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Annual Review of Genomics and Human Genetics. This article—a mini-memoir—focuses on the first half of my half-century-long career as a human geneticist: its accidental beginnings; its early bad and then good fortunes at the National Institutes of Health; its serendipitous successes and career-making scientific productivity at Yale; and its incalculable fortuity in the form of the large of talented and resourceful mentors, colleagues, postdoctoral fellows, graduate students, and technicians who worked with me.

These years acted as a launchpad for positions of visibility and leadership that followed them. My personal odyssey, which began in Madison, Wisconsin, and meandered with no fixed plan to New York, Bethesda, New Haven, and Princeton, has offered me life views as a human and medical geneticist that are panoramic, splendid, and indelible. I doubt that many people have been as fortunate as I have been in the professional life I have lived—and continue to live. These words were forcibly thrust in my direction in by a prominent professor in the Department of Internal Medicine at the Yale University School of Medicine.

I had just told him that I intended to specialize in genetics rather than in nephrology—his field. I wasn't surprised that he didn't recognize medical or human genetics as a discipline. Few people did at the time. My fateful decision might have been taken for a variety of reasons. I could have been influenced by an inherited disorder in my family, but I knew of none—then. I could have been fascinated by one or more courses in genetics that I had taken as an undergraduate or medical student at the University of Wisconsin, but I hadn't taken any.

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I could have been captured by seeing patients with phenylketonuria or cystic fibrosis as a medical student, or with sickle-cell anemia or thalassemia as an intern, but they did not hold my attention more than patients with a variety of other childhood or adult illnesses. Then, you might ask, what did influence me to respond to a clarion call in that has continued to sound for 50 years? The answer in brief: a chance clinical encounter; a serendipitous selection of a research mentor; and a field genetics that was already thrilling its small cadre and beginning to impress the community of life scientists.

To tell this story and the many stories that followed it, I must retrace my steps to I came to the hospital believing that I would learn how to take care of sick people, and that such caring would be the principal direction of my professional life. Nothing had occurred during the 18 months of internship and residency that had disturbed my bent toward this well-trod path.

Nothing, that is, except the decisions being made by my fellow house Yale Padova sex chat. Several of them announced that they were going to the National Institutes of Health NIH in Bethesda, Maryland, to become full-time associates read: fellows in basic or clinical research. Although I had spent two summers during medical school doing research, neither experience had been powerful or had moved my career vector.

Nevertheless, I was intrigued enough by the vague idea of spending a couple of years in the laboratory, and had esteem enough for those of my compatriots heading in this direction, that I decided to traipse after them.

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In it was easy to get a job at NIH. MDs from the country's most prestigious hospitals were flocking there to try their hand at becoming physician-scientists. Accordingly, in June my wife, our two children, and I trundled off to Bethesda. We moved into a small, tan, single-story rented house. It was box shaped and had two bedrooms, a fenced-in back yard, and a front stoop of four stairs. This made it the grandest place my wife, Elaine, and I had lived in during our five years of marriage. Once the family had been settled to a degree, I bounded off to NIH, only a few blocks from our house.

ByNIH already Yale Padova sex chat a large campus. Though tiny compared to today's sprawling footprint, it already had seven institutes, named for diseases or organ systems that were being investigated. The National Cancer Institute, the first of these categorical organizations, had been established in Each institute was housed in its own building. Sitting in the middle of all these squat 3- or 4-story structures was the imposing story Clinical Center: a research hospital capable of housing several hundred patients who volunteered to participate in clinical investigative studies.

My clinical associate position meant that I would spend the majority of my time doing clinical research under the supervision of a senior scientist, and the remainder caring for patients on one or another kind of study protocol. I soon learned that our service was populated with several outstanding scientists.

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Sadly, my supervisor was not among them. Let me tell you why I describe him in such an unattractive way. At our initial meeting deed to sketch out my research project, we sat down in a windowless room lined on three sides with shelves filled with lime green—shaded, clothbound notebooks. My supervisor, a handsome man in his forties with a shock of light brown hair, pointed to the shelves and said that he and his team had been admitting patients with a variety of cancers for a decade, and had proceeded to study their metabolic parameters in great detail.

This meant that caloric intake and caloric expenditure had been measured; that dietary carbohydrate, fat, and protein had been quantified to the last gram; that concentrations of nearly 20 substances had been measured in blood, urine, and feces; and that all of this information had been carefully recorded in the bound notebooks.

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I remained sitting for a good long while, feeling like I'd been a hit on the head by a two-by-four. If this guy doesn't know why he's been measuring all these parameters for a decade—at great cost of time, effort, and money—why does he think I'd be able to find out? Why does he think I'd want to? That evening I told Elaine about the day's horrendous events. Maybe I should devote myself to clinical medicine—something I understood and am good at. The next morning I went to see the chief, Nathaniel Berlin. He was a diminutive, bespectacled, balding, quiet-voiced man in his early forties.

His response came quickly. He agreed that the project proposed was a poor one, and that I shouldn't do it. He refused to accept my offer to leave NIH, and said I should take whatever time I needed to find a new supervisor and new research project—anywhere in NIH. Berlin's response was among the most important events in my life. In retrospect, he became the third person—along with my father and Robert Loeb, the chief of medicine at Columbia—Presbyterian Hospital—who mentored me. After liberating me, Berlin followed through by arranging appointments, making himself accessible, becoming a personal friend, and seeing how things were going.

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I was to leave NIH before he did, but that only added to the strength of a relationship that lasted more than 40 years. The trauma and stress of this hour period had barely passed when something new entered my life, like an unwanted guest. I began to sleep fitfully and awaken in the middle of the night. I lost all interest in food, sex, and children.

My vaunted quantum of energy and sense of self-worth evaporated, and life felt slow and empty. I had a strange feeling behind my eyes, as if I were in a fog. This slow-motion, glass-nearly-empty state hung on for a few weeks, but I forced myself to continue working. At this time my duties included taking care of children with acute leukemia who were being treated with one or more chemotherapeutic drugs.

This was a baneful, but necessary, time in the history of cancer chemotherapy. The side effects of the medicines were horrendous: baldness; bacterial and fungal infections; bleeding resulting from extremely low platelet counts. Worst of all, none of the children I ministered to survived. It was to be nearly 20 more years before drug cocktails were developed that cured acute leukemia in children. But these cures would not have occurred without the trials and errors that I witnessed day by day.

However sobering and saddening this clinical experience was for me, it served to jolt me out of my funk. After about one month, the emotional fog lifted and the other symptoms disappeared as well.

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Though I didn't make the diagnosis then, I came later to realize that I had been typically, clinically depressed. I attributed this emotional disturbance to the circumstances surrounding the transition to NIH. I had left something I was good at—clinical medicine—for something that was completely new and strange—research.

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That may have been part of the answer, but it was not the entire answer. This was the first of many episodes of clinical depression that have haunted me throughout my life and that were manifestations of bipolar disorder, which was rampant in my family.

During the next few months, I searched for a new advisor and a new project. I went to see a distinguished PhD biochemist named Elbert Peterson, who, with a more senior colleague, Herbert Sober, had developed a means for separating proteins from one another using diethylaminoethyl cellulose. When I showed up at Peterson's office, I was still wearing the long white coat we wore when seeing patients, a stethoscope protruding from the coat's pocket. Peterson wore his black, neatly trimmed hair slicked down, and his eyes were dark and penetrating. Peterson viewed the stethoscope as the arch symbol of a physician, a group he disparaged as researchers.

He wasn't in any way interested in clinical problems or those who studied them. He was focused on the basic science of protein separation and would accept me only if I shared that interest. I ed his lab and learned how to do protein separation expertly, but failed to get excited about this exclusively technologic investigation.

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DNA and Other Strands: The Making of a Human Geneticist