/ 28 November 1997

Using human cells to save the laboratory

rats from torture

Alternative methods of drug testing could save animals from experimentation. Danny Penman reports

Two weeks ago at an Aids meeting in Johannesburg, watchers were so horrified by film of animal tests of a new herbal immune system booster that they demanded the screening be halted. But European Commission scientists in Italy have been putting the finishing touches to new procedures that they hope will eventually replace millions of animals in medical research.

Researchers at the European Centre for the Validation of Alternative Methods estimate that the number of animals used in all kinds of medical experiments could be cut by 50% to 60% over the next decade. Around 16% of experiments are toxicity tests to assess whether drugs and commonly used chemicals are poisonous. Over a million animals are used in such tests annually across Europe.

The centre was set up in 1991 by the European Commission to help develop replacements for animal experiments. The focal point of its work is the development of cultured human cell lines to replace live animals.

At present, toxicity tests dose live animals with suspect chemicals and observe the effects. These conventional methods not only raise animal welfare issues, but may also fail to allow for the subtle biochemical differences between humans and animals.

The cell cultures developed at the centre and affiliated labs allow scientists to see the effect on actual human cells. They claim it is far more accurate than experimenting on rats and extrapolating the results to humans.

Michael Balls, the centre’s head and professor of medical cell biology, says: “The aim is to develop a battery of tests so that researchers can select those that can answer their specific questions.”

At present, the centre’s human cell lines are only available for phototoxicity tests to detect whether a normally non-toxic chemical becomes dangerous when the body is exposed to sunlight.

In a conventional test, scientists would feed the suspect chemical to an animal, bathe it in sunlight and observe the effects. Using the new procedure, cultured human cells are simply washed in the suspect chemical, immersed in sunlight and analysed. Balls estimates that all conventional phototoxicity tests could be replaced by the new method within two years.

Although this would only replace “a few thousand animals per year” across Europe, the methods the centre has developed for proving the alidity of replacements for animal experiments, are of far greater significance.

The centre carried out a battery of blind trials and complex statistical models in nine labs across Europe. In essence, the results of the new methods were cross- matched with those from conventional tests by doctors, animal technicians and statisticians.

Within two years, the centre hopes to have proved that new ways to test the effects of chemicals on bone marrow, kidney and embryo cells actually work.

Colin Blakemore, professor of physiology at Oxford University and long-time target of animal rights activists, is also optimistic about reducing the number of animal experiments using the centre’s methods.

“It seems realistic that in the arena of toxicity testing the numbers of animals could be reduced by 50%. But it would not be of service to raise false hopes about replacing animal experiments completely. For example, in my area, it’s hard to see how you could study vision without studying a whole animal with eyes and a brain.”

But the procedures undergoing development by the centre and other organisations are facing an uphill struggle for acceptance, says Balls.

The primary problem, he says, is the regulators. “The hurdles placed in the path of non-animal tests are much harder than the equivalent animal-based test. The regulators feel more comfortable with animal tests, but a feeling is not scientific.”

These hurdles are in place for a reason, says Mark Matfield, director of the Research Defence Society, which represents the interests of pharmaceutical companies and medical researchers. “They must safeguard human health and welfare. If a test has worked well for 25 years, why change it?”

The search for alternatives is also speeding up. Pharmagene, a venture capital- backed pharmaceutical company set up last year, does not perform any animal-based drug tests. Instead, all research is done on human tissues from hospitals and mortuaries. The 8-million company has ruled out animal experimentation for scientific as well as ethical reasons.

Bob Coleman, chief scientific officer of Pharmagene, argues: “We take a rational approach. If you wanted to develop a drug for a racehorse, you wouldn’t test it on a dog, would you? We know the drawbacks of working with animals. When you work on human tissues you know that the results you get will be relevant. You can’t say that if you work solely on animals.”

Researchers are also developing computer programmes to screen potential drugs for toxicity before they undergo testing. For example, Derek (deductive estimation of risk from existing knowledge) software at Leeds University screens products for chemical clues to toxicity. It is already used by government and industry. If the computer projection says the product is likely to be toxic, then it need not be tested on animals.