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Articles: Science | Reinventing Yesterday
- Mr. Sreedhar Venkata Sunkara
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Dear Friends.....
'Reinventing yesterday'
ONCE upon a time, much of the man-made world consisted of things that had been grown. Clothes, carpets, bed-sheets and blankets were woven from wool, flax, cotton or (if you were lucky) silk. Shoes were made of leather. Furniture and fittings were made of wood, which also served as fuel for heating and cooking. Then humanity discovered coal, oil and chemistry. Today only the poorest and the richest people burn wood, and many of its other uses have been taken over by plastics. Natural fibres, too, have ceded much of the market to artificial ones. But biology may be about to revenge itself on the synthetic, petroleum-based industrial world by providing new materials and fuels. And in this guise, it may even become acceptable to the environmental movement.
In truth, biotechnology has been quietly working away at industrial applications for some years. It started with enzymes. A business in purifying and selling bacterial enzymes for use in food manufacturing, washing powders and so on has existed for decades, but in 1988 a Danish firm called Novozymes produced the first transgenic enzyme, a fat-digester for detergents. Partly thanks to this lead, Novozymes is now the world's largest enzyme manufacturer, hotly pursued by several other firms.
Enzymes are proteins, which have a reputation for being fussy molecules. Expose them to the wrong temperature, acidity, salinity or pressure and they stop working, sometimes permanently. And the temperature, acidity, salinity and pressure of industrial chemistry is often very different from that found in familiar living organisms. However, it has become clear that lots of bacteria thrive in conditions that used to be regarded as hostile to life. Quite a cottage industry, known as bioprospecting, has developed to collect these bacteria from hot springs, soda lakes, arctic rocks, industrial-effluent outlets and so on. Enzyme companies then analyse the bugs for proteins that look like useful starting points for the sort of directed evolution used by firms such as Applied Molecular Evolution, Genencor and Maxygen in their search for drugs.
Enzyme-catalysed processes have always been a more efficient way of making molecules than traditional chemistry. They often involve fewer synthetic steps, and the yield of each of those steps is almost always close to 100%, whereas the cumulative losses from step to step of doing things in a complicated traditional synthesis mean that the yield may easily end up below 10%. But until recently, the range of reactions for which enzymes could be used was limited, and their fussiness confined them to high-value products such as drugs and vitamins. Now, thanks to directed evolution, there is serious talk of using enzymes to make cheap, bulk chemicals. And not only talk: action, too.
Material progress
The most promising applications for the new model enzymes over the next decade are plastics and fuels. The two most advanced plastics projects are those of DuPont, one of the world's biggest chemical companies, and Cargill-Dow, a joint venture between the agricultural and chemical firms of those names. DuPont's process, developed in collaboration with Genencor, took biochemical pathways from three different micro-organisms and assembled them into a single bacterium. The raw material for the process is glucose syrup made from maize starch. This is converted into a molecule called 1,3 propandiol, which is used to make a polyester called Sorona. But Sorona is only half biological. It is a copolymer—that is, it is made out of two sorts of monomer—and the other one, a molecule called terephthalate, still has to be made from oil, so there is some way to go.
Cargill-Dow is closer. Its product, Ingeo, is made out of lactic acid, which in turn is made from glucose. Traditional techniques are used only for the polymerisation of the individual lactic-acid monomers into polylactic acid (the chemical name for Ingeo). The stuff is being made in commercial quantities at a plant in Nebraska, and is about to go on the market. At the moment it is rather more expensive than its petrochemical competitors, but Cargill-Dow hopes to brand it as a premium product in the market for environmentally friendly goods.
Biopolymers are environmentally friendly twice over. Since their manufacture uses little in the way of fossil hydrocarbons, they do not add to global warming. And because they are biodegradable, they cause no pollution when discarded. The firms' bigwigs seem hopeful that this will prove a big enough attraction to allow them to reap economies of scale that will then make their products truly cost-competitive.
DuPont and Dow are giants, but biopolymers can be for minnows too. Metabolix, a small firm based in Cambridge, Massachusetts, takes the process for making them to its logical conclusion—by getting living organisms to do the polymerisation as well as making the monomers.
Animals and plants store surplus energy in the form of carbohydrates, oils and fats. Some bacteria, though, use a different molecule, called a polyhydroxyalkanoate, or PHA. About a decade ago, when they were working at the nearby Whitehead Institute, James Barber and Oliver Peoples, the founders of Metabolix, realised that this material might be put to use as a plastic. They have spent the past ten years proving the point.
Having prospected the bacterial world for appropriate enzymes, and assembled enzymatic pathways in the same way that Genencor did for DuPont, they came up with something new: bugs that actually make plastics and store them inside themselves, in large quantities (about 80% of the weight of a grown bacterium is plastic) and in great variety. PHAs are not a single chemical, but a vast molecular family. Different enzyme pathways can turn out different monomers, producing plastics with different properties. Indeed, it is possible to have two different enzyme pathways within the same bacterium. The result is a co-polymer that expands the range of properties still further.
Metabolix, which plans to start commercial production later this year, has shown that its PHAs, too, can be produced at a price which is competitive with at least the more expensive existing polymers, such as polyesters. That in itself may not be enough to convince manufacturers to switch from tried and trusted materials to Metabolix's novel ones, but the firm hopes that in the large market for single-use items the added feature of biodegradability will be a clincher. If manufacturers do not make the change unprompted, then a nudge from the regulators might be expected. Currently, plastic is a persistent form of rubbish, whereas an object made of PHA will disappear in a few weeks if dumped in a landfill, or even in the sea.
Get the price right, then, and the opportunities are enormous. According to a report published in 2001 by McKinsey, a consultancy, by 2010 biotechnology will be a competitive way of producing about a fifth of the world's chemical output by value. That means white biotech will be competing in a market worth $280 billion, of which McKinsey thinks the technology might capture about $160 billion. As biotech processes become cheaper, those numbers will increase.
All the companies working in this field have projects designed to bring down the costs. Metabolix, for example, hopes to switch from growing plastics in bacteria (which have to be fed) to growing them in plants (which will make them out of water, carbon dioxide and sunlight). The firm's researchers have already shown that this is possible in the laboratory. They are now scaling up the process.
The enzyme firms, meanwhile, are working on an idea that would allow whole plants to be used as chemical feedstock. Glucose syrup is a refined product, made from maize grains, which form only a small part of the plant. Maize grains cost about $80 a tonne. That is cheaper than petroleum, weight for weight, but the researchers think they can improve on this. Instead of the grains, which are the most valuable part of the plant, they are trying to find ways of using the waste, which fetches only about $30 a tonne for silage. Unfortunately, it consists mainly of cellulose, a natural polymer of glucose but a recalcitrant one.
Help, though, is at hand. The reason dead plants do not stay around indefinitely is that they are eaten by bacteria. These bacteria contain cellulose-digesting enzymes known as cellulases. Genencor and several of its rivals are using this as the starting point for building a better cellulase. Verdia, Maxygen's plant-biotechnology subsidiary, is hoping to go one better. Its researchers are working on developing a cellulase that the plant would make in its own cell walls. To prevent the enzyme digesting the living plant, it would be tweaked to work most effectively in conditions found not inside plants but in bioreactors.
If these ideas come off, then an era of limitless supplies of glucose could follow. That would allow the production not only of as much plastic as anyone could want, but also of another product that can easily be made from glucose: ethanol. This is not only the active ingredient of booze, but also an efficient fuel. Henry Ford's first car was powered by it. Today, some of the motor fuel sold in Brazil is pure ethanol, which modern engines can be tuned to run on happily, and the rest is 20% ethanol. Even in the United States nearly a tenth of all motor fuel sold is a blend of 90% petrol and 10% ethanol. And since the carbon in ethanol made from plants came out of the atmosphere, putting it back there cannot possibly cause any global warming.
At this point some people in the industry turn starry-eyed and start talking about a future “carbohydrate economy” that might replace the existing “hydrocarbon economy”. The countryside would be rejuvenated as a source of raw materials. Land now taken out of cultivation would be put back to use. Small-scale chemical plants to process the stuff would pop up everywhere. And the oil-producing countries would find themselves out of a job.
Surprisingly, these visionaries are often hard-headed businessmen. Even more surprisingly, the numbers they are bandying do not sound all that exotic. The American market for bioethanol is already 8 billion litres a year (see chart 5). The enthusiasts at Genencor reckon it could be as high as 75 billion litres a year by 2020. That would be enough to replace two-thirds of America's current petrol production. In January, a Canadian firm called Iogen opened a small cellulase-powered pilot plant that converts straw into ethanol.
The germ of an idea
Finding enzymes such as cellulases involves, as mentioned earlier, bioprospecting. But there is bioprospecting, and then there is Craig Venter. Dr Venter was the man behind Celera, the company that took on the Human Genome Consortium. The firm got its scientific edge from a technique called whole-genome shotgun sequencing, which he had developed to work out the genetic sequences of bacteria in one go. Using the money Celera had raised, Dr Venter applied the technique to the much more complicated task of working out the human genome in one go. Now, he proposes to apply it to entire ecosystems, working out the genomes of all the critters in them by a similar, one-step approach. Admittedly the critters are bacteria, and the ecosystems are water samples from the Sargasso Sea. But such samples will have thousands of species in them, most of which cannot be cultured in the laboratory and are therefore inaccessible to standard sequencing methods.
Whole-genome shotgunning works by shredding the DNA of an organism into tiny pieces, sequencing the pieces, then sticking the results together again in the right order, using a powerful computer and clever software. Whole-ecosystem shotgunning aims to do the same with all the DNA in a sample, regardless of how many species it comes from. If the software is good enough, it will be able to sort the pieces into the individual genomes.
Dr Venter is full of ideas about what might be done with his discoveries, even before he has made them. But he is particularly excited by the possibilities for energy generation, and recently set up a new organisation, the Institute for Biological Energy Alternatives, to investigate them further. In his view, replacing petrol with ethanol is old-think. New-think would power the world not with internal combustion engines but with fuel cells. And fuel cells use hydrogen.
One way to make hydrogen biotechnologically might be with a bug called Carboxydothermus, which was discovered in a hydrothermal vent (an undersea volcanic spring) off the coast of Russia. This species lives by reacting carbon monoxide with water. One of the waste products is hydrogen. A more promising route might be to intercept the hydrogen ions produced in the first step of photosynthesis. Another of Dr Venter's pet projects, creating a bacterium with a completely synthetic genome, could come into its own here. By leaving out the genes for the sugar-forming pathways that normally use these hydrogen ions, such a creature could be made to devote all its energies to producing hydrogen. Nor could it escape into the outside world (always a worry with bio-engineered bugs), because it would lack the biochemical apparatus to survive there. Thus trapped, it could, he muses, be used in solar-powered fuel cells for such applications as portable computers.
That points to the power of industrial biotechnology to create completely new products. The idea of a partly living fuel cell may be merely dipping a toe in the ocean of possibilities. Another dipped toe is that of Nexia Biotechnologies, based in Quebec, which is using technology similar to that of GTC Biotherapeutics to turn out spider silk in goats' milk. Spiders, observes Jeffrey Turner, the firm's boss, have been perfecting silk for the past 400m years. Such silk comes in many varieties, which do different jobs for spiders and can thus do different jobs for people. For Nexia's products, these jobs range from stopping bullets when the silk is worn as body armour to stitching up eyeballs after surgery.
Some firms, such as Genencor, are starting to explore wilder shores. As proponents of nanotechnology (the incipient field of building devices a few billionths of a metre across) are wont to observe, biology is natural nanotechnology. Why, then, go to all the trouble of creating an artificial nanotechnology from scratch? Genencor is collaborating with Dow Corning, a big materials company, in this area. Among other things, the firms are looking at rhodopsins, the protein molecules that act as light-detecting pigments in a range of organisms from bacteria to people. Genencor has bred 21 rhodopsin-type molecules, each of which responds to a particular wavelength of light. These molecules might have applications as switches in photonics, the as yet largely hypothetical idea that data could be processed by light instead of by electronics. These are small-scale investments, and may come to nothing, but they are worth a flutter.
However, there are shores yet wilder than these awaiting, where big battles are almost guaranteed. For among the prospects offered by biotechnology is one hitherto reserved for science fiction: tailor-made humans.
So my dear friend .... what do u think.... think today before they 'reinvent yesterday'.....
Yours Originally,
Sreedhar S. Venkata.
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