Historical Perspectives

When neonatology was emerging as a clinical discipline in the late 1950s and early 1960s, it had the advantage of a strong foundation of basic research in fetal and neonatal physiology. In particular, the new clinical enterprise (it was not yet a subspecialty) focused on cardiorespiratory pathophysiology. This foundation came from a few distinguished research laboratories studying fetal and neonatal physiology and the processes of the transition from fetal to neonatal life. The preeminent laboratory in the field was the Nuffield Institute for Medical Research at Oxford, directed by Geoffrey S. Dawes.Geoffrey Dawes became the director of the Institute in 1948. He received his medical degree in 1943, and in the following 5 years, he gained recognition as a prominent investigator in pharmacology and physiology. The very short interval between receiving his degree and being named director of an important research institute indicates how quickly the academic leadership recognized his exceptional qualities. As the new director, Dawes set the primary focus of research for the Nuffield Institute as developmental physiology. In this role, the Nuffield became the successor to the path of research started by Sir Joseph Barcroft at Cambridge early in the twentieth century. Dawes and his coinvestigators concentrated particularly on the preparations for and mechanisms of adaptation to extrauterine life. A central focus of the research was the adaptive mechanisms in the circulatory and respiratory systems, including placental function, establishment of lung function, and changes in the pulmonary and systemic circulations. Although most of the work examined cardiorespiratory physiology and its neurohumoral regulation, researchers also studied fetal growth and metabolism, and their studies included the responses to stresses such as hypoxia and hemorrhage. One of the hallmarks of the research of this highly productive group was the elegance of their experimental designs.The clinical implications of this work were self-evident. What happened when the adaptive mechanisms for extrauterine life failed? What were the responses to stresses such as asphyxia? Beginning in 1958, Dawes and his associates had an ideal opportunity to expand this line of research. The United States National Institutes of Health were supporting studies on the mechanisms of brain injury in the fetus and newborn being performed in a primate laboratory in Puerto Rico, and various groups of investigators were invited to participate in the different aspects of the research. Dawes and the Nuffield team were among those invited to collaborate and made several extended visits over the next few years to conduct research with other investigators, particularly Stanley James and Karlis Adamsons. They made extensive observations of the sequences of responses to progressive asphyxia. The resulting studies brought forth the paradigm of the progression of cardiorespiratory changes during asphyxia. The FigureF1 from Dawes’ book that illustrates this paradigm has been reproduced both in its original form and with minor modifications in many clinical textbooks, usually as the starting point for a discussion of fetal asphyxia. (For example, see Figures 1.6 and 1.7 on page 1–7 of the Fourth Edition the American Academy of Pediatrics Textbook of Neonatal Resuscitation). They also started to study the responses to various components of resuscitation. For example, they demonstrated that when heart failure is due to acute asphyxia, correction of acidosis by an infusion of alkali quickly restores normal myocardial contractility.During the formative era of “modern” neonatology, ie, neonatal care based on cardiopulmonary pathophysiology in the mid to late 1950s and early 1960s, many conferences dealt with the general topic of how to deploy a system of physiology-based care for newborns. Dawes was highly sought after for such conferences as much for his insightful, probing commentary on the work of others as for presentation of his own research. A good example of these times was the Ross Conference “Adaptations to Extrauterine Life,” held in Vancouver in November 1958. The Session Chairs were Dawes and McCance from Cambridge, and Harvard's Clement Smith, the author of the text Physiology of the Newborn Infant, which was required reading for budding neonatologists. Mildred Stahlman, L. Stanley James, Thomas Oliver, Sidney Segal, and Jim Sutherland were among the attendees who were emerging as some of the early leaders in neonatology. In this program, Dawes’ presentation was effects of anoxia on newborn animals. The proceedings of the conference reflect the interests and intellectual energy of the formative years of neonatology. The program ended with a roundtable discussion on clinical applications in which McCance commented on “euthermia versus hypothermia” and Smith commented on “the effects of placental transfusion,” both subjects of research publications in 2006 and 2007.In 1967, Julius Comroe, the director of at the Cardiovascular Research Institute at the University of California, San Francisco (UCSF), invited Geoffrey Dawes to take a sabbatical at the Institute to write the book on fetal physiology. Dawes accepted and came to San Francisco for the latter half of 1967. Comroe provided Dawes with editorial staff, a medical illustrator, and an editorial advisory committee of physiologists who met with him weekly to critique his most recent chapter. Dawes clearly wanted the text to appeal to clinicians as well as physiologists, meeting frequently with Bill Tooley, the head of neonatology at UCSF, to discuss his strategy for upcoming chapters and regularly attending the weekly neonatal/perinatal clinical conferences, where he was an imposing presence.The product of the sabbatical was the superbly written and beautifully illustrated Fetal and Neonatal Physiology, published by Year Book Medical Publishers, Inc, in 1968. Although not a clinical text in the strict sense, most of the book is highly relevant to the practice of clinical neonatology. It quickly became required reading for serious students of neonatology. It remains highly relevant today and is so well written and illustrated that it probably still should be required reading for neonatologists in training.The original home for the Nuffield Institute for Medical Research was in an abandoned astronomical observatory in central Oxford. The building was designed by Christopher Wren, the great 17th century architect who designed many of the important buildings built after the great fire of London. However, this fine building of historic interest was not well suited for experimental physiology. When a new hospital of Obstetrics and Neonatal Pediatrics was built at Headington on the outskirts of Oxford, the Nuffield Institute moved into a large new facility immediately adjacent the clinical buildings, which was symbolic of Dawes’ close ties to clinical perinatology and neonatology. There was continuous exchange between the buildings, and Dawes regularly attended and participated actively in the weekly perinatal/neonatal clinical conferences. The proximity of the clinical units facilitated the Institute's close collaboration with obstetricians and pediatricians.When Dawes began using the chronic in utero fetal lamb preparation, he noticed that fetal lambs made intermittent respiratory movements that occurred during rapid eye movement sleep. Moving to the human, his obstetrically trained research fellows could detect fetal breathing movements by ultrasonography that also were intermittent. These observations spawned a burst of clinical research in many centers as perinatologists studied the effects of various maternal states on fetal breathing. In time, fetal breathing movements became part of the biophysical profile of fetal well-being.As Dawes became familiar with the clinical methods of assessing fetal well-being, he was unhappy with the way fetal heart rate tracings were used to detect a fetus in distress because the system depended on expert recognition of particular patterns. He accumulated a very large database of digitized human fetal heart rate tracings and, with his strong background in mathematics, launched on a large-scale analysis. Ultimately, he developed a program that would allow automated detection of fetal distress. An instrument company produced a microprocessor that used his method to detect troublesome patterns of the fetal heart rate.Another major contribution of Dawes was the development of leaders in academic neonatology and perinatology. There were three types of researchers at the Nuffield. The first were what might be considered the permanent scientists, some of whom stayed on for many years and others of whom were there for several years, then moved to other academic positions, usually in physiology. The second group was the research fellows in training. Some of these were predoctorate, but in later years, many were postdoctorate pediatricians and obstetricians. The attraction of the Nuffield for physicians headed for careers in academic neonatology and perinatology were obvious, so talented young clinicians flocked to the Institute. They later filled many university faculty positions in neonatology and perinatology, particularly in the United Kingdom, Canada, the United States, Australia, and New Zealand. The third group of investigators was the established academicians, usually in perinatology, neonatology, or physiology, who spent a sabbatical leave (generally 6 months to 1 year) working in the Institute before returning to their home medical schools. The investigators who passed through the Nuffield became a sort of informal network that continued to communicate and often collaborate in research.Many of Geoffery Dawes’ long list of awards are related to neonatology and perinatology. Some of these include Fellow, Royal Collage of Obstetricians and Gynaecologists, the American Academy of Pediatrics, and American Collage of Obstetricians and Gynecologicts; the Apgar Award from the American Academy of Pediatrics; and the James Spence Award from the British Pediatric Association.Geoffrey Dawes stepped down as the director of the Nuffield Institute in 1985 and died in 1996. A more complete appreciation of him by Sir Graham Liggins appeared in Biographical Memoirs of Fellows of the Royal Society 1998.

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