Today, we shall talk about theory of causality in pathology. And they would like to mention and discuss most fruitful doctrines in medical determinism. There are three of them: monocausalism, conditionalism and constitutionalism. And it is not just matter of medical history because all three doctrines impacted medicine profoundly and modern synthetic theory of causality in pathology stands on their achievements, you may blame the scholars of previous centuries for they did not understand something which is now obvious. But they're giants, and we are standing on the shoulders of the giants. So step by step, we will go through their achievements and how their ideas finally combined into modern understanding of the causality in medicine, although initially, these schools sharply confronted and conflicted with each other. The story starts with that person. This is Leucippus from Abadera, ancient Greek philosopher who coined the idea of determinism in world science. He said, "Nothing occurs in vain, for everything there is an appropriate basis." And it was first ever coined strict deterministic idea. Some of those who inherited this idea were medical doctors and the earliest of them, Hippocrates. And you can find in Hippocrates books, "All diseases have their reasons, no disease without a cause," which is earliest known formulation of medical determiners. Now, let me jump across 10 centuries, and a person which you can see in this portrait is Abu Ali Ibn Sina, medieval Tajik and Persian physician, who developed first detailed concept of general etiology. And, surprisingly, his concept, although it was proclaimed in 11th century, is very close to modern synthetic views. Abu Ali Ibn Sina or Avicenna, as they call him in western countries, he thought, "Not every cause reaching the body, can render its action on the body." So he understood that you may have causal factor or disease, but it does not mean that you will obligatory have disease. You probably will need something else, and causality in medicine is complex. And Avicenna, in his Canon of Medical Science dated back to 1020 Anno Domini, he revealed three different kinds of the causes of disease: external causes, preexisting causes and linking causes. External reasons of disease, in fact, it is very close analog of modern causative factors. It is something external, which acts on the body from outside the body, like microbes or high temperature or low temperature or something else. But these particular external causation is not sufficient to establish the development of disease because there are also exists so-called preexisting cause. Preexisting cause in Avicenna's writings is something which is analogous to modern conditions of disease. That is a factor which is not able to elicit disease itself but may increase its probability or decrease it, condition of disease or preexisting cause according Avicenna. And the third category, linking cause, linking cause is internal. Avicenna was the first who systematically mentioned internal causes of diseases in combination with external ones. So a linking cause in his understanding is something related to body properties or body peculiarities. It is very close to our current understanding of somatotype or reactivity, individually activity of the organism. So you can appreciate that for 10th century, it was very advanced approach. And according Avicenna, for the start of a disease, a coincidence of all three types of causes is necessary. Interaction of all three types of reasons at the same time or consequently. And Avicenna's ideas, as it often occurs in the history of medicine, were abandoned. And for many centuries, medicine return to very simplified causality. If there is external factor, there is disease. If there is no external factor, there is no disease. 900 years elapsed, and the doctrine of monocausalism have come into power. It was in 19th century and, of course, it was inspired by the achievements in microbiology when new germs were discovered responsible for certain concrete diseases, which previously looked absolutely enigmatic. You can see here the historical father of monocausalism, Friedrich Gustav Jakob Henle and his famous principle, "contagium vivum et animatum" concept of 1840. Monocausalism was a fruit of bacteriological era, and its main principles are the following: one disease always has one cause; the same reasons always provoke the same diseases. There are no poly-etiological diseases. This term poly-etiological is not recognized in classical Orthodox monocausalism. In monocauslism, the term cause and the term causative factor are absolutely synonymous because monocausalism always interprets the cause of disease as something external in nature from outside the body. The category of bodily activity is not analyzed in Orthodox monocausalism at least in context of etiology. According to classical Orthodox monocausalism, cause is equal to action. It is not only mandatory for concrete disease but also sufficient enough to trigger concrete case of appropriate disease. Conditions of disease are also recognized, but they are essential only as far as they can influence causative agent and alter the body contact with causative agent. For example, as soon as micro-bacteria is causative agent of tuberculosis, we can discuss conditions, but as regards to the influence of micro-bacteria pathogenicity or the conditions of contact between body and germ, I shouldn't say that this concept was limited. It was very useful for medicine, and it achieved very great results. Great heritage in medicine was inherited from monocausalism. The closest disciple of Henle, Robert Koch, he brought to life the idea of hestiture. He discovered the causes of tuberculosis, cholera, anthrax and he co-authored following postulates, so-called Koch Henle postulates, a cradle of monocausalism. First postulate, the microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms. Second postulate, the microorganism must be isolated from a diseased organism and grown in pure culture. Third postulate, the cultured microorganism should cause disease when introduced into a healthy organism. And finally, microorganism must be re-isolated from the inoculated experimental host and identified as being identical to the original specific causative agent. And on the basis of these four mono-causal postulates, scholars discovered the causative agents of very many bacterial, viral, and fungi infectious diseases as well as protozoa ones. What Goods brought monocausalism into treasury of the general pathology? Its main achievement is affirmation of preferential role of causative agent as a main, decisive condition for the development of concrete case of some disease. Causa est [inaudible] nomia, without causative agent, you can not have the case of this particular disease. For every concrete case of a given disease, causative agent is most important. The next good inherited from monocausalism and we 100 percent agree with that until now. The concrete course is necessary for the concrete case of an illness. That is correct. But you know for different cases of the same disease, for different examples of the same diagnosis in different individuals, is it also true? Modern medicine believes that it may be not sufficient for every particular case of disease in various individuals. So, according to classical monocausalism, causative agent is required for disease. But now, we believe that it is required, but not sufficient. The next very good heritage brought by monacausalism, the same agent may cause the same sequels. That's why the same causes regularly elicit the same diseases, but provided if the conditions and if individual reactivity is similar. For example, there is causative agent, Epstein-Barr virus, EBV. And it is causative agent for acute mononucleosis, acute infectious disorder. But you know, the millions and millions of people carry this virus in the body. You can locate the norm of this virus in their cells but they never suffered acute mononucleosis. So, we have causative agent, but we have no disease. It is called carriage. They carry the virus but do not suffer from disease. And even more you know, Epstein-Barr virus is causative agent not only for acute mononucleosis, it is associated with the ideology of Burkitt's lymphoma, which is malignant oncologic plasma. It is associated also to some cases of nasopharyngeal cancer. And these facts cannot be embedded into monocausal doctrine because in this case, we have one causative agent, EBV, but three different diseases, Burkitt's lymphoma, nasopharyngeal cancer, acute mononucleosis and moreover, we have millions and millions of people who has the virus but never suffered from these diseases. So probably, this needs more profound explanations. Anyway, the great merit of monocausalism is aetiotropic principle of disease treatment and disease prevention. This is still important although in many cases, aetitropic treatment is not possible. But we inherited that approach from monocausalism. And in conclusion, I would like to show you the first Russian monocausalist, Veniamin O. Portugalov, Russian rural doctor of middle 19 century who said, real cause of a disease must be always constant and definite, that means, single. Orthodox Monacausalism is singular theory of causality in medicine. One reason, one disease, always the same. Now, few words about crash and revenge of monocausalism. You know, anti-monocausalist seemingly almost crushed this doctrine in the beginning of 20 century by bright examples of principle absence and impossibility ever discovered the concrete germs or microbes causing a lot of important non-infectious somatic diseases. They asked, can you show us a microbe which causes myocardial infarction, obesity, psychic disorders? Can you show me a virus which causes alzheimer's disease or for example, sugar diabetes? Oh, you cannot. It means monacausalism is crushed. But you know, in the last quarter of 20 century, several discoveries were made which probably could witness about some revenge or revival of monocausalistic approach. Although to that moment, for a major part of pathologists, monocausalism looked like archaic doctrine. What do I mean? I mean, the autoimmune disorders. In the end of last century, it turned out that many non-contagious somatic diseases illicit due to autoimmune response provoked against certain self tissues by some concrete exogenous pathogens microbes. And you know, not all people respond with autoimmune complications but only those who have genetic predisposition. And genetic predisposition in these individuals is related to so-called major histocompatibility complex of the proteins controlling the strength and repertoire of immune responses. Simply speaking, there are some people whose immune system poorly distinguishes between self and alien targets. And it is all related with haplotype of HLA system or major histocompatibility antigens. So in fact, in part of population immune system is short-sighted. It poorly distinguishes between self and alien targets, and it is related to the genetically determined specific of HLA proteins inherited from father and mother. Because these proteins construct their receptors of immune system. They determine the strength and repertoire of lymphocyte response. And although generally, certain microbe does not provoke these somatic disease in some individuals with some specific of HLA system. It may provoke secondary autoimmune criss-cross reaction which involves certain organs and as a result, person has somatic non-contagious disease. Good example is a enterovirus, Coxsackie type and the sugar diabetes type 1. This virus can provoke sugar diabetes, but it doesn't mean that this virus will provoke it in all individuals. Only in those who has a genetic predisposition and certain specific of HLA haplotype. So, we can say that there is some rational element even in monocausal approach to etiology.
