The Human Genome Project (HGP), an international research project aimed at mapping all of the genes that make up the human genetic make-up, held much promise. Many scientists and laypeople alike were convinced that we would finally get the answers we need to effectively treat cancer, heart disease, and many other health conditions. The disappointment was huge when it was realised that this was not going to happen. Genetic analyses showed that the theory that many common diseases are caused by mutations in just one or a couple of genes was highly flawed. That doesn’t mean that genetics aren’t important in health and disease; however, it does mean that we should abandon old, invalidated theories related to the genetics of disease in favor of ones that are more scientifically sound…
Few diseases are caused by a single genetic mutation
The results of the HGP and other genetic studies have shown that, in most cases, there isn’t any clear relationship between single genes and individual diseases. It has been firmly established that some diseases are caused by a single gene, but these conditions, classified as single gene disorders, are very rare.
For common diseases such as colon cancer, type-2 diabetes, acne vulgaris, and cardiovascular disease, the picture is much less clear. Associations have been found between these conditions and different alleles – variants of a gene – but these associations tend be weak: not everybody who has the allele will necessarily get the disease, and even if you don’t have the allele, you’re not immune to the disease.
For example, obesity is associated with several different genes, but no clear pattern has been established. Some obese individuals have mutations in the Melancortin-4 Receptor Gene (MC4R); others don’t have these mutations, but instead carry other so-called “obesity genes”; and yet others may be obese even though they don’t seem to be genetically prone to developing the condition.
Single genetic mutations can, by itself, induce obesity, but this happens very rarely. Polygenic obesity, a type of obesity that is associated with a number of different genes, represents the vast majority of cases of obesity worldwide. Monogenic obesity (the condition that is triggered by a single gene), on the other hand, is very rare.
Some people may find it surprising to hear that there is no clear genetic basis for most diseases. The idea that when we get sick, “bad genes” are to blame, is so ingrained in the mind of some people that they find it hard to change how they think about health and medicine. Often, they don’t want to change their mindset. After all, it’s much easier to just blame it all on something they have no control over, their genetic make-up that is, rather than having to admit that the reason they got sick is that they haven’t been taking proper care of their body.
People blame everything on genes: the excessive fat they carry around their hips, their bad heart, and their inability to eat healthy. In rare cases, one or a couple of genes are indeed to blame; however, most of the times, the genes don’t actually pull the trigger, they just load the gun.
What happens when you put ancient genes in a novel environment?
So, why do we get sick? If bad genes are not to blame, what is?
Some scientists and health practitioners have been surprised by the fact that, after years of genetic research, a solid link between genes and disease has only been found for some rare diseases. However, others, in particular evolutionary biologists and people who are involved in the emerging field of Darwinian Medicine, have not been surprised by this. The difference between these people and the ones who cling(ed) to “the genetic theory of disease”, is that the former uses an evolutionary model to guide their understanding of health and disease.
The finding that most diseases and chronic health problems have no clear genetic basis is not surprising when we consider the fact that many, if not most, of the chronic health conditions that affect contemporary human populations were rare in the past. A large body of evidence shows that hunter-gatherers (both contemporary and ancient) and traditional, non-westernized people rarely or never get colon cancer, heart disease, and many of the other chronic diseases that today claim hundreds of thousands of lives every year (1, 2, 3, 4). Even among the elderly part of these traditional populations, degenerative disease is rare.
When we think about, this isn’t really surprising. Back in Paleolithic times, physical fitness was tightly linked with reproductive fitness. If you weren’t fit enough to hunt and gather for food, evade dangerous animals, and fight-off pathogenic microorganisms, you didn’t make it very long, and hence, you didn’t get to pass on your genetic material to future generations.
The reason ancient humans didn’t get type-2 diabetes or breast cancer isn’t that they carried a different genetic make-up than modern humans, but rather, that their genes were operating in a different environment. The human genome has changed relatively little over the past 12.000 years. We’re all hunter-gatherers at our core. Our environment (including our microbiomes, which could be considered to be a part of the environment), on the other hand, has changed dramatically.
Most of the genes that have been linked with obesity, myopia, and so forth are not new. They haven’t magically appeared over the past couple of centuries – a period of time in which there has been a rapid rise in the incidence of obesity, diabetes, and many chronic health conditions. Rather, they have been with us for a long time. The reason preagricultural hunter-gatherers didn’t get myopia isn’t that they were genetically immune to the disease, but rather that they didn’t express their genes in such a way that this disorder of the eye had a chance to developed.
The current conditions in which the human eyes operate differ markedly from those in which they evolved. It’s only very recently – on an evolutionary time scale – that we humans developed a written language, started reading and writing, invented computers and mobile phones, and moved indoors. Our eyes now find themselves in a novel environment that natural selection never prepared them for. They’ve ceased to function according to “design” because they are no longer getting the stimuli they depend on to function appropriately.
Unlike our primal forebears, which spent their days outside, exposed to the sun, and used their eyes to gaze at far-away objects, most people today spend almost all of their time indoors, looking at a computer screen that’s placed about a meter in front of their face. Perhaps needless to say, this has caused a mismatch between our environment and the genes that are involved in the regulation and development of our eyesight; a mismatch that manifests itself as myopia and other disorders of the eye (5, 6).
It’s how you express your genes that matters the most
All diseases are caused by genes. Everything that goes on inside your body happens as a result of the expression of genes. When you’re inflamed, your genes are to “blame”, in the sense that they code for the inflammatory cytokines that circulate in your body. When you are in a great mood, genes are (partly) to blame, because without genes, there wouldn’t be any production of dopamine, serotonin, or other “happy hormones”.
The key thing to understand though is that our gene expression pattern is not set in stone. How we express our genes largely depends on what kind of stimuli we subject our body too. Just because a gene, or a set of genes, have the potential to make us sick, doesn’t necessarily mean that they will. It all depends on the instructions they receive.
In the discussion of the genetic basis of disease, it’s often forgotten that we humans are very similar from a genetic point of view. If you take two random people on the street and sequence their genomes, you’ll find that they are more than 99% alike, genetically (7). This isn’t necessarily surprising given what we know about the evolutionary origins of our species.
Genetic studies indicate that we (modern humans) all descend from a common ancestor who lived in Africa about 200.000 years ago. Since that time, we’ve spread across the continents and the size of the human population has grown massively; but that doesn’t mean our genomes have necessarily changed that much. It can take hundreds if not thousands of generations for significant changes in the human genome to occur, particularly if the selection pressure is weak.
The fact that there’s such a huge overlap in the types of genes different people carry suggests that it’s way too simplistic to blame our genes when we get sick. You and your neighbor may carry roughly the same genes, but as we know, that doesn’t mean you will necessarily experience the same health problems. It all depends on the instructions the genes receive.
All of this is not to say that genetics aren’t important to consider in the context of health and disease; it obviously is. All I’m trying to say is that the weight of the evidence suggests that most diseases aren’t caused by “bad genes”, but rather by suboptimal gene expression.
Key take-home points
- Most diseases have no clear genetic basis. Only rare health disorders are caused by single genetic mutations.
- The primary cause of the diseases of civilization isn’t “bad genes”, but rather a mismatch between environment (including microbes) and genes. The human genetic make-up has changed relatively little over the past millennia. The environment we live in, on the other hand, has changed dramatically, which means that our genes are now operating in a novel milieu.
- Whether we get sick or not largely depends on what kind of stimuli we subject our body to, and hence, how our genes express themselves.
- Humans are very similar genetically. We all descend from a common African ancestor.
