The debut issue of Science Translational Medicine a journal intended to help speed basic research advances into clinics and hospitals describes a microfluidics device for detecting tiny amounts of estrogen, which could potentially improve breast cancer screening.
Science Translational Medicine, a new journal from AAAS, the publisher of Science, focuses on outstanding science with promise to improve human health and quality-of-life. The first issue of the new journal, which includes both original research and commentary, will be published on 7 October 2009.
Elias Zerhouni, M.D., senior fellow at the Bill & Melinda Gates Foundations Global Health Program and former director of the U.S. National Institutes of Health, serves as chief scientific adviser for Science Translational Medicine. Katrina Kelner is editor of the new journal, which is guided by an advisory board including leaders in the field of translational medicine.
Cover of Science Translational Medicine
Pocket-Size Breast Cancer Detection
In one of three inaugural research articles, Noha A. Mousa and colleagues at the University of Toronto report that estrogen can be measured in minutes, using a tiny chip to purify the hormone in samples of blood or breast tissue thousands of times smaller than those required for conventional screening methods. Their invention may lead to a new era of quick and convenient routine screening for breast cancer risk or for monitoring of breast cancer therapies. In addition, the device could aid in treatment of a wide range of conditions infertility, for example that require frequent monitoring. The apparatus is based on digital microfluidics, a powerful technology that controls the movement of tiny droplets of liquid samples without pipes or valves.
Instead, liquid droplets are coaxed by electricity across a chip smaller than a credit card. Drops of liquid dissolve a dried sample of tissue and are moved to a reservoir containing a second liquid. The drops are then circulated within the reservoir, which removes contaminants and other biological components, leaving a purer extract of estrogen. The result is a purer estrogen extract.
 A schematic of the Digital Microfluidic (DMF) Device for Estrogen Extraction (top), which includes sample and solvent reservoirs and the liquid-liquid extraction zone bounded by a "wall". Below, a series of frames from a movie illustrating the key steps in the DMF-based extraction of estrogen from a droplet of human blood. (Click to enlarge image) [Image courtesy of Dr. Aaron Wheeler]
In the study, the researchers extracted the estrogen present in breast tissue samples from two breast cancer patients and analyzed the purer sample using a series of techniques. They were subsequently able to determine the amount of estrogen in the tissue. It is thought that measuring the amount of local estrogen in breast tissue could be useful for identifying women at risk for developing breast cancer. Nonetheless, local breast estrogen is not routinely measured because conventional techniques are painful, costly procedures that require removal of large amounts of breast tissue. The “lab on a chip” device the researchers created will allow scientists to test this theory.
Additional research in the debut edition of Science Translational Medicine includes advances in immunology and osteoporosis drug development.
A New Weapon Against Immune Attack
In a new study, Jeff K. Davies of the Dana Farber Cancer Institute and colleagues have identified a novel mechanism that protects patients from graft-versus-host disease after bone marrow transplants. Graft-versus- host disease occurs when donor immune cells attack the recipients body, causing serious organ damage. The group reports new findings on patients from previous human trials, where researchers used a special method to treat donor bone marrow cells before they are introduced to recipients that reduces graft-versus-host disease; even when the donor isnt an ideal match.
T cells are blood cells that orchestrate and participate in immune defense. Certain types of T cells cause graft-versus-host disease, while others protect against infection and cancer. Current methods of preventing graft-versus-host disease involve trying kill the destructive T cells in donor bone marrow but this also destroys the protective T cells, a potentially hazardous approach that often results in complications. The method used by the researchers in the previous study is fundamentally different. Before the donor T cells were transplanted, the group manipulated the cells, instead of killing them, to prevent the ones likely to cause graft-versus-host disease from multiplying. Patients injected with the treated donor T cells had less severe graft-versus-host disease and faster immune recovery than patients who received regular donor T cells.
The researchers have now found that a striking increase in the quantity of a particular kind of immune cell called regulatory T cells occurred in patients who received treated bone marrow, months after their transplant. After purifying these cells, the researchers found the regulatory T cells were able to specifically suppress the T cells that cause-graft-versus host disease. Their findings suggest that regulatory T cells may actually have a role in controlling graft-versus-host disease after this kind of bone marrow transplant. The technique they used to treat donor bone marrow could be adapted to make regulatory T cells for treatment of other conditions, such as autoimmune diseases.
The Balancing Act of Building Better Bones
Our bones are constantly remodeled throughout life, maintained by a delicate balance of destruction and rebuilding. In a study that points the way to better osteoporosis drugs, Diane Getsy-Palmer of Duke University Medical Center and colleagues were able to stimulate bone growth in mice without the negative effect of bone degradation. Osteoblasts build bone, while osteoclasts dissolve bone, and both types of cells are regulators of bone remodeling. Under normal conditions, the parathyroid hormone ensures balance between the two cells. When there is too little rebuilding, the usual equilibrium that maintains strong, healthy bones goes awry; bones become brittle and weak, and diseases like osteoporosis take hold.
Patients with osteoporosis often are treated with bisphosphonate drugs, which prevent bone loss but weaken the microstructure of bone, resulting in fractures with long term use. Better bone microstructure can be built with daily injections of parathyroid hormone, which directly stimulates osteoblasts. But parathyroid hormone also indirectly stimulates osteoclasts, and has to be injected daily to prevent the osteoclast-driven breakdown from reversing the induced bone growth.
Getsy-Palmer and colleagues now report that bone growth involves the action of a class of drugs called biased agonists. In the study, mice showed a significant increase in bone formation when treated with a biased agonist called PTH-barr that selectively binds to the parathyroid hormone receptor. The results show that this class of drugs can trigger only the good effects of the receptor it hits and not the bad in this specific case causing bone growth while minimizing the undesirable effect of bone breakdown, a key component to improving osteoporosis drugs. More significantly, the type of the receptor the biased agonist acts on is of the same class as the targets of many widely used heart drugs, hypertension drugs, and pain drugs. Consequently, these biased agonists could lead to a new generation of improved prescription drugs.
What is Translational Medicine?
Often described as an effort to carry scientific knowledge “from bench to bedside,” translational medicine builds on basic research advances studies of biological processes using cell cultures, for example, or animal models and uses them to develop new therapies or medical procedures.
Translational medicine is becoming ever-more interdisciplinary. For example, researchers need new computational approaches to deal with the large amounts of data pouring in from genomics and other fields, and as new advances in physics and materials science offer new approaches to study or diagnose medical conditions.
Science Translational Medicine is being launched to help researchers more efficiently access and apply new findings from many different fields, explained Bruce Alberts, Sciences editor-in-chief. Specifically, the journal will serve researchers and management in academia, government, and the biotechnology and pharmaceutical industries, physician scientists, regulators, policy-makers, investors, business developers, and funding agencies.
“The new journal should help scientists and engineers work toward bigger-picture goals for improving patient care, by allowing them to better assimilate information that currently is coming at them from multiple sources,” Alberts said. “Too often, information with the potential to improve human quality-of-life is available only through silo-like channels. For example, cardiologists who only attend specialized meetings and read the basic cardiology literature, but not the physics or computer science literature, might miss an important breakthrough that could advance their own research. Science Translational Medicine will help keep researchers informed about advances across all disciplines.”
Editor Katrina Kelner added: “Science Translational Medicine will encourage the flow of information from the lab to the clinic but also from the clinic back to the lab. We believe that continuous feedback and communication among the diverse players in this system are essential for success.”