Microbiologists find extremophiles fascinating because they are all, or nearly all, archaea - the most ancient division of life on Earth. Three thousand five hundred million years ago, when life first appeared on our planet, conditions were tough. These bacteria - the first complex survival machines evolved by DNA to protect it and help it replicate - were rugged pioneers whose capacity to prosper in appalling conditions is unequalled. That is why the archaea have survived in conditions, on our contemporary planet, which have proved lethal to more effete, though more advanced and more recently evolved life forms.
Professor Bill Grant at Leicester University, an enthusiastic extremophilist, says: "If we assume the early Earth was hot, salty (because of evaporation) and devoid of oxygen, then we'd expect the first micro-organisms to have had to grow without oxygen, at high temperatures and at high salt levels. The three main groups of archaea do precisely that."
Bill Grant specialises in the study of halophiles - archaea found inside salt crystals deep in salt mines; they are probably descended from ancestors which lived in salt lakes on the primitive Earth. The salt deposits were buried with the living halophiles trapped inside them. They may have the ability to survive in suspended animation for hundreds of thousands of years.
Some microbiologists believe extremophiles may also survive beneath the surface of Mars; halophiles could be among them. Though there is no oxygen or water on the surface of Mars today, there was almost certainly water in the past. Life could have evolved on the surface of the planet, survived evaporation and retreated underground, just like the bacteria in the salt mines. "There are provisional plans to search for life again on Mars, and if we're lucky we may get some salt crystals to look at," says Bill Grant.
Other candidates for life on Mars have been discovered in the pitch-dark, warm, humid Movile cave in Dobrogea in Romania, where life has evolved sealed off from the outside world for more than five million years. The bacteria at the bottom of the food chain in the cave - on which blind white scorpions, spiders and centipedes ultimately depend for their existence - trap carbon dioxide to build into body material, as plants do. But the bacteria get their energy not by photosynthesis from sunlight but by oxidising hydrogen sulphide gas which bubbles up into the cave.
"If there is life under the surface of Mars," says Professor Brian Kinkle of Cincinnati University in the US, "it has to get its energy not from sunlight but by oxidising chemicals beneath the surface - just like the micro-organisms in the cave. Bacteria that live in the deep seas around the vents of undersea volcanoes make a living out of hydrogen sulphide in the same way."
These deep-sea bacteria are the best-known extremophiles. Superheated lava oozes intermittently out of vents as deep as 3,000m beneath the surface of the oceans, at temperatures up to 400C. Bacteria such as Pyrococcus furiosus (the "Flaming Fireball") are found living nearby, not from necessity but by preference. These "thermophiles" survive at around, and even above, 100C.
At these depths they also live happily at pressures 300-400 times those on the surface of the Earth. Their enzymes, the complex catalysts that drive the chemical reactions occurring in even the simplest living things, have to be incredibly tough to survive intact and carry on working in such conditions.
It is this toughness that is increasingly attracting the interest of chemists and chemical engineers. Because of their strength and stability, enzymes from the "Flaming Fireball" are already being used in genetic "photocopying" techniques, in which forensic scientists hunting a rapist or doctors diagnosing an infection have to multiply minuscule amounts of DNA to provide enough to identify. Enzymes from P furiosus will churn copies endlessly without breaking down.
Unlike man-made chemical catalysts, enzymes do not require dangerously high temperatures to do their job (though those from deep-sea thermophiles work happily at temperatures and pressures high enough to speed up reactions to useful rates). Enzymes make just what is wanted, but with no wasteful, polluting by-products. Most important of all, an enzyme makes the molecule that is its product in either a left-handed or a right-handed form, and not in the other form.
Most molecules can exist in two forms that are mirror images of each other. If they are drug molecules, it is likely that one form will be beneficial while the other has little or no therapeutic effect. Conventional catalysts make 50-50 mixtures of both forms, but if an enzyme can be found which is able to do the job, and sufficiently tough to do it for long enough to be of some use, then it can be relied upon to make only one form of the drug molecule - with a bit of luck, the one that is wanted.
The advantages of extremophiles are clear: they can deliver enzymes tough enough for use in industry, where they provide clean, green technology; at a stroke they can also double the value of a medicinal drug produced by conventional means. Of course, thermophiles fished up from the deep oceans may not have chanced to evolve precisely the enzyme chemists are looking for. But by learning which genetic blueprints thermophiles have evolved to construct their tough enzymes, genetic engineers can learn the same tricks to draw up blueprints for the wanted enzymes.
The discovery of the environmentally-minded chemist's dream enzyme was reported in the Journal of Current Biology a few weeks ago, by Dr Jurgen Peters of the Max Planck Institute at Martinsreid in Germany. The enzyme is a protease exuded on to the surface of a bacterium called Staphylothermus marinas, another deep-sea thermophile. It is on the surface because its job is to break down proteins - complex chemicals floating in the water - into smaller molecules which the bacteria can then absorb and feed on.
Jurgen Peters is impressed by the potential of his discovery - an enzyme that can work at up to 135C, higher than any other known enzyme. "An egg made of proteins like this enzyme," he says, "would never become a boiled egg, because the proteins would be protected against the changes that solidify the egg white and yolk. The enzyme is also able to withstand acids and other destructive chemicals. This is because, unlike most enzymes that are inside cells in constant, protected environments, this one is out on the surface in superheated water full of disruptive chemicals and competing organisms." As a tribute to its remarkable properties, he has named it "Stable".
Such an enzyme could find large-scale applications in high-temperature washing powders, for instance, dissolving stains out of clothing. It could be put to work in the food or skin-cream industries, where large protein molecules have to be broken down into smaller ones that are easier to absorb.
Jurgen Peters has discovered that the enzyme is embedded in a network of fibres covering the surface of Staphylothermus marinas, christened the Slayer. "The Slayer is even tougher than Stable," says Peters. "It supports the enzyme, holds it in shape and protects it against damage by corrosive chemicals." The remarkable properties of the Slayer aren't yet fully understood, but German scientists are already investigating ways of recreating it without the rest of S marinus so as, hopefully, to use a synthetic version of the Slayer to support and protect other enzymes used in biotechnology.
A synthetic Slayer might eventually be wrapped around two more enzymes from deep-sea thermophiles which, thanks to work by American and British scientists and engineers, may open the way to the long-dreamt-of "Hydrogen economy" - a world in which the fuel used for cars, aircraft, heating and cooking will be hydrogen gas. When hydrogen is burnt as a fuel, it produces nothing but energy and water. It is environmentally ideal and, being easily the most common element in the Universe, is available in unlimited quantities.
Hydrogen could easily be piped over long distances, for instance, for use in heating or cooking in offices and homes. Alternatively, it could be liquefied by cooling and used to power aircraft or rockets. It could equally be made into a solid compound (a metal hydride) to power cars and lorries.
So much for hydrogen's advantages, but what about its drawbacks? By far the biggest problem in putting it to work has been the large amount of energy, whether electrical or chemical, required to separate it from water. Thermophiles may provide the answer. Work conducted by an international team, co-ordinated by Dr Jonathan Woodward of the US Oak Ridge National Laboratory in Tennessee, has shown that enzymes from thermophiles can be to produce hydrogen from sugar very economically.
"There are huge amounts of hydrogen in natural resources that go unused today," Dr Woodward says, "in the shape of agricultural wastes such as straw, that are burnt or buried. We set out to find ways of breaking these down in an environment-friendly way using enzymes, until hydrogen was released. We already knew how to convert the main constituents of such wastes - cellulose, starch and lactose - into glucose sugar using an enzyme. The next step was to find an enzyme which could oxidise glucose, release hydrogen gas and be used industrially. We've found one, and it works."
The enzyme that breaks down glucose to produce hydrogen was discovered by Dr Michael Danson at Bath University. A Centre for Extremophile Research is being inaugurated there on 27 September this year. The enzyme comes from yet another thermophile that lives around deep-sea volcanic vents - a bacterium called Thermoplasma. The other enzyme needed, the one that breaks down cellulose to produce glucose, was isolated from our old friend Pyrococcus furiosus by a third research team, at the University of Georgia in the US.
Jonathan Woodward saw the potential of combining the two to unleash the hydrogen economy. Not only do these two enzymes acting together provide a reliable way of producing large amounts of hydrogen from what are now wastes. They also produce gluconic acid - a raw material required for making a number of industrial chemicals. This extra commercial advantage, coupled with the proven toughness of thermophile enzymes, makes Dr David Hough of Bath University, who is involved in setting up the new Centre, believe the hydrogen economy is at last on the horizon.
"I would say it is certainly a possibility," he says, "if we can develop a bioreactor that contains the two enzymes. You would pump in agricultural raw materials at one end, and collect hydrogen at the other. One requirement would be stable enzymes, able to work at high temperatures and high rates for long periods - which hopefully thermophiles can provide. It's possible that you could get large volumes of hydrogen from such a process."
Extremophiles that can survive excessive heat are not the only ones with potential. Down at the other end of the thermometer are the psychrophiles, which prefer to live at temperatures down to or even below the freezing point of water. Professor Nick Russell of Wye College in Kent, who goes on trips to the Antarctic to collect psychrophiles, says some can be found closer at hand, in the fridge. "You can find them in food that is going off, and the food industry is very interested in those. Some of them - micro-organisms such as listeria and clostridium - are responsible for severe food poisoning."
Those psychrophiles are being studied to find ways to cure the diseases they cause. Others are of interest because they could prove useful in themselves. "One aspect of psychrophiles that we are studying in great detail," says Nick Russell, "is their ability to keep the membranes around them fluid at very low temperatures. When you take butter out of the fridge, it is hard and you can't spread it immediately. Margarine, by comparison, can be spread straight away because it has a different lipid, fat composition. Psychrophiles produce lipids that are naturally very unsaturated with hydrogen; they have the ability to stay flexible at very low temperatures. The enzymes that produce psychrophile lipids could have a big future in the food industry as a natural way of making healthy fats that spread from the fridge."
Perhaps the nastiest of all the environments preferred by extremophiles is concentrated sulphuric acid. Acidophiles are already widely used in mining operations to dissolve gold out of low-grade ores. As rich deposits of less valuable metals are exhausted, acidophiles are being researched as a way of extracting metals like nickel. Professor Paul Norris of Warwick University has just what is needed - thermoacidophilic oxidising archaea. These are bacteria which revel in life at 85C in strong sulphuric acid, produced as they oxidise metal sulphides and release metals while at the same time providing themselves with energy.
If extremophiles do survive on Mars, an international expedition could well go there some time next century, drill down deep and bring some examples back to Earth. Far from posing any threat to humanity, such specimens could prove invaluable to industry. Having evolved for a very long time in very inhospitable conditions, enzymes from Martian extremophiles may be even tougher than those on Earth. Professor Karl Stetter of Regensburg University in Germany, an extremophile enthusiast, confirms this: "Martian extremophile enzymes may be extremely stable at both high and low temperatures. They could have a fantastic future in industry."
Biochemical engineers - whose job it is to design the bioreactors in which extremophiles, or enzymes extracted from them, can do their job - are working in close partnership with genetic engineers. They are learning how to improve on nature by designing genetic blueprints for even tougher enzymes, and how to transfer the genes into other micro-organisms. Meanwhile, respect for these ancient life forms keeps growing as more is discovered about them. Among microbiologists, it is considered politically incorrect to refer to any life form as "primitive". But the "Flaming Fireball" - if it were able to - might think of us not only as primitive, but as effete and degenerate. !Reuse content