Joseph Engelberg

Rationale for a Universal Genetic Code

A mutation in the genetic code would place new amino acids in certain loci and entirely eliminate amino acids from other loci of practically all proteins in an organism. It is reasonable to postulate that mutations of this kind cannot supplant the original code. The genetic code, once established, would therefore remain invariant.

On deterministic origins of mitotic variability

Abstract A significant part of the variability of the duration of the mitotic cycle may arise simply from the fact that the cell cycle is the product of the interaction of a large number of regulated subcellular systems which are loosely coupled to one another. It is suggested that mitotic variability would be a feature of the mitotic cycle even if non-deterministic (probabilistic) factors (e.g. critical processes in the cell cycle resulting from the action of a small number of molecules) played no role in the cycle.

Determination of the cell doubling-time distribution from culture growth-rate data

Abstract The fundamental integral equation governing the growth of a cell culture is solved for the cell doubling-time distribution with the use of Laplace transform methods. Both analytic and numerical solutions are discussed. The statistical moments of the doubling-time distribution are obtained without inverting the Laplace transform of the distribution. A very simple equation makes it possible to calculate the standard deviation of the doubling-time distribution from the decay of synchronization of a synchronized cell culture.

Decay of cell synchronization: solutions of the cell-growth equation.

Growth-rate functions in analytic form have been obtained for cell cultures in which the doubling times follow the Gaussian and Poisson distributions. The growth-rate functions are calculated by using Laplace transforms to solve an integral equation previously presented. Oscillatory solutions result if a substantial fraction of the cells in a culture are synchronized to divide at some particular time. The synchrony and, hence, the oscillatory character of the growth-rate function eventually disappear because of the non-zero variance of the doubling-time distribution. If their variances are sufficiently small, the Gaussian and Poisson doubling-time distributions lead to growth-rate functions that become identical in the limit of large time.

An analog of cell-culture growth

Abstract A formal analogy is drawn between the growth of a cell culture and the amplification process in a regenerative feedback amplifier. Quantitative comparisons between these two systems are given. A relatively simple analog computer is described with which it is possible to study relationships among the growth-rate, initial-state, and doubling-time-distribution functions of the cell culture. The doubling-time distribution function is represented by the impulse response of a filter. The statistical moments of the impulse response can be used in the synthesis of the filter.

Tracheal-vascular and vascular-pleural electrical potentials in the rat lung

Abstract The trachea, pulmonary artery, and left atrium were cannulated, and the isolated lungs floated, trachea oriented downward, on a layer of paraffin oil in an incubated chamber at 37 °C. With the trachea partially filled with fluid to establish electrical continuity, the electrical potential of the tracheal fluid, and of the pleural surface were measured with respect to the fluid in the vascular bed. With phosphate-buffered Ringer solution in the trachea, in the vascular bed and on the pleural surface, the tracheal vascular potential, and the vascular-pleural potential, were found to be on the order of — 12 and — 5 mV, respectively. These potentials were greatly reduced or abolished by low temperature, lack of oxygen, cyanide, and ouabain, suggesting that they were generated by an energy-dependent transport of ions. When isotonic sodium chloride solution was used in place of Ringer solution, potentials similar to the above were obtained. However, when choline was substituted for sodium, or sulfate was substituted for chloride, the vascular-pleural potential was abolished. This suggests that both sodium and chloride ion are necessary for the genesis of the vascular-pleural potential. In the intact rat the tracheal-vascular potential (measured between the inside of the trachea and the blood in the carotid artery) was on the order of — 7 mV; with the chest open the vascular-pleural potential (measured between the blood in the carotid artery and the pleural surface of the lungs) was on the order of -4mV.

The academic medical center of the future: a center for integrative study.

The integrative sciences, which are of great practical and conceptual interest, investigate complex systems (cells, multicellular organisms, families, institutions, communities, nations, etc.) at the higher levels of organization. Academic medical centers are intrinsically integrative because of their mission and thus are likely places for integrative study to flourish. They also possess vast resources of the kind needed to implement integrative studies. They can thus begin to address, from a scholarly point of view, a variety of integrative issues: how myriad parts (molecules, cells, organisms) form stable, complex, living wholes; the dynamics of health, illness, healing, dying, and death; problems of integration relating to patient care, health care delivery systems, and medical education. If academic medical centers undertake this mission they can be springboards for scholarly advances that will potentially affect all areas of thought. The authors describe how an integrative studies program can be started, and share the experiences of the University of Kentuckys Office of Integrative Studies.

Integrative study in physiology and medicine: obstacles on the road to integration.

A recent report of the Long-Range Planning Committee of the American Physiological Society identifies physiology with “integrative biology” and urges that physiologists make their field “a unique branch of biology that deals with synthesis and integration.” However, certain institutional, procedural, and psychological obstacles lie in the way of those who would embark upon this task. The hurdles to be overcome include the following: the erroneous belief that biomedical scientists are already integrative; the inapplicability of the powerful methods of areas of specialization to integrative study; the fear of failure; the identification of integrative biology with the study of function; the disregard of hierarchy; the undervaluation of the abstract; and the loss of a sense of mystery. These obstacles, though insidious, pervasive, and powerful, can be surmounted.

On the dynamics of dying

This study is concerned with dynamic processes that underly the rapid, degenerative changes associated with the “dying” stage of the multicellular organisms life cycle. The interaction between negative and positive feedback cycles is discussed: negative feedback cycles underly the superstability characteristic of health and illness. When negative feedback cycles fade in the dying phase of life, positive feedback cycles, previously held in check by the negative feedback cycles to which they had been coupled, rise explosively, driving physiologic variables from their normal values towards extremes. This results in the rapid downturn that we associate with dying—an accelerating disintegration terminating in death. A medical case history is analyzed.

One child, two homes, two cultures.

At the University of Kentucky Albert B. Chandler Medical Center, Integrative Clinicopathological Conferences are held regularly to explore various dimensions—economic, psychosocial, ethical, preventive, and medical—of health care. They are organized by Dr. Engelberg, Professor of Physiology and Biophysics, who moderated this conference. The conference format included a dialogue between Drs. Cottrill and Engelberg, followed by comments and questions from the audience.