“No one told you when to run, you missed the starting gun/So you run and you run to catch up with the sun but it’s sinking”
Mason, Water and colleagues (1973) could well have been referring to the long-term effects of premature birth, which refers to all babies born before the thirty- seventh week of pregnancy. Globally, around fifteen million babies are born premature every year, and this rate is rising according to the World Health Organisation. Premature birth imposes a huge health burden on individuals, including a four to five times greater likelihood of developing disorders of the heart, lungs and brain, with the latter costing more than one million dollars to manage over a lifetime.
However, not everyone born premature will get sick, so researchers have for many years been looking for equivalent of a crystal ball to predict future health. Such predictions would lead to treatments specific for early prevention of major illnesses. Doctors can do so many things to keep such babies alive but prediction of future health is incredibly difficult.
That is where my recent research comes in. In a paper published late last year, my colleagues and I showed that premature birth is associated with measurable biological marks, some of which are present at birth and eighteen years later.
The marks are epigenetic – literally “on top of the DNA”. Such marks were predicted over sixty years ago by the British researcher Conrad Hal Waddington who described epigenetics as “the interactions of genes with their environment” that make us what we are. Some years later, researchers discovered the mechanism behind epigenetics: small molecules that can stick to our DNA and change the volume settings on our genes without changing the genetic sequence of the underlying DNA.
One such molecule is the methyl group – one of the simplest molecules in nature, comprising a carbon and three hydrogens. Over the years, this has been the most well-studied epigenetic mark. We have learned that whenever it sticks to the region that controls a gene’s activity, it can act as a dimmer switch to lower the activity of the gene, effectively making it manufacture less of its protein product.
Nowadays we can scan people’s DNA for methyl groups and see which genes have this molecular dimmer switch stuck to them. DNA can be obtained from biological samples such as cheek cells and blood. Researchers can easily obtain such samples from those of us willing to part with them but how can they see what they were like way back when we were born?
In 2008, we answered this question. Within a week after birth, almost all babies have their heels pricked for tests to provide a few drops of blood that are used to screen for major debilitating disease such as cystic fibrosis. After this testing, two or three dried blood spots are left behind and can be stored for a number of years. We showed that the blood spots could be smashed open to yield DNA that could be used for measuring the methyl molecule dimmer switch.
Seven years later, we compared twelve 18-year-olds born premature and twelve 18-year-olds born at the normal time (around 40 weeks). We prepared DNA from blood taken at 18 years with DNA extracted from dried blood spots taken at birth and in both sets of samples, measured the methyl dimmer switch at almost half a million locations along the subjects’ DNA.
What we found was that at birth, there were huge differences between the two groups of babies, which was understandable because as epigenetic changes drive our development, the babies born at the “right” time will have had more mature setting on their methyl dimmer switches. However, at 18 years of age, a small number of epigenetic differences remained, which showed that our body “remembers” that we were born premature and that this memory is encoded by epigenetics.
But how does knowing that we may have a molecular memory of how far though pregnancy we were born? The answer lies in studies that have shown that our time in the womb can “program” our future health through changing our epigenetics. Although not referring to epigenetics, the Dalai Lama explains the general idea in his book The Art of Happiness: “A certain type of event may have occurred in an earlier period of your life which has left a very strong imprint on your mind which can remain hidden, and then later affect your behaviour”.
We aim to scale up the study to look at hundreds of young adults born premature and ask which memory marks math up with which health problems: heart, lungs of brains? Our ultimate aim is to target the right treatments to the right kids in early childhood, to effectively change their destiny to a healthier one.