HHS Public Access Author manuscript Author Manuscript
Gastroenterology. Author manuscript; available in PMC 2016 July 19. Published in final edited form as: Gastroenterology. 2016 June ; 150(7): 1673–1677. doi:10.1053/j.gastro.2016.04.031.
Presentation of the Julius M. Friedenwald Medal to C. Richard Boland, MD, AGAF John M. Carethers and Division of Gastroenterology, Department of Internal Medicine, Department of Human Genetics, and the University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan
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Ajay Goel Center for Gastrointestinal Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas
Author Manuscript Author Manuscript Reprint requests Address requests for reprints to: John M. Carethers, MD, Department of Internal Medicine, University of Michigan, 3101 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-5368. [email protected]; fax: (734) 615-2645. Conflicts of interest The authors disclose no conflicts.
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C. Richard Boland, MD, AGAF We are extremely delighted and thrilled that the American Gastroenterological Association (AGA) Institute chose to bestow C. Richard Boland with the Julius M. Friedenwald Medal during Digestive Disease Week in San Diego, California, in May 2016. As the singular highest honor given to any AGA member, the award was established in 1941 and recognizes “an individual who has contributed significantly to the AGA and has made lifelong contributions to the field of gastroenterology.” Rick fits that description aptly not only for
Gastroenterology. Author manuscript; available in PMC 2016 July 19.
Carethers and Goel
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Author Manuscript
his groundbreaking and world-renowned research contributions to the greater understanding of the field of heritable colorectal cancer, which were largely shaped by his own family’s exposure to a devastating cancer syndrome, but also for his stellar leadership of 2 separate gastroenterology divisions and the AGA Institute. An additional dimension of his contributions to the field of gastroenterology is the multitude of trainees Rick has mentored that have furthered his and other research in the field of gastroenterology, from which both of the authors have greatly benefited, and which has led to the development of many into leaders within gastroenterology.
Upbringing and Education
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On the occasion of Rick’s installation as president of the AGA Institute in 2011, we provided an in-depth description of Rick’s upbringing and education.1 We will highlight several aspects here for context in regard to his career choice. Rick is the second eldest of 4 siblings, the son of a pediatrician who graduated from Georgetown Medical School and a homemaker who served in the women’s naval corps during World War II. Rick is the namesake of his father (the C in his name stands for Clement, which his father was called, and Rick is the shortened version of his middle name). Before Rick’s birth, his father entered military service and was sent to Italy, where he became ill with what was believed to be an ulcer. Upon his return to the United States in 1946, at the age of 25 years, it was discovered during surgery that he had a stage III colon carcinoma originating from the cecum. The surgery cured his father for another 24 years and allowed him to live and practice as a pediatrician until the age of 49 years. Rick was born in 1947 in Johnson City, New York, and grew up in nearby Endwell, a town with a population of 12,000. Rick inherited his father’s athleticism, participating in cross-country, track, and swimming. Rick graduated from Maine-Endwell High School as one of the top students in his class and wanted to pursue his passion for understanding what was inside living organisms.
Author Manuscript
Rick enrolled at the University of Notre Dame, where he would graduate magna cum laude. Rick then followed his father’s footsteps into medicine, matriculating at Yale University in 1969, alongside incredible classmates who would later have an impact on medicine, including George Lister, Bob Bucholz, Lee Goldman, Jerry Rosenbaum, David Bailey, Rick Young, and others. Rick had more of a penchant for longitudinal relationships that helped him pursue internal medicine over surgery, and his desire to help others led him to a rotation in New Mexico as a student in the Indian Health Service. His professors at Yale University (including Jim Boyer, Gerry Klatskin, and Howard Spiro) initially steered him toward gastroenterology, and this became cemented as a career choice because of his father’s cancer. In 1969, during Rick’s first year of medical school, his father became ill with 2 synchronous cancers in his colon with liver metastasis; he died in July 1970 at the age of 49 years. This event greatly influenced Rick’s career and led to his in-depth examination of his family pedigree. Without his father’s financial support, Rick completed medical school with a combination of scholarships, loans, and a Public Health Service scholarship that committed him to spend 2 years after his medical school and internship training (St Francis Hospital, Hartford, CT) with the Indian Health Service in Gallup, New Mexico. After fulfilling his Public Health Service commitment, Rick completed his residency in internal medicine at the Public Health Service Hospital in San Francisco. With input from Steve Gastroenterology. Author manuscript; available in PMC 2016 July 19.
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Sulavik, the chair of medicine during his internship, and Mark Rosenberg, the chief of gastroenterology during his residency, Rick began to craft a career path toward academic gastroenterology. He took residency electives at the University of California, San Francisco (UCSF), which allowed faculty there to get to know him; he joined the GI fellowship program in 1978, which was led by Rudi Schmid, Marv Sleisenger, John Cello, and other luminaries. He then joined the laboratory of Young S. Kim, a world-preeminent colon cancer researcher, for his second and third year of fellowship. Young’s laboratory was teeming with basic researchers interested in gastrointestinal oncology, and Rick helped train the likes of Steve Itzkowitz and Bob Bresalier and worked with others, including Peter Lance and Dennis Ahnen.
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Another great influence on Rick’s life and career was Pat, his soulmate and wife (Figure 1A). Rick met Pat after his sophomore year at Notre Dame and married her in September 1970, a few weeks after his father’s death. Rick and Pat have three daughters. Tara, the eldest, is a guidance couselor at the Cathedral Boys School in San Francisco (married to Richard Maggiotto and the mother of two of Rick’s grandsons, Elliot and Nicholas); Maureen is the director of a free women’s clinic in San Francisco (married to Will Hutchinson and the mother of Rick’s granddaughter, Camilla); and Brigid, an academic gastroenterologist at the University of California San Diego (UCSD) (married to Dr Jeremy Pettus and the mother of another of Rick’s grandsons, Cooper) (Figure 1B).
Lifelong Contributions to the Field of Gastroenterology
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In 2015, Rick published a book about his personal and family’s journey regarding the extreme presentation of cancer in his relatives. Over his career, as technology advanced, Rick used his training and dogged determination to discover the cause of his family’s cancer problem.2 The book is impressive and passionate, providing insight to the readers of what was driving Rick and understanding the toll on him and his family as he chose, developed, strategized, and grew his career, never forgetting his original mission of what he could do with his medical and research training after his father’s death.3 Rick’s 1973 Yale Medical School thesis was titled “A Familial Cancer Syndrome” and focused on his family’s pedigree and some rudimentary laboratory experimentation. In addition to Rick’s father, who had synchronous and metachronous colon cancers before 50 years of age, Rick’s paternal grandfather had colon cancer at 27 and 45 years of age; his paternal greatgrandfather also died of colon cancer. Ten of the 13 siblings in Rick’s father’s family had endometrial, ovarian, brain, colon, and stomach cancers, most before the age of 50 years. These facts ultimately drove Rick to try to understand what was happening in his family, an answer that would come decades later through the initial research of others as well as the direct discovery of the cause in his own laboratory.2 Rick’s stellar career took him from UCSF to the University of Michigan, UCSD, and then Baylor Research Institute. At UCSF, under Young Kim and before the genomic era, Rick studied colonic mucin and carbohydrate epitope changes using lectins during normal tissue differentiation and malignant transformation. He continued this line of investigation and was recruited by Tadataka Yamada to the University of Michigan in 1984, where he had multiple publications in Proceedings of the National Academy of Sciences, Gastroenterology,
Gastroenterology. Author manuscript; available in PMC 2016 July 19.
Carethers and Goel
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American Journal of Physiology, and Journal of Clinical Investigation, among others. Simultaneously and as a follow-up to his Yale thesis, he discovered the prior work of Aldred S. Warthin, a pathologist at the University of Michigan, and the ongoing work of Henry T. Lynch, an oncologist at Creighton University, regarding “cancer family syndrome” (without antecedent polyposis); he published several manuscripts regarding the natural history of what he coined “Lynch syndrome” in 1984 to recognize Henry Lynch’s remarkable observations. In the late 1980s, Rick began reading newly published articles regarding mutated oncogenes that were driving cancer formation, and he was intrigued by Bert Vogelstein’s work regarding genetic changes in colorectal cancers. He realized that genetics, not glycoproteins, were the key to the pathogenesis of colon cancer. Rick pursued a 6-month sabbatical with Andrew Feinberg, Vogelstein’s first fellow, who was a University of Michigan faculty member and Howard Hughes investigator. Rick acquired and passed on to his laboratory trainees modern genetic information and techniques that could be applied to DNA extracted from resected human colorectal cancers, and he completely changed the focus of his laboratory. This included the utilization and amplification of repetitive sequences termed DNA microsatellites, which later proved to be an extremely fortunate opportunity for understanding the key to his family’s cancer syndrome. After 3 separate research groups linked ubiquitous mutations in microsatellites, termed microsatellite instability, to some sporadic colorectal cancers as well as to a hereditary cancer syndrome that was ultimately shown to be Lynch syndrome in 1993, Rick happened to be at the forefront with his now genetically oriented laboratory and created in vitro models that corrected microsatellite instability with the whole chromosome transfer technique provided by a talented cytogeneticist, Minoru Koi. This cell model proved that the genes causing microsatellite instability, DNA mismatch repair genes, were also tumor suppressor genes, and Rick’s model continues to be relevant today to study DNA mismatch repair more than 20 years after their creation in his laboratory.
Author Manuscript
Further highlights from Rick’s research in the genomic era that spanned from the University of Michigan to UCSD and Baylor Research Institute include (1) providing a standard definition for microsatellite instability, now internationally recognized and used, to standardize studies; (2) initiating and directing studies regarding basic DNA mismatch repair function, including its recognition of altered nucleotides within DNA, and its role in reglating the cell cycle and preventing mitosis until defects are corrected; (3) initiating studies showing how 5-fluorouracil influences DNA mismatch repair function at the cellular level, which predicted its ineffectiveness for use in colorectal cancers caused by microsatellite instability; (4) demonstrating the role of DNA mismatch repair during transcription; (5) demonstrating the stoichiometry of DNA mismatch repair expression, which ultimately explains the mechanism for the attenuated phenotypes of Lynch syndrome associated with mutations in the MSH6 and PMS2 genes; (6) showing how oxidative stress can relax the activity of DNA mismatch repair; (7) developing techniques to quantify microsatellite instability in vitro; (8) discovering the etiology for microsatellite instability– low via downregulation of MSH3; and (9) identifying families that mimic Lynch syndrome and specific genes in certain families as the cause. Rick has published more than 370 papers in high-impact journals during his career (including Nature, Science, Nature Medicine, Cancer Research, Gastroenterology, Journal of Clinical Investigation, Journal of Biological
Gastroenterology. Author manuscript; available in PMC 2016 July 19.
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Chemistry, Proceedings of the National Academy of Sciences, and others), and his international contributions to this field have changed the approach to clinical practice. Although Rick has studied some other lines of investigation, his passion and major efforts have been the understanding of Lynch syndrome, its relationship to defective DNA mismatch repair, and its biomarker microsatellite instability; his research has been continuously funded for more than 37 years. His research career work earned him election into the American Association of Physicians in 2001; in 2015, he was recognized with the AGA William Beaumont Prize and honored with the Lifetime Achievement Award from the Collaborative Group of the Americas on Inherited Colorectal Cancer.
Author Manuscript
The most satisfying research that Rick or any other investigator can undertake is to answer a burning question with science that is personal. Matthew Yurgelun, then a junior at Dartmouth University, joined his Uncle Rick’s laboratory; in 8 weeks, he cloned and helped develop a polymerase chain reaction–based assay to detect the previously undetectable DNA mismatch repair gene mutation that was the cause of the cancers in Rick’s family. Thus, science completed the clinical circle that defined Rick’s familial cancer pedigree, and his fortuitious embarkment on an academic medical career many years antecedent to this discovery finally laid to rest the generations-old mystery within his family.2
Author Manuscript
We would be remiss if we did not mention Rick’s enormous clinical contributions to gastroenterology. Rick ultimately paired his research interests with his clinical interests, eventually building up one of the most impressive practices that focused on hereditary colon cancer, which allowed him to synergize translational research with his outstanding clinical skills and bedside manner. His clinical model of marrying a focused high-risk clinic with genomic research capabilities not only aided patients and their diagnosis but also served as an aspiring goal for other institutions to replicate.
Contributions to the AGA, Leadership Roles, and Mentorship
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Rick has been a member of the AGA since 1978, and he has given himself freely and completely to help advance the science and knowledge of gastroenterology for the AGA. Rick has served as chair of the Program Review Committee, chair of the Oncology Section, associate editor of Gastroenterology, chair of the Research Committee, chair of the GI Malignancy Task Force, chair of the GI Oncology Task Force, chair of the Research Subcommittee of the Public Policy and Advocacy Committee, chair of the GI Training Examination Subcommittee, and chair of the Ethics Committee, and he served on the Program Committee for the AGA-ASCO Joint Annual Meeting at its inception. He has also served on several other committees and functions for the AGA. Rick was nominated and elected vice president of the AGA Institute in 2009, became president-elect in 2010, and then served as president in 2011–2012, during which Rick advanced many items for gastroenterologists at the national level. Rick is the principal investigator on the AGA’s National Institutes of Health R25 grant, enhancing minority undergraduate and medical student exposure to investigative gastroenterology and potential future careers. In 1984, Rick was recognized as a leader by Tadataka Yamada, who appointed him GI section chief at the Ann Arbor VA 3 years out of his fellowship. Eleven years later, Rick was
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recruited by Steve Wasserman to succeed Jon Isenberg as the GI division chief at UCSD; several years after that, he was recruited by John Fordtran to Baylor Research Institute, where he intensified his focus on the laboratory. At all of the stops Rick made in his career, he gave passion and effort to grow and excel. Indeed, at the University of Michigan, Rick aided Tadataka Yamada’s drive for a new National Institutes of Health–funded GI Center grant. At UCSD, Rick helped in achieving the Cancer Center’s National Cancer Institute– designated “comprehensive” status and chaired the selection committee that brought Ed Holmes as dean and vice chancellor. At Baylor Research Institute and Baylor University Medical Center, Rick greatly enhanced the translational research capabilites and national recognition for genetic research.
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During Rick’s career, he has trained and developed outstanding researchers and mentored the creation of future leaders. The list of mentees is indeed impressive and includes multiple division chiefs, a chair of medicine, a chair of surgery, residency and fellowship directors, and key program leaders at highly respected institutions. He has trained MD and PhD investigators, gastroenterologists, pediatricians, and surgeons and guided the careers of researchers from at least a dozen countries. Rick has touched the lives of at least 63 investigators exclusive of students and residents. His laboratory has trained the likes of John Carethers4 and Ajay Goel, the authors of this communication, as well as Steve Itzkowitz, Bob Bresalier, and Matthew Yurgelun (mentioned previously, now on the faculty of Harvard Medical School), Chris Arnold, Francesc Balaguer, Dong Chang, Christoph Gasche, Mary Hawn, Sherry Huang, Mike Kochman, Luigi Laghi, Graeme Macdonald, Giancarlo Marra, Luigi Ricciardiello, Yaron Niv, Juichi Sato, Jim Scheiman, and Erica Villa, among others. He has and continues to provide mentorship and advice to many who have not directly worked in his laboratory. His mentorship has truly spread one of the tenets of the AGA: advance the science and knowledge of gastroenterology. Rick has not only advanced it, he has amplified it! He was recognized with the AGA GI Oncology Section Distinguished Mentor Award in 2011.
The Future Rick’s recognition with the Freidenwald Medal is no doubt one of the crowning achievements of Rick’s longstanding and incredible career. From his life’s investigative journey triggered by his father’s death to witnessing and experiencing technological changes that enabled him to solve the puzzle of his family required dedication and focus, and he is a remarkable role model for anyone studying medicine as a career. His drive and passion were truly palpable and forefront as the authors trained with Rick and certainly felt when reading his recent book about his journey.2
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Rick has slowly been spending more time with Pat in La Jolla, which has become the nidus for Boland clan gatherings, particularly to enjoy his 4 grandchildren. The authors suspect that this may become more full-time in the near future, because the draw of his grandchildren will be too great. Rick continues to work part-time at Baylor University Medical Center. He will continue to advise and shape many careers as well as contribute to the clinical and translational aspects of Lynch syndrome and colorectal cancer in general for many years to come. We are extremely fortunate and proud to have been trained and
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mentored by Rick, and we pass on our heartfelt enthusiasm for this high and well-deserved recognition by the AGA.
Acknowledgments Funding J.M.C. is supported by the US Public Health Service (DK067287, CA162147, and CA206010) and the A. Alfred Taubman Medical Research Institute of the University of Michigan. A.G. is supported by the US Public Health Service (CA072851, CA181572, CA184792, and CA187956). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.
References
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1. Carethers JM, Goel A. Our new AGA Institute President – C. Richard Boland, MD. Gastroenterology. 2011; 140:1675–1679. 2. Boland, CR. Cancer family: the search for the cause of hereditary colorectal cancer. Bloomington, IN: Author-House Publishers; 2015. 3. Burt RW. Print and digital media reviews. Cancer family: the search for the cause of hereditary colorectal cancer. Gastroenterology. 2016; 150:1248. 4. Carethers JM. GRG profiles: John M. Carethers. Dig Dis Sci. 2016 Feb 5. [Epub ahead of print] http://dx.doi.org/10.1007/s10620-016-4058-9.
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Figure 1.
(A) Pat and Rick Boland in May 2015, on the occasion of being recognized with the AGA William Beaumont Prize. (B) The Boland family in December 2015. From left to right, back row: son-in-law Richard Maggiotto, daughter Brigid, son-in-law Dr Jeremy Pettus, and sonin-law Will Hutchinson. From left to right, front row: daughter Tara, with grandson Nicholas Maggiotto in her lap, wife Pat with grandson Cooper Pettus in her lap, Rick, grandson Elliot Maggiotto, and daughter Maureen with granddaughter Camilla Hutchinson in her lap.
Author Manuscript Author Manuscript Gastroenterology. Author manuscript; available in PMC 2016 July 19.
Gastroenterology. Author manuscript; available in PMC 2016 July 19. Published in final edited form as: Gastroenterology. 2016 June ; 150(7): 1673–1677. doi:10.1053/j.gastro.2016.04.031.
Presentation of the Julius M. Friedenwald Medal to C. Richard Boland, MD, AGAF John M. Carethers and Division of Gastroenterology, Department of Internal Medicine, Department of Human Genetics, and the University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan
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Ajay Goel Center for Gastrointestinal Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas
Author Manuscript Author Manuscript Reprint requests Address requests for reprints to: John M. Carethers, MD, Department of Internal Medicine, University of Michigan, 3101 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-5368. [email protected]; fax: (734) 615-2645. Conflicts of interest The authors disclose no conflicts.
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C. Richard Boland, MD, AGAF We are extremely delighted and thrilled that the American Gastroenterological Association (AGA) Institute chose to bestow C. Richard Boland with the Julius M. Friedenwald Medal during Digestive Disease Week in San Diego, California, in May 2016. As the singular highest honor given to any AGA member, the award was established in 1941 and recognizes “an individual who has contributed significantly to the AGA and has made lifelong contributions to the field of gastroenterology.” Rick fits that description aptly not only for
Gastroenterology. Author manuscript; available in PMC 2016 July 19.
Carethers and Goel
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Author Manuscript
his groundbreaking and world-renowned research contributions to the greater understanding of the field of heritable colorectal cancer, which were largely shaped by his own family’s exposure to a devastating cancer syndrome, but also for his stellar leadership of 2 separate gastroenterology divisions and the AGA Institute. An additional dimension of his contributions to the field of gastroenterology is the multitude of trainees Rick has mentored that have furthered his and other research in the field of gastroenterology, from which both of the authors have greatly benefited, and which has led to the development of many into leaders within gastroenterology.
Upbringing and Education
Author Manuscript Author Manuscript
On the occasion of Rick’s installation as president of the AGA Institute in 2011, we provided an in-depth description of Rick’s upbringing and education.1 We will highlight several aspects here for context in regard to his career choice. Rick is the second eldest of 4 siblings, the son of a pediatrician who graduated from Georgetown Medical School and a homemaker who served in the women’s naval corps during World War II. Rick is the namesake of his father (the C in his name stands for Clement, which his father was called, and Rick is the shortened version of his middle name). Before Rick’s birth, his father entered military service and was sent to Italy, where he became ill with what was believed to be an ulcer. Upon his return to the United States in 1946, at the age of 25 years, it was discovered during surgery that he had a stage III colon carcinoma originating from the cecum. The surgery cured his father for another 24 years and allowed him to live and practice as a pediatrician until the age of 49 years. Rick was born in 1947 in Johnson City, New York, and grew up in nearby Endwell, a town with a population of 12,000. Rick inherited his father’s athleticism, participating in cross-country, track, and swimming. Rick graduated from Maine-Endwell High School as one of the top students in his class and wanted to pursue his passion for understanding what was inside living organisms.
Author Manuscript
Rick enrolled at the University of Notre Dame, where he would graduate magna cum laude. Rick then followed his father’s footsteps into medicine, matriculating at Yale University in 1969, alongside incredible classmates who would later have an impact on medicine, including George Lister, Bob Bucholz, Lee Goldman, Jerry Rosenbaum, David Bailey, Rick Young, and others. Rick had more of a penchant for longitudinal relationships that helped him pursue internal medicine over surgery, and his desire to help others led him to a rotation in New Mexico as a student in the Indian Health Service. His professors at Yale University (including Jim Boyer, Gerry Klatskin, and Howard Spiro) initially steered him toward gastroenterology, and this became cemented as a career choice because of his father’s cancer. In 1969, during Rick’s first year of medical school, his father became ill with 2 synchronous cancers in his colon with liver metastasis; he died in July 1970 at the age of 49 years. This event greatly influenced Rick’s career and led to his in-depth examination of his family pedigree. Without his father’s financial support, Rick completed medical school with a combination of scholarships, loans, and a Public Health Service scholarship that committed him to spend 2 years after his medical school and internship training (St Francis Hospital, Hartford, CT) with the Indian Health Service in Gallup, New Mexico. After fulfilling his Public Health Service commitment, Rick completed his residency in internal medicine at the Public Health Service Hospital in San Francisco. With input from Steve Gastroenterology. Author manuscript; available in PMC 2016 July 19.
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Sulavik, the chair of medicine during his internship, and Mark Rosenberg, the chief of gastroenterology during his residency, Rick began to craft a career path toward academic gastroenterology. He took residency electives at the University of California, San Francisco (UCSF), which allowed faculty there to get to know him; he joined the GI fellowship program in 1978, which was led by Rudi Schmid, Marv Sleisenger, John Cello, and other luminaries. He then joined the laboratory of Young S. Kim, a world-preeminent colon cancer researcher, for his second and third year of fellowship. Young’s laboratory was teeming with basic researchers interested in gastrointestinal oncology, and Rick helped train the likes of Steve Itzkowitz and Bob Bresalier and worked with others, including Peter Lance and Dennis Ahnen.
Author Manuscript
Another great influence on Rick’s life and career was Pat, his soulmate and wife (Figure 1A). Rick met Pat after his sophomore year at Notre Dame and married her in September 1970, a few weeks after his father’s death. Rick and Pat have three daughters. Tara, the eldest, is a guidance couselor at the Cathedral Boys School in San Francisco (married to Richard Maggiotto and the mother of two of Rick’s grandsons, Elliot and Nicholas); Maureen is the director of a free women’s clinic in San Francisco (married to Will Hutchinson and the mother of Rick’s granddaughter, Camilla); and Brigid, an academic gastroenterologist at the University of California San Diego (UCSD) (married to Dr Jeremy Pettus and the mother of another of Rick’s grandsons, Cooper) (Figure 1B).
Lifelong Contributions to the Field of Gastroenterology
Author Manuscript Author Manuscript
In 2015, Rick published a book about his personal and family’s journey regarding the extreme presentation of cancer in his relatives. Over his career, as technology advanced, Rick used his training and dogged determination to discover the cause of his family’s cancer problem.2 The book is impressive and passionate, providing insight to the readers of what was driving Rick and understanding the toll on him and his family as he chose, developed, strategized, and grew his career, never forgetting his original mission of what he could do with his medical and research training after his father’s death.3 Rick’s 1973 Yale Medical School thesis was titled “A Familial Cancer Syndrome” and focused on his family’s pedigree and some rudimentary laboratory experimentation. In addition to Rick’s father, who had synchronous and metachronous colon cancers before 50 years of age, Rick’s paternal grandfather had colon cancer at 27 and 45 years of age; his paternal greatgrandfather also died of colon cancer. Ten of the 13 siblings in Rick’s father’s family had endometrial, ovarian, brain, colon, and stomach cancers, most before the age of 50 years. These facts ultimately drove Rick to try to understand what was happening in his family, an answer that would come decades later through the initial research of others as well as the direct discovery of the cause in his own laboratory.2 Rick’s stellar career took him from UCSF to the University of Michigan, UCSD, and then Baylor Research Institute. At UCSF, under Young Kim and before the genomic era, Rick studied colonic mucin and carbohydrate epitope changes using lectins during normal tissue differentiation and malignant transformation. He continued this line of investigation and was recruited by Tadataka Yamada to the University of Michigan in 1984, where he had multiple publications in Proceedings of the National Academy of Sciences, Gastroenterology,
Gastroenterology. Author manuscript; available in PMC 2016 July 19.
Carethers and Goel
Page 5
Author Manuscript Author Manuscript Author Manuscript
American Journal of Physiology, and Journal of Clinical Investigation, among others. Simultaneously and as a follow-up to his Yale thesis, he discovered the prior work of Aldred S. Warthin, a pathologist at the University of Michigan, and the ongoing work of Henry T. Lynch, an oncologist at Creighton University, regarding “cancer family syndrome” (without antecedent polyposis); he published several manuscripts regarding the natural history of what he coined “Lynch syndrome” in 1984 to recognize Henry Lynch’s remarkable observations. In the late 1980s, Rick began reading newly published articles regarding mutated oncogenes that were driving cancer formation, and he was intrigued by Bert Vogelstein’s work regarding genetic changes in colorectal cancers. He realized that genetics, not glycoproteins, were the key to the pathogenesis of colon cancer. Rick pursued a 6-month sabbatical with Andrew Feinberg, Vogelstein’s first fellow, who was a University of Michigan faculty member and Howard Hughes investigator. Rick acquired and passed on to his laboratory trainees modern genetic information and techniques that could be applied to DNA extracted from resected human colorectal cancers, and he completely changed the focus of his laboratory. This included the utilization and amplification of repetitive sequences termed DNA microsatellites, which later proved to be an extremely fortunate opportunity for understanding the key to his family’s cancer syndrome. After 3 separate research groups linked ubiquitous mutations in microsatellites, termed microsatellite instability, to some sporadic colorectal cancers as well as to a hereditary cancer syndrome that was ultimately shown to be Lynch syndrome in 1993, Rick happened to be at the forefront with his now genetically oriented laboratory and created in vitro models that corrected microsatellite instability with the whole chromosome transfer technique provided by a talented cytogeneticist, Minoru Koi. This cell model proved that the genes causing microsatellite instability, DNA mismatch repair genes, were also tumor suppressor genes, and Rick’s model continues to be relevant today to study DNA mismatch repair more than 20 years after their creation in his laboratory.
Author Manuscript
Further highlights from Rick’s research in the genomic era that spanned from the University of Michigan to UCSD and Baylor Research Institute include (1) providing a standard definition for microsatellite instability, now internationally recognized and used, to standardize studies; (2) initiating and directing studies regarding basic DNA mismatch repair function, including its recognition of altered nucleotides within DNA, and its role in reglating the cell cycle and preventing mitosis until defects are corrected; (3) initiating studies showing how 5-fluorouracil influences DNA mismatch repair function at the cellular level, which predicted its ineffectiveness for use in colorectal cancers caused by microsatellite instability; (4) demonstrating the role of DNA mismatch repair during transcription; (5) demonstrating the stoichiometry of DNA mismatch repair expression, which ultimately explains the mechanism for the attenuated phenotypes of Lynch syndrome associated with mutations in the MSH6 and PMS2 genes; (6) showing how oxidative stress can relax the activity of DNA mismatch repair; (7) developing techniques to quantify microsatellite instability in vitro; (8) discovering the etiology for microsatellite instability– low via downregulation of MSH3; and (9) identifying families that mimic Lynch syndrome and specific genes in certain families as the cause. Rick has published more than 370 papers in high-impact journals during his career (including Nature, Science, Nature Medicine, Cancer Research, Gastroenterology, Journal of Clinical Investigation, Journal of Biological
Gastroenterology. Author manuscript; available in PMC 2016 July 19.
Carethers and Goel
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Chemistry, Proceedings of the National Academy of Sciences, and others), and his international contributions to this field have changed the approach to clinical practice. Although Rick has studied some other lines of investigation, his passion and major efforts have been the understanding of Lynch syndrome, its relationship to defective DNA mismatch repair, and its biomarker microsatellite instability; his research has been continuously funded for more than 37 years. His research career work earned him election into the American Association of Physicians in 2001; in 2015, he was recognized with the AGA William Beaumont Prize and honored with the Lifetime Achievement Award from the Collaborative Group of the Americas on Inherited Colorectal Cancer.
Author Manuscript
The most satisfying research that Rick or any other investigator can undertake is to answer a burning question with science that is personal. Matthew Yurgelun, then a junior at Dartmouth University, joined his Uncle Rick’s laboratory; in 8 weeks, he cloned and helped develop a polymerase chain reaction–based assay to detect the previously undetectable DNA mismatch repair gene mutation that was the cause of the cancers in Rick’s family. Thus, science completed the clinical circle that defined Rick’s familial cancer pedigree, and his fortuitious embarkment on an academic medical career many years antecedent to this discovery finally laid to rest the generations-old mystery within his family.2
Author Manuscript
We would be remiss if we did not mention Rick’s enormous clinical contributions to gastroenterology. Rick ultimately paired his research interests with his clinical interests, eventually building up one of the most impressive practices that focused on hereditary colon cancer, which allowed him to synergize translational research with his outstanding clinical skills and bedside manner. His clinical model of marrying a focused high-risk clinic with genomic research capabilities not only aided patients and their diagnosis but also served as an aspiring goal for other institutions to replicate.
Contributions to the AGA, Leadership Roles, and Mentorship
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Rick has been a member of the AGA since 1978, and he has given himself freely and completely to help advance the science and knowledge of gastroenterology for the AGA. Rick has served as chair of the Program Review Committee, chair of the Oncology Section, associate editor of Gastroenterology, chair of the Research Committee, chair of the GI Malignancy Task Force, chair of the GI Oncology Task Force, chair of the Research Subcommittee of the Public Policy and Advocacy Committee, chair of the GI Training Examination Subcommittee, and chair of the Ethics Committee, and he served on the Program Committee for the AGA-ASCO Joint Annual Meeting at its inception. He has also served on several other committees and functions for the AGA. Rick was nominated and elected vice president of the AGA Institute in 2009, became president-elect in 2010, and then served as president in 2011–2012, during which Rick advanced many items for gastroenterologists at the national level. Rick is the principal investigator on the AGA’s National Institutes of Health R25 grant, enhancing minority undergraduate and medical student exposure to investigative gastroenterology and potential future careers. In 1984, Rick was recognized as a leader by Tadataka Yamada, who appointed him GI section chief at the Ann Arbor VA 3 years out of his fellowship. Eleven years later, Rick was
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recruited by Steve Wasserman to succeed Jon Isenberg as the GI division chief at UCSD; several years after that, he was recruited by John Fordtran to Baylor Research Institute, where he intensified his focus on the laboratory. At all of the stops Rick made in his career, he gave passion and effort to grow and excel. Indeed, at the University of Michigan, Rick aided Tadataka Yamada’s drive for a new National Institutes of Health–funded GI Center grant. At UCSD, Rick helped in achieving the Cancer Center’s National Cancer Institute– designated “comprehensive” status and chaired the selection committee that brought Ed Holmes as dean and vice chancellor. At Baylor Research Institute and Baylor University Medical Center, Rick greatly enhanced the translational research capabilites and national recognition for genetic research.
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During Rick’s career, he has trained and developed outstanding researchers and mentored the creation of future leaders. The list of mentees is indeed impressive and includes multiple division chiefs, a chair of medicine, a chair of surgery, residency and fellowship directors, and key program leaders at highly respected institutions. He has trained MD and PhD investigators, gastroenterologists, pediatricians, and surgeons and guided the careers of researchers from at least a dozen countries. Rick has touched the lives of at least 63 investigators exclusive of students and residents. His laboratory has trained the likes of John Carethers4 and Ajay Goel, the authors of this communication, as well as Steve Itzkowitz, Bob Bresalier, and Matthew Yurgelun (mentioned previously, now on the faculty of Harvard Medical School), Chris Arnold, Francesc Balaguer, Dong Chang, Christoph Gasche, Mary Hawn, Sherry Huang, Mike Kochman, Luigi Laghi, Graeme Macdonald, Giancarlo Marra, Luigi Ricciardiello, Yaron Niv, Juichi Sato, Jim Scheiman, and Erica Villa, among others. He has and continues to provide mentorship and advice to many who have not directly worked in his laboratory. His mentorship has truly spread one of the tenets of the AGA: advance the science and knowledge of gastroenterology. Rick has not only advanced it, he has amplified it! He was recognized with the AGA GI Oncology Section Distinguished Mentor Award in 2011.
The Future Rick’s recognition with the Freidenwald Medal is no doubt one of the crowning achievements of Rick’s longstanding and incredible career. From his life’s investigative journey triggered by his father’s death to witnessing and experiencing technological changes that enabled him to solve the puzzle of his family required dedication and focus, and he is a remarkable role model for anyone studying medicine as a career. His drive and passion were truly palpable and forefront as the authors trained with Rick and certainly felt when reading his recent book about his journey.2
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Rick has slowly been spending more time with Pat in La Jolla, which has become the nidus for Boland clan gatherings, particularly to enjoy his 4 grandchildren. The authors suspect that this may become more full-time in the near future, because the draw of his grandchildren will be too great. Rick continues to work part-time at Baylor University Medical Center. He will continue to advise and shape many careers as well as contribute to the clinical and translational aspects of Lynch syndrome and colorectal cancer in general for many years to come. We are extremely fortunate and proud to have been trained and
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mentored by Rick, and we pass on our heartfelt enthusiasm for this high and well-deserved recognition by the AGA.
Acknowledgments Funding J.M.C. is supported by the US Public Health Service (DK067287, CA162147, and CA206010) and the A. Alfred Taubman Medical Research Institute of the University of Michigan. A.G. is supported by the US Public Health Service (CA072851, CA181572, CA184792, and CA187956). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.
References
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1. Carethers JM, Goel A. Our new AGA Institute President – C. Richard Boland, MD. Gastroenterology. 2011; 140:1675–1679. 2. Boland, CR. Cancer family: the search for the cause of hereditary colorectal cancer. Bloomington, IN: Author-House Publishers; 2015. 3. Burt RW. Print and digital media reviews. Cancer family: the search for the cause of hereditary colorectal cancer. Gastroenterology. 2016; 150:1248. 4. Carethers JM. GRG profiles: John M. Carethers. Dig Dis Sci. 2016 Feb 5. [Epub ahead of print] http://dx.doi.org/10.1007/s10620-016-4058-9.
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Figure 1.
(A) Pat and Rick Boland in May 2015, on the occasion of being recognized with the AGA William Beaumont Prize. (B) The Boland family in December 2015. From left to right, back row: son-in-law Richard Maggiotto, daughter Brigid, son-in-law Dr Jeremy Pettus, and sonin-law Will Hutchinson. From left to right, front row: daughter Tara, with grandson Nicholas Maggiotto in her lap, wife Pat with grandson Cooper Pettus in her lap, Rick, grandson Elliot Maggiotto, and daughter Maureen with granddaughter Camilla Hutchinson in her lap.
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