The Boy Who Gave Birth to His Twin

Dr Martin Brookes

December 2003

It must be quite something to discover you've been walking around all your life with your twin inside you. This is what happened to Alamjan Nematilaev, a seven-year-old boy from Kazakhstan. A strange feeling no doubt. Can we really think of Alamjan's twin as just that, a twin? Technically the answer is yes. A foetus in foetu, or baby within a baby, is a developmental hiccup that happens very rarely to identical twins. But the mistake comes so early in development that the twin inside never really had any chance of being a real live twin. Here we take a look at the pitfalls of embryonic development and reveal just what a rocky road it can be.

We know how difficult it can be travelling around sometimes: traffic, roadworks and a million other inconveniences often obstruct our smooth passage from A to B. But the next time you're stuck in a logjam on the M25, remember that you've already made it down the most difficult road of all. It was the first journey of your life, and it puts the worst bank holiday traffic in the shade.

The journey from egg to embryo is the most perilous trip that any of us will ever have to endure. The majority of human embryos never make it; they are lost along the way to an obstacle course of developmental wrong turns and genetic blunders. Only a lucky few survive to face the tight squeeze into the outside world.

The great journey

We all start life as a fertilised egg; a single cell tumbling down the oviduct of our mother. Heading down towards the uterus, the cell begins to divide and multiply. One cell becomes two cells, two cells become four, four become eight and so on. By the time it reaches the uterus, the nascent embryo is already a hundred cells strong. As it prepares for implantation into the uterus lining, the embryo's cells start to assume regional identities, organising themselves into layers of distinctive tissue. Already, the ground plan of placenta, skin and bone is taking shape.

As the embryo continues to grow, the sheets of tissue curl over at their edges, eventually joining up to form a cylinder of cells. The hollow tube at its centre is destined to become the baby's gut. By four weeks the embryo has a distinct head and tail, a heart and a basic nervous system. Everywhere, cells are diversifying into the disparate tissues that make up the body – blood, skin, muscles, nerves and bone. Some cells even commit suicide, dissolving away to bring limbs, fingers and toes into sharp relief. By eight weeks, the embryo resembles the form of a human being.

Embryonic puzzle

A simple description of these first few hectic weeks is one thing but understanding how it all works is something else altogether. Even today, embryonic development remains one of the biggest puzzles in biology. Studies in fruit flies, frogs and mice have provided some important and fascinating insights into the common threads that unite development in all higher animals, including ourselves. Yet, many secrets are left waiting to be revealed.

The basic puzzle of embryo development is one of information and organisation. How is the whole complex business of building a body controlled? How does each one of the embryo's cells 'know' what it should be doing? After all, each cell carries an identical genetic recipe; the same set of genetic instructions that first came together when the father's sperm fertilised the mother's egg. If every cell is genetically the same, how does a cell turn into a nerve cell, a muscle cell, a skin cell, or any of the other cell types? And what's more, what tells each cell its path and when to follow it? What makes a head develop on the end of a neck instead of between two legs? What makes a heart develop inside the body cavity instead of outside? And what makes a backside face backwards rather than forwards? These, and a million other questions, are the subjects of developmental debates.

One part of the puzzle has already been solved. In the 1960s, it was discovered that genes could be turned on and off like light switches. Although every cell in an embryo carries an identical set of genes, any one cell will only use a subset of the total. In other words, cells assume distinct identities simply by employing different batteries of active genes. Only the genes appropriate to a cell's function are switched on. Skin cells, for example, produce lots of keratin (a protein that gives strength and elasticity) where it is most needed – at the body's surface. So skin cells have their keratin gene switched on. But genes irrelevant to the skin's function (such as haemoglobin genes) remain switched off.

Although this can help to explain how genetically identical cells assume different identities, a deeper question still remains. What is turning the switches on and off in the first place? What is overseeing the design, organisation and planning of the embryonic building site?

Control genes

For the last 30 years, biologists have been struggling to identify the architects of embryonic development. In their search they have stumbled across a special class of genes whose sole function is to control suites of subordinate genes. These control genes work like molecular addresses, specifying the location of regions or structures within the developing embryo. For example, one gene might say 'eye'. In cells where this gene is active, a suite of subordinate genes swings into action as the cells become directed towards the formation of an eye. In practice, the developmental decision-making involves the hierarchical action of different sets of control genes. These combine in sequence to organise the progressive regionalisation of the body.

Developmental control genes were first found in flies, but they have since turned up in a whole host of animals, including ourselves. In fact, control genes seem to be remarkably similar across the animal kingdom. It's as if evolution found an effective way of building a body and then stuck firmly to it. These genes are so similar that you can remove a fruit fly control gene and replace it with the human equivalent and the fly will develop as normal.

To illustrate the importance of control genes in successful development, you only have to look at mutant fruit flies in which one or more of the genes have become damaged or defective. With the molecular address book thrown into confusion, the fruit fly body plan is literally turned upside down. Legs can end up on heads where the antennae are supposed to be, and eyes can sprout on the tips of legs. In one unfortunate mutant, the head disappears altogether, and is replaced by a second anus.

Though control genes are a major factor in the programmed pattern of embryonic development, they are clearly not the whole story. For at least in the first few days of its life, an embryo is still very much under its mother's control, relying on her chemical signals to see it through the first few rounds of cell division. Even though the embryo soon gains genetic autonomy, maternal influence extends throughout pregnancy. After all, a human embryo is nothing without its mother, and the placenta becomes a place of both sustenance and susceptibility.

Fraught business

The first two months are the most hectic time for a developing embryo, as it changes from a fertilised egg to a recognisable human form. Not surprisingly, it is during this period that the developmental schedule is most likely to go awry. Most human embryos die in their first eight weeks of life, often before the mother is even aware that she is pregnant. It has been estimated that as many as three quarters of all human embryos perish during this critical phase. It's an astonishingly high rate compared to other mammals, and the reason is unclear. But with development relying on the interaction of so many factors, it's no wonder things do go wrong.

And if the process is complicated with one embryo, imagine what it's like with two. Twins, especially identical ones, can throw an extra degree of unpredictability into the mix. Identical twins arise when a fertilised egg splits in two before it implants into the uterus. But again, there are a multitude of ways in which this can go askew. One twin, for example, may end up completely enclosed inside the other, resulting in the rare condition known as 'foetus in foetu'. Or the embryos may fail to separate completely, resulting in conjoined twins.

Given the many pitfalls that litter the developmental journey of an embryo, it may seem a miracle that any of us are here at all. But with six billion people living on Earth today, all who completed that journey, something must be working right.

Find out more

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Websites

The Boy with a Twin Inside
www.timesonline.co.uk/article/0,,7-919323,00.html
Article based on Alamjan Nematilaev who had an extremely rare condition called foetus in foetu. While the condition is well documented, doctors are unsure what causes it.

Conjoined Twins
www.conjoined-twins.i-p.com
Informative site offering detailed medical information on the different types and forms of conjoined twins. Includes high-quality images and video material of surgery conducted at The Children's Hospital of Philadelphia.

Joined: The world of Siamese twins
www.channel4.com/health/microsites
/H/health/magazine/conjoined/history.html
Channel 4 site that looks into the social and medical aspects of conjoined twins.

Singapore Science Centre
www.on101.co.uk/foetal.html
Interactive site that uses photographic images and models to show how a fertilised egg develops into a baby. A narration explains each stage and answers questions.

Vanishing Twin Syndrome
www.emedicine.com/med/topic3411.htm
Medical explanation of the vanishing twin syndrome where initial scans show a multiple birth, but one of the foetuses subsequently vanishes.

The Visible Embryo
www.visembryo.com/baby/
Provides a visual journey through each stage of human development from conception to birth with beautiful graphics. Also offers a detailed pictorial account of normal and abnormal development.

Books

	The Secrets of Life: Genes and genetics from evolution to engineering (Channel 4, 2001) £4.95 (inc P&P) Cheque or postal order payable to Channel 4 Television, send to: The Secrets of Life, PO Box 400, Wetherby, LS23 7LG or phone + 44 (0) 8701 246 444 Colour booklet, published to accompany the Channel 4 screening of the Royal Institution 2001 Christmas Lectures. Follows Sir John Sulston's journey from the beginnings of life to the latest developments in biotechnology and into the future. Discusses ethics of cloning.
	Human Embryology by William J Larsen (Churchill Livingstone, 2001) Details the concepts and principles that underlie human development. Each stage is clearly described in a logical, step-by-step fashion, helping readers grasp the complex processes involved. Get this book
	Human Embryology and Developmental Biology by Bruce M Carlson (Mosby, 1999) Comprehensive and clearly written textbook, presenting current, accurate, in-depth information about embryological development. Emphasising the molecular basis of development, the focus is on human embryology. Many full-colour clinical photographs and illustrations stress the function of embryological structures and the progression of development. Get this book
	The Developing Human: Clinically oriented embryology by Keith L Moore and P V N Persaud (Saunders, 2003) Comprehensively covers human embryology, presenting all of the complex clinical and scientific concepts in a practical way, emphasising the clinical aspects throughout by using case studies and clinical correlations. Get this book
	Entwined Lives: Twins and what they tell us about human behaviour by Nancy L Segal (Plume Books, 2000) A study of twins, bringing together the latest scientific research and case studies to explore the complexities of human behaviour and development with a very good overview on conjoined twins. Get this book
	Joined at Birth: The lives of conjoined twins by Elaine Landau (Franklin Watts, 1997) Aimed at 9 to 12-year-olds, this book explores the issues of conjoined twins, including a discussion of the difficult decision regarding physical separation that parents must face. Get this book
	Teach Yourself Genetics by Morton Jenkins (Hodder Arnold, 2003) An extremely readable introduction to genetics for the layperson, exploring issues such as genetic inheritance, the ethics of genetic engineering, eugenics and the Human Genome Project. Get this book
	Male, Female: The evolution of human sex differences by David C Geary (APA, 1998) Reveals how one of our most fundamental goals in life, survival through reproduction, is key to understanding such differences as preferred attributes in mates; level of investment in parenting; the evolution and development of the mind; and even rates of violence, mental disorders, academic abilities and occupational interests and achievement. Get this book
	Y: The descent of men by Steve Jones (Abacus, 2003) Since Darwin's day, humans have been displaced from their place just below the angels in the grand scheme of life. And now to further our descent, within the human genome, the male Y chromosome has been described as 'the most decayed, redundant and parasitic of the lot'. Furthermore, man himself may become redundant, for his sperm can be grown in animal testes, and in mice at least an egg can be fertilised with a body cell from another female. Get this book
	Almost Like a Whale: The 'Origin of Species' updated by Steve Jones (Black Swan, 2001) An exhilarating update of Darwin's Origin of Species for the modern reader, including modern genetics and its implications for evolutionary theory. Get this book
	Nature via Nurture: Genes, experience and what makes us human by Matt Ridley (Fourth Estate, 2003) Ridley takes on a centuries-old question: is it nature or nurture that makes us who we are? He asserts that the question itself is a 'false dichotomy' and by using copious examples of human and animal behaviour, he presents the notion that our environment affects the way our genes express themselves. Get this book

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