Homage to Victor McKusick…founding father of medical genetics and creator of the OMIM
It is hard to imagine where the field of rare disease research and treatment would be without the immense contribution of Victor McKusick, who died in July at the age of 86 years. Responsible for the development of key theories and practices that take a genetic approach as their basis, the association of specific genes with certain clinical manifestations (the genotype/phenotype relationship), theories of inheritance, the development of prenatal genetic testing, newborn screening, and the burgeoning field of gene therapy can all be traced to the initial efforts of the man who set the ball in motion.
Victor A. McKusick, M.D., University Professor of Medical Genetics at the Johns Hopkins University School of Medicine, and an international pioneer in the field of genetics research, diagnosis and treatment, was born on 21 October, 1921, along with his twin brother Vincent. One of five children, he grew up on a dairy farm in Maine, although his parents were both educators at different points in their lives.
Dr. McKusick decided to pursue medicine following an illness at the age of 15, during which he was administered recently developed antibiotic treatment. He was deeply impressed by the work of the doctors treating him. Following his education, he worked initially in the field of cardiology. Dr. McKusick developed an interest in rare disorders early in his career after encountering a patient with Marfan syndrome, a disorder characterised by heart defects, tall stature, and eye anomalies. Dr. McKusick became fascinated with the condition and its transmission and soon began seeing other Marfan syndrome patients as well as others with inherited illnesses.
"Some of my colleagues thought I was committing professional suicide because I had a reputation in cardiology and was shifting over to focus for the most part on rare, unimportant conditions and so forth," Dr. McKusick once told the Baltimore Sun newspaper. "But it didn't bother me. I felt certain it was going somewhere."
Dr. McKusick began keeping detailed records of the patterns of inheritance and clinical phenotype that he encountered. Utterly captivated by the field, Dr. McKusick in 1957 founded the Division of Medical Genetics at the Johns Hopkins Institute. It was the first such centre in the world. He began working with subjects possessing isolated gene pools, including the Pennsylvania Old Order Amish population. From these groups, he discretely obtained the medical and genetic profiles that permitted identifying specific genes with certain disorders and anomalies, such as dwarfism amongst the Amish population. It has been suggested that his experience living and working on a farm as a child helped him to penetrate the private world of the Amish and gain their trust.
Throughout the 1960s gene mapping slowly increased and Dr. McKusick established the foundation for the identification of genes responsible for thousands of inherited conditions. At a conference in 1969, he proposed mapping every human gene as a method for identifying (and eventually solving) birth defects and genetic conditions. Considered a farfetched suggestion by some at the time, the human genome went on to be completely mapped in 2001. In 1966, Dr. McKusick created the first edition of the Mendelian Inheritance in Man (MIM), probably the most comprehensive human genetic database catalogue. Twelve printed editions have since appeared, along with OMIM, the online version created in 1985, which is continuously updated to include new information. Amongst the plethora of Dr. McKusick’s remarkable achievements, the creation of MIM is considered by many to be his crowning accomplishment. The American Journal of Human Genetics published an article by Dr. McKusick in April 2007 in which he describes the creation of MIM, and the evolutions over the years in organising and categorizing information.
Of Mice and McKusick
In 1960, Dr. McKusick co-founded the Short Course in Medical and Experimental Mammalian Genetics, held in conjunction with the Jackson Laboratory in Bar Harbor, Maine, an internationally recognised centre of excellence in mouse genetics. Dr. McKusick was one of the earliest human geneticists to recognise the value of the mouse as a model for understanding human disease, because of similar developmental and physiological traits between the two species. He thus facilitated collaboration between scientists in both fields and served as a co-director of the Short Course for 49 years. He was planning the 50th such course at the time of death.
In 1988 Dr. McKusick and Giovanni Romeo, professor of Medical Genetics at the University of Bologna, founded the European School of Genetic Medicine (ESGM) in Italy. Taking the Bar Harbor course as a model, the ESGM offers advanced scientific and professional training courses to physicians and scientists across Europe and the Mediterranean countries. The school rapidly established a reputation for excellence and in the last twenty years over 800 faculty members and 5000 students have participated in its ground-breaking courses. In 2007, on the occasion of the 2Oth edition of the Course in Medical Genetics organised by the ESGM, Dr. McKusick, along with Nobel Laureate Mario Capecchi, received an honorary degree from the University of Bologna. A commemorative booklet was created by the European Genetics Foundation to record the occasion.
On his webpage at the Johns Hopkins Medical Center, Dr. McKusick gives a description of his principal activities:
“My interest in the comprehensive collation of information on human genes and genetic disorders is represented by Mendelian Inheritance in Man (and its online counterpart OMIM), to the upkeep of which I devote three-fourths of my full-time schedule. I still see new patients with hereditary disease in consultation, particularly patients with heritable disorders of connective tissue, such as Marfan syndrome, Ehlers-Danlos syndrome, and skeletal dysplasias and follow-up on the course of patients that I have seen in the past. My involvement with the Amish, which was heavy in the past, is limited largely to consultation with others at Hopkins in the design of studies. My ongoing research in the history of Medical Genetics has taken the form of a long chapter in the Emery-Rimoin Principles and Practice of Medical Genetics and several biographical studies. I edit two journals, Medicine (founded in the year that I was born) and a newer journal, Genomics (founded by Frank Ruddle and me in 1987)”.
Thus for decades, Dr. McKusick led the world in searching, mapping and identifying genes responsible for innumerable inherited conditions including Down syndrome, Duchenne muscular dystrophy, achondroplasia, and many other forms of dwarfism. Such discoveries have not only uncovered the mechanisms responsible for the transmission of disease, but have also led to treatments that have profoundly altered the life of patients.
Although a recipient of scores of prizes, distinctions and accolades, it would appear that for Dr. McKusick the ultimate honour came from being able to pursue the field he cherished. We are grateful to that Marfan syndrome patient who altered his path so many years ago and are deeply indebted to Dr. McKusick for the advances in genetics he undertook that have so profoundly impacted rare disease research and treatments.
Dr. Victor McKusick died of cancer on 22 July, 2008, at the age of 86 years.