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Philip D. Pallister of Montana

2018; Wiley; Volume: 179; Issue: 1 Linguagem: Inglês

10.1002/ajmg.a.60695

1552-4833

John M. Opitz, Pierce Mullen, Abdallah F. Elias,

Prenatal Screening and Diagnostics

During the night of Thursday to Friday, March 8 to 9, Dr. Philip D. Pallister died peacefully in his sleep at age 96 on his ranch south of Boulder, Montana, where he had been the only doctor for almost 70 years. Of course, Phil (as he was known to all) had been more, much more than that. He is the reason we now speak of the Pallister–Hall syndrome, Pallister–Killian mosaic aneuploidy syndrome, W syndrome, KGB syndrome, and more. And we do so with full respect not just for the enrichment of nosologic catalogs in clinical genetics, but for the meticulous phenotype analysis and scholarship evident in all of Phil's work worthy of emulation by all aspiring to the field of clinical genetics. “Clinical” rather than medical genetics because these eponymic conditions were once patients in Phil's consultation or private practice, not just diagnosed, but cared for, over years or decades, sometimes over generations, some even delivered by Phil. Needless to mention here that this involved exceptional gifts, drive, enthusiasm, diligence, and carefully nurtured collaborative relationships at the Universities of Washington and Wisconsin and at Montana State University in Bozeman where Phil also had adjunct appointments (Figure 1). His beginnings as a rural a GP who would become a 20th century pioneer were recounted by Phil himself at the occasion of the first Pallister–Opitz Genetics Symposium in Helena in 2015: “In 1947, I began the general practice of medicine in Boulder, MT, hoping to never live in a big city again. Boulder offered some steady income to supplement my non-existent practice; $75 a month as the County Physician and Health Officer and $125 a month to take sick call at the Montana State Training School three times a week – there were about 487 retarded patients at the institution. And there was an ocean of abysmal ignorance! But there were some answers, chief of which was solid basic medicine – histories, physicals and laboratory. And thus, we started. Soon we had defined those patients who were there because of trauma (birth or otherwise), congenital defects, various known post-infections and a mighty list of unknowns.” In 2014, at a conference held in honor of Phil Pallister at the Shodair Children's Hospital in Helena, Montana (Elias, 2014), Ian Krantz, and John Opitz retraced Phil's trajectory to become the “undisputed founder of Montana medical genetics, whose passion arose from the necessity of caring for those unable to care for themselves – now called the ‘intellectually disabled’,” then housed at the Boulder River School and Hospital in Boulder (Figure 2). They each had a name, but most were there with nameless conditions. A few of their names are now immortalized eponymically based on the initial(s) of their surnames (W syndrome, KBG syndrome, KOP translocation), but almost none of their conditions, except for a few with Down syndrome, were understood in terms of cause and pathogenesis, until Phil Pallister came along. It was the study of individuals with neurodevelopmental disorders that, in Pallister's own words “stirred my awakening to human genetics.” To be sure, medical genetics as an established clinical discipline was not even born yet. It was only in 1953, when the double helix structure of DNA was discovered by Watson and Crick. It was not until 1956, when the number of human chromosomes, previously incorrectly assumed to be 48, was correctly reported as 46. Down syndrome, today also known as trisomy 21, was found to be caused by three copies of chromosome 21 in 1959. And Victor McKusick of Johns Hopkins Hospital was just starting to pave the way for what later would become Medical Genetics. Phil Pallister became deeply interested in the study of human genetics and learned by attending conferences and reaching out to the leaders in the field. At one of these conferences, Pallister met with George Jervis, who was the first to establish the direct relationship between biochemistry and genetics in brain dysfunction by isolating the enzyme deficiency that results in the genetic disorder phenylketonuria or PKU, which if untreated causes severe intellectual disability. Pallister decided to study PKU in Montana. Returning to Boulder he soon identified more than 30 cases of PKU. His findings led to successful treatments and eventually to legislation in 1965 that made Montana the fifth state in the nation to have a PKU newborn screening law. In the spring of 1965, Phil Pallister had an encounter that would change the trajectory of his quest to bring medical genetics to Montana. He used to love telling the story and so it seems appropriate to let him tell it in his own words: “The University of Wisconsin medical school had set up a five-day course on mental retardation especially designed for physicians from our Region. The second speaker was a giant (6’ 9 1/2” at the time) who went into a “tirade” on how badly institution doctors did their work – poor histories and physicals and on and on. I stood up and interrupted him, told him I was doing screening for PKU, chromosomes etc. That I was here to learn, not be insulted and such. He then went on. I met him on the walkway at noon, stopped him, told him he gave the best lecture I had ever heard, and would he teach me …. I invited him to come to Boulder to see patients and teach and he did so three times within the next year and did so many times for many years until he joined me at Shodair and stayed 17 years.” It was with Dr. John Opitz and it was the beginning of a friendship and fruitful collaboration for 50 years. In 1975, the genetics program in Boulder was relocated at Shodair Children's Hospital. In 1979, Dr. Pallister recruited Dr. Opitz to the program at Shodair and they worked together until Phil's retirement in 1982. Together, they laid the groundwork for a uniquely successful genetic service model in Montana that continues to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation. Phil Pallister's publications in medical genetics are appended, cited again from Krantz and Opitz (2014). Strong willed as he was, Phil did not shy away from reaching out for help and consulted with leading geneticists all over the world bringing their experience to Montana. Beginning in 1966, he organized annual genetic seminars, first in Boulder and then at Shodair which in Phil's own words “included many of the world's greatest Human Geneticists and specialists in Birth Defects and Neuropathology, Ethicists and Moralists, Historians and Philosophers. These have included these 26: Jürgen Herrmann (U of Wisconsin and Private Practice) who became my son-in-law, Robert Gorlin (U of Minnesota), Harold Cross (Johns Hopkins Medical School), Jürgen Spranger (Mainz, Germany), Victor McKusick (Johns Hopkins), Arno Motulsky (U of Washington), David B. Shurtleff on Myelodysplasia (U of Washington), Charles Scott (U of Utah), Jack Stimpfling (McLaughlin Institute – Great Falls), Pierce Mullen PhD (Historian – Montana State University), Harry Waisman, Theo Gerritsen, Stan Inhorn, Jay Levy (cardiologist), June Osborne (virologist), Enid Gilbert (pathologist from U of Wisconsin), Robert Baumiller S.J. (St. Louis University), F. Clarke Fraser (Montreal University), Michael Bayles philosopher (U of Kentucky), Richard A. McCormick, S.J. (Kennedy Center for Bioethics), Philip Reilly MD and Lawyer (Yale Law School), Gordon Tuffli Endocrinologist(Madison Wisconsin), Gordon DeWald PhD (Cytogenetics Unit, Mayo Clinic Rochester), Judith Hall (U of Washington), Neuropathologists Cheng Mei Shaw and Ellsworth (Buzz) Alvord of the U of Washington and many others.” The death of Philip Pallister marks the close of an almost mythological era in our field, an era of giants who defined clinical genetics as we know it with prodigious labors, the resources of all of medicine, and highest ethical standards. Preserving access to this enlightening pioneering period in the history of medical genetics appears not sentimental but rather crucial at a time when original contributions are not cited anymore, epistemological requirements of phenotype analysis are being diminished, and an epistemological crisis in genomics has been postulated (Dougherty, 2008). For clinical genetics to stay relevant we need to rekindle our interest in the human being behind the genome. In the end, Phil Pallister's life can be traced back to a lifelong need to discern the human condition. He was present in the moment, consciously and intensely experiencing emotionality, aspirations and conflict and all the qualities that constitute our existence. He led a vita activa (active life) in the sense of Hannah Arendt (Arendt, 2013), with all its aspirations and successes, but also conflicts and failures, and ultimately confronting imperfection and mortality. How he experienced, viewed and advocated for individuals with intellectual disability might give us a window into Phil's dialogue with the human condition. As described in his own words above, his first job as a young doctor in 1947 included the position as medical director of the Montana State Training School, later called the Boulder River School and Hospital which housed close to 500 residents, most of them with cognitive disabilities. The diagnosis of disability had connotations branded by the social values and perceptions of the time, which did not explicitly grant affected individuals basic human rights, and it is almost impossible to imagine today the difficult humanitarian conditions that institutionalized people with disabilities had to live under. The training school was no exception. For Phil Pallister however, its residents were all his patients and most of all, they were human beings. Nonetheless, Pallister acted and interacted within the paradigms of his time, just as our actions today happen within the accepted norms of the culture we live in. Consequently, while he was to become one of the driving forces of a paradigm shift over the next 30 years, the development toward acknowledgement of individuals with disabilities as human beings with the same kind of aspirations, emotions, fears, and rights, was a long, complex, and often difficult road (Wood, 2017). It was also personal as he realized as a physician how little he knew about this population (it became personal again when his youngest son, Adam Pallister, was born with a developmental disability later found to be caused by a complex chromosomal rearrangement. Adam was granted an almost ideal life, at home with a loving family and pets he loves, and it stretched his limits working at home and on the ranch). The medical community displayed a pervasive lack of knowledge regarding individuals with developmental disabilities. Let us not forget that this culture of ignorance reflected the norms of the society at the time. Individuals with disabilities were tolerated with indifference at best, and at worst, were viewed as a danger to society. Nobody lobbied for those affected, and politicians did not care to fund care for people with developmental and physical disabilities. Not many scientists were interested in learning about intellectual disability. The result was a life in the shadows of institutionalization, out of sight from public and family life. There were exceptions. Phil Pallister was an exception. He did not turn away. He stayed at the institution because of his patients, because he was curious, because he wanted to better understand their challenges and how to help them. Doing so, he used symbiotic approaches that continue to live on in the Montana Genetics Program at Shodair, which he built from ground up: Compassion and Advocacy; Curiosity and Education; Leadership and Public Health; Collaboration and Research. May they serve as guides as we are developing the Genetic Medicine for Montana in the 21st century. Phil held an idealistic view of the physician as a “good person” and adopted Kant's proposition that “we must base our moral precepts on the concept of a good person who acts as if each act legislates for a moral universe.” It formed his moral compass to navigate loaded societal issues he faced as a rural county physician, such as the sequalae of the eugenics movement, deplorable state sterilization statutes, technological advances, end-of-life questions, and others. In the mid-1970s, he received a grant from the Montana Committee of the Humanities to start “formal discussions of these ethical-moral dilemmas,” which were held first in Boulder and then in 1977 at Carroll College in Helena. These public seminars brought together geneticists, philosophers, historians, theologians, and priests. One of the historians then participating was our friend and colleague Pierce Mullen of Montana State University who has joined us in paying tribute to Phil. Over his lifetime, Phil became an outspoken, frequently uncompromising and inconvenient voice, an advocate for his patients, supporting parents' grassroots efforts including the Montana Association for Retarded Children, whose efforts helped pass legislation that created special education classes in Montana's public schools in 1955. Gradually, and with the help of many, views and attitudes about people with disabilities in Montana improved. With Phil we lost a true giant of medical genetics, a friend, and a good person.