Disease. It defines us. The common cold can make Monday mornings uncommonly grim. Cancer can harass us into victimhood or can hone us into heroes. Neuro-psychiatric disorders such as schizophrenia and bipolar affective disorder photoshop our perceptions, tinting and filtering how we see the world and ourselves, and how the world sees us.
Disease defines us all through our experience of it. It is the background hum to our daily lives, the tinnitus that drives us mad, sad, or just glad to be alive. For surely we all experience disease throughout our lives and have our perception of the world modified by that experience.
Disease comes in many guises, but most often has a genetic component. Genetic diseases are frequently inherited, as in the case of Down Syndrome, congenital heart disease and breast cancer. Or they can be acquired through our lifetime as with many skin, lung and liver cancers. In all these instances it is our own genetic code that conspires against us.
Each of us carries hundreds of deleterious mutations which may or may not make their presence felt with time. And as we get older we accumulate many more, the number depending to some extent on what we get up to (smokers, you know the drill). Many of our genes have even been defined solely through what happens to us when they acquire mutations.
BRCA1, for instance, is one of an arsenal of DNA repair genes vital for our survival. Yet we know it as a ‘breast cancer gene’, encoding the breast cancer type 1 susceptibility protein. And indeed it does that, but only if a mutation occurs within it and its code is altered. Thus our naming system seems a little unfair on the gene itself which normally works so hard for us, but does highlight the truth that disease not only defines us but also our very genes. Literally.
But on top of that, disease defines us in another, far more fundamental way. And, I would argue, in a rather more constructive and empowering way. For it is through disease, or more specifically our attempts to study, control and combat disease, that we gain a better understanding of ourselves as living creatures and what makes us human. And this is particularly true of genetic diseases, be they inherited disorders or acquired conditions.
Any modification to our genetic code risks the genesis of disease. In the wrong place, a mutation can have a profound effect, on its own or in concert with other parts of the genome. A single mutation within a parent’s gonad can lead to a son being burdened with haemophilia. Exposure to DNA-damaging ultra-violet light can lead to skin cancer.
In all cases the code is changed; the message altered, rephrased, is accentuated or falls silent. Often, the effects are modest, unnoticed even. But sometimes, as in the case of haemophilia or skin cancer, the results are dramatic and terrible.
But these changes also lead us to a greater understanding of how all our genomes work. And with each new technological advance in high-throughput sequencing it becomes more and more practical to read the genetic code of individuals and make comparisons. For comparison is the key to unlocking the complexity of the human genome. And it is in this context that genetic disease becomes our Rosetta stone.
Disease causing mutations can now be detected with unprecedented precision. High throughput sequencing technologies now make it possible for us to compare parental genomes with that of the child, or normal cell DNA with that taken from a tumour. And when we do so we can see, with absolute clarity, what change, or changes led to the disease; and when we can’t it highlights, not for the first time, how incredibly complex our genomes are, prompting ever more detailed investigations until understanding is achieved. And our genomes are incredibly complex. Far more complex than we currently comprehend.
When the human genome was first sequenced and this breathtaking achievement announced back in 2000, there was much talk of how disease would be combated; all we needed to do was compare genomes and then disease causing mutations would reveal themselves.
Ambitious and extensive multi-genome comparisons were conducted for this very purpose and revealed… well…, they revealed things were far more complex than we had ever imagined, so much so that now in 2013 our view of our own genomes has changed from a simple necklace of genes to something far more complex and frankly, far more plausible (biology is, after all, never simple).
This inability to find no more than a hand-full of ‘disease genes’ is sometimes viewed as a set-back or even a failure. It’s not a failure of course. It is progress and exciting progress at that. For it means we are getting ever closer to the day when we will properly understand our own genomes and in so doing have real knowledge to combat disease. And when we reach that point we will have achieved real knowledge, not only of the diseases we are prone to, but also of ourselves. And what it means to be human.