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Saturday, November 24, 2007

Life After Embryonic Stem Cells

Twenty-five days. That's how long it took Dr. Shinya Yamanaka of Kyoto University to undo more than 30 years of exquisitely programmed biology packed into a woman's cheek cell — and just maybe change the world. In a procedure that some scientists thought could take decades to discover, Yamanaka tricked the cheek cell into acting like an embryonic stem cell — capable of dividing, developing and maturing into any of the body's more than 200 different cell types. And he wasn't alone: on the same day that he published his milestone in the journal Cell, James Thomson, a pioneering University of Wisconsin molecular biologist, reported similar success in Science.

Their papers cap a year of remarkable research, in which scientists have surged ahead of ethicists and politicians in finding ever more clever ways to generate stem cells. But where other breakthroughs relied on using cells from living embryos — tiny bits of inchoate life, fraught with ethical issues — the work by Yamanaka and Thomson sidesteps that abyss by nursing adult cells into a state in which their cellular destiny is yet to be fulfilled. No embryos, no eggs, no hand-wringing over where the cells come from and whether it is ethical to make them in the first place.

Stem cells generated by this method are ideal not just because they are free of political and moral baggage. They can also be coaxed into becoming any type of tissue, and then be transplanted back into the donor with little risk of rejection. Still, these cells are far from ready for medical use. The viruses used to ferry the genes that manipulate the cells can introduce genetic mutations and cancer. And with myriad ways to reprogram a cell, sorting out the best ones will take time — meaning that stem cells from embryos will remain useful (and controversial) for a while. Both Yamanaka and Thomson admit that we still know too little about how the process works to exploit the method's full potential. Nevertheless, their discovery has moved stem-cell research back to an embryonic state of its own — in which anything, it seems, is possible.

Stem Cell Basics
Research on stem cells is advancing knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. This promising area of science is also leading scientists to investigate the possibility of cell-based therapies to treat disease, which is often referred to as regenerative or reparative medicine.

Stem cells are one of the most fascinating areas of biology today. But like many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

The NIH developed this primer to help readers understand the answers to questions such as: What are stem cells? What different types of stem cells are there and where do they come from? What is the potential for new medical treatments using stem cells? What research is needed to make such treatments a reality?

Stem cells have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that renew themselves for long periods through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.

Scientists primarily work with two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells, which have different functions and characteristics that will be explained in this document. Scientists discovered ways to obtain or derive stem cells from early mouse embryos more than 20 years ago. Many years of detailed study of the biology of mouse stem cells led to the discovery, in 1998, of how to isolate stem cells from human embryos and grow the cells in the laboratory. These are called human embryonic stem cells. The embryos used in these studies were created for infertility purposes through in vitro fertilization procedures and when they were no longer needed for that purpose, they were donated for research with the informed consent of the donor.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, stem cells in developing tissues give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

It has been hypothesized by scientists that stem cells may, at some point in the future, become the basis for treating diseases such as Parkinson's disease, diabetes, and heart disease.

Scientists want to study stem cells in the laboratory so they can learn about their essential properties and what makes them different from specialized cell types. As scientists learn more about stem cells, it may become possible to use the cells not just in cell-based therapies, but also for screening new drugs and toxins and understanding birth defects. However, as mentioned above, human embryonic stem cells have only been studied since 1998. Therefore, in order to develop such treatments scientists are intensively studying the fundamental properties of stem cells, which include:

1/determining precisely how stem cells remain unspecialized and self .renewing for many years; and
2/identifying the signals that cause stem cells to become specialized cells.

What are embryonic stem cells?
What stages of early embryonic development are important for generating embryonic stem cells?
Embryonic stem cells, as their name suggests, are derived from embryos. Specifically, embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body. The embryos from which human embryonic stem cells are derived are typically four or five days old and are a hollow microscopic ball of cells called the blastocyst. The blastocyst includes three structures: the trophoblast, which is the layer of cells that surrounds the blastocyst; the blastocoel, which is the hollow cavity inside the blastocyst; and the inner cell mass, which is a group of approximately 30 cells at one end of the blastocoel.


Stem cells created without embryos
Scientists have made a startling breakthrough that allows them to "reprogram" ordinary skin cells to act like embryonic stem cells.

Stem cells are considered the body's ultimate master cell, able to become almost any other kind of cell, such as heart or lung cells. They have thus been called "pluripotent," meaning they have the ability to differentiate into other cell types.

Until now, the best source of stem cells has been from cloning cells from discarded human embryos. But the use of embryos has been fraught with ethical questions. Now, two new studies suggest there may be an easier way.

On Tuesday, it was announced that laboratory teams working on two continents have both been able to publish landmark studies on the use of skin cells to create pluripotent stem cells that look and act like embryonic stem cells.

They call the cells "induced pluripotent stem cells," or iPS cells for short.

Dr. Janet Rossant, chief of research at Ottawa's Hospital for Sick Children, said the findings are a "very important step forward."

"You take the cell that has become quite specialized, making skin in this case, and by changing the genetic environment you can take the cell and make it think it's back in the embryo and it has the full potential to make every cell in the body," Rossant told CTV's Canada AM on Wednesday.

She said there are still major questions about the research and how it will effect treatment for serious diseases such as diabetes or Parkinson's, noting it needs to be clear the cells will not create tumours or disorganized tissue in patients.

Rossant said some cancer-related effects were detected in the testing, and the process still needs to be fine-tuned.

"On the other hand, this whole process already tells us we should be able to make cells we can study in a petri dish, cells from people who have serious disease, and be able to understand the biology of that diseases in a petri dish and develop new drugs and treatments right there in the dish that you could later test in people."

The findings may have political repercussions in the United States, where President George Bush rejected bills that would have funded embryonic stem cell research.

He had said that medical breakthroughs were possible without destroying embryos. Democrats had said that because of Bush's ideological beliefs he had blocked research that could have uncovered cures to diseases afflicting millions of people.

The authors of the study note that iPS cells are similar -- not identical -- to embryonic stem cells and differences have been noted. But more research is needed to determine what those differences mean.

The two studies are published in two journals: Science and Cell. The Cell paper is from a team led by Dr. Shinya Yamanaka of Kyoto University; the Science paper is from a team led by James Thomson and Junying Yu of the University of Wisconsin in Madison.

Both studies detail a "direct reprogramming" recipe that includes just four ingredients to transform ordinary skin cells, called fibroblasts, into iPS cells.

Yamanaka's team introduced the genes OCT3/4, SOX2, C-MYC, and KLF4 to get their iPS cells. The Thomson team used a slightly different cocktail: OCT4, NANOG, SOX2 and LIN28.

Yamanaka's team reports that they were able to use iPS cells to produce cardiac muscle cells. After 12 days of growth in laboratory dishes, the clumps of cardiac muscle cells actually started beating.

Technique far from perfect

But neither Yamanaka's nor Yu's recipe is perfect. The technique involves using a retrovirus to deliver the genes into the skin cells, which in turn disrupts the DNA of the skin cells. That creates the potential for developing cancer.

But the DNA disruption is just a byproduct of the technique, and experts say they believe it can be avoided.

Thomson, who also produced the first successful human embryonic stem cell lines in 1998, admits that a lot more research is needed on this new technique, "but these methods should be useful for developing disease models and for drug development," his team wrote.

Ian Wilmut of the Scottish Centre for Regenerative Medicine at the University of Edinburgh, who helped clone the first mammal in 1997, Dolly the sheep, said the findings are hugely significant.

"We can now envisage a time when a simple approach can be used to produce stem cells that are able to form any tissue from a small sample taken from any of us," Wilmut said in a statement.

"This will have enormous implications for research and perhaps one day for therapy."

The therapeutic implications of the research are likely years away. Besides overcoming the DNA disruption obstacle, scientists still have to answer basic questions about these cells.

In the short term, these cells would probably be used first for lab studies to create artificial human tissues to test potential drugs.

Scientists also say it's still important to pursue the strategy of using cloned cells from embryos.

The hope is that one day, scientists can use stem cells to treat a variety of diseases, including creating brain cells for Parkinson's disease, pancreatic cells for diabetes and nerve cells for spinal-cord injuries.

The new iPS techniques would likely qualify for federal research funding in the U.S., unlike projects that extract stem cells from human embryos for which funding has been strictly limited.

The iPS cell work would also likely win the approval of bioethicists and religious leaders.

R. Alta Charo, a University of Wisconsin-Madison professor of law and bioethics, says this research alters the debates surrounding both human embryonic stem cell research and human cloning.

"This is a method for creating a stem cell line without ever having to work through, at any stage, an entity that is a viable embryo," Charo says. "Therefore, you manage to avoid many of those debates with the right-to life community."

A pair of astronauts went on a spacewalk Saturday to finish wiring up the international space station's

Astronauts Take Spacewalk for Wiring
A pair of astronauts went on a spacewalk Saturday to finish wiring up the international space station's newest room, the last hurdle that must be cleared before the shuttle Atlantis can deliver a new European laboratory.

Commander Peggy Whitson and Daniel Tani need to hook up more electrical and fluid connections linking the space station and the Harmony compartment that was delivered by the shuttle Discovery last month.

That will allow Harmony to serve as a docking port for the European lab, named Columbus, which is scheduled to be delivered in December. A Japanese lab set to be delivered early next year also will dock to the school bus-size module.

Much of Saturday's work involved lugging a second 18 1/2-foot, 300-pound tray holding fluid lines to Harmony and bolting it down. The lines carry ammonia, a coolant. The astronauts moved and installed another fluid tray on Tuesday.

"Don't rush," Whitson told Tani as they struggled to move the bulky tray. They took turns handling the equipment, with one astronaut passing it to the other and then crawling forward for another hand-off.

Later Saturday, Tani plans to inspect a jammed joint that is needed to turn one of the space station's two sets of huge solar wings. The gear has been experiencing electrical current spikes and must be repaired over the coming months to continue station construction.

Tani found steel shavings inside the joint while spacewalking last month during Discovery's visit.

On Saturday, he plans to remove one of the joint's covers so he can take digital pictures and collect samples of any debris. He will leave the cover off so the astronauts can shoot videos of the gear later.

The space station's three residents have been working almost nonstop since Discovery's departure on Nov. 5, and just last week moved Harmony to its permanent location. This is their third spacewalk and the last planned before Atlantis arrives.

Online retailers prepare for shoppers as Cyber Monday approaches

While shoppers hit brick-and-mortar stores in droves on Friday, another wave of shoppers are expected to hit retailers again Monday through the Internet with sales that are expected to reach well over half a billion dollars this year.

Andrew Lipsman, senior analyst with Internet research firm comScore Networks Inc., said in a Reuters article this week his firm is expecting Cyber Monday sales of more than $700 million this year, which would outpace the $608 million in online sales for last year.

While online sales have taken off, some shopping experiences people still want to do in person.

"Being a winery, the experience still happens inside the building. You can't get that online," said Brad Schmiling, a co-owner of Von Stiehl Winery in Algoma. "This may be the one thing they don't want to buy online. Get in the car and 'Let's go do some sampling.'

"It's a fun break from your standard Christmas shopping," he said.

While the winery can't ship to all states, there are 13 where it can, including Wisconsin. That limits some of the online sales potential, but Von Stiehl does run holiday specials to encourage web traffic.

Schmiling said online sales are about 15 percent of the winery's business, a number that has come up a little in recent years but trails far behind other sales avenues like wholesale. While the summer tourist season may be their busy season, the holidays are good for generating additional business.

"I'd call it a second spike," he said. "It isn't what we see during the tourist season but, like most retail businesses, it starts the Friday after Thanksgiving."

Work is apparently a popular place for online shopping, according to research done for

This year, according to a BIGresearch survey conducted for, 54.5 percent of office workers with Internet access, or 68.5 million people, will shop for holiday gifts from work, according to the survey.

That's up from 50.7 percent in 2006 and 44.7 percent in 2005.

Those online sales will also make up a larger percentage of all holiday-related sales this year with the Internet influencing 30.2 percent of holiday sales this year, according to the survey. In 2006, that number was set at 28.9 percent.

While Cyber Monday has garnered its own term, Mastercard said it sees purchases peaks later in the shopping season.

In 2005, the busiest online shopping day in terms of total MasterCard-processed e-commerce transactions was Dec. 5, according to a news release from that company. In 2006, it was a week later and with Thanksgiving falling early, this year's busiest day will likely be nearly three weeks later on Dec. 10.

Infinity Technology in Green Bay — which offers services like Web site and software development, network solutions and telephone services — has ridden the wave of increasing online shopping popularity over the past few years.

They got into the market with around the turn of the century but Curt Beams, the firm's technology product manager, said as the industry has matured over the past few years, retailers have asked for more dynamic sites allowing them to create their own look and feel.

"What you're seeing more of a migration to is not just an online store, but an online store where the average Joe can update the information without having significant training," he said.

"We had some customers that have had incredible success with their online stores we created, but we've put the time and energy into it and so have they.

"Anyone can stick a store out there but if they don't do anything with it … it's just another page sitting out there no one sees," Beams said.

Hollywood Launches Legal Digital Copying of DVD Movies

Buyers of the new 'Live Free or Die Hard' and 'Harry Potter' movie DVDs will be allowed to make digital copies. But are these offers enough to stem illegal activities?

You've already bought the DVD to enjoy on your big-screen TV at home. But you also want to watch the flick on your portable media player or on your laptop without using the disc.

Until now, you had two options: Rebuy the movie digitally (an expensive, often limited proposition), or circumvent the copy protection on the disc and make your own digital copy of the movie. Two film studios are taking baby steps toward offering a third, legal alternative, permitting you to copy the movie to your device from the DVD itself.MOV
Twentieth Century Fox is first out of the gate. With the two-disc Live Free or Die Hard Collector's Edition DVD, out today, Fox debuts Fox Digital Copy, the studio's fledgling infrastructure for allowing consumers to transfer digital copies of a movie from the disc to a PC and to a portable device.

Warner Brothers follows suit on December 11, with the DVD release of Harry Potter and the Order of the Phoenix.

Similarities Between the Two Digital Versions

The Fox and Warner initiatives share several similarities. Both include the digital-copy feature at no extra charge on the special-edition DVDs, which run at about a $5 premium over the standard editions. Both studios are using Windows Media DRM and require Windows Media Player 10 or above. Both offer two digital versions of the films, one for PC and one for a portable device.

Fox says that its PC version of the Die Hard sequel is encoded at 1.6 megabits per second (taking up about 1.5GB of space), while the portable version runs at 768 kilobits per second (about 1GB of space). Warner says that its PC version of the latest Harry Potter movie averages about 1 mbps, while the portable version averages about 700 kbps.

The two studios have chosen a similar strategy for their initial digital-copy transfers, placing the digital versions on the second disc of the two-disc special-edition DVDs. (An interesting side note: Warner says that industrywide only about 20 to 25 percent of buyers opt for the more expensive special editions of DVDs, a point that underscores that the studios are slowly easing into this brave new digital world.) The studios also cite the same reasoning for including the digital movies on the disc: Doing so offers a more immediate experience as compared with a download via the Internet.

Warner experimented with Internet downloads this past summer, on the epic battle movie 300. DVDs of 300 sold in Target and Wal-Mart, for example, came with a download code for accessing the film via the Internet. For Harry Potter, though, Jim Wuthrich, senior vice president of electronic sell-through for Warner Brothers, says that the studio chose to put the movie on the disc instead.

"It's because of the superior consumer experience; you don't have to wait for the bits to be downloaded," he says. "The transfer time is dependent only on how fast your DVD-ROM drive is. It's not tied to your broadband speed."

Danny Kaye, executive vice president of global research and technology strategy at Twentieth Century Fox Home Entertainment, says that the inclusion of digital copies on-disc is a precursor to broadening the digital movie downloads business beyond the niche that it occupies today.

"That's the vision," he says. "We have to start somewhere and we're starting right here."

Hands-On: Live Free or Die Hard--How the Copy Works

I had the chance to test Fox's Live Free or Die Hard copy functions, and I found much to like. But not all was rosy.

Accessing the digital copies was easy. Pop the second disc into your PC, and it comes up with a menu that lets you choose between accessing special features or going to Digital Copy. I selected Digital Copy, and waited a few moments while the disc verified the state of my Windows digital rights management software; turned out I needed an update, a situation Microsoft remedied in just a few seconds.

Once my DRM was up-to-date, the disc prompted me for a 16-digit code that's printed on an insert that came with the DVD. Fox's server quickly validated the code; once I was approved, the Digital Copy Manager launched. I selected my movie from column A, chose the destination (hard drive, portable device) from column B, and clicked the 'Start Sync' (odd choice of nomenclature) button. The transfers were fast, taking 2 minutes for the PC version of the film and 2 minutes, 20 seconds to transfer it to a portable device.

The PC version's image quality looked surprisingly good on my 19-inch LCD monitor. The image appeared on a par with movie download-to-buy options (such as Apple's iTunes Music Store).

I didn't have the opportunity to view the portable version. For starters, I learned the hard way that the Digital Copy Manager isn't smart enough to recognize that the Samsung YP-P2 isn't a Windows PlaysForSure device: I ended up copying the portable version of the film directly to the YP-P2. Oops.

For now, the Die Hard digital copy will work only with Windows PlaysForSure devices. This is a notably odd choice, given that even Microsoft has backed off from PlaysForSure, and the company's own new Zunes don't support the standard. Fox's Kaye says that other formats may be supported in the future.

The system is set up to allow only one transfer each of the PC and portable versions. If something goes wrong--for instance, your hard drive fails or you lose your portable device--Kaye says that Fox's customer service will provide a one-time-only disaster-recovery exception for a second copy. Warner has not established any parameters for such scenarios as of yet.

Warner's Harry Potter DVD wasn't yet available for me to try its digital-copy functionality, but from what Wuthrich describes, it's very similar to how Fox's implementation worked. Two small differences: One, the portable version transfers to your PC hard drive first and then moves to your portable unit. Two, Wuthrich says the portable version will work on any device that supports Windows Media digital rights management, including media players and some mobile phones.

A simmering unease about threats to privacy from a new feature on Facebook

Privacy fears over Facebook feature
simmering unease about threats to privacy from a new feature on Facebook is threatening to come to the boil, presenting the fast-growing social network with the first test of its unusual plans for making money from its site.

By automatically alerting a user's online network of friends to things bought on other websites, the feature can reveal highly personal information, critics say.

Facebook, however, says its users can choose to keep their purchases secret, or to limit the number of online friends to whom their purchases are disclosed.

Known as Beacon, the feature was one of several money-making ideas Facebook launched this month to try to turn its users' actions - such as their online purchases and their stated preferences for certain brands - into recommendations that might influence the buying habits of their friends.

Though it caused unease around the internet when first announced, the Beacon system has attracted a renewed burst of unwelcome attention in recent days thanks largely to the efforts of, the online political action group.

The attention has been fuelled further by this week's Thanksgiving holiday, which marks the high point of the seasonal boom in online shopping.

MoveOn launched an online petition calling on Facebook to apply Beacon only to users who have specifically opted in to the system. At present, Facebook says its users are given two chances to opt out of sending a Beacon alert to their friends - when making a purchase on a website that uses the system, and again on Facebook itself.

However, some online shoppers have complained that these warnings have not always been given, or that they are easy to miss.

One analyst, Charlene Li at Forrester, reported that her husband's purchase of a coffee table on had been reported to her own network of Facebook friends, since the computer they shared could not tell which of them had made the purchase. Also, no warning had been given by Overstock, she said.

"The biggest problem is the lack of transparency," Ms Li wrote on her blog. "There's a fine line that gets crossed when behaviour data slips from being a convenience to being Big Brother. This is one of those times."

Facebook faced similar unease more than a year ago when it launched a feature, known as Newsfeed, that alerts friends to everything a user does on the site.

The social networking site responded by giving users more power to limit the items that appear on the Newsfeed, and the ability to restrict who can see it.

Since then, the feature has become one of the site's most popular.

Facebook Social network service

A social network service focuses on the building and verifying of online social networks for communities of people who share interests and activities, or who are interested in exploring the interests and activities of others, and which necessitates the use of software.

Most social network services are primarily web based and provide a collection of various ways for users to interact, such as chat, messaging, email, video, voice chat, file sharing, blogging, discussion groups, and so on.

The main types of social networking services are those which contain directories of some categories (such as former classmates), means to connect with friends (usually with self-description pages), and recommender systems linked to trust. Popular methods now combine many of these, with MySpace, Bebo and Facebook being the mostly widely used in the anglosphere.[1][2]

There have been some attempts to standardize them (see the FOAF standard) but this has led to some privacy concerns.

Facebook Users Complain of New Tracking

NEW YORK - Some users of the online hangout Facebook are complaining that its two-week-old marketing program is publicizing their purchases for friends to see.

Those users say they never noticed a small box that appears on a corner of their Web browsers following transactions at Fandango, Overstock and other online retailers. The box alerts users that information is about to be shared with Facebook unless they click on "No Thanks." It disappears after about 20 seconds, after which consent is assumed.

Users are given a second notice the next time they log on to Facebook, but they can easily miss it if they quickly click away to visit a friend's page or check e-mail.

"People should be given much more of a notice, much more of an alert," said Matthew Helfgott, 20, a college student who discovered his girlfriend just bought him black leather gloves from Overstock for Hanukkah. "She said she had no idea (information would be shared). She said it invaded her privacy."

The girlfriend was declining interviews, Helfgott said.

An Inc. spokesman said no one was immediately available for comment Wednesday.

Facebook has long prided itself on guarding its users' privacy, but the walls have gradually lowered. In 2006, a "news feeds" feature allowing users to track changes friends make to profiles backfired when many users denounced it as stalking and threatened protests. Facebook quickly apologized and agreed to let users turn off the feature.

The new program lets companies tap ongoing conversations by alerting users about friends' activities through the feeds. About 40 Web sites have decided to embed a free tool from Facebook, known as a Beacon, to enable the marketing feeds.

The idea is that if users see a friend buy or do something, they'd take that action as an endorsement for a movie, a band or a soft drink.

But it also raises privacy concerns.

Mike Mayer, for instance, saw a feed item saying his boyfriend, Adam Sofen, just bought tickets to "No Country For Old Men" from movie-ticket vendor Fandango.

"What if I was seeing 'Fred Claus'?" said Sofen, 28. "That would have been much more embarrassing. At least this was a prestigious movie."

In some cases, companies can buy an ad next to the feed item with the friend's photo. Although Fandango didn't do that, Mayer, 28, still found Beacon unsettling.

"If my identity is going to be used to promote something for someone else, that seems problematic," said Mayer, who was previously employed in online advertising. "It could be a misrepresentation of my purchases."

Fandango officials referred inquiries to Facebook, which issued a statement defending its practices. Facebook officials have also said advertising supports the free service.

"Beacon gives users an easy way to share relevant information from other sites with their friends on Facebook," the statement said. "Information is shared with a small selection of a user's trusted network of friends, not publicly on the Web or with all Facebook users. Users also are given multiple ways to choose not to share information from a participating site, both on that site and on Facebook."

Users are able to decline sharing on a site-by-site basis, but can't withdraw from the program entirely.

On Wednesday, Facebook launched a mechanism for users to indicate what types of news feeds they like and dislike. Individuals could possibly use that to lower the frequency of marketing items, though the company has said they won't be able to reject them completely.

Liberal advocacy group formed a protest group Tuesday and had more than 6,000 members by Wednesday. The group is calling on Facebook to stop revealing online purchases and letting companies use names for endorsements without "explicit permission."

"We want Facebook to realize that their users are rightly concerned that private information is being made public," MoveOn spokesman Adam Green said, adding that Facebook could quell concerns by seeking "opt in" consent rather than leaving it to users to "opt out" by taking steps to decline sharing.

Facebook user Nate Weiner, 23, said he uses a tool for the Firefox Web browser called BlockSite, which he says prevents sites from sending data to Facebook.

"What if you bought a book on Amazon called 'Coping with AIDS' and that got published to every single one of your friends?" he said.

'Micro' livers could aid drug screening

MIT researchers have devised a novel way to create tiny colonies of living human liver cells that model the full-sized organ. The work could allow better screening of new drugs that are potentially harmful to the liver and reduce the costs associated with their development.

Liver toxicity is one of the main reasons pharmaceutical companies pull drugs off the market. These dangerous drugs slip through approval processes due in part to the shortcomings of liver toxicity tests. Existing tests rely on liver cells from rats, which do not always respond to toxins the way human cells do. Or they rely on dying human cells that survive for only a few days in the lab.

The new technology arranges human liver cells into tiny colonies only 500 micrometers (millionths of a meter) in diameter that act much like a real liver and survive for up to six weeks.

Sangeeta Bhatia, associate professor in the Harvard-MIT Division of Health Sciences and Technology (HST) and MIT's Department of Electrical Engineering and Computer Science, and HST postdoctoral associate Salman Khetani describe their model liver tissue and its behavior in the November 18 online issue of Nature Biotechnology.

To build these model livers, Khetani uses micropatterning technology--the same technology used to place tiny copper wires on computer chips--to precisely arrange human liver cells and other supporting cells on a plate. Khetani adapted this method from Bhatia's early work as an HST graduate student building micropatterned co-cultures of rat liver cells and supporting cells.

Such precisely arranged cells results in what Bhatia calls a "high-fidelity tissue model" because it so closely mimics the behavior of a human liver. For example, each model "organ" secretes the blood protein albumin, synthesizes urea, and produces the enzymes necessary to break down drugs and toxins.

To predict how close their model tissue is to real liver tissue, which has over 500 different functions, they also evaluated its gene expression profiles, measures of the levels of gene activation in the tissues. They found that these profiles are very similar to those of fresh liver cells, "giving us confidence that other [liver] functions are preserved," said Khetani.

For drug testing purposes, this affinity to the human liver allows each colony to provide a window into the human liver's response to a drug without having to expose human patients to the drug in a clinical trial, said Bhatia.

Further, because the engineered tissue lives for so long, it has the potential to make new types of toxicity tests possible. For instance, it opens the door to testing the effects of long-term drug use akin to taking one pill a day over multiple weeks. It also will allow more extensive testing of drug-drug interactions.

In addition to being a good biological model, the engineered tissue is designed to be seamlessly integrated into an industrial pharmaceutical science setting.

To mass-produce plates of the miniature liver models, Khetani relies on a technique called soft lithography. This technique fashions a reusable micropatterned rubber stencil from a silicon master. Each stencil contains an array of 24 wells, and each well contains a matrix of 37 tiny holes. Khetani "peels and sticks" the stencil onto plates and places the liver cells into the holes, patterning over 888 miniature model livers across the microwells in a matter of minutes.

In tests of drugs with a range of well-known toxicity levels, assays (chemical detection tests) on the miniature liver models showed the expected levels of toxicity. "Our platform was able to predict the relative toxicity of these drugs as seen in the clinic," said Khetani. For instance, troglitazone, a drug withdrawn from the market by the FDA due to liver toxicity, showed toxicity levels much higher than its FDA-approved analogues, Rosiglitazone and Pioglitazone.

The model uses a fraction of the costly human liver cells used in other test platforms and can be assembled using frozen cells. Moreover, the expanded toxicity testing capabilities have the potential to allow drug developers to identify toxicity earlier in the development process, thereby avoiding the expense of investing in formulas that are bound to fail.

A startup company called Hepregen has licensed the technology and is working to introduce it into the pharmaceutical marketplace.

"My hope is that this new model will make drugs safer, cheaper and better labeled," said Bhatia.

This work was funded by the National Science Foundation, the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases, the MIT Deshpande Center, and the David and Lucile Packard Foundation.

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MIT launches new global innovation initiative

MIT today announced a new initiative that will strengthen, connect and accelerate its innovation efforts around the globe. The International Innovation Initiative (I3, pronounced "I-cubed"), which MIT President Susan Hockfield announced today at a conference in New Delhi, India, will provide a focal point for future interactions between MIT researchers and the global venture capital community.

"I3 will usher in a new era of partnership and collaboration, and provide new opportunities for innovation," said Hockfield. "The initiative will be a catalyst for new strategies to solve world problems -- such as climate change, energy and the environment -- and to drive economic growth."

I3 will use as its model the Deshpande Center for Technological Innovation, established at the MIT School of Engineering in 2002 to identify and incubate novel early-stage research developed at MIT, with the aim of turning great ideas into real-world products and processes. Founded with an initial donation by technology entrepreneur and visionary Desh Deshpande and his wife, Jaishree, the center has funded more than 65 projects; 12 of those have spun out of the center into commercial ventures with outside financing.

"The newly formed International Innovation Initiative provides a streamlined organizational umbrella to strengthen and enhance the innovation ecosystem by applying the best practices of the Deshpande Center in the School of Engineering to our international activities and collaborations," said Subra Suresh, dean of engineering and Ford Professor of Engineering.

Among its many objectives, I3 will work with international partners to identify and select collaborative research projects across multiple disciplines that could lead to new company formation; connect researchers to local and global venture capital networks; and develop courses for students that address technological innovation and go-to-market strategies.

I3 will be organized through the Deshpande Center within the MIT School of Engineering, and will be headed by Professor Charles L. Cooney, faculty director of the Deshpande Center.

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MIT launches new global innovation initiative

MIT today announced a new initiative that will strengthen, connect and accelerate its innovation efforts around the globe. The International Innovation Initiative (I3, pronounced "I-cubed"), which MIT President Susan Hockfield announced today at a conference in New Delhi, India, will provide a focal point for future interactions between MIT researchers and the global venture capital community.

"I3 will usher in a new era of partnership and collaboration, and provide new opportunities for innovation," said Hockfield. "The initiative will be a catalyst for new strategies to solve world problems -- such as climate change, energy and the environment -- and to drive economic growth."

I3 will use as its model the Deshpande Center for Technological Innovation, established at the MIT School of Engineering in 2002 to identify and incubate novel early-stage research developed at MIT, with the aim of turning great ideas into real-world products and processes. Founded with an initial donation by technology entrepreneur and visionary Desh Deshpande and his wife, Jaishree, the center has funded more than 65 projects; 12 of those have spun out of the center into commercial ventures with outside financing.

"The newly formed International Innovation Initiative provides a streamlined organizational umbrella to strengthen and enhance the innovation ecosystem by applying the best practices of the Deshpande Center in the School of Engineering to our international activities and collaborations," said Subra Suresh, dean of engineering and Ford Professor of Engineering.

Among its many objectives, I3 will work with international partners to identify and select collaborative research projects across multiple disciplines that could lead to new company formation; connect researchers to local and global venture capital networks; and develop courses for students that address technological innovation and go-to-market strategies.

I3 will be organized through the Deshpande Center within the MIT School of Engineering, and will be headed by Professor Charles L. Cooney, faculty director of the Deshpande Center.

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MIT and India to create health science and technology institute

MIT and the government of India's Department of Biotechnology today launched a partnership that will result in the creation of a new Translational Health Science and Technology Institute (THSTI) in India.

This new institute, which will be modeled after the Harvard-MIT Division of Health Sciences and Technology (HST), will include faculty from multiple disciplines and professions, offer degrees through multidisciplinary programs and develop strong ties with other institutions. Funded by the Indian government, the Indian HST will be a multidisciplinary, multiprofessional research and training center that is highly interconnected with regional centers of excellence.

The institute will increase India's capacity for translating scientific and technological advancements into medical innovations that have the potential to improve healthcare both in India and around the world.

HST Director Martha Gray and Dr. M. K. Bhan, Secretary, Department of Biotechnology, Ministry of Science & Technology, Government of India, signed a letter of intent for this partnership today at a symposium in New Delhi titled "India and MIT: A Conversation about the Future."

"Tremendous potential exists in India, with its excellence in engineering and science. This partnership is an opportunity to create a long term, synergistic relationship that will result in wide ranging benefits to global health," said Bhan.

"Launching this new partnership with India's Department of Biotechnology will build on HST's pioneering model of medical education that integrates science, medicine and engineering to solve problems of human health," said Susan Hockfield, president of MIT. "We look forward to a future of significant collaboration across disciplines, across institutions and around the world."

To foster a culture of innovation in THSTI, HST will help recruit and train new THSTI faculty members. Each year starting in September 2008 and continuing until 2011, four recruited THSTI faculty fellows will join the HST faculty. These faculty fellows will train at HST for two years. During their stay they will develop translational research programs, design courses and curricula for THSTI, and develop close relationships with HST faculty and students.

These fellows will benefit from HST's nearly 40 years of experience bringing together science, engineering and medicine in education and translational medical research. HST's success stories include medical innovations such as functional magnetic resonance imaging, a low-cost AIDS detection kit and novel implantable drug delivery mechanisms.

HST and MIT will also benefit from having these fellows on campus. "We will have people immersed in our program who actually know about the unmet medical needs in India and who will expose our students and faculty to those needs," said Gray.

This exposure will help drive innovations that can make a real difference in global public health, said Gray. "I don't believe we can have a global impact on health if we don't have international partners as part of our community."

MIT and India have embarked on partnerships before. The two joined forces nearly 50 years ago to form the India Institute of Technology (IIT) in Kanpur, one of India's top-ranked engineering and science schools. "THSTI has the potential to be a second success story that could revolutionize medicine in India the same way the IIT schools revolutionized engineering and science," said Shiladitya Sengupta, assistant professor of medicine and an HST faculty member at Harvard Medical School.

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MIT hosts (little girl of 7 years ) Make-A-Wish event

When I grow up, I want to be a scientist. How many MIT students uttered these words when they were children? Though not an MIT student, Juliana Bach, a 7-year-old from Miami, discovered her passion for science at a young age. On Tuesday, Nov. 13, MIT, in conjunction with the Make-A-Wish Foundation, made her wish to be a scientist come true.

As Juliana works in the lab, she looks like a miniature scientist, wearing a white lab coat with her name stitched across the front. With her earnest demeanor and straight posture, Juliana exhibits all the characteristics of an eager science student. The only indications of her young age are the pink pants peeking out from below her lab coat, the high ponytail swinging on top of her head, and her tiny infectious giggle. What her physical appearance and positive demeanor cannot tell you, however, is that Juliana has leukemia.

Juliana's parents approached the Make-A-Wish Foundation about her desire to be to a scientist and were promptly directed to MIT, which was delighted to host her on campus. Juliana's requests while at MIT were to experiment with chemical reactions, discover how liquids change color, find out why there are different colors of sand, and make "goop."

Juliana first met with Heidi Nepf, director of the Environmental Fluid Mechanics Lab and professor of civil and environmental engineering. Nepf worked with Juliana to demonstrate aspects of how water moves in rivers, lakes and the coastal zone. The experiments were all based on previous or current research in Nepf's laboratory, but scaled down in size and concept to be understandable to a 7-year-old.

"She looks at Heidi with awe, like she's Santa Claus," said Juliana's father, Charles Julian. He said that Juliana has been doing her own science experiments for as long as he can remember, mixing together kitchen items such as salt and water and experimenting with chemistry sets to test acids and bases.

Professor Philip Gschwend of the Department of Civil and Environmental Engineering was the second MIT professor to work with Juliana. They worked together to find out if the lakes in Florida, Michigan and Massachusetts might be sensitive to pollution from acid rain, with associated risks for the animals and plants living in them. In their second experiment, they created a material, or "goop," that might be a useful substitute for rubber.

"I enjoyed preparing for Juliana's visit, and I used my own daughters, ages 6 and 8, to test each of the experiments in advance. In fact, this was an essential step, because not everything worked as smoothly as I initially thought," said Nepf. "Juliana seemed to enjoy her visit tremendously. Her curiosity and enthusiasm reminded me of how fun research really is."

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