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Microbe INVASION! FINAL PROGRAM SCRIPT

Audio/Narration

/MUSIC, EFFECTS

We live in a microbial world.

Every day we’re exposed to billions of invading bacteria and other microscopic creatures.

But after years of trying to exterminate or exclude them, scientists now realise many of them are allies, not enemies. Some are so essential to us, we should consider them as a vital human organ. Scientists argue that instead of waging war on bugs, in many cases we should welcome

… the Microbe Invasion.

For three and a half billion years Earth has been ruled by bacteria. iThey have colonised every corner of the planet…and its occupants.

As far as they and other microscopic creatures are concerned, the human body is simply another virgin territory to invade and occupy.

“We have emerged as a species on a planet that’s predominated by microbes. Microbes have learned over the course of millions of years of very stringent selection how to insinuate themselves onto and into their mammalian partners.”

So far we’ve treated microbes more like enemies than partners, defending ourselves against attack with antibiotics and vaccines.

But in the war against disease, scientists are discovering many bacteria actually fight on our side.

By studying their strategies and weapons we can learn from our microscopic allies

“ They should be viewed as our teachers. They have been forced to devise a whole range of means of manipulating the biology of their hosts in a way that benefit the microbes but do not harm their hosts.”

For every microbug that causes disease, there are hundreds more that do no harm at all.

Some are even our best line of defence against death and disease.

Scientists now believe that by understanding the complex partnership between our bodies and their billions of microbes, we may be better equipped to fight deadly infections.

“They have developed strategies for manipulating our genes and by turning to them we should be able to forge new ways of manipulating our biology to promote health and to prevent disease.”

Just like the earth itself, our body is a living planet, a network of ecosystems where bacteria are the dominant life form. There’s only one time in our lives when it isn’t so.

While it’s in the womb, this baby lives in a sterile cocoon, protected from an invading army of bacteria and other bugs. ii

For Sarah Tregonning, this is her fourth baby, but it’s still a miraculous and slightly scary experience.

/Lightning and Thunder FX/

/Natsot/ Birth noises/

This is the moment everyone has been waiting for: the baby, his mother, his father, and the combined forces of the microbe invasion.

The first offensive takes place in the birth canal. iii

For generations, occupying armies of bacteria have lived on Sarah and now, they’re ready to invade this new world and all its terrain. [PAUSE]

As the baby emerges from the womb and begins to slide past the birth canal walls, the first tiny microbes leave his mother and attach to the baby’s skin.

The invasion has begun.

Billions of microbial competitors join in. They land, dig in, and secure a beachhead wherever they can.

While some of these invaders are our enemies, many will become our closest allies.

At this vulnerable stage of life, a baby needs all the protection he can get. Dangerous microbes could win the battle for territory and take his life in a matter of hours.

But even as this child takes his first breath, a second invasion has begun.

This second wave of microbes launches itself as soon as the baby emerges

Hundreds of competing species race to take up a strategic position on the baby’s body.

Some are potentially harmful.

All of them are common in every mother’s intestines. iv

/NATSOT/“It’s a wee boy..it’s a wee boy…”

Most bugs will be marooned on the baby’s skin and die there; but some will make it into his mouth and be swallowed.

Eventually they’ll occupy his intestines

/NATSOT/“You’ve got a grandson.

“And his name is?”

“Alexander Charles”

“Oh isn’t that nice?”

If he doesn’t pick them up at birth, there’ll be plenty more chances in the days and weeks after. Touching, kissing and even spitting on him, everyone he meets will cover him in bugs. v

But these bacteria are a precious gift: an army that will defend this baby throughout his life. Bugs like Lactobacilli secrete acid onto our inner surfaces, which discourages other, more harmful bacteria from settling there. vi

Bifidobacteria are another ally. Inside the baby’s intestines, they reproduce quickly and protect him from bad bacteria, simply by overcrowding them. vii

So it’s actually a good idea to welcome some of these microscopic invaders. Scientists believe our body may even encourage bacteria with nutrient signposts, just before or after birth.

“These signposts consist of nutrients, nutrients that are manufactured by the cells that line our intestine. Now an early colonizing species of micro-organism is able to use these signposts to set up shop in a particular location of the intestine and can use these nutrients as important food sources.”

Breast-feeding positively encourages helpful bacteria. Mother’s milk contains antibodies that specifically target harmful microbes. But it allows helpful species like Bifidobacteria to thrive. viii

It’s a telling example of our close partnership with many types of bacteria.

As Sarah’s child grows, all of his available territory - inside and out, will be conquered by microbes.

By the age of two, he’ll be occupied by many different species of bacteria. He will never be alone. In fact, like all of us - his cells will be vastly outnumbered by the microbes.

“The total number of microbes that colonise our surfaces exceed the total number of cells in our body by at least a factor of ten. We are more microbial than we are Homo sapiens.” ix

Our entire lives are spent in partnership with friendly bacteria. They have evolved so closely with us that we can even consider them part of our own family.

But other microbes aren’t so committed to that relationship. There are plenty of opportunists out there, ready to take what they can from us and move on.

Whether we live or die matters little to them.

So we and our microbial allies, have evolved some sophisticated weapons to protect our vulnerable territory.

BREAK ONE

Act 2

The mouth is an open door to microscopic opportunists.

Every day, we and our microbial partners have to guard against disease causing organisms like salmonella that enter here. x

The constant supply of food, warmth and moisture, make our mouth an ideal home for billions of microbes.

Swarms of bacteria like spirochetes live in this rich sea of saliva, and so do their giant predators.

Protozoans like Trichomonas prey on them as well as dead skin cells and scraps of food. xi

Music and fx

When human populations boom in a confined area, they create elaborate structures and societies we call cities.

The same thing happens in our mouth, only it’s called a biofilm. xii

Using our teeth as foundations, Streptococcal bacteria stick themselves to the enamel surface. They and billions of others build blocks and towers as busy and crowded as any modern metropolis. 50

The longer it grows, the more complex life in the biofilm becomes.

But just like a human city, these dense populations can produce pollution.

Some bacteria create the sulphur compounds responsible for bad breath. xiii

Others feed on sugars, and excrete acid powerful enough to strip the enamel off our teeth. xiv

There’s a good reason why brushing and flossing stops these bugs from damaging our teeth and gums.

The action tears down the protective biofilm, and lets in fresh air. Many of the bacteria living here are anaerobic; for them oxygen is a lethal poison.

As the biofilm collapses, so does their world.

While Streptococci are the dominant bacteria in this oral society they come in many species, most of them friendly.

“In your mouth, you have massive populations of these friendly streptococci but they’re not there to harm us, in fact they’re our closest friends. They’re our own if you like personal army of protectors, there to defend us against the occasional rogue streptococcus”

Professor John Tagg knows all about rogue strep. As a child, he was plagued with streptococcal infections that gave him sore throats and rheumatic fever – a disease that kills five hundred thousand people every year xv. John Tagg survived but it left him with a burning ambition

“ I was quite determined then to get one back on the streptococcus”

“It became a lifetime obsession”

It took thirty years of research, but Professor Tagg, of New Zealand’s Otago University has made a major discovery.

Not only are some strains of Strep harmless, at least one produces its own natural antibiotic, known as BLIS.

“BLIS is the little term that we’ve developed if you like for this smart weaponry that bacteria seem universally to apply to deal with the competitors that they will encounter in nature.”

The good Strep use BLIS to sabotage the growth of their competitors.

BLIS are chemical weapons that target rival groups of fast growing Strep bacteria.

These micro-missiles penetrate the surface of the enemy cells allowing vital nutrients to leak out. And so, an entire community of competitors starves to death.

By understanding how this biological control system works, the BLIS research team are developing a natural alternative to antibiotics.

Trials so far suggest that giving children helpful strep in a tablet establishes populations of these good bacteria in the mouth.

The good bugs then go into battle to keep the bad bugs under control.

As a result, the chances of getting strep infections are significantly reduced.

As Dr. Tagg sees it –it’s smarter and more economical to adopt nature’s sophisticated weaponry instead of blasting the body with broad-spectrum antibiotics.

“BLIS are the equivalent of the laser-guided weaponry being developed today to take out specific targets. Rather than the somewhat more crude approach of dropping an atomic bomb and taking out all the terrain as well as the inhabitants.”

Working with friendly bugs to discourage certain harmful microbes in the mouth and throat is a clever idea. Meanwhile other micro-organisms are swallowed and find themselves on a one way trip through the human gut.

The digestive system offers a rich array of habitats for good bugs and bad. This is where we and our microbial partners work hard to keep treacherous opportunists under control.

The first line of defense is the stomach.

This half-gallon pool of enzymes and hydrochloric acid is enough to tear most microbes to pieces.

But it’s not foolproof.

For years scientists assumed that the stomach was sterile but they have now discovered that some bacteria actually make their home in this liquid hellhole.

Helicobacter pylori live in the stomach lining. They create their own chemical shield to protect themselves from stomach acid. xvi

“Helicobacter pylori is a spiral shaped bacterium that sets up shop in half the humans that live on this planet. For most humans this organism colonises the intestine, produces a short-term inflammation of the lining in the intestine, but then enjoys a relatively – what we think – a relatively innocent relationship with its host.”

But for 20 per cent of people with this bacteria xvii, the benign relationship turns nasty. The immune system tries to attack these spiral-shaped bugs.

Instead of killing the bacteria, however, the powerful chemicals damage the stomach lining, causing painful ulcers.

Other microbes can make it past the stomach safely, provided they know a trick or two.

Salmonella is the most common food poisoning bug. It often crops up in badly prepared meat or dairy products. xviii

These foods contain fat globules that offer bacteria a protective coating against stomach acids.

And so, Salmonella slip past our defenses in a kind of Trojan horse made of grease.

But the body does have a means of fighting back against these aggressive marauders:

..its own fat-busting detergent called bile.

Bile is like dishwashing liquid – it breaks up fat into tinier globules we can absorb. It also happens to be lethal to many kinds of bacteria. xix

However, some microbes survive these perils in protective coats or spores. They head for the small intestine - a rich feeding ground for friendly microbes and opportunists. But bacteria have a hard time settling down here.

They must fight against the churning rapids of liquidised food and digestive juices. Any creature that wants to stick around here has to be specially equipped. xx

The only ones that are, are real monsters.

Tapeworms are the ultimate parasites, superbly adapted for life in the human gut. xxi

Some species grow to almost fifteen feet long. Others can reach more than thirty feet. xxii

Some species grow to more than 4 metres long.

Others can reach over nine metres

Such monsters can block the intestine, or consume so much food their hosts suffer malnutrition.

They reproduce by detaching egg sacs that pass through the intestine to be picked up by another unsuspecting host. xxiii

These parasites feed while latched on to the intestinal lining with a bunch of hooks and suckers attached to their ugly heads. 21

Most bacteria get swept harmlessly downstream along with the food.

But one tough customer will always cause havoc - given half a chance.

Clostridium enters the gut in its own protective spore. Once activated, it becomes a protein feeder. xxiv

It digests the meat in the diet, but it can also make a meal of our intestinal lining. Victims can end up with deadly abdominal infections. xxv

To stop these bacteria and their toxic waste products from damaging our tissues, every week or two we shed the layer of cells that lines our intestine. xxvi

“These cells sit at the interface between a toxic wasteland and the rest of the body and their renewal probably is part of an ancient mechanism designed to take away damaged cells as a result of their exposure to the toxins that exist in the diet.”

The shed cells make a feast for bacteria like Clostridium, and they’re welcome to it.

But down at the bottom of our intestinal folds, budding young cells are vulnerable to attack. Recently scientists discovered the powerful defence system that protects them. xxvii

Paneth cells are like anti-aircaft batteries. They launch packets of destructive enzymes that protect the cell “nursery” from bacterial attack.

For microbes that have survived this far, the hazardous journey is almost over. After travelling 20 feet ( six metres) through the small intestine they are about to reach the promised land – the colon. xxviii

This is where bacterial numbers explode and where the partnership between our bodies and our bacteria truly flourishes. We rely so heavily on our friendly bugs that many scientists now consider them as vital as any human organ.

“We have a kilogram and a half of bacteria in our gut which constitutes an organ, an organ that is as important to our physiology as our lungs or our kidneys or our liver. And this organ does things like helping it to digest food, it provides a lot of vitamins, it breaks down a lot of drugs, it provides various essential lipids and precursor molecules, so it is very much a part of our physiology…we are partly bacterial.”

BREAK 2

ACT III

What we choose to consume affects our health. But just as important is the mounting recognition that our health also depends on the colonies of bacteria that live in our intestines.

From her teenage years, Sarah Tregonning suffered terrible digestive problems. She had flatulence, bloating and stomach cramps.

“Sometimes I’d be constipated and other times I’d be having dreadful, dreadful diarrhoea, and I had no idea of when that would be or what foods would set me off.”

Sarah was put on high fibre diets and treated with steroids but nothing really worked. Eventually she was diagnosed with irritable bowel syndrome - a chronic illness that affects up to 25 per cent of the population, mostly women. xxix

“When I first started working I had problems with irritable bowel syndrome and it was really difficult because I was working in the food industry and you can’t just keep running off to the toilet every two minutes when you desperately need to go and there’s nothing you can do to control it.”

/Audio tape /

“I got to the stage where I was so thin because of the constant diarrhoea and the constant pain in my stomach was preventing me from eating because anything I ate would still upset my stomach.”

The causes of irritable bowel syndrome are not clear but most of the symptoms are associated with the colon.

We mightn’t think of our colon as the land of milk and honey but for trillions of bacteria – this is heaven.

And it’s here that science is uncovering an extraordinary relationship between humans and microbes.

This is where the bacterial population explodes – fuelled by fibre.

Our bacterial allies break down what’s left of our food – the roughage we can’t digest. xxx

In the process, they create waste products, mainly in the form of gas. xxxi

The gas may be a discomfort but it’s a fair trade for the extra nutrients we get from the bacterial activity. All in all, it makes for a mutually beneficial relationship.

“We’ve come to an arrangement, with our gut flora, and we provide a home for them, we provide a surface for them to live on, the mucosal surface and they provide the nutrient and they provide the protection.”

In such ideal conditions, everyone jostles for a prime position.

The good bacteria expand quickly to fill the space available. Fortunately for us, that helps keep harmful bugs away from our colon walls.

“So our normal bacterial flora provide a major barrier to any new organisms that would like to come and live in our gut and that applies of course to poisoning organisms like salmonella and things, that might wander down there. They’re the first defense against invading species.”

To protect their patch, friendly bacteria like Lactobacilli produce acid that discourages harmful microbes from breeding. xxxii

As bad bacteria reproduce and grow they often give themselves away by broadcasting toxins into the area.

Our friendly bugs listen for such enemy broadcasts, as well as communicating among themselves. xxxiii

“One thing that’s becoming quite clear, is that there is a lot of molecular chattering going on, not only between the bacteria themselves, but also between the bacteria and our own cells.”

This constant chit-chat gives bacteria a good idea of their own numbers and the number of possible enemies too.

If our bacterial allies decide there are too many bad bugs in the neighbourhood, they’ll attack them with their own biochemical weapons.

But the body’s defence force, the immune system is “listening in” too. If it detects a mounting threat of insurrection, it’s always ready to enforce the peace. xxxiv

But when there are too many bad bugs, the immune system just evacuates the area.

We experience this as vomiting or a bad case of the runs.

“It just throws everything out the nearest way. If the damage is being done in the stomach then up it comes. If it’s being done in the colon then down it goes and if it’s in between it can go both ways.”

But there is a drawback to this drastic evacuation. Our empty spaces become ripe for colonisation by harmful species. The same thing can happen after taking antibiotics.

“Broad spectrum antibiotics affect the normal healthy flora of the bowel. And a not infrequent problem in people taking antibiotics is of course they develop diarrhoea – because some of the good bacteria die off and the bad ones start to grow up and produce toxins.”

/Sound fx/

Luckily, we can repopulate our intestines with good bacteria from the supermarket shelf.

Yoghurt and other live-bacterial products, known as probiotics are proving to be life-changing health supplements. xxxv

After 15 years of chronic pain and discomfort, Sarah Tregonning chanced upon a solution to her problems. One day she walked into a health food store and got talking to natural therapist Georgie Chisholm.

The therapist recommended Sarah take a daily dose of live bacteria. She thought these good bugs might just help.

Sarah was ready to try anything – even swallowing capsules of live bacteria.

After 3 months, Sarah’s irritable bowel settled down.

“I don’t have the constant urge to go to the toilet. I don’t have the dreadful bloating or the stomach cramps and I can eat not quite whatever I fancy but certainly I can eat with a lot more comfort than I used to. It is a miracle cure and it’s literally cleaning me up from the inside out.”

Probiotics - the idea that taking live bacteria might be beneficial to human health is only now beginning to gather scientific support.

“The scientific community were very sceptical about this at first – the major claims for the benefits of probiotics, I think, are really that they stimulate the immune system and secondly that they strengthen this barrier of resistance to invading bacteria and therefore they would help to protect you against food poisoning, infectious diarrhoea and help improve your gut after you’d had an episode.”

But it now seems scientific evidence and backing for probiotics is taking off.

When Russian cosmonauts developed digestive problems during long missions in space, medical staff developed a special yoghurt to settle their stomachs. xxxvi

They cultured bacteria from the intestines of crewmembers who were doing fine and fed it to the troubled cosmonauts.

By eating yoghurt containing their comrades’ bacteria, the cosmonauts’ troubled digestions were happily fixed.

Commercial voice: “…it’s culture at the highest level”

What to do with astronauts’ intestinal bacterial is an issue that’s troubled NASA since the sixties. It’s a matter of volume and weight.

“There are trillions of bacteria in our colon, and when we defecate each day half the mass of our stool are live bacteria that emanate from this microbial society.”

The last thing Nasa wanted on their spacecraft were waste units full of live bacteria.

So they devised foods intended to shut down the astronauts’ gut dwelling bacteria altogether.

“When the Americans wanted to put a man on the moon, they had to get around this problem of defecation. They designed this special diet which was totally residue free, there was nothing for the gut bacteria to feed on, and so the idea was that the gut bacteria effectively died. They could go for three or four weeks without defecating. When the time come it was an agonizing experience. But, they could go for three or four weeks, they could do a moonshot.”

But the idea never took off. Astronauts would have nothing to do with the special diet.

Without bacteria colonising our “Inner Space” we’d all be in deep trouble.

But if we allow bacteria into our forbidden zones, the consequences can be dire.

Third Break

Act IV

The outer surface of an adult human offers around twenty square feet ( 2 square metres) xxxviiof skin.

For microbes there’s a wide choice of climates and habitats.

With little sweat or other secretions, our legs are like dry deserts. Here there are about 70,000 microorganisms per square inch. xxxviii

11,000 microorganisms per square centimetre

There are even more in the forest of the scalp.

But the steamy jungles of the armpits and groin support the densest populations of microbes. Up to six and a half million bacteria occupy every square inch.

Up to one million bacteria occupy every square centimetre.

With its oily secretions, the face is microbe paradise.

By the end of a typical day, the bacterial population here is exploding well into the millions. xxxix

Clostridium spores constantly settle on our skin. In the right conditions, they can become flesh-eaters. To protect ourselves from these bacterial infestations..

..we simply move them on. Dead skin cells detach in small clustersxl……taking any hitch-hikers with them.

If bad bugs do get in, they can inflict terrible damage.

Mark Inglis is one of New Zealand’s most successful wine-makers – but it wasn’t his first career choice. He used to be a mountaineer until he lost both legs at the age of 22.

While climbing Mt Cook, New Zealand’s highest mountain, Mark and a fellow mountaineer became trapped by bad weather. It was fourteen days before they could be rescued. They were lucky to be alive but by then frostbite had set in to their feet.

“ I always remember on the way to the hospital Phil and I discussing that we’d perhaps lose the big toe; at the worst perhaps we’d lose all of our toes. You know there’s plenty of climbers around missing toes. We didn’t even consider the thought of gangrene or the extent of the frost bite, losing whole legs.”

In the hospital, Mark’s feet were slowly thawed out but the damage was done.

“Every day in hospital, the feet swelled up and then started to discolor and then started to turn black.”

Frostbite had turned the water in his body cells to ice, rupturing the cell walls and killing the tissue.

The destruction opened the way for bacterial infection by Enterobacter xli, causing gangrene.

“With the wet gangrene, they puffed right up, first one foot, then the other. Then after treatment with antibiotics, the foot almost mummified.”

In the end, surgeons had no choice but to amputate. On Christmas eve 1982, Mark Inglis had both legs removed just below the knee.

“Nothing can ever prepare you to waking up and seeing the sheets end so much shorter on your bed. Those were the worst three days of my life.”

Keeping bacteria out of the body’s forbidden zones requires constant vigilance.

Dead or damaged tissue is just one way in for rogue bacteria, but the body has other access points that it must defend.

The eyes and ears are protected by a powerful antibacterial compound called lysozyme.

Earwax collects trespassers like flypaper. And then lysozyme molecules home in on their captive targets. xlii

These antibacterial molecules attack by chopping bits out of the invaders’ cell walls. xliii

Airborne microbes like Clostridium are trapped and killed here every day, but there are billions more floating in the air.

And so we have a series of clever traps for dealing with them.

In the nostrils, giant hairs and sticky surfaces catch some invaders. xliv

But others manage to slip past these defences.

/Music and FX/

If a dangerous intruder like a Clostridium spore infiltrates the lungs, then bodyguards called macrophages arrive swiftly to deal with them. xlv

/FX/

The Macrophage engulfs the invader… and removes it for disposal

Millions of tiny hairs on the walls of our airways carry unwelcome bugs back up towards the throat. xlvi

Once there, we either drop them into the acid bath of our stomach by swallowing, or eject the bugs back into the air with a cough. xlvii

Every minute of the day these traps prevent microbes from invading our forbidden zones. At the same time, in places where they’re welcome, we tolerate our microbes as part of a healthy ecosystem.

But what happens to the microbes when we die?

The latest scientific research reveals there is indeed life after death.

FOURTH BREAK

ACT V

There is one final journey that we and our microbes will take together.

The journey to death, and beyond.

When we die, our bodies are prepared for burial or cremation. While such respect is quite natural, it interferes with the processes of Nature.

In this unusual outdoor laboratory, people have donated their bodies so that forensic scientists can uncover the secrets of natural decomposition.

(SOUND ON TAPE)L.W. ..at this point in time”

Dr. Richard Jantz and his team of anthropologists from the University of Tennessee study the process of decay - to help criminal investigators identify the time and cause of death. xlviii

“Bacterial proliferation in the body is pretty active and a lot of bacteria grow, so, they’re working from inside out. And then with the warmer weather the flies become more active and lay eggs, so you’ll have a larger maggot population and they work form the outside in; so, they’re efficient soft tissue carnivores. So they’ll go relatively quickly – three and a half, four weeks.”

While insects play their part in dismantling the body, the forensic scientists are uncovering the hidden role performed by microbes.

“Even in the absence of insects, the body will putrefy and eventually decompose. So the decomposition process sort of starts from the inside out, and the body’s own microbes consume it, so to speak.”

Some of our decomposers may even be descendants of the bacteria our mothers handed down to us at birth.

Many of them have helped keep us alive and healthy since the day we were born.

Now, without the living ecosystem we provide, they face the end too.

As the skin cools and dries out, it becomes an inhospitable place for most bacteria. xlix

While the body is alive, the soldiers of the immune system fight to keep rogues like Clostridium out of sensitive areas.

But now the immune system is out of action. l

Without macrophages to keep them under control, vast numbers of Clostridium spores hatch out and rampage through the body.

Caught up in a feeding frenzy, the expanding population’s activity raises the temperature to over 120 degrees fahrenheit. li (over 50 degrees celsius)

As the last supper continues, the feasting hordes create large amounts of gas. With all the exits closed, it has nowhere to go.

The body begins to bloat as the bacterial party goes out of control. lii But the contents of the intestine are soon used up.

“There are some bacteria which just live off carbohydrates and fibre and that’s it, they don’t have anything to eat they’re done for.”

Starving and overwhelmed by the protein eaters, our allies begin to die.

“There are other bacteria which can digest protein very happily and they’ll start digesting you.”

Clostridium and other decomposers finally serve as our undertakers, breaking down our organs and tissues. As they see us into our afterlife, they’re also planning their own.

Clostridium produces spores for when the party ends. In these time capsules, they can travel freely and reactivate..

…centuries later. liii

About five to ten days after death, the skin bursts. In a flash, billions of partying microbes die when they are suddenly exposed to oxygen and cold temperatures. liv

Those that have prepared for this moment will escape on a breeze, or perhaps on the body of a feeding insect. lv

The rest will die and break down as our flesh dries out and is eaten by scavengers. Only the skeleton will endure, and we’ll be alone, for the first time since we left the womb.

For most of our lives, we’ll be unaware of our body’s inhabitants and the battles they fight for us.

Good or bad, they can’t live without us, and we’d be in trouble without many of them.

From the moment we’re born, our good bugs will dig in and become our first line of defence.

“ We acquire these partners from the beginning of our life as we enter this world. We live with them and we die with them. And the question that I think is so exciting is to decipher the significance of this microbial partnership to our own biology, how microbes shape and participate in shaping our physiology and how that contributes to our health and how that sets us up for vulnerabilities or resistances to a variety of different diseases”

No matter where life takes us, we’ll never be alone. We’ll always be accompanied by our microbial allies, the armies of the microbe invasion.

/Theme Music to end/

/SFX OVER LOGO/

i “Australian rocks 3,485 million years old contain eleven or more types of rcognisable fossil bacteria. The oldest rocks on Earth thus contain vestiges of life.” Margulis, L. and Sagan D. 1995. What is Life? Simon & Schuster, p.53.

Madigan M.T., Martinko J.M. and Parker J. 2000. Brock, Biology of Microorganisms. Ninth edition. Prentice-Hall International Editions, p.424.

ii Tannock, G.W. 1995. Normal Microflora. Chapham&Hall, p.37.

iii Tannock, G.W. 1995. Normal Microflora. Chapham&Hall, p.37.

iv “At the moment of birth or shortly thereafter, microbes in faeces that have been expelled involuntarily by the mother during labour…have the opportunity to colonize the neonate.” Tannock, G.W. 1995. Normal Microflora. Chapham&Hall, p.37.

v “Suckling, kissing and caressing of the infant after birth provide additional insurance that members of the microflora are transmitted from one generation to the next.” Tannock, G.W. 1995. Normal Microflora. Chapham&Hall, p.37.

vi “Lactobacilli are often found in dairy products, and some strains are used in the preparation of fermented milk products….The lactobacilli are rarely ever pathoghenic.” (p.506-7). Madigan M.T., Martinko, J.M and J. Parker 2000. Biology of Microorganisms. Prentice-Hall International Editions.

“…these aerotolerant rods produce lactic acid from simple carbohydrates. The acidity inhibits competing bacteria, but lactobacilli grow well in acidic environments. In humans, lactobacilli are located in the vagina, intestinal tract, and oral cavity.” (p.287) Tortora, G.J., Berdell, R.F. and C.L. Case 1992. Microbiology. An introduction. The Benjamin/Cummings Publishing Co. Inc

vii The study referenced here shows the probiotic effect of bifidobacteria by direct inhibition of the adherence of pathogenic bacteria. (Bernet MF, Brassart D, Neeser JR, Servin AL. (1993) Adhesion of human bifidobacterial strains to cultured human intestinal epithelial cells and inhibition of enteropathogen-cell interactions. Appl Environ Microbiol; 59(12):4121-8).

viii Tannock, G.W. 1995. Normal Microflora. Chapham&Hall, p.44.

Hill, J.M., Path, F.R.C., and Marsh, P.D. 1987. Human Microbial Ecology. CRC Press, p 92.

ix This microbial collection, generally referred to as the normal microflora, is acquired soon after birth. It is estimated to consist of about 1014 microbial cells, outnumbering the approximately 1013 human cells that make up the body.” (p.1) Tannock, G.W. 1995. Normal Microflora. Chapham&Hall.

x “One important biological property of the outer membrane layer of many gram-negatve Bacteria is that it is frequently toxic to animals. Gram-negative Bacteria that are pathogenic for humans and other mammals inlude members of the genera Salmonella, Shigella, and Escherichia, among others.” Madigan M.T., Martinko J.M. and Parker J. 2000. Brock, Biology of Microorganisms. Ninth edition. Prentice-Hall International Editions, p.74.

xi http://www.homepages.uel.ac.uk/d.p.humber/trichtut.htm

Lange, D.E, Stockmann, H., and Hoecker, K., “Vorkommen und Identifizierung von Protozoen in der menschlichen Mundhoehle”, Dtsch. Zahnaerztl. Z., 38, 906, 1983. [Presence and identification of protozoans in the human mouth]

xii Spake A. Taking aim at the citadels of slime

“In the same way that organisms that everyone is familiar with birds or coral reefs or what have you…form very complex communities complex both physically and biologically- bacteria do the same thing…so biofilms can be a few species or many many species moreover the physical structure can be very complex – just like the physical structure of a coral reef or a rainforest is very complex. In a biofilm you get towers of cells in this extracellular matrix and channels and bits coming off that move further down into the biofilm. A metaphor people have used is cities …and if you can imagine cities as having office blocks and smaller buildings and roads and alleys then that is not a bad analogy.”

Transcript taken from UB136 – Biosignal 00:11:22:00:

xiii http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s222.htm

xiv Prof. John Tagg during a telephone conversation on the 25 May 2001 (paraphrased):” Lactic acid is produced by the organisms that colonise the teeth, like streptococci. It is the most powerful organic acid. It is able to break down the enamel in the teeth.”

xv Of over 15 million deaths due to circulatory diseases, 7.2 million were caused by coronary heart disease, 4.6 million by stroke, 500 000 by rheumatic fever and rheumatic heart disease, and 3 million by other forms of heart disease.

http://www.who.int/whr/1997/factse.htm

xvi “H pylori is unique in its ability to thrive in the human stomach. It does this by activating its own cytoplasmic urease, which converts urea into carbon dioxide and ammonia. The ammonia first neutralises the gastric acid that enters the outer membrane of the bacteria, preventing acidification at the inner membrane. This allows the bacteria to colonise the stomach” Berger, A. Scientists discover how helicobacter survives gastric acid. BMJ 2000;320:268 ( 29 January )

xvii % of population H Pylori positive: 66%

% of ulcers related to H Pylori: 85%

(from CDC website)

% of those who are H Pylori positive and who get ulcers = 21%, (or 7x the number who are H Pylori negative)

http://www.jr2.ox.ac.uk/bandolier/bandopubs/hpyl/hpall.html#prevalen

xviii “All salmonellae are considered pathogenic to some degree, causing salmonellosis or Salmonella Gastroenteritis” Tortora, G.J., Berdell, R.F. and C.L. Case 1992. Microbiology. An introduction. The Benjamin/Cummings Publishing Co.Inc. p.624.

“Meat products are particularly susceptible to contamination by Salmonella. If these products are mishandled, the bacteria can grow to infective numbers rather quickly. The sources of the bacteria are the intestinal tracts of many animals, and meat can be contaminated readily in processing plants. Poultry, eggs, and egg products are often contaminated.” Tortora, G.J., Berdell, R.F. and C.L. Case 1992. Microbiology. An introduction. The Benjamin/Cummings Publishing Co.Inc. p.624.

xix “Bile is a potent selective agent since, while most bacterial species are killed by relatively small concentrations of bile acids, some are resistant and some species…are stimulated by the presence of bile.” Hill, J.M., Path, F.R.C., and Marsh, P.D. 1987. Human Microbial Ecology. CRC Press. p.63

Neufeld, F., Ueber eine specifische bacteriologische Wirkung der Galle, Z. Hyg. Infektionskr., 34, 454, 1900. [About a specific bactericidal function of bile]

xx “Bacteria in the upper small intestine are exposed to high concentrations of bile salts, proteolytic enzymes…The rapid flow of fluid through the small bowel and the flushing effect of the small bowel secretions assist in maintaining small bowel cleanliness and the resting small bowel is only heavily colonized in conditions of stasis. Hill, J.M., Path, F.R.C., and Marsh, P.D. 1987. Human Microbial Ecology. CRC Press. p.72.

xxi “The head, or scolex, has suckers for attaching to the intestinal mucosa of the host. Some species also have small hooks for attaching to the host. Tapeworms do not ingest the tissues of their hosts; in fact, they completely lack a digestive system. To obtain nutrients from the small intestine, they absorb food through their cuticle.” (p.320-1) Tortora, G.J., Berdell, R.F. and C.L. Case 1992. Microbiology. An introduction. The Benjamin/Cummings Publishing Co.Inc

xxiv In table 13.28 (p.510) C.[lostridium] sporogenes, C. tetani, C. botulinum, C.tetanomorphum and C. propionicum are listed as amino acid fermenters. Madigan M.T., Martinko J.M. and Parker J. 2000. Brock, Biology of Microorganisms. Ninth edition. Prentice-Hall International Editions

xxv “Clostridium difficile is a major cause of antibiotic-associated diarrhea. While treatment regimens for C. difficile have been available for decades, they remain less than optimal due to the frequent recurrences that occur after therapy is completed. Moreover, the morbidity and expense associated with C. difficile have underscored the need for more effective preventive measures than are currently available.” Ciesla WP, Bobak DA. Management and Prevention of Clostridium difficile-Associated Diarrhea. Curr Infect Dis Rep 2001 Apr;3(2):109-115

“Clostridium difficile causes 300 000 to 3 000 000 cases of diarrhea and colitis in the United States every year.” Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile--Associated diarrhea: A review. Arch Intern Med 2001 Feb 26;161(4):525-33

xxvi “..crypts are the principal sites of cell regeneration, replacing cells which migrate up the epithelial escalator. The epithelium is renewed in approximately 3-5 days. At villus tips senescent cells are shed.” (p.297) Mims, C., Nash A., and Stephen J. 2001. Mim’s patogenesis of infectious disease. Academic Press. San Diego

xxvii “Paneth cells live in the bottom of microscopic pits -- called crypts -- in the lining of the intestinal wall. The crypts create new cells that line the intestinal wall; this wall of cells is replaced every four to six days and is the only barrier between the bloodstream and bacteria ingested with food. Paneth cells are like sentinels that protect this cell renewal process from bacterial infestation by forming a chemical barrier of immunity.”

xxviii “In most animals, the length of the small intestine is roughly 3.5 times body length - your small intestine, or that of a large dog, is about 6 meters [20 feet] in length.” Colorado State University; Hypertext for biomedical sciences

xxix Irritable bowel syndrome: an update on therapeutic modalities. : Expert Opin Investig Drugs 2001 Jul;10(7):1211-22

Farhadi A, Bruninga K, Fields J, Keshavarzian A.

Department of Internal Medicine (Division of Digestive Disease), Pharmacology, Molecular Biophysics and Physiology, Rush University Medical Center, Chicago IL, USA.

“Irritable bowel syndrome (IBS) is the most common condition that a physician faces in the GI clinic. Of the general population, 10 - 25% suffer from symptoms judged to be IBS. The negative impact of this disease includes not only pain, suffering and direct medical expenses but also significant social and job-related consequences.”

Irritable bowel syndrome in women: the physician-patient relationship evolving. J Am Osteopath Assoc 2001 Dec;101(12 Suppl Pt 2):S12-6

Foxx-Orenstein AE, Clarida JC.

Department of Gastroenterology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA. aefoxx@hsc.vcu.edu

“Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders seen by primary care physicians and specialists. The disorder affects approximately 15% to 20% of the world's population and is predominately found in women.”

xxx “Your body thinks it has taken everything that is any good out of the food and all that goes down into the colon is just rubbish that’s unusable. And the bacteria use that rubbish to so good effect that 30% of the weight of the content is just pure bacteria. The bacteria are shoulder to shoulder you know, they are really tightly packed in there and they just multiply and multiply and multiply. And they have broken down the fibre, and when they break down the fibre you get about 10% or more of the energy.” Prof Michael Hill, Southbank University, London during interview on 13 Sept. 2000. UB9 0:12:44

xxxi “Some foods which are poorly absorbed in the stomach and intestines can be metabolized by fermentative bacteria resulting in the production of hydrogen and carbon dioxide. In many individuals, methanogenic bacteria then convert some of the H2 and CO2 to methane gas (CH4).” (p.395) Brock, T.D. and Madigan M.T. 1991. Biology of Microorganisms. Sixth edition. Prentice-Hall International Editions

xxxii “…studies with antibiotic treated animals suggest that the flora protects individuals from pathogens. Investigators have used streptomycin to reduce the normal flora and have then infected animals with streptomycin-resistant Salmonella. Normally, about 106 organisms are needed to establish a gastrointestinal infection, but in streptomycin-treated animals whose flora is altered, fewer than 10 organisms were needed to cause infectious disease. Further studies suggested that fermentation products (acetic and butyric acids) produced by the normal flora inhibited Salmonella growth in the gastrointestinal tract.”

xxxiii :” Bacterial communication, toxin production tied to intriguing cell

Protein”. Weidenbach, K., Stanford University.

xxxiv Telford G, Wheeler D, Williams P, Tomkins PT, Appleby P, Sewell H, Stewart GS, Bycroft BW, Pritchard DI. The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone has immunomodulatory activity. Infect Immun 1998 Jan;66(1):36-42

xxxv “Probiotics [Greek pro, for, and bios, life], the oral administration of either living microorganisms or substances to promote health and growth, has the potential to reestablish the natural balance and return the host to normal health and nutrition.” p.558. Prescott, Lansing M., John P. Harvey and Donald A. Klein, 1996. Microbiology. WCB Publisher

xxxvi BBC World News 12 August 1999:

New Scientist from 14 August 1999 reported the same story:

xxxvii An average human adult has about two m2 [21.5 feet2] of skin surface, containing a variety of different microenvironments…” Brock, T.D. and Madigan M.T. 1991. Biology of Microorganisms. Sixth edition. Prentice-Hall International Editions.

“The skin … constitutes 10% of the total bodyweight and in an adult has an area of approximately 1.8 square metres [19.4 feet2].” Marples, M.J. 1965. The ecology of the human skin. Charles C. Thomas, Publisher

[Researcher’s note: This makes 20 feet2 a good intermediate.]

xxxviii “The figures go something like this (per cm2) [per inch2] for a grown man: 1 million [6,500,000] in the armpit, 1.5 million on the scalp, 200.000 [1,300,000] on the forehead, but only 50.000 per cm2 on the back and 11.000 [71,500] on the forearm.” (p.58) Andrews, M.L.A.1976. The Life that lives on Man. Faber & Faber, London. [Researcher’s note: We considered the environment of the forearm and the leg as very similar, thus interchangeable]

xxxix Bacterial count on face. (p. 200) Bodanis, D. 1986. The Secret house. Simon & Schuster, New York

xl “About 10.000 million [10 billion] skin scales or squames peel off each of our bodies every 24 hrs.” (p.166) Andrews, M.L.A.1976. The Life that lives on Man. Faber & Faber, London

xli The enterobacteria family includes numerous inter-related genera, all of which are microscopically indistinguishable. The group includes E coli and Salmonella species ref: Bacteriology Illustrated, Gillies & Dodds

His medical records state that Mark Inglis grew Enterobacter & some E coli from his feet. 1 swab post amputation grew Staph epidermidis. Some Enterobacter are normal gut commensals, others are normally present in the environment, However they may also be pathogens. They are the most common cause of intra-abdominal infection and urinary tract infection, especially post surgery.

xlii Petrakis NL, Doherty M, Lee RE, Smith SC, Page NL: Demonstration of lysozyme and immunoglobulins in human cerumen. Clinical and genetic implications. Nature 229: 119-120, 1971

xliii “Lysozyme is an enzyme that cleaves glycosidic linkages in peptidoglycan in the bacterial cell wall, leadening zu weakening of the wall and cell lysis.” (p.777). Madigan M.T., Martinko J.M. and Parker J. 2000. Brock, Biology of Microorganisms. Ninth edition. Prentice-Hall International Editions.

xliv “The normal microbiota of the nose is found just inside the nares. Staphylococcus aureus and S. epidermidis are the predominant bacteria present and are found in approximately the same numbers as on the skin of the face….The upper and lower respiratory tracts (trachea, bronchi, bronchioles, alveoli) do not have a normal microbiota.” (p.556) “Microorganisms larger than 10?m are usually trapped by hairs and cilia lining the nasal cavity.” (p.575) Prescott, Lansing M., John P. Harvey and Donald A. Klein, 1996. Microbiology. WCB Publisher

xlv “If microorganisms actually reach the lungs, then certain phagocytic cells – the alveolar macrophages, or dust cells – usually locate, ingest, and destroy most of them.” (p.590) Tortora, G.J., Berdell, R.F. and C.L. Case 1992. Microbiology. An introduction. The Benjamin/Cummings Publishing Co.Inc

xlvi “The mucociliary blanket of the respiratory epithelium traps microorganisms less then 10 ?m in diameter that are deposited on the mucosal surface and transports them by ciliary action away from the lungs.” (p.575) Prescott, Lansing M., John P. Harvey and Donald A. Klein, 1996. Microbiology. WCB Publisher

xlvii This so-called ciliary escalator keeps the mucous blanket moving toward the throat at a rate of 1 to 3 cm per hour; coughing and sneezing speed up the escalator.” (p.409) Tortora, G.J., Berdell, R.F. and C.L. Case 1992. Microbiology. An introduction. The Benjamin/Cummings Publishing Co.Inc.

xlix Most fungi are classified as saprophytes because they live on dead or dying material and obtain energy by breaking down organic matter in dead plants and animals. Trautmann N., and Olynciw, E. Compost microorganisms.

l “White blood cells move about for at least six hours [after death].” Mims C., 1998. When we die. Robinson, London. P.113-120

li “The metabolic changes caused by maggots and anaerobic bacteria cause the internal temperature of the carcass to rise up to 53?C [127?F].” Goff, M. Lee, 2000. A fly for the prosecution; How insect evidence helps solve crimes. Harvard University Press, Cambridge, Massachusetts; London, England

lii The abdomen shows signs of inflation as result of putrefaction. As by-product of the metabolic activity of anaerobic bacteria that invade the body from the guts gasses are produced. Mims points out that “…at this stage, reached in temperate countries four to six days after death, there will be a disagreeable odour due to release of the gases hydrogen sulphide and methane, and traces of mercaptans. The smell of a decomposing body is remarkably persistent and penetrating.” (p. 121) Mims C., 1998. When we die. Robinson, London

liii “A number of gram-positive bacteria can form a special resistant, dormant structure called an endospore. Endospores develop within vegetative bacterial cells of several genera: Bacillus and Clostridium (rods), Sporosarcina (cocci), and others….. These structures [endospores] are extraordinarily resistant to environmental stresses like heat, ultraviolet radiation, chemical disinfectants, and desiccation. In fact, some endospores have remained viable for well over 500 years…” Prescott, Lansing M., John P. Harvey and Donald A. Klein, 1996. Microbiology. WCB Publisher, p.67

liv The combined feeding frenzy of maggots and anaerobic bacteria finally leads to breaking the skin, allowing the gasses to escape and the corpse to deflate….[and] the corpse’s temperature returns back to the temperature of the surroundings. By the end of the decay stage only 20% or less by weight of the body remain, consisting mainly of bones and skin. (days 5-11) Goff, M. Lee, 2000. A fly for the prosecution; How insect evidence helps solve crimes. Harvard University Press, Cambridge, Massachusetts; London, England

lv As Dr Brian Batson (Southern Institute of Technology, Invercargill, NZ) pointed out to me during a phone conversation on the 26 April 2001 (paraphrased): “Even when an organism is not able to survive on the decomposing body anymore, not only spore forming organisms have a chance of survival. For instance the many visiting insects may take up droplets of body liquids containing huge amounts of anaerobic bacteria and drop them on your sandwich.”

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