I have always wondered why I was such a poor runner. Now Jonjoe McFadden, writing in the Guardian, has supplied the answer; it’s all down to my faulty gene switches. It’s too late for me now but according to McFadden, in the future anyone wishing to rival Usain Bolt and run a sub-10 second 100 metres will just take a gene switch drug. McFadden also tells us that diseases like diabetes, heart disease, cancer and Alzheimer’s disease are all caused by faulty gene switches. In diabetes, he says, a liver cell may be “genetically tripped to stop absorbing blood sugar”. Silly me, I had always thought insulin had something to do with diabetes.
McFadden’s musings were occasioned by the recent publication of the results of the ENCODE consortium. About 10 years ago the DNA sequence of the human genome was reported. Surprisingly, the part of the genome containing the information for building new proteins, the genes, constituted less than 2% of the sequence. The other 98% was, at the time, of unknown function and some rather unwisely dubbed it “junk” DNA. ENCODE set out to study this large part of the human genome that does not code for proteins. ENCODE’s data rewrite our knowledge and show that much of this misunderstood DNA is functional. Functional here is a rather broad term and includes several possible mechanisms that can be loosely described as regulating how the genomic DNA is expressed. This regulation is important for determining why certain proteins are expressed only in certain cell types thus establishing the unique identity of liver cells, heart cells etc. The regulation may go wrong, and this dysregulation may be at the core of some common diseases.
No one can doubt the importance of ENCODE’s work in rewriting our view of the human genome but it is very important to be clear about the implications. McFadden uses the term “gene switch” to describe all the regulatory activities outlined above. This idea in fact derives from the Press Release that accompanied the data. I find the term gene switch to be misleading as it suggests a mechanistic understanding we do not have. ENCODE showed, in a variety of ways and in different cell types, that there were potential regulatory functions associated with the non genomic DNA but they did not show how all of these worked. It will require huge amounts of research to understand the regulatory mechanisms and using a term like gene switch trivialises the present findings and the task ahead.
McFadden then goes on to build a huge edifice around the idea of gene switches. Gene switch drugs will in time be developed to counter defects in the regulatory mechanisms that lead to diseases but these drugs will be also be used , he suggests, to manipulate “physiology, mood, intelligence, libido, anxiety, and appetite”, also to create new Usain Bolts and to stave off the symptoms of old age. He also states that “many scientists believe …. that the differences between us and our closest relatives …. are mostly due to differences in gene switching”. The corollary of this, he says, is that a chimp might be enabled to talk by treatment with a gene-switch drug. This wealth of speculation is entertaining but is pure science fiction as it can be neither proven nor disproven at present.
When the Human Genome was reported, it was accompanied by claims that the information would revolutionise clinical medicine. The Human Genome has sparked a biological revolution but it has so far had little effect on clinical medicine leading to some disappointment. The results of the ENCODE project are important and require serious discussion. Making exaggerated claims about the outcomes means that the real impact of the results may not be appreciated. Those who read these predictions may end up disillusioned and disappointed when, inevitably, the predictions are not realised. This is bad for science.