Balu Athreya
Division of Rheumatology, Department of Pediatrics, Alfred I. duPont Hospital for Children, Delaware, USA

Primitive cultures attributed disease and natural disasters to evil influences. These evils may emanate from wrathful God or an ancestor or a planet or another evil person. It was not until the period of Greek civilization that scholars moved away from accepting supernatural causes of events and started to look deeper into the nature of the world we live in for clues to diseases and disasters.

In medicine, Hippocrates tried to separate medicine from religious and physical theories. For example, he wrote that seizures were not caused by divine influence. In his days, epilepsy was considered a "sacred" disease. He wrote: " It is with regards to the disease called sacred : it appears to me to be nowise more divine nor more sacred than other diseases, but has a natural cause from which it originates like other afflictions". He was the first to study human disease as a natural phenomenon whose cause and cure can be studied. He described diseases based on careful observations and showed how this can help predict the course of the disease (prognosis). However, there was very little understanding of the anatomy, physiology and pathology. Since dissection of the human body was prohibited, most of the known anatomy was from accidental observations of humans and dissection of animals.

The idea that earth, air, fire and water are the essential elements of nature was suggested by Empedocles. Later this idea was developed into four associated qualities, namely heat, cold, dryness and moisture and four humors, namely blood, phlegm, yellow bile and black bile. This was made popular by Plato in his play Timeus in which he suggested that human disease is due to imbalance between these humors. In India we, of course , have our own theory of vatha, pittha and kapa. The idea that normal health is when these elements are in equilibrium and diseases are due to imbalances between these humors (the humoral theory) was dominant until recently.

Although Aristotle developed several concepts on observation of nature and logical reasoning, it was Galen’s ideas that dominated western thinking for almost twelve centuries. Challenging these old dogmas of Galen by Paracelsus, Andre Vesalius, William Harvey and others was what made scientific progress possible.

In 1543, Andre Vesalius published his book on anatomy (De Fabrica Humani Corporis) based on dissection of human cadaver. Although human dissections have been done earlier, this was the first organized effort to base knowledge on actual observations of the human body. Since Galen’s anatomy had the support of the church, and Vesalius’s findings did not support Galen’s assertions, this book received a mixed reception. Vesalius left anatomy completely and moved from Italy to France.

The next major step was the systematic study of changes in organs in the bodies of individuals dying of specific diseases (autopsy). Giovanni Battista Morgagni kept records of the gross anatomy of organs from patients for several decades and compiled them into the first book on pathology (De Sedibus et Causis Morborum, 1769). This correlated the symptoms during life with diseased organs at death. This showed for the first time that studying clinical findings in life will help identify the affected organs (s). It also showed that the explanations for symptoms should be sought in the human body itself and not in the so-called humors, the stars or divine forces.

Early observations of human anatomy by artists like Leonardo Da Vinci led to the idea of studying the body as a mechanical system. William Harvey’s study of the circulation of blood was along this line of thinking. His experiments were elegantly designed. His reasoning from direct observations of the flow of blood during animal dissections not only in the arteries and veins but also through the valves of the heart and his interpretation of the functions of the valves in the venous system were important steps in scientific understanding of the human physiology.

His study also led to the question of how the blood came back to the veins once they reached the distal ends of arteries. This is as any good science should do, namely develop testable hypothesis to fill in logical holes in the conclusions. He did not know and suggested "pores" as the passageway between arterial and venous system. Later Malpighi showed these "pores" were the capillaries.

Up to this time enormous progress was made purely on careful and systematic observations of what was there all along for anyone to see. The idea of using instruments to see what eyes cannot see and hear what ears cannot hear started with the invention of stethoscope and X-Ray and is relentlessly pushing the frontiers of our knowledge of the universe and of biology. Although measuring instruments such as telescope and microscope were invented earlier, Galileo is credited with the use of careful observations with accurate measurements and documentation as critical steps in scientific research.

Designing experiments to understand nature was the next step. Some of those experiments included measurement of blood pressure in horses by Stephen Hale, studies on the afferent and efferent nerves by Haller, Charles Bell and Francois Magendie.

Some of the most important experiments which established medicine in scientific footing are those of Robert Hooke, considered to be England’s Leonardo Da Vinci. He was the curator of experiments for the Royal Society and in that capacity developed the air pump for Boyle’s experiments. Together they showed that it was the oxygen in the air that was important for life and that "pablum vitae and flammae" were the same element in the air. Thus air was demoted as one of the four essential elements. He also showed that a dog can be kept alive after the thorax had been opened as long as air was pumped in and out of the lungs.

There were several other pioneers who studied human and animal physiology using experimental designs. The most important of them was Claude Bernard, who summarized many of the principles of scientific investigation as applied to human biology in his famous book on An Introduction to the Study of Experimental Medicine. This book should be the first book anyone interested in medical research should read.

In the next article I plan to summarize Doctor Bernard’s main points from Chapter 2 of his book.

Further Reading:

  1. Platt JR. Strong Inference. Science. 1964; 146:347-353.
  2. Chamberlin TC. The method of multiple working hypothesis. Science. 1965; 148; 754-761. (original publication in Science 1890; 15: 92)
  3. Bloom FE. The endless pathways of discovery. Science. 2000; 287: 229.
  4. Gould SJ. Deconstructing the “science wars” by reconstructing an old mold. Science 2000; 287: 253-261.
  5. Raoult D. Creationsim – remember the principle of falsifiability. Lancet. 2008; 372:2095-2096.
  6. Anderson PW. More is different. Science. 1972; 177: 393-396.
  7. Mashelkar RA. Irreverence and Indian science. Science. 2010; 328: 547.
  8. Beveridge WIB. The Art of Scientific Investigation. 3rd edition 1957. William Heinemann Ltd. London.
  9. Bernard C. An Introduction to the Study of Experimental Medicine. 1957. Dover Publications, New York.


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