4. Pathogenes and development of man

The most palpable result of interaction between para­site/host populations is manifest in selection as a conse­quence of the mass death of infected hosts. The killer epidemics of the past decimated the inhabitants of vast territories to the extent of depopulation. Today infec­tious diseases continue to be in the lead as to the socioeconomic damage inflicted on humankind. Seven dis­eases (TB, AIDS/HIV, malaria, diarrheas, respiratory infections, virus hepatitis and measles) account for half of the deaths of small children and adolescents world­wide.

In the United States, for instance, the downtrend in the mortality rate had held on until the 1980s. However, it went up 58 percent in the following thirteen years due to the incidence of a "new" disease, AIDS/HIV, and "re-emerging" TB. The same uptrend has been regis­tered in Russia, too: the current growth in the death-rate began in 1991. The incidence of TB doubled in the seven subsequent years, and today it is killing twice as many people as all the other infections combined.

Dr. John Holdane, a British biologist (foreign hon­orary member of the USSR Academy of Sciences from 1942 to 1948) was the first to point at the cause-and-effect of such pathologies. He postulated in 1949 that infection as one of the basic selection pressures for evo­lution leads to genetic polymorphism in Homo sapiens. Hereby the organism inherits characters whose presence increases the survival rate or alleviates a disease. The lat­est discoveries in molecular biology demonstrate that the highest diversity is detected in genes responsible for protecting the organism against pathogenic agents. Thus, the histocompatibility system (an association of immune response genes) comprises about 2,000 allele variants.* In fact, not only interracial but also interethnic distinctions are conspicuous in the occurrence rate of particular specificities.

TB (tuberculosis) is thought to have been the main factor of genetic selection among Caucasoids (white men). The examination of remains found in burial tombs dating from the fifth to the third millennia B.C. reveals traces of bone TB-caused lesions. During the recent five centuries TB has triggered pandemics in Western Europe and North America. In the 17th and 18th centuries this disease killed 20 percent of white adults. The lethality rate continued high later on, too: over one billion people died of TB from 1850 to 1950. The TB incidence rate rose again from 1985 on after the TB causative agents had developed resistance to antibi­otics. Today every year as many as 1.9 men die of TB every year, largely due to the widespread circulation of strains with multiple drug resistance.

Another infectious disease, malaria, has played a major part in the development of man. According to some experts, blood groups antigens were formed in response to the malaria causative agents. The Negroid race was worst hit: living in the tropical belt, this race became the target of malaria-effected genetic selection. Yet specific anomalies have been identified among all races populating territories of the most violent outbreaks of the infection. Such characteristics are clearly distinct in the composition of blood. We know that oxygen takes hemoglobin to tissues from the respiratory organs, while carbon dioxide carries it from tissues to the respiratory organs (hemoglobin is part of erythrocytes, the red blood cells). But under the action of selection pressure, with malaria as agent, hereditary defects, the hemoglobinopathies, came into being-by way of protection against the disease.

People of West and Central Africa have developed a specific mutation, the absence of the Duffy factor in erythrocytes. Its carriers-and this is more than 98 percent of the population—are immuneable to one form of the disease, tertian fever (benign tertian malaria) since the protozoan Plasmodium vivax is incapable of getting into red blood cells devoid of, the above-mentioned factor. Thus far this is the only genetic anomaly caused by malaria pathogens, and its negative aftereffects have not been explained yet.

Thalassemias (Cooley's anemias) are yet another instance of mutation. This is a class of anemias caused by anomalies in genes coding for hemoglobin output. The higher incidence of this pathology in Europe has been found on the Mediterranean coast. It also occurs in Africa, in the Near and Middle East, on the Arabian Peninsula, in India, in Central and Southeast Asia, South China as well as on islands in the western Pacific all the way from the Philippines in the north to the Timor Sea in the south, and to New Guinea and Melanesia in the east. This hemoglobinopathy in homozygotes and heterozygotes alike halves the risk of malaria.

The lack of the enzyme glucoso-6-phosphate-dehy-drogenase (G6PD) was first identified as hemolysis (blood pathology characterized by the destruction of red blood cells with loss of hemoglobin) that sets in after the eating of legumes (French beans, peas and the like). This anomaly ensures 50 percent protection against the grave clinical form of tropical malaria. As shown by studies carried out at our research center, the percentage of cases afflicted with this pathology in the CIS countries (former Soviet republics) ranges from 3 percent in Moldova to 30 percent in Azerbaijan. The zone of G6PD deficiency concurs with the territory ravaged by tropical malaria in the past. The same peculiarities are shown in the other parts of the world.

Sickle-cell anemia (hemoglobin S disease or S-hemoglobinosis) is still another pathology caused by gene mutation. Today its victims survive up to the middle age (formerly, before present-day healthcare, they usually died in childhood). Hemoglobin S disease occuts throughout the African continent with the exception of southern Africa, along the southern and eastern coasts of the Mediterranean, on the Arabian and Indian Penin­sulas up to the eastern border of what is now Bangladesh. Children with hemoglobin S seldom die of tropical malaria, while those having the normal hemoglobin A perish ten times as often.

The connection between the occurrence rate of the hemoglobin S gene and the risk of the malaria infection is indirectly confirmed by comparative studies of Africa's aboriginals and Afro-Americans (Negroids) in the United States whose ancestors were brought to North America in the slave trade times. African Blacks show a much higher presence of the hemoglobin S gene. However, the occurrence of this gene among the' Afro-Americans of North America has been down, since there is no hazard of infection and selection pressure.

The above-cited examples of polymorphism are observed in populations hit hardest by malaria for cen­turies at least. As a consequence, even today 300 thou­sand to 1.5 million babies are born with bad forms of such congenital genetic anomalies. That is why the natives of northern Europe (except the Low Countries), of northern Asia, Australia, the Americas and islands of eastern Oceania, who have not been subjected to the pressure of this infection, are free from such anomalies.

Diseases to which African descendants show predispo­sition are also thought to be connected with the malaria-effected selection. For instance, Afro-Americans suc­cumb oftener to hypertension and show a higher content of iron in their organism.

In recent years the implication of polymorphism has been established in the clinical picture and characteris­tics of many infections. Likewise detected have been hereditary changes of the human genome which are responsible for resistance to AIDS/HIV or affecting the clinical symptoms of these diseases. Thus, deletion (chromosomal mutation) controlling synthesis of the chemokine receptor CCR5 (deletion designated as Δ32) is also assigned to mutations which in the homozygotic state can determine resistance to HIV infection. Among Caucasoids the mutant allele occurs at a rate of 12 to 18 percent in the heterozygotic state, and about 1 per­cent—in the homozygotic. This figure is significantly lower among other races (say, not above 2 percent for Afro-Americans). In our country the CCR5 A32 muta­tion is fairly common (among the ethnic Russians the heterozygotic genotype occurs in 17-24.4 percent of cases, and the homozygotic one—in 1-2 percent). This genotype provides 9.9 percent protection against the HIV infection in heterosexual contacts, transmission of the virus from mother to fetus or in blood transfusion.

The above facts confirm the hypotheses on the impor­tance of the selection-mediated effects of microorgan­isms on the evolution of the human genome. However, the impact of pathogens is not only restricted to the mod­ification of the biological characteristics of Homo sapiens. Acute infectious and parasitogenic diseases spilling over into epidemics affect the social and economic conditions and destinies of peoples and civilizations. Here are just a few examples, Tropical (falciparum) malaria that hit the northern Mediterranean in the first century A.D. devas­tated the southern tip of the Apennine Peninsula, a region that had been developing with much success for nearly 1,000 years. Because of the infection hazard these dis­tricts of Italy had persisted desolate up to the onset of the 20th century. Traveling to the European continent in the beginning of the first millennium A.D., tropical malaria led to the rapid decay of the Hellenic civilization.

The spread of the Justinian plague in the 6th century A.D. finished off what remained of the Roman Empire. Smallpox, carried: by the Spanish conquistadors to America, undermined the Incan empire-in 1520 alone this disease kill more than 3 million American Indians. The import of syphilis by Columbus's sailors from the New World late in the 15th century and its propagation contributed to the twilight of the European Renaissance. The dysentery epidemic in the armies of Austria and Prussia advancing on the revolutionary Paris of 1794 compelled the troops incapacitated by diarrhea to fall back, which in no small measure helped save the French Revolution.

Just as dramatic are instances of social panic, as seen in the example of real or imaginary, epidemics of the last fifty years. The outbreak of cholera caused by El Tor vib­rio in Indonesia (1961) and in other regions of the globe resulted in an actual economic blockade of the countries involved. The first epidemic of the Ebola fever in Africa (Sudan, 1976) stalled air traffic there. Such kind of inad­equate "anti-epidemic" measures were also taken in respect of a "pneumonic plague" in India (1994), though no cases of that disease were actually reported. The same is true of the atypical pneumonia SARS (Severe Acute Respiratory Syndrome) said to have hit China, Viet Nam and other countries in 2003.

It's a paradox: periodic epidemics excite but a fleeting "interest" among the public. Policy-makers and even top healthcare officials close their eyes to the socioeconomic role of infectious diseases as the prime cause of, mass incapacitation and premature death of people the world over and do not allocate essential funds for combating this hazard jeopardizing the very existence of humanity.

Well aware of the primary role of causative pathogenic agents and the fact of interspecific competition between microorganisms and man, we cannot afford to pin hopes on consecutive adaptation of Homo sapiens as a biologi­cal species in the context of the Darwin-Wallace theory. Millions and millions of lives will have to be sacrificed in epidemics and in the struggle for survival, as it has hap­pened time and again. Dr. Joshua Lederberg, a US geneticist (Nobel Prize, 1958), had a point when he said that in the race for survival with microbial genes our weapon should be human intelligence, not the natural selection of our genes.

5. Bio – shield

This far Russia is not ready to address biohazards, Academician Mikhail Paltsev, rector of the Moskov Medical Academy and chairman of the Russian Health Ministry Exspert Board, says. He was one of the organizers of the Second International Conference “Molecylar Medicine and Biosafety”. The conference, attended by Russia’s leading virologists, as well as representatives from the U.S Department of Health and Human Servises and the State Department, discussed, among other things, the threat of bird flu in the world.