Duke - Dennis Meredith https://alumni.duke.edu/magazine/author/dennis-meredith en A History of Many Missions https://alumni.duke.edu/magazine/articles/history-many-missions <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <p><span class="text">Research was the central purpose of the original field station—later to become the Duke Primate Center—established in 1960. That year, Yale anthropologist John Buettner-Janusch moved his collection of eighty prosimians, including both lemurs and bushbabies, to cages in Duke Forest. </span></p><p><span class="text">The concrete-block building—which now houses the Primate Center’s staff, administrative offices, gift shop, kitchen, veterinary rooms, tissue and cadaver storage, indoor animal quarters, and fossil collection—was originally built in 1968 to house the behavioral research of two scientists. At that time, the center was partially supported by federal funding, and the university continued to contribute heavily to its budget. In 1974, university budgetary shortfalls caused by a declining economy led to plans to close the center. However, a campaign against the closure led by Duke faculty brought about a foundation grant to support operating expenses, allowing the center to remain open. </span></p><p><span class="text">In 1977, Yale primatologist Elwyn Simons became director. Under his leadership, the center secured facilities-support funding from the National Science Foundation, which currently provides about $300,000 per year toward the budget. The animal colony grew in size to more than 600 animals, while Simons and his colleagues developed an extensive fossil collection during decades of expeditions to Egypt and Madagascar. Under Simons, James B. Duke Professor in Biological Anthropology and Anatomy, the center also received research support from the National Institutes of Health and NSF. </span></p><p><span class="text">In 1991, Simons became scientific director of the center—a title he held until 1998—and Kenneth Glander, biological anthropology and anatomy professor, was named director. He was charged with spending 15 percent of his time directing the center, in addition to his teaching duties and research on the dietary habits of monkeys.</span></p><p><span class="text">During his tenure, Glander became known among the staff and university development officers as a champion of the center. As director, he sought to balance the center’s research, teaching, and conservation missions, while accommodating its growing popularity among the community school groups and the public. This explosion of interest saw visitor numbers more than triple from about 4,000 annually in 1991 to the current 13,000. Besides increasing income from the paid tours, entrepreneurial staff members expanded the gift shop to augment revenues from the “captive” audience of visitors. </span></p><p><span class="text">Laboring under diverse missions of hosting visitors, educating students, and conducting research, the center has been described by Duke officials and external reviewer as efficiently managed and the animals meticulously cared for. Reviewers include Duke’s Institutional Animal Care and Use Committee and the U.S. Department of Agriculture—the federal agency charged with monitoring zoos and other animal facilities. Administrators also praise the staff’s dedication to the animals’ welfare, which goes beyond basic husbandry needs. For example, staff members recently launched an “environment enrichment” program in which novel objects, from surplus fire hose to children’s play houses, are introduced into the animals’ cages to engage them mentally and physically. </span></p><p><span class="text">Such high-quality care and management has resulted in “squeaky clean” reviews, says center operations manager Dean Gibson, who was hired in 1997. Under Gibson’s management, the center has also shown budget surpluses during the last two years. And, as directed by the administration, the colony size has been reduced from about 450 to 280 animals, with many animals loaned or donated to zoos, and many in the colony put on birth control.</span></p> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2014-09-01T00:00:00-04:00">Monday, September 1, 2014</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/default_images/dukmag-horizontal-placeholder.jpg" width="238" height="140" alt="" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue Mon, 01 Sep 2014 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18499471 at https://alumni.duke.edu A Forty-Year Partnership https://alumni.duke.edu/magazine/articles/forty-year-partnership <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top" height="73"> </td></tr><tr><td valign="top"><div class="media-header fll " style="width: 240px; padding-right: 10px;"><img src="/issues/070811/images/070811_ultrasound_7.jpg" alt="Going mobile" width="240" height="349" border="0" /></div><p><span class="bodycontent">This year, as the Pratt School’s biomedical engineering department celebrates its fortieth anniversary, it is marking an extraordinary double partnership—between engineering and medicine, as well as between academe and engineering. </span></p><p><span class="bodycontent">The partnership has been a fertile one. Besides advances in ultrasound research, the department’s researchers have developed new magnetic-resonance, X-ray, and nuclear-imaging techniques. And the department’s researchers are inventing new technologies for biomechanics, biomolecular and tissue engineering, electrobiology, and neuroengineering. </span></p><p><span class="bodycontent">Says one of those researchers, Olaf von Ramm Ph.D. ’73, of the engineer-physician collaboration, “The developments that have come out of Duke really have been driven by a medical need, rather than some crazy idea of an engineer.” </span></p><p><span class="bodycontent">The partnership has had a powerful educational impact, says Stephen Smith Ph.D. ’75. “I believe every one of my students has been successful in carrying the course of his or her research all the way from the original clinical problem to actually testing it out on a human or an animal study.” </span></p><p><span class="bodycontent">The engineers’ other partnership—with industry—is exemplified by a display case festooned with dozens of old identification badges in the hallway of the ultrasound labs. Many of their owners are now high-level engineers at Siemens, Philips, GE, and other companies that maintain a close relationship with the department. </span></p><p><span class="bodycontent">These partnerships give Duke bioengineers premier access to the latest machines, says Gregg Trahey Ph.D. ’85. “We can grab raw data and build custom features on these machines to make them excellent research tools. Our students also go out there and do internships, so they learn the systems in detail. And we have close contacts, so if we run into a roadblock, we can call the engineer who designed a particular circuit board to solve the problem.” </span></p><p><span class="bodycontent">Of course, the benefits go both ways, say the engineers. The researchers’ scientific papers have proven rich fodder for industrial development, such as safety helmets for sports, new cancer drugs and treatments, and a better understanding of how Tasers used by law-enforcement officers can affect the heart. </span></p><p><em>–Dennis Meredith</em></p></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2011-08-01T00:00:00-04:00">Monday, August 1, 2011</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/default_images/dukmag-horizontal-placeholder.jpg" width="238" height="140" alt="" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue Mon, 01 Aug 2011 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18501631 at https://alumni.duke.edu Sound Thinking https://alumni.duke.edu/magazine/articles/sound-thinking <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><div class="brwntextheader-2010"> </div></td></tr><tr><td valign="top"><p> </p><div class="media-header flr" style="width: 340px;"><div class="caption caption-center"><div class="caption-width-container" style="width: 340px;"><div class="caption-inner"><img src="/issues/070811/images/070811_ultrasound_1.jpg" alt="Mysteries of the heart" width="340" height="428" border="0" /><p class="caption-text"><div class="media-h-caption"><strong>Mysteries of the heart:</strong> Medical diagrams, such as this one from 1875, could help diagnosticians only so much; more than a century later, it’s gotten easier, thanks to ultrasound.<br /><span class="photocredit">Corbis</span></p></div></div></div></div></div><p class="bodycontent-2010">The elderly man lies on the examining table, his expression taut with pain and fear. Earlier that morning, a crushing angina attack left him clutching his chest in panic. Placing a small ultrasound wand onto the man’s chest, the cardiologist peers up at a wall-sized screen in the examining room. A three-dimensional image materializes, showing the man’s pulsing coronary arteries, like a flowing river system with its winding tributaries. The physician touches a joystick to zoom in on the arterial landscape, pinpointing the blockages and providing a map for surgery that will save the man’s heart and his life.</p><p class="bodycontent-2010">In a remote South American forest, a white van lurches along the rutted dirt road into a village and comes to a stop. A group of women greets the mobile screening clinic, filing into the van for their examinations. They take turns on the examining table as the clinic nurse guides an ultrasound wand over each woman’s breasts. The nurse scrutinizes a computer screen showing a 3D image of each breast. Several of the women have lumps in their breasts; the ultrasound analysis reveals most to be nothing more than benign, fluid-filled cysts.</p><p class="bodycontent-2010">But the lump in one woman’s breast shows tell-tale characteristics of a solid tumor. The nurse types commands into a laptop computer. A small robotic arm equipped with a biopsy needle glides smoothly into position. The robot pin-points the suspicious mass via an ultrasound array in its tip. Guided by artificial intelligence, the robot eases the biopsy needle gently and precisely into the breast to extract a tissue sample. Soon the woman will know whether her worries are justified.</p><p class="bodycontent-2010">These scenarios represent dreams of Duke bioengineers who, over four decades, have invented technology that transformed ultrasound imaging from a laboratory curiosity into an essential clinical instrument. They’re dreams for now, but today, clinicians routinely use ultrasound to provide images of fetuses, as well as the heart and other organs. Over the coming decades, researchers expect ultrasound to influence medicine even more profoundly— including diagnosing and treating heart disease, liver disease, stroke, brain cancer, breast cancer, prostate cancer, and even battlefield wounds.</p><p class="bodycontent-2010">Ultrasound imaging appeals to physicians because its basic technology is simple and benign. Ultrasound machines, unlike multi-ton MRI machines or room-sized CAT scanners, are typically no larger than a baby buggy and just as portable. And unlike X-rays or radioactive-tracer PET scans, ultrasound does not expose patients to ionizing radiation. Ultrasound is also far cheaper. Even the most elaborate ultrasound scanner costs no more than $100,000, versus millions of dollars for MRI or CAT scanners.</p><p class="bodycontent-2010">A tour of the Duke biomedical engineering department’s ultrasound labs— where some of the field’s most important technology was born—reveals a collection of equipment as exotic and, yes, sometimes peculiar as any creative research laboratory. Visitors may expect to see electronics-assembling clean rooms, robotic arms, and circuit-slicing saws with hair-thin diamond blades that spin at 30,000 rpm. But they might not expect to see turkey breasts or a garbage can full of murky river water—both of which have figured in key Duke experiments.</p><p class="bodycontent-2010">Ultrasound—sound at a frequency higher than the human ear can detect— had been in scientific use largely as a laboratory tool for studying the body since the 1940s. However, the creative ingenuity that transformed the technology into everyday clinical instruments began at Duke in 1967. That year, Theo Pilkington M.S. ’60, Ph.D. ’63, a brash, young associate professor and the driving force behind biomedical engineering at Duke, recruited ultrasound engineer Frederick “Fritz” Thurstone to the new department. Thurstone was an avid proponent of medical ultrasound, although his earliest experiments were primitive. He would immerse patients in water and “ping” them with a parabolic reflector, much as submarines pinged enemy warships.</p><p class="bodycontent-2010">But it was two of Thurstone’s early graduate students—Olaf von Ramm Ph.D. ’73 and Stephen Smith Ph.D. ’75—who would join with him to invent technology that would propel ultrasound into just about every medical center in the world.</p><div class="media-header fll " style="width: 340px; padding-right: 10px;"><div class="caption caption-center"><div class="caption-width-container" style="width: 340px;"><div class="caption-inner"><img src="/issues/070811/images/070811_ultrasound_2.jpg" alt="Advanced at the time" width="340" height="230" border="0" /><p class="caption-text"><div class="media-h-caption"><strong>Advanced at the time: </strong>Early ultrasound testing using Thurstone’s sixteen-transducer prototype.<br /><span class="photocredit">Courtesy Olaf von Ramm </span></div><div class="media-h-credit"> </p></div></div></div></div></div><p class="bodycontent-2010">One major aim was to revolutionize a device called the transducer, which serves as both the transmitter and receiver of ultrasound pulses. Thurstone and von Ramm advanced transducer technology: What had been simple devices that emitted a single pulse became multiple arrays that produced up to thousands of pulses at once. The intricate reflections of these pulses from body tissues and organs could be processed by computers into the first ultrasound images.</p><p class="bodycontent-2010">In their work, the engineers collaborated closely with Duke physicians. When the cardiologists saw the first ultrasound image of a beating heart, “they didn’t know what they were looking at,” von Ramm recalls. “Their mental image was based on static X-rays. So, we all learned together what a living heart looked like.” Ultrasound enabled cardiologists to measure noninvasively a heart’s “ejection fraction”—the volume of blood that it pumps. No catheter insertion was needed, and no X-rays required, to obtain this critical measure of heart function.</p><div class="media-header flr" style="width: 250px;"><div class="caption caption-center"><div class="caption-width-container" style="width: 250px;"><div class="caption-inner"><img src="/issues/070811/images/070811_ultrasound_4.jpg" alt="Committed to action: A Bahraini Shiite cleric chants slogans against Saudi and Bahraini leaders in front of the Saudi Embassy in Tehran as Iranian police stand by." width="250" height="546" /><p class="caption-text"><br /><div class="media-h-caption"><strong>Internal perspective:</strong> Scan of a heart from the original ultrasound machine at Duke.<br /><span class="photocredit">Courtesy Olaf von Ramm</span>The next major advance in ultrasound technology was triggered by a plane crash. In 1982, an Air Florida jet slammed into the Potomac River, sinking immediately. Divers could not find bodies in the dark waters. Hearing of the tragedy, Smith envisioned that a 3D ultrasound machine would allow search parties to “see” in real time what was at the bottom of murky bodies of water.</p></div></div></div></div></div><p class="bodycontent-2010">Smith and von Ramm set out to invent such a machine, developing complex transducer arrays and fast computer systems that could analyze the cascade of ultrasound reflections and produce a three-dimensional moving ultrasound image in real time. In 1987, they realized their vision. In early experiments, they carted a garbage can full of brownish water from the nearby Eno River back to the lab and used a submerged wrench as their target. They could locate the wrench using the new technology.</p><p class="bodycontent-2010">With the success of their system, they joined with partner John Oxaal B.S.E. ’76 to form Volumetrics Medical Imaging to develop the first real-time 3D commercial system. Since then, 3D ultrasound technology has come into wide clinical use for imaging tissues and organs.</p><p class="bodycontent-2010">But ultrasound technology has the potential to produce an even more detailed view of the body. Von Ramm’s vision of the future is to use advanced imaging processing and high-frequency transducers to create high-resolution images of even smaller segments of tissue, down to the level of the coronary arteries. “I want to see the coronary artery tree hanging in 3D space,” he says. “We’ve imaged them for short distances, but they are very tortuous vessels that curve around the heart, and the heart is a 3D object.”</p><p class="bodycontent-2010">Smith and staff engineer Ned Light B.S.E. ’89, M.S.E. ’97 have continued to develop more specialized ultrasound probes, concentrating particularly on smaller ones that can be inserted into the body for a clearer view of internal organs. They first invented endoscopic probes that could fit into the throat or through incisions in the body. But their latest project has gotten even smaller.</p><p class="bodycontent-2010">In his laboratory, Light holds up a thin tube—a catheter that surgeons thread into the body to carry such devices as heart valves and tiny clot-blocking wire cages to be inserted into blood vessels. But the tip of this catheter is different from ordinary devices. It has embedded in it a ring of tiny wires. These wires are ultrasonic transducers that will act like the equivalent of a flashlight beaming pulses. This “flashlight” will give surgeons a close-up view of the progress of the catheter through blood vessels, as well as the procedure they are conducting. Such devices could reduce or eliminate the need for Xray imaging and potentially toxic dyes currently used to guide such procedures.</p><p class="bodycontent-2010">Like all creative researchers, Duke ultrasound engineers think in “what-ifs,” then set out to make them reality. Among them:</p><p class="bodycontent-2010"><em>What if oncologists could insert an ultrasound probe into a brain tumor, not only to image the tumor but to kill it as well? </em>Graduate student Carl Herickhoff M.S.E. ’09, Ph.D. ’11, a member of Smith’s lab, is experimenting with an ultrasound-equipped catheter that could be inserted into the brain to locate a tumor. Physicians hypothesize that they might then apply more power to the ultrasound probe to gently heat the tumor. The patient would already have been injected with cancer-killing chemicals encapsulated in heat-sensitive fatty bubbles called liposomes. The ultrasound heating would be just enough to melt the bubbles in the tumor, delivering a targeted chemotherapy dose.</p><p class="bodycontent-2010"><em>What if stroke victims could be diagnosed in the home or ambulance and clot-busting therapy given immediately?</em> Such quick treatment would more likely fall within the “golden hours,” during which vital brain functions can be saved. To enable such rapid treatment, Smith and graduate student Brooks Lindsey are developing a 3D ultrasound “brain helmet” that emergency technicians would fit onto a stroke victim’s head. The helmet could transmit an ultrasound brain image to the hospital neurologist and immediately show whether the stroke was caused by a clot or a bleeding vessel. If it were a clot, the doctor could prescribe clotbusting drugs to be given on the way to the hospital, rather than waiting to perform a CT scan.</p><p class="bodycontent-2010"><em>What if ultrasound could distinguish potential breast cancers from harmless cysts?</em> And what if that imaging could guide a robotic arm to obtain a biopsy sample? Using an ultrasound wand fitted on a commercially available robot arm, bioengineering student Kaicheng Liang B.S.E.’10, working in Smith’s lab, has shown that the device can locate an artificial cyst in flesh—in this case, a turkey breast. The next step is to test how well the ultrasound system can locate real breast tumors, compared to physicians relying on 2D ultrasound or mammograms. Liang and his colleagues are also exploring whether such a robotic system could locate and take samples of prostate tissue.</p><p class="bodycontent-2010"><em>What if ultrasound could guide a robotic arm to extract shrapnel on the battlefield?</em> Albert J. Rogers B.S.E. ’09 has shown that an alternating magnetic field will subtly vibrate tiny bits of metal in water, rendering them visible enough on ultrasound to guide the tip of a robotic arm to their location. The finding raises the promise of an artificially intelligent battlefield surgeon that could deftly remove shrapnel quickly before it does more damage.</p><p class="bodycontent-2010"><em>What if ultrasound could not only “see” tissues but also “feel” them?</em> Physicians’ sense of touch is one of their most valuable diagnostic tools, as they palpate their patients’ bodies to detect tumors and other abnormalities. Bioengineering professors Gregg Trahey Ph.D. ’85 and Kathryn Nightingale B.S.E. ’89, Ph.D. ’97 and their colleagues are developing a technology called Acoustic Radiation Force Impulse (ARFI) imaging, which uses strong ultrasound pulses to “poke” tissues or organs deep in the body. The tissue movement is infinitesimal— about a hundredth of the diameter of a human hair. But the ultrasensitive ultrasonic detection system is designed to detect the subtle reflected signals from these tiny motions—amidst the relatively huge motions of the heart and other organs—to measure the stiffness of the target tissue.</p><div class="media-h-caption"> </div><div class="media-header flr" style="width: 346px;"><div class="caption caption-center"><div class="caption-width-container" style="width: 345px;"><div class="caption-inner"><img src="/issues/070811/images/070811_ultrasound_3.jpg" alt="Committed to action: A Bahraini Shiite cleric chants slogans against Saudi and Bahraini leaders in front of the Saudi Embassy in Tehran as Iranian police stand by." width="345" height="543" /><p class="caption-text"><br /><div class="media-h-caption"><strong>Exquisite specificity: </strong>Kathy Nightingale, above left, uses ultrasound imaging for detailed diagnostics; ultrasound image of a canine brain, above, shows blood vessels in color and images of lateral ventricles (LV), base of the skull (B), internal carotid artery (ICA), and anterior cerebral artery (ACA).<br /><span class="photocredit">Top: University Photography; Bottom: Courtesy Stephen Smith</span></p></div></div></div></div></div><p class="bodycontent-2010">Trahey recalls that a phone call from the director of Duke’s breast cancer clinic in 1993 triggered him and his colleagues to consider ARFI as a clinical tool. Using ultrasound, the clinic’s director complained, “We can’t even do the simplest thing. We can’t tell the difference between a cyst and a solid lesion. You guys are worthless.”</p><p class="bodycontent-2010">Nightingale, a graduate student of Trahey’s, set out to explore whether ARFI’s poking mechanism could distinguish between harmless fluid-filled cysts and potentially malignant solid masses. She found that the technique worked, and she is now exploring whether ARFI can more definitively spot malignant tumors. “Some cancers and some benign masses can be similar in stiffness,” she says. “But cancers tend to be more tethered within the breast and prostate, more connected to the surrounding tissue. So, we have begun exploring techniques to highlight the differences in order to distinguish cancers.”</p><p class="bodycontent-2010">ARFI’s ultrasonic poking can also tell squishy living tissue from stiffer dead tissue. Trahey, fellow bioengineer Patrick Wolf Ph.D. ’92, and cardiologist Tristram Bahnson are developing ARFI probes that could guide cardiologists when they perform the tissue-killing procedure called cardiac ablation. In this procedure, they use a probe that emits intense radio frequency waves to kill bits of heart tissue selectively and to block the dangerous wave of arrhythmia moving through the heart. “Currently they fly blind,” Trahey says. “You can’t really tell which part of the heart you’ve cooked and which part is intact. They watch the patient’s arrhythmia and use invasive electroanatomic mapping techniques, and some of these procedures can take eight, ten, twelve hours.”</p><p class="bodycontent-2010">Nightingale is working with Duke hepatologists to explore ARFI as a technique to detect fibrosis in the liver, a sign of cirrhosis and elevated risk of liver cancer. “Given that the technique is noninvasive, it could be preferable to needle biopsies, in which a plug of tissue is extracted and the overall extent of fibrosis inferred,” she says. “The needle might land in a ‘bad neighborhood’ that doesn’t accurately portray the overall status of the liver, while the ARFI method can be performed painlessly, in multiple locations.”</p><p class="bodycontent-2010">For Nightingale, a related interest is whether ARFI could guide biopsies of the prostate to detect cancer. The technique would be a high-tech version of the physician’s digital rectal exam, she says. “What physicians do in those exams is to feel for regions that are stiffer, but biopsies are systematically taken from a grid of locations in the prostate. So, the idea is that we could use ARFI to identify regions where they should aim their biopsy needle."</p><p class="bodycontent-2010">Anaesthesiologists could use ARFI to guide a needle administering regional anesthesia. Nightingale and assistant research professor Mark Palmeri B.S.E. ’00, Ph.D. ’05, M.D. ’07 are developing ARFI techniques to map the change in stiffness of tissue as the needle infuses anaesthetic into a region. Such guidance would enable anaesthesiologists to more precisely place a needle to deaden nerves more effectively.</p><p class="bodycontent-2010">Faster processing and improved transducers are enabling von Ramm and his colleagues to track ever-finer motions of the heart. Such advances, they believe, will reveal— at cell-level detail—the instantaneous wave of contraction sweeping across the heart. Seeing the finest details of a heartbeat means they could pinpoint the regions of the heart damaged by heart attacks or the effects of congestive heart failure.</p><p class="bodycontent-2010">Trahey and his colleagues are experimenting with a new imaging strategy that promises to greatly enhance clarity of ultrasound scans—just as high-def TV has superseded low-def. Called “coherence imaging,” the technique involves forming images not just from the ultrasound reflections themselves, but also from the reflections of finer “wavelets” formed when one ultrasound wave interferes with another. Trahey, research professor Jeremy Dahl Ph.D. ’04, and graduate student Muyinatu Lediju are developing the concept.</p><p class="bodycontent-2010">In the view of George Truskey, chair of the biomedical engineering department, ultrasound and other technologies can be a big factor in a changing health-care landscape— notably by reducing the number of expensive and invasive biopsies. “A lot of people do have the perception that technology drives up health-care costs, and there are certainly cases where technology is overused,” he says. The use of expensive MRI scans on patients who don’t really need them is an obvious example.</p><p class="bodycontent-2010">“There will always be the caveat that you have to monitor how these technologies are used. But the flip side is that the technology benefits patients by providing early diagnosis. That can lead to successful treatment, to prolonging someone’s life, and to stretching out that individual’s productive years.”</p><p class="bodycontent-2010"> </p><p class="bodycontent-2010"><em>Meredith is a science writer and research communication consultant. He is the author of </em>Explaining Research: How to Reach Key Audiences to Advance Your Work<em> (Oxford University Press, 2010)</em>.</p><p class="bodycontent-2010">For the latest news from the B.M.E. department: <a class="onlinetitl" href="http://bme.duke.edu/research/biomedical-imaging">http://bme.duke.edu/research/biomedical-imaging</a>.</p></td></tr><tr><td valign="top"> </td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2011-08-01T00:00:00-04:00">Monday, August 1, 2011</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/dm-main-images/sound.png" width="620" height="265" alt="" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section><section class="field field-name-field-issue field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Issue:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/issue/jul-aug-2011" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Jul - Aug 2011</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue<section class="field field-name-field-sub-header field-type-text-long field-label-above view-mode-rss"><h2 class="field-label">Sub-header:&nbsp;</h2><div class="field-items"><div class="field-item even">Duke bioengineers, who played an important role in the development of medical ultrasound four decades ago, continue to find new uses for the tool, using it to illuminate disorders from cancer to heart disease.</div></div></section> Mon, 01 Aug 2011 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18501630 at https://alumni.duke.edu The Accidental Scientist https://alumni.duke.edu/magazine/articles/accidental-scientist <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><div class="media-header"><div class="caption mceTemp draggable"> </div></div><p class="articletitle">The same merciless sun that blasted a drought-stricken North Carolina in the summer of 2002 shone like a spotlight of triumph on Mary Eubanks. The scientist says she felt vindicated, exultant even, as she gently pushed her way through the lush green foliage of thriving corn plants festooned with fat ears of corn that hung over her head. The plants had sprung from the same desiccated soil that had left the commercially grown cousins on an adjacent plot shriveled brown husks. Eubanks had refused to coddle her hybrid plants, allowing them not a drizzle of irrigation. Instead, she had given them something far more valuable: a genetic heritage that enabled them to flourish amidst the drought.</p><p>"It was truly amazing, because at the end of the summer when I went in to harvest, there were no ears on the regular corn, and all of the ears on my plants were completely filled out," she recalls. "They were as beautiful as the ears of the fancy inbred lines that you see when you go to the seed trade association shows."</p><p>Eubanks, an adjunct professor of biology, had developed her remarkably drought- and pest-resistant hybrids by crossing two wild grasses related to corn. But, despite the demonstrated vitality of the plants, she was met with vociferous criticism from other scientists. They denounced her scientific articles on the origin and evolution of corn, leading some of the most prestigious scientific journals to refuse to publish her findings. Some scientists said they doubted the existence of her hybrids. She had literally suffered for her science, enduring years of personal attacks on her findings and her competence.</p><p>The scientific heresy that Eubanks espoused is that modern corn, Zea mays, did not evolve solely from a Central American grass known as teosinte, as was commonly thought. Rather, she contended, her experiments demonstrated that corn could have arisen from a serendipitously viable cross between teosinte and another corn relative, gamagrass or Tripsacum. Such crosses, argued the critics, could not possibly be fertile, just as the cross between a horse and a donkey--a mule--is always sterile. (None of the critics contacted by Duke Magazine would speak on the record.)</p><p>While fighting over the origin of corn in the murky millennia of the past might seem but an esoteric academic controversy, understanding that genetic origin has profound practical implications. Given the world's critical dependence on corn, resurrecting its genetic past could lead to a more secure agricultural future for the whole world. Mother Nature does not treat agriculture gently, continually conjuring pests and pestilences to attack existing strains. By drawing on antique genes, plant breeders can create resistant hybrids to battle these onslaughts.</p><p>For Eubanks, the success of 2002 marked a turning point. Throughout, she has proven as resilient as the plants she has bred, driven by the humanitarian dream that they could help feed people in famine-ridden countries and dramatically benefit U.S. agriculture. They could lower irrigation requirements, improve pest resistance, and reduce toxin contamination of a $30 billion-a-year harvest that supports vast livestock herds and yields industrial products ranging from clothing to ethanol. Now, her dream is moving steadily toward reality, with field trials of her corn hybrids proving their worth.</p><p>Eubanks is modest about her evolution into an accomplished genetics researcher, a process that involved several detours and yielded tales of serendipity populated by corn-decorated pottery, bronze door knockers, and chance encounters. But as Pasteur would have countered, "In the field of observation, chance favors only the prepared mind"; and, despite her self-effacement, Eubanks does exemplify the power of a prepared mind.</p><p>Her preparation began not in hard science but in anthropology, in the early 1960s, when she was a graduate student at the University of North Carolina at Chapel Hill. The subject of her work, the origins of American agriculture, was inspired by a memorable lecture. "I really stumbled into it," she says. "I was working on my master's in anthropology, and one day my professor in Mesoamerican archaeology gave a lecture on Zapotec urns from the valley of Oaxaca in southern Mexico." The urns featured bas-relief images of corn created by molding actual ears of corn.</p><p>"The way he crafted the whole lecture was as a mystery" about the origins and significance of these urns as historical artifacts, says Eubanks. "And I loved plants, and I loved art and archaeology, because I really wanted to be a classical archaeologist, originally. And that's because the only woman professor I had as a college undergraduate was a classical archeologist. She was the one role model in my whole college career that I had that I could say, 'Oh, a woman can do this.'"</p><div class="media-header" style="width: 301; float: left;"><div class="caption caption-center"><div class="caption-width-container" style="width: 300px;"><div class="caption-inner"><img src="/issues/050606/images/lg_corn4400329.jpg" alt="Examples of Eubanks' gamagrass-teosinte crosses, which closely resemble the oldest corn in the archaeological record " width="300" height="448" /><p class="caption-text"><div class="media-h-caption">Examples of Eubanks' gamagrass-teosinte crosses, which closely resemble the oldest corn in the archaeological record. Les Todd</p></div></div></div></div></div><p>Intrigued by the idea that images of the corn on the ancient Zapotec urns could constitute visions of past agriculture, she tracked down Paul Mangelsdorf, a botanist who had retired from Harvard University and was teaching part time at the University of North Carolina at Chapel Hill. Mangelsdorf, she had learned, was involved in a botanical archaeology project in Mexico. "When I walked in and told him what I was interested in, he said, 'You're just the student I have been looking for for years and could never find at Harvard.' "</p><p>Mangelsdorf was interested in exploring the corn images on the Zapotec urns as a possible archaeological treasure trove for understanding the origins of corn. Eubanks traveled to Oaxaca to study the urns as botanical artifacts--an effort that meant she had to learn botany, as well. "So, very early I was getting into interdisciplinary research between two widely divergent fields--the natural sciences and the social sciences," she says. "And it was difficult managing my dissertation committee, because members literally didn't understand how to talk to each other."</p><p>Following this initial exploration, Eubanks says that her study of the origins of corn "went dormant," although she continued to publish and teach on archaeological and anthropological subjects. Then she was reunited with Mangelsdorf, oddly enough, by way of a door knocker. Earlier, as she was finishing her Ph.D., Eubanks had come across a handsome, bronze door knocker decorated with cast ears of corn. She bought one for herself and gave one to her mentor.</p><p>Years later, when Mangelsdorf moved out of his house and into an apartment in Chapel Hill, he had to leave the door knocker behind. Missing his trademark decoration, he contacted Eubanks to ask where he could find another. "I didn't know where to get them, so I just took the door knocker off my door and mailed it to him," she says. "He was pretty flabbergasted, I guess, and we reconnected. When I visited him, I got interested in a new hypothesis he was testing in the laboratory--that modern corn originated from a cross between a primitive corn and a rare perennial teosinte that had just been discovered in Mexico." Eubanks readily learned the necessary laboratory techniques and began to explore the details of the chromosomes of the rare plant.</p><p>She found that when she crossed the teosinte with corn, the number and position of characteristic "knobs" on the chromosomes of the resulting plants did not square with the theory that corn had arisen from teosinte. "We were seeing amplification and transposition of chromosome knobs that were definitely against dogma and very exciting and interesting," she says.</p><p>At this point, Eubanks, who was going through a divorce and had small children, was fruitlessly applying for tenure-track jobs in anthropology. "It was 1984, and although I got on the short list of all the best jobs, a woman was not hired for any of the job openings in anthropology that year," she says. When Mangelsdorf recommended her to corn cytogeneticist Marcus Rhodes for a postdoctoral fellowship at Indiana University, she jumped at the chance. There, as she studied in more detail the chromosomes of teosinte-corn crosses, she encountered another "accident." In the experiment station where she worked, a former student had left a collection of gamagrass plants, Tripsacum. Eubanks began to examine the chromosomes of this grass under her microscope. "It was very clear to me that the architecture of the perennial teosinte chromosomes, which was quite different from the other Zeas, was very similar to Tripsacum."</p><p>That discovery launched Eubanks on an effort to produce hybrids by cross-pollinating teosinte and gamagrass. To the utter surprise and delight of Eubanks and her colleagues, the recombinant plants not only grew and flowered but also "produced little ears, and the little ears looked a lot like the oldest archeological ears." Further studies showed that when she crossed the teosinte-gamagrass recombinants with corn, the hybrids were both drought-resistant and resistant to rootworm, a major corn pest.</p><p>Eubanks says she believes that one key to the hybrids' hardiness is their root system, which is more extensive than that of modern corn strains. The roots of the plants she developed reach deeper into the soil to draw up moisture, she theorizes. In addition, the roots of her strains possess hollow chambers called "aerenchyma" that carry oxygen into even the most compacted soils. The aerenchyma also render the roots distinctly unfriendly to pests. "If you compare these roots to regular corn roots that do not have aerenchyma and are filled with lots of wonderful tissue for the bugs to feed on, you realize there is nothing in the roots of hybrid plants for the larvae to eat," says Eubanks. "They just don't get much nutrient when they feed on the roots. In fact, in our earliest experiments when we recovered larvae and weighed them, there were fewer, much smaller larvae coming off the recombinant corn plants by comparison with the extensive populations of healthy larvae that were twice as large coming off the corn control plants."</p><p>"Clearly, these plants are different," Eubanks says of her teosinte-gamagrass-recombinant strains. "They are perennial, so you don't have to grow them from seed. You just stick a cutting in the ground like a begonia, and it will root. And they can tolerate severe drought, acid soils, and even swamps. If, indeed, natural recombinants were involved in the domestication of corn, it could dramatically shift the paradigm of where and how corn originated." That "unshifted" paradigm holds that only teosinte was the ancestor of modern corn and not some oddball cross between teosinte and gamagrass.</p><p>Despite her successes, Eubanks' research continued to be called into question, with other researchers expressing doubts that her plants were true teosinte-Tripsacum crosses, even though she had solid DNA fingerprinting data proving the crosses.</p><div><p>"So, even in spite of all that, there were people, very important people, who were in complete denial," she recalls. "And they got up and said I didn't have hybrids. And I made my response, and I presented my evidence, and that's all I could do, because they were not ever going to accept it." Purdue plant geneticist Jules Janick found himself with a front-row seat at the controversy in 2001, when he sent out for scientific review an article by Eubanks for publication in the journal Plant Breeding Reviews, which he edited. "As I remember, there were three reviewers against her and two for her," says Janick. "After she answered all their questions, I decided to publish it." Janick notes that Eubanks at that time was "up against the world," calling her "gutsy" for her stand.</p><p>Another expert, Walton Galinat, a renowned professor emeritus in plant and soil sciences at the University of Massachusetts at Amherst, has been more outspoken on Eubanks' behalf. "She did something that nobody else was able to do--mainly get a hybrid between two of the relatives of corn, Tripsacum and teosinte," says Galinat. "And she is the only person that has knowingly gone ahead and done that." Says Galinat of Eubanks' detractors, "Partly it is a sexist thing, and they are kind of mad because they didn't do it. A lot of men are that way. They hate someone else that beats them to the draw. When it was pretty obvious she was going to win, they refused to acknowledge that."</p><p>Today, however, the steady flow of solid evidence has won much of the plant-science community to her side, and she has been publicly vindicated. She has been invited to speak at scientific symposiums, to contribute commentaries on scientific articles on maize origins, and to write a chapter on her hypothesis about corn's origins for a new book, Darwin's Harvest (Columbia University Press). She's even achieved some celebrity, having been featured in a new photography book, Faces of Science (W. W. Norton) along with luminaries such as Nobelists Francis Crick and Murray Gell-Mann and pioneering Harvard biologist E. O. Wilson.</p><p>Eubanks has now largely shifted her attention from studying corn's origins to realizing the potentially stunning agricultural benefits of her hybrid strains. She is planning a scientific expedition to Guatemala to search for natural hybrids, but that scientific study will be combined with a more practical objective. She will also seek to develop collaborations with local subsistence farmers to reintroduce genes from "ancient" strains into their crops to invigorate productivity and enhance drought and pest resistance in their crop strains.</p><p>Closer to home, Eubanks' company, Sun Dance Genetics, has formed numerous collaborations to field test her new hybrids. One set of field trials has already shown that the hybrids produce protein yields comparable with the best commercial hybrids. Other trials are exploring the hybrids' resistance to rootworm and the deadly mold aflatoxin and also whether the hybrids can be profitably grown in the drought-prone regions of North Carolina. Yet another trial now under way is examining how well the hybrids tolerate low levels of nitrogen--with the aim of reducing fertilizer requirements for corn.</p><p>"One major problem, amplified by Hurricane Katrina, is that nitrogen runoff from farmlands that drain into the Mississippi River Basin has created a large dead zone in the Gulf of Mexico," she says. "And most of the nitrogen runoff--the cause of the large algal blooms that deplete oxygen and kill aquatic organisms--comes from fertilizer applied to corn, which requires high levels of nitrogen to boost crop yields. So, if we can develop commercial corn hybrids that use far less nitrogen, it would be a huge benefit for this country and for the environment."</p><p>"The important thing is that all these traits came out of one breeding program," says Eubanks. "Even though I started by selecting for rootworm tolerance, we discovered some of the inbred lines were also resistant to drought and aflatoxin. So, you can develop hybrid corn that offers a complete package of traits in one plant, because the teosinte-gamagrass recombinants enable movement of suites of genes for different traits all at the same time with conventional plant breeding. It's unlike the biotechnology approach, where one transgene at a time is typically engineered into a plant."</p><p>Even when she is immersed in the arcana of genomics, Eubanks keeps her ... well ... roots deeply planted in the hard-pan realities of the farmers she seeks to help. She recalls with emotion when she presented her results to a group of some 600 Midwestern farmers. They told her they were at the mercy of large seed companies selling proprietary, genetically modified strains at high prices. "They cheered, gave me hugs, kisses, and told me incredible stories about the problems the takeover by genetically modified crop technology is causing the American farmer and small seed producers; and many had tears in their eyes," she recalls. "I was so inspired by those farmers, I will do my best to provide a product that will help save the American farm and move us toward more sustainable food-production methods that will benefit the environment." Looking back on her serendipitous journey from studying Mexican pottery to exploring the intricate depths of plant genes, she exclaims, "It was like it was meant to be. I tell you, I am really the accidental scientist!"</p></div><span class="text"></span></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2006-06-01T00:00:00-04:00">Thursday, June 1, 2006</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/dm-main-images/lg_corn4400304.jpg" width="622" height="265" alt="Mary Eubanks. Les Todd" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section><section class="field field-name-field-issue field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Issue:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/issue/may-jun-2006" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">May - Jun 2006</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue<section class="field field-name-field-sub-header field-type-text-long field-label-above view-mode-rss"><h2 class="field-label">Sub-header:&nbsp;</h2><div class="field-items"><div class="field-item even">A biologist began studying ancient Mexican pottery and ended up making genetic discoveries that could help feed the world.</div></div></section> Thu, 01 Jun 2006 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18501723 at https://alumni.duke.edu Transparent Motives https://alumni.duke.edu/magazine/articles/transparent-motives <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><p>Floating in the warm depths of the Gulf of Mexico, Sönke Johnsen is surrounded by "ghosts," swirls of ethereal entities whose glimmerings tell him he is not alone in the see-forever cerulean waters. He is enveloped in a clear-as-glass menagerie of creatures that make the open ocean their home. They survive because they have evolved to be nearly invisible.</p><p>Unlike his spectral companions, Johnsen is an all-too-obvious, tempting morsel of rubber-wrapped flesh. Suspended by safety tethers, he's like bait on a fishing line in the featureless sea. His sense of peril is heightened because he and similarly appetizing companions once fended off a marauding shark--only small plastic poking sticks between them and precisely two-zillion needle-sharp teeth.</p><p>Johnsen's vulnerability makes him appreciate all the more the survival value of the sea creatures' crystalline camouflage in a realm where there is nowhere to hide but in plain sight. The larval fish, worms, shrimp, jellyfish, and flea-like amphipods wafting past him exemplify evolution at its most ingenious. And unlike the exterior disguises worn by many land animals--a fawn's colored fur or a snake's patterned scales--the disguise these creatures embody is by definition much more than skin deep, extending even to internal organs. Some creatures have developed cunning ways of concealing the telltale signs of any undigested dinner: mirrored stomachs that hide the food by reflecting the infinite blue around them. Others have needle-shaped stomachs that swivel and can be made to point downward, minimizing shadows that would be a dead giveaway.</p><p>Like most organisms, they need light-absorbing pigments in their retinas in order to see. But to minimize the pigments' compromising effect on their camouflage, some have evolved eyes on stalks extended far from their bodies; others, compact retinas that are mere dots in the water, or even diffuse, pale retinas that show up only as faint smudges. To help carry the appearance of invisibility, even shadows must be minimized. Many of the creatures are flat and thin--some as thin as a few sheets of paper--so that light passes more easily through their transparent tissues, and any shadow they cast is only an indistinct line. Where complete physiological transparency is not available, organisms resort to tricks of the eye, evading predators by sporting bioluminescent "light bulbs" along their under surface, for example, that help minimize shadows.</p><table width="11%" border="0" cellspacing="11" cellpadding="1" align="right"><tbody><tr><td align="center"><div class="caption caption-center"><div class="caption-width-container" style="width: 300px;"><div class="caption-inner"><img src="/issues/111205/images/lg_swim1.jpg" alt="The collector: Johnsen gathers animals in Gulf of Mexico " width="300" height="225" border="1" /><p class="caption-text"><p>The collector: Johnsen gathers animals in Gulf of Mexico. <span class="photocredit">Marshall, University of Queensland</span></p></p></div></div></div></td></tr></tbody></table><p>But evolutionary ingenuity is not just the province of prey. Predators, too, have developed their own adaptations to thwart invisibility in this silent, subtle duel for survival. Some have eyes that can see polarized light, rendering prey more visible. Some carry biological flashlights--photophores--that may illuminate prey. And others have eyes on top of their heads, so they can constantly scan the waters above them, seeking subtle shadows that reveal the presence of a potential meal.</p><p>Observing this intricate evolutionary duel is another exotic species--the breed of rare, curious scientists called "visual ecologists," of which Sö;nke Johnsen, a Duke assistant professor of biology, is an exemplar. His aim, he says, is to understand the "arms race between the hiders and the seekers." His scientific perspective comprises an "outside" and an "inside": "The 'outside' is trying to understand the ecological function of optical camouflage and what animals have done to break this camouflage," says Johnsen.</p><p>The "inside" questions, he says, are those aimed at understanding the physiology of these exotic creatures. "What are they doing to their bodies to make these strange optical properties? How are they making their body clear? How are they managing to reflect light at only certain wavelengths? How are they managing to focus light so well, despite having ball-shaped lenses?" But Johnsen doesn't just study eyeballs and photophores in isolation; he tries to make sense out of how these creatures use their visual capabilities in the life-or-death thrust and parry of predator and prey.</p><p>The exotic elegance of these creatures is reason enough to study them. But there are other compelling motivations as well. Of all life on the Earth, sea life is perhaps the most ecologically significant. About half the oxygen in each breath we take originated from the photosynthetic activity of phytoplankton floating in the ocean. And these phytoplankton are part of the intricate--and fragile--ecology that includes the creatures studied by Johnsen and his cohorts. Then there's the importance of ocean ecology to our food supply. Phytoplankton are the base of an intricate marine food chain at whose apex are the fish we eat. We are blindly whacking away at this food chain--scouring vast regions with sprawling fishing nets, injecting massive pollution into the ocean, altering ocean temperatures via global warming, and increasing ultraviolet radiation reaching Earth by destroying protective ozone. To understand the ultimate effects of this vast ecological attack, we must understand in detail the biology of its victims, Johnsen says. And in so many cases, we know so little.</p><p>That's where what he refers to as the "embarrassment factor"--our ignorance of so much of the life that inhabits our planet--propels his studies of midocean creatures. "We know more about the surface of the moon than we know about the bottom of the ocean," says Johnsen. "And over 99.5 percent of the Earth's inhabitable space is the midwater of the ocean."</p><p>"It's been said that if a space alien came down with a net and scooped out an animal from a random spot on Earth, it would probably be one of these weird gelatinous animals. So, while to us they seem very unusual, and to us they have this sort of freaky unearthly appearance, we're the weird-looking ones when you get down to it."</p><p>As an example, Johnsen points to the Diel vertical migration. While the migration patterns of birds, butterflies, and other land creatures have long been the subject of research, they are inconsequential compared with the Diel migration, a gargantuan movement that occurs daily, around the globe, as ocean creatures move upward or downward with the changing daylight. Still, our ignorance about the reasons for this largest of all migrations is as deep as, well, the ocean, says Johnsen.</p><table width="100%" border="0" cellspacing="10" cellpadding="1" align="center"><tbody><tr><td align="center"><div class="caption caption-center"><div class="caption-width-container" style="width: 580px;"><div class="caption-inner"><img src="/issues/111205/images/lg_john097005002.jpg" alt="Johnsen with image of deep-sea octopus whose suckers have evolved into photophors, or light-emitting organs" width="580" height="326" border="0" /><p class="caption-text"><p>Johnsen with image of deep-sea octopus whose suckers have evolved into photophors, or light-emitting organs. <span class="photocredit">Les Todd </span></p></p></div></div></div></td></tr></tbody></table><p>"In some cases we do know it's the light," he says, "but we don't know exactly what it is about the light, except in a few cases. Is it that the animals always stay in the same level of brightness, so that as the sun goes down they move up? Or is it that they start moving up when the light changes very quickly, as it does at dawn and dusk? That seems to be true for some animals. Or is it something to do with a change in color of the light?</p><p>"In some cases, it may actually not be light at all. They could be following other organisms. It could be that the phytoplankton are moving up and down, and everybody else is just following up and down for lunch. And in other cases, it may actually be just to avoid sunburn, because ocean water is very clear compared to coastal water, and UV light can get down through the surface layers."</p><p>Even beginning to understand this massive movement means understanding the basic biology of the animals--a major challenge in the ocean, Johnsen points out. "Most of the migrations on land aren't as big a mystery, because people can see both ends of the migration. They know that birds do their breeding at one site, and they do feeding at another site. They can see it happen. For us, we don't even know the reproductive ecology of most of these animals. So, we don't know what's going on."</p><p>Observing the fragile, elusive creatures, much less making scientific measurements on them, has proven an enormous challenge, says Johnsen. "On land, you can have a graduate student sit near a beaver lodge or set up a camera and observe the animals without disturbing them. You can have somebody studying forest ecology go right up to the plants or animals and observe them without disturbing them too much. And you can learn a great deal about how the whole system fits together."</p><p>By contrast, humans in the oceans are bulls in an ecological china shop. "The old technique was trawl netting, but that was sort of like flying over London with a big grappling hook, yanking up some poor guy, and trying to understand the culture of the English people. Then we developed submersibles, but that's about the equivalent of showing up in a school bus with all the lights on and the horn honking, two feet from a bunny rabbit, and expecting it to behave normally."</p><p>Now, however, visual ecologists use what they call "stealth observation technologies" to study their delicate, light-sensitive quarry. One recent innovation is the "Eye in the Sea" camera developed by Johnsen's colleague Edith Widder at the Harbor Branch Oceanographic Institution in Florida. The camera uses a red light, which is invisible to ocean creatures. "We always say that we catch the slow, the dumb, and the small," says Johnsen. "We don't see the amazing crazy megafauna, because they are smart enough, fast enough, and big enough to get away."</p><table width="100%" border="0" cellspacing="11" cellpadding="1"><tbody><tr><td align="center" width="533"><div class="caption caption-center"><div class="caption-width-container" style="width: 580px;"><div class="caption-inner"><img src="/issues/111205/images/lg_crab.jpg" alt="Light and shadow: bioluminescent emissions of galatheid crab viewed on coral under white, blue, and red light" width="580" height="128" /><p class="caption-text"><p>Light and shadow: bioluminescent emissions of galatheid crab viewed on coral under white, blue, and red light. <span class="photocredit">Widder, HBOI</span></p></p></div></div></div></td></tr></tbody></table><p>But last fall, when Widder, Johnsen, and their colleagues deployed the Eye along with a bag of bait, to search for deep-ocean creatures in the Gulf of Mexico, they managed to capture images of the fast, the smart, and the large after all. "During the first successful deployment, we saw this two-meter-long squid that nobody has ever seen before come in and just nail this bait bag. It was this solid, muscular, monster-of-the-deep kind of animal."</p><p>Later, he continues, the scientists saw "this huge six-gill shark, somewhere in the seventeen-to-twenty-five foot range. And it just stayed there and tried to eat the tripod. So, there is some very impressive stuff down there."</p><p>Besides such dramatic fishing expeditions, the researchers also conduct more delicate experiments using new optical instrumentation to glean insights into animals and their behavior. In one set of experiments, Johnsen and his colleagues explored what colors gave creatures the best chance at invisibility. The problem was far from straightforward. He explains that in the ocean depths, there are two kinds of evasion taking place. "There's just hiding under the normal ambient light. But then, there's also hiding from all the animals that are swimming around with 'flashlights.' A lot of fish and arthropods have photophores directly under or over their eyes, so they're swimming around with headlights."</p><p>In their study, the researchers first mathematically predicted the colors of animals hiding from ambient light versus those that might be evading predators' bioluminescent searchlights. After collecting a multitude of animals and measuring their colors at all wavelengths, the researchers discovered that evolution had dictated the best strategy. Basically, the researchers found that the animals were "darkest"--reflecting the least light--at precisely the wavelength of the predators' flashlights.</p><p>In an evolutionary response, other denizens, such as the aptly named dragonfish, use bioluminescent "light bulbs" along its bottom surface as "counter illumination" to offset its shadow, as seen by predators lurking below. The problem, says Johnsen, is that "most of these light bulbs are widely spaced, which means they're not going to blend in perfectly when a predator looks up at them."</p><p>While Johnsen says he first thought that water turbidity might blend the light from the bulbs, in the depths where the creatures live, the water was quite clear because of the lack of suspended particles. After some careful calculations of the optics of water and of the images of dragonfish under various conditions, the researchers realized that it was the predators' fuzzy vision that saved the prey. "Some of these predatory animals have sharp vision, but only in a very narrow field of view right over their heads. But they're nearsighted in other directions." Unless the dragonfish happens to blunder directly overhead, Johnsen says, its rows of light bulbs blend nicely.</p><table width="322" border="0" cellspacing="11" cellpadding="1" align="right"><tbody><tr><td align="center" width="533"><div class="caption caption-center"><div class="caption-width-container" style="width: 300px;"><div class="caption-inner"><img src="/issues/111205/images/lg_tomopterisfinal.jpg" alt="Ghosts of the deep: swimming worm" width="300" height="450" /><p class="caption-text"><p>Ghosts of the deep: swimming worm. Widder, HBOI</p></p></div></div></div></td></tr></tbody></table><p>Studies by Johnsen and other visual ecologists have shed only the faintest light on the puzzle of bioluminescence. "Ninety percent of the species down there are bioluminescent," he says. "We really don't know why. We have some ideas, and a few hypotheses seem well borne out, like the idea of counter illumination. But then there are these other, barely tested possibilities--that prey use light to startle a predator or even to bring in a bigger predator, called the 'burglar alarm' theory. It's energetically expensive to make light. It's obviously there for a good reason and probably serves a multitude of purposes."</p><p>Also puzzling, he says, is how predators use polarization--the plane of vibration of light--to detect prey. We humans, for example, use polarized sunglasses to eliminate glare, as off the surface of water. Since such glare consists mainly of light that is polarized horizontally, sunglasses with vertical polarized filters selectively block glare. "We're looking at polarization vision as a way to see better in the ocean," says Johnsen. "Many animals appear to have it, but we have no idea why. We're thinking it might be a way to break camouflage."</p><p>In such research, he says, "we resort to 'forensic biology,' where we figure out the best hypothesis by piecing together what we can measure from animals we collect and from measurements in the environment." For example, Johnsen uses technology to put himself into the place of his quarry. "We go down with filters and special polarization cameras to mimic the way it actually looks to these animals, which gives you a better idea of who's well-hidden and who's not; which patterns on a fish are important, and which don't matter at all."</p><p>Even as Johnsen takes knowledge from the sea, he also gives that knowledge back, in the form of insights that could protect ocean animals. One of his projects is protecting endangered sea turtles, which are often inadvertently hooked by fishermen after swordfish and marlin. "What they want is something that will be visible to the fish, but invisible to the turtles," he says. "And so, one of our projects is designing lures based on the visual differences between these animals--trying to make something visible to one and invisible to another." Alternatively, he says, they could "design a deterrent that's visible to the turtles, but invisible to the fish. And so, we're making these giant sharks of clear Plexiglas sheets that are opaque in UV light. Turtles can see UV. Sharks can't."</p><table width="322" border="0" cellspacing="11" cellpadding="1" align="right"><tbody><tr><td align="center" width="533"><div class="caption caption-center"><div class="caption-width-container" style="width: 300px;"><div class="caption-inner"><img src="/issues/111205/images/lg_viper180.jpg" alt="viper fish" width="300" height="217" /><p class="caption-text"><p>Viper fish. <span class="photocredit">Widder, HBOI</span></p></p></div></div></div></td></tr></tbody></table><p>Working with Duke medical researchers, Johnsen is also using techniques he's learned to study cataracts in humans. "It's not completely known how the different kinds of cataracts work, what's causing the opacity," he says. "There are many changes in an older person's lens, but people argue over which changes really matter. Is it the granulation of the cytoplasm, or is it these funny little spherical balls that show up?</p><p>To find that out, you need to figure out what their optical effects are." New studies by Johnsen and medical collaborators are revealing that abnormal substances once believed to be the central causes of vision-impairing cataracts are, in fact, not the most important.</p><p>Even as Johnsen delights in the insights he's gaining through his study of creatures that inhabit the open ocean, he is aware that his life's work may well be a coda to their existence. The very creatures he studies are at the mercy of human folly, which persists in altering the nature of light that penetrates the ocean depths and blighting the purity of its waters.</p><p>"Probably the worst thing about being a biologist is watching everything die," he says. "You're basically watching humans wipe it all out, bit by bit. You know there's almost nothing you can do about it. A lot of what I do is for practical reasons, but, a lot of it is just to get people to care. We put out as many beautiful pictures, as many interesting stories, to get people to care enough to maybe slow it down some. But, it almost seems inevitable. We're growing more and more people, and everything else is dying."</p><p>Ironically, his sadness is made all the more acute by his experiences in places like the deep-ocean reef that is one of the study sites--the exhilaration over what is found there contrasting with the near certainty that it may all soon disappear, he says.</p><p>A thousand feet down, "it's this underwater Eden. There are these huge fish going back and forth--all these different kinds of strange snails and corals and weird little critters. It's neat to see everybody's faces coming up from a dive. They all come up with this big beatific smile. You know, like, Wow!"</p></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2005-11-30T00:00:00-05:00">Wednesday, November 30, 2005</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/dm-main-images/lg_cystisoma117b.jpg" width="620" height="293" alt="Cystisoma: its large, pale retina minimizes its shadow when viewed from below. Widder, HBOI" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section><section class="field field-name-field-issue field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Issue:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/issue/nov-dec-2005" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Nov - Dec 2005</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue<section class="field field-name-field-sub-header field-type-text-long field-label-above view-mode-rss"><h2 class="field-label">Sub-header:&nbsp;</h2><div class="field-items"><div class="field-item even">&#039;Visual ecologist&#039; Sönke Johnsen pursues elusive, fragile undersea phantoms for their biological secrets.</div></div></section> Wed, 30 Nov 2005 10:00:00 +0000 Joseph Sorensen, JOSEPH E. 18500328 at https://alumni.duke.edu The IGSP: 'Asking Big' https://alumni.duke.edu/magazine/articles/igsp-asking-big <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><p class="articletitle">When Huntington Willard, director of the Institute for Genome Sciences & Policy (IGSP), prepared to move into his office at his new headquarters, he requested that a doorway be built directly between his office and his laboratory, in addition to the existing doorway leading to the rest of the IGSP.</p><p>His research staff knows that when the lab door is open, they have free access to Willard the scientist. And his IGSP staff knows that when the hall door is open, they have free access to Willard the IGSP director.</p><p>In a similar manner, Willard, who became director in 2003, has launched himself into the intellectual doorway business--both creating and opening them. That's vital, he says, because Duke conceived the IGSP as drawing on faculty members across the university, from widely disparate fields: scientists, engineers, physicians, lawyers, policymakers, business economists, ethicists, theologians, and humanists. His conceptual carpentry has sought not only to construct doorways between all of these disciplines, but also to include them under one "metaphorical roof," as he puts it. The IGSP should take an integrated approach to helping society cope with the profound, pervasive impact of the genome revolution, he says.</p><p>Still, the institute's motto, "Ask Big," reflects an ecumenical philosophy that isn't widely appreciated at other universities. "They don't understand putting science and policy together. Very few places are doing that, and no place is doing it as seriously and with the breadth and depth that we are. Frankly, the concept of the genome revolution impacting not just science, but literally everything else that goes on in life, does not yet resonate with other institutions. They can't believe that we teach classes on genomics in the English department or in the Divinity School."</p><p>When speaking of the IGSP's research aspirations, Willard emphasizes that Ask Big does not mean Ask Everything. "We're not going to solve every problem that's out there either on the ethical and policy front or on the discovery front," he says. "But, I think we can pick key questions where Duke has the right set of tools, the right people, the right ethos to figure out approaches that other groups can't."</p><p>A prime example of his strategy is IGSP's new Center for Genomic Medicine. The center will create health-care systems that apply genomic discoveries to clinical practice. "Changes in health care frighten people," says Willard, "and very few institutions are well positioned to grapple with what could be bewildering wholesale changes in medicine--going from the reactionary system that we have now to one that is prospective and highly personalized. But that is the mark Duke is going to make. And the impact of creating an effective genomic medicine system here will go far beyond making one key discovery or even a handful of key discoveries. The center really will provide an example that can be shared nationally and internationally."</p><p>Willard envisions an IGSP where scientific discoveries will help usher in an era of genomic medicine in which analysis of a drop of a baby's blood can reveal whether she will be vulnerable, as she ages, to heart attack, stroke, or cancer. But Willard believes that IGSP's ethicists, policymakers, and legal scholars will venture far beyond clinical advances to solve the broad social problems that will enable this powerful knowledge to create a healthier life for that child.</p></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2005-08-01T00:00:00-04:00">Monday, August 1, 2005</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/default_images/dukmag-horizontal-placeholder.jpg" width="238" height="140" alt="" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue Mon, 01 Aug 2005 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18500605 at https://alumni.duke.edu Your Friend, the Chromosome https://alumni.duke.edu/magazine/articles/your-friend-chromosome <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><table width="324" border="0" cellspacing="11" cellpadding="1" align="right"><tbody><tr><td><div class="caption caption-center"><div class="caption-width-container" style="width: 300px;"><div class="caption-inner"><img src="/issues/070805/images/lg_bc319600111B.jpg" alt="Sausage-shaped: chromosomes, left and opposite, the focus of Willard's esoteric research, are made up of tightly coiled strands of DNA " width="300" height="336" border="1" /><p class="caption-text"><p><span style="text-align: -webkit-center;">Sausage-shaped: chromosomes, left and opposite, the focus of Willard's esoteric research, are made up of tightly coiled strands of DNA</span><br style="text-align: -webkit-center;" /><span class="photocredit" style="text-align: -webkit-center;">Adrian T. Sumner</span></p></p></div></div></div></td></tr></tbody></table><p class="articletitle">Without chromosomes, your cells would be an untidy, malfunctioning mess. In fact, without chromosomes, you would never have evolved to the pinnacle of supreme intellect that enables you to read and appreciate this fine article.</p><p>Each cell in your body contains roughly six feet of string-like DNA, the repository of your genetic information. Strung like beads along the length of your DNA's molecular chains are some 20,000 encoded segments--genes--that form the blueprints for proteins. Through a process called "gene expression," a gene copies its genetic information in the form of a "messenger RNA" molecule. The messenger RNA then wends its way to the cell's protein-making machinery. There it acts as the blueprint for the proteins that catalyze life-giving chemical reactions.</p><p>Rather than crumpling this critical genomic blueprint haphazardly into the cell's nucleus, nature has evolved a neat method of winding that DNA into precise spools around special proteins and packing them ever so neatly into the sausage-shaped chromosomes that you see under the microscope. This packing job, which would thrill Martha Stewart, reduces the length of your six feet of DNA by some 10,000-fold.</p><p>You have twenty-three pairs of such well-ordered chromosomes--one set each from Mom and Dad. And besides the garden-variety chromosomes, you have two sex chromosomes--a pair of X chromosomes if you are a female, and an X and a Y if you are male.</p><p>Each pair of chromosomes connects at a midpoint called the centromere--another example of nature's orderly housekeeping. As each chromosome duplicates itself during cell division, the centromere provides a critical attachment point. Each cell sends out spindle fibers that grab the duplicated chromosomes at the centromere and separate them into the two new "daughter" cells.</p><p>In the earliest days of genetics, scientists faithfully, and, it turned out, naively, believed the "central dogma" that each gene provides the blueprint for one protein. The only "genetic code" they thought existed was the one that specified how a given sequence of DNA units provided the code for the structure of a given protein.</p><p>However, in the last decade, scientists have come to the unsettling realization that the cell is a far more intricate cryptographer than they had ever dreamed. Besides the protein-making code, the cell also uses other as yet unknown codes to read mysterious "epigenetic"--that is, outside the genetic code--signals from the vast regions of what had seemed like "junk" DNA that scientists had discovered among genes. In fact, it's quite likely that within this "junk" lies the very epigenetic information that enabled us to evolve into humans.</p><pre style="font-family: Arial, Helvetica, sans-serif; font-size: 12px;"> </pre></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2005-08-01T00:00:00-04:00">Monday, August 1, 2005</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/default_images/dukmag-horizontal-placeholder.jpg" width="238" height="140" alt="" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue Mon, 01 Aug 2005 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18500603 at https://alumni.duke.edu Unraveling the Human Genome https://alumni.duke.edu/magazine/articles/unraveling-human-genome <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><p>Huntington Willard, it could be said, is a true X-man. In algebra, X denotes the archetypal unknown quantity. The aptly nicknamed "Hunt" Willard confesses to an inordinate fondness for the unknown. He revels in tackling profound genomic mysteries that confound other researchers and could lead to astonishing new scientific insights--or simply to more mysteries.</p><p>The X-Men of comic-book and movie fame find that their superpowers set them at odds with society. Willard has found himself at times disparaged by colleagues for sticking to research paths they believed led only to career-killing dead ends. And, like the X-Men, Willard has assumed dual identities. He is both an active scientist and the activist director of Duke's Institute for Genome Sciences & Policy (IGSP)--the campuswide, multidisciplinary program created to enable Duke to address the broad implications of twenty-first-century genetic advances.</p><p>Perhaps most important, X denotes Willard's research on the X chromosome--the sex-determining chromosome that occurs in twos in women, but is paired with a Y sex chromosome in men. After years of studying the way that some genes on the X chromosomes of women are active while others lie dormant, Willard and his colleagues recently reported startling findings. Comparing gene activity on the X chromosomes of forty women, the scientists found unexpected amounts of variation among individuals.</p><p>The results have important implications for understanding the differences between men and women in areas such as health and disease. They also offer potential explanations for well-established differences between the sexes. "In essence," Willard says, "there is not one human genome but two--male and female."</p><p><br />In the early days of genetic research, nearly fifty years ago, scientists discovered that female embryos go through a critical process called "dosage compensation," switching off duplicate genes on one or the other of its X chromosomes to avoid being, in effect, "overdosed" on those genes. When genes are switched on, they cause proteins, which constitute the cell's basic molecular machinery, to be produced in the cell. If, for example, a gene on one X chromosome was making protein for a specific metabolic process and another gene on the other X chromosome was doing the same thing, the cells would suffer, and likely die, from the resulting excess.The genome is an organism's complete set of genetic material, including all of its chromosomes. Chromosomes are the microscopic, sausage-shaped packages encasing the DNA molecules that are the genetic blueprints for all of our cellular machinery. Compared with the X chromosome's 1,000 or so genes, the Y chromosome is a genetic runt, with only about 100. These largely determine male traits.</p><p>The early researchers believed that dosage compensation completely inactivated or "silenced" one or the other X chromosome. That way, all women--and women and men--would have the same dosage levels of encoded genes on their X chromosomes. However, during the 1980s, Willard and his colleagues discovered that some genes on the silenced X chromosomes of women actually remained active. (Male chromosomes are X-chromosomal couch potatoes. They don't practice such dosage compensation. Because they have only one X chromosome, they need all their X-chromosome genes active.)</p><p>Despite Willard's early findings that some X genes escape silencing, many scientists still believed that all women had the same patterns of active and silenced genes on their X chromosomes. His most recent research study--co-authored by a former trainee in Willard's lab, Laura Carrel, now an assistant professor of biochemistry and molecular biology at Pennsylvania State University--was published in the March 17 issue of Nature. It compared gene activity on the X chromosomes of forty women. The scientists found surprising variations among the women in the patterns of their genes that were switched on.</p><p>The discovery is significant, according to Willard, because "the findings suggest a remarkable and previously unsuspected degree of expression heterogeneity among females in the population," he says. Among other things, this means that women are genetic "mosaics," with any of their cells potentially switching on genes on either of the pair of X-linked genes.</p><p>This wide variation among women in X-chromosome gene expression not only points to differences in traits among females, but also between females and males,</p><p>Willard says. And an understanding of the genomic differences between the sexes could lead to explanations for the differences in such areas as susceptibility to certain diseases.</p><table border="0" cellspacing="10" cellpadding="1" align="center"><tbody><tr><td align="center"><div class="caption caption-center"><div class="caption-width-container" style="width: 580px;"><div class="caption-inner"><img src="/issues/070805/images/lg_01A8574.jpg" alt="Chromosomes" width="580" height="271" border="0" /><p class="caption-text"><p>Chromosomes.<span class="photocredit"> © Howard Sochurek / CORBIS</span></p></p></div></div></div></td></tr></tbody></table><p class="articletitle">"We've always known that the X chromosome was important for disease, and that there are a great many X-chromosome-linked diseases in males," he says. Such rare genetic diseases more likely strike men, because a disease-causing mutation on the lone male X chromosome cannot be compensated for by a protective normal gene on the paired X chromosomes of women. "What fascinates me about these new studies is that they may give us an insight into far more common disorders that show characteristic differences in the frequency between males and females.</p><p>"Autism, for example, is about four times more common in males than in females. Why? Rheumatoid arthritis and many other autoimmune disorders are much more common in females than in males. Why? Our results at least raise the possibility that these genes are failing to be fully dosage-compensated, creating a characteristic dosage difference between males and females. And those genes could likely play a role in increasing or lowering the susceptibility of one sex compared with the other to some of these conditions.</p><p>"But we also have no idea whether the variation is the same in a fetus in utero or in a newborn, or in a ninety-year-old woman," says Willard. "And it may be that gene expression is changing during that time, and that change may associate with late-onset diseases such as heart disease."</p><p>The new findings are only the latest emerging from decades of Willard's research on the phenomenon of dosage compensation. His scientific quest began as a Eureka! moment he had as a Harvard undergraduate. "I was sitting in a library flipping through a journal waiting for a professor who was late. And I came across this paper on X inactivation, and it just struck my fancy. The basic lesson from this paper was, 'we haven't a clue what's going on here.' To me, that was the greatest way to enter a scientific problem, because your imagination can run wild. People were just shrugging their shoulders and saying, 'It makes intuitive sense why males and females would need to equalize dosage of genes.' It was as if a 'miracle' occurs, and it just happens."</p><p>Willard recalls that he became instantly fascinated by the scientific mystery of this unknown biological mechanism, which is central to the development of every female. "I must have written every one of my papers as a biology undergraduate on this topic. And I kept reading and writing and exploring different models in my mind." The uncharted machinery of dosage compensation resonated with his (perhaps genetic?) predilection for black-box problems. "I've always been bored by projects where the answer was too obvious--where the answer was going to be one or another known possibilities," he says. "I found it much more interesting to dream about possibilities that just hadn't been described yet."</p><p>The fascination endured. When Willard started his own research laboratory after receiving a Ph.D. in human genetics from Yale University in 1979, his first goal was to figure out the machinery the cell uses to shut down X-linked genes during embryonic development. Fifteen years of painstaking work led to the identification of a master genetic switch that turns off such X chromosome genes. But this switch was a peculiar gene, indeed. The huge majority of known genes are blueprints for "messenger RNA" that produces proteins; however, this gene, dubbed XIST, instead produces a type of RNA that controls other genes. These genes that control other genes represent the next great frontier in genomic research, Willard says. Traditionally, geneticists have focused on how genes code for proteins; now they are beginning to explore the "epigenetic" machinery by which genes themselves are controlled.</p><p>As he delved into the machinery of X inactivation, he encountered other surprises. The X chromosome control system did not function as a single on-off switch, like the master circuit breaker in a house. Rather, Willard was to discover, it acted more like the multitude of individual electrical switches within that house, with different switches for different genes. He recalls the first inkling he had that X inactivation wasn't an all-or-nothing proposition. "I was teaching an undergraduate class at the University of Toronto back in the late 1980s, and I assigned students what I thought was a simple little project--to look at gene expression on the X chromosome. And the students came up with an answer that made absolutely no sense at that time. They found a gene still being expressed, even though it was on the inactive copy of the chromosome instead of the active copy. And even though I was tempted to simply say, 'You're wrong. It can't happen,' and put a big X across the lab report, we started looking into that question."</p><p>At that point, Willard's black box transformed into a treasure chest. He and his colleagues discovered a dozen examples of genes that escaped silencing. In recent years, as the Human Genome Project has yielded the complete structure of the X chromosome, the researchers have used that knowledge to find hundreds more.</p><p>They are now exploring not only how the cell decides which genes should escape silencing, but also, why. And they are seeking the origins of the startling variations they discovered among women in the genes that escape silencing. "Maybe the patterns are random, but it's much more intriguing to me to consider that the pattern of this gene activation is inherited," Willard says. "If so, when we compare the X chromosomes of mothers and daughters, or of sisters, or of identical twins, we should see a familial pattern. If it is a pattern in the genome, then we're off on another hunting expedition. Somewhere amidst the vast stretches of DNA on the X chromosome there is some sequence of DNA that tells those genes to be expressed or not expressed. It's another genetic code that we don't understand and can't even begin to articulate."</p><p>If the machinery of X inactivation is a fascinating set of nested black boxes, Willard's other major research object, the centromere, has proven a murky Stygian nightmare. The centromere--the point at which paired chromosomes are attached to enable them to navigate through cell divisions--had been largely shunned by scientists, because it was thought to be a genomic wasteland. It seemed to be nothing more than genetic "stuttering"--regions of inanely repetitive DNA code that had no purpose other than to take up space and frustrate biologists.</p><p>In fact, the so-called "complete" sequencing of the human genome, announced with great fanfare in 2000, did not include any sequences of the seemingly unfathomable centromeric regions. Willard recalls that, in the 1980s, "there was this series of wonderful papers arguing over whether all this repetitive DNA should be called 'junk,' 'garbage,' or other pejorative terms. But I just sort of took it on faith that nature wouldn't do that. This is 5 percent of the entire genome--a stunning amount to be unimportant and just sitting in a garbage heap at the center of the chromosome."</p><table border="0" cellspacing="10" cellpadding="1" align="center"><tbody><tr><td><div class="caption caption-center"><div class="caption-width-container" style="width: 580px;"><div class="caption-inner"><img src="/issues/070805/images/lg_chromocompare.jpg" alt="Blue=human chromosome, Green/yellow=centromeres, Red=human artificial chromosome" width="580" height="243" border="0" /><p class="caption-text"><p><span style="text-align: -webkit-center;">Blue=human chromosome, Green/yellow=centromeres, Red=human artificial chromosome. </span><span class="photocredit" style="text-align: -webkit-center;">Katie Rudd / Duke University</span></p></p></div></div></div></td></tr></tbody></table><p>It was Willard's search to understand the X chromosome that led him to the centromere. He and his colleagues were searching the centromeric region of the X chromosome for DNA sequences that might somehow control X inactivation. He hypothesized that the repetitive elements specific to the X chromosome might act as tags that would key the silencing mechanism. "We did find repetitive sequences specific to the X chromosome centromere," he recalls, "but they had nothing to do with X inactivation whatsoever. So, the experiment didn't work the way we thought it would, but rather than throw it away, it caught my fascination." Willard devoted his efforts to searching for evidence that the repetitive DNA found in the centromeric region was functional rather than just a pile of garbage.</p><p>This may mark the point that Willard assumed an X-man persona. "I think that was probably the low point of my reputation in the scientific community," he says, "because people really thought I was crazy. They asked, 'Why are you working on this? It's total junk. You're wasting your time. There can't be a code in there, because it's the same little sequence over and over again. So, by definition, it can't be telling us anything.' I don't know whether I like a challenge or whether I'm pig-headed, but we kept at it."</p><p>So, the "pig-headed" Willard and his colleagues invented analytical genetic techniques that enabled them to decipher DNA sequences in the hall-of-mirrors realm of the centromere. One thought was that maybe this repetitive DNA, called alpha satellite DNA, "was just a camouflage that was hiding some other magic sequence that would be buried in there, and we'd have to develop tools that would allow us to get to that magic sequence."</p><p>Willard's search for a "magic sequence" was still causing head shaking among colleagues, he says, when his laboratory dropped a scientific bombshell: It announced the creation of a functioning artificial human chromosome. Willard reasoned that if the stuttering DNA was central to the centromere's function in dividing cells, then an artificial chromosome with an artificial centromere containing only "junk" DNA should waltz right along with its natural brethren during the dance of cell division. Sure enough, when Willard and his fellow centromerists synthesized the chromosome and added it to a human cell, they found it worked beautifully. The human cells harboring the artificial chromosomes divided happily ever after, reproducing the artificial chromosomes along with the natural ones.</p><p>"Our cells have forty-six chromosomes, and we stuck in a tiny forty-seventh chromosome, and it worked just the way our natural ones do. That was the key breakthrough in that field," he says. "It showed for the first time, definitively, that these alpha satellite sequences confer centromere function."</p><p>Willard insists that nature must have evolved these stuttering sequences to mean something important to the cell, since successful cell division is so critical to all life. Still, the nature of that "something" remains unknown. "I'm the first to admit that the fact that our artificial chromosomes work doesn't tell us the code the centromere uses," says Willard. "That just tells us where the code is."</p><p>The scientific community reacted to his attempts to build an artificial human chromosome with "a lot of eye-rolling," Willard says. "It was sort of, 'Here he goes again, not giving up on this idea.'" However, he recalls, when he presented his results formally at a 1997 conference in Madrid, "it put to rest the notion of a magic sequence buried in the DNA and established that it was the alpha satellite DNA itself that was being read by the cell." Willard and his colleagues are now tinkering and testing versions of the artificial chromosome, to search for the key characteristics that make the centromere work. The search will be an arduous one, given that the centromeric region comprises some 3-million DNA units on each chromosome.</p><p>As a veteran of the scientific centromere wars, Willard deeply appreciates the fact that the science of genomics is full of unknowns--X's--yet to be determined. He has no fear of confronting the unknown. "We now understand only 2 percent of the genome in terms of how it encodes information," he says. "That leaves 98 percent to go."</p></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2005-08-01T00:00:00-04:00">Monday, August 1, 2005</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/dm-main-images/lg_will05450529.jpg" width="620" height="815" alt="Huntington WIllard. Chris Hildreth." /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section><section class="field field-name-field-issue field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Issue:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/issue/jul-aug-2005" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Jul - Aug 2005</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue<section class="field field-name-field-sub-header field-type-text-long field-label-above view-mode-rss"><h2 class="field-label">Sub-header:&nbsp;</h2><div class="field-items"><div class="field-item even">Huntington Willard</div></div></section> Mon, 01 Aug 2005 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18500599 at https://alumni.duke.edu First "Sad Gene" https://alumni.duke.edu/magazine/articles/first-sad-gene <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><p class="articletitle">A central mystery of mental disorders such as depression is how infinitesimal typos in the genetic blueprint for the brain can cause a predisposition to such disease. Researchers have long known that depression tends to run in families, but they have yet to pinpoint a single genetic flaw that could help explain why--until now.</p><p>In the December 2004 issue of Neuron, Marc Caron, James B. Duke Professor of cell biology, and his colleagues reported that, compared with normal people, those with major depression were more likely to show a specific variation in a gene that is the blueprint for a bit of cell machinery called an enzyme. The variation produces a flaw in the enzyme, which is a key link in the cellular production line for the brain chemical serotonin.</p><p>Serotonin is an important neurotransmitter. It is the chemical ammunition that one nerve cell fires at another to trigger a nerve impulse in the target cell. Propagation of those nerve impulses among networks of brain cells lays down the signaling pathways throughout the brain that are responsible for memory and other brain functions.</p><p>Some of the depressive patients who had the flawed gene also had a family history of mental illness, drug or alcohol abuse, suicidal behavior, or generalized anxiety symptoms, the researchers found. All of the patients with the mutant gene were unresponsive to treatment with "selective serotonin reuptake inhibitors"--a class of antidepressive drugs that includes Paxil, Zoloft, and Prozac.</p><p>The discovery of the genetic flaw is only the beginning of a massive hunt for other such crippled genes, as well as explorations of how they predispose people to depression and other mental disorders. While such studies may take many years to yield improved treatments, say Caron and his colleagues, a more immediate payoff might be a diagnostic test for an individual's tendency to depression.</p></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2005-06-01T00:00:00-04:00">Wednesday, June 1, 2005</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/default_images/dukmag-horizontal-placeholder.jpg" width="238" height="140" alt="" /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue Wed, 01 Jun 2005 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18500463 at https://alumni.duke.edu Deep in the Heart of Memory https://alumni.duke.edu/magazine/articles/deep-heart-memory <div class="field field-name-body field-type-text-with-summary field-label-hidden view-mode-rss"><div class="field-items"><div class="field-item even" property="content:encoded"> <table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><p class="articletitle">Take a journey back into the most vivid memories of your life. For me, there's the terrifying childhood attack by a deranged rooster; the gut-roiling public embarrassment of a forgotten speech; and, ah yes, the sweet, transporting taste of my first kiss. Such memories don't just benignly percolate up in our minds, like the mundane recall that we need to buy bread at the market. Rather, they envelop our consciousness in a nerve-tingling fog of sensory remembrance.</p><p>It's no surprise, then, that memories packing an emotional punch are not imprinted on the brain using routine memory circuits. Rather, our terrifying traumas and our delicious delights spark activity in a small but potent almond-shaped structure called the amygdala, buried deep in our neural gelatin. This little neural nugget abets our very survival--charging memories with an emotional force that compels us to avoid lunatic fowl, practice our speeches, and look for love in all the right places.</p><p>But this little clump of brain tissue also can smother our lives in the torment of post-traumatic stress disorder (PTSD), the corrosive dread of phobias, or the black dog of depression. The medical impact of traumatic disorders is immense. One in six soldiers in Iraq reports that his or her experience has produced major depression, anxiety, or PTSD, according to a study by the U.S. Army. Some mental-health experts estimate that at least 100,000 veterans of that war will need mental-health treatment. Here at home, our efforts to escape the anxiety provoked by the stresses of daily life have been prodigious, as evidenced by the 142-million prescriptions written in this country in 2003 for Prozac, Paxil, Zoloft, and other antidepressants.</p><p><br />Routine memories are stored in the brain with the aid of the wishbone-shaped hippocampus, which filters the stream of sensory data flooding into our brains and helps imprint that data as lingering memories. But a jolt of danger--and the accompanying blast of adrenalin into our bloodstream--activates both of the amygdalae attached to the tips of the hippocampus. These structures somehow stamp the indelible imprint of emotion on the resulting memories. The scientific mystery being tackled by LaBar and Cabeza is how the amygdalae blaze such permanent and vivid memory pathways in the brain's circuitry.The profound importance of emotional memory has impelled Duke neuroscientists Kevin LaBar and Roberto Cabeza to make it their scientific mission to understand the complexities of its neural machinery. In a wide variety of experiments, they expose volunteer subjects to stimuli designed to provoke an emotional response--tear-jerking scenes from movies, for example, or mild shocks to the wrist. Then, using magnetic resonance imaging (MRI), they examine how and, more important, where the brain responds when the subjects are asked to recall what happened. Their efforts will not only contribute to better treatments for anxiety disorders, but also could yield a deeper understanding of how emotional memories influence, and sometimes rule, our lives.</p><p>Getting into people's heads, particularly into the brain's depths where the amygdalae nestle, has been among the biggest challenges for researchers like LaBar and Cabeza, both of whom are on the faculties of Duke's Center for Cognitive Neuroscience and the department of psychological and brain sciences.</p><p>Neuroscientists first explored emotional memory by studying patients with specific damage to the amygdalae or surrounding structures from accident or disease. "But studies of such patients are very difficult, given that the locations of the lesions are not always clear; and finding patients with lesions in particular brain areas is a matter of chance," says Cabeza. Even if neuroscientists did find the right patients, he says, "the brain undergoes adaptive changes to such lesions. So it's difficult to know whether any changes we measure are due to the lesion itself or adaptation of the brain to the lesion."</p><p>Finally, he says, brain lesions might not directly affect a structure such as the amygdala that is critical to a particular function. Instead, they might only block a neural pathway serving that structure--just as blocking a highway might not directly affect the operation of a roadside hamburger stand, but only block the pathway by which hungry customers can reach it. So, scientists studying the effects of such a lesion--or diners looking for a hamburger--could be misled by a lack of activity in the structure to think it's closed for business.</p><p>The real revolution in exploring brain function came with the development of functional magnetic resonance imaging (fMRI), which allows researchers to direct harmless magnetic fields and radio waves into the brain to produce detailed scans of brain activity while the subject is performing a specified mental task. These scans can reveal differences in magnetic properties between oxygenated blood and deoxygenated blood. Because regions of the brain that are in heavy use during mental tasks trigger influxes of oxygenated blood into the region, they can be readily distinguished on fMRI scans.</p><p>Thus, researchers can get an invaluable, albeit indirect, measure of brain activity in specific regions such as the amygdalae. "Some people compare the impact of brain imaging on cognitive neuroscience to the impact of the telescope on astronomy," says Cabeza. "In both cases, a new instrument has allowed scientists to see things they couldn't see before."</p><table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><table border="0" cellspacing="10" cellpadding="1" align="right"><tbody><tr><td align="center"><div class="caption caption-center"><div class="caption-width-container" style="width: 360px;"><div class="caption-inner"><img src="/issues/050605/images/lg_ab710.jpg" alt="An MRI" width="360" height="344" border="1" /><p class="caption-text"><p>An MRI</p></p></div></div></div></td></tr></tbody></table><p>Seeing things they couldn't see before has led Cabeza and LaBar to ingenious new ways of exploring and monitoring brain activity. Their latest experiments, reported in the June 2004 issue of the journal Neuron, revealed for the first time that the brain's emotional centers affect or "modulate" the function of the memory centers as memories of emotion-laden events are being formed.</p><p>In the experiments, they slid volunteers into MRI machines and scanned their brains while showing them pictures that evoked both positive (romantic scenes, sports victories) and negative (aggressive acts, injured people) emotions. They also showed neutral pictures of buildings or scenes of routine shopping. After the scanning sessions, the researchers measured the emotional impact of the images by testing how well the participants remembered them. In their subsequent analysis of the brain scans, Cabeza and LaBar found that the emotional and memory regions interacted more during the formation of emotional than of neutral memories. The findings provide firm evidence that the amygdala modulates the function of the hippocampus and other memory regions, Cabeza said in the report. "Other studies have focused on the general enhancing effects of emotion on memory," he wrote. "But this study provides the first direct evidence for the modulation hypothesis in humans."</p><p>In an earlier discovery, published in the Proceedings of the National Academy of Sciences in 2002, LaBar and other colleagues used fMRI studies to show that fear-producing stimuli travel along separate brain pathways from tasks, such as driving, that require concentration. The two streams join in the prefrontal cortex--the higher processing area of the brain--and at that point can interfere with each other. "These findings are important because diseases that involve distractability, from Alzheimer's to attention-deficit disorder, always seem to involve the prefrontal cortex," says Gregory McCarthy, director of the Duke-UNC Brain Imaging and Analysis Center (BIAC). "Understanding the biology of this will speed efforts to develop drugs or therapies that may influence these systems."</p><p>In ongoing experiments, the researchers are studying the effects of "fear-conditioning." In one study, LaBar and his colleagues teach subjects to associate the image of a particular type of square with a mild shock to the wrist. Then the scientists add some type of social stress, such as asking the subjects to deliver a public speech. The following day, they bring the subjects back into the laboratory and test their physiological response to the square--increased perspiration caused by stress--to determine how well they have retained the fear response. "In psychiatry, it's known that stress can impair learning and memory," says LaBar. "This experimental approach gives us a way to study the role that the amygdala plays in mediating stress responses and how stress can aid or impair learning and memory."</p><p>Phobias constitute a far more general fear of specific situations, and LaBar has invented a way to mimic in the laboratory the development of these fears, which are what researchers call "context-dependent." In this case, the researchers use a specific setting to create the context. They place subjects in a small room where they teach them to associate the image of a square of a certain size and color with a mild shock. Keeping the subjects in that same room, the researchers proceed to "extinguish" the association by showing the square without administering the shock.</p><table border="0" cellspacing="10" cellpadding="1" align="right"><tbody><tr><td align="center"><div class="caption caption-center"><div class="caption-width-container" style="width: 360px;"><div class="caption-inner"><img src="/issues/050605/images/lg_amyg3.jpg" alt="An MRI" width="360" height="322" border="0" /><p class="caption-text"><p>© BrainConnections.com</p></p></div></div></div></td></tr></tbody></table><p>The researchers then remove the subjects from the "shock" room and, after a short period, either return them to it or place them in an entirely different room. They then test how quickly the subjects recover the unpleasant association of the square with the shock--a measure of their created "phobia" of the room.</p><p>"We've found that the person only recovers this 'phobia' if the shock happens in the same room," says LaBar. If the shock happens in a different room, he says, the subject is no longer fearful. "This context-specific recovery of fear is thought to be important for phobias."</p><p>As anyone knows who has ever tried to get through a workday while in a blue funk, mood can also affect mental functioning. So, LaBar and his colleagues have also devised experiments to test how mood affects emotional, as well as cognitive, processing. First, the researchers establish a mood by showing subjects scenes from a happy or a sad movie--Bambi, Titanic, Shadowlands, and Death of a Salesman, among others. Then, while scanning the subjects' brains, the researchers give them a counting task, at the same time presenting them with emotional "distractors"--glimpses of sad clips that elicit an emotion, or neutral clips as a control. "We know little about how longer-lasting mood states can modulate the fast response to emotional stimuli in the amygdala," says LaBar. "In this study, we're looking at amygdala activation, as well as at how people perform cognitively in such situations." Studies like this can give important insights into how mood can affect cognitive function, and thus how people might be expected to perform tasks when they are under the added burden of sadness, he says.</p><p>Within his broader studies of memory's intricate machinery, Cabeza is also zeroing in on the processing of emotion, studying, for example, its function in depressed people. "There is some evidence that, while depressed people don't have a general memory deficit, they have difficulty remembering pleasant events and a better memory for negative events," says Cabeza. This tendency could help feed their depression, he adds. Cabeza is collaborating with Duke psychologist Timothy Strauman and his colleagues to investigate how well people who are depressed remember pictures depicting sad events, in comparison with people who are not depressed.</p><p>The researchers show their subjects pictures depicting sad events, while at the same time scanning their brains to measure differences in activity in the amygdala and connected memory structures. "A particularly exciting possibility is that we'll be able to combine drug treatments with such studies, to measure how effectively they change brain activity associated with depression," says Cabeza. "We might even be able to detect changes in the brain before they show up in behavior."</p><p>Aging also alters the processing of emotion, says Cabeza, and so he and his colleagues are planning fMRI studies of brains of elderly people to explore the activity of their emotional circuitry. "There is some evidence that regions critical to emotional processing might be affected in forms of pathological aging such as Alzheimer's disease," he says. "So, it may be possible to analyze activity in these regions using fMRI to detect early signs of Alzheimer's."</p><table width="98%" border="0" cellspacing="0" cellpadding="2"><tbody><tr><td valign="top"><table width="21%" border="0" cellspacing="10" cellpadding="1" align="right"><tbody><tr><td align="center"><div class="caption caption-center"><div class="caption-width-container" style="width: 300px;"><div class="caption-inner"><img src="/issues/050605/images/lg_laba543.jpg" alt="LaBar: wired for "fear conditioning"" width="300" height="449" border="1" /><p class="caption-text"><p>LaBar: wired for "fear conditioning". Les Todd.</p></p></div></div></div></td></tr></tbody></table><p>As LaBar and Cabeza learn more about the amygdala and its associated circuitry, they are coming to appreciate the subtle complexity of the modest little structure. "When we started this work, it was thought that the amygdala was a specialized fear modulator," says LaBar. "We do still believe that, but we're also finding that it influences maternal and sexual behaviors. We know very little about its role in such reward-based behaviors." Nor, says LaBar, do researchers understand how the amygdala might affect unconscious learning, such as skills or habits.</p><p>An especially fascinating question arising from studies of emotional memory is whether scientists could ever invent a "magical memory pill" to alleviate PTSD or traumatic memories. Some preliminary clinical studies around the world have raised the possibility. A handful of subjects in the U.S. and France are participating in studies in which they were given the drug propranolol immediately after a terrorizing experience such as an attempted rape. The drug blocks the action of stress hormones, including adrenalin, that activate the amygdala to imprint emotion-charged memories on the brain.</p><p>So far, the studies have only given early hints that the drugs might reduce the disturbing intensity of such memories, and research is continuing. Says LaBar, "While there could be designer drugs to either enhance or suppress emotional memories, there are huge problems in terms of ethics and specificity." He says the new appreciation of the amygdala's complex role in making memories means that "designing drugs to target specific emotions within the amygdala is going to be a major challenge." And how about the likelihood of a drug or treatment to erase specific memories, as depicted in the movie Eternal Sunshine of the Spotless Mind, in which a woman deletes memories of her ex-boyfriend? Never going to happen, assert the researchers: Recalling even the most specific memories involves the entire landscape of the brain.</p><p>Nevertheless, they say, future studies will likely provide additional insights into the neural circuitry of memory, including emotional memory--revealing more, for example, about how genes control the formation of such neural circuitry, as well as its function in influencing behavior. A prime example of the far-reaching implications of those studies was a discovery--reported in the December 2004 issue of Neuron by Duke cell biologist Marc Caron and his colleagues--of the first genetic defect specifically linked to depression and resistance to antidepressive drugs.</p><p>Cabeza emphasizes that among the most important advances required to understand the brain will be correcting the mental biases of brain scientists themselves. "We need to break free from the taxonomy of cognitive processes we inherited from the last century," he says. "We've all been trained to think of cognitive abilities in terms of discrete functions such as memory, attention, perception, imagery, and so forth. However, we now realize that the same brain regions are activated by a variety of functions. So, it's a bit funny that when you read a scientific paper, if the paper is about memory, the authors say activity in a given region is due to memory. And if you read a paper about language, the authors say the same region is involved in language. But we're now at a point where it's obvious we cannot keep attributing a brain region to our favorite process."</p><p>"We have to find new ways to explain activation of regions that can accommodate many processes and get beyond this rigid classification," says Cabeza. "We need to build bridges between the two different worlds of studies of cognition--the psychological tradition and the neuroanatomical tradition. It's a big challenge, but it offers great promise for understanding the brain and its disorders."</p><p>The impact of deeper knowledge of emotional processing will be profound. Understanding our own neural demons might mean, ironically, not only trying to vanquish them, but also, ultimately, embracing them. After all, we are the culmination of all our memories, those of rampaging roosters--and of tender kisses.</p><br /><span class="text"></span></td></tr></tbody></table></td></tr></tbody></table></td></tr></tbody></table> </div></div></div> <h3 class="field-label"> Published </h3> <span class="date-display-single" property="dc:date" datatype="xsd:dateTime" content="2005-06-01T00:00:00-04:00">Wednesday, June 1, 2005</span><section class="field field-name-field-main-image field-type-image field-label-above view-mode-rss"><h2 class="field-label">Main image:&nbsp;</h2><div class="field-items"><figure class="clearfix field-item even"><img typeof="foaf:Image" class="image-style-none" src="https://alumni.duke.edu/sites/default/files/dm-main-images/lg_caba5054.jpg" width="620" height="927" alt="Site detectives: Cabeza, left, and LaBar. Jim Wallace." /></figure></div></section><section class="field field-name-field-author field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Writer:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/author/dennis-meredith" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dennis Meredith</a></li></ul></section><section class="field field-name-field-issue field-type-taxonomy-term-reference field-label-above view-mode-rss"><h2 class="field-label">Issue:&nbsp;</h2><ul class="field-items"><li class="field-item even"><a href="/magazine/issue/may-jun-2005" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">May - Jun 2005</a></li></ul></section> <h3 class="field-label"> Featured article </h3> No <h3 class="field-label"> Background color </h3> blue<section class="field field-name-field-sub-header field-type-text-long field-label-above view-mode-rss"><h2 class="field-label">Sub-header:&nbsp;</h2><div class="field-items"><div class="field-item even">Factoring Fear</div></div></section> Wed, 01 Jun 2005 08:00:00 +0000 Joseph Sorensen, JOSEPH E. 18500462 at https://alumni.duke.edu