He wants to replace physicians with molecular machines that diagnose and treat diseases with phenomenal precision.
In just five years, Benenson has taken the concept from drawing board to test-tube prototype. Working at the Weizmann Institute of Science in Rehovot, Israel, he has built molecular devices – essentially DNA strands and enzymes – able to analyze genetic changes associated with lung and prostate cancers and to release a drug in response. These prototypes are “a beautiful work of molecular and conceptual integration, pointing the way toward truly integrating diagnostics with therapeutics,” says George Church, director of the Center for Computational Genetics at Harvard Medical School. “Using these tiny diagnostic machines, we could selectively treat only the diseased cells,” Benenson says. For example, the prototype device for small-cell lung cancer assesses the activity of four genes. Cancerous cells produce extra RNA copies of each of these genes. Consecutive sections of the DNA strand in the prototype bind, in turn, to these RNA strands; when they do, an enzyme chops them off. If all of the cuts are made properly, the enzyme releases and activates an anticancer drug that has been tethered to the DNA in an inactive form. Benensons molecular machines offer a unique combination of precision and flexibility. A single one of them can be designed to look for up to 10 different diagnostic markers before it releases its drug payload. The devices can also be tailored to several different diseases through simple-to-make changes in their DNA sequences. These machines represent a quantum leap not only in medicine but also in DNA computing. Benensons molecular “doctors” – which are computers in the sense that they store information and analyze it following a yes/no logic – are “directed at a practical interface with biomedicine rather than losing an abstract race with existing computers on their own turf,” says Church.
Found a way to spot colon cancer earlier than was previously possible.
Found a way to spot colon cancer earlier than was previously possible – and well before it has spread – by measuring the changes that occur when white light interacts with tumor cells.
Develops photonic technologies that use targeted nanomaterials to detect, monitor, and treat breast and gynecologic cancers painlessly, and at a fraction of the cost of conventional approaches.
Slashed the cost of producing a DNA chip from hundreds of dollars to a few dollars by combining microfluidics, computer control, and novel electrochemistry.
Cofounded Oxford, Englands Oxamer with genetic-analysis pioneer Edwin M. Southern to commercialize the technology.
Combines existing genes to build artificial biological pathways, or "circuits," that operate inside cells.
The goal: better understanding how cellular behavior is naturally controlled – and how it might be reprogrammed.
Constructs computer models of cellular pathways in order to optimize bacteria for energy production and environmental remediation.
Cofounded Cellicon Biotechnologies in Boston, MA; the company uses the cellular models to improve antibiotics.
Aims to more than double human trials success rate by virtually prescreening drugs in computer models of human cells.
Four out of five drugs fail in human trials. But Colin Hill says that at his Ithaca, NY, startup, “We think we are the answer.” The physicist turned entrepreneur aims to more than double human trials success rate by virtually prescreening drugs in computer models of human cells. His company uses these “virtual cells” to uncover how the compounds work and predict which ones will fare best in human tests. Drugmakers share his enthusiasm: his company has deals with two of the top five drug firms.
Builds nanoscale electrochemical and electrical sensors to detect medically relevant gene sequences and proteins.
Cofounded San Diego, CAs GeneOhm Sciences to produce molecular diagnostics based on one such technology.
Devised a way to remove kidney stones more cost effectively and less invasively by taking advantage of the ureters tendency to dilate around foreign objects.
Her Boston-based company has two devices on the market.
Designed an electrically switchable surface coating that can alternate between attracting and repelling water.
Such “smart surfaces” could coat biomedical implants for use in tissue engineering, sensing, or drug delivery.
Eric C. Leuthardt
Showed that a patient could achieve real-time control of a computer via electrodes placed on the brains surface.
Such an interface could allow paralyzed people to communicate and, eventually, control prostheses.
Applies evolutionary principles to synthetic molecules by linking starting materials to DNA strands.
The strands sequences determine which of them bind to each other, and thereby direct reactions between the starting materials.
Aims to reprogram cancer cells to be more like normal cells by developing compounds that block the aberrant modification of DNA in cancer cells.
Helped public-health officials control epidemics of walking pneumonia and SARS with sophisticated mathematical models that predict how a disease will spread through networks of human interactions.
Bridging the gap between research and patient care.
Cofounded his Baltimore, MD, firm to bridge the gap between research and patient care. One of its technologies will enable implantable cardiac devices to detect incipient heart attacks.
Facilitated noninvasive optical imaging of proteins and other molecules in the body, which could lead to ultraprecise diagnosis of cancer and other diseases.
Models how individual cells in tissues migrate, multiply, and develop during processes such as blood vessel growth. The models should aid tissue engineering and drug development.
Discovered an enzyme that could enable environmentally benign production of fluorine-containing compounds such as Teflon and Prozac, which are now made via noxious chemical processes.
Determined how small, natural proteins boost the immune response.
Inimex, in Vancouver, British Columbia, develops synthetic versions of the proteins for antibiotic-resistant infections.
Vikram Sheel Kumar
Developed interactive software that motivates patients to manage chronic diseases such as diabetes and AIDS.
Founded Dimagi in Boston to develop interactive software that motivates patients to manage chronic diseases such as diabetes and AIDS. His PDA-based systems are being used in rural India and South Africa.
Fine-tunes the activity of individual genes via an adaptable technology.
The technology is potentially useful in biosensors, gene therapies targeted to specific types of cells, and the development of new antibacterial, antifungal, and anticancer treatments.
Came up with the first method that allows researchers to pattern proteins and cells directly onto glass or plastic surfaces or within microfluidic channels without complicated preparation.
The technique is potentially a boon not only for basic research but also for the development of chemical and biological sensors.
Devised sophisticated and accurate computer algorithms for analyzing data generated using DNA microarrays.
These algorithms allowed her to identify genes involved in a host of diseases, including lymphoma, lung cancer, and gastric cancer.
Development of drugs to assist in the battle against TB.
Tuberculosis kills two million people every year, a tragedy of which Smruti Vidwans was all too aware growing up in India. Resistance to TB drugs is on the rise, and Vidwans thinks the solution may be new drugs that dont kill the bacteria but block the proteins that allow them to reproduce in people. Shes launching a company to develop such drugs. Its a huge challenge, but those who know her say shes up to the task.
Expanded the genetic code in order to allow living cells to incorporate new, unnatural building blocks into the proteins that they make.
The technique could one day allow biologists to create new proteins and even entire organisms that have enhanced or novel properties.
Sandra Waugh Ruggles
Uses clever testing schemes to determine which protein- slicing enzymes make the cut as potential drugs.
Her South San Francisco company is developing the protease-based treatments for cancer and inflammation.
She has filmed a single influenza virus infecting a cell.
Xiaowei Zhuang makes movies of the invisible. Peering into a microscope, she has filmed a single influenza virus infecting a cell. Her studies mark the first time anyone has recorded the stages of this process. Zhuang accomplished this feat by attaching fluorescent molecular tags to the virus; when excited with a laser, the tags emit specific colors of light. She has used the approach to track the behavior of not only individual viruses but even individual molecules, such as strands of RNA, at unprecedented levels of detail. Coming from a traditional physics PhD program, Zhuang very quickly began to lead experiments in single-molecule biophysics as a postdoc in Steven Chus lab at Stanford University. “With total ease, she immersed herself in biological physics and did an astounding amount of seminal work,” Chu says. Since establishing her own lab at Harvard, Zhuang has continued to do “landmark experiments at a blistering pace,” he adds. Direct observations of individual molecules are essential to really understanding how life works, Zhuang believes. “In the biology world, there are a lot of very small things that are doing critical functions,” she says. “There is a lot of interesting dynamic information one can get out of this kind of single-particle approach.” In her work on the flu virus, for example, Zhuang discovered that viruses move through the cell in three stages – one of which is so short that it could only be directly observed with high-speed imaging. “This experiment revealed unprecedented details of virus infection pathways,” says Harvard chemist Sunney Xie. Eventually, this in-depth understanding of how viruses work will help researchers find entirely new ways of blocking viral infection, Zhuang says. Indeed, virologists have begun asking to work with Zhuang, hoping to use her methods to study their own pet viruses.