Series:
Essay #5:
Synopsis:
Causation
Cancer as Case Study in Complexity
Respect your enemy for what it is: a complex and living system that demands to be understood in the whole
I’ll use cancer as a case study for complex systems. I recently listened to an EconTalk podcast (March 2020) with Azra Raza MD, author of The First Cell: And the Human Costs of Pursuing Cancer to the Last. Dr. Raza is on the front lines of the cancer war, treating 30 to 40 cancer patients every week for the last 40 years. Her job is to treat the whole patient and therefore the whole cancer. She said this about cancer:
“My contention, Russ, is that all research on cancer should have one, and only one, goal, which is to benefit the cancer patient. .... And, spending hundreds of billions of dollars to identify the next intracellular signaling pathway in a tumor that is artificially created in a mouse is a complete waste of money for me. Especially when we talk about drug development--the idea that we can create a tumor in an animal model, treat it with a given agent and then bring those results to the human bedside. Well, this is met with unmitigated disaster. And the reason that you have very clearly pointed out is, yes cancer begins in one cell, but the cell keeps dividing. It's covering one generation within hours, which it should normally cover in months, if not even longer. So, that these rapidly dividing cells made DNA copying errors, which are known as mutations, every time a cancer cell divides into two, it picks up new mutations, which means now there are potentially two entirely new cancers.
It's something like the brain has 100 billion cells, but one quadrillion connections. The same way a cancer begins in a cell but then it has the potential of constantly moving, constantly changing and undergoing metamorphosis so that within days there is now a mixture of heterogeneously, biologically distinct populations of cells within a tumor. And, I always say that treating cancer like one disease is like treating Africa like one country. It's not the same even in two sites in the same patient, or two days in the patient. The tumor has changed.
So, how can we apply a reductionist approach in this tsunami of chaos within a tumor, along with its micro-environment, the intracellular signaling, the immune response, the blood supply, the angiogenesis, taking all of this complexity and trying to bring a reductionist scissors to it and trying to find one molecule and develop one magic bullet for it, it hasn't worked for 50 years... this is why 50 years later we are still using slash, poison, and burn, and the other 30% patients are still dying the same way, and for the 70% we are using slash, poison, burn, we don't even understand how those things are working.”
If I may paraphrase Dr. Raza, the problem is that we’re using simple mechanistic and probabilistic causation on a highly complex system, trying to explain the whole from single, unconnected pieces. Which makes perfect sense. What would I do if I were a cancer researcher and I needed grant money? My guess is, I’d write a laser-specific proposal involving experiments on mice. I’d sell the experiment as targeting some particular cellular pathway, and claim that this small piece might shed light on the whole that is cancer. When I get my federal grant, I’d go into the lab and create bulbous amalgamations of mouse and tumor, run experiments on a chemical pathway in this new species of grotesquery, then announce the results to no one listening. Meeces to pieces!
The results won’t explain cancer anywhere in the real world – neither in mice nor humans. It's a problem of foundational image. If my foundational image of reality is materialist, it means that I see the individual cancer cells (parts) combining like Lego blocks to generate new and surprising properties that emerge from the aggregate. If my foundational image of reality is holistic, it means that I see cancer as a whole being that acts as a whole to control its individual cells-- here I refer back to the third characteristic of a complex system: the whole is more than the sum of its parts.
I tend to the holistic account and I believe Dr. Raza does too. Dr. Raza expresses the problem as “reductionist,” that is, the scientist reduces the awful complexity of cancer to a constituent part, then tries to explain the whole from the part. Dr. Raza asks that, instead, we focus holistically on cancer. She says, look at the system of cancer as a whole, including DNA, RNA, proteins, metabolites, more.
What happened here? Our cancer researcher needs to run a laboratory experiment that shows simple mechanistic or probabilistic causation, because that gets funded. He has a problem: those two causal theories don’t work on complexity. But money talks, so he reduces cancer to something simple and small that fits in a laboratory where he can use his preferred causal theories, reality be damned. And reality ignores him and keeps on laughing. A domesticated lab experiment means little to a feral being like cancer.
My cancer researcher says to me, “thanks for nothing, Mr. Knowitall, what the hell do you propose?” I propose a rule of relevancy: to understand something, look at it, not something else. To understand cancer, look at cancer, not an intracellular pathway. Respect your enemy, in this case, cancer in the whole. We underestimate cancer when we reduce its complexity to little parts, then lever the parts to explain the whole.
Looking at the whole, maybe we see patterns and symmetry. Or maybe we try a crazier theory: if cancer patients feel like cancer is a living being inside them, then act like it’s true, that cancer really is a living causal agent with its own purposes. When we approach cancer as a fellow living being, we shift perspective and maybe we see something new. 50 years in, it's worth a try.