Cancer. It’s a condition that’s been around almost as long as humanity has. And with all that time, we’ve come a long way in understanding how it works. When it comes to the research and advances we’re making, there’s no better time to be alive. If you have cancer, there’s no better time to be alive.
But, let’s be real.
It used to be a whole lot worse, but cancer still takes about 30,000 lives every day. The machines might look more refined, but they still resort to cutting, burning, or poisoning tumours and hoping they’ll disappear. We’re trying our best, but our best isn’t enough. If we’re talking about a working cure, we’ve barely made a dent.
If, after all our work, millions of people keep dying every year, we shouldn’t blame it on the disease. After all, cancer doesn’t care.
Clearly, something’s extremely wrong with how we’re approaching things — and it’s our fault. The only explanation is that we’ve laid a faulty foundation on cancer, and every treatment and piece of knowledge we’ve built on it isn’t reliable.
That’s an even scarier thought. What if we’ve been fooling ourselves all along? What if cancer was a completely different beast than we’ve prepared ourselves to fight? If it is, what can we do about it?
Let’s talk about that.
Why Is This So Complicated?
Cancer is a genetic disease.
Even if you weren’t herded into that school of thought in high school or university, you probably just know this as common knowledge. Mutations in your DNA lead to cells growing out of control. Bad genes equal cancer. It’s biblical at this point. It’s literally part of how we define it.
But before we run against the grain of that idea, let’s understand what genetic really means here:
In our massive body of scientific knowledge on cancer, we package its origins into what we call the “somatic mutation theory. “
Using observations from thousands of papers on cell behaviour, it traces cancer back to bad genes. It makes a rock-solid case, and it’s one of the most well-supported theories in modern biology. Rightly so, because it makes complete sense.
But, let’s be a bit more specific about this. For starters, we’ll try orienting ourselves by reviewing some cellular geography.
The cells in humans — and every multi-celled organism — fall into the category of eukaryotes (you-care-yotes). For now, we can consider them as large, complex types of cells that can interact with other cells and act as part of a whole.
If you looked at a eukaryotic cell, you’d notice that it’s configured like a nested Matryoshka doll. Inside its large, spherical membrane, you’d see many smaller, membrane-bound “blobs”, called organelles:
Organelles are systems inside cells that serve a specialized function in helping it survive. They include the nucleus (to store DNA), lysosomes (to get rid of waste), mitochondria, and many more that we name with long acronyms and foreign words.
For now, let’s focus on the nucleus. You’ll see it as a large mass near the centre of any cell — housing a stringy clump that’s 1.8 metres (about 6 feet) worth of tightly bundled DNA. These genes help the cell produce proteins and let it divide normally. It’s like being the conductor in an orchestra, or a CEO in a company. If they go crazy, things go downhill pretty fast.
When we’re talking about genetic mutations in the classical theory to cancer, we’re talking about genetic mutations in the nucleus. They’re alterations to the precisely engineered chemical instructions coded into its DNA. By chance, some of those alterations ramp up the cell’s division rate or prevent it from dying. Now, you have a cancer cell. Simple enough.
But here’s where things break down. If nuclear mutations really were the root cause behind cancer, you’d expect every single cancer cell in existence to have at least one nuclear mutation. But they don’t.
Although most cancer cells do have mutations in their nucleus, not all of them do, and that means a lot. The very existence of a cancer cell that doesn’t have nuclear mutations disproves the concept that mutations cause cancer. It tells us there’s something else at play in the formation of a cancer cell. Something other than plain genetic mutations.
Over the thousands of years we’ve been documenting cancer, we put together a shortlist of all the ways we suspected someone could get it. After we studied this on enough people and verified our findings with enough research, we named these factors carcinogens:
If you looked into the background of each and every carcinogen on that list, you’d be pretty surprised about the sheer variety and lack of a defining pattern between them. Cadmium in cigarette smoke, compounds in barbecued meat, toxins in peanuts, and even certain viruses all found their way into that list.
So, for all those years, we tried to answer the question: “How can all these seemingly unique and unrelated factors have the one common trait of causing cancer?” Saying it stumped us would be an understatement. We spent almost five decades trying to figure the answer out.
As it turns out, there really was a pattern to that list. It’s DNA. Almost all every one of these carcinogenic substances can mutate our genetic information. In other words, most carcinogens are mutagens. That realization was the final pillar that gave the somatic mutation theory something to stand on.
Except, when we noticed this curiosity of carcinogenic mutations, we didn’t pay much attention to why any of this happened:
Let’s say you were analyzing a frog with a tumour. What would happen if you isolated one of its cancer cells, and transplanted its nucleus — containing lots of supposedly cancerous mutations — into a new frog embryo?
Considering the somatic mutation theory, it’d be safe to assume that you’d end up creating some cancer cells. If mutations cause cancer, then the expected source of the issue (the nucleus) should turn its new host into a cancer cell. But, we don’t see that.
Alright — but we don’t need to make this hypothetical at all. We’ve already done it. Can you guess what we found?
After implanting the mutated nucleus into a frog embryo with intact mitochondria, not only did it grow properly, but it didn’t develop any signs of cancer. Who would’ve thought? We grew a totally new life form from a cancerous cell — using mutated DNA — and nothing happened:
If you’re feeling iffy about how we tested this on animals and that this isn’t accurate to people, that makes sense. For obvious reasons though, we don’t want to be recreating this sort of test in humans. But to make up for that, we’ve put almost every animal that’s genetically similar to us through this battery of transplants, and checked if they get affected the same way.
You get the exact same results.
Take another nuclear transplant experiment MIT did on mice. In this trial, researchers extracted the nuclei of many different forms of skin and brain cancer and grew dozens of mice with them. If we pull the quote straight out of the team’s results, here’s what we see:
“There was unequivocal genomic evidence that the R545–1 NT ES cell was cloned from a tumorigenic nucleus of the R545 tumor cell line. Furthermore, these characteristic genomic alterations were present in all R545–1 NT ES cell derivatives.”
Even after being proven to harbour negative mutations in their nuclear DNA, the mice still didn’t develop cancer. After stress-testing these embryos, they achieved the same results as we saw with the frogs.
In every possible way, these results contradict the somatic mutation theory. Most of this news broke out over half a century ago, and we aren’t even talking about it.
With this evidence, there’s no logical way that that nuclear mutations could be what drive cancer. At best, those mutations might be correlated to the disease or make it even worse, but they definitely aren’t the cause.
But that begs the question: “If it’s not the nucleus, then what it is?”
Powering Up (Way Too Much).
There’s a growing body of research suggesting a completely different explanation behind why cancer cells go rogue. It starts with a seemingly innocent cellular powerhouse that’s pasted on every biology textbook out there. That’s right — I’m talking about our mitochondria.
Remember how we originally expected that cancer cells to form in our nuclear transplant? Now, imagine we attempted the same sort of organelle transfer, but with mitochondria.
What do you think would happen if we transferred the mitochondria from a cancer cell into a healthy cell? What would happen if we did the reverse?
Going with the somatic mutation theory, we’d expect nothing to change. That’s because we’d think mitochondria don’t have a role to play in cancer. Let’s see if this holds up in real-life.
In a series of cell culture experiments, a group from Baylor University executed a two-way mitochondrial transfer procedure. That means they took mitochondria from cancer cells and inserted them into healthy ones. Meanwhile, they also repeated this the other way around — by replacing the mitochondria in cancerous cells with new set of unscathed ones:
You can be the judge of this. When the researchers transferred cancer mitochondria into a colony of quiescent (slow-dividing) cells, their growth exploded. When they “renovated” a group of cancer cells with healthy mitochondria, their growth stabilized to around zero.
Those quiescent cells became cancerous, but there was a lot more to it than just that. After the mitochondria transfer, their nuclear DNA began mutating.
Think about that for a second. Not only did the mitochondria encourage cell growth, but they lead to changes in a completely separate organelle.
You couldn’t see this happen in our Frankenstein-esque experiments on frogs and mice. Nuclear transplants just lead to more healthy cells. And yet, replacing the mitochondria of a cell changed how it divided, along with the state of its genome. We’ve got something completely different on our hands.
This finally lets us peer into where cancer really comes from. As expected, mitochondria are our prime suspects.
As an organelle, the mitochondrion’s only job is to take substances (substrates) from our body and convert them to energy. On the cellular level, though, energy looks a bit different from what powers your desk-lamp or iPhone. Here, the basic currency for energy’s a molecule called adenosine triphosphate, or ATP.
Don’t get me wrong — the full start-to-finish process of how mitochondria generate energy is really fascinating, but it’s also painfully complex. So, for simplicity’s sake, let’s simplify it down into its two main steps: Glycolysis and oxidative phosphorylation (OXPHOS).
Together, both steps form an extremely efficient fuel generation system for our cells. The end products are free-floating molecules of ATP that store massive amounts of energy in their chemical bonds. When our cells want to run their machinery or divide, they can break up the molecules to get a quick surge of power.
It all starts with glucose, and the magic of Glycolysis. Let me explain.
Glucose is a sugar. It’s not exactly what you’d find in a cake (sucrose), or in an orange (fructose), or in the backbone of your DNA (deoxyribose), but it tastes just as sweet and stores just as much energy.
From a simplified molecular point of view, you could see glucose a chain of six carbon atoms. When glucose from our bloodstream enters our cells, Glycolysis works its magic and snips the sugar into two chains of three carbon atoms, known as pyruvate. This all happens outside the mitochondria:
For about every 200 grams (half a pound) of glucose our cells absorb and cut into pyruvate, they churn out two molecules of ATP in the process. But, as you’ll see later, that’s not the most energy-efficient way of doing things.
That’s where OXPHOS comes in.
OXPHOS is a series of chemical reactions that constantly run in our mitochondria. Using a byproduct produced by Glycolysis, along with a few oxygen molecules, OXPHOS turns our compounds into 36 molecules of ATP. It blows Glycolysis out of the water, and that’s why our cells use it whenever they can.
There’s just one catch. OXPHOS needs oxygen to work, so it can’t work all the time. For example, when you exercise as hard as you can, your blood can’t transport oxygen throughout your body fast enough for OXPHOS to work. When that happens, your body switches its metabolism to Glycolysis so you don’t die instantly.
In usual conditions, you can expect your cells to get 90% of all their ATP from OXPHOS, and about 6% from Glycolysis. That is, if you’re talking about healthy cells.
Cancer cells don’t like that spread very much. Research shows that they modulate their metabolism to get about 20% of their energy from Glycolysis — even when they have enough oxygen around them to use OXPHOS.
In the early 1930’s, German biochemist Otto Warburg noticed this method in action and decided to call it the Aerobic Glycolysis. The term literally translates to Glycolysis in the presence of oxygen. Since Warburg won a Nobel Prize for his work later on, we better know this property of cancer as the Warburg effect:
The Warburg effect is partly why tumours cells have low oxygen levels (oxygen saturations) inside them. They opt for the less efficient method, even though they have a better choice of energy. With the somatic mutation theory, we didn’t have a reasonable explanation on why they’d do that.
But now, we have a really compelling one. What if cancer didn’t choose Aerobic Glycolysis? What if it was forced to rely on the less efficient method instead?
What do I mean? Well, OXPHOS needs the mitochondria to function. Damage to a cell’s mitochondria makes OXPHOS impossible.
Now, the cell can’t use oxygen and glucose for energy, and has to rely on Glycolysis to survive — even if there’s oxygen around. Sound familiar? That’s Aerobic Glycolysis, and it’s where cancer begins.
But don’t take my word for it. Otto Warburg described it himself in his research:
“The prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.” — Otto Warburg.
He fully believed that damage to mitochondria handicapped the OXPHOS pathway and forced cells into Aerobic Glycolysis.
What’s the proof?
Almost every single carcinogen is a mutagen, and not all cancers have mutated DNA. That doesn’t make the strongest case for the somatic theory. But, every carcinogen shares the ability to damage mitochondria. Every single cancer cell shares damaged mitochondria. There isn’t an exception to that:
The HPV virus binds to sites in the mitochondria and disrupts its ability to generate energy with oxygen. Asbestos wrecks the geometry of your mitochondria and disrupts its ability to generate energy with oxygen. Arsenic puts your mitochondria through high levels of stress, and…you guessed it — disrupts their ability to generate energy with oxygen:
Also, as a side-effect of the inefficiency of Glycolysis, a cancer cell would need to take in 18x more glucose to get the same amount of ATP.
As expected, another hallmark of cancer is an intense hunger for sugar.
Connecting The Dots
How does all this lead to uncontrolled cell growth? The short answer is that it’s forced, too. Everything’s forced in cancer.
Before a cell divides, it’s got to grow to about twice its original volume and generate twice as many organelles. If cells didn’t do that, they’d get smaller and smaller with every division. But where do cells get all those raw materials to grow so big?
Healthy cells tend to slowly stockpile resources to divide from their environment. That’s why they divide slowly.
Cancer cells handle the situation in their own way. They have to grow bigger, since they’re absorbing so much glucose that they can’t store it all. That’s why cancer cells integrate those excess glucose molecules into their structure and expand. They have to grow, because they’re forced to eat so much more than they should:
Here’s the issue. By the time a cell gets to the right size, growth processes in the cell make division almost automatic. The cancer cell can’t control that, either. The best it can do is prepare for when it’ll eventually get big enough and divide.
If you think of DNA using the common analogy of a twisted ladder, a cancer cell would need to construct 6 billion new rungs (base-pairs) out of thin air to divide normally. That makes cancer cells really, really desperate for DNA. There’s just one problem. DNA’s almost entirely made of nitrogen, but glucose doesn’t have any nitrogen in it:
But you know what does have nitrogen in it? Proteins. To be more exact, cancer cells use a protein building block (amino acid) called glutamine.
Because they constantly need those fuels to survive, cancers can never get enough of them. It’s why people with cancer have low blood-glucose levels and low muscle mass. As the cancers keep doubling in size and number, they constantly feed off of neighbouring tissues for glucose and cannibalize on their muscles for glutamine.
There’s the common misconception that cancer cells are out to get us. They aren’t. All they’re doing is taking the most logical course of action after they couldn’t get enough energy. If they didn’t do that, we wouldn’t have any cancer patients because we’d all be dead.
One more thing. If you’re wondering where those nuclear mutations came from after our mitochondrial transfer experiment, there’s an answer to that, too. When our mitochondria get damaged, they release a unique group of cellular compounds called Reactive Oxygen Species (ROS):
ROS describes hydrogen peroxide and oxygen atoms that can wreak havoc on the delicate internal structure of cells. That’s exactly why mitochondrial mutations can lead to gene alterations in the nucleus. They’re the same mutations we use to support somatic mutation theory. We just don’t look at the tiny organelle that toppled over the first domino:
Cancer isn’t genetic. It’s metabolic. This isn’t an alternative explanation to cancer. This is the explanation to cancer.
Why does this matter? Because we might be killing people without even knowing what we’re doing.
The act of putting someone through anaesthesia for cancer surgery increases their blood glucose levels from stress. The steroids we inject patients with after the surgery increases their protein and glutamine levels. No one has a clue, and it’s all because we don’t pay attention to the basics.
Most drugs for cancer barely work, and some make the disease worse. The few that actually work accidentally find ways to rehabilitate our mitochondria. Imagine where we’d be if we just targeted the cells at their source instead of hitting them indirectly.
If we don’t know even understand how cancer even develops, how can we create reliable cures to it without a fluke? We can’t. This is what we’re missing, and it isn’t rocket science.
I’m not a conspiracy theorist, and I hope this article didn’t come off that way. If this means anything, we’ll have to clear our minds and rethink the situation. At the very least, let’s just think for ourselves.
It’s back to square one for cancer, but it’s better late than never.
Thanks for reading,
If you have any questions or rebuttals against my points, email me at email@example.com or reach out to me on LinkedIn. I’ll answer ASAP.