Digital Communication Technology Helps Clear Path To Personalized Therapies

(Jan. 12, 2009) — Researchers at the Burnham Institute for Medical Research (Burnham) have shown that search algorithms used in digital communications can help scientists identify effective multi-drug combinations. The study, led by Giovanni Paternostro, M.D., Ph.D., was published in the December 26, 2008, issue of PLoS Computational Biology.

---

Using the stack sequential algorithm, which was developed for digital communications, the team of scientists searched for optimal drug combinations. This algorithm can integrate information from different sources, including biological measurements and model simulations. This differs from the classic systems biology approach by having search algorithms rather than explicit quantitative models as the central element. The variability of biological systems is the fundamental motivation for this strategy.

“Combination therapies have demonstrated efficacy in treating complex diseases such as cancer and hypertension, but it is difficult to identify safe and effective combination treatment regimens using only trial and error,” said Dr. Paternostro. “As personalized medicine moves from the present emphasis on diagnosis and prognosis to therapy, the problem of searching for optimal drug combinations uniquely suited to the genetic and molecular profile of each patient will need to be solved. This research is a first step in that direction.”

Current methodology for identifying effective combination therapies involves exhaustive testing. However, the exponential expansion of possibilities precludes exploring large combinations using this approach. For example, many chemotherapy regimens include six drugs from a pool of 100. A study that included all combinations (including partial combinations containing only some of these compounds) at three different doses would have to digest 8.9 x 1011 possibilities. The problem requires a new approach rather than more efficient screening technology.

In the study, a small subset of the possible drug combinations identified using the algorithms were tested in two biological model systems. One system studied improvement in the physiological decline associated with aging in Drosophila melanogaster (fruit flies) and the other system tested for selective killing of cancer cells. In both cases, effective drug combinations were identified by combining the algorithm with biological tests.

“Our work was greatly helped by collaborators with expertise in medicine, engineering and physics from Burnham, University of California, San Diego and Michigan State University,” said Dr Paternostro. “We especially benefited from suggestions from Dr. Andrew Viterbi, inventor of the Viterbi algorithm so widely used in digital communications, who pointed to parallels between this biological problem and signal decoding.” Dr. Andrew Viterbi cofounded Linkabit Corporation and Qualcomm Inc., with Dr. Irwin Jacobs. He is currently the president of the venture capital firm, The Viterbi Group.

This work was funded by the Ellison Medical Foundation, National Institutes of Health and the National Science Foundation.

Military Use Of Robots Increases

War casualties are typically kept behind tightly closed doors, but one company keeps the mangled pieces of its first casualty on display. This is no ordinary soldier, though — it is Packbot from the iRobot Corporation.

Robots are increasingly taking over more soldier duties in Iraq and Afghanistan, with predictions that as much as 30 percent of the U.S. Army will be robotic by 2020. WUSTL computer scientists who work on robots say the machines still need the human touch. (Credit: Image courtesy of Washington University in St. Louis)

Robots in the military are no longer the stuff of science fiction. They have left the movie screen and entered the battlefield. Washington University in St. Louis's Doug Few and Bill Smart are on the cutting edge of this new wave of technology. Few and Smart report that the military goal is to have approximately 30% of the Army comprised of robotic forces by approximately 2020. Of course, they aren't envisioning robotic soldiers from movies like "Star Wars" and "I, Robot."

"When the military says 'robot' they mean everything from self-driving trucks up to what you would conventionally think of as a robot. You would more accurately call them autonomous systems rather than robots," says Smart assistant professor of computer science and engineering.

All of the Army's robotic force is teleoperated, meaning there is someone operating the robot from a remote location, perhaps often with a joystick and a computer screen. While this may seem like a caveat in plans to add robots to the military, it is actually very important to keep humans involved in the robotic operations.

"It's a chain of command thing. You don't want to give autonomy to a weapons delivery system. You want to have a human hit the button," says Smart. "You don't want the robot to make the wrong decision. You want to have a human to make all of the important decisions."

Not like the Terminator

While movies display robots as intelligent beings, Smart and Few aren't necessarily looking for intelligent decision-making in their robots. Instead, they are working to develop an improved, "intelligent" functioning of the robot.

"It's oftentimes like the difference between the adverb and noun. You can act intelligently or you can be intelligent. I'm much more interested in the adverb for my robots," says Few.

Few, who is Smart's Ph.D. student, is also interested in the delicate relationship between robot and human. He is working to develop a system in which the robot can carry out a task while keeping a human in the loop and with the ability to create new goals for the robot. Few says that there are many issues that may require "a graceful intervention" by humans and these need to be thought of from the ground up.

"When I envision the future of robots, I always think of the Jetsons," says Few. "George Jetson never sat down at a computer to task Rosie to clean the house. Somehow, they had this local exchange of information. So what we've been working on is how we can use the local environment rather than a computer as a tasking medium to the robot."

To work toward this goal, Few has incorporated what many would simply consider a toy into robotic programming. Using a Wii controller, Few capitalizes on natural human movements to communicate with the robot. Using something as simple and as common as this video game controller also has added benefits in a military setting. Rather than carting around a heavy laptop and being forced to focus on a joystick and screen, soldiers in battle can stay alert and engaged in their surroundings while performing operations with the robot.

"We forget that when we're controlling robots in the lab it's really pretty safe and no one's trying to kill us," says Smart. "But if you are in a war zone and you're hunched over a laptop, that's not a good place to be. You want to be able to use your eyes in one place and use your hand to control the robot without tying up all of your attention."

Robots are already finding a place among deployed troops. There are unmanned aerial vehicles and ground robots for explosives detection. Robotics advancements do, however, raise new ethical questions, such as where to place the blame if a robot kills someone. Nevertheless, as the technology progresses, more robots are being sent into battle first. The mangled Packbot on display at iRobot is just one such example of a fortunate casualty.

"When I stood there and looked at that Packbot, I realized that if that robot hadn't been there, it would have been some kid," reflects Few.

Researchers Discover New States Of Electrons That Behave Like Light

A team of researchers at Princeton University's Materials Research Science and Engineering Center has observed electrons moving through a crystal of bismuth metal behaving like light.

This discovery, supported by the National Science Foundation (NSF) and detailed in today's edition of the journal Science, could lead to new kinds of electronic devices.

Electrons, or the particles of electricity, fly through space like tiny baseballs. Alternatively, when an electron speeds between a crystal's periodic arrangement of atoms it behaves very differently. The fundamental equations that describe its motion in the crystal are very different from those of a free-flying baseball. For example, in bismuth, the fundamental equations of electron motion resemble those that describe the behavior of light. Although the electrons whirl about the crystal slower than at the speed of light, the electrons behave as if they are without mass like photons, the tiniest unit of light.

Over a decade ago, theoretical physicists supported by NSF studied electrons confined to artificial layered structures made of semiconductors--the stuff of which transistors are made of. They predicted that new kinds of electronic matter governed by the rules of quantum mechanics would emerge from the electrons in different layers coordinating their motions. Scientists hypothesized that bismuth crystals should also exhibit analogous electronic states.

The Princeton group, led by physics professor N. Phuan Ong, fixed a crystal of bismuth onto a flexing beam, or cantilever, and then placed this apparatus in a high magnetic field created at the NSF National High Magnetic Field Laboratory, which can generate magnetic fields that are more than a million times stronger than the earth's faint magnetic field.

Under such enormous magnetic fields, the cantilever twists. The way it twists tells the Princeton researchers about the subtle new kind of matter in the bismuth crystal.

In a single crystal of bismuth, electrons are often confined to three valleys in a complex abstract landscape that scientists use to represent an electron's energy in the crystalline structure. Through careful study of the twisting cantilever, they observed a transformation from a state where the electrons prefer to occupy only one valley to a state in which the electrons share their time among all the valleys in a dance choreographed by the fundamental rules of quantum mechanics.

"This is exciting because this was predicted but never shown before, and it may eventually lead to new paradigms in computing and electronics,"said Thomas Rieker, NSF program director for materials research center.

With this work, the theory of electrodynamics suggests a rich landscape of electronic states of semiconductors, and the Princeton researchers are continuing their adventure. Someday, these newly discovered electronic states of matter may enable powerful new electronic devices that exploit the principles of quantum mechanics to compute and communicate. For now we can marvel at the subtle beauty of nature that lives in a universe of electrons that lies beneath the shiny skin of a metal crystal.