Читать книгу Secrets of the Human Body - Andrew Cohen - Страница 10
ОглавлениеGROWING UP, UP, UP …
When it comes to growing up, the van Kleef-Bolton family from London are world-class. At 6 ft 5 in (195 cm) and 7 ft (213 cm) respectively, Keisha and Wilco are the tallest couple in Great Britain and have only just been knocked off the global top spot, outranked by the lofty Chinese couple Sun Ming, 7 ft 8 in (233 cm), and Xu Yan, 6 ft 1 in (185 cm), in 2016.
While Keisha and Wilco are outliers at the far end of the distribution of human height, collectively as a species we have all gone through an incredible growth spurt in the last 150 years or so. Since the middle of the nineteenth century records show that the average height in industrialised countries has increased by about 10 cm. That’s a serious increase in such a short space of time, and as far as we know it is unprecedented. In fact the study of early human skeletons strongly suggests that human height stayed pretty much the same from the Stone Age until the mid-part of the nineteenth century. So what happened around the 1820s? Well, all of the available evidence suggests that this swift increase in height was not driven by any rapid-fire evolutionary selective pressures. The time frame is far too short for evolution by natural selection to play out and there is no reason to think that height has been under particular selective pressure in the last 100 years or so. The environmental influences, on the other hand, seem to track very tightly with the increase in height. We know that if a child is malnourished or suffering from disease at particularly critical moments in childhood, they will never reach their full potential adult height. But since boys stop growing around their late teens and girls in their mid-teens, proper nutrition before puberty is essential to fulfil genetic potential for height. Protein, calcium, vitamins D and A all have an effect on height, and deficiency in all of these nutrients in the early nineteenth century was commonplace. But starting around the mid-1800s the punishing lives of populations through the early years of the industrial revolution began to give way to more widespread benefits, including better sanitation, clean running water and improved nutrition. Slowly this allowed the populations of countries like the UK to start fulfilling the genetic potential of human height. The truth is (as many parents instinctively know) that eating up your greens and drinking your milk really will make you grow up strong and tall.
EAT YOUR GREENS PROTEINS
During childhood the most important food that influences your final height is protein. Meat, fish, eggs, nuts, legumes and dairy products are all good sources of protein (which is why it is a considerable nutritional challenge to bring children up on a vegan diet). Other minerals, in particular calcium, and vitamins A and D also have a direct influence on height. For this reason malnutrition during the key stages of childhood can have a direct and significant effect on growth. This means good nutrition is particularly important before and around the growth spurts of puberty. For girls this begins around 10 years old and continues until their mid-teens when maximum height is reached. For boys it’s later, with maximum height not being reached until the late teens.
The most startling journey from low to high across this time has been made by the Dutch. For the data shows that the average nineteenth-century Dutchman waslooking up enviously at almost all of their European neighbours, but then a dramatic climb fuelled by increased living standards has taken them slowly but surely to the top of the global height charts. Although not without a few blips – both World Wars triggered a reversal in the upward trend in many countries as the availability of resources tightened dramatically. In recent years widespread increase in height has slowed down, stopped or even reversed. This is the case in the United States, where a lack of free health care, and a diet high in calories but low in nutrients, may be the major contributing factors. It is likely that the Dutch are approaching the maximum height their genes will allow. Supplementation with extra vitamins, calcium and protein beyond the recommended daily amounts will not increase gains (and in fact there are large studies showing that excess vitamin supplementation shortens life).
BOY HEIGHT PREDICTOR
(Father’s Height [cm] + Mother’s Height [cm] + 13 cm) / 2
GIRL HEIGHT PREDICTOR
(Father’s Height [cm] + Mother’s Height [cm] − 13 cm) / 2
But tall people aren’t just tall because they have eaten better as children. Human height is determined by both genetics and environment. Your genes are a hand of cards you are dealt. Your environment is the way you play them. It’s a case of nature via nurture. The major environmental influence on height is nutrition, affected by both diet and disease. Around 80 per cent of the variation in height between people is determined by their genes, and around 20 per cent can be attributed to the environment, although these numbers vary with different populations around the world.
You can work out how much of your height has actually been influenced by your parents demanding you clear your plate, and how much was set in stone from the moment of conception. The average height of a man in the UK is around 5 ft 9 in (175 cm). Take me for example. I’m 6 ft 1 in (185 cm) so I’m 10 cm taller than the average. Eight of those 10 cm are determined by my genes (my dad is a 6 ft 4 in [200 cm] Dutchman) and 2 cm by my diet (my mother is, in the words of P. G. Wodehouse, ‘God’s gift to the gastric juices’). I tower over Xand by a full centimetre simply because I listened to mum a bit more.
You don’t need to be a population scientist to see that tall parents beget tall children by passing on genes for tallness.
In the case of Keisha and Wilco van Kleef-Bolton, this certainly seems to be playing out predictably. They are the proud parents of five children, Lucas, the oldest at 11, is already 5 ft 4 in (c. 163 cm) and towering over his classmates; Eva, 8, is the average height of an 11-year-old; and 4-year-old Jonah is standing shoulder-to-shoulder with boys twice his age. While it’s still a little too soon to judge the newest arrivals to the family, early indications point them to the skies as well: Ezra, the tallest of the 1-year-old twins, is in the 91st percentile, and Gabriel is not far behind.
Map showing variation in average adult male height in various nations across the world.
But we don’t really need to wait to see roughly how tall any of their children will be. Since the 1970s we’ve been using a rough and ready formula to predict the eventual height of offspring with nothing more than just the parents’ measurements. By simply adding the height of two parents together, adding 13 cm to the sum of the two numbers for boys and subtracting 13 cm for girls and then dividing the result by two (see here), you end up with a pretty good estimation for the height of the children. So in the case of the van Kleef-Boltons, the boys would be expected to be 210.5 cm, and the girls 195.5 cm.
This is not, of course, a precise calculation, but its rough reliability does indicate that height is a trait that is significantly inherited. That doesn’t mean there is a single gene for height; very few traits have a direct one-to-one relationship. Instead your height, like many other characteristics, is controlled by a multitude of genes interacting with a multitude of environmental factors.
Average female growth chart from birth to 20 years old: showing from the 3rd to the 97th percentiles.
We now know that in the case of height your genes are about 80 per cent of the story in determining how tall you and your children will be. The reason we know this with such accuracy is because there have been a wide variety of studies that have explored the heritability of human height using a long-established method of teasing out the influence of nature vs. nurture.
The principle of these studies is simple. Take a group of identical or monozygotic twins, to use the technical term, like Xand and myself, twins who have developed from a single fertilised egg and so share 100 per cent of the same genes. You then compare a trait such as height difference between each of the identical twins in the group with a group of dizygotic twins, or non-identical twins (or even just siblings) who all share only about 50 per cent of their genes.
It is assumed that identical and non-identical twins grow up in equally similar or different environments, so this method of comparing groups of identical and non-identical twins enables you relatively easily to quantify the heritability of a trait. So, for example, in the case of a height study, if it shows that the identical twins are considerably closer in height than the non-identical twins then this strongly indicates that genes play an important role. The actual analysis that can be applied to a study like this, both statistically and genetically, is far reaching and complex but the principle remains the same – the greater the similarity between identical twins compared to non-identical twins, the greater the heritability of the trait.
One of the most recent of these large studies conducted by Peter Visscher of the Queensland Institute of Medical Research in Australia looked at 3,375 pairs of Australian twins and siblings and found that the heritability of height is around 80 per cent. Other studies have come up with similar findings, including one that looked at 8,798 pairs of Finnish twins, in which the heritability was found to be 78 per cent for men and 75 per cent for women. Interestingly, similar studies in Asia and Africa have found the per cent heritability to be around 65 per cent or lower, because these regions tend to have populations that are less mobile and so more ethnically and genetically defined compared to the greater genetic homogeneity we see in the west.
Regardless of the height you reach as an adult, the journey to get there is not steady, and only now are we beginning to truly understand the extraordinary process behind this rapid growth, a process that is dependent on an intricate interplay between your genes, brain, a cascade of chemicals and every bone in your body.
GROWING PAINS
In the first six months of your life, you grew more than at any other time since. It’s a growth spurt unlike anything else our bodies experience, with most of us growing a massive 30 cm in that first year. As a new parent this is particularly evident. It seems some days as if my daughter is growing in front of me. If we continued to grow at this rate, we would be 10 feet (~3 m) tall by the time we were 10 years old, but by the end of that first year that frenzied growth rate has slowed down and will continue at a far more subtle speed until the madness begins again at puberty.
The secrets behind the process of growth reveal how the body works as an integrated system, not just separate organs and limbs functioning in isolation. Starting at the business end of the process, the bones that really define your growth are the long bones of your body, in particular the femurs in your thighs, the fibulas and tibias in your lower legs, and the humerus, ulna and radius in your arms. These are the site of the major longitudinal growth during that first year of development. These bones don’t just uniformly increase in size as they lengthen; the growth is focused around a particular part of the bone called the metaphysis found at the end of each long bone. If you looked at an X-ray of the metaphysis region of the fibula and tibia of a 10-year-old, you might conclude that the child has a broken leg. But what you are actually seeing in the ‘fracture’ across the bone is the location of growth, a line that is called the epiphyseal plate or growth plate. This is a soft disc made of hyaline cartilage (the same cartilage that you can feel in your nose) and it’s here that cells called chondrocytes divide throughout the first 15 or so years of life and the rate of division increases furiously during a growth spurt. As the chondrocytes divide they secrete cartilage, a protein matrix that forms the template for bone, and the continuous division pushes the older cells towards the shaft. These gradually die and become ‘mineralised’. The chondrocytes die, and cells called osteoblasts move in and secrete bone tissue into the cartilage. It’s this process that results in the elongation of the bone – this is how we grow.
The long bones of the human skeleton.
It’s only once you reach adulthood that the activity in this area stops due to a process of programmed cell death (oddly controlled by oestrogen, the female hormone, in both boys and girls) and the growth plate closes and stops growing. The old growth plate becomes visible on X-rays as an epiphyseal line, a faint scar notched into your bones that you will carry for the rest of your life. At this point, bones can no longer elongate, growing any taller is now impossible.
BRAIN–BODY INTERFACE
The full story of your miraculously extending bones starts far away from your skeleton. Nestled deep inside the centre of your brain, just behind your eyes, is a structure no bigger than the size of an almond, called the hypothalamus. It is from here that growth is controlled.
Your brain facilitates your conscious desires by sending signals to your muscles. This is your ‘somatic’ nervous system, the one that allows you to consciously move about, to speak, to look at things. But, in parallel, you have another subconscious, or autonomic, nervous system governed largely by the hypothalamus. It integrates more data than it’s possible to calculate, from all your sense organs, your memory and experience, your cerebral cortex and amygdala, and it uses this data to control functions of your body that you likely take for granted. Digestion, heart rate, sweating, the size of your pupils and also growing. The hypothalamus is the link between the brain and the body.
Part of this regulation is control of the body’s hormones or endocrine system. The hypothalamus secretes hormones itself which include vasopressin (which controls thirst and water reabsorption by the kidneys) and oxytocin (the ‘love’ hormone, which has a range of effects including stimulation of milk secretion and uterine contractions).
But most of your endocrine or hormone system is located around your body in specialist endocrine organs, like your thyroid, gonads or adrenal glands. The hypothalamus controls these organs remotely through a cascade of hormone signals sent first to the pituitary. The pituitary gland is around the size of a pea and dangles beneath the hypothalamus from the underside of your brain, on a stalk. It sits behind and between your eyes resting in a little bowl of bone in the base of your skull called the sella turcica or Turkish seat. Via this tiny organ your hypothalamus controls your reproduction, sex drive, lactation, metabolism and of course your growth.
It’s not a simple process. The hypothalamus secretes the unimaginatively named growth hormone releasing hormone (GHRH) or growth hormone release inhibiting hormone (GHRIH). These in turn signal to the pituitary to release or stop releasing growth hormone. Growth hormone then directly acts on the cells of your body, instructing them to divide, and it stimulates the liver to produce insulin-like growth factor 1 (IGF-1) which also makes you grow. It takes the brakes off cell division and causes the growth of almost every cell in the body.
Levels of IGF-1 and growth hormone can be affected by a huge range of processes which feed into the hypothalamus: insulin levels, disease, protein intake, stress, genes, physical fitness and sex hormones.
We see this kind of signalling cascade with almost all biological processes, whether it’s the immune signalling pathways inside cells that Chris studied in his PhD, or the whole body cascades of chemical signals from organ to organ. They allow for delicate control of biological processes at multiple levels, with each organ feeding back information to regulate the process. They are also remnants of our evolutionary past. As organisms became more complex, it was easier for evolution to add another layer of control than to redesign from scratch. As we’ve seen in other chapters, we still have ancient systems in our modern bodies but with extra lines of code to allow for more regulation.
We all produce growth hormone (and thus IGF-1), every day throughout our lives. In adulthood the average healthy individual produces about 400 micrograms a day (a scarcely visible amount), and it plays a crucial role in the maintenance and renewal of our bodies as well as controlling a host of other bodily functions. In children and teenagers, the levels of growth hormone are much higher, reaching 700 micrograms a day in the midst of our most rapid periods of growth, and it’s these levels that drive the process in the growth plates of young bones. In this way, through the cascade of hormones from the brain, which travel through the blood vessels of your body to command the cells in the growth plates of your long bones to divide and push those bones a little longer, millimetre by millimetre, you grow.
As is often the case in medicine, we have understood how body systems function in healthy people by studying those for whom these systems have gone wrong. Dwarfism occurs when IGF-1 is not produced or when the receptors on the cells’ surfaces that should detect it are absent or defective.
Conversely, tumours of the pituitary may secrete excess growth hormone, and if this happens in childhood prior to fusion of the epiphyseal plates, then gigantism results. Although these tumours are extremely rare in childhood, they have produced two extremely well-known actors, including Richard Kiel (the infamous ‘Jaws’ villain from two James Bond movies) and Andre the Giant, a wrestler and actor from The Princess Bride.
As well as being giants over 7 ft (213 cm) tall, both of these stars exhibited the other effects of excess growth hormone secretion, a condition called acromegaly. If growth hormone secretion occurs after the long bones have fused, then you can’t grow any taller, but bones and other tissues continue to grow. The brow ridge and jaw thicken, the tongue and hands become vast and thick, and the voice deepens. In athletes using growth hormone as an illegal performance-enhancing drug, jaw changes often necessitate orthodontic braces to realign teeth – a subtle tell-tale sign for doping.
It’s a beautiful, complex cascade that we have been able to understand in greater and greater detail through the revolution in molecular biology and genetics over the last 50 years, but one particularly strange thing about our growth through childhood and adolescence has remained a mystery. Unlike any another primate, we have a very odd pattern of growth through to adulthood. As we’ve already seen in this chapter, the first six months of life witness the most rapid period of growth, but then this slows dramatically through the next 10 years – a time we humans call childhood. Unlike any of our nearest relatives, including chimpanzees and bonobos, we grow at a fraction of the maximal rate through this period. It’s as if the race to adulthood is on hold, until suddenly we burst into activity again around the age of 10 as we experience the growth spurt of puberty. The mystery is why. Why do we all follow this oddly stunted pattern of growth? In the last few years an intriguing hypothesis has emerged to explain the biological oddity we call childhood.
GOOD THINGS COME TO THOSE WHO GROW
In June 1765 Daines Barrington, the British lawyer, naturalist and distinguished fellow of the Royal Society, made his way the one mile from his home in King’s Bench Walk in the heart of legal London, to a rather less respectable address on the east side of Soho. The reason for his journey into this more unsavoury area of London was to visit the temporary occupants of 21 Frith Street – an Austrian man named Leopold and his two children 14-year-old Nanneri and 8-year-old Wolfgang.
Under his arm Barrington carried a clutch of documents and papers, but most importantly a newly composed music manuscript written in a ‘challenging, contemporary Italian style’. The purpose of bringing the manuscript was to place it in front of the young boy Wolfgang so that Barrington could check for himself whether the rumours that had spread across London regarding this boy’s precocious musical talent were really true. The boy was, of course, Wolfgang Amadeus Mozart and Barrington’s test would be an easy trial for him to pass. Just by sight, the young Mozart played the piece effortlessly and perfectly, at the very first time of trying. ‘The score was no sooner put upon his desk than he began to play the symphony in a most masterly manner, as well as in the time and style which corresponded with the intention of the composer,’ he wrote.
Barrington went on to further test the abilities of the 8-year-old boy, challenging him to improvise a song of ‘love and a song of rage’. Writing in a now famous letter to the Philosophical Transactions of the Royal Society some years later, Barrington described how Mozart’s
astonishing readiness, did not arise merely from great practice; he had a thorough knowledge of the fundamental principles of composition … and his transitions from one key to another were excessively natural and judicious.
‘EVEN TODAY, AFTER A CENTURY OR SO OF SCIENTIFIC STUDY OF CHILD DEVELOPMENT, PRECOCIOUS TALENT REMAINS A MYSTERY. WE ARE STILL AS CURIOUS ABOUT TALENT NOW AS PEOPLE WERE IN THE EIGHTEENTH CENTURY.’
PROFESSOR UTA FRITH
Barrington’s visit, tests and subsequent publication of his observations are widely regarded as one of the first examples of Behavioural Science. As Professor Uta Frith, a current FRS and one of Britain’s most distinguished cognitive scientists, wrote some 250 years later, ‘Naturally, the methods of observation he used are rather crude to our modern eyes, but, the crucial point is that he gives concrete examples of behaviour and not just opinions.’
It did not just take Barrington to prove that Mozart was undoubtedly a child genius. The historical records are full of details of his precocious talent, from his first compositions as a 4-year-old, to his first symphony, composed during that extended stay in London. This was a childhood that was truly full of extraordinary achievement, a unique talent that was maturing before the eyes and ears of the world. As Frith went on to conclude, ‘Even today, after a century or so of scientific study of child development, precocious talent remains a mystery. We are still as curious about talent now as people were in the eighteenth century.’
Achievement and emerging talent however, is not something that is in short supply with children of 4, 5, or 6 years of age. This is the moment that many of us sit our children down at the piano for the first time, sign them up for the local football team or send them off to ballet class as well as seeing them grasp the fundamentals of reading, writing and arithmetic skills that they will carry throughout their lives.
Subconsciously or not, we are aware that this is a precious time, a moment when children are more than just sponges; they are receptive to developing new skills and abilities with an ease that will not be repeated at any other time in their lives.
The foundation of all of this new-found knowledge, skill and ability is of course the brain, and intriguingly we now think the brain power that goes into all of this intensive learning is intricately linked to that mysterious and odd pattern of growth we were puzzling on earlier in the chapter.
On a daily basis your brain demands a huge amount of the energy your body uses. Weighing around 1.4 kg, just 2 per cent of our total body weight, the average adult human brain consumes 20 per cent of our body’s energy expenditure (to be precise that is 20 per cent of the resting metabolic rate [RMR]). To put this massive power demand into some context, if your body needs 1,400 calories just to sit on the couch all day doing sod all (that’s what the RMR is), then your brain will be consuming 280 of those calories just to keep things ticking over, like deciding which channel to watch, or when to eat dinner. Put another way, it takes one Mars bar plus an extra bite for your brain to exist. No other organ in the body is so hungry for energy, but what is interesting is that the energy demands of the brain are far from constant throughout your life.
