Between the spring and autumn of 1918, the United States, like much of the world, was struck by the
sweeping influenza pandemic.

Unlike many other flu-hit regions already ravaged by World War I, however, the US was a relatively well-off, healthy country.

There, health care was of a higher standard than in many other places at the time, and pregnant women were mostly well-nourished. If they caught the flu, some died, but others contracted a mild flu or pneumonia and lived.

This set of circumstances provided researchers with a perfect “natural experiment”: comparing the babies conceived during the influenza season with those conceived immediately before and after.

As it turned out, people born in 1919, which means they were conceived at the peak of the flu season, had higher rates of cardiovascular disease than those born in 1918 or 1920.

When all young men enlisted for duty in World War II, those born in 1919 were a smidgen shorter on average, even after chance effects were ruled out, than those born in 1918 or 1920.

These findings suggest that when women are exposed to infectious diseases while pregnant, there is a lasting impact on their offspring.

Other studies have found that the same goes for maternal exposure to famine and chemical toxins.

For example, children conceived during the Dutch Hunger Winter of 1944 to 1945 had lower birthweight and a higher risk of cardiovascular disease later in life. Women who were exposed to a class of chemicals called phthalates, which are used to make plastics more flexible, gave birth to sons who had a higher rate of genital abnormalities.

And even people who had post-traumatic stress disorder – say, assault victims or soldiers after a war – showed changes in their immune-system gene expression.

What all this means is that humans are tremendously sensitive to external influences both in the womb and immediately after birth.

From animal and human-genetics studies, researchers have found that such changes can affect the expression of genes, even as the underlying genetic code remains the same.

This relatively new field of study, which has taken off in the past five or so years, is known as epigenetics, meaning “over or above genetics” in Greek.

The research has important implications – it could find out how much a child is affected by external factors, and will help parents understand how to keep their children healthy, or save them from potential problems such as diabetes or heart disease in the future.

Last month, some 120 researchers met in Singapore for a Keystone Symposium – part of a worldwide series of biology conferences, here co-organised by the Agency for Science, Technology and Research (A*Star) – to discuss epigenetics.

Some participants, such as Edinburgh scientist Adrian Bird, described how studying molecular structures in finer detail had led to new discoveries about the mechanisms by which environmental influences might work their effects to cause illness.

Others, such as University of Auckland researcher Peter Gluckman, gave the big picture. Dr Gluckman, who is also chief science adviser to New Zealand’s Prime Minister, directs an A*Star research programme
in growth, development and metabolism.

His theory is that there is a mismatch between a relatively nutrient-poor environment in the womb and the nutrient-rich environment outside. And today, people are less physically active than they were throughout evolutionary history.

So, he said, when humans are born, their bodies expect to struggle to store fat to survive, but they get more than they expected – resulting in metabolic diseases such as diabetes and obesity.

This means that scientists need to retool their ways of thinking about the world, he argued.

In the old model of genes interacting with environment, he said, your genetic code carried vulnerabilities to conditions such as diabetes or cardiovascular disease. If you did not eat well or exercise, you were more prone to developing those conditions.
 
Now, he urged scientists to adopt a newer and more complex model of inheritance, in which the environment, almost as much as DNA, plays a central part as generations succeed one another.

Your underlying genetic code may carry the same vulnerabilities to disease, but they are not writ in stone. Small changes, chalked up over time by exposure, increase or reduce your risk of developing disease,
sometimes even if you eat well or exercise. Of course, eating well and working out will reduce everybody’s risks, but developmental and life-course factors may play a bigger role than previously thought.

Singapore’s own Growing Up in Singapore Towards Healthy Outcomes (Gusto) study aims to tease out the effects of those factors.

The study, launched last year as part of the $25 million Developmental Origins: Singapore translational and clinical research programme, tracks babies of all races in the womb and during development.

It aims to look at the effects of genetics and environment during pregnancy and after birth, and environmental and cultural effects later.

Led by National University of Singapore Associate Professor Chong Yap Seng, Gusto will recruit 1,200 pregnant women by this month. It will track babies till they are three years old at first, and then to adulthood, contingent on further funding.

In future, scientists hope, the data from the study will help design ways to reduce the burden of chronic metabolic diseases.

While you cannot change your genes, you can change the external factors that have effects on the way your genes and your children’s are expressed.

For example, in one study, undernourished infant rats were injected a few days after birth with leptin, a hormone that fooled their bodies into thinking they were fat and well-nourished.

In later life, the rats treated with leptin in infancy did not grow slow and obese, while rats underfed early on but which were not treated with leptin fared worse.
 
The study points to possible treatments and interventions in early childhood and in the womb.

So there is hope, even though humans will never be able to play evolutionary catch-up to the rapidly changing environment.

“We can change our environment or use modern science to manipulate the way our body responds to the environment,” said Dr Gluckman.

“That’s why this discussion of processes and signals is so important. Because, in the end, that’s the only way we’re going to get there.”