Genome Editing, Lab Grown Blood Vessels, and TB Vaccine for Diabetes

Biomedical News: Genome Editing, Lab Grown Blood Vessels, and TB Vaccine for Diabetes

Editing the genome to correct a genetic defect in live animals, blood vessels grown from cultured skin cells, and TB vaccine improves diabetes.

EMILY SINGER

Genome editing to treat hemophilia

For the first time, researchers have used a precise method of editing the genome to correct a genetic defect in live animals. In this case, researchers treated mice with hemophilia, replacing a blood clotting protein called human factor 9. After the treatment, the mice produced enough of the protein to make their blood clot normally.

The editing technology relies on proteins known as zinc fingers, which bind to specific pieces of DNA to regulate nearby genes. By engineering different zinc fingers and attaching them to a gene cutting enzyme, researchers have created precise editing tools that can snip a specific piece of the genome and insert a new gene. Researchers hope the technology will help overcome one of the major problems with existing forms of gene therapy, which allow the gene to insert itself into the genome randomly. That can disrupt important genes, in some cases causing leukemia.

According to the New York Times,

[Katherine High, a hematologist and gene therapy expert at The Children's Hospital of Philadelphia] said it was too soon to try the technique in people, given that an adequate treatment for hemophilia already exists. She plans to test it next in dogs, which are a standard model for new hemophilia treatments. One of the possible problems with the technique is that the zinc fingers sometimes cut at sites other than the intended target site.

Patients get lab-grown blood vessels

Three dialysis patients in Poland have been successfully implanted with blood vessels grown from cultured skin cells. The engineered essels, which were about a foot long and nearly five millimeters wide, were used as shunt to provide access to the blood for dialysis. Shunts created from patients' own vessels or synthetic materials are notoriously prone to failure, according to a release from the American Heart Association.

At follow-up exams up to eight months after implantation, none of the patients had developed an immune reaction to the implants, and the vessels withstood the high pressure and frequent needle punctures required for dialysis.

Investigators previously showed that using vessels individually created from a patient's own skin cells reduced the rate of shunt complications 2.4-fold over a 3-year period. The availability of off-the-shelf vessels could avoid the expense and months-long process involved in creating custom vessels for each patient, making the technique feasible for widespread use.

The blood vessels, which are made by Cytograft Tissue Engineering, could provide a cheaper alternative to those made from a patient's own cells. "This version, built from a master donor, is available off the shelf and at a dramatically reduced cost," estimated at $6,000 to $10,000, Cytograft Chief Executive Todd McAllister told the Associated Press. The grafts also have the potential to be used in lower limb bypass to route blood around diseased arteries, to repair congenital heart defects in pediatric patients, and to fix damaged arteries in soldiers, who might otherwise lose a limb, said McAllister.

A TB vaccine improves type 1 diabetes.

A small clinical trial of people with severe type 1 diabetes shows that bacillus Calmette-Guerin (BCG), a generic drug developed as a vaccine against tuberculosis, can reverse the disease, at least temporarily.

"We found that even low doses of BCG could transiently reverse type 1 diabetes in human patients," said Denise Faustman, director of the Massachusetts General Hospital Immunobiology Laboratory, in a release from the hospital. "One of the key components of this study was our development of a way to measure the death of the autoreactive T cells that destroy the ability of the pancreas to produce insulin. Not only did we observe and measure the death of these self-targeting immune cells, but we also saw evidence of restoration of insulin production even in patients who've had type 1 diabetes for more than a decade."

According to the release,

BCG is known to elevate levels of the immune modulator tumor necrosis factor (TNF), which previous work in Faustman's lab showed can temporarily eliminate the abnormal white blood cells responsible for type 1 diabetes in both humans and mice.

Most participants treated with BCG showed increases in both the death of autoreactive T cells and in levels of the protective regulatory T cells. A temporary but statistically significant elevation in C-peptide levels, suggesting a restoration of insulin production, was also observed in the BCG-treated patients. Unexpectedly, the same responses were seen in one of the placebo-treated patients who, after enrolling in the study, coincidently developed infection with the Epstein-Barr virus, which is known to induce expression of TNF.

The research was presented Monday at the American Diabetes Association scientific sessions in San Diego

Lovotics': The New Science of Engineering Human, Robot Love

"After industrial, service and social robots, Lovotics introduces a new generation of robots, with the ability to love and be loved by humans"

Bi-directional love between a human and a robot -- realistic, genuine, biologically-inspired love -- is the goal of Hooman Samani, an artificial intelligence researcher at the Social Robotics Lab at the National University of Singapore. He calls this new discipline Lovotics.

Across nearly a dozen papers, he has developed a comprehensive artificial intelligence simulation of the emotional and endocrine systems underpinning love in humans, allowing his robots to be "an active participant in the communicative process, [adjusting] its affective state depending on its interactions with humans."

Samani's robots are equipped with both an emotional and a hormonal climate. They display a spectrum of emotions, from happiness to disgust. Based on the videos Samani has produced, they appear to experience something akin to jealousy, and are only content when being stroked by their human companions.

For simplicity's sake, these robots resemble over-size Tribbles. They trill like R2D2, vibrate, move about and flash LED lights in order to qualify their moods.

Whether or not this work "could lead to a revolution in the way humans and robots interact and love each other," it's fascinating to watch a researcher pole-vault right over the question of whether or not humans can ever accept robots into the realm of whether or not we will find them as indispensable as pets, friends and -- dare we say it -- lovers.

Drug Reverses 'Accelerated Aging' in Human Cells

Age reducer: Cells taken from patients with a rapid aging disease were treated with the drug rapamycin. In the top image, a toxic protein called progerin (green) is spread evenly throughout the cells. In the treated cells at bottom, the protein was concentrated and removed much more effectively.
Credit: Science/AAAS

BIOMEDICINE

Drug Reverses 'Accelerated Aging' in Human Cells

The discovery has implications for the treatment of several diseases—as well as normal aging in healthy people.

• BY KENRICK VEZINA

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The drug rapamycin has been found to reverse the effects of Hutchinson-Gilford progeria syndrome, a fatal genetic disease that resembles rapid aging, in cells taken from patients with the disease. Rapamycin, an immunosuppressant drug used to prevent rejection of transplanted organs, has already been shown to extend life span in healthy mice. Researchers hope the findings will provide new insight into treating progeria as well as other age-related diseases.

Skin cells from patients with progeria show a slew of defects: deformities in their membranes, decreased growth, and early death. Kan Cao, an associate professor of cell biology and molecular genetics at the University of Maryland, and her colleagues found that rapamycin could reverse these defects by enhancing the cells' ability to degrade the protein progerin, which accumulates in abnormal amounts in progeria patients. The study was published today in the journal Science Translational Medicine.

It's not yet clear whether the drug will have similar effects on animals or patients. But progeria researchers are planning a clinical trial of rapamycin. No treatments currently exist for the disease, which is typically fatal by age 12. Children with progeria have health issues typically associated with old age, including balding, hardened skin, pain in joints, hip dislocations, and heart disease.

Researchers say the findings could be relevant beyond this rare genetic disease. Although accumulation of progerin is associated with progeria, the protein also accumulates in small amounts in normal cells, and may be partially responsible for the aging process.

Some age-related diseases, such as Parkinson's and Alzheimer's, also result in defects in the cells' "trash-removal" system, says Dimitri Krainc, associate professor of neurology at Harvard Medical School and one of the authors of the paper. In fact, previous research has shown that the failure of cellular maintenance is a key component of aging. "With normal aging ... you start accumulating by-products of normal cell functions," explains Krainc. Rapamycin may be able to help clean up other toxic proteins as well, though this study only looked at its effects on progerin.

"I would hope that the study increases the search for molecules to replace rapamycin," which don't have the immunosuppressant side effects, says David Sinclair, director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School. Such alternatives could be a major step forward in the fight against aging, says Sinclair, who was not involved in the current study.

A Wristwatch that Monitors Blood Pressure

A wired version of the Healthstats monitor is currently in use in hospitals in Singapore and other parts of the world. The company began developing its wireless version about a year ago in collaboration with HP, which has developed a software platform that can be paired with this and other wireless monitors. 

BIOMEDICINE

A Wristwatch that Monitors Blood Pressure

Researchers hope a device that tracks vital signs around the clock will help patients better control their blood pressure.

• BY EMILY SINGER

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"We have developed an application for a patient and physician portal where all this information will be delivered to the appropriate person," says Lloyd Oki, vice president of Asia Pacific sales, communications, and media solutions at HP. "It could be an adult buying a mobile monitoring device for their parents, or a younger person being monitored, with the information sent to a clinician or adult caregiver." He says that Such devices might also interest professional athletes, perhaps calling attention to seemingly healthy athletes with undetected heart issues.

One issue still to be answered is how accurate the device is at measuring blood pressure when people are moving around. Healthstats has shown that the monitor works as well as other measures when users are sitting still, but has yet to publish comparable results for people in motion. "The bottom line from my standpoint is that it is a great idea that still needs to be fine-tuned to be usable in ambulatory patients," says Dena Rifkin, a physician and assistant professor of nephrology at the University of California, San Diego.

A clinical trial underway in Singapore is designed to assess how the device affects patient and physician behavior, rather than its accuracy. A hundred patients, some healthy and some with a high risk of chronic illness or a history of strokes, will use the device over eight weeks. "Every morning, they will receive a summary of the findings via SMS," says Ting. "A call center will look at data round the clock and intervene if needed."

Researchers will then determine whether the monitor helped people with hypertension better control it, and whether it could detect abnormal blood pressure in people who were seemingly healthy. As more people measure their blood pressure throughout the day and night, physicians are discovering different patterns of abnormal blood pressure, such as hypertension only at night, or blood pressure spikes in the early morning, which may contribute to the high percentage of strokes that occur early in the morning, says Ting.

Although high blood pressure can be monitored, and treated effectively, with a number of drugs, a quarter of the people with the condition don't even know they have it, according to the American Heart Association. Of those who know they have high blood pressure, only two-thirds get treatment, and fewer than half have it under control.

Now a new wireless monitor from Hewlett-Packardand a Singapore company called Healthstats aims to make it much easier for patients and doctors to monitor blood pressure. The device, which has the size and look of a wristwatch, can monitor pressure continuously—which provides a much more accurate picture than infrequent readings in the doctor's office. Until now, the only way to do such continuous monitoring has been with a cumbersome inflatable cuff for the arm or wrist.

The new monitor comes with related software designed to keep patients and doctors informed of the wearer's vital signs, including blood pressure. Data is transmitted from the device to the user's cell phone, and then to the cloud, where clinicians can review it. Patients and their doctors can view 24-hour graphs of blood pressure, and the system can sound alerts when it detects abnormalities in pressure or other measures.

The research is part of a growing effort to use wireless monitors to capture round-the-clock medical data outside of the hospital. Physicians hope such devices will inspire patients to better monitor their own health, and help uncover difficult-to-diagnose conditions, such as nighttime hypertension.

Unlike standard equipment, the Healthstats device relies on a sensor that rests against an artery in the wrist and detects the shape of the pressure wave as blood flows through it.  (The device is first calibrated with a standard blood pressure monitor.) "Together with algorithms we have developed, the indices can be processed to get heart rate, diastolic and systolic pressure, and other measures," says Ting Choon Meng, a physician and Healthstats CEO.

Making Speedy Memory Chips Reliable

COMPUTING

Making Speedy Memory Chips Reliable

IBM believes a new way of encoding the bits in phase-change memory will be reliable for server use.

• BY KATHERINE BOURZAC

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IBM researchers have developed a programming trick that allows storing large amounts of data using a promising new technology called phase-change memory. The company hopes to start integrating this storage technology into commercial products, such as servers that process data for the cloud, in about five years.

Like flash memory, commonly found in cell phones, phase-change memory is nonvolatile. That means it doesn't require any power to store the data. And it can be accessed rapidly for fast computer boot-ups and more efficient operation. Phase-change memory has a speed advantage over flash, and Micron and Samsung are about to bring out products that will compete with flash in some mobile applications.

These initial products will use memory cells that store one bit each. But for phase-change memory to be cost-competitive for broader applications, it will need to achieve higher density, storing multiple bits  per cell. Greater density is necessary for IBM to achieve its goal of developing  phase-change memory  for high-performance systems such as servers that process and store Internet data much faster.

The IBM work announced today offers a solution. In the past, researchers haven't been able to make a device that uses multiple bits per cell that works reliably over months and years. That's because of the properties of the phase-change materials used to store the data. Scientists at IBM Research in Zurich have developed a software trick that allows them to compensate for this.

Each cell in these data-storage arrays is made up of a small spot of phase-change materials sandwiched between two electrodes. By applying a voltage across the electrodes, the material can be switched to any number of states along a continuum from totally unstructured to highly crystalline. The memory is read out by using another electrical pulse to measure the resistance of the material, which is much lower in the crystalline state.

To make multibit memory cells, the IBM group picked four different levels of electrical resistance. The trouble is that over time, the electrons in the phase-change cells tend to drift around, and the resistance changes, corrupting the data. The IBM group has shown that they can encode the data in such a way that when it's read out, they can correct for drift-based errors and get the right data.

The IBM group has shown that error-correcting code can be used to reliably read out data from a 200,000-cell phase-change memory array after a period of six months. "That's not gigabits, like flash, but it's impressive," says Eric Pop, professor of electrical engineering and computer sciences at the University of Illinois at Urbana-Champaign. "They're using a clever encoding scheme that seems to prolong the life and reliability of phase-change memory."

For commercial products, that reliability timescale needs to come up to 10 years, says Victor Zhirnov, director of special projects at the Semiconductor Research Corporation. IBM says it can get there. "Electrical drift in these materials is mostly problematic in the first microseconds and minutes after programming," says Harris Pozidis, manager of memory and probe technologies at IBM Research in Zurich. The problem of drift can be statistically accounted for in the IBM coding scheme over whatever timeframe is necessary, says Pozidis, because it occurs at a known rate.

But phase-change memory won't be broadly adapted until power consumption can be checked, says Zhirnov. It still takes much too much energy to flip the bits in these arrays. That's due to the way the electrodes are designed, and many researchers are working on the problem. This spring, Pop's group at the University of Illinois demonstrated storage arrays that use carbon nanotubes to encode phase-change memory cells with 100 times less power.

A Tablet that Wants to Take Over the Desktop

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New look: The Cius tablet features a radically different version of Android.
Credit: Cisco.

COMPUTING

A Tablet that Wants to Take Over the Desktop

Cisco has redesigned the Android operating system to make a tablet that also works as a desktop computer--but it takes some control away from users.

• BY TOM SIMONITE

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The latest entrant in the increasingly crowded tablet computing field, Cisco's Cius, is bulkier than the iPad, and has a smaller screen (7-inches wide, compared to the iPad's 9.7). But it packs a number of tricks all of its own, designed to woo business users. The Cius is designed to integrate closely with Cisco's voice and video phone systems, and it can even replace a desktop computer when docked to a new Cisco deskphone, which connects to a monitor, keyboard and mouse.

A Cius tablet makes a user's desk number mobile, enabling a person to make and receive voice and video calls anywhere, if their company has a Cisco phone system. The tablet features HD quality cameras front and back and can be used with a Bluetooth headset for more private calling. The tablet can also be used as a desktop videoconferencing device when docked on a special desktop phone, and can smoothly switch between a WiFi a cellular network connection.

That dock can also be plugged into a monitor keyboard and mouse to act like a desktop computer. "It can replace my desktop operating system," says Tom Puorro, senior director for Cisco's collaboration technologies.

The Cius runs Google's Android mobile operating system, which is used on a rapidly growing number of smartphones and tablets as well. Android is open source, meaning it can be modified by anyone for free, yet so far most companies that have built gadgets running Android have tinkered with it little. The Cius, in contrast, features a radical reworking of Android.

This gives an IT department much greater control over what a Cius user can do. IT managers can shut down access to the Android app market to protect a company from malicious apps. Cisco has also created its own app store, AppHQ, that contains only apps deemed stable and secure by Cisco. Companies can even create their own app store within AppHQ and limit employees to certain applications, or apps built in house.

A WiFi only version of the tablet will be available worldwide from July 31 at an estimated price of $750. Cisco will sell it along with related services and infrastructure, so the cost to businesses will vary, and could be as low as $650. AT&T and Verizon will each offer versions for their 4G networks this fall.

A person can use the tablet's own OS or Windows even via a virtual desktop that runs in the cloud, as Puorro demonstrated at a launch event held in San Jose today. The tablet's powerful 1.6GHz Intel Atom processor allows desktop-like performance when hooked up to a keyboard, mouse and monitor. Although iPads are showing up in workplaces, they can't offer the same integration with everyday tasks like phone calls, and are limited to email, Web browsing and video, says Puorro.

Cisco worked with Google to get advice on its modifications to Android, says Puorro. These modifications enable Android to deal with video and operations like group calling and transferring calls, and make use of a dedicated chip in the tablet that encrypt all its data.

However, the Cius lags other Android tablets in that it uses a now-outdated version of the operating system, code-named FroYo, which was intended only for phones. Cisco say they will catch up, but are waiting for the fall release of Android, code-named Ice Cream Sandwich, a version that Google says will seamlessly span phones and tablets.

Ken Dulaney, a VP and analyst with Gartner specializing in mobile devices says that Cisco has likely delivered something that none of the 200 or so other tablets launching this year can match. "Samsung's latest Galaxy Tab has much more advanced hardware," he says, "what Cisco has done is create a special case of Android that adds things the enterprise needs and is a unique combination of phone, tablet and videoconferencing device."

Other companies have hinted at plans for enterprise-friendly revamps of Android, says Dulaney, including Motorola, but none have so far yet delivered.

Although the Cius may not seem competitive with Apple's iPad 2 to consumers, to businesses concerned about their security it likely see distinct advantages. Apps such as MobileIron exist to help IT staff control iPads used by their staff, but Apple's operating system fundamentally limits the extent to which the iPad can be managed remotely, says Dulaney. "With Android, Cisco could go in at a low level and change how the device is managed so a company can manage everything for the user."

Without an existing investment in Cisco phone and communication systems, though, many company may see little appeal. Puorro says that Cisco continues to develop and release iPad and iPhone apps for its collaboration software, a strategy Dulaney says is wise. "Of course Cisco will also aggressively support iPads," he says, "I think they're gonna see how the Cius does, and if it doesn't work out, work hard to support the most popular tablets."