November 2003
Insulin injections without needles
The NanoPump is a tiny silicon array on the skin in which
dozens or hundreds of tiny,
hollow pyramids, are set, barely detectable by the naked eye.
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Nov. 2, 2003 - Diabetes patients have long been required to administer their daily injections with an inch-long needle. But soon, thanks to NanoPass Technologies, an Israeli company based on a technology developed at the Technion Israel Institute of Technology, millions of Americans will be able to say goodbye to those uncomfortable, painful injections.
The NanoPump device, developed by Technion lecturer Dr. Shuki Yeshurun, will enable diabetics to painlessly and easily inject themselves with insulin and will also assist the patients to injections of additional medications and various immunizations.
"Diabetics are known to be pain tolerant but for needle-phobes and kids, these needles are a nightmare." said Yeshurun, NanoPass's founder and president.
The NanoPump is a tiny silicon array on the skin in which dozens or hundreds of tiny, hollow pyramids, are set, barely detectable by the naked eye. This unique system is intended to deliver large molecules, such as insulin, which until now could not be introduced into the body without painful and invasive injections. The system is operated by an insulin pump. The company's future systems will integrate a mechanism for internal propulsion of the drug so that patients can inject the material themselves without the need of a pump.
Convenience is not the only advantage of this new development. According to Yeshurun: "Injecting the material into the upper layer of skin may yield better results than deeper penetration. In the case of immunizations, for example, the new method can save large sums of money because shallow injection may enables the use of smaller quantities of a vaccine - less than required for conventional injections immunization."
Dr. Yotam Levin, the CEO of NanoPass says that the NanoPump is a unique device for insulin injections. A handful of small-scale micro-needle developers exist, but Levin says NanoPass's technology is more cost-effective. In addition, NanoPass micro-needles do not break in the body, resist clogging with tissue and overcome skin elasticity.
"There are micro-needles that have been developed at the renowned centers such as the University of California in Berkeley and at Georgia Tech, as well as some commercial companies. They have good techniques, but are quite different from our technology. We are using pyramids, which is a feature that is unique to us. It's a very robust structure, and its sharp tip allows it to penetrate most effectively," he told ISRAEL21c.
"Large molecules simply cannot pass through the skin," said Levin. "Existing ways for delivering proteins such as insulin, antibodies, and vaccines are limited and usually painful. These molecules cannot be delivered by a conventional patch and they degrade too fast in the stomach or liver to be put in a tablet."
NanoPass will also combine micro-needles with jet injection. It has been found that administering vaccine to the skin's shallow layer, a central area for immune-potent cells, may provide a better response compared to other delivery depths.
"Some sources found they needed 1/1000 of the vaccine for an equivalent response. These cost savings are phenomenal," Levin said.
In the U.S., treating diabetes costs about $100 billion a year, with the main treatment insulin injections. But as the disease progresses, many patients need continually increasing amounts of the hormone, and the injections become less effective. The discovery of a more effective treatment could significantly improve the quality of life of patients.
Approximately 17 million people in the United States, or 6.2% of the population, have diabetes. Some 5 percent of the world suffers from diabetes, making it a major public health concern. Complications from diabetes include heart disease, strokes, kidney failure, blindness, and limb amputation.
Sales of the NanoPump are projected to begin in 2005 following clinical trials and identifying co-developers. Levin said the company is working on a number of active agreements with leading pharmaceutical and medical device companies around the world.
"We've approached a number very large commercial entities, some in the U.S. and we've received great interest to work on co-development. We are looking for potential collaborators like medical device companies in America," he said.
NanoPass, the winner of the "Best of the Best Award for Innovation" at the 2002 Capital IT Competition in Paris, was founded in 2000 and is based in Haifa. Since its inception, NanoPass has demonstrated successful delivery feasibility with insulin in animals; filed nine twelve pending patents, of which two are officially approved, and completed its production process for silicon micro-pyramids.
Courtesy http://www.israel21c.org/
DNA used to create self-assembling nano transistor
The Technion research points to a possible future method of creating the smallest-ever molecule-sized circuits.
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Nov. 23, 2003 - Scientists at the Technion-Israel Institute of Technology have harnessed the power of DNA to create a self-assembling nanoscale transistor.
The research, published in the Nov. 21, 2003 issue of Science, is a crucial step in the development of nanoscale devices, and is viewed as a major step towards developing nanoscale electronics. The advance points to a possible future method of creating the smallest-ever molecule-sized circuits.
Erez Braun, lead scientist on the project and associate professor in the Faculty Physics at the Technion, says science has been intrigued with the idea of using biology to build electronic transistors that assemble without human manipulation. However, until now, demonstrating it in the lab has remained elusive. "This paper shows you can start with DNA proteins and molecular biology and construct an electronic device," he said.
It is significant that the transistor self-assembles instead of having to be painstakingly put together molecule by molecule, a slow and inefficient way of constructing these tiny devices.
"Erez Braun and his colleague Uri Sivan are some of the few pioneers in this field," said Horst Stormer, professor in Columbia University's Departments of Physics and Applied Physics and scientific director of the Nano Science and Engineering Centers. "This is outstanding research in the area that matters most in nanotechnology: self-assembly."
To get the transistors to self-assemble, the Technion research team attached a carbon nanotube - known for its extraordinary electronic properties - onto a specific site on a DNA strand, and then made metal nanowires out of DNA molecules at each end of the nanotube. The device is a transistor that can be switched on and off by applying voltage to it.
The carbon nanotubes used in the experiment are only one nanometer, or a billionth of a meter, across. In computing technology, as scientists reach the limits of working with silicon, carbon nanotubes are widely recognized as the next step in squeezing an increasing number of transistors onto a chip, vastly increasing computer speed and memory. Braun emphasized that computers are only one application; these transistors may, for example, enable the creation of any number of devices in future applications, such as tiny sensors to perform diagnostic tests in healthcare.
Though transistors made from carbon nanotubes have already been built, those required labor-intensive fabrication. The goal is to have these nanocircuits self-assemble, enabling large-scale manufacturing of nanoscale electronics.
DNA, according to Braun, is a natural place to look for a tool to create these circuits. "But while DNA by itself is a very good self-assembling building block, it doesn't conduct electrical current," he noted.
To overcome these challenges, the researchers manipulated strands of DNA to add bacteria protein to a segment of the DNA. They then added certain protein molecules to the test tube, along with protein-coated carbon nanotubes. These proteins naturally bond together, causing the carbon nanotube to bind to the DNA strand at the bacteria protein.
The new technique takes advantage of a biological process known as recombination, where a segment of DNA is swapped out for an almost identical piece. The cell uses recombination to repair damaged DNA and to swap genes. By attaching a nanotube to the protein, the nanotube moves to an exact location along the DNA strand.
"The DNA serves as a scaffold, a template that will determine where the carbon nanotubes will sit," Braun said. "That's the beauty of using biology." Finally, they created tiny metal nanowires by coating DNA molecules with gold. In this step, the bacteria protein served another purpose: it prevented the metal from coating the bacteria-coated DNA segment, creating extending gold nanowires only at the ends of the DNA strand.
The goal, Braun explained, was to create a circuit. However, "at this point, the carbon nanotube is located on a segment of DNA, with metal nanowires at either end. Theoretically, one challenge here would be to encourage the nanotube to line up parallel to the DNA strand, meet the nanowires at either end, and thus make a circuit.
"There are some points where nature smiles upon you, and this was one of those points," Braun continued. "Carbon nanotubes are naturally rigid structures, and the protein coating makes the DNA strand rigid as well. The two rigid rods will align parallel to each other, thus making an ideal DNA-nanotube construct. In a nutshell, what this does is create a self-assembling carbon nanotube circuit," he concluded.
Scientists controlled the creation of transistors by regulating voltage to the substrate. Out of 45 nanoscale devices created in three batches, almost a third emerged as self-assembled transistors.
Braun added, however, that while this research demonstrates the feasibility of harnessing biology as a framework to construct electronics, creating working electronics from self-assembling carbon nanotube transistors is still in the future.
Braun conducted the research with colleagues Kinneret Keren, Rotem S. Berman, Evgeny Buchstab, and Uri Sivan.
Courtesy http://www.israel21c.org/
Jerusalem research team hails cystic fibrosis genetic breakthrough
Nov 23, 2003 - Israeli researchers have found that an antibiotic used for years against common infections may have the remarkable ability to correct a genetic flaw in cystic fibrosis, a finding that ultimately may lead to a new way of treating that and other intractable genetic diseases.
Their findings, published recently in the New England Journal of Medicine, could be applied to other genetic disorders, including muscular dystrophy, Hurler's syndrome, and various types of hemophilia and cancer, say Dr. Michael Wilschanski and Prof. Eitan Kerem, who headed the team.
Experts in the field have called their accomplishment a "major breakthrough" in the treatment of CF.
Cystic fibrosis occurs mostly in whites and strikes one in every 3,200 live Caucasian births in this country, and 1,000 new cases are diagnosed annually, according to statistics from the Cystic Fibrosis Foundation. An estimated 30,000 children and adults in the United States are afflicted and have an average life expectancy of 33.4 years. There are some 500 Israelis diagnosed with CF.
The researchers have managed to repair a form of the mutant gene that causes the inherited lung disease cystic fibrosis (CF) with antibiotic nasal drops commonly used for eye infections called Gentamicin. The antibiotic, long a staple in the fight against bacteria, has the unusual ability to override a major genetic defect in cystic fibrosis and tweak DNA transcription involved in the entrance and exit of chloride in cells.
Just as a memo must be transcribed for dispersal to workers, something similar must occur in the transcription of messages from DNA, the master text of life. Messages contained within DNA must be read and then transcribed by the cellular stenographer, RNA, before a key protein involved in proper chloride activity can be made. People with cystic fibrosis have specific DNA mutations, garbling instructions for production of the protein that chaperones chloride through channels.
The Israeli study has shown that gentamicin corrects the nonsense, allowing chloride to be escorted effortlessly in and out of cells. Wilschanski and Kerem, conducted most of their work at Sha'are Zedek Hospital, studying 19 children with well-defined miscues in a gene dubbed CFTR (cystic fibrosis transmembrane conductance regulator).
"Our study is preliminary, and it's just on the nose, bear in mind," Wilschanski told ISRAEL21c. "At this point we couldn't try it on the lungs, as there could be lots of side effects. So we used the nose as a living laboratory. We had a whole bunch of volunteers from around the country. They were tested, given the drops to use for two weeks, tested again, given another set of drops for two weeks, and then tested a third time."
That administering the antibiotic as nose drops - two drops given three times daily for 14 days - corrected the genetic flaw, but only in cells lining nasal tissue. The CFTR function was restored and the electro-physiological abnormalities were corrected. Their next step is to test gentamicin's ability to affect pulmonary function.
About 1,000 different types of CFTR miscues have been identified. The type defined by Wilchanski, called a "stop mutation," affects a majority of people with cystic fibrosis in Israel .
"Genetic mistakes are very specific for communities. In Israel, there's a very specific type of genetic mistake in CF patients - the 'stop mutation' - which is found in about 60% of Israelis who have CF. That's compared to 5% worldwide who have the stop mutation,"said Wilschanski, who immigrated to the Gush Etzion town of Elazar from London in 1985 and was recently named the head of the pediatric gastroenterology department at Hadassah Hospital Ein Kerem.
Another type, known as delta-508, is more commonly diagnosed in the United States, Europe and Canada. But regardless of the mutation, disease manifestations are the same.
The team had completed a smaller but successful pilot study on only nine patients nearly four years ago; this was the first time that researchers were able to cause the repair of a genetic mutation that causes CF. But the current study is larger and, more persuasively, a randomized, double-blind controlled study, according to health reporter Judy Siegel of The Jerusalem Post.
CF is a potentially fatal disease in which the lungs get clogged with mucous, causing severe infections. The only definitive treatment is a lung transplant, but because donor organs are rare, most patients have no alternative but to swallow many pills of different antibiotics and pancreatic protein supplements each day, eat a special high-calorie diet, and undergo intensive physiotherapy to break up the mucous. Many different CFTR mutations can cause CF, and only a small percentage has the STOP mutations that would respond to aminoglycoside treatment.
In genetic diseases, mutations disrupt or completely prevent the production of proteins in the cell that are vital for the proper functioning of body systems. The STOP mutations give an erroneous order to halt the production of the protein. The nasal drops caused the appearance of the protein, which previously was not produced in the patients' cells; the protein caused chloride ions and water to be released from the cell and the mucous to be washed out of the nose. The implication is that if the same drug can be administered to clogged mucous membranes deep inside the body, their cells would normalize as well.
The work by the researchers promises a way of controlling the disease, but probably not curing it, doctors say. Moreover, the drug likely will be effective only against the type of mutation predominantly seen among people of Ashkenazi Jewish descent. Yet developing gentamicin as a therapy remains years away.
"We're at the beginning, and we have a long way to go. But it's a novel way of looking at genetic disease, and it's also applicable to other diseases as well," said Wilschanski. "It holds hope for this group of patients in a few years time. Giving to babies right off a diagnosis, there's a good chance of avoiding global symptoms."
"The bottom line here is not to think of gentamicin as an antibiotic," Dr. Peter Durie, director of the Cystic Fibrosis Center at the Hospital for Sick Children in Toronto, told Newsday. "Its role in this study has nothing to do with [treating] infection."
Durie, an expert on cystic fibrosis who was not associated with the experiments, said the discovery opens a window on research, demonstrating that a well-known drug may have the power to influence genes. "The idea behind this paper is that this concept can be used in other genetic diseases," he said.
"This is a very important proof of principle," Dr. Robert Beall, president of the Cystic Fibrosis Foundation in Bethesda, Md., said of the Israeli findings. "There is still a long way to go," he added, to show that gentamicin can correct the anomaly in the lungs.
Beall told Newsday that other disorders, such as Duchenne's muscular dystrophy and Hurler's syndrome, also may respond to correction by a member of the antibiotic family to which gentamicin belongs.
Courtesy http://www.israel21c.org/
Archaeology: A newly-found spa from ancient Beersheba
Nov 2003: Excvators from the Israel Antiquities Authority have uncovered a luxurious Roman-Byzantine period (third to sixth centuries) public bathhouse at excavations near Wadi Beersheba.
For the first time in Beersheba, structures from the period of the Judean Kingdom - First Temple period (8th century BCE) were found below and adjoining the Byzantine structure. Amongst the finds are: a residential building with courtyards, and cooking installations. The excavation director on behalf of the Antiquities Authority, Peter Favian, reports that these remnants have been identified as belonging to the ancient settlement of Beersheba cited in the Bible ("from Dan to Beersheba").
Magen David Adom host first disaster management workshop
Nov. 12, 2003 - Magen David Adom in Israel (MDA) hosted its first disaster management workshop on November 9-12. The workshop was organized in cooperation with the International Committee of the Red Cross (ICRC), the International Federation of Red Cross and Red Crescent Societies (Federation), and the American Red Cross (ARC).
"The goal of the workshop was to give MDA and Red Cross experts an opportunity to share their experience in disaster assessment, management, and international assistance," explains Chaim Rafalowski, Head of MDA Emergency Department.
The workshop consisted of frontal presentations, discussion work groups and a final assessment simulation organized and conducted by Mr. Douglas Allen, Director of the International Disaster Response Team in the American Red Cross.
Some of the issues presented were: The Red Cross Movement and its fundamental principles; the Federation's role in disasters - from prevention to relief; Health in Emergencies; ICRC's role in disasters in conflict areas; National Society role in disasters; Health in Emergencies; Disaster Preparedness, Resource Management; Turkish Earthquake lessons; and more.
Participants in the workshop were MDA managerial staff as well as various experts from the International Committee of Red Cross (ICRC), the International Federation of Red Cross Red Crescent Societies, American, German, Norwegian, and British Red Cross, Palestine Red Crescent, the International Federation's regional delegation in Amman and Israel, as well as the ICRC's delegation in Israel. Representatives from the Israel Defence Forces and Ministry of Health also attended.
The opening ceremony and closure briefing counted with the presence of Mr. Yochanan Gur, Chairman of MDA's Executive Committee, Mr. François Bellon, Head of the ICRC delegation in Israel and Ms. Anna Segall, the International Federation's delegate in Israel. All the speakers pointed out the importance of this workshop, regarding its relevant subject, and the fact that this is one more step in the rapidly growing collaboration between MDA and the Red Cross Movement.
The workshop proved to be a unique opportunity for professionals to share experience and views regarding disaster management. Mr. Yochanan Gur pointed out the importance of the collaboration with the different components of the International Red Cross, and assured the guests that MDA would be ready at all times to assume its share in Disaster Management.
See previous month's articles.