Drug development and monoclonal antibodies

Traditionally, drugs were extracted from plants and microorganisms:

• Digitalis — a heart drug, from foxgloves.
• Aspirin — a painkiller, originally from willow bark.
• Penicillin — an antibiotic, discovered by Alexander Fleming from the Penicillium mould.

Today, most new drugs are synthesised by chemists in the pharmaceutical industry. However, the starting point may still be a chemical extracted from a plant.

New drugs must be extensively tested and trialled before they can be used, to check three things:

• Toxicity — is the drug harmful, and does it have side effects?
• Efficacy — does the drug actually work?
• Dose — what is the optimum amount to give, and how often?

1. Preclinical testing — the drug is tested in the laboratory on cells and tissues, then on live animals, to check for toxicity and efficacy.
2. Clinical trials — the drug is tested on healthy volunteers first, using very low doses, to check it is safe.
3. If the drug is found to be safe, further trials are carried out on patients with the illness, to find the optimum dose and confirm it works.

Results are checked by other scientists (peer review) before they are published, to prevent false claims.

In clinical trials on patients, some receive the drug and others receive a placebo — a dummy treatment with no drug in it, such as a sugar pill. Comparing the two groups shows whether any improvement is really due to the drug.

In a double-blind trial, neither the patients nor the doctors know who is getting the drug and who is getting the placebo. This stops their expectations from biasing the results.

Monoclonal antibodies are identical copies of one type of antibody, all targeting the same specific antigen.

1. A mouse is injected with the chosen antigen, and its lymphocytes start making the matching antibody.
2. Lymphocytes make antibodies but can't divide. Tumour cells don't make antibodies but divide rapidly.
3. A lymphocyte is fused with a tumour cell to make a hybridoma cell, which can both divide and make the antibody.
4. The hybridoma is cloned to produce many identical cells, which all produce the same antibody.
5. Large amounts of the antibody are collected and purified.

Because they bind to one specific antigen, monoclonal antibodies can target a specific chemical or cell. Uses include:

• Pregnancy tests — they detect the hormone hCG, found in the urine of pregnant women.
• Diagnosis and measurement — in laboratories and hospitals, to measure hormone levels or detect pathogens in blood.
• Research — attached to a fluorescent dye, they locate or identify specific molecules in cells or tissues.
• Treating disease, e.g. cancer — bound to a radioactive substance, a toxic drug, or a chemical that stops cells dividing, they deliver it straight to cancer cells without harming other cells.

However, they have caused more side effects than expected, so they are not yet as widely used as first hoped.