Some time ago I had the privilege of meeting Elling Ulvestad, a Norwegian microbiologist who is also a philosopher. He is a man of tremendous warmth and energy, as well as having inexhaustible enthusiasm for his subject. It takes little time for him to convince anybody that the world is in great need of a philosophy that is properly informed by microbiology, not to mention the other way around. Here are the kinds of facts that Professor Ulvestad has on the tip of his tongue. First, we carry ten times as many bacterial cells around on our bodies as we do of our own cells (microbes are very much smaller than our own cells, which is why this is possible). If you also count the viruses that inhabit bacteria – known as bacteriophages – the ratio of microbes to human cells on each of us is probably more like 1000:1. Next, although we commonly regard bacteria as enemies, only around a hundred species regularly infect human beings, while literally millions of others either ignore us or co-operate with us in ways that would make our survival impossible without them. We are, in other words, not isolated individuals but walking ecologies. Our lumbering, multi-cellular bodies act as unwitting landlords to a vast community of far more resilient lodgers who could happily move to alternative accommodation in someone else’s gut or skin – and quite often do.
Ulvestad’s understanding of the interaction between humans and microbes goes far beyond numbers. He points out that microbes have been the ‘chief molecular innovators’ of the biological world. Evolution has been built on microbes’ ability to develop, combine, or incorporate themselves into more complex forms. For a start they are, quite literally, our ancestors – with all modern life forms being their different descendants. They have also managed to become absorbed within our own DNA. Forty-five per cent of human DNA consists of sequences derived from microbes that are not only able to copy themselves during reproduction but also to move around within our chromosomes. The mitochondria that produce all the energy in our cells are themselves the descendants of formerly free-living bacteria. Although they have lost the ability to reproduce independently, they have compensated by managing to shield themselves from destruction by the human immune system.
Our intestines, immune systems and even our brains are dependent on their resident bacteria. For example, if laboratory mice are raised with intestines entirely free of germs, they behave differently from mice living in natural environments who automatically pick up friendly bacteria. If those laboratory mice are allowed to pick up bacteria while still in infancy, their behaviour becomes normal. If they are already adults, their behaviour remains abnormal: in other words, it is too late for the bacteria to help them with their own development. As Ulvestad argues, development ‘ties the organism up in a system of references to other living and non-living entities’. Immunity from disease, he points out, is more than a simple matter of one organism fighting off another. Instead, he argues, it should be understood as ‘a relational property that transcends the boundary of the organism’. It should not surprise us if eradicating a germ like Helicobacter pylori from the stomach (because it can cause ulcers) may result in a microbial backlash with a possibly increased incidence of asthma, along with diabetes and other medical problems.
Humans are sometimes held up as the ultimate example of the ability to transfer information from one generation to the next, through the use of language and culture. However, bacteria are equally adept at social learning. They transfer some of their genes between each other with massive frequency, so that in some of their species only about forty per cent of the DNA is common to all individuals. Ulvestad describes how they are able to take up ready-made genes from a mobile gene pool, and he likens this to the rapid uptake of new ideas by humans of information from the internet. This can sometimes be to the disadvantage of humans, for instance in the way that the germ causing gonorrhoea has developed resistance to all known drugs. It can also benefit us. One example is the way that the Japanese people who regularly eat seaweed can digest a sugar called porphyran because the bacteria on seaweed can transfer their gene for the appropriate digestive enzyme to the bacteria who live in the human intestine, making it possible for them to do the digestion on our behalf.
Bacteria also indulge in what Ulvestad calls ‘cross-talk’: they release and sense molecules that allow them to respond to the environment in a co-ordinated manner – for example by manufacturing protective films around themselves as a group, to defend against antibiotics. They often do so by a process known as ‘quorum sensing’: this enables them to know when their numbers are sufficient for such collaborative projects to be feasible.
One of Ulvestad’s missions is to try to help everyone move away from the ‘war’ metaphor when talking about microbes (as in headlines like ‘doctors defeat invasion of deadly bugs’). This pervasive metaphor in medicine arose in the nineteenth century, largely because most researchers were doctors, and they focused almost exclusively on the bacteria that cause diseases. He reminds us that at least one of the great early immunologists – the Russian, Ilya Mechnikov – was more concerned with studying how competition and co-operation were finely balanced in biology. More than a century after Mechnikov, this perspective has become almost universal in evolutionary and biological studies. A modern evolutionary view does not see any organisms – from viruses to humans – as intrinsically good or bad, but applies scientific curiosity in order to establish how hosts and infectious agents negotiate relationships along a scale from lethal hostility to symbiotic harmony. Ulvestad writes: ‘As scientists, we need to acknowledge the fact that we are only studying a brief interlude of biological time, which represents the current trade-offs reached by contemporary organisms subject to a number of evolutionary forces… These forces are still acting to diversify and complicate the biological processes, and the results of the trade-offs reached will be the challenges encountered by future scientists.’
If Ulvestad is right, the view that doctors often have of themselves as heroic warriors has surely run its course. We need to start thinking about infectious diseases, and maybe all diseases, not in terms of the battlefield but in the kind of mature, ecologically informed view that he sets out. A hopeful development in this respect in the Human Microbiome Project, which aims to identify all the groups of microbes on the human body, and to analyse their roles in health human functioning and development. Many of our health-giving microbes have never been isolated or grown in laboratories before. One outcome of this project has been to establish that that there is a remarkable diversity of organisms among healthy people, with each of us bearing a relatively unique ‘microbiome’ alongside our unique genome. While some microbiomes may turn out to be associated with particular diseases or syndromes, others may confer protection.
Every generation of doctors and scientists is inclined to regard itself as having reached a pinnacle of understanding. We incline rather easily to the belief that our overall framework for understanding the world has been perfected, and it is only the details that remain to be filled in. Ulvestad’s view has the potential to shake this complacency for the next generation of medical researchers and clinicians. If the last fifty years has been the age of the genome, we may be about to enter the era of the microbiome, when we start to pay respect not only to ourselves, but also to the far more ancient, numerous, adaptable and largely collaborative microbes on which our existence depends.