Antimicrobial Resistance, Global Warming, & Overpopulation

A Perfect Apocalypse

Michael C. Storrie-Lombardi

Kinohi Institute, Santa Barbara, California 93109

Humanity currently faces threats from three closely linked phenomena: [1] antimicrobial resistance (AMR); [2] global warming (GW); and [3] population growth (PG). From first principles we would hypothesize that increases in GW and PG will most likely facilitate the appearance of AMR. Unfortunately, no single agency is currently monitoring the global interaction between these three processes. Consequently, we currently have no mechanism to evaluate in real time the impact of GW and PG as AMR drivers, or elucidate the global economic burden, epidemiology, and transmission of AMR.

Background. The 21st century, a period of dramatic achievement in our understanding of everything from genomics to the fundamental physics of the Universe itself, has also presented us with 3 life-threatening phenomena: microbial resistance to antibiotics, global warming, and overpopulation.

Antimicrobial Resistance (AMR). Surveys by the World Health Organization (WHO) document alarming increases in AMR in a wide range of infectious organisms [1]. Governments and financial institutions worldwide confirm that the problem threatens the ability of modern medicine to combat infectious disease and directly threatens the global economy [2]. WHO data indicate that a post-antibiotic era in which common infections can quickly kill is far from being an apocalyptic fantasy. A world decimated by plagues and pandemics seems a very real possibility for the 21st century.

Global Warming. Analysis of land-surface temperature records going back 250 years shows that the average world land temperature has increased approximately 1.5 oC over the past 250 years and 0.9 oC during the past 50 years [3]. The temperature changes are accompanied by diminished water supplies resulting in crop failures, starvation, and the collapse of sanitation systems.

Overpopulation. The environmental demands to sustain a global population of 6-7 billion human beings is rapidly eroding Earth’s life-support system. The inexorable demographic momentum of the increasing global population is so strong it would be resistant to either a rapid transition to a worldwide one-child policy, or a catastrophic mass mortality event of 2 billion deaths [4].

Each of these pose a significant challenge for humanity, but how do they interact? Are they synergistic? Is the combined assault worse than the sum of the parts? Will our survival depend on intervening in all three in concert? Unfortunately, no single easily interrogated data repository exists to investigate the interactions in this “perfect storm” of environmental and biomedical challenges.

A logical course of action.

[1] Establish a central repository for AMR, global warming, and population data in such a way that it is easily accessible to investigators of all nations - an international “observatory” to monitor and understand the interactions between these three phenomena.

[2] Implement cooperative agreements between WHO, NASA, the World Bank, and academic sites for rapid access to AMR, health care, warming, and population data streams;

[3] create a central database and publicly available web site to enable coordinated tracking and analysis of environmental, health care, and epidemiological data.

Preliminary Investigations. At our institution we have tested the hypothesis that GW and MG may be serving as drivers or facilitators for AMR. over the past several months. The effort required accessing multiple data sources from WHO, academic centers, and international financial organizations including databases that, unfortunately, are fragmented and not easily interrogated. We have manually extracted data from: WHO’s global report on AMR [1]; the MINE Project [5] which consolidated 253 WHO health care and socioeconomic indices for 203 countries; the Berkeley Climate Project [6] which collected temperature data from 1960 to 2014 for 237 countries; and World Bank population estimates [7].

Data were sufficiently complete to investigate 102 countries including 21 African nations. Figure 1 depicts AMR levels as a function of both annual increases in population and global warming in all 102 countries (Fig. 1A) and in the 21 African nations (Fig. 1B). Maximum AMR levels (colored orange and red) occur most often both globally and in Africa when a country experiences an annual growth rate of 2.5-3.0% and annual temperature increase of ~ 2 oC. AMR levels increase as a function of growth rate (Fig. 1C) and global warming (Fig. 1D) in 16 of 21 Africa nations (+). Eight African nations maintain AMR rates at less than 20%. Five of these (o) appear resistant to the effects of significant warming. In contrast, European nations exhibit decreasing AMR rates with warming (Fig. 1E). European nations exhibit significantly less population growth (Fig. 1F) than African nations, a factor that may slow the spread of AMR (see below).

What is concerning: The eight African nations maintaining relatively low AMR rates including the five significantly resistant to warming are not distinguished from countries with high AMR rates by differences in levels of health care or availability of treatment for infectious diseases. If antibiotic usage were the single pertinent variable, countries with increased levels of health care and increased incidence of infectious diseases would be expected to exhibit increases in AMR. The data do not support that prediction. In fact, the only reliable predictors of AMR levels in these data are temperature increases and population growth.

AMR certainly begins as the result of the extensive use of antibiotic medications. But, once established in a single microbial species, AMR spreads to other species by plasmid or viral horizontal gene transfer (HGT). One possible explanation for the results in this preliminary investigation would be that the loss of water supplies and subsequent crop failures produced by global warming not only results in terminal starvation, but also contributes to immune system impairment in the surviving members of a population. Immune system degradation combined with overcrowding would accelerate the spread of all bacterial species including those carrying AMR genes. Increased survival for AMR species increases the opportunity for AMR transfer to new bacterial species by HGT. In this scenario, Europe’s low population growth rates would inhibit the spread of AMR.

Note that once we identified nations where AMR levels rose only minimally with global warming and crowding, it was feasible to ask ‘how do these countries differ from high AMR countries?” Review of the 253 WHO health care and socioeconomic indicators revealed that 4 of these five countries provide high levels of MCV immunization and exhibited some of the lowest death rates for measles in one year olds. Without the combined data set, we would not have uncovered this clue about the potential impact of early immunization programs on AMR epidemiology. At present testing these and other hypotheses is, at best, difficult if not impossible. Humanity will not be able to document the epidemiology, understand the pathophysiology, or devise a global adaptive response to evolving microbial infective agents without readily available international access to AMR, global warming, and population information.

Implementation: Our next generation of science and engineering students need to be involved in this project - an effort that could dramatically alter the the world they will inherit from us. The database, web site, and analytical software should be developed by undergraduate physics, computer science, mathematics, and bioengineering students under the supervision of senior scientists in those disciplines.

Next phase: If we have chosen the proper database sources then the new data will (a) either confirm or reject the apparent differences in AMR epidemiology for Africa and Europe apparent in this initial analysis, (b) help us understand what enables a handful of African nations to maintain low AMR rates, and (c) help extend those insights to other regions including Asia and the Americas. The next phase will be to (a) establish a support system to maintain the database as a permanent international repository, (b) implement a mechanism to progressively fine-tune both the spatial (smaller than region/nation-state) and temporal (one year or less) precision of the database, and (c) build an autonomous intelligent system capable of generating real time predictive models of the global evolution of AMR.

References

[1] “Antimicrobial Resistance: Global Report on Surveillance” (2014) WHO www.who.int

[2] “The Review on Antimicrobial Resistance” (2014) O’Neill, J. http://amr-review.org

[3] NASA Climate Model Data Service (2016) https://cds.nccs.nasa.gov/nex-gddp/

[4} Bradshaw, C. J. A. and Brook, B. W. (2014) PNAS 111 (46), 16610–16615.

[5] MINE project http://www.exploredata.net/Downloads/WHO-Data-Set

[6] The Berkeley Earth database (2014) http://berkeleyearth.lbl.gov/country-list/

[7] World Bank Group population database (2014) http://data.worldbank.org/indicator/SP.POP.TOTL