Cancer is our biggest biological killer. In the process of trying to understand cancer and get better at killing it, scientists discovered a biological paradox that remains unsolved to this day: large animals, like whales, seem to be immune to cancer, which doesn’t make any sense. What is it about whales that makes them immune to cancer? If we know the secret to whales’ success, can it be applied to humans? To unpack this mystery, we first need to take a look at the nature of cancer itself.
Our cells are made out of hundreds of millions of parts. Guided only by chemical reactions, they create and dismantle structures, sustain a metabolism to gain energy, and reproduce themselves. With billions of trillions of reactions happening in thousands of networks over many years, tiny mistakes add up until the grandiose machinery gets corrupted. To prevent this from getting out of hand, our cells have kill switches that make them commit suicide. But these kill switches are not infallible. Most abnormal cells are slayed by the immune system very quickly, but when the switch fails, a cell becomes a cancer cell. It’s a numbers game. Given enough time, a cell can make enough mistakes to slip away unnoticed and start making more of itself.
All animals have to deal with this problem. In general, the cells of different animals are the same size. The cells of a mouse aren’t smaller than humans, and it just has fewer cells in total. Normally, it makes sense to think that fewer cells and a short life mean a lower chance of things going wrong. However, that is not the case. Humans live about 50 times longer and have 3,000 times more cells than mice, yet the rate of cancer is basically the same in humans and in mice. Not to mention, blue whales with about 3,000 times more cells than humans don’t seem to get cancer at all. Despite evidence that larger individuals within a single species are more likely to develop cancer, there appears to be no correlation between body size, longevity and cancer across species. This is Peto’s paradox. The baffling realization that large animals have much less cancer than they should.
Scientists think there are two main ways of explaining the paradox.
As multicellular beings developed 600 million years ago, animals became bigger with more cells, hence the greater chances that cells could be corrupted. Therefore, they must invest in better and better cancer defense systems. Those who didn’t, became a blob of cancer.
The process of cancer involves many individual mistakes and mutations in several specific genes, called proto-oncogenes, within the same cell. However, these oncogenes have an antagonist, tumor suppressor genes. They prevent critical mutations from happening. It turns out that large animals have an increased number of them. Because of this, elephant cells require more mutations than mice cells to develop a tumor. They are not immune but more resilient. This adaption probably comes with a cost in some form but researchers still aren’t sure what it is.
But the solution to the paradox may actually be something different, such as hypertumors. Cancer cells are selfish and only work for their own short-term benefit. Although tumors can be very hard to kill, making a tumor is hard work as well. Billions of cancer cells trick the body to build new blood vessels to sustain rapid mutation. Here, the nature of cancer cells may become their own undoing.
Some rapidly mutating cells may stop cooperating at some point. This means that the original tumor suddenly becomes an enemy, competing for equally scarce nutrients and resources. Thus, newly mutated cells can create a hypertumor. Instead of helping, they cut off the blood supply to their former buddies, which will starve and kill the original cancer cells. Cancer is killing cancer. This process can repeat over and over, and this may prevent cancer from becoming a problem for a large organism.
Cancer has always been a challenge. Figuring out how large animals are so resilient to one of the deadliest diseases we know, could open the path to new therapies and treatments. There are other proposed solutions to Peto’s paradox, such as different metabolic rates or different cellular architecture. But we haven’t found out which one is the correct answer. Nevertheless, we are making strides towards understanding cancer, and by doing so, one day we might finally overcome it.
Our cells are made out of hundreds of millions of parts. Guided only by chemical reactions, they create and dismantle structures, sustain a metabolism to gain energy, and reproduce themselves. With billions of trillions of reactions happening in thousands of networks over many years, tiny mistakes add up until the grandiose machinery gets corrupted. To prevent this from getting out of hand, our cells have kill switches that make them commit suicide. But these kill switches are not infallible. Most abnormal cells are slayed by the immune system very quickly, but when the switch fails, a cell becomes a cancer cell. It’s a numbers game. Given enough time, a cell can make enough mistakes to slip away unnoticed and start making more of itself.
All animals have to deal with this problem. In general, the cells of different animals are the same size. The cells of a mouse aren’t smaller than humans, and it just has fewer cells in total. Normally, it makes sense to think that fewer cells and a short life mean a lower chance of things going wrong. However, that is not the case. Humans live about 50 times longer and have 3,000 times more cells than mice, yet the rate of cancer is basically the same in humans and in mice. Not to mention, blue whales with about 3,000 times more cells than humans don’t seem to get cancer at all. Despite evidence that larger individuals within a single species are more likely to develop cancer, there appears to be no correlation between body size, longevity and cancer across species. This is Peto’s paradox. The baffling realization that large animals have much less cancer than they should.
Scientists think there are two main ways of explaining the paradox.
As multicellular beings developed 600 million years ago, animals became bigger with more cells, hence the greater chances that cells could be corrupted. Therefore, they must invest in better and better cancer defense systems. Those who didn’t, became a blob of cancer.
The process of cancer involves many individual mistakes and mutations in several specific genes, called proto-oncogenes, within the same cell. However, these oncogenes have an antagonist, tumor suppressor genes. They prevent critical mutations from happening. It turns out that large animals have an increased number of them. Because of this, elephant cells require more mutations than mice cells to develop a tumor. They are not immune but more resilient. This adaption probably comes with a cost in some form but researchers still aren’t sure what it is.
But the solution to the paradox may actually be something different, such as hypertumors. Cancer cells are selfish and only work for their own short-term benefit. Although tumors can be very hard to kill, making a tumor is hard work as well. Billions of cancer cells trick the body to build new blood vessels to sustain rapid mutation. Here, the nature of cancer cells may become their own undoing.
Some rapidly mutating cells may stop cooperating at some point. This means that the original tumor suddenly becomes an enemy, competing for equally scarce nutrients and resources. Thus, newly mutated cells can create a hypertumor. Instead of helping, they cut off the blood supply to their former buddies, which will starve and kill the original cancer cells. Cancer is killing cancer. This process can repeat over and over, and this may prevent cancer from becoming a problem for a large organism.
Cancer has always been a challenge. Figuring out how large animals are so resilient to one of the deadliest diseases we know, could open the path to new therapies and treatments. There are other proposed solutions to Peto’s paradox, such as different metabolic rates or different cellular architecture. But we haven’t found out which one is the correct answer. Nevertheless, we are making strides towards understanding cancer, and by doing so, one day we might finally overcome it.
