Genes, Medicine, Moods: A Memoir of Success and Struggle

Epilogue

Prologue

I am proof that it is possible to live a highly successful career in medicine and science, and to struggle with a complex, serious mental illness at the same time. This is the central message of my memoir. In my case, the professional career centered on the field of Human Genetics; the mental illness on a mood disorder called Bipolar Disorder II (BP II). The career story, the outside one, is how the public knows me. It is visible if you look at my Wikipedia entry. The story that describes the myriad ways that BP II has affected my life, the inside story, has largely been hidden from view until now.

The outside story is a narrative of success from early on. I was a gifted student with an almost unblemished scholastic record. Upon graduation from medical school I trained in internal medicine at two prominent hospitals affiliated with highly respected medical schools. Once electrified by a eureka moment when I was a postdoctoral fellow at the National Institutes of Health, I have lived a rewarding, successful career in Human Genetics during which I—along with many colleagues— discovered several childhood disorders, rose rapidly through the ranks of academia, achieved my fair share of national and international visibility, and was given many opportunities to serve as leader, spokesman and advocate.

But the above portrait doesn’t even hint at the person beneath the canvas, the one with BP II. I experienced neither of BP’s cardinal features—mania or depression—until age 26 when I developed a month-long, full-blown clinical depression with its cardinal features: pervasive sadness; difficulty sleeping; loss of energy; and the disappearance of any sense of life’s pleasures. I didn’t know then that BP II caused this depressive episode, because I had not experienced the telltale signs of BP—hypomania or mania—at that time—and wouldn’t for another 13 years. Even then, I mistook the cardinal features of hypomania—a burst of creative energy, indefatigability, and little need for sleep—as nothing more than the exuberance born of making the two most important scientific discoveries of my career. Thereafter, a combination of many episodes of depression, and the diagnosis of BP I in my older brother, led me to realize that I, too, had BP. My signs and symptoms were typical of BP II, rather than the more severe BP I.

It is my intention to integrate the outside and inside stories of my life into a single narrative. This will allow me to emphasize the ways they have played off each other, to point out some ironies, and to posit an explanation for the remarkably few memoirs of this type that treat a person’s two stories as they are: two sides of one coin, each with a different face and words.

The genes I inherited from my parents bequeathed me a blueprint that made high intellectual attainment possible, while also passing on the roots of my predisposition to a mood disorder. The initial joining of my outside and inside stories occurred when a professional disappointment triggered the first depressive episode of my life. On reflection it is clear that some of the key twists and turns of my career— moving from one job to another, even from one type of institution to another—were my way of warding off the premonitory signs and symptoms of depression, a means of recharging my emotional batteries by making big changes rather than small ones. The high side of BP II was as consequential. During a lengthy episode of hypomania, I played risky scientific hunches that proved to be correct, had remarkable energy for sustained experimental work, and made rapid progress because I required little sleep.

This interplay has displayed plenty of ironies. I stumbled into the world of Human Genetics 59 years ago not because I had relatives with BPII—I knew of none then—but because I became responsible for the care of an eight year old boy with a previously unreported genetic illness. I dove into the study of mutant genes not to define those responsible for BP II, but because my colleagues and I discovered several genetic disorders of other children, and followed their scientific traits from the bedside to the laboratory. I searched genealogies and family trees not because I wanted to find out who else in my family had BP II, but because I was trying to determine whether the children just mentioned had conditions inherited as recessive, dominant, or X-linked traits.

The third major reason for integrating my outside and inside stories is more in the form of a confession than an exposition. For most of my life, I have resisted admitting that I even had an inside story that accompanied the obvious outside one. Why? Because I feared being stigmatized for having a mental illness, a usually pejorative term for what is more correctly a brain sickness—a sickness of the brain just as asthma is a sickness of the lung, or coronary artery disease is a sickness of the heart, or cancers are sicknesses of an organ’s cells. Our society still seems to say that mental illnesses are something entirely different than physical ones—conditions that too often provoke shame rather than compassion, conditions that may interfere with good judgment or being taken at one’s word. I was unwilling to see my career threatened by the dread that my veracity or integrity would be deemed suspect. Our society seems to say that it is okay for creative artists, actors, writers, or poets to be eccentric as a consequence of a mood disorder. That concession, however, has not been extended to scientists, physicians—or, for that matter, to lawyers, business leaders, politicians, or the vast majority of affected patients who are not members of any of these groups. To be respected and believed, we must appear to be unblemished. And so I hid for decades, hid until my reputation and professional standing were no longer at risk.

I have begun this story on four separate occasions during the past 21 years – and have even gotten to a nearly complete draft once. In 1998, I quit writing when a suicidal depression nearly caused me to quit living. When I started writing again about 5 years later, I was brought up short by my daughter, Alexa—in her early twenties at the time—who, when I told her that I was writing a memoir, asked but Dad, who is going to read it? Ten years later I aborted the labor because I knew I wasn’t ready to tell the whole story—not just the uncontroversial or self-congratulatory parts. At that time I wasn’t willing to drill into my cognitive and emotional brain, and relive the misunderstandings, failings and sorrows, as well as the joys and triumphs. And last year, just as I had begun retirement with the drive to complete this work, I developed a cancer that spread to a lymph node in my neck; a malignancy requiring both surgery and proton radiation therapy.

No such impediments constrain me now. I am prepared to recall the events and the large number of people who have played significant parts in my life. Many of them have died by now. Of the living, those whom I recall positively won’t mind being named and mentioned. Those few whom I have placed in one or another of Dante’s circles of Hell will simply have to forgive me as I have, with varying degrees of success, forgiven them.

This book is called a memoir rather than an autobiography for good reason. It is a collection of my memories rather than being an exhaustively researched biography of myself. Humans sit at the apex of living things because of the capacity of the human brain, the most remarkable organ in the universe, to remember, to interpret, to feel. I am ready to remember because I must do so while I am still able to remember. The brain, unlike the flavor of some vintage wines, does not usually grow more complex and richer with time, and there is no way to tell whose brain will lose its cognitive capacity quickly, and whose will decline slowly. And, of course, there is that universal moment when memory—like everything else—stops. Neuroscientists who study memory have begun to understand the remarkable complexity of how we process and store memories. Some memories are easily accessed. Others appear to be lost but then are, at some later moment, found. Sometimes the act of remembering something distorts that very memory temporarily or permanently. I have chosen to be undaunted by the caveats presented by such dazzling, and still largely unexplained, biological complexity and plasticity. I will try to be scrupulously honest with my recollections while accepting the reality that they may, at times, be biased or unreliable.

The people, places and events described in these pages are but a small subset of things that have happened to me in 86 years. On several occasions, I have refreshed my recollections by discussing them with relatives and friends. When they pointed out factual errors, I have tried to correct them. On other occasions, close relatives have different memories than mine of the same event, or different emotional responses to the same event. This delicate matter was brought to my attention several years ago by a dear member of my family. When I said I was writing this memoir, my sister-in-law, Civia, chided me, saying but Lee, it will all be from your point of view. I smiled and replied, true, but that’s what a memoir is. This is my memoir. These are my memories.

If my intention was to write something exclusively for my wife, children, grandchildren, great grandchildren, close relatives and a few friends that they would receive now, or at some less propitious time later, I might simply write linearly from the day I was born in 1933 to the day I finished writing. But my ambition is greater than that. Doubtless, I want those I love most to know me best: the heights and the depths; the seeker and the sought after; the things I am proud of and those I regret; the sense of it all. But I have had the privilege, the destiny, to metamorphose in several ways and at several times: from child to husband to father to grandfather to great grandfather; from student to professor; from physician to scientist; from academician to corporate executive; from religiously faithful to faithless; from brainwell to brainsick.

It is these several strands that I will try to weave and braid together, starting not at the beginning, but toward the middle, when I made a career-changing, life-changing decision. Then I’ll circle back to my origins in Madison, Wisconsin and describe my odyssey from there to Princeton, New Jersey, with intermediate stops in New York City, Bethesda, Maryland, and New Haven, Connecticut. If I’m successful, reading my memoir will be the kind of pleasurable experience occasioned when one views a hand-loomed antique folk rug from Kazakhstan: its colors, patterns, idiosyncrasies, mistakes, symbols, and jokes—its uniqueness. If I’m not successful, my life-rug will be like a new oriental carpet: usable, identical to others, of modest value, barely worth passing on to one’s heirs.

But I must remind myself that I do not have time to tarry. Old age is not kind to the human brain. I am losing countless neuronal cells every day, and even larger numbers of connections between such cells. I must tell my life story while my faculties allow me to remember people and events accurately. Even more consequential to completing this task are the published actuarial tables of life expectancy. They show that, statistically, I am likely to live about another 5.6 years. That’s not very many, but it gives me time enough to complete this task.

CHAPTER ONE

An Existential Choice

Life is a sum of all your choices. So what are you doing today? wrote Albert Camus, the twentieth century French philosopher of the Absurd, and winner of the Nobel Prize in Literature. Some choices are personal—such as whom to marry; others professional—such as which job to take; some inconsequential—such as what to eat for breakfast; others life-changing—such as who to fall in love with; some wise—such as treating each of your children equitably; others ruinous—such as attempting to end one’s life.

The most fateful choice of my professional life, which turned out to have major implications for my private life as well, occurred in 1991. I was 58 years old then, and serving as Dean of the Yale University School of Medicine —a post I had held for seven years. The month was March. The occasion was a daylong meeting on the importance of genetic factors in heart disease. The place: Caspary Hall of Rockefeller University in New York City. As I walked through the front door, I bumped into Edgar Haber, whose unexpressive countenance looked expressively grave and sad. We had known each other for more than 20 years. Each of us had built respected research careers in academic medicine—his at Harvard, mine at Yale.

Three years earlier, Haber had surprised me, and many others, by leaving academia and moving to a prominent post in the Pharmaceutical Research Institute (PRI) at the E.R. Squibb Company. Moving from academia to industry was a rare event at the time, and provoked much conversation, consternation, and second-guessing. Less than a year later, Bristol-Myers and Squibb consummated a so-called merger of equals—in reality a takeover of Squibb by Bristol-Myers—thus creating the Bristol-Myers Squibb Company (BMS.) Haber had been appointed Chief Scientific Officer (CSO), a huge task that involved merging nearly 4000 scientists and support staff from the two parent companies. This would have been a difficult goal for a person trained and experienced in industry. But mergers and takeovers didn’t occur in academia, and this one would turn out to be even more challenging because the scientific cultures, strengths and weaknesses of the two parent companies were notably different, and because there were nearly a dozen sites in the United States and abroad that would need to be brought under a single management team.

After exchanging greetings, I told Haber that I had stolen a day from my dean’s duties to attend the meeting, focused as it was on my area of interest: genetics. I expected that Haber, a prominent researcher in the area of cardiovascular diseases, was there for the same reason. I’m not here for the symposium, he said. I came to chat with David—referring to David Baltimore, then the President of Rockefeller University, and earlier a Nobel Prize-winning biologist. How are things going at BMS I asked. He shrugged, took a step away, and said he didn’t want to be late for his meeting with Baltimore.

Less than a week later, the newspapers answered the question I had asked Haber. They reported that Haber had stepped down as CSO, and would return to Harvard immediately. A search for his successor had already begun, the papers said. No reason for this seemingly abrupt decision was given. My curiosity was whetted, but, I had no scientific contacts at BMS to learn from or gossip with, so the matter ended there briefly.

Two weeks later I got a call from Frank Sprole, a devoted Yale alumnus who was a senior vice-president at BMS, and an intimate of Dick Gelb’s, the company’s CEO and chairman. How about coming down to New York and have a visit with Dick, he asked. I had an inkling the subject would be scientific leadership at BMS, but Frank was coy. Because we’d known each other for 20 years, and because he had been instrumental in convincing Gelb—another loyal and generous Yale alumnus—and Bristol-Myers to make substantial early financial contributions to Yale’s Department of Human Genetics that I’d helped form and chair, I agreed to visit with no more questions asked.

Within a week, Gelb and I met in his spacious, elegant suite on the 43rd floor of BMS headquarters at 51st Street and Park Avenue. As I awaited his arrival, I observed a glass case filled with Bristol-Myers products, another containing golf trophies, and a table neatly covered with family pictures. What struck me most, though, was a framed document prominently hung on the wall: the Bristol-Myers Squibb Pledge. More precisely, it was a series of 7 pledges: to consumers; to employees; to suppliers; to shareholders; to communities; to foreign countries; and to the world.

These pledges read as follows:

• "To those who use our products…we affirm Bristol-Myers Squibb’s commitment to the highest standards of excellence, safety and reliability in everything we make. We pledge to offer products of the highest quality, and to work diligently to keep improving them.

• To our employees and those who may join us…we pledge personal respect, fair compensation, and equal treatment. We acknowledge our obligation to provide able and humane leadership throughout the organization, within a clean and safe working environment. To all who qualify for advancement, we will make every effort to provide opportunity.

• To our suppliers and customers…we pledge an open door, courteous, efficient, and ethical dealing, and appreciation of their right to a fair profit.

• To our shareholders…we pledge a company-wide dedication to continued profitable growth, sustained by strong finances, a high level of research and development, and facilities second to none.

• To the communities where we have plants and offices…we pledge conscientious citizenship, a helping hand for worthwhile causes, and constructive action in support of civic and environmental progress.

• To the countries where we do business…we pledge ourselves to be a good citizen and to show full consideration for the rights of others while reserving the right to stand up for our own.

• Above all, to the world we live in…we pledge Bristol-Myers Squibb to policies and practices which fully embody the responsibility, integrity, and decency required of free enterprise if it is to merit and maintain the confidence of our society."

I was impressed by these elegant words, framed in lofty moral and ethical tones. I’ve never found out who wrote them, or how widely they were read within and outside the company. If they had been followed faithfully, BMS might have become a true beacon of corporate respectability and leadership. Sadly, I was to witness the company fall far short of its promises to itself and others on numerous occasions.

As Gelb entered, I was struck by how thin his angular face looked, how bent over he was— not knowing that he had fought—and won— a battle with stomach cancer less than two years earlier. We hadn’t seen each other for nearly 20 years. His hair had turned gray and thinned, but his warm smile and strong handshake were as I had remembered them. He retained his elegant, austere bearing. We talked a bit about the state of Yale University, of the medical school, of work in its Cancer Center. He commented on being able to resume his passion for golf once again, and about his special dietary needs subsequent to having had his stomach removed. He wasted little time on social niceties. I’d like you to be a candidate for the presidency of PRI [the official title for the CSO position] at BMS, he said. I’m flattered, Dick, but I’ve never set foot in a laboratory in industry and I’m a bit old to be changing horses, I replied. This is a phenomenal opportunity for the right person, he went on. You have a great scientific track record and the necessary people skills. After a few more flattering exchanges, I agreed to think about it.

That night I discussed the idea with Diane. She and I had been married for 12 years and had one child together—a nine year old daughter named Alexa. Diane—a Wellesley College-educated, regularly irreverent, always bright and charming woman—and I had met through her work as a star acquisitions editor for publishers of medical and scientific books and journals. Rather than write the human genetics textbook she wanted me to author, I fell in love and married her instead. After Alexa’s birth, Diane had made a decision to redirect her life toward being a wife and mother, a decision that had benefitted Alexa and me greatly, but which Diane revisited from time to time then and for the next 40 years until the present. That is, she wondered whether she might have broken through the glass ceiling of the publishing industry if she hadn’t given up trying.

Diane was more intrigued about the conversation with Gelb than I was. I reminded her that people joked about Yale being a terminal disease, meaning that faculty didn’t leave the place until they died. I’d been at Yale for 26 years. Though not in any way an old blue, the institution had been remarkably supportive of me as a scientist, clinician, teacher, and administrative leader. It was the place where I had satisfied my ambition to be a faculty member at an outstanding medical school. I had flirted with many other institutions during my tenure at Yale, including Washington University, Harvard, Stanford, the University of Pennsylvania, New York University, and the University of California San Francisco, and couldn’t imagine why BMS would pull me away when none of them had. Further, I was sure that BMS wouldn’t offer me the job as CSO because I had no idea how research and development were organized and carried out in industry, and would have only seven years to get something done before having to retire at age 65—a widely held corporate rule in the pharmaceutical industry.

All of these self-protective caveats aside, I was curious, too. BMS employed more than 4000 scientists. Its therapeutic areas included cancer, cardiovascular disease, bacterial and viral infectious diseases, and the central nervous system. The job would represent a huge challenge, a chance to make a kind of difference in the health world that I had never had before. I liked challenges, and had repeatedly sought professional and personal change. Accordingly, I called Gelb a few days later and said I’d be a candidate, but asked that this be kept absolutely quiet. I didn’t know then just how quiet industry was capable of keeping such matters, and what a contrast that presented with academia, which leaked all information like a coarse sieve. You’ll be getting a phone call from Ted Borman, Gelb said. He’s conducting the search.

That very day I received a phone call from Borman. This is Ted Borman, he said in a loud, baritone voice brimming with confidence. I’d like to get together with you at your office he went on. I’ll bring along some information about BMS. Having had no prior experience with headhunters, as professional search firms are called, I had no one to compare Borman with, but I recall guessing that he was good at what he did.

That impression was reinforced at our first meeting. He was large—like his voice —and had broad shoulders, an ever-smiling face, and a large hand and handshake. He carried several inches of booklets about Bristol-Myers Squibb: a glossy description of the company’s businesses—pharmaceuticals, nutritionals, orthopedic devices, over-the-counter medicines, women’s hair care; its most recent presentation before Wall Street analysts depicting, in detail, its pharmaceutical pipeline; and some clippings from the Wall Street Journal and the New York Times reporting on the less-than-two-year-old merger between Bristol-Myers and Squibb.

When I asked why Haber had given up the job as President of the PRI, Borman said only that things just hadn’t worked out, leaving me to imagine which things and why they hadn’t worked out. When I asked about the search’s tempo, he said BMS wants a new CSO in place soon – by July if possible. Completing such a recruitment in three to four months seemed impossibly fast-paced to me. Academic searches almost never took less than nine months and sometimes dragged on for years. Now I understand why. In academia, searches are a critical part of faculty governance and prerogatives: presidents and deans select the search committee composed mostly of faculty; candidates are sought broadly by advertising openings, and inviting referral of candidates via letters sent all over the country. Winnowing the long list down to a short list takes many weeks because search committees are composed of members whose research, teaching, and service responsibilities come first. The interview process is cumbersome and inclusive; and finally, an offer is made and negotiated. By the time a recruitment has been completed, every sentient member of the particular academic unit in question knows who has been asked to join them, and almost every field-related person in the country knows, too. This transparency not only allowed for a thorough canvassing of potential recruits; it also reduced the likelihood that people in the section, department, or school in which the new faculty member was to reside, would act to second guess the choice.

Corporate searches, I was to learn, reflect the top-down nature of corporate governance and the effect that high-level appointments may have on the holy of holies— the share price of the company’s stock. Hiring managers select a search firm whose responsibility is to identify and screen potential candidates. This candidate list, usually no more than five people, is then discussed by a small group of corporate officers; interviews with a few potential candidates then proceed; an offer follows, and the candidate is instructed to make a quick decision. This process has two serious drawbacks: the candidate often has little, if any, contact with the people he’ll be working with or for; and the people with or for whom the candidate will work have had no opportunity to buy in to the recruitment. As will become apparent, this matter is of more than theoretical importance.

Soon after Borman’s visit I read the material about BMS – particularly its pharmaceutical portfolio and pipeline. The merger between Bristol-Myers and Squibb had created the country’s second largest pharmaceutical company—only Merck was larger. BMS was second in size only to Johnson and Johnson as a health care conglomerate. The company’s main marketed pharmaceuticals included captopril, a new kind of drug for the treatment of hypertension and the first billion dollar blockbuster marketed by any pharmaceutical firm, and several important anti-infectives, antidepressants, and anti-cancer agents.

I was excited by the description of the pipeline. Pravachol, only the second approved statin capable of lowering the bad LDL form of serum cholesterol had just been marketed. A new once-a-day angiotensin converting enzyme (ACE) inhibitor, fosinopril, was being launched to treat hypertension—and follow Captopril. A third generation cephalosporin antibiotic was in late phase III clinical development, and ddI – a first generation reverse transcriptase inhibitor for HIV/AIDS was in phase II. The novel anti-cancer compound, Taxol, had recently been licensed from the NIH and had shown clear antitumor effects in phase I trials in patients with ovarian and breast cancers.

The discovery pipeline was equally large, promising and even more innovative. I was particularly impressed by two compounds: one designed to treat both hypertension and heart failure by a novel mechanism; the other aimed at treating hyperlipidemia (increased blood lipids) by acting in a totally different way than statins did.

Diane, whose experience in publishing made her knowledgeable about medical science, was as interested in the pipeline as I was. You’ve made important contributions in human genetics, she said, but you’ve spent your entire research career working on rare inherited metabolic diseases that almost no one has. Why not spend the rest of your scientific career trying to do something about the conditions everyone has— cancer, heart disease, AIDS, and depression?

I could not argue with her logic. Nor could I discount her other reasons for being willing, perhaps eager, to leave Yale and New Haven. Diane was my second wife, and she felt that the Yale first wives club had kept her at a distance, lest their marriages be contaminated by ours. With some notable exceptions, the women of Guilford, whose lives centered around their families and the Guilford yacht club, were equally cool. We were interlopers. I was Jewish, and we had purchased an exquisite, widely admired and coveted, century-old, shingle-style sea cottage at the point of Sachem’s Head harbor. Finally, each of us had an ever present, low level of anxiety about bumping into my first wife, Elaine, whose bitterness was disquieting to us and excruciating for the three children Elaine and I had raised.

But I had not considered these reasons for relocating determinative. The few anti-Semitic buffoons in the neighborhood didn’t much bother me; I had learned well what it meant to be a Jew in a gentile world. I was sure that our nine-year-old daughter, Alexa, was getting a good education in a public school, something that resonated with my own education: all public schools. I had become more emotionally insulated from Elaine’s bitterness, and our children had always been as much mine as hers. I loved our house on the shore: its setting; its authenticity; its shallow roof line that seemed to huddle it and us against the winds of Long Island Sound. And most of all, I identified myself with Yale.

My identification with Yale University could hardly have been stronger. I had come as a 33-year-old assistant professor, and had been successful in moving up the faculty ladder. I had been given every opportunity to succeed as a scientist, clinician, teacher, and leader. Not least, I had the highest respect and regard for the words and actions of two Yale presidents, Kingman Brewster and A. Bartlett Giamatti.

Brewster had been Yale’s president for only two years at the time I joined the faculty in 1965. I recall how proud I was to be a member of his faculty when Yale became the first of the big three to open its undergraduate doors to women in 1968 two years before Harvard and four years before Princeton. I was as proud when, in 1969, Brewster literally opened Yale’s gates to the Black Panthers and their compatriots, thereby averting the riots in that angry year which had befallen such prominent academic bastions as Columbia, the University of California in Berkeley, and my alma mater, the University of Wisconsin.

Many of Yale’s alumni were not nearly as enthusiastic about these bold, liberal actions as I was. The doors and gates Brewster threw open offended many of them permanently, but not as angrily as his comments about the trial of the leader of the Black Panthers, Bobby Seale, about which Brewster had expressed doubt that a black revolutionary could get a fair trial anywhere in the United States. This brave assertion provoked vicious outcries from high places: Henry Kissinger mused about Brewster’s possible assassination; Vice-president Spiro Agnew demanded Brewster’s resignation. I was an unintended target of the hostility Brewster’s actions generated when I went to Pittsburgh in 1973 to raise funds for our fledgling department of Human Genetics. I was duly ushered in to see Richard Scaife in his large, stately decorated office at the Mellon Bank. He began the conversation with the following question: What do you think of Kingman Brewster? I replied, I think he is the most outstanding president of a major university in the country. He scowled, rose to his feet, and said we had nothing more to discuss. I flew back to New Haven, not in the least disappointed that this foray had added nothing to the department’s coffers.

Brewster twice intervened in my own career. First, in 1968, when he phoned me at home the night before I was prepared to accept an attractive offer from Washington University in St. Louis to lead the section of genetics in that school’s strong department of pediatrics. Yale wants you to lead the medical school’s interdepartmental program in medical genetics, he said. That statement, devoid of any promise of a university’s typical resources, that is laboratory space, money, and positions, was enough. The President of Yale has reached out to me, a little-known assistant professor, I thought. Brewster wasn’t just Yale’s President: he epitomized the academic aristocracy that had long awed me. Accordingly, I said no to Wash U. Three years later Brewster demonstrated his confidence in me again. This time the stakes were higher.

Three nationally visible Yale geneticists had received offers from other universities at the same time: Frank Ruddle from Washington University; Sherman Weissman from the University of Chicago; and I from Harvard. This posed a major threat to Yale’s determination to build strength in human genetics, an area of science that was truly exploding with excitement. I believe, though I have never had it confirmed, that three people convinced the president to take bold action. One was Ed Adelberg, an esteemed bacterial geneticist whose personal trademarks were soft-spoken earnestness and national respect. The second was Charles Davenport Cook, the chair of Pediatrics who saw that genetics was going to have a major impact on child health. The third was Fred Richards – as in-your-face as Adelberg was diplomatic, and as influential as a giant in protein chemistry, who barely missed receiving the Nobel Prize, had earned the right to be. Behind the scenes they convinced Brewster to establish a new department of Human Genetics in the medical school. I was asked to be the chairman and was offered a few million dollars with which to build the department. I will always remember the words of one of my friends, who observed tartly, Lee, Brewster didn’t give you a department; he gave you a hunting license.

I have one more recollection of Brewster. In 1972, the School of Medicine was looking for a new dean. I, along with about 15 other faculty members had been appointed to the search committee that Brewster chaired. At one of our lengthy meetings during which candidates were discussed—some even dissected—we turned to the possibility of recruiting a stellar pediatrician named Mary Ellen Avery, who had recently moved from McGill to Harvard where she was appointed chair at Harvard Medical School and chief at Boston Children’s Hospital. Several committee members observed that Avery would be a superb candidate, but that she was unlikely to relocate again after so recently moving to Boston. Well, said a male member of the committee, You know the old saying, a woman may not accept, but she never minds being asked. Brewster extended his entire arm with forefinger prominently pointing toward the offender and said in an unusually loud voice, that is not a joke at Yale anymore. Avery was interviewed in Boston, but graciously demurred.

Brewster was succeeded as Yale’s president in 1978 by A. Bartlett Giamatti. It would be difficult to exaggerate the contrasts between these two accomplished and formidable men. Brewster was a handsome, always-elegantly-coiffed patrician and he knew it. Giamatti was good looking too, but he hid his face in a beard that was sometimes trimmed, often scruffy. Brewster strode confidently. Giamatti slouched and shuffled. The shuffling gait was a manifestation of an inherited neurologic disorder that his father also had, and that caused weakness of his lower legs. It is called Charcot-Marie-Tooth disease and I believe I was the first person to diagnose it in Giamatti. Brewster acted as if he deserved the spotlight. Giamatti sought it too, as long as the light bathed him in a positive aura.

Brewster was a Mayflower-descended barrister; Giamatti a revered professor of comparative literature whose grandfather was a worker in a clock factory after emigrating from Italy. In Brewster’s presence, I felt like I was having an audience with a king, who had chosen to dub me. He occupied a tiny office in Woodbridge Hall, which I thought was the essence of reverse snobbery. My visits with Giamatti in that same compressed space, much smaller than the dean’s office in the School of Medicine, felt different. Whereas I often felt that I should kiss Brewster’s ring upon exiting, my reflex with Giamatti—never consummated—was to give him a hug, and tell him that everything would be okay.

No one was surprised when Brewster resigned the Yale presidency in 1977 to become the United States ambassador to the court of St. James, a post offered him by President Jimmy Carter. Brewster was weary, and had already failed to follow his recommendation that a person should hold a big job no more than seven years to avoid becoming complacent or stale. As the Yale Corporation (the university’s name for its board of trustees) searched for Brewster’s successor, Giamatti emerged as a major internal candidate, but not the first choice overall. The search committee wanted to go outside to galvanize new directions, and shake up the place. Yale’s finances were in disarray. The university had run deficits annually for most of Brewster’s presidency, and the endowment principle was being invaded—this, a punishable sin. The trustees were seeking someone of proven managerial ability. They turned to Henry Rosovsky, Dean of the Faculty of Arts and Sciences at Harvard. But, after protracted negotiations, Rosovsky withdrew as a candidate. This episode, not unexpectedly leaked far and wide, proved embarrassing to Yale, and to the person the trustees then offered the job—Giamatti. Although he had professed, with tongue in cheek, that the only presidency he ever sought was that of the American (baseball) League, Giamatti wanted to be Yale’s president, and quickly accepted.

He set about assembling his leadership team, and tackling the financial problems that had so vexed the trustees and many Yale alumni. Within three years, the university’s budget had been balanced, and remained so for the remainder of his tenure. But this required fiscal restraint that chairmen and deans were unaccustomed to, thus eroding Giamatti’s popularity in some quarters. Because the medical school depended remarkably little on funds from the university, I was only vaguely aware of the distress being felt across town. The department of Human Genetics was thriving: federal grants were pouring in, new faculty were being successfully recruited; and many of the best M.D. and Ph.D. fellows in the country were choosing us for additional training. I viewed Giamatti’s early years almost exclusively from the vantage of reading and listening to his writings and speeches, and being thrilled by his eloquence.

To say that Giamatti had gifts of written and oral expression is to understate strenuously. His speeches to freshman, to graduating seniors, to alumni, to the Modern Language Association, and beyond, are elegant, clear, high-minded, candid. These messages—or as he sometimes called them, homilies—fill two volumes: The University and the Public Interest and A Free and Ordered Space. He believed that … the educational process… is an act of the will fusing values about excellence and equity into a single … generous ideal. He reminded Yale that civility was central to his idea of a university, where the most free-swinging and intense intellectual exchange takes place without any intent to damage or coerce other human beings… Civility, Giamatti said, has to do with decency and mutual respect, but nothing to do with gentility… good breeding, or polite manners.

I have long thought that Giamatti’s lofty expression of educational ideals must have felt ironic to him as he toiled with his presidential labors. There was nothing idealistic about balancing the budget. There was nothing soaring about addressing the sad conditions of Yale’s buildings and grounds. There was nothing inspiring about dealing with a long, dispiriting strike of Yale’s clerical and technical workers. Each of these chores, and many more, were faced unflinchingly with the invaluable aid of his dedicated Provost, William Brainard, who had put his promising career in Economics on hold to help Giamatti. But the criticism—from faculty and trustees—and the always ready second-guessing that accompanied his decisions— took their toll on Giamatti’s sensitive, stubborn being.

In 1983, Giamatti’s sixth year as president, my association with