20 DECEMBER 1930, Page 7

Science : Yesterday and To-day _

[The following is the sixth of a series, not mainly intended to convey knowledge of particular conclusions that are being reached in various sciences—this will only be incidental—but rather to give some conception of the new modes of thought and changes of method. that are being developed with the extension of scientific knowledge, in a manner which is comprehensible and interesting to the lay reader.

Pathology

BY PROFESSOR G. S. WILSON,

of the London School of Hygiene and Tropical Medicine. pathologist at that time was in the relatively gross changes met with in the post-mortem room. Schwann's generalization in MN, that the fundamental unit of tissue structure is the cell, gave the impetus to the investigation of a new field, and formed the starting point of modem pathology.

From that time on progress has been unceasing. The new science of pathological histology was developed by Rudolf Virchow, who likewise recognized the great principle of the continuity of cell life. Within thirty years the finer changes accompanying inflammation, degeneration, and tumour formation were studied with such effect that the knowledge then accumulated has been transmitted with but little modification to the present time. The underlying causes responsible for these changes, however, remained obscure, and it was not till the use of bacteriology, in the 'eighties, following the propagation of the germ theory of infectious disease, that the stimuli most commonly involved in the pro- duction of inflammation were recognized. The subse- quent development of pathology has followed along three main lines—morphological, experimental and chemical.

Morphologically, work on the microscopic anatomy of diseased tissues has been greatly aided by the intro- duetidn of staining processes that have made possible the finer differentiation of intracellular structure. By similar means a great variety of bacteria have been recognized, some leading an essentially parasitic existence in the tissues and giving rise to disease, others residing more or less harmlessly on the skin and in other parts of the body, but capable under appropriate conditions of being roused into activity. The microscope, however, though capable of rendering evident differences in shape between the bacteria, is practically valueless in deter- mining the exact nature of their intracellular content. It is owing to this that the morphological study of micro- organisms is largely at a standstill. The failure of microscopical technique is dependent on factors which are not suitable for discussion in this article ; but briefly it may be said that the ability of a lens to distinguish between two points set very closely together is deter- mined mainly by the wave-length of the light used. Mr. Barnard, working under the Medical Research Council, has of recent years been attempting with a considerable measure of success to employ light, such as ultra-violet rays, of a shorter wave-length than that of daylight. By this means he has been able to distin- guish within bacteria a degree of structure far greater than that revealed by any previous method. The utilization of this principle is clearly capable of indefinite extens:on ; and there seems to be no reason why, if certain diflicultie:$ accompanying the manufacture of suitable objectives and other optical materials can be overcome, the filtrable viruses, which have so far remained invisible, and even smaller particles, such as the protein molecules, should not be rendered visible by photography.

The experimental method of approach to pathology was devised to supplement the imperfect information yielded by pure morphology. Its value in this respect has been so great that it has come to occupy the dominant position in the investigation of disease. It would be no gross exaggeratiOn to say that it has, in some measure, been responsible for practically every important advance in the last fifty years. Its abolition would mean the virtual sterilization of medicine. The reason is clear.

Morphological examination alone reveals merely the end-result of disease ; it tells little or nothing of the factors that are primarily responsible for its production;

nor of the process by which the structural changes in the tissues are -produced. The experimental method

gives a clue to alterations in cellular function, to the reaction of different types of cells and tissues to external stimuli, and to the mechanism by which -inflammatory and degenerative changes arc brought about.

It is the misfortune of the biologist that he is compelled to work with living material. The chemist is dealing with substances of relatively fixed constitution ;, the subject matter of the biologist, on the other hand, • is endowed with the property of variability, and no examination of dead material can in any way compensate for the complexity introduced by this single property. The use of experimentation on living animals is therefore indispensable to any biological science, once it has passed the preliminary stage of morphological classifica- tion. This is no place to discuss.the subject of vivisection, but it must be made clear that animal experimentation and vivisection, in the sense in which this latter term is usually understood by the lay public, are two entirely different things. So far as pathological investigation in this country is concerned, vivisection simply .does not exist. The great majority of pathological experiments on animals consist in feeding them on different diets, and in simple inoculation and' venesection—procedures which are for. all practical purposes painless.. No experiment of any sort ma? be performed without ,a licence ; the holding of that licence is subject to stringent regulations ; and those regulations are rigidly enforced. The idea, held by many people, that the production of antitoxin to diphtheria or tetanus is rendered possible only at the expense of inflicting pain on horses is so utterly false as to appear to those who are fully acquainted with the facts as almost ridiculous. Without animal experimentation medical- bacteriology would have re- mained in the most elementary stage, the science of immunology would have been a closed book, experi- mental epidemiology would never have been born, and all hope of finally solving the problem of cancer might as well be abandoned.

The third, or chemical, method of investigation in pathology is one that has come to the front in recent years, and is one that is indissolubly bound up with the experi- mental method.

A study of the changes that occur in certain consti- tuents of the blood plasma in conditions such as diabetes, goitre, rickets, and many bone diseases has gone a long way towards revealing the underlying factors responsible for these metabolic disturbances. It has, moreover, brought to light something of the extraordinary, com- plexity involved in the maintenance of certain equilibria in the body. For example, alterations in the calcium content of the blood arc liable to be followed by marked disturbances in the nervous system and in the bones. The calcium exists in at least three chemical forms. One of these forms—the ionizable calcium—is influenced very largely by the degree of acidity of the blood, and by the amount of certain phosphorus salts present. The control of calcium metabolism appears to be mainly under the influence of certain very small ductless glands, which are situated in the neck and are known as the parathyroid glands. These are able, when the blood calcium falls, to mobilize the stored-up calcium in the bones. But it has been recently found that a rise in the blood calcium can also be brought about by the oral administration of irra- diated ergosterol, and it has been suggested that this substance, which is no other than the well-known vitamin D, may, by acting through the parathyroid glands, be the ultimate regulator of calcium metabolism.

It is chemical pathology that has produced insulin, synthesized thyroxin, opened up the whole world of defi- ciency diseases, and is now engaged, amongst other innumerable pursuits, in the study of the substances re- sponsible- for the sexual cycles in man and the lower animals. In bacteriology the chemical method promises to explain the cause of antigenic specificity, or more broadly the reason why infectious diseases breed true. Later it will probably unravel the intricate mechanism by which the bacterial toxins affect the living cell, and will pave the way to a more effective method of im- munization.

Progress in pathology is hampered in this country by the lack of suitably trained workers. The time hag come when certain problems can be attacked only by men who have had an adequate training both in pathology and in chemistry. Such men are rare. There is-an abundance of chemists who, with comparatively little training- in biology, are making praiseworthy attempts to understand the chemical basis of living matter ; but there arc very feW pathologists who have a sufficient knowledge of chemistry to attack the same problems from the opposite side. Team work is only a partial remedy,. and it is pro- bably fair to say that the English character does not lend itself well to this particular type of co-operation. More- over, the main synthesizing ideas are less likely to come from a group of men engaged in several fields than from the brairi of one man who is able to assimilate and inte- grate the knowledge gained in a number of different fields.