Throughout history, many important drugs were discovered from NATURAL SOURCES:
PENICILLIN — discovered by Alexander Fleming (1928) from the Penicillium mould. He noticed bacteria on a petri dish were being killed near a mould contamination.
ASPIRIN — derived from salicylic acid found in willow bark. Used as a pain reliever for centuries before the active compound was isolated.
MORPHINE — derived from opium poppies — a powerful painkiller still used today.
QUININE — extracted from cinchona tree bark — historically the main treatment for malaria.
Modern drug discovery also uses:
Synthetic chemistry — designing molecules in the laboratory.
Computer modelling — predicting how molecules interact with biological targets.
Biotechnology — using genetically modified organisms to produce medicines (e.g. human insulin produced by GM bacteria).
Pre-Clinical Testing
Before any new drug is tested on humans, it must undergo PRE-CLINICAL TESTING:
CELL CULTURES — the drug is tested on cells grown in the laboratory. Checks basic toxicity and whether the drug has any biological effect.
COMPUTER MODELS — simulate the drug's behaviour and interactions in the body before any living organism is used.
ANIMAL TESTING — the drug is tested on animals (usually mice or rats) to check:
Whether it is safe in a living organism.
How it is absorbed, distributed and broken down.
What side effects occur.
Whether it has any effect on the target disease.
Many potential drugs fail at this stage and are abandoned. Only those that show promise and acceptable safety proceed to human trials.
Clinical Trials — Testing on Humans
Drugs that pass pre-clinical testing move to CLINICAL TRIALS — testing in human volunteers. This happens in three phases:
PHASE 1 — Safety:
Small group of healthy volunteers.
Very low doses given initially, then gradually increased.
Aim: check the drug is safe in humans and identify any side effects.
PHASE 2 — Efficacy:
Larger group of patients who have the condition the drug treats.
Aim: check the drug actually works and find the optimal dose.
PHASE 3 — Large-scale comparison:
Hundreds or thousands of patients.
The drug is compared to either an EXISTING TREATMENT or a PLACEBO.
DOUBLE-BLIND TRIALS are used — neither the patients nor the doctors administering the trial know who is receiving the real drug or the placebo. This eliminates bias.
A PLACEBO is an inactive dummy treatment (e.g. a sugar pill) that looks identical to the real drug. Used to control for the PLACEBO EFFECT — where patients improve simply because they believe they are receiving treatment.
If Phase 3 is successful, the drug is submitted for regulatory approval. In the UK this is the MHRA (Medicines and Healthcare products Regulatory Agency).
Thalidomide — A Cautionary Tale
Thalidomide was developed in the 1950s as a sedative and treatment for morning sickness in pregnancy.
It had not been adequately tested for effects on developing embryos.
When taken by pregnant women, it caused severe birth defects — particularly abnormal limb development (phocomelia — very short or absent limbs).
An estimated 10,000 babies were affected worldwide before the drug was withdrawn in 1961.
This case led directly to much stricter drug testing requirements worldwide — particularly the requirement to test drugs on pregnant animals before use in humans.
Thalidomide's lesson: drugs must be tested thoroughly for ALL potential uses and ALL population groups, including pregnant women.
Interestingly, thalidomide is now used again under very strict controls to treat some cancers (multiple myeloma) and leprosy — illustrating that even a harmful drug can have safe medical uses in the right context.
⚠️ Common Mistake
A DOUBLE-BLIND trial means NEITHER the patient NOR the doctor knows who is getting the real drug. A SINGLE-BLIND trial means only the patient doesn't know. Double-blind removes bias from both sides. A PLACEBO is a dummy treatment — not a low dose of the real drug.