Memorial Minutes on Carroll Williams (FAS) and Aaron Gissen (HMS) and Louis Zetzel (HMS)

CARROLL MILTON WILLIAMS

The death of Carroll M. Williams from lymphoma on October 11, 1991, ended a distinguished career of more than half a century at Harvard University. One of the foremost physiologists and developmental biologists of his generation, Williams, along with the late Sir Vincent Wigglesworth of Cambridge University, revealed the network of hormones that govern the growth and development of insects.

In the 1950s Williams became the first to extract and characterize the juvenile hormone, the substance that holds insects in the immature, larval stage until they have grown to the appropriate size to transform into adults. Adequate blood titers of juvenile hormone, for example, retain butterflies in the caterpillar stage, so that when the substance is reduced below threshold level, the caterpillar molts into a pupa, within which it transforms into a winged, sexually mature imago.

Pressing this and other findings with his collaborators, Williams conceptualized what has become known as the Third Generation Pesticides, the synthetic analogs of juvenile hormone which in very small amounts retard and halt normal development as well as ovarian growth. These materials have the advantage of being non-toxic to most other forms of life -- in other words, an approach to the much sought-after "magic bullets" of ecology. A substantial industry has been based on this early research; one of the first applications, presided over by Williams, was the eradication of a huge infestation of Pharaoh's ants from the walls of Harvard's Biological Laboratories.

Other principal contributions by Williams include the discovery of the brain hormone, a pituitary-hormone substance that turns on yet another endocrine organ, the prothoracic glands. The latter organs release ecdysone, the steroid hormone that mediates development. Williams' isolation and partial characterization of ecdysone, performed with Peter Karlson and Adolf Butenandt of Germany, was the first such advance accomplished for an insect hormone.

Among Williams' many other contributions were the discovery of the enzymes cytochrome b5 and cocoonase, and the demonstration that the extraordinary sarcosomes of insect flight muscle are in fact giant mitochondria used to power flight.

In personality Carroll Williams was a traditional Southerner, a man of charm and unfailing courtesy who kept his rich Tidewater accent untainted by clipped Yankee tones throughout his life. His dedication to science was intense and pure, his influence on his legions of students and admirers charismatic. He urged his acolytes go for big discoveries, but to be prepared to approach them one step at a time as necessary. Go for home runs, he said, but don't disdain modest, short-term objectives, the singles of the research game. "You can't steal second," he added, "until you get on first." And don't linger too long with a losing enterprise; turn away from the many "will-'o-the-wisps in cul-de-sacs" that prevail in the scientific enterprise.

He was a private man who genuinely disliked talking about himself, even as he praised the best qualities and accomplishments of others. He followed a wide range of journals closely, and talked enthusiastically about the most important results reported in each. He was a superlative critic: he spurned poor work firmly but lightly, and he praised well, with reflection and information. He counseled boldness and risk-taking -- but modesty always, even in the midst of triumph. "Now and then," he once said to his brilliant student Howard Schneiderman, "you are entitled to an ego trip, but I urge you to go coach."

Carroll Williams was born on December 2, 1916, in Oregon Hill, a working-class neighborhood of Richmond, Virginia. He was a prodigy, skipping a grade in elementary school, graduating from high school at the age of 16, and attaining the rank of Eagle Scout along the way. An enthusiastic naturalist, he began serious research on the biology of moths and other insects as an undergraduate. After finishing with honors at the University of Richmond in 1937, he began graduate studies at Harvard, completing the Ph.D. in 1941. He then embarked on two terms as a Junior Fellow in the Society of Fellows, during which he earned an M.D. summa cum laude from Harvard Medical School. He was appointed Assistant Professor in Harvard's Department of Biology in 1946, and moved successively to Associate Professor in 1948, Professor of Zoology in 1953, and Bussey Professor of Biology in 1965. He served as Chairman of the Department of Biology during 1959-62, Chairman of the newly created Department of Cellular and Developmental Biology in 1972-73, and Chairman of the Executive Committee of the Science Center in 1975-79. During his forty years on the faculty he guided the training of twenty-five Ph.D. students.

Widely admired in the larger scientific community, Williams was a very active member of the National Academy of Sciences and Institute of Medicine, and Fellow of the American Academy of Arts and Sciences and American Philosophical Society. His awards include the George Ledlie Award and Boylston Medal of Harvard University, the AAAS-Newcomb Cleveland Prize of the American Association for the Advancement of Science, the Howard Taylor Ricketts Award of the University of Chicago, and the Founders Memorial Award of the Entomological Society of America.

Carroll Williams was a close and devoted family man. He is survived by his wife, Muriel, also a biologist as well as an expert photographer who assisted him in his research throughout most of his long career, and the two surviving sons, Roger L. and Wesley C. Williams, of four born to him and Muriel.

Respectfully submitted,

Daniel Branton

Fotis C. Kafatos

Edward O. Wilson, Chairman

Memorial Minute

Dr. Aaron J. Gissen

In 1917 the world was still at war as Aaron Julius Gissen was born May 11th into a family of Russian-American émigrés. His parents were a product of that Russian-Jewish culture so marvelously recorded by Shalem Aleichem and stunningly depicted in one of the great adapted Broadway musicals, Fiddler on The Roof. Born in the Crimea, Gissen's parents brought with them to America a culture rich in Jewish tradition. But like Tevya's children, they broke free of the geographical confines and emigrated to New York City. The father was in the business of passementerie, she a homemaker raising two children in the Flatbush section of the borough of Brooklyn. Aaron, the first born, was precocious enough to enter the public school system at four and one-half years of age. Because of his youthful European attitudes, those early years in the New York school system were apparently socially difficult. However, as he grew more confident and conformed to the ethos, he complemented scholastic achievement with involvement in many a social activity. Thus he became a class leader and a graduate at age 15 from Boys High School in Brooklyn, a member of Arista, the society that recognizes distinguished academic achievement.

Because the family was one of insubstantial means, there was especial rejoicing when Aaron Gissen was awarded a full tuition scholarship to Johns Hopkins University. In 1932, during his second year at the Hopkins, he contracted a disease characterized by migrating joint pains and low-grade fever, the syndrome of rheumatic fever which went unrecognized and in those days had no medical remedy. Unwittingly, the cause of his ultimate death was foreordained. A stellar student, he graduated with election to Phi Beta Kappa in 1936. Once again there was great celebration in the Gissen clan, by now in the category of lower middle-class, when Aaron was accepted at New York University Medical School and Bellevue Hospital. But there was great concern as well since the family could summon little of the financial support necessary. His brother, Harold, volunteered to delay plans for his own additional education to help with expenses. By means of loans and odd jobs, Aaron completed medical school in 1940 again with honors in election to Alpha Omega Alpha. Parenthetically, it was while engaged in the physical diagnosis course, that Gissen first came to understand rheumatic fever as the illness contracted at Hopkins.

The next two years were consumed in a rotating internship at the Cumberland Hospital in Brooklyn. With the world once again at war but, because of a heart murmur, Aaron was denied enlistment in the armed forces. Characteristically he volunteered to help in the war effort and served as a draft-exempt physician at the Hercules Powder Plant in Roanoke, Virginia. The return to New York City in 1943 was signalled with a residency in general surgery at the Mt. Sinai Hospital. It was there that he met his wife to be, Dr. Janet Greenberg, a medical intern. After three years as a surgical house officer, both Janet and Aaron Gissen departed Mt. Sinai to spend the next 12 years as family physicians practicing out of their home in Westbury, Long Island. Aaron sustained his abiding interest in education by becoming a member, then President of the local School Board and in that capacity having the pleasure of presenting his daughters with their high school diplomas. Gradually he became dissatisfied with the pressures of family medicine. And because his practice embraced all but the major surgical interventions, Gissen understood through first-hand experience the importance of the then emerging specialty of anesthesiology.

At age forty therefore he sought the counsel of Professor Emanuel M. Papper, Chairman of the Department of Anesthesiology at the Columbia Presbyterian Medical Center. Papper has written of their early interactions: "I met Aaron Gissen sometime in 1957, when he was forty years old and wanting to change his career from that of general practice with an emphasis on surgery to anesthesiology with an academic career in mind. As Chairman of Anesthesiology at Columbia and only two years older than Aaron, this first encounter to say the least, was an unusual and extraordinary experience for both of us. From the very beginning of our relationship I learned much about the human condition and the way in which career development can occur among people of great imagination coupled with their sturdy convictions. That first encounter would never be forgotten and I decided that it was in my own best interest, let alone for that of the department I was charged to lead, if I were to continue to learn from Aaron Gissen's maturation and from his views thereof.

"With a life experience totally untuned to the then still relatively newly developing specialty of academic anesthesiology and with no discernible background or experience in that field prior to age forty, Aaron Gissen made remarkable strides and most notably, without negative impact upon other people as he was moving tactfully and quietly past them at a rapid pace toward achievement of goals which had to be difficult to attain for anyone - and certainly for 'an older resident'."

As an anesthesia resident, Gissen sought no special consideration either for his age or experience to become by tacit consent a leader of his peers. Clinical skills were developed rapidly, his scientific development in keeping with the patterns of scholarship in the Department at that time, where highly intelligent people would have the opportunity to study with distinguished basic scientists at Columbia's College of Physicians and Surgeons. Gissen learned his science from Professor William Nastuk in the Department of Physiology, and was soon recognized locally as expert in the understanding of the electrophysiology of excitable membranes, as affected by anesthetics. A publication co-authored with Johanis Karis on "The effect of halothane on neuromuscular transmission," (JAMA 1966) is considered to be of benchmark quality. His growing reputation as a scholar was recognized by an Assistant Professorship in 1965 followed in 1970 by appointment as Associate Professor of Anesthesiology and then as chief of neuroanesthesia at the Neurologic Institute.

In 1971 the Harvard Medical School and the Massachusetts Eye & Ear Infirmary enticed Gissen to go to Boston as Anesthetist-in-Chief of the Infirmary's Department of Anesthesiology and Professor at Harvard. However, after a year it became clear that the administrative responsibilities of a chief of service seriously eroded the time available for bench research. After seeking counsel of the medical leadership at the Infirmary and especially of the School's Dean Robert Ebert, he accepted a position as chief of neuroanesthesia at the Massachusetts General Hospital.

In 1979, Aaron Gissen joined a long-time professional colleague at the newly created Brigham and Women's Hospital where Dr. Benjamin G. Covino had just been appointed Anesthesiologist-in-Chief. Gissen became his Residency Program Director, consequently able to resume his studies on the effects of anesthetic drugs on excitable membranes. These activities coincided with the emergence of that anesthesia department's pre-eminent position in regional anesthesia. Professor Gary Strichartz, Gissen's research colleague, writes. "Aaron was a mainstay of the newly developed research laboratories inspired by Covino's chairmanship. Addressing the scientific basis for the clinical observation of differential functional loss during regional anesthesia, Aaron applied techniques he had learned at Columbia to the study of impulse inhibition in isolated nerve. With focus and determination, he made a series of discoveries, published as six original reports, that challenged the half-century old (and incorrect) belief in the greater susceptibility of smaller nerve fibers to local anesthetics. His purpose was not diverted by initial widespread unwillingness to accept those findings, an opposition that would have swayed one less resolute."

During this period, his work was recognized by a co-investigatorship of a continuously funded NIH grant, also co-authorship of a definitive review on differential nerve block in the Handbook of Experimential Pharmacology and the mentoring of numerous junior faculty in the department as well as hosting national and international faculty on sabbatical leave. He was also honored as a recipient of the Excellence in Research Award of the American Society of Regional Anesthesia. His research continues to provoke further studies in anesthesia and pain control.

Leroy D. Vandam, the Brigham's Professor of Anaesthesia, Emeritus, describes Gissen's impact: "When Aaron arrived he brought with him a much needed mantle of calm, stature, and accumulated wisdom. We had been working with a relatively young staff and a Chairman who at first was able to be in the Department for only one day a week. Having an elder statesman, full professor, researcher and clinician at hand, was the catalyst needed to keep the Department on track.

"Aaron had the unique ability to see all sides of a problem or controversy and the wisdom to explain options so that only the best choice was implemented. Consequently, he was available at all times to any who sought his help. He provided depth to the clinical side, experience on the research side and was able to present and implement the new Chairman's mandates without coloring his own judgment. Subsequently, as the melding of the three former divisions of anesthesia became a reality at the BWH, Aaron had the time and opportunity to carry out original and novel studies in our division of Neuroscience."

At age sixty-five, Gissen relinquished the clinical setting to spend full time in his research laboratories. In 1987, he became Professor Emeritus and was awarded the "Distinguished Service Award" by the American Society of Regional Anesthesia for his research leading to a greater understanding of the effect of anesthetic agents on nerve membranes. He was then able to indulge in the life-long hobby of raising award-winning orchids in a spacious greenhouse attached to his home.

Behind all of these stellar accomplishments and without complaint on his part, Aaron was beset with a deterioration of his heart and circulation, the result of scarring by that once dreaded disease, rheumatic fever. A previous operation for repair of multivalvular cardiac dysfunction had to be redone, even then followed by relentless deterioration, recurrent anemia and the need for periodic blood transfusion. As befitted his character and courage he was a vital force until the end.

Aaron Julius Gissen succumbed to heart failure on December 10, 1989. He is survived by his wife of 45 years, Dr. Janet Gissen. A daughter, Carolyn, is a radiologist at the Lahey Clinic, and Elizabeth an architect in Boston. His only son, David, practices

anesthesiology in Nevada. Aaron's brother, Harold, later completing his medical education, recently retired as a pediatrician in White Plains, New York.

Respectfully submitted,

Janet Gissen, M.D.

Leroy D. Vandam, M.D.

Gary Strichartz, Ph.D.

Emanuel M. Papper, M.D., Ph.D.

Ms. Helen Gallahue

Richard J. Kitz, M.D., Chairman

MEMORIAL MINUTE

Louis Zetzel, M.D.

Louis Zetzel, Clinical Professor of Medicine, Emeritus, died on September 14, 1993. He was born in 1909 in Chelsea, Mass. He graduated from Chelsea High School, entered Harvard College on scholarship at age 16, and graduated Phi Beta Kappa in 1929. He was raised in a strongly traditional Jewish setting and his early intention was to become a rabbi. At Harvard College he concentrated in Semitic Languages and History, which (in his words) "seemed to fulfill my intellectual and spiritual needs." He went on to Harvard Medical School, Class of 1934, but only after his college tutor, the great Hebraic scholar, Professor Harry Wolfson, "for the longest time, refused to send in, as then required, his recommendation and approval (for my medical school application,) hoping to persuade me to remain in his field." He did maintain a life-long interest in Jewish affairs and a commitment to Jewish causes.

After Lou's medical training, which included fellowships in New York and Philadelphia, he joined the staff of the Beth Israel Hospital, with which he remained closely associated throughout his career. He was Chief of Gastroenterology from 1956 to 1968. During World War II he served in the Army Medical Corps, rising to the rank of Lieut. Colonel. He was a member of the faculty of the Harvard Medical School from 1939 and retired as Clinical Professor of Medicine in 1975. For many years he served on the Admissions Committee.

An internist, he was an expert on diseases of the digestive tract. He was a distinguished teacher and mentor to younger doctors and continued in private practice until 1986. Deeply committed to each of his patients, he made house calls until his retirement at the age of 77.

His bibliography includes almost 40 important research papers, scholarly reviews, and book chapters in leading medical textbooks. His first paper, which was published in 1930, dealt with the identification of components in chicken liver that could be used in the treatment of pernicious anemia. His efforts to understand the role of the gastrointestinal tract in the pathogenesis of anemia led him to carry out intubation studies first on himself, and later on human volunteers. In 1943 his landmark paper on the motility of the human stomach, duodenum, and jejunum was published in the Journal of Clinical Investigation. In 1953 he and Dr. Benjamin Banks published another important paper in the New England Journal of Medicine on the prognosis of patients with gastric ulcers treated without surgery.

Lou's major research contribution was elucidating the course and treatment of non-specific ulcerative colitis and what is now know as Crohn's disease. He described the natural history of both diseases, helped define the clinical distinctions between them, and demonstrated the usefulness of corticosteroids in their treatment. This work was published in a series of papers in the New England Journal of Medicine.

He was profoundly influenced throughout his medical career by Dr. Herrman Blumgart, who was his (in Lou's words) "mentor, role model, physician and patient, friend and fishing companion" and whose "wisdom, humility, compassion and joy in his work" he greatly admired.

In this day when primary care is at last beginning to achieve the recognition it merits, Lou's view will perhaps attract even more attention than when he set it forth for his Harvard College 50th anniversary volume:

"My idea of what a family physician should be means his availability to his patients, even if this entails the inconveniences and interruptions of his private life. The advantages to the physician in seeing, knowing, and understanding better his patient when viewed in his natural setting at home are rewards which more than compensate for the extra effort."

In this report he also said that his "gratitude to Harvard College and its Medical School knows no bounds. Whatever I have attained would not have been possible without their contribution."

All who knew him as teacher and colleague speak almost with reverence of his qualities as a doctor. To obtain the perspectives of his patients the committee turned to a few:

Professor Victor Weisskopf said, "He was our family doctor - the old fashioned, human doctor. He really cared. What was incredible was the fact that he was always available. He was just perfect for all of us."

Professor Walter Kaiser also commented on "his profound compassion and his personal concern for patients." Professor Kaiser mentioned as well the celebrated Zetzel ferocity. During his first visit to Lou's office, Lou took a phone call from another patient and seemed to erupt because the caller had clearly violated instructions with respect to activity. "Lou began shouting at the hapless caller," Professor Kaiser wrote, and "terminated the call by promising that 'I am coming to see you this afternoon, and I want to find you at home and in bed.'" Professor Kaiser reported that it could have been quite scary, except, he said, even as a new patient, he recognized that "Lou was incapable of being scary. It was fabricated fury." Professor Kaiser went on to say that Lou subsequently "scolded me once or twice in almost the identical way. I came away from those scoldings consoled by his evident caring and feeling, not so much chastised, as caressed."

Joseph Kirsner, Professor of Medicine at the University of Chicago, and one of the nation's most distinguished gastroenterologists, expressed his gratitude for Lou's help in the care of his brother. He spoke of Lou as a "very wise, very kind and perceptive physician, a good human being who ... combines the continuing search for knowledge with the warmth of the humane doctor."

A colleague who helped look after Lou's patients when Lou was not in the city reported that when he "departed on his vacations, he left his itinerary and phone number not just with me, but also with his answering service in case his patients wanted to call him directly."

Lou's example remains alive with all in medicine whom he touched. One of his lessons left a profound mark on housestaff and on medical students, and as one of our committee can attest, on the then physician-in-chief of the Beth Israel Hospital. The classroom was a nurses' station at the Hospital. The year was in the mid-1960s, and the month one during which Lou and Howard Hiatt were both on service -- he for patients on the fourth floor, and Howard for those on the sixth. At 1 a.m. Howard had returned to the hospital because a patient had developed an emergency problem. The problem was resolved and Howard was about to leave when the resident in charge told him of an urgent situation that had arisen on the fourth floor. Clearly the housestaff had already managed things well, and the resident asked whether he should disturb Dr. Zetzel. Howard asked about his instructions from Dr. Zetzel concerning such issues, although he knew well the answer. The resident reported that Dr. Zetzel had asked that he be called whenever a patient on his service developed any problem that might be serious. "But," said the resident, we do have things in hand and we could quickly review them with you and thereby spare Dr. Zetzel a trip to the hospital." Then, knowing Lou far better than did the resident, Howard suggested that he telephone Lou, tell him that things were in hand, indicate that Dr. Hiatt was in the hospital for other reasons, could see the patient and was willing to certify to him that the proper steps had been taken. Howard had privately anticipated the nature of Lou's response to that call, but had underestimated its forcefulness. The somewhat red-faced resident returned a few minutes later to say that he had awakened Dr. Zetzel and that Lou had been somewhat more emphatic than was his wont. He said he had been instructed to "tell Dr. Hiatt that I'm grateful for his offer, but when decisions are made on patients for whom I'm responsible, I'll take part in those decisions." At morning report Howard learned that Lou had arrived within 15 minutes. He also found a group of residents and medical students who had had imprinted in their consciousness how a committed physician looks at the issue of responsibility for his patients.

Recognition of his professional achievements came from many quarters and include a visiting professorship in his name at Beth Israel Hospital, which was established on the occasion of his 75th birthday by his grateful patients, friends and colleagues. Since the professorship's inception in 1985, leading international authorities in the area of digestive diseases have served as the Louis Zetzel Visiting Professor.

Until almost the end of his life his hobbies included growing orchids and tennis, but the latter only "when a young, vigorous and enthusiastic doubles partner is available who will not poach excessively on my carefully staked out territory." He also had a long standing infatuation with fly-fishing which took him to many parts of the world, but he allowed himself to be seduced at times by blues, tarpon, snook, and Atlantic salmon.

He was a man of great energy and feeling. He could be gratified beyond description by the caring performance of a medical student or an intern, passionately outraged by a colleague's callousness toward a patient, overjoyed about a Ted Williams home run, angered by a tennis partner's lapse on the court, and made wonderfully happy by a day's fly-fishing in the Adirondacks.

Lou's first marriage was in 1934 to Muriel Bashlow, a social worker, who died in 1947. Their two daughters are Ellen Z. Lambert of New York and Judith Z. Nathanson of Philadelphia. Lou's second marriage was to Elizabeth Rosenberg Guttman, a psychiatrist, who died in 1970. Their son is James E. G. Zetzel of New York. Lou is also survived by his third wife, Geraldine Warburg Kohlenberg, an educator and poet, whom he married in 1972, her two children, his stepchildren, Teresa Kohlenberg of Watertown and Andrew Max Kohlenberg of Providence, RI, three grandchildren, and two stepgrand-children.

A common theme emerges about Lou Zetzel -- a decent, loving, intelligent, thoroughly committed man who touched deeply all of those who were fortunate enough to have known him. He helped his patients overcome or, when that was not possible, deal with adversity. He shared their joys and their sorrows. He helped his colleagues, and particularly his students, discover what a rewarding profession medicine can be. Lou enriched us all. Not surprisingly, there was a price. And that price was paid in no small part by his family, who shared him with others and who added immeasurably to his strength.

Dr. Zetzel Memorial Minute Committee Members,

Dr. Raj K. Goyal

Dr. Howard Hiatt, Chairman

Dr. George Kurland

Dr. Stanley Rosenberg

Professor James Vorenberg