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Genes key to health gone awry NICOLAS ROTHWELL p15. Inquirer. The Australian June 01, 2013 \

http://www.theaustralian.com.au/news/features/genes-key-to-health-gone-awry/story-e6frg6z6-1226654732515

JOHN Boulton first met Dakota Johns five years ago when she was an infant, small and frail, at the clinic in the remote Aboriginal community of Mulan, close to Lake Gregory on the Great Sandy Desert's northernmost fringe.

The doctor told her parents their child was undernourished, but Dakota's grandmother, Anna Johns, a traditional woman, desert-born and rail-thin herself, told him firmly that Dakota's "spirit was strong", and those words stuck in Boulton's mind.

He was at the start of his landmark research on the frontline of the Aboriginal community child health crisis back then; that encounter broadened and shifted his ideas. It helped him see that the desert notion of childhood is distinctive, and traditional child-rearing had its own priorities.

Today Boulton, one of the country's best-known pediatrics experts, at once an academic and a field clinician, is back in Mulan's little medical centre, greeting the Johns family and Dakota, now a six-year-old, alert, flourishing, and with green-painted fingernails to match her bright green school uniform.

From this reunion begins a tale that spreads in multiple directions: out into the present day, and the entrenched pattern of indigenous disadvantage and dysfunction doing permanent harm to children in remote communities; back to the frontier past, and its long-term, well-masked effects; and into the deep reaches of human evolution, when the machinery of our genetic heritage was first shaped.

The stage is the desert inland. The small remote communities where Boulton works have become a battlefield of chronic illnesses, and the most devastating of them -- diabetes, kidney failure and heart disease -- are linked.

Their interaction has been well understood for the past decade. It even has a scientific name: metabolic syndrome. If an unborn child is malnourished in the womb, blood is directed as the first priority to the brain, leaving the kidneys and other organs insufficiently developed.

As a result of this fetal reprogramming, the child will grow up with a degree of insulin resistance, and this triggers an abnormally high level of insulin in the blood to process the glucose and fat from the food it consumes. This in turn leads to early-onset diabetes, which is increasingly in evidence throughout the remote indigenous population.

The child will also have a propensity to high blood pressure, heart disease, stroke and eventual kidney failure, caused both by its underdeveloped organs and the elevated fat and glucose content in its blood. Thus the different faces of the medical devastation now emerging across remote Australia are in fact all aspects of the same cascading, complex breakdown in the body's regulatory system.

Things go awry from birth. As a result, doctors are likely to encounter the first, tell-tale signs of the syndrome in the strange condition that was once labelled "failure to thrive". The preferred term now is "growth faltering", since the child victim is hardly guilty of a failure of any kind.

Growth faltering is a paradoxical business. Affected children grow normally in their first six months,

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then all but stop growing; it can be hard for harassed clinic nurses to realise quickly that something's wrong. The immediate faltering is caused by undernourishment or poor food, but it can also be in part a result of fetal undernourishment's effects, which may descend from the mother's drinking during pregnancy, or from episodes of domestic violence, hunger or stress: the circumstances that bring a child into the world with a low birth weight.

If unchecked, growth faltering ushers the infant swiftly down the pathway towards metabolic syndrome's linked conditions, and these can appear at a frighteningly early stage in life. At one of the small, remote communities Boulton visits there are three adolescent sisters with advanced diabetes, frontrunners of an emerging youth-onset epidemic.

Across the desert and the north, indigenous patients in their early 30s with grave kidney failure are being identified with growing frequency. There is one clear clue to the syndrome's presence: central adiposity, a pronounced tendency to put on fat around the middle of the body while still young, and this distinctive symptom is widely visible in remote communities, and plainly connected to poor diet.

Given this picture, and the knowledge specialists now have of the syndrome's workings, it might seem that the preventive health policies being promoted in remote communities -- food security programs, pre-schooling, childcare and parent training projects -- are well designed to make an impact. Of course many communities are hard-scrabble places: anomie, drug use and near-universal welfare dependency remain the stubborn status quo.

But surely if mothers could be persuaded to refrain from drinking, and domestic violence could be stamped out, and assured nutrition provided for parents and children -- all feasible enough on paper as part of a concerted renovation scheme -- then the syndrome's grip might slacken: the factors that create the diabetes and renal disease pandemics would disappear.

If only things were so simple. Increasingly, modern medicine is coming to accept, and prove through experiment, the existence of close links between mind, body and emotions; between what lies in a child's memory, its bodily inheritance and what it will become. The past shapes our medical prospects in myriad ways: indeed, metabolic syndrome was first identified by a Norwegian researcher who correlated high rates of infant mortality during episodes of large-scale poverty in a population with spikes of heart disease that emerged only decades later.

Enter Boulton, a scholar doctor with close Scandinavian connections and a keen interest in social medicine. His forebears in the north of England had been involved in public health campaigns; he had spent an academic and hospital career devoted to child wellbeing. New ideas were coming to the fore: the notion, above all, that a child's developmental background shaped its health in life.

Boulton inflected his sense of how he should work, and fulfil his goals; he kept his honorary professorships and went out into the bush as a senior pediatrician. He also plunged into evolutionary biology, and the outback history lying in Australian archives.

One thing he found in his researches struck him forcibly: Aboriginal babies born in remote communities or in the desert missions half a century ago were twice as likely as mainstream babies to be born underweight -- a key predictor of ill-health in later life. Despite the massive medical interventions of recent years in remote indigenous Australia, that rate has not changed. Why not? Has everything been a waste of time or is there another causal factor, or set of factors, lying beneath the skin?

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By now, Boulton was in close touch with the international researchers investigating the mechanisms that send disease susceptibility down the generations. The blooming field of epigenetics was one vital avenue: it aimed to explain how environmental impacts on the body could be transmitted in the genes to future generations.

Close history and records from contact times were another avenue: they showed what foods Aboriginal groups in the bush used to eat, how they shared them, and how they treated children.

Here were vital insights, which lie at the heart of the plight of remote communities today. Three or four generations ago, when Anna Johns was raised in the bush, children were rare in remote Aboriginal populations, and grandmothers to care for them plentiful. The age pyramid was wide at the top, and narrow at the bottom. Today, it is reversed: children are everywhere, and the young mothers failing to care for them well are often adolescents themselves -- in the communities on the northern fringe of the Great Sandy Desert, almost 40 per cent of the population are teenagers or younger.

In the pre-contact bush, a particular concept of the child held sway: children were seen as autonomous, not helpless. If they chose not to eat well, that was their decision: they were loved, cared for and valued as the future of their family, but not infantilised. If seasons were hard, as they often were, and food scarce, then they went undernourished, and they grew up small -- much like many desert men and women of today's oldest generation.

In the old world, this made a kind of evolutionary sense: adults of slight stature needed less food, and their meat-rich, sugar-free diet supplied their needs. Now, the nutritional options in remote Australia are very different: flour, sugar, sweetened drinks and fried foods dominate the indigenous community menu and help produce today's catastrophe of diabetes and kidney disease.

So far, so standard and conventional. In essence, this is the disquieting new medical consensus pieced together in past decades by a set of brilliant Australian researchers: the fine details and implications are still being filled in. In their distress, Aboriginal people remain fascinating subjects for study.

But for Boulton, on the frontline, dealing with child and infant patients every day, wearing his distinctive, neat-labelled "Kid's Doctor" shirt, the picture lacked something. He knew many bush families like the Johns at Mulan: well-organised, sophisticated people with baffling medical problems. Jeffrey Johns, Dakota's father, says his daughter was simply a "fussy eater" when she fell into growth faltering five years back.

Boulton also knows and visits many community leaders, young adults whose health is poor despite their own best efforts. They are more than statistics to him. Advances in population genetics, immunology and the grand ideas of evolutionary biology play on his thoughts, and they help flesh out what he sees.

Evolution research gives a background for the adaptive effects medicine can see in the unborn child. When early humans were developing in Africa, it was a time of fast-paced climate shifts, and this would have favoured a quick-switch mechanism in the mother's body to redirect blood to the fetal brain. How does that switch work? The metabolic syndrome is now understood in some detail, and what we know goes a long way to clarifying the social landscape of remote Australia.

Once there were vague ideas that Aboriginal people possessed a "thrifty gene" that made them store every ounce of fat they ate against lean times that might lie ahead. The system unveiled to date is far more complex.

The syndrome works as a signal, passing down the generations. When a malnourished mother harbours a malnourished child in her womb, or the stress in her environs has an impact on her body chemistry, that impact reaches down through time: the genetic material of the unborn child changes, adapts -- and the change appears in the child's own child.

Maternal nutrition in generation A affects the egg production in the growing fetus that will become generation B, and that change will result in a bodily alteration when the generation B adult gives birth in its turn to a child of generation C: the impact is cumulative. In this way, a kind of multigenerational pile-up of effects develops.

This is nothing theoretical. We know the pathways. We can see the effects. We can hardly measure shifting genes and intra-cellular chemicals in live Aboriginal subjects, but we have clear animal models. The process -- this build-up of genetic signals -- takes five generations to reverse in laboratory rats.

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All this fits with what we know of the Aboriginal bush. Not only were pre-contact nomadic family groups in the harsher parts of Australia subject to great and frequent environmental stress, which they responded to in fine-honed ways: stresses of a different kind came into their world when they were gathered in, and their old ways abandoned; when they were placed in missions, and the food supplied to them was often quite exiguous.

Settled life in remote communities became, in recent decades, disease-plagued life: a world of camp dogs and bad housing, of scabies sores and unfamiliar influenzas, and imported viruses and golden staph. The cascade of sicknesses began to flow, and the biochemical pathway for producing small babies with underdeveloped organs was triggered repeatedly: new causes, same stress response.

Such are the conditions that underlie the present picture of widespread growth faltering in the bush. It can seem like a phantasmagoric landscape: the clinic, in most remote communities, is the hub and heart of social life, the daily place of recourse. The plane circling overhead is very often the flying doctor's plane.

At tiny Mulan, with its population of 200-odd, 10 flying doctor evacuations of children to the Broome hospital emergency ward each year is standard. Health is not the background to life but its ever-pressing frontier limit.

Much flows from this new picture of the Aboriginal desert bush and the medical mechanisms at work there. First, the crushing sense of culpability lifts a little. If both outside administrators and indigenous leaders grasp that at least a part of the current health collapse in remote communities stems from genetics, and from patterns embedded deep in time, the sense that Aboriginal populations are wholly to blame for their troubles shifts: traditional life ways, so much lamented, become, in new times, a compromising heritage.

This recast understanding of today's indigenous community health profile also suggests a new policy approach. A serious government would intervene not just to limit access to alcohol or drugs, but to control diet and provide a smooth nutritional supply, minus sugar and minus fatty foods.

A new understanding of the long-term nature of the present crisis is critical. If we now know that today's young bush men and women, adapting rapidly as they are to the onrush of contemporary life, are still hostage to the past's medical consequences, that knowledge has consequences of its own.

Normalising remote communities and seeking to give them all the opportunities Australia holds must be balanced against a strange, protracted duty of care: a kind of care few societies to date have been able to identify, let alone fulfil.

Such are the quandaries in the new bush doctor's craft.

And here's Dakota Johns, a medical success story, laughing, pretty, a little small still for her age, greeting Boulton in the veranda's softly shaded light, then playing and running off to school at her grandmother's command. All round are her classmates, many of them with scabies scars on their legs, and the scars of skin staph infections on their cheeks; and their young mothers look on, a handful of them showing the tell-tale early signs of central adiposity.

It is the kingdom of metabolic syndrome: shadows everywhere -- from the present, and from the past as well.