A few days ago, Jonathan Latham of The Guardian newspaper decried the failure of modern genetics to make inroads on common diseases. I think he got things very wrong.
Latham claimed that:
Despite more than $100 billion having been spent on the Human Genome Project, geneticists have not found more than a “fractional genetic basis” for human disease.
One of the most widely cited studies into the human genome – an experiment measuring genetic variation versus environmental variation in twins – is actually contested by geneticists.
Essentially, Latham argues, the most expensive scientific project ever conceived has failed to reach a goal it assured the world it would.
I thoroughly disagree.
Genetics has never been in such a commanding position to uncover the biological mechanisms underpinning common diseases such as diabetes, heart disease and autoimmune diseases.
The Human Genome Project has provided researchers with the sequence of the human genome, the most valuable single piece of information in biology since the discovery of the structure of DNA itself.
Ironically, even if the Latham article were correct (which it most definitely is not), the sequence of the human genome would be required to prove his argument.
Sceptics are always sceptical
The arguments of the genome-sceptics revolve around the large degree of complexity being discovered in the genetics of these common diseases.
For example, we know of over 50 genes that can contribute to the risk of developing Multiple Sclerosis (MS).
Such findings are similar to those for other autoimmune diseases. This is many more genes than had been predicted by early simulations, and greater genetic complexity than many researchers can currently manage.
The fact very few studies to date have identified all of the genetic risk for these diseases has led to exclamations of failure.
Nonsense. All it means is that we still have a lot to learn about the genetic complexity of common diseases.
Where things stand
We can only look for common genetic variants at present, and yet it’s very likely many of the gene variants contributing to autoimmune diseases will be rare.
We will have the technology to search for these variants within the next two-to-five years.
Again, this technology is directly dependent on the genome sequence and the DNA sequencing technologies it has spawned.
But we have learned a large amount.
Many of the genes contributing to the genetic risk of MS are also found in other autoimmune diseases, leading to the proposal that many of these disease have similar mechanisms.
We know what we don’t know
Studies of model diseases in mice have given us an expectation that the genetics of these common diseases will be complex.
Type 1 diabetes in the mouse has been attributed to the action of over 30 different genes, and this is only in a small number of genetically different animals.
Some of these gene variants play only a very small part in the disease and others need partners before their effect is played out.
We know that these common diseases have an environmental component. There is a close interaction between environment and genome.
Let’s take MS as our example again; UVB sunlight and exposure to viral infections early in life are key contributors to the environmental risk. These are modified by the genetic make-up of the patient.
As things stand, we can explain 85% of the total environmental and genetic risk of of MS.
This is no failure: it is a roaring success.