Category Archives: Human Genetic Engineering

ScienceDaily (May 2, 2012) Having a virtual copy of a patient's blood in a computer would be a boon to researchers and doctors. They could examine a simulated heart attack caused by blood clotting in a diseased coronary artery and see if a drug like aspirin would be effective in reducing the size of such a clot.

Now, a team of biomedical engineers and hematologists at the University of Pennsylvania has made large-scale, patient-specific simulations of blood function under the flow conditions found in blood vessels, using robots to run hundreds of tests on human platelets responding to combinations of activating agents that cause clotting.

Their work was published in the journal Blood.

Patient-specific information on how platelets form blood clots can be a vital part of care. Normally, clots prevent bleeding, but they can also cause heart attacks when they form in plaque-laden coronary arteries. Several drugs, including aspirin, are used to reduce the size of such clots and prevent heart attacks, but, as platelets differ from person to person, the efficacy of such drugs differs as well.

"Blood platelets are like computers in that they integrate many signals and make a complex decision of what to do," said senior author Scott Diamond, professor of chemical and biomolecular engineering in the School of Engineering and Applied Science. "We were interested to learn if we could make enough measurements in the lab to detect the small differences that make each of us unique. It would be impossible to do this with the cells of the liver, heart or brain. But we can easily obtain a tube of blood from each donor and run tests of platelet calcium release."

When blood platelets are exposed to the conditions of a cut or, in a more dangerous situation, a ruptured atherosclerotic plaque, they respond by elevating their internal calcium, which causes release of two chemicals, thromboxane and ADP. These two activating agents further enhance calcium levels and are the targets of common anti-platelet drugs such as aspirin or clopidogrel, also known as Plavix. By preventing platelets from increasing their calcium levels, these drugs make them less able to stick together and block blood vessels, decreasing the likelihood of a heart attack.

Since blood is a liquid, the liquid-handling robots originally developed for drug screening tests were ideal to test platelet function.

"We used a technique developed in our lab called 'pairwise agonist scanning' on platelets from three different donors to generate a massive data set of how their cells responded to all different pairs of these activating agents," Diamond said. "Then we trained neural network models for each donor based on this data to simulate how each and every cell in a blood clot is responding."

Neural networks are a way of looking at the relationship between inputs and outputs for very complex processes, rather than at the details of the process.

"They summarize the overall function of all the chemical reaction networks that are occurring within a single platelet," Diamond said.

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Large-scale simulation of human blood is boon to personalized medicine

Here, for your viewing pleasure, is a very important part of a very special flu virus. It may look like an ordinary protein, but in fact its been at the center of a blazing debate about whether our increasing power to experiment on life could lead to a disaster. Not that long ago, in fact, a national security advisory board didnt even want you to see this. So feast your eyes.

For those who are new to this story let me start back at the beginning, in 1997.

In that year, a child in Hong Kong died of the flu. Doctors shipped a sample of his blood to virus experts in Europe, but they didnt bother taking a look at it for months. When they did, they were startled to discover that it was unlike any flu theyd seen in a human being before.

Each year, several different flu strains circulate from person to person around the world. Theyre known by the initials of the proteins that cover their surfaceH3N2, for example, is one common strain. The H stands for haemagglutinin, a protein that latches to a host cell so that the virus can invade. The N stands for neuraminidase, which newly produced viruses then use to hack their way out of the cell.

Birds are the source of all our flu strains. Our feathered friends are hosts to a huge variety of H and N type viruses, which typically infect their guts and cause a mild infection. From time to time, bird flu viruses have crossed the species barrier and adapted to human hosts, infecting our airways and then spreading in air droplets. Since flu spreads so fast around the world, a fair amount of the planets population has had some exposureand thus some immunityto the flu strains in circulation today. But if a new bird flu should manage to make the leap, we could face a very grim situationa situation that some scientists worry could rival the 1918 pandemic, which killed some 50 million people.

Thats why the scientists in 1997 were so flustered. The Hong Kong boy had died of a strain of bird flu that hadnt been found in people before. It came to be known as H5N1.

It turned out that around Hong Kong, chickens were rife with H5N1, including the chickens for sale in live open-air markets. Public health workers slaughtered huge numbers of chickens to stop the outbreak, and, for a time, it seemed like they had beaten the virus. In fact, H5N1 had simply gone into hiding. A few years later it was backand spreading. Birds carried it across Asia, into Africa and Europe. The New World and Australia have been spared so far, but theres no reason to think that the virus cant colonize those continents as well. It will just take the right bird.

Doctors found that the majority of patients hospitalized with H5N1 died. The only comforting thing about H5N1 was that it remained a bird flu. Once inside a human being, the virus couldnt churn out lots of new viruses capable of spreading to another human. But many bird flu experts consider that a cold comfort. Like all flu viruses, H5N1 has been continually evolving. When the viruses replicate they pick up new mutationssome of which help them replicate faster. Sometimes, two H5N1 viruses co-infect a single cell at once and swap some of their genes, producing hybrids. If this high-speed evolution leads to human-adapted H5N1, we could be dealing with a global cataclysm.

Yet some flu experts doubted this grim prospect. Its been some 15 years since H5N1 was first discovered, and despite all those years of evolution, the virus has yet to nose its way into our species. Perhaps, some scientists suggested, there was something about the biology of the strain that prevents natural selection from transforming it into a human virus. Skeptics have more recently raised another question about the risk of H5N1: is its mortality rate really all that high? In many studies, scientists have estimated the mortality rate of H5N1 based only on sick people who come to hospitals. Its possible that a lot of people recover from bird flu infections on their own, and go missing from the statistics. (Its worth bearing in mind, though, that the 1918 flu only had a mortality rate of 2%. If a virus can infect billions of people, even a low rate like that can lead to terrifying numbers of deaths.)

A few years ago, some bird flu experts decided to test the proposition that H5N1 was a potential human scourge. They would tinker with it to see if it could be transmitted from mammal to mammal, instead of bird to mammal. They might be able to see some warning signs for how this transition could happen in nature. The scientists applied for money from the National Institutes of Health, which considered their idea important enough to sink millions of dollars into it.

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Behold The Forbidden Flu: A Loom Explainer | The Loom

Blade Runner: What It Means to Be Human in the Cybernetic State

By John W. Whitehead

Were not computers, Sebastian. Were physical.Roy Batty

Thirty years ago right around this time, Ridley Scott was wrapping up production on his filmBlade Runner.By the summer of 1982, it had opened in over 1,200 theaters across the country. Routinely panned and even attacked by test audiences, the film fared little better in theaters. In fact, it was a certified box office flop. Virtually no one, it seems, likedBlade Runner. Fortunately, in the three decades since it first debuted on the big screen, viewers discovering the film on cable TV and DVD have come to appreciate it as not only a cult film par excellence but an emotionally challenging, thematically complex work whose ideas and subtexts are just as startling as its now famous production designs.

Set in Los Angeles in the year 2019,Blade Runnerdepicts a world where the sun no longer shines. Instead, a constant rainy drizzle adds to the dark character of this futuristic landscape. Although the opening shots aerial perspective suggests a modern Los Angeles, the audience soon discovers a very different city in which the endless archipelago of suburbs have been replaced by a dark and ominous landscape lit only by occasional flare-ups of burning gas at oil refineries. An energy shortage has crippled life in the future. The earth is decayed, and millions of people have been forced to colonize other planets. Those who remain behind live in huge cities consisting of a conglomeration of new buildings four hundred stories high and the dilapidated remains of earlier times.

The streets teem with Asians, Hare Krishnas and men in fezzes, all lit by a lurid blaze of flashing neon. The crunch and crush of modern population seems overwhelming and totally dehumanizing. Genetic engineering has become one of the earths major industries, with humans now assuming the role of maker and creator. Since most of the worlds animals have become extinct, genetic engineers now produce artificial animals. And artificial humans called replicants have been created to do the difficult, hazardous and often tedious work necessary in the colonies on other planets.

If Michelangelo were alive in Ridley Scotts future world, rather than portraying God on the ceiling of the Sistine Chapel, he would likely paint the human creators of the Tyrell Corporation, the worlds leading manufacturer of replicants which has just introduced the Nexus-6, a replicant with far greater strength and intelligence than human beings. These latest-model replicants represent an obvious potential danger to human society, and their introduction on Earthan offense calling for the death penaltyhas been strictly outlawed. When the replicants somehow make their way back to Earth, they are systematically retired (but not killed since they are inhuman) by special detectives or Blade Runners trained to track down and liquidate the infiltrators.

Police receive an emergency report that four combat model Nexus-6 replicantstwo male and two femalehave killed the crew of a space shuttle and returned to Earth. The Blade Runner assigned to track them down and terminate them is Deckard (Harrison Ford, in his best performance).

The film shifts dramatically when the replicants, who are on a mission to extend their short life span, display a stronger sense of community than the human beings on Earth. With his three partners now destroyed by explosive bullets, the silver-blonde replicant Roy Batty (Rutger Hauer) succeeds in finding his way to Tyrell himself, the master of the Tyrell Corporation and the genetic engineering genius who actually designed him. Batty wants to have his genetic code altered to extend his assigned four-year life span. He simply wants to live. But when he discovers he cannot, Batty kills Tyrell in a despairing rage, calling him (as Zeus to Cronos) Father. At one point, Batty remarks: Its a hard thing to meet your maker.

Blade Runnercannot be understood without comprehending the deeply felt moral, philosophical, ecological and sociological concerns that are interwoven throughout the story. Three key, yet profound, questions contribute to the core ofBlade Runner: Who am I? Why am I here? What does it mean to be human? Thus, the eternal problems in the film are essentially moral onesthat is, should replicants kill to gain more life? Should Deckard kill replicants simply because they want to exist?

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Blade Runner: What It Means to Be Human in the Cybernetic State

ANN ARBOR The University of Michigans second human embryonic stem cell line has just been placed on the U.S. National Institutes of Healths registry, making the cells available for federally funded research. It is the second of the stem cell lines derived at UM to be placed on the registry.

The line, known as UM11-1PGD, was derived from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproductive purposes, tested and found to be affected with a genetic disorder, deemed not suitable for implantation, and would therefore have otherwise been discarded when it was donated in 2011.

It carries the gene defect responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder characterized by a slowly progressive degeneration of the muscles in the foot, lower leg and hand. CMT, as it is known, is one of the most common inherited neurological disorders, affecting one in 2,500 people in the United States. People with CMT usually begin to experience symptoms in adolescence or early adulthood.

The embryo used to create the cell line was never frozen, but rather was transported from another IVF laboratory in the state of Michigan to the UM in a special container. This may mean that these stem cells will have unique characteristics and utilities in understanding CMT disease progression or screening therapies in comparison to other human embryonic stem cells.

We are proud to provide this cell line to the scientific community, in hopes that it may aid the search for new treatments and even a cure for CMT, says Gary Smith, Ph.D., who derived the line and also is co-director of the UM Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute. Once again, the acceptance of these cells to the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines.

UM is one of only four institutions including two other universities and one private company to have disease-specific stem cell lines listed in the national registry. UM has several other disease-specific hESClines submitted to NIH and awaiting approval, says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School. The first line, a genetically normal one, was accepted to the registry in February.

Stem cell lines that carry genetic traits linked to specific diseases are a model system to investigate what causes these diseases and come up with treatments, says Sue OShea, professor of cell and developmental biology at the UM Medical School, and co-director of the Consortium for Stem Cell Therapies.

Each line is the culmination of years of preparation and cooperation between UM and Genesis Genetics, a Michigan-based genetic diagnostic company. This work was made possible by Michigan voters November 2008 approval of a state constitutional amendment permitting scientists to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

The amendment also made possible an unusual collaboration that has blossomed between the University of Michigan and molecular research scientists at Genesis Genetics, a company that has grown in only eight years to become the leading global provider of pre-implantation genetic diagnosis (PGD) testing. PGDis a testing method used to identify days-old embryos carrying the genetic mutations responsible for serious inherited diseases. During a PGD test, a single cell is removed from an eight-celled embryo. The other seven cells continue to multiply and on the fifth day form a cluster of roughly 100 cells known as a blastocyst.

Genesis Genetics performs nearly 7,500 PGD tests annually. Under the arrangement between the company and UM, patients with embryos that test positive for a genetic disease now have the option of donating those embryos to UM if they have decided not to use them for reproductive purposes and the embryos would otherwise be discarded.

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Second UM Stem Cell Line Now Available To Help Cure Nerve Condition

Public release date: 25-Apr-2012 [ | E-mail | Share ]

Contact: Kara Gavin kegavin@umich.edu 734-764-2220 University of Michigan Health System

The University of Michigan's second human embryonic stem cell line has just been placed on the U.S. National Institutes of Health's registry, making the cells available for federally-funded research. It is the second of the stem cell lines derived at U-M to be placed on the registry.

The line, known as UM11-1PGD, was derived from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproductive purposes, tested and found to be affected with a genetic disorder, deemed not suitable for implantation, and would therefore have otherwise been discarded when it was donated in 2011.

It carries the gene defect responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder characterized by a slowly progressive degeneration of the muscles in the foot, lower leg and hand. CMT, as it is known, is one of the most common inherited neurological disorders, affecting one in 2,500 people in the United States. People with CMT usually begin to experience symptoms in adolescence or early adulthood.

The embryo used to create the cell line was never frozen, but rather was transported from another IVF laboratory in the state of Michigan to the U-M in a special container. This may mean that these stem cells will have unique characteristics and utilities in understanding CMT disease progression or screening therapies in comparison to other human embryonic stem cells.

"We are proud to provide this cell line to the scientific community, in hopes that it may aid the search for new treatments and even a cure for CMT," says Gary Smith, Ph.D., who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute. "Once again, the acceptance of these cells to the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines."

U-M is one of only four institutions including two other universities and one private company to have disease-specific stem cell lines listed in the national registry. U-M has several other disease-specific hESC lines submitted to NIH and awaiting approval, says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School. The first line, a genetically normal one, was accepted to the registry in February.

"Stem cell lines that carry genetic traits linked to specific diseases are a model system to investigate what causes these diseases and come up with treatments," says Sue O'Shea, Ph.D., professor of Cell and Developmental Biology at the U-M Medical School, and co-director of the Consortium for Stem Cell Therapies.

Each line is the culmination of years of preparation and cooperation between U-M and Genesis Genetics, a Michigan-based genetic diagnostic company. This work was made possible by Michigan voters' November 2008 approval of a state constitutional amendment permitting scientists to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

Excerpt from:
New embryonic stem cell line will aid research on nerve condition

ALAMEDA, Calif. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--

BioTime, Inc. (NYSE Amex:BTX) and its wholly owned subsidiary LifeMap Sciences today announced that they have signed a definitive agreement to acquire XenneX, Inc. through a merger of XenneX into LifeMap Sciences. The acquisition is expected to close within thirty days.

XenneX holds the exclusive, worldwide licenses to market GeneCards and PanDaTox. GeneCards is a searchable, integrated, database of human genes that provides concise genomic, transcriptomic, genetic, proteomic, functional and disease related information, on all known and predicted human genes. GeneCards was developed by a world-leading bioinformatics team at the Weizmann Institute of Science in Israel. PanDaTox is a recently developed, searchable, database that can be used to identify genes and intergenic regions that are unclonable in E. coli, to aid in the discovery of new antibiotics and biotechnologically beneficial functional genes, and to improve the efficiency of metabolic engineering.

Since 2003, XenneX has been generating revenue from customers worldwide including biotechnology, pharmaceutical and other life sciences companies, as well as organizations dealing with biotechnology intellectual property. GeneCards and PanDaTox are marketed by XenneX under a license from Yeda Research and Development Company Ltd, the Technology Transfer Company of the Weizmann Institute.

Through the merger, XenneX stockholders will receive approximately 1,362,589 shares of LifeMap common stock, which will represent approximately 13% of the LifeMap common stock outstanding upon the closing of the transaction. XenneX shareholders will also receive approximately 448,430 BioTime common shares as part of the transaction.

Separately, LifeMap Sciences announced that it anticipates acquiring a license from Yeda to market the new MalaCards database of human diseases. Like GeneCards and PanDaTox, MalaCards has been developed by the Weizmann Institute and is expected to be launched at the end of 2012.

Background

The field of biomedical research has expanded greatly in recent years due to the enormous growth of DNA sequencing technology, bioinformatics, and stem cell biology. The growth in research has produced a very decentralized body of information. The mission of BioTimes subsidiary LifeMap Sciences is to centralize access to this information through database technology that will make it much more feasible for researchers around the world to find and utilize information about tens of thousands of genes and thousands of cell types.

LifeMaps team of scientists is building an integrated map of the thousands of cell types in human development, beginning with the fertilized egg and ending in the developed human. Combined with genomics information, the database is expected to become a road atlas of human biology benefiting medicine and research. In addition, LifeMap is developing its own proprietary technology to effectively analyze data gathered from the databases for use in the development of cell-based therapies.

In addition to expanding LifeMaps database offerings through the acquisition of XenneX, BioTime plans to make LifeMap the principal marketing subsidiary for BioTime research products, including ACTCellerate human progenitor cell lines, GMP human embryonic stem (hES) cell lines, hES cell lines carrying inherited genetic diseases, and ESpan growth media for progenitor cell lines for non-therapeutic uses. LifeMap will utilize its databases as part of its online marketing strategy to reach life sciences researchers at biotech and pharmaceutical companies and at academic institutions and research hospitals worldwide.

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BioTime and Subsidiary LifeMap Sciences Announce Agreement to Acquire XenneX, Inc.