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Journalism of Courage
Behold yourself, for a moment, as an organism. A trillion cells stuck together, arrayed into tissues and organs and harnessed by your DNA to the elemental goals of survival and propagation. But is that all? An electron microscope would reveal that you are teeming with other life-forms. Any part of your body that comes into contact with the outside world8212;your skin, mouth, nose and especially digestive tract8212;is home to bacteria, fungi and protozoa that outnumber the cells you call your own by 10, or perhaps a hundred, to one.
Their ancestors began colonising you the moment you came into the world, and their descendants will have their final feast on your corpse. There are thousands of different species, found in combinations 8220;as unique as our DNA or our fingerprints,8221; says Stanford biologist David Relman, who is investigating the complex web of interactions microbes maintain with our digestive, immune and nervous systems.
Microbes, Relman holds, are 8220;a part of who we are8221;. Relman is a leader in rethinking our relationship to bacteria. 8220;It8217;s awful the way we treat our microbes,8221; he says, not intending a joke; 8220;people still think the only good microbe is a dead one.8221; We try to kill them off with antibiotics and hand sanitisers. But bacteria never surrender; if there were one salmonella left in the world, doubling every 30 minutes, it would take less than a week to give everyone alive diarrhoea. In the early years of antibiotics, doctors dreamed of eliminating infectious disease. Instead, a new paper in The Journal of the American Medical Association reports on the prevalence of Methicillin-resistant Staphylococcus aureus MRSA, which was responsible for almost 19,000 deaths in the US in 20058212;about twice as many as previously thought.
As antibiotics lose their effectiveness, researchers are returning to an idea that dates back to Pasteur, that the body8217;s natural microbial flora aren8217;t just an incidental fact of our biology, but crucial components of our health, intimate companions on an evolutionary journey that began millions of years ago. The science writer Jessica Snyder Sachs summarises this view in four words in the title of her ground-breaking new book Good Germs, Bad Germs. Our microbes do us the favour of synthesising vitamins right in our guts; they regulate our immune systems and even our serotonin levels: germs, it seems, can make us happy. They influence how we digest our food, how much we eat and even what we crave. The genetic factors in weight control might reside partly in their genes, not ours.
We8217;ve made a Faustian bargain with our antibiotics, because most researchers now believe that our supersanitised world exacts a unique price in allergies, asthma and auto-immune diseases, most of which were unknown to our ancestors. Sachs warns that many people drew precisely the wrong conclusion from this, that contracting a lot of diseases in childhood is somehow beneficial. What we need is more exposure to the good microbes, and the job of medicine in the years to come will be sorting out the good microbes from the bad.
That8217;s the goal of the Human Microbiome Project, a five-year multinational study that its advocates say could tell us almost as much about life as the recently completed work of sequencing the human genome. One puzzling result of the Human Genome Project was the paltry number of genes it found8212;about 20,000, which is only as many as it takes to make a fruit fly. Now some researchers think some of the 8220;missing8221; genes may be found in the teeming populations of microbes we host.
And the microbe project8212;which as a first step requires sampling every crevice and orifice of 100 people of varying ages from a variety of climates and cultures8212;is 8220;infinitely more complex and problematic than the genome,8221; laments or boasts one of its lead researchers, Martin Blaser of NYU Medical School. Each part of the body is a separate ecosystem, and even two teeth in the same mouth can be colonised by different bacteria. In general, researchers know what they8217;ll find8212;Escherechia including the ubiquitous E. coli in the bowel, lactobacilli in the vagina and staphylococcus on the skin. But the mix of particular species and strains will probably turn out to be unique to each individual, a product of chance, gender men and women have different microbes on their skin but are similar in their intestines and socioeconomic status and culture. Race seems not to matter much.
The most intriguing question is how microbes interact with each other and with our own cells. 8220;There is a three-way conversation going on throughout our bodies,8221; says Jane Peterson of the National Human Genome Research Institute. 8220;We want to listen in because we think it will fill in a lot of blanks about human health.8221;
The vast majority of human microbes live in the digestive tract; they get there by way of the mouth in the first few months of life, before stomach acid builds to levels that are intended to kill most invaders. The roiling, fetid and apparently useless contents of the large intestine were a moral affront to doctors in the early years of modern medicine. But to microbiologists, the intestinal bacteria are a marvel, a virtual organ of the body which just happens to have its own DNA. Researchers at Duke University claim it explains the persistence of the human appendix. It serves, they say, as a reservoir of beneficial microbes which can recolonize the gut after it8217;s emptied by diseases such as cholera or dysentery.
Microbes play an important role in digestion, especially of polysaccharides, starch molecules found in foods such as potatoes or rice that may be hundreds or thousands of atoms long. The stomach and intestines secrete 99 different enzymes for breaking these down into usable sugars, but the humble gut-dwelling Bacterioides theta produces almost 250, substantially increasing the energy we can extract from a given meal.
Of course, 8220;energy8221; is another way of saying 8220;calories.8221; Jeffrey Gordon of the University of Washington raised a colony of mice in sterile conditions, with no gut microbes at all, and although they ate 30 percent more food than normal mice they had less than half the body fat. When they were later inoculated with normal bacteria, they quickly gained back up to normal weight. 8220;We are finding that the nutritional value of food is pretty individualized,8221; Gordon says. 8220;And a big part of what determines it is our microbial composition.8221;
And that8217;s an essential step in the development of a healthy immune system. The immune reaction relies on a network of positive and negative feedback loops, poised on a knife edge between the dangers of ignoring a deadly invader and over-reacting to a harmless stimulus. But to develop properly it must be exposed to a wide range of harmless microbes early in life.
8220;Modern sanitation is a good thing,8221; says Sachs, 8220;but they keep kids at a distance from microbes.8221; The effect is to tip the immune system in the direction of overreaction, either to outside stimuli or to the body8217;s own cells. If the former, the result is allergies or asthma. Sachs writes that 8220;children who receive antibiotics in the first year of life have more than double the rate of allergies and asthma in later childhood.8221; But if the immune system turns on the body itself, you see irritable bowel syndrome, lupus or multiple sclerosis.
And there8217;s one more thing that microbes can do, perhaps the most remarkable of all. Mycobacterium vaccae, a soil microbe found in East Africa that has powerful effects on the immune system, was tested at the University of Bristol as a cancer therapy. The results were equivocal, but researchers made the startling observation that patients receiving it felt better regardless of whether their cancer was actually improving. Neuroscientist Chris Lowry injected mice with it, and found that it activated the serotonin receptors in the prefrontal cortex8212;in other words, it worked like an antidepressant, only without the side effects of insomnia and anxiety.
There is the tantalising, if disconcerting, suggestion that microbes may be able to manipulate our happiness. Could the hygiene hypothesis help explain the rise in depression? We8217;re a long way from being able to say that, much less use that insight to treat people. But at least we are asking the right questions: not how to kill bacteria, but how to live with them.
8212; With Matthew Philips, Raina Kelley and Karen Springen
-JERRY ADLER and JENEEN INTERLANDI Newsweek
