Volume 4, Issue 2 Spotlights

SPOTLIGHTS Stanford Holds Trials for New Avian Flu Vaccine Arvind Ravi

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midst growing concerns of an imminent pandemic, many eagerly await the results of the first human trials of a new avian flu vaccine at the Stanford School of Medicine. Developed by the Chiron Corporation in Emeryville, California, the vaccine consists of an inactivated viral strain obtained from a bird flu patient in Vietnam. In all, 81 participants are taking part in the seven month study conducted by Cornelia Dekker, MD, Associate Professor of Pediatric Infectious Disease and Director of the StanfordLucile Packard Children’s Hospital Vaccine Program. Researchers plan to track the immune response of participants to two shots of vaccine taken one month apart. By measuring the levels of serum antibodies—molecules that play a critical role in helping the body ward off infection—researchers aim to get an idea of the vaccine’s efficacy and optimal dosage. Future trials extending the participant range to children and the elderly are also being designed. Stanford is one of four medical centers in the nation conducting trials on this vaccine, and the first results are expected to be available by the end of the summer.

Stanford researchers are working to find a way to prevent avian flu

Designing a Bionic Eye Evelyn Ling

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rofessor Daniel Palanker’s research project at the James H. Clark Center for Biomedical Engineering and Sciences, also known as Bio-X, involves seeing eye to eye with other scientists, literally. Palanker’s team, also affiliated with the Department of Ophthalmology and the Hansen Experimental Physics Laboratory at Stanford, has recently developed an optical retinal prosthesis that was featured in the February 22nd issue of the Journal of Neural Engineering. This “bionic eye” could someday help restore the vision of patients with blindness caused by retinal degeneration.

“This ‘bionic eye’ could someday help restore the vision of patients with blindness caused by retinal degeneration.”

Artificial Vision More than 100 million cells called photoreceptors - rods for night vision and cones for day and color vision - line the retina, which is located in the back of the eye. When an eye functions normally, the photoreceptors capture light from the environment. These light waves are then converted into neural signals, which are sent to the brain through the optic nerve to be processed into images. However, in eyes afflicted with retinal disease, the photoreceptors degenerate, resulting in vision loss. Fortunately, a recent discovery that electrical stimulation of retinal neurons produces phosphenes - spots or flashes of light perceived by the eye - offers a potential way to restore some degree of sight in patients suffering from retinal degeneration. When the retina loses its capability to detect light, it still retains, to a certain degree, its neural network, which can transmit signals to the brain when stimulated by electric fields. Therefore, as the researchers observe in their publication, “If one could bypass the photoreceptors and directly stimulate the inner retina with visual signals, one might be able to restore some degree of sight.” The retinal prosthesis developed by Palanker’s team utilizes this remaining neural circuitry in the retina. The prosthesis is comprised of several components. A small camera mounted onto goggles captures images from the environment. 

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These images are then relayed to and processed in a portable microcomputer. The resulting image is transferred to infrared goggles, which optically project the images - now converted into infrared waves - to the retina. A sub-retinal chip contains thousands of small photodiodes (pixels that detect light), which are powered by a photovoltaic battery implanted in front of the iris. The photodiodes translate the infrared light into biophasic pulses of electric current, which are sent to the retina and deciphered into images.

“This is very interdisciplinary research,” says Palanker. “It’s the very essence of Bio-X.”

Sharpening the Eye A crucial factor that must be considered in designing an effective retinal prosthesis is the system’s spatial resolution, commonly called visual acuity. This strongly depends on the distance between the electrodes in the chip and the target neural cells - currently a few micrometers. Because of physical limitations, it is very difficult to place the chip in closer proximity to thousands of cells. However, through a phenomenon called retinal migration, the retinal cells themselves travel closer to the electrodes. As Palanker explains, “We actually invite cells to come to the electrode sites, and they do it very quickly - in two to three days.” Currently, Palanker’s group has been testing two different designs in which the position and shape of the electrodes vary to see which can better accommodate the cell migration to yield better proximity and pixel density. The current retinal prosthetic system is designed to achieve visual acuity of up to 20/80, corresponding to about 18,000 pixels on a 3-millimeter chip. Retinal migration into arrays with such high pixel density has already been achieved. A visual acuity of 20/80 is sharp enough to clearly perceive faces and read large fonts. This advancement will offer hope to those suffering from retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. Palanker believes that in three years, this device may be available to the public.

Public Lecture Series: Uncovering the Mystery of Human Skin Color Amanda Marshall

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rom slavery within ancient societies to the United States’ Civil Rights movement only several decades ago, skin color has been one of the most divisive aspects of human existence. Dr. Keith Cheng hopes to illustrate that, despite its influence on the ways in which groups of people relate with one another, skin color is a genetically minute and trivial variation. During February, as part of Stanford Scientific’s Public Lectures in Science series, Cheng shared his work with the Stanford community and general public. Cheng’s work began ten years ago as an examination of a mutation of cancer cells in zebrafish. However, his group discovered surprising similarities between SLC24A5 (a zebrafish gene controlling skin color) and a human genetic analog. His paper discussing parallels between the zebrafish and human genes, titled “SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans,” was published in Science magazine last December. Beyond its sociopolitical implications about the trivial nature of skin color differences, Cheng’s research could offer valuable information about genetic origins of various diseases. For example, people of certain races may be more susceptible to skin cancer than people of other races. As an underlying theme for his talk, Cheng stressed the importance of collaboration. To reinforce the rewards of working together creatively, Cheng and a longtime friend treated the audience to a piano-cello duet. What began as a study of zebrafish will offer valuable insight into ways for both scientists and policymakers to improve people’s health and relationships with one another. layout design:Sarah Johnson and Dominique Cobb

Keith Cheng shares his research of genes controlling zebrafish pigmentation, which may be closely related to genes controlling human skin color. Photo Credit: Alvin Chow

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SPOTLIGHTS

Target: Cancer Cells – An Update on Innovative Solid Tumor Treatments Casey Means

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reakthrough oncology research is closing the door on “slash and burn” treatments that target both healthy and cancerous cells. These traditional treatments weaken the immune system and cause debilitating side effects—often the case in chemotherapy and radiation therapy. Scientists are developing treatments that search and destroy only oxygen-deficient cancerous cells, leaving millions of healthy cells in your body intact.

Exploitation of Tumor Hypoxia Solid tumors do not receive as much blood supply as normal cells. The tumor cells grow faster than the blood vessel supply can differentiate, so that capillaries cannot reach every cell within the tumor. Since the hemoglobin protein in blood carries the oxygen to cells, cells deep within a solid tumor that receive little blood flow are called hypoxic—oxygen-deficient - essentially living in an anaerobic environment. Dr. Martin Brown and his colleagues at the Stanford Cancer Center have created two therapies that exploit hypoxic environments in the body. The first involves the injection of a drug called tirapazamine (TPZ), which becomes toxic only in hypoxic areas, and thus only in the tumor, killing only cancer cells. This drug is currently in phase-III clinical trials, and soon to undergo final reviews by the FDA. Collecting suitable data during these trials is often an arduous process for drug-developers - it has taken Brown 20 years to develop TPZ. The second therapy is a tumor-specific gene therapy that utilizes genetically engineered anaerobic bacteria. These nonpathogenic bacteria, known as Clostridium sporogenes, are innocuous and situate only in hypoxic tissue—inside of the tumor - where they produce a specific enzyme. When a non-active drug (called a prodrug) is injected into the body, the enzyme from C. sporogenes converts it into a pharmacologically active compound hat kills the tumor tissue. Brown’s treatments are a promising alternative to traditional cancer therapies. Since chemotherapy is more effective in oxygenated, rapidly dividing tissues, it is not very effective in killing the hypoxic cells in tumors, and results in the destruction of many healthy cells. But, the combination of Brown’s therapies with chemotherapy, called “smart chemotherapies,” has the potential to wipe out Courtesy of James A. Brown all parts of a tumor, including those that are Depiction of Tumor-Specific Gene Therapy resistant to existent chemotherapies. It is through the efforts of scientists like Brown that only cancer cells can be sought out and destroyed. New cancer treatments promise to save millions of lives and improve the quality of life for cancer patients across the globe. 

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Going for the Gold: Explanation of Olympic Performance in Different Cultures Michelle Meyer

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omeone had to knock him off his pedestal, and I’m just glad it was me.” “I definitely want to win in this game: I should get gold at best, and at least.” What do these quotations have in common? They are excerpts from American and Japanese media coverage of athletes’ performances at the 2000 and 2002 Olympic Games. By analyzing quotes from Olympic media coverage, Professor Hazel Rose Markus of the Department of Psychology, uncovered different American and Japanese perceptions of athletic performance. Recent findings suggest that American and Japanese media differ in how they represent and explain performance due to different socio-cultural “models of agency” - models that reflect descriptive and normative understandings of human behavior. By choosing an event such as the Olympics “that would be reasonably similar in both contexts,” says Markus, Americans and Japanese could relate to the “many examples of people explaining their behavior and performances.” One study recently published in Psychological Science, “Going for the Gold,” details the analysis of the 2000 Summer and 2002 Winter Olympic media coverage relevant to America and Japan. Individuals from these countries were asked to view the media coverage and to examine how the coverage differed. By first assigning media coverage into specific themes ©SXC.hu/mordoc and then assigning these themes to seven broad Americans value positive personal attributes when describing an athlete’s performance. categories, Markus and her team discovered that American and Japanese media have varying models of agency. According to the studies, the American media tended to use an “entity-like” disjoint model of agency in which behavior is described in terms of the individual and his or her attributes when explaining athletic performance. On the other hand, media outlets in Japan tended to use a conjoint model of agency, meaning that athletic performance was influenced by “multiple factors…such as the athlete’s background, experience, current emotional state, and relations with other people,” says Markus. She adds that these models are relevant to explaining behavior in general, even though we may be unaware that we are applying these models. “It is wrongful to imagine that all people think like we do… We only see our own particular framework, our own background and experience, and we can’t necessarily apply that to everyone else,” Markus remarks. For example, American parents tend to focus on their children’s positive aspects, Media coverage themes of the believing that they should “praise their kids or it will hurt their 2002 Winter Olympics varied across self-esteem,” while Asian parents “have different theories about countries successful behavior… Parents of some cultures believe that when children fail, they should be criticized so they can learn from it.” Markus suggests that teachers should be aware of these different social contexts so that they can interact effectively with both the parents and their children in order to give children the best education possible. Markus also recommends increasing awareness of the differences in socio-cultural models by implementing more classes - at Stanford and other institutions - that address such issues. Students come to Stanford from a very wide variety of backgrounds, but they might not necessarily understand and appreciate the culture of the international student from Kuwait who’s in their chemistry section, or the background of the native New Yorker who lives ©SXC.hu/Aleng across the hall. layout design:

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