Drug testing

Animals are used in drug testing in 2 main ways, firstly to see if new drugs work against particular diseases, and secondly to see if drugs are safe.

Animal studies to discover new drugs

To see if a drug works, diseases are deliberately produced in animals. For example:

harmful chemicals are injected into the joints of rats to produce arthritis;
cancer is produced by giving animals chemicals or by grafting human tumours into immune-deficient mice;
animals are infected with viruses such as HIV, hepatitis and herpes;
a diabetes-like disease is produced by giving animals a chemical that damages the pancreas.

Obviously these diseases make the animals very sick, and in some cases cause a lot of pain. At the end of the experiments animals are nearly always killed.

Apart from being cruel to animals, this approach is also not effective. Different species respond in different ways to drugs. The fact that something works in rats doesn't mean it will work in humans. For example, of the 25 drugs that seemed to be useful for treating strokes in animals over a 10 year period, not a single one is being used in human medicine.

Another example is the National Cancer Institute (NCI). For 35 years it tried out 400,000 chemicals in millions of mice deliberately bred to develop leukemia. The NCI was looking for anti-tumour chemicals, but this approach was not effective.

Using human cell cultures

The NCI now uses 60 human tumour cell lines to look for chemicals that might be effective against cancer. They use cancer cells from the colon, lung, skin, kidney, ovary, brain and blood for their tests. There is no shortage of human tumours in hospitals because they are removed during operations. They can be used for testing. In both the USA and the UK there are now human tissue banks where researchers can get normal and diseased tissue for testing. Alternatively, researchers can buy many different human cell lines from commercial companies.

The cells are grown in test tubes and the effect of various chemicals on their growth is studied. There are now more and more studies where human tumour cells are being used to study the effectiveness of different drugs for particular kinds of cancer, and also to work out the best dosage of these drugs.

Some other ways in which human cells have been used to look for effective drugs:

White blood cells in test tubes can be infected with the AIDS virus. Chemicals are added to the cell culture to see whether they can stop the virus replicating.

Human liver cells can be infected with hepatitis. Once again chemicals are added to the cell culture to try to stop the virus growing.

Brain slices can be made to produce discharges similar to those in epilepsy. Chemicals are added to see if they can stop these discharges, that is, prevent seizures. Brain tissue can be obtained from operations for tumours or intractable epilepsy.

Synovial membranes taken from people with rheumatoid arthritis have been used to see if chemicals could reduce inflammation.

Computers are now being used to design new drugs. To have an effect, drugs have to bind to particular receptors in the body. The binding is very precise, and is like a lock and key arrangement. Many receptors have now been precisely described, so computers can design molecules that will fit exactly into these receptors.

Testing the safety of drugs

The safety of drugs is tested on animals in a number of different ways.

LD50 test - how much of a drug does it take to kill half the animals? Groups of animals are fed increasing doses until half of them die. The rest are then killed and dissected.

Chronic toxicity - will the drug cause any damage in the long term? Animals are fed the drug daily, often for 90 days, before being killed and dissected.

Carcinogenicity - will the drug cause cancer? Rats and mice are fed high doses of the drug for 2 years. They are then killed and examined for tumours.

Teratogenicity - will the drug cause birth defects? Pregnant animals are fed the drug, and the foetuses are later examined for abnormalities.

These tests not only kill large numbers of animals, but also cause a lot of suffering before the animals die. You might think that at least the drugs will be safe after this testing, but that isn't the case.

Animal tests don't guarantee safety

Of the 198 drugs approved by the US Food and Drug Administration from 1976-1985, 51.5% had serious side effects. The effects were serious enough to cause withdrawal of the drug or, more often, relabelling with more danger warnings. Effects included heart failure, shock, breathing difficulties, seizures, kidney failure, liver failure and death. Remember that all these drugs had passed animal tests before going on the market.

In 1995 there were 130,950 reports of adverse drug reactions made to the US Food and Drug Administration.

Over the years many drugs that passed animal tests were subsequently withdrawn after causing injury and even death to humans. For example:

Clioquinol (Entero-Vioform, Mexaform), an anti-diarrhoea drug. It caused the nervous system disosrder, subacute myelo-optic neuropathy in Japan. At least 10,000 people suffered walking difficulties, numbness, paralysis or eye problems, including blindness.
Benoxaprofen (Opren), an anti-arthritis drug. It caused 3500 adverse reactions and 61 deaths in the UK alone. Deaths were due to liver damage.
Other anti-arthritis drugs withdrawn from sale due to adverse reactions and deaths include Zomax, Flosint, Alclofenac, Ibufenac, and Osmosin .
Zimelidine (Zelmid), an anti-depressant. It caused 300 adverse reactions in the UK, including liver damage and convulsions. It also produced 7 deaths.
Practolol (Eraldin), a heart drug. It caused severe eye problems, including blindness, and 23 deaths in the UK. Eventually 1000 people were compensated by the drug company for injuries.

Animal tests don't guarantee that a drug is safe. All these drugs were thoroughly tested on animals, who didn't show the adverse reactions seen in humans.

The most infamous case of animals not responding to drugs in the same way as humans is thalidomide. Women took this drug for morning sickness during pregnancy. Their babies were born with very shortened arms and legs. Human foetuses are very sensitive to this drug, but most animals are not. Only in rabbits and primates does thalidomide produce similar birth defects.

Alternative safety tests

There are alternative tests to find out how poisonous a drug is and whether it is likely to damage particular organs, cause cancer, or cause birth defects.

A five year study based in Sweden has just found that human cell cultures are better than rat and mouse LD50 tests at predicting the concentration of a drug likely to kill a human. Human cell cultures can also be used to test whether a chemical is likely to damage a particular organ. For more details about these tests see Toxicity testing .

Bacteria tests are already being used to find out whether a chemical will cause genetic damage that can lead to cancer. Human cell tests are also used for this purpose. Embryonic cell cultures are used to test for birth defects, as are fruit fly eggs and the tiny hydra organism. For more details about these tests see Cancer and birth defects .

If you would like to see a more detailed version of this document on drug testing, including references, go to More on drug testing.