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Field work. Grantee Kathleen Kreiss (left) and Carol Epling of the National Jewish Center for Immunology and Respiratory Medicine discuss field work at a Denver construction site. |
In the late 1980s, several reports, including one from the Institute of Medicine, identified the teaching of environmental and occupational medicine at most medical and osteopathy schools as virtually nonexistent. The Institute of Medicine report further maintained that the field was held in low regard by most medical practitioners and students, resulting in few primary care physicians being knowledgeable about environmental health issues. The report stated that primary care physicians should be able to identify illnesses related to environmental agents. A report from the American College of Physicians went further, recommending that physicians should also recognize patients who need counseling about environmental risk and be able to refer them to appropriate sources if the physicians cannot provide that counseling.
To address this need, NIEHS announced its first competition for environmental and occupational medicine academic awards in February 1990. The awards had the dual purpose of improving the quality of environmental and occupational medicine curricula and fostering graduate research careers in environmental and occupational medicine among medical students and residents. Today, the long-term goals of the program continue to be twofold: to develop and sustain the best possible curricula at the awardees' institutions and to develop these plans in such a way that they can be made available to other institutions with fewer resources and faculty. In addition, to institutionalize the goals of the award beyond the duration of the grant, the awardees are expected to provide leadership in faculty development in environmental and occupational medicine.
Thirteen Environmental/Occupational Medicine (E/OM) Academic Award grants have been awarded to medical schools. "The response to the first program announcement was overwhelming," said Annette Kirshner, head of the NIEHS Scientific Programs Branch within the Division of Extramural Research and Training. "By the first application deadline on 1 June 1990, the institute received 34 applications for review, two to three times the anticipated response." In that first round, eight awards were made totaling $1 million, using $500,000 of extra funds transferred into the budget for that purpose. The following year, 12 applications were received and 3 awards funded, and in the third competitive round, 14 applications resulted in 2 awards.
Environmental/Occupational Medicine Academic Award Grantees
John R. Balmes, MD
Department of Medicine
Center for Occupational and
Environmental Health
San Francisco General Hospital
San Francisco, CA
Mark R. Cullen, MD
Department of Internal Medicine
Occupational Medicine Program
Yale University School of Medicine
New Haven, CT
Raymond Y. Demers, MD
Department of Family Medicine
Division of Occupational and
Environmental Medicine
Wayne State University
Detroit, MI
Rose H. Goldman, MD
Department of Medicine
Cambridge Hospital
Cambridge, MA
James P. Keogh, MD
Department of Medicine
Occupational Health Project
University of Maryland
Baltimore, MD
Howard M. Kipen, MD
Department of Environmental
and Community Medicine
University of Medicine and
Dentistry of New Jersey
Piscataway, NJ
Kathleen Kreiss, MD
Department of Medicine
National Jewish Center for Immunology
and Respiratory Medicine
Denver, CO
Steven Markowitz, MD
Department of Community Medicine
Environmental and Occupational
Medicine
Mount Sinai School of Medicine
New York, NY
Steven McCurdy, MD
Department of Medicine
School of Veterinary Medicine
University of California at Davis
Institute of Toxicology and Environmental Health
Davis, CA
Linda Rosenstock, MD
Department of Medicine
School of Medicine
Harborview Medical Center
University of Washington
Seattle, WA
Rosemary K. Sokas, MD
Department of Medicine
Division of Occupational and Environmental
Medicine
School of Medicine and Health Sciences
George Washington University
Washington, DC
Nancy L. Sprince, MD
Department of Preventive Medicine
and Environmental Health
University of Iowa
Iowa City, IA
Mark J. Utell, MD
Environmental Health Sciences Center
School of Medicine and Dentistry
University of Rochester Medical Center
Rochester, NY |
The E/OM Academic Award program is an integral part of NIEHS's emphasis on clinical research and prevention and intervention strategies. Moving research results from "laboratory to bedside" has been a recurring theme. Recently, NIEHS joined with the University of North Carolina School of Medicine and Duke University Medical Center in an agreement that allows NIEHS staff to collaborate with university researchers at university clinical research units funded by the National Institutes of Health, in effect giving NIEHS a clinical center and giving the universities greater access to NIEHS laboratories and staff scientists. NIEHS is also funding a clinical trial at a number of centers around the country to study succimer, a therapeutic drug for lead toxicity.
"Ultimately, the public must rely on physicians, and especially those in primary care, to carry the benefits of environmental health science research to patients," said Kenneth Olden, NIEHS director. "For a very modest investment, we are reaching out to class after class of students in medical schools, through their faculty, and preparing them to make a rapid transfer of research advances to detect, treat, and prevent environmentally related diseases and dysfunctions." The relatively low cost of the widespread benefits is cost effective in a time of tight budgets. As a condition of the E/OM Academic Award grants, awardees meet once a year to exchange ideas, methods, and program evaluations.
NIEHS encourages faculty grantees at the universities to adapt their projects to the particular institutional characteristics and needs of each university, and the grantees have responded with a diversity of approaches. A grantee at the Mount Sinai School of Medicine in New York City, for example, is providing instruction to students and residents within existing courses and clinical seminars. Three elective courses are also offered in coordination with the Mount Sinai summer elective program for medical students, as well as a mini-course series of lectures offered within a primary care resident lecture series. The Mount Sinai program has emphasized the development of lecture and seminar material to strengthen their efforts because they have found that faculty are more likely to incorporate teaching environmental and occupational medicine in existing courses and clinical settings if high-quality curriculum material is available.
Another key effort has been coordinated by Mark R. Cullen at Yale and his colleague Linda Rosenstock at the University of Washington, where a new comprehensive test is nearing completion that will, according to Cullen, "greatly enhance access to specialty knowledge of the field." Cullen points out that the research program in environmental medicine has broadened to integrate new aspects of molecular biology into existing clinical and epidemiogical components.
At some institutions, teaching techniques have been adapted to the needs of the program. James P. Keogh, of the University of Maryland, reports that the sophomore occupational/environmental medicine course piloted the exclusive use of a technique called small-group, problem-based learning, which pairs a small group of students with faculty mentors.
Said Keogh, "We found that students can learn technical content and problem-solving skills by participating in an active learning experience. . . . This approach helps with the curricular goal of creating lifelong learners."
One of the major tools in environmental and occupational medicine, especially for primary care physicians, is the enviromental and occupational history of the patient. Knowing how to compile this history is a fundamental skill for discovering which patients may be at risk for environmental and occupational diseases. Howard M. Kipen of the University of Medicine and Dentistry of New Jersey and his colleagues have developed a mnemonic to enhance recall of the critical components in taking patient histories. "We hope that eventually students will be as comfortable with this long-neglected portion of the medical encounter as they are with more traditional content," Kipen said.
The National Jewish Center for Immunology and Respiratory Medicine in Denver, Colorado, another grantee institution, has organized an official environmental/occupational medicine rotation for internal medicine students as well as a resicency program. Kathleen Kreiss of the Department of Medicine said, "The presence of the residency program and the increased curricular offerings have a ripple effect that increases awareness of environmental and occupational health issues and interest in other residents and medical students in clinical rotation."
The grant recipients are also generally involved in research that builds the knowledge base within environmental health sciences and enriches the educational experience of students in the programs at grantee institutions. For example, Steven McCurdy of the University of California at Davis is conducting occupational health studies among two groups. A study of workers in the semiconductor industry found an increasing dose-response relationship between hours spent in semiconductor fabrication rooms and upper respiratory tract symptoms, as well as musculoskeletal complaints of the hand and forearm, which he says are "likely due to repetitive motion exposures." Published studies of farm workers described respiratory disease and dermatitis, especially decreased vital lung capacity in grape workers. McCurdy conducted a pilot study of respiratory and general health among Hispanic workers in a rural Southern California community, and the results of this study are currently being analyzed.
Anne P. Sassaman, director of the NIEHS Division of Extramural Research and Training said, "Hearing firsthand from faculty conducting research enhances students' ability to interpret research results and make use of such results once students begin their practices." Sassaman added that NIEHS is also participating in a study conducted by the Institute of Medicine to explore training opportunities in nursing education and research.
For information about the NIEHS Environmental/Occupational Medicine Academic Awards, contact Annette Kirshner at NIEHS, MD 3-02, PO Box 12233, Research Triangle Park, NC 27709; (919) 541-0488, FAX (919) 541-2843.
Trihalomethanes and Colorectal Cancer
Studies conducted at NIEHS have shown that administration of certain trihalomethanes, by-products of water chlorination, and several brominated chemicals cause colorectal cancer in experimental animals. Epidemiologic studies now suggest a link between the consumption of chlorinated water and increased human risk for colorectal cancer.
Colorectal cancer is a major cause of morbidity and mortality in the United States, with an estimated 150,000 new cases and 60,000 deaths per year. In recent years there has been a tremendous burst of knowledge of the molecular events involved in the development of human colorectal cancer. Consequently, the molecular genetics of colorectal cancers are among the best understood of any human cancer. Because genetically inherited cases account for only 15% of all colorectal cancers, it is likely that both inheritance and environmental factors play important roles in the pathogenesis of this disease.
Scientists at NIEHS organized an interactive workshop last fall among researchers in environmental carcinogenesis and those studying the molecular biology of colorectal cancer to examine potential interactions between environmental factors and molecular genetics in this cancer.
At the workshop, June Dunnick, one of the workshop organizers, with Dale Sandler and Ronald Melnick and NIEHS colleague Michael R. Elwell, reviewed studies done within the Department of Health and Human Services primarily at NIEHS as a part of the National Toxicology Program. Of 435 chemicals tested in long-term rodent studies by National Cancer Institute, and later by NTP, 14 have shown some evidence for colorectal cancer in the rat. Colorectal cancer is rarely found as a spontaneous tumor in these rodent models, occurring in the historical database at an incidence of less than 0.1%. Future research will include studies to characterize the spectrum of genetic changes in colorectal cancers induced by bromodichloromethane and other brominated chemicals.
Dunnick noted, "Further research on the metabolism of brominated chemicals is needed to identify specific enzyme systems involved." She said that studies are being conducted by Robert Langenbach at NIEHS using isolated cell cultures with specific P450 isozymes to identify P450-dependent mutational changes caused by brominated chemicals that may reflect early genetic events in the multistep carcinogenic process.
Epidemiologists at the workshop recommended that epidemiology studies be expanded to geographic areas where there are high exposures to trihalomethanes and to other sources of exposure to brominated chemicals. Melnick stated that interrelating the findings from toxicology, epidemiology, and molecular biology studies will help elucidate the contribution of environmental factors in colorectal cancer.
Tsien Delivers Falk Lecture
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1993 Falk Memorial Lecture. (left to right) Lecture coordinator Elizabeth Murphy; lecturer Roger Y. Tsien; Director Kenneth Olden; Falk's widow, Gabrielle Falk; Falk's son, Donald H. Falk; and Falk's sister, Eva Wulkan. |
Roger Y. Tsien, currently professor in the Departments of Pharmacology and Chemistry at the University of California, San Diego, and an investigator of the Howard Hughes Medical Institute, gave the ninth Hans L. Falk Memorial Lecture 17 November 1993 at NIEHS. Hans L. Falk, the internationally known environmental health science authority for whom the lecture is named, was one of the first scientific staff members of NIEHS and one of its founding members and shaping forces.
In his lecture, "How Cells Compartmentalize Internal Messengers: An Imaging Perspective," Tsien discussed his work on the design, synthesis, and application of fluorescent indicators for monitoring intracellular ions and messengers such as calcium, sodium, and cyclic AMP. Using video and slides, Tsien illustrated many examples of how these fluorescent indicators can be used in understanding cell communication. He illustrated the role of calcium in the immune response by showing that a rise in calcium, viewed in real time with the fluorescent indicator fura-2, occurs in T-lymphocytes as they kill their target cells.
Using a fluorescent indicator to monitor cyclic AMP, Tsien showed that a rise in cyclic AMP is involved in memory in neuronal cells. Molecular biology can be used to introduce a sequence coding for a naturally occurring fluorescent molecule into proteins of microorganisms. Application of this technique to mammalian cells will greatly expand the use of fluorescent indicators.
How Cells Regulate Calcium
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Cell scientists. Carla M.P. Ribeiro and Gary S.J. Bird (standing) work with James W. Putney, chief of the Laboratory of Cellular and Molecular Pharmacology. |
Scientists have for some time appreciated the importance of calcium in cell biology, especially in the cellular actions of toxic substances. In the 9 December 1993 issue of
Science, James Putney of NIEHS reviewed the work from his group as well as two recent reports published in
Nature by C. Randriamampita and R. Y. Tsien and A.B. Parenkh et al. that detail breakthroughs which may lead to a better understanding of these processes.
In normal, healthy cells, the concentration of calcium in the cytoplasm is regulated within rather narrow limits and at a very low level, about 1/10,000 of the concentration in the blood. Hormones and growth factors may transiently increase this level of calcium as part of a signaling mechanism, which is important in a large variety of cellular response patterns including the signal for cells to grow or differentiate appropriately.
However, aberrant, inappropriate increases in calcium in the cytoplasm of cells can lead to cell death or to misdirected growth and oncogenesis. When hormones, growth factors, and other chemicals regulate cell calcium, they do so by regulating the release of calcium from intracellular organelles and also by regulating the flow of calcium across the plasma membrane of the cell. Although the molecular basis of regulating calcium release from intracellular organelles is known, the mechanism regulating calcium flow across the plasma membrane has been a mystery.
In 1991, Putney and his collaborators in the NIEHS Laboratory of Cellular and Molecular Pharmacology published circumstantial evidence that a signal is somehow sent to the plasma membrane from the endoplasmic reticulum of cells, which activates the plasma membrane calcium inflow mechanism. Putney and Gary S. Bird, also of NIEHS, have found evidence that a small regulatory protein, called a G-protein, plays some obligatory role in this regulatory mechanism signaling. The specific G-protein involved has not been identified yet, but Putney finds it interesting that the genes coding for a number of these small G-proteins have been shown to be precursors for oncogenes.
The two Nature reports provide the first direct evidence for the small, diffusible messenger molecule that Putney's earlier work predicted. In keeping with Putney's findings, this small messenger could be a small G-protein, or it could be an even smaller molecule.
Says Putney, "These findings may herald the advent of a new era of intracellular endocrinology. This may involve signaling pathways occurring in the cytoplasm of cells with a complexity similar to that of the well-characterized endocrine system at the organism level. Clearly, an understanding of this cytoplasmic endocrinology will provide new insights into the cellular actions of hormones and growth factors, as well as cellular toxins."
NTP Expands Mission through Grants
The National Toxicology Program, established in 1978, coordinates toxicological studies within the Department of Health and Human Services. Although much of NTP's visibility has been tied to its two-year rat and mice studies as well as other, short-term studies, NTP has always had a vigorous program to develop new, better, and more rapid ways to study toxicity. Until recently, this research was done by NIEHS staff or through contractors, but now NTP is expanding by using the NIEHS grant program to bring university and other scientists outside government into the NTP effort.
The first NIEHS/NTP initiative using the grant mechanism was announced in the October 29 issue of the NIH Guide for Grants and Contracts. A request for applications titled, "Toxic Substance Effects on Developmental Gene Expression," was announced to stimulate research into how environmental agents alter the basic process of development and contribute to birth defects in humans. When awarded, these will be the first grants specifically designed to fulfill the NTP mission.
This particular request for applications is the outgrowth of a series of workshops on molecular and cellular mechanisms of early mammalian development that was sponsored by NIEHS. The workshops provided a forum in which developmental biologists reviewed and discussed advances in their basic research field with genetic toxicologists, developmental toxicologists/ teratologists, and human embryologists/ fetal pathologists to provide a framework whereby these advances might be applied to an understanding of abnormal development and to further identify and prioritize key research areas. A major recommendation from these workshops was that progress in understanding the etiologies and pathogenesis of abnormal development would be vastly improved through continued communication between developmental biologists and developmental toxicologists via collaborative initiatives.
A research grant was considered to be the best vehicle to accomplish this goal and at the same time provide data relevant to the goals of the NTP. It is expected to be the first in a series of NIEHS/ NTP-sponsored requests for applications and program announcements that may cover other areas of interest to the NTP, including, for example, carcinogenicity, immunotoxicity, neurotoxicity, and pulmonary toxicity.
NAPE to Study Effect of Air Pollution on Organ Systems
The National Association of Physicians for the Environment has received support from NIEHS to initiate a program on the impacts of air pollution on body organs and systems. The program is to include a preconference meeting, a national conference, development of a document, and preparation of a physician and public education program on specific health effects including those on the brain and neurological system, ears, nose, throat, taste, smell, sinuses, gastrointestinal tract, lungs, blood, bone, kidneys, liver, heart, skin, and bladder. Emphasis will be placed on populations at significant risk, including minority populations in the inner cities, children, and seniors. Indoor air pollution will be included in the study.
Each of the interested medical specialty orgnizations is being invited to prepare, before the conference, a peer-reviewed chapter on specific organs and systems. These chapters will be compiled to develop the document, which will be widely circulated in the medical community.
For information on this effort, contact G. Richard Holt, c/o NAPE, 6410 Rockledge Drive, Suite 203, Bethesda, MD 20817-1809; (301) 571-9791, FAX (301) 530-8910.
Rodbell Receives Honor
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Martin Rodbell. |
At its 213th annual meeting, the American Academy of Arts and Sciences elected 195 new members, among them Martin Rodbell, chief of the Signal Transduction Section in the Laboratory of Cellular and Molecular Pharmacology at the NIEHS. Rodbell is internationally recognized for his discoveries regarding the proteins and mechanisms that mediate cell surface receptors of light, hormones, and a variety of chemical signals. The proteins are important both to cellular communication in plants and animals and to the development of a number of diseases. These transducers are related both in structure and function to cancer-linked oncogenes.
The academy, which includes more than 3800 fellows and foreign honorary members, was founded in 1780 by John Adams and other leaders of the new republic. It is an honorary society and interdisciplinary studies center that includes scholars and national leaders in four categories: mathematics and physical sciences; biological sciences; social arts and sciences; and the humanities. The academy conducts interdisciplinary studies of current public, social, and intellectual issues and sponsors conferences and seminars that bring together scholars and leaders whose research, experience, or knowledge can help to clarify contemporary problems and place them in perspective.
Last Update: August 21, 1998