Obituary 3242 The Journal of Clinical Investigation      http://www.jci.org      Volume 118      Number 10      October 2008 A tribute to Victor A. McKusick Victor  A.  McKusick,  MD,  University  Professor of Medical Genetics emeritus at  the  Johns  Hopkins  University  School  of  Medicine, died of cancer on July 22, 2008,  at the age of 86. With James Neel and Arno  Motulsky, Victor was a founder of the dis- cipline of medical genetics. Victor  had  only  one  earned  degree,  the  MD, from Johns Hopkins in 1946. Because  of World War II, he was able to enter medi- cal  school  after  only  three  years  at  Tufts  University and he referred to himself as a  college dropout. He became chief resident  of the Osler Medical Service under A. McGe- hee  Harvey,  perhaps  his  most  important  mentor (1). In 1973, Victor succeeded Har- vey as the William Osler Professor of Medi- cine  and  physician-in-chief  of  the  Johns  Hopkins Hospital. Initially, he pursued car- diology and championed a new technique,  phonocardiography. A few years after his  appointment as assistant professor in 1954,  he published the book Cardiovascular sound in health and disease,  which  established  his  clinical  and  academic  reputation.  When  he surprised his colleagues by deciding to  pursue  genetics,  some  suggested  he  was  committing academic suicide. But Victor  was intrigued by genetics early in life. First,  he was one of monozygotic twins. Second,  he was raised on a dairy farm in Parkman,  Maine. His first paper, unfortunately never  published,  concerned  the  inheritance  of  coat color in cattle. Third, as an intern, he  cared  for  several  patients  with  polyposis  and pigmented macules on the lips; he col- laborated with Harold Jeghers in 1949 on a  paper in the New England Journal of Medicine  that firmly established recessive inheritance  of  this  condition,  originally  described  by  J.L.A. Peutz in 1921. Additionally, as a cardi- ologist, he encountered patients with Mar- fan syndrome. Dilatation of the aortic root  and aortic dissection were reported a few  years earlier by Helen Tausig at Hopkins,  among  others.  In  1955,  Victor  published  a seminal paper in Circulation in which he  not only identified the causes of death of  dozens of patients with Marfan syndrome  but established a new nosology, the heri- table  disorders  of  connective  tissue.  His  1956 monograph on this topic described  seven quite distinct disorders that appeared  to be associated by primary defects in the  extracellular matrix. Eventually, over 200  disorders would be thus classified. By 1960, he was a full professor and pur- sued the study of rare disorders full time  as director of the outpatient Moore Clinic.  He approached the Old Order Amish first  as a physician and second as an investiga- tor and thereby identified a host of “new”  autosomal recessive syndromes made evi- dent by consanguinity. Always the catalogu- er,  he  established  Mendelian inheritance in man (MIM) in 1960. Victor recognized much  earlier than most the value of computers  and maintained this catalog on magnetic  tape,  starting  in  1964.  As  one  of  Victor’s  trainees, I assisted him in the composition  of MIM entries with a first-generation desk- top  computer  and  word  processing  pro- gram in 1980. Eventually, MIM morphed  into OMIM, the online version now main- tained by the National Library of Medicine  (2). Nearing 19,000 entries, OMIM remains  a vital resource for clinicians and investiga- tors. Victor was also a pioneer in mapping  human genes and an early practitioner of  linkage analysis in humans. A student of  his  established  the  first  autosomal  link- age, Duffy blood group to chromosome 1,   in 1968. Subsequently, Victor helped estab- lish  the  Human  Gene  Mapping  Work- shops, was an early advocate of the Human  Genome Project, and was the first president  of the Human Genome Organisation. While  never self aggrandizing, he was secure in his  importance  to  academic  medicine,  and  a  number of personal reflections document  his contributions (3–7). Any homage to Victor must emphasize  his mentorship, for which he was greatly  respected  and  beloved.  He  counted  121  trainees. Some of his earliest trainees are  long retired, but those still active and their  many “descendants” populate institutions  around  the  world.  One  enduring  legacy  began with his 1955 paper on Marfan syn- drome and continued when he introduced  me to a patient with that condition on my  first day at Hopkins as an Osler resident.  Together  with  talented  colleagues,  we  implemented  treatments  that  improved  life  expectancy  to  near  normal  and,  in  1991,  discovered  the  cause  of  this  syn- drome. More recently, the first incumbent  of the Victor A. McKusick Professorship in  Medicine and Genetics, Hal Dietz, discov- ered the basis of the pathogenesis of this  syndrome, which, if it leads to a cure, will  be an early triumph of translational medi- cine. This half-century saga gave Victor tre- mendous satisfaction. His most powerful  — and unspoken — lessons were always the  value of persistence and hard work. Virtu- ally no one was his equal. Well into his 80s,  he  would  be  viewing  posters  at  national Image credit: Keith Weller, Johns Hopkins Medicine. obituary The Journal of Clinical Investigation      http://www.jci.org      Volume 118      Number 10      October 2008  3243 meetings before breakfast, scribbling notes  for entry into OMIM later that day. When  I incorrectly introduced him as emeritus a  couple of years ago, he publicly noted that  he was still on the active faculty but only  working part time — 12 hours a day. Victor was recognized with 23 honorary  degrees, election to the National Academy  of Sciences, the Gairdner Foundation Inter- national Award, the George M. Kober Medal  of the Association of American Physicians,  the National Medal of Science, the Albert  Lasker Award for Special Achievement in  Medical Science, and the 2008 Japan Prize  for Medical Genomics and Genetics. Victor  was well enough to attend the ceremony in  Tokyo in April with Dr. Anne B. McKusick,  his wife of nearly 60 years. On his return,  he regaled us with tales of the pomp of the  ceremony and of dining with the emperor  and empress. At the end of the banquet, he  spontaneously took the empress’ hand to  introduce her to his twin, Vincent, the for- mer chief justice of the supreme court of  Maine. His eyes twinkled as he recounted  how the security detail swiftly intervened  in this breach of protocol. Reed E. Pyeritz Division  of  Medical  Genetics,  Depart- ment  of  Medicine,  University  of  Penn- sylvania  Center  for  the  Integration  of  Genetic Healthcare Technologies, Univer- sity  of  Pennsylvania  School  of  Medicine,  Philadelphia, Pennsylvania, USA. E-mail:   reed.pyeritz@uphs.upenn.edu.   1. McKusick,  V.A.  2003.  Abner  McGehee  Harvey,  1911-1998. Proc. Assoc. Am. Phys. 111:365–368.   2. McKusick-Nathans Institute of Genetic Medicine,  Johns  Hopkins  University,  and  National  Center  for Biotechnology Information, National Library  of  Medicine.  2008.  OMIM  —  Online  Mendelian  Inheritance in Man [database]. http://www.ncbi. nlm.nih.gov/omim/.   3. McKusick,  V.A.,  Naggert,  J.,  Nishina,  P.,  and   Valle, D. 1999. 40 years of the annual ‘Bar Harbor  Course’ (1960–1999): a pictorial history. Clin. Genet.  55:398–415.   4. McKusick, V.A. 2001. The anatomy of the human  genome: a neo-Vesalian basis for medicine in the  21st century. JAMA. 286:2289–2295.   5. Francomano, C.A., McKusick, V.A., and Biesecker,  L.G. 2003. Medical genetic studies in the Amish:  historical perspective. Am. J. Med. Genet. 121C:1–4.   6. McKusick, V.A. 2006. A 60-year tale of spots, maps,  and genes. Annu. Rev. Genomics Hum. Genet. 7:1–27.   7. McKusick,  V.A.  2007.  Mendelian  Inheritance  in  Man  and  its  online  version,  OMIM.  Am. J. Hum. Genet. 80:588–604.