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Take a large onion and chop finely. Place the pieces in a mediumsized casserole dish. Now mix ten tablespoons of washing-up liquid with a tablespoon of salt, and make up to two pints with water. Add about a quarter of this mixture to the onion and cook in a bain-marie in a very cool oven for five minutes, stirring frequently, and liquidise at high speed for just five seconds.
Now strain the mixture and add a few drops of fresh pineapple juice to the strained liquid, mixing well. Pour into a long chilled glass and finish off by dribbling ice-cold alcohol (vodka will do) down the side so that it floats on top of the mixture. Wait a few minutes and watch cloudiness form where the two layers meet. Now lower a swizzle stick into the cocktail and carefully hook up the cloudy material. It should collapse into a web of fibres that you can pull out of the glass. This is DNA (short for deoxyribonucleic acid).
DNA is the stuff that genes are made of. Genes carry biological information, which is translated into the characteristics of living things and is passed on down the generations. So genes determine the colour of a butterfly's wings, the scent of a rose, and the sex of a baby. DNA is just a chemical – not a more complex entity like a chromosome or a cell – and it is only in a biological context that it acquires its status as the molecular signature of an organism.
Our first task in the beginning of this book is to attempt to define the process of aging. By the end, you will find this task will be mostly unaccomplished.
The reason for this ambiguity is manifold, and perhaps surprising. The problem is that there are so many ways to look at the roots of biological maturity. Some look to aging's final obligation, death, and attempt to work backwards from the event to describe what aging means. But even death can be difficult to define absolutely, in an it–makes–sense–to–thebiologist language. We will understand this ambiguity best by attempting a definition of our own. And we will do so in the same backwards style, first examining the process of death and then working our way in reverse.
A working definition
At first blush, the inability to define death, and the body's prior preoccupation with survival, might sound odd. We have no ambiguities, for example, surrounding the material facts of such notable nonagenarians as the playwright George Bernard Shaw.
Biotechnology, the exploitation of biological materials and processes for human needs, has a long history. The ancient Egyptians applied mouldy bread to infected wounds for its antibiotic effect – today we turn that mould into penicillin. Also, the fermentation of fruits and grains to make wine, beer and spirits has been going on all over the world for thousands of years.
In biotechnology, we use microbes and cells as factories, and enzymes as the workers. Between them they turn out food, fuel, medicine and a wide range of other products in everyday use, with a market value of billions of dollars. Now genetic engineering and other techniques from molecular biology have given biotechnology a huge boost.
Enzymes are the master molecules of biotechnology
Much of biotechnology relies on the transforming power of enzymes. As we saw in Chapter 1, enzymes are proteins originating in cells, and each is usually specific for a particular biochemical process. Some enzymes are involved in basic cellular functions, such as extracting energy from food and making DNA. Others carry out more specialist tasks, manufacturing molecules that do not appear to be essential to the organism's survival. Instead they are used in ‘chemical warfare’, either to prevent competition or avoid predation. This is where antibiotics come from. We can imagine how, in ancient soils, competing communities would fight for their territory by using their own individual antibiotic molecules to try to wipe each other out. These products – known as secondary metabolites (metabolism is the term given to the enzyme-controlled chemical activity of the cell) – appear to be exclusive to the cells of microbes, simple marine organisms and plants.
We will begin our discussion of the root causes of aging by describing not the death of a cell, but the death of a king. The monarch was King Charles II of England (1686) and is a tragic case of deliberate if naive, error. We know about it because of the diary of Charles Scarburgh, the chief Physician to the King.
‘I flocked quickly to the King's assistance,’ Scarburgh wrote upon hearing of a sudden illness on the part of His Majesty. The king had been at his morning shave earlier in the day when he let out a terrific scream. He quickly collapsed into a quivering heap, rolling around the floor before slipping into unconsciousness (modern diagnosticians believe he suffered a sudden stroke that was accompanied by a seizure). Edmund King, a physician staying as a guest of the crown, was quickly summoned. He promptly adminstered emergency care, which consisted of cutting a slit in Charles' arm and withdrawing 16 ounces of blood. The call went out for Scarburgh, who took not only the best technology available to the 17th century, but also his diary.
The king had not responded to the emergency measures. Scarburgh, after consultation with six other professionals, decided that insufficient blood had been taken. The king's shoulder was cut in several places and an additional 8 ounces were extracted.
It was a horrific painting. The focal point was a wild-eyed monster, inserting a bloody, headless corpse into its mouth.
‘Are you sure this was created 200 years ago?’ My colleague whispered in my ear. ‘It almost looks like an abstract painting of a concentration camp. Or maybe a cartoon by Jeffrey Dahmer.’ My colleague's comment, a reference to the late cannibalistic American serial killer, was with great amusement overheard by others in the auditorium. The comic relief was welcome, because of the grim nature of the subject – the probable deaths of famous painters. On the screen was a slide of a painting by Fransisco de Goya, created during one of his ‘black periods.’ I shuffled uneasily in my chair.
‘The name is “Saturn Eating His Children,”’ the lecturer began. ‘It is an amazing example of Goya's artistic transformation, which began when he was middle-aged.’
The speaker described the fact that prior to his 46th birthday, Goya was a talented but absolutely conventional painter. His paintings were charming, picturesque, predictable, boring. But something happened to Goya that almost killed him. His brush with death unleashed a genius, perhaps a monster, and Goya would never paint the same way again. That something, and its cumulative effects on his art, was the subject of the lecture. I still found it difficult to watch.
‘My complexion is black and white and every wrong colour,’ an exasperated Jane Austen wrote in her diary. ‘I am more and more convinced that bile is at the bottom of all I have suffered.’
The famous author was describing the dermal particulars of a disease that had afflicted her for two years – and would eventually take her life. Although unknown to medicine at the time, Austen was suffering from Addison's disease, the same syndrome that more than a century later, would afflict John F. Kennedy. Austen thought she was plagued with ill humors, specifically bad bile, a general pathological idea that muddied much of Western medicine in those days. It wasn't until 150 years later, in 1964, that the truth came out. A physician writing in the British Medical Journal made the correct diagnosis by poring over some of the remarkably detailed descriptions in her diary.
The physician found a perfect summary of Addison's symptoms, an insidious and progressive deterioration of the adrenal cortex. These organs, which secrete a variety of important hormones, sit on the roof of your kidneys in the same manner that snow sits on a mountain top. Their atrophy leads to a severe drop in blood pressure, to weight loss and an overall feeling of weakness. If left unchecked (it is usually treated with steroids), Addison's also causes an overproduction of the skin pigment melanin. This pigment causes the skin to darken considerably, producing an uneven, blotchy black/brown/white complexion all over the body.
When foreign DNA is transferred by genetic engineering to a microbe, plant or animal, a so-called transgenic organism is the result. These new life forms are created for a variety of reasons: to improve on nature, to act as ‘bioreactors’ that make useful products, or to act as models for understanding basic biology.
A transgenic organism usually contains just one gene from another organism within a vast sea of its own DNA. So it is hardly surprising that transgenic sheep, for example, with a gene for a human protein, do not suddenly acquire human faces (or any other noticeably human characteristics). But however reassuringly normal transgenic organisms may appear, they are somewhat different from the creatures that have emerged during the course of evolution.
How radical this difference is depends on your viewpoint. You could argue that humans have been ‘interfering’ in evolution since the dawn of agriculture, with the development of conventional plant and animal breeding, and genetic engineering is just a rather sophisticated breeding technology. You could point to nature's own ‘genetic engineering’ – the spread of antibiotic resistance, the transfer of taxol genes (see p. 74) from the yew to a fungus, and even Griffith's discovery of the transforming principle, to name but three examples. Or you may side with those who regard genetic engineering as deeply suspicious because of the way it allows the setting aside of species barriers.
Inevitably, like any new technology, the creation of transgenic animals raises a number of important issues – animal welfare, environmental and ecosystem concerns and safety.
Alfred Bernhard Nobel has come as close as any human to achieving immortality.
Born in Stockholm, Sweden in 1833, this chemist, who was also the author of the prize that bears his name, grew up to be a man of diverse interests. He was a scientist, inventor and first-rate industrialist, amassing a fortune worth almost $9 million by the time of death. Most of this he threw into an account to fund the prize.
Nobel's occupational interest, however, was explosives and munitions. He made a number of important contributions, including the invention of dynamite. But he was interested in any kind of chemical that could explode. One of these research avenues caused a great tragedy to occur in his life. It may have been part of the reason he established the prize.
Alfred Nobel was researching the properties of nitroglycerin, a volatile explosive of great power. Though he didn't invent the stuff (the honor going to an Italian chemist), Nobel did discover a solution to a very hazardous problem. As you may be aware, nitroglycerin is so explosive that the slightest physical jar can detonate it. Many experimenters were maimed trying to understand the nature of this curious instability. Still more were frustrated because it was a very useful explosive, but could not be transferred from one place to another without great risk. Nitroglycerin remained an oddity of the chemist's research bench for a decade and a half.
The sum total of the DNA in an organism is known as its genome. Although DNA was discovered within the nucleus, this is not the only place where it is found in cells. Some cells do not even have a nucleus.
As far as molecular biology is concerned the distinction between having a nucleus and not having one turns out to be rather important, and is used for classifying organisms at a cellular level. A daisy and a giraffe have hardly anything in common as far as outward appearance is concerned, but to a molecular biologist they are similar because they are both made of cells that have nuclei.
Organisms like this are called eukaryotes. Their DNA is found in the nucleus, but also in cellular structures called mitochondria and chloroplasts. These are the sites of important biochemical activity. Energy production takes place in mitochondria, while the synthesis of glucose from carbon dioxide and water in the presence of sunlight (photosynthesis) happens in the green chloroplasts of plant cells. The fact that mitochondria and chloroplasts have their own DNA suggests that they may have been free-living organisms earlier in evolution (the significance of this is discussed further in Chapter 4).
Organisms whose cells do not have a nucleus (or at least not one surrounded by a membrane like the eukaryotic nucleus) are called prokaryotes. Their DNA lies free in the cell, usually in a closed loop. In addition to this, some bacteria contain small circles of DNA called plasmids.
DNA is a database. The information it contains allows the assembly of the all-important protein molecules within the living cell from their component parts, the amino acids. This database is passed on from one cell to another by the DNA molecule's power of self-replication, as we saw in Chapter 1. Now we look at how the protein recipes are extracted from DNA during the lifetime of an individual cell.
Information flow in most organisms is a one-way street: from DNA to protein. This rule is known as the Central Dogma of molecular biology. This term was coined by Francis Crick in 1956, many years before the details of the molecular processes involved were actually worked out.
The genetic code
The concept of the gene as an inheritable factor responsible for an organism's characteristics was first put forward by the Austrian botanist and monk Gregor Mendel in 1865. Mendel looked at how characteristics such as flower colour, height and seed shape were inherited during carefully controlled experiments with pea plants.
Peas are normally pure-breeding. They reproduce by self-pollination, in which pollen and ovules (the male and female sex cells) from the same plant unite, to give offspring that are similar to their parent. So a pea with white flowers would normally produce more peas with white flowers, and so on.
Mendel removed the stamens (which produce pollen) from his experimental plants, so they could no longer self-pollinate. Then he chose pairs with different characteristics: smooth or wrinkled seeds, red or white flowers, for example. He cross-pollinated these pairs by brushing pollen from one plant onto the stigma (the tip of the female sex organ) of the other.
This last part of our tour opens up the back panels of The Clock of Ages and examines its ticking innards. To start this process, I would like to return to a discussion of the contents of human wills and testaments, a subject previously mentioned in the introduction to Part Two.
Wills reveal an interesting helplessnes in the human condition. We write them to exert authority over our possessions, because we are powerless to do anything about them once the inevitable occurs. Some of these wills make for some interesting reading, and not just as a repository for practical jokes. They can highlight some very human attitudes about the strange ambiguity of death.
For example, there was a will left by a wealthy banker who did not allow the following people any part of his vast estate: ‘To my wife and her lover, I leave the knowledge I wasn't the fool she thought I was. To my son, I leave the pleasure of earning a living; for twenty-five years he thought the pleasure was mine.’
‘You what?’ her mother screamed across the dining-room table. The fire in her mother's voice matched the fire in the nearby family hearth. ‘How could you possibly bring ruin on the name of this good family?’ A young Florence Nightingale outwardly cringed at the outburst.
‘I will not have my daughter taking on the role of a chamber-pot maid!’ her father roared in response to his wife. ‘And in a hospital, for God's sake!’ He stormed out of the room, his dinner untouched. Florence, suffering the steely glares of the rest of her family, grew short of breath. She began to feel weak.
‘see what you've done to your father …’ her mother started. And then, noticing her daughter's sudden frailty, ‘And here we go again, with yet another famous dizzy spell. If you cannot stand up to your family, how will you stand up to a doctor?’
Florence Nightingale stumbled out of her chair and virtually crawled to her bedroom. Since she had announced to her wealthy family her intentions of becoming a nurse, there had been immediate and non-stop conflict. This shortness of breath and heart palpitation had started just as suddenly. Socially, nursing was the closest thing to low-born slavery the elder Nightingales could conceive. To Florence, it was the only thing she wanted to do.
Fortunately for the rest of the world, her family's objections only solidified her resolve.
She was dying. Not much had changed since I had last seen her. She still had a full head of hair, making her look much younger than her 64 years. Her voice betrayed some of her tenure, though. It was almost half an octave higher than the one I had heard as a little boy, the product of a natural stiffening of the vocal cords. The lines on her face spoke of her years too, already sculpted by the finger of time, greatly deepened by decades of loving laughter. These marks always concerned her, though she had once read that wrinkles were a natural, unstoppable part of growing older. She often looked in the bathroom mirror – even as a young mother – to examine their progression. ‘The Clock of Ages’, I would sing to her at the top of my lungs, making a pun from a hymn she loved to hear at church. She paused. ‘But not cleft for me, unfortunately,’ she sighed, tilting her head for the hundredth time, still looking in the mirror.
When I came to see her, she was lying in her bed. It was a darkened room, lit only by the soundless snow from an unwatched TV. I turned off the attached video tape machine. She had fallen asleep watching an old black and white movie from Hollywood.