# The Cancer Resolution?

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](https://en.wikipedia.org/wiki/Warburg_hypothesis)). It proposes
that damage to mitochondria is a key factor in cancer development. I
wrote a [mixed
review](https://bayesianinvestor.com/blog/index.php/2019/04/13/the-metabolic-theory-of-cancer/)
of a book about it.

Lintern points out evidence that mitochondria are [turned off by
signals](https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14446),
not damaged. He also notes that tumors with malfunctioning mitochondria
[are relatively
benign](https://www.cell.com/molecular-cell/fulltext/S1097-2765(16)00095-2).

### 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](https://www.lesswrong.com/posts/wj6A9ExXiHuNdJN4n/the-cancer-resolution#u3wtsZdi9KRNgdSS8) 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](https://aacrjournals.org/cancerdiscovery/article/12/1/31/675608/Hallmarks-of-Cancer-New-DimensionsHallmarks-of),
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](https://en.wikipedia.org/wiki/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](https://aacrjournals.org/cancerres/article/63/11/2733/510012/Mouse-Embryos-Cloned-from-Brain-Tumors1).

### 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](https://www.weizmann.ac.il/mcb/Straussman/research-activities/tumor-microbiome),
with tumor-specific fungal profiles.

There's even talk of using fungal DNA signatures to [distinguish cancer
patients from healthy
individuals](https://www.nature.com/articles/s41392-023-01334-6).

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](https://www.goodreads.com/book/show/469489.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](https://en.wikipedia.org/wiki/Spontaneous_generation#Early_tests)
about what it took to create a sterile environment.

Lintern reports that fungal infections have also been implicated in
[Parkinson's
disease](https://www.pnas.org/doi/full/10.1073/pnas.1318830110) and
[multiple sclerosis](https://pubmed.ncbi.nlm.nih.gov/20214953/), 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](https://www.experimental-history.com/p/whos-got-the-guts-to-go-to-the-moon)
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](https://daveasprey.com/mark-lintern-1155/).