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Special Communication  |   September 2018
The One Health Initiative as a Basis for Research Development in the Department of Pharmacology at Midwestern University
Author Notes
  • From the Department of Pharmacology at the Midwestern University/Chicago College of Osteopathic Medicine in Downers Grove, Illinois. 
  • Financial Disclosures: None reported. 
  • Support: None reported. 
  •  *Address correspondence to Walter C. Prozialeck, PhD, Department of Pharmacology, Midwestern University/Chicago College of Osteopathic Medicine, 555 31st St, Downers Grove, IL 60515-1235. Email: wprozi@midwestern.edu
     
Article Information
Cardiovascular Disorders / Emergency Medicine / Medical Education / Preventive Medicine
Special Communication   |   September 2018
The One Health Initiative as a Basis for Research Development in the Department of Pharmacology at Midwestern University
The Journal of the American Osteopathic Association, September 2018, Vol. 118, 610-616. doi:https://doi.org/10.7556/jaoa.2018.135
The Journal of the American Osteopathic Association, September 2018, Vol. 118, 610-616. doi:https://doi.org/10.7556/jaoa.2018.135
Web of Science® Times Cited: 1
Abstract

The One Health Initiative focuses on the complex relationships among the health of humans, animals, plants, microbes, and the environment. There are dynamic and delicate balances among these various elements, and disruption of these elements can have adverse effects on human health. Over the past 5 years, the Department of Pharmacology at the Midwestern University/Chicago College of Osteopathic Medicine has used the One Health Initiative as a framework for the growth and development of ongoing research programs in the area of environmental toxicology. As described in this article, this One Health approach has been successful, as evidenced by increases in the number of publications and level of grant-seeking activity by department faculty. With its emphasis on holistic patient care, the osteopathic medical profession is well positioned to be a leading advocate for the One Health Initiative.

One of the greatest challenges in osteopathic medical education and practice involves the fostering of research activities within the profession. Research is required in preclinical and clinical education and in postgraduate training programs.1,2 With the agreement to establish a single accreditation system for graduate medical education through the Accreditation Council for Graduate Medical Education, osteopathic medical students will need more opportunities to engage in research to competitively match against students from research-oriented allopathic programs. In this environment, leaders of the American Osteopathic Association and many of the individual colleges of osteopathic medicine (COMs) and osteopathic postdoctoral training programs are attempting to foster the growth of research programs.3,4 Over the years, the topic of increasing research and scholarly activity has been the subject of several extensive reviews and commentaries.3,5-9 Some of the major problems in expanding research at many COMs include the relatively small size of the faculty,6,10 a primary emphasis on teaching,6,10 a lack of research culture or infrastructure,3,6 and a lack of incentives for faculty to engage in research.6 Schools have implemented different strategies to address these issues, and, although some have been successful, many COMs still struggle in this area.3,5,8 
In the current report, we describe the One Health Initiative, which focuses on the complex relationships among the health of humans, animals, plants, microbes, and the environment.11 There are dynamic and delicate balances among these elements that, if disrupted, can have adverse effects on human health. By emphasizing research in this area over the past 5 years, the Department of Pharmacology at the Midwestern University/Chicago College of Osteopathic Medicine (MWU/CCOM) has managed to grow its research program, as evidenced by an increase in the number of publications, level of extramural funding, development of research collaborations, grant-seeking activity, and participation in regional, national, and international scientific meetings. The experiences at MWU/CCOM could serve as a model for growing One Health–focused research in other COMs. 
History of MWU/CCOM and Its Tradition of Research
Founded in 1900, MWU/CCOM is one of the oldest COMs. Over the years, it has had a strong record of achievement in the 4 major areas of medical education (ie, teaching, service, patient care, and research).4 In the early 1990s, MWU/CCOM began an era of marked growth and expansion that resulted in the creation of MWU and the establishment of the Chicago College of Pharmacy, the College of Health Sciences, the College of Dental Medicine-Illinois, and the Chicago College of Optometry. During the same period, the university developed a sister campus in Glendale, Arizona, that now includes a wide variety of academic programs that are similar to those at the original campus in Downers Grove, Illinois. 
Although MWU emphasizes quality teaching in all of its academic programs, research and scholarly activity are also expected and encouraged. Faculty are expected to advance knowledge in their fields of expertise, and evidence of research productivity weighs heavily in faculty rank and tenure decisions.12 Through the 1990s, MWU/CCOM had a very strong track record of research productivity, evidenced by the number of faculty publications and level of grant-seeking activity. However, as happened at most COMs, the NIH funding crisis of the early 2000s had a negative impact on research activities in MWU/CCOM, including the Department of Pharmacology.3 Consequently, the Department of Pharmacology and MWU/CCOM as a whole began seeking strategies to grow research programs. One of the key strategies involved the adoption of the One Health Initiative. 
Understanding the complex interactions among humans, animals, and the environment is central to the One Health Initiative. For example, Edwards et al13 demonstrated the complexity of these relationships through an incident of lead poisoning that occurred in 2010, when elevated lead exposure in rural communities in northwestern Nigeria resulted in the death of an estimated 400 children younger than 5 years in a 12-month period. Before the children became ill, waterfowl began to die in great numbers. Along with summarizing the toxicodynamics and the neurotoxic effects of lead in the developing central nervous system, the review13 highlighted the use of animals to monitor lead environmental contamination and exposure. 
One Health Research in the Department of Pharmacology
In 2013, the MWU Leadership Team announced the goal of integrating the One Health Initiative into the research, teaching, and service activities of MWU. Each academic department and program was asked to develop and implement plans to achieve this goal. The Department of Pharmacology was well positioned to embrace the One Health Initiative as a focus for research because several senior faculty members (including W.C.P. and J.R.E.) had long-standing research projects that focused on areas related to environmental toxicology, which is an area of research that reflects many One Health concepts. Other senior pharmacology faculty members had valuable expertise in the areas of cardiovascular pharmacology and molecular biology, particularly issues related to the effects of environmental exposures on cardiovascular and organ system function, which could be readily applied to One Health themes. 
Moreover, the growth of new academic programs, such as dental medicine and optometry, provided an opportunity to add faculty with research interests and expertise. Between 2013 and 2014, the Department of Pharmacology recruited 2 additional faculty members, which brought the total roster to 7 full-time equivalent faculty members. These 2 new faculty members were specifically recruited for the research interests and expertise they could bring to the One Health Initiative. The Table lists the current roster of pharmacology faculty and a general description of their primary research interests. 
Table.
Department of Pharmacology Faculty Members at the Midwestern University Chicago College of Osteopathic Medicine and Their Primary Research Interests
Faculty Research Area
Walter C. Prozialeck, PhD Mechanisms and biomarkers of cadmium toxicity; mechanisms of chemically induced nephrotoxicity
Alejandro M.S. Mayer, PhD Immunopharmacology and immunotoxicology of marine natural products
Jacob D. Peuler, PhD Vascular pharmacology; pharmacologic regulation of smooth muscle function
Michael J. Fay, PhD Molecular regulation of cancer; role of micro RNA in cancer and toxic injury
Joshua R. Edwards, PhD Etiology of hyperglycemia and hyperinsulinemia resulting from exposure to the environmental toxicant cadmium
Phillip G. Kopf, PhD Role of environmental pollutants in the development of cardiovascular disease
Kirk E. Dineley, PhD Role of metals in neurologic and endocrine pathophysiology
Table.
Department of Pharmacology Faculty Members at the Midwestern University Chicago College of Osteopathic Medicine and Their Primary Research Interests
Faculty Research Area
Walter C. Prozialeck, PhD Mechanisms and biomarkers of cadmium toxicity; mechanisms of chemically induced nephrotoxicity
Alejandro M.S. Mayer, PhD Immunopharmacology and immunotoxicology of marine natural products
Jacob D. Peuler, PhD Vascular pharmacology; pharmacologic regulation of smooth muscle function
Michael J. Fay, PhD Molecular regulation of cancer; role of micro RNA in cancer and toxic injury
Joshua R. Edwards, PhD Etiology of hyperglycemia and hyperinsulinemia resulting from exposure to the environmental toxicant cadmium
Phillip G. Kopf, PhD Role of environmental pollutants in the development of cardiovascular disease
Kirk E. Dineley, PhD Role of metals in neurologic and endocrine pathophysiology
×
In addition, MWU established professional and financial incentives to reward faculty members who engage in meaningful research and obtain extramural funding for their work. The university also has a well-defined faculty development program that enables the department chair to work with faculty members to develop specific goals related to the participation of each faculty member in One Health research. Under the direction of the department chair, faculty members were encouraged to consider possible collaborative projects both within and outside the department. These discussions resulted in the rapid development of several collaborative projects with other institutions, such as Harvard University, Northwestern University, and Stroger Hospital. 
Two of these projects focused on cadmium toxicology. Cadmium is a widely disseminated environmental pollutant that affects human health, animal health, and entire ecosystems. Research that resulted from these collaborative projects is highly relevant to various aspects of environmental toxicology. For example, 2 studies14,15 that examined the effects of cadmium on rat kidneys showed that cadmium can selectively disrupt the adherens junctions between epithelial cells in the proximal tubule, and this disruption may represent a major event in cadmium-induced kidney injury. This finding may have more general implications regarding mechanisms by which cadmium affects many other organisms. For example, recent studies have shown that cadmium can disrupt cell-cell junctions in the gills of sea bass and other species that swim in cadmium-contaminated water.16,17 
Additional studies14,18,19 related to cadmium toxicology showed that 2 urinary proteins, kidney injury molecule-1 and cystatin C, may be especially useful in identifying early stages of cadmium-induced kidney injury. Results of these biomarker studies are now being applied to the biomonitoring of cadmium-exposed human populations.20,21 A more recent study22 showed that cadmium alters urinary patterns of micro RNA excretion, a major finding that has implications for both the mechanisms of cadmium toxicity and the biomonitoring of exposed populations. 
In another cadmium project, the role of cadmium in the development of diabetes and diabetic nephropathy was examined. It was shown that cadmium accumulates in the pancreas, increases blood glucose levels, and may increase the risk of diabetes-related kidney problems.23 These findings may have major implications for human and animal health in that they could explain the link between environmental factors, such as cadmium exposure, and the development of metabolic disorders, such as diabetes. 
Another long-standing project with a One Health theme is ongoing research on marine natural products. This work has implications for many diverse areas, including Alzheimer disease and problems associated with red tides and fresh water algae blooms.24,25 One aspect of this project focused on cyanobacteria in fresh water. An increasing body of literature suggests that massive growth of gram-negative cyanobacteria in water reservoirs has become an issue of concern for both animal and human health because these photosynthetic prokaryotic organisms may produce toxins, such as cyclic hepatotoxic peptides (eg, microcystins), neurotoxic alkaloids (eg, anatoxin-a), and lipopolysaccharides, which may contaminate drinking water.26-28 From the One Health project focused on cyanobacteria in fresh water, several articles29-31 have documented the effect of cyanobacterium Microcystis aeruginosa lipopolysaccharides on rat brain microglia. 
As part of another collaborative project relevant to the One Health Initiative, one study32 examined the effects of social isolation on the cardiovascular function of prairie voles. Results showed a marked increase in the incidence of stress and endothelial dysfunction when prairie voles, which are very social animals, were denied social interactions with other voles.32 This work may have implications for the importance of social interactions in reducing risk of depression and cardiovascular disease in humans. 
The latest project to evolve from the pharmacology department's One Health Initiative involves a study regarding polybrominated diphenyl ethers (flame retardants) and bisphenol A (component of plastics).33,34 Results have shown that polybrominated diphenyl ethers and bisphenol A are powerful endocrine disruptors20,21 that alter the function of hormones and adversely affect reproductive, behavioral, and immune systems, as well as cause neurologic problems and tumors. These adverse effects can occur in both humans and animals. Preliminary results of additional studies35,36 showed that the flame-retardant chemicals alter the secretion of aldosterone and other corticosteroids in adrenal cells, which can lead to the development of cardiovascular disease. 
One Health Concepts in Teaching and Service
It should be noted that, although the primary objective of the One Health Initiative was to foster research activities, the pharmacology faculty at MWU/CCOM also began exploring ways to incorporate One Health concepts into the teaching and service missions of the department. Currently, the department offers general pharmacology coursework for MWU students in osteopathic medicine, pharmacy, biomedical sciences, physician assistant studies, and dental medicine. In addition, the department is planning the pharmacology curriculum for a new optometry program. 
While the primary focus of each course is on general human pharmacology, topics related to the One Health Initiative are integrated into each course. Each course includes a series of lectures (usually 3-4 hours) related to environmental toxicology. These lectures include discussions of a variety of environmental pollutants, such as lead, arsenic, mercury (organic and inorganic), cyanide, polychlorinated biphenyls, dioxin, carbon monoxide, sulfur dioxide, and insecticides. For each topic, the presentations include discussions of the source of these agents in the environment, their integration into the food chain and water supply, their impact on human and animal health, and appropriate interventions to ameliorate this impact. Additional topics related to animal pharmacology and zoonotic diseases are also presented. For example, coverage of opioid analgesics includes a brief discussion of idiosyncratic responses to opioids in specific species, such as cats. In addition, zoonotic diseases, such as malaria and the pork tapeworm (Taenia solium), are discussed in terms of the parasitic organism's lifecycle, routes of transmission, and pharmacologic intervention. Topics related to the use of antibiotics in agriculture and food animals are also included. During these teaching sessions, faculty members often discuss research opportunities that are available to students. 
Many of the pharmacology faculty members are heavily involved in service activities that are directly relevant to the One Health Initiative. Faculty members have served on National Institutes of Health grant application review committees and policy advisory panels that focus on issues related to xenobiotic exposures, are active members of the Society of Toxicology, and have served in significant leadership roles for various societies and programs (eg, W.C.P. served as program chairman for the 45th Annual American Osteopathic Associations Research Conference, which had a theme of “Environmental Factors in Health and Disease”). These types of service activities are in line with the One Health Initiative and will continue to be a focus of the department. Participation in these service and leadership roles have also resulted in several productive collaborations between MWU/CCOM pharmacology faculty and investigators at institutions such as Harvard University, National Cancer Institute, Northwestern University, Northern Illinois University, and Florida Atlantic University. 
Expanding the One Health Initiative
When the One Health Initiative was adopted in 2013, there were no active major grants in the Department of Pharmacology. Over the past 3 years, faculty engaged in One Health research have obtained 3 National Institutes of Health academic research enhancement award grants, and 2 additional applications for these grants have received competitive scores and may be funded. Although most of the One Health research in the Department of Pharmacology has focused on in vitro and animal models (rats, mice, voles), the projects are highly relevant to human health. The experience of the Department of Pharmacology suggests that the adoption of One Health as a central research theme can result in increased research productivity. However, we do not know whether this holds true for other institutions that have incorporated One Health concepts into their research missions. In considering this point, it is important to note that even though the term One Health is relatively new, the general concepts on which the One Health Initiative is based began to emerge more than a century ago.37-40 Many academic institutions, including at least 2 osteopathic medical schools (MWU/CCOM and the Edward Via College of Osteopathic Medicine), have incorporated One Health concepts into their research, teaching, and service activities.40 
The One Health Initiative has also provided ample opportunities for students to engage in research. Osteopathic medical students have been participating in all of the ongoing One Health research projects by pharmacology faculty. In the time since the Department of Pharmacology adopted the One Health Initiative in 2014, 32 osteopathic medical students have participated in research projects mentored by the 7 full-time faculty members. The recruitment of students often results from informal discussions among students and faculty or when faculty members meet with students at the annual “Research Day” on campus. Of the 32 students who have conducted research with pharmacology faculty members since the adoption of the One Health Initiative, 26 have been listed as coauthors on 15 major publications. 
Although many publications have described the proliferation of One Health–centered research programs39-41 and highlighted the potential benefits of such programs, we found no studies that directly examined the relationship between the adoption of One Health and the level of research productivity in a given institution. It is noteworthy that in one of the most comprehensive analyses of the effects of One Health on research outcomes, Galaz et al39 concluded that “despite widespread rhetorical support for the approach [One Health], its uptake in practice has been patchy.” In this context, our observation that adoption of the One Health Initiative provided a framework that the department followed in hiring new faculty and encouraging existing faculty to focus their research in specific areas for the growth of research in an academic department could be significant. Additional analyses are needed to determine whether such trends are evident at broader institutional levels (ie, entire colleges or universities that have emphasized One Health research). 
Conclusion
The Department of Pharmacology at MWU/CCOM has been actively engaged in the One Health Initiative, with concepts interwoven throughout the department's teaching programs, research efforts, and service activities. The strength of the department in the areas of toxicology and environmental medicine could serve as focal points in the effort to increase teaching and research programs within MWU/CCOM's One Health Initiative. The One Health Initiative provided a focus for research and eventually fostered the growth of research within the Department of Pharmacology at MWU/CCOM and could serve as a model for fostering the growth of research in the osteopathic medical community. In light of the osteopathic medical profession's holistic approach to patient care, it would make sense for One Health concepts to be integrated into osteopathic research, education, and patient care. 
Acknowledgments
We thank Laura Phelps and Vicki Sears from the MWU/CCOM Department of Pharmacology for their help in preparing the manuscript. 
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Table.
Department of Pharmacology Faculty Members at the Midwestern University Chicago College of Osteopathic Medicine and Their Primary Research Interests
Faculty Research Area
Walter C. Prozialeck, PhD Mechanisms and biomarkers of cadmium toxicity; mechanisms of chemically induced nephrotoxicity
Alejandro M.S. Mayer, PhD Immunopharmacology and immunotoxicology of marine natural products
Jacob D. Peuler, PhD Vascular pharmacology; pharmacologic regulation of smooth muscle function
Michael J. Fay, PhD Molecular regulation of cancer; role of micro RNA in cancer and toxic injury
Joshua R. Edwards, PhD Etiology of hyperglycemia and hyperinsulinemia resulting from exposure to the environmental toxicant cadmium
Phillip G. Kopf, PhD Role of environmental pollutants in the development of cardiovascular disease
Kirk E. Dineley, PhD Role of metals in neurologic and endocrine pathophysiology
Table.
Department of Pharmacology Faculty Members at the Midwestern University Chicago College of Osteopathic Medicine and Their Primary Research Interests
Faculty Research Area
Walter C. Prozialeck, PhD Mechanisms and biomarkers of cadmium toxicity; mechanisms of chemically induced nephrotoxicity
Alejandro M.S. Mayer, PhD Immunopharmacology and immunotoxicology of marine natural products
Jacob D. Peuler, PhD Vascular pharmacology; pharmacologic regulation of smooth muscle function
Michael J. Fay, PhD Molecular regulation of cancer; role of micro RNA in cancer and toxic injury
Joshua R. Edwards, PhD Etiology of hyperglycemia and hyperinsulinemia resulting from exposure to the environmental toxicant cadmium
Phillip G. Kopf, PhD Role of environmental pollutants in the development of cardiovascular disease
Kirk E. Dineley, PhD Role of metals in neurologic and endocrine pathophysiology
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