(SALT LAKE CITY) -- As a teenager just moved to Iowa from war-ravaged Germany in 1950, John M. Opitz, M.D., wanted to study developmental biology, but his "very Prussian" mother insisted he go to medical school instead.
The intervening 65 years have shown the wisdom of her insistence. A professor of pediatrics at the University of Utah School of Medicine, Opitz is one of the world's foremost authorities in medical genetics, the discipline dedicated to identifying, treating and understanding human genetic disorders, some so rare that only a handful of people worldwide are known to have them. His phone rings regularly with calls from physicians around the globe seeking information about genetic syndromes: What are the physical and biological characteristics of particular disorders? What causes them? Can they be treated?
Since beginning his medical career in the 1960s, he has defined and documented numerous genetic syndromes, more than a dozen of which bear his name, pioneered phenotype, or the analysis of the physical and biological manifestations of genetic disorders, and laid foundational work for finding genes associated with genetic disorders. In the process, he built the framework for medical geneticists worldwide to learn how to analyze phenotypes.
In the 1950s, while still a student, he rediscovered the concept of the developmental field, which comprises groups of cells that organize an embryo from an evolutionary basis by passing traits and characteristics of a species from generation to generation over thousands of years. "The developmental field is what makes a mallard a mallard and not a teal, and a teal not a mallard," Opitz says, "and because of this, a mallard and a teal can tell the differences between them, hence don't interbreed and are, by definition, different species." His introduction of the developmental field concept into medial genetics made a major contribution to understanding human malformations and malformation syndromes.
In 2011, the American Society of Human Genetics recognized Opitz's seminal contributions to medical genetics when it awarded him the organization's highest honor -- the William Allan Award, given annually to a scientist who has made far-reaching contributions to human genetics for a sustained period.
Now 81 and retired from seeing patients for failing eyesight, Opitz has gained another prestigious honor, this one from his birth country. On Dec. 3, 2016, in a ceremony in Salt Lake City, he received the Order of Merit of the Federal Republic of Germany - also called the Bundesverdienstkreuz (BVK) or Federal Cross of Merit -- the only national decoration awarded by the German government. The award recognizes those who have had a profound impact on building the relationships between Germany and other nations. Opitz has taught and conducted scholarly work in Germany and other European countries for decades and was nominated for the BVK by two esteemed German physician-colleagues, Christoph Viebahn, of the University of Göttingen, and Jürgen Spranger, emeritus chair of pediatrics at the University of Mainz.
"John is gifted with a sharp eye, utter carefulness, bedazzling memory, ability to focus on the essential facet, immense working power and incessant curiosity," Spranger says. "He has delineated so many new conditions that he had to use his patients' initials to name them."
Salt Lake City attorney Charles W. Dahlquist, II, former honorary German consul in Utah, wholeheartedly recommended Opitz for the award. "Any time scientists of Dr. Opitz's brilliance and capability work together across national borders, it builds a relationship between our two nations," Dahlquist says. "He is a wonderful representative of both the United States and Germany."
A Life Shaped By War
Born in Hamburg, Germany, near the North Sea, his life was indelibly shaped by World War II. Separated from his mother for almost seven years before and during the war, he contracted tuberculosis and spent 15 months in the isolation ward of a sanitarium. The soft-spoken Opitz remembers as a child looking out over his hometown, buildings aflame and bodies in the streets.
"One becomes a survivor," he says. "Life as a survivor is very difficult." After his father died of tuberculosis in 1941, his mother was unable to care for him in that bomb-ravaged city, so she sent young Opitz to live with his grandfather until the war was over. Finally, in 1947, he and his mother reunited and lived in Nuremburg for three years. Prior to that she had served as U.S. interpreter during the war-crimes trials. In 1950, they immigrated to Iowa City where his uncle was a professor of cello and chamber music at the University of Iowa. Opitz immediately took to his new country.
"There was something about America," he says. "Its openness and the kindness and goodness of the people - even to a child former enemy -- appealed to me."
He studied zoology at the University of Iowa under Emil Witschi, a renowned zoologist and expert in genetics, developmental biology, and evolution, and began medical school at the University of Iowa in 1955. After graduating in 1959, he began his residency and then fellowship in pediatrics at the University of Wisconsin, where he studied under Klaus Patau, Ph.D., a plant cytogeneticist, and David W. Smith, M.D., a pediatric endocrinologist considered the father of dysmorphology -- the study of structural defects, particularly congenital malformations, in people. Smith introduced Opitz to a facility in Wisconsin where severely mentally disabled children and adults lived, and shortly after that he began his life's work of learning to recognize physical and biological signs and symptoms of disorders. When patients died, he took part in the autopsies to learn the biological basis of their disorders.
At that time, in the early 1960s, Opitz devoted himself to understanding the genetic, developmental, and evolutionary factors that influence abnormal human development. This, combined with his observations of patients, says his U of U colleague John C. Carey, M.D., a medical geneticist and professor of pediatrics, allowed Opitz to begin laying the foundation for clinical genetics, delineating phenotypes and identifying syndromes, including:
- Smith-Lemli-Opitz syndrome (SLOS), a development disorder caused by a defect in the way cholesterol is synthesized, which can result in profound mental disability, learning and behavioral problems and physical malformations and maladies such as fused second and third toes or extra fingers and toes; malformations in the heart, lungs, and kidneys; microcephaly (small head), and numerous other congenital anomolies.
- Opitz G/BBB syndrome, a condition with two forms with physical malformations that include wide-spaced eyes; defects of the larynx; trachea; and esophagus; heart defects; absence of tissue connecting the left and right halves of the brain, and other defects.
- C syndrome, an extremely rare disorder in which severe mental disability is common, along with physical malformations that include a triangular shaped head, caused by the premature union of the frontal skull bones; narrow pointed forehead; flat nasal bridge; short nose; abnormalities of the ear; loose skin, and other problems.
- Opitz-Kaveggia (FG) syndrome, an X chromosome-related disorder that affects intelligence and behavior, and causes a range of physical malformations and maladies, including a large head (macroencephaly); heart defects; seizures; weak muscle tone; broad thumbs and toes; widely set eyes; abnormalities in the tissue connecting the left and right halves of the brain; small ears, and downward pointing outside corners of the eye. Only several hundred cases of FG syndrome types 1-7 have been reported worldwide.
Although he is widely known for identifying and discovering genetic disorders, Opitz, whose tall and slender figure was unmistakable as he walked the hallways of University of Utah Hospital and Primary Children's Hospital for years, says identifying genetic syndromes has never been his primary objective. "My goal simply was to care for the patients and their families."
Along with the landmark work he began in the '60s, Opitz, founded the American Journal of Medical Genetics in 1976, becoming its first editor-in-chief and remaining in that position until 2001. A highly regarded forum for scholarly analysis of phenotypes of genetic disorders, the first volume appeared in 1977. The journal was initially published quarterly, but the reception and demand for it led to monthly publication the following year.
"The seminal work of Dr. Opitz extends to the early days of the history of what we now consider clinical genetics," says Carey, who served as editor-in-chief of the American Journal of Medical Genetics from 2001 until recently. "He is unarguably a pioneer in the field."
His valuable contributions to identifying and describing genetic syndromes and diseases earned Opitz an international reputation, but his passion for medicine and science extends even further.
A keen student of the history of science, he has written about major figures such as Mary F. Lyon, an English geneticist who discovered X-chromosome inactivation -- the process that inactivates one of the two female X chromosomes in mammals and has important biological implications -- and John L. Down, the British physician who first described Down syndrome. His interest in history intertwines with a third passion, one that will benefit the U through Opitz's generosity: collecting rare historical books and documents.
Donating a Rare Collection
Opitz now is working with the U's Spencer S. Eccles Health Sciences Library to donate books such as a 1725 edition of "De humani corporis fabrica" (On the Fabric of the Human Body), originally written and illustrated by Andreas Vesalius and one of the most influential books on human anatomy; an 1848 letter about barnacles written by Charles Darwin; an 1866 reprint of the first paper on Mendalian Genetics, written by Gregor Mendel, the founder of the science of genetics; and a less-than-flattering report card that Mendel signed and issued to a student for the 1860-61 school year. Dozens of other books and documents will be donated, including a 1538 Latin translation of the collected works of Aristotle.
The voluminous collection can attract scholars worldwide to the University, according to Melissa L. Rethlefsen, MLS, deputy director of the Eccles Health Sciences Library. "We're very excited," she says. "It's just really good for the University to have such a strong collection in developmental biology and the origin of the field of genetics."
The library is building a vault to house the collection in the appropriate temperature and humidity to preserve the documents. Many of the older texts are written in Latin - no problem for Opitz, a classical scholar who reads the language, and speaks Italian and his native German and English as well. With additional training in embryology, anatomy, pathology, developmental biology and other disciplines, he has skills few can avail.
Although retired from seeing patients, Opitz maintains an office at the U Department of Pediatrics while pursuing research in the subject that piqued his interest before he studied medicine: developmental biology. He still publishes and collaborates with other physicians and scientists -- he has published more than 500 peer-reviewed studies, books, chapters and other works -- quietly going about his work.
Opitz has received numerous other awards in his career, including induction into the German Academy of Science -- the Leopoldina -- and honorary degrees from universities in Bologna, Italy, Kiel and Lübeck, Germany, Copenhagen and Ohio State University. Not one to draw attention to himself, Opitz, in his own way, takes pride in receiving the BVK.
"There have been some very good people who have received the award," he quietly says.