TRENDS IN FOOD SCIENCE ELSEVIER Trends in Food Science Technology 15(2004)3-18 GtECHNOLOGY Biotechnologies: past history, The British physicist Lord Kelvin gave as his opinion that if you can define precisely and measure exactly that of which you speak,your opinions can be counted as present state and credible;if not,they must be deemed doubtful. Let me begin with a definition relevant to this discus- sion:"Biotechnologies are processes that seek to pre- future prospects serve or transform biological materials of animal. vegetable,microbial or viral origin into products of commercial,economic,social and/or hygienic utility and value".Bioengineers are men and women qualified to design,develop,operate,maintain and control bio- Joseph H.Hulse technological processes.One could cite instances in which (i)'Biotechnology'is exclusively equated with Visiting Professor in Industrial Biotechnologies, genetic modifications and transgenesis,(ii)"Bio- UMIST,Manchester,UK and at CFTRI,Mysore,India technology"denotes a bioscientific activity that has not and MS Swaminathon Research Foundation,India progressed beyond the research laboratory.In one American dictionary "biotechnology"is defined as synonymous with 'ergonomics':the study of human The paper presents a chronological review of biotechnologies, work in relation to a prevailing environment. ancient and modern.It outlines the discovery of naturally The name 'Biotechnology'first appeared in Yorkshire occurring drugs by Babylonians,Egyptians,Chinese,Greeks and early in the 20th century.A Bureau of Biotechnology Romans,and the evolution of extraction,preservation and began as a consultant laboratory in Leeds which from transformation technologies.It describes how pharmaceuticals 1899 provided advisory services in chemistry and progressed from empiricism,through chemical identification microbiology to fermentation industries in the north of and synthesis to modern advances in genomics,proteomics England. bio-informatics and syntheses by cultured cells from various The two Manchester universities (soon to be fused genetically modified organisms.While biotechnologies for into one)have long and distinguished records in fer- drugs first progressed through chemistry,until relatively mentation biochemistry.In 1912.Dr Chaim Weizmann recently food technologies evolved by mechanisation,the gra- isolated a strain of Clostridium acetobulylicum which dual replacement of human hands by machines.Present and converted carbohydrate into butanol,acetone and predicted industrial demand for bioengineers exceeds supply. ethanol,a discovery extensively used for industrial The cost and complexity of emerging biotechnologies call for production of acetone and butanol. significant revision of curricula and reorganisation of ace- In 1923,Dr Thomas Kennedy Walker welcomed the demic departments related to life sciences and biotechnol- first students into his Department of Fermentation ogies.Urgently needed is active interdisciplinary cooperation Industries,possibly the first of its kind,in what is now in research and development,both in universities and the University of Manchester Institute of Science and industries,cooperation involving biochemists,bioengineers Technology.Later the departmental name was changed mathematicians,computational scientists,systems analysts to Industrial Biochemistry,semantically similar to and specialists in bioinformatics.Bioscientists and bio- biotechnology'.The undergraduate course was an technologists must acquire more sensitive awareness of civil amalgam of bioscience and bioengineering.From 1923 societies concerns and the ability to communicate with until he retired 35 years later,Professor Walker's students private citizens,politicians and the media.Recognising the advanced to senior positions in food,pharmaceutical and inexorably rising demand for reliable health services,for safe related bio-industries in very many countries. and adequate food supplies,present and future opportu- nities for employment in industries devoted to food and The interrelation of food and drugs drug technologies have never been greater. This presentation assumes that most graduates in C 2003 Elsevier Ltd.All rights reserved. bioengineering will progress to senior positions in food, 0924-2244/$-see front matter C)2003 Elsevier Ltd.All rights reserved. doi10.1016/50924-22440300157-2
Biotechnologies: past history, present state and future prospects Joseph H. Hulse Visiting Professor in Industrial Biotechnologies, UMIST, Manchester, UK and at CFTRI, Mysore, India and MS Swaminathon Research Foundation, India The paper presents a chronological review of biotechnologies, ancient and modern. It outlines the discovery of naturally occurring drugs by Babylonians, Egyptians, Chinese, Greeks and Romans, and the evolution of extraction, preservation and transformation technologies. It describes how pharmaceuticals progressed from empiricism, through chemical identification and synthesis to modern advances in genomics, proteomics, bio-informatics and syntheses by cultured cells from various genetically modified organisms. While biotechnologies for drugs first progressed through chemistry, until relatively recently food technologies evolved by mechanisation, the gradual replacement of human hands by machines. Present and predicted industrial demand for bioengineers exceeds supply. The cost and complexity of emerging biotechnologies call for significant revision of curricula and reorganisation of acedemic departments related to life sciences and biotechnologies. Urgently needed is active interdisciplinary cooperation in research and development, both in universities and industries, cooperation involving biochemists, bioengineers, mathematicians, computational scientists, systems analysts and specialists in bioinformatics. Bioscientists and biotechnologists must acquire more sensitive awareness of civil societies concerns and the ability to communicate with private citizens, politicians and the media. Recognising the inexorably rising demand for reliable health services, for safe and adequate food supplies, present and future opportunities for employment in industries devoted to food and drug technologies have never been greater. # 2003 Elsevier Ltd. All rights reserved. The British physicist Lord Kelvin gave as his opinion that if you can define precisely and measure exactly that of which you speak, your opinions can be counted as credible; if not, they must be deemed doubtful. Let me begin with a definition relevant to this discussion: ‘‘Biotechnologies are processes that seek to preserve or transform biological materials of animal, vegetable, microbial or viral origin into products of commercial, economic, social and/or hygienic utility and value’’. Bioengineers are men and women qualified to design, develop, operate, maintain and control biotechnological processes. One could cite instances in which (i) ‘Biotechnology’ is exclusively equated with genetic modifications and transgenesis, (ii) ‘‘Biotechnology’’ denotes a bioscientific activity that has not progressed beyond the research laboratory. In one American dictionary ‘‘biotechnology’’ is defined as synonymous with ‘ergonomics’: the study of human work in relation to a prevailing environment. The name ‘Biotechnology’ first appeared in Yorkshire early in the 20th century. A Bureau of Biotechnology began as a consultant laboratory in Leeds which from 1899 provided advisory services in chemistry and microbiology to fermentation industries in the north of England. The two Manchester universities (soon to be fused into one) have long and distinguished records in fermentation biochemistry. In 1912, Dr Chaim Weizmann isolated a strain of Clostridium acetobulylicum which converted carbohydrate into butanol, acetone and ethanol, a discovery extensively used for industrial production of acetone and butanol. In 1923, Dr Thomas Kennedy Walker welcomed the first students into his Department of Fermentation Industries, possibly the first of its kind, in what is now the University of Manchester Institute of Science and Technology. Later the departmental name was changed to Industrial Biochemistry, semantically similar to ‘biotechnology’. The undergraduate course was an amalgam of bioscience and bioengineering. From 1923 until he retired 35 years later, Professor Walker’s students advanced to senior positions in food, pharmaceutical and related bio-industries in very many countries. The interrelation of food and drugs This presentation assumes that most graduates in bioengineering will progress to senior positions in food, 0924-2244/$ - see front matter # 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0924-2244(03)00157-2 Trends in Food Science & Technology 15 (2004) 3–18
Joseph H.Hulse Trends in Food Science Technology 15(2004)3-18 pharmaceutical and related biotechnological industries. the raw materials and processed products.Foods found Though their historical patterns of growth and devel- to be acceptable and satisfying,and medicinals that opment have differed,food and drugs and the industries cured or alleviated particular maladies were discovered that produce them have long been closely associated. by chance,trial and error,and painful experience. Standards of quality and safety for foods and drugs are The history of food processing,in large part,is a his- customarily administered by the same regulatory tory of bioengineering,the gradual replacement of agency,the US Food and Drug Administration being human hands and energy first by animals,later by typical.As is discussed later,modern food and phar- machines.Industrial processes of fractionation and maceutical processors employ similar technologies and transformation used today were developed hundreds of methods of product and process control. years ago.What began as labour-intensive artisanal Among the earliest historical records(ca 2900 BCE), crafts were progressively mechanized.In addition to the Chinese proclaimed a close association of foods with providing an immense diversity of food products, medicines,both being essential to good health,both food industries have progressively reduced the human derived from plant and animal sources.The Chinese effort and energy needed in factories,restaurants and believe many ailments can be cured by diet.They were homes. the first to add burnt sponge,an aquatic source of iodine,for people suffering from goitre. Food preservation The Emperor Fu-Hsi and his successors advocate that The basic principles of food preservation:control of health depends on two principles:Yin and Yang.Yin (1)active water content,(2)ambient atmosphere.(3) weakness comes from malfunctions among internal temperature,(4)pH;and (5)thermal inactivation of organs and is indicated by a 'hot'condition.red tongue microbial and biochemical sources of spoilage,were and weak pulse.Yang weakness results when internal discovered empirically hundreds of years ago.Medi- organs fail to absorb essential nutrients,indicated by a terranean,Asian and Amerindian people used sun dry- 'cold'condition,Chinese medicinal foods are classified ing to preserve milk,meat,fish,fruits and vegetables, as 'hot'or 'cold','strong'or 'weak'. into their sun-dried pemmican northern Amerindians Among an impressive list of Chinese medicinal foods. added dried berries that provided ascorbic acid.Sliced some are no doubt effective:others of dubious cred- potatoes were freeze-dried by early Amerindians,ice ibility.Horn from deer antlers is claimed to relieve fati- gradually subliming in the dry air and low atmospheric gue,impotence and skeletal deformities.Ginseng root pressure of the high Andes. (Panax schinseng)is claimed,with little reliable phar- Stone age Britons dried grains over open fires to macological evidence,to alleviate diabetes,cardiovas- prevent sprouting.Over 4000 years ago,the Chinese cular,digestive,liver and other diseases.Analyses of preserved fish by osmotic dehydration with salt. different samples from similar ginseng remedies show Republican Romans reduced water activity in meat and significant variance in composition. fruits by adding salt or honey.About 5000 years ago, Oriental beliefs in therapeutic foods is attracting Middle Eastern farmers stored grains in earthenware North Americans,one-third of whom are said to buy amphora each hermetically sealed by an impervious herbal remedies as alternatives to prescription drugs. goat skin.All stages of insect metamorphosis were Americans'search for a nutritional Elixir vitae has been asphyxiated by respired CO2. evident for over half a century.During the 1950s vita- Seneca described how Romans preserved prawns in min supplements were in fashion;during the 1960s pro- snow from the Appenines.The frozen food industry teins and amino acids were in favour:in the 1970s developed after Clarence Birdseye,an American, extensive publicity was given to essential fatty acids and observed how whale,seal and reindeer meat were cholesterol in relation to cardiovascular disfunctions; naturally preserved during the cold Canadian winter. during the 1980s dietary fibre was of paramount inter- Modern canning,bottling and boil-in-the-bag were est.At present the fashion is with 'functional foods' anticipated in Republican Rome where chopped spiced (which beg the question:what are non-functional meats were sealed and boiled inside the cleaned womb foods?)and 'nutraceuticals',foods believed to possess of a sow or the body cavity of a squid. beneficial pharmacological properties.It is not surpriz- Fermentation and pickling of fruits and vegetables is an ing that the Chinese claim to be the originators of ancient practice among Asian and Mediterranean people. nutraceutical concepts. The Babylonians preserved their milk by lactic fermenta- tion.Ethanol was distilled in China over 3000 years ago. Food and drugs:science and technology Homer described wine as“A gift from the gods'”. A characteristic common to food,drugs and most other basic need industries is that technologies dis- Grain milling-the first continuous process covered by perceptive empiricism long preceded any Fractionation of cereal grains by pulverization,siev- scientific understanding of the biochemical properties of ing and winnowing,and extraction of olive oil by
pharmaceutical and related biotechnological industries. Though their historical patterns of growth and development have differed, food and drugs and the industries that produce them have long been closely associated. Standards of quality and safety for foods and drugs are customarily administered by the same regulatory agency, the US Food and Drug Administration being typical. As is discussed later, modern food and pharmaceutical processors employ similar technologies and methods of product and process control. Among the earliest historical records (ca 2900 BCE), the Chinese proclaimed a close association of foods with medicines, both being essential to good health, both derived from plant and animal sources. The Chinese believe many ailments can be cured by diet. They were the first to add burnt sponge, an aquatic source of iodine, for people suffering from goitre. The Emperor Fu-Hsi and his successors advocate that health depends on two principles: Yin and Yang. Yin weakness comes from malfunctions among internal organs and is indicated by a ‘hot’ condition, red tongue and weak pulse. Yang weakness results when internal organs fail to absorb essential nutrients, indicated by a ‘cold’ condition, Chinese medicinal foods are classified as ‘hot’ or ‘cold’, ‘strong’ or ‘weak’. Among an impressive list of Chinese medicinal foods, some are no doubt effective; others of dubious credibility. Horn from deer antlers is claimed to relieve fatigue, impotence and skeletal deformities. Ginseng root (Panax schinseng) is claimed, with little reliable pharmacological evidence, to alleviate diabetes, cardiovascular, digestive, liver and other diseases. Analyses of different samples from similar ginseng remedies show significant variance in composition. Oriental beliefs in therapeutic foods is attracting North Americans, one-third of whom are said to buy herbal remedies as alternatives to prescription drugs. Americans’ search for a nutritional Elixir vitae has been evident for over half a century. During the 1950s vitamin supplements were in fashion; during the 1960s proteins and amino acids were in favour; in the 1970s extensive publicity was given to essential fatty acids and cholesterol in relation to cardiovascular disfunctions; during the 1980s dietary fibre was of paramount interest. At present the fashion is with ‘functional foods’ (which beg the question: what are non-functional foods?) and ‘nutraceuticals’, foods believed to possess beneficial pharmacological properties. It is not surprizing that the Chinese claim to be the originators of nutraceutical concepts. Food and drugs: science and technology A characteristic common to food, drugs and most other basic need industries is that technologies discovered by perceptive empiricism long preceded any scientific understanding of the biochemical properties of the raw materials and processed products. Foods found to be acceptable and satisfying, and medicinals that cured or alleviated particular maladies were discovered by chance, trial and error, and painful experience. The history of food processing, in large part, is a history of bioengineering, the gradual replacement of human hands and energy first by animals, later by machines. Industrial processes of fractionation and transformation used today were developed hundreds of years ago. What began as labour-intensive artisanal crafts were progressively mechanized. In addition to providing an immense diversity of food products, food industries have progressively reduced the human effort and energy needed in factories, restaurants and homes. Food preservation The basic principles of food preservation: control of (1) active water content, (2) ambient atmosphere, (3) temperature, (4) pH; and (5) thermal inactivation of microbial and biochemical sources of spoilage, were discovered empirically hundreds of years ago. Mediterranean, Asian and Amerindian people used sun drying to preserve milk, meat, fish, fruits and vegetables, into their sun-dried pemmican northern Amerindians added dried berries that provided ascorbic acid. Sliced potatoes were freeze-dried by early Amerindians, ice gradually subliming in the dry air and low atmospheric pressure of the high Andes. Stone age Britons dried grains over open fires to prevent sprouting. Over 4000 years ago, the Chinese preserved fish by osmotic dehydration with salt. Republican Romans reduced water activity in meat and fruits by adding salt or honey. About 5000 years ago, Middle Eastern farmers stored grains in earthenware amphora each hermetically sealed by an impervious goat skin. All stages of insect metamorphosis were asphyxiated by respired CO2. Seneca described how Romans preserved prawns in snow from the Appenines. The frozen food industry developed after Clarence Birdseye, an American, observed how whale, seal and reindeer meat were naturally preserved during the cold Canadian winter. Modern canning, bottling and boil-in-the-bag were anticipated in Republican Rome where chopped spiced meats were sealed and boiled inside the cleaned womb of a sow or the body cavity of a squid. Fermentation and pickling of fruits and vegetables is an ancient practice among Asian and Mediterranean people. The Babylonians preserved their milk by lactic fermentation. Ethanol was distilled in China over 3000 years ago. Homer described wine as ‘‘A gift from the gods’’. Grain milling—the first continuous process Fractionation of cereal grains by pulverization, sieving and winnowing, and extraction of olive oil by 4 Joseph H. Hulse / Trends in Food Science & Technology 15 (2004) 3–18
Joseph H.Hulse Trends in Food Science Technology 15(2004)3-18 pressing,began in Egypt and nearby Mediterranean the steam engine,was mechanized faster than food countries 7000 years ago.Commercial bakeries and processes. breweries existed in Babylon and Egypt 5000 years In the British baking industry,mechanical dough before Eduard Buchner and Emil Fischer discovered the mixers were not much in evidence until after 1920. enzymic conversion of carbohydrates. Mechanization moved more rapidly after World War II The history of grain milling illustrates how labour- During the 1930s,in a typical Manchester bakery,six intensive artisanal processes were progressively men working an 8 h shift produced about 2400 loaves. mechanized.The primitive pestel and mortar gave way In 1990,three men working an 8 h shift could produce in Egypt to the saddle stone:where grain spread on a over 65,000 loaves:400 versus 22,000 loaves per man. stationary smooth stone slab was pulverized by an The first significant change came in the 1960s when upper stone pushed backwards and forwards by a British scientists replaced traditional long fermentation kneeling slave.Later,the Greeks devised a shearing processes by high energy mixing of bread doughs con- action by incising herring-bone grooves into the inter- taining ascorbic acid. faces of the upper and lower stones. Continuous malting in breweries began with the In the rotary quern,evident in several ancient Medi- Wanderhaufen moving malt couch.Continuous fer- terranean countries,an upper stone was continuously mentations.in which the substrate passes over an rotated over a lower static stone.By cutting an eye-hole immobilized microorganism or biocatalyst,are now in the centre of the upper stone,grain was fed in a common among modern bioindustries. steady stream,the pulverized product being carried to Humphrey Davy's discovery of finely divided plati- the periphery by centrifugal force.Grain milling was the num as a catalyst led to the catalytic hydrogenation of first known continuous industrial process.Rotary vegetable oils to produce hard fats for shortening and querns were at first driven by slaves walking on a margarine.About the same time,solvent extraction of treadmill,later by camels or donkeys. vegetable oils competed with mechanical expression.In After the Romans invented the water wheel,through- contrast to food processing,pharmaceutical industries out the Roman empire grain mills were built close by advanced more from chemistry than engineering,start- rivers or running streams.The Domesday Book.Wil- ing in the 18th century in the German dyestuffs indus- liam I's inventory of the nation's assets published in tries after von Hofmann was appointed Professor of 1085,recorded over 5000 water mills in Britain.The first Chemistry at the University of Berlin. windmills appeared in Persia (now Iran)in the 10th century CE.In 1784,an early version of James Watt's Pharmaceuticals in ancient times steam engine was installed in a London flour mill.Less Survival and health.the fate of the human soul and than 100 years ago,in North America,more grain mills body after death,and the supernatural influence of the were powered by water wheels than by steam engines. sun,moon and stars intrigued many of our early ante- The first mill powered by electric motors came on cedents.Primitive peoples searched for panaceas and stream in 1887 in Wyoming. palliatives to cure their diseases.Early Palestinians and Though more precisely engineered,modern roller Sumerians believed disease was a punishment for sin mills with their incised steel break rolls operate on the and could be mitigated by magical charms and drugs same principles as the early saddle stone and rotary with supernatural powers.Shen-Nung (ca 2700 BCE)is quern.Hand winnowing has its modern equivalent in acclaimed as the Chinese founder of acupuncture and the middlings purifier,an enclosed vibrating gravity drug therapy.He and his contemporaries described table with screens of diverse mesh size.Separated bran diabetes,smallpox,measles.cholera and various dysen- is removed by suction fans. teries.Their 1800 medical prescriptions included ephe- A smart indigenous software programme enables drine,camphor,and cod liver oil.Arsenic and mercury modern wheat flour mills in India to be operated from compounds acted as bactericides.Respiratory diseases a desk top computer.At the same time,poor rural were treated by surrounding the patient in a pile of Indian women grind local grains by pestel and mortar burning herbs. or saddle stone,and extract oil from groundnuts by The Egyptian Ebers papyrus (ca 1550 BCE),dis- rotary querns. covered by 20th century archeologists,describes treat- ments for rheumatism.schistosomiasis,diabetes and Mechanization of traditional biotechnologies intestinal parasites.It lists 875 drugs compounded from The patterns and pace of mechanization have pro- ca 500 substances:metallic salts,such vegetable extracts gressed differently among different industries.Though as gentian,senna,castor oil,vermifiuge and henbane. the transition from rural domestic spinning and weaving Sumerian cuneiform tablets from Hammurabi's reign into large mechanized factories evolved over more describe hepatic diseases,fevers,gonorrhoea,various than two centuries,in Britain the textile industry, strokes and scabies.Drugs included hellebore (believed stimulated by cheap coal carried on canal barges,and to cure madness),mandrake root and opium
pressing, began in Egypt and nearby Mediterranean countries 7000 years ago. Commercial bakeries and breweries existed in Babylon and Egypt 5000 years before Eduard Buchner and Emil Fischer discovered the enzymic conversion of carbohydrates. The history of grain milling illustrates how labourintensive artisanal processes were progressively mechanized. The primitive pestel and mortar gave way in Egypt to the saddle stone: where grain spread on a stationary smooth stone slab was pulverized by an upper stone pushed backwards and forwards by a kneeling slave. Later, the Greeks devised a shearing action by incising herring-bone grooves into the interfaces of the upper and lower stones. In the rotary quern, evident in several ancient Mediterranean countries, an upper stone was continuously rotated over a lower static stone. By cutting an eye-hole in the centre of the upper stone, grain was fed in a steady stream, the pulverized product being carried to the periphery by centrifugal force. Grain milling was the first known continuous industrial process. Rotary querns were at first driven by slaves walking on a treadmill, later by camels or donkeys. After the Romans invented the water wheel, throughout the Roman empire grain mills were built close by rivers or running streams. The Domesday Book, William I’s inventory of the nation’s assets published in 1085, recorded over 5000 water mills in Britain. The first windmills appeared in Persia (now Iran) in the 10th century CE. In 1784, an early version of James Watt’s steam engine was installed in a London flour mill. Less than 100 years ago, in North America, more grain mills were powered by water wheels than by steam engines. The first mill powered by electric motors came on stream in 1887 in Wyoming. Though more precisely engineered, modern roller mills with their incised steel break rolls operate on the same principles as the early saddle stone and rotary quern. Hand winnowing has its modern equivalent in the middlings purifier, an enclosed vibrating gravity table with screens of diverse mesh size. Separated bran is removed by suction fans. A smart indigenous software programme enables modern wheat flour mills in India to be operated from a desk top computer. At the same time, poor rural Indian women grind local grains by pestel and mortar or saddle stone, and extract oil from groundnuts by rotary querns. Mechanization of traditional biotechnologies The patterns and pace of mechanization have progressed differently among different industries. Though the transition from rural domestic spinning and weaving into large mechanized factories evolved over more than two centuries, in Britain the textile industry, stimulated by cheap coal carried on canal barges, and the steam engine, was mechanized faster than food processes. In the British baking industry, mechanical dough mixers were not much in evidence until after 1920. Mechanization moved more rapidly after World War II. During the 1930s, in a typical Manchester bakery, six men working an 8 h shift produced about 2400 loaves. In 1990, three men working an 8 h shift could produce over 65,000 loaves: 400 versus 22,000 loaves per man. The first significant change came in the 1960s when British scientists replaced traditional long fermentation processes by high energy mixing of bread doughs containing ascorbic acid. Continuous malting in breweries began with the Wanderhaufen moving malt couch. Continuous fermentations, in which the substrate passes over an immobilized microorganism or biocatalyst, are now common among modern bioindustries. Humphrey Davy’s discovery of finely divided platinum as a catalyst led to the catalytic hydrogenation of vegetable oils to produce hard fats for shortening and margarine. About the same time, solvent extraction of vegetable oils competed with mechanical expression. In contrast to food processing, pharmaceutical industries advanced more from chemistry than engineering, starting in the 18th century in the German dyestuffs industries after von Hofmann was appointed Professor of Chemistry at the University of Berlin. Pharmaceuticals in ancient times Survival and health, the fate of the human soul and body after death, and the supernatural influence of the sun, moon and stars intrigued many of our early antecedents. Primitive peoples searched for panaceas and palliatives to cure their diseases. Early Palestinians and Sumerians believed disease was a punishment for sin and could be mitigated by magical charms and drugs with supernatural powers. Shen-Nung (ca 2700 BCE) is acclaimed as the Chinese founder of acupuncture and drug therapy. He and his contemporaries described diabetes, smallpox, measles, cholera and various dysenteries. Their 1800 medical prescriptions included ephedrine, camphor, and cod liver oil. Arsenic and mercury compounds acted as bactericides. Respiratory diseases were treated by surrounding the patient in a pile of burning herbs. The Egyptian Ebers papyrus (ca 1550 BCE), discovered by 20th century archeologists, describes treatments for rheumatism, schistosomiasis, diabetes and intestinal parasites. It lists 875 drugs compounded from ca 500 substances: metallic salts, such vegetable extracts as gentian, senna, castor oil, vermifiuge and henbane. Sumerian cuneiform tablets from Hammurabi’s reign describe hepatic diseases, fevers, gonorrhoea, various strokes and scabies. Drugs included hellebore (believed to cure madness), mandrake root and opium. Joseph H. Hulse / Trends in Food Science & Technology 15 (2004) 3–18 5
6 Joseph H.Hulse Trends in Food Science Technology 15(2004)3-18 During the 4th and 5th centuries,BCE,the Greek rational distinction.Though it needed Maxwell's math- school of Hippocrates,published over 70 treatises on ematical genius 40 years later to transform Faraday's medical theories and practices,and prescribed more electromagnetic induction principles into electric motors than 300 remedies,most from plants,to be administered and power generators,the 1850s mark the point from orally or via other orifices.The Greeks were aware of which new technologies based on scientific principles potential dangers in drug therapy;the Greek word appeared alongside empirically discovered technologies oapuokov (Pharmakon)being translated as 'drug', used to process foods,textiles,drugs and ceramics. 'medicine',poison'or 'magic potion'.The Greeks After his mentor Humphrey Davy discovered the believed that health (eucrasia)resulted from a harmonic anaesthetic nitrous oxide,in 1818 Michael Faraday blend,disease (dyscrasia)from imbalance among four demonstrated that ether was a more effective anaes- humours:black bile,yellow bile,phlegm and blood.A thetic.But before von Liebig published his 'Organic tri-humorous concept of air,bile and phlegm existed Chemistry in its Application to Physiology and Pathol- among Ayurvedic Indians. ogy'in the mid-19th century,studies on the effectiveness Some 300 years after Hippocrates,Dioscorides,a of drugs can best be described as blindly empirical. Greek physician,regarded as the father of Materia For many centuries in Europe,pharmacy was the Medica,formulated over 600 remedies from plant and business of apothecaries who extracted and com- animal tissues.Dioscorides'medicines were prescribed pounded medicines from natural vegetable and mineral for more than 1500 years.Galen of Pergamon,a sources.In Ancient Greece,physicians and apothecaries physician of the 2nd century CE,added more veget- were discrete professions (an anoOek was a shop that able remedies,known as Galenicals,to Dioscorides' sold drugs).In 1617,King James I created the collection. Society of Apothecaries,giving them responsibility for Until the middle of the 19th century,medicine and production and sale of drugs and some poisons.Benja- pharmacy were more magical and mystical than scien- min Franklyn defined the respective roles of American tific.Plantagenet physicians treated fevers by burying physicians and apothecaries,with laws that licensed victims up to the neck in a dunghill;gout was treated apothecaries to sell drugs,poisons and narcotics.The with asses'hooves;wealthy patients afflicted with ague, first codified food and drug laws were enacted in 1860 in itch or erysipelas were dosed with finely ground the United Kingdom amethysts,pearls and sapphires. In the 19th century,British apothecaries worked with It is difficult to discover what useful drugs the alche- a Materia Medica cabinet containing 270 samples of mists discovered in their pursuit of the Elixir vitae,the roots,barks,leaves,seeds and chemicals.The British elusive substance that would ensure eternal life.Alche- Pharmaceutical Society received a Royal Charter in mists wrote their reports in cryptic codes and obscure 1843.A consolidated British Pharmacopoeia was pub- symbols to confuse their competitors.What is compre- lished in 1864 and revised in 1898 and 1914.The 1864 hensible is more redolent of the kitchen than the edition described only four synthetic drugs;over 80 laboratory.Alchemical substances included sugar of were listed in the 1914 edition,almost all imported from lead,butter of antimony,oil of vitriol,cream of tartar Germany.Before World War I,Britain had no synthetic and milk of lime. pharmaceutical industry,only a few vaccines being Paracelsus,a Swiss alchemist of the 15th century,is processed. sometimes regarded as the father of chemistry.He dis- puted Galen's theories and developed the notion of From empiricism to science iatrochemistry:examination of substances to detect From the mid-1800s analytical chemistry,microscopy possible medicinal potency.He proposed various medical and cytology made impressive progress.Chemotherapy prescriptions. was stimulated by identification of microbial pathogens The first printed medical book:'Laxierkalender'-a and means by which they could be controlled.Wohler's treatise on laxatives-came from the Gutenberg presses conversion of ammonium isocyanate into urea showed in 1457.In 1564,the world's first Pharmacopoeia that naturally occurring organic substances can be syn- Augustina was published in Augsburg.In 1616,the thesized from non-biological chemicals.Pharmacology Royal College of Physicians published the Pharmaco- progressed through research begun in Strasbourg on poeia Londonensis which listed drugs then permitted in specific actions of drugs on particular body tissues.The Britain. world's first Chair of Pharmacology was in Estonia. Discovery of hormones,extracted from endocrine and Pharmaceutical industries ductless glands and later synthesized,added an important In his book'Brave New World',Aldous Huxley pro- dimension to therapeutic medicine and to development of posed that the history of economic and industrial pharmaceutical industries. development is of two periods:pre-and post-Henry Until the 20th century food processing progressed Ford.I would argue pre-and post-Faraday as a more through engineering, pharmaceutical technologies
During the 4th and 5th centuries, BCE, the Greek school of Hippocrates, published over 70 treatises on medical theories and practices, and prescribed more than 300 remedies, most from plants, to be administered orally or via other orifices. The Greeks were aware of potential dangers in drug therapy; the Greek word farmakon (Pharmakon) being translated as ‘drug’, ‘medicine’, ‘poison’ or ‘magic potion’. The Greeks believed that health (eucrasia) resulted from a harmonic blend, disease (dyscrasia) from imbalance among four humours: black bile, yellow bile, phlegm and blood. A tri-humorous concept of air, bile and phlegm existed among Ayurvedic Indians. Some 300 years after Hippocrates, Dioscorides, a Greek physician, regarded as the father of Materia Medica, formulated over 600 remedies from plant and animal tissues. Dioscorides’ medicines were prescribed for more than 1500 years. Galen of Pergamon, a physician of the 2nd century CE, added more vegetable remedies, known as Galenicals, to Dioscorides’ collection. Until the middle of the 19th century, medicine and pharmacy were more magical and mystical than scientific. Plantagenet physicians treated fevers by burying victims up to the neck in a dunghill; gout was treated with asses’ hooves; wealthy patients afflicted with ague, itch or erysipelas were dosed with finely ground amethysts, pearls and sapphires. It is difficult to discover what useful drugs the alchemists discovered in their pursuit of the Elixir vitae, the elusive substance that would ensure eternal life. Alchemists wrote their reports in cryptic codes and obscure symbols to confuse their competitors. What is comprehensible is more redolent of the kitchen than the laboratory. Alchemical substances included sugar of lead, butter of antimony, oil of vitriol, cream of tartar and milk of lime. Paracelsus, a Swiss alchemist of the 15th century, is sometimes regarded as the father of chemistry. He disputed Galen’s theories and developed the notion of iatrochemistry: examination of substances to detect possible medicinal potency. He proposed various medical prescriptions. The first printed medical book: ‘Laxierkalender’—a treatise on laxatives—came from the Gutenberg presses in 1457. In 1564, the world’s first Pharmacopoeia Augustina was published in Augsburg. In 1616, the Royal College of Physicians published the Pharmacopoeia Londonensis which listed drugs then permitted in Britain. Pharmaceutical industries In his book ‘Brave New World’, Aldous Huxley proposed that the history of economic and industrial development is of two periods: pre-and post-Henry Ford. I would argue pre-and post-Faraday as a more rational distinction. Though it needed Maxwell’s mathematical genius 40 years later to transform Faraday’s electromagnetic induction principles into electric motors and power generators, the 1850s mark the point from which new technologies based on scientific principles appeared alongside empirically discovered technologies used to process foods, textiles, drugs and ceramics. After his mentor Humphrey Davy discovered the anaesthetic nitrous oxide, in 1818 Michael Faraday demonstrated that ether was a more effective anaesthetic. But before von Liebig published his ‘Organic Chemistry in its Application to Physiology and Pathology’ in the mid-19th century, studies on the effectiveness of drugs can best be described as blindly empirical. For many centuries in Europe, pharmacy was the business of apothecaries who extracted and compounded medicines from natural vegetable and mineral sources. In Ancient Greece, physicians and apothecaries were discrete professions (an apoyek was a shop that sold drugs). In 1617, King James I created the Society of Apothecaries, giving them responsibility for production and sale of drugs and some poisons. Benjamin Franklyn defined the respective roles of American physicians and apothecaries, with laws that licensed apothecaries to sell drugs, poisons and narcotics. The first codified food and drug laws were enacted in 1860 in the United Kingdom. In the 19th century, British apothecaries worked with a Materia Medica cabinet containing 270 samples of roots, barks, leaves, seeds and chemicals. The British Pharmaceutical Society received a Royal Charter in 1843. A consolidated British Pharmacopoeia was published in 1864 and revised in 1898 and 1914. The 1864 edition described only four synthetic drugs; over 80 were listed in the 1914 edition, almost all imported from Germany. Before World War I, Britain had no synthetic pharmaceutical industry, only a few vaccines being processed. From empiricism to science From the mid-1800s analytical chemistry, microscopy and cytology made impressive progress. Chemotherapy was stimulated by identification of microbial pathogens and means by which they could be controlled. Wohler’s conversion of ammonium isocyanate into urea showed that naturally occurring organic substances can be synthesized from non-biological chemicals. Pharmacology progressed through research begun in Strasbourg on specific actions of drugs on particular body tissues. The world’s first Chair of Pharmacology was in Estonia. Discovery of hormones, extracted from endocrine and ductless glands and later synthesized, added an important dimension to therapeutic medicine and to development of pharmaceutical industries. Until the 20th century food processing progressed through engineering, pharmaceutical technologies 6 Joseph H. Hulse / Trends in Food Science & Technology 15 (2004) 3–18
Joseph H.Hulse Trends in Food Science Technology 15(2004)3-18 小 through chemistry.Ancient remedies and plant extracts substances found in medicinal plants.The first propri- were the first raw materials of pharmaceutical indus- etary drug Aspirin-acetylsalicylic acid-was synthesized tries.Several drugs in early pharmacopoeias were later by reacting acetic anhydride with salicylic acid from declared ineffective or dangerous. willow bark (Salix spp).Later,codeine was produced by Active substances were dissolved in ethanol and/or methylation of morphine. water;compounded with diluents and pressed into pills In the late 1900s,Paul Ehrlich observed how certain coated with gelatin or sugar;or into tablets with poly- dyes injected into animals,stained specific tissues.Ehr- saccharide gums as binders,and lubricants to permit lich explored whether similar dyes would stain and release from tableting machines.For treatment of skin inactivate microorganisms.He unsuccessfully tested 500 wounds and infections,antiseptic drugs were dispensed dyes on 2000 mice inoculated with pathogenic trypano- as ointments in lanolin or water-in-oil emulsions. somes.He then synthesized more than 600 arsenic compounds with chemical structures similar to diazo Drugs:natural and traditional dyes.His 606th compound inactivated the trypano- Though today roughly 20%of all commercial phar- somes without adverse effect on the mice.The effective maceuticals are derived from natural and genetically compound,named 'salvarsan',contained an -As=As- modified microorganisms,there is lively commercial group analagous to the -N=N-group in diazo dyes and interest in natural and traditional sources.The Pfizer showed affinity with protein in the pathogen compar- drug company was among the first to collect and screen able to the affinity of diazo compounds with protein botanical specimens from tropical forests.Merck in fibres in wool.Salvarsan and its successor neosalvarsan. cooperation with the national Institute of Biodiversity is effective against Spirochaeta pallida the pathogen that screening plants,insects and microorganisms from causes syphilis,laid the basis for chemotherapy. Costa Rica.Ethnobotanical expeditions in the tropical In 1919,Heidelberger and Jakobs in Germany dis- forests of the Amazon have delivered more than 10,000 covered that some azo derivatives of sulphanilamide species for examination.From Colombia over 1500 destroyed bacteria.In 1935,a scientist at the Bayer species,reported by local people to be biologically use- company found the red azo dye prontosil to be effective ful,are being studied. against Streptococci that caused puerperal and scarlet The ethical issue of biopiracy is being raised where fevers.In the 1930s,scientists at May and Baker in foreign companies and their agents,engaged in botani- Britain synthesized over 600 sulphanilamide derivatives. cal collecting,are taking away biological materials and The 693rd.which effectively treated bacterial pneumo- indigenous experience in traditional medicine without nia,was named M&B693.May and Baker synthesized reimbursement to local people.As observed by an Asian over 3000 related compounds,several being effective scientist:"We have the biodiversity,they [the affluent bactericides. nations]steal it to support their biotechnologies".In In 1936,the British Medical Research Council defined response to public interest in ancient and traditional 'Chemotherapy'as medical treatment by synthetic che- medicines,in 1992 the United States National Institutes mical compounds that react specifically with infective of Health established an Office of Alternative Medi- organisms.The process of synthesizing chemother- cines.Data bases on 'natural medicinals'exist at the apeutic substances and determining potency in labora- Royal Danish School of Pharmacy in Copenhagen,and tory animals is expensive and time consuming.Between at the University of Illinois,Chicago School of Medi- 1936 and 1960,one of Britain's largest pharmaceutical cine.The latter,known as NARPALERT,is adminis- companies tested over 45,000 synthetics out of which tered by Professor Norman Farnsworth. only 16 became marketable drugs.During World War Across the planet,there exists a vast unexplored II,Britain lost access to Peruvian bark,the natural source of plants and microorganisms.Of over 100.000 source of the anti-malarial quinine.Antimalarials were identified species,fewer than 200 microorganisms pro- urgently needed to protect armed forces men and duce substances used by food,pharmaceutical or other women posted to humid tropical countries.The only industries.The higher orders of terrestrial plants repre- two synthetics available caused undesirable side effects sent more than 65%of the world's biomass but fewer Between 1942 and 1946.the ICI Pharmaceutical com- than 6%of identified species are commercially culti- pany tested ca 1700 synthetics before discovering pro- vated.Of the 80.000 plants believed to be edible,fewer guanil hydrochloride,given the trade name Paludrine than 20 provide 90%of the world's food calories. 'Malaria'(literally 'bad air'),is also known as palud- ism'or swamp fever (Latin 'palus'='swamp'). Synthetic drugs and chemotherapy During the late 19th century,encouraged by their Antibiotics success with synthetic dyes,the German companies While pursuing his microscopic studies,Pasteur sug- Bayer.Hoechst and Merck began chemical synthesis of gested that microorganisms might be induced to attack drugs,first making analogues and derivatives of active one another.In 1928,Alexander Fleming,at London
through chemistry. Ancient remedies and plant extracts were the first raw materials of pharmaceutical industries. Several drugs in early pharmacopoeias were later declared ineffective or dangerous. Active substances were dissolved in ethanol and/or water; compounded with diluents and pressed into pills coated with gelatin or sugar; or into tablets with polysaccharide gums as binders, and lubricants to permit release from tableting machines. For treatment of skin wounds and infections, antiseptic drugs were dispensed as ointments in lanolin or water-in-oil emulsions. Drugs: natural and traditional Though today roughly 20% of all commercial pharmaceuticals are derived from natural and genetically modified microorganisms, there is lively commercial interest in natural and traditional sources. The Pfizer drug company was among the first to collect and screen botanical specimens from tropical forests. Merck in cooperation with the national Institute of Biodiversity is screening plants, insects and microorganisms from Costa Rica. Ethnobotanical expeditions in the tropical forests of the Amazon have delivered more than 10,000 species for examination. From Colombia over 1500 species, reported by local people to be biologically useful, are being studied. The ethical issue of biopiracy is being raised where foreign companies and their agents, engaged in botanical collecting, are taking away biological materials and indigenous experience in traditional medicine without reimbursement to local people. As observed by an Asian scientist: ‘‘We have the biodiversity, they [the affluent nations] steal it to support their biotechnologies’’. In response to public interest in ancient and traditional medicines, in 1992 the United States National Institutes of Health established an Office of Alternative Medicines. Data bases on ‘natural medicinals’ exist at the Royal Danish School of Pharmacy in Copenhagen, and at the University of Illinois, Chicago School of Medicine. The latter, known as NARPALERT, is administered by Professor Norman Farnsworth. Across the planet, there exists a vast unexplored source of plants and microorganisms. Of over 100,000 identified species, fewer than 200 microorganisms produce substances used by food, pharmaceutical or other industries. The higher orders of terrestrial plants represent more than 65% of the world’s biomass but fewer than 6% of identified species are commercially cultivated. Of the 80,000 plants believed to be edible, fewer than 20 provide 90% of the world’s food calories. Synthetic drugs and chemotherapy During the late 19th century, encouraged by their success with synthetic dyes, the German companies Bayer, Hoechst and Merck began chemical synthesis of drugs, first making analogues and derivatives of active substances found in medicinal plants. The first proprietary drug Aspirin—acetylsalicylic acid—was synthesized by reacting acetic anhydride with salicylic acid from willow bark (Salix spp). Later, codeine was produced by methylation of morphine. In the late 1900s, Paul Ehrlich observed how certain dyes injected into animals, stained specific tissues. Ehrlich explored whether similar dyes would stain and inactivate microorganisms. He unsuccessfully tested 500 dyes on 2000 mice inoculated with pathogenic trypanosomes. He then synthesized more than 600 arsenic compounds with chemical structures similar to diazo dyes. His 606th compound inactivated the trypanosomes without adverse effect on the mice. The effective compound, named ‘salvarsan’, contained an –As¼As– group analagous to the –N¼N– group in diazo dyes and showed affinity with protein in the pathogen comparable to the affinity of diazo compounds with protein fibres in wool. Salvarsan and its successor neosalvarsan, effective against Spirochaeta pallida the pathogen that causes syphilis, laid the basis for chemotherapy. In 1919, Heidelberger and Jakobs in Germany discovered that some azo derivatives of sulphanilamide destroyed bacteria. In 1935, a scientist at the Bayer company found the red azo dye prontosil to be effective against Streptococci that caused puerperal and scarlet fevers. In the 1930s, scientists at May and Baker in Britain synthesized over 600 sulphanilamide derivatives. The 693rd, which effectively treated bacterial pneumonia, was named M&B693. May and Baker synthesized over 3000 related compounds, several being effective bactericides. In 1936, the British Medical Research Council defined ‘Chemotherapy’ as medical treatment by synthetic chemical compounds that react specifically with infective organisms. The process of synthesizing chemotherapeutic substances and determining potency in laboratory animals is expensive and time consuming. Between 1936 and 1960, one of Britain’s largest pharmaceutical companies tested over 45,000 synthetics out of which only 16 became marketable drugs. During World War II, Britain lost access to Peruvian bark, the natural source of the anti-malarial quinine. Antimalarials were urgently needed to protect armed forces men and women posted to humid tropical countries. The only two synthetics available caused undesirable side effects. Between 1942 and 1946, the ICI Pharmaceutical company tested ca 1700 synthetics before discovering proguanil hydrochloride, given the trade name Paludrine. ‘Malaria’ (literally ‘bad air’), is also known as ‘paludism’ or swamp fever (Latin ‘palus’=‘swamp’). Antibiotics While pursuing his microscopic studies, Pasteur suggested that microorganisms might be induced to attack one another. In 1928, Alexander Fleming, at London Joseph H. Hulse / Trends in Food Science & Technology 15 (2004) 3–18 7