Joseph Wilder

BASIMETRIC APPROACH (LAW OF INITIAL VALUE) TO BIOLOGICAL RHYTHMS

This paper discusses not only what the basimetric approach could do for the study of biological rhythms but also what the study of biological rhythms could do for basimetry. Basimetry is the study and application of the Law of Initial Value (LIV) (Wilder, 1935, 1958, 1960, 1961) in biological sciences. The LIV, an empirical-statistical rule, claims that the following is a general rule for the quantitative relation of response and stimulus. Given a standard dose of stimulus and a standard period of measurement the response, that is, the change from the initial (pre-stimulus) level, will tend to be smaller when the initial value (IV) is higher; this applies to function-raising stimuli. For function-depressing or function-inhibiting stimuli this negative correlation becomes positive. Furthermore, beyond a certain medium range of IV’s there is an increasing tendency sometimes toward absent and frequently toward reversed (paradoxic) responses; the higher these extreme IV’s the more frequent are the reversals on function-raising stimuli; the lower the IV’s the more frequent are the reversals on function-depressing stimuli. In FIGURE 1 the abscissas show ranges of IV’s of blood pressure or pulse increasing from left to right; the ordinates show changes from these IV’s as mean rise or fall for the group above or below zero. The stimuli used for each of the graphs were various autonomic drugs. We see that beyond certain ranges of IV’s the mean direction of the reaction reverses itself, in other words drop instead of rise and the reverse. The abscissas still indicate the increasing ranges of pulse and blood pressure after the smoking of a cigarette. The ordinates, however, indicate the mean percentage of paradoxic reactions in each group, that is, drop instead of rise. This is shown by the white columns. With rising IV’s the paradoxic reactions reach 80 per cent for the blood pressure and 60 per cent for the pulse rate. The black columns indicate the deviations from this pattern in a series of patients oversensitive to nicotine. There is hardly a branch of medicine today in which the LIV has not been amply confirmed, but it is still being ignored by the majority of workers and textbooks. To my knowledge, the law is little considered in biological sciences other than medicine. This is unfortunate, for if you accept the LIV as valid (and no serious doubts beyond some technical-statistical controversies have been published), this implies that innumerable evaluations of experimental results are fallacious and also that interesting results are being discarded because their regularities can be seen only by considering the LIV. Of course, the rare lucky worker whose experiments all start with identical IV’s has no problems. Basimetry workers are still seeking the solution of many problems arising FIGURE 2 shows something different.

THE LAW OF INITIAL VALUE

This chapter discusses the history of the law of initial value (LIV), the theory of vagotonia (eppingerandhess), general considerations regarding LIV, Weber–Fechners law and the LIV, paradoxic and absent reaction, the theories of the law of initial value, and the Pavlovian theory. The LIV refers exclusively to the response of the organism to one and the same dose of one and the same stimulus. A different stimulus and different doses may have different effects qualitatively and quantitatively. The LIV deals with one principle of self-maintenance as observed in living organisms. The LIV deals with responses. A response is a change from the pre-experimental condition. The law does not deal with the condition of the organism following the change. It refers to the process or rather progress of change itself. The LIV includes the claim that initial value (IV) is a very important factor in determining the outcome of an organismic reaction. It does not claim that the IV is the only determining factor. Other factors enter into play too, some known, some remaining unknown.

PHARMACOLOGY AND THERAPY

This chapter discusses the applications of law of initial value (L.I.V.) in pharmacology and therapy. LIV reminds that all the functions of the organism are fluctuating in various degrees. LIV shows that these fluctuations differ in various individuals and under various conditions. It teaches that the momentary level of every function affected by a certain stimulus determines to a very high degree the extent, duration, speed, latency, and even the direction of response; the latter is of greatest practical importance. It highlights that at every single moment, the various functions of the organism are at various levels and directions of activity and will be differently affected by the same stimulus. LIV shows that most responses to stimuli are biphasic or multiphasic, implying overshooting in the opposite direction. It also shows that often the IV determines the degree and direction of response stronger than the dose will and even more than the kind of stimulus applied. The above refers to both function-raising as well as function-depressing stimuli of any kind: chemical, physical, or psychic. The ideal therapy, therefore, must not only consider the somatic constitution, the psychic personality, and the environmental condition of the patient in general. It must pay the greatest attention to the momentary state of the patient at the very moment of the application of treatment.

DOES THE L.I.V. HAVE A SOCIAL SIGNIFICANCE

This chapter discusses the social significance of LIV. One should first distinguish between natural groups (family, tribe) for which one can claim that, like the organism, they seem to present to the scientist no other unifying principle as that of the maintenance of boundaries of survival. Natural groups, like a family or a tribe, may even be considered as an enlargement of parental boundaries; one would expect them to be more subject to the LIV. Artificial groups, like clubs, business enterprises, charitable organizations, unions, etc., cannot be viewed in such a simple way. Some of them lend more power to the individual in exchange for surrendering some of his/her power. Others have a goal serving not the survival of the individual but the survival of a much larger group, like a nation, the future generations, and the human race.

NEUROLOGY AND PSYCHIATRY

This chapter discusses the application of law of initial value (LIV) in neurology and psychiatry. The central nervous system has been approached with the use of the LIV in a number of other ways. Based on the experiments with the effect of the stimulation of the vestibular apparatus on the autonomic system, Puettmann tested the response of blood-pressure, leucocytes, blood-sugar, resistance of erythrocytes, and serum proteins to vestibular stimuli. While in normal individuals, a rise in blood-pressure was always accompanied by a rise in the number of leucocytes and a left-shift, in brain tumours, the leucocytes always dropped and there was no regular left-shift. Dependent on the IV, there is in brain tumor a change, either quantitative or qualitative in character. These changes do not progress parallel with the growth of the tumor, but there is always a reversal after an operation. Certain disturbances in autonomic function can, thus, be evidenced objectively by means of vestibular stimuli. A mere cold nose douche produces smaller changes.

PHYSICAL STIMULI: PHYSIOTHERAPY, RADIOTHERAPY

The law of initial value (LIV) applies to the stimuli of any kind: chemical, psychic, as well as physical. This chapter presents a series of examples of the application of LIV to physical stimuli. It also describes some of the practical and therapeutic aspects of LIV by using the field of physiotherapy for that purpose. The stimuli used in physiotherapy are mostly thermic and to a lesser extent mechanical and electric. Radiology has confirmed the LIV particularly in those responses of the organism that are not too difficult to measure. Langeri found that over-excited sympathetic nerves can be brought back to norm by small X-ray doses that do not affect healthy nerves. Glauner in his studies on the course of the X-ray erythema noted corroborating evidence in the blood-sugar and leucocytes. Vieten devoted a number of experimental articles to the subject of the LIV in functional X-ray therapy. He could confirm it for the response of eosinophils, lymphocytes, sugar, K, and Ca.

CHAPTER II – PHYSIOLOGY

Publisher Summary This chapter discusses the physiological data regarding the law of initial value (LIV), which originated from the study of the autonomic nervous system. The deficiency of the concept of the sympathetic-parasympathetic nerves as the exclusive basis of the LIV is clearly demonstrated on the organs wthat have only sympathetic innervation like the nictitating membrane, pilo-motor muscles, and sweat-glands. The LIV applies not only to the stimulation of the peripheral autonomic nerves but also to the autonomic centers in the diencephalon. W. R. Hess proved that the localization of functions in that area is not sharp and it was always wondered whether it would become sharper if the IVs of the functions studied are taken into account. Still less sharp is the demarcation of ergotropic and trophotropic areas in the brain cortex. A special source of information on the role of the LIV in the protein metabolism is studies dealing with the specific-dynamic effect of a protein meal on basal metabolism.

CHAPTER VII – BIOLOGY

Publisher Summary This chapter discusses the applications law of initial value (LIV) in biology. LIV also applies to unicellular organisms and to multicellular without nervous systems, just as well as to higher organisms. There are facts in biology that are compatible with paradoxic reactions: a substance can flow towards the region of higher concentration, cell proteins can buffer acid as well as alkaline solutions towards neutrality; various rhythms in plants and animals contain the reversals of many functions. With increased excitability, according to Selbach, dissimilatory substances may exert an assimilatory effect because the tendency to reversal is stronger; assimilatory substances increase excitability still more. Selbach thinks that plants, too, work according to Wilders Law and quotes Buennings experiments showing that with middle doses of light, the response depends on their endogenous 24-hour rhythm and may become paradoxic. He also quotes Spiegels theory that denervation frees the cell from dissimilatory impulses, leads to relative increase in assimilation, storing of reserve substances, and, thus, stronger responses to stimuli. Rhythms, which are mostly based on the LIV, can be observed in cultures of cells, like glia cells, and even on fragments of cells, like parts of infusoria without nucleus, or pulsating vacuole of sectioned amoeba. Besides rhythms, there is another indication that the LIV may also apply to unicellular organisms, that is, the validity of the Arndt–Schultz Law.

Bemerkungen zum Wilderschen Ausgangswertgesetz

9,3 10,0 I0,0 9,8 9,8 9.8 20,4 19,1 20,2 arbeite~ bei einiger Ubung mindestens mi t derselben Pr/~zision yon -j: 4 5 % Fehlerbreite, in der Hand einer routinierten Laborant in sogar meist noeh etwas genauer. Fiir die Eichkurven sollt~en immer frische L6sungen Verwendung linden. Tabelle 2 zeigt die Indifferenz der mitbeteiligten The rapen t i ca und PAS-Metaboliten, sowie deren EinfluB auf die Erfassung freier PAS bei gleichzeitiger Anwesenheit im Serum. Wir sehen, dab N-Acetyl-PAS, Rimifon und Streptomycin, wie Serum selbst, im MeBbcreieh yon 630 m# keine Extinkt ion anfweisen; sie stSren die Reaktion mit PAS nicht, wenn man yon einer geringffigigen (systematischen) ErhShung tier MeBwerte absieht. Aueh unter diesen Bedingungen lggt sich PAS mit einer Genauigkeit yon etwa 5% wiederfinden, indem man dieser ErhShnng (etwa 0,4 rag-%) gechnung tr~gt.