Mathematical Oncology

Malignant threats to humankind

Behind the paper

Written by James DeGregori, Niles Eldredge - December 03, 2019

Parallel Causation in Oncogenic and Anthropogenic Degradation and Extinction

James DeGregori1 and Niles Eldredge2

Read the manuscript
  1. Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  2. Division of Paleontology, American Museum of Natural History, New York, NY, USA.

Almost all of us have experienced the devastating effects of cancer, either by our own battles with the disease or through its impacts on our friends and family. In fact, 40% of people in industrialized countries develop cancer, and about half will die of their disease.

It is also widely accepted (with notable exceptions) that species diversity and environments on Earth are under serious threat, due both to human-caused climate change and habitat destruction. The Earth is currently in the midst of the 6th Extinction, with massive losses in species diversity resulting from human-caused habitat destruction, climate change, and direct killing of species.

But what do these tragic conditions have in common, and how can one inform the other? The two of us recently wrote an article in Biological Theory that we hope can shed some light on these problems. We explore the commonalities shared by cancer assault on us and our assault on the Earth. We propose lessons that can be learned from each to inform the other, with ecologically-informed approaches to address each problem. There is growing evidence that cancer is an evolutionary disease, which like “classical evolution” is highly dictated by the state of the tissue environment at early stages and the tumor environment at later stages. Understanding tissue and tumor ecology should allow us to better develop interventions to prevent and treat cancers. Similarly, the destructive impacts of humans on earthly environments often result from our ignorance or our apathy towards critical ecological interdependencies, and any efforts to mitigate this destruction will require appreciating and leveraging these interdependencies.

The development of cancer represents a somatic evolutionary process within us, or any animal, that requires both phenotypic changes (conferred by mutations, including epigenetic changes) and tissue environments (“microenvironments”) that select for such changes. Cancer evolution requires more than just oncogenic mutations, but tissue changes that render these mutations adaptive. Understanding how contexts like smoking, radiation exposure or old age contribute to increased cancer risk requires consideration for how such contexts influence the tissue microenvironment, and any approaches to mitigate these risks will need to incorporate the tissue environment. It may seem counterintuitive, but we and other animals have evolved stem and progenitor cell pools that are well adapted to their tissue environments, which thus results in stabilizing selection, whereby mutations that change phenotype (including oncogenic mutations) will be selected against. Thus, the “evolved phenotypes” of our self-renewing cell populations are favored, at least through youthful periods when reproductive odds were decent. Old age or exposures such as cigarette smoking change tissue environments for the worse, promoting selection for oncogenic mutations that are adaptive for cells within these new environments.

Following the development of agriculture starting some 10,000 years ago, humans have abandoned their primordial ecological roles, leading to a population explosion that now threatens our planet, analogous to how the uncontrolled growth of cancer cells threatens their host. In the article, we describe other parallels between cancers within us and our anthropogenic devastation to Earth’s ecology, including the lifting of normal “Malthusian” limits on growth, their invasive natures, their usurpation of key resources, their manipulation of other host populations to their own benefit, degradation of local environments, their increased rate of acquiring novel innovations (via mutations or new technology) and their ultimate destruction of their host. We detail how niche width theory may provide insight into both species conservation and the control of cancers. For the former, we need to appreciate how the eurytopic or stenotopic (tolerating wide or narrow ranges of habitats, respectively) nature of species influences their ability to withstand insults and their susceptibility to extinction. For the latter, we can consider how cancers are easier to eliminate when they are more stenotopic, and we should be able to manipulate conditions to favor cancer evolution in this direction.

It is important to emphasize that cancers have no goals in mind (including regarding the fate of their host), but their population size, which can exceed 1 trillion in a single person, their destructive and invasive nature, their monopolization of resources, and their excessive waste products often lead to the death of their host. Similarly, while humans do not seek to destroy Earth, our sheer numbers (exceeding 7 billion) and our destructive nature imperils our planet. Unlike cancer, we have the intelligence and foresight to understand that our annihilation of other species and ecosystems imperils our own survival. Ecological destruction has a cost for the destroyer.

In short, both cancers and anthropogenic extinction of other species result from population exit from normal sustainable ecological niches, resulting in rogue growth and ecological devastation. By abandoning their usual evolved roles in ecosystems, both humans and cancers will unwittingly threaten their own existence by bringing about the demise of their host.

Clearly, humans are integral to both systems. With cancer we are the host and victim of the rogue behavior of what starts out as a normal, healthy and functionally important part of our bodies. With the biodiversity crisis, we are the part of the system that has changed, expanded and proven so destructive to the system in which we live. We argue that given that these threats to our bodies and Earth are both essentially ecological diseases, that understanding the critical role of ecological interdependencies for avoiding both cancer’s and humankind’s destruction of their respective homes should hopefully promote better stewardship of both by the only animal capable of recognizing the problems – ourselves.

So how can parallels between cancer’s threat to our health and our own threat to Earth’s ecosystems inform strategies to mitigate some of the damage? For cancers, understanding the tight connections between microenvironmental perturbations for the initiation and progression of malignancies, including dependencies on other cell types (“species”), provides opportunities for rationale interventions that prevent or reverse these changes – ecosystem management for cancer prevention and therapy. Similarly, better maintenance of Earth’s ecosystems can help mitigate the destructive tendencies of constituent humans. We need to promote behaviors or policies that favor “the evolved type,” whether we are referring to an ecosystem in the absence of human impacts or the tissues of an ideal healthy young person.

Recent clinical trials have indicated that evolutionary-informed approaches to cancer therapy, dubbed Adaptive Therapy by Robert Gatenby and colleagues, can lead to better outcomes for patients by limiting but not eliminating cancer burden (and thus delaying selection for therapeutic resistance). A similar lesson my apply to humanity – limiting human population size should reduce our negative impacts on the planet, so long as our voracious appetites and destructive/invasive tendencies are also kept in check. Still, solutions for our planet will not be simple, as we are essentially dealing with a Stage IV metastatic disease. Nonetheless, we must mitigate some of the damage.

If only we could make cancers aware that their own death awaits them as they kill their host. Alas, cancers are not sentient beings. But humans are. Better recognition that human-engendered destruction of our host (Earth) will lead to human suffering if not our elimination should stimulate greater efforts to mitigate our destructive means. While Earth may not realize that it is under attack, we do. Just as we fear cancer, we should be afraid of the consequences of our behaviors on our planet. And we should leverage that fear to do something about it.
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