Lecture_1&2

Biotechnology

Lecture 1 of BIOTECHNOLOGY Definition

Ancient Biotechnology

Classical Biotechnology

Foundations of Modern Biotechnology

What is Biotechnology?Some Ideas?Some examples?

WHAT IS BIOTECHNOLOGY?The use of living organisms or their products to enhance our lives and our environment

Menurut EFB (European Federation of Biotechnology, 1983), Bioteknologi adalah penggunaan terpadu biokimia, mikrobiologi, dan ilmu-ilmu keteknikan dengan bantuan mikroba, bagian-bagian mikroba atau sel dan jaringan organisme yang lebih tinggi dalam penerapannya secara teknologis dan industri.

Bioteknologi mencakup proses-proses biologis oleh organisme yang dimanfaatkan oleh dan untuk kepentingan manusia. Bioteknologi sebagai ilmu terapan

biotechnology for millennia

WHAT IS BIOTECHNOLOGY ?

BiotechnologyAncientClassicalModernNEED + KNOWLEDGE => TECHNOLOGICAL ADVANCES

* Domestication and Agriculture

* Ancient Plant Germplasm* History of Fermented Foods and Beverages (the beginning of Classical Biotechnology) Ancient Biotechnology

Nomadic lifestyle of prehistoric peoples - gather food and hunt animals they abandoned their nomadic ways and started to domesticate plants and animals

-archaeological findings ancient farming sites New World, the Far East, and Europe at the same time

Domestication*Agriculture developed independently in several areas of the world

DomesticationWhat exactly prompted this sudden shift to a more sedentary lifestyleis not clear; - increasing demand for food due to population growth - natural dwindling of herds of migratory animals 9000 BC - First evidence of plant domestication in hills above Tigris River5000 BC - Agricultural communities exist in Mesopotamia

2000 BC - The Babylonians and Egyptians left pictorial evidence that dogs, sheep, and cattle had been domesticated

1000 BC - Domestication complete for all important food crops in the new world - Selected seeds, cuttings, or tubers from superior plants for the next planting. 700 BC - Assyrians and Babylonians - Hand pollination of date palm

Ancient Plant GermplasmLarge-scale organized seed production began in the early 1900s

Nikolai I. Vavilov (1887-1943), Russian plant geneticist and agronomist collected and catalogued thousands of ancient crop plants and their wild relatives.

-Between 1923 and 1931, he traveled extensively in the Soviet Union and in over 50 countries to collect economically important plant varieties - beans, pea, chickpeas, maize, lentils, oats, rye, wheat

-Established one of the first important gene banks for long-term storage of important plant germplasm.

Ancient Plant GermplasmDemonstrated the economic value of germplasm collection particularly with respect to breeding programs for disease resistance

Vavilov was arrested in 1940 on charges of espionage and died in prison from malnutrition

Lysenko (1898-1976), a leader in the Soviet Science favored Lamarckism:theory of science that argues that organisms can acquire physical traits in response to the environment, and pass on these traits to their offspringHe was opposed to Mendelian inheritanceThus, Lysenko was against selective breeding Ancient Plant Germplasm

As the Soviet government suppressed Mendelian genetics, the US was establishing centers for the preservation, study, and distribution of germplasm.National Seed Storage Laboratory - Fort Collins Colorado

National Center for Genetic Resources Preservation

Ancient Plant Germplasm

CGIAR - Consultative Group of International Agricultural ResearchStores house plant material such as seeds, plant cuttings, and tubers.- storage is either short-, intermediate, and long-term Ex. Seeds in intermediate-term storage are kept at -5 - 0 oC Dried seeds are stored in sealed containers at - 20 oC - long-term to last over 100 years - Periodic germination and viability tests are performed

Tissues are now also kept in tissue culture - individual cells capable of regenerating new platelets.

SGRPSystem-wideGeneticResourceProgramme CGIAR

4000 BC - Egyptians used yeast in wine and bread making

2000 BC - Chinese develop fermentation Ancient Biotechnology FERMENTATION

Once people settled in villages, the development of new foods was possible - accidental discovery!* food contamination often destroys the food reserve* in some cases the microbial activity enhances the flavor and texturekimchi - sauerkraut - yoghurt - cheeseFERMENTATION - (lat.) fervere => to boiladdition of yeast to fruit juice => wine yeast to malt and grain => beer aroma of bread baking => alcohol produced bread rises => because of trapped CO2Glucose --> - -> - -> Pyruvate ---> Acetaldeyhyde ------> EthanolCO2 Fermented Foods

Knowledge drives technologyscientific and applied knowledgepractical experience * From mid-nineteenth century knowledge of cell processes - refined fermentation technology

Brewers began producing alcohol on a large scale in the early 1700s

Classical Biotechnology* By the 1800s brewers knew to use pure yeast cultures

Louis Pasteur - germ theory- microbes are responsible for fermentation

- proved that fermentation is the result of activity of yeasts and bacteria. 1822-1895 Classical Biotechnology

*Sir Alexander Fleming1881 - 1995 * Nobel prize 1945 Classical BiotechnologyFleming did not attempt to purify penicillin. But in the late 1930s Australian Howard Florey and Chain and others developed penicillin into a clinical antibiotic in 1940-41.

Fleming, Florey, and Chain shared the 1945 Nobel Prize in Physiology or Medicine. Fleming left culture dishes lying around He found that an unusual mold had germinated on the plate. and inhibited the growth of the bacterium that was growingon this plate.

A crude extract of the mold was then shown to have antibacterial properties.This observation led Fleming to discover in 1928 and by 1929 an antibiotic that was produced by the mold Penicillium.

- Penicillin was produced by the fermentation of cultured Penicillium.

Whole organisms or individual cells rather than specific genes Classical Biotechnology

Classical Biotechnology - ANTIBIOTICS

Conversion of Cholesterol to steroids such as cortisone and sex hormones chemical synthesis of cortisone requires about 31 steps - low yieldin 1955 Upjohn researchers realized that Rhizopus arrhizusis capable of converting inexpensive plant sterols into cortisone synthetic compound $ 200 / gram biotransformation $ 6 / gram Classical Biotechnology - biochemical transformations

Knowledge of cell structurebiochemical reactionsgenetic make-up of organisms Foundation of Modern Biotechnology

Foundation of Modern Biotechnology

- Knowledge of genetic materialDr. Barbara McClintock (1902-1992)1983 Nobel Prize- discovery of transposable elements 35 years earlier- 1929 - reports 10 chromosomes in maize Maize cytogeneticist - provided a visual connection between certain inheritable traits and their physical basis in the chromosome. Foundation of Modern Biotechnology

Classical BiotechnologySIR ARCHIBALD EDWARD GARROD (1857-1936)

Garrod studied medicine at Oxford University and became a physician.

Garrod was studying the human disorder ALKAPTONURIA[turns the urine dark when exposed to oxygen]

Individuals lack homogentisate oxidase, leads to the excretion of HOMOGENTISIC ACID turns dark when exposed to aireHe collected family history information (as well as urine) from his patients.Based on discussions with Mendel, Garrod deduced that alkaptonuria is a recessive disorder. In 1902, Garrod published a book called The Incidence of Alkaptonuria: a Study in Chemical Individuality. This is the first published account of a case of recessive inheritance in humans.

Garrod was also the first to propose the idea that diseases were "inborn errors of metabolism." He believed that diseases were the result of missing or false steps in the body's chemical pathways. In 1923, his studies on alkaptonuria, and albinism were published as a book: Inborn Errors of Metabolism.

Garrod attributed a biochemical role to genes, and laid the groundwork for the next wave of discovery -- the molecular basis of inheritance.


ALFRED HENRY STURTEVANT (1891-1970)

Drosophila melanogaster FRUIT FLY

For his Ph.D. thesis, Sturtevant published the world's first genetic map based on the idea that GENES ARE LINKED IN A SERIES.

The single, mutant white-eyed fly was crossed with normal red-eyed flies => produced normal offspring (F1 generation)

F1 flies were crossed and more white-eyed flies were produced. This result from this crossing experiment was expected as Mendel found a similar pattern in peas.

Classical BiotechnologyIn 1928, Griffith - mice and pneumonia causing bacteria Streptococcus pneumoniae. THE TRANSFORMING PRINCIPLE

Smooth (S) strain - pathogenicRough (R) strain - non-pathogenic

Classical Biotechnology1944 - Avery, MacLeod and McCarty

isolated and fractionated cellular components from the heat killed pathogenic bacteria. introduced each fraction one at a time to harmless bacteria, which were then given to mice.

By this method, they found that only DNA would make the bacteria able to cause pneumonia and death in mice.

THE TRANSFORMING PRINCIPLE IS

- knowledge of genetic material

1953 Watson and Crick - Structure of DNA

used x-ray data collected by Rosalind Franklin to deciphered the structure of DNA


Holley, Khorana and Nirenberg SHARED THE 1968 Nobel Prize in Physiology or Medicine

FOR DECIPHERING THE genetic code


THE BEGINNING OF RECOMBINANT TECHNOLOGY- 1973Recombinant DNA procedures involve splicing one piece of DNA into another Stanley CohenPlasmids andAntibiotic resistanceHerbert BoyerRestriction enzymes

BACTERIUM Plasmids Chromosomal DNA THE BEGINNING OF RECOMBINANT TECHNOLOGY- 1973Antibiotic Resistance Marker

Classical BiotechnologyKary B. Mullis1993 Nobel Prize in Chemistryhttp://www.karymullis.com/

PCR: polymerase chain reactionused to detect small amounts of DNA present in a sample (blood, food, soil)the PCR chain reaction is used to amplify the amount of DNA present

General PCR Protocol

DNASequencing.3gp

Classical BiotechnologyDye-terminator sequencing technology * 1986 Leroy E. Hood's Laboratory at the California Tech and Smith announce the first semi-automated DNA sequencing machine* 1987 Applied Biosystems markets first automated sequencing machine, the Prism 373

involving a variety of natural and applied sciencescell and molecular biologymicrobiologygeneticsphysiologychemistry and biochemistryengineeringcomputer science / bioinformaticsnanotechnology Biotechnology is multidisciplinary

Many Applications of BiotechnologyRecombinant vaccinesProduction of new and improved foodsIndustrial chemicalsPharmaceuticalsLivestockDisease-resistant crop plants and livestockDiagnostics for detecting genetic diseasesGene therapy

Biotechnological - hope for - restoring the environment - protect endangered speciesMicroorganisms are used to clean up toxic wastes from industrial and oil spillsConservation biologists use genetic methods to identify particularpopulations of endangered or threatened species.By determining the genetic diversity of various plantand animal populations, genetic analysis can helpzoos and field biologists improve conservation practices.

********The nomadic lifestyle of prehistoric peoples - gather food and to hunt animals- 10K years ago-abandoned their nomadic ways- beginning to domesticate plants and animals.-archaeological findings ancient farming sites New Wold, the Far East, and Europe at the same time agriculture developed independently in several areas of the world.What exactly prompted this sudden shift to a more sedentary lifestyle is not clear; but it may have well been the increasing demand for food as the population increased and/or the natural dwindling of herds of migratory animals.*The nomadic lifestyle of prehistoric peoples - gather food and to hunt animals- 10K years ago-abandoned their nomadic ways- beginning to domesticate plants and animals.-archaeological findings ancient farming sites New Wold, the Far East, and Europe at the same time agriculture developed independently in several areas of the world.What exactly prompted this sudden shift to a more sedentary lifestyle is not clear; but it may have well been the increasing demand for food as the population increased and/or the natural dwindling of herds of migratory animals.******Once people settled in villages, the development of new foods was possible.often through accidental discovery. While food contamination often destroys the food reserve; in some cases the microbial activity enhanced the flavor and texture**from experiments and discoveries of the past has provided a solid foundation for the many industrial processes that today provide us with a plethora of products and services*Germ theory rather than spontaneousmysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed to the development of the first vaccines. He debunked the widely accepted myth of spontaneous generation, thereby setting the stage for modern biology and biochemistry. He described the scientific basis for fermentation, wine-making, and the brewing of beer. Pasteur's work gave birth to many branches of science, and he was singlehandedly responsible forsome of the most important theoretical concepts and practical applications of modern science.

*Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed into brightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. **Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. **Germ theory rather than spontaneousmysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed to the development of the first vaccines. He debunked the widely accepted myth of spontaneous generation, thereby setting the stage for modern biology and biochemistry. He described the scientific basis for fermentation, wine-making, and the brewing of beer. Pasteur's work gave birth to many branches of science, and he was singlehandedly responsible forsome of the most important theoretical concepts and practical applications of modern science.

*Germ theory rather than spontaneousmysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed to the development of the first vaccines. He debunked the widely accepted myth of spontaneous generation, thereby setting the stage for modern biology and biochemistry. He described the scientific basis for fermentation, wine-making, and the brewing of beer. Pasteur's work gave birth to many branches of science, and he was singlehandedly responsible forsome of the most important theoretical concepts and practical applications of modern science.




**Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. ***Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. *Fleming loved to play, both in the laboratory and out. He always loved snooker and golf and had many whimsical variants on the rules. In the lab he made "germ paintings,"in which he would draw with his culture loop using spores of highly pigmented bacteria, which were invisible when he made the painting, but when cultured developed intobrightly colored scenes. He followed what Max Delbruck would later call the "principle of limited sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture disheslying around for weeks and would often discover interesting things in them. Though the story has been told in many sometimes conflicting ways, something like thisresulted in the discovery of penicillin. He seems to have left a culture dish lying on the lab bench and then gone away on vacation. When he returned a few spores of anunusual mold had germinated on the plate. When he cultured the bacteria on the plate he found that they grew up to within a few centimeters of the mold, but there werekilled. A crude extract of the mold was then shown to have antibacterial properties. Fleming made this discovery in 1928 and by 1929 had named it penicillin (he was told bya colleague that the mold was a type of Penicillium and "penicillozyme" must have seemed cumbersome).Fleming continued to use penicillin in his lab but not with any great enthusiasm and certainly not to the exclusion of many other projects. He never developed it into aclinically useful compound, though in 1929 he suggested that it might have important clinical applications. Because he was a bacteriologist and not a chemist, Fleming didnot attempt to purify penicillin. He seems to have run into a dead end with penicillin and so during the 1930s, though he kept it in his lab, he did not do much with it. In thelate 1930s Australian Howard Florey came to London to work with Charles Sherrington. He worked on lysozyme for a while and then became interested in penicillin. It wasFlorey, with Chain and other of his group that developed penicillin into a clinincal antibiotic. They did this during 1940-41. Fleming, Florey, and Chain shared the 1945Nobel Prize in Physiology or Medicine. ***

Lecture_1&2

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