6.3.4 Antibiotics

• Antibiotics are drugs that inhibit the growth of microorganisms
  • Most antibiotics kill or stop the growth of bacteria (prokaryotes) but do not harm the cells of the infected organism
  • This is because they block specific processes that occur in prokaryotic cells but do not have the same effect on eukaryotic cells
• Processes that might be targeted include:
  • Transcription
  • Translation
  • DNA replication
  • Ribosome function
  • Cell wall formation

• Some antibiotics are derived from living organisms such as saprotrophic fungi
  • Penicillin is produced by certain fungi in the genus Penicillium
  • When growing in the wild the antimicrobial secretions of the fungus helps it to compete by killing nearby saprotrophic bacteria

• Antibiotics can also be made synthetically (in a laboratory)

How penicillin works

• Penicillin is not effective against all bacteria (eg. tuberculosis) because the bacteria may have:
  • Thicker cell walls which reduce permeability
  • Enzymes which breakdown penicillin
• There are many different examples of antibiotics which are effective against a range of bacterial diseases

• Howard Florey and Ernst Chain carried out experiments to test penicillin on bacterial infections in mice in the 1930s
• First of all, they developed a technique for purifying and concentrating penicillin from liquid cultures of Penicillium
  • The method they used was very inefficient and only produced small quantities of the antibiotic
• Secondly, they showed that Penicillin was effective in preventing bacterial growth on agar plates
• After they had collected this evidence, Florey and Chain used mice to show the effect of penicillin at the level of an organism
  • In order to carry out these tests on mice, the mice first needed to be infected with a known bacterial pathogen. A deadly Streptococcus bacteria was used to develop pneumonia in 8 mice
  • Of these 8 mice, 4 were injected with penicillin and 4 were left untreated
  • In less than 24 hours, the 4 untreated mice had all died whereas those that were treated with penicillin survived

Florey and Chain showed that penicillin could aid the recovery of mice infected with Streptococcus bacteria

Human tests

• After successful trials using penicillin to treat mice, Florey and Chain were ready to begin testing human patients
• It took some time to build up a large enough supply of penicillin using their purification techniques
• They then started treatment on their first patient, a policeman who was suffering from a life-threatening bacterial infection resulting from a scratch on his face
• The patient showed improvement but unfortunately, the supply of penicillin was not enough to complete the treatment and so the man died of his infection
• Following this, a series of other patients were treated with varying success and Florey and Chain realised that they needed to produce much larger quantities of penicillin than their current capacity
• Larger scale testing and treatment (using penicillin) became possible after an American pharmaceutical company started mass production
• It was after this that the true level of efficacy for penicillin was established

NOS: Risks associated with scientific research; Florey and Chain's tests on the safety of penicillin would not be compliant with current protocols on testing

• New drugs carry new risks as scientists can not always predict how the body may respond to the drug, whether the drug will be effective or how significant any side effects might be
• Before drugs become licenced and available for use, they must go through a rigorous series of tests and trials to minimise the risks
• A summary of the procedure is as follows:
  • Initially, after a computer analysis has been carried out on the structure of the drug, trials are carried out with animals to see the effect on a whole organism level
  • Next, a small number of healthy humans will trial the drug to measure the toxicity
  • If these first 2 stages are successful, testing will be carried out on a progressively larger number of patients suffering from the target disease
    • In this final stage, the aim is to establish how effective the drug is and collect as much information as possible about side effects
  • Once the clinical trials are complete, the new drug can be approved and licenced for medical use
  • The process usually takes years to reach the approval stage
• When Florey and Chain carried out their trials with penicillin, these protocols for safe testing were not in place and their work was only carried out over a matter of months
  • This meant that some patients received treatment very rapidly for infections that were previously incurable, however, there was a huge risk that the new drug, penicillin, could have caused significant side effects

New drugs go through a series of tests and trials in order to be approved for medical use

Previous drugs trials

• Carefully designed drugs testing protocols do now exist, but serious problems can still arise
  • Thalidomide was a drug that was used in the 1950s to treat a variety of conditions including some cancers and leprosy
    • It was found that thalidomide provided an effective cure for morning sickness and so pregnant women were prescribed thalidomide as a treatment
    • The effects of the drug on a foetus had not been tested and in subsequent years, babies were born with a range of disabilities including the absence of limbs, sensory impairment and disfigurement, amongst others
    • It took several years for the link to be made between Thalidomide and the disabilities of the thousands of children who were born
    • Thalidomide was withdrawn from use in the early 1960's

  • A drugs trial was carried out in 2006 to test an experimental leukaemia drug, TGN1412
    • The drug had successfully passed the animals trials where it was given to monkeys, so it moved to the next stage of testing
    • Eight healthy volunteers took part in the trial and after an hour of receiving the drug, six of them were rushed to intensive care with multiple organ failure
    • Although they all recovered, the long term effects on their immune systems are unknown
    • This is one of the most infamous clinical trial emergencies of modern day

Antibiotics and viruses

• Antibiotics are ineffective against viruses as they are non-living
• Viruses are particles and not cells
  • They have no metabolism or cell structure and therefore cannot be targeted in any of the ways that antibiotics target a bacterial cell

• When a virus replicates, it uses the host cell’s mechanisms for transcription, translation and other metabolic pathways, so not even these processes can be targeted as antibiotics do not bind to the proteins that host cells use in these processes
  • Drugs that would target these processes would damage the host cells and cause even more harm
• Antivirals are drugs that target viral enzymes without harming the host cell