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1978 Nobel Laureate in Medicine

Hamilton O. Smith, MD
1978 Nobel Laureate in Medicine

My mother and father each came from simple country backgrounds, but both showed an early inclination for scholarly pursuits. They eventually met as school teachers in a local Panama City, Florida high school and were married in 1929. The following year, my father was appointed Assistant Professor of Education at the University of Florida at Gainesville, and in that year my brother was born. In 1931, my father went on leave to Columbia Universtity in New York City to complete his doctoral work in education. I was born there on August 23, 1931 while he was a graduate student. Though the family commuted annually between New York City and Gainesville over the next five years, I retain the strongest memories of our life in the city. In particular are recollections of life in a small, intimate apartment, walks in the city parks, and quiet evenings spent with my mother and father who entertained us with arithmetic problems and a small Gilbert chemistry set.

In 1937, our family moved to Champaign-Urbana, Illinois. My father had joined the faculty of the Department of Education at the University of Illinois and was to spend the major part of his academic career there until retirement. My entire boyhood was spent in this small midwestern academic community. Despite the fact that our life in Urbana spanned the late depression years and World War II, the community continued to function pretty much as if untouched by world events. At home, an atmosphere of intense intellectualism was maintained. My father was perpetually working and writing. At the same time, my mother struggled to establish herself as a writer, but she was to remain frustrated in her ambitions. However, she, in particular, imbued us with a respect and desire for the creative life.

My brother and I received private French lessons during our pre-teen years. I began piano lessons at age eight and my brother took up violin. We studied with a talented musical family, the Fosters and Sonderskovs. I was in no way gifted and found practice to be a chore until one memorable day when I was about age thirteen. On that day, a friend introduced me to the local music shop and by chance I picked up a recording of Artur Rubinstein playing Beethoven’s Pathetique Sonata. I had been struggling with the piece for sometime, but had never appreciated its dramatic beauty. Listening to Rubinstein’s magnificent performance for the first time was a truly awakening experience. From then on I became a devoted pupil and music lover.

My boyhood friends were mostly sons of university faculty. Our interests included football, basketball, music, chemistry, electricity, and electronics. My brother and I spent many hours in our basement laboratory stocked with supplies purchased from our paper route earnings. We attended University High School, a superb small college preparatory school with an array of exceptionally talented students drawn largely from university faculty families. To my knowledge, two Nobel Laureates are counted among “Uni-High’s”graduates, as well as numerous successful professionals, and no less than three current professors at Johns Hopkins. I completed high school in three years largely due to a wonderful science teacher, Wilbur E. Harnish, who allowed me to complete chemistry and physics during the two summers preceding ninth grade. Two other teachers at “Uni-High” influenced my development profoundly: Vynce Hines, who taught me the beauties and rigor of plane geometry and Miles C. Hartley, who gave me a sound foundation in algebra.

After completing high school, I matriculated at the University of Illinois, majoring in mathematics for which I had a flair but no deep talent. I had not yet decided on a particular field of science. My brother, who was considerably more gifted in the abstract areas than I, was studying theoretical physics, but this did not appeal strongly to me, nor was I interested in pure chemistry. At that time biology, as taught, was largely descriptive. It was not especially appealing for one brought up on “real” science. However, during my sophomore year, my brother introduced me to a book on mathematical modeling of central nervous system circuits by a biophysicist named Rashevsky. It caught my interest and I began reading about the nervous system. I continued this interest after transferring to the University of California at Berkeley in 1950. There, for the first time, I found courses in cell physiology, biochemistry, and biology that interested me. I recall in particular at that time, a guest lecture by George Wald describing his studies of retinal biochemistry. I was converted overnight into an avid student of visual physiology. It had become clear that mathematics, while providing an excellent basic training, was not my real interest. With a broadening appreciation of biology and a budding interest in human visual- and neurophysiology, I decided to apply to medical school.

In 1952, I began my studies at the Johns Hopkins University Medical School in Baltimore, Maryland. I was immediately caught up in the excitement of a new kind of life, and without firm commitments to any particular area of research, I was to continue a fairly conventional medical career for several years. I received my M. D. degree from Hopkins in 1956 and proceeded to Barnes Hospital in St. Louis for a medical internship. There I experienced for the first time a true feeling of freedom and independence. In my second month of internship I met Elizabeth Anne Bolton, a young nursing student. She was from a family of doctors and engineers, had been born in Spain, reared in Mexico City, and had come to the States for college and nurses’ training. We immediately liked each other, and a few months later, were married.

In July, 1957, I was called up in the Doctor’s Draft, and rather than seek any of several avenues of deferment, decided it was an opportune time to be done with my service obligation. I chose the Navy and we received a two year assignment in San Diego, California. It was a relaxed and easy time for us after so many years of schooling. For the first time in my life I was faced with greatly reduced demands on my time and the problem of idleness. I began to search for ways to occupy myself. A report of the then new research in human chromosomal aberrations caught my interest. Soon I was reading textbooks on genetics. Because of my mathematical background, I delved deeply into the population genetics of Sewell Wright and Ronald Fisher.

In 1959, with the Navy service completed, my wife and I moved to Detroit, Michigan with our one-year old son to begin my medical residency training at the Henry Ford Hospital. There I found a well-stocked library that included “Bacteriophage” by Mark Adams, the first issues of the Journal of Molecular Biology containing the classica Jacob and Monod paper describing the operon model for gene regulation, and two collections of papers by Adelberg and Stent. I suddenly became aware of the beautiful work of the “phage school” and of Watson and Crick and DNA. After many years of haphazard searching for the “right” area of research, I knew I had found it.

In 1962, armed with a N.I.H. postdoctoral fellowship, I began my research career with Myron Levine in the Department of Human Genetics at the University of Michigan in Ann Arbor. Mike was a geneticist studying Salmonella Phage P22 lysogeny. The choice to work with him, while governed more by expediency than by considered planning, turned out to be most fortuitous. Mike was an easy-going young investigator with a solid phage background and well established among the phage crowd. He allowed me just the right blend of independence and encouragement. Together we carried out a series of studies demonstrating the sequential action of the P22 C-genes which controlled lysogenization. In 1965, we discovered the gene controlling prophage attachment, now known as the int gene. By 1967, I had published this work and had carried out a study of defective transducing particles formed after induction of int mutant prophage. During 1966-67, Mike took a sabbatical year with Webner Arber in Geneva and through correspondence, I learned for the first time about Arber’s remarkable work on restriction and modification phenomenon in bacteria.

In 1967, I came to Johns Hopkins as an Assistant Professor of Microbiology and have remained there since. My research work includes studies of restriction and modification enzymes, enzymology of genetic recombination, mechanism of bacterial transformation, and genetic regulation in prokaryotes and eukaryotes. In 1975-76, as a Guggenheim Fellow, I collaborated with Max Birnstiel at the University of Zurich in Switzerland on histone gene arrangement and sequence. It was a superbly enriching year for both myself and for my family.

My wife, Elizabeth, is artistically inclined, enjoys a variety of “Handarbeit”, sings in a church choir, enjoys classical music, and is a moderately proficient linguist (English, Spanish, German, and French). My major non-scientific diversions are classical music and piano. We have four sons and a daughter, none of whom currently indicate a strong interest in science.

Principal worksSmith, H.O. and Wilcox, K.W. A restriction enzyme from Hemophilus influenzae. 1. Purification and general properties. J. Mol. Biol. 51, 379 (1970).Kelly, T.J., Jr. and Smith, H.O. A restriction enzyme from Hemophilus influenzae. 11. Base sequence of the recognition site. J. Mol. Biol. 51, 393 (1970).Roy, P.H. and Smith, H.O. The DNA methylases of Hemophilus influenzae Rd. 1. Purification and properties. J. Mol. Biol. 81, 427 (1973).Roy, P.H. and Smith, H.O. The DNA methylases of Hemophilus influenzae Rd. 11. Partial recognition site base sequences. J. Mol. Biol. 81, 445 (1973).

From Les Prix Nobel. The Nobel Prizes 1978, Editor Wilhelm Odelberg, [Nobel Foundation], Stockholm, 1979

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate. To cite this document, always state the source as shown above.