When Is A Disease Not A Disease?

Today we’re moving out of the arena of strict palaeopathology and instead we’re going to look at something a little different. The topic is evolutionary medicine, which is in part the study of how diseases have evolved and how we have evolved in response. So we’ll start with a question: when is a disease not a disease?

Most of us probably have a fairly solid idea of how we would define a ‘disease’, it would probably involve something caused by bacteria, viruses or even fungi invading the body and triggering a response, but there are also some diseases that aren’t the result of outside invaders. Sometimes our bodies go wrong, and this can be the result of inheriting a faulty gene which means our body can’t manufacture a specific protein, or has developed incompletely. Many of these diseases are debilitating and often sadly lethal but from an evolutionary perspective they are also something of a paradox. If a mutated gene kills its hosts then how is it that this gene has persisted in the population for so long? For example think of cystic fibrosis, a disease caused by inheriting two copies of a faulty recessive gene which causes a build-up of mucus in the lungs and digestive system. It is fatal, and although improving medical treatments have drastically improved life expectancy and quality of life, historically sufferers would have died before reaching reproductive age. It is easy, biologically speaking, to imagine how this disease first evolved as an error in one tiny strand of the host’s DNA, but it is much harder to imagine how it has persisted. Even though carrying only one copy of the damaged gene is not fatal it dramatically increases your risk of having one or more children with cystic fibrosis, and that should mean statistically that you have a reduced chance of healthy grandchildren to carry your genes into posterity. In evolutionary terms this should cause the cystic fibrosis genes to be gradually filtered out of the population at large. Diseases like this can therefore be seen as a challenge to current evolutionary thinking but the apparent paradox instead led to an intriguing theory. What if there is actually an advantage to these diseases? What if instead of being errors they are actually adaptations?

Normal and sickle red blood cells under the electron microscope. Source: Wikipedia

In order to illustrate this concept a little more clearly we’re going to move away from cystic fibrosis for a moment (although we’ll come back to it later) and look at a totally different condition entirely. Sickle cell anaemia is another disease caused by a gene malfunction and if you carry two copies of the faulty DNA strand then you will develop red blood cells that are curved like a sickle. Normal red blood cells are flat and round and pass through your tiny veins and capillaries with no problems but the sickle-cells get stuck. They also have damaged haemoglobin (the molecule responsible for carrying oxygen) and therefore reduce the amount of oxygen available to your muscles and tissues. It can be quite serious causing lethargy, excessive tiredness and breathlessness. Interestingly though it is far more common in some populations then others for instances those of African, Caribbean, Middle Eastern and Asian descent seem far more likely to carry the defective gene then Western Europeans, and there turns out to be a very good reason for this. That reason is malaria. Malaria is a parasitic infection caused by Plasmodium, a genus of single-celled organisms spread by the bite of infected mosquitoes. Once they infiltrate a human the parasites migrate to the red blood cells where they begin to reproduce and spread causing a constellation of serious symptoms which can be fatal. According to statistics from the World Health Organisation a child in Africa dies from malaria every minute which is a shocking mortality rate and illustrates just how severe this disease is. Bearing that in mind we return to sickle-cell anaemia because it turns out that if you carry single copy of the sickle-cell gene you are resistant to malaria. It doesn’t mean you’ll never contract it, but it does mean your symptoms will be far less serious and in evolutionary terms that means you will have more children and pass those genes on to them at the expense of your un-mutated competitors. This advantage is enough to allow the sickle-cell gene to survive and thrive within populations where malaria is endemic because the protection it conveys outweighs the risk of having a child born with the debilitating anaemia. Alternatively in places were malaria is virtually unknown any sickle cell anaemia-causing mutation would be penalised by natural selection and would rapidly die out.

Did the coming of farming cause anaemia in Northern Europe? Source: Wikimedia Commons

Since the discovery of the connection between sickle-celled anaemia and malaria there has been a great deal of interest in the potential link between other diseases and the unexpected advantages they might confer, but few have been uncontroversial. The water gets even muddier when you look further back into our evolutionary history. An example from the palaeontological record is hemochromatosis. This is a condition caused by faulty genes which causes a build up of excess iron in the blood. You can almost think of it as the opposite of normal anaemia, which is a lack of iron, but it can cause joint damage and even organ failure if left untreated. How could something like that possibly be adaptive? Well the argument is that it isn’t, not any more, but once it was. Statistically the disease is far more common in Europeans, especially the Irish and Scandinavians and so researchers looked for a local explanation and they found one. During the last Ice Age the hunter-gatherer populations living in these areas mostly subsisted from whatever they could hunt. Their diets were full of red meats and therefore correspondingly rich in iron but then, in the blink of a geological eye, farming came to Northern Europe and with it white meats and grains. Iron levels in food plummeted and this could have easily led to wide spread deficiencies and anaemia. Any way of scavenging more iron from food or retaining it more efficiently would have been a tremendous advantage and so, the theory states, that is exactly what happened. Now though with our better diets and lack of widespread famine in Western Europe what was once an advantage can be fatal.

So what about cystic fibrosis? Well believe it or not this terrible disease might actually have first arisen for very similar reasons to sickle-celled anaemia. Back in 2006 researchers from Yale University in the US announced that they had discovered that carrying a single copy of the cystic fibrosis gene actually conferred protection against tuberculosis. This bacterial infection of the lungs used to be rife across much of the world and historically is known better as ‘consumption’. Despite our sometimes romanticised view of the illness it is a lingering, painful disease that causes victims to die coughing up blood and it killed thousands in Europe alone. It is still endemic today in many countries and in that light it is a little easier to see how a gene that could protect you against such a contagion might have evolved and persisted, even when it causes such suffering to people unlucky enough to inherit two copies. The risks of tuberculosis far outweighed the evolutionary risks of cystic fibrosis.

This then is a very brief overview of a vast and nuanced subject and naturally much of this is speculative but it is also intriguing and important. We must never lose sight of the fact that these are real world diseases that cause tremendous suffering but by placing them in their evolutionary context we can begin to understand them. If we really want to treat these conditions we need to know where they come from and this kind of research also offers a novel way of thinking about human health and disease.



  1. Luzzatto, L., 2012. Sickle Cell Anaemia and Malaria. Mediterranean Journal of Hematology and Infectious Disease. DOI: 10.4084/MJHID.2012.065
  2. Naugler, C., 2008. Hemochromatosis: A Neolithic Adaptation to cereal grain diets. Medical Hypotheses. 70(2). DOI: 10.1016/j.mehy.2007.06.020
  3. Poolman, E.M., & Galvani, A.P., 2007. Evaluating candidate agents of selective pressure for cystic fibrosis. Royal Society; Interface. DOI: 10.1098/rsif.2006.0154

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