Biographical Overview

"I became known as a cardiologist. . .before I became known as a geneticist. Some thought I was committing professional suicide in leaving cardiology to focus on rare and "unimportant" genetic disorders. They asked why I switched from cardiology to genetics. Actually it was a matter of phasing down cardiology and ramping up genetics after 1957."

– Victor McKusick, "A 60-Year Tale of Spots, Maps, and Genes," Annual Review of Genomics and Human Genetics 7 (2006): 5

Victor McKusick is widely considered to be the founding father of medical genetics. An innovative clinician, medical educator, and researcher, he established the first medical genetics program and clinic at Johns Hopkins in 1957, conceived and compiled Mendelian Inheritance in Man, an annually updated catalog of human phenotypes (first published in 1966 and now published online), and conducted landmark studies of hereditary disorders in the Amish. He was an early advocate of mapping the human genome, and was closely involved in the early years of the Human Genome Project, and served as founding president of the Human Genome Organization (HUGO). In 1997 in recognition of his lifelong contributions he received the Lasker Award for Special Achievement in Medical Science.

Victor Almon McKusick was born in Parkman, Maine, on October 21, 1921. He and his identical twin brother, Vincent, were the youngest of five children. Raised on the family dairy farm, the twins attended a one-room schoolhouse for eight years, and graduated from a small local high school (in a class of 28). Like their older siblings, they were expected to attend college--their father was a college graduate, and had been a school principal in Vermont before returning to his home town and the farm. In his teens, Victor considered becoming a minister, but a close encounter with medicine during the summer of 1937 changed his plans: he developed an abscess under one arm, and the infection (caused by an unusual streptococcus strain) spread and would not heal. McKusick spent 10 weeks in hospitals, both in Maine and at Massachusetts General in Boston, where he was treated successfully with the new antibiotic sulfanilamide. Inspired by the experience, he chose to pursue a career in medicine, and entered a pre-medical program at Tufts University in 1940. (His brother Vincent chose to practice law and later became chief justice of Maine's Supreme Court.) McKusick left Tufts in 1943 without finishing his degree because Johns Hopkins University School of Medicine (JHUSM) had begun admitting advanced pre-med students into an accelerated program, due to a wartime shortage of physicians. McKusick began his medical studies in March 1943, received his MD in 1946, and remained at Johns Hopkins for the rest of his career.

McKusick's original plan was to complete his internship at Johns Hopkins and then return to Maine to establish a general practice. But circumstances conspired to keep him in Baltimore. He received the prestigious Osler Medical Service internship, which emphasized training for academic medicine, and then served two years as chief of the cardiology unit at the Baltimore U.S. Marine Hospital to fulfill his military obligation (a U.S. Army program had paid for his medical education in exchange for two years in the U.S. Public Health Service). In 1949, he married a fellow Hopkins physician, Anne Bishop, who was then completing her training in rheumatology. In 1950, he returned to Johns Hopkins and the Osler Medical Service, as senior and then chief resident. He joined the faculty in 1951 as an instructor, and was promoted to full professor in 1960. From 1973 to 1985, he served as Physician-in-Chief of Johns Hopkins Hospital and Chairman of the Department of Medicine. From 1985, he was University Professor of Medical Genetics, and remained active in teaching and research.

McKusick took his first step into medical genetics in 1947 during his internship. A teenager with intestinal polyps and curious pigmented spots on his lips became McKusick's patient; within two years, McKusick had seen four other patients with this combination, three of them in the same family, indicating a hereditary condition. Hearing that a Boston physician, Harold Jeghers, had seen five such cases, McKusick contacted him, and the two wrote up their cases for the New England Journal of Medicine. This became McKusick's first medical publication. Because the syndrome had been noted many years earlier by J. L. A. Peutz, a Dutch physician, it was later named the Peutz-Jeghers syndrome (PJS). McKusick had been intrigued by genetics since taking a pre-med genetics course at Tufts, and wondered if PJS was a case of genetic linkage, i.e., individual genes causing separate symptoms, that were inherited together due to their proximity on a given chromosome. His mentor, Bentley Glass, persuaded him that pleiotropism--a single mutant gene causing diverse symptoms--was a more likely cause. (Later research confirmed Glass's clinical intuition about PJS.)

Medical genetics was not a specialty at the time, however, and in the course of his residency, McKusick was drawn to cardiology. Subsequently, he worked for two years on the cardiovascular unit at the U.S. Public Health Service Marine Hospital, doing cardiac catheterizations and studying the movement in the heart borders with a new imaging method called electrokymography. During his early faculty years at JHUSM, he pursued a study of heart sounds and murmurs using sound spectrography, which had been developed at the Bell Telephone Laboratory for studying speech sounds. Adapted to cardiac studies, the technology could pick up and record the frequency spectrum of heart sounds, allowing physicians to visualize what they were hearing with their stethoscopes. McKusick renamed it spectral phonocardiography, and used the studies as the basis for a comprehensive treatise on heart sounds titled Cardiovascular Sound in Health and Disease, published in 1958.

As a cardiologist, McKusick encountered many patients with congenital heart problems such as defective valves or deformed aortas. These were sometimes accompanied by other symptoms such as the skeletal and eye abnormalities that characterized a condition known as Marfan syndrome. He thought the various features of this inherited disorder, like those of PJS, were pleiotropic rather than linked, and probably due to a mutation-determined defect in one element of connective tissue wherever it occurred in the body. In parallel with his cardiographic studies, he also carried out a comprehensive study of Marfan syndrome and four similar disorders, collecting patients and family histories from his own practice and from many other clinical departments at Johns Hopkins. This work produced his first book, Heritable Disorders of Connective Tissue, first published in 1956.

Medical genetics as a distinct clinical and academic discipline at JHUMS began in 1957, when McKusick was asked to serve as director of the multifaceted chronic disease clinic developed at Johns Hopkins by J. Earle Moore in 1952. McKusick accepted the position, on the condition that he could develop a Division of Medical Genetics within the Department of Medicine, based in this clinic. Arguing that genetic disease is the ultimate chronic disease, he envisioned the new division carrying out teaching, research, and patient care related to hereditary disorders, much as other subspecialty divisions did for, e.g., cardiac or endocrine disorders. Increased understanding of rare genetic disorders would vastly improve differential diagnosis and treatment, and enable physicians to better counsel affected patients and their families. At the Moore Clinic (as it was renamed in 1957) the research focused on nosology (defining the multiple distinct forms of genetic diseases) and on gene mapping (tracing the chromosomal locations of inherited disease genes and their linkages to other genes.) The program soon became a premier postdoctoral training ground for specialists from many areas of medicine, including dentistry and veterinary medicine, and its alumni helped propagate the new field of medical genetics in the United States and abroad.

During the 1960s, McKusick expanded his genetic investigations beyond the clinic to study inherited disorders in Amish populations in Pennsylvania, Ohio, and Indiana. There he identified a number of rare recessive disorders, some of them new. He and his colleagues also expanded their knowledge of skeletal abnormalities by establishing ties with Little People of America, a support organization for people with dwarfism.

Soon after the medical genetics program was founded, McKusick and his colleagues began doing comprehensive annual reviews of the relevant medical and scientific literature, which were published in the Journal of Chronic Diseases from 1958 to 1963. Concurrently, McKusick compiled and published an annotated catalog of traits known to be carried on the X chromosome in humans. As McKusick began his genetic studies of Amish populations--which promised to reveal new inherited disorders--he and his colleagues decided to replace the annual reviews with a comprehensive catalog of known Mendelian phenotypes (inherited physical or physiological traits, including disorders and deformities), to which additions could be made as new phenotypes were described, and more information became available on older phenotypes. With such a reference list, clinicians could readily find information on rare inherited diseases they encountered in their patients. Genetics researchers would have current information about the state of the art in gene mapping. The catalog, titled Mendelian Inheritance in Man, was first published in 1966; in collaboration with the National Library of Medicine, the Online Mendelian Inheritance in Man became available in 1987, and remains a standard reference work.

McKusick played a key role in expanding and organizing the medical genetics field beyond Johns Hopkins. An important part of the educational mission of McKusick's program was the annual two-week course held at Bar Harbor, Maine. Organized jointly by McKusick at JHUSM and John Fuller at the independent Jackson Laboratory in Maine (JAX), the first "Short Course in Medical Genetics" was held in 1960, staffed by faculty from JHUSM, JAX, and other institutions. More than 5,000 students have taken the course since then. McKusick also helped organize annual conferences on the Clinical Delineation of Birth Defects, starting in 1968; from 1973 to 1991, he collaborated in organizing a series of international Human Gene Mapping workshops.

By 1986, advances in gene mapping and in molecular biology had generated much discussion about projects to map and sequence the entire human genome. Not surprisingly, McKusick played a leading role on the National Research Council (NRC) committee charged with assessing the feasibility of what became the Human Genome Project. In 1988, he became founding president of the Human Genome Organization (HUGO), an international coordinating agency for the global mapping and sequencing efforts. During the next few years he would also serve on the ethics committees for the Human Genome Project and HUGO. In the early 1990s, he chaired another NRC committee charged with establishing guidelines for the use of DNA analysis in law enforcement.

McKusick was a prolific writer throughout his career and published over 500 medical articles and 7 books in addition to the ongoing compilation of Mendelian Inheritance in Man. He also pursued a lifelong interest in the history of medicine; many of his clinical publications included historical components, and he wrote a history of medical genetics for a standard textbook in the field. Other projects included a study of hemophilia in colonial New England, and an annotated edition of selections from William Osler's classic medical text Principles and Practice of Medicine.

McKusick's work earned him many honors and awards, including the Johns Phillips Award of the American College of Physicians for distinguished contributions in internal medicine (1972); election to the National Academy of Sciences (1973); the Gairdner International Award (1977); the William A. Allan Award of the American Society of Human Genetics (1977); the James Murray Luck Award from the National Academy of Sciences (1982), the Sanremo International Prize for Genetic Research (1983); the American Association of Physicians' George M. Kober Award (1990); the Lasker Award for Special Achievement in Medical Science (1997); the National Medal of Science (2002), and the Japan Prize in Medical Genomics and Genetics (2008), along with more than 20 honorary doctorates.

Victor McKusick died on July 22, 2008, at the age of 86.