Why Elephants Don’t Get Cancer (As Much)
Elephants don’t get cancer very often.
Is this interesting? Well yes, since they are mammals just like us, but are made up of many more dividing cells. Since cells divide and dividing cells are at risk of becoming cancerous, we would expect larger animals to be at increased risk of cancer.
In the 1970s, epidemiologist Richard Peto proposed what is now known as ‘Peto’s Paradox’, why are large animals not at increased risk of cancer? In 2015, two independent studies finally gave us a partial answer to this biological conundrum of nearly half a century. Here, I will explain Peto’s paradox in lay terms. Don’t worry, I will bring it back to elephants in the end.
Dividing cells can become cancerous.
Most living organisms are made up of cells, ranging from single cellular organisms to enormously complex beings with dozens of different cell types, such as the sloth. The life of a cell revolves around replication. In order to replicate, the cell first prepares itself by replicating all its parts, including its DNA, and then splitting up into two equal cells.
The DNA of the cell is its most precious part, as this sequence of nucleotides we have called A, T, C, and G, outlays the entire blueprint not only of this particular cell, but of all cells within the organism. It is strange then, that it is quite a common occurrence for little mistakes to be made during the replication of DNA. But here comes the shocking news; these mistakes happen on purpose.
Evolution, the adaptation and survival of species in response to changing circumstances, relies on the possibility of change. Now remember, that this mechanism is not beneficial for you as an individual. Evolution happens over multiple generations and doesn’t hold the value of the individual in high regard.
The changes that will gradually appear in our DNA are random at first. Survival of the fittest dictates that changes that lead to a positive outcome will be retained by those individuals having more offspring (i.e. longer legs equals faster running equals not being eaten by a lion and then fathering children). Whereas changes that have negative consequences will eventually be lost if these individuals have no or less offspring.
So, coming back to DNA. In general, mistakes in the replication of our DNA are fixed immediately, by vigilant ‘DNA repair mechanisms’ that can be seen as the quality control officers of our little replication factory. There are also strict mechanisms in place that ensure that the cell only divides when it should. There are even pathways that will force the cell to self-destruct should it be malfunctioning badly or be at risk of uncontrolled replication.
However, with so many cells (there are about 37.2 trillion cells in your body) replicating every day (although replication seed varies wildly between cell types, about 230 billion cells are produced every day in the average adult body) you can imagine that things could go wrong. And they do go wrong. Changes, or mutations, can pile up in a cell and cause some of the control mechanisms to fall away. Especially when the mutations take place in the control mechanisms themselves. Cancer occurs when a cell loses control mechanisms and starts replicating uncontrollably. Rogue cells like this are usually identified by our immune system and killed. Sometimes, however, they are not.
More cells do not equal more cancer.
And this is Peto’s Paradox. Peto noticed that in general, larger animals do not get cancer more frequently then smaller ones. And this is surprising, as large animals have considerably more cells that replicate and each replication opens a window to mutation and the possibility of cancer. Peto postulated that there must be mechanisms in place that protect large animals from cancer.
And as it turns out, he was right. The human gene called p53 is a tumour suppressor gene, it activates when our cells sustain DNA damage and its product either restores the damage or ensures the cell gets killed. Elephants, have not one but twenty copies of this gene in every single cell of their enormous body. When their cells sustain DNA damage, the cell will almost always opt for suicide, as opposed to trying to fix the damage and save the cell. In the case of tumour suppressor genes more is better it seems, because elephants get cancer significantly less than humans do (around 3% compared to over 40%, respectively).
This finding explains Peto’s paradox, at least partially. Scientists agree that there are probably other factors involved in protecting large animals from cancer. A notable difference between larger and smaller mammals is the decreased metabolism of the former. Elephants are known to be rather sluggish, and this sluggishness also affects their cells, which divide at a decreased rate compared to smaller animals.
If anyone reading this is now thinking ‘why the hell do we care about elephant cancer?’. First of all, you are wrong, elephants are magnificent. And second, insights into the origins of cancer, or absence thereof, in other species can significantly improve our understanding of how our own bodies function, and hopefully lead to breakthroughs in the near future.
Abegglen, L. M. et al. J. Am. Med. Assoc.
http://dx.doi.org/10.1001/jama.2015.13134 (2015).
Peto, R., Roe, F. J., Lee, P. N., Levy, L. & Clack, J. Br. J. Cancer 32, 411–426 (1975).
Sulak, M. et al. Preprint at bioRxiv http://dx.doi.org/10.1101/028522 (2015).

