The next microbial revolution

First broadcast April 2, 2000.

One of the well-known facts of history is the sudden discovery by Louis Pasteur of germs as the main cause of disease. Before Pasteur, dreadful smells and miasmas ruled the roost, the only accepted causes of illness, while after Pasteur, disease was all down to the germs. What could be more simple? One minute, diseases are caused by the smells and vapours around you, and the next minute, that's all gone, and we know that diseases are caused by tiny life forms all around us.

Like all well-known facts, this one bears, if you'll pardon the expression, a germ of truth, but at both ends, there are just a few minor quibbles. For a start, Daniel Defoe, the author of Robinson Crusoe seems to have known a thing or two, long before Pasteur. Defoe wrote his Journal of the Plague Year, in 1712, but it was probably based on his uncle's experience, during the plague, and perhaps even on a journal or diary kept by the uncle - so maybe it was the uncle who knew about germs.

Either way, in his book, Defoe offers us a wealth of detail about what it was like to live through the Great Plague that swept London just before the Great Fire of London. This was a time of great scientific activity - Newton went off to the country to avoid the plague and worked out the answers to all sorts of vexing problems, but in London, Robert Hooke was just about to popularise the newly-invented microscope with his book of engravings called Micrographia.

In this work, Hooke reveals the fine detail of many different life-forms, and makes us wonder what else he saw, but didn't draw. And why do I suspect there might've been other things that Hooke saw?

I think Defoe gives us the answer to that when he writes that he cannot believe

" . . . talk of infection being carried on by the air only, by carrying with it vast numbers of insects and invisible creatures, who enter into the body with the breath, or even at the pores with the air, and there generate or emit most acute poisons, or poisonous ova or eggs, which mingle themselves with the blood, and so infect the body."

Well so much for Pasteur inventing the microbial theory of disease, late in the 19th century! By the way, when Defoe mentions "insects", he doesn't mean the six-legged creatures that we know. Any small creature was an insect then, and this is why we find Oliver Goldsmith, in "The Philosopher and the Spider", writing "The insect I am now describing lived three years . . ." and meaning by that a spider.

Others, though, may have disagreed as to whether Goldsmith was really capable of getting it right. Dr Johnson, according to Macaulay, said of Goldsmith "If he can tell a horse from a cow, that is the extent of his knowledge of zoology." Still, I digress.

In the generation before Pasteur, there were others, of course, who at least suspected that germs existed, people like Ignaz Semmelweiss, who prevented childbed fever in maternity wards by making medical students wash their hands after carrying out post mortems on women who'd died of that disease.

Before, the students had been carrying the germs of the disease from the dead back to the still-living, but Semmelweiss broke this chain of infection. It may not have been a germ theory as such, but he realised that something was being removed when people washed their hands, something capable of causing disease. Of course, he faced the problem in setting forth a germ theory that by then, medical people knew scurvy was caused by poor diet, even though, just two years later, the adventurers heading for the California goldfields would suffer from scurvy, suggesting that whatever medical people knew, the rest failed to pay enough attention. Still, I'll come back to scurvy in a moment.

Then there was John Snow, surely one of the few medical practitioners to have a pub named after him - I've had a beer there, and I have the T shirt to prove it. Snow successfully proposed stopping a cholera outbreak in London's Soho in 1853, simply by removing the handle on one water pump in Broad Street, a pump which was the source of contaminated drinking water. Snow may not have known about germs, but he must surely have suspected that something in the water was causing the disease.

As Pasteur's model took hold, more evidence appeared. Then Robert Koch proposed what we now call Koch's postulates. This set of rules for accurately identifying the microbes causing a disease, let us test things in a scientific way, and contributed to our faith in microbes as the cause of all disease. So did Koch's assistant, Julius Petri, who invented the Petri dish, so beloved of generations of germ cultivators.

By the turn of this century, nobody had much doubt that all those nasty contagious diseases were caused by foreign organisms invading our bodies. Bacteria, fungi and amoebae were all known, though viruses were still in the future, but if anybody found a new disease, the microbe hunters would spring into action seeking out the wicked organism that dared make us ill.

In fact one of the classic books on disease that quite a few older Ockham's listeners would know well, bore a title that celebrates this hunt, Paul de Kruif's The Microbe Hunters. Once that book was on the shelves, we were all firmly locked into the microbial paradigm. Or were we?

The condition sailors called simply "disease", the condition we now call "scurvy" was also well-known. It became apparent to European observers as soon as ships started venturing off on long journeys, at least as far back as Vasco da Gama's crew, who were suffering scurvy by the time they reached Mombasa in 1498, where Moorish traders sold them enough oranges to get them back into good health.

Vasco da Gama credited the fine air of Mombasa for the cure, but it seems rather more likely that the Moorish traders knew all about scurvy - after all, they'd been trading around the Indian Ocean for quite a while by then.

The Europeans were a bit slow to learn. A generation or so later, in 1536, Jacques Cartier's men suffered from scurvy in Canada, where ignorant savages told them the cure: a spruce infusion. Boil up some spruce leaves, they were told, and drink the result. Over the years, until James Lind established that citrus fruit prevented scurvy, most people accepted that scurvy was a problem of poor diet. They disagreed about the best dietary supplements to use, but they agreed that either the food eaten was the cause, a variation on the miasma theme, or they held that a lack of some food caused the disease.

Arthur Phillip ensured that the First Fleet arrived in good health, almost free of scurvy, but the Second Fleet was nowhere near as healthy, because the leaders were nowhere near as convinced that food and scurvy were related - it was still a matter of fashion or opinion, rather than scientific knowledge.

Lind and his supporters, including James Cook, were lucky that there were no clear germ paradigms afloat when they announced the cause and the cure, or they might never have got a look-in at all. Look at what happened to Joseph Goldberger, when he set out to demonstrate that pellagra was caused by a vitamin deficiency.

You see, by the time Goldberger started to investigate pellagra, the microbial paradigm held almost total sway, and if there is one thing harder than isolating the germ that causes a disease, it's proving that there exists no germ able to cause that disease. It's a bit like trying to prove you're innocent of some unspecified crime.

Goldberger's team could point to any number of volunteers who'd developed the symptoms of pellagra, just from eating a restricted diet. They could show that this disease didn't spread to others nearby on normal diets, and they could point to large-population studies in orphanages where only children between 8 and 12, never older or younger, developed the symptoms. Older and younger children, and orphanage staff, seemed to be immune to the disease.

In the end, they were reduced to attempting to infect themselves with pellagra. They tried blood transfusions from pellagra sufferers, then they got more daring, swabbing the noses and throats of victims, and applying those swabs to the sixteen "guinea pigs" who included, let me add, Goldberger and his wife.

Nothing happened, no pellagra developed. In desperation, they even swallowed pellets of dough made from bread, combined with the victims' urine, faeces, and scrapings from the pellagra sores.

On top of that, Goldberger's team were able to cause pellagra in healthy convict volunteers, just by feeding them on a diet of nothing but maize . And then, having started the disease, they cured the victims by shifting their volunteers to a better diet.

So deficiency as a cause of disease was established, and by now people were beginning to identify the vitamins that were behind most deficiency diseases, and we came to accept that diseases can also be caused by things in the environment. Asbestos caused mesothelioma, unless you sold asbestos, just as smoking caused cancer - unless you were in the tobacco trade.

And everybody agreed that ulcers were caused by stress, heart disease was caused by bad diet, and people speculated that cancers mostly came from stray radiation causing mutations, or sometimes it might be chemicals that we'd let loose into the environment. In a different guise, and with more scientific backing, miasmas were back in favour as a valid cause of disease. We called them environmental factors, but they had a marked resemblance to the miasmas of old.

In the end, a few people started to ask questions. Kwashiorkor, a "classic" deficiency disease in the 1970s, came under suspicion as a disease probably caused by aflatoxins produced by a fungus.

Then in 1983, two Perth doctors established that ulcers were caused by a bacterium, Helicobacter pylori. It is now accepted that some 90% of all stomach ulcers are caused by this bacterium, and more recently, it appears to be implicated also in heart disease, and in some types of cancer.

As far back as 1911, Peyton Rous noted what we would now call a retrovirus, which caused tumours to form in healthy chickens, and he managed to transfer this infection to fresh chickens. Now, we know of any number of viruses which, quite incidentally to the infection they cause, set the scene for a later tumour to form, so it's fair to say that many of the cancers we know and fear appear to be caused by some sort of virus or another.

In early 1998, the germs got a bit more credit when it was shown that oral bacteria, the ones that cause plaque to form on our teeth, cause human platelet cells to clump, and soon after, other workers reported a virus which seems to prepare blood vessels for later damage by hardening of the arteries, and they speculated that if you lack this virus, you may be able to eat, drink and smoke to your heart's content, and still not have problems with your heart.

Even insulin-dependent diabetes may be a direct result of an earlier infection by a virus, with Coxsackie B4 as the main suspect right now as the trigger for an autoimmune reaction which attacks selected cells in the pancreas, and I've even seen people speculating on a microbial trigger for dyslexia. In January 2000, the common mouse was identified as a likely source of a virus that causes some breast cancers.

In short, the past two decades have seen a slow and secretive second microbial revolution, with fungi, bacteria and viruses taking the blame or the credit, or at least coming under suspicion, for many conditions that we used to think were the result of natural decay or environmental effects

Well, what does it matter if the microbes have staked a comeback, and revealed themselves as the cause of more diseases than we once thought? We've survived the viruses, the fungi and the bacteria in the past, so we'll survive them in the future, won't we?

It may not be that simple. As we open up new areas, pushing into places that were once uninhabited, so we expose ourselves to new microbes. And one group, the bacteria, are gaining casual exposure to antibiotics, enough to build up high levels of resistance. As we expose ourselves and our surroundings to new and interesting mutagens, chemicals that cause mutations, who knows what nasty little new beasties we may be hatching? Meanwhile, fast jetliners rush freshly infected human culture vessels across the globe, laden with novel microbes, giving related but separated strains the chance to get together, recombine and share their resistance to antibiotics.

Forget the cries of doom of the Rifkinites, the people who say we'll bring ourselves undone with genetic engineering. Concentrate instead on the normal natural genetic engineering that's been going on for eons, the recombination that we've just boosted so drastically.

I for one will be mightily annoyed if somebody shows in the next five years that so-called "natural ageing" is caused by a simple bacterium, but even more so if I then find that the bacterium has developed a strain that is totally immune to any of the magic bullets our medical researchers have put together, just to deal with such annoying microbes. And what'll we do if Alzheimer's turns out to be bacterial, and we've just made the bug resistant to every known antibiotic by dishing them out in the casual way that has been the norm since the 1950s?

That's what really worries me. We've managed the first two microbial revolutions, but how will we deal with the third microbial revolution?


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