The Cancer Resolution?

Link post

Book review: The Cancer Resolution?: Cancer reinterpreted through another lens, by Mark Lintern.

In the grand tradition of outsiders overturning scientific paradigms, this book proposes a bold new theory: cancer isn’t a cellular malfunction, but a fungal invasion.

Lintern spends too many pages railing against the medical establishment, which feels more like ax-grinding than science. I mostly agreed with his conclusions here, but mostly for somewhat different reasons than the ones he provides.

If you can push through this preamble, you’ll find a treasure trove of scientific intrigue.

Lintern’s central claim is that fungal infections, not genetic mutations, are the primary cause of cancer. He dubs this the “Cell Suppression theory,” painting a picture of fungi as cellular puppet masters, manipulating our cells for their own nefarious ends. This part sounds much more like classical science, backed by hundreds of quotes from peer-reviewed literature.

Those quotes provide extensive evidence that Lintern’s theory predicts dozens of cancer features better than do the established theories.

Older Theories

  1. The DNA Theory (aka Somatic Mutation Theory): The reigning heavyweight, this theory posits that cancer results from an accumulation of genetic mutations in critical genes that control cell growth, division, and death.

  2. Another old theory that still has advocates is the Metabolic Theory. This theory suggests that cancer is primarily a metabolic disease, characterized by impaired cellular energy production (the Warburg effect). It proposes that damage to mitochondria is a key factor in cancer development. I wrote a mixed review of a book about it.

Lintern points out evidence that mitochondria are turned off by signals, not damaged. He also notes that tumors with malfunctioning mitochondria are relatively benign.

Evidence Discrediting the DNA Theory

The standard version of the DNA Theory predicts that all cancer cells will have mutations that affect replication, apoptosis, etc.

Around 2008 to 2013, substantial genetic data became available for cancer cells. Lintern wants us to believe that this evidence fully discredits the DNA Theory.

The actual evidence seems more complex than Lintern indicates.

The strongest evidence is that they found cancers that seem to have no mutations. [Updated 2024-07-25: DirectedEvolution suggests that this evidence isn’t very strong.]

Almost as important is that the mutations that are found seem more randomly distributed than would be expected if they caused consistent types of malfunctions.

Lintern’s theory seems to explain all of the Hallmarks of Cancer, as well as a few dozen other features that seem to occur in all cancers.

He argues that the DNA Theory does a poor job of explaining the hallmarks. DNA Theorists likely reject that characterization. They appear to have thought their theory explained the hallmarks back before the genetic data became available (mostly just positing mutations for each hallmark?). My guess is that they are busy adding epicycles to their theory, but the situation is complex enough that I’m having trouble evaluating it.

He also points out that the DNA Theory struggles with Peto’s Paradox (why don’t larger animals get more cancer?), while his theory neatly sidesteps this issue.

Additionally, mouse embryos formed from cancer cells showed no signs of cancer.

Evidence of Fungi

A key game-changer is the growing evidence of fungi in tumors. Until 2017, tumors were thought to be microbe-free. Now? We’re finding fungi in all types of cancer, with tumor-specific fungal profiles.

There’s even talk of using fungal DNA signatures to distinguish cancer patients from healthy individuals.

It’s not a slam dunk for Lintern’s theory, but it shifts the odds significantly.

Medical Establishment Inertia

It looks like people in the medical mainstream respond respectfully to the ideas in the book, when they react at all. Yet the DNA Theory seems to remain the prevailing dogma. The shortage of reactions to Lintern is disappointing.

My impression is that researchers are hedging their bets when they can conveniently do so, but many of them have built careers that depend on the DNA Theory.

It’s possible that some important parts of the establishment are pivoting their research in the directions that Lintern suggests, and are being quiet until they have something worth publishing.

It seems likely that some parts of the establishment are treating the DNA Theory as a religion rather than a theory. I can’t tell how widespread that problem is.

Possibly some apathy toward fungal infections is because solutions are somewhat less likely to involve patentable treatments. But there’s still some room for patenting new anti-fungals, so I doubt that this is the primary obstacle to accepting Lintern’s theory.

Paul Ewald’s book Plague Time anticipated some of Lintern’s claims, arguing that pathogens are the root cause of many chronic diseases. It was published in 2000, and overlooks fungi (little of Lintern’s evidence was available then). Ewald’s reasoning is more theoretical than Lintern’s.

My limited attempt to spread Ewald’s theory stopped when someone pointed to evidence that mice raised in a sterile environment developed most of the same chronic diseases. Lintern counters that there are many microbes that aren’t detected by the tests that supposedly confirmed that the mice were microbe-free, so we should wonder whether the experiments demonstrated much. I feel foolish for not wondering about that 20+ years ago.

This reminds me of how long it took to refute the theory of spontaneous generation, due to mistaken beliefs about what it took to create a sterile environment.

Lintern reports that fungal infections have also been implicated in Parkinson’s disease and multiple sclerosis, yet many sources still say we don’t know the causes of those diseases. Is there a pattern here?

I often say to myself that much of the medical establishment acts as if they believe our bodies are the result of semi-intelligent design rather than evolution. E.g. their disinterest in a paleo diet. This book reinforced that impression.

Experimental History has some relevant comments about the state of cancer research.

Many Cancers?

Maybe parts of the medical establishment have rejected the whole idea of a theory of cancer.

Researchers who try to take the DNA Theory seriously end up confused by the variety of different mutations that they end up studying. This focus makes it hard to see the similarities between tumors.

I’ve seen many denials that cancer is a single disease. I see a good deal of tension between those denials and the DNA Theory. And don’t the Hallmarks of Cancer point to it being a single disease?

Ironically, Lintern advocates a single-disease model, even though his theory implies that a wide range of different fungi are responsible. Presumably many different anti-fungals are needed for the different types of fungi. So in some sense the many-cancers view is likely to be partly correct.

Implications for Treatment

Lintern doesn’t offer much hope for reliable cures. He offers many somewhat new ideas for treatments that will sometimes work. The most obvious ones are anti-fungal drugs.

Progress at treating diseases that are known to be fungal infections may be a bit better than progress at curing cancer, but deaths from fungal infections have still been increasing.

Much of Lintern’s advice for people who have cancer now consists of standard recommendations to adopt a healthy lifestyle. That shouldn’t be surprising: if most chronic diseases are due to pathogens, there will be plenty of overlap in strategies for fighting them.

That includes a long section on the benefits of organic food. I was unimpressed by how it started, with a correlational study that likely had confounders that couldn’t reasonably be controlled for. But he made up for that by explaining several causal models that I hadn’t previously considered.

E.g. fungicides. Indiscriminate use of fungicides on non-organic crops means that there are fewer beneficial fungi which provide nutrients to the plant, leading the plant to have less nutritional value. More importantly, plants defend themselves against fungi, similar to the fungi that endanger us, by generating anti-fungal compounds that are well targeted against those fungi. Organic foods have more of those anti-fungals, because they’re produced in reaction to fungal attacks. Those anti-fungals sometimes work in our bodies when we eat them.

I ended up deciding to give slightly higher priority to buying organic food.

Lintern suggests that chemotherapy is generally a bad idea. One clear reason is that it damages the immune system, and the immune system is the main defense against additional cancers. But he still supports it in cases where it shrinks the tumor enough to enable surgery. I continue to be concerned about how hard it would be to evaluate a doctor’s recommendation to get chemotherapy.

What does Lintern’s theory mean for Aubrey de Grey’s proposed cure for cancer (WILT)? That looks much less promising now. WILT no longer looks like it addresses the root cause of cancer. Even if Lintern’s theory is somewhat wrong, cancer stem cells now seem much more important than regular cancer cells as a source of excessive cell replication. Cancer stem cells don’t depend on telomerase in the way that other cells do. It looks like Aubrey has a new version WILT 2.0 which does something to address cancer stem cells. What little I understand of it leaves me skeptical.

The good news is that cancer rates can likely be reduced to roughly the rates seen in young adults if other parts of Aubrey’s plan work, particularly the parts that affect the immune system.

Concluding Thoughts

There’s actually an important similarity between the DNA Theory and Lintern’s theory. In both, eukaryotic cells have evolved to serve their own interests, in ways that conflict with the host’s interests. The key difference is when that evolution started: years before the cancer was detected, or millions of years?

Evolutionary theory should create a moderate presumption that hostile organisms do more harm to our bodies than do mistakes.

Lintern’s theory seems to have more explanatory power than any other theory.

Whether or not Lintern is entirely correct, his work highlights two crucial points:

  1. We shouldn’t demand that all proposed cancer treatments conform to the DNA Theory.

  2. We need to rethink how we evaluate the effectiveness of cancer treatments. There’s large room for improvement in the choice of criteria without adopting a strong opinion on which theory of cancer is correct. The evidence concerning cancer stem cells seems like a strong argument against relying on tumor shrinkage as evidence of success.

At one level, scientists have failed badly at explaining cancer, and it seems like only an outsider was able to point out that the emperor has no clothes.

But that’s at the level of broad theory. At the level of small experiments, the medical establishment has been diligently uncovering plenty of evidence to reject the DNA Theory and to focus some attention on pathogens.

The book isn’t as professionally written as I’d like. E.g. he sometimes cites news stories instead of the peer-reviewed papers on which the stories are based.

Parts of the book are difficult to read. Most people should feel free to skip parts of the book, mainly after page 250.

H/​T Dave Asprey.