Living interface: Muscle cells (shown here) are grown on a biological scaffold. Severed nerves remaining from the lost limb connect to the muscle cells in the interface, which transmits electrical signals that can be used to control the artificial arm. Credit: Paul Cederna
Tiny implants that connect to nerve cells could make it easier to control prosthetic limbs
MIT Technology Review, October 19, 2009, by Emily Singer — A novel implant seeded with muscle cells could better integrate prosthetic limbs with the body, allowing amputees greater control over robotic appendages. The construct, developed at the University of Michigan, consists of tiny cups, made from an electrically conductive polymer, that fit on nerve endings and attract the severed nerves. Electrical signals coming from the nerve can then be translated and used to move the limb.
“This looks like it could be an elegant way to control a prosthetic with fine movement,” says Rutledge Ellis-Behnke, a scientist at MIT who was not involved in the research. “Rather than having a big dumb piece of plastic strapped to the arm, you could actually have an integrated tool that feels like it’s part of the body.”
Today, movement of most prostheses is effortful and limited. The limbs are controlled by conscious movement of remaining muscle–the wearer might contract a chest muscle to move the arm in a certain direction, for example. Wiring residual nerves directly to artificial limbs would provide a more intuitive way to control them. But efforts to build peripheral nerve interfaces have been hampered in large part by the growth of scar tissue, which limits the utility and durability of implanted devices.
The most successful method for controlling a prosthesis to date is a surgical procedure in which nerves that were previously attached to muscles in a lost arm and hand are transplanted into the chest. When the wearer thinks about moving the hand, chest muscles contract, and those signals are used to control the limb. While a vast improvement over existing methods, this approach still provides a limited level of control–only about five nerves can be transplanted to the chest.
The new interface, developed by plastic surgeon Paul Cederna and colleagues, builds on this concept, using transplanted muscle cells as targets rather than intact muscle. After a limb is severed, the nerves that originally attached to it continue to sprout, searching for a new muscle with which to connect. (This biological process can sometimes create painful tangles of nerve tissue, called neuromas, at the tip of the severed limb.) “The nerve is constantly sending signals downstream to tell the hand what to do, even if the hand isn’t there,” says Cederna. “We can interpret those signals and use them to run a prosthesis.”
The interface consists of a small cuplike structure about one-tenth of a millimeter in diameter that is surgically implanted at the end of the nerve, relaying both motor and sensory signals from the nerve to the prosthesis. Inside the cup is a scaffold of biological tissue seeded with muscle cells–because motor and sensory nerves make connections onto muscle in healthy tissue, the muscle cells provide a natural target for wandering nerve endings. The severed nerve grows into the cup and connects to the cells, transmitting electrical signals from the brain. Because it is coated with an electrically active polymer, the cup acts as a wire to pick up electrical signals and transmit them to a robotic limb. Cederna’s team doesn’t develop prostheses themselves, but he says the signals could be transmitted via existing wireless technology.
So far, scientists have tested the interface in rodents with a severed peripheral nerve, showing that the nerve will grow into the cup and make connections with the muscle cells. “If they can keep the end of the neuron intact in that area, that’s a major breakthrough,” says Ellis-Behnke. The nerves in rats are about the same size as those that would be targeted in humans. The research was presented today at a conference of the American College of Surgeons in Chicago.
The device can also feed sensation back into sensory nerves, which relay heat, pressure, and other information from the skin to the brain. Like motor nerves, sensory nerves make connections onto the muscle cells in the cup. In rodent tests, scientists capped two nerves in a single animal–one motor and one sensory. While the rat did not have a prosthesis, scientists were able to show that the implant could bridge the severed nerve, transmitting neural messages across it; tickling the rat’s foot triggered muscle cell activity in the implant.
Sensory capability is a major missing component of today’s prostheses–tactile, pressure, and temperature feedback is vital for picking up a fragile egg or a hot pan. Ultimately, prosthetic limbs could be outfitted with heat or pressure sensors that could transmit that information to muscle cells in the interface and allow this information to be sent to the brain.
The research is still in its early stages, and a number of questions remain to be answered. “We need to find out how long it takes for the connections to become functional, and what the durability and robustness will be,” says Joseph Pancrazio, a program director at the National Institute for Neurological Disorders and Stroke, who was not involved in the research. “But it looks very exciting.” The research is funded by the Department of Defense.
One of the major issues with neural implants to date has been the stability of the devices, because implanted electrodes often become coated in scar tissue and stop working. So far, for the six months that the scientists have been assessing the interfaces in rats, there have been no signs of scarring. While scientists aren’t sure why, it may be that the cup protects the implant from the inflammatory reactions that lead to scarring, or that providing a target for the nerve cells dampens these reactions altogether by recreating a more normal environment for the severed nerve. The researchers are now monitoring the implants on a daily basis to determine their durability over time.
One particularly promising early finding, however, is that the tissue surrounding the interface grows new blood vessels to feed the implanted muscle cells, supplying them the nutrients they need to survive.
It’s not yet clear how many of these nerve caps patients would need for adequate control over a sophisticated artificial limb. Someone who has lost their arm at shoulder level, for example, would need enough nerve caps to flex and extend the elbow, wrist, and fingers, as well as those for sensory nerves. “The only limit,” says Cederna, “is going to be how high-tech they can make the prosthetics.”
Ray Kurzweil speaking to a conference as a hologram in 2006. He first proposed the idea of a school for futurologists two years ago.
Photograph: Ed Murray/Corbis
The Singularity University will offer courses in artificial intelligence, nanotechnology and biotechnology
GoogleNews.com, Guardian.co.uk — Ray Kurzweil, the American inventor who plans to live for ever, has been appointed head of a new school for futurologists backed by Google and the US space agency NASA.
Ray Kurzweil, who worked as a computer scientist before turning to future gazing in the late 1980s, will become chancellor of the Singularity University based at NASA’s Silicon Valley campus in California.
The institution gains its name from a controversial 2005 book by Kurzweil, entitled The Singularity is Near. In it, he argues that the exponential advance of technology is set to transform society by giving rise to computers that are more clever than humans. The leap in computing power will drive rapid advances in other fields, he claims, that together could solve the problems of climate change, poverty, famine and disease.
In an earlier book, Kurzweil predicts the creation of “nanobots” that will patrol our bloodstreams, repairing wear and tear as they go, and keeping our bodies perpetually young.
“The law of accelerating returns means technology eventually will be a million more times powerful than it is today and cause profound transformation,” Kurzweil told Associated Press after his appointment was announced.
The new institute will offer courses on artificial intelligence, nanotechnology and biotechnology and opened its doors to its first class of 30 students this past summer.
Kurzweil began discussing the concept for the school two years ago with Peter Diamandis, chairman of the X Prize Foundation, which offers multimillion dollar prizes for technological breakthroughs. The school is backed by Diamandis and Google co-founder Larry Page. Google has already contributed more than $1 million to the institution, and several other major companies are planning to contribute at least $250,000, Diamandis said.
“One of the objectives of the university is to really dive in depth into these exponentially growing technologies, to create connections between them, and to apply these ideas to the great challenges [facing humanity],” said Kurzweil.
Nasa has agreed that the school can use buildings at its Ames Research Centre in Moffett Field, which is near the offices of US tech giants Google, Yahoo!, Intel Corp and Cisco Systems.
A nine-week course at Singularity University will cost $25,000. The first three weeks will be spent studying 10 different subjects, with the next three weeks focusing on one in detail. The final three weeks will be taken up by a special project. Details of the new institution, which despite its name is not an accredited university, were unveiled at the annual Technology, Entertainment and Design (TED) conference in Long Beach, California.
Kurzweil, who famously consumes more than 100 supplement pills a day and regularly checks around 50 health indicators, has been criticized by some experts who see his predictions as outlandish. In a 2007 interview, Douglas Hofstadter, the Pulitzer prizewinning author and professor of cognitive science at Indiana University compared his ideas to a blend of very good food and “the craziest sort of dog excrement”.
In an earlier book, Fantastic Voyage: Live Long Enough to Live Forever, Kurzweil and co-author Terry Grossman lay out their vision of humans living radically longer lives within the next three decades or so.
The first step involves adopting a good enough diet and exercise regime to live long enough for biotechnology to unravel the ageing process and for nanotechnology to be capable of slowing it down and ultimately reversing it.
Among Kurzweil’s other predictions are a pill that lets you eat what you want without getting fat – which he believes could be available within ten years; a world where all energy comes from renewable sources within 20 years; and a life expectancy that increases at a rate faster than you age within 15 years.
Chemical operation: This machine uses mass spectrometry to make molecular maps of tissue during surgery. Fumes generated by an electroscalpel are sucked into the machine through the tubing at lower left.
Credit: Zoltán Takáts
A cutting tool distinguishes tissue types based on their chemical profiles
MIT Technology Review, October 14, 2009, by Katherine Bourzac — In the hope of helping oncologists remove every piece of tumor tissue during surgery, researchers are developing new imaging tools that work in real time in the operating room. European researchers have now demonstrated that a chemical analysis instrument called a mass spectrometer can be coupled with an electroscalpel to create a molecular profile of tissue during surgery. The researchers have shown that the method can be used to map out different tissue types and distinguish cancerous tissue. The device will begin clinical trials next month.
“When a surgeon is performing cancer surgery, he doesn’t have any direct information on where the tumor is,” says Zoltán Takáts, a professor at Justus-Liebig University in Giessen, Germany. Instead, surgeons rely on preoperative imaging scans and on feedback from pathologists examining tissue biopsies under a microscope. “We want to provide a tool that’s right in their hands, so that if they think a structure looks suspicious, they can just test it,” says Takáts.
Mass spectrometry, a very precise method for identifying molecules by analyzing the ratio between their mass and charge, is already being used by a handful of research groups to study biological samples. Researchers have known for many years that tumor tissue and healthy tissue have different molecular profiles and that this can be used to tell them apart, or even to determine how aggressive a particular tumor is. Other research groups have used mass spectrometry to analyze biopsied tissue and have shown that it can make these differentiations. The problem with using mass spectrometry in the operating room is sample collection. Before molecules can be analyzed, they have to be ionized and sucked up into the machine. Creating ions requires bombarding a sample with a stream of charged particles, often a gas, and these methods aren’t suitable for the operating room. “A high-voltage nitrogen jet is not compatible with the human body,” says Takáts.
Takáts realized that some surgical cutting tools, including electroscalpels, produce gaseous ions as a kind of waste product that are suitable for analysis with mass spectrometry. And these fumes, often called “surgical smoke,” are already collected during surgery because they’re harmful to the lungs. Takáts and his collaborators found that mass spectrometry of surgical smoke can be used to make a molecular map of a tumor. After the fumes are sucked into the mass spectrometer, the chemicals in the sample are identified and checked against a database to give the surgeon a readout. Gathering and analyzing a chemical sample takes a few hundred milliseconds. “We can draw a map and say this part is healthy liver, that is connective tissue, this is adipose tissue, that is cancer,” says Takáts.
“This work represents a milestone in the application of mass spectrometry to medicine,” says R. Graham Cooks, a professor of chemistry at Purdue University who was not involved with the research.
Mass spectrometry is just one of many imaging techniques being evaluated for use during surgery. Another approach is to inject a patient with fluorescent dyes that bind to tumor molecules and are visible under infrared light. But mass spectrometry can provide more comprehensive information about tissues’ molecular profiles. The new system not only provides real-time information, but also produces an image of the tumor, using chemical information, which could also help guide postoperative care. The imager could, for example, reveal a particularly aggressive form of cancer, and this information could guide oncologists in prescribing the right drug.
Cooks is developing a different type of mass-spectrometry system for tissue analysis. His system, called DESI, requires spraying a mist of charged particles onto the tissue, but it can analyze a wider range of molecules and might provide more detailed information. Takáts’s technique mostly samples the fatty molecules called lipids that make up cell membranes.
So far, the German researchers have tested the surgical mass-spectrometry system in several animals, including rodents, with cancer. The group is also working with veterinarians to use the scalpel during tumor-removal surgeries in dogs with naturally occurring tumors. Next month the device will go into human clinical trials, and Takáts is working with Meyer-Haake, a German electrosurgical device company, to develop the machinery.
The most important remaining hurdle to getting mass spectrometry into the operating room may be the expense. An electrosurgery system typically costs $8,000, while a commercial mass-spectrometry system starts at $120,000. Takáts notes that the market for mass spectrometry is currently very small, but opening up the surgical market may help bring costs down. By using instruments tailored to the kind of analysis relevant to biological tissue, which doesn’t need to be as high-performance as that in chemistry labs, Takáts hopes to make a machine that costs about $20,000.
Stress sensor: This scanning-electron-microscope image shows a stress-triggered transistor in cross section. The zinc oxide nanowire, 25 nanometers in diameter, is embedded in a polymer (black area), leaving the top region free to bend.
Credit: ACS/Nano Letters
A novel nanoscale sensor responds to mechanical stresses
MIT Technology Review, October 14, 2009, by Katherine Bourzac — Nanoscale sensors have many potential applications, from detecting disease molecules in blood to sensing sound within an artificial ear. But nanosensors typically have to be integrated with bulky power sources and integrated circuits. Now researchers at Georgia Tech have demonstrated a nanoscale sensor that doesn’t need these other parts.
The new sensors consist of freestanding nanowires made of zinc oxide. When placed under stress, the nanowires generate an electrical potential, functioning as transistors.
Zhong Lin Wang, professor of materials science at Georgia Tech, has previously used piezoelectric nanowires to make nanogenerators that can harvest biomechanical energy, which he hopes will eventually be used to power portable electronics. Now Wang’s group is taking advantage of the semiconducting properties of zinc oxide nanowires–the electrical potential generated when the new nanowires are bent, allowing them to act as transistors.
The Georgia Tech researchers used a vertical zinc oxide wire 25 nanometers in diameter to make a field-effect transistor. The nanowire is partially embedded in a substrate and connected at the root to gold electrodes that act as the source and the drain. When the wire is bent, the mechanical stress concentrates at the root, and charges build up. This creates an electrical potential that acts as a gate voltage, allowing electrical current to flow from source to drain, turning the device on. Wang’s group has tested various triggers, including using a nanoscale probe to nudge the wire, and blowing gas over it.
Wang’s group is “unique in using nanostructures to make something like this,” says Liwei Lin, codirector of the University of California, Berkeley Sensor and Actuator Center. Nanowire sensors could be used for high-end sensing devices such as fingerprint scanners, Lin suggests.
Previous nanowire sensors have been tethered at both ends, limiting their range of motion. Wang says that the freestanding nanowires resemble the sensing hairs of the ear. If grouped into arrays of different lengths, each responsive to a different frequency of sound, the nanowires could potentially lead to battery-free hearing aids, he says.
The next step is to make arrays of the devices. “This is challenging because you have to make the electrical contact reliable, but we will be able to do that,” says Wang.
FierceBioTech.com, October 15, 2009 — One developer is on the verge of a potential approval for a breakout new blockbuster, another has a therapy in closely-watched trials which could lay the foundation for a new drug capable of unleashing significant pent-up demand. There’s a biotech company in talks with partners on a late-stage product now in a cleverly designed clinical trial. One cancer drug is under the spotlight in a risky trial–while another cancer drug appears to be just weeks away from a possible success. All of them appear in our new issue of On the Radar, which this month comes from two top analysts at Leerink Swann: Howard Liang and Joseph P. Schwartz.
Radar features analysts’ projections on five biotech companies that are nearing a crucial crossroad in the next two or three months. Each of them face a moment of truth that has been years in the making. This is how Liang and Schwartz see the chips falling in the weeks and months to come for Human Genome Sciences, Auxilium Pharmaceuticals, Inspire Pharmaceuticals, GTx and Poniard Pharmaceuticals. – John Carroll
We expect Human Genome Sciences (HGSI to become the next large cap Biotech. Benlysta could be the first true disease-modifying therapy for lupus, a multi-billion dollar opportunity. We have high conviction in our estimate of ~85 percent likelihood of success for HGSI’s Benlysta BLISS-76 Phase III data in November, based on our statistical power analysis and previous positive data from the BLISS-52 trial. Full details of BLISS-52 data, to be released at the American College of Rheumatology on Oct. 20, should confirm the strong efficacy and clean safety profile. An NDA filing is expected in 1H10. We currently estimate worldwide Benlysta sales of $364M in 2010 growing to $7.2B in 2015. HGSI share of revenue is 50 percent, or ~$3.6B in 2015. Regarding Partnering & Acquisition potential, Benlysta is currently partnered with GSK, and we believe the incremental 50 percent rights to Benlysta is likely worth much more than HGSI’s ~$2.5B market cap. HGSI also has around $2B of NOL’s which could be attractive to other potential acquirors. – Joseph P. Schwartz
2) – Auxilium Pharmaceuticals (Outperform)
Just as Botox revolutionized the field of plastic surgery, we expect Auxilium’s (AUXL ) Xiaflex to create significant new growth opportunities in underserved hand surgery and urology markets where invasive treatment is currently the only option. We see significant pent-up demand for Xiaflex among patients. Accordingly, our market model projects peak U.S. revenue potential for Xiaflex exceeding $400MM in each of the Dupuytren’s contracture and Peyronie’s disease indications. We believe that FDA approval of Xiaflex for the Dupuytren’s indication is relatively secure given the recent unanimous panel decision highlighting the favorable risk/benefit with surgery-like efficacy and a clean safety profile. And we are optimistic for positive Phase IIb clinical data in Peyronie’s disease in 4Q:09 based on a promising Phase IIa experience and based on the use of subjective reporting measures in this trial. The recent deal with PFE for Xiaflex rights in ROW offers validation, capital, reimbursement, development and marketing expertise that should support the opportunity. We estimate a 90 percent chance of Xiaflex approval in Dupuytren’s (based on unanimous panel decision and robust clinical data) and a 75 percent chance in Peyronie’s disease (reflecting its earlier stage of development). – Joseph P. Schwartz
3) – Inspire Pharmaceuticals – (Outperform)
Inspire (ISPH) currently has an attractive mix of lower-risk specialty pharma products on the market followed by several highly innovative biotech candidates in the pipeline that could change the character of the company significantly. Its two lead Phase III candidates, denufosol (cystic fibrosis) and Prolacria/diquafasol (dry eye), target respiratory and ophthalmic disease markets with significant unmet medical need and potential reward for innovation. ISPH’s Prolacria (dry eye) has strong market potential as evidenced by $500M in partial worldwide sales for Restasis. Phase III data is due in 1H:10. Management has stated that trials were enrolling faster than expected and ISPH has done an excellent job designing the study to eliminate any placebo effect. However it may also be difficult to obtain a zero staining score for patients on therapy, so we ascribe a 65 percent probability of success. We estimate Prolacria WW sales of $2M in 2010 growing to $136M in 2018. Regarding Partnering & Acquisition potential, while Prolacria is already partnered, ISPH holds WW rights for denufosol for cystic fybrosis and is actively seeking an ex-North American development and commercialization partner. Partnership announcement could come in late 2009 or early 2010. According to our P&A analysis, BMRN, GENZ, and SHPGY are interested in orphan drug assets. – Joseph P. Schwartz
4) – GTx (Market Perform)
With a focus on urology and oncology, GTx has pioneered the use of a selective estrogen receptor modulator (SERM) for prostate cancer prevention and for bone loss associated with standard prostate cancer treatment known as androgen deprivation therapy or ADT. Both programs for Acapodene (SERM) are currently in or have completed Phase III trials. For the prostate cancer prevention trial (PIN), which we view to be the more interesting commercial opportunity, we believe the failed, well powered interim analysis reflects negatively on the efficacy for the drug in this setting, and reduces the likelihood of its eventual success. Acapodene for ADT has an upcoming PDUFA date of October 30. Although positive top-line results from the ADT trial were announced, we believe regulatory and commercial risks remain due to debatable risk / benefit profile (similar numbers of fractures prevented versus additional venous thromboembolic events). We believe the recent finding of QTc prolongation with Acapodene could further complicate approval. We estimate probability weighted 2013 U.S. Acapodene sales of $39.5M for PIN and $24.1M for ADT, based on a 40 percent probability of success for ADT and 25 percent for PIN. – Howard Liang
5) – Poniard Pharmaceuticals (Outperform)
Poniard is a late-stage company with picoplatin nearing completion of a Phase III trial for small cell lung cancer (SCLC). Picoplatin as a member of the platinum class is likely an active anti-cancer agent and the key is finding a path to market. While clearly a binary event, we believe that this trial has a favorable chance of success as picoplatin is being compared to supportive care and another drug (topotecan) has shown the feasibility of demonstrating survival benefit in this setting. We expect top-line data from the SPEAR Phase III trial in 4Q09 with a possibility for a full data presentation at the EORTC/NCI/AACR meeting on November 15-19th. PARD expects to initiate filing of the NDA by YE09 after SPEAR readout. Outside SCLC, we see potential upside in colorectal cancer (CRC) for picoplatin. With the ongoing Phase II data currently showing less neuropathy and comparable efficacy as oxaliplatin-based regimen, we believe that picoplatin may have an opportunity in the big CRC market with additional survival data from a randomized Phase II CRC trial coming before YE:09. We estimate probability weighted U.S. picoplatin sales of $13M in 2010, growing to $195M in 2012. Regarding Partnering & Acquisition potential, PARD has indicated strong interest in picoplatin and that there have been partnering discussions with several large pharma and biotech companies and a positive SPEAR outcome would serve as a catalyst for partnership. – Howard Liang