JOURNAL OF EMERGING AND RARE DISEASES (ISSN:2517-7397)

Five major extinctions (Table 1) are responsible for creating the environments for a change in direction of the evolutionary process [1-3]. The Permian extinction permitted dinosaurs and their ancestors to become the major Mesozoic megafauna. The Cretaceous extinction paved the way for mammals to similarly achieve subsequent prominence. It is unclear what was wrought by the Pleistocene extinction, except perhaps the rise of modern humans and the opportunity for our own self-destruction.

The source of the most recent extinction has been subject to great debate. Four hypotheses have been offered: Environmental (climate) change, human “intervention” (e.g., hunting related overkill), extraterrestrial impact and hyperdisease [4,5]. Disease was clearly present throughout at least the late Pleistocene. Presence of the Mycobacterium tuberculosis complex was documented both by DNA and lipid analyses in bovids (e.g., bison, cattle, big horn sheep, musk oxen) and mastodon through at least the last 100,000 years of the Pleistocene [6,7]. The population prevalence of bone evidence of disease ranged from 25 to 50%. Since not all individuals with the disease have bone involvement, the implication is that virtually 100% of those species were afflicted with tuberculosis. That would suggest that tuberculosis was responsible for their extinction. However, that population prevalence remained unchanged for 100,000 years. While penetrance of the disease into the population was essentially complete, sustainability of the involved species was apparently not impaired-until the latest Pleistocene.

As only 5% of humans with tuberculosis have active, debilitating disease [8], it is clear that a very effective mechanism is present that reduces the impact/spread and metabolic effects of tuberculosis. It is only when a stressor is “applied” that the majority of tuberculosis-afflicted individuals succumb to the disease [9]. The debate has persisted for over a century as to the responsibility of climate change, human action (e.g., hunting), extraterrestrial impact or disease for the Pleistocene extinction [3,4,10]. Lyons et al. [4] went as far as to suggest that humans were the source of the dooming infections, so the hypothesized causes of extinction are not necessarily distinct.

Some, including the author (BMR), have suggested that a single cause was unlikely, but that a multiple “hit” phenomenon was in play. Perhaps it was stresses induced by climate change or human activity that compromised the accommodation to the disease?

Tuberculosis, however, was not a new disease when extinction occurred [7]. Hosts had a long opportunity to develop an accommodation. Perhaps the result would have been very different if there had been a sudden exposure to a new disease. The history of American Indian response to long-standing European afflictions illustrates the draconian effect of such contamination [11].

Whatever the role of humans in producing or abetting global warming, there is a clear and present danger to continuation of that process. As temperatures rise, natural barriers to spread of infection have been compromised. More equatorial and temperate diseases extend their range to newly hospitable environs [12]. Thus, phoma stem canker disease of oil seed rape plants is now found in the northern United Kingdom, Lyme as far north as Canada, and expansion of bovine tuberculosis in Great Britain and chytridiomycosis to amphibians [13-15]. Diseases which had been thermally “quarantined” have now expanded their ranges. Previous territorial limitations to infectious disease recommendations for vaccination are no longer sufficient, resulting in an expanded susceptible pool with an epidemiologicallyexpansile potential. Some diseases have apparently been eliminated or have been so reduced in prevalence and distribution as to have little epidemiological significance. Habitat alteration (e.g., spraying for the mosquitoes carrying the virus or utilizing protective modalities) has been a major factor in minimizing their environmental impact [16], but the environment is now creating new opportunities for disease spread.

Global warming alters plant zones and growing seasons [17], which has the potential to impact food supplies. Such could potentially be an extinction-“directing” event, but there are other more direct dangers lurking.

The permafrost has been a buffet for study of ancient DNA and protein [18,19]. The level of preservation is so pristine that cloning has been contemplated for animals preserved within [20]. Animals, however, are not the only preserved organisms. Viability of contained bacteria and viruses has been suggested. These organisms have had the opportunity for “containment” in the permafrost refrigerator since the Pleistocene creation of that ecological zone. Burial (natural or human activity-related) have added more modern organisms, including those of Babesia sp., Bacillus anthracis, Vibrio cholera, Bordetella pertussis, Francisella tularensis, Yersinia pestis, Influenza, Variola and West Nile Virus [4,21-27].Giant viruses, Pithovirus and Mollivirus, have been found in 30,000 year old Siberian permafrost, retaining sufficient viability to infect amoebae [20,28,29]. The last two viruses were revived from 30,000 year-old Siberian permafrost. Viable Carnobacterium pleistocenium have been isolated from 32,000 year old permafrost and much older bacteria have been isolated in viable form from the Antarctic [30]. Exposure of permafrost burials have transmitted anthrax and smallpox [25,30-33]and those who met their demise from the 1917 influenza epidemic may well harbor organisms with potential for infecting new victims. One concern has been for contamination of those who excavate such sites, leading to hazard suit usage and other preventative and decontamination approaches. Such precautions are quite reasonable and actually feasible to pursue when potential exposure sites are identifiable. Global warming, however, provides a general opportunity for new environmental exposures, ones not under scrutiny and therefore with great opportunity for undetected spread (at least initially).

Extinction and extinction-level effects by infectious agents has been noted in the land snail Partula turgida (microsporidium Steinhausia-related), black-footed ferrets Mustela nigripes (canine distemper virus-related), Tasmanian devils Sarcophilus harrissi (transmissible cancer), koala Phascolarctos cinereus (Chlamydia pecorum-related), little brown bat Myotis lucifugus (Geomyces destructans-related), frogs (Batrachochytrium dendobatidis-related) and Christmas Island rat Rattus macleari (Trypanosoma lewisi-related) [26,34-38]. Animal contamination with permafrost-derived diseases (e.g., anthrax) has already occurred [30,31-33], Organisms of concern include Mycobacerium tuberculosis and atypical mycobacteria, fungi, Brucella sp., Yersinia pestis, Variola, Influenza virus, Hantavirus and zoonoses and animal epidemics.

There is an additional consideration: Multiple approaches allow recognition of known pathogens, but an extinct pathogen, brought back to life by permafrost melting, escapes such targeted analyses. When a priori knowledge is lacking as to which organisms may be present, such targeted analyses often fail, even for contemporary organisms. Metagenomics overcomes those limitations and provides an opportunity for detection of organisms independent of current knowledge of their pathogenicity or even of their very existence [39]. Also referred to as “shotgun” sequencing [40], it allows identification of all organisms present, not just those for which one has the insight to search [41-43].

Arens and West [44] suggested the effect combination of “long term pressure on the eco-system” and a sudden catastrophe. The same two-hit opportunity for extinction exists today, although the pressure and upcoming catastrophe are integrally connected. Global warming exposes permafrost-contained pathogens to an unprotected population. This certainly is a time of stress and new introduction of an old disease could be catastrophic. Many have been skeptical about the infectious disease extinction hypothesis, but there is now reasonable fear we are about to test that very hypothesis.