SMITH These achievements have been recognized by the University of Groningen and Colby College, which have given him honorary degrees, and his colleagues in neonatology who chose him to receive the first Virginia Apgar Award this past October. The findings sometimes came from careful measurement-to quote one of his favorite lines, "The fact is the sweetest dream that labor knowsv-sometimes from a thoughtful overview of the endeavor, such as his famous Rachford Lectures "The Valley of the Shadow of Birth." It is not so much a single discovery that highlights Dr. Smith's professional career, although many were made in his laboratories, but rather a sensitivity to the needs of the newborn infant, and their mothers, and an appreciation of the opportunity for understanding that could be given to those who took the time to think and to care.
And now the present. It is our good fortune that Dr. Smith attends regularly the Perinatal Rounds at the Boston Hospital for Women as well as Grand Rounds at the Children's Hospital. He is currently the historian of the Children's Hospital, Boston, and also editorial advisor to the Physician-in-Chief. In fact this talk is one of the few he has not had a chance to edit! A word about his environment. Mornings he can be found in his "greenhouse" where his need to nurture meets continual fulfillment. Summers he may be in Vermont, and winters too, or in Hanover. In the words of Robert Frost, "He couldn't keep away from doing something." We know he can't keep from doing something, and pediatricians around the world are grateful that such is the case. It is a special pleasure that he will bring us a message today.
Pediat. Res. 10: 858-862 (1976)
Acceptance of the Howland Award (From the American Pediatric Society, April 28, 1976, St. Louis, Missouri) CLEMENT A. SMITH15 Boston Hospital for Women, and Children's Hospital, Boston, Massachusetts, USA
This is one of those rare times when, as Wordsworth wrote, "we feel that we are greater than we know." It is also a time for looking back over all the events and, especially, all the people, whose influence shared in bringing about this astonishing state of affairs. T o name any of those people would cause the unforgivable omission of many others. But I must mention my family, of two generations in the past and another two in the present, numerous teachers (including some very special ones), and even more friends than the many dear ones I see here. I wish I knew how to respond in proportion to how much I owe them. Anyone in my position is old enough to recall what many others have said about it. Very few have attempted prophecy. Not many have felt still sufficiently nu courant to explain-or even to discuss-the immediate state of their particular art. And though I can still recognize the modern neonate or perinate in my years of retirement I wouldn't even try to introduce them to you in the presence of some in this company. S o I join the majority who have found it safer to speak of the past, and especially those who speak of its people. The People were far more important than the Pediatrics of 50 years ago, which has only an antiquarian interest, if that, for us. But the minds and hands that made such good use of simpler tools then would use ours that much better today. Things may change. People haven't changed at all. S o Edwards A. Park (I), first recipient, wisely spoke about a person-naturally John Howland, the young Dr. Park's colleague of 35 years before. Dr. Gamble (2), 2 years later, briefly revisited in his acceptance what he called "that lush meadow of opportunity," Howland's laboratory. As time brought us a second generation of recipients, the original greatness continued its influence. So, in 1971, Helen Taussig (3), a spiritual grand-daughter of Dr. Howland, described her inheritance-and ours-from Dr. Park. And lately, Lou Diamond, my own spiritual brother, recalled the quiet and powerful influence
on our generation of Kenneth Blackfan (4), 9 years Howland's Chief Resident. Therefore, I grasp the opportunity to attempt an account of my debt (and that of so many others) to Howland's other first generation settler in Boston, James Gamble. Admittedly, he figured as a previous Award recipient (2), but though Allan Butler described him handsomely in 1955, two celebrations of Dr. Gamble in 21 years are none too many. Moreover, I have a particular reason. The room I'm happy still to occupy at the Children's is entered by a door between two portraits some of you will remember from the old Laboratory Study. So, as I go and come, I overhear occasional strangers pausing on their way to important business with Mary Ellen Avery or Judah Folkman, to read the names under the pictures. (That anyone should need to do so always seems to me slightly surprising.) Before one portrait I have heard sometimes a note of pleased recognition: "Blackfan! He's the one they named the street after." (So, indeed, they did-if that were all.) Too often before the other, I hear only: "Gamble? I wonder who he was." S o I want to tell you a little about that, not just because he was important to me but in the hope of giving younger people a flash of recognition, while delighting those who knew Dr. Gamble, with that warm inner stirring that comes from recalling a rare soul. Just for the record, James Lawder (his mother's name) Gamble was born in Millersburg, Kentucky, not far south of Cincinnati, in 1883. He went from primary education a t the Millersburg Female College (of all things!) to secondary education at the Millersburg Military Institute (of all places for him!). Still, then he passed entrance examinations for Harvard, though Massachusetts looked too cold to be healthy to his parents, who sent him instead to California. There, he graduated from Stanford in 1906, braved the rigors of Boston, and received his Harvard M.D. in 1910. There followed internship a t the Massachusetts General, and 6 months more of it (with Bronson Crothers) a t the Children's
ACCEPTANCE OF HOWLAND AWARD Hospital, some medical travel abroad, and familiarization, back in Boston, with the new chemical methods of Otto Folin and calorimetric techniques of Francis Benedict. Then began an investigator's career, in the chemistry laboratory of the Massachusetts General-which provided the valuable companionship of three young men who later headed important Departments of Medicine: Walter Palmer, James Means, and L. H. Newburgh. 1t is a hopeless task for the appreciator of Dr. Gamble to speak as about him as Loeb did in presenting him the Kober Medal for the Association of American Physicians, in 1951 (5). 1 here break down and quote Of Dr. first On publication, with Means and and Creatinine Elimination," Dr. Loeb said: u
(During) . . . these studies there entered into Gamble's life a profound influence . . . , . . . the directing force of his career as an investigator. His room-mate, Bill Palmer, was at work under the direction of Professor L. J. Henderson . . . upon fundamental studies of acid-base and osmotic pressure regulation . . . . In visits to the laboratory, Henderson's catalytic propensities began to act not only on the substrate of Palmer but also on that of Gamble (whose) close contact with Henderson continued to stimulate his imagination in problems of electrolyte physiology. That influence long recurred. Dr. Gamble's best known publication, his Chemical P h ~ s i o b Tand ~ Pathology of Extracellular Fluid, first published in 1939, opens with two quotations on the milieu interieur, one by Claude Bernard, the other by L. J. Henderson (6). Much later still, indeed, 7 Years after kknderson's e (7) with mention of the death, amble began his ~ a n Lectures origin of life in sea water. his, he said, being water, "had, according to Lawrence Henderson, an incomparable biological fitness. BY . . . fitness," Gamble continued, ''we are to understand, I suppose, a suitability of themany components of the Great Experiment which was eventually so successful as to produce a Lawrence Henderson." In 1915, Dr. Gamble, aged 33, entered that "lush meadow of opportunityv-the new laboratory of the new professor of what was clearly the New Pediatrics, at Johns Hopkins. There, he decided to leave clinical medicine for "the study of disease by chemistry." In this, to quote Dr. Loeb (5) again, he "early developed the capacity to design simple experiments which yielded definitive answers. He worked with his own hands. . . , rarely with technical assistance-an invaluable approach all too often neglected today." (SO said Dr. Loeb, speaking in 1951. Fortunately for this speaker, Dr. Gamble in the 1930's firmly recommended that practice to young men who came under his spell and into his laboratory in Boston, even at some expense of broken glass and spilled mercury. I never saw him angry, though sometimes rather sadly amused.) But to return to the Hopkins years. Among those early "simple experiments yielding definitive answers" was one in which the actual experiment (if a trial of recommended therapy can be so called) was Dr. Howland's own investigation of whether the ketosis of fasting actually controlled the convulsions of epilepsy. Dr. Gamble's carefully planned use of the metabolic by products of that work produced a landmark study, far outlasting in significance Dr. Howland's results. 1 like to see where an old bound volume on the Countway Library shelves falls open from frequent use; for the Journal ~ i ~ [chemistry, ~ ~ i volume ~ ~ 57, l 1923, this happens-sure enough-at page 633: Gamble, Ross, and ~ i ~ d ~u l l~: metabolism h ~ of fixed base during fasting- (g), and for the next 50 pages (long for a Gamble paper) the fingermarks and surreptitious pencillings are heavy. Of this early classic, Dr. Loeb (5) says:
of
. . . At a time when most clinical investigation consisted of. . . recording endless observations based on some new method, Gamble planned a crucial experiment to elucidate basic problems of function and applied chemical means to this end . . . . It was thrilling for us . . . in Baltimore to see something happening to figures other than
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tabulation, to see them come to life and illuminate the processes of acid-base equilibrium. . . .(That) general design. . .continues to be the pattern for most studies. . .(of) electrolytes and water metabolism today. Even the expression of data by simple graphic means, now known as . . . Gamblegrams, has been generally adopted . . . a blessing for students, teachers, and investigators, alike. I hope we'll have time to say more about t h o e diagrams, but now
we press on to that fortunate event for Boston and Harvard, Dr. Gamble.s invitation there by Professor Oscar Schloss, in 1922. In spite of his unhappiness in Boston, Dr. Schloss left impressive accomplishments for a 2-year stay. Among these, Arthur Anderson, his Resident in 1922, singles out "the erection of the pediatric laboratory, and, most important of all, the appointments of Dr. James Gamble and Dr. Lynne Hoag to his staff" (9). In his Annual Report for 1922, Dr. Schloss himself notes the Hospital's "good fortune in having as its Laboratory Director, Dr. James L. Gamble," and his next paragraph mentions "the discovery of the active principle of the Pancreas by Banting . . . (as) . . . a ray of hope in the otherwise gloomy outlook for diabetes in children" (lO)-thus placing Dr. Gamble's arrival at Children's in temporal context. The appointment of Kenneth Blackfan, Gamble's clinical associate at Hopkins, to succeed Dr. schloss, is inconspicuous~y mentioned in the next Annual Report, but what a wonderful thing it was, for both of them and for the Hospital! A photograph (Fig. 1) shows them, probably not long after, for Dr. Gamble's pre-bowtie period was past when I came in 1930. Incidentally, the picture reminds me that I never saw him in a white coat, probably one of his several defenses against being led by Dr. Blackfan from the laboratory, where he was absolutely safe, to the bedside, where he was less certain. I hope my colleagues of those days will agree that they're standing by the side of the new laboratory. As a historian, I wish I knew which side. That structure began as a single story, but Dr. Blackfan reports for 1927 (1 1): "an epochal gain . . . . An entire second story has been constructed over the original laboratory building . . . , its outstanding feature a large and very beautiful room . . . to be known as the Laboratory Study . . . A memorial gift, its purpose is best described by the legend above the fireplace: 'In loving memory of Anne, 1918-1926, this room is given for study and reflection with the hope thereby to facilitate discoveries helpful to the healing of children.' It is impossible," Dr. Blackfan continued, "to . . . appraise the potential fruitfulness of this gift . . . or to state our gratitude to the vision and generosity of its donors." "The remainder of the new story provides four additional laboratory rooms. . . for research purposes, scarcely finished before they were actively in use." When I first saw it, that building had been completed only 3 Years, but the dark floors and panelling, the comfortable chairs, and the ranks journals and the Study seemed But they had have been there and-incidentall~-the~ were not to be. Swept away some 30 Years later the Laboratory Study, its panelling, its overmantel painting, big central table, and small tablet to Anne, are all somewhere in storage-awaiting a glorious resumectiOn, which Though the first low structure must have been a precondition of Gamble's coming, I suspect him of considerable share in the enlargement. From his own small office next door, I know he saw to it that the books and journals were bought, bound, and properly shelved, and that Marian Greene and Peggy Kame came over from the Chiefs office in late afternoons to set out tea in the bay window. He often dropped in and had a cup with anyone working there. Lou Diamond and Jim Baty did their Hematology at the other end of the second floor; LeRoy Fothergill and Marian Sweet their Service and Investigative Bacteriology downstairs, where
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Fig. 1. James L. Gamble (left) and Kenneth D. Blackfan (right), about 1925.
space was later found for Alfred Shohl, then wrestling with the difficulties of making intravenous amino acids safe before the invention of the Millipore filter. But Dr. Gamble's chemical laboratory, as you entered the first floor, the Laboratory Study directly above it, and Dr. Gamble himself at his small slant-top desk (or in his big chair) next to that, were the true heart of the place. So there it all was, waiting for me when I arrived as a House Officer and fell immediately inder the spell of the whole hospital, with its little ward buildings strung along their glass-walled corridors. When I went back to that relatively massive University Hospital in Ann Arbor in 1932, previously my home, I was homesick. I recall seeking out Dr. Newburgh, a favorite Professor in my student days (and always), to ask him about Dr. Gamble, and feeling a great bond between us when he said: "I both know him and love him." Encouraged by this to risk some youthful sentimentality, I said: "He always seemed to me to have almost an air of nobility. Don't you think that in the Middle Ages Dr. Gamble would have been a knight, or a baron?" Dr. Newburgh didn't think so. He thought, instead, and probably nearer the mark than I, "Jim Gamble would have been a monk." You will see why I was back in Boston 2 years later, and why,
even after I planted one foot on the other side of Longwood Avenue, I continued to spend time at the Children's, often to discuss the water and salt metabolism of the newborn with Dr. Gamble and his group-particularly in the great days of Bill Wallace. Today, I marvel at the simplicity, the openness, and the strategically central location of that laboratory building, still thought of by some as the Laboratory Study Building. Coming through the hospital's main corridor from breakfast in the morning, or for one last look at that disturbing baby on Infant's Upper before you went to bed, you stepped into the Lab Building for a few minutes-the first door along the central corridor-to see the blood culture you drew the night before, to check on some other determination or measurement, or to consult a reference in the Lab Study. Downstairs, you soon learned where the data books were kept; if no one was there you found in them the results you needed. Then, poking carefully around the Chemical Laboratory for some simple reagent or to make something for your own little ward laboratory with the glass tubing and blow torch, you discovered fascinating bottles containing remnants from earlier investigations, labeled in Dr. Gamble's strong and legible hand. Alan Ross said he had seen one marked "Synthetic Rat"; I knew an even more mysterious one whose contents were identified as "Synthetic Urine." Though I'm unsure about other doors, Dorothea Moore agrees with me that the Laboratory Study was never locked. Someone was always working up there, at all hours, of any day. Late one night it was this Society's current president, surrounded by large volumes, and looking even more tired than did his rumpled white suit when I had left him that morning beside one of those nightmare children who sometimes linger so stubbornly between hopeful and hopeless, in hospital cribs. Tired as he was, Dr. Pratt was still intent. When you get old you forget names, but he recently, and immediately, told me our patient's name was Randy, and that he had, among other things, erythrodermia desquamativa. When I asked, "Ed, what do you do up here so late at nights?" he said "Oh, lots of things-for instance, I find out how to cure Randy." I knew we probably couldn't do that, he knew that I knew, but we shared for a boundless moment that wonderful spell of searching in a good library for what you might find. I'm not sure that even Dr. Gamble's office next door was locked in his absence. I've certainly been there alone, consulting some book of his, though not feeling it quite proper to sit in the single large easy chair. In that, it was universally believed, he began any investigation scheduled for a year, by sitting and thinking for the first 9 or 10 months exactly how it should be done, and then doing it perfectly and completely by the year's end. We so often used most-or all-of a year doing our studies wrong. At his little desk there he wrote his lectures-rewriting each until it met his high standard of perfection-and then memorizing it for delivery to one of many scientific audiences, including the second year medical students. Because he disliked darkness and lantern slides, and preferred to see his listeners, his main points were illustrated by large hanging charts, on which-exactly as Dr. Loeb had said-he made "figures come to life and illustrate the processes of acid-base equilibrium." For those of you who never knew the major collection of them in the Syllabus (6), because you had the misfortune to be educated too recently, I show you (Fig. 2) the title page of that universally read book, out of print 15 years or more, and two representative samples. From them you may understand my dislike of the term "Gamblegram." Though a pleasant reminder of the originator, it has a suggestion of cuteness. There was none of that. Masterpieces of directly conveyed information, they were as clean and spare as a good etching. Two less representative ones happened to be hanging behind Dr. Gamble when an excellent photograph (Fig. 3) was taken by Jack Metcoff. It could not have been at a lecture, for only one chart at a time was ever presented on those occasions. An accompanying ritual was the glass of water, always placed by on the lectern to be sipped as he required, at some attending intervals, and at the lecture's end, raised and drained in an
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Fig. 3. James Lawder Gamble, from a photograph taken by Dr. Jack Metcoff, about 1952.
unspoken toast to the class-and to body water. Many of you will know of the surreptitious substitution of another colorless and somewhat more stimulating fluid by members of one class in which a James Gamble, Jr., was enrolled. The traditional account most familiar to me had Dr. Gamble, Sr., carefully concealing, at his first sip, both his surprise and his total understanding of the plot, and with almost inhuman concentration continuing his regular sips (and his memorized lecture), and (at its conclusion) draining the remainder amid thunderous applause-and then lying down all the afternoon. James Gamble, Jr., and William Berenberg, however, as two of our brethren who were present, describe the lecturer's hand repeatedly and tantalizingly extended toward the glass and always absent mindedly withdrawn, as the students sat with repeatedly bated breath-until, with the first sip, in the final minutes, a look of amused surprise and-in conclusion-an ample toast. Did Dr. Gamble know, all the time? If so, this silent, teasing riposte would have been in keeping with his quiet sense of humor,
more commonlv found in his words than in his acts. I believe he coined the superb phrase "precise misinformation" for the pseudoscientific papers where every calculation is carried to the third decimal place. Similarly, when Allan Butler and he were investigating for the Navy the water requirements of castaways during the second World War (12), Dr. Gamble delighted in the fact that Allan was named in the Government's Contract as the Responsible Investigator. This, he happily acknowledged, identified him as the Irresponsible Investigator. Occasional, and never too many, bits of humor were tucked into his lectures. Speaking at Leland Stanford in 195 1 (7), he described a balance study whose results were at first quite at variance with the theory he expected them to substantiate. But when corrected for appropriate though unmeasured insensible losses, he said " . . . our balance measurements and estimations of volume changes are now sweetly reasonable: we find the expected increase. . .of intracellular. . .and reduction of extracellular fluid volume. This," he continued, "is an illustration of unrighteous determination to have an experiment come out the way you want it to. And, as you see, the wages of sin are as they so often are, delightful." But I like even more his unpublished observation that there were numerous precedents for a Bostonian behaving outrageously in California. A Children's Hospital colleague urged me to mention Dr. Gamble's shyness and his humility. I knew what he meant but didn't entirely like either word. Instead, I shall say that he was by nature deeply sensitive and never assertive. In 1955, when we met with British and Canadian colleagues in Quebec, where he became the fourth recipient of the Howland Award, a co-author and I had sneaked off from the morning session to put some final touches on a paper, when Dr. Gamble, looking rather miserable, knocked at my hotel room door. "Could I, please," he said, "just quietly lie down on your bed for an hour? You see, Allan is up in my room writing a citation about me." That's what I mean. But let us return to his lectures. What was in them beside the bits of humor? Since he left no book except the wire-bound Lecture Syllabus (6) (which itself also contained the distillate of his published papers) one seeks in the Syllabus the essence of what he taught to us, to pediatricians, and to other physicians, everywhere. And one finds not so much chemical
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anatomy, but chemistry in action, purposeful-as though by its own intelligence, measurable, and interpretable. He did, indeed, "make figures come to life." His way of seeing things-and his skill in making us see them-stands out in this short passage from early in the Syllabus: T h e regulatory a p p a r a t u s governing extra-cellular fluid possesses mechanisms of adjustment behind the kidney which d o not prevent but which greatly limit change in physical properties in the presence of change in chemical pattern. Rigidity, then, is not t o be expected either in chemical structure o r in physical properties. T h e cardinal merit of any physicochemical system in the body must be resilience, otherwise it would be sure t o be smashed by the rapidly changing currents of chemical events. I n order t h a t the organism m a y survive severely adverse circumstances, this recoverability from distortion must have a width f a r beyond the usual requirement. T h e physicochemical system in extracellular fluid exhibits this necessary elasticity very beautifully.
He showed us that beauty in page after page, chart after chart. Once we began to see dehydration, acidosis, alkalosis, body size, and the special secondary roles of lungs, intestines, and kidneys, in relation to "the rapidly changing currents of chemical events," we could use laboratory measurements more intelligently in diagnosis and fluids far more effectively in therapy. Perhaps for the first time, he made a large portion of pediatrics know what it was doing. If this all seems merely commonplace to many of today's explorers among genes and enzymes, their familiarity with the surrohnding extracellular landscape they owe largely to James Gamble. No physician (or nurse practitioner) uses intravenous therapy today without some indebtedness to him. The growth of his Syllabus from 39 to 69 charts over its six editions in 15 years shows how diligently he continued to explore the territory he had so completely made his own. But by the final edition, in 1954, 3 years after his official retirement-with his health slowly failing-we could see a change from explorer to observer. Others were boldly beginning to repair deficits of intracellular ion intravenously. Dr. Gamble admitted (1951) that he had "felt it would not be safe to add potassium to a repair solution. However," he continued, "Darrow, who is not afraid of a postulation, has recently demonstrated that potassium can be safely used" (7). It was the turn of other and younger workers to go ahead. I recently found among the James L. Gamble papers in the Countway Library, a half sheet of typing headed, "Good Bye Bill." Its words were those he had written to say to William Wallace, on his departure in 1952 for the Professorship at Western Reserve. He began, bluntly: Y o u a r e the best leader of a laboratory group t h a t I have ever encountered. . . . Y o u have used the best of all methods-informal companionship. This method costs a lot of time and you have practiced it with an generosity. your cheerful and ever ready helpfulness, each of us owes you a debt which can't be ~
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Copyright @ 1976 International Pediatric Research Foundation, Inc.
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measured . . . I especially congratulate you o n having avoided the attitude of a Director of Research. Y o u have never mescribed o u r thinking, but you have helped us t o develop o u r thoughts a n d work them into the pattern of o u r undertakings. . . . Also, you have persistently taught us methodology. . . . T h e s u m of this is t h a t we just couldn't avoid having a grand time together . . . .
He was saying what we wish we could have said so well of him, and to him. To such words I would add two other brief statements. In 1959, at the time of his death, Dr. Janeway, in the Harvard Medical Alumni Bulletin (13), turned from mention of awards, honors, and accomplishments, to conclude that "in the hearts of his friends and his associates, his memory will be kept warm because his rare gift of intellect was combined with genuine simplicity and integrity of character, warmth of heart and great personal charm. As one friend has put it, 'There was not a spurious fibre in him'," and, finally, the words of Harold Faber and Rustin McIntosh (14): "James Lawder Gamble, fifty-sixth president, and Howland Medalist . . . . With keen insight he attacked the problems of fluid and mineral losses by methods combining simplicity and precision, portraying their characteristics with clarity and elegance. Uncounted lives of infants and children have been spared by the discoveries that he and those inspired by him unearthed . . . . His character and accomplishments are glories of the American Pediatric Society's history." That is who Dr. Gamble was. REFERENCES I. Park, E. A.: John Howland Award Address. Pediatrics, 10: 32 (1952). 2. Presentation of the John Howland Medal and Award of the American Pediatric Society to Dr. James L. Gamble: Introduction and Presentation by Dr. Allan M. Butler; Acceptance by Dr. James L. Gamble. AMA Am. J. Dis. Child., 90: 483 (1955). 3. Taussig, H. B.: Acceptance of the Howland Award. Pediat. Res., 5: 569 (1971). 4. Diamond, L. K.: Acceptance of the Howland Award-Reflections on pediatric care. Pediat. Res. 7: 858 (1973). 5. Loeb, R. F.: Presentation of the George M. Kober Medal to Dr. James L. Gamble. Trans. Amer. Phys., 64: 29 (1951). 6. Gamble, J . L.: Chemical Anatomy, Physiology and Pathology of Extracellular Fluid: A Lecture Syllabus (Department of Pediatrics, Harvard Medical School, Boston, 1939). 7. Gamble, J . L.: Companionship of water and electrolytes in the organization of body fluid, The Lane Medical Lectures, pp. 9, 10 (Stanford University Press, Stanford, 1951). 8. Gamble, J . L., Ross, S. G., and Tisdall, F. F.: The metabolism of fixed base during fasting. J . Biol. Chem., 57: 633 (1923). 9. Anderson, A. F.: Personal correspondence, 1975. 10. The Children's Hospital, Boston, Mass. Fifty-Fourth Annual Report, for the year 1922, pp. 83, 84. The Medical Department. I I. Idem: Fifty-ninth Annual Report, Part 11, pp. 9-1 1, for the year 1927. 12. Gamble, J . L.: Physiological information gained from studies on the life raft ration. Harvey Lect. Ser. 42: 247 (1946-47). 13. Janeway, C. A,: James Lawder Gamble, 1883-1959, Med. Alum. Bull. Harvard. July, p. 4 (1959). 14. Faber, H. K., and Mclntosh, R.: History of the American Pediatric Society 1887-1965, p. 294 (McGraw-Hill Book Co., New York, 1966). 15. Requests for reprints should be addressed to: C. A. Smith, M.D., 300 Longwood Ave., Boston, Mass. 021 15 (USA). Printed in U.S.A.
And now the present. It is our good fortune that Dr. Smith attends regularly the Perinatal Rounds at the Boston Hospital for Women as well as Grand Rounds at the Children's Hospital. He is currently the historian of the Children's Hospital, Boston, and also editorial advisor to the Physician-in-Chief. In fact this talk is one of the few he has not had a chance to edit! A word about his environment. Mornings he can be found in his "greenhouse" where his need to nurture meets continual fulfillment. Summers he may be in Vermont, and winters too, or in Hanover. In the words of Robert Frost, "He couldn't keep away from doing something." We know he can't keep from doing something, and pediatricians around the world are grateful that such is the case. It is a special pleasure that he will bring us a message today.
Pediat. Res. 10: 858-862 (1976)
Acceptance of the Howland Award (From the American Pediatric Society, April 28, 1976, St. Louis, Missouri) CLEMENT A. SMITH15 Boston Hospital for Women, and Children's Hospital, Boston, Massachusetts, USA
This is one of those rare times when, as Wordsworth wrote, "we feel that we are greater than we know." It is also a time for looking back over all the events and, especially, all the people, whose influence shared in bringing about this astonishing state of affairs. T o name any of those people would cause the unforgivable omission of many others. But I must mention my family, of two generations in the past and another two in the present, numerous teachers (including some very special ones), and even more friends than the many dear ones I see here. I wish I knew how to respond in proportion to how much I owe them. Anyone in my position is old enough to recall what many others have said about it. Very few have attempted prophecy. Not many have felt still sufficiently nu courant to explain-or even to discuss-the immediate state of their particular art. And though I can still recognize the modern neonate or perinate in my years of retirement I wouldn't even try to introduce them to you in the presence of some in this company. S o I join the majority who have found it safer to speak of the past, and especially those who speak of its people. The People were far more important than the Pediatrics of 50 years ago, which has only an antiquarian interest, if that, for us. But the minds and hands that made such good use of simpler tools then would use ours that much better today. Things may change. People haven't changed at all. S o Edwards A. Park (I), first recipient, wisely spoke about a person-naturally John Howland, the young Dr. Park's colleague of 35 years before. Dr. Gamble (2), 2 years later, briefly revisited in his acceptance what he called "that lush meadow of opportunity," Howland's laboratory. As time brought us a second generation of recipients, the original greatness continued its influence. So, in 1971, Helen Taussig (3), a spiritual grand-daughter of Dr. Howland, described her inheritance-and ours-from Dr. Park. And lately, Lou Diamond, my own spiritual brother, recalled the quiet and powerful influence
on our generation of Kenneth Blackfan (4), 9 years Howland's Chief Resident. Therefore, I grasp the opportunity to attempt an account of my debt (and that of so many others) to Howland's other first generation settler in Boston, James Gamble. Admittedly, he figured as a previous Award recipient (2), but though Allan Butler described him handsomely in 1955, two celebrations of Dr. Gamble in 21 years are none too many. Moreover, I have a particular reason. The room I'm happy still to occupy at the Children's is entered by a door between two portraits some of you will remember from the old Laboratory Study. So, as I go and come, I overhear occasional strangers pausing on their way to important business with Mary Ellen Avery or Judah Folkman, to read the names under the pictures. (That anyone should need to do so always seems to me slightly surprising.) Before one portrait I have heard sometimes a note of pleased recognition: "Blackfan! He's the one they named the street after." (So, indeed, they did-if that were all.) Too often before the other, I hear only: "Gamble? I wonder who he was." S o I want to tell you a little about that, not just because he was important to me but in the hope of giving younger people a flash of recognition, while delighting those who knew Dr. Gamble, with that warm inner stirring that comes from recalling a rare soul. Just for the record, James Lawder (his mother's name) Gamble was born in Millersburg, Kentucky, not far south of Cincinnati, in 1883. He went from primary education a t the Millersburg Female College (of all things!) to secondary education at the Millersburg Military Institute (of all places for him!). Still, then he passed entrance examinations for Harvard, though Massachusetts looked too cold to be healthy to his parents, who sent him instead to California. There, he graduated from Stanford in 1906, braved the rigors of Boston, and received his Harvard M.D. in 1910. There followed internship a t the Massachusetts General, and 6 months more of it (with Bronson Crothers) a t the Children's
ACCEPTANCE OF HOWLAND AWARD Hospital, some medical travel abroad, and familiarization, back in Boston, with the new chemical methods of Otto Folin and calorimetric techniques of Francis Benedict. Then began an investigator's career, in the chemistry laboratory of the Massachusetts General-which provided the valuable companionship of three young men who later headed important Departments of Medicine: Walter Palmer, James Means, and L. H. Newburgh. 1t is a hopeless task for the appreciator of Dr. Gamble to speak as about him as Loeb did in presenting him the Kober Medal for the Association of American Physicians, in 1951 (5). 1 here break down and quote Of Dr. first On publication, with Means and and Creatinine Elimination," Dr. Loeb said: u
(During) . . . these studies there entered into Gamble's life a profound influence . . . , . . . the directing force of his career as an investigator. His room-mate, Bill Palmer, was at work under the direction of Professor L. J. Henderson . . . upon fundamental studies of acid-base and osmotic pressure regulation . . . . In visits to the laboratory, Henderson's catalytic propensities began to act not only on the substrate of Palmer but also on that of Gamble (whose) close contact with Henderson continued to stimulate his imagination in problems of electrolyte physiology. That influence long recurred. Dr. Gamble's best known publication, his Chemical P h ~ s i o b Tand ~ Pathology of Extracellular Fluid, first published in 1939, opens with two quotations on the milieu interieur, one by Claude Bernard, the other by L. J. Henderson (6). Much later still, indeed, 7 Years after kknderson's e (7) with mention of the death, amble began his ~ a n Lectures origin of life in sea water. his, he said, being water, "had, according to Lawrence Henderson, an incomparable biological fitness. BY . . . fitness," Gamble continued, ''we are to understand, I suppose, a suitability of themany components of the Great Experiment which was eventually so successful as to produce a Lawrence Henderson." In 1915, Dr. Gamble, aged 33, entered that "lush meadow of opportunityv-the new laboratory of the new professor of what was clearly the New Pediatrics, at Johns Hopkins. There, he decided to leave clinical medicine for "the study of disease by chemistry." In this, to quote Dr. Loeb (5) again, he "early developed the capacity to design simple experiments which yielded definitive answers. He worked with his own hands. . . , rarely with technical assistance-an invaluable approach all too often neglected today." (SO said Dr. Loeb, speaking in 1951. Fortunately for this speaker, Dr. Gamble in the 1930's firmly recommended that practice to young men who came under his spell and into his laboratory in Boston, even at some expense of broken glass and spilled mercury. I never saw him angry, though sometimes rather sadly amused.) But to return to the Hopkins years. Among those early "simple experiments yielding definitive answers" was one in which the actual experiment (if a trial of recommended therapy can be so called) was Dr. Howland's own investigation of whether the ketosis of fasting actually controlled the convulsions of epilepsy. Dr. Gamble's carefully planned use of the metabolic by products of that work produced a landmark study, far outlasting in significance Dr. Howland's results. 1 like to see where an old bound volume on the Countway Library shelves falls open from frequent use; for the Journal ~ i ~ [chemistry, ~ ~ i volume ~ ~ 57, l 1923, this happens-sure enough-at page 633: Gamble, Ross, and ~ i ~ d ~u l l~: metabolism h ~ of fixed base during fasting- (g), and for the next 50 pages (long for a Gamble paper) the fingermarks and surreptitious pencillings are heavy. Of this early classic, Dr. Loeb (5) says:
of
. . . At a time when most clinical investigation consisted of. . . recording endless observations based on some new method, Gamble planned a crucial experiment to elucidate basic problems of function and applied chemical means to this end . . . . It was thrilling for us . . . in Baltimore to see something happening to figures other than
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tabulation, to see them come to life and illuminate the processes of acid-base equilibrium. . . .(That) general design. . .continues to be the pattern for most studies. . .(of) electrolytes and water metabolism today. Even the expression of data by simple graphic means, now known as . . . Gamblegrams, has been generally adopted . . . a blessing for students, teachers, and investigators, alike. I hope we'll have time to say more about t h o e diagrams, but now
we press on to that fortunate event for Boston and Harvard, Dr. Gamble.s invitation there by Professor Oscar Schloss, in 1922. In spite of his unhappiness in Boston, Dr. Schloss left impressive accomplishments for a 2-year stay. Among these, Arthur Anderson, his Resident in 1922, singles out "the erection of the pediatric laboratory, and, most important of all, the appointments of Dr. James Gamble and Dr. Lynne Hoag to his staff" (9). In his Annual Report for 1922, Dr. Schloss himself notes the Hospital's "good fortune in having as its Laboratory Director, Dr. James L. Gamble," and his next paragraph mentions "the discovery of the active principle of the Pancreas by Banting . . . (as) . . . a ray of hope in the otherwise gloomy outlook for diabetes in children" (lO)-thus placing Dr. Gamble's arrival at Children's in temporal context. The appointment of Kenneth Blackfan, Gamble's clinical associate at Hopkins, to succeed Dr. schloss, is inconspicuous~y mentioned in the next Annual Report, but what a wonderful thing it was, for both of them and for the Hospital! A photograph (Fig. 1) shows them, probably not long after, for Dr. Gamble's pre-bowtie period was past when I came in 1930. Incidentally, the picture reminds me that I never saw him in a white coat, probably one of his several defenses against being led by Dr. Blackfan from the laboratory, where he was absolutely safe, to the bedside, where he was less certain. I hope my colleagues of those days will agree that they're standing by the side of the new laboratory. As a historian, I wish I knew which side. That structure began as a single story, but Dr. Blackfan reports for 1927 (1 1): "an epochal gain . . . . An entire second story has been constructed over the original laboratory building . . . , its outstanding feature a large and very beautiful room . . . to be known as the Laboratory Study . . . A memorial gift, its purpose is best described by the legend above the fireplace: 'In loving memory of Anne, 1918-1926, this room is given for study and reflection with the hope thereby to facilitate discoveries helpful to the healing of children.' It is impossible," Dr. Blackfan continued, "to . . . appraise the potential fruitfulness of this gift . . . or to state our gratitude to the vision and generosity of its donors." "The remainder of the new story provides four additional laboratory rooms. . . for research purposes, scarcely finished before they were actively in use." When I first saw it, that building had been completed only 3 Years, but the dark floors and panelling, the comfortable chairs, and the ranks journals and the Study seemed But they had have been there and-incidentall~-the~ were not to be. Swept away some 30 Years later the Laboratory Study, its panelling, its overmantel painting, big central table, and small tablet to Anne, are all somewhere in storage-awaiting a glorious resumectiOn, which Though the first low structure must have been a precondition of Gamble's coming, I suspect him of considerable share in the enlargement. From his own small office next door, I know he saw to it that the books and journals were bought, bound, and properly shelved, and that Marian Greene and Peggy Kame came over from the Chiefs office in late afternoons to set out tea in the bay window. He often dropped in and had a cup with anyone working there. Lou Diamond and Jim Baty did their Hematology at the other end of the second floor; LeRoy Fothergill and Marian Sweet their Service and Investigative Bacteriology downstairs, where
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Fig. 1. James L. Gamble (left) and Kenneth D. Blackfan (right), about 1925.
space was later found for Alfred Shohl, then wrestling with the difficulties of making intravenous amino acids safe before the invention of the Millipore filter. But Dr. Gamble's chemical laboratory, as you entered the first floor, the Laboratory Study directly above it, and Dr. Gamble himself at his small slant-top desk (or in his big chair) next to that, were the true heart of the place. So there it all was, waiting for me when I arrived as a House Officer and fell immediately inder the spell of the whole hospital, with its little ward buildings strung along their glass-walled corridors. When I went back to that relatively massive University Hospital in Ann Arbor in 1932, previously my home, I was homesick. I recall seeking out Dr. Newburgh, a favorite Professor in my student days (and always), to ask him about Dr. Gamble, and feeling a great bond between us when he said: "I both know him and love him." Encouraged by this to risk some youthful sentimentality, I said: "He always seemed to me to have almost an air of nobility. Don't you think that in the Middle Ages Dr. Gamble would have been a knight, or a baron?" Dr. Newburgh didn't think so. He thought, instead, and probably nearer the mark than I, "Jim Gamble would have been a monk." You will see why I was back in Boston 2 years later, and why,
even after I planted one foot on the other side of Longwood Avenue, I continued to spend time at the Children's, often to discuss the water and salt metabolism of the newborn with Dr. Gamble and his group-particularly in the great days of Bill Wallace. Today, I marvel at the simplicity, the openness, and the strategically central location of that laboratory building, still thought of by some as the Laboratory Study Building. Coming through the hospital's main corridor from breakfast in the morning, or for one last look at that disturbing baby on Infant's Upper before you went to bed, you stepped into the Lab Building for a few minutes-the first door along the central corridor-to see the blood culture you drew the night before, to check on some other determination or measurement, or to consult a reference in the Lab Study. Downstairs, you soon learned where the data books were kept; if no one was there you found in them the results you needed. Then, poking carefully around the Chemical Laboratory for some simple reagent or to make something for your own little ward laboratory with the glass tubing and blow torch, you discovered fascinating bottles containing remnants from earlier investigations, labeled in Dr. Gamble's strong and legible hand. Alan Ross said he had seen one marked "Synthetic Rat"; I knew an even more mysterious one whose contents were identified as "Synthetic Urine." Though I'm unsure about other doors, Dorothea Moore agrees with me that the Laboratory Study was never locked. Someone was always working up there, at all hours, of any day. Late one night it was this Society's current president, surrounded by large volumes, and looking even more tired than did his rumpled white suit when I had left him that morning beside one of those nightmare children who sometimes linger so stubbornly between hopeful and hopeless, in hospital cribs. Tired as he was, Dr. Pratt was still intent. When you get old you forget names, but he recently, and immediately, told me our patient's name was Randy, and that he had, among other things, erythrodermia desquamativa. When I asked, "Ed, what do you do up here so late at nights?" he said "Oh, lots of things-for instance, I find out how to cure Randy." I knew we probably couldn't do that, he knew that I knew, but we shared for a boundless moment that wonderful spell of searching in a good library for what you might find. I'm not sure that even Dr. Gamble's office next door was locked in his absence. I've certainly been there alone, consulting some book of his, though not feeling it quite proper to sit in the single large easy chair. In that, it was universally believed, he began any investigation scheduled for a year, by sitting and thinking for the first 9 or 10 months exactly how it should be done, and then doing it perfectly and completely by the year's end. We so often used most-or all-of a year doing our studies wrong. At his little desk there he wrote his lectures-rewriting each until it met his high standard of perfection-and then memorizing it for delivery to one of many scientific audiences, including the second year medical students. Because he disliked darkness and lantern slides, and preferred to see his listeners, his main points were illustrated by large hanging charts, on which-exactly as Dr. Loeb had said-he made "figures come to life and illustrate the processes of acid-base equilibrium." For those of you who never knew the major collection of them in the Syllabus (6), because you had the misfortune to be educated too recently, I show you (Fig. 2) the title page of that universally read book, out of print 15 years or more, and two representative samples. From them you may understand my dislike of the term "Gamblegram." Though a pleasant reminder of the originator, it has a suggestion of cuteness. There was none of that. Masterpieces of directly conveyed information, they were as clean and spare as a good etching. Two less representative ones happened to be hanging behind Dr. Gamble when an excellent photograph (Fig. 3) was taken by Jack Metcoff. It could not have been at a lecture, for only one chart at a time was ever presented on those occasions. An accompanying ritual was the glass of water, always placed by on the lectern to be sipped as he required, at some attending intervals, and at the lecture's end, raised and drained in an
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Fig. 3. James Lawder Gamble, from a photograph taken by Dr. Jack Metcoff, about 1952.
unspoken toast to the class-and to body water. Many of you will know of the surreptitious substitution of another colorless and somewhat more stimulating fluid by members of one class in which a James Gamble, Jr., was enrolled. The traditional account most familiar to me had Dr. Gamble, Sr., carefully concealing, at his first sip, both his surprise and his total understanding of the plot, and with almost inhuman concentration continuing his regular sips (and his memorized lecture), and (at its conclusion) draining the remainder amid thunderous applause-and then lying down all the afternoon. James Gamble, Jr., and William Berenberg, however, as two of our brethren who were present, describe the lecturer's hand repeatedly and tantalizingly extended toward the glass and always absent mindedly withdrawn, as the students sat with repeatedly bated breath-until, with the first sip, in the final minutes, a look of amused surprise and-in conclusion-an ample toast. Did Dr. Gamble know, all the time? If so, this silent, teasing riposte would have been in keeping with his quiet sense of humor,
more commonlv found in his words than in his acts. I believe he coined the superb phrase "precise misinformation" for the pseudoscientific papers where every calculation is carried to the third decimal place. Similarly, when Allan Butler and he were investigating for the Navy the water requirements of castaways during the second World War (12), Dr. Gamble delighted in the fact that Allan was named in the Government's Contract as the Responsible Investigator. This, he happily acknowledged, identified him as the Irresponsible Investigator. Occasional, and never too many, bits of humor were tucked into his lectures. Speaking at Leland Stanford in 195 1 (7), he described a balance study whose results were at first quite at variance with the theory he expected them to substantiate. But when corrected for appropriate though unmeasured insensible losses, he said " . . . our balance measurements and estimations of volume changes are now sweetly reasonable: we find the expected increase. . .of intracellular. . .and reduction of extracellular fluid volume. This," he continued, "is an illustration of unrighteous determination to have an experiment come out the way you want it to. And, as you see, the wages of sin are as they so often are, delightful." But I like even more his unpublished observation that there were numerous precedents for a Bostonian behaving outrageously in California. A Children's Hospital colleague urged me to mention Dr. Gamble's shyness and his humility. I knew what he meant but didn't entirely like either word. Instead, I shall say that he was by nature deeply sensitive and never assertive. In 1955, when we met with British and Canadian colleagues in Quebec, where he became the fourth recipient of the Howland Award, a co-author and I had sneaked off from the morning session to put some final touches on a paper, when Dr. Gamble, looking rather miserable, knocked at my hotel room door. "Could I, please," he said, "just quietly lie down on your bed for an hour? You see, Allan is up in my room writing a citation about me." That's what I mean. But let us return to his lectures. What was in them beside the bits of humor? Since he left no book except the wire-bound Lecture Syllabus (6) (which itself also contained the distillate of his published papers) one seeks in the Syllabus the essence of what he taught to us, to pediatricians, and to other physicians, everywhere. And one finds not so much chemical
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anatomy, but chemistry in action, purposeful-as though by its own intelligence, measurable, and interpretable. He did, indeed, "make figures come to life." His way of seeing things-and his skill in making us see them-stands out in this short passage from early in the Syllabus: T h e regulatory a p p a r a t u s governing extra-cellular fluid possesses mechanisms of adjustment behind the kidney which d o not prevent but which greatly limit change in physical properties in the presence of change in chemical pattern. Rigidity, then, is not t o be expected either in chemical structure o r in physical properties. T h e cardinal merit of any physicochemical system in the body must be resilience, otherwise it would be sure t o be smashed by the rapidly changing currents of chemical events. I n order t h a t the organism m a y survive severely adverse circumstances, this recoverability from distortion must have a width f a r beyond the usual requirement. T h e physicochemical system in extracellular fluid exhibits this necessary elasticity very beautifully.
He showed us that beauty in page after page, chart after chart. Once we began to see dehydration, acidosis, alkalosis, body size, and the special secondary roles of lungs, intestines, and kidneys, in relation to "the rapidly changing currents of chemical events," we could use laboratory measurements more intelligently in diagnosis and fluids far more effectively in therapy. Perhaps for the first time, he made a large portion of pediatrics know what it was doing. If this all seems merely commonplace to many of today's explorers among genes and enzymes, their familiarity with the surrohnding extracellular landscape they owe largely to James Gamble. No physician (or nurse practitioner) uses intravenous therapy today without some indebtedness to him. The growth of his Syllabus from 39 to 69 charts over its six editions in 15 years shows how diligently he continued to explore the territory he had so completely made his own. But by the final edition, in 1954, 3 years after his official retirement-with his health slowly failing-we could see a change from explorer to observer. Others were boldly beginning to repair deficits of intracellular ion intravenously. Dr. Gamble admitted (1951) that he had "felt it would not be safe to add potassium to a repair solution. However," he continued, "Darrow, who is not afraid of a postulation, has recently demonstrated that potassium can be safely used" (7). It was the turn of other and younger workers to go ahead. I recently found among the James L. Gamble papers in the Countway Library, a half sheet of typing headed, "Good Bye Bill." Its words were those he had written to say to William Wallace, on his departure in 1952 for the Professorship at Western Reserve. He began, bluntly: Y o u a r e the best leader of a laboratory group t h a t I have ever encountered. . . . Y o u have used the best of all methods-informal companionship. This method costs a lot of time and you have practiced it with an generosity. your cheerful and ever ready helpfulness, each of us owes you a debt which can't be ~
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Copyright @ 1976 International Pediatric Research Foundation, Inc.
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measured . . . I especially congratulate you o n having avoided the attitude of a Director of Research. Y o u have never mescribed o u r thinking, but you have helped us t o develop o u r thoughts a n d work them into the pattern of o u r undertakings. . . . Also, you have persistently taught us methodology. . . . T h e s u m of this is t h a t we just couldn't avoid having a grand time together . . . .
He was saying what we wish we could have said so well of him, and to him. To such words I would add two other brief statements. In 1959, at the time of his death, Dr. Janeway, in the Harvard Medical Alumni Bulletin (13), turned from mention of awards, honors, and accomplishments, to conclude that "in the hearts of his friends and his associates, his memory will be kept warm because his rare gift of intellect was combined with genuine simplicity and integrity of character, warmth of heart and great personal charm. As one friend has put it, 'There was not a spurious fibre in him'," and, finally, the words of Harold Faber and Rustin McIntosh (14): "James Lawder Gamble, fifty-sixth president, and Howland Medalist . . . . With keen insight he attacked the problems of fluid and mineral losses by methods combining simplicity and precision, portraying their characteristics with clarity and elegance. Uncounted lives of infants and children have been spared by the discoveries that he and those inspired by him unearthed . . . . His character and accomplishments are glories of the American Pediatric Society's history." That is who Dr. Gamble was. REFERENCES I. Park, E. A.: John Howland Award Address. Pediatrics, 10: 32 (1952). 2. Presentation of the John Howland Medal and Award of the American Pediatric Society to Dr. James L. Gamble: Introduction and Presentation by Dr. Allan M. Butler; Acceptance by Dr. James L. Gamble. AMA Am. J. Dis. Child., 90: 483 (1955). 3. Taussig, H. B.: Acceptance of the Howland Award. Pediat. Res., 5: 569 (1971). 4. Diamond, L. K.: Acceptance of the Howland Award-Reflections on pediatric care. Pediat. Res. 7: 858 (1973). 5. Loeb, R. F.: Presentation of the George M. Kober Medal to Dr. James L. Gamble. Trans. Amer. Phys., 64: 29 (1951). 6. Gamble, J . L.: Chemical Anatomy, Physiology and Pathology of Extracellular Fluid: A Lecture Syllabus (Department of Pediatrics, Harvard Medical School, Boston, 1939). 7. Gamble, J . L.: Companionship of water and electrolytes in the organization of body fluid, The Lane Medical Lectures, pp. 9, 10 (Stanford University Press, Stanford, 1951). 8. Gamble, J . L., Ross, S. G., and Tisdall, F. F.: The metabolism of fixed base during fasting. J . Biol. Chem., 57: 633 (1923). 9. Anderson, A. F.: Personal correspondence, 1975. 10. The Children's Hospital, Boston, Mass. Fifty-Fourth Annual Report, for the year 1922, pp. 83, 84. The Medical Department. I I. Idem: Fifty-ninth Annual Report, Part 11, pp. 9-1 1, for the year 1927. 12. Gamble, J . L.: Physiological information gained from studies on the life raft ration. Harvey Lect. Ser. 42: 247 (1946-47). 13. Janeway, C. A,: James Lawder Gamble, 1883-1959, Med. Alum. Bull. Harvard. July, p. 4 (1959). 14. Faber, H. K., and Mclntosh, R.: History of the American Pediatric Society 1887-1965, p. 294 (McGraw-Hill Book Co., New York, 1966). 15. Requests for reprints should be addressed to: C. A. Smith, M.D., 300 Longwood Ave., Boston, Mass. 021 15 (USA). Printed in U.S.A.
