Radoslav K. Andjus

Radoslav K. Andjus was born (1926) and raised in Belgrade, Serbia. He majored in biology at the University of Belgrade, entered the graduate program at the same University in 1950, and defended his PhD thesis in 1953 in the field of thermophysiology. Beginning in 1951, he moved through the ranks at the University of Belgrade from teaching assistant to full professor. Professor Andjus also held numerous positions in the various scientific and educational institutions at that University during his 50-year career. Among others, he was the Head of the Department of Physiology in the School of Sciences, Associate Dean of the School of Sciences, Director of the Institute for Biological Research and Center for Multidisciplinary Studies, President of the Committee for Cryobiology at the International Institute of Refrigeration (1967), President of the Committee for Natural and Exact Sciences of the Yugoslav National Commission for UNESCO, and President of the Committee for Biology of the Federal Research Council of Yugoslavia.

Internationally, he held positions as a researcher at the College de France, Paris, as a staff member at the National Institute of Medical Research, London, and as a visiting professor at the Department for Surgical Research, School of Medicine, University of Pennsylvania, Philadelphia, and the Department of Physiology, University of Colorado, Fort Collins. Professor Andjus was elected to the Serbian Academy of Sciences and Arts (1959), the International Academy of Astronautics (1960), and the Montenegrin Academy of Sciences and Arts (1973). He was appointed to the editorial boards of several international and domestic scientific journals, including Cryobiology (USA), Resuscitation (UK), and Astronautica Acta (IAA).

“Guardians of the flame”
“Guardians of the flame”

Professor Andjus was constantly engaged in active scientific research until the end of his life. He was a productive scientist, publishing over 200 scientific papers in domestic and international journals, which have been cited over 850 times. With respect to his scientific interests, Professor Andjus was a renaissance man. His main field of investigation was thermophysiology. He studied hypothermia, suspended animation and resuscitation, hibernation and biological rhythms, brain metabolism, neuroendocrinology and endocrinology, retina and electroretinography, as well as biophysical modeling and theoretical biology. In addition, he was involved in studies on hypoxia, ischemia and radiation protection, neuropharmacology and drug developments, and fish physiology, ecology, and aquaculture. Here, we will discuss just a few of his scientific accomplishments. For details on his other work, see Stojilkovic et al. (2005).

Unquestionably, the most significant results of Professor Andjus’s career are those achieved in his early studies on deep hypothermia, suspended animation and resuscitation. Previous studies in his group showed that 15°C marks a turning point in the physiology of the rat. As discussed above, at 15–20°C, animals exist in a state of cold narcosis in which hypophysectomy and other major operations can be performed (Djaja and Andjus, 1949). After cooling below 15°C, animals were unable to re-warm or to spontaneously increase their oxygen consumption. Certainly, the resuscitation of animals that have been subjected to body temperatures below 15°C or cessation of breathing and heartbeat might have practical applications to resuscitating accidentally cooled humans, as well as in cardiac surgery to facilitate the use of hypothermia for anesthesia.

As a young graduate student, Andjus was the first to resuscitate rats with a colonic temperature between 0 and 2°C even after heartbeat and respiration had been arrested for 40–50 minutes (Andjus, 1951). Previously, rewarming was usually performed by transferring the cold animal to a warm environment. Andjus’ technique instead reestablished circulation by applying heat locally to the cardiac area (by applying a hot metal spatula to the chest wall) and giving artificial respiration before re-warming the whole body.

During his postdoctoral studies in the United Kingdom, Andjus and Smith improved this methodology using a focused beam of light to reestablish the heartbeat, combined with artificial respiration. The authors also observed that spontaneous breathing was resumed in the majority of animals when the colonic temperature reached approximately 15°C and after the neck had been heated. Only then were the reanimated rats transferred to a warm bath (Andjus and Smith, 1955). Complete recovery and long-term survival in 80–100% of the animals was also obtained using microwave diathermy for resuscitation. This technique was introduced to avoid the burning of peripheral tissues that occurred with the two other techniques (Andjus and Lovelock, 1955). Once this method of reanimation was established, Andjus investigated a number of related problems, including the maximum duration of suspended animation, the effects of repeated cooling to zero, and the possibility of reanimating rats cooled to subzero temperatures (Andjus, 1955).

He and his collaborators also showed that animals whose body temperature had been lowered below 15°C exhibit a significant impairment in problem-solving performance. On the other hand, no significant differences were found between the performances of control animals and those with a body temperature brought to approximately 15°C, confirming the view of a turning point in the physiology of the rat at this temperature. Other functions of rats were fully established within 2–3 days. Observations of breeding performance gave evidence of a temporary impairment of fertility, but the majority of animals produced progeny within three months of exposure to extreme hypothermia. The offspring were healthy and were reared normally by their mothers (Andjus et al., 1955).

These initial discoveries by Andjus received favorable assessments by leading scientists in the field of thermophysiology. Here we will quote only a few: “We have found that the best method of reanimation was Andjus method of reanimation… We have religiously followed his prescriptions…” (E.F. Adolph, Symposium on Hypothermia, XV Internat. Congress Milit. Med. and Pharmacol., 1959, p. 483); “Dr. Andjus himself was responsible for the establishment of an entirely new principle in physiology and medicine… A great school of physiology has grown up in Belgrade…” (A.U. Smith: Progress in Refrigeration Science and Technology; Pergamon Press, Oxford, 1960, p. 498); “The techniques of Dr. Andjus altered completely pre-existing ideas about thermal death points in mammals and permitted a major breakthrough in the study of extreme hypothermia in homeotherms.” (A.S. Parkers: Biological aspects of freezing and drying, L. Rey, Editor; Hermann, Paris, 1962, p. 4). These scientific achievements were later included as teaching material in 18 foreign university physiology textbooks and more than 40 scientific monographs.

The brain metabolism experiments that Professor Andjus carried out in the early 1960s established an excellent basis for subsequent investigations in the field of neurobiology. He developed a relatively simple isolated, perfused rat brain, with preserved spontaneous and stimulated activity. This was achieved in rats, which are adequately anesthetized by deep hypothermia without the use of any chemical agent. The preparation was perfused with an artificial blood by means of a small roller-type pump. Spontaneous electroencephalographic activity was preserved in isolated brain preparations and persisted for 5 hours. Using this preparation, he also investigated the effects of pentylenetetrazol and loud sounds on electroencephalographic activity and glucose consumption. This work significantly influenced investigations in the field, as documented by over 220 citations by his colleagues (Andjus et al., 1967).

Together with Professor Desanka Marić and her collaborators, Professor Andjus worked on establishing a laboratory for fundamental investigations in reproductive neuroendocrinology at the University of Novi Sad. Among the numerous studies generated by this laboratory, those related to the characterization of endocrinological variables in growing male rats received the most attention. Initially, they studied the developmental patterns of gonadotropin, prolactin and androgen secretion in the developing male and found a marked age-dependent sensitivity of androgen variables to a pharmacologically-induced prolactin deficit (Kovacevic et al., 1982). Further studies revealed that elevated prolactin, if maintained long enough prior to puberty, might significantly attenuate or delay the intensified secretion of androgens characteristic of puberty, presumably by suppressing the intensive prepubertal gonadotropin secretion. The authors also observed a prolactin-induced increase in the responsiveness of the prostate tissue to androgens (Maric et al., 1982).

Andjus and collaborators also analyzed the steroidogenic maximum of the testis at the peripubertal age in controls and hypoprolactinemic rats. They found that hypoprolactinemia induced a precocious increase in number of Leydig cells and suggested that this could have resulted from the facilitation of proliferation by high prepubertal gonadotropin levels (Kovacevic et al., 1987). Andjus and coworkers also studied the dependence of the peripubertal relationship between prolactin, gonadotropin, and androgen secretion on testicular opiates. They showed that intraperitoneal administration of naloxone, an opiate antagonist, in peripubertal rats induces a significant decrease in basal in vitro androgen production by removing the testes 15 or 30 min following treatment. However, this inhibitory effect on basal steroidogenesis was not observed in control multiple-dose experiments in which incubated testes from naloxone-naive rats were directly challenged with naloxone; on the contrary, this produced enhancing effects. The possibility thus remains open that indirect inhibitory effects of injected naloxone may occur in intact animals (Maric et al., 1987).

Professor Andjus was an exceptionally gifted individual, with enormous energy and tireless devotion not only to science but also to teaching. Besides teaching a course in animal physiology for biologists, Professor Andjus founded a course on cell physiology and biophysics for molecular biologists, as well as a physiology course for psychologists. He also contributed to the organization of a graduate multidisciplinary program at the University of Belgrade and mentored numerous PhD candidates. His former graduate students now teach physiology and biophysics in several cities of the former Yugoslavia, the United States, the United Kingdom, Canada, and Morocco. Others are working as independent scientists in several prestigious international research institutions. He died in 2003 while working on a module of his multi-volume textbook, “General Physiology and Biophysics” (Andjus, 2002). This outstanding and unique work represents a synthesis of his decades-long teaching, research, and intellectual activities. It is not only a textbook written in the best tradition of American authors, but also a history book addressing many aspects of major discoveries in physiology and biophysics, and a monographic summary of the contributions of Yugoslavian scientists to these discoveries.