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Biotechnology and Society---Part X

Was there biotechnology before DNA? Yes and no. Yes, because biotechnology is an age-old discipline dating back to several centuries before Christ and before we had any knowledge of DNA. No, because there was always DNA when life started in its simplest form - the tiniest bacterium.

DNA’s function was discovered in early 20th century and its structure was determined in mid-20th century. DNA as the master molecule of life was always part of biotechnology - ancient or modern. Before the function and structure of DNA were determined DNA was doing its job as an unsung hero. Now that the marvel of DNA is recognised, it is being put to use in the service of humanity. Let us examine some aspects of biotechnology that were known to humanity before the modern era of genomics.

Ancient biotechnology: Today fermentation (the process of growing microorganisms such as bacteria, fungus, and yeast) and cell culture (growth of animal cells) constitute the bulk of biotechnology industry to produce alcohol, antibiotics, biochemicals and therapeutic proteins. However, fermentation was known to people - Dravidians and Aryans - four thousand years ago.

Dravidians were familiar with tapping the palm tree and consumed toddy (kaL in Thamizh) as a beverage. Rig Veda mentions soma and sura, two beverages that the Aryans knew and used fermentation and distillation to make their drinks in the period 2000 to 800 BCE.

Fermentation involved the application of engineering techniques to biological systems. The early fermentation was done without knowing the principles. Soma was considered a divine wine - it was made from a bitter herb very much similar to the modern day hops. It did not produce inebriety. Sura, on the other hand, was a secular drink - very potent and intoxicating. Microorganisms present in the environment, especially yeast, were at work in doing such fermentation. The microorganisms were consuming the food themselves for growth and propagation and produced alcohol as a byproduct.

The ancient art of cheese-making involved the fermentation of milk - by the microorganisms which produced the enzymes to convert milk into cheese. Likewise, the soy sauces of the Orient have been made from fermented beans. For centuries, Balkan people enjoyed fermented milk (yogurt). Leavened bread, almost as old as agriculture itself, involves fermentation of wheat flour dough by yeast. The discovery of fruit fermentation by yeast was made so long ago that the ancient Greeks believed wine had been invented by one of their gods, Dionysus. Beer is only slightly behind wine in antiquity. A Mesopotamian clay tablet, written in Sumerian and Akkadian about 500 years before Christ, indicates that brewing had been a well-established profession for several 1,000 years. Egyptian documents dating back to 2600 BCE describe the malting of barley and the fermentation of beer.

Microorganisms: The first scientist to suggest that microorganisms caused fermentation was L J Thenard in France. Thenard announced in 1803 that the yeasts used by the winemakers were alive and were responsible for the formation of alcohol from fruit juice. He was ridiculed by other scientists who held that fermentation was a pure chemical reaction. Thenard was finally proved right when Louis Pasteur, in 1857, proved that yeasts were living cells. He also went on to prove that there were several diseases caused by microorganisms. He also found microbes, just like human beings, had their own enemies and engaged in internecine warfare among themselves.

For example, he found that when a bottle containing specimens of the bacillus, which causes anthrax (malignant boil) in cattle, was exposed to air, the anthrax bacilli were destroyed by other airborne microbes. This was an important discovery which enabled future scientists in learning how to use germs to fight other germs. A truly Machiavellian concept - divide et rigna!

While the science of microbiology was sound, the technology needed to be perfected. By early 20th century the microorganisms were exploited to make products like citric acid (used to provide an acid tang to foods and beverages) from sugar, and acetone (a chemical needed during World War I) from corn mash.

Antibiotics: In September 1928, Scottish microbiologist Alexander Fleming had a profound experience in his laboratory. While trying to isolate an infectious bacterium Staphylococcus aureus, a vicious germ responsible for boils, he noticed a clear zone in the centre of the dish where a foreign substance had invaded and wiped out the bacterial colony. He removed the invading species and found it was alive. It was a mould called Penicillium notatum.

He went on to extract the chemical out of the mould and used it to kill other colonies of bacteria. He named it penicillin (means brush in Latin). He carefully preserved the organism in a living culture. It was a serendipitous discovery which changed the course of medical and military history.

Penicillin was the first antibiotic produced in massive quantities in the United States during World War II and used extensively on the European warfront to save thousands of lives. The pharmaceutical company Pfizer produced 90 percent of the penicillin that went ashore with Allied forces at Normandy on D-Day in 1944. By war’s end the US was utilising new discoveries and established industrial techniques to produce 7 trillion units of penicillin a year - enough to treat 7 million patients. The primitive brewer’s magic thus ascended a pedestal.

With the success of penicillin against a variety of diseases, scientists set out to find other antibiotics capable of fighting diseases against which penicillin was ineffective. They were looking for microorganisms in the soils in different regions of the world. These organisms, though the tiniest, were capable of surviving in the harshest environments, making food for themselves and fighting off other microorganisms.

No microbe is without enemies and none is invulnerable to attack. There was virtually a chemical warfare between these mini-creatures. Worse than human beings, one would think! By isolating various species of bacteria, yeast and fungus from the soil, scientists identified them, classified them, grew them in the laboratory and studied the properties of the chemicals they produced by testing them against other microorganisms.

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Growing bacteria in an appropriate medium was also easy. Typically, a single bacterium can divide and become 17 million in 12 hours! Several new antibiotics were discovered. Streptomycin was one such miracle drug which was effective against tuberculosis. Other drugs such as terramycin, neomycin, polymyxin, bacitracin and cephalosporin followed and several derivatives were prepared by chemical modification of these antibiotics so as to create an armamentarium of drugs to fight an infinite variety of disease-causing bacteria, yeast and fungi.

It is common knowledge that the whole is worth more than the sum of its parts. Biotechnology is the whole and the constituent parts are mycology (study of fungus), organic chemistry, fermentation chemistry, biochemistry, molecular biology, genetics, bacteriology, physics, chemical engineering and mechanical engineering. Without the interaction of all these disciplines, antibiotics, vitamins, hormones and industrial biochemicals would have remained just a laboratory curiosity. The technology required sterile building and equipment so that the operations were not sabotaged by other hostile microorganisms different from the one that was being utilised.

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The transition: However, all this success against the disease-causing microbes was proving to be short-lived. The microbes are smart little creatures. They understand the Shakespearean maxim, ‘Sweet are the uses of adversity’. They learnt quickly how to overcome the adverse effect of antibiotics - what is called antibiotic resistance. They would create a barrier against the antibiotics or chew them up. Once they learnt a new trick, they shared it with their friends (but not with their enemies!) which played a crucial role in the rapid spread of antibiotic resistance. But science stays one step ahead of the microbes. New antibiotics are being designed with the help of new knowledge in biotechnology to circumvent the resistance problem.

Around the 1940s, DNA was acknowledged to house the genes - a realisation that led to further revolution in the pharmaceutical industry. In 1944 it was clearly shown that DNA constitutes the genetic material in cells. Further research on DNA led to the mechanism by which it operates and the determination of its structure. Discovery of new enzymes which can clip, trim and splice DNA, enabled the scientists to transfer DNA pieces from one organism to another, giving birth to a new discipline called recombinant DNA technology. We will look at the genesis of recombinant DNA and its utility in the next article. The determination of the structure of DNA in 1953 followed by advances in molecular biology heralded the modern era of biotechnology. It, however, remains a fact that biotechnology is one continuum of development (rather than an abrupt jump) from the pre-historic times to the present.