Learning from the Lungfish: Studies of Hiberation, 1963-1988

After more than a decade as a trailblazing cardiac surgeon and medical educator, Swan gave up the chairmanship of the department of surgery in 1960, weary of the endless meetings and paperwork that the position demanded. The following year he resigned from the University of Colorado faculty entirely after a series of confrontations with the administration regarding the use of fees generated in the department of surgery. In 1963, he accepted a post at the Colorado State University School of Veterinary Medicine, where he taught surgery but also developed research facilities for the department, along with a doctoral program in surgical research (the first such veterinary program in the United States). It was an unusual move for a successful academic surgeon in mid-career, but Swan had for some time wanted to spend less time on clinical medicine and more time pursuing research. (And, as he once remarked, "Just because you can do something well doesn't mean you have to do it for the rest of your life!") During his years of painstaking studies of hypothermia, he had become fascinated with the relationship between body temperature and the lowered metabolism of hibernating animals. Thus, in 1962, when his friend Charles Hufnagel (another pioneering surgeon and inventor of the first artificial heart valve) suggested that Swan investigate the African lung-fish, it changed his life.

Lungfish (Protopterus aethiopicus) are estivators, i.e., they enter a dormant state in hot weather, just as hibernating animals do in winter. When the rivers dry up in the intense heat, lungfish burrow deep into the river bank mud, staying in a state of torpor (suspended animation) until the rains fill the river again. Unlike hibernators, however, lungfish can stay in this dormant state for over two years, and their body temperature does not decrease significantly. This suggested to Swan that their greatly reduced metabolic state might be mediated primarily by an anti-metabolic hormone, rather than being a function of body temperature. If such an agent could be found, it might eventually be possible to induce a short-term "artificial hibernation" state in clinical patients and achieve some of the benefits of hypothermia without the risks of deep cooling. In 1963, Swan obtained a research grant from NASA, which was interested in research that might help astronauts survive extended space flights. The following year, he took his new wife, Geri, on a honeymoon to Africa, to explore the upper Nile basin in search of estivating lungfish. Swan reasoned that the metabolism-slowing hormone would be easier to identify in the dormant than in the active fish. Finding the fish proved more difficult than anticipated; with heavier than average rains that year, the rivers didn't dry up and the lungfish didn't estivate. Swan had to arrange for others to find the fish and ship them to the United States. (Several shipments of lungfish perished during stopovers in New York before Swan and his assistants designed a special shipping container.) Once in Swan's lab, the fish were housed in large tanks with several feet of mud on the bottom. They were induced to estivate by gradually reducing the water levels and food supply. After thirty days of estivation, still in torpor, they were killed and the brains removed. An extract of the brain tissue was then injected into laboratory rats, which were monitored for up to four hours. The estivating lungfish extract caused the rats to become torpid, reducing their body temperature by 5°C, and their metabolic rate by 35%. Swan named the active anti-metabolic substance "antabolone", and his later research revealed its presence in other hibernators, such as the ground squirrel (Citellus tridecemlineatus.)

In 1974, Swan published Thermoregulation and Bioenergetics: Patterns of Vertebrate Survival, a detailed synthesis of the current state of knowledge regarding hibernation states and metabolism. Drawing on his own investigations as well as others, he examined many aspects of the constant interplay of temperature and metabolism that characterizes life in vertebrates, especially the blend of behavioral, physiologic, and metabolic control mechanisms at work. In his introduction, he put this in laymen's terms: "Why do people die of cold when a marmot can hibernate with a body temperature of 3°C? Why can a lizard stay active over a range of body temperatures 20°C wide, when a mouse would die at any body temperature in the entire range? How do animals utilize energies to maintain body temperature within their own specific limits for survival? Within what limits can man expect to modify himself or his environment safely?" The book examined the biochemical processes of metabolism and temperature regulation in warm-blooded and cold-blooded animals, changes during hypothermic and frozen states, and hibernation and estivation patterns. As Swan demonstrated then, these are complex phenomena, and their mechanisms still are not completely understood, though recent investigators have been able to explore them at the level of gene expression. Unfortunately, researchers have yet to fulfill Swan's hope that "antabolone" or a similar substance might be isolated and eventually used for clinical medicine.

Swan retired from the Colorado State University School of Veterinary Medicine in 1982, partly due to a slowly progressing neuromuscular disease. He continued to do research part-time and developed a synthetic buffer solution for clinical use, which received a patent in 1993. Meanwhile, he devoted more time to his numerous other interests. These included home renovations such as adding solar energy panels, and installing a double kitchen so he and Geri had more room to cook for their friends. The couple kept an extensive garden, where they developed new varieties of tomatoes and winter squashes (later patented and sold commercially); he also became a serious wine connoisseur. And as long as his health permitted, Swan continued to enjoy traveling, hunting, and fishing.

Henry Swan died of the progressive neuromuscular disease on July 13, 1993, at his home in Denver. Though he made substantial contributions to the field of hibernation studies during the second half of his career, his major legacy to medicine remains in cardiac surgery, surgical education, and surgical research. Swan often noted that cardiac surgery transformed the entire surgical landscape. Between the 1940s and the early 1960s, those who ventured into heart surgery had to solve myriad problems. Their work generated new knowledge and techniques that benefited all types of surgery, vastly improving standards of care and patient survival. For example, these pioneers learned how to recognize and manage the effects of low oxygen levels on cardiac output and circulation, how to better control blood volume and manage blood loss, and how to better maintain adequate respiration. They also perfected the management of acute cardiac arrest and techniques for resuscitation, thus greatly reducing the chance of sudden death in the operating room. They developed new instruments and prosthetic devices such as valves and arterial grafts, along with special equipment to monitor patients during and after surgery, and special units for post-operative care. Finally, the work of Swan and his fellow heart surgeons also firmly established laboratory research as an important part of surgical training. As he observed, it was clear even by the early 1960s that "[N]o previous branch of surgery had so clearly shown the importance of developing in the laboratory the techniques and instrumentation necessary to solve the challenges of operating on new and difficult anatomic problems."