Egypto-mania 2000
MEGASTAR

Volume 3, Issue 1
January 2000

Rearing a Discipline:
A tribute to the contribution of Prof. Victor A. McKusick, 
the "father of medical and community genetics."

By Dr. Talaat I. Farag FACP, FRCP (Edin)

 

The self-proclaimed "lucky gene-hunter"

"Syndromology is the art and science of recognizing distinct genetic entities by characteristic combinations of clinical manifestations," explains the father and pioneer extraordinaire Prof. McKusick, MD, ScD, DMedSci, FACP, FRCP, founder of the discipline of clinical genetics.  "Robert Gorlin and John Opitz are two American syndromologists from among the many capable ones," he added.

Prof. Victor McKusick's story with medical genetics spans a lifetime extending over more than half a century. His first published piece of clinical investigation was on a genetic topic, the syndrome of spots and polyps (Peutz-Jehur Syndrome) in 1949. However, Prof. McKusick started his career as a cardiologist and his first book was, "Heritable Disorders of Connective Tissue" in 1956. When he was asked why he shifted from cardiology to medical genetics, his response was, "I didn't. In fact my activities in the two fields developed in parallel. It was a matter of phasing out cardiology and phasing in medical genetics."

On July 1st, 1957 he joined the newly established unit of medical genetics in Johns Hopkins University, where he has spent his career to this day uninterruptedly, without even taking a sabbatical break! Ever since, the work that absorbed his interest and energies has been in the specialized career of "genetic nosology," which is concerned with the delineation of discrete genetic entities. When asked of the motivations behind his achievements, he humbly proclaims that his illustrious career was sparked by challenging teachers, colleagues and students. 


The "Father of medical and community genetics," 
Prof. Victor A. McKusick (front-center) with his colleagues
 at the Genetics Unit, John's Hopkins University, 1967.

The Second Mendel


Gregor Mendel (1822-1884)




Victor A. McKusick (1921-)

Prof. McKusick is considered by many in his field to be the "second Mendel." Gregor Mendel is the nineteenth century Austrian monk, whose experimental scientific work became the basis of modern hereditary theory. McKusick's comparable contribution is exemplified by the his authorship of the comprehensive gene encyclopedia entitled, "Mendelian Inheritance in Man: Catalogs of autosomal dominant, autosomal recessive & X-linked phenotypes"  (MIM), which was first published in 1966. The catalogue's latest (12th) edition was published in 1998 by Johns Hopkins University Press with a continuously updated online version available worldwide at the URL (http://www3.ncbi.nlm.nih.gov/omim). These volumes are a testament to his interest and commitment to genetic nosology. 

Over his many years in the profession, McKusick has come to be know not only as the professional originator of medical and community geneticists, but is also considered by many to be "the teacher of teachers!" in the discipline. But these accomplishments did not come without aspirations and motivations. While McKusick defined clinical genetics as, "the science and practice of diagnosis, prevention and management of genetic disorders," in order to fulfill his scientific dreams, he established an association between Johns Hopkins University and Jackson's Laboratory in Bar Harbor, Maine. The lab was specialized in the study of maize, drosophilae, mice and human genetics. In 1960, he was the co-founder & director of Bar Harbor annual 2-week short course in medical and experimental genetics to teach the teachers, particularly university faculty. 

My personal participation in this course was of great benefit since it established interest in both animal and human genetics. There is no doubt that the Jackson Laboratory-Johns Hopkins collaboration challenged the development of somatic cell genetics and molecular genetic techniques, which have been supported by March of Dimes campaigns. He mentioned, "Much of the foundation for my work in medical genetics and much valuable tutelage, comes from my association with Jackson Laboratory, Bar Harbor. The body of knowledge they had gathered on the genetics of the mouse was highly to my developed."

McKusick who, over the years, has been a professor of biology, epidemiology and medicine at Johns Hopkins University, is the author of 13 medical genetics textbooks. He was also awarded honorary degrees from 17 international medical colleges worldwide in recognition for his contribution to the field. In 1995, he was granted the Mendel Medal from Villanova University.

His contribution also extends to scientific publications through his positions as the editor-in-chief of MEDICINE (1985-present), the founding editor of GENOMICS (with Prof.F.H.Ruddle), the foundering president of The Human Genome Organization (HUGO), and a member of the editorial board of 12 other international scientific journals. His main research interest, in addition to heritable disorders of connective tissue, continues to be the investigation of genetic linkage and chromosome mapping. 

Schimke & McKusick Studies

In the 60's, Prof. McKusick in association with Prof. Neil Schimke (Director of Medical Genetics at Kansas University) established a nationwide search for cases of suspected homocystnuria, a disorder which has some eye and skeletal similarities with Marfan Syndrome. Samples from around the country were submitted to them by ophthalmologists from patients with dislocated lens, and they published a study of 20 families with 38 affected persons, two of those cases had completed PhD degrees! 


McKusick's research among the 
Amish challenged others to study
 inbred populations 

The Amish & Inbred Populations

In 1962, an article published by family practitioner, Dr. David Krusen, mentioned that achondroplasia is unusually  frequent among the Amish of Lancaster County, PA. This stimulated McKusick's interest in the Amish. He teamed up with Hosteler and studied dwarfism among this population and reported two autosomal recessive forms of dwarfism: the cartilage-hair hypoplasia (found also to be common in Finland) and the six-fingered dwarfism (Ellis-Van Creveld Syndrome). 


Prof. Victor McKusick paid 
particular attention to those
 who were short stature

Following in his footsteps, I enjoyed the two visits I made to the Amish population in Pennsylvania with Prof. Laird Jackson, Director of Medical Genetics at Thomas Jefferson University, noting the great respect and appreciation the people had for Prof. McKusick, Prof. Hosteler, Prof. Jackson and their colleagues. This level of respect was more than mutual for Prof. McKusick too. "The Amish studies had a large nosologic aspect," he said. He further explains that their characteristic "inbreeding, large families, and 'tight' sociological characteristics made for increased visibility of ordinarily rare autosomal recessive disorders," and In 1978, McKusick compiled a selection of his published papers of medical genetic studies among the Amish. 

His work and findings triggered a chain reaction in research among different populations. Sir Peter S. Harper published his own work among the gypsies; Prof. Goodman his data on the Jewish populations; and my colleague Prof. Ahmed S. Teebi and myself to publish our book on the Arab populations and Bedouins. Other studies were published on Finnish, Japanese, Hutterites, Inuit, etc. Recently, research done among French Acadians in Yarmouth Nova Scotia published by Dr. Wenda Greer, a distinguished Canadian molecular geneticist, revealed her findings on a variant form of Niemann-Pick disease found among the inbred French Acadians in Yarmouth, Nova Scotia.

Human Genome Project (HGP)

McKusick's work with mice and human both at Johns Hopkins and in Bar Harbor created the fertile foundations for the four-billion dollar international research to map the human genome (HGP). The ambitious program is expected to have the blueprint - the complete DNA sequences of the human genome by 2003. The draft sequence will be a valuable tool that energizes the new millennium in the what McKusick calls the "Biology Century." He believes that the two fundamental scientific revolutions ahead of mankind in the upcoming century will be in biology and information. Both of which he sees "verge in the human genome initiative."

Evolution of Medical & Human Genetics

McKusick has been not a witness but an active participant in every stage of his discipline's evolution. He mentioned that since 1956, medical genetics has been blessed with new methodological breakthroughs that have revolutionized the field. These are: chromosomology (beginning about 1956), somatic cell hybridization (beginning 1966), molecular genetics (beginning in 1976), and the Human Genome Project (beginning in 1990). Hence, the discipline became medicalized, then sub-specialized, then professionalized, then molecularized and McKusick forsees it being commercialized in years to come.

McKusick said, "it is a source of great pleasure to me that clinical genetics has achieved full professional status, with its own certifying board (founded in 1980) even more than increasing the professionalism of clinical genetics - I am delighted to see the extent to which basic genetics has been woven into the fabric of clinical medicine. Mapping genes on chromosomes is the modern anatomy, knowledge in the area is providing a neo-Vesalian basis of all medicine."

I consider myself fortunate to be a student, one way or another, of McKusick's many disciples. I am honored and privileged to pay tribute, as one of thousands of students and followers, to the father of medical and community genetics. 

References:

Dr. Talaat I. Farag MBBCH, DCH, MSc, DMSc, FACP, FRCP (Edin)  is an adjunct professor at Dalhousie University in Halifax, NS, Canada. He is the author and co-author of more than 150 medical studies. His research interests lie in community and preventive genetics, paleo-pathology, and the critical analysis of cultures and civilizations.


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