The Evolution of Airborne Pathogen

INTRODUCTION

Since the Stone Age and before, man and his ancestors have sought refuge from the elements by taking shelter within caves, tents and wooden structures. The common protection they obtained also fostered the exchange and proliferation of airborne pathogens. These viruses and bacteria have experienced not only a coevolution with man, but also with man's habitats. As man's structures became progressively cozier and more airtight, these pathogens became more adapted to survive indoors and less likely to survive outdoors. A study of the origins and adaptations of these microorganisms should lead ideally to identification of the common vulnerabilities and general principles by which indoor environments can be maintained free of airborne pathogens.

THE EVOLUTION OF PROKARYOTES AND PATHOGENS

It is of interest to first establish the phylogenetic relationship of pathogens in general, and their relation to each other as well as to vertebrates, and also the time scale within which all the diversifications have occurred.

Metazoan evolution is relatively well understood, primarily due to the morphological similarities among the species and differences between the various phyla. Not so well understood is the mode of bacterial evolution, as phenotypes are so diverse, which is as one would expect in such ancient lifeforms. The obscurity of their origins and the present paucity of micropaleontological evidence further complicates matters. Nevertheless, certain patterns can be inferred, partly based on morphology but mostly based on genomic comparisons of ribosomal and transfer RNA.

Prokaryotes are single celled organisms, and are distinct from eukaryotes, or multi-celled organisms like ourselves. Prokaryotes can be divided into two main classes, eubacteria and archaebacteria, which evolved from common progenitors called progenotes 3.5 billion years ago (Schleifer and Stackebrandt, 1989). It wasn't until the development of an oxygen rich atmosphere that eukaryotic cells appeared some 1.5 billion years ago. It is not absolutely certain that viruses existed at this point, but bacteria certainly did and this period must represent the beginnings of both symbiotic and parasitic relationships between prokaryotes and eukaryotes. The divergence of higher life forms would inevitably have carried any associated pathogens along their evolutionary path right up to the present.

In final perspective, the first vertebrates appeared 600 million years ago (Litman et al, 1993), the first mammals 200 million years ago and bipedalism first occurred 7.5 million years ago. As sheltering in caves or other natural formations was already a natural tendency by this time, it is likely that the evolution of airborne pathogens was already underway.

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IMMUNE SYSTEM EVOLUTION

All vertebrates possess antibody responses, but in jawed vertebrates, antibody diversity is specified by the same heterodimeric immunoglobulin molecule. The diversity of antibodies is generated both by inherited characteristics as well as by somatic rearrangement within the host. High degrees of nucleotide similarity occur in these immunoglobulin gene loci, but marked differences in organization and recombination mechanisms exist between phylogenetically divergent species (Litman et al, 1993). This evidence seems to indicate a very ancient divergence of the types of pathogens afflicting the various vertebrate species, possibly in direct accordance with the divergence of the species themselves, but also indicates a recurring similarity of the mechanisms which these pathogens use to infect their hosts.

This same pattern could be expected within the realm of airborne pathogens; with initial diversity of the primordial types of pathogens, and the emergence or re-emergence of characteristics which enable respiratory infection. Therefore regardless of the specific origin of airborne pathogens, their analogous characteristics should entail an analogous array of characteristics and vulnerabilities.

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ORIGIN AND COEVOLUTION OF AIRBORNE PATHOGENS

Although the ultimate origin of most pathogens, especially viruses, is obscure, certain inferences can be made due to various genetic and morphological similarities. Smallpox, for example, is considered a mutant form of cowpox (Davey and Halliday, 1994). Measles resembles canine distemper, and likely jumped species soon after the dog was domesticated by hunter-gatherers at least 14,000 years ago, and probably much longer. Diphtheria, caused by Corynebacterium diphtheria, is transmitted from cattle, which were domesticated about 7000 BCE, but is relatively new, being not more than 2000 years old. Cattle also suffer from a form of TB caused by Mycobacterium tuberculosis bovis, and evidence of TB can be found in neolithic skeletons from 5000 BCE. Horses are the only other animal to harbor rhinoviruses, and although they may not have been domesticated until about 4000 BCE, and may have been husbanded for food much earlier than this as they were hunted for ages before this.

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THE EVOLUTION OF HUMAN HABITATS AND PATHOGEN ADAPTATION

Since airborne pathogens do not remain viable for long in outdoor air, and are difficult to transmit outdoors, one would expect their genesis to occur coincidentally with the first use of enclosed shelters. Undoubtedly the earliest shelters were found shelters, caves in particular, which offered protection against the weather and predators. Huddling together for warmth, as other primates are known to do, would have fostered viral and bacterial exchange even if the pathogens were not very viable in air. The time period of these first exchanges in natural shelters probably predates the appearance of bipedalism in 7.5 million BCE.

Archeological evidence has been found indicating Homo habilis was constructing crude forms of shelter about 1.8 million years BCE, probably wood/branch/leaf enclosed tentlike structures secured with stones at the base (Jelinek, 1975). The airtightness of such structures is minimal, but the close quarters are likely to have preserved the already existing forms of airborne pathogens.

The Aechulean period, around 1.5 to 0.5 million BCE, saw an improvement in toolmaking skills, including hand axes, and the first archeological evidence of tents. The oldest tent found in this period was actually constructed inside a cave and made of animal skins draped over a wooden structure, and about 12' x 35' in size and divided into two rooms, sufficient for sleeping a large family. The improvement in airtightness would inevitably have improved, or perhaps initiated, the possibility of evolving pathogens dependent on airborne transmission.

The sudden increase in tool technology at 500,000 BCE, the Mousterian Period, inevitably corresponded with a refinement in the quality of the shelters and clothes that could be made with these tools. Tents and huts with increasingly sophisticated structures, larger sizes and designs for heating appear right down to the Upper Paleolithic, from about 50,000 BCE. Both Neanderthals and Cro-Magnons coexisted with similar neolithic technologies at this time, indicating some degree of trade and interaction despite the limited overlap of their preferred climates. It is possible that airborne pathogens were being exchanged between these two species of humans while meeting inside tents, huts or caves.

During the last ice age about 30,000 to 15,000 BCE, when Neanderthals were already extinct and Cro-Magnons were adapted to cold environments, the practice of living inside tents and temporary huts must have been the norm. The mammoth hunters of Eastern Europe at this time spent millennia hunting mammoths to extinction, and lived in tents made of mammoth hides and bones. The stability of this lifestyle probably provided a steady rate of transmission of airborne pathogens through the period. About the same time in the warmer climates to the south, in the Middle East, Africa, Asia, Australia and South America people were already building wooden huts, herding and possibly husbanding animals.

Although permanent houses are thought to correspond with the beginnings of agriculture about 12,000 to 9,000 BCE, the existence of trade in hunter-gatherer societies could place the first permanent housing much earlier. Permanent structures would have provided the first ideal environment for airborne to develop more sophisticated means of respiratory infection.

In ancient mild climates buildings were naturally ventilated, but in cold climates, especially Europe during the Little Ice Age, 1350 - 1850 AD, homes were suddenly made much more airtight. This period corresponds with the explosive spread of a number of airborne pathogens, including TB and also the Plague.

The advent of modern technology brought forced ventilation into buildings, and although this provided fresh, tempered, air and reduced disease over much of the past century, the trend has recently reversed, partly due to attempts to save energy by reducing outdoor airflow, and partly due to the continued adaptation of airborne pathogens both to human habits and human technologies.

We have seen a number of outbreaks directly traceable to buildings and their ventilation systems in recent decades. More attention is now being paid to building design, maintenance and microbial disinfection than has been the case in the past, but the problem is likely to continue, and furthermore, selective pressures are now at work.

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SELECTIVE PRESSURES IN INDOOR ENVIRONMENTS

The selective pressures in indoor environments are mostly innocuous to airborne pathogens because indoor environments are comfortable living/working spaces by design. The shielding from sunlight, the available host reservoir, the presence of moisture from various sources and a transport mechanism, the ventilation system, to aid in wide dispersion should all be highly favorable to airborne pathogens as they will allow for the release of pressure on genomic resources. Pathogens established in these environments should be capable of evolving increased diversity and virulence, with the building playing, to a limited degree, the part of the arthropod vector in nature. With humans to further vector the microbes from building to building, they can reestablish themselves indefinitely in new buildings and future mega-buildings.

There are several factors which could produce selective pressures on well-established indoor pathogens. HEPA filters, for example, could select for smaller pathogens and/or motile pathogens which won't remain attached to fibres. Perhaps naked viruses will be the ultimate product of this downsizing process as the nucleocapsid could prove unnecessary in controlled environments. Viruses which can tolerate momentary chilling to 12oC or momentary heating to 50oC as they pass through the cooling and heating coils may be selected over time. Also the occupancy schedule of the buildings, being often unoccupied over night for 8-10 hours or over a weekend for 48 hours, could place requirements of dormancy on pathogens as they would have to remain on surfaces or recirculating for this length of time. M. tuberculosis, for example, is already capable of surviving this length of time on surfaces.

Another factor which could play a part in selecting for future pathogens is the attempt to sterilize the air with such methods as ultraviolet light. If these methods are not completely effective, they will merely place a continuous mild selective pressure on the pathogens in exactly the same way that inadequate dosages of antibiotics have produced drug-resistant TB in individuals. Any such sterilization techniques used in buildings must be designed to be perfectly efficient, otherwise they will eventually become perfectly ineffective over time.

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CONCLUSIONS AND DISCUSSION

The previous examples and case studies have provided evidence both for the coevolution of airborne pathogens with man and with his domesticated animals. The links between this process and the evolution of his habitats have been discussed. Pathogenic and morphological similarities have been tabulated, and although the available information is limited at present, some patterns can be observed, such as parallel defense mechanisms, affinities for attachment sites, sizes and temperature ranges for growth. Susceptibilities of these pathogens to various factors remain to be studied further, but it could be fully expected that most pathogens will be found to have some common vulnerabilities in some varying degrees.

In spite of the limited data available, an attempt has been made to quantify the relationships between the evolution of man, his habitats, and airborne pathogens by identifying their earliest possible appearance. This chart, The Hypothetical First Appearance of Airborne Pathogens, represents bounded limits where there is any actual or hypothetical reason to set them. The viruses, for example, are placed in a recent context due to their remarkable sophistication and streamlined genomes, although it could perhaps be argued almost as strongly that they represent a primordial life-form. The majority of the chart, however, represents a great deal of speculative and arbitrary placement and should be taken as only a rough draft.