Bacteria: Disadvantages

• Bacteria are our 'foes' as they are associated with several diseases of plants and animals including man due to parasitic mode of nutrition of some bacteria. Bacterial attack is less severe on plants than it is on animals.
• Important bacterial diseases on plants are:
  1. Canker of Citrus (citrus canker) Xanthomonas citri
  2. Angular leaf spot of cotton X. malvacearum
  3. Fire blight of apples Erwinnia amylovora
  4. Crown gall of crops Agrobacterium tumefaciens
  5. Tondu of wheat Corynebacterium tritici
     • Important bacterial diseases on man are:
  6. Cyphillis Tryponema pallidum
  7. Plague (Black Death) Pasteurella pestis (Y. pestis)
  8. Chlorea Vibrio cholerae
  9. Anthrax Bacillus anthracis
  10. Pneumonia Diplococcus pneumonae
  11. Tuberculosis (TB) Mycobacterium tuberculoses
  12. Typhoid (Enteric fever) Salmonella typhi
  13. Bacterial dysentery Bacillus dysentrae (Shigella)
  14. Amoeboid dysentery Entamoeba histolytica (Protozoa)
  15. Tetanus (Lock jaw) Closteridium tetani
  16. Ptomaine (deadly food poisoning) Closteridium botulinum
  17. Leprosy Bacillus lepri (Mycobacterium lepri)
  18. Diptheria Corynebacterium diptherae
  19. Erysepalas (deadly blood Streptococcus

Poisoning; Death of RBC's)

20. Whooping cough Bordetella partusis
21. Gonorrhoea Neisseria gonorrhoae

Bacterial diseases like cholera, typhoid, dysentery etc are water borne diseases: tuberculosis, plague etc are air-borne diseases whereas disease like tetanus spreads through wounds. Syphilis is transmitted through sexual contact. Transmission of leprosy through contact is a matter of dispute. India based Mother Teresa was awarded Nobel Prize for her service to leprosy patients in West Bengal and other parts of India

Bacteria : Forms

1. On the basis of shape, bacteria may be cocci (Singular coccus), Bacilli (Bacillus), Vibrio, Spirillum etc. Cocci are spherical bacteria, smallest in size. They may be single (monoococucus), in pairs (Diplococcus), in chains (streptococcus), in bunches (staphylococcus) or cuboid (sar cinnae). Bacteria causing pneumonia are Diplococcus Bacilli are rod shaped bacteria they may be single or in chains (Streptobacilli). Majority of parasitic bacteria are rod shaped bacteria. Streptobacilli surrounded by mucilaginous sheath form Zoogloea. Vibro are comma shaped bacteria. Bacteria causing cholera are vibrio bacteria. Spirillum and spirochaete are zigzag spring like bacteria, Spirillum volutans is recognized as largest bacteria. The terms like coccus, bacillus, vibrio etc were coined by Mueller.
2. On the basis of cilia, a bacterial cell may be:

Atrichous : Bacterial cell without cilia.

Monotrichour : Bacteria cell with single cilia.

Lopotrichous : Bacteria cell with tuft of cilia at one end.

Cephalotrichous : Bacterial cell with tuft of cilia at both the ends.

Amphitrichous : Bacterial cell with one cilia at both the ends.

Peritrichous : Bacterial cell with cilia throughout the body.

Bacteria causing cholera disease is comma shaped & Lophotrichous.

3. On the basis of nutrition, bacteria may heterotrophy or autotroph. Heterotroph bacteria are further divided as saprophytic bacteria & parasitic bacteria. Similarly, autotroph bacteria are further divided as chemosynthetic and photosynthetic bacteria.
   • Bacteria, which obtain their food from dead organic matter, are saprophytic bacteria. They perform significant role of decomposers in ecosystem. Bacteria, which obtain their food from other living entity, are called parasitic bacteria. The living entity, which provides food to parasite, is termed as host. Host-parasite relation is specific. Parasite is called pathogen when it spreads in host.
   • Bacteria, which obtain their food through the inorganic reactions in which they participate, are called chemosynthetic bacteria. They are named after the inorganic reactions, us that they are involved. Thus, N-Bacteria S-Bacteria & Fe-Bacteria etc are examples of chemosynthetic bacteria. Chemosynthetic bacteria are basically autotroph but do not require pigment chlorophyll for energy requirement. Chemosynthetic bacteria will survive alone if chlorophyll pigment disappears from the world; rest will perish.
   • Bacteria, which obtain chemical energy through glucose formation, are called photosynthetic bacteria. They are autotrophs and depend on chlorophyll like pigments i.e., Bacteriochlorophyll & chlorobium chlorophyll (Bacterio viridies) for glucose formation. Green-S-Bacteria, Purple-S-Bacteria & Rhodospirillium etc. are examples of photosynthetic bacteria.

Comparison between normal and bacterial photosynthesis
Normal Photosynthesis	Bacterial Photosynthesis
1. Raw materials are CO2 & H2O	1. Raw materials are CO2 & H2S
2. H for reduction of CO2 into glucose comes from H2O	2. H- for reduction of CO2 into glucose comes from H2S.
3. Principal pigment is chlorophyll a	3. Principal pigment Bacteriochlorophyll a.
4. Intermediate H-acceptor is NADP	4. Intermediate H-acceptor is NAD.
5. PS I & PS II both are present in light phase.	5. PS I only is present in light phase; PS II is absent.
6. O2 is released as by product	6. S is released as by product
7. Biochemical reaction 6CO2 + 12H2O = C6H12O6+6H2O+6O2	7. Biochemical reaction. 6CO2 + 12H2O = C6H12O6+6H2O+12S
Generalised equation for both of the above 6CO2 + 12H2A = C6H12O6 + 6H2O + 12A A may be oxygen or sulfur.

Photosynthesis in bacteria was first studied by Van Neil of Germany who was first to support the idea of Robino Hill that O₂ released in normal photosynthesis comes from H₂O and not from CO₂.

Bacteria: Introduction

1. Study of Bacteria is called 'Bacteriology'. Leeuwenhoek is recognized as pioneer worker in Bacteriology. Pasteur, Koch & Lister are other earlier workers in Bacteriology.
2. The term bacteria were coined by Ehrenberg for the smaller 'animalcules' or the 'wretched beasts' of Leeuwenhoek. Bacteria are found everywhere and in all sorts of climates however they do not survive in acidic medium of Pickle solution or highly concentrated sucrose solution due to plasmolysis.
3. Bacteria activity is reduced greatly at low temperature; this explains why foodstuff remains safe for longer period in cold devices like fridge and refrigerators etc. Bacteria behave in different manner in different range of temperature.

Natural Defenses against Viral Infections:

1. Interferons (Isaacs and Lindenmann, 1957). Interferons are antiviral proteins (a class of glycoproteins) which diffuse out from infected cells, enter into the cells in the neighbourhood and impart a defense mechanism to these cells against viral infections by inhibiting the synthesis of viral proteins. These are therefore used for therapeutic and preventive purposes in viral infections, interferons are always secreted by host cells against viral infection.

2. Body Immunity. Viruses are good antigens to induce active production of specific antibodies (by lymphocytes).

3. Immunoprophylaxis – Vaccines: Vaccines contain inactivated (attenuated) virions, which cannot cause the concerned diseases, but still act as antigens to induce antibody production by the immune system of the body.

4. Chemotherapy – Antiviral Drugs: The chemotherapeutic agents antibiotics which are used in the treatment and control of bacterial diseases are ineffective for viral diseases. However, some antiviral drugs have been prepared. These include (i) Thiosemicarbozone (for treatment and prevention of smallpox), (ii) Ribavirin or Virozole (for influenza),
(iii) Deoxyuridines, Acylovir (for herpes), (iv) Foscarnet (for hepatitis-B) etc.

2g) Viruses: Study of Bacteriophages

1. Discovery of bacteriophages is associated with Twort when he reported viral disease in bacteria. The term bacteriophages was coined by De Herelle. They are viruses, which attack bacteria. A typical bacteriophage looks like a tadpole/sperm comprising a hexagonal head of protein and a tail also a protein they show binal symmetry. Head is 1000A long and 650A in width; length of the tail is 1000A. Thus, head and tail are equal in length. Infective part of the bacteriophage in most of the cases is ds-linear DNA and it is present in hexagonal head. Joint of head and tails is neck, which is covered by collar of protein. Tail ends in end plate that develops 3 pairs of tail fibers of protein. Bacteriophages that attack E.coli are called coliphage or T-phages. They were numbered as T₁, T₂, T₃, T₄, T₅, T₆, T₇ etc by Delburck, T₂, T₄, T₆ etc are T-even phages T₁, T₃, T₅, etc or T-odd phages.
2. A bacteriophage comes into contact with the bacterial (host) cell through tail fibres. A passage is created in the host cell once the mucocomplex cell wall of bacteria is broken by lysozyme of bacteriophage. Once the passage is created, ds-linear DNA of bacteriophage is dropped inside the host cell. Empty protein coat i.e. Ghost protein remains out the host cell and disappears later on. Infective part or genetic material in ÆX174 phages is ss circular DNA and it is RNA in MS-2 & R17 phages.
3. Phage DNA dropped inside host cell may be virulent or temperate. Bacterial cell is destroyed if phage DNA is virulent, bacterial cell is not destroyed is phage DNA is temperate.
4. Destruction of bacterial cell by virulent phage DNA is called lysis. The sequence of events leading to lysis of bacterial cell are:
   • Virulent phage DNA dropped inside bacterial cell.
   • Multiplication of phage DNA inside host cell i.e. Formation of prophage. Formation of complete phages. (End of latent period or period of eclipse of phages).
   • Destruction or lysis of bacterial cell (Total time: 15-20 minutes).*
5. A bacterial cell is not destroyed if phage DNA is temperate. Temperate phage DNA is attached with host DNA; this is called lysogeny. A lysogenic bacterial cell behaves normally till temperate phage DNA is attached. Lysogeny in bacteria was first reported by Lwoff. Lwoff also coined the term l-phage for those phages in which tail terminates into single tail fibre.
   • Lysogeny may be of 3 types. They are l-phage lysogeny; P₁-phage lysogeny and mu-phage lysogeny. In l-phage lysogeny, temperate phage DNA is attached with bacterial DNA at specific place i.e. at 'gal' & 'bio' genes of bacterial DNA. In P₁-phage lysogeny, temperate phage DNA is attached with any place other than gal's genes. In mu-phage lysogeny, temperate phage DNA is never attached with bacterial DNA, remain in bacterial cytoplasm as plasmid.
   • A lysogenic bacterial cell shows different behaviour when exposed to different dosages of UV rays:

Some Important Modern Viral Diseases

1. Cancer or Carcinoma:

Despite the fact that virus causing cancer is yet to be identified, still cancer is considered like a viral disease because of typical viral symptoms like Hyperplasia & hypertrophy, are reported in cancer. Certain genes called proto-oncogenes (c-onc) are present in human cells, which are involved in normal cell function. Mutation of proto-oncogenes may give rise to oncogenes, which stimulate cell division leading to an uncontrolled growth of the cells causing cancer. All retoveiruses and some DNA containing viruses (such as poxvirus, adenovirus, Herpes virus, hepatitis-B virus etc.) possess oncogene (v.onc) in their genome. These viruses are potential cancer producing pathogens. Study of cancer is called Oncology. Temin and Baltimore's studies on Rous sarcoma virus [RSV] have provided new dimensions in the knowledge of cancer. RSV is RNA containing virus and RNA of RSV forms DNA inside host cell through reverse transcription or 'Teminism'. Newly formed DNA develops malignant tumours in host. Harmful tumor is called malignant tumours whereas tumours, which are not harmful, are termed as benign tumours. Are lethal in advanced stage.

2. Acquired Immunodeficiency Syndrome (AIDS):

AIDS is a viral disease in which our acquired immunity defense system is gradually shattered, and the patient dies of multiple infectious diseases. The first indication of AIDS disease came to light in USA in 1981 amongst a group of young homosexuals who were addicts of herion and other narcotics. Luc Montagnier (1983) and Robert Gallo (1984) discovered that a new type of retrovirus is the causative pathogen of AIDS. In 1986, The International Committee of virus Nomenclature (ICVN) named the AIDS virus as Human Immunodeficiency Virus (HIV).

Although AIDS is hardly a two and half decades old disease, it has spread virtually all over the world, becoming pandemic. According to the estimates of world Health Organization (WHO), about 52 million people in the world harbour HIV and thousands of new cases are detected every day. In India HIV infection was first detected in 1986 in some sex workers of Tamil Nadu. Since then, about 4 million cases have been detected and infection is fast spreading.

Structure of HIV:

HIV is a spherical, enveloped virus of about 90-120 nm diameter. Its genome consists of a single stranded RNA filament segmented into two identical filaments and associated with a 'reverse transcriptase enzyme'. Due to the presence of two identical filaments of RNA, HIV is considered to be 'diploid'. The envelope is comprised of a lipid bilayer derived from host cell membrane, and projecting, knob like glycoprotein spikes with pedicels formed of virus coded glycol-proteins (gp).

Pathogenesis and Symptoms:

The sentinels of our defense system are a type of white blood cells called lymphocytes. These cells are of different types to play different roles in acquired immunity. One type of lymphocytes called T₄(T_H) lymphocytes, play the crucial role in activation of other components of the immune system and production of antibodies. HIV attacks T₄ lymphocytes and destroy them. As a result the T₄ lymphocyte count in blood gradually diminishes (<>4 lymphocytes through several years ultimately leads to a full blown AIDS disease, during which a patient suffers from persistent fever and diarrhea, loss of appetite and weight, weakness and fatique, body pain, dry cough, white lesions in mouth and alimentary canal and warts upon anus and genitals. Eventually, the patient loses immunity and dies of multiple infectious diseases.

Transmission:

HIV is present in blood and other body fluids of infected persons. Hence it is transmitted from one to another person through activities involving exchange or transfer of body fluids. Thus, HIV is primarily transmitted through sexual activities. Unprotected sex, sharing of syringes and needles by intravenous drug addicts, use of unsterilized syringes by doctors and health workers etc. are responsible for transmission of HIV. Transfusion of infected blood and blood products, transplantations from infected to healthy one through breast milk feeding after birth are the other potential mode of transmission of HIV.

Diagnosis:

Some genes of HIV genome code for synthesis of some antigens which are released into the blood by infected T₄ lymphocytes. The immune system of body produces antibodies against these antigens, which can be detected by serological test called Elisa (Enzyme Linked Immunosorbent Assay), western blotting and PCR polymerase reaction test are the confirmatory test.

Symbol used to describe AIDS disease is ' ' (red ribbon). Noted Hollywood star Rock Hudson & Lawn Tennis Player Arthur Ashe of US were notable AIDS-causalities.

NARI (National AIDS Research Institute Puna).

NACO (National AIDS Control Organisation).

ARV (Anti Retro Viral Drug).

Prevention and Treatment:

General precautions such as safer sex and extensive use of condoms, strict screening of blood and blood products used for transfusions and tissue and organ transplantations, and extensive health education can prevent AIDS. December, 1 is observed as World's AIDS Day to arouse general awareness amongst people about HIV infection.

At present, there is no effective drug to save the immune system of AIDS patient from collapse. However, there are some drugs which are known to delay the progress of AIDS. These include Zidovudine (Azidothymidine-AZT), XQ-9302, Amphotericine-B and its methyl ester etc.

3. Pox:

Following types of pox diseases are reported in man:

Small Pox : Caused by DNA containing Pox viridae, Varoila.

Chicken Pox : Caused by DNA containing Herpes Virus, Vacicella.

German Pox : Caused by RNA containing Para influenza virus, Rubella.

Measles or Khasra : Caused by RNA containing Para influenza virus or Paramyxoviridae with minus strand RNA. AS already mentioned, vaccines of small pox were prepared by Jenner. Earlier small pox was very lethal disease in epidemic form in India. Officially, it has been eradicated from India with the help of WHO

MICROBIOLOGY: STUDY OF VIRUSES

2a) Viruses: Introduction

1. Study of viruses is called virology and Beijerinck is recognized as 'father of virology'. He reported enormous power of multiplication of viruses inside host cell. He also studied mechanism of nitrogen fixation by microorganisms like bacteria.
2. The term 'virus' has been derived from Greek word 'virion' which means 'poison'. Viruses are defined as hyperparasites and 'filterable entities' not having any cellular organization and defined as hyperparasites and 'filterable entities' not having any cellular organization and because of this cell theory is not applicable on them. They are thus exceptions to cell theory. They form crystals when taken out of the host cell. This shows non-living nature of viruses, which was first revealed by Stanley while working on 'Tobacco Mosaic Virus'. Nucleoprotein structure of viruses was first studied by Bawden & Pierre. In nucleoprotein structure of viruses, core of nucleic acid is surrounded by coat of protein. Viruses are unique as they contain only one type of nucleic acid. Mutation in viruses was first reported by Delbruck. Mutation and enormous power of reproduction confirm living nature of viruses. Viruses are thus the only entities, which have characters of non-living and living entities both. They are thus 'connecting links' between non-living entities and lining entities.

2b) Viruses: Historical Studies

Studies in viruses started with independent works of Pasteur and Adolf Mayer. Pasteur prepared vaccines of rabies virus and used the term 'virus' for first time. Mayer reported mosaic like spots on leaves of tobacco plant infected with virus. He described the virus as Tobacco Mosaic Virus [TMV]. Ivanowski passed the cell sap of infected tobacco leaves through bacteria proof bacteria proof filter and sprayed the filtrate on healthy leaves. Mosaic spots appeared again. Ivanowski through his experiment described viruses as filterable entities. Famous conclusion of Beijerinck about viruses i.e. 'contagium vivum fluidum' means sap retains the infection of viruses (living fluid infectant). Takami of Holland studied transmission of viruses through various agencies. He observed that insects are important agencies in transmission of viruses. Insects that transmit viruses are called 'vertors'. Viruses-vector relationship is highly specific.

Culture of viruses was prepared for the first time by Ender. It was poliomyelitis virus. Hershey and Chase observed that nucleic acid is the infective part of virus. They selected Bacteriophages for their experiment. Bacteriophages are DNA containing viruses which attack bacteria. They were discovered by Twort; further studies were made by DeHerelle. Experiment of Hershey & Chase is another example which confirms status of DNA as genetic material. Safferman & Morris discovered 'Cyanophages' i.e., viruses which attack blue green algae like Lyngbya, Phormidium & Plectonema. They are also called LPP-1 on the basis of hosts. Mycophages were discovered by Sinoten. They contain ds RNA.

Issac & Lindeman discovered a protein called Interferon secreted by host cells against infection of viruses. They selected cold virus for their experiment. Gibbs described viruses in coded form which is called 'Cryptogram of viruses' Cryptogram of viruses is based on 4 pairs of characters:

First pair : Type of nucleic acid in virus i.e. R or D

Number of thread in nucleic acid 1 or 2

Second pair : Molecular weight of viruses in millions i.e. 2

Percentage of nucleic acid of the viruses 5

Third pair : Shape of the virus in total i.e. E (elongeted) or S (spiral) or

X (unknown)

Shape of the protein coat of the virus E or S or X

(E' means elongated structure or rod shaped structure with blunt ends)

Fourth pair : Host/vector i.e. S (seed plant), I(invertebrate), V(vertebrate),

B(bacterium), Fu(fungus), Di(diptra), Af(aphid), Zero or 0 (novector),

X(unknown vector) Vector of the virus X

Thus, for example R/1; 2/5; E/E; S/X is cryptogram of TMV.

For Polia Virus (Poliovirus Primus) cryptogram is R/1; 5/30; S/S; V/O.

For Influenza Virus (mixovirus influenzae) R/1; 2-3/10; S/E; V/O.

For T4 phage D/2; 130/40; X/X; B/O.

2c) Viruses: Some Terms

1. A complete virus having a core of nucleic acid and coat of protein is called virion. Protein coat of the virus is termed as capsid; units of capsid are capsomeres. A virus drops its infective part i.e., nucleic acid alone inside host cell; empty protein coat remains outside. This empty protein coat, which remains outside the host called ghost protein, disappears later on. Raw material for new protein coat of the progeny viruses is contributed by the host.

Þ A few proteins in some viruses are enzymatic in functions e.g. lysozyme in bacteriophages, reverse transcriptase(RNA dependent DNA polymerase) in retrovituses, neuraminidase in influenza virus etc.

2. Viriod: Subviral agent having infectious nucleic acid alone is called viroid. Viroids are RNA & particles lacks protein coat. Spindle disease in photo tuber is caused by viroid, which is PSTV. Viroids were discovered by Diener & Rayner.
3. Prion or Slow Virus: Protein macromolecules causing infections are called prions. They lack ucleic acids. Scrappes & Kuru diseases (Severe brain infection) is sheep are caused by prions. They were first reported by Priusner who was awarded Nobel Prize for reporting Mad Cow disease caused by PrP (prion related protein). Bovine spongiform encephalopathy or Creulzfeldt Jacob disease (a type of insanity in young people), Kuru disease (the laughing death), Alzheimer's disease are caused by prions. In 1976 D.C.Gujdusek was awarded Nobel Prize for his work on prion based diseases.
4. Viruses transmitted by insects are called Arboviruses. Viruses causing Dengue, encephalitis etc are arboviruses.
5. Viruses which contain ss-DNA are called 'Gemini viruses'. ÆX174 phages are geminiviruses. They were reported by Sinsheimer.
6. Viruses which enter inside host cell as intact structures, are called Adeno viruses. Well defined protein coat is absent in Adenoviruses.
7. Virusoids or Satellilte RNAs (Rundle et. Al 1981). These are small circular RNAs similar to viroids, but are located inside the protein coat of a true virus. Virusoids required the assistance of virus for their replication.

2d) Viruses: Classification and Nomenclature

Earlier it was believed that plant viruses i.e. Phytophagineae contain RNA whereas animal viruses i.e. Zoophagineae contain DNA. This is, however, no more correct now. The only thing which is true about viruses is presence of only one type of nucleic acid. Cold virus i.e. Rhinovirus and poliovirus i.e. Enterovirus is together placed under Picorna virus.

2e) Viruses: Disease on Plants – Symptoms

1. Mosaic like spots may develop on leaves.
2. Leaves may show rolling or curling.
3. Leaves may show loss of chlorophyll (Chlorosis) or death of tissues (necrosis).
4. Plants may show abnormal or stunted growth.
5. Plants may show uncontrolled cell division i.e. hyperplasia(cell number increase) and unwanted swelling i.e. Hypertrophy in host.
6. Plants may show loss of entire inflorescence or flowers may become green i.e. virescence in flowers.

2f) Viruses: Some Common Viral Diseases

1. Plant Viral Diseases. Tobacco Mosaic, Potato Mosaic Pumpkin Mosaic, Apple Mosaic, Tulip Mosaic (Broken Tulip), Wheat Mosaic Streak, Bhindi Yellow Vein Mosaic, Potato Leaf Roll, Tobacco Leaf Curl, Papaya Leaf Curl. Banana Bunchy Top, Tomato Bunchy Top, Rice Tungro etc.

2. Animal Viral Diseases. Foot and Mouthm, Enquine encephalitis, Rinderpest, Kysanur Forest Disease (KFD) of monkeys (also humans), New Castle or Ranikhet of Fow].

3. Human Viral Diseases. Poliomyelitis, Rabies, Mumps, Measles, German Measles, Chickenpox, Smallpox (eradicated), Dengue, Encephalitis, Common cold, Flu, some gastrointestinal diseases, Yellow Fever, Herpes, Hepatitis, SARS, AIDS.

MICROBIOLOGY: INTRODUCTION

1. Micro-biology is study of microorganisms like viruses, Bacteria, Protozoa, 1-celled algae and 1-celled fungi etc. Antonie van Leeuwenhoek of Holland, Louis Pasteur of France, Robert Koch of Germany and Joseph Lister of England were earlier, workers in Microbiology. Leeuwenhoek is recognized as 'pioneer' worker in microbiology, he discovered bacteria for the first time as 'animalcules' or the 'wretched beastes'. Pasteur was fist to study role of microorganisms in fermentation process involved in wine preparation. Koch studied anthrax disease, caused by bacteria Bacillus anthracis. On the basis of his study Koch proposed Law of Pathogenicity, which was later on recognized as Koch's Postulates. Koch's Postulates are not applicable for viruses & organisms causing TB and leprosy. Lister introduced antiseptic surgery and also prepared culture of bacteria first time.
2. The two major research institutes of microbiology in world are: Pasteur Institute of Microbiology in Paris, France and Lister Institute of Microbiology, England. Workers at Lister Institute discovered 'naked' bacteria i.e. bacteria without cell of mucopolysaccharide complex. They were called 'L-form' of bacteria, named after Lister Institute. Mycoplasma like organisms, PPLO, is called L-form of Bacteria.
3. Triple Antigen Programme includes, immunization against Diptheria, Pertusis (Whooping cough) and Tetanus. It is also called D.P.T. Oral drops of polio are delivered separately. BCG vaccines are first vaccines given to new borns after 3-4 weeks of birth. Vaccines of: Polio was discovered by Salke; Small pox by Jenner, BCG by Calmett-Guire; Anthrax by Koch and Rabies by Pasteur. Vaccines of anthrax were prepared first. Pasteur, for developing vaccines of rabies was rewarded handsomely by Czar of Russia.