[Paleopsych] Microbial brains in New Scientist article

[Joel Isaacson]

Eshel Ben-Jacob is cited in the latter part of this New Scientist article.   
-- Joel


A BILLION BRAINS ARE BETTER THAN ONE

New Scientist vol 184 issue 2474 - 20 November 2004, page 34


A single microbe won't have much to say for itself. But put a lot of them 
together and it's a different story, says Mark Buchanan


IN A small dish in a lab at the University of Chicago, millions of bacteria 
are deliberating among themselves. For hours there is no activity then 
suddenly, having taken a vote and come to a decision, the bacteria all light 
up, filling their world with a soft blue glow. Nearby, other bacteria are 
navigating as a pack. In response to unseen signals, individual bacteria 
have grown tendrils and gathered together, forming a raft that glides easily 
over the solid surface.

Extraordinary behaviour for bugs? Biologist Jim Shapiro doesn't think so. He 
watches this sort of thing every day in his lab. And he regards it as yet 
more evidence that the popular view of microbes is way off track. For most 
of the two centuries since scientists first peered into the microscopic 
world, they have viewed life's tiniest members as loners, living individual, 
independent lives. But Shapiro and other biologists know that there is no 
such thing as an antisocial microbe. Bacteria, amoebas and yeast are not 
renowned for their social skills, but Shapiro thinks they should be.

Wherever microbes coexist in rich profusion - which is pretty much 
everywhere, from the scum on a pond to a cockroach's gut - teamwork and 
cooperation count every bit as much as cut-throat competition. And behind it 
all stands a talent for communication that is turning out to be far more 
sophisticated than anyone imagined. Bacteria use a bewildering range of 
chemical messages not only to attract mates and distinguish friend from foe, 
but also to build armies, organise the division of labour and even commit 
mass suicide for the good of the community. Some experts even talk about 
"microbial language", with its own lexicon and syntax. That is a radical 
interpretation, but microbes are certainly much cleverer than we thought. 
They are not just stupid little bags of enzymes, insists Shapiro, but 
"formidable and sophisticated actors on the stage of life".

The idea that microbial communities might be intensely social has been 
around for about 20 years, but most biologists did not take it too 
seriously. In the lab, researchers usually keep microbes as prisoners in 
well-stirred suspensions, which prevents them getting together to form 
colonies. That is fine for many types of research, but anyone interested in 
animal behaviour knows that the only way to get a real insight into what 
creatures do is to study them in their natural settings.

And away from the artificial simplicity of the lab, microorganisms adore 
surfaces. You'll find them almost anywhere, from the hulls of boats and the 
walls of pipes and drains to the surfaces of ponds, water tanks and living 
organisms. "Of all the cells that make up the healthy human body," points 
out biologist Jim Deacon of the University of Edinburgh, UK, "more than 99 
per cent are microorganisms living on the skin, in the gut or elsewhere." 
These surface-dwelling communities, often containing hundreds of distinct 
species, are known as biofilms. The microbes within a biofilm collectively 
weave a matrix of sugary polymers called exopolysaccharides that form the 
physical infrastructure of a slimy microbial city (New Scientist, 31 August, 
1996, p 32). The community living within often has a strength and integrity 
its individual citizens lack.

Earlier this year, biologist Staffan Kjelleberg and colleagues at the 
University of New South Wales in Australia showed, for example, how forming 
a biofilm can enable bacteria to defend themselves against predators. The 
versatile bacterium Pseudomonas aeruginosa thrives in sewage-treatment 
plants and in the soil, but everywhere it falls prey to voracious 
protozoans. "On the surface of a pipe," says Kjelleberg, "protozoa move just 
like vacuum cleaners." He and his colleagues found that colonies of P. 
aeruginosa could develop into dense biofilms that were resistant to attack. 
"They form a structure that protozoa find hard to eat," says Kjelleberg. In 
comparison, colonies of mutant bacteria deficient in the art of biofilm 
development remained easy prey.

The biofilms in these experiments are extremely rudimentary. Natural 
biofilms - in everything from dental plaque to spoilt food - are so complex 
that researchers still cannot reproduce their full glory in the lab. Yet by 
studying microbes in somewhat simplified settings, they are peeking into 
their social lives and learning how they get it together.

Group action

One of the most important techniques microbes use to coordinate teamwork is 
known as quorum sensing. In the laboratory of Bonnie Bassler at Princeton 
University, a bacterium called Vibrio harveyi shows how it works. These 
bacteria routinely produce a molecule known as an autoinducer, which they 
release into the environment. The result under many conditions is precisely 
nothing. But at a high enough concentration, the autoinducer triggers a 
chemical response in other V. harveyi, making them glow. The concentration 
of autoinducer reflects the density of the bacterial population so, when 
numbers are high enough, the bacteria will spontaneously light up with a 
dull blue luminescence.

So, while V. harveyi will not shine as an individual, it does in a group. 
Biologists are not yet sure what it gains by this behaviour, but many other 
bacteria perform similar feats, and in some cases researchers have found out 
why. Outside the lab, the marine bacterium V. fischeri - a close relative of 
V. harveyi - often lives in dense colonies on the Hawaiian bobtail squid. 
The squid gives the bacteria a protected environment in which to multiply 
and, in return, the bacteria light up, helping to camouflage the squid in 
its deep-sea habitat. When swimming alone in the sea, the bacteria don't 
bother to glow - they save their energy.

Biologists discovered the basic logic of quorum sensing in V. fischeri in 
the 1980s. Over the past decade, Bassler and others have learned that most 
microbes exploit similar tricks. In the lungs of cystic fibrosis patients, 
for example, P. aeruginosa uses quorum sensing to decide when to deploy 
virulence factors - molecules that ease its entry into tissues or help it to 
counter host defences. By relying on a system that is only triggered into 
action when a crucial threshold is reached, the colony avoids stirring up 
the immune system too early. Instead it assembles a formidable force before 
launching the invasion proper.

When threatened with starvation, the soil-dwelling bacterium Myxococcus 
xanthus responds with a similarly impressive display of social coordination. 
When the concentration of autoinducer reaches a critical level, many 
individuals commit what appears to be socially inspired suicide. The cells 
disintegrate, releasing raw materials that ensure the survival of a lucky 
few. These become quiescent spores wrapped within a fruiting body formed of 
less lucky cells, which gives them a good chance of surviving to germinate 
when conditions improve.

Hundreds of microbes use quorum sensing, but experiments with V. harveyi in 
particular have revealed the potential flexibility of this communication 
strategy. Two years ago, Bassler and colleagues discovered that V. harveyi 
has not just one quorum-sensing circuit but two, and uses them in 
combination, like tools in a carpenter's workshop, to orchestrate more 
subtle acts of cooperation.

One of the circuits in V. harveyi triggers light production only when it 
senses a quorum of bacteria of the same species. But the second circuit, 
operating through a distinct set of autoinducer molecules, is not so picky. 
It triggers light production when enough bacteria of any species happen to 
be nearby. "It seems paradoxical," says Bassler, "that these bacteria use 
two systems when either alone should be sufficient." But she suggests that 
having two systems might allow V. harveyi to modify their behaviour in 
subtle ways, depending on whether they are in the minority or the majority 
in a community of species.

Microbial signals are like a real language in that they represent words 
whose meaning can differ in different contexts
The discovery of quorum sensing and its widespread use in the microbial 
world has ushered in a new view of microbes as highly social creatures. 
Indeed, the level of cooperation between individuals can be so complex that 
they act less like a coordinated group of single-celled organisms and more 
like a microbial "superorganism". Just as multicellular organisms depend on 
cellular differentiation to create specialised cells to make muscles and 
nerves, for example, microbial colonies do the same. "You look at these 
biofilms and you find a lot of differentiation," says Kjelleberg. "They 
really are like higher organisms."

Shapiro points out that even simple colonies of the same species can be 
highly sophisticated, as cells in distinct regions differentiate to produce 
what amounts to different tissues. The bacterium Proteus mirabilis swims 
easily in a liquid using its few whip-like flagella, but individuals cannot 
move over a solid surface. A colony growing on a surface can, through 
chemical communication, orchestrate a collective metamorphosis in which many 
of the bacteria turn themselves into elongated cells covered with thousands 
of flagella, which they can use to move over the surface. "These cells are 
sensitive to touch," says Shapiro, "and they like to line up next to one 
another." The resulting raft of specialised bacteria helps the colony to 
spread by swarming over surfaces on which ordinary individuals would remain 
stuck. The swarming bacteria can later return to the normal condition, which 
is more suited to swimming.

Given that quorum sensing allows microbes to talk to one another in order to 
cooperate, it is not surprising that some organisms have learned how to 
disrupt their enemies' communication systems. As a saboteur, the bacterium 
Bacillus subtilis produces a molecule that modifies the autoinducers used by 
many other bacteria, thereby ruining their effectiveness. And the marine red 
alga Delisea pulchra, common on the coast of southern Australia, produces 
chemicals called furanones. Similar to autoinducers, these molecules 
effectively swamp the receptors of microbes' quorum-sensing systems, jamming 
communication. "The algae paint their surfaces with these molecules," says 
Kjelleberg, and so defeat microbial attack.

This particular countermeasure turns out to be popular among microbes. "We 
have a whole freezer full of organisms that do similar things," says 
Kjelleberg. "There are really a lot of them." Stimulated by this discovery, 
he and his colleagues have produced synthetic molecules that they are trying 
to develop into new antibacterial drugs. Unlike conventional antibiotics, 
these would function not by killing the individual microbes, but by 
destroying their ability to communicate and cooperate.

It's not just outsiders that are bent on subverting the teamwork of social 
microbes. Sometimes the sabotage comes from within. In any society where you 
have individuals cooperating for the good of the group, you are likely to 
get freeloaders who refuse to pull their weight but still enjoy the benefits 
of being part of a collective. Microbial societies are no exception. Last 
year, biologists Gregory Velicer and Francesca Fiegna of the Max Planck 
Institute for Biological Cybernetics in Tübingen, Germany, witnessed the 
consequences of cheating in a colony of M. xanthus, which would ordinarily 
form a "fruiting body" in response to a crisis. Normally, it seems to be a 
lottery as to which individuals sacrifice themselves and which benefit from 
the collective response by becoming spores and passing on their genes to the 
next generation. But when Velicer and Fiegna augmented the colony with a few 
mutant individuals from populations that could not form fruiting bodies, 
they found that these mutants contributed less than the normal bacteria to 
fruiting-body formation, and were more likely to become spores.

As well as giving a fascinating insight into the biology of cheating, the 
study also throws light on one of the classic puzzles of evolutionary 
biology - why cooperation between individuals persists despite the potential 
threat from freeloaders. Velicer found that the mutant bacteria contain the 
seeds of their own destruction. Because they greedily push their own genes 
into the next generation, the freeloaders proliferated rapidly in the 
community, displacing cooperators. This outbreak of cheating eventually led 
to a dramatic population crash, and in some cases the colony perished 
entirely. This isn't an ideal outcome for anyone, and it is likely that 
microbes have evolved ways to police cheating and preserve cooperation.

How cheaters could be stymied remains a mystery. Velicer points out that a 
society of microbes might direct extra benefits to those who don't cheat, or 
might directly punish cheaters. This would probably entail forms of 
communication that are so far unknown. But he is hopeful of finding them, 
given the great progress in uncovering the vast and complex world of 
microbial communication. Velicer is certainly not alone in his belief that 
there is much more to be discovered about microbial communication. "We fully 
expect that this is merely the tip of the iceberg," says physicist Eshel 
Ben-Jacob of Tel Aviv University in Israel.

What's more, if Ben-Jacob is correct, microbial communication is more than 
just an intricate exchange of chemical messages. He believes it is something 
akin to language. In a recent article, he and his colleagues argue that when 
other researchers talk about the "syntax" of microbial signals, or their 
"contextual" meaning, they should consider the possibility that this is more 
than a metaphor (Trends in Microbiology, 2004, vol 12, p 366).

Words and meanings

Microbial signals are like a real language, they argue, in that they 
represent "words" whose meaning can differ in different contexts. As with 
human language, bacteria possess a lexicon, or vocabulary, of possible 
signals with which to communicate the various signaling chemicals they 
produce and recognise, such as those used in quorum sensing. And the meaning 
conveyed through these signals depends strongly on the semantic context. 
Bacteria carry internal information reflecting their history as well as 
current external conditions, and can respond to the same signal in different 
ways at different times, showing a rich behavioural repertoire.

Ben-Jacob's interest in microbes indicates a changing attitude towards 
Earth's smallest inhabitants. At last people are waking up to the fact that 
most of life is microscopic, and that the macroscopic bits wouldn't be what 
they are without microbes. The discovery that these two worlds have much 
more in common than we thought is intriguing. More and more researchers 
agree with Ben-Jacob's assertion that microbes have the kind of social 
intelligence previously considered to be the exclusive preserve of the most 
intelligent animals. Microorganisms recognise the social groups to which 
they belong, and readily pick out strangers who might pose a threat.

As we find out more, we will perhaps perceive microbes as more like 
ourselves, or discover the roots of our own social behaviour in the 
supposedly "simple" microbial world. Perhaps our own ability to talk and 
communicate, to form teams and root out and punish freeloaders, goes all the 
way back to our days as bacteria.


Mark Buchanan
Mark Buchanan is a writer based in Cambridge