McKusick specialized in cardiology at Hopkins, where he was soon joined the faculty. Here, McKusick became particularly interested in Marfan syndrome, a heritable disease characterized by severe aortic malfunction, dislocated eye lenses, and unusually tall stature. He began treating many Marfan patients and was able to show that this syndrome was due to an anomaly in a single gene that disturbs the formation of connective tissue. Soon, patients with a wide spectrum of genetic diseases came seeking consultation, and participating in the numerous studies McKusick was conducting to record and analyze patterns of genetic disease inheritance.


In response to this increasing demand, in 1957 McKusick founded the Division of Medical Genetics at Hopkins. This clinical and research division was one of the first in the world dedicated to studying the genetic bases for diseases, promoting not only the integration of genetics (specifically gene mapping) into clinical practice, but also the use of clinical experience to guide genetics research. For the following two decades the Division trained myriad medical, paramedical, and scientific professionals who became leaders in the field throughout the world. The Medical Genetics Division at Hopkins soon became a model for research, teaching and clinical care.

In 1960, McKusick founded the Short Course in Experimental Mammalian Genetics at the Jackson Laboratories in Bar Harbor, Maine. Today, along with David Valle, he continues to direct the Course, which has trained over 4000 students. Through the Bar Harbor Course and the Clinic at Hopkins, “Victor has trained nearly all medical geneticists and workers in the area of medical genetics,” according to Valle.

In the early part of his career, McKusick studied extensively the genetic disorders of the Amish, an inbred founder population in Pennsylvania. Because of the increased “visibility” in such populations of recessive disorders that are very rare in the general population, he was able to delineate some dozen “new” conditions that occur in all ethnic groups but had hitherto escaped attention. The most noteworthy of these is the condition he named cartilage-hair hypoplasia or “McKusick-type metaphyseal chondrodysplasia.” This research was seminal in creating the field of genetic nosology, the study of the classification and natural history of genetic disease.

“Thanks to Victor, medical genetics has been evolved from a backwater academic discipline to one of the most active areas of clinical practice . . . . It’s not unreasonable to predict that in ten years clinical genetics will be the largest and most pervasive of the medical subspecialties.”
McKusick’s Amish studies in large part informed Mendelian Inheritance in Man, an encyclopedic compendium on genetic disorders that he published in 1966. This work catalogs all human genes discovered, their corresponding phenotypes, and their associated disorders. It has gone through 12 print editions, and in 1987 McKusick made it available online (OMIM = Online Mendelian Inheritance in Man). so that it could be updated daily as new discoveries were made. It currently contains about 5,000 phenotypes.

In 1968, in a landmark study, McKusick was able to map the Duffy blood group to chromosome 1, representing the first time a human gene had been localized to one of the 22 autosomes. Prompted by the first gene maps of the fruit fly, he began advocating mapping the human genome:

“I propose that detailed exploration of the genetic constitution of man is ripe for an all-out attack. What we should know in full detail are the structure and geography of the chromosomes of man: the full nucleotide sequence of all genes determining the amino acid sequence of proteins and the location of each on the chromosomes of man” (1969).

Despite an incredulous audience, McKusick persisted, collaborating with Frank Ruddle in 1973 to organize biannual workshops to coordinate the gene mapping effort and to collate any information submitted. At the time, only 31 loci were mapped; today almost 2,000 loci have been mapped. He served on the National Research Council/National Academy of Science committee on mapping and sequencing the human genome (1986-1988), he founded and served as President of the Human Genome Organization (HUGO, established in 1988), he founded and served as coeditor-in-chief of Genomics (first published in 1987), he served on the National Institute of Health (NIH) Human Genome Advisory Committee (from 1988-1992) and in the joint NIH/Department of Energy Ethical, Legal, and Social Issues Working Group (1990-1995).

In these capacities, McKusick was able to play a pivotal role in the formation and development of the Human Genome Project, which he officially launched in 1989 with James Watson.