Catching up with the sun: the consequences of premature birth and how to prevent them

“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.

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Why Do Birds Sing?

This story starts with a visit to Readings Bookshop in Lygon Street, Melbourne. Occasionally I go in and browse and buy what catches my attention. On the last occasion, the book that caught my eye was “Why Birds Sing” by David Rothenberg. David is a philosopher and clarinetist who likes to play along with birds. In the book, he examines with both an artistic and scientific perspective how and why birds sing. Along the way, he delves into how birdsong has inspired poets and musicians over the ages to write works of art in appreciation of bird song, and how birdsong has inspired scientists to dissect every microsecond of each song and to dissect the birds themselves to find out more about how they do it. 

Let me start with how birds sing. Humans have a voicebox or larynx, or at the top of their windpipe, which contains two muscular vocal cords, which vibrate when we pass air through them. Birds have a syrinx located at the bottom of their windpipe, where it has two air supplies – one from each lung. Birds can sing through both halves of the syrinx simultaneously. Canaries can even sing with one side of their syrinx and breathe with the other. Birds can also make use of between 2 and 8 different vocal cords. No wonder they produce such an amazing array of sounds.

Rothenberg details the history of how scientists and musicians have tried to annotate bird song – from simple transliteration – chee, choo, chee, choo or teakettle, teakettle, teakettle through simple musical notation through to sonograms – graphical reproductions of frequency versus time. He notes that if you slowed down birdsong, their song sounded a bit like jazz music, with changing tunes & rhythm. One of my favourites is a bird called the Veery.

Now on to why birds sing. There are a few “obvious” reasons: to attract mates, to declare their territory, to warn of predators and to basically say “Hi, I’m here, where are you? However, the one recurring question Rothenberg asks in his book is “OK, birds, like us, sing because they can but do birds sing for pleasure? Scientists don’t think so but David Rothenberg asks us to keep an open mind. In evidence, he states that birds can sing mating songs well after mating season and territorial songs when there’s are no other birds around. The real answer to this is that these are more likely times when birds are practicing their song. Interestingly, it was by dissection of canaries’ brains that we came to realise that both birds and human grow can grow new neurons throughout their life, in response to particular stimuli. In male birds, the regions of the brain that are involved in singing actually grow up to twice in volume during the mating season, in response, they later found, to testosterone. Indeed, if you feed a female canary testosterone, it will sing (as they do in some pet shops).

When thinking about why birds sing, it’s important to distinguish the different situations in which they sing. Generally speaking, territorial songs (or calls) are simple and innate (that is to say “in their genes”) and mating songs are learned, and practiced and perfected over days, months and even years before the bird is happy with it. This way, each individual bird has a slightly different song and thereby they can compete for a mate. Studies have found that many females prefer males with the most complex songs.  

Many birds are therefore thirsty for new songs to add to their repertoire. They can mix and match their existing songs, or as an evolutionary step, started to borrow songs from other birds and even any other sounds they like, all to impress the women. They have even been shown to copy birds from other continents that they have met on their migration. These are the virtuosos of the birdland – the mimics. I’m talking about birds such as mockingbirds, starlings and of course, lyrebirds, which I’ll come to in a minute.

The Mockingbird is one of Rothernberg’s favourite birds, and so is the starling. The starling can mimic other birds and has also been know to mimic humans. In one US study at the University of Indiana, 5 starlings were let loose in the labs for a few months and the researchers just waited to see what they would come up with. The results were interesting. The birds would recognise simple phrases & recombine them in odd ways. One would say “Basic research”. “Basic research; its true; I guess that’s right.” One bird, which needed to have its claws treated for an infection, squirmed while held, screaming “I have a question!” Now, are you familiar with the Paul Robeson song “Old Folks at home” what starts “Way down along the Swannee river? Well, one bird often whistled the first few notes: “way down upon the Swa” without ever feeling inclined to add “…nee river”. It just liked that part of the tune.

Rothenberg finished his book by coming to Australia to track down a lyrebird called George and attempt a jam session with him with his clarinet, and he does succeed for a few seconds. I first heard a lyrebird while running through the Dandenongs one winter’s morning. I heard what I though was a variety of birds all coming from the same direction, then I spotted the lyrebird. Of course, many of you will be aware that lyrebirds have been know to mimic things like camera shutters, car alarms and chainsaws. Here is a great clip from a David Attenborough program and another here

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Before finishing, I’d just like to mention my other favourite Aussie bird singers. I love the electrical warblings of the magpie and of course, the Kookaburra. I love the Willie Wagtail – the little black and white bird that loves to sing day and night. One of its calls is quite musical and sounds to me like” you Far-Eastern women” or “when Janie goes swimming”.  

Can we compare scientists to rock stars?

Yesterday I was promoted to the level of Honorary Associate Professor and for some reason it got me thinking about the parallels between scientists and rock stars.

You can’t see it? Let me explain. Most musicians start out by learning an instrument, by training their voices and by learning about music in general; most scientists learn train within in a specific area of science while learning about the broader field. A musician may join a band early on, just as a scientist will join a lab pre- and post-PhD. Most musicians start out writing and releasing songs without recognition; some may be classics, but most are average quality. Most scientists start out by writing scientific papers; some may be citation classics but some wallow in obscurity for years garnering single figure citations. And maybe being awarded a platinum disc for selling a million records is like reaching 1,000 citations?

However, we all know that rare case of a musician or scientist seemingly coming out of nowhere and zooming meteorically up the charts with their first release/paper.  Often such people are lauded and sometimes, hype creeps in. Some may continue at that level, others crash and burn.

What other parallels are there? Is finding a good music manager akin to finding a good lab head or mentor? Do young scientists ever get ripped off by a lab head “borrowing” their ideas. You bet, although a great synergy between a mentor/lab head and young Postdoctoral researcher can really bolster their career and help them navigate “The Business”.

How about salary? Well, surprisingly there are parallels there too. Both musicians and scientists are mainly in it for the love of it and often settle for a pittance and on rare occasions may be financially rewarded for performance. When they make it big and play large stadiums or  lecture halls, they may get their fares and hotel paid for. I even once saw a scientist trash their hotel room.

Recognition? Here are where things start to get a little different. Rock stars are recognised wherever they go by a broad section of the public. Top scientists get recognised only at their specialised conferences. Very rarely, your Sir Richard Dawkins or your Baroness Greenfield will be recognised by many, but even then, at levels much lower than rock stars or sports players.

Finally and almost inevitably, some rock stars and scientists drop out of the field because of disillusionment, burn-out or lack of funds. Coincidentally, both seem to end up rather unexpectedly as school teachers. But we all know the true heroes of science – the Mick Jaggers and the Leonard Cohens of the field. They have triumphed despite rough beginnings and bad living. Let us celebrate the whole span of the scientific career and aspire to be as they are, for one day, someone may just stop you in the street and say, “I know you, you’re… that old science guy/gal”.  

You are what you eat: why humans can travel the world and eat anything

If you have often wondered why human have conquered planet Earth’s most extreme environments and survived for millennia, the answer may be at hand. It looks like we got a little help from our bacterial friends.

In the human body, our cells are outnumbered one hundred to one by bugs and we have evolved in a mutually-beneficial relationship. Just like cows, the bugs enable us to ferment foods such as proteins (the main constituent of meat) and carbohydrates (sugar, starch and fibre found in plants). In this tit-for-tat relationship, this fermentation frees up vital nutrients in these foods that we can’t digest by ourselves and provides food for the bugs in return.

With the diversity of human habitats in mind, a recent paper in the scientific journal Nature took things to extremes. It asked what happened to the diversity of bugs within our guts when people were fed vegetarian-only or meat-only diets for two days. Researchers found that the diversity of bugs, which included bacteria, fungi and viruses, changed rapidly in response to diet. The vegetarian diet produced more bugs that can ferment carbohydrates and the meat diet produced more bugs that ferment proteins. This provides evidence that humans and the bugs that live within us, can rapidly adapt to different nutritional conditions.

Apart from telling us about how rapidly we can adapt to different diets and environments, the researchers found that an exclusively carnivorous diet feeds the “wrong” type of bacteria that produce harmful waste products that have been shown to promote cancer and inflammatory bowel disease. This signals that we should eat meat in moderation.   

The good news is that the effects of the extreme diets lasted only as long as the diets themselves. This goes some way to explaining why temporary diets are not effective in the long term.

So where do the bugs come from in the first place? Well, some of them there are probably lurking there within us all the time lying low, waiting for a rainy day. Others hitch a ride with our food. Examples of hitch-hiking bugs researchers found were bacteria that ferment milk-based products such as yogurt and those that ferment meat-based products such as sausages. They even found that viruses that infect plants including spinach can hitch a ride into our insides.

Remarkably, most of these bugs remain alive in our intestines and can be grown in the lab. However, most bugs cannot be coaxed into action under the bright lights of the lab and researchers have developed a simple way to study these shy creatures.  One useful product of the Human Genome Project is that we have learned to sequence DNA and its protein-making cousin RNA rapidly and in huge quantities. This means that given a biological sample such as poo, a gene sequencer can tell us precisely how many and what quantities of any species of bacteria, virus of fungus it contains.

So what does this paper tell us about what we should eat? Because the study dealt with extremes,   the answer is not that much. The likely recommendation, though, is to follow the usual guidelines of a balanced diet with plenty of fresh fruit and vegetables and most likely a little less meat that you usually eat.  And next time you eat a sausage or yogurt remember the mostly good bugs they contain  and  how they have helped us, for better or worse, take over planet Earth.