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by Yevgeny ROTSHILD, Dr. Sc. (Biol.), RAS Institute of Problems of Ecology and Evolution (named after A. Severtsov)

Much has been said and written over the past few years about the role of man-made changes of the environment in provoking large-scale epidemics among people and animals. But apart from general declarations, the problem, unfortunately, remains unresolved. We really do not know yet which are the main specific factors under suspicion, when and why can they come into play and, last but not least, what methods can and should be used for investigations in this field?

Articles in this rubric reflect the opinion of the author. - Ed.

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Speaking of ourselves, we began tackling this problem, so to say, in the late 1970s. By way of a hypothesis we "put under suspicion" the menu of chemical elements present in the biosphere. It was common knowledge even then that microelements, above all some metals, produce an appreciable impact on what we call the vital activities at any level. Their shortages, or excesses are the causes of various ailments resulting from upsets in metabolism of both animals and humans. Links of this kind have become the object of a whole scientific discipline, called geochemical ecology. But, in line with the traditional approach, infectious diseases were not considered from this angle, so to speak, because according to the opinion their outbreaks are caused not so much by factors of the environment as by social, or "domestic" factors due to which the causal agents are transmitted from the infected individuals to healthy ones (direct contact, drinking water, bloodsucking insects, etc.)

On the other hand, medical experts also paid enough attention to such factor as the role of metals in provoking infectious diseases. But such studies, as a rule, were limited either to the conditions for the artificial cultivation of microbes, or to the microorganisms typical of humus and laboratory animals. Prevailing in such investigations were assumptions that these or those elements can somehow influence the course of an infectious disease which was already in progress. And the problem of the chemical composition of the environment as a factor promoting the outbreak of a disease was not event put on the agenda. That being so, when we started studying chemical elements in the foci of plague epidemics among wild animals we found ourselves as if on no man's land.

Meanwhile diseases among settled animals, like gophers or mice, offer a very convenient model in wild nature for studies of the general regularities of the appearance and development of infections. How, for example, can we trace the dependence between the onset of a disease and the composition of animals' rations? Working in the field, for example, one can trace the burrows, or holes in which the contaminated animals dwelled and the areas of their habitat. One obvious fact in such cases is that all of them consumed one and the same grass which grows only in that place. So the most simple solution of the problem would be to collect this fodder, study the list of its components and then compare the findings with data from a test site where the same wild animals dwell and stay healthy.

The very first experiments we conducted in 1979-1981 in a semi- desert zone of the Pricaspian (near Caspian) region provided answers to the main questions which we had put before ourselves. At the same time outbreaks of plague were recorded, which affected gophers in several small areas with clayey soils, and in sandy areas an intense outbreak of the same infection struck two varieties of sanderlings. In both cases the infection appeared after a reliably traced interval of many years.

Using what we call sufficiently plentiful material (50-60 samples), we demonstrated that metals concentrations in vegetation on the territory of the plague epizootic was substantially different from the control - we traced several times smaller amounts of copper, zink and molybdenum and there were respectively higher levels of cobalt and manganese. And that means that plague infection of animals linked with an unusual contents of chemical elements in objects of the natural environment is something quite real. And we also noted that the anomalous state of the latter factor matches not only the presence of an infection, but its very appearance, or to be more exact, a massive outbreak of plague in places were animals had been quite healthy only a few months before.

On the example of infection of two varieties of these rodents in the Pricaspian region, and later in a similar experiment with Ochotona pallasi in the Gomy Altai, we identified certain regularities in this kind of dependence. First of all we traced a link of the disease with a sharp change in the concentrations of chemical elements within a short span of time. In both cases information was obtained about the levels of chemical elements in the animals' food not only during a plague epizootic, but several months or weeks before the outbreak. It turned out that the outbreak occurred in places where some time before the levels of copper and zink in the animals' food had been reduced by 5 to 6 times. In such places the outbreak started earlier and progressed more intensively in proportion with the aforesaid shortage of the indicated metals. And in Ochotona pallasi infections prevailed on stretches of valleys of mountain springs where there had been sharp drops in the levels of copper and vanadium shortly before the outbreak and also low levels of nickel.

It was also established at the same time that the elementary composition of the environment is having an effect not only upon the sick, but also on healthy animals. In the above experiments several relatively small areas were selected where over a period of many years (16 and 11 years) there had been practically no cases of plague among the wildlife. At the same time on some neighboring patches, only a few kilometers or even hundreds of meters away, we observed over many years (up to 6-9 years of observations) infected animals and arthropoda. These places are associated with some peculiarities in the composition of metals in the natural environment. In green plants growing in areas with plague infections there was a deficit of iron and cobalt and also relatively stable amounts of copper, nickel and vanadium at high and medium levels.

Later on we tried to find out how widespread in nature is the observed dependence. It was important to find answers to the questions of what territories this appears on - everywhere or locally? Does this concern all sick animals or just some species? Does this situation apply to different infections or only to plague? In looking for the answers to these questions we carried out observations in several spots on a vast territory - from the Pricaspian to the Russian Far East. In the desert zone of Kazakhstan and Uzbekistan, and also in the mountain steppes and forest-steppe of Siberia and Mongolia, we studied the areas of plague propagation affecting various rodents (Apodemus, Microtus) -long-tailed gophers, Mongolian marmots and places of murrain (cattle plague) from pasteurellosis of steppe antelopes - Mongolian dzerens. In the south of the Primorsky territory we collected fodder plants in the foci of tick-bome encephalitis and hemorrhagic fever among smaller rodents.

All in all, we staged from 1979 to 1989 a total of ten experiments, and studied samples of green plants from

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186 spots. These studies yielded results which were quite in keeping with the earlier hypothesis: in all places where sick animals were found the concentrations of at least one or two metals in green plant were below, or above the norm by no less that 2 to 3 times. Thus it turns out that the connection of infections with upsets in the elementary composition of the environment is a very common regularity And this concerns not only plague, but also other diseases of bacterial and viral nature.

We obtained some additional data of the same kind from experiments in which we used other methods - traditional for medico-geographical studies. On the example of the Voronezh Region (Russia's chemozem center) we compared data on the accumulation of metals in soil and various materials and the spread of bacterial and viral infections among people and animals. With this aim in view we divided the whole territory into 58 squares and in each of them we took soil samples and analyzed the contents of various metals in them. Finally, using archive materials, we calculated the number of cases of illnesses of people and animals as registered within each square over 16 years. As a result we traced an authentic correlation between metals concentrations in soil and the spread of a whole group of infections, including anthrax and rabies in animals and also leptospirosis and Q-fever in people.

The aforesaid convinces us that there is a direct link between diseases and the dynamics of chemical elements composition in the natural environment. However, according to scientific methodology, this fact gives no grounds for drawing a conclusion as to what factors here are of decisive importance. And in order to identify the dynamics of the chemical composition of the environment as the direct cause of the appearance of infections one has to put this assumption to an experimental test, reproducing some of the typical phenomena which accompany various infections of wild animals in nature.

And we have been able to build an appropriate model in laboratory conditions. Rodents caught in the wild were given food containing salts of several metals over a period of 2 to 4 weeks. Then this procedure was stopped and the animals were infested with plague after an interval. In several of those experiments animals which had been given salts of iron and copper turned out to be sufficiently protected from infection (out of 49 test animals only two died). And in the control group of rodents which received food without additives, and also among sanderlings which received salts of cobalt and nickel, the death rate was 70 percent. In our view this experiment convincingly demonstrates the causal dependence between the chemical composition of the environment and the dynamics of infections of wild life.

Pages. 77

Our observations in nature and laboratory experiments make it possible to characterize to some extent the links of infections with nine metals which follow one another in the Mendeleyev Table. They are titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper and zink. These metals can be split up into three groups by their degree of influence on the appearance of bacterial infections among wild animals.

The first includes zink and manganese, which have practically no effect on epizootic diseases. In our experiment the addition to fodder of zink salts also had no effect upon the gravity of plague infection.

Metals of the second group (iron, cobalt, titanium) are positively linked with infections: in areas with plague their levels in green vegetation and soil were much higher than in the control. At the same time, in the conditions of an acute deficit of iron in green fodder, and with a sharp decline in the level of cobalt, no infections were observed. And the presence of titanium in soil authentically attested to the cause of the spread of anthrax.

Elements of the third group include copper, nickel and vanadium. Abrupt and profound drops in their levels in soil precede the advent of ailments. Especially typical are cases when an obvious excess of these metals is reversed to their sharp deficit within a short period of time. But in any case they are the most probable agents which provoke the outbreaks of infections. The pride of place among them belongs to copper and nickel and it could be that chromium also belongs to the above group.

As for viral infections, their dependence on certain chemical elements is of an inverse order, so to say. For example, in places with concentrations of vanadium we observed propagation of tick- bome encephalitis, and for rabbis we established an authentic negative connection with the accumulation of titanium in soils. Nickel alone has

proved to be what we call a "universal" causal agent of ailments. Its deficit in the natural environment was accompanied, with obvious consistency, by the appearance among wild animals of both bacterial and viral infections.

Now, let us take a look at what we call the universal ability of metals to have a direct influence on infections. On the strength of well-known and new facts, and on the example of iron, let us try and paint a general picture of relations between warm-blooded animals, microbes and factors of the environment.

As demonstrated by numerous studies, there begins a kind of stiff competition between an organism and the pathogenic bacteria contaminating it for the utilization of this metal, which is of vital importance for bacteria. A living organism synthesizes a complex of proteins, binding the ions of iron, after which the latter become inaccessible for microbes. In their turn the parasites take almost the same counter-measures, because they can propagate

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successfully if the host organism has enough of free, and unbound with proteins, ions of the given metal.

In a word, everything seems to be clear: the more there is food, the better it is for microbes, and the more there are microbes the worst it is for the host. On the other hand - why should a parasite kill the host? Why has the evolution of pathogens of such lethal diseases as plague proceeded along the road of choosing adaptations hardly conducive to their survival? But let us put aside these questions unanswered for a while and turn to an alternative variant.

According to our observations, the aforesaid system of relations between the parasite and the host takes place only when an infection has already started. As for the decisive moment of its outbreak, this is proceeded by some very different circumstances. After some time, in the conditions of excessive levels of some metals, wild animals suddenly feel a shortage of a habitual food component. And the disease begins in this transitional crisis situation when the stable supply of the necessary resources is interrupted.

And it would be only natural to ask: and where do pathogens come from in this case? It has been known for quite some time that many microorganisms affecting people and animals can exist in various forms in the environment - in soil, natural bodies of water and green plants. For example, the plague pathogen "dwells" in the substratum of burrows of rodents, "coexisting" with soil bacteria and the Protozoa (sapronoses). And there is also another possibility It is no secret that many pathogenic microorganisms of different systematic groups can "indwell" for a long time in the body of a host without betraying their presence in any way (this condition is known as persistence).

Also of interest is yet another question: if changes in the chemical composition of the environment can cause diseases, then the reaction of what organisms produces a decisive impact on the process? According to a common assumption of decisive importance is the weakening of the immunity, or of the body resistance. But observations of what we call natural models of infections do not bear out this view. The outcome of a disease - favorable or lethal - depends on the sensitivity of particular animals to pathogens. And as for the very fact of the outbreak of a disease, the situation is quite different. In wild nature epizootic diseases break out at one and the same time among the highly sensitive and also relatively resistant species. And it remains for us to assume that the crucial factor here is the response of the microbes themselves in which their inherited pathogenic "ambitions" increase due to changes in the environment.

An assumption of this kind contradicts in no way to the already established facts. We do know already that because of the changing conditions of

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cultivation and different states of the environment, bacteria can increase their virulence, that is the ability to kill their warm-blooded hosts. Way, a microbe of pseudo-tuberculosis, a common dweller in soil and vegetative organics, becomes more "aggressive" under the influence of cold. And in the strains of plague pathogenes and certain other microbes with weakened virulence the introduction of iron ions into the organism of test animals serves to restore their pathogenic potential.

In other words, we again come across the familiar rule according to which sufficiently high contents in the organism of chemical elements, which are of vital importance for bacteria or viruses, is one of the decisive conditions for the development of an infection. But, as shown by our own observations, such links look really much more complex than those suggested above and outbreaks of diseases obey different laws. As has already been pointed out, we come across a strong dependence of such events upon a deficit of relatively rare metals, including those toxic for the vital functions of an organism.

This conclusion, seemingly unexpected, is in full agreement with the known biological laws. It is no secret that accumulations of rare chemical elements in natural objects are subject to greater variations than of the "common" elements. And organisms, including bacteria, can adapt themselves to high concentrations of even toxic elements. And with time this becomes a norm for these given populations. And they react to any reductions as to a threat of "mineral starvation". The mechanisms of preservation of their homeostasis will be directed at increased capture of the element "in the short supply". Aggressive "aspirations" of pathogenes are traditionally viewed as normal, habitual manifestations of their vital processes. And in the aforesaid conditions this behavior on their part looks like a protective reflex, a response to a warning signal of coming mineral starvation. And this is an emergency measure, used in exceptional cases and under a threat of extinction, as a means for suppressing competition for survival in microbial communities. And that accounts for its excessive and wasteful nature. Figuratively speaking, an infection can be described as a hunger riot of microbes.

And what is important is not whether this metaphor really rings the bell, but the message it contains. And if we accept the pathogenic properties of microorganisms as adaptation, used only in exceptional circumstances, it becomes easier to understand and explain many strange peculiarities in the course of infections, such as intervals of many years between massive epidemics among people and animals and the appearance of numbers of hitherto unknown diseases.

Опубликовано 14 сентября 2018 года

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