The Epigenetics Revolution

This might make us wonder if there is any point following advice on healthy living. If we are all victims of epigenetic determinism, this would suggest that our dice have already been rolled, and we are just at the mercy of our ancestors’ methylation patterns. But this is far too simplistic a model. Overwhelming amounts of data show that the health advice issued by government agencies and charities – eating a healthy diet rich in fruit and vegetables, getting off the sofa, not smoking – is completely sound. We are complex organisms, and our health and life expectancy are influenced by our genome, our epigenome and our environment. But remember that even in the inbred agouti mice, kept under standardised conditions, researchers couldn’t predict exactly how yellow or how fat an individual mouse in a newborn litter would become. Why not do everything that we can to improve our chances of a healthy and long life? And if we are planning to have children, don’t we want to do whatever we can to nudge them that bit closer to good health?

There will always be things we can’t control, of course. One of the best-documented examples of an environmental factor that has epigenetic consequences, lasting at least four generations, is an environmental toxin. Vinclozolin is a fungicide, which tends to be used particularly frequently in the wine industry. If it gets into mammals it is converted into a compound that binds to the androgen receptor. This is the receptor that binds testosterone, the male hormone that is vital for sexual development, sperm production and a host of other effects in males. When vinclozolin binds to the androgen receptor, it prevents testosterone from transmitting its usual signals to the cells, and so blocks the normal effects of the hormone.

If vinclozolin is given to pregnant rats at the time when the testes are developing in the embryos, the male offspring are born with testicular defects and have reduced fertility. The same effect is found for the next three generations[51]. About 90 per cent of the male rats are affected, which is far too high a percentage to be caused by classic DNA mutation. Even the highest known rates of mutation, at particularly sensitive regions of the genome, are at least ten-fold less frequent than this. In these rat experiments, only one generation was exposed to vinclozolin, yet the effect lasted for at least four generations, so this is another example of Lamarckian inheritance. Given the male transmission pattern, it is likely this is another example of an epigenetic inheritance mechanism. A follow-on publication from the same research group has identified regions of the genome where vinclozolin treatment leads to unusual DNA methylation patterns[52].

The rats in the studies described above were treated with high doses of vinclozolin. These were much larger than humans are believed to encounter in the environment. Nonetheless, effects such as these are one of the reasons why some authorities are beginning to investigate if artificial hormones and hormone disrupters in the environment (from excretion of chemicals present in the contraceptive pill, to certain pesticides) have the potential to cause subtle, but potentially transgenerational effects in the human population.

Chapter 7. The Generations Game

The animals went in two by two, hurrah! Hurrah!

Traditional song

Sometimes, the best science starts with the simplest of questions. The question may seem so obvious that almost nobody thinks to ask it, let alone answer it. We just don’t challenge things that seem completely self-evident. Yet occasionally, when someone stands up and asks, ‘How does that happen?’, we all realise that a phenomenon that seems too obvious to mention, is actually a complete mystery. This is true of one of the most fundamental aspects of human biology, one we almost never think about.

When mammals (including humans) reproduce, why does this require a male and a female parent?

In sexual reproduction the small, very energetic sperm swim like crazy to get to the large, relatively sedentary egg. When a winning sperm penetrates the egg, the nuclei from the two cells fuse to create the zygote that divides to form every cell in the body. Sperm and eggs are referred to as gametes. When gametes are produced in the mammalian body, each gamete receives only half the normal number of chromosomes. This means they only have 23 chromosomes, one of each pair. This is known as a haploid genome. When the two nuclei fuse after a sperm has penetrated the egg, the chromosome number is restored to that of all ordinary cells (46) and the genome is called diploid. It’s important that the egg and the sperm are both haploid, otherwise each generation would end up with twice as many chromosomes as its parents.