the microbes that live inside of us. We have identified more microbes in our guts than the 100 trillion human cells we have in our bodies. We have also catalogued the tens of thousands of microbes and viruses that are in the air we breathe.
These modern tools of genomics and DNA sequencing are rapidly revealing to us the incredible world of microbes that we exist within and exist within us.Young students of science can today make more discoveries in one year than major institutions or countries could make in a decade just a short while ago.
So, what is the value of these discoveries? The answer is many things but one of the most important is a better understanding of life and its evolution on Earth. And what can we do with all this new information that is coming at an exponential pace? We can use these millions of newly discovered organisms and genes to tell us how the environment is changing as a result of human activities.
But above all I believe the best examples of disruptive technologies that could change our future are in the new fields of synthetic biology, synthetic genomics, and metabolic engineering. These fields can change the way we think about life by showing that we can use living systems to increase our chances of survival as a species. Simply put: this area of research will enable us to create new fuels to replace oil and coal.
Imagine scientists in the near future sitting at their computers and designing the chromosome of a new organism, an organism that perhaps could produce fuels biologically, fuels like octane, diesel fuel, jet fuel even hydrogen all from sugar or even sunlight with the carbon coming from carbon dioxide.
Imagine that after designing the new chromosome, the computer directed a robot to chemically make the DNA strand encoding all that information, and that once constructed, the new chromosome would be inserted into a bacterial cell where it becomes activated causing the cell to turn into the species that the scientist designed. And now imagine that new species in a bio-reactor making millions of copies of itself and each copy is producing a new fuel from only renewable sources. Sounds like science fiction right? Not to me, because I believe this is the future.
For the past 15 years at ever faster rates we have been digitising biology. By that I mean going from the analog world of biology through DNA sequencing into the digital world of the computer. I also refer to this as reading the genetic code. The human genome is perhaps the best example of digitising biology. Our computer databases are growing faster per day then during the first 10 years of DNA sequencing. The databases have been filling even faster with the results of our global ocean sequencing project. As a result we have now over 10 million genes in the public databases, the majority of which have been contributed by my teams.
We and others have been working for the past several years on the ability to go from reading the genetic code to learning how to write it. It is now possible to design in the computer and then chemically make in the laboratory, very large DNA molecules. A few months ago we published a scientific study in the journal Science where we described the ability to take a chromosome from one bacterium and place it into a second bacterial cell. The result was astonishing - the new DNA that we added changed the species completely from the original one into the species defined by the added DNA. You could describe this as the ultimate in identity theft.
Again, maybe this sounds like science fiction, but I think it is actually a key mechanism of evolution, that could be largely responsible for the wide range of diversity that we see. Instead of evolution happening only due to random mutations that survived selective pressure, we can see how by adding chromosomes to or exchanged between species, that thousands of changes could happen in an instant.
Now they can happen not just by random chance but by deliberate human design and selection. Human thought and design and specific selection is now replacing Darwinian evolution.
One of the most significant and unique features of our research in synthetic genomics that often gets overlooked by the news media, is the long history, starting from the beginning of this work in 1995 and continuing today, of ethical review. As with the past 30 years of molecular biology, the organisms being designed cannot survive outside of the laboratory and are subject to strict containment. While we don't want students doing this work in their basements, this new field is stimulating an exciting new interest in biological studies.
Right now extensively modified bacteria are being used to make food additives and industrial chemicals. DuPont has a plant in the US state of Tennessee with four very large silos where they are using metabolically engineered bacteria to convert sugar into a new polymer, propanediol which is the key component in their stain resistant carpets and clothing. Several teams, including my own, are modifying bacteria to make the next generation biofuels. For example, my team has a new fuel chemical made from sugars as a starting material that has the potential to be one of the first green jet fuels.
But we don't always have to modify bacteria or design new ones. What has occurred on Earth from Darwinian evolution is pretty amazing in that the unique metabolism of these microbial powerhouses can often provide exactly what we need. For instance, we have a team at my institute headed by Ken Nealson that has developed microbial fuel cells using naturally occurring bacteria. These organisms can process human and animal waste to produce electricity and or clean water.
At my company Synthetic Genomics, we have a major program underway in collaboration with BP to see if we can use naturally occurring microbes to metabolise coal into methane which can then be harvested as natural gas. While not a renewable source of carbon, it could provide as much as a 10 fold improvement over mining and burning coal. We also have organisms that can convert CO2 into methane thereby providing a renewable source of fuel.
The biggest question in my mind is the one of scale. Last year we consumed more than 83 million barrels of oil per day or 30 billion barrels during the year. In addition we used over 3 billion tons of coal. These are mind boggling numbers and the only way that I can see replacing oil and coal is through a widely distributed system. If there were one million bio-refineries around the globe each one would still need to produce 17,000 liters per day. For the UK my vision would entail thousands of bio-refineries distributed around the country near where the fuel would be consumed and where the starting raw material such as cellulose would be available. On a global scale there will be millions of new fuel producers perhaps favoring the agricultural rich developing world. This could be the ultimate disruptive model by changing the entire infrastructure for energy production and consumption and helping us toward a carbon neutral world.
In closing:
It is my hope that we can embrace, not fear, the necessary science to help our planet. I feel it is imperative that we begin to find ways to adapt to climate change, while at the same time working to mitigate it. Unfortunately we are already on a path toward significant change, but if we apply ourselves I believe we can find ways to create alternatives to burning oil and coal. We need multiple simultaneous approaches to solve this problem, with the goal of net zero carbon emissions to stabilize atmospheric concentrations and ensure our survival. These are massive challenges for each and every one of us. For our children's future and for the future of our species and our planet I hope that we can rise to the challenge.
Thank you very much.
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Reykjavik, ICELAND---deCODE genetics announced the launch of deCODEme™, a pioneering service that enables individuals to get a detailed look at their own genome.
Through your subscription to deCODEme™, you can learn what your DNA says about your ancestry, your body --traits such as hair and eye color-- as well as whether you may have genetic variants that have been associated with higher or lower than average risk of a range of common diseases. This information will be continually updated as new discoveries are made.
Subscribers will create a secure password-controlled personal account. Just a few weeks after sending in a simple cheek swab, customers will receive expert analysis of more than a million key variants across their genome, accessible through an easy-to-use and intuitive user interface.
With deCODEme™, your DNA is in the hands of a global leader in human genetics. In more than a decade of pioneering research, deCODE has analyzed the genomes of hundreds of thousands of people from around the world, developing an unrivalled track record in gene discovery, in systems for genetic analysis, as well as data and privacy protection. deCODEme™ puts this expertise to work for you. The introductory promotional price of a subscription to deCODEme is $985. Starting today, deCODEme™ is accepting subscription orders and we will be soliciting feedback from these first customers to optimize the service experience. To learn more about deCODEme™ and how to order, visit www.deCODEme.com, and watch the webcast announcement today at 9AM am EST through deCODE’s website, www.decode.com.
“We are pleased to announce the launch of this ground breaking service. Just a few short years after the first completed sequencing of a human genome in 2003, it is now possible to analyze on a single computer chip a large proportion of all of the variations in the genome that make each and every one of us unique. Your genome is yours to discover. In an era when we are encouraged to take greater personal control of our lifestyle and health, we believe we should all have the opportunity to learn what our own genome can tell us about ourselves," said Kari Stefansson, MD, PhD, CEO of deCODE. "You have the opportunity to take advantage of the best that science has to offer when you learn about disease risks associated with your genetic variations and ancestry with deCODEme™ and you have the opportunity to engage in a fun and interesting exchange when you compare your results to those of your friends. This service is about you, and so we will integrate the feedback that we get from our first subscribers to continue to optimize it, to make deCODEme™ what you want it to be. We invite you to learn more about the service and yourself."
deCODEme™ – It’s all about you
deCODEme™ is a unique way to get to know yourself better -- from the inside out. Our genomes are more than 99% identical, but in that one percent are millions of tiny variations that make you unique. Through deCODEme™ you can take steps toward learning how your genome makes you unique, in the context of cutting edge science and in ways that are both fascinating and informative. You can learn about your ancestry, about obvious and potentially quirky traits, and whether you have certain genetic variations that are known to be associated with an above or below average risk of certain common diseases. You can even decide with family and friends to compare genomes and discover which blocks of DNA code you share. As new discoveries are made, you will receive updates and be able to check your genome against the breakthroughs in the headlines.
When you open your deCODEme™ account you create your own username and password and have full control of information and data comparison with your friends and family. You can even create an anonymous account if you wish. And if you have questions, you can consult with our experts at no additional cost. Best of all, you have the peace of mind of knowing that deCODEme™ is offered by deCODE genetics – a proven leader in the field.When your DNA comes to us, our expert staff analyze it and post it to a secure web portal right here at deCODE. Neither your sample nor any of your data will be accessible to or shared with anyone but you and those that you designate.
About decode
deCODE genetics (Nasdaq:DCGN) is a global leader in applying human genetics to develop drugs and diagnostics for common diseases. Our population approach has enabled us to discover and target key biological pathways involved in conditions ranging from heart attack to cancer. We are turning these discoveries into new medicine to better treat and prevent many of the biggest challenges to public health. deCODE is delivering on the promise of the new genetics SM. Visit us on the web at www.decode.com, and on our diagnostics site at www.decodediagnostics.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.These risks and uncertainties include, among others, those relating to technology and product development, integration of acquired businesses, market acceptance, government regulation and regulatory approval processes, intellectual property rights and litigation, dependence on collaborative relationships, ability to obtain financing, competitive products, industry trends and other risks identified in deCODE’s filings with the Securities and Exchange Commission.deCODEundertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.
The deCODEme services are being offered by deCODE's Icelandic subsidiary, deCODE genetics ehf.
A Policy Report on Synthetic Genomics : by J. Craig Venter Institute (JCVI), the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT)
October , 2007—Policy experts from the J. Craig Venter Institute (JCVI), the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT) announced the release of a report, “Synthetic Genomics: Options for Governance,” which outlines areas for interventions and policy options to help mitigate potential risks with this promising area of research. The report, funded by a grant from the Alfred P. Sloan Foundation, resulted from 20 months of in-depth study, review and analysis by the teams above and a core group of 14 experts.
Synthetic genomics is a field of research in which scientists use chemically created pieces of DNA (called oligonucleotides or oligos) to design and assemble chromosomes, parts of chromosomes, genes and gene pathways. Scientists foresee many potential positive applications including new pharmaceuticals and biologically produced, green fuels. However, as with many technologies, there is the potential for misuse and accidents.
The core group set out to analyze the state of the technology in synthetic genomics and to develop a comprehensive set of options for policy makers, researchers, and companies in the field. The report includes options that help to enhance biosecurity, foster laboratory safety, and protect the communities and environment outside of laboratories.
“Designing ways to impede malicious uses of the technology while at the same time not impeding, or even promoting beneficial ones, poses a number of policy challenges for all who wish to use or benefit from synthetic genomics” said Michele Garfinkel, policy analyst at JCVI and lead author of the report. Gerald Epstein, of the CSIS Homeland Security Program and a co-author on the report added, “We have formulated governance options that attempt to reduce security- and safety risks without imposing undue burdens on researchers, industry, or government.”
In addition to Garfinkel and Epstein, the core group was led by Robert M. Friedman of JCVI and Drew Endy of MIT, and convened a series of workshops to hear directly from synthetic genomics researchers, commercial suppliers of synthesized DNA, policy analysts who focus on bioterrorism issues, and those who focus on the legal, ethical, and societal implications of biotechnology. After these workshops, the group developed a preliminary report and offered this for discussion and input at a public meeting held in Washington, DC for policymakers, the media, non-governmental groups and scientists. These interested parties were also invited to submit comments to the authors for potential inclusion into the final report.
The group identified three areas for policy intervention and outlined policy options for each intervention point. Drew Endy noted, “Our report draws upon the perspectives of many different stakeholders, including developers and users of DNA synthesis technology, as well as the biosecurity community. We hope that our efforts will help ongoing discussions of the responsible use of synthetic genomics techniques and tools.”
The first set of options applies to firms that supply synthetic DNA, both those that supply gene- and genome length strands of DNA and those that supply much shorter oligonucleotides. This set includes the option, for example, that firms must use special software to screen orders for potentially harmful DNA.
The second set of options is aimed at the oversight or regulation of DNA synthesizers and reagents used in synthesis. For example, owners of DNA synthesizers might be required to register their machines, or that licenses might be required in order to purchase specific chemicals needed to synthesize DNA.
The final set of options is aimed exclusively at legitimate users of synthetic genomics technologies. The options cover both the education of users (e.g., modules in university courses that explicitly discuss the risks and best practices when using these new technologies) and prior review of experiments (for example, expanding the roles of institutional biosafety committees to review a broader range of “risky” experiments).
For more information about the report and to download a copy, please visit
The JCVI is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org.
Center for Strategic & International Studies
CSIS is an independent, nonpartisan policy research organization. It has provided world leaders with strategic insights on—and practical policy solutions to—current and emerging global issues for over 40 years. The Center has extensive experience examining issues at the intersection of science and security, analyzing and mitigating terrorist threats, and combating weapons of mass destruction. The CSIS staff includes more than 120 analysts working to address the changing dynamics of international security and economics. http://www.csis.org
Massachusetts Institute of Technology
MIT is an educational and research university located in Cambridge, Massachusetts. The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the 21st century. Its five schools and one college encompass 34 academic departments, divisions, and degree-granting programs, as well as numerous interdisciplinary centers, laboratories, and programs whose work cuts across traditional departmental boundaries. http://web.mit.edu/
Alfred P. Sloan Foundation
Alfred P. Sloan Foundation, a philanthropic nonprofit institution, was established in 1934 by Alfred Pritchard Sloan, Jr., then president and chief executive officer of the General Motors Corporation. The Foundation makes grants in science, technology and the quality of American life. The Foundation's bioterrorism program promotes plans and practices that citizens and organizations can use to defend themselves against terrorism and also supports efforts to monitor dangerous research in the life sciences. http://www.sloan.org
Source: JCVI Institute Press Release
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PERSONAL GENOME SEQUENCING PROJECTS: JAMES WATSON AND CRAIG VENTER
e-published on MedicineandBiotech.com, October 1st, 2007
When the Human Genome Project started, it was anticipated that it would take 15 years to sequence the 3 billion base pairs and identify all the genes. It was completed in 13 years in 2003 – coinciding with the 50th anniversary of the publication of the work of Dr. James Watson and Dr. Francis Crick that described the DNA double helix.
In May 2007, 454 Life Sciences Corporation, in collaboration with scientists at the Human Genome Sequencing Center, Baylor College of Medicine presented James Watson a DVD containing his personal genome – a project completed in only two months! This was followed by the publication of the personal genome of Craig Venter, President of the J. Craig Venter Institute in September, 2007. The personal genome of Craig Venter is published in the journal PLoS at http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050254
The mapping of Dr. Watson’s genome was completed using the Genome Sequencer FLX™ system developed by 454 Life Sciences Corporation and marks the first individual genome to be sequenced for less than $1 million.
The sequencing of Dr. Watson’s genome validates the approach taken by 454 Life Sciences in developing a technology that makes sequencing of individual human genomes quick and affordable. This is another step by 454 Life Sciences on the path towards the $10 million Archon X Prize for Genomics and reducing the cost of human genome sequencing to $10,000. This is a hope towards a new era of medicine that is tailored to a patient's unique genetic profile.
The sequencing of Dr. Watson’s genome has been done on production Genome Sequencer FLX™ systems, which took advantage of the instrument’s high quality data and long read lengths. Using the unbiased 454 Sequencing™ technology, a near complete picture of Dr. Watson's genome was obtained and the missing pieces of the public reference genome generated by the Human Genome Project were identified. 454 Life Sciences is now acquired by Roche.
Researchers at the J. Craig Venter Institute (JCVI), along with collaborators at The Hospital for Sick Children (Sick Kids) in Toronto and the University of California, San Diego (UCSD), have published a genome sequence of J. Craig Venter that covers both of his chromosome pairs (or diploid genome), one set being inherited from each of his parents.
The other versions of the human genome currently include—one published in 2001 by Dr. Venter and colleagues at Celera Genomics, and another at the same time by a consortium of government and foundation-funded researchers. The first sequence and analysis of the human genome was published in Science in 2001 by Dr. Venter and colleagues at Celera Genomics. The publicly funded genome project also published their version of the human genome at the same time in the journal Nature. These genomes were not of any single individual, but rather were a mosaic of DNA sequences from various donors. In the case of Celera it was a consensus assembly from five individuals, while the publicly-funded version was based on patching together sequences from over 100 anonymous human sources. Both versions greatly underestimated human genetic diversity.
This new genome (called “HuRef”) represents the first time a true diploid genome from one individual—Dr. Venter, has been published. The research is available in the open access public journal, PLoS Biology. With this publication, Craig Venter’s team has shown that human to human variation is five to seven-fold greater than earlier estimates proving that we are in fact more unique at the individual genetic level than we thought.
For the HuRef project, the team at JCVI used a more traditional method of sequencing—whole genome shotgun assembly which is built upon Sanger dideoxy sequencing. Then, Applied Biosystems 3730xl high-throughput DNA sequencing machines were employed since these methods still produce the longest and most accurate lengths of DNA.
Within the human genome there are several different kinds of DNA variants. The most studied type is single nucleotide polymorphisms or SNPs, which are thought to be the essential variants implicated in human traits and disease susceptibility. A total of 4.1 million variants covering 12.3 million base pairs of DNA were uncovered in this analysis of Dr. Venter’s genome. Of the 4.1 million variations between chromosome sets, 3.2 million were SNPs. This is a typical number expected to be found in any other human genome, but there were at least 1.2 million variants that had not been described before. Surprisingly, nearly one million were different kinds of variants including: insertion/deletions (“indels”), copy number variants, block substitutions and segmental duplications.
While the SNP events outnumbered the non-SNP variants, the latter class involved a larger portion (74%) of the variable component of Dr. Venter's genome. This data suggests that human-to-human variation is much greater than the 0.1% difference found in earlier genome sequencing projects. The new estimate based on this data is that genomes between individuals have at least 0.5% total genetic variation (or are 99.5% similar) The researchers suggest that much more research needs to be done on these non-SNP variants to better understand their role in individual genomics.
Another important feature that is made possible by having an individual, diploid genome is the ability to generate more informed haplotype assemblies. Haplotypes are groups of linked variations along the chromosomes. Other studies have generated many common haplotypes, however these are based on averages of large populations rather than individuals. Individual haplotypes enable scientists to study rare or 'private' variants that might explain and help predict traits and diseases in that particular person—allowing an individualized approach in genomic applications.
In the HuRef analysis, the team used the heterozygous portion of the 4.1 million variant set and new algorithms to build haplotype assemblies. These haplotype assemblies were typically an order of magnitude larger than what can be achieved by genotyping a single individual, with over half the genome contained in segments greater than 200,000 base pairs in length. The JCVI researchers expect this number to improve significantly as additional sequence coverage is added to HuRef using a variety of new sequencing technologies.
With this type of knowledge now in hand, the stage is set for an era of personalized medicine where genome sequence information becomes a critical reference to assist with health-related decisions.
Assessing the Significance of Conserved Genomic Aberrations Using High Resolution Genomic Microarrays
Authors: Mitchell Guttman 1,2¤*, Carolyn Mies2, Katarzyna Dudycz-Sulicz2, Sharon J. Diskin3, Don A. Baldwin4, Christian J. Stoeckert Jr.1,5, Gregory R. Grant1,5
Citation: Guttman M, Mies C, Dudycz-Sulicz K, Diskin SJ, Baldwin DA, et al. (2007) Assessing the Significance of Conserved Genomic Aberrations Using High Resolution Genomic Microarrays. PLoS Genet 3(8): e143 doi:10.1371/journal.pgen.0030143
Genomic aberrations recurrent in a particular cancer type can be important prognostic markers for tumor progression. Typically in early tumorigenesis, cells incur a breakdown of the DNA replication machinery that results in an accumulation of genomic aberrations in the form of duplications, deletions, translocations, and other genomic alterations. Microarray methods allow for finer mapping of these aberrations than has previously been possible; however, data processing and analysis methods have not taken full advantage of this higher resolution. Attention has primarily been given to analysis on the single sample level, where multiple adjacent probes are necessarily used as replicates for the local region containing their target sequences. However, regions of concordant aberration can be short enough to be detected by only one, or very few, array elements. We describe a method called Multiple Sample Analysis for assessing the significance of concordant genomic aberrations across multiple experiments that does not require a-priori definition of aberration calls for each sample. If there are multiple samples, representing a class, then by exploiting the replication across samples our method can detect concordant aberrations at much higher resolution than can be derived from current single sample approaches. Additionally, this method provides a meaningful approach to addressing population-based questions such as determining important regions for a cancer subtype of interest or determining regions of copy number variation in a population. Multiple Sample Analysis also provides single sample aberration calls in the locations of significant concordance, producing high resolution calls per sample, in concordant regions. The approach is demonstrated on a dataset representing a challenging but important resource: breast tumors that have been formalin-fixed, paraffin-embedded, archived, and subsequently UV-laser capture microdissected and hybridized to two-channel BAC arrays using an amplification protocol. We demonstrate the accurate detection on simulated data, and on real datasets involving known regions of aberration within subtypes of breast cancer at a resolution consistent with that of the array. Similarly, we apply our method to previously published datasets, including a 250K SNP array, and verify known results as well as detect novel regions of concordant aberration. The algorithm has been fully implemented and tested and is freely available as a Java application at http://www.cbil.upenn.edu/MSA.
AUTHOR SUMMARY
Cancer is a genetic disease caused by genomic mutations that confer an increased ability to proliferate and survive in a specific environment. It is now known that many regions of genomic DNA are deleted or amplified in specific cancer types. These aberrations are believed to occur randomly in the genome. If these aberrations overlap more than would be expected by chance across individual occurrences of the cancer this suggests a selective pressure on this aberration. These conserved aberrations likely represent regions that are important for the development, progression, and survival of a specific cancer type in its environment. We present a method for identifying these conserved aberrations within a class of samples. The applications for this method include accurate high resolution mapping of aberrations characteristic of cancer subtypes as well as other genetic diseases and determination of conserved copy number variations in the population. With the use of high resolution microarray methods we have profiled different tumor types. We have been able to create high resolution profiles of conserved aberrations in specific cancer types. These conserved aberrations are prime targets for cancer therapies and many of these regions have already been used to develop effective cancer therapeutics.
INTRODUCTION
In cancer cells, aberrations can turn on or off various pathways necessary for tumor development and survival [1]. Array comparative genomic hybridization (aCGH) is a highly parallel microarray-based method for detecting DNA copy number aberrations. aCGH detects genomic aberrations at a higher resolution than previous methods including metaphase chromosome–based CGH ([2,3], reviewed in [4,5]), and has proven to be a powerful tool for determining genomic aberrations of interest in various cancer types [6–8]. Similarly, this technology is quickly becoming widely used to characterize the genomic aberrations in various genetic disorders ([9,10] reviewed in [11]).
The analysis of new high resolution CGH data has proven challenging because most of the technical issues present in microarray gene expression analysis are also present in aCGH, as well as some new CGH-specific challenges. The most fundamental problem is to transform raw microarray data into the most accurate copy-number calls at the highest resolution possible (see [12] for review). This is known as the single sample problem, and there have been numerous publications suggesting approaches to this problem, including hidden Markov models [13], Circular Binary Segmentation (CBS) [14], and wavelets [15]. The common theme of these methods is that they attempt to find aberrant segments in the genome by using neighboring probes as replicates to give evidence of aberration at proximal locations.
Such single sample approaches can significantly decrease the native resolution of the array and result in a loss of information because important aberrations can be short enough to be detected by only one, or very few, array elements. If only one array is being analyzed, or if one is interested in the aberrations that are unique to a given individual, then there is little choice but to use one of the single sample methods. However, when the goal is to find concordant aberrations across a class of samples, we can take a different approach. In the multiple sample case we can perform statistical tests for concordant signal across samples, for each array element individually. This allows multiple (class-specific) samples to provide replication for each array element individually, in order to control the error rates statistically. In this way, resolution can be as fine as the probe spacing allows. This approach allows for leveraging multiple samples to simultaneously increase the resolution and the power of the analysis. To date, few methods have attempted to address this multiple sample problem statistically [16–19].
1 Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 3 Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America, 4 Penn Microarray Facility, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 5 Department of Genetics. University of PennsylvaniaSchool of Medicine, Philadelphia, Pennsylvania, United States of America
* To whom correspondence should be addressed. E-mail: mguttman@mit.edu
¤ Current address: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
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The J. Craig Venter Institute to Aid Asiatic Centre for Genome Technology to Establish New Genomics Facility
---The program will also provide for in-depth training of Malaysian scientists on new tools and techniques of genomics---
Rockville, Maryland, U.S.A. And Kuala Lumpur, Malaysia—July 11 , 2007—The J. Craig Venter Institute (JCVI) announced an agreement with the Asiatic Centre for Genome Technology Sdn Bhd (ACGT), a center that focuses on the application of genome technology to improve oil palm and other crops, to help ACGT establish a new genomics research facility in Malaysia. The JCVI will also provide hands-on training for Malaysian scientists.
“As part of the Venter Institute’s mission to advance the science of genomics through education and training worldwide, we are excited to work with ACGT to build their new genomics facility,” explains J. Craig Venter, Ph.D., chairman and president of JCVI. “Genomics holds the key to solve so many worldwide issues including developing new sources of cleaner energy. Coupling our knowledge and expertise about genomics with ACGT’s expertise in the oil palm should enable the scientists of Malaysia to become leaders in this promising field.
Through the agreement JCVI will help ACGT establish a state-of-the-art genomics research facility, develop standard operating procedures, and will provide other technical assistance for the genomics center. In November 2006 ACGT was awarded the BioNexus Status by Malaysian Biotechnology Corporation Sdn Bhd (BiotechCorp), a government agency under the Ministry of Science, Technology and Innovation (MOSTI) set up to promote and accelerate the biotechnology industrial development in the country.
ACGT is led by Dr Cheah Suan Choo, a recognized Malaysian oil palm genomics expert who is credited as co-inventor of three patents on oil palm genes and genetic markers. ACGT established a laboratory at the TechnologyParkMalaysia in Kuala Lumpur early this month and has begun its research and development activities. ACGT is a wholly owned subsidiary of Asiatic Development Berhad, an oil palm plantation company listed on BursaMalaysia (Malaysian Stock Exchange) and a member of Genting Group.
“This collaboration is an international effort to create a platform for training and developing Malaysian scientists in the field of high-throughput genomic sequencing and bioinformatics,” said Tan Sri Lim Kok Thay, Chief Executive of Asiatic. “We are confident that the development of such expertise will expedite ACGT’s efforts to improve the productivity of oil palm and other crops.”
About the J. Craig Venter Institute
The J. Craig Venter Institute is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 500 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c) (3) organization. For additional information, please visit http://www.JCVI.org.
About Asiatic Development Berhad
Asiatic Development Berhad (“Asiatic”), a 55%-owned subsidiary of Genting Berhad, commenced its operations in 1980 as the plantation arm of the Genting Group. Over the years, the Asiatic Group had embarked on several significant acquisitions in Malaysia, thus increasing its land bank from a mere 13,700 hectares in 1980 to nearly 66,000 hectares currently. In line with its long term strategy, the Asiatic Group had, in June 2005, further expanded its operations to Indonesia, on a joint venture basis, to develop some 98,300 hectares. The Asiatic Group also owns 5 oil mills with a total milling capacity of 235 tonnes per hour and is reputed to be one of the lowest cost palm oil producers with fresh fruit bunches production of over one million tonnes. For more information, visit www.asiatic.com.my.
JCVI Scientists Publish First Bacterial Genome Transplantation Changing One Species to Another
----Research is important step in further advancing field of Synthetic Genomics----
ROCKVILLE, MD — June 28, 2007 — Researchers at the J. Craig Venter Institute (JCVI) announced the results of work on genome transplantation methods allowing them to transform one type of bacteria into another type dictated by the transplanted chromosome. The work, published online in the journal Science, by JCVI’s Carole Lartigue, Ph.D. and colleagues, outlines the methods and techniques used to change one bacterial species, Mycoplasma capricolum into another, Mycoplasma mycoides Large Colony (LC), by replacing one organism’s genome with the other one’s genome.
“The successful completion of this research is important because it is one of the key proof of principles in synthetic genomics that will allow us to realize the ultimate goal of creating a synthetic organism,” said J. Craig Venter, Ph.D., president and chairman, JCVI. “We are committed to this research as we believe that synthetic genomics holds great promise in helping to solve issues like climate change and in developing new sources of energy.”
Methods and techniques The JCVI team devised several key steps to enable the genome transplantation. First, an antibiotic selectable marker gene was added to the M. mycoides LC chromosome to allow for selection of living cells containing the transplanted chromosome. Then the team purified the DNA or chromosome from M. mycoides LC so that it was free from proteins (called naked DNA). This M. mycoides LC chromosome was then transplanted into the M. capricolum cells. After several rounds of cell division, the recipient M. capricolum chromosome disappeared having been replaced by the donor M. mycoides LC chromosome, and the M. capricolum cells took on all the phenotypic characteristics of M. mycoides LC cells.
As a test of the success of the genome transplantation, the team used two methods — 2D gel electrophoresis and protein sequencing, to prove that all the expressed proteins were now the ones coded for by the M. mycoides LC chromosome. Two sets of antibodies that bound specifically to cell surface proteins from each cell were reacted with transplant cells, to demonstrate that the membrane proteins switch to those dictated by the transplanted chromosome not the recipient cell chromosome. The new, transformed organisms show up as bright blue colonies in images of blots probed with M. mycoides LC specific antibody.
The group chose to work with these species of mycoplasmas for several reasons — the small genomes of these organisms which make them easier to work with, their lack of cell walls, and the team’s experience and expertise with mycoplasmas. The mycoplasmas used in the transplantation experiment are also relatively fast growing, allowing the team to ascertain success of the transplantation sooner than with other species of mycoplasmas.
According to Dr. Lartigue, “While we are excited by the results of our research, we are continuing to perfect and refine our techniques and methods as we move to the next phases and prepare to develop a fully synthetic chromosome.”
Genome transplantation is an essential enabling step in the field of synthetic genomics as it is a key mechanism by which chemically synthesized chromosomes can be activated into viable living cells. The ability to transfer the naked DNA isolated from one species into a second microbial species paves the way for next experiments to transplant a fully synthetic bacterial chromosome into a living organism and if successful, “boot up” the new entity. There are many important applications of synthetic genomics research including development of new energy sources and as means to produce pharmaceuticals, chemicals or textiles.
This research was funded by Synthetic Genomics Inc.
Background and Ethical Considerations The work described by Lartigue et al. has its genesis in research begun by Dr. Venter and colleagues in the mid-1990’s after sequencing Mycoplasma genitalium and beginning work on the minimal genome project. This area of research, trying to understand the minimal genetic components necessary to sustain life, underwent significant ethical review by a panel of experts at the University of Pennsylvania (Cho et al, Science December 1999:Vol. 286. no. 5447, pp. 2087 – 2090). The bioethical group's independent deliberations, published at the same time as the scientific minimal genome research, resulted in a unanimous decision that there were no strong ethical reasons why the work should not continue as long as the scientists involved continued to engage public discussion.
In 2003 Drs. Venter, Smith and Hutchison made the first significant strides in the development of a synthetic genome by their work in assembling the 5,386 base pair bacteriophage φX174 (phi X). They did so using short, single strands of synthetically produced, commercially available DNA (known as oligonucleotides) and using an adaptation of polymerase chain reaction (PCR), known as polymerase cycle assembly (PCA), to build the phi X genome. The team produced the synthetic phi X in just 14 days.
Dr. Venter and the team at JCVI continue to be concerned with the societal implications of their work and the field of synthetic genomics generally. As such, the Institute’s policy team, along with the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT), were funded by a grant from the Alfred P. Sloan Foundation for a 15-month study to explore the risks and benefits of this emerging technology, as well as possible safeguards to prevent abuse, including bioterrorism. After several workshops and public sessions the group is set to publish a report in summer 2007 outlining options for the field and its researchers.
About the J. Craig Venter Institute The J. Craig Venter Institute is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 500 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org.
The Voyage of the Sorcerer II Global Ocean Sampling (GOS) Expedition
More than Six Million New Genes, Thousands of New Protein Families, and Incredible Degree of Microbial Diversity Discovered from First Phase of Sorcerer II Global Ocean Sampling Expedition
Unprecedented amount of data deposited in CAMERA database; features enhanced tools to visualize and analyze metagenomic data
ROCKVILLE, MD—March 13, 2007— Researchers from the J. Craig Venter Institute (JCVI) announced the publication of several studies from the Sorcerer II Global Ocean Sampling Expedition (GOS) in PLoS Biology (www.plosbiology.org) detailing the discovery of millions of new genes, thousands of new protein families and specifically the characterization of thousands of new protein kinases from ocean microbes using whole environment shotgun sequencing and new computational tools. Researchers believe these data will lead to better understanding of key biological processes which could eventually offer new ideas for alternative energy production and could offer solutions to deal with climate change and other environmental issues.
The GOS dataset is 90-fold larger than other marine metagenomic datasets, thus making it the largest ever released in the public domain. The GOS analysis also nearly doubles the number of previously known proteins. This enormous amount of data allowed the researchers to better understand the genomic structure and evolution of microorganisms, as well as the function of important protein families such as protein kinases, which are key regulators of cellular function in all organisms. Although invisible to the naked eye, microbes make up the vast majority of life on the planet and are responsible for creation and maintenance of Earth’s atmosphere, it is important to understand the role and function of these organisms to ensure the survival of the planet and human life on it.
“This publication is not only providing an unprecedented level of new genes and protein family discoveries, but is also pivotal in that we have provided compelling analysis of evolution and function of these genes and proteins within the larger context of organisms interacting with their environment,” said J. Craig Venter, Ph.D., founder and chairman, the J. Craig Venter Institute. “Given the findings, it’s clear that we’ve only begun to scratch the surface of understanding the microbial world around us.”
The Sorcerer II Expedition began with a pilot project in 2003 in the Sargasso Sea near Bermuda in which more than one million new genes and hundreds of new photoreceptors were discovered in what was thought to be an area of low diversity. The GOS publication today is a result of ocean water sampling conducted from Halifax, Nova Scotia to the Eastern Tropical Pacific during the two year circumnavigation by the Sorcerer II Expedition. The Gordon and Betty Moore Foundation and the United States Department of Energy, Office of Science, funded the sequencing and analysis of the Expedition. The JCVI funded the operation of the vessel.
The group also announced today the launch of a new online database and high-speed computational resource, Community Cyberinfrastructure for Advanced Marine Microbial Ecology Research and Analysis (CAMERA). Funded by a grant from the Moore Foundation of $24.5 million over seven years, CAMERA was developed by the UC San Diego Division of the California Institute for Telecommunications and Information Technology (Calit2) in partnership with JCVI and UCSD’s Center for Earth Observations and Applications (CEOA) at Scripps Institution of Oceanography.
"The scale and complexity of the GOS data required Calit2 to architect a powerful new cyberinfrastructure to enable both interactive access as well as high performance computation on the data by the global metagenomic community, " said Larry Smarr, Calit2 director and principal investigator on CAMERA.
CAMERA houses metagenomic data and provides the advanced software tools and computer hardware to analyze these data. Using dedicated optical circuits, CAMERA permits scientists to connect their local laboratory computers directly to the CAMERA database and tools using the National LambdaRail or international optical circuits, resulting in up to a hundred-fold increase in bandwidth over current standards. CAMERA has been in beta testing since January 2007 and today is available to researchers worldwide. In addition to the CAMERA database, the GOS data is also being deposited in the U.S. National Institutes of Health’s public database, GenBank.
The GOS publication was a result of intensive analysis of these data by scientists from the JCVI along with collaborators at four University of California campuses (San Diego, Los Angeles, Berkeley and Davis), University of Southern California, Salk Institute for Biological Studies, Burnham Institute, University of Hawaii, Brown University, Universidad Nacional Autonoma de Mexico, Universidad de Costa Rica, Universidad de Concepcion, Bedford Institute of Oceanography, Smithsonian Tropical Research Institute, and Rutgers University.
PLoS Biology Publications: The Global Ocean Sampling (GOS) Expedition
The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Pacific
Rusch et al. describe the results of metagenomic analysis of 37 samples taken aboard Sorcerer II during its voyage between Halifax, Nova Scotia and French Polynesia in 2003 to 2004, combined with seven samples collected during the pilot study in the Sargasso Sea. To capture the DNA, scientists onboard the Sorcerer II collected water every 200 nautical miles and then filtered it through progressively smaller filters to collect bacteria and then viruses. The DNA extracted for these publications were from the filter that collects mostly bacteria.
The group analyzed a massive dataset consisting of 7.7 million DNA sequences totaling 6.3 billion base pairs. Following from the Sargasso Sea pilot study, they continued to find a great degree of diversity both within and across the sampling sites. Researchers identified 60 highly abundant ribotypes (roughly equivalent to species) however, the inter-species variation and the variation of organisms within the same environment suggests that while the microbes might be similar at an rRNA level they can differ greatly at a biochemical and genomic level.
While variation is known to be closely linked to environment, this all encompassing genetic survey has identified new and unexpected links between variation and the environment. For example, the class of proteins known as proteorhodopsins absorbs either blue or green light. This study revealed that the blue and green variants are found in different environments with blue light preferred in the open ocean and green light preferred in coastal environments. Identifying these associations should greatly enhance our understanding of marine systems and the environmental factors upon which they depend.
To handle the enormous volume of data generated from this phase of the Expedition, the team developed new computational methods to assemble and analyze these data. One comparative genomic method termed “fragment recruitment,” allowed researchers to look at genome structure, microbial evolution, and diversity on many levels. Another, “extreme assembly”, as the name implies, enabled researchers to assemble very large segments of DNA from the abundant but previously hard to analyze genomes of organisms. Finally, they developed a tool to assess the similarity between whole metagenome databases.
According to lead author Doug Rusch, Ph.D., computational scientist at the JCVI, “We know so little about the organisms in our environment mostly because we have lacked the genomic and computational tools for understanding and examining these organisms. We believe that this publication and the new tools we developed will help to unleash a new era of enhanced knowledge of the biological processes of microbial communities and this new understanding will begin to unlock the mysteries of unseen life.”
The Sorcerer II Global Ocean Sampling Expedition: Expanding the Universe of Protein Families
Characterization of microbial communities has been limited in the past by the difficulty in culturing organisms in the laboratory. With whole environment shotgun sequencing techniques, environments such as ocean microbial communities can now be better understood at the DNA and protein level.
Yooseph et al. report on the 6.12 million new proteins uncovered from 7.7 million GOS sequences by using a novel sequence clustering approach. This nearly doubles the number of known proteins. The researchers found that the GOS dataset covered almost all of the known prokaryote (bacterial and archaeal) protein families and that there were 1,700 totally unique large protein families in the GOS dataset, not matching any known families. A surprising number of the new protein families discovered are in viruses. Researchers were also able to match 6,000 previously unmatched sequences in current protein databases to proteins found in the GOS dataset.
Given the extraordinary rate of discovery of new proteins and protein families, the researchers conclude that there are likely many more protein families to be discovered both in microbes and viruses given the rate of discovery in this first phase of the GOS Expedition. The data also suggest that this is much more yet to be discovered about biological diversity of microbes.
The team also found that several protein domains (the conserved structural units in proteins) that were previously thought to exist only in one of the four kingdoms of life (bacteria, archaea, eukaryotes, viruses) have GOS examples in another kingdom. These kingdom-crossing families may be proteins whose lineages are more ancient than previously assumed or they may have arisen due to lateral gene transfers.
To assess the impact of the GOS data on known protein families, the team also investigated several protein families in detail. In addition to increasing substantially the size and diversity of these families, the GOS sequences increased the understanding of the evolution and function of these proteins.
One example is those that repair DNA damage due to UV light (photolyases). While sunlight has benefits to the microbes, like with humans, sunlight also has the potential to be harmful to cells exposed to it. The team discovered many new proteins that protect these organisms from UV ray damage and some that are involved in repairing UV damage. These proteins were found in all organisms in the dataset, even in viruses.
Another example is glutamine synthetase (GS), the protein that plays a key role in nitrogen metabolism. More than 9,000 GS or GS-like sequences were uncovered, with a large number of sequences of type II GS (one of the three GS types). This was unexpected because type II GS is associated more with eukaryotes, not bacteria and viruses, and not many eukaryotes are expected in the filters that were analyzed. The researchers theorize that this could be due to lateral gene transfer from eukaryotes, or more likely due to gene duplication before prokaryotes and eukaryotes diverged into two branches of life.
Shibu Yooseph, Ph.D., lead author and computational scientist at JCVI said, “The analysis we have done so far with this publication shows a tremendous diversity of organisms at the protein level and going forward, I think we will continue to see this tremendous amount of diversity. These data open up a whole new set of research efforts from a computational perspective in designing better tools to be able to deal with this sort of data, as well as making observations on evolution and how functions evolved for these protein families”
Structural and Functional Diversity of the Microbial Kinome
The availability of the GOS metagenomic data along with other large microbial genome data sets is enabling more research into specific kinds of protein families. Of particular interest to a wide variety of researchers are kinase families. Protein kinases are protein enzymes that regulate many of the most basic cellular functions in humans and other eukaryotes. They are key targets for cancer and other disease drug development.
Previously, it was thought that different families of kinases were responsible for these types of cell regulation in prokaryotes (bacteria) versus eukaryotes (animals and other non-bacteria). Eukaryote protein kinases (ePK) were most common in eukaryotes, histidine kinases in bacteria. However, in their PloS Biology publication Kennan et al. show that with the scope and diversity of the GOS data that ePK-like kinases (ELKs) are indeed very prevalent in bacteria, in fact, more so than histidine kinases. This finding is even shedding some light on human kinases.
The research team has shown that the ePK is just one family in a diverse superfamily of enzymes that all share a common protein kinase-like (PKL) fold (shape). Using sensitive profile methods, the researchers discovered more than 45,000 kinase sequences from the GOS and other public data sources and grouped these into 20 diverse families, of which ePKs were just one. The GOS data doubles the size of most PKL families and triples the number of known ePK-like kinases (ELK). Many of these families exhibited eukaryote-like structure and function of their proteins and thus the researchers conclude that several of these protein families existed before the divergence of the three domains of life.
The authors concluded this work shows the power of metagenomic data in allowing better understanding of any gene family and has opened the door to further research into the mechanisms of protein families and their function, structure and evolution.
About
JCVI The J. Craig Venter Institute is a not-for-profit research institute which through its two operating divisions, The Institute for Genomic Research (TIGR) and The Center for the Advancement of Genomics (TCAG) advances the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 500 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The JCVI is a 501 (c)(3) organization. For additional information, please visit www.jcvi.org
Moore Foundation The Gordon and Betty Moore Foundation, established in September 2000, works in collaboration with grantees and other partners to achieve significant and measurable outcomes in three areas: environmental conservation, science and the San Francisco Bay Area. In April 2004, the Foundation launched its 10-year Marine Microbiology Initiative, with the goal of attaining new knowledge regarding the composition, function and ecological role of microbial communities in the world’s oceans. www.moore.org
Calit2 The California Institute for Telecommunications and Information Technology, a partnership between UC San Diego and UC Irvine, houses over 1,000 researchers organized around more than 50 projects on the future of telecommunications and information technology and how these technologies will transform a range of applications important to the economy and citizens' quality of life. www.calit2.net
US Department of Energy Office of Science DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the nation, manages 10 world-class national laboratories, and builds and operates some of the nation's most advanced R&D user facilities. Its website address is www.science.doe.gov. DOE's Genomics: GTL program aims to use the department's unique computational capabilities and research facilities to understand the activities of single-cell organisms on three levels: the proteins and multi-molecular machines that perform most of the cell's work; the gene regulatory networks that control these processes; and microbial associations or communities in which groups of different microbes carry out fundamental functions in nature. Once researchers understand how life functions at the microbial level, they hope to use the capabilities of these organisms to help meet many of our national challenges in energy and the environment. The program will combine research in biology, engineering and computation with the development of novel facilities for high-throughput biology projects. More information on the department's genomics programs is on the Web at www.doegenomes.org.
PLoS Biology PLoS Biology is a peer-reviewed , open-access journal that features research articles of exceptional significance in all areas of biology. It is ranked in the top tier of life science journals by the Institute for Scientific Information (ISI) , with an impact factor of 14.7.
FDA Clears Breast Cancer Specific Molecular Prognostic Test
Feb 6, 2007. The U.S. Food and Drug Administration (FDA) today cleared for marketing a test that determines the likelihood of breast cancer returning within five to 10 years after a woman's initial cancer. It is the first cleared molecular test that profiles genetic activity.
The MammaPrint test uses the latest in molecular technology to predict whether existing cancer will metastasize (spread to other parts of a patient's body). The test relies on microarray analysis, a powerful tool for simultaneously studying the patterns of behavior of large numbers of genes in biological specimens.
The recurrence of cancer is partly dependent on the activation and suppression of certain genes located in the tumor. Prognostic tests like the MammaPrint can measure the activity of these genes, and thus help physicians understand their patients' odds of the cancer spreading.
MammaPrint was developed by Agendia, a laboratory located in Amsterdam, Netherlands, where the product has been on the market since 2005.
"Clearance of the MammaPrint test marks a step forward in the initiative to bring molecular-based medicine into current practice," said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs. "MammaPrint results will provide patients and physicians with more information about the prospects for the outcome of the disease. This information will support treatment decisions.
Agendia compared the genetic profiles of a large number of women suffering from breast cancer and identified a set of 70 genes whose activity confers information about the likelihood of tumor recurrence. The MammaPrint test measures the level of activity of each of these genes in a sample of a woman's surgically removed breast cancer tumor, then uses a specific formula, known as an algorithm, to produce a score that determines whether the patient is deemed low risk or high risk for spread of the cancer to another site. The result may help a doctor in planning appropriate follow-up for a patient when used with other clinical information and laboratory tests.
The MammaPrint is the first cleared in vitro diagnostic multivariate index assay (IVDMIA) device. Several months ago, FDA issued a draft guidance document concerning the need for these complex molecular tests to meet pre-market review and post-market device requirements even when the tests are developed and used by a single laboratory. Although FDA regulates diagnostic tests sold to laboratories, hospitals and physicians, it uses discretion when regulating tests developed and performed by single laboratories.
On February 8, FDA will hold a public meeting to discuss its draft guidance document describing its regulatory approach to this type of test.
"There have been rapid advances in microarrays and other pioneering diagnostics, and a corresponding increase in the use and impact of these complex tests. This has prompted FDA to take a closer look at the potential risks as well as the benefits associated with such tests when they are developed and used in laboratories," remarked Steven Gutman, M.D., Director, Office of In Vitro Diagnostic Device Evaluation. "This test clearance takes into account the development of these innovative technologies and ensures public health by carefully evaluating their performance."
Prior to clearance, FDA requested evidence that the MammaPrint had been properly validated for its intended use. Agendia submitted data from a study using tumor samples and clinical data from 302 patients at five European centers. These studies confirmed that the test was useful in predicting time to distant metastasis in women who are under age 61 and in the two earliest stages of the disease (Stage I and Stage II) and who have tumor size equal to or less than five centimeters and no evidence that the cancer has spread to nearby lymph nodes (lymph node negative). FDA plans to publish a special controls guidance document within the next 60 days describing types of data that should support claims for genetic profiling for breast cancer prognosis.
According to the American Cancer Society, an estimated 178,480 new cases of invasive breast cancer will be diagnosed among women in the United States this year and over 40,000 women are expected to die from the disease.
Source: FDA Press Release
Cancer and Genomics - Real time qRT-PCR as a reliable tool for gene-expression analysis
By Dr. Kent Persson, Ph.D. and Dr. Neerja Sethi, Ph.D., Astragen LLC
Human cancer is fundamentally a disease of the genome, resulting from accumulation of complex genetic changes in the genome, including chromosomal aberrations, inactivation of tumor suppressor genes, single nucleotide polymorphisms (SNPs), activation of cellular oncogenes or oncogenes introduced by exogenous infectious agents. Currently, there is an urgent need to develop technologies to accelerate the field of cancer genomics that have diagnostic and therapeutic applications in wide areas of cancer research. Each type of cancer has its characteristic aberrations in the genetic composition that result in alteration in gene expression levels. Since each cancer has its own molecular signature, the essential scientific goals are to develop high-throughput technologies that will allow us to catalog the genetic origins of malignancies for various cancers for improved detection, diagnosis and treatment.
SNPs. The mapping of the human genome has revealed that the extent of genetic variation is much larger than previously estimated (1,2). The most common sequence variation in the human genome is the stable substitution of a single base, the single-nucleotide polymorphism (SNP). SNPs arise because of point mutations that are selectively maintained in populations. Most SNPs are 'silent' and do not alter the function or expression of a gene. The total number of SNPs in the human genome is estimated to be more than 10 million (3).
Genomic instability has been characterized in many human cancers and its signature is the pattern of sequence deletions or rearrangements, frequently resulting in allelic imbalance. Until recently, efforts to capture global patterns of genomic imbalance have employed microsatellites, but the utility of dense SNP markers has been demonstrated in proof-of-principle studies. Global patterns of genomic imbalance can be detected by allelotyping of cancers, and point to regions where allelic imbalance could contribute to cancer. Since loss of heterozygosity (LOH) within one or more chromosomal region is a common form of allelic imbalance, sites of LOH can be investigated for the presence of tumor-suppressor genes. Studies in bladder, lung and prostate cancers have discovered previously unknown allelic imbalances in multiple sites using SNPs for LOH analysis (4,5 ). It is likely that patterns of LOH, through SNP analysis, could have diagnostic and prognostic implications. Specific LOH pattern could be correlated with expression array profiles to identify causal variants.
Biomarkers. As the age of genomics proceeds forward in search of genetic variants (i.e. SNPs) that influence disease susceptibility and outcome, a great effort has been directed at picking Biomarker genes as markers for cancer progression and as diagnostic tools. The candidate gene approach examines SNPs, chosen from genes that 'make sense' or Biomarkers for a disease. In other words, they fit a plausible understanding of the biology. SNPs can also be chosen from a region previously identified by linkage study or gene expression analysis. Intense effort has focused on Biomarkers that alter protein function or gene expression. It has been estimated that there are perhaps 50,000-250,000 SNPs which confer a biological effect, most of which are distributed in and around the 30,000 genes (6,7,8).
Pharmacogenomics. The accumulation of new information on various Biomarkers has propelled the field of Pharmacogenomics, which will bring about changes in the process of Drug Development. Genomics information will direct more personalized treatment regimens by identifying patients with genetic biomarkers who will be most likely to respond to a treatment and those who will respond adversely. Similarly, high-throughput genomic technologies will be increasingly used to identify Toxicology Biomarkers in Drug Development. Toxicology biomarkers will be crucial in identifying short-term and long-term genetic effects of drug-exposure. Currently, the use of Toxicology biomarkers is limited, but will play an important role in future clinical trials. The FDA is now encouraging Pharmaceutical industry to employ pharmacogenomics data in drug development to get a better understanding and reap the benefits of genomic analysis.
Real-time quantitative RT-PCR as a high-throughput tool for Biomarkers and Pharmacogenomics studies. qRT-PCR provides a powerful technique for examining alterations in gene expression from virtually any type of biological sample. The assay comes with many advantages (high sensitivity, reproducibility, no post-PCR steps required and capability of high throughput) which makes it an attractive tool for biotechnological research in molecular diagnostics, gene function and pharmacogenomics. Research and molecular diagnostics laboratories have been implementing qRT-PCR over several years and the technique is becoming increasingly popular. The assay can employ different real time chemistries suitable for a particular study and budgets. Fluorescent dyes represent an economical approach for gene expression analysis. This approach can easily accommodate high-throughput gene expression analysis. Different types of hybridization probe chemistries are more expensive than fluorescent dyes due to manufacturing costs. Similar to fluorescent dyes, the hybridization probes can accommodate high-through put analysis. In addition, this approach also allows for the option of multiplexing. Using adequate instrumentation and correctly designed assays, up to four genes can be multiplexed, which further increases the throughput.
Further, multiplexing allows for substantial sample savings which is beneficial when sample material is scarce. While the throughput for qRT-PCR is less than that of microarray based technologies, qRT-PCR offers currently unparalleled sensitivity in gene expression analysis, and this to a price affordable to most research facilities.
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Venter, J. C., Adams, M. D., Myers, E. W., et al. (2001) The sequence of the human genome Science 291, 1304-51.
Botstein, D. & Risch, N. (2003) Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease Nat Genet 33 Suppl, 228-37.
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Lindblad-Toh, K., Tanenbaum, D. M., Daly, M. J., et al. (2000) Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays Nat Biotechnol 18, 1001-5.
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Integrative Genomics
By Dr. Neerja Sethi, Ph.D., Managing Editor, Email: editor@medicineandbiotech.com
Volume 6. February 2005. In the post-genomic era, "Integrative Genomics" has become a buzz-word. Integrative Genomics has different definitions for different people. The healthcare and life-sciences industries prefer to call it the critical step towards "personalized medicine" where genomics is integrated into the whole process of drug discovery and clinical research. The concept of personalized medicine aims at tailor-made therapeutics that match an individuals genetic makeup. However, its important to understand that it may never reach the extent of "one individual-one target drug".
Integrative Genomics represents integration of different technology platforms, including genomics, proteomics, high-throughput cell biology and Bio-IT leading to biological and clinical research data-integration. Integrative genomics offers the prospect of understanding the pathology of a disease at an individuals genetic level and hence, allowing for target identification.
Integrative Genomics will enable better design of clinical trials and its potential and benefits are gaining support from the Food and Drug Administration (FDA). Drugs are tested during clinical trials in a sub-population that is perceived to be the representative target population. In reality, there is a vast genetic diversity in sub-populations, much more than previously anticipated. Genomics or Pharmacogenomics will enable identifying an appropriate clinical trial population, where a drug delivers optimum results. Currently a number of clinical trials are ongoing in which a specific gene targeted by the drug is known and characterized. However, the clinical trials design does not take it into account finding a specific population which has the right target allele for the drug. It is possible that patients with certain other genetic factors might react unfavorably to the drug. In the next five years, hopefully, such genomic parameters will be taken into consideration for the development of safe and effective drugs.
The concept of using an individuals genetic makeup as a factor in deciding therapeutic treatment is referred to as pharmacogenomics. Pharmacogenomics allows identification of genetic variances in patients causing either adverse or favorable reaction towards certain compounds. These genetic markers or biomarkers are commonly found as small changes in DNA sequences in different individuals and are called single nucleotide polymorphisms (SNPs).
In pursuit of personalized medicine, a study has been launched to characterize the genetic makeup of Asian populations by a collaborative effort of Asian scientists. The Pacific Pan-Asian SNP Initiative will study genetic variances of various Asian groups to identify why some clusters respond unfavorably to a drug or why some are more susceptible to certain diseases. This Project is conducted by the Human Genome Organization (HUGO).
The countries participating in this project are China, India, Indonesia, Japan, Singapore and South Korea, with about 3000 participants who will provide blood samples for this study. The study will start in mid-2005 and may take two years to complete. Affymetrix, based in Santa Clara, California, will co-sponsor the study by providing a new microarray technology that will enable 50,000 SNPs analysis in each person. Results from this study will be available in public databases for various studies for a wide group of researchers.
As a step towards personalized medicine, in November 2004, BiDil, a heart-failure drug developed by NitroMed (Lexington, MA), was shown to reduce death rates from heart diseases specifically in African-Americans. BiDil did not work effectively in the Caucasian populations. Approval of BiDil may be the first of its kind where a drug will be marketed for the use a specific race based on genetic factors responding to a particular drug.
We have to keep in mind that besides genetic factors, other factors like environmental differences, habits, access to medical care, etc. also play an important role in a treatment outcome. Nonetheless, detecting individual genetic differences has a great potential value in detecting and treating disease. Towards this goal, Integrative Genomics will improve the process of drug discovery and development leading to effective treatment outcomes.
New Initiative to Study Societal Issues Associated with Synthetic Biology -- A Rapidly Developing Field where Novel Organisms are Constructed from The Building Blocks of DNA
Discovery of Common Versions of Two Single-letter Variations in the Human Genome (SNPs) that Confer Risk of Basal Cell Carcinoma (BCC)-Most Common Form of Skin Cancer
Lead Author: Daniel G. Gibson, Ph.D., JCVI
