ASKING THE WHY QUESTIONS: A CAREER IN SCIENCE Margaret M. Heitkemper Department of Biobehavioral Nursing and Health Systems, Department of Biobehavioral Nursing and Health Systems, Divisions of Gastroenterology, School of Medicine, University of Washington, Seattle, WA, USA.
This paper describes the career path of one woman scientist and identifies the factors that promote a productive and rewarding career. Factors include a strong personal interest in the area of study, mentorship at all stages of development, collaborative relationships with colleagues in and beyond one’s discipline, and family and social support. A career focused on understanding the role of stress in gastrointestinal distress is described.
Key Words: career, female scientist, gastroenterology, mentorship, stress (Kaohsiung J Med Sci 2010;26(6 Suppl):S22–7)
To be asked to reflect on one’s career is a true honor. A career in science is a life-long journey. For me, this journey began quite early when I received a biology set as a Christmas gift at the age of 8 years. This kit included a microscope, tools for dissection, and a preserved frog. As a teenager volunteering and then working at a local hospital, my career interests drifted to providing care for individuals and families with health problems, and ultimately a career in health care. The practical realities of college tuition and family expectations led me to embark on an undergraduate education in nursing, but always with the thought that this would be the first step in a life-long journey. During my undergraduate program at Seattle University, I was re-introduced to science through courses in chemistry, microbiology and physiology.
Received: Dec 30, 2009 Accepted: Jan 5, 2010 Address correspondence and reprint requests to: Professor Margaret M. Heitkemper, Department of Biobehavioral Nursing and Health Systems, Divisions of Gastroenterology, School of Medicine, University of Washington, NE Pacific St. Box 357266, Seattle, WA 98195, USA. E-mail:
[email protected]
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However, the possibility of merging my professional identity as a nurse with that of a scientist did not take hold until I was a graduate student (Masters level) at the University of Washington. There, I had the unique opportunity to be mentored by two School of Nursing faculty members (Drs Sue Donaldson and Barbara Hansen) who held PhDs in physiology and biophysics. Both had managed to take questions from their clinical experiences as nurses and answer them in the laboratory. In turn, their laboratory findings helped to inform the clinical care that they provided to patients and their family members. This was the career model to which I aspired. However, it was clear that additional education and preparation were essential to make this a reality.
WHY GASTROINTESTINAL (GI) PROBLEMS? Since the time of Captain William Beaumont, a United States Army surgeon serving during the early to mid19th century, evidence has existed about the relationship of stress to increases in gastric acid secretion. Kaohsiung J Med Sci June 2010 • Vol 26 • No 6 Suppl © 2010 Elsevier. All rights reserved.
Asking the why questions: a career in science
He described the changes in the gastric mucosa of a French trapper, Alexis St. Martin, in response to food and liquids but also in the context of various emotions (e.g. anger) [1]. Extending this work on the roles of emotions and stress were physiologists Drs Walter Cannon and Hans Selye, both pioneers in describing the adverse effects of physical and psychological stress and GI pathology [2,3]. It is important in science, as in any field, to acknowledge the past and to read the early works in one’s area of research. For me, the link between the mind and the GI tract was more personal. My mother and grandfather had both been diagnosed with peptic ulcer disease early in their adult lives. At that time, ulcers were thought to be primarily associated with psychological distress. The common belief was that simply reducing your stress and eating bland foods would decrease the probability of developing an ulcer. Thus my desire to study GI function and stress was directly linked to early experiences in helping my mother as well as my patients understand that selfmanagement strategies, including diet and relaxation, could help reduce GI distress. It was still a decade later before links between the bacterium Helicobacter pylori, non-steroidal anti-inflammatory drugs and ulcer formation would be established.
THE IMPORTANCE OF MENTORSHIP Creating a balance between career and family life is crucial for women and men in science. For me, the pursuit of a doctoral degree necessitated relocating 1,700 miles from my family and more importantly, my husband. Driving across the United States from Seattle, Washington to Chicago, Illinois, it was difficult not to think of the family moments I would be missing during the 4-year separation from family and friends. The encouragement of my husband and family were crucial to my ultimate success in obtaining the PhD degree I needed to answer the questions that I believed were important. During my graduate program in physiology and biophysics at the University of Illinois–Chicago, I encountered invaluable mentorship. My advisor Dr Sabath Marotta was a well-established biomedical researcher who focused on the physiological consequences of stress. Under his guidance and support, the original focus of my interest in GI function was Kaohsiung J Med Sci June 2010 • Vol 26 • No 6 Suppl
broadened to the examination of stress and its potential contribution to GI motility and activation of the hypothalamic–pituitary–adrenal axis. Working with a senior mentor passionate about bench research and health science education provided me with a balanced perspective on what my future academic life would entail. The selection of a mentor with prior experience in advancing the career of female scientists (including those with backgrounds in nursing) was also crucial. He taught me a number of skills including scientific writing and experimental design. More importantly, he led by example and demonstrated creativity, accountability, and steadfastness in tackling questions. His mentorship of me persisted long after I had left his laboratory and only ended with his death in 1996. He was the type of mentor that I aspire to be. The results of my dissertation work provided evidence that experimentally induced stress (acute and chronic) produces neurochemical changes in the developing male rat gut [4,5]. These findings would be the launching pad for work that I would do both independently and collaboratively. In addition, my graduate students would build on these initial results.
COLLABORATION IS IMPORTANT FOR SURVIVAL Following completion of my PhD, I became an Assistant Professor in the School of Nursing at the University of Washington. At about the same time, there was the creation of the National Center of Nursing Research at the National Institute of Health. This institute facilitated and funded the research conducted by doctorally prepared scientists engaged in health research. Their funding priorities included health promotion, self management, vulnerable populations, and biomarker development. This agency has provided the 25 plus years of funding needed to conduct my research. As I worked up the academic ranks, I became a Professor in Nursing and an Adjunct Professor in the Division of Gastroenterology in the School of Medicine at the University of Washington. During the early years of my academic career, I extended the basic research I had started as a predoctoral graduate student. In particular, I delved further into the effects of stress, and in particular, thyrotropin releasing hormone on GI motility in a developing rat model. At the University S23
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of Washington, I found a new mentor in Dr Akira Horita, a neuropharmacologist in the Department of Pharmacology. Dr Horita provided expertise in the design of studies focused on assessing the links, in particular the neurochemical serotonin and its receptors, between the brain and peripheral organ systems such as the GI tract. He was among the first to observe that the administration of thyrotropin releasing hormone intracisternally resulted in rapid intestinal transit in rabbits [6]. Through work in his laboratory, I was able to develop additional skills to keep pace with rapid advances in research technology. Within the School of Nursing I was fortunate to have colleagues including Drs Nancy Woods and Joan Shaver and the facilities of the Center for Women’s Health Research (funded by the National Institute of Health). They consulted with me on the clinical implications of my work related to stress. For example, why were women more likely to experience symptoms such as abdominal pain when stressed? What is the physiological link between reproductive hormones such as estrogen and progesterone and GI symptoms (pain, bloating and constipation) in women? Together, we designed studies to examine healthy women of menstruating age with and without dysmenorrhea, and later, women with a specific diagnosis of irritable bowel syndrome (IBS) [7]. At about the same time, my colleague Dr Monica Jarrett, a nurse with a PhD in psychology, and I began a collaboration that has lasted over 20 years as we have worked to unravel the underpinnings of GI symptom experiences of both men and women.
WHY STUDY IBS? IBS is a common chronic functional bowel disorder [8,9]. The impact of IBS has been measured in the significant amount of health care resources used, for example, 8–10 doctor visits, 5 million prescriptions per year [10,11]. Excess surgery is among the health care events related to a diagnosis of IBS [12,13]. There are numerous published reports about the negative impact of IBS on quality of life, as well as work and school performance [14,15]. IBS remains a symptombased diagnosis that affects primarily young to middleaged adult women [16]. IBS is characterized by a constellation of GI symptoms outlined in the Rome III criteria. These include abdominal pain relieved S24
by bowel movement or associated with changes in stool consistency for at least 3 days per month. It has been suggested that IBS is a multi-component disorder that is characterized by dysfunction in GI motor activity, visceral sensation, inflammation/permeability, autonomic nervous system imbalance, and/or the processing of internal and external information by the central nervous system. Given the range of bowel pattern characteristics and other symptoms, it is not surprising that different etiologies may produce a variety of reports of GI and extra-intestinal symptoms. The challenge in the treatment of IBS is identifying subgroups of patients most likely to benefit from promotility, gut-flora-targeted (e.g. probiotics), behavioral, anti-anxiety and/or antinociceptive therapy.
WHY STUDY WOMEN WITH IBS? In the US and other Western industrial countries, more women than men seek health care services for IBS. Studies from Asian countries provide equivocal evidence for a gender difference in IBS, that is, some demonstrate a female predominance [17,18] while others do not [19,20]. Gender differences exist in types of GI symptoms (e.g. women report greater problems with constipation while men more frequently report diarrhea) as well as other extra-intestinal symptoms such as poor sleep, fibromyalgia, and chronic fatigue. Dr Lin Chang from University of California, Los Angeles and I recently conducted a systematic review of the published literature related to gender and IBS [21]. In studies with male and female rats, my colleague Dr Eleanor Bond and I have described the effects of estrogen and progesterone on basal motility and intestinal transit, as well as in response to thyrotropin releasing hormone [22]. We have established that the presence of estrogen and progesterone influences animal gut motility response to stress. These findings have informed us as we have considered the effects of the menstrual cycle on bowel function and symptoms in women with IBS. These findings have been disseminated in the published literature as well as through national and international presentations [23–47]. Our studies have established that IBS symptoms (1) are exacerbated at menses; (2) co-exist with other functional somatic and visceral pain symptoms; (3) are more severe/frequent in women with comorbid anxiety and depression; (4) are exacerbated by acute Kaohsiung J Med Sci June 2010 • Vol 26 • No 6 Suppl
Asking the why questions: a career in science
stress; (5) are associated with higher levels of selfreported chronic stress and reduced quality of life; (6) vary by autonomic nervous system balance indicators and symptom severity; (7) are linked to sleep quality; and (8) are characterized by neuroendocrine differences. Our current studies are focused on explaining pain-related mechanisms involved in women with IBS. The autonomic nervous system provides the major linkage between the gut and the brain and remains a continued focus of our work.
THE NEED FOR INTERDISCIPLINARY AND TRANSLATIONAL RESEARCH As this program of research has evolved over the past 25 years, it has taken several twists and turns. The types of questions that were asked have varied because our findings, as well as others have continued to point us in different directions. Often such explorations mandated that we develop new collaborators with expertise needed to answer the questions. Our team grew to include psychiatrists, gastroenterologists, psychologists with expertise in behavioral therapy, and pediatricians. These collaborations have taken us from the bench to the clinic and back to the bench. Based on earlier descriptive work, we have designed and implemented two randomized clinical trials of behavioral therapy for women with IBS [36,47]. We tested a comprehensive intervention including diet instruction and cognitive behavioral therapy, delivered either in person or primarily via the telephone, which reduced GI symptom distress and enhanced quality of life in adults with IBS. At this time, we are about to launch a clinical trial with a probiotic preparation to compare its effectiveness relative to behavioral therapy. The benchwork component of our studies has moved from measures of stress hormones to collaboration with a geneticist and measures of genetic polymorphisms involved in the regulation of serotonin and catecholamines [40,46]. For example, specific polymorphisms in the serotonin reuptake transporter protein are associated with psychological distress in IBS patients. Our current pursuit of a biomarker for symptom vulnerability entails the use of mass spectroscopy and proteomics. The long range goal of this work is to determine those individuals most susceptible for development of chronic pain, as well as those Kaohsiung J Med Sci June 2010 • Vol 26 • No 6 Suppl
most likely to respond to behavioral management approaches.
WOMEN AND SCIENCE CAREERS In the early 1990s, the National Institute of Health established the Office of Research in Women’s Health to focus on enhancing health science in areas unique to women. In addition, one important mission of this institution is to develop opportunities and support for recruitment, retention, re-entry, and advancement of women in biomedical careers. In the United States, women make up a growing percentage of students who train to become biomedical scientists. Today, female scientists are as competitive as men in obtaining research grants at all career stages. However, trends illustrate that the career attrition of women is disproportionate to that of their male counterparts. If these trends continue, we may experience a shortage of biomedical scientists in the near future. The attrition of women from scientific career paths represents a crucial loss of intellectual capital for biomedical research. The key to solving this problem is to identify what are the challenges and barriers for women in science careers. More importantly, it is imperative that we understand the keys to success. First, it is clear that women face many of the same work life challenges as men, such as the balance of teaching with research, competing for finite resources, disseminating findings in peer-reviewed journals, and ultimately achieving promotion and tenure. For many women, there are the additional challenges of balancing family life, including care of children and parents. For many, the characteristics of a successful scientific career include a sense of personal satisfaction, intellectual stimulation, avoidance of a sense of burnout, and well-deserved recognition. In my career, family priorities did overrule some professional activities such as work-related travel and outside engagements. Efforts were made to meld the two when possible. For example, I would take my two daughters and husband on business travel with me whenever possible. As a visiting professor to Chiang Mai University, Thailand, the entire family accompanied me for the month-long stay. Living geographically close to my extended family also facilitated my career in innumerable ways from childcare to social support. S25
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SUMMARY When reading about the careers of many stellar female scientists, I am reminded of how fortunate I have been. My career has been facilitated by thoughtful and creative individuals who readily embraced the importance of mentorship and collaboration. My work held a strong personal interest for me. However, I would be remiss in not acknowledging the long hours studying as a student, the long days and nights in the laboratory, the unavoidable time away from family, the disappointments of proposals or papers not being accepted, and at times, the frustration of dealing with academic bureaucracy. With few exceptions, these have been balanced by the satisfaction of finding answers, sharing findings with colleagues and patients, the joy of working with students, and training of the next generation of scientists.
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ACKNOWLEDGMENT I would like to thank the National Institute for Nursing Research (NINR) at the National Institutes of Health for their long-standing support of my research efforts.
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REFERENCES 1.
2. 3. 4.
5.
6.
7.
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Beaumont W. Experiments and Observations on the Gastric Juice and the Physiology of Digestion. New York: Peter Smith, 1833. Cannon WB. Review of bodily changes in pain, hunger, fear, and rage. Am J Physiol 1930;42:322–5. Selye H. The Stress of Life. New York: McGraw-Hill, 1956. Heitkemper MM, Marotta SF. Development of neurotransmitter enzyme activity in the rat gastrointestinal tract. Am J Physiol 1983;244:G58–64. Heitkemper MM, Marotta SF. Stress and the developmental activity of gastrointestinal neurotransmitter enzymes. Res Comm Psychol Psychiatr Behav 1985;10: 241–59. Horita A, Carino MA. Centrally administered thyrotropin-releasing hormone (TRH) stimulates colonic transit and diarrhea production by a vagally mediated serotonergic mechanism in the rabbit. Pharmacol Exp Ther 1982;222:367–71. Heitkemper MM, Shaver JF, Mitchell E. Gastrointestinal symptoms and bowel patterns across the menstrual cycle in dysmenorrheic and non-dysmenorrheic women. Nurs Res 1988;37:108–13.
17.
18.
19.
20.
21.
22.
Drossman D, Corazziari E, Delvaux M, et al. Rome III: The Functional Gastrointestinal Disorders, 3rd ed. McLean, VA: Degnon Associates, 2006. Lee V, Guthrie E, Robinson A, et al. Functional bowel disorders in primary care: factors associated with healthrelated quality of life and doctor consultation. J Psychosom Res 2008;64:129–38. Brun-Strang C, Dapoigny M, Lafuma A, et al. Irritable bowel syndrome in France: quality of life, medical management, and costs: the E. coli study. Eur J Gastroenterol Hepatol 2007;19:1097–103. Spiegel BM, Kanwal F, Naliboff B, et al. The impact of somatization on the use of gastrointestinal health-care resources in patients with irritable bowel syndrome. Am J Gastroenterol 2006;10:2262–73. Lu CL, Liu CC, Fuh JL, et al. Irritable bowel syndrome and negative appendectomy: a prospective multivariable investigation. Gut 2007;56:655–60. Longstreth GF, Yao JF. Irritable bowel syndrome and surgery: a multivariable analysis. Gastroenterology 2004; 126:1665–73. Cremonini F, Talley NJ. Irritable bowel syndrome: epidemiology, natural history, health care seeking and emerging risk factors. Gastroenterol Clin N Am 2005;34: 189–204. Faresjo A, Grodzinsky E, Johansson S, et al. A populationbased case control study of work and psychosocial problems in patients with irritable bowel syndrome— women are more seriously affected than men. Am J Gastroenterol 2007;102:371–9. Hammer J, Talley NJ. Value of different diagnostic criteria for the irritable bowel syndrome among men and women. J Clin Gastroenterol 2008;42:160–6. Kim YJ, Ban DJ. Prevalence of irritable bowel syndrome, influence of lifestyle factors and bowel habits in Korean college students. Int J Nurs Stud 2005;42: 247–54. Lu CL, Chang FY, Chen CY, et al. Significance of Rome II-defined functional constipation in Taiwan and comparison with constipation-predominant irritable bowel syndrome. Aliment Pharm Ther 2006;4:429–38. Han SH, Lee OY, Bae SC, et al. Prevalence of irritable bowel syndrome in Korea: population-based survey using the Rome II criteria. J Gastroenterol Hepatol 2006; 21:1687–92. Gwee KA, Wee S, Wong ML, et al. The prevalence, symptom characteristics, and impact of irritable bowel syndrome in an Asian urban community. Am J Gastroenterol 2004;99:924–31. Heitkemper MM, Chang L. Do fluctuations in ovarian hormones affect gastrointestinal symptoms in women with irritable bowel syndrome. Gend Med 2009;6: 152–67. Bond EF, Heitkemper MM, Perigo R. Gastric emptying and gastric intestinal transit in rats with varying ovarian hormone status. Nurs Res 1996;45:218–24. Kaohsiung J Med Sci June 2010 • Vol 26 • No 6 Suppl
Asking the why questions: a career in science 23. Heitkemper MM, Jarrett M. Pattern of gastrointestinal and somatic symptoms across the menstrual cycle. Gastroenterology 1992;102:505–13. 24. Heitkemper MM, Charman A, Shaver J, et al. Self-report and somnographic measures of sleep in women with irritable bowel syndrome. Nurs Res 1998;47:270–7. 25. Heitkemper MM, Burr R, Jarrett M, et al. Evidence for autonomic nervous system imbalance in women with IBS. Digest Dis Sci 1998;43:2093–8. 26. Jarrett M, Heitkemper MM, Cain KC, et al. Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Digest Dis Sci 2000; 45:952–9. 27. Heitkemper MM, Jarrett M, Taylor P, et al. Sexual and physical abuse in women with irritable bowel syndrome. Nurs Res 2001;50:15–23. 28. Burr RL, Heitkemper M, Jarrett M, et al. Comparison of autonomic nervous system indices base on abdominal pain reports in women with irritable bowel syndrome. Biol Res Nurs 2000;2:97–196. 29. Heitkemper M, Jarrett M, Cain KC, et al. Autonomic nervous system function in women with irritable bowel syndrome. Digest Dis Sci 2001;46:1276–84. 30. Motzer S, Jarrett M, Heitkemper M, et al. Natural killer cell function in women with and without irritable bowel syndrome. Biol Res Nurs 2002;4:31–42. 31. Heitkemper M, Cain K, Jarrett ME, et al. Symptoms across the menstrual cycle in women with irritable bowel syndrome. Am J Gastroenterol 2003;98:420–30. 32. Jarrett M, Burr RL, Cain KC, et al. Anxiety and depression influence autonomic nervous system function in women with irritable bowel syndrome. Digest Dis Sci 2003;48:386–94. 33. Burr R, Motzer S, Cowan M, et al. LOGIT50: A nonlinear transformation of pNN50 with improved statistical properties. J Electrocardiol 2003;36:41–52. 34. Motzer S, Hertig V, Jarrett M, et al. Sense of coherence and quality of life in women with and without irritable bowel syndrome. Nurs Res 2003;52:329–37. 35. Heitkemper M, Cain K, Jarrett M, et al. Relationship of bloating to other GI and menstrual symptoms in women with IBS. Digest Dis Sci 2004;49:88–95.
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36. Heitkemper MM, Jarrett ME, Levy RL, et al. Self management for women with irritable bowel syndrome. Clin Gastroenterol Hepatol 2004;2:585–96. 37. Heitkemper M, Jarrett M, Cain K, et al. Subjective and objective sleep indices in women with irritable bowel syndrome. Neurogastroenterol Motil 2005;17:523–30. 38. Burr RL, Motzer SA, Chen W, et al. Heart rate variability and 24-hour minimum heart rate. Biol Res Nurs 2006; 7:256–67. 39. Cain K, Headstrom P, Motzer S, et al. Symptoms and quality of life in women with irritable bowel syndrome. Am J Gastroenterol 2006;101:124–32. 40. Jarrett M, Kohen R, Cain K, et al. Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome. Biol Res Nurs 2007;9: 161–9. 41. Cain K, Jarrett M, Burr R, et al. Heart rate variability is related to pain severity and predominant bowel pattern in women with irritable bowel syndrome. Neurogastroenterol Motil 2007;19:110–8. 42. Hertig VL, Cain KC, Jarrett ME, et al. Daily stress and GI symptoms in women with irritable bowel syndrome. Nurs Res 2007;56:399–406. 43. Jarrett ME, Burr RL, Cain KC, et al. Autonomic nervous system function during sleep among women with irritable bowel syndrome. Digest Dis Sci 2008;53:694–703. 44. Park HJ, Jarrett MJ, Cain K, et al. Psychological distress and GI symptoms related to severity of bloating in women with irritable bowel syndrome. Res Nurs Health 2008;31:98–107. 45. Cain KC, Jarrett ME, Burr RL, et al. Gender differences in gastrointestinal, psychological, and somatic symptoms in irritable bowel syndrome. Digest Dis Sci 2008; 54:1542–9. 46. Burr RL, Jarrett ME, Cain KC, et al. Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome. Neurogastroenterol Motil 2009;21: 1148–97. 47. Jarrett ME, Cain KC, Burr RL, et al. Efficacy of a telephone versus in-person cognitive-behavioral intervention in adults with irritable bowel syndrome. Am J Gastroenterol 2009;104:3004–14.
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