From William Withering's digitalis soup to modern three-phase clinical trials — how medicines are discovered, tested and approved.
Understand the development of drug testing from historic to contemporary protocols
Describe William Withering's discovery of digitalis and its significance
Explain the purpose and use of placebos in drug trials
Describe the three phases of clinical trials and double-blind methodology
Explain why drugs must be effective, safe, stable, easily administered and manufacturable
Discuss the ethical issues surrounding animal testing and clinical trials
Test what you already know before we begin. Don't worry about getting these wrong — that's the point. Attempting to retrieve answers, even incorrectly, primes your brain to learn the material more deeply.
1. William Withering discovered that an extract from which plant could treat dropsy (oedema)?
2. What is a placebo?
3. In a double-blind trial, who knows which patients receive the real drug?
4. Approximately how long does it take and how much does it cost to develop a new drug?
5. Which phase of clinical trials involves the largest number of patients?
Your score is tracked at the bottom of the page. Don't worry about mistakes — they help you learn.
Throughout history, almost every culture has used plants to treat diseases. In the 21st century, modern pharmaceutical companies still recognise the value of plant-based medicines — but the way drugs are developed and tested has changed dramatically.
Imagine you're a detective in the 1700s. You hear that a local "wise woman" has a secret soup recipe that cures a mysterious illness. You don't know which ingredient in the soup is doing the work — it has 20 different herbs! So you spend 10 years testing each ingredient one by one on different patients to figure out which one is the magic bullet. That's exactly what William Withering did.
William Withering (1741–99) was a British doctor and keen botanist. In 1775, a patient with severe heart failure came to him. Withering had no effective treatment, so his patient visited a local "wise woman" who used herbal remedies. After drinking her soup, the patient recovered.
Withering was fascinated. He bought the recipe — it contained about 20 different herbs. He guessed that foxglove contained the active ingredient. This plant contains a chemical called digitalis, which had been known as a poison for centuries but was also linked to reports of curing oedema (dropsy) — swelling caused by fluid retention when the heart and kidneys fail.
Over the next 10 years, Withering tested a variety of foxglove preparations on 163 patients at Birmingham General Hospital. He discovered that:
The drug based on foxglove chemicals is now called digoxin, and it's still prescribed by doctors today — about 230 years after Withering's work.
Consider Withering's approach to drug discovery. Think carefully about what you notice, what it makes you think, and what questions it raises.
Fill in the blanks using the word bank:
William Withering discovered that the plant contained a chemical called that could treat the condition known as . He tested his treatments on patients over years. The modern drug based on this work is called .
Explain the following in your own words:
a) Why was Withering's method considered both groundbreaking and risky?
b) Why did boiling the foxglove leaves reduce the drug's effectiveness?
Compare & Evaluate:
William Withering tested his foxglove preparations directly on sick patients at Birmingham General Hospital. Today, drugs must pass through pre-clinical testing, animal testing, and three phases of clinical trials before they can be prescribed.
Evaluate the strengths and limitations of Withering's approach compared to modern drug testing protocols. Consider: reliability of results, patient safety, and the pace of discovery. [6 marks]
Every medicine that comes onto the market today is the result of years of research and development (R&D). It takes about 10 years and around US$2.6 billion to develop a new drug. A new medicine must meet all five of the following criteria:
1. Effective — It must cure, prevent, or relieve the symptoms of the disease it is designed for.
2. Safe — It must be non-toxic and without unacceptable side effects.
3. Stable — It must be stored for a reasonable period and used under normal conditions without breaking down.
4. Easily taken in and removed — It must reach its target in the body and be excreted (removed) once it has done its job.
5. Manufacturable — It must be possible to produce it in a very pure form, in large quantities, and quite cheaply.
Think of a new drug like a dish at a 5-star restaurant. It must: taste great (be effective), not make you ill (be safe), survive in the fridge overnight (be stable), be digestible (easily absorbed and removed), and be replicable by any trained chef (manufacturable at scale). If it fails even one of these tests, it doesn't make the menu.
In the past, herbal remedies were a common source of new medicines. Today, scientists use more targeted approaches:
One method is to investigate chemicals that bind to our protein receptors or to the active sites of our enzymes. Researchers often use computer models to fit new molecular structures into the active site of enzymes or receptors that are important in disease processes. This can identify useful starting points for further work.
When scientists find a promising compound, they may patent it. A patent gives the inventor the exclusive right to make and sell the invention for the next 20 years. However, much of those 20 years will be consumed by the testing process.
Match each drug criterion to its description:
"It must not break down during normal storage"
"It must reach its target in the body and be removed once it has done its job"
Explain why a drug that is highly effective but impossible to manufacture cheaply might never reach patients.
Application question:
A researcher discovers a chemical compound that binds strongly to a receptor involved in Alzheimer's disease. In lab tests on cell cultures, it reduces toxic protein build-up by 85%. However, when given orally to mice, less than 2% of the compound reaches the brain.
Using your knowledge of drug criteria, explain which requirement this compound fails and suggest how scientists might try to overcome this problem. [4 marks]
From initial discovery to a medicine on the pharmacy shelf, there is a long and rigorous process. Thousands of compounds are screened, but very few ever make it to market.
Imagine 10,000 people audition for a singing competition. In the first round (lab tests), most are eliminated because they can't hold a tune (the compound doesn't work in cell cultures). A handful proceed to bootcamp (animal testing), where many more are cut because they can't handle the pressure of performing live (the drug causes harmful effects in a whole organism). Only about 5 make it to the live shows (human clinical trials), and often just 1 wins the competition (gets approved). That one winner then has to prove they can sustain a career (post-market surveillance).
Drag the stages into the correct order from first to last:
Drop stages here in order (1st → 6th):
If animal testing is successful, a regulatory authority will take decisions about whether the drug can be trialled on people. The testing varies from country to country, but internationally it must follow strict criteria.
The new drug (or in some cases, a placebo) is given to a small number of healthy volunteers. The goal is to check that the drug works as expected in the human body and doesn't cause any unexpected side effects.
At the same time, scientists continue looking at the effects of longer-term use of the drug in animal trials.
Phase 1 asks a simple question: "Is this safe for humans at all?" It's like dipping your toe in the pool before jumping in. Small group, healthy people, cautious doses.
If Phase 1 is successful, the drug moves to Phase 2 trials. This is when the new drug is used with patients who actually have the target disease. Between 100 and 500 patient volunteers are recruited.
Patients are given either the new drug or a similar number receive the best current treatment (or sometimes a placebo). This is the first chance for scientists and doctors to see how the new medicine affects the disease in a real patient.
Volunteers are closely monitored to find out more about the ideal dose, the effectiveness of the drug, and any side effects. Success at this stage means the compound has a good chance of becoming a useful medicine.
A placebo is a substance that looks like the drug being tested but has no active ingredient. It serves as a control in the experiment.
Why use a placebo? Patients often appear to respond to a treatment simply because they believe it will help them — not because of any chemical effect. This is called the placebo effect. Using a placebo eliminates this possibility, so scientists can be sure any improvement is caused by the actual drug.
Imagine two students both think they've drunk an energy drink before an exam. One actually drank an energy drink; the other drank coloured water (the placebo). If both students perform equally well, the energy drink doesn't actually work — the improvement was just in their heads. The placebo is what lets you tell the difference.
Phase 3 trials confirm the effectiveness and safety of the new drug. The numbers of patients involved are large — typically over 5,000 volunteer patients — so the trials have a better chance of showing up any unexpected adverse side effects.
Patients are randomly allocated to receive either the new medicine or the control/placebo. Data on effectiveness, side effects and other information are collected and assessed to see if there are any statistically significant differences between the new medicine and the placebo or currently available drug.
It is difficult to achieve a complete set of results because many patients stop taking the medicine for various reasons — some don't take it regularly.
In some trials, the drug is so successful that the trial is halted early — it becomes unethical to deny the new treatment to patients receiving the old treatment or placebo.
Phase 2 and 3 trials are normally carried out as double-blind trials. This means neither the doctor/scientist nor the patient knows whether the patient is receiving the new medicine, a control medicine, or a placebo.
Why double-blind?
Patients often appear to respond to a treatment because they believe it will do them good — this is the placebo effect. But doctors can also unconsciously influence results. If a doctor knows a patient is receiving the new drug, they might interpret symptoms more favourably. Double-blinding removes bias from both sides.
Instead of a placebo, a control medicine (the best-performing available treatment) is sometimes used to avoid denying any patient treatment entirely.
Think of a blind taste test for Coca-Cola vs. Pepsi, but the person pouring the drinks doesn't know which is which either. This way, neither the taster's preference nor the server's body language can influence the result. That's double-blinding.
1. How many patient volunteers are typically involved in Phase 2 trials?
2. Why might a clinical trial be halted early?
Complete the comparison table — fill in each cell:
| Feature | Phase 1 | Phase 2 | Phase 3 |
|---|---|---|---|
| Participants | |||
| Main purpose |
Evaluate this claim:
"Double-blind trials are the gold standard, so single-blind or unblinded trials should never be used."
Do you agree or disagree? Justify your answer with reference to specific scenarios. [4 marks]
Drug development raises important ethical questions at every stage — from animal testing to the use of placebos in human trials.
Some people have strong ethical objections to the use of animals in drug testing. However, the law currently states that animal testing must be carried out before drugs can be tested on people.
Key considerations:
Consider this statement: "Animal testing is a necessary evil — without it, we cannot guarantee the safety of new medicines for humans."
Sometimes a doctor may want to prescribe a drug before it has completed full human trials — for example, for a terminally ill patient with no other options.
Suggest two arguments FOR and two arguments AGAINST prescribing a drug before it has completed all stages of testing. [4 marks]
These are structured like IAL Biology exam questions. Attempt each one before checking the mark scheme. Writing out your answers by hand is the most effective retrieval practice.
Question 1
State two properties that a new medicine must have before it can be sold to patients.
Question 2
Describe the role of William Withering in the development of the drug digoxin.
Question 3
Explain why double-blind trials are used in the testing of new drugs.
Question 4
Compare William Withering's methods of discovering digoxin with modern drug testing protocols. In your answer, you should consider the methods used, the reliability of results, and patient safety.
Question 5 — Interleaved Retrieval
FROM EARLIER TOPICS: Biological Molecules & Transport
Digoxin must travel through the blood to reach the heart muscle cells. Explain how substances are transported in the blood and describe how digoxin might enter a heart muscle cell.
Question 6 — Interleaved Retrieval
FROM EARLIER TOPICS: Enzymes
Scientists use computer models to fit new molecular structures into the active site of enzymes. Explain what is meant by the "active site" of an enzyme and why its shape is important.
Rate your confidence on each learning objective, then complete the final retrieval challenge.
1. I can describe Withering's discovery of digitalis
2. I can explain the five criteria for a new drug
3. I can describe the three phases of clinical trials
4. I can explain placebos and double-blind methodology
5. I can discuss ethical issues around animal testing and clinical trials
Reflect on how your understanding has changed during this lesson.
Without looking back at any of the lesson content, write everything you can remember about drug development. Try to include key terms, names, numbers, and processes. This is the most powerful form of retrieval practice.