14 June 2020, Cancer and complexity science, Essay #1

Cancer and complexity science
Essay #1
14 June 2020

My research focuses on how cancer arises based on complexity theory. I find it helpful to write and talk about it, not just to physicians and scientists but to my friends, family and neighbors. In these essays, I will cover the highlights of my work. I welcome your comments or questions by replying below or emailing me at NatPernick@gmail.com.

What is complexity science, and why is it important in understanding cancer?

1. The war on cancer has failed.
It is important to acknowledge that the war on cancer, announced by President Nixon in 1971 (https://www.youtube.com/watch?v=peb47Z-jPqc  at 15:03), has failed. Although cancer death rates have declined and survival is improving (https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf), cancer will soon be the leading cause of US death (https://www.cdc.gov/pcd/issues/2018/18_0151.htm). When a major problem persists despite the expenditure of substantial resources, it may be due to a fundamental misunderstanding of its nature.

2. Traditional biologic thinking is inadequate to understand cancer.Traditional biology relies on reductionism, namely that the behavior of the whole is equal to the sum of the behavior of the parts. According to this view, life is merely a collection of sophisticated machine-like systems with an aggregation of their individual properties (https://pubmed.ncbi.nlm.nih.gov/18174892/).  Reductionism is illustrated by my broken refrigerator. I neglected to vacuum the vents. This led to a buildup of heat in the refrigerator motor. It overheated and failed, causing the refrigerator to stop working. To solve this problem, the motor was replaced, the vent was cleaned, and to prevent a recurrence, I regularly vacuum the vents. The entire process is logical and predictable.

However, life functions as a complex system, not as a sophisticated machine. The properties of the entire system are greater than the sum of the properties of each part due to important interactions between the parts (http://natpernick.com/TheLawsJune2017.pdf). These interactions cause complex systems to exhibit many nontraditional properties.

(a) Complex systems have characteristics that often cannot be predicted, even with substantial knowledge. For example, protein function is based on three dimensional shape, but even if we know the amino acid sequence that determines the protein, we cannot predict how the protein will fold in three dimensions. We have to wait and see. In sickle cell disease, a single substitution of one nucleotide for another produces a marked change in the function of hemoglobin, which prevents red cells from bending when entering small blood vessels, causing severe pain and damaging organs. What will be the impact of a different mutation? It may be trivial or life threatening. We cannot predict because we don’t know how the resulting protein will fold and how it will interact with other proteins.

(b) This inability to predict may also be due to emergence, a bottom-up property due to agents that spontaneously self-organize. Larger entities arise through interactions among simpler entities and possess properties not found or even thought possible from the simpler entities. Water, for example, possesses properties completely different from hydrogen and oxygen. In biology, evolution uses existing structures, such as the jawbones, to build entirely different structures, such as the middle ear ossicles.

(c) Complex systems possess stability that makes them resistant to unwanted change under most circumstances. Our cells and organ systems can encounter a tremendous amount of biologic stress and still function well. This is due to “attractors”, a stable equilibrium state which develops even among networks that have components that are constantly in flux (https://pubmed.ncbi.nlm.nih.gov/19595782/). This explains why cancer arises only after decades of chronic biologic stress. But cancer cells themselves have attractors, which unfortunately makes them resistant to treatment.

(d) Finally, complex systems have adaptive properties that increase their survival in a changing environment. This explains why tumors may stop responding to treatment that initially is effective. Fortunately, my refrigerator does not evolve.

In summary, principles of complexity theory create a more robust framework for understanding the origins and dynamics of biologic systems, including cancer, and must be better understood if we are to significantly reduce the death and misery associated with this disease.

Future essays will provide more details on how life arises and how cancer disturbs the control mechanisms that typically maintain order.