MEDICAL researchers, like most of the rest of us, tend to be reductionists. They try to explain complex phenomena by breaking them down to their constituent parts. If we understand these basic building blocks, the theory goes, then we can understand the larger picture. But over the past century or so, physicists, chemists and other scientists have cast doubt over whether complex systems can be explained away like this.

Chaos theory, emergence theory, the study of dynamic systems and myriad other disciplines have shown how complex phenomena have nonlinear structures without neat causal chains. Properties emerge that cannot be predicted from constituent parts; feedback loops can reverse the causal direction; and macroscopic properties can be described without making any assumption about a system’s microscopic nature.

Such ideas have transformed physics, chemistry, sociology, psychology, economics, information technology, quantum mechanics and countless other areas of investigation. Medical research, however, has largely ignored the work that has been done on complex systems.

That might be about to change, says Dr Elizabeth Sigston, a head and neck surgeon at Monash Health who has codeveloped a new “emergence framework” for understanding cancer.

“The whole way science research has developed – and I started off doing the same thing – is that you have something you’re interested in, maybe a protein or a gene, and you become an expert in that and know everything about it. And you want your one thing to be the one thing, the magic bullet that solves whatever issue you’re dealing with. But the problem is that nature isn’t like that.”

The prevailing theory of carcinogenesis for the past half century has been the somatic mutation theory, which considers cancer as a genetic disease, caused by a mutation at cell level which leads to unfettered cell proliferation. More recently, another theory, the tissue organisation field theory, locates the problem at the tissue level: disorganised tissue leads to a pathological environment for cells, which then proliferate to form a tumour. Although these two theories appear to be contradictory, Dr Sigston thinks that they can be dissolved into an approach that sees cancer as an “emergent system”, where there is no ultimate causative level. Focusing solely on the microscopic level is not going to enable an understanding of cancer as an emergent complex phenomenon, she says.

“Of course genetics play a role but we’ve been unduly fixated on genes in cancer research,” she says. “It goes right back to the 1920s. Then in the 1970s, we had Richard Dawkins and his selfish gene and then later the Human Genome Project. We’ve poured billions of dollars into genomics and, yes, we’ve made some progress. But not a huge amount when you look at the sums of money involved. It hasn’t been a great return on investment.”

When we diagnose cancer, we find it occurring at the tissue level, and that’s where we need to focus on, she says, rather than the gene level.

“Once you define your functional tissue unit and look at it in the sense of a system, then we can look at how it’s different in cancer. We can look at risk factors, how the disease progresses, what things impact environmentally, and of course also genetics that may create change in the components at the tissue level. The trouble is that there aren’t enough people looking across the whole range of things, and pulling these disparate things together.”

She says that we need to shift our focus from causal relationships that are fundamentally difficult to predict towards interpreting the patterns of cancer as an emergent system.

Dr Sigston points to her own recent research on oral cancers. Leveraging insights from her work looking at cancer as an emergent system, she has identified a subset of patients whose cancers are very likely to recur regardless of whether they have radiotherapy or chemotherapy.

“There’s the potential to put them in immunotherapy to see if they get a better result. But at the moment they have to wait until they fail everything else. Immunotherapy is making advances, but it still only benefits 10–30% of patients. We’ve developed this new therapy but we still have to work out who’s going to benefit.”

But change is hard. Emergent systems can be counterintuitive, and reductionism so hard-wired that it’s hard to accept phenomena in a system that can’t be predicted at a lower level.

“And yet that’s how nature works,” says Dr Sigston. “Even in something as simple as baking a cake, you can’t infer it from the initial ingredients alone. If you mix them in the wrong order, it will be different. If the oven’s not hot enough, the cake won’t rise. We’ve got to get people looking at things in a totally different way, and not just focusing on the minutiae.”


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7 thoughts on “Could a new paradigm change the way we think about cancer?

  1. JP Sturmberg says:

    There already is a – 20 year old – new paradigm, cancer is a stochastic (or evolutionary) disease, i.e. it is not genetic but rather genomic (resulting from gene-gene interaction). For a full exploration see Henry Heng’s research, summarized in a recent book entitled: Debating Cancer.

  2. Dr Louis Fenelon says:

    Thank goodness for broader thinking. Our understanding of health and health care does seem to be narrow minded at least in part to secure funding or access to treatment options. Reductionism has been a failure in nutrition health but it continues to be lauded. An alternate theory for cancer does not sound like drawing a long bow.

  3. Max Whisson says:

    Slowly we seem to be moving in the right direction. Cancer seems to me to be an evolutionary process: many variations occur in cell behaviour and occasionally one chance anomaly confers survival value on a cell, with insensitivity to the signals and interaction with normal surrounding cells that inhibit the growth of inappropriate cells. It is suborganismal evolution of new species; a microscopic replica of Darwinian evolution with a much shorter time scale. My cancer research was frustrated for more than half a century by the focus on DNA running cells like an autocratic dictatorship.

  4. Anonymous says:

    Good news …, but difficult to overcome entrenched cultures. Living systems are that, “systems”, with interrelating networks, not linear causation.

  5. Anonymous says:

    Dr.Sigston There is no speculation on the genesis of cancer but very robust scientific evidence. When people move out of their comfort zone and even just step over to see what is on the other side of the fence they learn a great deal more. Sometimes we wish we are the on,y people who have all the knowledge, and we are unmatched, but as far as cancer is concerned we must always get our knowledge from the pioneers and trend setters. check out thr You tube presentation of Dr.Douglas Wallace “the mitochondrial etiology of metabolic and degenerative and cancer and aging”forwarded by none other than the NIH director himself.

  6. Dr. Elizabeth Sigston says:

    Anonymous. Thank you for your comment. I have seen the presentation of Dr Wallace which is very enlightening, but this paper is not about stating any specific cause of cancer. It provides a systems based framework for understanding cancer as it occurs in a living organism. Mitochondria as an aetiology fit within this framework as mitochondria are one of the keys that enable living things to metabolism and defy the second law of thermodynamics and they specifically relate to Principles 3, 5, 7 and 11. However mitochondria do not exist outside a system to cause cancer, they are part of it and must interact with the other components. Saying mitochondria are the sole cause of cancer is the same as saying genes are the sole cause. There is no single cause for cancer, it is a number of factors coming together in to create ‘the perfect storm’, the emergence of a cancer system. This framework draws upon a large body of work generated by pioneering scientists, physicists, philosophers and clinicians, including Dr Wallace:
    96. Wallace DC. Mitochondria and cancer. Nat Rev Cancer (2012) 12:685–98. doi:10.1038/nrc3365
    I have simply pulled it altogether into a single practical framework.

  7. Anonymous says:

    Dr. Sigston the purpose of my response is not to prove I am right but to explore what you have proposed in your paper. Firstly philosophers do not use the scientific method and deal issues outside this, it would be same as including theologians in this framework “Lawrence Krause vs philosophers” Swedish academy check it out on You tube. What you are suggesting as a framework has already been verified (thank you educating some of our hard headed medical cadre) in the “China Study” by T. colin Campbell,and he looked at entire societies and people to try and work out what causes cancer. In the “Emperor of all maladies” Siddhartha Mukerjee writes about many many such studies in the American and British context ( being a product of those 2 civilizations). But Wallace takes it to one level beyond and transplants mitochondria from healthy robust cell and re-energises sick and diseased cells. I think that he can show this,so studies can be done to see the reverse, or studies to see how sick cells become malignant through genetic mutations, and can robust healthy cells be made malignant by inducing genetic changes ONLY, I think we both know what the outcome may be! We see this in insitu cells with carcinomatous changes, and they may never go on to become invasive if they have their “engines recharges, cleaned and optimised”, that is what D Wallace was trying to convey- I THINK! But thank you for this wonderful discussion and good luck with your work. It was nice knowing of you.

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