Inside this issueCover storiesThe big questionsNew Kavli center for neuroscience research will untangle mysteries of the human brain Molecular gambleYale physiologist elected to National Academy of Sciences TrailblazerMagazine innovator celebrates 101 years with gifts for his medical school “family” PeopleLifelines: Expert on gene-swapping joined molecular biology at its very beginningsFor new deputy dean, focus is on top-notch care, service to patientsKidney researchers celebrate a banner yearUnconventional physician-filmmaker receives “genius” grantNew HHMI investigator says appointment liberates his scienceAwards & honorsScienceAnalysis of genome reveals clues to macular degenerationVaccinating wildlife suggests a new strategy in continuing battle against Lyme diseaseAdvances: Salmonella “syringe” ready for its close-up | Possible cancer inhibitor found in worm studyHealthA heart is repaired, the patient grows up: Program helps growing number of adult survivors of congenital diseaseMore integrated care for cancer patients, collaboration of scientists and clinicians are goals of proposed new YNHH buildingAdvances: New test easier for patients to swallow. | Study finds payoff in wider HIV testingPartnershipsPfizer and Yale join forces for research and educationA long, fruitful collaboration: Bristol-Myers Squibb and YaleDrive to cure blindness hits $5 millionClass of 1954 makes a lasting impact with scholarship giftGrants and contracts
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AdvancesHealth and science news from YaleSalmonella “syringe” ready for its close-upSalmonella bacteria are tiny, but they wreak mighty havoc on human health, causing serious, sometimes fatal, food poisoning. In 1998, Jorge Galán, Ph.D., D.V.M., the Lucille P. Markey Professor of Microbial Pathogenesis, threw new light on Salmonella’s virulence when his research team revealed that the bacteria infects cells by forming “needle complexes,” syringe-like tubes through which Salmonella exchanges proteins with its host.
Now Galán and his colleagues have joined forces with the laboratory of Vinzenz M. Unger, Ph.D., associate professor of molecular biophysics and biochemistry, to paint a vivid three-dimensional portrait of the Salmonella syringe using a state-of-the-art technique known as cryoelectron microscopy. In this method, an electron microscope scans samples that contain many copies of the object of interest suspended in an ice-like solid at every possible angle (background in image at right). Researchers then feed scores of images of the object seen from these myriad perspectives to powerful computers, which combine the information in the two-dimensional views to calculate the object’s three-dimensional structure. Possible cancer inhibitor found in worm studyYale scientists studying the microscopic worm C. elegans have discovered a cellular brake on a gene implicated in about 20 percent of human cancers, especially lung cancer. The finding opens up new possibilities for cancer diagnosis and treatment, says Frank J. Slack, Ph.D., assistant professor of molecular, cellular and developmental biology. Slack and his colleagues found that a snippet of genetic material in the worms called let-7 shuts down the activity of Ras, an “oncogene” that can cause cell proliferation to spiral out of control, as happens in cancer. In Slack’s experiment, in developing worms that lacked let-7, cells continued to divide instead of differentiating. Scientists use C. elegans in the laboratory because the worm shares many genes with more complicated animals. According to Slack, let-7 and Ras are almost identical in humans and C. elegans, and Ras protein, the product of the oncogene, is abundant in human lung cancers. Lung cancer has a poor prognosis, but the lungs may be an ideal target for inhalable gene therapy agents. This may not cure the cancer, Slack said, but “gene therapy with let-7 may be a way to alleviate it or slow it down.” New test easier for patients to swallowPhysicians at the Yale Medical Group (YMG) are using a remarkable new procedure to diagnose digestive disorders. Instead of undergoing standard endoscopy, in which a long tube is threaded through the mouth into the esophagus, stomach and small intestine, some YMG patients can now swallow a pill about the size of a large vitamin capsule that contains a tiny video camera. 
As the PillCam—manufactured by Given Imaging of Israel—makes an eight-hour journey through the upper digestive tract, the camera transmits full-color image data at a rate of two frames per second to an array of sensors in a belt worn by the patient. Doctors then upload the data from the belt to a workstation, where they can view the collected information either as still images or as a movie.
“The procedure is totally noninvasive, no radiation is involved, there is no discomfort and no need for sedation,” says Deborah D. Proctor, M.D., associate professor of medicine (digestive diseases). “Once the camera and belt are in place, patients can go about their normal day.” Study finds payoff in wider HIV testingOne of the deadliest features of the human immunodeficiency virus (HIV; micrograph at right) is its insidiousness. Those infected often live for years without obvious symptoms, unwittingly passing the virus on to others while their own immune systems steadily weaken. Public health experts estimate that nearly a third of the 900,000 Americans infected with HIV are unaware that they carry the virus. 
The Centers for Disease Control and Prevention recommends regular HIV testing for high-risk groups with infection rates of 1 percent or more, but A. David Paltiel, Ph.D., of the Department of Epidemiology and Public Health wondered whether the United States could cost-effectively expand testing to include groups at lower risk. To find out, Paltiel and Boston-based colleagues devised a mathematical model, and as reported in The New England Journal of Medicine, they found that expanding HIV testing to all but the lowest-risk groups would be well worth the additional cost, and would have a greater survival benefit for every dollar spent than other currently routine screenings, such as those for breast cancer, high blood pressure and diabetes.
According to Paltiel, the findings present “a golden opportunity to jumpstart the expansion of HIV testing services in the United States.” 
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Medicine@Yale Magazine
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June/July 2005 Volume 1 Issue 1
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