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Historical Perspectives

2008; American Academy of Pediatrics; Volume: 9; Issue: 4 Linguagem: Inglês

10.1542/neo.9-4-e137

1526-9906

Nicholas Nelson,

Child and Adolescent Health

His beginnings (presciently) were in language, to the extent that he dropped out of medical school to study English and “Freshman Rhetoric” for a 2-year period. We in medicine can be grateful for Clem's return to the fold, armed with the biblical background, articulate power, and insight to entitle a paper “The Valley of the Shadow of Birth.” His father, Shirley W. Smith, had been Professor of English at the University of Michigan and, after an interlude in the Philadelphia insurance business, returned to Ann Arbor as its Vice-President and a (sometime) screenwriter. Some of Clem's continuing research funds were comprised of Shirley's royalties from his delightful story for It Happens Every Spring, a 1949 movie about a magical baseball that repelled bats and allowed actor Ray Milland to become the winning pitcher of the World Series. Another funding source was the American Cancer Society because his Harvard colleague, Bill Castle (elucidator of intrinsic factor, vitamin B12, and megaloblastic anemia), had suggested to him that babies, as well as cancers, grow. Clem's most faithful and lasting funding was from Leonard Mayo of the Association for the Aid of Crippled Children and, during his last active years, to the newly formed National Institute of Child Health and Human Development.Born in 1901, Clem was wholly educated through medical school at Ann Arbor. Following a 2-year pediatric residency at Michigan, he began his long association with Harvard as a Children's Hospital resident in 1931 under Kenneth Blackfan, remaining there until 1943, when he briefly returned to Michigan as pediatric chair at Wayne State.Although I cannot delineate just when Clem's interests gravitated across Longwood Avenue to the Boston Lying-in (“BLi”) from the Children's Hospital, his first article on the newborn is dated 1939, and by 1941, the BLi was listed as his reprint address. He was, by this time, evidently and understandably fascinated with the differences between O2 and CO2 carriage in the blood of mother and fetus, as detailed by Barcroft in sheep. As a clinician, he recognized that cord blood was one fetal material ethically available for detailed study. His well-developed interest in the newborn brought him back in 1945 from his 2-year exercise in departmental administration to the BLi (now Brigham and Women's) Hospital as Director of Research, where Duncan Reid (obstetrics), Stewart Clifford (pediatrics), Claude Villee (biochemistry), and Kurt Benirschke and Shirley Driscoll (pathology) became his frequent facilitators and occasional collaborators. Facilitators became necessary from time to time because the large private delivery service at BLi, although comprised of many pediatricians and obstetricians supportive of clinical research, also harbored some practitioners so protective of their infant charges that one occasionally could find a note pinned to a bassinet saying (paraphrased) “Under NO condition should Dr Smith, or any of his Fellows, examine this baby.”Clem married his first wife, Margaret Earhart, in 1926 and, except for the years 1932 to 1933 and 1943 to 1945, they lived in Cambridge with 4 children in a marvelous house on Brattle street, whose third floor in later years usually was occupied by a deserving, needy, and nonrelated student. Widowed in 1960, Clem was sustained by his greenhouse (Fig. 1), his children, friends (especially Alex Nadas, a founder of pediatric cardiology), and his Fellows, who began appearing at BLi in 1945.Because of Margaret's long association as a trustee with Radcliffe College, Clem came to know Mary I. (“Polly”) Bunting, Radcliffe's president (and previously my own father's boss as Dean at Douglass College of Rutgers University), charged with the difficult task of enfolding Radcliffe within Harvard's grasp. Their friendship ripened into marriage in 1975. Clem vastly enjoyed the fact that Polly's prominence was much better established (hers was a Time magazine “cover story” in 1961) than his own, such that he barely was mentioned in newspaper accounts of their marriage. Somewhere in his late 60s, Clem had been assaulted by a severe case of rheumatoid arthritis that gradually was controlled by his talented rheumatologist and a program featuring supportive socks, bedrest, bourbon, and aspirin. As his wife and faithful nurse, Polly continued this program until Clem's passing in 1988.Clem maintained a beloved summer and weekend home in Peacham, Vermont. At a service of remembrance in Harvard's Memorial Church, Clem's grandson fondly recalled him not as doctor, author, or educator, but as the man who had taught him how to run the Peacham tractor. This was in an earlier and more conservative Vermont that once was characterized for me by Clem's faithful caretaker, Jim Quimby. “Up here,” said Jim, “if it's gettin' cold and your wood ain't cut because your leg is broke, don't worry—your neighbors'll cut it for you. On the other hand, if your wood ain't cut and your leg ain't broke, you're gonna freeze to death!”Clem's correspondence and often his speech was graced by frequent and lengthy quotations of Shakespeare and the more minor poets. He knew the constellations, music, and a great deal about art—he was the definition of a Renaissance Man. At a dinner celebrating the retirements of Clem and his Harvard colleague, Lou Diamond (Lou went on to several more productive years at University of California–San Francisco, which evidently was pleased to continue benefitting from retired Harvard talent), Clem recalled with delight how a young woman from Tennessee was (many years earlier) in his Children's Hospital office pleading for academic support for her striving Hungarian husband. With a twinkle Clem said, “I felt like Scarpia!,” a reference to Puccini's archvillain in “Tosca.” Thus began the Nadas-Smith friendship. Clem became godfather to the young baseball fanatic, Johnny Nadas, who, during a summer's break from college, tried Wall Street, loved it, and shared with Clem his unease at revealing this fact to his famously progressive father.It was Clem's tradition to celebrate the departure of each Fellow with a bit of whimsical doggerel. For Klaus Reigel, who returned to Tübingen to found German neonatology in 1965 after a Boston year of measuring blood oxygen content (in the Natelson microgasometer, which involved a lot of loud slamming of the machine against a metal stop), Clem composed “Eine Kleine ‘Knock' Musik.”My own personal acquaintance with Clem began in 1956, when I spent 2 years in uniform defending French civilization at the 34th General United States Army Hospital (La Chapelle-St. Mesmin, Orléans, France). There I discovered Clem's Physiology of the Newborn Infant, fell in love with same, and determined to finish my residency (begun at Bellevue under Emmett Holt) at Boston (under Charlie Janeway) and apply to Clem for a Fellowship (not quite known as such at the time) in neonatology (completely unknown at the time). I had applied to Clem's program (but not yet met him) just before my first child was born at BLi. That birth in 1958 was a miserable experience. Husbands were discharged from mothers’ rooms with the first shot of oxytocin or scopolamine (whichever came first in the “House of Twilight Sleep”), and my wife developed mastitis (a very scary business for new parents in a day that lacked “lactation consultants”), relieved only by the attentions of our very skilled, but often elsewhere, obstetrician. One Sunday, at lunch in my white suit, I was complaining so loudly of this experience to my resident colleagues that I didn't notice them kicking me under the table as an eminence grise approached, saying, “I understand that someone here doesn't approve of BLi's management of births.” I weakly raised my hand in admission, but my eyes were respectfully lowered too much to tell whether Clem had a twinkle in his eye as he said, “I just want you to know that … [personal sweat] … I agree with you!” Clem was a master of droll comic timing.Over a period of 25 years, the Fellows passing through Clem's small laboratory became involved in a distinctly eclectic range of clinical investigations, often taking advantage of the scientific intellectual ferment available across Longwood Avenue in Harvard Medical School's Department of Physiology and the School of Public Health, particularly emphasizing the cardiopulmonary system. The clinical material available at the BLi was comprised of nearly 8,000 annual deliveries, most of which were private patients. Joslin Clinic diabetic pregnancies were followed and delivered at BLi, so infants of diabetic mothers as an “at-risk” population frequently served as “normal” infants for cardiopulmonary investigations as well as investigations of glucose metabolism, their approving parents often personally (and gratefully) observing these procedures of gas sampling and blood collecting. This was a much more gratifying and comfortable mode for clinical investigations than the heavily documented and legalistic environment of today's “informed consent” (pace, Bill Silverman). Some investigations, particularly those involving water and acid-base balance, were driven by the clinical fashions of the day as these habits (eg, withholding feedings in the first few days of preterm life) began to come under question.Nearly none of Clem's Fellows were supported by the National Institutes of Health, whose training programs did not begin until the early 1960s. Many of those from overseas brought their own support; most North Americans were supported by Clem. His Fellows also could be grouped by their previous involvement in clinical research. Overseas Fellows tended to arrive in Boston with their research ideas (and often techniques) well in hand, looking primarily for the opportunity for clinical investigation in the supportive environment created by Clem. The North American Fellows tended to arrive fresh out of their residencies, hoping to learn something of the world of clinical investigation and driven more by intellectual interest than by any need for academic career preparation, sub-Board certification being far in the future.Clem's personal interest in nutrition and metabolism were among his earliest areas of investigation and were culminated by Dmitri Nicolopoulos' demonstration that the denial of nutrition per os in the first days after birth “to protect the airway” was forcing negative nitrogen balance in preterm infants that exceeded that observed in Navy fliers shot down and surviving after 80 days of fasting on Pacific life rafts. The necessary intellectual and clinical corroboration of Dmitri's observations soon came down to Boston from the North. Newborn care was essentially custodial in the late 1950s, but one had to take note of Bob Usher in Montreal, who had begun to offer intravenous glucose to preterm infants in the first hours after birth and was receiving much laudatory praise in the Canadian press for reversing the “sine-wave EKG” (of hyperkalemia) with a simple infusion of glucose. It had not yet become apparent how well-deserved this praise was, and in the middle of tedious oxygen analyses with the micro-Scholander apparatus, Peter Auld and I grousingly agreed that it would be pleasant to see Bob's approach fail, so we could rewrite “The Fall of the House of Usher.” We were too shortsighted to note that Bob's approach had, in fact, converted the custodial preterm infant to an active patient, fully deserving of “intensive care.” The subsequent development of umbilical artery catheters, blood gas analyses, respirator support, and total parenteral nutrition mercifully closed the custodial era.Throughout all of these studies, Clem's role was very much that of enthusiastic facilitator and scholarly interpreter rather than hands-on director, so the published output of his Fellows was distinctly more diverse in focus than that of most other programs. By 1959, those who had passed through Clem's small BLi lab included Alex Minkowski (France); John Hansen (South Africa); Gerald Neligan and Jim Farquhar (United Kingdom); and Jim Sutherland, Jerry Lucey, and Jack Rudolph (United States). The focus on pulmonary function began in the early 1950s, with the arrival of Petter Karlberg from Sweden, working principally with Dav Cook and Donough O'Brien. They developed much of the knowledge of infant pulmonary function that stands today, taking advantage of the close proximity of the Harvard School of Public Health, which long had been a leader in adult pulmonary physiology. The later natural progression of such studies involved Peter Auld, Klaus Riegel, Sam Prod'hom, and Nick Nelson, particularly focusing on the development of technology that permitted the measurement of blood gases and blood pressure, all of which contributed to the scientific bases for modern life support of the stressed newborn. Respirator support for infants, however, initially was developed in New York, Toronto, and Nashville, rather than Boston (which calls itself “the hub,” perhaps forgetting that the hub is that part of the wheel that merely rotates).As all these ideas were being developed by young investigators of infants in his lab, Clem could be frustratingly slow to achieve physiologic insight into some of the more abstruse concepts (eg, pulmonary transfer factor, pressure-volume hysteresis). However, once he grasped the concept under discussion, he could unerringly express it in plain English better than any of those who had tried to “educate” him.A steady presence in Clem's lab was his associate of many years, Ruth Cherry (elder sister of the eminent James Cherry of UCLA). Ruth was very much the mother hen of Clem's lab, both personally and professionally. One did not fully matriculate as a Fellow until mastering the calculation of standard deviations with the Monroe Hand(!) Calculator under Ruth's tutelage.Three individuals bear special mention because although their interests were largely peripheral to the general thrust of investigations in Clem's lab, their work was greatly facilitated by Clem's cooperation, guidance, and encouragement.Mary Ellen (“Mel”) Avery arrived from Baltimore in the late 1950s, already determined to find (or not) that the lungs of preterm infants dying of “idiopathic respiratory distress syndrome” (RDS) were surfactant-deficient. Mel had formulated these ideas after her exposure at Johns Hopkins to the pathology observations and thinking of Peter Gruenwald as well as the delineation of surfactant physiology and biochemistry by John Clements at nearby Fort Dietrich. She was advised by Richard Riley to seek out Boston, which contained a major intellectual resource (Jere Mead) at the School of Public Health, as well as a large population of preterm infants across Longwood Avenue at BLi. She spent most of her time at the Harvard School of Public Health, but occasionally returned to BLi to harvest the lungs of preterm infants who had succumbed to RDS (née “hyaline membrane disease”). Present-day Fellows who have had their “breakthrough” research underappreciated can take heart from the decision of the pediatric Alte Herren of 1959 that Mel's paper on the high surface tensions she found in these lungs was of insufficient interest for presentation at the spring pediatric meetings. Clem had been happy to lay out his welcome mat for Mel and vastly enjoyed the success of her mission.At about the same time, Abe Rudolph (as a Fellow in cardiology with Alex Nadas) was looking for evidence of anatomic shunts to explain the profound hypoxemia in RDS. He observed during cardiac catheterization of such infants at the BLi that the ductus arteriosus was wide open and carrying unoxygenated blood right-to-left. Thus began Abe's long pursuit (often with Mike Heymann) of the ductus as key to the understanding and management of congenital heart malformations, culminating in the present control of the ductus with indomethacin and prostaglandin.In the late 1960s, Jeff Maisels arrived at the BLi from South Africa with no previous research experience and seized on the suggestion of David Nathan (Chief of Hematology at the Children's Hospital) that there was considerable interest among hematologists in the rate of carbon monoxide production from the breakdown of hemoglobin. Since the release of carbon monoxide from hemoglobin leaves a residue of bilirubin and a surfeit of bilirubin produces jaundice, Jeff's interest was immediately aroused. Moreover, there happened to be lying around in Clem's lab the equipment required to permit the necessary infant rebreathing for serial measurements of blood carboxyhemoglobin. Thus began Jeff Maisels' long and productive effort to understand bilirubin metabolism in the newborn.Clem greatly enjoyed his stewardship as Editor of Pediatrics, in which he was followed by Jerry Lucey. The single low point was when some poor author's academic magnum opus was printed facing the particularly large proboscis of an orangutan, advertising some manufacturer's nasal decongestant. Pediatrics’ editorial board examined the question of interspersed advertising (manufacturers’ preference) versus end-paper advertising (scholars’ preference). However, investigation demonstrated that not even the complaining academics were willing to sustain the estimated $5.00 increase in subscription price that noninterspersed advertising would have cost. Clem was disheartened, but still very proud of the “Karsh of Ottawa” photographic portrait of him with Pediatrics rolled up in his hand.Hanging on the wall near Clem's desk was a photograph of Sir Joseph Barcroft, by whose scholarship and eminence he had long been inspired. I'm not sure whether they had ever met, but the picture was accompanied by a letter fragment from Barcroft that said, “remember that the essence of the missionary enterprise such as yours is to expel the people one by one… .” And he did. In my own case, I had been wondering whether I had made a late decision for medicine (I had foresworn a career in arachnidology) only to end up in a laboratory measuring oxygen contents and standard deviations by hand, so I was considering entering private practice. Knowing that Clem had briefly done the same in 1932 to 1933, I asked his advice and was not dissuaded, although he did express mild regret. Charlie Janeway said only, “Don't get too used to the money!” ($25k as a full private partner—this was a long time ago!)Clem was gracious enough to accept me back at the BLi 3 years later, and the 20th-year reunion of his Fellows commemorated by his Academic Family Tree (Fig. 2) followed 1 year later. That happy occasion in 1965 was 3 years before his scheduled Harvard retirement, and with his customary mischievous twinkle, Clem remarked that the timing of the party was rather like “singing Christmas carols in September.” He also noted, in explanation of why 50-odd pediatricians had chosen to associate with him over the preceding 20 years, that, “If you were interested in babies and liked Boston, I was the only wheel in town!”In addition to his many other honors, in 1975 Clem received the first annual Virginia Apgar Award (of the American Academy of Pediatrics) for “an individual whose career has had a continuing influence on the well-being of newborn infants.” Four of his Fellows have followed him in such recognition: Petter Karlberg (1990), Mel Avery (1991), Jerry Lucey (1993), and Jeff Maisels (2007).Res ipsa loquitur!What was the essence of Clement Andrew Smith: Scholar, educator, author, gentle humorist, gentle man? He was all of these.