KEY POINTS:
Overweight couch potatoes who would rather scoff a packet of chips than snack on a crunchy apple, and whose daily exercise regime consists of waving the remote at the TV, could be the product of their epigenetics.
Thanks to an unfortunate combination of their genetic make-up and the
environment in their mothers' wombs, they are literally programmed from birth for a lifetime of obesity and poor health.
While that might sound like determinism gone mad, there's growing evidence that a genetic predisposition to common ailments like obesity, cancer, diabetes and heart disease can be "switched on" by early environmental factors such as maternal under-nutrition.
Epigenetics, the study of how genes interact with the environment, is a whole new take on the age-old nature versus nurture debate, and researchers at the University of Auckland are at its forefront.
The Auckland-based Epi Gen Research Consortium, formed by the university's Liggins Institute, AgResearch, the University of Southampton, and the UK Environmental Research Centre in mid-2006, is focusing on developmental epigenetics - the way in which the environment in the womb and in early childhood influences the expression of a person's genes.
Epi Gen's science operations manager, Steve Hodgkinson, tells the story of a particularly unhealthy lab rat, modelled by Liggins scientist Mark Vickers, to illustrate just how profound that influence can be.
The rat was conceived in a mother that was 30 per cent under-nourished before and during pregnancy, but was otherwise normal. This maternal environment triggered certain key metabolic genes in the rat fetus, says Hodgkinson.
"The animal senses it's going to be born into a deprived world and that it will have to be frugal with resources. So it lays down calories into tissues that have high metabolic yields, such as fat. It will probably be less energetic and run around less, and it won't bother itself by being the smartest rat on the planet.
"It will be content to sit there and eat - all because it was conceived and developed early on in a deprived rather than an enriched environment."
With a preference for high-fat food and minimal exercise, it not surprisingly grows up to be overweight and lethargic. Because its hippocampus is under-developed compared with other rats, it also learns at a slower rate.
Hodgkinson says these results have been reproduced many times in experiments, and the Epi Gen consortium is now working to show that the same thing happens in humans.
It is mining the University of Southampton's biological database of 5000 people, which includes detailed data about women during pregnancy and umbilical cord samples from children who are now 7 years old.
This research will lead to the validation of biomarkers that can show whether a new-born baby has a predisposition for metabolic diseases. The consortium already has one provisional patent based on biomarkers in rats, with four more in progress relating to humans. Hodgkinson says when the tests have been fully validated they will be commercialised, possibly by licensing them to medical diagnostic companies.
Fortunately for those marked for obesity or other metabolic disorders, Hodgkinson says it is possible to reverse early epigenetic programming. "We see the test and the remedy going hand in hand."
In rats, it has been shown that if a hormone called leptin is given early in life they behave more like normal animals. While Epi Gen isn't promoting leptin, he says this proves the principle that a predisposition to diseases can be remedied.
Instead, Epi Gen is investigating food ingredients for their ability to cancel out epigenetic influences. It has identified six lead candidates which Hodgkinson says show that foods can be effective, "which creates enormous potential for the New Zealand food industry".
Dr Peter Gluckman, director of the Liggins Institute and the driving force behind the establishment of Epi Gen, says the organisation's science is moving "very, very fast".
"Everything suggests we are onto something very big and unique."
He believes marrying knowledge about the interaction between genes and the early childhood environment with research into foods that can reverse that effect could revolutionise our food industry.
"In future, foods that claim to have health benefits will have to be proven to be healthy or safe. Epigenetics is the most powerful tool for doing that."
Gluckman has extensive experience in commercialising scientific developments, including through medical start-ups Neurenz and Brainz. "While [epigenetics] might sound a little more 'out there', I think for New Zealand's economy this is the biggest thing I've been involved in by a country mile."
