Drug Development

Traditional Drug Extraction

You can easily buy a packet of painkillers at the supermarket today, but for centuries, humans had to rely entirely on nature's pharmacy.
Historically, most drugs were extracted directly from plants and microorganisms.
Digitalis is a drug used to treat heart conditions (such as heart failure and irregular heartbeats) by strengthening the heart muscle. It was traditionally extracted from foxgloves (the Digitalis purpurea plant).
Aspirin is a painkiller (analgesic) used to reduce fever and inflammation. It originates from salicylic acid, a chemical found in willow bark.
Penicillin is an antibiotic discovered by Alexander Fleming in 1928 from the Penicillium mould. Fleming noticed that bacteria on a petri dish would not grow near the fungus because the mould released a chemical that killed them, creating a visible clear ring/zone around the mould.

Modern Drug Discovery and Synthesis

The starting point for many highly advanced modern medicines is actually still a chemical extracted from a simple plant or microorganism.
However, most new drugs are now synthesised by chemists within the pharmaceutical industry.
The process often begins with identifying a biological target, such as a specific protein molecule involved in a disease.
Scientists then use computer modelling software to simulate how potential drug molecules will interact with these targets before any physical laboratory work takes place.

Preclinical Testing: Cells and Animals

How do scientists know a newly synthesised chemical won't just poison the person taking it?
All new drugs must undergo preclinical testing. This stage does not involve humans.
In vitro testing: First, the drug is tested in a laboratory using computer models and human cells or tissues to identify potential toxicity and preliminary efficacy.
Animal testing: Next, the drug is tested on live animals to check its effect on a whole organism (including the complex interactions between multiple organ systems).
In the UK, it is a legal requirement for new medicines to be tested on two different live mammals (e.g., mice and rabbits) before human trials can begin. Only about 1 in 5,000 to 10,000 chemicals pass this stage.

Clinical Trials: Human Testing

Testing a drug on isolated cells in a dish is completely different from testing it on a living, breathing human being.
Phase 1 (Healthy Volunteers): Initial clinical trials involve giving a very low dose of the drug to a small group of healthy volunteers. Healthy people are used to ensure that any side effects are not masked by existing illness, primarily testing for safety and toxicity.
Phase 2 and 3 (Patients): If the drug is safe, it is then tested on small, and later large, groups of patients who actually have the target disease. This tests for efficacy and helps to find the optimum dose.

Worked Example: Finding the Optimum Dose

More of a drug is not always better; finding the perfect balance requires careful data analysis.
If you need to calculate how much more effective a specific dose is compared to another, you use the percentage change formula:

\text{Percentage Change} = \frac{\text{New Value} - \text{Original Value}}{\text{Original Value}} \times 100

Question: A clinical trial tests a new drug. At a dose of $40\,\text{mg}$ , efficacy is $30\,\%$ . At $50\,\text{mg}$ , efficacy plateaus at $85\,\%$ , but side effects are minimal. At $60\,\text{mg}$ , efficacy remains at $85\,\%$ , but side effects increase sharply.

Calculate the percentage increase in efficacy when the dose is increased from $40\,\text{mg}$ to $50\,\text{mg}$ .
What is the optimum dose?

Step 1: Calculate the percentage increase.

Original Value = $30\,\%$
New Value = $85\,\%$

\text{Percentage Change} = \frac{85 - 30}{30} \times 100 = \frac{55}{30} \times 100 = 183.3\,\%

Step 2: Recall the definition of optimum dose.

It is the dose providing maximum efficacy with minimum toxicity.

Step 3: Analyse the data provided.

$40\,\text{mg}$ has low efficacy.
$50\,\text{mg}$ achieves maximum efficacy ( $85\,\%$ ) with minimal toxicity.
$60\,\text{mg}$ provides no extra benefit but increases toxicity.

Step 4: State the conclusion.

The optimum dose is $50\,\text{mg}$ .

Trial Validity: Placebos and Peer Review

Imagine taking a completely plain sugar pill and suddenly feeling your headache disappear.
To account for this "placebo effect" (where patients feel better simply because they expect the treatment to work), clinical trials use a placebo. This is a dummy treatment containing no active ingredient, serving as a control group.
Trials are usually designed as a double-blind trial, meaning neither the patients nor the doctors know who has received the real drug and who has received the placebo. This eliminates bias, preventing doctors from subconsciously treating patients differently and stopping patients from reporting symptoms based on their expectations.
Patients are split into groups using randomisation to ensure the test and control groups are comparable.
Before any findings can be published, they must undergo peer review. Independent scientists scrutinise the methodology to ensure the data is valid and to prevent false claims.

Sign up to continue reading

Get full access to revision notes, key terms, and exam tips for every subtopic.

Exam Tips

Common Mistake
Students often state that healthy volunteers are used in Phase 1 trials to see if the drug works, but they are actually used only to check for safety and side effects, as they do not have the disease to test efficacy.
2
In 6-mark questions describing Fleming's discovery, examiners specifically look for the phrase 'clear ring' or 'clear zone' to describe where the bacteria were killed by the mould on the petri dish.
3
When explaining why drugs must be tested on live animals, always state that it checks the effect on a 'whole organism' to observe interactions between complex organ systems.
4
To get full marks when defining a double-blind trial, ensure you explicitly state that it eliminates bias (both observer bias from doctors and participant bias from patients).

Key Terms(11)

Digitalis: A drug traditionally extracted from foxgloves, used to treat heart conditions by strengthening the heart muscle.
Aspirin: A painkilling drug traditionally originating from willow bark, used to reduce fever and inflammation.
Penicillin: An antibiotic discovered by Alexander Fleming from the Penicillium mould.
Toxicity: A measure of whether a drug is poisonous or has harmful side effects.
Efficacy: The ability of a drug to produce the intended or desired effect (i.e., whether it actually works).
Dose: The specific amount or concentration of a drug that should be administered.
Optimum dose: The specific dose that is most effective at treating a disease with the fewest possible side effects.
Placebo: A dummy treatment that contains no active ingredient, used as a control in clinical trials.
Double-blind trial: A clinical trial in which neither the participants nor the researchers know who is receiving the active drug or the placebo.
Bias: An inclination that might unfairly influence results, such as a doctor's or patient's expectations affecting the trial outcome.
Peer review: A process where results are scrutinised by independent scientists to check for methodology flaws and ensure the data is valid before publication.

Previous Subtopic: Antibiotics and MedicinesAntibiotics and Medicines Next Topic: Monoclonal AntibodiesAntibody Production

Back to Drug Development

Put your knowledge into practice — try past paper questions for Biology

Key Terms(11)

Digitalis: A drug traditionally extracted from foxgloves, used to treat heart conditions by strengthening the heart muscle.
Aspirin: A painkilling drug traditionally originating from willow bark, used to reduce fever and inflammation.
Penicillin: An antibiotic discovered by Alexander Fleming from the Penicillium mould.
Toxicity: A measure of whether a drug is poisonous or has harmful side effects.
Efficacy: The ability of a drug to produce the intended or desired effect (i.e., whether it actually works).
Dose: The specific amount or concentration of a drug that should be administered.
Optimum dose: The specific dose that is most effective at treating a disease with the fewest possible side effects.
Placebo: A dummy treatment that contains no active ingredient, used as a control in clinical trials.
Double-blind trial: A clinical trial in which neither the participants nor the researchers know who is receiving the active drug or the placebo.
Bias: An inclination that might unfairly influence results, such as a doctor's or patient's expectations affecting the trial outcome.
Peer review: A process where results are scrutinised by independent scientists to check for methodology flaws and ensure the data is valid before publication.

Drug Development

Traditional Drug Extraction

You can easily buy a packet of painkillers at the supermarket today, but for centuries, humans had to rely entirely on nature's pharmacy.
Historically, most drugs were extracted directly from plants and microorganisms.
Digitalis is a drug used to treat heart conditions (such as heart failure and irregular heartbeats) by strengthening the heart muscle. It was traditionally extracted from foxgloves (the Digitalis purpurea plant).
Aspirin is a painkiller (analgesic) used to reduce fever and inflammation. It originates from salicylic acid, a chemical found in willow bark.
Penicillin is an antibiotic discovered by Alexander Fleming in 1928 from the Penicillium mould. Fleming noticed that bacteria on a petri dish would not grow near the fungus because the mould released a chemical that killed them, creating a visible clear ring/zone around the mould.

Modern Drug Discovery and Synthesis

The starting point for many highly advanced modern medicines is actually still a chemical extracted from a simple plant or microorganism.
However, most new drugs are now synthesised by chemists within the pharmaceutical industry.
The process often begins with identifying a biological target, such as a specific protein molecule involved in a disease.
Scientists then use computer modelling software to simulate how potential drug molecules will interact with these targets before any physical laboratory work takes place.

Preclinical Testing: Cells and Animals

How do scientists know a newly synthesised chemical won't just poison the person taking it?
All new drugs must undergo preclinical testing. This stage does not involve humans.
In vitro testing: First, the drug is tested in a laboratory using computer models and human cells or tissues to identify potential toxicity and preliminary efficacy.
Animal testing: Next, the drug is tested on live animals to check its effect on a whole organism (including the complex interactions between multiple organ systems).
In the UK, it is a legal requirement for new medicines to be tested on two different live mammals (e.g., mice and rabbits) before human trials can begin. Only about 1 in 5,000 to 10,000 chemicals pass this stage.

Clinical Trials: Human Testing

Testing a drug on isolated cells in a dish is completely different from testing it on a living, breathing human being.
Phase 1 (Healthy Volunteers): Initial clinical trials involve giving a very low dose of the drug to a small group of healthy volunteers. Healthy people are used to ensure that any side effects are not masked by existing illness, primarily testing for safety and toxicity.
Phase 2 and 3 (Patients): If the drug is safe, it is then tested on small, and later large, groups of patients who actually have the target disease. This tests for efficacy and helps to find the optimum dose.

Worked Example: Finding the Optimum Dose

More of a drug is not always better; finding the perfect balance requires careful data analysis.
If you need to calculate how much more effective a specific dose is compared to another, you use the percentage change formula:

\text{Percentage Change} = \frac{\text{New Value} - \text{Original Value}}{\text{Original Value}} \times 100

Calculate the percentage increase in efficacy when the dose is increased from $40\,\text{mg}$ to $50\,\text{mg}$ .
What is the optimum dose?

Step 1: Calculate the percentage increase.

Original Value = $30\,\%$
New Value = $85\,\%$

\text{Percentage Change} = \frac{85 - 30}{30} \times 100 = \frac{55}{30} \times 100 = 183.3\,\%

Step 2: Recall the definition of optimum dose.

It is the dose providing maximum efficacy with minimum toxicity.

Step 3: Analyse the data provided.

$40\,\text{mg}$ has low efficacy.
$50\,\text{mg}$ achieves maximum efficacy ( $85\,\%$ ) with minimal toxicity.
$60\,\text{mg}$ provides no extra benefit but increases toxicity.

Step 4: State the conclusion.

The optimum dose is $50\,\text{mg}$ .

Trial Validity: Placebos and Peer Review

Imagine taking a completely plain sugar pill and suddenly feeling your headache disappear.
To account for this "placebo effect" (where patients feel better simply because they expect the treatment to work), clinical trials use a placebo. This is a dummy treatment containing no active ingredient, serving as a control group.
Trials are usually designed as a double-blind trial, meaning neither the patients nor the doctors know who has received the real drug and who has received the placebo. This eliminates bias, preventing doctors from subconsciously treating patients differently and stopping patients from reporting symptoms based on their expectations.
Patients are split into groups using randomisation to ensure the test and control groups are comparable.
Before any findings can be published, they must undergo peer review. Independent scientists scrutinise the methodology to ensure the data is valid and to prevent false claims.

Sign up to continue reading

Get full access to revision notes, key terms, and exam tips for every subtopic.

Exam Tips

Common Mistake
Students often state that healthy volunteers are used in Phase 1 trials to see if the drug works, but they are actually used only to check for safety and side effects, as they do not have the disease to test efficacy.
2
In 6-mark questions describing Fleming's discovery, examiners specifically look for the phrase 'clear ring' or 'clear zone' to describe where the bacteria were killed by the mould on the petri dish.
3
When explaining why drugs must be tested on live animals, always state that it checks the effect on a 'whole organism' to observe interactions between complex organ systems.
4
To get full marks when defining a double-blind trial, ensure you explicitly state that it eliminates bias (both observer bias from doctors and participant bias from patients).

Key Terms(11)

Digitalis: A drug traditionally extracted from foxgloves, used to treat heart conditions by strengthening the heart muscle.
Aspirin: A painkilling drug traditionally originating from willow bark, used to reduce fever and inflammation.
Penicillin: An antibiotic discovered by Alexander Fleming from the Penicillium mould.
Toxicity: A measure of whether a drug is poisonous or has harmful side effects.
Efficacy: The ability of a drug to produce the intended or desired effect (i.e., whether it actually works).
Dose: The specific amount or concentration of a drug that should be administered.
Optimum dose: The specific dose that is most effective at treating a disease with the fewest possible side effects.
Placebo: A dummy treatment that contains no active ingredient, used as a control in clinical trials.
Double-blind trial: A clinical trial in which neither the participants nor the researchers know who is receiving the active drug or the placebo.
Bias: An inclination that might unfairly influence results, such as a doctor's or patient's expectations affecting the trial outcome.
Peer review: A process where results are scrutinised by independent scientists to check for methodology flaws and ensure the data is valid before publication.

Previous Subtopic: Antibiotics and MedicinesAntibiotics and Medicines Next Topic: Monoclonal AntibodiesAntibody Production

Back to Drug Development

Put your knowledge into practice — try past paper questions for Biology

Key Terms(11)

Digitalis: A drug traditionally extracted from foxgloves, used to treat heart conditions by strengthening the heart muscle.
Aspirin: A painkilling drug traditionally originating from willow bark, used to reduce fever and inflammation.
Penicillin: An antibiotic discovered by Alexander Fleming from the Penicillium mould.
Toxicity: A measure of whether a drug is poisonous or has harmful side effects.
Efficacy: The ability of a drug to produce the intended or desired effect (i.e., whether it actually works).
Dose: The specific amount or concentration of a drug that should be administered.
Optimum dose: The specific dose that is most effective at treating a disease with the fewest possible side effects.
Placebo: A dummy treatment that contains no active ingredient, used as a control in clinical trials.
Double-blind trial: A clinical trial in which neither the participants nor the researchers know who is receiving the active drug or the placebo.
Bias: An inclination that might unfairly influence results, such as a doctor's or patient's expectations affecting the trial outcome.
Peer review: A process where results are scrutinised by independent scientists to check for methodology flaws and ensure the data is valid before publication.