The inclusive stakeholding framework can help explain the emergence of cancerous behaviors between humans, and it also may help us better understand cancer itself.
Based on Hamilton’s rule, the same individual can display nurturing behaviors toward kin and extractive behaviors toward non-kin. For example, a tyrant may extract from his people but lovingly nurture his own children. The person hasn’t changed between these two scenarios. What has changed is the context; specifically, the tyrant’s degree of vested interest in the relationships, which affects goal congruence, alignment of interests and degree of interdependence.
The human body can be considered a society of cells with identical genes. The trillions of cells in a normal body run their algorithms as a coordinated, interdependent superorganism. Cells in the body are known to nurture and behave altruistically toward one another: apoptosis is one example, and functional specialization is another. When the network of interconnected algorithms manifests a mutually vested interest in each other’s success, the organism thrives.
Intercellular interdependence, however, appears to decline as we get older, and this may contribute to the aging process. Which processes lead to the loss of intercellular interdependence remains to be determined. Perhaps the loss of a central biological clock after pineal involution promotes dyssynchrony among cells. Maybe a loss of power, control systems or repair mechanisms also contribute to the loss of intercellular interdependence.
Another possibility is the emergence of intrinsic microchimerism—genetic diversity inside one body—through cell divisions over a person’s lifetime, which is different than extrinsic microchimerism caused by transplacental cell crossings. If you think about humanity as one superorganism, mutual kin skin in the game (inclusive fitness) declines rapidly among descendants, leading to increased competition among people over time. What if the analogous phenomenon also occurs inside our bodies as we age?
We know this happens in plants: The degree of intrinsic microchimerism increases as the branches of a tree arborize, leading to greater competition among branches that are farther from the main trunk. Perhaps the descendent cells that replenish our bodies as we age also diverge, genetically or through HLA variations and other mechanisms, such that the degree of eusociality among cells in our body declines. Inflammation and aging may be downstream epiphenomena of an emerging strangerhood among cells in the body, promoting intercellular competition.
Taken further, perhaps the loss of intercellular interdependence promotes selfish behaviors among cells whereby existing bioalgorithms are subverted to promote extractions. Internalities are externalized, leading to perverse incentives, and competition for resources emerge. Not unlike self-dealing nations, tissues in the body become tribal and appear to extract from the total system. For example, tissues appear to hoard high-density stores of energy such as fat not unlike how nations hoard hydrocarbons. Indeed, an increasing degree of adiposity is observed in every tissue of the body as we get older.
Consider cancer through this same lens. When normal cells lose intercellular interdependence, they act more independently. Once independence is established, a conflict of interest develops. Essentially, from the perspective of cancer, the host becomes an externality that cancer pollutes while exploiting. Think of it as a system of intercellular imperialism devouring a system of intercellular interdependence—not unlike when colonialists arrive in the land of natives.
Thereafter, evolution can select for more extractive behaviors. Whereas alignment of interests and competition is a race to the top, malalignment of interests and competition is a race to the bottom. Over many divisions of the cancer cell, selection favors the emergence of ever more extractive algorithms that drive the cell to become a self-expanding beast at the expense of the host. The fractal analogies to extractive social, political and economic institutions are self-evident.
This lens offers a new target for treating cancer: to reestablish interdependence among cells.
One of the conventional theories about how to treat cancer is to attack extractive algorithms in mutant cells. Blocking growth factor pathways is an example. This approach, however, may prove futile if intercellular interdependence is not reestablished. Unless first-order intercellular alignment problems are addressed, whack-a-mole solutions to second-order symptoms will only create third order issues. For example, current approaches to treat cancer can backfire by acting as an evolutionary selector for more aggressive algorithms, the way antibiotics can select for resistance. The approach is reminiscent of the Sisyphean hell of revolutions.
We envision a completely different approach to cancerous situations. We hypothesize that reinserting algorithms of intercellular interdependence may allow all those extractive behaviors to self-domesticate into regulated normal behaviors that serve the host rather than the cancer. Reestablishing mutual vested interests restores the “win-as-others-win” biological algorithm of kin networks to multi-stakeholder, separatist communities which have otherwise been spinning their wheels on “win-win” or “win-lose” paradigms. It would be akin to two warring monarchies marrying off their children to each other to restore mutual kin skin in the game. At the human level, invested self-interest could prove to be a more sustainable operating algorithm of human sociality than enlightened self-interest. The same could be said of the society of individual cells that make up your body.
We are early in our thinking about this approach. For example, we wonder about injecting oxytocin into tumors to increase a nurturing tendency among cells, since the hormone is known to promote nurturing behaviors in humans. Intuitive, it seems too downstream to be a curative approach, but there is some preliminary data to at least directionally support this idea. More upstream, decoding how nature programs interdependent behaviors among cells in biofilms, which are thought to be predecessor systems that led to the emergence of multicellular organisms such as humans, might yield better insights on intercellular interdependence in our bodies. Indeed, it is our hope that future research that generates novel understanding of the mechanisms of intercellular interdependence and novel algorithms that foster vested interest in the success of the system may inspire new strategies for treating cancer, aging and many related conditions.
For these reasons, we believe that the biological basis of intercellular interdependence—and the mechanism of its loss in cancer and aging—warrant further investigation.
Joon Yun and Eric Yun are principals of the Yun Family Foundation.
