Convocation Address

Health Sciences Convocation

McGill University

May 30, 2006

Oslerian Medicine in the Age of Genomics

Chancellor Pound, Principal Vice Chancellor Munroe-Blum, Dean Fuks:

Thank you for this honorary degree from this distinguished University. I treasure it. Dr. Mussalem, it is a special honor to receive a degree along with you. My respect and congratulations to you.

Graduates in the Health Sciences, Ladies and Gentlemen: One reason I am pleased to be an honorary alumnus of McGill is the strong historic link between this university and Johns Hopkins. That historic link is William Osler. I remind you that Osler graduated in medicine from McGill in 1872 and became a professor here and at the University of Pennsylvania. When the Johns Hopkins Hospital opened in Baltimore in 1889, Osler became its first Physician-in-Chief, a position he held for 16 years, until 1905 when he went to Oxford University as the Regius Professor. Thus, we share an Osler tradition. You have Osler’s magnificent collection of books and his ashes; we at Johns Hopkins have the room where he wrote his famous textbook in 1891 and the academic department of medicine he founded.

During those 16 years at Johns Hopkins, Osler established a brand of medicine, call it Oslerian medicine, that became a gold standard. It was expounded in his famous textbook and extensive other writings. It was founded on the clinical descriptions of specific medical disorders and their diagnosis by careful physical examination, corroborated by autopsy. It integrated medical students into the care of patients on the wards. It involved post-graduate training of interns and residents in a program that became a model. Importantly, Osler established the teaching and practice of clinical medicine as an integral function of a university. A man of immense charisma, talent, and energy, Osler emphasized the historical roots of the medical profession and medicine as a calling not a mere occupation. The ideals and counsel for students, young medical practitioners and nurses, contained in his essays and addresses, became part of the ethos of medicine.

Fast forward about one hundred years to 2003. In that year, the Human Genome Project achieved its goal--determination of the complete line-up of the 4 types of nucleotides in the DNA of the chromosomes and the genes they contain. Furthermore, in the last 3 years, great progress has been made in determining the extent of variation in that line-up in the genome of different persons. Each person’s genome sequence differs from that of all others on this globe, unless you are like me an identical twin. The uniqueness of the genome in the individual is, of course, the basis of DNA testing for forensic identification.

We long predicted that complete mapping and sequencing the human genome would have major impact on both the science and the practice of medicine -- which brings me to my title: Oslerian medicine in the age of genomics (or in the post-genomic era).

I graduated from Johns Hopkins Medical School 60 years ago, in 1946. That was 41 years after Osler had left for Oxford but the Osler aura was still strong, still is, and the residency training I got was Oslerian. As you heard, for 12 years I was Osler’s successor as Physician-in-Chief of the Johns Hopkins Hospital. Already before that, gene mapping was a major part of the research program of my group in the new clinical specialty of medical genetics, and I was early to argue the usefulness of the Human Genome Project.

Now back to the last century. When Osler died in Oxford in 1919, his immediate successor as Regius Professor was Archibald Garrod. In the first years of the 1900’s, Garrod had invented the term inborn errors of metabolism for some rare genetic disorders. He pointed to these as examples of chemical individuality. In 1931, Garrod generalized his ideas of chemical individuality to suggest that each of us is unique in our chemical constitution and that these differences determine our susceptibility or resistance to common disorders such as infections, heart disease, diabetes, mental illness and cancers, as well as our responses to drugs. We would now conclude that this chemical individuality is mainly a reflection of variability in the genome.

There is yet another important and more contemporary McGill-Hopkins link. That is the link involved in interpreting and publicizing the work of Garrod. I feel privileged to be hooded by your Professor Charles Scriver. It is he and Barton Childs, Johns Hopkins pediatrician-geneticist-philosopher, who rediscovered Garrod’s thinking about biochemical individuality and its role in susceptibility to common diseases. In 1989 Scriver and Childs republished in facsimile Garrod’s 1931 book Inborn Factors in Disease, with insightful commentary. Largely as an extension of Garrod’s thinking, Barton Childs developed what he called a logic of medicine, defining logic as a statement of the formal principles of a branch of knowledge. From these analyses came a vision of individualized medicine, what we will call Garrodian medicine--a brand of medicine designed to match the uniqueness of the individual patient.

Childs points out that Oslerian medicine is based on a machine model; disease is when the machine is broken. The cardinal questions are: What is the specific disease from which the patient suffers and what is the appropriate treatment? Garrodian medicine (individualized medicine) on the other hand, asks, Why does this individual have this disorder at this time? The “why” resides not only in the uniqueness of the individual’s genome but also in the uniqueness of the individual’s development, intrauterine and postnatal, and life experiences.

What is the status of Oslerian medicine in the post-genomic era? Oslerian medicine with its questions “What is wrong?” and “What can be done about it?” represents “bare-bones” medicine. Oslerian medicine and Garrodian medicine are not mutually exclusive. They fit hand-and-glove. Oslerian medicine is still fundamental and indispensable but is clearly not sufficient to take full advantage of the information provided by genome studies: information that can be critically important to adequate diagnostic evaluation, effective treatment, and successful health maintenance of the individual.

I am certain Osler would be delighted with the concept of individualized medicine and by the possibilities for recognizing individual genetic predispositions provided by knowledge of the genome. “It is as important to know the patient who has the disease as it is to know the disease that affects the patient.” I cannot confirm that Osler said that but he could have--it sounds Oslerian. But I feel certain Osler would emphasize also dimensions of patient uniqueness not directly defined simply by the genome sequence but no less important in the care of the patient. Call them the psychosocial or even spiritual dimensions. Osler is credited with “an unusual facility to make all patients feel that he was interested in them as persons, whether they were on the public wards or on the private pavilion.”

Traditions are a precious asset of institutions such as McGill and Johns Hopkins, as long as they are not permitted to stifle progress. You McGill graduates can be proud of the Osler tradition and take counsel from it. Whether you follow the lead of Osler, the clinician-teacher, or of Garrod, the physician-scientist, keep in mind the uniqueness of each patient you care for.

All of you graduates have exciting years ahead of you. I envy you and wish you as much soul satisfaction as I have gained from teaching, research and patient care during the 60 years since I graduated from medical school. I salute you. God speed.

Victor A. McKusick, M.D.

University Professor of Medicial Genetics

Johns Hopkins University

Baltimore, Maryland