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WHEN Karl von Frisch reported 60 years ago that bees communicate their foraging successes through figure-of-eight dances, he was met with criticism and disbelief. In 1973, this German biologist won a Nobel prize for that work, and it is now clear that bees rely on chemical signals as well as body movements to get their messages across. Chemical communication enables bees to distinguish cousins from strangers, coordinate attacks on hive intruders and, in their own sort of way, be as social as the best human host or hostess.

The idea of bees “speaking” with chemicals raised questions about animal language and cognition that are hotly debated to this day. But at least bees have a rudimentary nervous system and a multiplicity of different cells in their bodies. Never before has the debate spilled over into the world of the humble microbe. Until now.

The chemicals bacteria secrete are no longer being dismissed as uninteresting byproducts of metabolism, as “waste”. “Bacteria are spitting things out so they can talk to each other,” insists Douglas Kell, a microbiologist at the University of Wales in Aberystwyth. In soil, in the spaces between our teeth, along the stinky edges of hot springs, bacteria are using chemical signals to network with relatives, negotiate with allies and deter enemies – and why shouldn’t they? After all, birds, mammals and insects emit pheromones to guide mating, aggression and other social behaviours.

The difference is that bacterial communication is so subtle it has succumbed to scientific investigation only in the past few years, with the advent of better methods for growing and studying bacteria. One key technique is flow cytometry, a technology which allows researchers to tease apart different types of bacterial cells. Another is the use of genetic engineering to identify the genes in bacteria that are crucial to the ability to emit or respond to chemical signals.

Understanding the chemical chatter of bacteria is just the start. Under attack is the whole, deep-seated notion of bacteria as dumb cells that act robotically on the information in their DNA. Chemical crosstalk, claim today’s microbiologists, enables bacterial cells to cooperate in ways approaching the complexity of animal communities; to specialise like those of multicellular organisms; to behave socially. At the annual meeting of the American Society of Microbiology, held in May in Washington DC, an entire symposium was devoted to the way bacteria aggregate into specific structures and then take on special roles in this new organisation. Such ventures – once thought nonexistent, or at least rare – may be the norm for many kinds of bacteria, says Julian Davies from the University of British Columbia in Vancouver.

What makes such discoveries all the more newsworthy is the burgeoning problem of drug-resistant infections. As supposedly thwarted microbial pathogens return with a vengeance, producing virulent cholera epidemics and a resurgence of tuberculosis, research into the genetic flexibility which underlies drug resistance has taken on new importance. To date, the focus has been mainly on DNA, and for good reason. Bacteria are unusually adept at swapping and rearranging genes in response to environmental changes and attack by antibiotics. But now researchers are taking their questions beyond this genetic crosstalk. Could bacterial versatility also be caused by their ability to converse using chemicals?

To answer such questions, you first need to know how the chemical language of bacteria influences their genetic language. And to know that, you need to translate the chemical language. As with any social situation, bacterial chatter involves a mix of antagonistic and friendly gestures, and identifying and decoding those gestures has been a long job. Sixty years ago, microbiologists discovered that bacteria can emit proteins – known as bacteriocins – to repel or kill other bacteria. Then in the 1960s, Julius Adler, of the University of Wisconsin at Maddison, discovered that bacteria will move towards or away from a variety of nutrients. But only now are the broader implications of bacterial communication, as well as many of the molecular details, becoming clear.

Microbiologists recognise, for example, that bacteriocins come in all shapes and sizes. Yet most of them work in the same way, penetrating the target organism and disrupting its membrane.

Territorial tendencies

Armed with bacteriocins, in theory a microbe species could stop other species muscling in on its territory and resources. And in practice, this is what seems to happen. Last year, Daniel Smith and Martin Dworkin of the University of Minnesota, Minneapolis, described a vivid example involving two species of Myxococcus. Place these bacteria in the same culture dish, the researchers found, and they will stake out territories and grow as separate colonies. In liquid media, the antipathy is even more striking. One microbe, Myxococcus virescens, ends up greatly outnumbering the other. In both cases, argue the researchers, bacteriocins are at work, but they have yet to isolate the substances used to define the territories.

Bacteria that cannot produce bacteriocins run the risk of being wiped out by competitors. Last year, a team of Spanish and British investigators reported the quick demise of one such strain of lactic acid bacteria. To better understand the fermentation process involved in producing green olives for export, a group led by Jose Luis Ruis-Barba of the Institute of Oils and Fats in Seville, Spain, added several strains of lactic acid bacteria to olive brine and allowed them to ferment. All these strains persisted except one that was unable to produce any bacteriocin. It disappeared within seven weeks.

It may take a crisis to get bacteria talking. In a nutrient-rich medium, for example, Bacillus subtilus will divide in an apparently aloof manner, radiating out from a starting point to create a circular colony. But reduce the nutrient supply and cooperative behaviour kicks in. The growing cells seem to sense, and obligingly move away from, chemicals emitted by their neighbours. The result is reduced competition for resources and a colony that takes on a spiralling pattern, notes Eshel Ben-Jacob of Tel-Aviv University. As the amount of food decreases, long branching arms radiate and spiral away from a central spot. When the nutrients are very low, the branches become quite fine and the colony structure appears to become very well organised.

Ben-Jacob has developed mathematical models that mimic this pattern formation. The patterns generated by his models look most realistic when he introduces data describing the chemical cues produced by the bacteria themselves. This has convinced him that the bacteria are communicating with one another and not just responding to nutrients in the dish.

Other bacteria are constantly on the lookout for a get-together. Vibrio fischeri, the bacteria that make fish bioluminesce, and landlubbers such as Pseudomonas, will emit a chemical – dauntingly entitled beta-keto-caproyl homoserine lactone – to attract compatriots. At a certain point, and because of the signal, such bacteria “sense” a quorum and respond by altering their internal biochemistry and behaviour. For V. fischeri, the result is bioluminescence. But other bacteria respond by turning into highly social colonies akin to multicellular organisms.

Here individual bacteria give up their ability to act independently and take on specialised roles within the colony. At Stanford University in California, Dale Kaiser studies this kind of social role-play in myxobacteria. Myxobacteria gather together for feeding – they prey on dead, decaying or dying microorganisms – and for surviving tough times. When food runs low, they gather in millions, rearranging themselves into fruiting bodies once there are enough of them. Some species form small blobs, others grow into finely branched stalks, and several develop bright colours. Outer cells become a protective, often slimy or cartilaginous, coat for inner cells that transform into dormant myxospores.

The point of the exercise is to acquire collective bulk. “The microorganisms become a macroscopic object that can be moved in the soil,” explains Kaiser. Unlike small, undifferentiated colonies, myxobacterial clumps are liable to be wafted by air, or washed by water, to new food sources.

Harder to understand is the biochemistry driving this kind of bacterial specialisation. But even here progress is being made. Over the past five years, Kaiser and his colleagues have identified the chemicals that command the bacteria first to aggregate, then to form fruiting bodies, and in some cases to become spores. The key was to create a series of gerietic mutants, each lacking a gene needed to produce one of the command chemicals. The behaviour of these mutant bacteria told the researchers what each of the command chemicals did.

The next step will be to work out how bacterial cells “know” when to issue chemical commands and how those commands succeed in influencing the behaviour of neighbouring bacterial cells. Tracing the genes involved will be crucial. Myxobacteria have about 6000 genes, few enough, explains Kaiser, to be able to work out what each of those genes is doing.

In practice, however, things can get complicated. The way a bacterial cell responds to a particular chemical signal may depend on much more than just the nature of the chemical. Take the case of Bacillus subtilisis in which a single cell divides to produce two new daughter cells of different sizes. The bigger of the two engulfs the smaller, which eventually becomes a spore, encased and dormant. Why the difference? Richard Losick of Harvard University believes that the position and size of the two cells influences the way they respond to chemical commands. In one cell, chemical signals activate the “spore” genetic program. But Losick still can’t explain for sure how it all happens.

But far from being dismayed by the complexity of bacterial chatter, microbiologists are profoundly excited by it. What they believe they are discovering is a chemical and genetic language reminiscent of the one that guides the embryonic development of multicellular organisms.

In embryos, all the signs are that cells discover what kind of tissue to grow into by “tuning in” to chemical signals emitted by other cells. Each cell’s location determines how it reacts to a succession of chemical signals, and ultimately whether it switches on genes that turn it into muscle tissue or brain tissue or something quite different. That, at least, is the hypothesis. Discovering which combination of chemical and spatial cues stimulate embryo cells to switch on certain genes and not others is one of modern biology’s biggest crusades – and microbiologists are keen to join. Cellular specialisation is “the essence of a multicellular organism”, says Losick, and the message of microbiology in the 1990s is that bacteria do it too.

Sometimes that specialisation even takes the form of a “partnership” between species. In hot springs, microbial mats develop as different types of bacteria come together. The cells grow and divide, eventually building up tiny mushroom-shape bodies separated by channels of flowing water. Bacteria on the edges of these channels use the water’s dissolved oxygen. A few also have whip-like structures, possibly for circulating water. But at the core of the “mushrooms” lies a different species, one that can survive without oxygen. Nutrients, but not oxygen, are transported to these inner cells, according to research by Richard Castenhols at the University of Oregon in Eugene. Set up like this, he says, the mat “begins to resemble a primitive multicellular organism”.

Some microbiologists push the case for bacterial sophistication further. “What goes on in bacteria is not fundamentally different from what goes on in human beings,” says Adler. “Social interactions, multicellularity, it’s more the rule than the exception with bacteria,” says James Shapiro, from the University of Chicago. “Everywhere we look for it, we see it going on.” Shapiro even uses the term “sentient” to describe the way some bacteria mutate in an apparently nonrandom manner.

But at this point, sceptics tend to weigh in. Social behaviour includes emotional responses, something bacteria lack, argues Mitchell Sogin, a molecular evolutionist at the Marine Biological Laboratory in Woods Hole, Massachusetts. How, he asks, can one seriously think of bacteria as social creatures when they lack the ability to recognise – and consequently look after – kin? When they have neither the nervous systems nor the cognitive ability to “respond” to cues of genetic relatedness?

The answer, it seems, is to give bacteria the benefit of the doubt, and plenty of it. Microbes do, after all, prefer to form colonies with their own kind: could not that be seen as a function of kin recognition of some sort? And bacteria do seem “aware”, in a chemical sense, of the world around them: could not that be construed as evidence of a “nervous system”?

At the University of Wisconsin at Madison, Adler, clearly believes so. He has developed a way to grow bacterial cells that are big enough to have their membranes probed by electrodes. With these giant cells, he hopes to show that bacteria function like one-cell nervous systems. Davies even considers bacteria “emotional”, in the sense that like people they have needs which they act to satisfy.

Repressed memories?

The idea of microbial emotions is probably not one whose time has yet come. The same, though, may not be true of microbial memories and learning.

Social animals, whether they are birds, humans or other mammals, pass traditions and skills from one generation to the next through culture, education and imitation. Kell suggests that similar kinds of information transfer can occur between generations of bacteria. This happens when certain chemicals released from a “mother” cell are absorbed by a “daughter” cell. The antibiotic streptomycin is one example. As well as killing off competitor bacteria, streptomycin galvanises its own bacterial colony by activating genes needed for growth and producing more streptomycin. A daughter cell that absorbs streptomycin is in a sense absorbing the information it needs to “work out” how to make this potent chemical. “There’s your memory,” says Kell, “in one molecule.”

When von Frisch’s work hinted that bees can communicate in an intelligent manner, it took decades of experiments for others to begin to agree. Achieving that kind of recognition for microorganisms may prove even more difficult. “Most people are really hung up on this idea that intelligence is limited to humans,” says Shapiro. “We assume that bacteria are rather simple, rather primitive and rather limited. I think that’s to our detriment.”