Microbe Struggles
In 1847, the Hungarian-German physician Ignaz Semmelweis was trudging around Vienna with a burdened conscience.
Semmelweis was an obstetrician, a doctor specialising in pregnancy and childbirth, and was in charge of the maternity ward at Vienna General Hospital. The hospital had set up two clinics to offer free maternity care to the poor women of the city. And in return, one of the clinics was used to train new midwives while the other was used to train new doctors.
To Semmelweis’s dismay, there was a large difference in maternal mortality rates between the two clinics. At the midwife-training facility, four per cent of mothers died during childbirth, but at the facility training new doctors, more than ten per cent of mothers perished. The cause was a mysterious disease called ‘childbed fever’.
The poor women of Vienna were well aware of the different mortality rates. They begged and pleaded to be taken to the safer clinic when going into labour. Some even chose to give birth on the street rather than risk ending up in the hands of the young doctors.
Semmelweis was deeply unhappy about the situation, and did everything in his power to identify the cause. He tried to align all procedures and instruments between the two clinics, but mortality rates just didn’t budge.
One day, Semmelweis’s friend Jakob Kolletschka was accidentally cut by a student’s scalpel while he was performing an autopsy. The cut gave Kolletschka a bad infection, and not long afterwards, he passed away. At his autopsy, doctors found suspicious similarities to the women with ‘childbed fever’ and then, something finally clicked for Ignaz Semmelweis.
Back then, it was normal for doctors to go straight from conducting autopsies to attending deliveries: that is, from cutting open dead people to assisting women in childbirth. Semmelweis became convinced there was a connection; he reasoned doctors transferred ‘cadaverous particles’ from corpses to the expecting mothers. After some reflection, he suggested that the particles could be removed by handwashing with calcium hypochlorite (the ‘chlorine’ used today for disinfecting swimming pools). He immediately made it obligatory for all doctors at the hospital to wash their hands before getting anywhere near the women in childbirth.
The new initiative provided the breakthrough Semmelweis had sought, and the mortality rate at the hospital plummeted. In April, just before the introduction of handwashing, 18.7 per cent of expecting mothers passed away. By June, only 2.2 per cent did. And by July, mortality rates had dropped all the way down to 1.2 per cent.
Semmelweis immediately set about reporting his discovery to the medical community. This was a big deal and could save countless lives. However, to Semmelweis’s surprise, the reception was mostly hostile. Some doctors were deeply offended that he would even suggest they were unclean. Others pointed out that Semmelweis’s observations didn’t fit the prominent scientific theories of the day.
One critic was the respected Danish obstetrician Carl Levy, who also struggled with sky-high maternal mortality rates in Copenhagen. Levy wrote that it was absurd to think that something microscopically small – so small you couldn’t even see it – could cause such a serious disease. The numbers from Vienna had to be a coincidence.
For years, poor Semmelweis fought the criticism hailing down on him from all directions. He wrote letter after letter to prominent people in the medical establishment but to no avail. The resistance eventually made him so furious that he accused his opponents of being murderers. Before long, he turned any conversation towards maternal mortality and handwashing.
As time went on, Semmelweis’s mental state began deteriorating. In 1861, he developed severe depression, and soon after began to experience nervous breakdowns. A few years later, he was admitted to a psychiatric institution. Here, he was beaten by the guards, developed an infection, and – ironically – died of blood poisoning at the age of forty-seven.
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Around the time of Semmelweis’s death, there were, fortunately, other people making strides in microbiology too. A trifecta of scientists from the European ‘big three’ – France, Britain and Germany – helped to establish the theory that microbes can cause disease. First, the Frenchman Louis Pasteur proved that microbes don’t arise out of thin air, as was commonly believed at the time. He also discovered that microbes are the cause of fermentation in beer and wine (the process that makes alcohol), and that microbes make food rot.
Food decay can be avoided in three different ways, Pasteur demonstrated: by using high heat (pasteurisation), by filtration, or by applying chemical solutions. This gave the English surgeon Joseph Lister an idea. Back then, patients often got infections after surgeries. Lister thought that chemical solutions might be used to avoid this, and developed methods to sterilise surgical equipment and wounds. Subsequently, the German scientist Robert Koch developed methods for growing bacteria in the laboratory, and finally started linking specific bacteria to the development of particular diseases, such as tuberculosis, cholera and anthrax.
Of course, all this progress happened under constant critical assault – but, over time, the evidence became irrefutable. Even the most stubborn critics had to yield.
It might be hard for us today to understand how people used to believe bacteria arose out of thin air, or how doctors thought it was fine to commute between corpses and patients without washing their hands. But the steep opposition to new ideas hits closer to home.
Today, we’ve developed an arsenal of weapons against microbes. We have antibiotics that can kill almost all the bacteria that used to haunt us. We have vaccines that can protect us from diseases that used to be deadly or incapacitating. And we have tons of knowledge of hygiene, paths of infection and sterility.
At one point, it even seemed like we could declare the final victory in our ancient battle against microbes.
But is that true?
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In the early 1980s in Perth, Australia, a pathologist named Robin Warren noticed something strange in laboratory samples from peptic ulcer patients. When examining them closely, he could see small, spiral-shaped bacteria in all of them. Warren approached a young doctor named Barry Marshall, who immediately began investigating.
At the time, people knew that peptic ulcers were caused by stress. They definitely didn’t have anything to do with bacteria. Most scientists assumed that the spiral-shaped bacteria Robin Warren found must have originated in the laboratory. There had probably been contamination of the samples. However, Warren and Marshall weren’t convinced, and decided to continue studying the mysterious microbes.
The first step was to isolate the bacteria and grow them in the laboratory. The two scientists gathered 100 patients with peptic ulcers and took biopsies from all of them. The effort was a disappointment, though, as no bacterial colonies grew from the samples. This continued in successive tries until luck finally shone on the Australians. Normally, patient samples were allowed to grow on Petri dishes for two days, as was the custom at the time. But on one occasion, one of the Petri dishes was left for a full six days because the scientists had their Easter holiday. That was enough time for a colony of spiral-shaped bacteria to develop.
Warren and Marshall were convinced that they’d found the real cause of peptic ulcers. It wasn’t stress, diet, lack of exercise, nor anything else that the textbooks claimed. Instead, it was all down to these small, spiral-shaped bacteria.
The two Australians shared their discovery with anyone who would listen, but the reception was mostly cold. Their peers argued that bacterial diseases were a thing of the past; they’d all been identified decades ago and cured with the invention of antibiotics. Now, scientists were working with much more sophisticated theories. It was no longer cool to look for bacteria – and by the way, it couldn’t possibly be as simple as the two Australians claimed. Bacteria would never even be able to survive the harsh gastric acid.
Besides, everyone already knew what caused peptic ulcers, and there was a large industry specialising in alleviating the symptoms using antacids. At the time, two to four per cent of Americans had antacids in their pockets, so this was big business.
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As it turns out, Warren and Marshall weren’t the first scientists to posit a link between infection and peptic ulcers. In the late 1800s, several researchers observed bacteria in laboratory samples from peptic ulcer patients. And at the dawn of the next century, Japanese researchers even brought on peptic ulcers in guinea pigs by using some suspicious spiral-shaped bacteria they had isolated from cats.
The theory never took hold, though, and the last bit of hope was extinguished in the 1950s when a famous pathologist decided to test it. He searched for bacteria in peptic ulcer patients, but found none because he’d used the wrong method.
Afterwards, the idea slipped out of the scientific consciousness, although it occasionally re-emerged – for instance, when a Greek doctor treated his own peptic ulcer with antibiotics and successfully used the method on his patients as well. No scientific journals wanted to publish his findings, though, and no drug companies were interested in the treatment. As a thanks, the Greek authorities fined the doctor and took him to court.
So, opposition to the bacterial theory of peptic ulcers was nothing new. Warren and Marshall managed to convince a couple of microbiologists who thought bacteria were the most fascinating thing ever. But other than that, their theory got drowned out by publication after publication with claims about stress, diet, gastric acid and so on.
It didn’t help that the two Australians had trouble demonstrating their theory in animals. When they tried to infect anything from pigs to mice, the spiral-shaped bacteria simply refused to take hold.
In time, Warren and Marshall grew desperate. They knew they were on to something, and could even cure their patients with antibiotics. So could the rest of the world’s doctors, but only if Warren and Marshall managed to convince the necessary authorities. The only option was to prove their theory in humans once and for all. But how?
With pure Australian nerve, Barry Marshall decided to use himself as a guinea pig. He isolated the spiral-shaped bacteria from a patient, let them grow established in a culture – and then swallowed them. After a few days, he became well and truly ill. Ten days later, the bacteria had spread throughout his stomach, giving him a precursor to peptic ulcers. And, after careful documentation, Marshall used antibiotics to eradicate the infection and cure himself.
The daring self-experiment was enough to finally turn the tide in the Australians’ favour. It would be another ten years before the last resistance was swept off the field (and the patent on antacids expired). However, the spiral bacterium,
Helicobacter pylori, was gradually recognised as the primary cause of peptic ulcers, and also as the cause of most cases of stomach cancer.
Victory was sweet for the stubborn Australians. In 2005, Robin Warren and Barry Marshall were awarded the greatest honour in science, the Nobel Prize, for their discovery.
Once upon a time, our understanding of how microbes cause disease went something like this: you get infected with a specific microbe, for instance a bacterium or a virus, and then you develop a corresponding disease. This was one of the reasons Robin Warren and Barry Marshall met resistance. They were working to prove that the bacterium Helicobacter pylori causes peptic ulcers and stomach cancer. But some people carry Helicobacter pylori in their stomachs with no problems. Nevertheless, the bacterium is the cause, and its eradication is a treatment. It simply turns out that the relationship between us and microbes is a lot more complicated than we once thought.
Back in the day, we used to think humans were mostly sterile. But in recent decades, technological advancement has revealed that’s anything but true. We’re actually teeming with trillions of non-human organisms – what is called the ‘microbiome’. In fact, there are more cells of foreign origin in your body than there are your own. These organisms (counting bacteria, viruses, fungi and others) live on your skin, in your mouth, in your intestinal system and everywhere in between. You can imagine the situation as something similar to a tree in the rainforest. While the tree may have preferred to be left alone, it is home to all sorts of insects, reptiles, birds, mammals and even other plants. In the same way, you’re not just a person, but an entire ecosystem of living things.
Among your microbial guests are those that are beneficial to you. There are also those that don’t affect you all that much. And finally, there are those you’d rather be without. The beneficial microbes include bacteria that perform important biological functions, for instance, bacteria in the intestinal system that aid your digestion. One example is bacteria that use indigestible dietary fibre to make a health-promoting compound called butyrate. Another example is the bacteria we’ve previously met that produce the autophagy-promoting compound spermidine. But there are also other – much weirder – examples of microbes helping us out, such as gut bacteria that can help runners improve their endurance by breaking down lactate so that it doesn’t build up.
There are also microbes that are primarily helpful because they protect us against other microbes. You see, the ecosystem in your gut (and elsewhere) is balanced by competition for food and space. Gut bacteria will actively try to crowd each other out, fight each other and even eat each other. Some disorders of the gut arise when this balance gets disrupted, for instance, when a course of antibiotics kill beneficial bacteria, allowing harmful ones to vastly expand their real estate.
While it might sound nice and cosy to think that some microbes are helping you, I want to stress that this is not due to some kind of empathy. The microbes in your body are interested in themselves and themselves only. As you are their home, it can sometimes be beneficial for them to help you out. But if conditions change, and they can get a leg-up at your expense, they’ll gladly do so.
For example, imagine a harmless bacterium coexisting peacefully somewhere in your body. The bacterium reproduces occasionally but is also kept in check by your immune system. At one point, a mutation changes the bacterium, allowing it to suddenly evade your immune system. This will probably allow the bacterium to make many more copies of itself and could help it beat its competitors and more easily spread to new hosts. This will come at your expense, though, as the bacterium starts using up valuable resources and may even hurt you in the process. Obviously, if the bacterium goes so far that it ends up killing you, it will lose its home. But even that can sometimes be an acceptable price in evolutionary terms, if it helps the bacterium spread. It’s a devilish and egoistic strategy, but of course not due to actual sentience. It’s just simple evolution. Microbes that manage to produce more copies of themselves prevail.
The most popular place for microbes to settle is on the skin and in the gastrointestinal tract. Here they have access to food, and there is less immune activity because both are a surface of the body rather than its inside (there’s a hole from the mouth and all the way through, so these surfaces are technically ‘outside’ too). But it is not only on the ‘outer’ surfaces of the body that microbes take up residence. In fact, it turns out that even the organs we once thought were sterile abound with life.
Take blood, for example. Until recently, medical science assumed that our blood was sterile. But we now know that’s not true. When you incubate blood samples from blood donors under the right conditions, you can grow all sorts of different microbes from it. (Maybe the secret of young blood is that it has fewer harmful microbes?)
The brain is an even more extreme example. Previously, it was thought that the brain had to be sterile because it is protected by something called the blood–brain barrier. As the name suggests, the blood–brain barrier is a barrier that separates the blood from the brain. Oxygen and nutrients can pass through, but it’s notoriously difficult for most molecules to enter the brain. This is one of the reasons why it is so difficult to develop drugs for mental illnesses. The brain is our most important organ, so it makes sense that we want to protect it and keep microbes out.
That said, there are microbes in the brain. Actually, scientists have identified more than 200 different kinds already – and they’re not done looking. Really, there are microbes in any place you can imagine – and we could continue with microbes in the muscles, in the liver, in the chest and so on.
The point is that all these microbes don’t just sit around. They affect everything that happens in your body. In fact, they even affect our medical efforts. Studies show that at least half of the most popular drugs are altered by bacteria before they even enter the body from the gut.
The life-extending, brain-controlling parasite
There’s a certain kind of parasite – a tapeworm – that cycles between birds and ants. The tapeworm lives in the guts of birds like woodpeckers, and its eggs are excreted in the birds’ faeces. When ants eat the contaminated faeces, the parasites hatch and take up residence in the ant’s abdomen. Here, they have a steady stream of nutrients on which to live. However, the parasites ultimately aim to return to the gut of a bird, as this is the only place where they can lay eggs. It’s a weird lifecycle. To achieve their goal, the tapeworms completely take control of the ant. The positive side – if there’s ever such a thing when infected with brain-controlling parasites – is that the tapeworms have found a way to prolong the lives of their hosts. Parasitised ants live at least three times longer than non-infected ants. We don’t really know how it all works, though. And of course, the parasites are not trying to be helpful. They just want the ant to live longer, so it has a higher chance of being eaten by a bird at some point. And if a bird does show up, the parasites leave their host no mercy. The tapeworm thwarts the ant’s natural fear response so instead of fleeing, the parasitised ant just sits around helplessly while staring blankly at the sky.