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Synthetic biologists have been creating the genomes of organisms such as viruses and bacteria for the past 15 years. They aim to use these designer genetic codes to make cells capable of producing novel therapeutics and fuels. Now, some of these scientists have set their sights on synthesizing the human genomea vastly more complex genetic blueprint. Read on to learn about this initiative, called Genome Project-write, and the challenges researchers will faceboth technical and ethicalto achieve success.

Nineteenth-century novels are typically fodder for literature conferences, not scientific gatherings. Still, at a high-profile meeting of about 200 synthetic biologists in May, one presenter highlighted Mary Shelleys gothic masterpiece Frankenstein, which turns 200 next year.

Frankensteins monster, after all, is what many people think of when the possibility of human genetic engineering is raised, said University of Pennsylvania ethicist and historian Jonathan Moreno. The initiative being discussed at the New York City meetingGenome Project-write (GP-write)has been dogged by worries over creating unnatural beings. True, part of GP-write aims to synthesize from scratch all 23 chromosomes of the human genome and insert them into cells in the lab. But proponents of the project say theyre focused on decreasing the cost of synthesizing and assembling large amounts of DNA rather than on creating designer babies.

The overall project is still under development, and the projects members have not yet agreed on a specific road map for moving forward. Its also unclear where funding will come from.

What the members of GP-write do agree on is that creating a human genome from scratch is a tremendous scientific and engineering challenge that will hinge on developing new methods for synthesizing and delivering DNA. They will also need to get better at designing large groups of genes that work together in a predictable way, not to mention making sure that even larger assembliesgenomescan function.

GP-write consortium members argue that these challenges are the very thing that should move scientists to pick up the DNA pen and turn from sequence readers to writers. They believe writing the entire human genome is the only way to truly understand how it works. Many researchers quoted Richard Feynman during the meeting in May. The statement What I cannot create, I do not understand was found on the famed physicists California Institute of Technology blackboard after his death. I want to know the rules that make a genome tick, said Jef Boeke, one of GP-writes four coleaders, at the meeting.

To that end, Boeke and other GP-write supporters say the initiative will spur the development of new technologies for designing genomes with software and for synthesizing DNA. In turn, being better at designing and assembling genomes will yield synthetic cells capable of producing valuable fuels and drugs more efficiently. And turning to human genome synthesis will enable new cell therapies and other medical advances.

In 2010, researchers at the Venter Institute, including Gibson, demonstrated that a bacterial cell controlled by a synthetic genome was able to reproduce. Colonies formed by it and its sibling resembled a pair of blue eyes.

Credit: Science

Genome writers have already synthesized a few complete genomes, all of them much less complex than the human genome. For instance, in 2002, researchers chemically synthesized a DNA-based equivalent of the poliovirus RNA genome, which is only about 7,500 bases long. They then showed that this DNA copy could be transcribed by RNA polymerase to recapitulate the viral genome, which replicated itselfa demonstration of synthesizing what the authors called a chemical [C332,652H492,388N98,245O131,196P7,501S2,340] with a life cycle (Science 2002, DOI: 10.1126/science.1072266).

After tinkering with a handful of other viral genomes, in 2010, researchers advanced to bacteria, painstakingly assembling a Mycoplasma genome just over about a million bases in length and then transplanting it into a host cell.

Last year, researchers upped the ante further, publishing the design for an aggressively edited Escherichia coli genome measuring 3.97 million bases long (Science, DOI: 10.1126/science.aaf3639). GP-write coleader George Church and coworkers at Harvard used DNA-editing softwarea kind of Google Docs for writing genomesto make radical systematic changes. The so-called rE.coli-57 sequence, which the team is currently synthesizing, lacks seven codons (the three-base DNA words that code for particular amino acids) compared with the normal E. coli genome. The researchers replaced all 62,214 instances of those codons with DNA base synonyms to eliminate redundancy in the code.

Note: A 17th synthetic neochromosome is not shown in the plot above. The number of DNA bases plotted is for the synthetic yeast chromosome as opposed to the native yeast chromosome. Synthetic chromosomes have been modified slightly from native ones to remove, for instance, transfer RNA coding segments that might destabilize the chromosomes. BGI is a genome sequencing center in Guangdong, China. GenScript is a New Jersey-based biotech firm. AWRI = Australian Wine Research Institute. JGI = Joint Genomics Institute of the U.S. Department of Energy. U = University. Source: Science 2017, DOI: 10.1126/science.aaf4557

Bacterial genomes are no-frills compared with those of creatures in our domain, the eukaryotes. Bacterial genomes typically take the form of a single circular piece of DNA that floats freely around the cell. Eukaryotic cells, from yeast to plants to insects to people, confine their larger genomes within a cells nucleus and organize them in multiple bundles called chromosomes. An ongoing collaboration is now bringing genome synthesis to the eukaryote realm: Researchers are building a fully synthetic yeast genome, containing 17 chromosomes that range from about 1,800 to about 1.5 million bases long. Overall, the genome will contain more than 11 million bases.

The synthetic genomes and chromosomes already constructed by scientists are by no means simple, but to synthesize the human genome, scientists will have to address a whole other level of complexity. Our genome is made up of more than 3 billion bases across 23 paired chromosomes. The smallest human chromosome is number 21, at 46.7 million baseslarger than the smallest yeast chromosome. The largest, number 1, has nearly 249 million. Making a human genome will mean making much more DNA and solving a larger puzzle in terms of assembly and transfer into cells.

Today, genome-writing technology is in what Boeke, also the director for the Institute of Systems Genetics at New York University School of Medicine, calls the Gutenberg phase. (Johannes Gutenberg introduced the printing press in Europe in the 1400s.) Its still early days.

DNA synthesis companies routinely create fragments that are 100 bases long and then use enzymes to stitch them together to make sequences up to a few thousand bases long, about the size of a gene. Customers can put in orders for small bits of DNA, longer strands called oligos, and whole geneswhatever they needand companies will fabricate and mail the genetic material.

Although the technology that makes this mail-order system possible is impressive, its not prolific enough to make a human genome in a reasonable amount of time. Estimates vary on how long it would take to stitch together a more than 3 billion-base human genome and how much it would cost with todays methods. But the ballpark answer is about a decade and hundreds of millions of dollars.

Synthesis companies could help bring those figures down by moving past their current 100-base limit and creating longer DNA fragments. Some researchers and companies are moving in that direction. For example, synthesis firm Molecular Assemblies is developing an enzymatic process to write long stretches of DNA with fewer errors.

Synthesis speeds and prices have been improving rapidly, and researchers expect they will continue to do so. From my point of view, building DNA is no longer the bottleneck, says Daniel G. Gibson, vice president of DNA technology at Synthetic Genomics and an associate professor at the J. Craig Venter Institute (JCVI). Some way or another, if we need to build larger pieces of DNA, well do that.

Gibson isnt involved with GP-write. But his research showcases what is possible with todays toolseven if they are equivalent to Gutenbergs movable type. He has been responsible for a few of synthetic biologys milestones, including the development of one of the most commonly used genome-assembly techniques.

The Gibson method uses chemical means to join DNA fragments, yielding pieces thousands of bases long. For two fragments to connect, one must end with a 20- to 40-base sequence thats identical to the start of the next fragment. These overlapping DNA fragments can be mixed with a solution of three enzymesan exonuclease, a DNA polymerase, and a DNA ligasethat trim the 5 end of each fragment, overlap the pieces, and seal them together.

To make the first synthetic bacterial genome in 2008, that of Mycoplasma genitalium, Gibson and his colleagues at JCVI, where he was a postdoc at the time, started with his eponymous in vitro method. They synthesized more than 100 fragments of synthetic DNA, each about 5,000 bases long, and then harnessed the prodigious DNA-processing properties of yeast, introducing these large DNA pieces to yeast three or four at a time. The yeast used its own cellular machinery to bring the pieces together into larger sequences, eventually producing the entire Mycoplasma genome.

Next, the team had to figure out how to transplant this synthetic genome into a bacterial cell to create what the researchers called the first synthetic cell. The process is involved and requires getting the bacterial genome out of the yeast, then storing the huge, fragile piece of circular DNA in a protective agarose gel before melting it and mixing it with another species of Mycoplasma. As the bacterial cells fuse, some of them take in the synthetic genomes floating in solution. Then they divide to create three daughter cells, two containing the native genomes, and one containing the synthetic genome: the synthetic cell.

When Gibsons group at JCVI started building the synthetic cell in 2004, we didnt know what the limitations were, he says. So the scientists were cautious about overwhelming the yeast with too many DNA fragments, or pieces that were too long. Today, Gibson says he can bring together about 25 overlapping DNA fragments that are about 25,000 bases long, rather than three or four 5,000-base segments at a time.

Gibson expects that existing DNA synthesis and assembly methods havent yet been pushed to their limits. Yeast might be able to assemble millions of bases, not just hundreds of thousands, he says. Still, Gibson believes it would be a stretch to make a human genome with this technique.

One of the most ambitious projects in genome writing so far centers on that master DNA assembler, yeast. As part of the project, called Sc2.0 (a riff on the funguss scientific name, Saccharomyces cerevisiae), an international group of scientists is redesigning and building yeast one synthetic chromosome at a time. The yeast genome is far simpler than ours. But like us, yeasts are eukaryotes and have multiple chromosomes within their nuclei.

Synthetic biologists arent interested in rebuilding existing genomes by rote; they want to make changes so they can probe how genomes work and make them easier to build and reengineer for practical use. The main lesson learned from Sc2.0 so far, project scientists say, is how much the yeast chromosomes can be altered in the writing, with no apparent ill effects. Indeed, the Sc2.0 sequence is not a direct copy of the original. The synthetic genome has been reduced by about 8%. Overall, the research group will make 1.1 million bases worth of insertions, deletions, and changes to the yeast genome (Science 2017, DOI: 10.1126/science.aaf4557).

So far, says Boeke, whos also coleader of Sc2.0, teams have finished or almost finished the first draft of the organisms 16 chromosomes. Theyre also working on a neochromosome, one not found in normal yeast. In this chromosome, the designers have relocated all DNA coding for transfer RNA, which plays a critical role in protein assembly. The Sc2.0 group isolated these sequences because scientists predicted they would cause structural instability in the synthetic chromosomes, says Joel Bader, a computational biologist at Johns Hopkins University who leads the projects software and design efforts.

The team is making yeast cells with a new chromosome one at a time. The ultimate goal is to create a yeast cell that contains no native chromosomes and all 17 synthetic ones. To get there, the scientists are taking a relatively old-fashioned approach: breeding. So far, theyve made a yeast cell with three synthetic chromosomes and are continuing to breed it with strains containing the remaining ones. Once a new chromosome is in place, it requires some patching up because of recombination with the native chromosomes. Its a process, but it doesnt look like there are any significant barriers, Bader says. He estimates it will take another two to three years to produce cells with the entire Sc2.0 genome.

So far, even with these significant changes to the chromosomes, the yeast lives at no apparent disadvantage compared with yeast that has its original chromosomes. Its surprising how much you can torture the genome with no effect, Boeke says.

Boeke and Bader have founded a start-up company called Neochromosome that will eventually use Sc2.0 strains to produce large protein drugs, chemical precursors, and other biomolecules that are currently impossible to make in yeast or E. coli because the genetic pathways used to create them are too complex. With synthetic chromosomes well be able to make these large supportive pathways in yeast, Bader predicts.

Whether existing genome-engineering methods like those used in Sc2.0 will translate to humans is an open question.

Bader believes that yeast, so willing to take up and assemble large amounts of DNA, might serve as future human-chromosome producers, assembling genetic material that could then be transferred to other organisms, perhaps human cells. Transplanting large human chromosomes would be tricky, Synthetic Genomics Gibson says. First, the recipient cell must be prepped by somehow removing its native chromosome. Gibson expects physically moving the synthetic chromosome would also be difficult: Stretches of DNA larger than about 50,000 bases are fragile. You have to be very gentle so the chromosome doesnt breakonce its broken, its not going to be useful, he says. Some researchers are working on more direct methods for cell-to-cell DNA transfer, such as getting cells to fuse with one another.

Once the scientists solve the delivery challenge, the next question is whether the transplanted chromosome will function. Our genomes are patterned with methyl groups that silence regions of the genome and are wrapped around histone proteins that pack the long strands into a three-dimensional order in cells nuclei. If the synthetic chromosome doesnt have the appropriate methylation patterns, the right structure, it might not be recognized by the cell, Gibson says.

Biologists might sidestep these epigenetic and other issues by doing large-scale DNA assembly in human cells from the get-go. Ron Weiss, a synthetic biologist at Massachusetts Institute of Technology, is pushing the upper limits on this sort of approach. He has designed methods for inserting large amounts of DNA directly into human cells. Weiss endows human cells with large circuits, which are packages of engineered DNA containing groups of genes and regulatory machinery that will change a cells behavior.

In 2014, Weiss developed a landing pad method to insert about 64,000-base stretches of DNA into human and other mammalian cells. First, researchers use gene editing to create the landing pad, which is a set of markers at a designated spot on a particular chromosome where an enzyme called a recombinase will insert the synthetic genetic material. Then they string together the genes for a given pathway, along with their regulatory elements, add a matching recombinase site, and fashion this strand into a circular piece of DNA called a plasmid. The target cells are then incubated with the plasmid, take it up, and incorporate it at the landing site (Nucleic Acids Res. 2014, DOI: 10.1093/nar/gku1082).

This works, but its tedious. It takes about two weeks to generate these cell lines if youre doing well, and the payload only goes into a few of the cells, Weiss explains. Since his initial publication, he says, his team has been able to generate cells with three landing pads; that means they could incorporate a genetic circuit thats about 200,000 bases long.

Weiss doesnt see simple scale-up of the landing pad method as the way forward, though, even setting aside the tedium. He doesnt think the supersized circuits would even function in a human cell because he doesnt yet know how to design them.

The limiting factor in the size of the circuit is not the construction of DNA, but the design, Weiss says. Instead of working completely by trial and error, bioengineers use computer models to predict how synthetic circuits or genetic edits will work in living cells of any species. But the larger the synthetic element, the harder it is to know whether it will work in a real cell. And the more radical the deletion, the harder it is to foresee whether it will have unintended consequences and kill the cell. Researchers also have a hard time predicting the degree to which cells will express the genes in a complex synthetic circuita lot, a little, or not at all. Gene regulation in humans is not fully understood, and rewriting on the scale done in the yeast chromosome would have far less predictable outcomes.

Besides being willing to take up and incorporate DNA, yeast is relatively simple. Upstream from a yeast gene, biologists can easily find the promoter sequence that turns it on. In contrast, human genes are often regulated by elements found in distant regions of the genome. That means working out how to control large pathways is more difficult, and theres a greater risk that changing the genetic sequencesuch as deleting what looks like repetitive nonsensewill have unintended, currently unpredictable, consequences.

Gibson notes that even in the minimal cell, the organism with the simplest known genome on the planet, biologists dont know what one-third of the genes do. Moving from the simplest organism to humans is a leap into the unknown. One design flaw can change how the cell behaves or even whether the cells are viable, Gibson says. We dont have the design knowledge.

Many scientists believe this uncertainty about design is all the more reason to try writing human and other large genomes. People are entranced with the perfect, Harvards Church says. But engineering and medicine are about the pretty good. I learn much more by trying to make something than by observing it.

Others arent sure that the move from writing the yeast genome to writing the human genome is necessary, or ethical. When the project to write the human genome was made public in May 2016, the founders called it Human Genome Project-write. They held the first organizational meeting behind closed doors, with no journalists present. A backlash ensued.

In the magazine Cosmos, Stanford University bioengineer Drew Endy and Northwestern University ethicist Laurie Zoloth in May 2016 warned of unintended consequences of large-scale changes to the genome and of alienating the public, potentially putting at risk funding for the synthetic biology field at large. They wrote that the synthesis of less controversial and more immediately useful genomes along with greatly improved sub-genomic synthesis capacities should be pursued instead.

GP-write members seem to have taken such criticisms to heart, or come to a similar conclusion on their own. By this Mays conference, human was dropped from the projects name. Leaders emphasized that the human genome would be a subproject proceeding on a conservative timescale and that ethicists would be involved at every step along the way. We want to separate the overarching goal of technology development from the hot-button issue of human genome writing, Boeke explains.

Bringing the public on board with this kind of project can be difficult, says Alta Charo, a professor of law and bioethics at the University of Wisconsin, Madison, who is not involved with GP-write. Charo cochaired a National Academy of Sciences study on the ethics and governance of human gene editing, which was published in February.

She says the likelihood of positive outcomes, such as new therapies or advances in basic science, must be weighed against potential unintended consequences or unforeseen uses of genome writing. People see their basic values at stake in human genetic engineering. If scientists achieve their goalsmaking larger scale genetic engineering routine and more useful, and bringing it to the human genomemajor changes are possible to what Charo calls the fabric of our culture and society. People will have to decide whether they feel optimistic about that or not. (Charo does.)

Given humans cautiousness, Charo imagines in early times we might have decided against creating fire, saying, Lets live without that; we dont need to create this thing that might destroy us. People often see genetic engineering in extreme terms, as a fire that might illuminate human biology and light the way to new technologies, or one that will destroy us.

Charo says the GP-write plan to keep ethicists involved going forward is the right approach and that its difficult to make an ethical or legal call on the project until its leaders put forward a road map.

The group will announce a specific road map sometime this year, but it doesnt want to be restrictive ahead of time. You know when youre done reading something, Boeke said at the meeting in May. But writing has an artistic side to it, he added. You never know when youre done.

Katherine Bourzac is a freelance science writer based in San Francisco.

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Writing the human genome - The Biological SCENE

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DELPHOS A Delphos couple were injured in a home invasion assault that occurred Saturday morning.

David and Dianna Allemeier of 209 S. Pierce St. in Delphos were both taken to St. Ritas Medical Center in Lima for treatment of injuries received when a man gained entry to their home and reportedly assaulted them.

Delphos Police were first called out at 6:05 a.m. Saturday on a report of a suspicious person in the 300 block of Jackson Street who was knocking on doors and then walking away. However, while en route to that call, officers were informed that a man had been injured and was bleeding in the 200 block of Pierce Street.

When officers arrived on the scene, they found Allemeier bleeding from an injury to his neck. The Delphos resident said he received the injury from a man who had gained entry into his home.

Officers approached the residence and found the back door unlocked and a lot of blood at the scene. The home was secured and a K-9 and Crime Scene Unit sought from the Allen County Sheriffs Office.

Allemeier then said his wife was still in the house and officers then entered and found Mrs. Allemeier, who was also injured, in the bedroom area of the residence.

After the Allemeiers were transported to the hospital, a K-9 search was made of the area, and the house was processed by an Allen County sheriffs deputy.

No information was released on whether items were taken from the Allemeier house.

Police are currently seeking a young, skinny white male with black hair, possibly wearing cutoff shorts. Anyone with information is asked to contact the Delphos Police Department or Allen County Sheriffs Office.

The investigation is continuing, with no further information forthcoming at this time.

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TOKYO & ALISO VIEJO, Calif.--(BUSINESS WIRE)--Konica Minolta, Inc. (Konica Minolta) (TOKYO: 4902) (ISIN: JP3300600008) and Ambry Genetics Corporation (Ambry) today announced the signing of a definitive agreement for a subsidiary of Konica Minolta to acquire Ambry. The transaction is partially funded by Innovation Network Corporation of Japan (INCJ). $800 million will be paid upon closure, and there will be an additional payment of up to $200 million based on certain financial metrics over the next two years, valuing the acquisition up to a total of $1.0 billion.

Founded in 1999, Ambry is a privately held healthcare company in the U.S., led by founder, President and Chairman Charles L.M. Dunlop and CEO Dr. Aaron Elliott. Ambry has the worlds most comprehensive suite of genetic testing solutions for inherited and non-inherited diseases as well as for numerous clinical specialties, including oncology, cardiology, pulmonology, neurology, and general genetics. They are recognized as a leader in diagnostic solutions for hereditary conditions in the United States, by having performed more than one million genetic tests and identified more than 45,000 mutations in at least 500 different genes. Ambry is known as a pioneer and thought leader in genetic testing being the first laboratory in the world to offer such tests as hereditary cancer panels and clinical exome sequencing.

Konica Minolta views the addition of Ambry as the first stepping-stone to create an exciting new medical platform aimed at fulfilling the potential of precision medicine an emerging approach to healthcare where genetic or molecular analysis is used to match patients with the most appropriate treatment for their specific disease. Precision medicine aims to improve a patients quality of life and save the healthcare system money by eliminating unnecessary and ineffective treatments. Konica Minolta plans to bring Ambrys capabilities first to Japan, and then to Europe.

This acquisition is the first in a series of strategic initiatives to secure a leading position for Konica Minolta in precision medicine, said Shoei Yamana, President and CEO of Konica Minolta. The future of medicine is patient-focused. Together with Ambry, we will have the most comprehensive set of diagnostic technologies for mapping an individuals genetic and biochemical makeup, as well as the capabilities to translate that knowledge into information the medical community can use to discover, prevent, and cost-effectively treat diseases. This will not only serve as the future foundation for our healthcare business, but will pave the way for a fundamental shift in the way medicine is practiced globally.

The acquisition of Ambry and the advancement of precision medicine marks a strategic and important shift for Konica Minoltas healthcare business. Leveraging its long history of innovation in materials science, nanofabrication, optics, and imaging, Konica Minolta has developed a comprehensive range of technologies and services in the healthcare field spanning digital X-ray diagnostic imaging systems, diagnostic ultrasound systems, and ICT service platforms for medical institutions.

Ambrys genetic testing capabilities complement Konica Minoltas advanced imaging technology to create the most comprehensive range of healthcare diagnostics for use by pharmaceutical companies, healthcare providers, payers, and consumers. In 2015, Konica Minolta pioneered advanced immunostaining technology High-Sensitivity Tissue Testing (HSTT)1 that uses fluorescent nanoparticles to detect and quantify the proteins that drive disease states and offers far greater precision and accuracy than conventional immunostaining techniques. With initial applications in oncology, the proprietary technology can determine the exact cellular location and amount of specific proteins that manifest in cells, offering an early-stage, highly precise diagnosis and insights into a patients disease that can inform research and a clinicians treatment plan.

Were excited by this opportunity to combine both our companies technologies to unlock new opportunities for precision medicine, said Charles Dunlop, President and Chairman of Ambry Genetics. As a part of Konica Minolta, we will have the resources, technology, and scale to advance biomedical research and enable the matching of more patients in more countries with specialized medicines that target the underlying cause of their illness.

Konica Minoltas HSTT technology will be further enhanced by Ambrys genetics-based screening techniques, which enable clinicians to analyze both tumor and normal tissue to diagnose hereditary cancer, while also providing guidance regarding drug eligibility and response. Ambry recently launched a combined genetic test for both inherited and acquired mutations in DNA mismatch repair genes to indicate appropriate treatment options for cancer patients who may benefit from PD-1/PD-L1 immunotherapy. PD-1 and PD-L1 checkpoint inhibitors help the patient's immune system recognize attack and destroy PD-L1-positive cancer cells that would otherwise evade detection by the immune system.

The combination of these bioinformatics capabilities, alongside Konica Minoltas HSTT technology, will create new opportunities for drug discovery and clinical trials not currently available, said Kiyotaka Fujii, Senior Executive Officer, President, Global Healthcare, Konica Minolta. Konica Minolta will look to accelerate innovations by drawing on the strengths of both companies. In addition to introducing Ambrys genetic-testing capabilities to the Japan market, we will look to develop new bio-imaging and proteomic services and solutions to benefit doctors, patients, and pharmaceutical companies.

Transaction Overview Under the terms of the agreement, Konica Minolta via Konica Minolta Healthcare Americas, Inc., (MHUS), a wholly owned subsidiary of Konica Minolta, and INCJ, will make an upfront, all-cash payment of $800 million to Ambry. MHUS will invest 60% and INCJ will account for the remaining 40%. In addition, Ambry shareholders will receive up to $200 million in incremental consideration based on certain financial metrics over the next two years, valuing the acquisition up to a total of $1.0 billion.

The transaction is expected to close in the third quarter of fiscal year 2017, subject to customary regulatory approvals. Ambry would thereafter become a consolidated subsidiary of Konica Minolta, continuing to operate under the Ambry name and headquartered in Aliso Viejo, California.

GCA Corporation acted as financial advisor to Konica Minolta and Baker McKenzie acted as legal advisor for this transaction. Intrepid Investment Bankers acted as financial advisor to Ambry and Jones Day acted as legal advisor.

ABOUT KONICA MINOLTA Konica Minolta, Inc. (Konica Minolta) is a global digital technology company with core strengths in imaging and data analysis, optics, materials, and nano-fabrication. Through innovation, we create products and digital solutions for the betterment of business and societytoday and for generations to come. Across our Business Technologies, Healthcare, and Industrial-facing businesses, we aspire to be an Integral Value Provider that applies the full range of our companys expertise to offer comprehensive solutions to our customers most pressing problems, work with our partners to ensure our solutions are sustainable, anticipate and address tomorrows issues, and tailor each solution to meet the unique and specific needs of our valued customers. Leveraging these capabilities, Konica Minolta contributes to productivity improvement and workflow change for our customers, and provides leading-edge service solutions in the IoT era.

Headquartered in Tokyo and with operations in more than 50 countries, Konica Minolta has more than 43,000 employees serving approximately two million customers in over 150 countries. Konica Minolta is listed on the Tokyo Stock Exchange, (TSE4902). For further information, visit: https://www.konicaminolta.com/

About Ambry Genetics Since 1999, Ambrys mission has remained focused on understanding disease so cures can come faster. Today, Ambry remains unwavering in its commitment to being tough, innovative, committed to quality and, most of all, focused to do what is right for patient care. For more information on Ambrys full suite of genetic testing, visit http://www.ambrygen.com

About INCJ Innovation Network Corporation of Japan (INCJ), a unique public-private partnership aimed at promoting innovation and enhancing the value of businesses in Japan, was launched in July 2009. For more information please see: http://www.incj.co.jp/english/

1 A portion of the research on HSTT was commissioned under a project by the New Energy and Industrial Technology Development Organization (NEDO), Japan.

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Konica Minolta to Acquire U.S.-based Ambry Genetics in a Deal ... - Business Wire (press release)

Outside of evolutionary biology, the human body is often spoken of as a miracle of engineering. But those more familiar with its workings point out evolution is no perfectionist, often favoring clunky ad hoc solutions over thosemore elegant in design. In fact, the comparison of evolution to a gambler might be the most apt, and nowhere is this more evident than in reference to genetic diseases like hemophilia. Now a recent study published in the Annals of Internal Medicine suggests far more people than previously thought are carrying variants of rare genetic diseases and could force us to redefine what is considered a healthy genome.

Genetic disorders are those resulting from mutations in ones DNA, often with horrendous results. Previously, scientists believedgenetic disorders were present in only a small fraction of the human population, 5 percent or less. After all, a population riven with genetic mistakes would quickly die out, or so went the logic. However, the present study puts the fraction of people with mutations linked to genetic diseases at something closer to 20 percent.

But is nature really so clumsy as to allow a veritable swarm of deleterious mutations to slip through her quality control mechanisms? It turns out many genetic disorders hide secret advantages. Take a person with the mutation that causes sickle cell anemia. A single copy of the mutation for sickle cellanemiaactually protects against the disease malaria. Its only if someone receivestwo copies of the defective gene that the problematic form of sickle cellanemia results. With many genetic disorders, nature seems to be hedging her bets, allowing some defects to slip through if they can provide a survival advantage to the population at large.

Counterintuitively, an individual suffering from a rare genetic disease may represent a successful population-level response to a given environment. This dance between genes and environments is at the heart of what we think of as health. But for most of history, medicine has considered the well being of an individual in isolation from population-level genetics. A more nuanced understanding of rare genetic diseases would take into account the various benefits genetic mistakes confer. This also suggests a cautious approach when editing our own genomes with tools like tools like CRISPR. Even seemingly terrible mutations we would be tempted to eliminate from the genetic pool may confer some secret advantage geneticists have yet to discover.

The study comes at a time when routine genetic testing is the subject of a far-ranging debate. Many doctors fear the release of genetic data to patients would cause undue anxiety. This study didnt support those claims, and goes a distance to undermine the paternalistic style of medicine currently practiced in many developed nations. In the United States, for instance, doctors remain a crucial chokepoint through which patients must pass through to access genetictesting. That said, anumber of direct-to-consumer genetic testing companies like 23andMe are breaking down these barriers, and a host of websites and even smartphone apps exist to help one make sense of their genetic data.

Now read: What is gene therapy?

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Far More People Than Thought Are Carrying Rare Genetic Diseases - ExtremeTech

Whenever biopharmaceutical experts and policymakers discuss medical innovation, they seem to focus only on drug discovery and development and access. While these aspects of innovation are critical to ensuring patients have safe and effective treatments, they dont provide a complete picture of the biopharmaceutical innovation model and the total investment needed to get the right medicine to the right patient at the right time. Whats missing? An understanding of the role of biopharmaceutical manufacturing and the need for a supportive policy environment in order to ensure the United States maintains its place as the leader in discovering, developing and delivering innovative medicines.

In the past decade, manufacturing has become an even more complex element of the biopharmaceutical innovation ecosystem as there have been several paradigm shifts in clinical treatments and pharmacology that make drug manufacturing significantly more challenging. First, therapeutic innovations previously developed to treat millions of patients the so-called blockbuster medicines have been replaced by the precision medicine model. This model integrates genetic information to help researchers understand which particular subgroup of patients will most likely benefit from a specific treatment. This scientific progress is leading to the development of medicines targeted for much smaller patient populations. Thus, biopharmaceutical companies now need to manufacture smaller batches and incorporate shorter production lines into their manufacturing process, which means they need to be more nimble and think beyond just efficiency to ensure production levels match the new innovative landscape in their manufacturing practices.

Second, diseases today are more often managed with medicines administered through intricate delivery systems. Complex therapies deliver important drugs directly to the site of the disease by bypassing traditional modes of delivery through oral intake. So now manufacturers have to think about how to make both the delivery device as well as the medicine.

Third, certain diseases are managed or prevented through biologics or vaccines. Unlike synthesized medicines which are made by combining specific chemical ingredients in a laboratory environment, these therapies are derived from living cell lines which cannot be fully characterized by traditional methods in a lab. For biologics and vaccines, the final product is influenced by the manufacturing process as the product is the process. An example of a therapy that requires this type of manufacturing complexity is a breakthrough vaccine for pneumococcal diseases. You may wonder what does it take to manufacture a single dose of that vaccine? It takes no less than 2.5 years, the collaboration of 1,700 researchers, engineers and other manufacturing experts, more than 400 raw materials and 678 quality tests in 581 steps to produce a single dose. Any minute deficiency in this long and laborious manufacturing process and/or ingredient integrity could possibly lead to failure.

Beyond better health, the benefit of manufacturing excellence is also captured in the economic value it generates for local communities in states all across the country. In the United States alone, there are close to 300,000 biopharmaceutical manufacturing jobs, with an average salary of close to $100,000 annually. This average salary is in the top 2 percent of all manufacturing jobs in the U.S. Pfizer currently has 17 manufacturing sites in 11 states and Puerto Rico that employ more than 12,000 people, and has invested $2 billion in these sites over the past five years. Estimates put Pfizers contribution to both direct and indirect jobs in the U.S. at 51,000.

The Pfizer facilities are not only responsible for manufacturing safe and innovative medicines, but some of the sites also produce active product ingredients. The API is the actual substance or raw material used to produce the medicine that patients consume. In fact, the Pfizer facility in Kalamazoo, Mich., is so cost-efficient that it manufactures APIs for methylprednisolone that Pfizer then sells to manufacturers in China and India, something not commonly observed in other traditional manufacturing sectors.

To make biopharmaceutical manufacturing a centerpiece of U.S. economic growth, policymakers need to address a few policy hurdles. First, they need to reform the U.S. tax code to encourage companies to further invest in U.S. pharmaceutical manufacturing. Next, the Food and Drug Administration ought to forge a proactive partnership with industry to develop practical regulatory solutions to advance and encourage domestic biopharmaceutical manufacturing expertise while protecting world-class quality control and good manufacturing processes. Lastly, the federal government needs to ensure appropriate and timely implementation of Section 3016 of the 21st Century Cures Act, which allows the FDA to issue grants to further the study of continuous manufacturing of drugs and biologics.

In an effort to get important medicines to patients in need, biopharmaceutical companies discover, develop, manage access and manufacture medicines. The innovation cycle is not complete if a company is not able to appropriately navigate the complicated yet crucial manufacturing process. A pro-active, supportive policy environment is the linchpin to ensuring the United States remains at the forefront of biopharmaceutical innovation and manufacturing.

Robert Popovian is the vice president of Pfizer U.S. Government Relations. He has two decades of experience in the biopharmaceutical health care industry and has published and presented extensively on the impact of pharmaceuticals and health care policies on health care costs and clinical outcomes.

Morning Consult welcomes op-ed submissions on policy, politics and business strategy in our coverage areas. Updated submission guidelines can be foundhere.

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The Future of Manufacturing a Medicine in America - Morning Consult

Driven by specialised analytics systems and software, big data analytics has decreased the time required to double medical knowledge by half, thus compressing healthcare innovation cycle period, shows the much discussed Mary Meeker study titled Internet Trends 2017.

The presentation of the study isseen as an evidence of the proverbial big data-enabled revolution, that was predicted by experts like McKinsey and Company. "A big data revolution is under way in health care. Over the last decade pharmaceutical companies have been aggregating years of research and development data into medical data bases, while payors and providers have digitised their patient records, the McKinsey report had said four years ago.

Representational image. Reuters

The Mary Meeker study shows that in the 1980s it took seven years to double medical knowledge which has been decreased to only 3.5 years after 2010, on account of massive use of big data analytics in healthcare. Though most of the samples used in the study were US based, the global trends revealed in it are well visible in India too.

"Medicine and underlying biology is now becoming a data-driven science where large amounts of structured and unstructured data relating to biological systems and human health is being generated," says Dr Rohit Gupta of MedGenome, a genomics driven research and diagnostics company based in Bengaluru.

Dr Gupta told Firstpost that big data analytics has made it possible for MedGenome, which focuses on improving global health by decoding genetic information contained in an individual genome, to dive deeper into genetics research.

While any individual's genome information is useful for detecting the known mutations for diseases, underlying new patterns of complicated diseases and their progression requires genomics data from many individuals across populations sometimes several thousands to even few millions amounting to exabytes of information, he said.

All of which would have been a cumbersome process without the latest data analytics tools that big data analytics has brought forth.

The company that started work on building India-specific baseline data to develop more accurate gene-based diagnostic testing kits in the year 2015 now conducts 400 genetic tests across all key disease areas.

What is Big Data

According to Mitali Mukerji, senior principal scientist, Council of Scientific and Industrial Research when a large number of people and institutions digitally record health data either in health apps or in digitised clinics, these information become big data about health. The data acquired from these sources can be analysed to search for patterns or trends enabling a deeper insight into the health conditions for early actionable interventions.

Big data is growing bigger But big data analytics require big data. And proliferation of Information technology in the health sector has enhanced flow of big data exponentially from various sources like dedicated wearable health gadgets like fitness trackers and hospital data base. Big data collection in the health sector has also been made possible because of the proliferation of smartphones and health apps.

The Meeker study shows that the download of health apps have increased worldwide in 2016 to nearly 1,200 million from nearly 1,150 million in the last year and 36 percent of these apps belong to the fitness and 24 percent to the diseases and treatment ones.

Health apps help the users monitor their health. From watching calorie intake to fitness training the apps have every assistance required to maintain one's health. 7 minute workout, a health app with three million users helps one get that flat tummy, lose weight and strengthen the core with 12 different exercises. Fooducate, another app, helps keep track of what one eats. This app not only counts the calories one is consuming, but also shows the user a detailed breakdown of the nutrition present in a packaged food.

For Indian users, there's Healthifyme, which comes with a comprehensive database of more than 20,000 Indian foods. It also offers an on-demand fitness trainer, yoga instructor and dietician. With this app, one can set goals to lose weight and track their food and activity. There are also companies like GOQii, which provide Indian customers with subscription-based health and fitness services on their smartphones using fitness trackers that come free.

Dr Gupta of MedGenome explains that data accumulated in wearable devices can either be sent directly to the healthcare provider for any possible intervention or even predict possible hospitalisation in the next few days.

The Meeker study shows that global shipment of wearable gadgets grew from 26 million in 2014 to 102 million in 2016.

Another area that's shown growth is electronic health records. In the US, electronic health records in office-based physicians in United States have soared from 21 percent in 2004 to 87 percent in 2015. In fact, every hospital with 500 beds (in the US) generate 50 petabytes of health data.

Back home, the Ministry of Electronics and Information Technology, Government of India, runs Aadhar-based Online Registration System, a platform to help patients book appointments in major government hospitals. The portal has the potential to emerge into a source if big data offering insights on diseases, age groups, shortcomings in hospitals and areas to improve. The website claims to have already been used to make 8,77,054 appointments till date in 118 hospitals.

On account of permeation of digital technology in health care, data growth has recorded 48% growth year on year, the Meeker study says. The accumulated mass of data, according to it, has provided deeper insights in health conditions. The study shows drastic increase of citations from 5 million in 1977 to 27 million in 2017. Easy access to big data has ensured that scientists can now direct their investigations following patterns analysed from such information and less time is required to arrive at conclusion.

If a researcher has huge sets of data at his disposal, he/she can also find out patterns and simulate it through machine learning tools, which decreases the time required to arrive at a conclusion. Machine learning methods become more robust when they are fed with results analysed from big data, says Mukerji.

She further adds, These data simulation models, rely on primary information generated from a study to build predictive models that can help assess how human body would respond to a given perturbation, says Mukerji.

The Meeker also study shows that Archimedes data simulation models can conduct clinical trials from data related to 50,000 patients collected over a period of 30 years, in just a span of two months. In absence of this model it took seven years to conduct clinical trials on data related to 2,838 patients collected over a period of seven years.

As per this report in 2016 results of 25,400 number of clinical trial was publically available against 1,900 in 2009.

The study also shows that data simulation models used by laboratories have drastically decreased time required for clinical trials. Due to emergence of big data, rise in number of publically available clinical trials have also increased, it adds.

Big data in scientific research

The developments grown around big-data in healthcare has broken the silos in scientific research. For example, the field of genomics has taken a giant stride in evolving personalised and genetic medicine with the help of big data.

A good example of how big data analytics can help modern medicine is the Human Genome Project and the innumerous researches on genetics, which paved way for personalised medicine, would have been difficult without the democratisation of data, which is another boon of big data analytics. The study shows that in the year 2008 there were only 5 personalised medicines available and it has increased to 132 in the year 2016.

In India, a Bangalore-based integrated biotech company recently launched 'Avestagenome', a project to build a complete genetic, genealogical and medical database of the Parsi community. Avestha Gengraine Technologies (Avesthagen), which launched the project believes that the results from the Parsi genome project could result in disease prediction and accelerate the development of new therapies and diagnostics both within the community as well as outside.

MedGenome has also been working on the same direction. "We collaborate with leading hospitals and research institutions to collect samples with research consent, generate sequencing data in our labs and analyse it along with clinical data to discover new mutations and disease causing perturbations in genes or functional pathways. The resultant disease models and their predictions will become more accurate as and when more data becomes available.

Mukerji says that democratisation of data fuelled by proliferation of technology and big data has also democratised scientific research across geographical boundaries. Since data has been made easily accessible, any laboratory can now proceed with research, says Mukerji.

We only need to ensure that our efforts and resources are put in the right direction, she adds.

Challenges with big data

But Dr Gupta warns that big-data in itself does not guarantee reliability for collecting quality data is a difficult task.

Moreover, he said, In medicine and clinical genomics, domain knowledge often helps and is almost essential to not only understand but also finding ways to effectively use the knowledge derived from the data and bring meaningful insights from it.

Besides, big data gathering is heavily dependent on adaptation of digital health solutions, which further restricts the data to certain age groups. As per the Meeker report, 40 percent of millennial respondents covered in the study owned a wearable. On the other hand 26 percent and 10 percent of the Generation X and baby boomers, respectively, owned wearables.

Similarly, 48 percent millennials, 38 percent Generation X and 23 percent baby boomers go online to find a physician. The report also shows that 10 percent of the people using telemedicine and wearable proved themselves super adopters of the new healthcare technology in 2016 as compared to 2 percent in 2015. Collection of big data.

Every technology brings its own challenges, with big data analytics secure storage and collection of data without violating the privacy of research subjects, is an added challenge. Something, even the Meeker study does not answer.

Digital world is really scary, says Mukerji.

Though we try to secure our data with passwords in our devices, but someone somewhere has always access to it, she says.

The health apps which are downloaded in mobile phones often become the source of big-data not only for the company that has produced it but also to the other agencies which are hunting for data in the internet. "We often click various options while browsing internet and thus knowingly or unknowingly give a third party access to some data stored in the device or in the health app, she adds.

Dimiter V Dimitrov a health expert makes similar assertions in his report, 'Medical Internet of Things and Big Data in Healthcare'. He reports that even wearables often have a server which they interact to in a different language providing it with required information.

Although many devices now have sensors to collect data, they often talk with the server in their own language, he said in his report.

Even though the industry is still at a nascent stage, and privacy remains a concern, Mukerji says that agencies possessing health data can certainly share them with laboratories without disclosing patient identity.

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Big data analytics in healthcare: Fuelled by wearables and apps, medical research takes giant leap forward - Firstpost

By Dr. Mercola

Do you want to live to be 100? How about 110, or even 120? Statistically, the younger you are, the greater your chances of reaching those milestonesthat much is known.

There is even a fairly strong possibility that lifespans beyond 150 will be possible in the next few decades as improvements in 3D printing, stem cell, and nanotech continue to improve.

But when it comes to understanding the complexity of human longevity and all of the factors that determine your lifespan, there is much we still don't understand. Researchers have the advantage of an ever-growing pool of centenarians and supercentenarians. Supercentenarians are those rare individuals who live past 110.

Both demographics are growing. And the good news is, most centenarians and supercentenarians are quite healthy until very near the end of their lives. Research tell us that the older the age group, the later the onset of degenerative diseases and cognitive decline.1 Here are a few interesting facts about centenarianswho now represent the fastest growing segment of the American population:2

Scientific explanations for longevity remain elusive. Researchers studying centenarians agree: there is no specific pattern.

There appears to be a connection between your longevity and the age your mother gave birth. Researchers at the University of Chicago Center on Aging found that if your mother was under age 25 when you were born, your chances of reaching age 100 are twice as high as for someone whose mother was older than 25. Makes me grateful my mother was only 19 when she had me.

This presumably has something to do with the robustness of a woman's eggs over time, but this is just one potential factor among many. According to Israeli physician Nir Barzilai of the Institute for Aging Research at Albert Einstein College of Medicine in New York:8

"There is no pattern. The usual recommendations for a healthy lifenot smoking, not drinking, plenty of exercise, a well-balanced diet, keeping your weight downthey apply to us average people. But not to them. Centenarians are in a class of their own."

Based on years of data from studying centenarians, Barzilai reports that when analyzing the data from his particular pool of centenarians, at age 70:

Despite this, centenarians as a population have 60 percent lower rates of heart disease, stroke, and high blood pressure.9 Depression and other psychiatric illnesses are almost nonexistent. Barzalai is quick to emphasize you should not disregard the importance of making healthy lifestyle choices (such as keeping your insulin level low). He explains:

"Today's changes in lifestyle do in fact contribute to whether someone dies at the age of 85 or before age 75. But in order to reach the age of 100, you need a special genetic make-up. These people age differently. Slower. They end up dying of the same diseases that we dobut 30 years later and usually quicker, without languishing for long periods."

The majority of centenarians do not feel their chronological age; on average, they report feeling 20 years younger. They also tend to have positive attitudes, optimism, and a zest for life. Could it be that personality characteristics and worldviews play a more significant role than genetics, diet, or exercise?

One way to determine this is to ask centenarians questions about how they see the world, what they value, and to what they attribute their own longevity. What are their secrets to aging well? These individuals represent centuries of wisdom that should not be overlooked. So that's what researchers are now doingmining the minds of centenarians for nuggets of wisdom. Regardless of which interviews you read, this is where patterns really DO emerge. In interviews and surveys with centenarians, the following themes come up time and time again when asked to explain why they've lived so long:10

Some jokingly said they attribute their longevity to "avoiding dying." Others give hints to their life philosophy, such as "Find your passion and live it," "Make time to cry," and "Practice forgiveness." Centenarians overwhelmingly cite stress as the most important thing to avoid. Their lives are marked by as many stressful events as the rest of us, but they differ in how well they manage their stress. Rather than dwelling on it, they let it go. And they are very happy people!

Happy people live longerby 35 percent, according to one study.11 Another study found that happiness and contentment increases health and longevity.12 Other studies show optimists live longer than pessimists.13 So it's no surprise that centenarians are a happy and optimistic lot. Positive thoughts and attitudes seem to somehow do things in your body that strengthen your immune system, boost positive emotions, decrease pain, and provide stress relief. In fact, it's been scientifically shown that happiness can alter your genes!

A team of researchers at UCLA showed that people with a deep sense of happiness and well-being had lower levels of inflammatory gene expression and stronger antiviral and antibody responses.14 This falls into the realm of epigeneticschanging the way your genes function by turning them off and on.

Part of your longevity may depend on the DNA you were born with, but an even larger part depends on epigeneticsover which you have more control. Your thoughts, feeling, emotions, diet, and other lifestyle factors exert epigenetic influences every minute of the day, playing a central role in aging and disease.15 Perhaps it's not as important to avoid that bowl of ice cream as it is to feel sheer bliss when eating it... at least, on occasion!

The fact that you can manipulate your genes with happiness doesn't mean you can completely disregard lifestyle choices, as that would be foolhardy. The basics are still importantdiet, exercise, sleep, etc. Research suggests the modern American diet is increasingly low in four important nutrients that have a direct bearing on aging, and our brains are suffering for it. If you hope to one day become a healthy, happy centenarian, you must address the following:16

Vitamin D's list of health benefits is amazingly long, including helping your brain combat the damage from free radicals, which helps prevent cognitive decline. The important factor when it comes to vitamin D is your serum level, which should be between 50-70 ng/ml year-round, and the only way to determine this is with a blood test.

Your skin produces vitamin D in response to ultraviolet light, so sun exposure or a safe tanning bed are the preferred methods of boosting your vitamin D. However, a D3 supplement can be used when necessary. Most adults need about 8,000 IUs of vitamin D3 per day to achieve serum levels of 40 ng/ml. If you take supplemental vitamin D3, you also need to make sure you're getting enough vitamin K2, as these two nutrients work in tandem to ensure calcium is distributed into the proper areas in your body.

Sources

DHA is an omega-3 fat that plays a role in keeping your cell membranes healthy, flexible, and resistant to oxidative stress, which decreases inflammation. Chronic inflammation is a key factor in many degenerative diseases, including dementia. Low DHA is has been linked with depression, memory loss, and even elevated hostility, which reflect its importance to optimal brain function.

The American diet has far too many omega-6 fats and not enough omega-3 fats due to its heavy reliance on processed food. You can boost your DHA by eating more fish, such as salmon and sardines, but so much of the fish today is contaminated with mercury and other toxic compounds that I prefer to take a high quality omega-3 fat supplement such as krill oil.

Folate helps prevent depression, seizure disorders, brain atrophy, and other neurological problems. Folate deficiencies correlate with impaired memory, slowed mental processing and overall cognitive decline, particularly in the elderly. Your body also needs folate to make red blood cells. Folate deficiency has been thought to lead to elevated homocysteine levels, which can be a major contributor to heart disease and Alzheimer's. However, recent studies may have disproven that idea.17

People often confuse folate with folic acid, and it's important to know the difference. Folate is the naturally-occurring form of the vitamin and contains all of the related isomers your body needs for optimal use. Folic acid is the synthetic form of the vitamin that is used in most supplements and in fortified foods.

It is always preferable to raise your folate levels by modifying your diet, as opposed to eating "enriched" foods or taking a multivitamin. Foods rich in folate include egg yolks, sunflower seeds, asparagus, avocados, broccoli, cauliflower, basil, parsley, and greens such as romaine, turnip, collards, and spinach.18 If you do think you need a supplement, make sure it lists "folate" on the label, rather than folic acid, as this suggests food sources were used.

Magnesium plays a role in your body's detoxification processes and is therefore important for minimizing damage from environmental chemicals, heavy metals and other toxins. Even glutathione, considered by many to be your body's most powerful antioxidant, requires magnesium in order to be synthesized. But this important mineral also helps your brain.

Magnesium acts as a buffer between neuron synapses, particularly those involved with cognitive functions (learning and memory). Magnesium "sits" on the receptor without activating it, in effect protecting the receptor from over-activation by other neurochemicals, especially glutamate. Glutamate is an "excitotoxin," which can harm your brain if it accumulates, and magnesium helps prevent this. That's why you often see magnesium advertised as a "calming" nutrient.

Good sources of magnesium are whole organic foods, especially dark green leafy vegetables, seaweed, dried pumpkin seeds, unsweetened cocoa, flaxseed, almond butter, and whey. If you choose to add a magnesium supplement, there are many forms so it can be a bit confusing. A newer type called magnesium threonate is particularly good due to its ability to penetrate cell membranes and cross your blood-brain barrier, which is important for preserving good cognitive function as you age.

There is no magic bullet when it comes to aging well. Generally speaking, the better you treat your body throughout your life, the better your aging experience will be. Most people do not revel in the thought of getting older because, for many, aging is synonymous with aches and pains, forgetfulness and loneliness. It is inevitable that you're going to get older, but I can tell you from personal experience that this need not be a bad thing!

Now, as I approach my 60th birthday in a few months, I am the fittest I have ever beenand I live every day to its fullest potential. I may have been able to run faster when I was younger, but I would never trade that for the muscle strength, flexibility and knowledge I have today. You too can achieve wellness on both physical and mental fronts, at any age. In fact, for me in many ways life continues to get better as the years go by.

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Centenarians Explain Their Secret to Happiness and Longevity

Could a diet of cheese, bread and wine be the secret to longevity?

For the people of Sardinia, it just might be, says Dan Buettner, a National Geographic magazine writer and Emmy award-winning documentarian.

Buettner, the noted author of "The Blue Zones: Lessons for Living Longer From the People Who've Lived the Longest," says certain aspects of the Sardinian diet seem to make a difference, adding about six years to life expectancy.

For one thing, the people of Sardinia -- the Italian island located in the Mediterranean -- drink very dark red wine.

That's because combining the Mediterranean diet with the dark wine creates antioxidants that scrub the arteries, Buettner said.

Not surprisingly, Buettner encourages the consumption of nuts, fruits and vegetables, and discourages a lot of meat.

"Meat is a once-a-week celebration," he said. "Not something you heap on your plate several times a day."

Surprisingly, though, he doesn't place too much emphasis on the importance of fish. He says that in the so-called Blue Zones -- the areas of the world he's studied where people live the longest -- fish consumption doesn't seem to be overemphasized.

"The longest-lived diets don't include a lot of fish," Buettner said. "If you're gonna include protein in your diet, I suggest this cheese that the Sardinians eat."

The cheese, called pecorino sardo, is made from the milk of grass-fed sheep, resulting in a product that is high in Omega-3 fatty acids.

Sardinia is also known for having another kind of cheese -- one that actually is infested with live maggots.

That cheese may contain bacteria that are good for the gut.

"We don't know," Buettner acknowledged. "We just know the longest-lived men in the world eat this. And they eat it as a manifestation of toughness."

Here are some things Buettner says you might find on the table in Sardinia:

Carta de musica A thin, whole wheat bread high in vitamin D.

Leavened bread Bacteria used to rise bread also create a variety of substances with positive effects, including vitamins, and lactic acid and may compete against possibly harmful bacteria in the digestive tract.

Fava beans High in fiber and folate.

Cannonau A dark, red wine with the world's highest levels of antioxidants for wine.

Pecorino Sard Comes from grass-fed sheep and is high in Omega 3.

Almonds and hazelnuts

Click here to return to the "Good Morning America" Web site.

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Does the Sardinian Diet Hold the Secret to Longevity ...

New Delhi: Coffee, for most people around the globe, is an essential apparatus to help kickstart the day. It is a cup for all seasons and without their favourite brew, the day seems incomplete.

Known for its high caffeine content, coffee has often been on the list of 'things to avoid' given to us by dieticians and health and fitness experts.

However, many studies in the past have shown coffee to contain numerous health benefits like weight loss, improvement in physical performance, reduction in risk of diabetes, protection from Alzheimer's and dementia, among others.

Now, US researchers have come up with some more good news for coffee lovers by concluding that drinking coffee could lead to a longer life!

As per the study, which included the participation of more than 180,000 volunteers, researchers found that people who drank regular or decaffeinated coffee experienced health benefits, such as increased longevity.

The researchers report in the journal Annals of Internal Medicine that people who consumed a cup of coffee a day were 12 percent less likely to die earlier compared to those who didn't drink coffee. This association was even stronger for those who drank two to three cups a day 18 percent reduced chance of death.

Lower mortality was present regardless of whether people drank regular or decaffeinated coffee, suggesting the association is not tied to caffeine.

Claimed to be the largest of its kind, the study had ethnically diverse participants who included African-Americans, Japanese-Americans, Latinos and whites. "Such investigations are important because lifestyle patterns and disease risks can vary substantially across racial and ethnic backgrounds, and findings in one group may not necessarily apply to others."

Since the association (between coffee drinking and longer life) was seen in four different ethnicities, it is safe to say the results apply to other groups, the authors claim. "Seeing a similar pattern across four different populations gives stronger biological backing to the argument that coffee is good for you whether you are white, African-American, Latino or Asian."

According to the authors, although this study does not show what chemicals in coffee may have this beneficial effect, it is clear that coffee "can be incorporated into a healthy diet and lifestyle".

(With IANS inputs)

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Coffee lovers, rejoice! Your favourite hot cuppa can increase your longevity - Zee News

Bloodlust, bad haircuts and the use of urine as a tooth whitener aside, the Romans did a whole lot of things right.

For starters, Romans connoisseurs of conveyance that they were developed the world's first highways, erected massive bridges and aqueducts and introduced the world to the convenience of sewers. But perhaps most notably, the master builders of the Roman Empire constructed hulking concrete edifices that were really built to last.

Calling Roman concrete "an extraordinarily rich material in terms of scientific possibility," Philip Brune, a research scientist at DuPont Pioneer and expert in ancient Roman construction, goes on to tell the Washington Post that it "is the most durable building material in human history, and I say that as an engineer not prone to hyperbole."

Kudos aside, the exact reason why Roman concrete known as opus caementicium, with ingredients including volcanic ash, calcium oxide or quicklime and hunks of volcanic rock which served as an aggregate is so damned durable has remained a mystery. Why has it withstood the test of time while modern concrete, which uses carbon-intensive Portland cement as a bonding agent, tends to crack and crumble into the sea over a relatively short time when exposed to salt water?

In addition to seawalls and subaquatic structures, the Romans built numerous millennia-spanning monuments such as the Colosseum with concrete made from lime, rock and volcanic ash. (Photo: Maria_Globetrotter/flickr)

According to a new study published in American Mineralogist, the answer has been sitting in front of us all along: Salt water, the same substance that hastens corrosion in modern concrete, is what has enabled some Roman piers and seawalls to stand strong for millennia.

More specifically, researchers have found that Roman concrete's seawater-aided endurance results from a chemical reaction that occurs when salt water seeps into the concrete fabric and comes in contact with the volcanic ash. The reaction creates aluminous tobermorite, a mineral that's difficult to produce in laboratory settings. This rare concrete crystal serves as a naturally occurring reinforcement that's matchless in modern times.

The great Roman author Pliny the Elder was certainly on to something when he wrote circa 79 A.D. in his "Naturalis Historia" that frequent lashings by an angry sea only made Roman harbors and seawalls more resilient "a single stone mass, impregnable to the waves and every day stronger."

"Contrary to the principles of modern cement-based concrete, the Romans created a rock-like concrete that thrives in open chemical exchange with seawater, " Marie Jackson, the study's lead author and a geologist at the University of Utah, tells the BBC. "It's a very rare occurrence in the Earth."

A University of Utah press release goes on to explain the chemical process:

"We're looking at a system that's contrary to everything one would not want in cement-based concrete," Jackson explains. "We're looking at a system that thrives in open chemical exchange with seawater."

Excellent. So does this research mean that some day down the line we'll experience a rebirth of ancient Roman building techniques? Will this antediluvian building material be used to as first line of defense when protecting our cities from rising seas unleashed by a rapidly warming planet?

Perhaps but not so fast.

The author of a new study on the chemical process that makes ancient concrete so durable believes that the seawater-strengthened material is the right fit for a proposed Welsh power plant that harnesses the power of the tides. (Rendering: Tidal Lagoon Power)

With the exact ingredients of Roman concrete having been discovered some time ago, Jackson and her fellow mineral cement sleuths now have a greater understanding of the chemical process behind the remarkable longevity of aquatic structures found across the ancient Roman Empire. Yet the exact method employed by Roman builders when mixing this ultra-durable building material remains a mystery. After all, if we knew exactly how they did it, wouldn't we have started replicating Roman concrete long ago?

"The recipe was completely lost," Jackson says in a press release.

While long-lasting, Roman concrete also lacks the compressive strength of Portland cement-based concrete, limiting its applications. And in a society that demands immediate results, structures that take decades centuries, even to gain optimum strength don't seem likely to gain serious traction anytime soon.

And there's another formidable obstacle: The basic aggregate found in Roman concrete volcanic rock collected by Roman builders from the region around present day Naples isn't easy to come by.

"Romans were fortunate in the type of rock they had to work with," Jackson says. "They observed that volcanic ash grew cements to produce the tuff. We don't have those rocks in a lot of the world, so there would have to be substitutions made."

And substitutions Jackson is making. Determined to find a satisfactory modern-day facsimile to reactive Roman concrete, Jackson has teamed with geological engineer Tom Adams to develop a "replacement recipe" composed of aggregate materials (read: rocks) collected from across the American West mixed with seawater pulled straight from the San Francisco Bay.

As the duo work to develop a potential seawater-aggregate mix that could yield the same crack-healing chemical reaction as the Pliny the Elder-beloved building material of civilizations past, Jackson is already thinking of potential applications for modern-day Roman concrete.

Earlier this year, she identified a proposed seawall in Swansea, Wales, as a structure in which Roman concrete would be a highly preferable choice over modern concrete reinforced with cement and steel. She believes that such a structure could potentially hold strong for upwards of 2,000 years.

"Their technique was based on building very massive structures that are really quite environmentally sustainable and very long-lasting," Jackson told the BBC in January. "I think Roman concrete or a type of it would be a very good choice. That project is going to require 120 years of service life to amortise [pay back] the investment."

Despite promises of longevity and putting an end to the planet-harming cement manufacturing process, there are sizable caveats that come along with the idea of protecting Swansea's tidal lagoon the world's first tidal lagoon power plant with a Roman-style seawall. As the BBC elaborates, local steel manufacturers are banking on the ambitious project being built with cement-based, steel-reinforced concrete. The environmental cost of transporting huge amounts of volcanic ash sourced from who knows where to the Welsh coast is also an issue.

"There's many applications but further work is needed to create those mixes. We've started but there is a lot of fine-tuning that needs to happen," Jackson tells The Guardian. "The challenge is to develop methods that use common volcanic products and that is actually what we are doing right now."

Matt Hickman ( @mattyhick ) writes about design, architecture and the intersection between the natural world and the built environment.

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Scientists unlock the mystery behind Roman concrete's amazing ... - Mother Nature Network (blog)

A team led by researchers at La Jollas Human Longevity reports developing a faster and more accurate method for determining immune type. The method will speed up immune matching for organ transplant and other purposes such as treating infectious and autoimmune diseases, the scientists say.

The method characterizes a region of the genome called human leukocyte antigen, or HLA, that regulates the immune system. Located on Chromosome 6, this region contains a high number of short, repetitive DNA sequences.

Because these repeats are so similar, placing them in the correct order is difficult. So even when people have their genome sequenced, the precise HLA type may not be clear. People can have HLA typing done separately, but that adds time and expense, said J. Craig Venter, one of the studys authors.

The study was published July 3 in the Proceedings of the National Academy of Sciences. Go to j.mp/humanhla for the study. Venter was senior author. The first author was Chao Xie.

The Human Longevity-led team invented an algorithm called xHLA to read these sequences correctly. Results are available within about 3 minutes from a desktop computer, instead of several minutes or even hours, the study stated. Moreover, the method helps identity potential matches that purely DNA-based methods would miss.

Making HLA typing a routine part of sequencing will help doctors advance the practice of precision medicine, the study stated.

For example, autoimmune disorder patients often have chronic problems with no exact diagnosis for many years after repeated doctor visits, the study stated. Knowing patients HLA types could lead to early diagnosis and reduce the burden on both patients and the healthcare system.

Venter said Human Longevity now offers HLA typing as part of its genome sequencing service. And in the future, this technology will be omnipresent and in the hands of patients.

If a family member needs a kidney transplant, you can just look it up on your iPhone and compare the sequences, and everybody will know immediately if theres a match in the family, or other places, Venter said.

Popular sequencing technologies cut up DNA into short pieces for sequencing. These pieces are reassembled by computer like an electronic jigsaw puzzle. But the many repetitive components in HLA can fool the computer programs, like similarly shaped or colored jigsaw puzzle pieces can do to a human.

The xHLA algorithm works with sequencing technology from Illumina to improve accuracy. An important component of the algorithm is that it examines the sequence of amino acids the DNA codes for, the study said. This helps accuracy by accepting DNA variations that happen to code for the same amino acid.

Since immune compatibility is determined at the protein level, using these synonymous variations produces a more accurate result than typing by DNA alone.

The problem with DNA-level alignment is that it cannot distinguish synonymous from nonsynonymous mismatches, the study stated. For example, it will rank five synonymous mismatches as more dissimilar than a single nonsynonymous one.

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Immune-matching process improved, reports Human Longevity-led study - The San Diego Union-Tribune

311 (from left: Chad Sexton, Nick Hexum, SA Martinez, Tim Mahoney and P-Nut) released its 12th studio album, Mosaic, earlier this year. Brian Bowen Smith/Courtesy of the artist hide caption

311 (from left: Chad Sexton, Nick Hexum, SA Martinez, Tim Mahoney and P-Nut) released its 12th studio album, Mosaic, earlier this year.

You'd be forgiven if it's been a while since you thought about the band 311; it was the mid-1990s when the Omaha, Neb., quintet's biggest hits, like "Down" and "All Mixed Up," came out. But after 27 years of 311's hard-to-peg sound a meld of rock, reggae, metal, funk, rap and ska hordes of fans are as in love with the band as ever. Billboard recently called 311 "one of the biggest cult bands in America, whether you love or hate them."

That's no exaggeration. 311 has its own Caribbean cruise, where fans can revel in a sea of fellow die-hards. It's got its own cannabis product, a vape pen aptly called the Grassroots Uplifter. And the band even has an unofficial holiday: Legions of devout followers celebrate March 11 (yes, that's 3/11) every two years by making a pilgrimage to a designated site for a special 311 concert that can go on for hours.

The cover art of 311's new album, Mosaic, is made up of almost 10,000 photos of the band's fans. Courtesy of the artist hide caption

The cover art of 311's new album, Mosaic, is made up of almost 10,000 photos of the band's fans.

On 311's 12th studio album, Mosaic, those devoted fans are front-and-center literally. The album's cover art features an image of the band made up of close to 10,000 photos taken with and submitted by fans. Frontman Nick Hexum has said the cover and album title speak to the "collective nature" of 311 and "the bond between the band members and our fans."

Hexum joined NPR for a conversation about navigating the challenges of longevity, the experimental attitude the band adopted in creating Mosaic and the positive message it's tried to spread over nearly three decades of making music. Hear the conversation at the audio link and read on for an edited transcript.

Lakshmi Singh: Bands like Pearl Jam and Nirvana, whose music tapped into youth angst, helped define the 1990s but your music seemed to sway in a different direction. Tell me about that.

Nick Hexum: I addressed it on [the] "Blue Album" in a song called "Misdirected Hostility," where I just felt that I didn't really relate with all the anger. I felt it was a time of prosperity, and we didn't have the Soviets getting ready to blow us up like we did in the '80s ... And these were a lot of suburban kids that were pretty angry about something, and so we felt we were gonna be the antidote for that ... We see the glass as more than half full. And that's the seeds of what turned us into a bit of a cult band, because we had our own unique attitude, and people see it as a way of looking at the world, a lifestyle.

How have the five of you in 311 the same members for the better part of three decades managed to stay together all this time?

Well, you have to be ready to not get your way, and know that what the group conscience decides is gonna be the rule. We know that we're better together than we could ever be apart ... It's like a marriage, and you have to be willing to do things you don't exactly wanna do, and keep the egos in check.

We were happy to find out the other day that we are the fourth-longest-running band of original members out today, with U2 being the first, Radiohead being the second, De La Soul being the third, and we're the fourth. So that's really cool company to be in. And I feel like, who knows, we could just be at the halfway point of our band. We always feel that success is measured in longevity and enjoying the process how long can we get to do something we really love instead of basing it on any sort of sales metric.

You've said that there's always a risk of repeating yourself when you get to album 12. What did it take to keep that from happening on Mosaic?

Really, it was just keeping an eye towards [the idea that] anything that was weird is good. Anything that is new, anything that is fresh those are the ideas that we pursued. And also just mixing up the process: Instead of being in our own little bubble, we asked other people into the room with us to record. ... I think that's an exercise in remaining teachable and being humble to realize that you can learn from others. And I think that's the biggest block that an artist of our age can have, is when you don't reach out, you don't keep mixing it up and bringing new people in, because your ego makes you feel like you can't accept help.

Everything you've just told me makes me think of the track "Wildfire," which sounds a little different than the others.

"Wildfire" was the first song written for Mosaic. ... I wanted something that started big and then had this real trip in the middle. And it goes through this sort of cinematic thing where there's even like beach sounds and waves and seagulls and stuff, because it represents what I'm talking about in the song the calmness of knowing that you have people that will be there for you singing about my family, singing about the band. So it's a very emotional song. And then it ends in a big guitar-shredding, almost classic-rock kind of thing, because at some point there's no words that can express, and you just need to express through music. ... I've had some fans on Twitter say, "You don't need to do epics, just keep it simple." But for me, that's where real creativity lies to just let yourself go.

You decided to end Mosaic with a song called "On A Roll." It seems to be an intimate message to fans what are you telling them?

It's about our longevity, it's a nod to the fans of gratitude. ... You know, the fact that we were able to have 10 top-10 albums [with] sporadic radio support, made us just feel really grateful. And this song, "On A Roll," it's kind of about that feeling of, like we don't have to have anxiety because we have this support of the bandmates, of our fans, and you know, we're on a roll.

Still, some fans have wondered if this is sort of a goodbye letter. Is this it for 311?

No, I don't see that at all. I'm saying, on a roll, here we go, we keep going, this feels good, we've got momentum. I've said before that we could be at our halfway point of our career. And some people say, "Well, you don't wanna be rolling out there in wheelchairs," but who knows? We could still be a good band to see in wheelchairs why not? All we know is that we're gonna do our best today, keep it going and take good care of what we've been so fortunate to find.

Radio producer Dustin DeSoto and web editor Rachel Horn contributed to this story.

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311's Nick Hexum On 'Mosaic,' Longevity And The Fans : NPR - NPR

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Study probes Greenland sharks' secret to long life - NATIONAL - The ... The Hindu Greenland sharks, the longest living vertebrates on Earth, which live for up to 400 years, could hold the secret to long life, geneticists mapping their DNA say. and more »

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Study probes Greenland sharks' secret to long life - NATIONAL - The ... - The Hindu

A father of two has taken the decision to undergo chemotherapy, despite not having cancer.

Roy Palmer lost the use of his legs 12 years ago as a result of his multiple sclerosis and has been seeking successful treatment ever since.

But it was while watching Panorama that the 48-year-old realised a combination of stem cell treatment and chemotherapy could be the answer he was looking for, GloucestershireLive reports.

The latter is strongly associated with cancer treatment , but its properties in rendering the body's immune system almost useless are a key part of the stem cell programme Roy hopes will see him up and about again.

He and his wife Helen decided they needed to make some calls and get appointments organised to be able to try and get this pioneering treatment going.

The onset of MS in Roy's case had been swift. In less than a week what began as pins and needles ended with him having no use of his legs.

Even with intense physiotherapy and a combination of steroids and drugs Roy relapsed several times and has been off his feet for 12 years. However when he saw the treatment that is out there, in a Panorama documentary, he and his wife cried.

Roy, 48, said: I just couldnt believe what I was seeing, the stories that I saw on the programme about how well people have been doing and the stem cell treatment actually worked.

I am really pleased that I am going to be able to start the treatment. I lost the use of my legs in 2005. I was encouraged by another woman that has been through it and she was in a wheelchair and now walking.

In the process to have treatment Ive had so many knockbacks being told that I did not fit the criteria but now I am finally getting the treatment.

His treatment will see him travel to the Imperial College Hospital in Hammersmith where a course of drugs will be administered to draw stem cells from Roy's bones into his bloodstream. Over a course of time, those stem cells will then transfer to a pack similar to a blood transfusion bag and be frozen.

It is then that Roy will undergo an intensive course of chemotherapy to render his immune system virtually useless - so much so he will live in isolation for four to six weeks to minimise risk of infection.

The treatment is called HSCT. The MS Society website states that: HSCT aims to 'reset' the immune system to stop it attacking the central nervous system. It uses chemotherapy to remove the harmful immune cells and then rebuild the immune system using a type of stem cell found in your bone marrow.

Roy's wife Helen, 45, said: After the chemo they will reintroduce the stem cells, and because his body will be at zero, it will be rebooted and the MS stopped in its tracks.

Roy has been on lots of different drugs over the years and his body has gradually got used to them and they stop working.

Roy has suffered with his hands not working properly and blurred vision which they call a brain fog. His legs ceasing to work has been a huge set-back for Roy as he used to work as a courier.

Roy said: I want to be able to get out the door without having to use the ramp, it is not a huge deal to anyone else but it is to me.

My goal now is to be able to reach the end point and be able to walk again.

Roy and Helen have two children Jack, 21 and Abigail, 12, and they are fully supportive of their fathers treatment.

Helen said: I am really pleased that we went to see the GP to get this going. Roy was desperate for this treatment.

It is difficult and my father is travelling from Wales to come and look after the children and I am really grateful to that.

The children are really supportive of their dads treatment and look forward to him coming out the other side.

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Dad set to undergo gruelling chemotherapy to kill his immune system despite not having cancer in bid walk again - Mirror.co.uk

What if curing cancer was as easy as getting an injection? Thats just what a pair of studies published this week in Nature tried to figure out.

The two teams of researchers conducted independent Phase I trials of personalized vaccines designed to prime the patients immune systems against melanomas, a category of skin cancers. In a scientific double whammy, both studies found that their vaccinessometimes in combination with other immunotherapieswere able to prevent recurrence of the cancers in nearly all their subjects.

We can safely and feasibly create a vaccine that is personalized to an individuals tumor, says Catherine Wu, senior author of one of the studies and associate professor at Dana-Farber Cancer Institute in Boston. Its not one-size-fits-allrather, its tailored to the genetic composition of the patients tumor.

Wu carried out her study with colleagues in Boston at Dana-Farber Cancer Institute and the Broad Institute. The other study was conducted in parallel by researchers in Germany, led by study first author Ugur Sahin, the co-founder and CEO of BioNTech, a biotechnology company that focuses on personalized immunotherapy treatments.

Both studies targeted the same type of cancer: melanoma. These skin cancers (best known for their link to UV radiation from tanning) are a good first target, Wu says, because scientists have a good understanding of the mutations that cause them. These mutations are the key, says Mathias Vormehr, a co-author on Sahin's study and a scientist at BioNTech.

"In principle, you can target any tumor that has mutations," Vormehr says. "And mutations are a main feature of tumors."

The goal of a cancer vaccine is to turn the patient's own immune system against the cancer by teaching it to fight the tumor cells. This is similar to other vaccines like the flu vaccine which contains dead or weakened flu viruses that can't actually do harm but can model what the the immune system should be prepared to fight.

Past attempts to create cancer vaccines have used gene-carrying viruses to reprogram immune cells to recognize cancerous cells. Others removed some immune cells from the patient's blood, taught them to recognize the cancer cells outside the body, then re-injected the trained immune cells into the patient to go to work.

The recent studies in Nature used neoantigen vaccines. Antigens are small proteins that decorate the outside of cells, and "neoantigens" refer to ones that are found only on cancer cells. Because they aren't found on any healthy cells, neoantigens make a perfect target for the immune systemafter all, you wouldnt want the immune system to start attacking its own healthy cells. Normally, cancer cells evade the immune system by weakening its effects and by feigning the appearance of normal cells. But, if the immune system learns to recognize the neoantigens delivered by the vaccine as harmful, it could then recognize and fight the cancer cells, too. Delivering mass amounts of neoantigens at once, which is what the vaccine would do, could trigger this recognition and the immune system might see neoantigens as harmful from then on.

Since all tumors are different, the vaccine had to be personalized. To figure out which neoantigens were unique to a patient's tumor, the researchers sequenced the tumor's DNA and each group of researchers developed their own computer algorithm to identify the unique segments of DNA that encoded the instructions to assemble these neoantigens.

This is the point where Wu and Sahins studies diverged. The goal was to get the neoantigens into the patient to prime their immune system. Wus team loaded up the vaccine with the neoantigens themselves, while Sahins vaccines delivered the corresponding RNA a cellular intermediary between DNA and proteinsso that the patient's own cells could create the neoantigen. Sahin's team chose to use RNA because RNA serves a two-in-one role in the vaccine, Vormehr says. Vaccines normally have an added component that boosts the immune response, and RNA can accomplish that on its own.

(Remember that these cancer vaccines arent preventative, like the ones that you take for the flu. They are therapeutic vaccines, designed after the onset of cancer to target each individuals tumor specifically.)

Both studies found that vaccination resulted in suppression of the cancer in many of their subjects. In the cases where the cancer was not successfully eliminated, Wu and Sahin both tried adding another treatment called checkpoint therapy, which keeps the cancerous cells from avoiding detection by the immune system. And two was, in fact, better than one: They found that the combination of the two methods improved vaccine response.

Of the six subjects in Wus study, four had stage III cancer and 25 months after vaccination, there was no sign of tumors. In the other two subjects, who had stage IV melanomas, they saw improvement with additional checkpoint therapy. Likewise, in Sahins study, eight out of 13 initially tumor-free subjects remained tumor-free 23 months later; normally half of them would be expected to relapse, Vormehr says. Of five subjects who relapsed, two responded positively to the vaccine, and a third responded when the vaccine was combined with checkpoint blockade therapy. Looking more closely, both sets of researchers found that their subjects' immune systems were learning to react to the neoantigens.

Using very different delivery systems, we arrived at very similar conclusions, Wu says. It gives more robust grounds for proceeding into future directions.

The purpose of the initial study was just to look for anti-tumor activity, says Matthias Miller, a senior project manager and co-author of the BioNTech study. In both cases, the trials were relatively small and did not have un-vaccinated control subjects. In a Nature News & Views piece that accompanied the two studies, Cornelis Melief, a professor at Leiden University Medical Center in the Netherlands who was not involved in either study, called for further Phase II clinical trials with larger samples and controls to more rigorously demonstrate the effectiveness of these vaccines.

One limitation of the studies was that not all cancer patients have neoantigen mutations that can be used to design these personalized vaccines, says Sasha Stanton, a physician-scientist in the University of Washington's Tumor Vaccine Group who was not involved in the study.

"Neoantigen vaccines are very exciting in metastatic cancer or in locally advanced cancer," Stanton says. "They are less beneficial in prevention and earlier stage cancer."

Additionally, the process is time intensivefor example, in Wu's study, it took three months for the patient to receive the vaccineand not all patients can remain stable for that long, Stanton says. Production of the vaccine will also have to become more streamlined, Wu says, but she believes the timeframe can be brought down to 4-6 weeks. Miller is also optimistic about the accessibility of the BioNTech vaccine.

"It will be affordable," Miller says. "It can definitely reach the broader public upon improvement of the process."

BioNTech is working with Genentech, a pharmaceutical company, to further develop their vaccine, while Wus team is participating in a multi-center combination therapy trial sponsored by Neon Therapeutics, a pharmaceutical company founded by Wu. If future trials are successful, Wu says, there will be many opportunities to apply personalized vaccines to other types of cancer; glioblastoma, a type of brain cancer, is one possible target.

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Personalized vaccines could help the immune system fight cancer - Popular Science

A gene mutation may explain theuncontrolled, inflammatory immune response seenin autoimmune and chronic inflammatory diseaseslikemultiple sclerosis, scientistsat the Research Institute of the McGill University Health Centre (RI-MUHC) report. Its a discovery that, they said, appears tobe a big step in the right direction.

According to the study, published in the journalScience Immunology, alterations in theFOXP3 geneaffect specificimmune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune systems response to a perceived threat.

We discovered that this mutation in the FOXP3 gene affects the Treg cells ability to dampen the immune response, which results in the immune system overreacting and causing inflammation, Ciriaco Piccirillo, the studys lead author andan immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release.

Tregs are known to be the immune system playersresponsible for keeping other immune cells under control, preventing them from attacking the hosts own tissues, while maintaining a properimmune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions.

TheFOXP3 gene is also well-known, and documented, to be essentialfor proper Treg cell function. However, the mechanisms by whichFOXP3 gene is involved in Treg cell activities are still poorly understood.

In the study, Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions, the research team in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan evaluated the impact of aFOXP3 gene mutation in autoimmunity response.

Taking advantage of cutting-edge technology, the team studiedsamples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation.

What was unique about this case of IPEX was that the patients Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response, saidPiccirillo.

Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions, addedKhalid Bin Dhuban, the studys first author and a postdoctoral fellow in Piccirillos laboratory.

The team developed a compound capable of restoring Treg cells ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, twochronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function.

Researchers now plan to developsimilar drugs that may be of use inother diseaseswhere Treg cells are known to be defective, including multiple sclerosis,type 1 diabetes, and lupus.

Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases, said Piccirillo. Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.

This discovery gives us key insights on how Treg cells are born and how they can be regulated, Piccirillo added. With this discovery, we are taking a big step in the right direction.

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FOXP3 Gene Mutations May Explain Immune System Excitability in MS and Other Diseases - Multiple Sclerosis News Today

Colon cancer. Uterine cancer. Pancreatic cancer. Whatever the tumor, the more gene mutations lurking inside, the better chance your immune system has to fight back.

That's the premise behind the recent approval of a landmark drug, the first cancer therapy ever cleared based on a tumor's genetics instead of the body part it struck first. Now thousands of patients with worsening cancer despite standard treatment can try this immunotherapy -- as long as genetic testing of the tumor shows they're a candidate.

"It's like having a lottery ticket," said Johns Hopkins oncologist Dr. Dung Le, who helped prove the new use for the immunotherapy Keytruda. "We've got to figure out how to find these patients, because it's such a great opportunity for them."

Today, doctors diagnose tumors by where they originate -- breast cancer in the breast, colon cancer in the colon -- and use therapies specifically tested for that organ. In contrast, the Food and Drug Administration labeled Keytruda the first "tissue-agnostic" treatment, for adults and children.

The reason: Seemingly unrelated cancers occasionally carry a common genetic flaw called a mismatch repair defect. Despite small studies, FDA found the evidence convincing that for a subset of patients, that flaw can make solid tumors susceptible to immunotherapy doctors otherwise wouldn't have tried.

"We thought these would be the hardest tumors to treat. But it's like an Achilles heel," said Hopkins cancer geneticist Bert Vogelstein.

And last month FDA Commissioner Scott Gottlieb told a Senate subcommittee his agency will simplify drug development for diseases that "all have a similar genetic fingerprint even if they have a slightly different clinical expression."

It's too early to know if what's being dubbed precision immunotherapy will have lasting benefits, but here's a look at the science.

Who's a Candidate?

Hopkins estimates about 4 percent of cancers are mismatch repair-deficient, potentially adding up to 60,000 patients a year. Widely available tests that cost $300 to $600 can tell who's eligible. The FDA said the flaw is more common in colon, endometrial and gastrointestinal cancers but occasionally occurs in a list of others.

"Say, 'have I been tested for this?'" is Le's advice for patients.

Mutations and More Mutations

Most tumors bear 50 or so mutations in various genes, Vogelstein said. Melanomas and lung cancers, spurred by sunlight and tobacco smoke, may have twice as many. But tumors with a mismatch repair defect can harbor 1,500 mutations.

Why? When DNA copies itself, sometimes the strands pair up wrong to leave a typo -- a mismatch. Normally the body spell checks and repairs those typos. Without that proofreading, mutations build up, not necessarily the kind that trigger cancer but bystanders in a growing tumor.

The Plot Thickens

Your immune system could be a potent cancer fighter except that too often, tumors shield themselves. Merck's Keytruda and other so-called checkpoint inhibitors can block one of those shields, allowing immune cells to recognize a tumor as a foreign invader and attack. Until now, those immunotherapies were approved only for a few select cancers -- Keytruda hit the market for melanoma in 2014 -- and they work incredibly well for some patients but fail in many others. Learning who's a good candidate is critical for drugs that can cost $150,000 a year and sometimes cause serious side effects.

In 2012, Hopkins doctors testing various immunotherapies found the approach failed in all but one of 20 colon cancer patients. When perplexed oncologists told Vogelstein, "a light bulb went off."

Sure enough, the one patient who fared well had a mismatch repair defect and a "mind-boggling" number of tumor mutations. The more mutations, the greater the chance that at least one produces a foreign-looking protein that is a beacon for immune cells, Vogelstein explained.

It was time to see if other kinds of cancer might respond, too.

What's the Data?

The strongest study, published in the journal Science, tested 86 such patients with a dozen different cancers, including some who had entered hospice. Half had their tumors at least shrink significantly, and 18 saw their cancer become undetectable.

It's not clear why the other half didn't respond. Researchers found a hint, in three patients, that new mutations might form that could resist treatment.

But after two years of Keytruda infusions, 11 of the "complete responders" have stopped the drug and remain cancer-free for a median of eight months and counting.

Catherine "Katie" Rosenbaum, 67, is one of those successes. The retired teacher had her uterus removed when endometrial cancer first struck, but five years later tumors returned, scattered through her pelvis and colon. She tried treatment after treatment until in 2014, her doctor urged the Hopkins study.

Rosenbaum took a train from Richmond, Virginia, to Baltimore for infusions every two weeks and then, after some fatigue and diarrhea side effects, once a month. Then the side effects eased and her tumors started disappearing. A year into the study she was well enough to swim a mile for a Swim Across America cancer fundraiser.

"Nothing else had worked, so I guess we could say it was a last hope," said Rosenbaum, who now wants other patients to know about the option.

2017 Associated Press under contract with NewsEdge/Acquire Media. All rights reserved.

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Landmark Cancer Drug Spurs Immune System | Sci-Tech Today - Sci-Tech Today

(Reuters Health) - Children whose parents separate and are not on speaking terms may be more vulnerable to catching colds as adults than kids whose parents stay together or go through an amicable breakup, a recent study suggests.

"There is evidence that children whose parents divorce are at increased risk for illness both during their childhood and as adults," said lead study author Michael Murphy, a psychology researcher at Carnegie Mellon University in Pittsburgh.

"However, our study indicates that parental separation itself may not account for this increased risk," Murphy said by email. "This is important because parental divorce is a common experience, affecting more than a million children annually in the United States alone."

For the study, researchers quarantined 201 healthy adults, exposed them to a virus that causes a common cold and monitored them for five days to see how their immune systems reacted and if they developed a respiratory illness.

Adults whose parents lived apart and never spoke during their childhood were more than three times as likely to develop a cold as participants who grew up in two-parent households, the study found. However, adults whose parents separated but communicated with each other were no more likely to catch a cold than people who came from intact families.

People whose parents separated and stopped speaking were 3.3 times more likely to develop a cold than people whose parents remained together during their childhood, the study found. These people also had higher levels of a marker of inflammation, which might help explain why they were more susceptible to catching a cold, the researchers speculate.

Participants in the study were about 30 years old on average, and 92 of them, or 46 percent, reported that their parents had divorced or separated during their childhood. Among the people with separated parents, 51 said their parents weren't on speaking terms.

All of them were given nasal drops containing rhinovirus 39 (RV39), a virus that causes the common cold.

Then, for the next five days, researchers collected nasal secretions to check for evidence of the virus and inflammation as well as to assess how much mucus people produced and how congested they were.

Overall, 149 participants, or 74 percent, developed an infection with RV39 and 60 people met the criteria for a cold based on having both an infection and objective symptoms, researchers report in the Proceedings of the National Academy of Sciences.

Limitations of the study include its reliance on participants to accurately recall and report on whether their parents communicated after a separation, the authors note. Even though researchers accounted for a number of factors that can influence the odds of catching a cold such as medical and psychiatric history and prescription use, it's still possible something other than divorce or parents' communication influenced the results.

"Although it's natural to suggest there's a causal process in play here from early parental divorce to later health, it's just as likely that the children of adults who never spoke with each other after their separation share many of the same personality dispositions as their parents - perhaps hostility, addiction or depression - and it is these variables that actually place the young adults at greater risk for colds," David Sbarra, a psychology researcher at the University of Arizona who wasn't involved in the study, said by email.

Even so, the findings add to growing evidence linking divorce-related stress to an increased risk of physical health problems, said Sharlene Wolchik, a psychology researcher at Arizona State University who also wasn't involved in the study.

"The good news is that we know a fair amount about the protective factors that reduce this risk," Wolchik said by email. "When divorce is followed by a new family structure in which parents have high quality relationships with their children, children spend sufficient time with each parent so their relationships can be meaningful and children are not directly or indirectly exposed to conflict between the parents, children can be resilient and thrive despite the stress of divorce."

SOURCE: bit.ly/2u2zLwn Proceedings of the National Academy of Sciences, online June 5, 2017.

(The story refiles to correct journal name in paragraph 10)

The Trump administration on Friday named Georgia public health Commissioner Dr Brenda Fitzgerald to lead the U.S. Centers for Disease Control and Prevention in Atlanta.

Eli Lilly and Co won a years-long patent dispute with Actavis on Friday after the UK Supreme Court ruled that the generic drugmaker's versions of Lilly's top-selling cancer drug Alimta directly infringe on certain Lilly patents in Britain, France, Italy and Spain.

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Nasty parental divorce may leave a mark on adult immune system ... - Reuters

Scientists now know how respiratory syncytial virus evades the immune system, a discovery that could potentially lead to a vaccine or treatment.

By age two, most children have been infected with respiratory syncytial virus (RSV), which usually causes only mild cold symptoms. But people with weakened immune systems, including infants and the elderly, can face serious complications, including pneumonia andin some casesdeath.

We solved the structure of a protein that has eluded the field for quite some time, says Daisy Leung, assistant professor of pathology and immunology, and of biochemistry and molecular biophysics at Washington University School of Medicine in St. Louis, co-senior author of the study in Nature Microbiology.

Now that we have the structure, were able to see what the protein looks like, which will help us define what it does and how it does it. And that could lead, down the road, to new targets for vaccine or drug development.

Each year in the United States, more than 57,000 children younger under 5 stay in the hospitaldue to RSV infection, and about 14,000 adults older than 65 die from it.

There is no approved vaccine for RSV and treatment is limitedthe antiviral drug ribavirin is used only in the most severe cases because it is expensive and not very effectiveso most people with RSV receive supportive care to make them more comfortable while their bodies fight off the virus.

For people with weakened immune systems, though, fighting RSV can be tough because the virus can fight back. Scientists have long known that a non-structural RSV protein is key to the viruss ability to evade the immune response. However, the structure of that protein, known as NS1, was unknown. Without seeing what the protein looked like, scientists were unable to determine exactly how NS1 interfered with the immune system.

Its an enigmatic protein. Everybody thinks it does many different things, but weve never had a framework to study how and why the protein does what it does, says co-senior author Gaya Amarasinghe, an associate professor of pathology and immunology.

The researchers used X-ray crystallographya technique that involves crystallizing the protein, bouncing X-rays off it, and analyzing the resulting patternsto determine the 3D structure of NS1. Then, in a detailed analysis of the structure, they identified a piece of the protein, known as the alpha 3 helix, which might be critical for suppressing the immune response.

To test their hypothesis, they created different versions of the NS1 protein, some with the alpha 3 helix region intact, and some with it mutated and then tested the functional impact of helix 3 and created a set of viruses containing the original or the mutant NS1 genes, and measured the effect on the immune response when they infected cells with these viruses.

The viruses with the mutated helix region did not suppress the immune response while the ones with the intact helix region did.

One of the surprising things we found was that this protein does not target just one set of genes related to the immune response, but it globally modulates the immune response, says Amarasinghe, also an associate professor of molecular microbiology, and of biochemistry and molecular biophysics.

The findings show that the alpha 3 helix region is necessary for the virus to dial the bodys immune response down. By suppressing the immune response, the virus gives itself a better chance of surviving and multiplying, or in other words, of causing disease.

RSV usually can only cause disease in people whose immune systems are already weak, so a vaccine or treatment that targets the alpha 3 helix to prevent immune suppression may be just what people need to be able to successfully fight off the virus.

Other researchers from Washington University in St. Louis and Georgia State University are coauthors of the study.

Support for the work came from the National Institutes of Health; the Defense Threat Reduction Agency of the Department of Defense; the National Science Foundation; the Childrens Discovery Institute; and the American Heart Association.

Source: Washington University in St. Louis

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How this common virus evades the immune system - Futurity - Futurity: Research News

By David Ikudayisi

Stem Cell Therapy comes in different types. Embryonic Stem Cell Therapy involves the use of embryonic stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo at 4 days old to around 12 days old, leading to the destruction of the blastocyst which raises ethical and religious issues. Therefore, this type of Stem Cell Therapy is not the focus of this piece. The focus is Adult Stem Cells (ADSCs) and Induced Pluripotent Stem Cells (iPSCs). iPSCs are produced in the laboratories by reprogramming adult cells to express embryonic stem cells characteristics whereas ADSCs are cells obtained from an adult patient who will also be the recipient of the same stem cells.

In the United States, we must transplant the cells back to the same patient on the same day, while in some countries, the stem cells can be cultured to increase the quantity of stem cells before transplanting them back to the same patient who donated them.

Stem Cell Transplantation is a complex process that needs the care of experts in Regenerative Medicine, a new speciality of medicine . In order to ensure that science remains as the vehicle for hope and not harm, the controversies associated with the legal, social and legal issues of certain areas of stem cells research and stem cells potential clinical applications must be carefully examined. Advancing treatment and care for patients to save a life is and must be the ultimate goal.

Regenerative Medicine helps people to naturally regenerate and rejuvenate their bodies from the different conditions they may be suffering from without using chemicals or the orthodox medicine we are used to, but Adult Stem Cells Platelet Rich Plasma (PRP), that is, blood plasma that has been enriched with platelets, and contains growth factors which may elicit the gathering of stem cells around the damaged region stimulating cellular proliferation and tissue regeneration. PRP can be used to promote healing of injured tendons, ligaments, muscles, joints and can be applied to various musculoskeletal problems. The process allows your own (autologous) stem cells to be re-introduced into/around areas of damage or chronic disease. As mentioned earlier, the extraction and transplantation of the stem cells are done on the same day in the United States. Bone marrow transplant has been the most widely used Stem Cell Therapy till date, but Adult Adipose-Derived (fat) Stem Cell Therapy is fast gaining popularity as fat harvesting is less invasive than bone marrow harvesting. You get more stem cells from fat than bone marrow, and fat stem cells are not age-dependent. Adult Stem Cell Therapy may hold answers to many questions and problems that we doctors believed had no solutions, especially neurological disorders. The therapy, with or without PRP, revitalizes and regenerates the body organs and systems; it also reverses and repairs many pending subclinical medical problems before they become apparent, including the diseases that are age-related. Generally, Adult Stem Cell Therapy is safe as shown by many published research reports and clinical trials. However, this does not guarantee that adverse effects cant occur if the treatment is done by physicians that are not properly trained.

The therapy has helped a lot of people all over the world to regain their lives from debilitating ailments and Nigerians are not left behind. There are people in Nigeria that were either wheelchair bound and walking with occasional use of a cane before but now walking without one; diabetes patients are able to have restoration of vision in their eyes, and some feel and look younger. It has helped chronic kidney disease patients in Nigeria that are on hemodialysis to either reduce the frequency of hemodialysis per week or like a patient that was recommended to have kidney transplant a year ago but who is now off hemodialysis and off diabetic medications, and remains stable for the past months. Men with Erectile Dysfunction are now feeling like young men again. I cannot but mention that the type of treatment protocol and dosage of stem cells used also play a role in the efficacy of the treatment, and not everyone will respond in the same manner. Most of the patients, in studies, showed improvements after the first treatment, and the few that needed second treatment went on to see great results after more treatments were done; needless to say that they were elated with the results. The only group of patients that will always need more than a couple of transplantation sessions are patients with neurological disorders. Latest researches and evidence-based studies showed the number of treatment sessions needed to get significant clinical results can decrease by adding Exosomes to the treatment sessions.

In a recently publication in Germany, the new concept, developed around 2010 of how stem cells works, was reinforced where it stated that most of the effects of stem cells are through the Paracrine effects, delivered by the Exosomes. Exosomes are extracellular cell-derived vesicles that are present in almost all biological fluids. When secreted by stem cells, Exosomes are those tiny communication vesicles that interact with surrounding cells, thereby creating therapeutic activity. This is called the Paracrine effect. The Paracrine soluble factors (communication vesicles) have specialized functions and play a key role in intercellular signaling and in the following properties immune modulatory, neuroprotective, anti-inflammatory, neurotrophic, angiotrophic, anti-apoptotic and anti-oxidatory. Stem cells also secrete other important proteins and cytokines that have healing properties.

There are some diseases that conventional treatments have no cure for, but Adult Stem Cell Therapy can reverse the symptoms of those diseases, repair and regenerate the damaged tissues or organs affected. In some cases, it significantly slows down the progression of the disorder. For example, it can regenerate the bony joints in arthritis, repair and strengthen partial rotator cuff tears and avascular necrosis of the hip without surgery, revitalize the sexual organs in men and women, regenerate renal cells in kidney diseases, modulate immune system without use of medications that have very serious side effects in conditions like Rheumatoid Arthritis, Lupus, Scleroderma, Crohns disease, etc. Another advantage is its application in neurological disorders like ALS and spinal cord injury.

Adult Stem Cell Therapy can gradually lower diabetic medications dosage and eventually may get the patients off diabetic medications. This is evidenced by stem cells in a hyperglycemic medium differentiating into pancreatic cells; therefore leading to increased development of new blood vessels, secretion of various products of the immune system, and upregulation of pancreatic transcription factors and vascular growth factor. This aids the pancreas to regenerate and boost its ability to produce insulin. In stroke patients, stem cells activate cells around the suffering brain tissue to catalyze rapid healing and to improve brain function, thereby restoring motor function. Until recently, it was believed that damage to the brain tissue was permanent. This is being challenged by the evidences of re-growth of brain cells and improvements of neurological function documented with the use of Adult Stem Cells.

A procedure called P-Shot for Men uses the PRP Therapy to resolve challenges relating to Erectile Dysfunction by regenerating the damaged tissues. It gives treated men the possibility of saving their relationships by increasing stamina, enjoying bigger and harder genitals, and eventually increasing the length and girth. Orgasm-Shot for Women, the regenerative medicine procedure for womens sexual function, leads to increased ability to have orgasm, better arousal from clitoris stimulation, decreased pain during intercourse, tighter vaginal opening, increased sexual desire and natural lubrication, and increased arousal from G-spot stimulation. In addition, because of the O-Shot rejuvenation capabilities, there is help available for women suffering from urinary stress incontinence without the need for invasive surgery.

Since the stem cells used are autologous, there is no risk of rejection of the stem cell transplant. Nevertheless, as with any procedure, there is a risk of infection which can be very minimal or non-existent if done under the right conditions. Adult Stem Cells Transplantation can also be considered by people looking for alternative treatments especially in the areas of diabetes, hypertension, kidney disease, female and male sexual dysfunction, joint pain, neurological disorder and autoimmune disease. The cost of treatment varies, and it is not for everyone. However, you cant place a price tag on life just as the saying goes that health is wealth.

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Stem Cell Therapy: You can be sexually active again - Vanguard ... - Vanguard