Quantum Physics gave me Brain Cancer

 

At the two-year anniversary of my November 2022 craniotomy (my two-year cranioversary), I’m thrilled to say I can now – with moderate confidence – explain how my brain cancer appeared.  I’m fascinated also that the answer starts with a story of biochemistry and quantum physics, nicely aligned with my undergraduate B. Sc. in Biochemistry with a Physics minor.  My answer may come with bias, but the science checks out.  In today’s post, I include references to appropriate sources but will refer to generally agreed-upon knowledge without reference.  The fast version is that while one of my brain cells was dividing quite normally, a small quantum fluctuation in one proton (hydrogen atom) in one DNA nucleotide caused one copy of the cell to include a single point mutation that changed everything.  This might leave one asking: “what are the chances of that???”, to which I’ll say the chance is non-zero, it’s calculable, but it’s vanishingly small.  If this low chance origin story sounds interesting, read on!  

Note: for those who might prefer to watch and listen, I posted a 1-minute TikTok summary watchable at https://www.tiktok.com/@oligo_stu/video/7433068792760061189 .  It's public, so you can watch even without a TikTok account.  The ~ 5-minute or so read below includes more detail.

Let’s start with my tumour pathology:

After my craniotomy and tumour resection, samples were sent for pathology testing including a variety of tests, including DNA analysis which confirmed my tumour cells contain a genetic sequence alteration described as: IDH1: c. 394C>T p. R132C, a mutation found only in the tumour cells, not elsewhere.  This means that in the instructions that guide the tumour cells in making the enzyme Isocitrate Dehydrogenase in the cell’s cytosol (the “IDH1” part), the coding DNA has a point mutation at position 394 where the nucleotide Cytosine is changed to Thymine (the “c. 394C>T” part).  This impacts the protein that builds IDH1, such that at the 132^nd space in the enzyme’s protein structure, the amino acid Arginine is replaced by Cysteine (the “p. R132C” part, sometimes written as “p. Arg132Cys”).  In the 2021 WHO Classification of Tumors of the Central Nervous System ⁽¹⁾, this IDH1 mutation forms part of the classification of an Oligodendroglioma like mine, and where it begins the rest of the transformation like deletions of small parts of chromosomes 1 and 19, where my tumour includes codeletions of chromosome 1p36 and 19q13 regions which I’ll get to later.

The pathology report says nothing of how this mutation came about, but quantum physics gives me the answer.  In the following sections, I’ll connect DNA nucleotide structures to quantum fluctuations inducing changes between keto and enol forms that create a C>T nucleotide change, and what happens next when that change is in just the ‘right’ spot of the gene encoding IDH1.

Quantum fluctuation and C>T mutations

Many of us may remember learning about the four base pairs in DNA (Adenine, Thymine, Guanine, and Cytosine:  A, T, G and C) and that A and T form pairs, as do G and C, as pictured in the accompanying graphic from Concepts of Biology - 1st Canadian Edition Copyright © 2015 by Charles Molnar and Jane Gair.  Some of us might also know a little of the quantum physics concepts that tell us that atoms and the molecules they form can be described as fluctuating ‘clouds’ of protons, neutrons, and electrons rather than as the fixed points depicted in diagrams like this.

We might not know (or remember) that these nucleotides typically come in one standard configuration – a keto tautomer – but can occasionally shift to the alternate enol tautomer when a proton or hydrogen atom moves.  When a keto nucleotide tautomer shifts to the enol form, it happens at the point where it pairs with its partner, impacting the hydrogen bonding between A and T, C and G.  When quantum fluctuation shifts a Guanine nucleotide from its keto form to its enol form, the hydrogen bonds that usually make it a match for Cytosine now make it a good match for Thymine.  Research has shown that this random fluctuation is short-lived, such that a G·G* DNA base mis-pair between enol and keto tautomers lasts only 8.22 x 10^-10  seconds, at nanosecond or billionth of a second time-frames.⁽²⁾  An enol tautomer of Guanine might be better-stabilized when paired with a Thymine, but this configuration will still be very short-lived!

Getting back to the chance of this happening, several sources will estimate that there are around 30 trillion human cells in an adult body, and that more than 1% of our cells are replaced by dividing each day.  Not all cells divide at the same rate, but that’s a LOT of cell division.  When a cell divides, it must copy the roughly 3 billion base pairs of DNA that form the human genome.  Luckily, the DNA polymerases our cells use to copy our DNA during cell division include error-checking mechanisms such that they make mistakes only on the order of one in a billion nucleotides. ⁽³⁾  These types of mistakes do happen, but with the number of cells dividing in our body and length of DNA in each one, the mistakes often happen in cells and / or sections of DNA that don’t have much downstream impact.  When such a nucleotide substitution does happen, a ‘C to T’ substitution is the most common. ⁽⁴⁾  If the right type of cell in my brain (we’ll get to that in a bit) was dividing and a nanosecond quantum fluctuation caused the Guanine at nucleotide 394 in the sequence coding for IDH1 to convert from keto to enol form at exactly the time the DNA Polymerase was making its DNA copy, the change in Guanine tautomer could have gone ‘un-noticed’ and produced the C>T nucleotide change in the copied strand.  With some quick math we could establish that the chance of this happening in exactly the right cell at exactly the right point in the DNA strand at exactly the right time, we could confirm that it’s a non-zero chance, but vanishingly small enough to make the odds of winning a lottery seem like a near certainty!  Next, I’ll walk through the meaningful impact this unlikely mistake had.

How a C>T change led to Oligodendroglioma.

After poring through articles about my Oligodendroglioma, it seems reasonable to conclude that the C>T change kicked things off, and that this happened in an early oligodendrocyte precursor cell.  I’ll gloss over details here, where during our earliest development, our brains begin growing the tens of billions of neurons that form the more than 100 trillion connections in our brain.  Through these connections, we interpret our external world through our senses, build our thoughts, emotions, and memory, and form our personalities and interactions throughout our lives.  Along with the neurons, our brains grow glial cells which form the structure to support the neurons and insulate them from each other so that the electrical impulses can be controlled.  After early brain cells differentiate themselves and mature into neurons, they do not continue to divide, and most of them continue to live for our full lifespans.  Some early cells differentiate into precursor cells ready to divide and replenish glial cells as needed to maintain our healthy brains through our lifespan.  More general glial precursor cells can differentiate into quiescent oligodendrocyte precursor cells ready to build oligodendrocytes as needed.  These oligodendrocytes form a protective layer for neurons, helping to insulate the electrical impulses from surrounding neurons, and the precursor cells are ready to proliferate and propagate (multiply and move) as needed.

It's plausible that the initial quantum fluctuation-induced C>T mutation happened in such a precursor cell which then drove the transformation into malignant glioma (brain cancer). ^{(4) (5)}  The C>T nucleotide change led to a change in the Isocitrate Dehydrogenase enzyme’s amino acid sequence, so that in the active site where the enzyme catalyzes the conversion of Isocitrate into α-ketoglutarate (AKG) as its usual metabolite, the mutated enzyme produces 2-Hydroxyglutarate (2-HG) instead. ^(6) (7)  This happens because the change in amino acid changes the shape of the final enzyme such that it produces a different output (metabolite), in the way that changing the shape of a machine in a factory assembly line might change the shape of the part it produces.  In the case of the cells now making 2-HG instead of AKG, they have gained a new function, but experience the unfortunate effect that this new 2-HG they produce has oncogenic (cancer-inducing) potential – it is an onco-metabolite.  As 2-HG accumulates, it leads to changes in the extracellular tumour microenvironment while increasing the likelihood of further mutations, such as the loss of portions of the short arm of chromosomes 1 and the long arm of chromosome 19, as described by the 1p36 and 19q13 co-deletion also present in the WHO classification of an oligodendroglioma ⁽¹⁾, such that the resulting cell line was now able to proliferate and propagate with new cells that look like oligodendrocytes and infiltrate the surrounding tissue.

Wrapping it up

To summarize this plausible sequence of events:

• A nanosecond quantum fluctuation took place in just the right type of cell (a glial precursor cell) right when the DNA encoding IDH was being replicated, and it caused a change in nucleotide base pair.
• The resulting C>T mutation caused a change in the amino acid sequence that gave IDH in one of the cell copies, giving it a new capability and leading to further mutations that gave rise to a super-charged cell line ready to multiple and move throughout the surrounding brain tissue.
• After a reasonable but unconfirmed length of time (months / years), I noticed unusual symptoms and sought medical assistance.
• A 2022 MRI showed the resulting tumour growth as an enhancing mass, visible in T2 FLAIR imagery.
• A November 1, 2022 surgery removed about a half cup of tumour (perhaps 80% or more of the bulk) to reduce symptoms, and
• Pathology testing confirmed the downstream impact of that chance nanosecond quantum fluctuation.

As a bold final statement that I take odd pleasure in being able to claim:

“Quantum physics gave me brain cancer.  (what are the chances of that???)”

 

Addendum - November 2nd, 2024

A day after I posted this, I'm adding just a brief addendum to acknowledge that the quantum fluctuation producing a short-lived keto-to-enol configuration change in Guanine isn't the only way that the Cytosine to Thymine mutation could have happened.  Sources of radiation such as high energy gamma ray or subatomic particle from a supernova collapse billions of light years away could have arrived after billions of years at just the right time and in the right place in the right cell.  The same could be said of a stray X-Ray from our Sun's corona, having been emitted from the Sun about 8 minutes and 20 seconds prior, or of several chemicals known to cause a higher rate of point mutations.  Whatever the reason for the C>T mutation, it still comes down to chance, and if we dig deep enough it's connected to the quantum fluctuations in subatomic particles, high-energy electromagnetic waves, or the proton, neutron, and electron clouds that form a molecule that might have found its way to the right cell at the right time.  I posit that the random chance change is still explainable within our understanding of quantum physics, and conclude that this was all an unpredictable chance result.

Works Cited

1. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. 8, Aug 2, 2021, Neuro Oncol., Vol. 23, pp. 1231-1251.

2. How does the long G·G* Watson–Crick DNA base mispair comprising keto and enol tautomers of the guanine tautomerise? The results of a QM/QTAIM investigation. Brovarets, Al'ha O. and Hovorun, M. Dmytro. 30, Kyiv, Ukraine : s.n., May 2014, Physical Chemistry Chemical Physics, Vol. 16, pp. 15886 - 15899.

3. The Molecular Perspective: DNA Polymerase. Goodsell, David S. 2, 2004, Stem Cells, Vol. 22, pp. 236-237.

4. Patterns of nucleotide substitution, insertion and deletion in the human genome inferred from pseudogenes. Zhang, Zhaolei and Gerstein, Mark. 18, 2003, Nucleic Acids Research, Vol. 31, pp. 5338-5348.

5. Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process. Galvao, Rui P., et al. 40, 2014, Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, p. 201414389.

6. NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis. Briançon-Marjollet, Anne, et al. 10, 2010, Carcinogenesis, Vol. 31, pp. 1718 - 1725.

7. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Dang, L., White, D., Gross, S. et al. November 22, 2009, Nature, Vol. 462, pp. 739 - 744.