Of men and microbes

  • Letters
  • Sunday, 27 Apr 2003


AFTER a lapse of some decades, germs and disease have again been very much on our minds, largely because of the dreadful impact of AIDS throughout the world. We have also had a reawakened consciousness that globally prevalent diseases like tuberculosis and malaria remain historic scourges. 

Now, the daily news tells us of new outbreaks such as SARS (severe acute pulmonary syndrome) spreading from China throughout the world, with an outcome that cannot be confidently predicted at this time. 

Throughout history, infectious disease has regulated our lives. Only in the 20th century, thanks to simple hygienic measures like washing our hands regularly and separating drinking water from sewage run-off, have we taken a larger role, for better or worse, in trying to control how microbes affect human life. 

Since the late 1920s, the metaphor we optimistically adopted concerning our relationship to germs has been that of the microbe hunters’ conquest over specific diseases. By the 1960s, reinforced by the wonder drugs and vaccines of mid-century, many were claiming that ‘‘plagues will be forever banished from Earth’’ – only to be humbled after the tragic advent of the AIDS epidemic. 

Clearly, complacency about infection was a by-product of our campaign against the germs. Now SARS is today’s new challenge. 

Rather than conquest and the notion of eradication of infectious disease, we should learn a more nuance lesson: that we best aspire to a relationship of symbiotic co-existence with germs. That co-existence can track the spectrum from vicious lethal pandemics to mutual tolerance. 

Microbes vs humans. Microbes abound in the zillions. These are tiny organisms that can grow and evolve in cycles of 20 minutes or less. Individuals are entirely dispensable when a community of a billion cells can be replaced overnight from a single seed. Tens of billions of cells can be cultured in a single small test-tube. 

By contrast, the human species has a population size of less than 10 billion, quite modest on the microbial scale. Each organism is multi-cellular and large with a costly, long developmental cycle. Each of us would be the first to resist violent fluctuations in population size. Nor could human society flourish without the nurture and protection of most individuals. 

In further contrast of the germs’ biological capacities, they readily exchange genes within and between various species. They don’t ‘‘speciate’’ or differentiate into genetically isolated organisms as we do. In fact, these bugs engage in ‘‘promiscuous lateral gene transfer,’’ making the microbial world a kind of DNA-based worldwide web that shares genetic information that can move from one bug to another. 

When, for example, antibiotics get into our sewage system and kill some bugs, it is the occasional resistant mutant that survives. These survivors can then transfer their newfound immunity to the genes of other microbes, including pathogenic species that foment human disease. 

These rapidly evolving bugs can gang up on humans through synergies of organisms that provoke mild disease which, when joined with others, become virulent. This may prove to be the case with SARS that appears to be a variation of the common cold virus. 

Not only are we genetically isolated from other species, the cells of the human germ line are sealed off in our gonads. Whatever that body might learn by way of generating immunity – let’s say against a new virus – cannot be passed on to one sperm or egg to the next generation. New generations have to learn it all over again in a fresh cycle. 

In short, the competitive evolutionary odds seem cast very much in favour of the bugs. We see this mismatch when great plagues and epidemics sweep the world. By the raw evidence, the capability of evolving bugs should have trounced us eons ago. 

So why haven’t they? Why are we still here, sharing the planet with the bugs? They haven’t extinguished us simply because microbes have a shared interest in the domestication and survival of the host – humans and other multi-cellular creatures. 

The bug that kills its host is at a dead end. If it is a victorious conqueror, it extinguishes its life as well as our own. 

The ground rules. This reality allows us to establish some of the ground rules of evolutionary success in the microbial world – the cardinal rules of parasite behaviour. 

They go forth and disseminate as their first rule. They multiply. 

Next, according to Malthusian and Darwinian doctrine, they have to be the fittest in order to survive and secure the largest number of offspring they can. 

Then they face a dilemma: If they extinguish their host too quickly, they will not be able to propagate. But, of course, they also have an imperative of securing a lodging post in the host, a bridgehead, fighting off local defences and establishing a reservoir for dissemination. 

The symptoms of disease that we see are very often secondary to our defence mechanism, but are exploited on behalf of the bug’s capacity to disseminate. 

For example, once an organism like cholera gets into your gut, it provokes the most intense diarrhoea imaginable. To effect diarrhoea, cholera secretes a hormone that results in the release of water in the gut. As long as the patient plays the game of massive rehydration, he is likely to balance the loss of fluid, survive and also have disseminated the bugs by the billions. 

Cholera doesn’t ‘‘want’’ to hurt us, but its survival as a species depends on polluting water supplies. The disease is then transmitted to other hosts. 

Sometimes, a germ will even protect the host against other competing pathogens. A promising example of this in AIDS research is the discovery that infection with a variant hepatitis C virus seems to be correlated with considerable resistance against the progress of HIV. It is not surprising that one virus would try to crowd out another one. That is part of its strategy to maintain its competitive advantage. 

The best strategy of all is to fuse with the host by becoming part of the host’s genome. 

After such a long evolution, we are, in fact, carrying around 500 different integrated retro-viruses in our own genomes that are a testimony to a history of experience with the relatives of the HIV virus. The ancient viruses we encountered now perform indispensable defence functions for the host. 

In short, the microbes that co-inhabit our bodies show considerable self-restraint by moderating the virulence of disease, especially in well-established relationships with animal hosts. 

Microbiome. It would thus broaden our philosophical horizons if we think of a human as more than an organism. It is a super-organism with an extended genome that includes not only its own cells but also the fluctuating microbial genome set of bacteria and viruses that share that body space. 

Some of these one-time invaders have become permanently established in our cells, even crossed the boundary line and entered our own genome. I call that extended set of companions the microbiome, and pray for more research on how they impact our lives, besides the flare-ups, the blunders, we call disease. 

Understanding this means that we live in a cooperative arrangement, a truce, with those microbes that don’t kill us. 

The implications of our new understanding are that we need more research, not only on how bacteria are virulent, but how they withhold their virulence and moderate their attacks. We need to investigate how our microbiome flora – the ones that we live with all the time – don’t cause disease and instead protect us against their competitors. 

Finally, we must realise that hygiene can sometimes be too much of a good thing. In the effort to have infinitely clean environments, we may sometimes deprive ourselves of the stimuli our bodies need to become ‘‘street smart’’ and develop defences against infection. – LAT-WP 

  • Joshua Lederberg won the Nobel prize in 1958 at age 33 for his pioneering work on genetic mutation of bacteria. He is formerly president of the Rockefeller University in New York.  

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