Contents
Public Health
The best tool for detecting prostate tumors used to be a physician's deft touch. Then, in the mid-1980s, came a simple blood assay--the prostate specific antigen (PSA) test--that could detect tumors long before they were palpable. In today's Science, a team of Harvard School of Public Health and Harvard Medical School researchers report findings that could lead to a method for predicting if a man is at risk for prostate cancer long before a tumor actually develops.
The findings focus on a long-known but, until recently, mysterious hormone, insulin-like growth factor-I (IGF-I). The HSPH team found that men with high, though still normal, levels of IGF-I in their blood have a much higher risk of developing prostate cancer than those with low levels of the hormone.
Researchers had suspected a link between IGF-I and prostate cancer since IGF-I is known to stimulate cell growth. But this link had only been demonstrated retrospectively, by measuring IGF-I levels in men who had already developed the disease. The HSPH study is the first to demonstrate the link in a prospective casecontrol study.
None of the 304 subjects had been diagnosed with prostate cancer when they entered the study in 1982. The 152 men who eventually developed the disease were found to be four times more likely to have high levels of IGF-I in their blood at the time of entry into the study than the 152 who did not develop the cancer.
| June Chan, Ed Giovannucci, and Meir Stampfer have identified a new risk factor for prostate cancer. |
"IGF-I is the strongest risk factor by far--so far," says coauthor Meir Stampfer, professor of epidemiology and nutrition at HSPH. Previous studies have suggested that age, race, weight, height, and diet might predispose men to developing the disease.
"Measuring IGF-I levels could, down the line, add to the predictive value of PSA," says June Chan, a graduate student in the department of epidemiology at HSPH and lead author of the study.
Prostate cancer--which caused over 41,000 deaths and substantial illness last year--is now the most commonly diagnosed cancer among American men. It is also at the center of one of the most heated controversies in medicine.
Until recently, most men diagnosed with the disease had large and advanced prostate cancers, demanding aggressive treatment such as radical prostatectomy or radiation. With the advent of PSA testing, microscopic tumors could be found. A dilemma has arisen because even though some of these tumors may mushroom quickly, most follow an indolent course--and older men who develop the disease often die of other causes before their tumors become lethal. Nor has it been shown definitively that surgically removing the prostate when a cancer is microscopic--rather than waiting until it has grown--actually extends the patient's life. The result is that some physicians are reluctant to recommend PSA testing.
Developing a method for measuring a new risk factor would provide more diagnostic information, which might do more than cast an old dilemma in new light. PSA is a marker that is produced by cancer cells, while preliminary studies suggest that IGF-I may help cause prostate tumors. If so, knowing a man's IGF-I level could open the door to preventive measures.
"For example, if you could alter it by changing something in your diet, you might make recommendations [for reducing risk of prostate cancer] based on that. But, at the moment, it's not clear how well IGF-I is related to diet," says coauthor Ed Giovannucci, assistant professor of nutrition at HSPH and of medicine at HMS.
The Molecular Roles
IGF-I and -II were discovered in the 1950s, but only recently have researchers begun to paint a picture of how they might cause prostate cancer. According to current understanding, the two interact with IGF-binding proteins (IGFBPs). These proteins modulate the activity of IGFs. For example, by binding to circulating IGFs, they may prevent the hormones from telling a cell to proliferate.
This inhibitory grip on IGF can be broken by a class of molecules called IGFBP proteases. These molecules cleave IGFBPs, preventing them from interacting with IGFs. Freed from their binding partners, IGFs may cause cells to proliferate uncontrollably.
Several years ago, researchers discovered that cultured prostate epithelial cells, which are the ones affected in prostate cancer, produce IGF-I receptors and some IGFBPs. They also found that PSA functions as a protease for one of these binding proteins, IGFBP-3.
Inspired by these discoveries, Giovannucci and Stampfer asked their colleague Michael Pollak, who is from McGill University and a study coauthor, to measure levels of IGF-I, IGF-II, and IGFBP-3 in the serum of 304 male subjects, half of whom had developed prostate cancer. The subjects were participants in the Physicians' Health Study, which was begun at Brigham and Women's Hospital in 1982 by Charles Hennekens, a study coauthor and professor of epidemiology.
Stampfer and Giovannucci handed over this data to Chan. She found that the men who had developed prostate cancer had lower levels of IGFBP-3 as well as much higher levels of circulating IGF-I (see chart).
| If there were no link between prostate cancer and IGF-I, men with prostate cancer would have been evenly distributed among the four quartiles. However, the researchers found that there were more than four times as many men in the highest quartile (representing the highest IGF-I level) as in the lowest. |
The researchers caution that their results must be confirmed before pursuing practical applications such as dietary or pharmacological approaches for decreasing IGF-I levels.
However, they do suggest that elderly men taking growth hormones for their anti-aging effects--such as increasing muscle mass--may be raising their risk of developing prostate cancer.
--Misia Landau
First Atomic Snapshot of DNA-Duplicating Enzyme at Work
Things are getting bigger. From television screens to NFL linebackers, down to the cookies served in cafeterias, the trend dictates that bigger appears better. And in some areas of science, it is no different.
Consider X-ray crystallography, the high-tech art of visualizing the vanishingly small. This discipline, too, aims toward revealing ever larger, bulkier proteins. Prized achievements these days are images of big complexes with several proteins that together perform an interesting biological function.
In an article in the January 15 Nature, a research collaboration of Quad-based biochemists and crystallographers present their latest trophy: the 3-D structure of T7 DNA polymerase, a viral enzyme that replicates DNA. Both Nature and the February Nature Structural Biology discuss this work in separate reviews.
Worked out by Sylvie Doublié, a postdoctoral fellow in the lab of Thomas Ellenberger, assistant professor of biological chemistry and molecular pharmacology, the structure depicts the molecular architecture of the largest protein complex ever to be revealed by a method dubbed MAD, for multiwavelength anomalous diffraction. This method, the leading technique to image structures at very high resolution, was previously considered feasible only for much smaller proteins. "Technically speaking, we consider this a real home run," says Ellenberger.
But the structure does more than broaden the scope of X-ray crystallography. It allows researchers to "see" for the first time DNA replication, a basic process of life that has been studied biochemically and genetically for decades.
Other researchers had previously figured out the crystal structures of related DNA polymerases but had never been able to include all the players necessary for DNA duplication. By finally doing so, Doublié and colleagues have made a snapshot of replication at work: the structure shows the polymerase bound intimately to a DNA double helix. Where the double helix ends, the DNA continues as a short, single-stranded stretch. This is where the researchers placed a modified DNA building block--or nucleotide--in the right position to be attached, and then crystallized the whole complex. In effect, they staged a complete replication scenario, with every player assuming its natural posture for the act of replication, and then froze this arrangement in a still frame.
| For almost 30 years, Charles Richardson (below) has studied how the enzyme T7 polymerase copies DNA. Collaborating with crystallographers down the hall, he now gets to lay his eyes on the enzyme at work. |
"Our structure is indisputably correct, not just an accidental structure where the DNA is randomly binding," says coauthor Charles Richardson, the Edward S. Wood professor of biological chemistry and molecular pharmacology.
In addition to answering a number of fundamental biological questions about how replication works, the study has implications for drug design and the development of better reagents for DNA sequencing.
In 1971, Richardson first described T7 polymerase. He has since continually studied this enzyme and led the biochemical work on this project with his colleague, lecturer Stanley Tabor.
This structure is significant because it is the first to depict a so-called replicative polymerase. Various DNA polymerases occur in every cell of every living thing, but the enzymes crystallized in earlier studies function more like repair enzymes that fill in small nicks in the DNA. They make errors frequently, and are slow because they fall off the DNA after attaching only a few nucleotides. By contrast, T7 polymerase can zip along the DNA and faithfully replicate the entire chromosome at a rate of 400 nucleotides per second, making only about one error per million base pairs.
This feat has for years raised two questions: what makes this enzyme so accurate--a crucial question because replication errors can lead to cancer--and how does it manage to stay clamped to the DNA for thousands of base pairs, while its close cousins, the repair enzymes, fall off so easily?
The crystal structure answers the first of these questions. It portrays the polymerase as a right hand held with the palm facing the viewer's eyes and the thumb held up. (See image. The wrist and arm of the imaginary hand do not exist, but would extend to the right of the image.) Researchers had long assumed that the hand somehow grips the DNA and slides along it as it carries out its reaction, but previous structures of DNA polymerases had never confirmed this hunch because they showed the fingers wide open. This structure, however, makes clear that when the enzyme is at work, the fingers indeed close tightly around the DNA and the incoming nucleotide.
| By shining X rays through a crystal containing all the ingredients necessary for DNA replication (left), HMS researchers have revealed the 3-D structure of replication. This crystal structure will help other researchers design new antiviral drugs. Below, the DNA polymerase (gray) envelops the DNA (pink and red), and is about to add a new nucleotide to the growing DNA strand (red arrow). |
The second question--about the enzyme's tight grip on the
DNA--remains partly elusive. In previous work, Richardson had shown that
the T7 virus needs a protein called thioredoxin from the bacterium it infects
to accelerate T7 polymerase. He and Tabor later found biochemical evidence
suggesting that the virus corrupts thioredoxin, making it sit on top of
the polymerase's thumb, and they speculated that this extended thumb creates
a lid over the DNA, trapping it firmly within the enzyme.
The scientists managed to crystallize the polymerase together with the bacterial protein. Yet, while the structure confirms that thioredoxin indeed is perched on the enzyme's thumb, it is not bent over the DNA but rather sticking up. The researchers say they might never be able to confirm their speculation with crystallography.
New Tools for Sequencing
Beyond these and other basic insights, the study has implications for applied research. For one, the work will be of special interest to researchers in laboratory chemical companies who seek to develop better reagents for DNA sequencing in this age of the Human Genome Project. Already, a modified version of T7 DNA polymerase, with the trade name Sequenase, is one of the enzymes most widely used by researchers performing manual DNA sequencing. The mutations that turned T7 polymerase--as well as its main competitor in the sequencing market, Taq polymerase--into commercially useful products are based on research by Tabor and Richardson and licensed by Harvard.
This work will also be of special interest to researchers who develop drugs targeting DNA replication. Many antiviral compounds, including the AIDS drugs AZT and DDT and medications against herpes simplex virus, work by inhibiting DNA polymerase. The exquisite atom-by-atom resolution of the first viral polymerase caught in the act may help rational drug designers come up with more and better compounds to interfere in this process, says Ellenberger.
--Gabrielle Strobel
All proteins help maintain the economy of the cell, but those at the surface might be said to do yeoman's duty. Membrane proteins--receptors, ion channels, transporters--perform a wide variety of services, from receiving signals to shepherding ions and enzymes in and out of the cell.
"Membrane proteins are very important--they are at the interface between the cell and the rest of the world," says Dana Boyd, lecturer on microbiology and molecular genetics. While some of these proteins lie on the membrane, others--known as integral membrane proteins--burrow, sometimes repeatedly, through its surface.
Integral membrane proteins are so critical, and interest in them so intense, that often the first question asked of a new protein will be: is it an integral membrane protein or not?
In the cover story of this month's Protein Science, Boyd and his
colleagues present a rule for identifying integral membrane proteins based
simply on their amino acid sequence. The method depends on measuring the
hydrophobicity--aversion to water--of a protein's most water-hating amino
acid segment. As the genomes of entire organisms flood in from sequencing
labs, the numerical approach could provide a quick and easy way of sorting
integral membrane from nonintegral membrane proteins.
| Clark Shierle and Dana Boyd have uncovered a surprising regularity in the way proteins are distributed. |
Applying the method has yielded some unexpected results. When Boyd and his colleagues Clark Schierle, research assistant, and Jon Beckwith, the American Cancer Society professor of microbiology and molecular genetics, applied the rule to a wide range of genomes, they uncovered an interesting trend: integral membrane proteins constituted 20 percent of every genome they analyzed.
"That's true for bacteria, for archaea, and it's true for humans," says Boyd. The result is surprising not just for its regularity but also because previous estimates had put the number higher--30 to 50 percent.
It was a suspicion that these previous estimates were too high that sent Boyd looking for a simple numerical approach to sorting integral membrane proteins from nonintegral membrane proteins. Early in his quest, he came across a paper written in 1985 proposing a statistical measure for identifying the integral proteins, called average maximum hydrophobicity (maxH). According to the original analysis, bacterial proteins possessing a particular maxH value had a 50 percent chance of being integral membrane proteins. But when Boyd applied the method to the recently sequenced E. coli genome, he found no integral membrane proteins with that particular maxH value. In fact, it was only by looking at proteins with much higher maxH values that he was able to find integral membrane proteins.
Tuning the Test
"That told me two things. The method was not working right. But it also told me it was promising, because it was separating things out," says Boyd. Using the E. coli amino acid sequences, he went back and applied the same method to generate a new value of maxH that would carry a 50 percent likelihood of identifying the target proteins. He tested this number against a mixed set of E. coli proteins--integral and nonintegral membrane--and found that it sorted them correctly.
Interestingly, the maxH value occurs right at the valley separating clusters of integral membrane and nonintegral membrane proteins--not just for E. coli but for all the organisms tested (see figure).
.
| The researchers' method predicts that 20 percent of the proteins in the genomes of all organisms are integral membrane proteins. Representatives of the three branches of life--bacteria, archaea, and eukaryotes--are shown here. |
Although the significance of this is unclear, Boyd speculates that the maxH value--which measures the hydrophobicity of the most water-hating segment, rather than all water-hating segments--may reflect an important biological mechanism.
"I think what's going on is that each integral membrane protein has to have at least one transmembrane stretch that is highly hydrophobic for some biological purpose," says Boyd. "Maybe that purpose is to ensure that the machinery that inserts it into the membrane can recognize it as integral membrane protein and won't send it off on the wrong pathway."
--Misia Landau
Enrollment of Medicaid beneficiaries in managed care health plans has increased more than fivefold in recent years, from 2.3 million people in 1990 to more than 13.3 million in 1996. Forty percent of all Medicaid beneficiaries now belong to managed care organizations. The shift to managed care has been a dramatic change for state Medicaid agencies and, to date, there has been little information about how the agencies are adapting to their new role. A new study by HMS researchers that appears in the Jan. 21 issue of JAMA helps to address this deficit.
Bruce Landon, instructor in health care policy at Brigham and Women's Hospital, and Arnold Epstein, chair of health policy and management at the Harvard School of Public Health, in collaboration with Carol Tobias, from the Medicaid Working Group at Boston University School of Public Health, conducted a telephone survey of all state Medicaid agencies that provide care under comprehensive managed care programs. Thirty-four states had Medicaid beneficiaries enrolled in such programs, and each was surveyed to determine how they were monitoring and encouraging quality of care.
By July 1996, all surveyed states had enrolled their Medicaid population receiving assistance from Aid to Families With Dependent Children (AFDC) in comprehensive managed care programs. But only 21 states had enrolled portions of their disabled Medicaid population, and 15 states had enrolled portions of their elderly Medicaid population.
In the period 1995 to 1996, the study found that 19 states were collecting data on patient care satisfaction among Medicaid beneficiaries enrolled in managed care programs, and many states hoped to begin collecting this data in 1997. The study also revealed that some quality improvement initiatives were under way.
Revenue from the sale of artificial nail primers was approximately $265 million in 1995, but it seems that little of that money is being spent on child-resistant packaging. In the January issue of the AMA's Archives of Pediatrics and Adolescent Medicine, HMS researchers at Children's Hospital and the Massachusetts Poison Control System in Boston report an analysis of injuries to young children resulting from contact with artificial nail products. Burns on the skin, eyes, or mouth were the most common injury.
In a sample of patients seeking treatment at U.S. emergency departments between 1991 and 1993, Alan Woolf, associate professor of pediatrics at Children's Hospital, and Judith Shaw, from the poison control system, found 32 children younger than six years old with injuries from nail primers, including 14 preschoolers with severe skin burns. Among 567 nail-product calls to U.S. poison control centers from 1993 to 1995, 56 children (9.8 percent) suffered moderate injuries, and three (0.5 percent) suffered major injuries due to methacrylic acid exposure. Methacrylic acid, contained in most artificial nail primers, etches the natural nail to increase adherence of the artificial nail. Due to its corrosiveness and the accessibility of the nail primers to children, the researchers calculated a hazard score on a par with kerosene and ethanol-containing beverages.
Woolf and Shaw believe that the increase in these types of injuries over the past few years is related to the trend towards cheaper home-use artificial nail kits. They recommend revised product labeling to adequately warn consumers of the caustic hazard of nail primers and product repackaging to prevent access by young children.
It is well accepted that genetics predisposes some people to develop insulin-dependent diabetes mellitus, or Type I diabetes, an autoimmune disease in which the patient's own T cells destroy the insulin-producing cells of the pancreas. But scientists do not know exactly why some people who seem to have the susceptible genetic makeup are apparently spared. A paper by HMS researchers published in the Jan. 8 issue of Nature sheds new light on the paradox.
Brian Wilson and Sally Kent, postdoctoral fellows at Harvard University and Brigham and Women's Hospital, respectively, attempted to identify abnormalities in the immune system that may be responsible for disease development. To reduce the genetic variation, the researchers analyzed T cells from identical twins and triplets, looking closely at sibling pairs in which only one member was diabetic. Wilson and Kent identified a subset of T cells that were decreased in all diabetic patients compared with their nondiabetic siblings.
As they continued to analyze these T cells, the researchers found that they also had an unusual characteristic compared with their normal counterparts. Upon stimulation, the T cells from the diabetic patients differed in their production and secretion of a cytokine (growth factor) called IL-4. Most of the cells from the nondiseased patients secreted IL-4, but it was not released from the cells of the diabetic siblings.
"Our results demonstrate a relationship between elevated IL-4 levels and resistance to the progression of diabetes," says David A. Hafler, associate professor of neurology (neuroscience) at Brigham and Women's Hospital and senior author of the Nature paper. "This relationship may represent a basic finding in the cause of Type I diabetes."
HMS researchers at McLean Hospital are embracing a new tool as they grapple with the nature of cocaine craving. The McLean team is the first to use functional magnetic resonance imaging (MRI) to directly visualize the effects of cocaine craving on the human brain. Using MRI, the researchers showed that the presentation of cocaine cues activated two parts of the brain involved in human emotional responses. Their findings are published in the January American Journal of Psychiatry.
Luis Maas, doctoral student at McLean's Brain Imaging Center, Perry Renshaw, associate professor of psychiatry at McLean Hospital and director of the center, and their colleagues showed a 10-minute videotape to each of the study subjects: six crack cocaine users and six nonusing males, ages 32 to 37. The 10-minute video showed alternate 2.5 minute scenes of butterflies fluttering and actors preparing and then smoking crack.
Each subject underwent a single MRI session while watching the video. Scans were generated every 5 seconds, resulting in a set of 1,200 brain images for each subject.
The researchers analyzed the scans and found that two parts of the brain, the anterior cingulate and the dorsolateral prefrontal cortex, were activated upon presentation of the cocaine cues. They showed that the brain turned "on" and "off" in response to the cues in less than 2.5 minutes, without substantial carryover effects. This is an important finding because craving has generally been thought to occur over much longer periods, according to Renshaw.
The MRI scans were also compared with the level of craving, as determined by a questionnaire on the strength and frequency of each subject's desire for cocaine.
"If we can identify and decrease the mechanisms for craving then we can begin to think about developing new ways to treat drug addiction," says Maas.
"The findings from this study provide a valuable tool to assist in the identification of the neurological basis of craving," says Alan Leshner, director of the National Institute on Drug Abuse, which helped fund the study.
--Kristin Weidenbach
The heralded Countway Library renovation--planned since '92 and launched last fall with preparatory projects--will enter its first of three construction phases next month on Lower Level 2. The final phase is scheduled to be completed by December 31, 1999, just in time for the next millennium. The library will remain open during this two-year period, and the staff is ready to work with users to minimize the inevitable inconveniences.
"We will be setting up a special renovation phone line and a Web page update, plus informing our diverse constituents through a variety of print and electronic resources to make sure users' needs are met as efficiently as possible under these difficult circumstances," says library director Judy Messerle.
Highlights of the $21 million renovation, which has been funded in large part through generous donations, will include:
* A first-floor reading room (see illustration);
| A new first-floor reading room will be part of the Countway renovation, which has three construction phases, the first beginning on Feb. 1. |
* New computer workstations and experimental high-end technology for research;
* Relocation of the popular Aesculapian collection to Lower Level 1;
* Dispersion of multiple data jacks and cluster computer workstations throughout the library for more widespread use of library and personally owned computers;
* A redesigned Rare Books and Special Collections Department on Lower Level 2 with multiple exhibit cases, scholar workstations, and a quiet area for historical research.
The Countway staff and HMS's Engineering and Construction Department are currently working with the architectural firm Shepley, Bulfinch, Richardson, and Abbott to refine floor plan designs. The project's construction company is William A. Berry & Son.
The preliminary time line for construction and the floors involved are:
* Phase 1, Feb. 1, 1998Jan. 31, 1999: Lower Level 2;
* Phase 2, Feb. 1, 1999July 30, 1999: Floors 2, 3, 4, 5, and 6;
* Phase 3, Aug. 1, 1999Dec. 31, 1999: Floor 1 and Lower Level 1.
Research Resources
Through the generosity of John F. Taplin and family, six departments in the Medical School and the School of Dental Medicine will receive a total of $1.4 million worth of new equipment and instruments to be used in their laboratories. The departments Biological Chemistry and Molecular Pharmacology, Cell Biology, Genetics, Microbiology, Neurobiology, Pathology, and the Dental School were each allotted $200,000.
Among the devices ordered are two fluorescence-activated cell sorters (FACS), one to be used by BCMP for non-mammalian applications such as yeast and bacteria, and one to be used by Cell Biology for mammalian applications. Separate equipment is essential to prevent contamination. Joan Brugge, professor of cell biology, explained that most cell biologists grew up without FACS technology, which greatly simplifies analysis. This tool now has "innumerable applications in most areas of cell and molecular biology," she says, which makes it useful to the entire department.
| John and Virginia Taplin established Funds for Discovery in 1992 to promote the development of marketable technologies. |
Taplin is providing equipment grants because it is easier for researchers to get individual research grants than to obtain funding for laboratory equipment. Brugge confirmed this reason, saying when she told her equipment supplier she was applying for money for the FACS, he laughed and said good luck. Luck it seems has come, in the form of the Funds for Discovery Program's new focus on equipment grants. Taplin established the FFD program in 1992 to support faculty research and promote the development of research into original technologies with a goal of improving the public's health and welfare. He hopes that the financial management of the FFD endowment and a strong securities market will enable the fund to award grants totaling $1.5 million each year to support new and improved instruments and equipment for research.-
-Tiffany Doyle
Med Student Tests Mettle As Jeopardy Champ
Second year HMS student Wes Ulm flew to California two weeks ago to compete in the Jeopardy Tournament of Champions and returned with pneumonia. We'll have to wait until the tournament is aired, starting Feb. 2 and running for two weeks, to find out if he also returned with the $100,000 winner's purse.
Ulm cannot discuss the competition results before they are broadcast, but he's unsure if his developing illness affected his performance. "I don't think there would have been a major impact on the outcome. Of course I can't say why-you'll see."
Ulm's fruitful Jeopardy involvement began after he graduated from Duke University in 1996. As a candidate, he was a finalist four times before making it onto the show-and winning more than $63,000.
The Tournament of Champions is an elite Jeopardy competition between the top 15 competitors from the previous season. Ulm, at age 23, was one of the youngest to take part, which he says may have put him at a slight disadvantage, noting Jeopardy's shift in emphasis from academic questions to those based on popular culture. "It was more difficult for me this time. Being a medical student, I almost never watch TV, and there were questions on popular culture from the 60s and 70s-before my time."
But Ulm had adjusted his preparation accordingly. From the encyclopedias and almanacs he relied on in the past, he turned to books of television history, movies, and music stars. Reading People magazine, listening to the radio, and cruising the World Wide Web enhanced his knowledge.
All the fame, excitement, and money hasn't changed Ulm's career plans. "Whether I won the grand prize or not, nothing was going to change for me. I knew I would be back slaving away in med school."
-Kristin Weidenbach
* Shontaye McGriff, Peabody '99, has been selected by the W.K. Kellogg Foundation to receive its 1998 Community Based Training Fellowship for Minority Medical Students. She was one of 15 second- and third-year minority medical students selected from the U.S. Each will receive $10,000 plus a $1,000 travel stipend.
* Deborah James, Castle '99, was one of twelve 1998 Metropolitan Life Foundation Scholars chosen for outstanding academic achievement, leadership, community involvement, and potential for distinguished contributions to medicine. The award includes a $3,500 stipend to help cover medical school expenses.
* C. Ronald Kahn, the Mary K. Iacocca professor of medicine at Joslin Diabetes Center, has been appointed executive vice president and director of JDC, after serving as its research director for sixteen years. He will oversee the professional and academic functions of the center's clinic and research divisions.
* Stephen J. Galli, professor of pathology at BID, has received the 1997 Scientific Achievement Award of the International Association of Allergy & Clinical Immunology (IAACI). The award, given every three years, recognizes Galli and his team's work in the development and use of new in vitro and in vivo approaches to analyzing the regulation of mast cell development and function and clarifying the roles mast cells play in health and disease. Galli's work was also acknowledged by the Paul Kallós Memorial Lecture Award, given every two years at the meeting of the Collegium Internationale Allergologicum, and by a MERIT Award from the NIAID/NIH.
* Joan Reede, assistant professor of medicine, assistant dean for faculty development and diversity, and director of the minority faculty development program, and Sharon Clayborne, senior assistant director of student financial aid, both received a 1998 YMCA Black Achievers Recognition Award on January 22. Reede is acknowledged for creating a program to support the career development of minority faculty at HMS and to address crucial pipeline issues for minorities interested in careers in medicine and science. Clayborne is recognized for her "honesty, fairness, and dependability" to the HMS students and department managers who rely on her assistance in financial aid matters.
* Robert Coles, professor of psychiatry and medical humanities at Cambridge Hospital, is one of 15 recipients this year of the Medal of Freedom, the nation's highest civilian award. The medals honor Americans who have made a special contribution to the nation's welfare. Coles has authored several award-winning books on the psychology of children, focusing on their resilience and courage in crises.
* John Brouder has been appointed assistant dean for clinical affairs at the Dental School, effective February 2. Brouder will lead the faculty and teaching practices in expanding their services, facing the challenges of health care market trends, and achieving financial stability. He comes to HSDM from his position as senior vice president at the First New England Dental Center Inc., where he has been responsible for insurance claim management and new business development. He has lectured extensively at national conferences on dental insurance and dental practice management and has published widely on these topics.
* The Department of Social Medicine has research funds available to HMS students for travel to research sites abroad for summer 1998. The Freeman Foundation Fellowship Program will support two students' research in East or Southeast Asia. An anonymous donation will support two other students' research in medical anthropology or social medicine in Africa, Asia, Latin America and the Caribbean, the Middle East, or Eastern Europe. Preference will be given to applicants who speak the local language and who are supervised by Social Medicine faculty. Projects should involve social medicine and medical anthropology perspectives and methods. Applications are due March 2, 1998, at noon and are available from Mary Bigelow, phone: 432-2558, fax: 432-2565, or e-mail: mbigelow@hms. harvard.edu. Questions should be directed to Joan Kleinman, phone: 495-3846, fax: 495-3557, or e-mail: gillespi@wjh.harvard.edu.
* Members of the second group of the Commonwealth Fund/Harvard University Fellows in Minority Health Policy have begun the second half of their program, which is designed to train future minority health leaders. They take courses at the Kennedy School of Government and are exposed to a variety of health leaders through site visits and lectures before earning their MPH degrees from HSPH. This year's fellows and their research interests are Joseph Betancourt, physician, New York Hospital-Cornell Medical Center, who studies public health policy issues relating to Hispanic populations and seeks to develop strategies for the recruitment and retention of Latinos in the health care professions and to investigate means to improve access to and quality of health care for general Latino populations; Ricardo Custodio, clinical assistant professor of pediatrics, University of Hawaii School of Medicine, is interested in the delivery of health care to underserved Asians and Pacific Islanders in Hawaii, and in the creation of provider networks to address quality in the community health care system; Michelle Johnson, cardiology fellow, Beth Israel Deaconess Medical Center, focuses on accessibility of health care and the epidemiology and prevention of cardiovascular diseases in minority populations; Roderick King, senior lecturer, University of Cape Coast, investigates public health policy issues with particular focus on improving the health of underprivileged children via education of patients, parents, and health professionals. He is also interested in fostering international efforts to study diseases affecting disadvantaged populations in the U.S. and abroad; Creshelle Nash, physician, George Washington University Hospital, seeks to establish medical services in low-income rural areas; Nancy Torres, pediatrician and medical director of the Level II Intensive Care Nursery, Kaiser Permanente Medical Group Inc., is interested in health care policies that improve access and education and better meet health care needs of Hispanic-Americans as well as other minority groups.
* Francis D. Moore, the Moseley professor emeritus of surgery at BWH, and Joseph E. Murray, professor emeritus of surgery at BWH, were featured in PBS's five-part series titled "A Science Odyssey." Moore and Murray appeared in the first segment, which was scheduled to air on January 11. Murray, who was awarded the Nobel Prize in Medicine for his pioneering kidney transplant work in the '50s, was the first surgeon to successfully perform an organ transplant on a human being, under the direction of Moore.
* Faculty and students are invited to the second annual Harvard-Forsyth Scientific Retreat to be held Friday, February 6 in the Haigh Auditorium of Forsyth Dental Center. Clinical and basic science research presentations will begin at 10:30 a.m., and will be followed by a competitive poster session by HSDM pre- and postdoctoral students at 5 p.m. Scheduled speakers include John Bartlett, William Crowley, Floyd Dewhirst, J. Max Goodson, Howard Howell, Robert Langer, Bjorn Olsen, Steven Sonis, Martin Taubman, and David Wong. To register by the January 28 deadline, contact Pam Mullaney at 262-5200 ext. 303 or e-mail: pmullaney@forsyth.org.
* Bridgewater Park Medical Associates, an affiliate of CareGroup, and Goddard Medical Associates have signed an affiliation agreement that will integrate the two groups of physicians located south of Boston. The agreement makes it possible for the combined practice to care for 150,000 patients and will allow greater access to managed care contracts, yet both groups will retain their commitment to community-based health care. Both practices have multiple specialties and will offer residents of Brockton, Easton, Falmouth, Raynham, Sandwich, Stoughton, and West Bridgewater extensive specialty services. In addition, the combined practice will create new programs including a comprehensive women's health service and a state-of-the-art oncology infusion center. Together, the practice will be the third largest employer in the area, and will provide all the medical services needed by the communities it serves.
* Harvard has granted Virus Research Institute Inc. an exclusive worldwide license to Therapore, a novel immunotherapy system based on the research of R. John Collier, the Maude and Lillian Presley professor of microbiology and molecular genetics at HMS. Therapore will be used to deliver products within the body to fight chronic viral infections and cancers. Virus Research Institute Inc. focuses on the discovery and development of vaccine delivery systems and novel vaccines, and is currently developing a portfolio of vaccine delivery systems designed to improve the efficacy, lower the cost of administration, and improve patient compliance for a variety of vaccine products.
* Harvard School of Public Health has appointed a committee to search for a François-Xavier Bagnoud professor and director of the FXB Center for Health and Human Rights. The FXB Center is devoted to developing and promoting new understanding of the connections between health and human rights and combining the academic strengths of research and teaching with a strong commitment to service and advocacy. The search committee for this tenured position is chaired by Lisa Berkman, the Florence Sprague Norman and Laura Smart Norman professor of health and social behavior and epidemiology, and seeks an individual in the field of health and human rights with demonstrated leadership, a superior record in research and scholarship, and the ability to make linkages across disciplines and institutions. Candidates should have professional experience in medicine or public health, extensive familiarity with human rights issues, and international experience. To apply, send a curriculum vitae, a short statement of interests and field activities, and names of three references to Chair, Search Committee, FXB Center for Health and Human Rights, HSPH, 677 Huntington Ave., Boston, MA 02115.
* Children's Studies at Harvard, an initiative of the Harvard Project on Schooling and Children has announced its most recent set of grants for research, mentoring, and course development. The program's mission is to enhance children's well-being by encouraging increased attention to children's issues in Harvard's graduate and undergraduate programs, fostering interdisciplinary research on children, and developing strong connections between Harvard and the greater Boston community. The HMS recipients and their project titles are William Beardslee, Donna Podorefsky, and Phyllis Curtis-Tweed, "Preventive Intervention in Culturally Diverse Urban Communities: Enhancing Partnerships with Community Leaders"; Lynn Hickey Schultz, "Promoting Young Children's Intergroup Awareness and Competence: The Development of a Measure of Children's Understanding of Diversity"; Claudio Toppelberg, "Language Proficiency in Bilingual Children: Emotional, Behavioral, and Adaptational Correlates"; Jessica Henderson Daniel, "Black Adolescents as Social Constructionists: Images of Black Women in Music Videos"; Alissa Coggins, "Language Proficiency in Bilingual Children: Psychiatric Correlates"; and Alexa Kemeny, "Pediatric Alliance for Coordinated Care."
* On Friday, February 6, HSPH will sponsor its tenth annual Career Day. The event will take place in the lobby and atrium of the FXB Building, from 10:00 a.m. to 3:30 p.m. Career Day is designed to provide students with information about public health employment and internship opportunities in a range of environments. A panel of HSPH alumni including Malcolm Bryant of Management Sciences for Health, Gail Costs of Care New England Health System, and Jean-Marc Saffar of Peat Marwick will address the topic "Leadership Skills."
* The West Roxbury Veterans Affairs Medical Center has been designated a Clinical Program of Excellence in Cardiac Surgery, one of only four VA centers nationally to earn the honor and the only one in New England. The designation is determined by a national VA review panel looking at five criteria: measuring excellence in clinical care outcomes, structures and processes, customer service and patient satisfaction, cost effectiveness, teaching and research, and use of human resources. The death rate for cardiac surgery patients, for example, was much lower than the national average despite the WRVA's status as a referral center attracting some of the sickest patients from New England.
On Becoming a Doctor
I loved the children. I loved their problems. I loved their issues. I loved their parents--which is not to say that I liked every patient or every parent, only that I loved taking care of children.
As much as I enjoyed the young patients, there is something very wrong about sick kids. I hated the procedures, especially in the middle of the night. Unable to understand why they needed the IV or the blood draw, the children screamed as we struggled to find their tiny veins. I hated the tortured looks on their parents' faces as they attempted to calm their children. One angry, hurt father grabbed the IV out of the intern's hand just as she got it into the vein, screaming, "No more of this! I don't care. No more! I'll take full responsibility!" and flung the bloodied IV catheter across the room.
Claudia was two and a half years old. Light brown curls of fine baby hair fanned out around her neck and temples. She regarded us with big brown eyes from the vantage point of her mother's hip. She had hereditary spherocytosis and had come in during the night for a blood transfusion. This blood disease causes a chronic anemia that can become acutely worse in the face of a viral illness.
Claudia had had a cold the previous week; it was going around her ballet class. Now her hematocrit had dropped to 12 from a normal range of 35 to 42. Her father had donated blood two days before, and it was finally ready for transfusion. She was ghostly pale, her skin a dull leaden white. As her parents brought her into the treatment room, she began screaming, "No blood! No blood!" And as one of her parents laid her on the table, she cried for a Band-Aid. "Put it on!" she begged, knowing that this meant the end of the stick. We had to stick her three times before we finally found a good vein in her pudgy arms. Then later on, at one o'clock in the morning, Claudia's nurse called us to check on a rash she had developed over the last hour. When we came into the room, Claudia was sitting up in bed crying, "I don't yike this. I don't yike this. I don't yike this ...."
We stopped the transfusion because she had developed a reaction to her father's blood. Her body had learned to recognize his blood as foreign. We gave her some Benadryl and then continued the transfusion--the last with her father's blood. Claudia was finally ready to go home at seven o'clock. Her parents looked haggard and exhausted as they walked with her to the elevator.
Despite horrible diseases like this, kids are resilient. They find ways to be children despite it all. Melissa and Sandy, eight-year-old identical twins with severe cystic fibrosis, spent much of their year in the hospital. Posted on a bulletin board were class pictures and annual holiday photos of the two girls dating back to when they were toddlers. A list they had made on orange construction paper hung from their door, titled "Things That Are Good To Do In The Hospital." It included: "Be nice to my sister. Cooperate with Chest PT [Physical Therapy]. Eat my whole dinner." Just below it was a sign that said, "Things Not To Do In The Hospital: Hit my sister. Play jump rope with my IV. Ride on my IV pole."
One morning I walked into the playroom to find Melissa, Sandy, Katy (with psychogenic abdominal pain), and Jennifer (who had AIDS) grouped around the child-size table with the play coordinator. They were playing the game "Operation." Melissa was complaining, "I don't see why she got more money than me for taking out the wishbone!" And the coordinator explained, "That's because she got the specialist card. The specialist always gets more than the generalist for doing the same procedure."
All of the patient names in this column are pseudonyms.
--Ellen Rothman, HMS '98
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