Tuesday, October 21, 2014
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Microbiology's World Wide Web

All the fashionable talk nowadays about computer “viruses” explains what these culprits do by forging an analogy to their biological namesakes. But it is equally enlightening to portray the biosphere of real, living microbes as a world wide web of informational exchange. Indeed, microbes exchange information with each other and their environment, with DNA serving as the packets of data going every which way. Microbes differ from computer viruses because they not only spread but evolve, and do so at a faster pace than their hosts. Microbes are in fact well designed to exploit this difference to their advantage in the war that occasionally erupts between them and other species - a war we see as disease and death.

It is the microbe’s capacity to transfer information to other organisms that makes the analogy with the World Wide Web plausible. Like computer viruses, many living viruses can integrate (download) their own DNA into their host’s genetic material (the genome), and this can be copied and passed on. Indeed, even our own, human, evolution is partly explained by these encounters with microbes. Many segments of human DNA originated from historical encounters with a particular type of viruses, known as retroviruses, which “downloaded” their information into human cells and integrated it into human DNA.

The field of molecular genetics, which began in 1944, when DNA was proven to be the mechanism by which inherited characteristics are passed on, brought microbes to the center of many biological investigations. Systems composed of microbes are often the most convenient models to study evolution in a laboratory.

What makes the evolution of microbes so intriguing - and worrisome - is their combination of vast populations and intense fluctuations within those populations. Some microbes possess a gene that enhances their variability, and this allows them to mutate at different rates in response to factors in the environment - something larger organisms rarely do. Also, while more advanced life forms, like humans, cannot mate with members of other species, microbial evolution is less constrained by this “species barrier.” Indeed, through a processes known as Aplasmid transfer,” microbes can exchange biological innovations among themselves, including - most importantly and dangerously - resistance to antibiotics, which one species of microbes can pass on to another.

The sheer number of microbes and their ability to exchange information is a formula for high-speed evolution. Populations of microbes fluctuate by many billions on a daily basis as they move between their host organisms and encounter antibiotics, antibodies, drought, or other natural hazards to which their genetic evolution may respond. A simple comparison of the pace of the evolution of microbes and their multicellular hosts suggests a millionfold or billionfold advantage to the microbe. One year in the life of a microbe, indeed, easily surpasses the ages it took for all mammals to evolve!

By that measure, mankind is playing out of its evolutionary league. Indeed, many complex species lost the war with microbes to become extinct. Human history, too, has been marked by catastrophic microbe-caused plagues. While humanity has survived all these microbe-inspired disasters so far, maintaining our survival in a world in which germs/viruses and their hosts continuously interact in new ways will require us to think in innovative ways as well, and to bring ever more sophisticated technical wit and social intelligence to the contest.

In my recent work, I explore the implications of this gross imbalance in the evolutionary pace of humans as compared to microbes and viruses.

Had the entire evolutionary drive of microbes been directed at optimizing their virulence and lethality, larger species would not have survived such murderous competition. But, of course, neither would many microbes have survived, because they depend on other species for their habitat. Despite the fact that microbes do not ordinarily seek to maximize their virulence, most research on infectious disease focuses on the mechanisms by which the harmful effects of microbes are felt, as well as on the ways in which host organisms adapt (mainly through the immune system) to fight that virulence. Very little attention has been given to the microbes’ internal mechanisms for sustaining themselves as inhabitants within their hosts, which includes the interest the microbe shares with its host in controlling and limiting the damage it does.

After all, microbes reside in their hosts in order to gain from the exchange. Startling examples show that a microbe’s goal is, indeed, joint survival with its host. In some cases, the host’s immune system is even manipulated by one parasite in order to enhance the host's resistance to super-infection by rival, invading parasites. We may thus have to learn how to exploit these synergies and use the weapons that microbes provide us, rather than look at them only as mortal enemies marked for peremptory extermination.

Just as scientists study entire ecological systems to see how the various parts interact, we must regard the human body as an extended genome. Its parts consist of the nuclear DNA genome (karyome), a chondriome (mitochondria), and what I call the microbiome: the menagerie of the body’s attendant microbes. We must study the microbes that we carry within us and on our surfaces as part of a shared embodiment.

If you can't beat them, join them! the old saying goes, and for better and worse our fates are joined with the microbes that share our bodies. We can and will benefit from a deeper understanding of just how they work within and with us.

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