Lastly, in considering the general methods of attack upon their problems used by physiologists, one sees clearly, although very faintly, a reconciliation being brought about with zoology. An increasing interest in so-called general physiology - or the physiology common to all organisms as opposed to the special physiology of any particular species - the awakening of zoologists to the functional side of their science, and the use of comparative physiological data to solve functional problems in the higher animals, all tend to indicate that a real comparative physiology may soon be flourishing along with other developments.

In a more concrete way, we may ask just what are the problems of function and just how are they attacked and partially solved? No better way of answering these questions can be found than by giving in some detail a few examples of how physiologists go about their job. These examples have been chosen from fields of work with which the author feels some familiarity; equally satisfactory examples could have been taken from many other provinces of the science.

Let us take first as an illustration a problem in connection with the circulation of the blood, a problem of first importance in this realm and one which was clearly grasped by the discoverer of the circulation himself. Thus, over three hundred years ago, Harvey wrote:"Meanwhile I know and state to all that the blood is transmitted sometimes in a larger amount, other times in a smaller, and that the blood circulates sometimes rapidly, sometimes slowly, according to temperament, age, external, or internal causes, normal or abnormal factors, sleep, rest, food, exercise, mental condition and such like." Harvey was here referring, of course, to the quantity of blood which circulated around the body in a given time, which is the same quantity as that pumped by the heart in the same time. The problem of the cardiac output is here clearly stated, and a qualitative expression of the main factors which influence the output is given.

Since Harvey's time, attempts have been made in various ways by a long line of investigators to determine the cardiac output of man and the variations of this function under different conditions. It is obvious, of course, that some indirect method must be devised; the output of the human heart cannot be measured directly. At first, guesses were made as to the amount of blood pumped out by the heart of man based on a measurement of the total capacity of the heart as determined on the cadaver. But, when it was later found from experiments on animals that the heart does not completely empty itself at each beat, the value of such estimates became doubtful. After the development of methods for keeping the isolated heart alive by perfusion, accurate direct measurements of the output of such a heart could be obtained. Based on the relative size of man and of the animal from which the heart was taken, a calculation could be made for the human cardiac output. However, although this line of investigation has added enormously to our knowledge of the function of the heart, it tells us rather what the heart can do than what it actually does in a normal man or animal.

With the heart remaining in situ in the intact animal, two methods have been extensively used to estimate the volume of blood pumped out. In one of these an ingenious apparatus, called a stromuhr, which is inserted into the aorta - or large artery leaving the heart - measures the amount of fluid flowing through it. In the other method, the heart is completely enclosed in an apparatus called a cardiometer, which can be easily constructed from an ordinary tennis ball and a piece of rubber, and is arranged to measure the volume changes of the heart. The change from its maximal volume to the minimal represents the amount of blood discharged at each beat; and since, therefore, the number of beats per minute is known, the amount discharged per minute can be easily calculated. The use of both of these methods has led to valuable knowledge concerning the activity of the heart, but, since extensive operative procedures are necessary, the question has been raised as to how far the values can be applied to the heart in the normal animal.

Over half a century ago, the German physicist and physiologist, Fick, announced a principle upon which many recent methods have been based. He did not attempt to try out a method based upon his idea, probably owing to the lack of suitable analytical methods for gas analysis in blood. The Fick principle, as it has come to be called, consists in determining the total quantities of oxygen or carbon dioxide in the blood of the right and left sides of the heart, respectively, and simultaneously estimating the quantity of oxygen absorbed or carbon dioxide given off by the animal through the lungs. Now, if M.V. represents the volume of blood in liters per minute discharged by one side of the heart, A„ the quantity of oxygen and Ac the quantity of carbon dioxide in the arterial blood, Vo the amount of oxygen and Vc the amount of carbon dioxide in the mixed venous blood of the right heart, 0 the oxygen absorbed and C the carbon dioxide given off by the lungs per minute, we have M.V = O/ (Ao -Vo) = C / (Vc - Ac) Since all of these quantities except the required M.V. can be experimentally determined, the problem is theoretically solved. Technical difficulties, however, in determining the necessary values in the above equation have prevented its wide application even to animals and have been only recently surmounted in the case of the human subject. The Fick principle has been used on animals, where blood samples can be taken directly from the right and left sides of the heart. In the human subject, it is a comparatively easy matter to determine the quantity of oxygen absorbed at the lungs or the quantity of carbon dioxide given off; such a determination is made in determining the so-called metabolic rate or basal metabolism so much used now in the diagnosis and treatment of thyroid disease. The content of oxygen or carbon dioxide in the arterial blood (that of the left side of the heart) can also be easily obtained by an indirect method of calculation and can be checked directly by obtaining blood for analysis from an artery, a procedure quite feasible in the human subject. The difficulty comes, however, in estimating the gaseous contents of the mixed venous blood of the right side of the heart, and because of this fact the simplicity and directness of the method as used on animals are lost. Blood, of course, can be easily obtained from various veins of the body, as is done every day in hospitals in making various blood tests; but such blood is not the same in its oxygen and carbon dioxide contents as that of the right heart. It has taken a quarter of a century of intensive research to work out satisfactory devices for determining the gas tensions, and hence the gaseous contents, of the mixed venous blood indirectly. All of these schemes depend on equilibrating a gas mixture in the lungs with the mixed venous blood, analyzing it, and then finding how much oxygen or carbon dioxide the venous blood of the subject will contain at these gas tensions.